The dates displayed for an article provide information on when various publication milestones were reached at the journal that has published the article
activities on preceding journals at which the article was previously under consideration are not shown (for instance submission
All content on this site: Copyright © 2025 Elsevier B.V., its licensors, and contributors. All rights are reserved, including those for text and data mining, AI training, and similar technologies. For all open access content, the relevant licensing terms apply.
Connecting decision makers to a dynamic network of information, people and ideas, Bloomberg quickly and accurately delivers business and financial information, news and insight around the world
As student enrollment across its 10 campuses hits an all-time high
the UC system is looking to raise debt to pay for capital projects and refinance older obligations
Retail investors will get a chance to place orders for the investment-grade issue on Wednesday
All content on this site: Copyright © 2025 Elsevier B.V.
The Cree sustainable modular construction system was born just over ten years ago in Austria. The Casais Group, one of the largest construction companies in Portugal, is already using this technology and believes it is the future of construction, its commercial director told a Luxembourg-Portugal business forum, hosted by the Luxembourg Chamber of Commerce on Tuesday.
“On the other hand, wood is a natural carbon sequester, so it has an impact in terms of CO2 emissions,” Laranjeiro added. “And construction time is reduced by 40%.”
Driven by EU environmental commitments and the country’s growing concern about its ecological footprint, Luxembourg is increasingly committed to promoting sustainable construction.
Modular construction and the use of green materials are two of the possible ways forward, and some projects are already underway.
“The Ministry of the Economy is committed to promoting sustainable construction practices, together with other public bodies and the private sector,” Paul Shosseler, the director of sustainable construction and circular economy at the ministry, told the event.
“We have resources, such as bio-based materials and we want to develop concrete recycling,” Shosseler said. “But also the management of national resources. We also want to promote smart city projects at the European level, geared towards digitalisation and, of course, logistical processes that help decarbonise prefabrication centres and construction consolidation centres. There are already projects on this in partnership with the University of Luxembourg,” he added.
Bruno Renders, CEO of the Luxembourg Council for Economic Development in Construction (CDEC), created a decade ago, stressed the importance of the transition from traditional methods to more sustainable and efficient construction techniques.
“We are aware that we can use 50% less material than we currently use [in construction],” Renders said, adding that while traditional materials will continue to be used, “nature-based technologies and traditional low-carbon materials” are growing in popularity.
A sustainable system means that not only can many construction projects use fewer materials
but it is also possible to streamline production processes
“Everyone knows that we can make a specific structure
emitting less than 50% the CO2 than we do today,” she said.The drive for industrialisation
digitalisation and prefabrication is all about efficiency
sustainability director at the Porto-based construction technology company Built Colab
“All the industrialisation of the process means that there are fewer failures in construction and execution
As soon as we make ten modules at once instead of ten different ones
(This article was originally published by Contacto. Translation, editing and adaptation by Alex Stevensson)
HousingPrivate developers disadvantaged in affordable housing sales, lobby claimsPrivate developers face stricter requirements for same properties than public bodies, argue real estate lobby group Chambre immobilière
Rising wagesLuxembourg's €55 hourly labour costs still the EU’s highest But average hourly wages in the Grand Duchy rose by just 2.1% between 2023 and 2024, one of the smallest increases in the eurozone
City redevelopmentPremiumRestaurant with park views planned in Hollerich renovation projectOffices are also set to be created in major revamp of former premises of Heintz van Landewyck cigarette company
Real estateThe eight construction projects transforming the Cloche d'Or districtAs the new headquarters of State Street takes shape, a look at the other planned residential and office projects in the neighbourhood
Construction freezeCity housing project in limbo as Capelli group faces receivershipPlans for site comprising homes and offices in Howald are on hold for now, but CEO Christophe Capelli remains optimistic about future operations
Real estateHow a Luxembourg property developer overcomes repeated crisesAfter bouncing back in 2024, Eaglestone is calling on public decision-makers for greater fluidity to facilitate successful completion of projects
Building projectFirst stage of Hollerich revamp set for completion in SeptemberUnicity complex, which will host offices, shops and homes, is expected to open later this year
Economic outlookConstruction sector confidence slumps to lowest level since 2009 crashThree in five companies in construction industry ‘currently complaining of insufficient demand’, Statec says
Advertiser contentTreat yourself to a stress-free holidayDreaming of a worry-free trip
What if the secret to a smooth getaway was simply good preparation and the right protection
Advertiser contentReal estate: Why should you take advantage of the start of 2025 to begin your real estate project?The main things we remember about the housing sector over the past 12 months are the rise in interest rates and the fall in property prices
Advertiser contentProperty: I've decided to invest!The various forms of government support for investment
Advertiser contentThe Luxembourg Times BusinessRun is happening again on 18th September!On Thursday 18th September
with the starting gun of the 11th Luxembourg Times BusinessRun fired at the Coque at 7 pm
Share this with instagramShare this with facebookShare this with linkedinSections
2012 at 3:13 pm ET.css-79elbk{position:relative;}The following arrests occurred between Nov
11/22/2012 12:00 am Location: Morris Avenue Detective Keith Doherty stopped a car after observing it weaving over the center line traveling on Morris Avenue
was subsequently arrested for Operating a Motor Vehicle While Under the Influence of Alcohol and Operating a Vehicle with a Suspended Driver License
He was later released with a Springfield Municipal Court appearance date
11/22/2012 4:15 am Location: Morris Avenue Officer Marcos Vaz stopped a car on Morris Avenue for making repeated unsignaled lane changes
was subsequently arrested for Operating a Motor Vehicle While Under the Influence of Alcohol
She was later released with a Springfield Municipal Court appearance date
11/23/2012 9:51 pm Location: Jade Meadow Drive Nicholas Pearl age 18 of Springfield NJ was arrested by Officer Melissa Esteves after the officer had investigated a complaint of persons making noise on Jade Meadow Drive
Pearl was arrested for the Possession of Less Than 50 grams of Marijuana
He was later released with a court appearance date in the Springfield Municipal Court
11/25/2012 2:01 pm Location: Springfield Avenue Jeffrey Laranjeiro age 34 of West Orange NJ was operating a motor vehicle that was stopped by Officer Brandon Lorenz
Laranjeiro was subsequently arrested for the Possession of Heroin
Possession of less than 50 grams of Marijuana and the Possession of Drug Paraphernalia
He was also charged with the Possession of a Handgun that was found hidden inside of the truck
He was later released after $10,000.00 bail was posted and has an initial court date in the NJ Superior Court of Union County in Elizabeth NJ on 12/05/2012
11/25/2012 8:07 pm Location: Restaurant on Morris Avenue Officer Anthony Reimer had stopped to pick-up dinner at a Chinese restaurant located in the business center of town on Morris Avenue
As he approached the counter he detected a strong odor of suspected Marijuana on the person of a customer who was picking up food
Theodore Sharkey age 25 of Summit NJ was arrested for the Possession of less than 50 grams of Marijuana and Possession of Drug Paraphernalia
He was later released with a Springfield Municipal Court date
11/27/2012 11:51 pm Location: Wabeno Avenue William Sneary age 38 of South River NJ was stopped by Officer John Laurencelle after it was found that he was wanted by the Middlesex County Sheriff's Office on a superior court issued bench warrant for non-support
He was turned over to the Middlesex County Sheriff's Office
11/29/2012 3:38 pm Location: Municipal Parking Lot on Center Street Officer Joseph Leniart was checking on parking violations within the municipal parking lot on Center Street by the NJ Motor Vehicle Commission Agency and found that a car with Maryland license plates had been reported as stolen by the Takoma MD Police
When the two male occupants were observed entering the agency
Officer Leniart and other officers entered the agency and arrested the two subjects
Timothy Brown age 43 of Newark NJ and Andre Jones age 20 of Newark NJ were both charged with the Possession of a Stolen Motor Vehicle
They have an initial court appearance set in the NJ Superior Court of Union County in Elizabeth NJ on 12/07/2012
Get more local news delivered straight to your inbox. Sign up for free Patch newsletters and alerts.
It’s a day and a trip that Canadian soccer supporter André Laranjeiro will likely remember for the rest of his life
The Canadian superfan flew more than 5,500 kilometres to see his favourite team FC Porto and he came home with the shirt off Stephen Eustáquio’s back
Armed with a homemade sign and a Canadian flag
Laranjeiro found himself in the right place at the right moment when Eustáquio spotted Laranjeiro’s message during the post-match celebrations at the Estádio do Dragão
From ?? with love ?#FCPGVFC @CanadaSoccerEN pic.twitter.com/gHd8v2SB6C
Laranjeiro was born and raised in Hamilton, Ontario where he played his youth soccer with Mount Hamilton SC. His parents were born just south of Porto before they immigrated to Canada, so it should come as no surprise that one of Europe’s biggest clubs easily became Laranjeiro’s favourite club. Growing up, he even wore the number 99 on the local Hamilton soccer fields in honour of his favourite player, goalkeeper Vítor Baía.
Fast forward to 2023 and his favourite Portuguese club now features a Canadian at midfield for the first time in club history. Eustáquio joined the club in 2022 and he helped them win the 2021-22 Primeira Liga. They finished second in the league in 2022-23 and reached the last 16 in UEFA Champions League while Eustáquio also had the honour of representing Canada at the 2022 FIFA World Cup in Qatar.
Laranjeiro had seen FC Porto in action before, but on this September trip it was the first time he got the chance to watch his favourite club while sitting next to his grandfather. They went together to both an away match against CF Estrela Amadora SAD and then a home match against Gil Vicente. It was in that home match that Eustáquio scored the 91st minute match winner and gave Laranjeiro the memento of a lifetime.
“I watched that first match with my grandfather and I brought my Canada flag to that match,” said Laranjeiro. “It’s a smaller stadium and I waved my flag, but I couldn’t get his attention. I thought I would try again the following week at their home match, but I figured my chances were going to be less likely.”
After the home win, Laranjeiro took his chances and moved down to the first row, but he may never have got the chance to draw Eustáquio’s attention had the Canadian not scored his first goal of the 2023-24 season. By winning Player of the Match honours, Eustáquio was positioned close to Laranjeiro to conduct the post-match interviews. When Eustáquio noticed the Canada flag and special poster, he made sure to toss Laranjeiro the jersey of his dreams.
It turned out to be quite the day for Laranjeiro, who also got to meet his hero Vítor Baía (who now works for the club). FC Porto scored first inside 10 minutes, Gil Vicente equalised less than half an hour later, and then Eustáquio came out the hero when he headed the match winner from a corner kick.
Laranjeiro has been collecting football jerseys for quite some time. He started with an FC Porto 2004-05 home kit and has since amassed more than 100 different jerseys in his collection. He has 31 different FC Porto jerseys, one of which he was wearing when he was amongst the 37,616 fans at the Estádio do Dragão in September.
Laranjeiro now has 19 match-worn shirts including the Eustáquio number 6.
“I try to get something that hits home,” said Laranjeiro. “I’m happy to get a shirt when I can, especially if there is a connection.”
On that memorable day in September, everything just fell into place for Laranjeiro. It was the right place, the right moment, and the perfect result, but ultimately it was that connection to Canada that got Laranjeiro his prized shirt off the back of FC Porto’s international star Eustáquio.
View this post on Instagram A post shared by FC Porto (@fcporto)
Environmental PollutionCitation Excerpt :Meanwhile
Pb concentrations have been positively correlated with a higher exposure to urbanised environments (Bauerová et al.
