“Mama B” Survives A Mean Head Kick From Tomar To Work Her Way Into A Perfect Armbar Submission On March 22
Check out the best photos from Shauna Bannon's second-round submission win over Puja Tomar at UFC Fight Night 255 at The O2 in London
A technical education facilitator from Indore has been granted a licence to keep sharp-edged weapons by the district administration after an eight-year-long legal battle
in what is being claimed as the first such case in the country
Indore man gets licence for sharp weapons after 8-year legal battle The licensee
clarified that his aim was not to carry weapons for personal use but to highlight criminal cases being lodged against tribal communities in western Madhya Pradesh for possessing such tools
which are often used in agriculture and daily livelihood
An official of the district administration confirmed on Monday that Tomar
has been issued a licence to possess sharp-edged weapons for three years
Tomar is permitted to keep one of the following weapons – a sword
or dagger – within the limits of Indore district until April 8
Tomar said his legal battle began in 2017 after he studied the Arms Act 1959
and filed a series of Right to Information applications after studying government documents and legal details
I have received a licence under which I am legally allowed to carry sharp-edged weapons within a designated area," Tomar told PTI
He clarified that his aim was not to carry weapons for personal use but to highlight the plight of tribal communities against whom criminal cases are registered unfairly for possessing such weapons even for farming purposes
"I came to know that several criminal cases were registered under the Arms Act against tribals in western MP for possessing sharp weapons
They use such weapons for farming and cutting grass," he said
Tomar wanted to spread awareness to save these tribals from unfair legal action
"I want to tell people that a license for sharp weapons can also be obtained legally," he added
Tomar’s application was rejected without stated reasons
but he continued his legal pursuit by filing petitions before the Madhya Pradesh High Court
questioning whether such a licence could even be issued," he recalled
Additional District Magistrate Roshan Rai confirmed that Tomar has been issued the licence was issued following a directive from the Indore bench of the High Court
When asked whether this was the first such licence in the country
I cannot confirm if such a licence has been issued elsewhere in the country
two or three such licences have been issued in the past"
he did not provide details on whether those licences specifically pertained to sharp weapons or their terms and conditions
The Indore bench of the High Court on February 27 this year directed the district administration to issue a sharp weapon license to Tomar within three weeks
following the order of the Commissioner of Indore Division dated September 12
termed the case a “historic development in the legal domain,” adding that the administration issued the licence only after a contempt petition was filed for non-compliance with the court’s order
He said the case highlights a lack of public awareness regarding the legal process for obtaining licences for sharp-edged weapons and urged the government to introduce a clear policy to address this gap
This article was generated from an automated news agency feed without modifications to text
Artificial Intelligence (AI) has become an indispensable component of modern product management, driving innovations that are reshaping industries worldwide. From automating workflows to delivering personalized experiences, AI's influence on product strategy and execution is undeniable. Prashant Tomar
exemplifies how strategic AI integration can enhance both product functionality and business outcomes
and Instagram offers valuable lessons on harnessing AI to build scalable
we delve into four key insights from Tomar's experience that demonstrate how AI can transform product development strategies for sustainable growth
Prashant's journey in product development spans 15 years
with leadership roles at global tech and consulting firms
Starting with hands-on experience at Informatica
he transitioned into driving AI innovation at PwC
where he built enterprise-grade AI products
he tackled user engagement challenges by integrating AI-driven personalization into the platform's core experiences
he leads teams delivering AI-powered solutions for billions of users
His achievements—including scaling Meta AI across messaging platforms—have made him a key figure in advancing AI adoption across consumer and business ecosystems
Prashant highlighted how AI can revolutionize product development by enhancing various functions such as automating workflows
One of AI's greatest strengths is its ability to scale business operations
Prashant's work on conversational AI at Meta serves as a prime example of how this can be achieved
Businesses using messaging platforms like WhatsApp often need to manage millions of customer interactions simultaneously
AI-powered agents solve this challenge by automating responses to common queries
These AI agents operate beyond static scripts—they continuously learn and adapt to different user intents
Whether handling a service request or facilitating a transaction
the AI system maintains contextual relevance
This adaptability is vital for platforms with diverse use cases and user needs
"AI solutions only succeed if they learn and scale with user interactions." Tomar explains
His team built an infrastructure capable of processing vast data sets to improve response accuracy over time
This enabled Meta to provide businesses with AI-driven tools that reduced operational costs while enhancing customer satisfaction—critical factors in the competitive landscape of business messaging
AI creates opportunities for product teams to focus on strategic improvements
This scalable approach has made AI a cornerstone of Meta's business messaging offerings
driving both enterprise adoption and revenue growth
Understanding user behavior is crucial to delivering a compelling product experience
and AI excels at analyzing large-scale data to uncover actionable insights
Tomar and his team leveraged AI to drive engagement by personalizing features like notifications
By processing billions of user interactions
AI algorithms can identify patterns that reveal what types of content users are most likely to engage with
These insights help product teams refine existing features and develop new ones that resonate with users
AI-driven recommendations can surface relevant content to users at the right time
Tomar emphasizes that personalization must be balanced with privacy considerations
"AI insights should enhance the user experience without crossing ethical boundaries," he says
