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Background: The high incidence of food allergy in childhood points to the need of elucidating early life factors dictating allergy susceptibility. Here, we aim to address in a mouse model how the exposure to a major cow's milk allergen through breastmilk of mothers with different immune status influences food allergy outcome in offspring.
Conclusion: Our study demonstrates the strong potential of breastmilk to modulate immune response to a major cow's milk allergen in the progeny. It highlights the importance of maternal immune status and of her consumption of the allergen during lactation in dictating the outcomes in offspring. This opens perspectives where modulating maternal immune status might increase the chance of cow's milk allergy prevention in breastfed children.
Volume 11 - 2020 | https://doi.org/10.3389/fimmu.2020.01545
Background: The high incidence of food allergy in childhood points to the need of elucidating early life factors dictating allergy susceptibility
we aim to address in a mouse model how the exposure to a major cow's milk allergen through breastmilk of mothers with different immune status influences food allergy outcome in offspring
Methods: BALB/cJ future dams were either kept naïve
or sensitized through the oral route using cholera toxin (“orally sensitized”) or through the i.p
or rendered fully tolerant (oral gavage without any adjuvant) to bovine β-lactoglobulin (BLG)
After mating with naïve males and delivery
mothers were orally exposed or not to BLG during the whole lactation
eight groups of lactating mothers were considered: naïve
In order to specifically address breastmilk effects on their allergy susceptibility
pups from naïve-synchronized mothers were cross-fostered by the different groups of treated dams and lactating mothers at delivery
mothers kept their own pups to address a possible in utero effect
and BLG-immune complexes were measured in breastmilk from the different lactating mother groups
Allergic sensitization was monitored in 5-weeks old female offspring (n = 7–8/group of lactating mothers) by determining BLG-specific antibodies in plasma and splenocytes cytokine secretion after i.p
Allergic reaction to oral BLG challenge was evaluated by measuring mMCP1 in plasma
Results: Offspring was protected from one allergic i.p
independently of BLG exposure during lactation
Orally sensitized dams conferred protection in offspring solely when exposed to BLG during lactation
while naïve mothers did not provide any protection upon BLG exposure
The levels of protection correlated with the levels of BLG-specific antibodies and BLG-immune complex in breastmilk
There was a trend for decreased sensitization in offspring breastfed by tolerant and exposed mothers
which was not associated with transfer of specific antibodies through breastmilk
Protection provided by nursing by treated/exposed mothers was not persistent after a boost i.p
injection of the progeny and then did not protect them from an allergic reaction induced at this time point
No additional in utero effects were evidenced
Conclusion: Our study demonstrates the strong potential of breastmilk to modulate immune response to a major cow's milk allergen in the progeny
It highlights the importance of maternal immune status and of her consumption of the allergen during lactation in dictating the outcomes in offspring
This opens perspectives where modulating maternal immune status might increase the chance of cow's milk allergy prevention in breastfed children
While the factors controlling food antigen shedding in breastmilk are poorly identified
at low doses and over a long period of time after ingestion (>24 h)
This might have a role in the education of the immune system to environmental antigens to which the newborn will be naturally exposed: actually
they might correspond to dietary habits of the family
In order to expand the knowledge on how to prevent food allergy by breastmilk
we aimed to address whether observations obtained with an egg allergen could be extended to the major cow's milk allergen
a frequent cause of food allergy in infancy
in order to better reflect the human setting
we also aimed to assess the role of the immune status of the mother in this protection
or highly sensitized mothers who were exposed or not to the food allergen during lactation
Female and male BALB/cJ Rj mice, 4 weeks-old, were purchased from CERJ (Centre d'Elevage René Janvier, Le Genest-Saint-Isle, France), and were housed in filtered cages under normal specific pathogen free husbandry conditions, with autoclaved bedding and sterile water. Mice received a diet deprived of animal proteins in which BLG was not detected using specific immunoassays (22)
Native BLG (BLG) was purified from raw cow's milk (non-heated, Ferme de Viltain, Saclay, France) using selective precipitation and chromatography, and further characterized, as previously described (23)
Lactating mothers were then exposed or not to 1 mg of BLG by gavage (200 μl/administration
diluted in PBS) every other day starting 48 h after delivery and until weaning
so they and their pups had the same handling/stress as in the group of exposed mothers
Experimental protocol: BALB/cJ future dams were either kept naïve
and Cholera toxin) or highly (intra-peritoneal administration of BLG/alum) sensitized to BLG
or rendered tolerant to BLG (intra-gastric gavage with BLG alone) before mating with naïve males
pups of treated mothers were replaced by pups from naïve-synchronized mothers in order to prevent interferences from in utero effects
Lactating mothers from each group then received BLG or PBS by i.g
Breastmilk was collected 10 days post-partum by pooling stomach contents from 6 to 10 male pups per mother group to assess BLG
The female progeny was then experimentally sensitized by i.p
injection of BLG and Alum when 5 weeks-old and BLG-specific IgE
A boost injection was performed 21 days after the first i.p
all mice were orally challenged with 15 mg of purified BLG
both to assess allergic sensitization and elicitation of the allergic reaction
Mice were then sacrificed and spleens were pooled to assess ex vivo BLG-specific cytokine secretion
In order to assess any additional in utero effect
another experiment was conducted in which pups were kept by their respective mother and protocol then performed as before
Breastmilk was collected 10 days post-partum from the stomach of 6–10 male pups per mother group
Males were sacrificed 4 h after gavage of the mother with BLG (or PBS) and stomach content was collected and pooled per mother treatment (2–3 mothers per treatment group)
Content was weighted and diluted in two volumes of PBS
After vortexing and centrifugation (10,000× g
supernatants were collected and stored at −20°C until analysis
Enzyme immunometric assays were performed in 96-well microtiter plates (Immunoplate Maxisorb
Microfill dispenser and spectrometer equipments from BioTek instruments
BLG antigen and BLG-specific IgG1, IgA, and IgE were quantified in serial dilution of breastmilk samples (from 1/5 to 1/625) as previously described (22, 25, 28)
As no standard is available for BLG-specific IgA
results are expressed as absorbance measured at 414 nm
A positive control of IgG1-BLG immune complex was provided by mixing purified anti-BLG IgG1 monoclonal antibodies (10 ng/ml) with purified BLG (1 ng/ml)
No specific IgA-BLG or IgE-BLG immune complexes were detected
whatever the group of lactating mothers considered
the female offspring nursed by the different groups of mothers (e.g.