Blood is useful for assessing short-term exposure to contaminants
when seabirds are accessible for sampling; Jouanneau et al.
and may be a good proxy of contamination in other internal tissues (see Albert et al.
the use of stable isotopes of carbon (δ13C) and nitrogen (δ15N) as proxies of foraging habitat and trophic position
has proven valuable in unravelling sources of contamination in seabirds
highlighting geographical and species-specific variations in the bioaccumulation of contaminants (Anderson et al.
Environmental PollutionCitation Excerpt :A Principal Component Analysis (PCA) was performed considering a group of 11 elements (i.e
in which most values were above the LoQ: As
and Zn) using the stats package under R 3.5.0 (R Core Team
The PCA was used to establish overall gradients of contamination based on all chemical element concentrations (PC1 and PC2)
and assess their relationships with trophic ecology
spatial use and oxidative stress (Laranjeiro et al.
To assess the effect of fish species on: a) the presence/absence of microplastics a Binomial GLM was used
and b) the total and mean size of microplastics a Kruskal-Wallis test
iScienceCitation Excerpt :The main furin inhibitor
was found significantly down-regulated in patients with LCS (Figure 1D)
The M2-like cells displayed a tolerogenic phenotype illustrated by the expression of the immune suppressor CCL1824 and the angiogenesis-promoting factor ANGPT4
the M2-like cells expressed several proteins promoting lipolysis (PLA2G4A)
altered lipid metabolism (PLIN2 and FABP4)
and lipid peroxidation (HMOX1) (Figure 4C)
Trends in Pharmacological SciencesCitation Excerpt :This effect was attributed to the small-molecule binding to CCL18
preventing CCL18 from interacting with its cognate receptors to elicit downstream signaling [26]
membrane-associated phosphatidylinositol transfer protein 3 (PITPNM3 or ACKR6)
and G protein-coupled receptor for estrogen (GPR30) [27]
A second strategy to impair chemokine-induced oncogenic signaling is to interfere with chemokine–GAG interactions
Science of the Total EnvironmentCitation Excerpt :Levels of essential elements are therefore regulated by physiological processes (Braune and Simon
but their accumulation or deficiency may promote alternative pathways that might produce metabolic disorders or even pathologies
Understanding their levels and the factor contributing to their variation is
a matter of importance in wild animals such as seabirds (dos Santos et al.
and Zn in different species and sites) to fit explaining models
which is probably linked to physiological regulation and lower dependence on external factors (Tables 2 and 3)
Environmental PollutionCitation Excerpt :Marine ecosystems constantly face contaminants input deriving mostly from the world's industries (Wilhelmsson et al.
with waters closer to more urbanized and industrialized areas (i.e.
each country's Exclusive Economic Zone (EEZ)) being
more susceptible to presenting higher levels of contamination when compared with more oceanic areas
and mercury (Hg) are notorious for their negative health impacts (Boening
but other less studied chemical elements have been receiving increased attention by researchers studying teleosts (da Silva et al.
2022) and elasmobranchs (Hauser-Davis et al.
The class of persistent organic pollutants (POPs) also represents a substantial threat to marine ecosystems (Wenning and Martello
particularly contaminants such as polychlorinated biphenyls (PCBs)
and polychlorinated dibenzo-p-dioxins and polychlorinated dibenzo-p-furans (PCDD/Fs)
ChemosphereCitation Excerpt :In the environment
and plastic fragments gradually degrade into NPs
making NPs with a diameter of about 100 nm the most widely distributed NPs in the environment (Jambeck et al.
NPs are easily ingested by living organisms
enter the human body through the food chain
and have some health effects on biological functions
Previous studies have shown that polystyrene nanoplastics (PSNPs) can accumulate in the gonads
and cause reproductive and nerve damage via promoting excessive production of reactive oxygen species (ROS) (Jung et al.
Applied Catalysis B: EnvironmentalCitation Excerpt :Within the past decades
the world has witnessed an unprecedented progress in industry
concomitantly brings human being egregious dilemma
energy scarcity and environment contamination [1,2]
capable of exploiting solar light to generate renewable energy and remedy environment
is considered an efficacious approach to address the crisis [3–7]
Metrics details
Whole-organism phenotypic assays are central to the assessment of neuromuscular function and health in model organisms such as the nematode C
we report a new assay format for engaging C
elegans in burrowing that enables rapid assessment of nematode neuromuscular health
In contrast to agar environments that pose specific drawbacks for characterization of C
here we use the optically transparent and biocompatible Pluronic F-127 gel that transitions from liquid to gel at room temperature
enabling convenient and safe handling of animals
The burrowing assay methodology involves loading animals at the bottom of well plates
casting a liquid-phase of Pluronic on top that solidifies via a modest temperature upshift
enticing animals to reach the surface via chemotaxis to food
and quantifying the relative success animals have in reaching the chemoattractant
We study the influence of Pluronic concentration
gel height and chemoattractant choice to optimize assay performance
To demonstrate the simplicity of the assay workflow and versatility
we show its novel application in multiple areas including (i) evaluating muscle mutants with defects in dense bodies and/or M-lines (pfn-3
(ii) tuning assay conditions to reveal changes in the mutant gei-8
(iii) sorting of fast burrowers in a genetically-uniform wild-type population for later quantitation of their distinct muscle gene expression
and (iv) testing proteotoxic animal models of Huntington and Parkinson’s disease
Results from our studies show that stimulating animals to navigate in a dense environment that offers mechanical resistance to three-dimensional locomotion challenges the neuromuscular system in a manner distinct from standard crawling and thrashing assays
Our simple and high throughput burrowing assay can provide insight into molecular mechanisms for maintenance of neuromuscular health and facilitate screening for therapeutic targets
engaging animals in burrowing environments and scoring their locomotory prowess might provide the sensitive dynamic range of outcomes to reveal previously indiscernible phenotypes
A limitation of this burrowing assay is that the methodology requires time-consuming steps including drilling holes in the pipette (later used for loading animals and food source)
followed by filling the pipettes uniformly with hot agar and waiting for them to cool
Additional challenges include injection of tens of animals into a localized spot (which may result in animal loss or damage)
and visualization difficulty due to the translucency of agar and refraction at cylindrical surfaces
the basic approach and the burrowing assay are highly valuable—stimulating animals to burrow in a dense
3D environment offers a way to challenge the neuromuscular system that is distinct from swimming or 2D crawling that may well approximate a more natural environment than either swimming or crawling
Here we report on a novel design for burrowing evaluation that addresses the limitations of the currently described agar-based burrowing assay and enables parallel evaluation of burrowing performance of wild-type and mutant C
The method utilizes well plates and Pluronic F-127—an optically transparent biocompatible hydrogel that undergoes a sol-gel transition in a temperature range that is safe for handling C
We tested the influence of system parameters including gel concentration
and chemoattractant type to optimize the assay performance
we evaluate animal distribution and behavior during burrowing
To demonstrate the flexibility and power of the assay
we show its suitability for diverse applications including (i) evaluation of muscle-defective mutants
(ii) tuning assay conditions to increase phenotypic distinction of a mitochondrial mutant
(iii) separation and recovery of fast/slow burrowers for differential gene expression analysis
and (iv) testing disease models of protein aggregation for locomotory impairment
We anticipate that this new and simple assay should provide insights into molecular mechanisms regulating maintenance of neuromuscular health
facilitate screening for pharmacological interventions
and create a path to novel discovery of therapeutic targets
animals are not easy to visualize due to the translucency of agar and refraction at the cylindrical surfaces of glass pipettes that are used
Basic principle of Pluronic (PF-127) gel-based burrowing assay
(a) The burrowing assay is conducted in a 12-well plate; in each well
animals are stimulated to move through a gel towards a food source placed at the top
The inset shows the nematodes that have successfully burrowed and reached the food source (E
coli) at the top of the gel (See also supplementary video S1)
(b) Burrowing performance of day 1 wild-type adults in the presence and absence of E
N = 39 and 35 animals in the presence and absence of bacteria
(c) Calcium imaging shows the muscle contractions as the nematode is burrowing in the PF-127 gel
Strain is HBR4: goeIs3 HBR4: goeIs3[Pmyo-3::GCaMP3.35::unc-54-3′utr
unc-119] expressing the calcium indicator GCaMP3 in body wall muscles
Arrow heads point to the tail that appears faded in i and ii due to the 3D locomotion
(d) Dynamic quantification of calcium signaling activity from an animal during a 10 second burrowing episode
Each pixel is 1 second apart on the x-axis
the overall direction of burrowing with respect to gravity does not influence burrowing performance
and chemotactic stimulus is essential for animals to burrow efficiently towards the surface and engage in 3D locomotion
the tail (arrows) appeared faded due to the animal’s 3D posture (i
the entire body emerged in the focal plane of the microscope (iii)
the animals undergo 3D locomotion in the PF-127 gel environment
To determine optimal performance for the burrowing assay
Animal performance during burrowing is expected to depend on the mechanical resistance offered by the gel
This resistance can be controlled by the gel’s mechanical properties
which in turn is governed by PF-127 concentration
the gel height dictates how far animals need to burrow
the chemotactic response can be sensitive to the type of chemoattractant used to stimulate the animals to burrow
we therefore studied the influence of gel concentration
gel height and chemoattractant choice on the burrowing performance of wild-type animals
Our initial trials showed that the second layer gels in less than 5 minutes under these conditions
Effect of Pluronic gel concentration and height on burrowing performance of wild-type animals
Burrowing performance in (a) four different concentrations of PF-127
28 and 30% w/w gels respectively; H = 0.7 cm
(b) 26% w/w PF-127 at four different gel heights
(c) 30% w/w PF-127 at four different gel heights
Our observation that fewer animals reach the surface as the Pluronic concentration increases suggests that the mechanical resistance offered by the gel is an important factor determining burrowing performance. Indeed, the measured elastic modulus and yield stress of the gel increase when the PF-127 concentration increases (Fig. S4)
The mechanical resistance can come from the nematode trying to overcome the yield stress to carve a hole in the gel in order to move
the viscous friction along the nematode body could contribute to resistance to motion in 3D
our results show that the mechanical resistance to burrowing can be easily tuned by modulating the PF-127 concentration
we chose PF-127 concentration of 26% w/w as the standard condition since the challenge for animal burrowing is intermediate
and the solution gels more quickly than the 24% w/w
With respect to gel height H, we anticipated that burrowing performance should decrease with an increase in gel height. In Fig. 2b
we indeed observed this trend when we tested gel heights of H = 0.66
and 1.1 cm at 26% w/w PF-127 concentration
The final 2-hour burrowing percentage decreased from 85% to 60% when using gel heights of H = 0.66 and 1.1 cm
the burrowing percentage reached close to 100% within the first hour and subsequently declined as some of the animals burrowed back into the gel
The burrowing performance was the worst in the highest gel thickness we tested (1.1 cm)
as less than 10% of the animals could reach the surface
we conducted burrowing assays with PF-127 concentration of 26% w/w and gel height of approximately 0.7 cm unless otherwise noted
we found that the burrowing percentage at the end of two hours was 70%-80% for wild-type animals
To achieve a reliable burrowing performance
a chemical stimulus with a maintained level of animal attraction over the assay time should be utilized
We therefore evaluated the burrowing performance of wild-type animals stimulated with E
coli in salt solution or odorant chemical compounds
Chemoattractant choice influences the burrowing performance in wild-type animals
Assay conditions are 26% w/w PF-127 and H = 0.7 cm
(b) Effect of different chemoattractants on burrowing performance
Assay conditions are 26% w/w PF-127 and H = 0.75 cm
Characterization of wild-type animal locomotion in a thin Pluronic gel layer
(a) Individual animal velocity obtained by tracking the body centroid every 15 seconds
The average burrowing velocity is 1.14 mm/min
(b) Undulatory frequency of individuals obtained from the time required to complete one sinusoid body movement
The average undulatory frequency is 0.07 Hz
In (a,b) no food source was used and the assay conditions were 26% w/w PF-127 and H ≈ 1 mm
The error bars represent standard error of mean calculated from 8 time intervals per individual animal
Since our intent is to demonstrate the power of the assay platform we designed
we consider our results in each of these applications as laying the foundation for future in-depth investigations
The corresponding genetic mutation and human ortholog are shown in the table
Burrowing performance and chemotactic scoring of mutants with defects in (b) both dense body and M-line
We tested the effect of four mutations that specifically affect the dense bodies (pfn-3, atn-1, uig-1, dyc-1) and three that affect both the dense bodies and the M-lines (zyx-1, unc-95, tln-1). Despite these proteins localizing to the same multi-protein complexes, previously reported phenotypes were often distinct (Table S1)
perhaps indicating specific functions of individual proteins or differences in the extent of the effect of the specific mutation studied
As chemotaxis is an important element of our burrowing assay
we conducted standard 2D chemotaxis assays on agar plates in parallel to ascertain if the phenotypic score of some mutants is more obvious in the burrowing assay as compared to the standard chemotaxis assay
This concordance in outcomes from 2D and 3D chemotaxis reveal that these mutants have locomotory defects
which are documented equally using either assay
pfn-3 showed a higher chemotaxis index compared with wild-type but failed to burrow effectively
while chemotaxis is an essential component of the burrowing assay
our results show that the mechanical resistance offered during burrowing can reveal differences in muscle mutants that are difficult to discern from standard 2D chemotaxis assays on agar plates
gei-8(gk693) animals have a 1 kb deletion in the gei-8 promoter region and
the potential for a modified gei-8 expression level
Tuning the burrowing assay conditions can reveal phenotypic differences
Testing the burrowing performance of wild type and gei-8(gk693) mutant in two different assay conditions of (a) a taller gel height
N = 31 and 32 for wild-type and gei-8(gk693)
One of the interesting features of the burrowing assay is that not all the animals reach the attractant at the same time
some individuals burrow quickly compared with others in the population
Since nearly all animals remain at the top once they reach the food source
the Pluronic-based burrowing assay provides a simple way of sorting and recovering sub-populations of animals for downstream molecular analysis
we harness this feature of the assay and show that gene expression analysis can be conducted to compare the fast burrowers with the slower ones
Muscle-specific gene expression in fast burrowers compared to slow burrowers
Normalized gene expression scores are shown as ratios for the successful burrowing class (among the top 10–15% that reached the top faster) to the levels for slower animals that remained in the gel by the end of the two-hour time period
and mup-2 were expressed significantly more for fast burrower animals in comparison to slower ones
Experiments were conducted with Day 1 adults
These findings indicate potential natural expression variation within a genetically identical population and holds potential to indicate the molecular components that might improve burrowing efficiency and locomotory prowess
elegans models of neurodegenerative diseases
(a) Burrowing performance of day 1 adults polyQ strains with glutamine expansions in muscles
α-synuclein-expressing strain and wild-type animals
0.0302 and 0.0016 for strains expressing Q35
(b) Images show visible protein aggregates in the Q40-expressing strain and not in the Q35-expressing strain
(c) Day 1 adult Q67-expressing and Q86-experssing animals with protein aggregation in neurons are deficient in burrowing
For the transgenic lines that expressed polyQ in neurons, Q67- and Q86-expressing animals were both distinctly impaired in their burrowing abilities compared with wild type (Fig. 9c)
the difference between wild type and Q86 was modest
and the primary differentiating factor between wild type and Q67 was the delayed rate at which Q67-expressing animals reached the surface
elegans expressing proteotoxic aggregates in neurons
therefore does not appear to be as strong as those expressed in body wall muscle
the burrowing assay has the capacity to detect neuromuscular deficits in neurodegenerative disease models and in some cases prior to major locomotory impairment
underscoring the importance of the burrowing assay for deciphering factors that influence the earliest events in degenerative processes
These recent investigations employed agar as a medium for burrowing
we have shown that the biocompatible and optically transparent Pluronic gel offers an alternative for burrowing studies with several advantages including ease of manipulation of animals
flexibility in changing assay conditions to modulate burrowing performance
parallel evaluation of assay conditions or different strains in multi-well plates
and easy recovery of animals for follow-up analysis
Even though systematic studies comparing locomotory prowess in these different media have not been conducted
available findings indicate that the Pluronic medium is likely to be a more demanding burrowing environment for C
The simplicity of our burrowing assay workflow lends itself to considerable throughput and versatility
using 12-well plates we perform 4 strains ×3 replicates in about 4 hours
which includes loading of 30 animals and the gel layer in each well and scoring every 15 minutes for a total duration of 2 hours
Other assay formats could also be designed
the fraction of animals on the gel surface is recorded only at the final time point
Such end-point assays could be performed with significantly higher throughput and in a miniaturized format involving 96-well plates
we have developed an improved burrowing method based on a thermoreversible Pluronic gel and expanded its application to diverse areas with novel findings
Our results show that mutants can be uniquely distinguished based on burrowing capacity, which is sometimes difficult to discern from 2D crawling locomotion and thrashing assays. As shown in Table S1
II.D-i could not be differentiated based on just one phenotypic assay
suggesting that subtle genetic defects might be difficult to detect by existing locomotory assays
The fact that burrowing distinguishes all the muscle mutants studied indicates its capacity to detect subtle defects in neuromuscular function
elegans burrowing assay in Pluronic gel medium offers the convenience of a simple workflow with high throughput
We systematically studied the influence of assay conditions on burrowing ability and modulated the physical challenge experienced by animals based on the needs of a particular application
The demonstrative applications we have chosen highlight the richness of the burrowing assay in diverse areas where the neuromuscular system is implicated
We anticipate that the Pluronic burrowing assay can be easily adopted in other laboratories
enabling comprehensive investigations of the molecular
cellular and tissue-level mechanisms required for the maintenance of neuromuscular health in C
elegans that might be translatable to human neuromuscular diseases
Caenorhabditis elegans wild type N2 was cultured at 20 °C on standard nematode growth medium (NGM) on 60 cm petri plates and never allowed to starve
The NGM plates were allowed to dry 24 hours prior to seeding with 450–550 μL of Escherichia coli OP50 bacteria overnight
Age synchronization was done by transferring 20–25 gravid animals to seeded plates and letting them lay eggs for 3–4 hours
After the desired number of eggs were laid
and the eggs were allowed to hatch and develop in a 20 °C incubator
The animals used for all experiments were day 1 adults
The day that the age synchronized animals started to lay eggs is counted as day 0 of adulthood
The following mutants were obtained from Caenorhabditis Genetics Center (CGC): dyc-1(cx32)
For calcium imaging the following strain was used: HBR4: goeIs3 HBR4: goeIs3[Pmyo-3::GCaMP3.35::unc-54-3′utr
unc-119] from CGC which expresses the calcium indicator GCaMP3 in body wall muscles
Strains used as protein aggregation disease models were obtained from CGC and have the following genotypes: pkIs2386[Punc-54::alphasynuclein::YFP + unc-119(+)]
To develop and optimize the burrowing assay
various Pluronic concentrations and gel heights were tested
Pluronic F127 (Sigma-Aldrich) was dissolved in deionized water to reach the desired concentration
reported as solute weight per solution weight (% w/w)
The suspension was kept at 4 °C until all the Pluronic pellets dissolved
The solutions were stored at 4 °C prior to the experiment to prevent gelation
The Pluronic concentration in all assays was the optimized concentration of 26% w/w
except for when other concentrations were tested
The Pluronic solutions were kept at 14 °C in a Waverly digital thermal bath for at least 30 minutes before conducting the experiment. 20–30 μL of solution was added to the bottom of a Corning™ Falcon™ Polystyrene 12-well plate (Fig. 1a)
A minimum number of 30 animals (day 1 adults) were hand-picked from NGM plates and released into the drop
a layer of Pluronic was cast on top of the initial droplet to the desired thickness
ranging from 0.44 cm to 1.1 cm depending on the experiment
The top layer needed around 5 minutes to gel at a room temperature of 20 °C
Gelation was confirmed by no fluid movement and inserting the tip of the worm pick somewhere close to the edge of the well
If no healing of the indentation was observed after piercing
and 20 μL of the chemoattractant was added directly to the top (t = 0 min)
The animals that had burrowed to the surface were scored by monitoring the top layer under the microscope and counting the ones that had reached the top every 15 minutes for a total duration of 2 hours
The percentage of animals on the top surface was defined as the number of animals on the top surface divided by the total sample size in that well
All the burrowing assays were conducted by hand picking animals, except Fig. 9a on neurodegenerative disease models
as those animals were rinsed off the plates with DI water and collected in Falcon tubes
The rinsing process is the same as preparing animals for chemotaxis assays (See Methods on Chemotaxis assays)
After rinsing off the animals from bacteria
10 µL of worm solution was placed on the bottom of well plate
500 µL of PF-127 was added to make a base gel layer
the Pluronic layer was cast on top to the desired thickness of 0.7 cm
The undulatory frequency (Hz) was defined as the number of full-wavelength sinusoidal movements the worm could make within one second
the required time for a full sinusoidal movement was measured for eight distinct sinusoidal movements
the inverse was taken to result in the frequency (Hz)
5-minute uninterrupted videos with the frame rate of 3 fps were captured using a Nikon Ti-E microscope at 4x
the videos were analyzed by assessing the time the animals spent moving forward
To investigate animal distribution across gel heights, the total gel height was divided into three equal layers (Fig. 5a)
and the number of animals in each segment at each time point was counted by scanning the z-axis through the gel height from bottom to the top surface using a Nikon Ti-E microscope with a 4x objective lens