orally sensitized exposed during lactation
tolerant exposed during lactation) was sensitized to BLG by i.p
immunization with alum (7–8 mice/group of mothers)
Plasma samples were collected 20 days later to assess allergic sensitization
a boost injection was performed 21 days after the first i.p
BLG specific IgG1, IgE, and IgG2a were quantified on plasma samples collected from progeny using BLG-coated microtiter plates (25, 26, 29). Due to high IgG concentrations that might mask epitopes for IgE binding after the i.p. boost (25)
a reverse assay using anti-mouse IgE coated plates and AChE-labeled BLG was also performed
Results are then expressed as mAU414nm (no standard available)
Non-specific binding was assessed using plasma samples collected from naïve progeny (non-sensitized progeny from naïve and non-exposed mothers)
a specific marker of intestinal mast cell activation (Moredun Scientific Limited
was assessed on plasma samples collected 60 min after BLG oral challenge following provider recommendations
spleens were harvested and pooled within each mother treatment group
After lysis of red blood cells (180 mM NH4Cl
splenocytes were resuspended in RPMI-10 (RPMI supplemented with 10% fetal calf serum
100 μg/mL streptomycin—all from Gibco)
Cells were incubated in 96-well culture plates (106 cells/well) in the presence of BLG (20 μg/mL)
positive control) for 60 h at 37°C and 5% CO2
Each culture conditions were performed in duplicates
10 min) and supernatants were collected and stored at −80°C until further assay for cytokines using multiplexed kits and apparatus from Biorad (Bio-Plex Pro™ Mouse Group I and Bioplex100™ apparatus; Marnes la Coquette
Due to the number of animal included per group (n < 30) and as data were not normally distributed
Presence of differences between groups was first tested using non-parametric Kruskall-Wallis test
and p-values calculated using Monte Carlo simulation (10,000 permutations)
Pairwise multiple comparison was then performed using Conover-Iman testing
including Bonferroni correction for multiple testing
Mann Whitney test was additionally performed between two specific groups
All statistical analysis were performed using XLSTAT™ 2019 (version 2.3
Using a BLG-specific sandwich immunoassay, we detected BLG in milk collected from naïve or tolerant mothers who had been exposed to BLG during lactation (Figure 2A)
we could not detect BLG in milk collected from orally (moderate sensitization) or i.p
(high sensitization) sensitized mothers orally exposed to BLG during lactation
IgA (white bars) and IgE (gray bars) and (C) IgG1-BLG immune complexes detected in milk collected 10 days post-partum from naïve
sensitized or tolerant mothers exposed (+) or not (–) to 1 mg of BLG every other day during lactation
Assays were performed on stomach contents collected from pups 4 h after the exposition of their fostered mothers
For BLG-specific IgA and IgG1-BLG immune complexes
absorbance signals (mAU414nm) obtained at the 1/25 dilution are reported
A positive control of IgG1-BLG immune complex was provided by mixing purified anti-BLG IgG1 monoclonal antibodies with purified BLG (right bar)
BLG-specific IgE, IgG1, and IgA (Figure 2B) and BLG-IgG1 immune complexes (Figure 2C) were undetectable in milk from naïve or tolerant mothers
whether they had been exposed or not to BLG during lactation
BLG-specific Ig and immune complexes were detected and their levels increased with BLG exposure during lactation
sensitized mothers had the highest levels of BLG-specific Ig and BLG immune complexes
They were not further increased by BLG-exposure during lactation
The susceptibility of offspring from various mothers' group to be sensitized to BLG was first assessed by measuring BLG-specific antibodies after one i.p. sensitization with BLG in Alum. Mice fostered by naïve mothers exposed or not to BLG during lactation demonstrated comparable sensitization levels, as evidenced by comparable concentrations of BLG-specific IgE and IgG1 (Figure 3)
A trend in decreased BLG-specific IgE and IgG1 antibodies concentrations were evidenced in progeny fed by tolerant and exposed mothers (p = 0.06 and p = 0.01
using Mann-Whitney test and when compared to naïve non-exposed mice)
whereas no effect was evidenced in absence of exposure
Progeny fostered by orally sensitized mothers were significantly protected from sensitization only if mothers were exposed to BLG during lactation
although a trend in decreased BLG-specific IgE concentrations was also noticed without this exposure (p = 0,01 vs
sensitized mothers were fully protected from sensitization
as evidenced by the nearly absence of specific IgE and the very low concentrations of BLG-specific IgG1
Plasma BLG-Specific IgE (A) and IgG1 (B) antibodies induced after one i.p
sensitization with BLG/alum in pups fostered by naïve or pre-natally sensitized or tolerated mothers
further orally exposed (+) or not (–) to BLG during lactation
Tukey box and whiskers from 7 to 8 mice/groups are shown
Statistical analysis evidenced differences between groups (p < 0.0001
Pairwise multiple comparisons were then performed using Conover-Iman testing
Groups indicated with different letters are different from each other's (p < 0.05)
p-values obtained using additional testing against control (naive and non-exposed mothers) by Mann Whitney test are also indicated between brackets
The only group that tended to be protected from the elicitation of an allergic reaction was the progeny fostered by tolerant and exposed mothers (p = 0.06 using the Mann-Whitney test)
No difference of IgG2a concentrations was observed between the different groups of sensitized progeny (data not shown)
sensitizations and then an oral food challenge with BLG in pups fostered by naïve or prenatally sensitized or tolerized mothers