To test the effectiveness of animal chemosensation
standard 2D chemotaxis assays were conducted
coli was concentrated in liquid NGM (as above without agar)
Isoamyl alcohol and diacetyl were diluted in ethanol to 1%
the chemoattractant solutions were freshly mixed with an equal volume of 0.5 M sodium azide as an anesthetic
Volatile compound chemotaxis assays on agar plates were conducted according to Margie et al.55 with a few modifications
chemotaxis agar (2% agar (Fisher Scientific)
5 mM potassium phosphate (Fisher Scientific)
1 mM magnesium sulfate (Sigma-Aldrich)) was prepared a day prior to the experiment and poured into 6 cm petri plates
The animals were collected in Falcon tubes by washing them from culture plates with deionized water and allowing them to pellet by gravity
and the tube was inverted a few times to wash the worms
so the supernatant on top looked clear and bacteria-free
the animal pellet was resuspended in water to obtain around 60 animals per 5 μL
5 μL of worm solution was pipetted onto the center of the chemotaxis plate
2 μL of test solution (chemoattractant) and 2 μL of control solution (diluent) were added to their designated quadrants
chemotaxis indices were calculated as the difference in the number of worms in the test and control quadrants (excluding the animals that did not migrate farther than 1 cm)
5 μL of the solution containing animals was added onto the center
the animals were gently dispersed using a worm pick
so they were not trapped within the liquid droplet
and the chemotaxis index was calculated as mentioned before
RNA extraction and quantitative PCR were carried out as previously described58
elegans after burrowing (~30 animals per sample) into TRIzol Reagent (Ambion) and immediately froze animals in liquid nitrogen
The quick burrowers were among the top 10–15% in burrowing performance
while the slow burrowers were recovered from the Pluronic at the conclusion of the two-hour time period
After freeze-thaw cycles with liquid nitrogen/37 °C heat block
we extracted total RNA following the manufacturer’s instructions (Ambion) and synthesized cDNA using the SuperScript III First-Strand Synthesis System (Invitrogen)
To compare mutants and disease models burrowing performance
two-way ANOVA was used in GraphPad Prism software
The statistical analysis on chemotaxis indices was done using two-sample student’s t-test in MATLAB
paired-sample t-test was done using MATLAB
Burrowing assay error bars represent standard error of the mean
All the assays were done in three replicates unless otherwise noted
N represents average of the number of animals used in the replicates
A role for Caenorhabditis elegans in understanding the function and interactions of human disease genes
The structure of the nervous system of the nematode Caenorhabditis elegans
Post-embryonic cell lineages of the nematode
elegans models of neuromuscular diseases expedite translational research
Muscular dystrophy: the worm turns to genetic disease
Neurodegenerative disorders: insights from the nematode Caenorhabditis elegans
Anne, C. Hart, E. Behavior. WormBook, ed. The C. elegans Research Community, https://doi.org/10.1895/wormbook.1.87.1 (July 3
Methods to assess subcellular compartments of muscle in C
NemaFlex: a microfluidics-based technology for standardized measurement of muscular strength of C
elegans muscular forces and locomotion patterns in microstructured environments
elegans: a piecewise-harmonic curvature representation of nematode behavior
Dimensionality and dynamics in the behavior of C
CeleST: computer vision software for quantitative analysis of C
elegans swim behavior reveals novel features of locomotion
The burrowing behavior of the nematode Caenorhabditis elegans: a new assay for the study of neuromuscular disorders
elegans behavioral genetics in 3-D environments
Method for the assessment of neuromuscular integrity and burrowing choice in vermiform animals
Physical exertion exacerbates decline in the musculature of an animal model of Duchenne muscular dystrophy
Proceedings of the National Academy of Sciences
NGT-3D: a simple nematode cultivation system to study Caenorhabditis elegans biology in 3D
Roll maneuvers are essential for active reorientation of Caenorhabditis elegans in 3D media
Disruption of mitochondrial dynamics affects behaviour and lifespan in Caenorhabditis elegans
Reversible and long-term immobilization in a hydrogel-microbead matrix for high-resolution imaging of Caenorhabditis elegans and other small organisms
Hydrogel-droplet microfluidic platform for high-resolution imaging and sorting of early larval Caenorhabditis elegans
On-demand optical immobilization of Caenorhabditis elegans for high-resolution imaging and microinjection
reversible and addressable immobilization of Caenorhabditis elegans in Pluronic F-127 using an optoelectric device
CLIP–continuous live imaging platform for direct observation of C
Heat-Induced Calcium Leakage Causes Mitochondrial Damage in Caenorhabditis elegans Body-Wall Muscles
The ESCRT-II proteins are involved in shaping the sarcoplasmic reticulum
Sustained release of VEGF from PLGA nanoparticles embedded thermo-sensitive hydrogel in full-thickness porcine bladder acellular matrix
From odors to behaviors in Caenorhabditis elegans
Odorant-selective genes and neurons mediate olfaction in C
Biomechanical analysis of gait adaptation in the nematode Caenorhabditis elegans
Proceedings of the National Academy of Sciences 107
The integrin-adhesome is required to maintain muscle structure
and movement forces in Caenorhabditis elegans
NCoR1 is a conserved physiological modulator of muscle mass and oxidative function
UNC-120/SRF independently controls muscle aging and lifespan in Caenorhabditis elegans
Selection and validation of a set of reliable reference genes for quantitative sod gene expression analysis in C
Muscle strength deficiency and mitochondrial dysfunction in a muscular dystrophy model of Caenorhabditis elegans and its functional response to drugs
Aggregation of alpha-synuclein in Lewy bodies of sporadic Parkinson’s disease and dementia with Lewy bodies
The threshold for polyglutamine-expansion protein aggregation and cellular toxicity is dynamic and influenced by aging in Caenorhabditis elegans
Proceedings of the National Academy of Sciences 99
Polyglutamine proteins at the pathogenic threshold display neuron-specific aggregation in a pan-neuronal Caenorhabditis elegans model
elegans model identifies genetic modifiers of α-synuclein inclusion formation during aging
Anti-ageing and anti-Parkinsonian effects of natural flavonol
tambulin from Zanthoxyllum aramatum promotes longevity in Caenorhabditis elegans
Nematode (Caenorhabditis elegans) movement in sand as affected by particle size
moisture and the presence of bacteria (Escherichia coli)
A mathematical analysis of a minimal model of nematode migration in soil
Magnetosensitive neurons mediate geomagnetic orientation in Caenorhabditis elegans
Microfluidic devices for analysis of spatial orientation behaviors in semi-restrained Caenorhabditis elegans
Journal of visualized experiments: JoVE (2013)
Chemotaxis by the nematode Caenorhabditis elegans: identification of attractants and analysis of the response by use of mutants
Proceedings of the National Academy of Sciences 70
Mutations that prevent associative learning in C
elegans induce key features of mammalian exercise
Analysis of relative gene expression data using real-time quantitative PCR and the 2−ΔΔCT method
Download references
which is funded by NIH Office of Research Infrastructure Programs (P40 OD010440)
We would like to thank Anam Mahmood for assistance with experiments and Guy M
This work is partially supported by funding from the National Institutes of Health (RO1 AG051995-04 to M.D
Cancer Prevention and Research Institute of Texas (RP160806 to S.V.)
National Aeronautics and Space Administration (NNX15AL16G to S.V
& J.B.) and the Biotechnology and Biological Sciences Research Council (BB/N015894/1 to N.J.S.)
acknowledges funding support from the Fulbright U.S
Student Program and the Germanistic Society of America
has been funded by postdoctoral fellowships from Life Sciences Research Foundation (sponsored by Simons Foundation) (award # Laranjeiro-2015) and American Heart Association (award # 18POST33960502)
Department of Molecular Biology and Biochemistry
Department of Molecular Genetics of Ageing
Max Planck Institute for Biology of Ageing
and Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD)
MRC/Arthritis Research UK Centre for Musculoskeletal Ageing Research
United Kingdom & National Institute for Health Research Nottingham Biomedical Research Centre
conceived the Pluronic gel-based burrowing assay
All authors analyzed and interpreted the data
All authors read and commented on the manuscript
The authors declare no competing interests
Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations
Download citation
DOI: https://doi.org/10.1038/s41598-019-51608-9
Anyone you share the following link with will be able to read this content:
a shareable link is not currently available for this article
Sign up for the Nature Briefing newsletter — what matters in science
Metrics details
An Author Correction to this article was published on 21 March 2022
This article has been updated
In order to improve the efficacy of conventional radiotherapy
which not only modulate cancer cell response to therapy but are also highly recruited to tumours after irradiation
the effect of ionizing radiation on macrophages
To evaluate how radiotherapy affects macrophage behaviour and macrophage-mediated cancer cell activity
human monocyte derived-macrophages were subjected
as used during cancer treatment (2 Gy/fraction/day)
Irradiated macrophages remained viable and metabolically active
NF-kappaB transcription activation and increased Bcl-xL expression evidenced the promotion of pro-survival activity
A significant increase of pro-inflammatory macrophage markers CD80
TNF and IL1B was observed after 10 Gy cumulative doses
suggesting the modulation towards a more pro-inflammatory phenotype
ionizing radiation induced macrophage morphological alterations and increased their phagocytic rate
without affecting matrix metalloproteases (MMP)2 and MMP9 activity
irradiated macrophages promoted cancer cell-invasion and cancer cell-induced angiogenesis
Our work highlights macrophage ability to sustain cancer cell activities as a major concern that needs to be addressed to improve radiotherapy efficacy
thus not relevant in a human clinical context
The present work aims to reveal the effect of fractionated ionizing radiation on human macrophages
mimicking a week of cancer patients’ treatment
human monocyte-derived macrophages were differentiated in the presence of M-CSF
a factor involved in the recruitment of monocytes to the tissues and exposed to cumulative ionizing radiation doses of 2 Gy each
A plethora of functions in macrophages was then characterized
We demonstrate that irradiated macrophages are viable and metabolically active
exhibit a reduced anti-inflammatory profile
increased phagocytosis and unaltered MMP-2 and 9-mediated proteolysis
We also evidenced that irradiated macrophages are still able to promote tumour cell invasion and angiogenesis
our work adds novelty to the current literature and reinforces the idea of targeting macrophage differentiation and/or their molecular targets as a complementary strategy to improve radiotherapy efficacy
Irradiated human monocyte-derived macrophages are viable and metabolically active
(A) Radiation-induced macrophage DNA damage is demonstrated by immunocytochemistry for Ser139-phosphorylated H2AX (γH2AX) (red)
while nuclei were counterstained with DAPI (blue)
Graph indicates the percentage of macrophages (n = 3 and 400 cells/donor counted) exhibiting γH2AX foci
(B) Western blot analysis of total and phosphorylated Chk2 (Thr68) expression on non-irradiated (−) or irradiated (2
(C) Western blot analysis of caspase-7 expression on non-irradiated (−) or irradiated (2
In all Western blots β-actin was used as loading control
(D) Brightfield microscopic images of non-irradiated (0 Gy) and irradiated macrophages (10 Gy)
(E) Quantification of the metabolic activity of irradiated macrophages (2
normalized to the activity of non-irradiated ones and expressed as percentage
The antibody which detects the full length caspase-3 (35 kDa) also recognizes the large fragment of cleaved caspase-3 (17 kDa)
Positive controls for caspase-3 and -7 activation as well as for PARP cleavage are presented in this western blot panel
no cleavage of caspase-3/–7 nor even of PARP were observed in irradiated macrophages
suggesting that apoptosis was not occurring
To complement previous observations, macrophage mitochondrial function was evaluated 20 h after exposure to 2, 6 and 10 Gy cumulative doses, using the resazurin reduction assay (Fig. 1E)
ionizing radiation did not affect macrophage metabolic activity
we concluded that irradiated macrophages are viable and metabolically active and do not activate apoptosis
Ionizing radiation induces macrophage NF-κB activation and increases Bcl-xL expression
(A) Evaluation of RelA phosphorylation (Ser536) and RelB
(B) RelB nuclear translocation 6 h after macrophage irradiation (10 Gy)
Histone deacetylase 1 (HDAC1) and β-actin were used as loading controls for nuclear and cytoplasmic fractions
(C) Evaluation of Bcl2 and Bcl-xL expression after macrophage irradiation
Western blot images are representative of protein expression/phosphorylation status in distinct donors (at least n = 4)
Irradiated macrophages present a reduced anti-inflammatory phenotype
Graphs represent mRNA expression of irradiated macrophages compared to non-irradiated ones (dotted line) (at least n = 7 per marker)
Wilcoxon signed rank test was used to compare the median of each dataset against a hypothetical median value of 1
(B) Expression of a monocyte/macrophage lineage (CD14)
pro-(HLA-DR and CD86) and anti-inflammatory (CD163) macrophage markers was determined
20 h after irradiation (at least n = 6 per marker)
Paired t-test was used for statistical analysis
IL-12/IL-23(p40)) and anti-inflammatory (TGF-β1 and IL-10) cytokines were determined in macrophage CM (n = 9) by ELISA
Data was normalized to protein concentration
Wilcoxon matched pair test was used for statistical analysis
Median is represented by the horizontal line inside the box plots
In IL-6 and IL-10 graphics outliers are also indicated
irradiated macrophages polarize towards a pro- or an anti-inflammatory phenotype
Non-irradiated and 10 Gy irradiated macrophages (n = 6) were stimulated
with LPS (100 ng/ml) and IFN-γ (20 ng/ml) towards a pro-inflammatory
or with M-CSF (10 ng/ml) and IL-10 (20 ng/ml) towards an anti-inflammatory phenotype
(A) Expression of monocyte/macrophage lineage (CD14)
pro-(HLA-DR and CD86) and anti-inflammatory (CD163) macrophage markers was determined by flow cytometry
IL-12/IL-23(p40)) and anti-inflammatory (TGF-β1 and IL-10) cytokines were determined by ELISA
Paired t-test and one-way ANOVA were used for statistical analysis
irradiated macrophages are still able to polarize towards a pro- or an anti-inflammatory phenotype
ionizing radiation by itself tends to promote the pro-inflammatory phenotype
Ionizing radiation increases macrophage area
but does not alter MMP-2 and -9 activities
(A) Actin (green) and tubulin (red) stainings of non-irradiated and 10 Gy irradiated macrophages (n = 4)
Quantification of cell area and aspect ratio was performed using Fiji software
(B) Phagocytic ability of non-irradiated and 10 Gy-irradiated macrophages (n = 5) was determined after 1 h incubation with FITC-labelled (green) Staphylococcus aureus particles
F-actin was stained with rhodamine phalloidin (red)
The percentage of macrophages able to phagocyte S.aureus particles was quantified using Fiji software
(C) MMP-2 and -9 activity was evaluated by gelatin zymography
using 1 and 15 μg of protein from CM of non-irradiated and 10 Gy-irradiated macrophages (n = 10)
White bands of proteolytic activity were revealed on a Coomassie Blue-stained gelatin gel
The same conclusion was extended to MMP-9 and pro-MMP-2 proteolytic bands
when 15 μg of macrophage CM protein were loaded
Our results evidence that ionizing radiation induces macrophage morphologic alterations and increases their phagocytic rate
without affecting macrophage MMP-2 and MMP-9 proteolytic activities
Ionizing radiation does not affect macrophage ability to promote cancer cell invasion and cancer cell-mediated angiogenesis
(A) Matrigel invasion assays were established confronting RKO cells (upper compartment) and macrophages (lower compartment) after being separately exposed or not to 10 Gy cumulative ionizing radiation dose
The six possible combinations are represented in the scheme
Invasive cells were counterstained with DAPI and counted on the microscope
with CM from non-irradiated or 10 Gy irradiated macrophages
The comparison of RKO+ CM Mac 0 Gy versus RKO+CM Mac 10 Gy was evaluated in two rings within the same fertilized egg (n = 18)
while the condition RKO+RPMI was performed in a single distinct egg (n = 16)
Analysis of RKO-induced angiogenesis was performed through quantification of the number of new vessels in control and experimental conditions
ANOVA analysis demonstrated a significant difference between groups
The median is represented by the horizontal line inside the box plots
proteolysis and the ability to promote cancer cell activities
were evaluated in irradiated human macrophages
Schematic representation of the effect of ionizing radiation on human blood monocyte-derived macrophages
Two main macrophage functional polarization status are recognized: a pro-inflammatory
responsible for killing intracellular pathogens and antitumour activity and an anti-inflammatory one
Pro-inflammatory macrophages produce high levels of TNF-α
while anti-inflammatory ones express CD163
MRC1 and produce high levels of TGF-β1 and IL-10 cytokines
we demonstrated that irradiated macrophages exhibit a decrease of anti-inflammatory (CD163
MRC1 and IL-10) and an increase of other pro-inflammatory (CD80
Although irradiated macrophages are more effective than non-irradiated ones at phagocytosis
a typical feature of pro-inflammatory macrophages
they fail to reach a classical pro-inflammatory phenotype
as they do not produce high levels of TNF-α
On the other hand and similarly to their counterparts
irradiated macrophages are able to promote cancer cell invasion and cancer cell-induced angiogenesis
Our data suggests that M-CSF differentiated macrophages
exposed to cumulative ionizing radiation doses up to 10 Gy
exhibit a reduced anti-inflammatory-like phenotype
probably moving towards a pro-inflammatory phenotype
although irradiated macrophages exhibit characteristics from both pro- and anti-inflammatory phenotypes
they do not perfectly match to any of these typical profiles
appearing to acquire intermediate characteristics
These considerations should be taken into account when extrapolating data from one species to another
the sustained promotion of cancer cell invasion by irradiated macrophages may be associated with the fact that MMP-2 and MMP-9 activity is not being affected by radiation exposure
we also showed that irradiated macrophages are still able to promote cancer cell-induced angiogenesis
Our data also demonstrates that irradiation maintains macrophage ability to promote cancer cell invasion and cancer cell-induced angiogenesis
although radiotherapy mainly induces cancer cell death
are also irradiated and could persist still sustaining the activity of residual radioresistant cancer cells
this knowledge opens new perspectives for macrophage clinical targeting
after or concomitantly to ionizing radiation
as a strategy to improve radiotherapy efficacy
in agreement with the Helsinki declaration
Informed consent was obtained from all subjects before each blood donation
were purchased from the American Type Culture Collection (ATCC)
in RPMI1640 (L-Glutamine) (Invitrogen) supplemented with 10% FBS (Lonza
100 U/mL penicillin and 100 μg/mL streptomycin (Invitrogen)
Photon beam was produced by a PRIMUS (Siemens
operated at 18 MV at the Radiotherapy Service of CHSJ
To avoid differences between non-irradiated and irradiated cells
caused by medium agitation during transport to/from the Radiotherapy Service
macrophages were incubated with resazurin redox dye (0.01 mg/mL) (Sigma-Aldrich) for 3 h at 37 °C and 5% CO2
Fluorescence intensity was measured (530 nm Ex/590 nm Em)
using the multi-mode microplate reader Synergy MX (BioTek) and values were normalized to protein concentration in the CM
measured with detergent-compatible (DC) protein assay (BioRad)
Data from irradiated macrophages was then compared with the respective controls and expressed as percentage
from non-irradiated or 10 Gy irradiated macrophages
was extracted using TriPure Isolation Reagent (Roche)
RNA was converted to cDNA using 150 U of SuperScript™ II Reverse Transcriptase
8U of rRNasin (Promega) and RNase/DNase free water (Gibco)
To evaluate mRNA expression levels of pro- and anti-inflammatory gene markers
quantitative PCR using Brilliant II Sybr green kit (Stratagene/Agilent Technologies) and specific MX3005P 96-well semi-skirted plates
Samples were analysed on the MX3005P qPCR platform (Stratagene/Agilent)
R: 5′-CCGACCACCACTACAGCAA-3′; TNF F: 5′- GGCTGGAGCTGAGAGATA-3′
Primer sets for ACTB (used as a normalizing gene)
MRC1 and VCAN were from Applied Biosystems
For cell surface receptor expression analysis
non-irradiated and 10 Gy irradiated macrophages
subjected or not to further cytokine-induced polarization
gently detached by scraping and resuspended in FACs buffer [PBS
Stainings with anti-human CD14-APC (clone MEM-18)
CD86-FITC (clone BU63) (Immunotools) and CD163-PE (clone GHI/61) (R&D Systems) antibodies were performed in the dark for 30 min
macrophages were fixed for 15 min in 4% paraformaldehyde (PFA)
Isotype-matched antibodies were used as negative controls
Cells were acquired on a FACS Calibur™ Flow Cytometer (BD Biosciences)
using Cell Quest Software (collecting 1 × 104 cells)
Analysis was performed with FlowJo software (v7.6.5)
Mean fluorescent intensity was calculated by subtracting the respective isotype control intensity
TGF-β1 free active and IL-10 cytokine levels were determined
according to manufacturer’s instructions (BioLegend)
in CM from non-irradiated and 10 Gy irradiated macrophages
subjected or not to further cytokine-induced polarization as above detailed
50 μL of cell culture supernatant were added to a 96-well plate pre-coated with the capture antibody of interest
The soluble proteins bound to the capture antibody were detected using a biotinylated antibody
followed by an avidin-HRP conjugated solution
which intensity was proportional to the amount of antigen captured
Absorbance was then read at 450 and 570 nm
Cytokine levels were determined by plotting values on a standard curve and normalizing them to CM protein concentration
Macrophages were incubated with monoclonal antibodies for phosphorylated histone-H2AX (Ser139) (γH2AX) (clone JBW301) (Millipore) or α-tubulin (Sigma-Aldrich)
followed by goat-anti mouse AlexaFluor-594-conjugated-secondary antibody (Invitrogen) incubation
F-actin was stained for 15 min with 0.5 μM Phalloidin-FITC (Sigma-Aldrich)
6-diamidino-2-phenylindole (DAPI) solution
Multiwell plate-based screening was performed with a Leica DMI6000 B inverted motorized fluorescence microscope (Leica Microsystems)
Microscopic images are represented at 300× magnification
The chick embryo CAM model was used to evaluate RKO-induced angiogenic response in the presence of macrophage CM
commercially available fertilized chick (Gallus gallus) eggs were horizontally incubated at 37.5 °C
a square window was opened in the shell after removal of 1.5–2 mL of albumen
The window was sealed with a transparent adhesive tape and eggs re-incubated
RKO cells (1 × 106) resuspended in CM from non-irradiated or 10 Gy irradiated macrophages were placed on top of the same CAM
RKO cells resuspended in RPMI medium were inoculated in a different egg
Eggs were re-sealed and returned to the incubator for additional 72 h
the CAM was excised from embryos and photographed ex-ovo under a stereoscope
The number of new vessels (<20 μm diameter) growing radially towards the inoculation area was counted in a blind fashion
All graphs and statistical analysis were performed using GraphPad Prism Software v5 (GraphPad-trial version)
Data was analysed for Gaussian distribution using the D’Agostino and Pearson normality test
To test the hypothesis that irradiated macrophages are different from non-irradiated ones
Wilcoxon matched pairs test was used for non-parametric samples
while t-test (either paired t-test or one sample t-test) was used for parametric data or when n < 8
Statistical significance was achieved when P < 0.05
A Correction to this paper has been published: https://doi.org/10.1038/s41598-022-08498-1
The role of radiotherapy in cancer treatment: estimating optimal utilization from a review of evidence-based clinical guidelines