Statistical analysis evidenced differences between groups (p = 0.002 for IgE and p = 0.038 for mMCP1
Pairwise multiple comparisons were then conducted using Conover-Iman testing
p-values obtained using additional testing against controls by Mann Whitney test are also indicated (MW)
exposure during lactation greatly decreased BLG-induced Th2 cytokine secretion in those groups
Feeding by tolerant mothers also rather led to a decreased Th2 cytokine secretion
Comparable results were obtained for Th2 cytokines and IL-10
Pups were born and fed by prenatally sensitized (i.p
further orally exposed during lactation (in utero + lactation)
or pups from naïve mice were fostered by prenatally sensitized or tolerant mothers further orally exposed during lactation (n = 5–12/group)
BLG-specific IgE (top panel) and IgG1 (bottom panel) were assayed in plasma from progeny after one (A) and two (B) i.p
Specific antibodies are expressed as percentage
with the mean value obtained in naive mothers not exposed during lactation used as a reference (100%)
Immune response was compared between “in utero + lactation” and “lactation” groups for a same mother pre-treatment
and p-values are indicated (Mann Whitney test)
This highlights the need to better understand the way to maximize the chance of food allergy prevention
we then aimed to determine how both the immune status of the mother and her ingestion of a clinically-relevant cow's milk allergen during breastfeeding will impact the allergic outcome in the progeny
we found that these factors do have a major impact on sensitization susceptibility in offspring
Effect on sensitization ranged between nihil for naïve mothers exposed to BLG to a very potent protection for i.p
sensitized mothers (highly sensitized) ingesting or not BLG during lactation
Tolerant mothers and orally immunized (moderate sensitization) mothers induced some protection from sensitization but only when exposed to BLG during lactation
No additional in utero effect was evidenced in our experimental set up
BLG-immune complexes levels are related with level of protection in the progeny
Exposure to the allergen is required to detect immune complex in breastmilk in the orally sensitized mothers
whereas exposure to BLG in the BLG/Alum model is dispensable
This might result from the deposit effect of alum allowing progressive release of the antigen
then available for forming immune complexes independently of oral exposure
Although we did not absolutely prove the direct causal role of Ig and immune complex on protection from sensitization
oral exposure to the allergen during breastfeeding might be critical to form the Ig-immune complexes necessary to induced efficient protection in the progeny
This might then imply that all mothers are actually excretors of allergens in their BM
but as a free and/or complexed form depending on the levels of exposure
This should be taken into account in the association studies relating allergen concentrations in breastmilk and allergic outcome in the progeny
tolerant mothers tended to protect offspring from sensitization when exposed to BLG during lactation and this protection was not associated with Ig levels or presence of immune complexes in breastmilk
such as transfer in breastmilk of specific immune cell or immuno-suppressive cytokines
might also be involved in the transfer of protection
The actors and mechanisms involved in the protection provided by tolerant and exposed mothers clearly need additional studies
It is worth noting that sensitization levels and mMCP1 concentrations after the OFCs were not directly correlated
This may be explained by difference in mast cell density and FceRI expression and will require further investigation
our study demonstrated the strong potential of breastmilk to modulate in the long term the immune response to food allergens in offspring
This protective effect is associated with the excretion of the food allergens and immune factors in breastmilk
some of which are increased by exposure to the allergen during lactation
Future studies will need to address whether early immune modulation to cow's milk allergen by exposure through breastmilk might lead to a more successful cow's milk allergy prevention by early introduction in child
The raw data supporting the conclusions of this article are available from the corresponding author to any qualified researcher on reasonable request
All animal experiments were performed according to European Community rules of animal care and with authorization N° 91–368 of the French Veterinary Services
All experiments were covered by agreement no
2009-DDSV-074 from the Veterinary Inspection Department of Essonne (France)
HB and SH help to perform some experiments and critically revised the manuscript
FF and CJ critically revised the manuscript
All authors approved the submitted version
This study obtained a financial support from INRAE (Institut National de Recherche pour l'Agriculture
l'Alimentation et l'Environnement) and received a grant from French National Alliance for Life Sciences and Health (Aviesan)
Multi-organization Thematic Institutes—Immunology
and Hematology and Pneumology (call Asthma and allergy)
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest
We would like to thank Jean-Charles Robillard and Sandrine Ah-Leung for their excellent care to animals and their suitable help in animal experiments
The Supplementary Material for this article can be found online at: https://www.frontiersin.org/articles/10.3389/fimmu.2020.01545/full#supplementary-material
Food allergy: a review and update on epidemiology
Human milk and allergic diseases: an unsolved puzzle
Immunologically active components in human milk and development of atopic disease
Shaping the gut microbiota by breastfeeding: the gateway to allergy prevention
Breast milk and its impact on maturation of the neonatal immune system