The Swedish Council on Technology Assessment in Health Care (SBU) systematic overview of radiotherapy for cancer including a prospective survey of radiotherapy practice in Sweden 2001–summary and conclusions
Radiation oncology: a century of achievements
Technological advances and the rising problems in cancer management
Strategies to improve radiotherapy with targeted drugs
Does ionizing radiation stimulate cancer invasion and metastasis
Anti-cancer therapies targeting the tumor stroma
Immune cells: plastic players along colorectal cancer progression
Normalizing tumor microenvironment to treat cancer: bench to bedside to biomarkers
Dying cell clearance and its impact on the outcome of tumor radiotherapy
Macrophages: obligate partners for tumor cell migration
Microenvironmental regulation of metastasis
Trial Watch: Anticancer radioimmunotherapy
Radiotherapy and the Tumor Stroma: The Importance of Dose and Fractionation
Biological mechanisms of radiation actions at low doses
A white paper to guide the Scientific Committee’s future programme of work
Reduced secretion of the inflammatory cytokine IL-1beta by stimulated peritoneal macrophages of radiosensitive Balb/c mice after exposure to 0.5 or 0.7 Gy of ionizing radiation
0.5 Gy gamma radiation suppresses production of TNF-alpha through up-regulation of MKP-1 in mouse macrophage RAW264.7 cells
Low and moderate doses of ionizing radiation up to 2 Gy modulate transmigration and chemotaxis of activated macrophages
provoke an anti-inflammatory cytokine milieu
but do not impact upon viability and phagocytic function
gammaH2AX: a sensitive molecular marker of DNA damage and repair
Crosstalk between chromatin state and DNA damage response in cellular senescence and cancer
Radiation response of mouse lymphoid and myeloid cell lines
Apoptotic death is shown by all lines examined
Hematopoietic stem cell: self-renewal versus differentiation
The biology of myeloid-derived suppressor cells: the blessing and the curse of morphological and functional heterogeneity
Recruitment of myeloid but not endothelial precursor cells facilitates tumor regrowth after local irradiation
CSF1R signaling blockade stanches tumor-infiltrating myeloid cells and improves the efficacy of radiotherapy in prostate cancer
Myeloid-derived cells in tumors: effects of radiation
The tumour microenvironment after radiotherapy: mechanisms of resistance and recurrence
Apoptosis: a review of programmed cell death
PARP-1 cleavage fragments: signatures of cell-death proteases in neurodegeneration
Parallel induction of ATM-dependent pro- and antiapoptotic signals in response to ionizing radiation in murine lymphoid tissue
Tumor necrosis factor induces Bcl-2 and Bcl-x expression through NFkappaB activation in primary hippocampal neurons
Polarization profiles of human M-CSF-generated macrophages and comparison of M1-markers in classically activated macrophages from GM-CSF and M-CSF origin
Transcriptional profiling of the human monocyte-to-macrophage differentiation and polarization: new molecules and patterns of gene expression
The chemokine system in diverse forms of macrophage activation and polarization
LPS induces rapid IL-10 release by M-CSF-conditioned tolerogenic dendritic cell precursors
Matrix metalloproteinases and tumor metastasis
Cell cycle progression and apoptosis after irradiation in an acidic environment
Overview of radiosensitivity of human tumor cells to low-dose-rate irradiation
The tumor-immune microenvironment and response to radiation therapy
Macrophage activation and polarization: nomenclature and experimental guidelines
Colony-stimulating factor 1 promotes progression of mammary tumors to malignancy
Radiation sensitivity of human and murine peripheral blood lymphocytes
The role of oxygen-derived free radicals in radiation-induced damage and death of nondividing eucaryotic cells
Radioresistance of the engulfing and degradative capacities of peritoneal phagocytes to kiloroentgen x-ray doses
Threonine 68 of Chk2 is phosphorylated at sites of DNA strand breaks
Ionizing radiation induces expression and binding activity of the nuclear factor kappa B
RelB regulates Bcl-xl expression and the irradiation-induced apoptosis of murine prostate cancer cells
Regulation of macrophage function in tumors: the multifaceted role of NF-kappaB
A distinct and unique transcriptional program expressed by tumor-associated macrophages (defective NF-kappaB and enhanced IRF-3/STAT1 activation)
Transcriptional regulation of macrophage polarization: enabling diversity with identity
Differential effects of irradiation with carbon ions and x-rays on macrophage function
TNF Induction of NF-kappaB RelB Enhances RANKL-Induced Osteoclastogenesis by Promoting Inflammatory Macrophage Differentiation but also Limits It through Suppression of NFATc1 Expression
Macrophages and therapeutic resistance in cancer
Immunomodulatory properties and molecular effects in inflammatory diseases of low-dose x-irradiation
Contribution of the immune system to bystander and non-targeted effects of ionizing radiation
Of mice and not men: differences between mouse and human immunology
Nitric oxide synthase is not a constituent of the antimicrobial armature of human mononuclear phagocytes
“Of mice and men”: arginine metabolism in macrophages
Macrophages stimulate gastric and colorectal cancer invasion through EGFR Y(1086)
Erk1/2 and Akt phosphorylation and smallGTPase activity
Resazurin assay of radiation response in cultured cells
Fiji: an open-source platform for biological-image analysis
Download references
This work was financially supported by the Portuguese Science and Technology Foundation FCT/MEC (PTDC-SAU-ONC/112511/2009 and UID/BIM/04293/2013)
co-financed by the FEDER via the PT2020 Partnership Agreement under the 4293 Unit I&D
We also acknowledge the Program COMPETE FCOMP-01-0124-FEDER-010915 and the Prize L’Óreal for Women in Science (Foundation L’Óreal/FCT/UNESCO)
Authors also thank the International Iberian Nanotechnology Laboratory (INL)
FCT (PhD fellowships: SFRH/BD/74144/2010 and SFRH/BD/81103/2011; FCT-Program Ciência2008 and FCT2012-Investigator Program)
North Region Operational Program (ON.2) (NORTE-07-0124-FEDER-000005-QREN)
Cancer Research UK (C99667/A12918) and Wellcome Trust (097945/B/11/Z) for their grant support
we would like to perform a special acknowledgement to all members of Radiotherapy Service (CHSJ)
availability and support provided to this project
I3S-Instituto de Investigação e Inovação em Saúde
Mário Adolfo Barbosa & Maria José Oliveira
Ana Teresa Pinto & Ana Patrícia Cardoso
ICBAS-Institute of Biomedical Sciences Abel Salazar
Susana Gomes dos Santos & Mário Adolfo Barbosa
IPATIMUP-Institute of Molecular Pathology and Immunology
IBMC-Institute for Molecular and Cell Biology
Department of Radiation Oncology and Experimental Cancer Research
performed the experiments and drafted the manuscript
protocol optimization and in vitro experiments
helped with macrophage polarization experiments
provided technical support on image acquisition and analysis
managed the irradiation schedule and provided clinical input
helped in the acquisition and interpretation of macrophage polarization data
provided scientific input and reviewed the manuscript
supervised the study data and drafted the manuscript
All authors read and approved the final manuscript
The authors declare no competing financial interests
Download citation
Sign up for the Nature Briefing: Cancer newsletter — what matters in cancer research
This website is using a security service to protect itself from online attacks
The action you just performed triggered the security solution
There are several actions that could trigger this block including submitting a certain word or phrase
You can email the site owner to let them know you were blocked
Please include what you were doing when this page came up and the Cloudflare Ray ID found at the bottom of this page
In the context of the internationalism that was the backbone of liberation struggles worldwide
women used images – mostly photography and film – as a weapon
this political engaged praxis was a sort of response to the use of images by political
which very much sustained the colonial order and ideology
among the women who photographed or made films for political purposes
Sarah Maldoror and Suzanne Lipinska stand out
The filmed materials – and not just the ones women authored – were given meaning by film editors Jacqueline Meppiel
Cristiana Tullio-Altan or Josefina Crato (the only woman among the four young Guineans sent
Isabel Noronha through their cinematographic fictions; Kamy Lara
through their documentary films; Eurídice Kala
Jota Mombaça and Grada Kilomba through their projects
make decisive contributions that reflect on (post-)colonial memories and experiences
ways of decolonizing the archive and re-imagine Portuguese colonialism and the struggle against it
No history of decolonization or of decolonizing praxes is ever completed without attention to gender
How did women view the liberation struggles in the former Portuguese colonies
How were their ways of seeing integrated or not in the imagination of colonialism
Was there a specific gaze to women over the liberation struggles
What knowledge and awareness do we have of/about these ways of seeing
And how do these ways of seeing intersect with those of contemporary filmmakers
curators and academics who are now questioning public and private archives
are visually recreating their memories or re-imagining colonialism
programming and curatorship have in questioning or prolonging (official) “politics of memory”
GATHERING(S) Gendering Decolonizations: Ways of Seeing and Knowing intends to contribute to the debate
photo ©Augusta Conchiglia (Angola, 1968)
10h – Reading of the manifesto “Gathering(s)”
10h10/11h15 – First Circle: Decolonial Image and Movement I
“From Submissive to Political: The Place of the Black Body in Visual Culture – conference-performance” (video
“Female Gaze and Subjectivity in The Murmuring Coast”
“Margarida Cardoso and the Casa Grande women: white fragility and (post)colonial memory”
12h15/13h15 – Catarina Laranjeiro and Tânia Dinis
“ Women-nation: representations in postcolonial cinema in Guinea-Bissau”
Cabral and the support network to Guinea-Bissau’s Revolution” (online)
“The production of knowledge about colonized and non-colonized women: methodological implications”
17h00/19h15 – Second Circle: Images and Liberation Chants – Augusta Conchiglia on the East Front tracks (Angola)*
Screening of excerpt of A proposito dell’Angola (Stefano di Stefani
and Maria do Carmo Piçarra on Guerre du Peuple en Angola and the migration of images to Monangambé (Sarah Maldoror
16’) and Festival panafricain d’Alger (William Klein
May 28th – Hangar (morning) / Museum of Aljube (afternoon)
10h-13h – Third Circle: Decolonizing the Archives
10h/10h20 – Screening of Terceiro Andar (versão monocanal, 17’)
11h/11h40 – Screening Fordlandia malaise (Susana de Sousa Dias
12h20/13h - Talk with Susana de Sousa Dias
Luciana Fina and Maria do Carmo Piçarra
14h30/15h10 – Forth Circle: Decolonial Image and Movement II
Screening of Essencial é a Fome (Raquel Lima
Talk on the creative processes and methods of Raquel Lima and Ana Cristina Pereira
15h10/15h50 – Screening of excerpts from Nôs Terra (2013
16h/18h30h – Fifth Circle: Unlearning Colonialism: ways of seeing and knowing
16h20/17h05 – Screening of excerpts from ANTICORPO: a Parody on the Colonial Ambition (Patrícia Lino
44’); Teko Haxy - ser imperfeita (Patrícia Ferreira and Sophia Pinheiro
10h/10h30 – Ana Balona de Oliveira “Women Artist Decolonizing the Archive”
10h30/13h – Sixth Circle: Public and Private Archives
Screening of Rorschach for a blindness (Vanessa Fernandes
5’) and Tradição e Imaginação (Vanessa Fernandes
9’) and Adventures in Mozambique and the Portuguese Tendency to Forget (Ângela Ferreira
“Rhizomes: from memory to imagination”
“On Adventures in Mozambique and the Portuguese Tendency to Forget”
Talk with Vanessa Fernandes and Ângela Ferreira moderated by Ana Balona de Oliveira
“The function of archives’ reuse and sensory reenactment in the elaboration of a counter-history of Portuguese late colonialism”
Screening and talk with the film director.
16h/18h30 – Seventh Circle: Maldoror’s decolonial gaze (Angola
“Political awareness and anti-colonialism through the poetic gaze of Sarah Maldoror”
16h40 – Screening of Cap-Vert: Un Carnaval Dans Le Sahel (1979
Talk with Annouchka de Andrade and Maria do Carmo Piçarra
development and coordination by Maria do Carmo Piçarra
Integrated in the research program at Hangar / Xerem and supported by DGArtes.