and homogenized/pasteurized cow milk: a comparison
A double-blind placebo-controlled study in milk allergic children
Beta-lactoglobulin secretion in human milk varies widely after cow's milk ingestion in mothers of infants with cow's milk allergy
Consumption of cow milk and egg by lactating women and the presence of beta-lactoglobulin and ovalbumin in breast milk
Presence of high levels of non-degraded gliadin in breast milk from healthy mothers
Detection of peanut allergens in breast milk of lactating women
Effect of cooked and raw egg consumption on ovalbumin content of human milk: a randomized
Effect of maternal egg consumption on breast milk ovalbumin concentration
Peanut allergens are rapidly transferred in human breast milk and can prevent sensitization in mice
Effects of maternal dietary egg intake during early lactation on human milk ovalbumin concentration: a randomized controlled trial
Prospective investigation on the transfer of ara h2
Detection of the peanut allergens ara h2 and ara h6 in human breast milk: development of 2 sensitive and specific sandwich ELISA assays
Long-term reduction in food allergy susceptibility in mice by combining breastfeeding-induced tolerance and TGF-beta-enriched formula after weaning
Breast milk-mediated transfer of an antigen induces tolerance and protection from allergic asthma
Breast milk immune complexes are potent inducers of oral tolerance in neonates and prevent asthma development
Oral tolerance induced by transfer of food antigens via breast milk of allergic mothers prevents offspring from developing allergic symptoms in a mouse food allergy model
Maternal IgG immune complexes induce food allergen-specific tolerance in offspring
Two-site enzyme immunometric assays for determination of native and denatured beta-lactoglobulin
Update on optimized purification and characterization of natural milk allergens
Peanut- and cow's milk-specific IgE
Th2 cells and local anaphylactic reaction are induced in Balb/c mice orally sensitized with cholera toxin
Evaluation of a high IgE-responder mouse model of allergy to bovine beta-lactoglobulin (BLG): development of sandwich immunoassays for total and allergen-specific IgE
Oral tolerance and Treg cells are induced in BALB/c mice after gavage with bovine beta-lactoglobulin
Immunomodulatory potential of partially hydrolyzed beta-lactoglobulin and large synthetic peptides
Induction of mucosal immune response after intranasal or oral inoculation of mice with lactococcus lactis producing bovine beta-lactoglobulin
Evaluation of the efficiency of hydrolyzed whey formula to prevent cow's milk allergy in the BALB/c mouse model
Timing of allergenic food introduction to the infant diet and risk of allergic or autoimmune disease: a systematic review and meta-analysis
The canadian childhood asthma primary prevention study: outcomes at 7 years of age
Reduced risk of peanut sensitization following exposure through breast-feeding and early peanut introduction
Randomized trial of introduction of allergenic foods in breast-fed infants
Early exposure to cow's milk protein is protective against IgE-mediated cow's milk protein allergy
The ingestion of cow's milk formula in the first 3 months of life prevents the development of cow's milk allergy
Oral tolerance is inefficient in neonatal mice due to a physiological vitamin A deficiency
Maternal-fetal interaction: preconception immunization in mice prevents neonatal sensitization induced by allergen exposure during pregnancy and breastfeeding
Maternal allergen-specific IgG might protect the child against allergic sensitization
Role of maternal elimination diets and human milk IgA in the development of cow's milk allergy in the infants
Junot C and Verhasselt V (2020) Prevention of Allergy to a Major Cow's Milk Allergen by Breastfeeding in Mice Depends on Maternal Immune Status and Oral Exposure During Lactation
Received: 27 March 2020; Accepted: 11 June 2020; Published: 21 July 2020
Copyright © 2020 Adel-Patient, Bernard, Fenaille, Hazebrouck, Junot and Verhasselt. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY)
distribution or reproduction in other forums is permitted
provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited
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*Correspondence: Karine Adel-Patient, a2FyaW5lLmFkZWwtcGF0aWVudEBjZWEuZnI=
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The Inside Press
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June 23, 2015 by Inside Press
you often wonder about the need for so much work
Will the endless hours of studying actually pay off
I was worried as I began my freshman year that I would be overwhelmed by the workload
but I soon found myself more than able to handle not only the work but extracurricular activities as well
arguably one of the most important skills one could have
All of this would not be possible without some incredible teachers
and Greeley is fortunate to be home to many
And so I salute a great number of them –11 teachers
to be exact—who retired at the end of this past school year
and Michele Glenn–have all had an incredible impact in their combined 294 years at Greeley
Former Greeley English teacher and assistant principal and new Seven Bridges Middle School principal Andrew Corsilia feels that this is an incredible loss for the district
and Chadwick – were English teachers with whom he worked for many years
welcoming spirit” upon their first meeting back in 1997 and Chadwick’s constant support of him throughout their years working together
these teachers are taking with them “decades of teaching experience and an incredible wealth of content knowledge,” says Corsilia
“They defined the [English] department when I started teaching
He also elaborates on the many contributions the retiring teachers have made to the Greeley community beyond the classroom
which helps form a community with some of the freshmen
I was fortunate to work individually with Mr
Furey as one of his Independent Literary Analysis students
where we shared our love of books and the deeper meanings within them
always excited to see me and hear about my college experiences (and give me new books to read!)
an example of how many teachers in this district care so deeply about their current and former students
Furey has touched the lives of thousands of students and has enjoyed working with his wonderful colleagues
He says one of his favorite things about the English department at Greeley was that “the teachers all teach differently
but in the end it all comes together,” creating students with varied and exceptional writing skills
Furey and the other retirees have shaped Greeley over the past few decades and their impacts will continue long after their retirements
was fortunate to have some truly phenomenal teachers during high school
who instilled in me important lessons and skills that eased my transition to college
While the retirees have all been so important to Greeley
Greeley and the Chappaqua community have also been important to them
“It’s more than leaving a job,” explains Corsilia about the feeling at the June retirement dinner
“You understood the impact that they have had on the school and how Greeley has become a home for them.”
Lindsay Hand has been writing and editing for Inside Chappaqua since eighth grade
She is now a sophomore Communication major at Cornell University
Editor’s Note: A list of retirees from all the schools in the district will be posted soon too
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22-year-old Ceratizit-WNT rider takes first elite title
Cédrine Kerbaol (Ceratizit-WNT Pro Cycling) won her first elite time trial title at French Road Championships on Thursday
holding off six-time champion Audrey Cordon-Ragot (Human Powered Health) by 19 seconds
who finished runner-up to Cordon-Ragot the past two years
completed the 31.3km course from Hazebrouck to Cassel in 46:24
Coralie Demay (St Michele-Mavic-Auber 93) earned the bronze medal
Marie Le Net (FDJ-SUEZ) was 51 seconds back in fourth
and the only other rider to finish under a minute behind Kerbaol
Results powered by FirstCycling
a sports marketing and public relations agency
which managed projects for Tour de Georgia
a Georgia non-profit to promote safe cycling
She is proud to have worked in professional baseball for six years - from selling advertising to pulling the tarp for several minor league teams
She has climbed l'Alpe d'Huez three times (not fast)
Her favorite road and gravel rides are around horse farms in north Georgia (USA) and around lavender fields in Provence (France)
daughter of Tadeus and Aurelie Maciejewski of North Smithfield
son of Christopher and Mary Craven of Blackstone
took place at the Cranston Country Club Aug
Marissa Hendrickson was the maid of honor and Jennifer Zion was the matron of honor
Andrea Gramolini and Samantha Salois were bridesmaids and Alicestasia Derrick was the flower girl
Jon Garboski served as the best man and Craig Kluchevitz
Kevin Hazebrouck and Kyle and Patrick Craven
The bride graduated from Bryant University and the University of Rhode Island and is with Retail Solutions in Providence
a graduate of Blackstone-Millville Regional High School
The couple honeymooned in the Dominican Republic and live in Woonsocket
A SNCF Regional Express Train is seen at Hazebrouck's train station in northern France on Thursday
France's train operators admit they made a mistake in ordering new trains that will require millions of dollars to modify station platforms
Some 2,000 new trains that were meant to help France expand its regional rail network are instead causing headaches and embarrassment
as officials have been forced to explain why the trains aren't compatible with hundreds of station platforms
The new trains are just a few centimeters too wide to fit
The country's rail operators say they're spending millions of dollars to modify platforms to accommodate the new trains
A French newspaper reported on the mix-up Tuesday
saying the platforms were too narrow for the trains to pass through
The story emerged in Le Canard Enchaîné, a satirical newspaper that blends humor with investigative pieces. As The Wall Street Journal has reported, the paper is both profitable and only minimally available on the Internet
The train platform episode is a black eye for a French rail system that's often cited as a success
But officials say there was a disconnect between RFF
and that now some 1,300 platforms must be modified
France 24 explains:
"The mix-up arose when the RFF transmitted faulty dimensions for its train platforms to the SNCF
which was in charge of ordering trains as part of a broad modernization effort
The news agency says the RFF's data only included platforms built less than 30 years ago and that many others had been built more than 50 years ago
"Repair work has already cost 80 million euros ($110 million)," France 24 reports
Both RFF and SNCF say the new trains were built to international standards and that the platforms will now observe those same standards
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Who bought that house? Greater Brockton property transfers from April 26 to 30The EnterpriseThis list of recent real estate sales was compiled from registries of deeds by The Warren Group and was published in Banker & Tradesman
This list is copyrighted and is reprinted with permission
Nicole Joyce to Matthew Harkins and Michaela Collins
Whalen to Rockwood Realty Trust and Jason Kennedy
Est and Stephen Cairns to Elizabeth Mccarthy
Jasmine Bonanca to Bryanna Derocha and Megan Derocha
Colwell to 180 Main St unit D91 Realty Trust and Matthew C
Gouthro to Jean Dibattista and Robert Dibattista
to Island Marketplace Limited Liability Co.