Visual archaeologist. She finished her Ph.D
Culture and Communication Studies at New York University
Her research interests are located at the intersection of visual culture
memory studies and decolonial theory-praxis and their articulation within the history of the Portuguese empire
in particular its contemporary modes of existence
She also holds a special interest in indigenous cosmogonies
in Contemporary Art History from FCSH-Universidade Nova de Lisboa and a B.A
branch Art History from Faculdade de Letras-Universidade de Lisboa
She also studied at the New School for Social Research (anthropology) and at Sorbonne-Paris IV
In addition she works in film and is currently developing the visual project Colonial Specters: a visual hauntology
Inês is the author of Sob o Olhar de Deuses sem Vergonha: Cultura Visual e Paisagens Contemporâneas (Lisboa: IHA-EAC/Colibri
Postdoctoral Researcher at the Centre of the Communication and Society Research of the University of Minho and the Centre for Comparative Studies of the University of Lisbon
Co-editor of Aniki – Portuguese Journal of the Moving Image
Propaganda colonial e censura no cinema do Estado Novo (Overseas blues
Colonial propaganda and censorship in the cinema of Estado Novo (2015)
Published under a Creative Commons License
Practical insights from and foracademics and university staff
Everything you need for each stepof your study abroad journey
More than 1,500 people have signed an open letter calling for the reinstatement of a chapter of a book on sexual misconduct in universities after it was withdrawn by its publisher following legal threats
Chapter 12 of Sexual Misconduct in Academia: Informing an Ethics of Care in the University details what its three female authors describe as their experiences of sexual harassment at an unnamed institution where they were formerly PhD students or postdocs
Boaventura de Sousa Santos, emeritus professor of sociology and director emeritus of the Centre for Social Studies at the University of Coimbra
was reported as being “taken aback” by the “very offensive paper”
Campus resource: What does ‘taking sexual violence seriously’ look like at universities?
The future of the title as a whole is now mired in uncertainty
Now an open letter calling on Routledge to reinstate chapter 12 and the book as a whole has been signed by more than 1,500 people
who call on the publisher to stand up to legal threats
Anna Bull, lecturer in education and social justice at the University of York
who wrote the book’s afterword and co-founded the 1752 Group
a research group addressing sexual harassment in higher education
said that the withdrawal of the chapter was “very concerning”
She warned that the move risked silencing victims of sexual harassment
“Routledge admit that they have bowed to legal threats in withdrawing the chapter
This move has serious implications for academic freedom in scholarly publications,” Dr Bull said
we are hoping to persuade them to stand up to legal threats and reinstate the book
While they are also in a difficult position
they have chosen to take the least risky option
if Routledge was not willing to reinstate the book
she hoped that another publisher would be willing to take it on
Routledge said the academic institution involved
and others had made statements leading to the identification of some of those involved in news articles and on social media
“Routledge then received a series of legal threats from various parties
including from a leading UK law firm acting for one of the accused
and was put in the difficult position of defending specific allegations against named
“After discussions failed to find a way forward
Routledge made the difficult decision to withdraw the chapter from publication and return the rights in the chapter to the authors.”
The publisher said it intends to reconvene with the editors at an appropriate time to explore options for the rest of the book
but that the title will remain unavailable pending the conclusion of this process and the full resolution of legal claims
Professor Santos has not responded to THE’s requests for comment
He has said in a YouTube interview that he had committed “errors
making comments that “would be considered male chauvinistic things” today
such as complimenting women on their appearance
patrick.jack@timeshighereducation.com
Already registered or a current subscriber
Editors claim voices of victims are being silenced as future of Routledge book on harassment in academia left in doubt
As several UK universities outlaw sex between academics and students
two writers offer differing views on the Office for Students’ proposed ban
higher education’s attitude towards student-faculty relationships is very different
The #MeToo movement has cast historical behaviour and curricula in a new
New restrictions following pro-Palestinian encampments appear to contravene Australian universities’ commitments on free speech
English universities pushing to show they are serious about tackling sexual misconduct ahead of new regulatory requirements but experts say efforts still ‘patchy’
An internationally supported online institution could give hope to the country’s young women
Bill proposing screening of all scholars working on ‘sensitive areas’ will create ‘huge administrative burden’
Subscribe today to receive unlimited news and analyses
commentary from the sharpest minds in international academia
our influential university rankings analysis and the latest insights from our World Summit series
A Portuguese university has issued a public apology to “people who consider themselves victims of harassment or abuse” at the institution
after allegations of sexual misconduct were raised in a book that became the centre of a publishing controversy
publicly claimed that that the work identified him in relation to the harassment allegations
In a statement, Routledge said it had made the “difficult decision” to withdraw the chapter after receiving “a series of legal threats”. More than 1,500 people subsequently signed an open letter calling for the chapter to be reinstated
A spokesperson for the publisher told Times Higher Education: “Routledge has not yet reached a decision with the editors of the book about its future
The Centre for Social Studies appointed an independent commission in response to the allegations after the book’s initial publication in March 2023, and an investigation commenced the following August. In its final report
the commission concludes that while it could not “clarify beyond doubt the existence or otherwise of all the situations reported”
there was evidence to suggest “patterns of conduct involving abuse of power and harassment on the part of some people who held senior positions in the CES hierarchy”
which does not name any alleged perpetrators
found that the centre’s “hierarchical structure” had resulted in “profound power imbalances and distrust among students towards the people who have held management positions in its bodies over the years”
the commission says CES management had demonstrated a “frivolous” response to allegations of misconduct
“Confusion” between the professional and private spheres may have led to abuse of power
while “situations of favouritism and bias” are noted
the CES board of directors said: “While it is true that the situations reported were the result of individual actions
they are also the result of institutional failures which
in the absence of adequate mechanisms to prevent harassment
allowed the conditions for forms of abuse of power
“We are determined to take every initiative to ensure that there are consequences to these complaints and that the bad practices that have been identified are not repeated at CES,” the letter continued
THE has approached Professor Santos for comment
He told Portuguese media that the report “focused on issues of abuse of power
responsible for the decentralisation of power”
and he suggested that these issues related to “people who held higher positions in the CES hierarchy”
“I believe that the more than 600 pages of evidence that I added to the process have contributed to the fact that nothing objective against me has been concluded,” Professor Santos told Observador
emily.dixon@timeshighereducation.com
Chapter withdrawn by Routledge after legal threats
with professor claiming that he had been identified
Article on MeToo movement in Iran named researcher
responses that point out its flaws should not be hidden from readers behind a paywall
As UK universities desperately seek savings
open science advocates must press both their moral and selfish cases
say Marcus Munafò and Neil Jacobs
Academics are being urged to boycott a publisher after it “unpublished” a book on sexual misconduct in universities which had triggered legal threats
A chapter of Sexual Misconduct in Academia: Informing an Ethics of Care in the University – which details allegations of sexual harassment at an unnamed institution – was previously withdrawn after an academic claimed he was identified as an alleged perpetrator
In doing so, Anna Bull, lecturer in education and social justice at the University of York
told Times Higher Education that Routledge and Taylor & Francis were “choosing to stand with the powerful and silence survivors of sexual misconduct”
“Their mishandling of the publication of Sexual Misconduct in Academia shows they are unable to cope with this issue,” said Dr Bull
we urge academics to boycott reviewing for or publishing with them wherever possible.”
Despite international outcry
the chapter in question was permanently withdrawn in September
Catarina Laranjeiro and Miye Nadya Tom – describe their experiences of sexual harassment at an unnamed institution where they were formerly PhD students or postdocs
However, Boaventura de Sousa Santos, director emeritus of the University of Coimbra’s Centre for Social Studies (CES)
publicly claimed that the work identified him in relation to the harassment allegations
Earlier this year, Coimbra issued a public apology to “people who consider themselves victims of harassment or abuse” after an independent report concluded that
while it could not “clarify beyond doubt the existence or otherwise of all the situations reported”
chief executive of the End Rape on Campus project
said it was “deeply disappointing” to see the “vital” publication removed from shelves
“This action only highlights the very silencing the book seeks to address,” she added in a post on Twitter/X
“I’m in solidarity with you [the editors] and hope that this gets resolved ensuring that your next collection remains unscathed.”
Routledge said it wrote to the editors with a “proposal to work collaboratively together to make the remainder of Sexual Misconduct in Academia
available again as a Routledge title” in September
we could not reach agreement with the editors on this proposal,” they added
to revert all the rights in the book to the editors and the contributors
giving them full freedom to explore options for publication elsewhere
including placing the book with another publisher.”
Investigation follows publishing controversy that saw chapter detailing allegations withdrawn by Routledge
Read today's Portuguese stories delivered to your email
Aldi opens its first store of the year in Portugal today
The new establishment is located in Monte de Caparica
the company explains that it "kicks off the new year with the opening of its first store in 2025 in Monte de Caparica"
"This investment consolidates the presence of the discount retailer in Almada
which now has four stores in this municipality
"the brand now has 21 stores in the district of Setúbal
this being the fourth in the municipality of Almada
We appreciate that not everyone can afford to pay for our services but if you are able to
we ask you to support The Portugal News by making a contribution – no matter how small
You can change how much you give or cancel your contributions at any time
Send us your comments or opinion on this article
Reaching over 400,000 people a week with news about Portugal
Two academics say a publisher has permanently withdrawn a chapter of a book they edited on sexual misconduct in universities
with doubts about the future of the entire collection
after a prominent Portuguese sociologist alleged it identified him in relation to claims of harassment
Sexual Misconduct in Academia: Informing an Ethics of Care in the University was published in March this year by Routledge
Chapter 12 details what its three female authors describe as their experiences of sexual harassment at an unnamed institution where they were formerly PhD students or postdocs
In an interview posted on YouTube, Boaventura de Sousa Santos, emeritus professor of sociology and director emeritus of the Centre for Social Studies at the University of Coimbra
said he was “taken aback by this paper that was published by Routledge – a very offensive paper”
also said then that “the book is already suspended
because it’s so serious – it’s a criminal accusation under the guise of a scientific paper”
a Brazilian politician was reported by Brazilian media to have alleged that she was a victim of sexual harassment by Professor Santos during her time as a PhD student at Coimbra
It does not name the institution in question or individuals – instead detailing allegations about a “star professor and his apprentice”
It also refers to anonymous graffiti repeatedly appearing on walls at the institution alleging sexual misconduct by the “star professor”
The pair told Times Higher Education in a statement that Routledge told them it had been contacted by a Portuguese lawyer and then received a “cease-and-desist letter” from an individual who claimed to be identified in the chapter
Routledge decided to permanently withdraw chapter 12 from the book and handed back the rights of the chapter to the authors
through an email,” Dr Pritchard and Dr Edwards said
“This final decision was not communicated with or agreed to by us as editors
We are very disappointed that Routledge has taken the decision to permanently withdraw the chapter and possibly the book
“This is effectively siding with those attempting to silence this book and making minimal attempts to push back against these legal threats without defending academic freedom or the rights of sexual harassment survivors to speak about their experiences.”
who did not respond to THE’s requests for comment
said in the YouTube interview that his centre had organised an independent commission to look into the issue
A Taylor & Francis spokesperson said that “the title Sexual Misconduct in Academia is currently under review” and it was “unable to comment while the review is ongoing”
said the authors “took reasonable steps not to name anyone” in relation to the experiences described in the chapter
added: “It is really important for survivors of sexual violence and harassment to be able to talk about their experience and to do so with their own names…People have the right to speak about their experiences.”
john.morgan@timeshighereducation.com
Already registered or a current subscriber?