Gerc Realty Trust and Gary Epstein to Michael P
J&E Liberty St Realty Trust 2 and Jeffery R
Lindsey to 1382 River Street Limited Liability Co.
Smith to Delilah Gorman and Michael Soremekun
Brown to Christopher Jean-Michel and Francesca J
Est and Deborah Dahlquist to Cruise Properties Limited Liability Co.
Ortiz to Miguel Cantor and Samuel Cantor-Hemandez
Evandra Aguiar to Guadalupe Jaquez and Roleid Hernandez-Vasquez
to 1 Bradshaw Street Limited Liability Co.
Faulio Lefevre and Lenise Sillionnat to Hung H
Amaro Rodrigues and Ana Rodrigues to Charles Areh and Helen Areh
Housemasters Realty Trust Limited Liability Co
James Marshall and Melinda Marshall to Lamarc Boyd
Carr to RI Property Wire Limited Liability Co.
Wesley StLouis and Barbara StLouis to Liza M
Oneill to 43 Lasell Street Limited Liability Co.
Ismael Hernandez to Rachelle Mathieu and Baby Germinal
Justin Braswell and Beverly Braswell to Justin Braswell
Key and Reverse Mtg Funding Limited Liability Co
Priolo Plymouth St Realty Trust Limited Liability Co
Davis to Matthew Stewart and Jennifer Stewart
Harley Smith and Heather Smith to Jeffrey A
Patrick Goodhue and Kristy Myers to John D
Brauneis to Courtney Brauneis and Andrew J
Rogers to Michael Jednak and Amanda Crbone
Driscoll to High Street Realty Trust and Elizabeth A
Eric Ouellette and Erica Ouellette to Larysa Olejnik
Magnuson Eric Est and Helen Magnuson to Jeremy Martin
Eaton and Joann Eaton to Thomas Bonarrigo and Kathleen Pladsen
Andronico to Sheila Gabel and Robert Gabel
Yara Crespo and Elton Crespo to Phil Dimillio
Kiran Ruparel and Meera Ruparel to Emerald Prop Dev Limited Liability Co.
Ho to Christopher Odonoghue and Emma Odonoghue
Oneil Family Trust and Janet Oneil to Kodjo Agblekpe and Delali A
Michael Mastrangelo to 6 Second Avenue Realty Trust and Linda D
Vermette to Michael Lundstedt and Christina A
Heartwood Development Limited Liability Co
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Chuong Pham LT and Chuong Pham to Joseph T
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Walsh to Drew Dibenedetto and Julianne Dibenedetto
Williamson to Benjami Fonsseca-Moreira and Brianna Peterson
Donnelly to Daniel Joughin and Erinn Joughlin
Labonte and Marielana Labonte to Missarrom Eller
Hardiman and Jason Hardiman to Opeoluwa Sotonwa
Mahoney to Clara 1 Property Limited Liability Co.
Crisfulla to Wayne Tuggle and Antonia Tuggle
Michael Barlow and Rebecca Boduch to Tachise J
Friel to Zachary Schleicher and Alexandria Schleicher
Alexandria Grimes and Zachary Schleicher to Shane D
Christopher Dinapoli and Janna Perez to Aidee A
Michael Mason (irrevocable trust) and Rosemarie Leosher to Lindsey M
Park to Josefine Allain and Alexander Richards
Toomey and Kirsten Mccue-Toomey to Michael J
Okeefe to 52 Plain Street Realty Trust and Joshua J
Timothy Therrien and Kelly Therrien to Scott Bockus and Kelsey Bockus
Mary Ann Dagostino LT and Evamarie Thomas to Stepping Stone Realty Trust and David S
Baldwin to Bernley Realty Group Limited Liability Co.
Richardson to Timothy Therrien and Kelly Therrien
Plymouth Cmnty Charitable to Courthouse Limited Liability Co.