As several UK universities outlaw sex between academics and students, two writers offer differing views on the Office for Students’ proposed ban
Five years on, higher education’s attitude towards student-faculty relationships is very different, says a UK-based academic
First results of landmark survey of 42,186 employees and students released
The #MeToo movement has cast historical behaviour and curricula in a new, shadowy light. Four writers give us their perspectives
An internationally supported online institution could give hope to the country’s young women, now confined to their homes, says an Afghan scholar
If a paper is published open access, responses that point out its flaws should not be hidden from readers behind a paywall, says Andrew Barnas
As UK universities desperately seek savings, open science advocates must press both their moral and selfish cases, say Marcus Munafò and Neil Jacobs
As the voice of global higher education, THE is an invaluable daily resource. Subscribe today to receive unlimited news and analyses, commentary from the sharpest minds in international academia, our influential university rankings analysis and the latest insights from our World Summit series.
2001 THE WINDSOR STAR C7 Deaths MACPHERSON
Pherson was a retired executive of the Canadian Broadcasting Corporation after 33 years of dedicated service in Toronto
Former Commanding Officer of the Queen's Own Cameron Highlanders (Winnipeg) and a former Commander of the Windsor Militia District
Andrew's Presbyterian Church( Windsor)
John Ambulance and King Edward Lodge AF AM
Visitation at the Windsor Chapel Funeral Home
A memorial service will be held on Thursday
Andrew's Presbyterian Church (405 Victoria)
donations may be made to the Windsor Regional Cancer Centre
Walter James (Wally) Matthews in his 73rd year
Beloved husband and friend of Noelle Matthews
Dear father to Jim (Loretta) Matthews of Tilbury
Also loved and missed by many grandchildren
Survived by sisters Doreen (Jack) Lawrie of Sarnia
Predeceased by his parents Lorraine and Walter Matthews and brother Robert (Shirley) Matthews
A Memorial Service will be held at the Memorial Funeral Home
donations to the charity of your choice would be appreciated
Loving father of Michelle Petrosenko and husband Bob
Gregg Martin Mazak and James Quentin Mazak
Dear brother of Emilia Rafaidus and husband George and brother-in-law of Bob Lovecky and wife Mary
Mazak was a GRADUATE 1961 from McGill University Faculty of Dentistry
FELLOWSHIP RECIPIENT American Endodontic Society
FELLOWSHIP RECIPIENT Academy of Dentistry International
FELLOWSHIP RECIPIENT International College of Dentists
FORMER GOVERNOR Ontario Dental Association
FORMER PRESIDENT Essex County Dental Society
FORMER EXECUTIVE COMMITTEE MEMBER American Association of Dental Consultants
FOUNDING PRESIDENT Canadian Association of Dental Consultants
FORMER DENTAL CONSULTANT REPRESENTATIVE Ontario Dental Association
CERTIFIED DENTAL CONSULTANT American Association of Dental Consultants
and EDITOR The Adjudicator (Canadian Association of Dental Consultants Newsletter)
East Sunday from 7-9pm and Monday from 2-5pm and 7-9pm
Family and friends are requested to meet on Tuesday July 17
from 10:30 am until time of Funeral Mass at 11:00 am
As donations may be made to the Deaths MOORE
Elsie Hilda (Bilusack) (nee Bluschke) At Hotel Dieu Grace Hospital
Beloved mother of Linda Bilusack of Windsor
Richard and wife Estelle Bilusack of Regina Rudy Bilusack of Surrey B.C.
Dear daughter of the late Heinrich (1982) and Helena Bluschke (1982)
Brent Bilusack Regina and Oma to Ryan and Dylan Boow of Windsor
Dearest sister of Arnold and wife Jane Blueschke of Okenagan Falls B.C.
Linda Cebry of Regina and the late Richard
Also survived by several nieces and nephews
donations to the Canadian Diabetes Association or the Canadian Kidney Foundation would be appreciated by the family
For further information please call Families First Funeral Home Chapel (969-5841)
You may send your online condolences at www.familiesfirst.net MUTTERBACK
Kathleen (Kay) (nee Knight) At Leamington Hospital
Funeral service from the funeral home on Tuesday
donations to the Ontario Heart and Stroke Foundation or Leamington Hospital would be appreciated
Dearest son of Verna and the late Elmer Pickering
Funeral Service from the funeral home Tuesday 2 p.m
2 grandsons and 2 greatgrandchildren in Yugoslavia
a member of the Serbian National Federation Lodge 4 45 and the Royal Yugoslav Army War Combats "Draza He retired from Chrysler's
Friends may call at the Anderson Funeral Home
Please note: Family and friends are requested to meet at St
Dimitrije Serbian Orthodox Church (2690 Seminole)
Interment Windsor Memorial Gardens Prayers Monday 7:00 p.m
Predeceased by her husband Frank (1996) and husband Pat Fitzpatrick (1972)
Loving father of Dan and Sheila Fitzpatrick of Windsor
Loving sister to Eileen Somerville and husband Reg of St
Betty and Mike Macyshyn of Windsor (deceased)
and brother Pat Baker and wife Agnes of St
Peggy was a lifetime member of the Essex Kent Naval Veterans and endless volunteer for the ladies auxillary
Funeral Services will be held on Wednesday
Memorial Tributes to the Liver Foundation would be sincerely appreciated by the family
IN MEMORIAM ACKNOWLEDGEMENTS SERVICES OF TRIBUTE THANK-YOU CARDS SOCIETIES LODGES For Announcement Notices Call 255-5544
Vera May At Hotel Dieu Grace Hospital on July 12
Predeceased by her parents John Mary (nee Timbers) Vincent
Loving mother of Bertha Scott and her late husband Wayman (1987)
Maidstone; John Franklin Sims and his wife Sara
Chatham; Darlene Highgate and her husband Ralph
Dresden; the late Donelda Curry (1998); Amos Fletcher Sims
Windsor; and Glen Murray Sims and his wife Carmel
grandchildren Also and survived yes great-grandchildren
Sims was a devoted member of the First Baptist Church Windsor and volunteer of the church's former Emergency Club
Visiting at the Sutton Funeral Home Chapel
Beloved husband of the late Winnifred (nee: Greenlund)
James and wife Roberta and Joseph Loving grandfather to fourteen grandchildren
of W.W.II and a member of the Royal Canadian Legion Branch If you so desire
donations to the Ontario Heart Stroke Foundation would be appreciated by the family
Funeral Tuesday 1pm at Families First Funeral Home Chapel (969-5841)
You may send your online condolences at www.familiesfirst.net WARNER
Dear stepfather of Derek Schroeder and Kimberley Schroeder
Windsor; and the late Dorothy Warner (1989)
Garry was a senior Conservation Officer proudly serving Ontario for 25 years
dedicated to the protection and enjoyment of Ontario's Natural Resources
Funeral service at the funeral home Wednesday
Donations to Canadian Cancer Society gratefully acknowledged
Gertrude Edith (nee Jennings) With much love and great sorrow in our hearts
announce the passing of Gertrude Weir on July 13th
now to be reunited with her "ever loving" husband Robert (1977)
Gert dedicated her life to raising and protecting her family and will be remembered with love in the hearts of her grandchildren
Dearest sister of Violet Phillips and the late George and Victor Jennings and favorite aunt to Audrey and Ed Soper
Gertie dedicated her life to helping others
She was a 54 year member of the Knox Presbyterian Church; a long time volunteer at Grace Hospital
a former member of the Jubilee Club Fun Band and the Free on Friday Club
donations to a Charity of Your Choice would be appreciated by the family
Now in peace in the arms of the Lord and watching over her family
she will be laid to rest by those who loved her the most on Monday
2001 at at Families First Funeral Home (969-5841) 2670 Dougall Avenue
Paterson of Paulin Memorial Presbyterian Church officiating
You may send your online condolences at www.familiesfirst.net In Memoriams Memoriams" are a prepaid classification) For your convenience accept VISA and MASTERCARD You see Chris
The most loving and caring human being that ever graced this earth
you will always be the "Wind beneath my HAPPY BIRTHDAY
1978 Today we thank God for giving you to us 23 years ago
We still hear your voice and see your gentle face
you're in our hearts every minute of the day
especially on this day for this is the day that all of our lives were blessed with you
THE FAMILY FACT FILE A HEAVENLY Our new estate organizer
Never any obligation call today for your free copy Planning
Remembering HEAVENLY REST CEMETERY 5005 Howard Ave
Today we celebrate Rosa's 30th Birthday
It was a glorious day for God had given us a precious gift our baby sister
Far from sin and Where Jesus said "Believe in Me And thou shalt see her again." I wish I could give you a big "30th" Birthday hug
Rosa can still hear your laugh We can still see your smile
We will always feel your presence --Missing you today and always
Dan In loving memory of my dear Cousin who passed away 4 years ago today
a Special face And in my heart a Special place
1996 Five years have passed and gone Since the one we loved so well Was taken from our home earth With Jesus Christ to dwell
lion The flowers we place upon her grave May wither and decay But the love for her who sleeps beneath Shall never fade away
Sadly missed and always remembered by John and Derek PITRE
Memories are our greatest treasure We will remember him forever and ever With Mary Pitre families POISON
1994 In loving memory of a wonderful Husband
And finds the time long since you went There is someone who thinks of you always And tries to be brave and content Gone is the face we loved so dear
Silent the voice we loved to hear; 'Tis sad but true we wonder why
William In loving memory of our dearest father and grandfather
Remember him with a smile today He was not one for tears
Reflect instead on memories Of all the happy years
Recall to mind the way he spoke Of all the things he said
1999 Ode to Nikolas You never had the chance to see the blue skies We never had the chance to hear your cries You never had the chance to crawl or walk We never had the chance to hear you talk
You never had the chance to run and play We never had the chance to tell you "Everything's You never had the chance to climb a tree
Mom never had the chance to kiss your scraped knee
You never had the chance to ride in Dad's truck
Dad never had the chance to show you a puck
You never had the chance to tease your big sister She never had the chance to let you kiss her
You never had the chance to get dirty and soiled
Your Grandparents never had the chance to see that you got spoiled
They never had the chance to show you their loving
But we are thankful to heave held you even though a brief time
You now have the chance to watch over us from above
We still have the chance to show you our love
you won't have the chance to know suffering and pain
And we pray for the day when we will meet you again
Nikolas Two years have gone by Since we last held you baby boy
Now you are flying free little one Where your star is brighter than the sun
When the Lord looked upon the earth that day Our sweet little boy he took away
Only the best I shall take For he has made no mistakes
Happy 2nd Birthday Our Sweet Bundle of Joy Love Nana Papa Vincent URBAN
see To see you To tell you everything's okay Even though you're far away
It's always easy forever to and We love you always
We wish to express our sincere thanks to the many friends and family who gave a kind word of sympathy
beautiful floral arrangements and spiritual offerings during the long illness and death of our beloved husband and father
and staff at Families First Funeral Home and Heavenly Rest Cemetery
Eva Rabideau Family To place your memoriam in Star Classified please call 255-5544
Please allow 2 business days for us to process your photo
(Photo is optional.) As A Service To Our Readers "In Memoriam" Verse Sample Booklets are available at the Classified Counter in the Main lobby at The Windsor Star
You may place a memoriam notice for any particular date by phoning THE WINDSOR STAR CLASSIFIED DEPARTMENT 255-5544 before 6:00 p.m
and the message will appear in the next day's paper
Classified phones are answered from 7:30 a.m
however ads for the very next day must be placed prior to 6:00 p.m
"In Memoriams" are a prepaid classification
For your convenience we accept Visa and Mastercard