Decoste to Gaddiel Rodriguez and Betty Pabon
Ohalloran and Stacy Ohalloran to Jonathan M
Daniel Tousignant and Lindsay Tousignant to Gillian Dellacioppa and Gennaro Dellacioppa
Weslley Meireles and Ludmilla Meireles to A
Gisley Soares to Paul Lukis and Cathleen Lukis
Huette and Brittany Huette to Stanley Piltch and Terrance Hauserman
Admirand to Michael Marzeotti and Caitlin Loud
Golia and Brieana Golia to Lyudmila Midler
Steeves to Robert Bradley and Cassie Bradley
Weiner Realty Trust and David Weiner to Patrick M
Augustino Diodato to Inferno Limited Liability Co.
Burnett to Mayflower Group Realty Limited Liability Co.
Cynthia Schlatz RET and Cynthia Schlatz to David E
Roast and Todd Roast to Richard Seligman and Helen Seligman
Toll MA Land LP to Albert Roppolo and Jacqueline A
Pierce to Nathan Collins and Katie Collins
Le and Mau Le to Vanisia Rodrigues and Kevin Payne
Silva to Agnes Guillaume-Heymann and Kimberlky O
Alixon Vincent and Berline Florestal to Benjamin A
Mercedes Garcia and Joseline Espanda to Irma Correa and Thomas Nguyen
Joyce Williams and Patrick Williams to Patrick O
Bredy and Bank Of New York Mellon to Eva&Ivy Realty Hldg Limited Liability Co.
Caliri and Theodore Fitopoulos to Mitchell A
Lauren Neville and Tyler Neville to Dam Sabina
Mussari-Russell and Jackie Russell to Amanda E
Olex to NY Cap Invs Grp Limited Liability Co.
Joshua Hussey to Chelsea Faria and Brandon Filippini
Patrick Higgins and Allison Higgins to Amela Hadziahmetovic and Mark Vautour
Donovan to Venkatachalam Athiseshan and Naga R
Leavey to Vernon 2 Realty Trust and Maureen Mahon
Wayne Tuggle and Antonia Tuggle to Mauricio Ramos and Juliana Ramos
Robert Samuels to Garrett Dever and Tina Snow
Peter Saich and Elizabeth Saich to Sean Saich
Justin Brown and Alexandra Brown to Jiani Hong
Mclaughlin to Monique Goodin and Sergi Hernandez-Pallares
Gennadiy Nemtsev and Nina Nemtsev to Chukwudi Udeh and Vivian Udeh
Diana Lynch to Theodore Tran and Miriam Avila
Giana Deacetis to Hasan Rajabi and Ariba Khwaja
Clement to Stephani Castillo-Barnes and Shakeen Barnes
Pattavina to Gerard Potts and Marie Petropolous
Christopher Ranero to Yan Tang and James M
Noble to Chimera Hldg&Invs Limited Liability Co.
Freedom Cap Solutions Limited Liability Co
and Elliot Schneider to Mark Clarke and Kathryn E
Melvin Ramirez to Xavier Abreu and Serena Viveiros
Christopher Bastien to Ashwa Marshall-Taitt and Jesse Taitt
Botelho to Francisca Gomes and Rudivoller DaCruz
Krystal Cardoso and Derek Rocha to Laura M
Bairos to Michael Leoncello and Melissa Leoncello
Craig Eaton and Stefani Eaton to Maxo Clermont and Mirlande Prosper
Joseph Smith and US Bank NA to Thomas Stryjewski
Medeiros to 569 Bay Street Limited Liability Co.
Colleen Guzman and Alissa Rodriguez to Kristina M
Temitope Shodunke and Adekemi Shodunke to Carlos Gomes
Run Brook Development Limited Liability Co
Cubellis to East Boston Mgmt&Dev Limited Liability Co.
Ladner to Neil Broderick and Christa Hutchinson
Goncalves to Joseph Falabella-Freden and R
Graf to 2856 Cranberry Hwy Limited Liability Co.
Santos Drive Realty Trust and Rebecca Moore to Homestead Realty Trust and Elizabeth R
Benoit to Repurpose Properties Limited Liability Co.
Gendron to Dennis Fasano and Makenzie Dupont
Russell to Zachary Gorman and Christine Gorman
Zachary Gorman and Christine Gorman to Gabriel Foster
Palardy to Darren Gibson and Mackenzie Gibson
J Giovannangelo and Leone Giovannangelo to Kliton Jani and Gerta Jani
Armirail finishes second while Latour takes third
Rémi Cavagna (Soudal-QuickStep) regained the elite men’s time trial title at the French Road Championships on Thursday
finishing 33 seconds faster than last year’s winner Bruno Armirail (Groupama-FDJ)
Pierre Latour (TotalEnergies) trailed 1:13 behind Cavagna for third
keeping Benjamin Thomas (Cofidis) off the podium by three seconds
Cavagna set the best times over the uphill time checks on the back half of the race by a few seconds over Armirail and then dominated the final kilometre for the win
Armirail was the last rider on the course but after recording the fastest time on the opening 7.5km
he then began to lose time to Cavagna.
To have this jersey again means a lot to me
It’s an honour to wear the colours of my country in the time trials for the next twelve months
it’s something that makes me very proud," Cavagan said after taking back the national jersey
I made some recons this week and was aware that on the final hill I needed to still have some power left
so I put in a solid ride from the beginning but kept some energy to increase the tempo there.”
The race against the clock began in Hazebrouck riding across the cobbles on the General de Gaulle square with mostly flat terrain for the opening three-quarters of the 31.3km course
two short climbs averaging between 5.2% to 6.2% led to the final 900-metre climb on more cobblestones to the finish
Baptist Gilet (OC Locmine) of Brittany landed in the hot seat with a time of 42:23
His time was eclipsed by 27 seconds when Mathias Ribeiro da Cruz (Laval Cycling 53) stormed across the course with the substantial time gains over the three final time checks
While the heavy favourites were on the early part of the course
Jérémy Cabot (total Energies) and Ewen Costiou (Team Arkéa-Samsic) briefly held the top times
Cabot finished fifth with 1:33 and Costiou sixth with 1:34
had not been tested in many races against the clock this season
but did finish third in the Critérium du Dauphiné ITT which offered a similar distance as the French National Championships
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Valentin Madouas overcame intense heat and a series of tough climbs in northern France to claim a dramatic solo victory in his country’s Road Championships
Summing up one of the toughest French National Championships of recent years
featuring over 4,100 metres of vertical climbing
made a point of thanking the Groupama-FDJ staff and teammates for their contribution to his success
Groupama-FDJ began toughening up the race from very early on
making the most of their 18 riders present on the startline.
The French squad placed eight riders in a group of 22
Other favourites like Alaphilippe began to struggle in the main peloton
and the Soudal-QuickStep leader was eventually dropped with 105 kilometres to go and then abandoned
Numerous attacks followed in the second half of the course
but none stuck until Gaudu made a decisive move with around 30 kilometres to go
but then Molard came across and it briefly looked as if Groupama-FDJ would have a clean sweep of the podium
and then after attacking alone and dropping Molard a couple of kilometres later
Not even a dropped chain mid-way through his lone effort
could stop him from winning and going two spots better in the Nationals than his father
whose best ever result in the Championships was a bronze back in 1995.
“The plan was to toughen up the race as soon as possible,” Madouas said
“I always had a bit extra left in the tank
There were three hours left to race and everybody was already dead
Alasdair FotheringhamSocial Links NavigationAlasdair Fotheringham has been reporting on cycling since 1991
He has covered every Tour de France since 1992 bar one
as well as numerous other bike races of all shapes and sizes
ranging from the Olympic Games in 2008 to the now sadly defunct Subida a Urkiola hill climb in Spain
he has also written for The Independent, The Guardian, ProCycling
2018 at 7:55 pm ET.css-79elbk{position:relative;}CHAPPAQUA
NY — This year's valedictorians and salutatorians in the Chappaqua school district are an extraordinary group of young people
Patch asked them to answer a few questions about their high school experience and what they look forward to in the future
especially my track team whom I’ve spent so much time with and grown so close with
What are you looking forward to in moving on to college
What clubs or extra-curricular activities were you involved in
Chappaqua School Foundation Student Advisory Council
private tutoring through Turning Point Tutoring Company
What advice would you give to underclassmen
Don’t worry about how much rejection and failure you run into - persistence always pays off in the long run
Any teachers/staff who stood out throughout your journey
Amy Kaiser - I’ve had her for three years
I had her for Ethics and my creative writing independent study
and in 12th grade she was my independent study faculty advisor again
She’s the absolute best and my constant source of support
Louise Hazebrouck whom I had freshman year for English - she made me love reading and improved my writing tremendously
the novel I’ve been working on will be published and I’ll be an established author
I’m not sure where I’ll be career-wise in 10 years though
I was an extra on Season 3 Episode 5 of Orange is the new black
Get more local news delivered straight to your inbox. Sign up for free Patch newsletters and alerts.
Mégane Lourenco
Carnaval de Dunkerque © www.jepi-dunkerque.frJ-3 avant les Trois Joyeuses les gars !
enfilez vos plus beaux déguisements et allons festoyer
et danser et se marcher dessus car la saison du Carnaval de Dunkerque est lancée
la SNCF brade les billets de train pour que vous puissiez vous y rendre sans encombre
Pour vous rendre aux carnavals de Dunkerque
vous pourrez donc voyager tranquillement grâce à des pass TER à 15€
Une publication partagée par Dunkerque (@visitdunkerque)
Des trains supplémentaires sont même prévus pour vous ramener à Lille les dimanches :
- Les dimanches 19/02 et 26/02 : au départ de Dunkerque à 21h06 - arrivée à Lille Flandres à 22h07 (gares desservies : Bergues 21h12
- Le dimanche 19/03 : au départ de Dunkerque à 19h56 - arrivée à Lille Flandres à 21h08 (gares desservies Bergues 20h02
Pour connaître les horaires et prendre vos pass, c'est ici.
Bienvenue dans la ville où ton chien sera (vraiment) le plus heureux
Les hobbies qui font le plus craquer à Lille selon happn
Lille va voir la vie en couleurs pour une bonne cause