AI systems should be designed with privacy-first principles
ensuring that data usage is transparent and aligned with regulatory standards
ultimately boosting long-term loyalty and growth
Product development is a resource-intensive process that involves multiple stages of prototyping
AI can significantly reduce these timelines by automating key workflows
Tomar's teams at Meta have integrated AI tools to streamline everything from UI testing to performance simulations
allowing for faster iterations with fewer manual inputs
AI tools can generate multiple prototype variations
enabling designers and engineers to test new concepts quickly
This automation not only accelerates the design cycle but also improves efficiency by reducing bottlenecks in cross-functional collaboration
This capability is especially valuable for startups and enterprises looking to innovate at scale
use AI to automate tasks like product categorization
These tools free up teams to focus on strategic initiatives
such as exploring new business models or expanding into emerging markets
By enabling rapid prototyping and automated analysis
AI empowers product managers to adopt a more agile development approach
where teams can quickly test ideas and pivot based on real-time feedback
While AI offers numerous operational benefits
it also presents challenges around monetization
particularly those involving generative models
require substantial investment in computational power
Companies need to evaluate carefully how these costs translate into customer value
Tomar's experience at PwC and Meta illustrates two common monetization strategies
AI capabilities are offered as premium services tailored to enterprise clients
These features—such as advanced customer support automation—deliver measurable ROI by improving response times and conversion rates
AI is embedded within core product offerings to enhance the overall user experience without an immediate price increase
"Tracking the impact of AI features on key business metrics like retention and revenue is crucial," Tomar explains
companies can determine whether to position AI features as standalone offerings or bundled enhancements
This strategic approach to monetization ensures that AI investments generate long-term business value
Companies that successfully integrate AI into their pricing models can maintain a competitive edge by offering differentiated solutions that drive customer success
AI's role in product development is transformative
offering unparalleled opportunities to enhance efficiency
successful integration requires a thoughtful approach—one that balances technological potential with strategic execution
Prashant Tomar's journey demonstrates that AI is not just a tool but a catalyst for sustainable product innovation
Organizations looking to harness AI's full potential must invest in both infrastructure and talent
By fostering a culture of continuous learning and experimentation
they can position themselves to thrive in a rapidly evolving digital landscape
The insights from Tomar's leadership serve as a blueprint for companies aiming to unlock AI's transformative power in the years ahead
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a tech-driven customer experience management firm
is deepening its investment in digital transformation and artificial intelligence with the addition of an experienced Chief Strategy Officer
Babita Tomar is joining Epicenter to lead the practical application of artificial intelligence in augmenting the call center operations and business process outsourcing needs of their customers
Epicenter's focus on customer-centricity and human-centric design enables it to deliver transformative outcomes..
Tomar has been helping major financial institutions and technology companies to deploy analytics to improve operations
while deepening their understanding and measurement of the customer experience
Working with companies like Wells Fargo and Amazon Web Services
and leading organization transformations makes her a powerful addition to the Epicenter team
"We are lucky to be adding such an experienced officer to our ranks
and Babita will focus on the strategic use of AI/ML technologies to provide maximum impact across our organization," expressed Epicenter CEO - Rajesh Thankappan
she will drive projects to identify and bring together the data needed to deploy machine learning and advanced data analytics
with the goal of providing end users/consumers with a better experience working with call center agents
we will identify opportunities to maintain our competitive advantages in technology through the application of artificial intelligence
"I am very excited to take on new challenges that will directly impact both the consumers we service and our enterprise customers who place their trust in us as an extension of their business
I have been responsible for the practical application of technology to finance and technology businesses
Working in the BPO space will provide new challenges
and the opportunity to apply my experience to gain traction and quickly make an impact at Epicenter," said Ms
Epicenter is a global partner in business transformation
leveraging over two decades of expertise to drive innovation and operational excellence
It specializes in cutting-edge technology solutions and data-driven strategies that optimize processes
Epicenter's focus on customer-centricity and human-centric design enables it to deliver transformative outcomes for Global Fortune 500 companies across diverse industries
Do not sell or share my personal information:
LONDON – Shauna Bannon was in deep trouble before rallying to score her first UFC finish
Just moments after getting dropped by a clean left high kick, Bannon (7-1 MMA, 2-1 UFC) was able to whip up an armbar off her back and submit Puja Tomar (9-5 MMA, 1-1 UFC) at the 3:22 mark of Round 2 in their strawweight prelim bout at UFC Fight Night 255 on Saturday at The O2 in London
Shauna Bannon def. Puja Tomar at UFC Fight Night 255: Best photos
Check out the replay of Bannon's finish below (via X):
WHAT A COMEBACK 😱 #UFCLondon@ShaunaBannon5 gets our first finish of the night
Watch our prelims LIVE NOW on @UFCFightPass 📺 pic.twitter.com/I2m03ZYVIh
— UFC Europe (@UFCEurope) March 22, 2025
After dropping her UFC debut to Bruna Brasil
Ireland's Bannon has now won two straight bouts
India's Tomar saw her five-fight winning streak snapped
Up-to-the-minute UFC Fight Night 255 results include:
RelatedUFC Fight Night 255 play-by-play, live results
UFC Fight Night 255: Official scorecards from London
For more on the card, visit MMA Junkie's event hub for UFC Fight Night 255
Publicis Groupe has appointed Pooja Tomar as Senior Director – Buying
Tomar announced her new role via a LinkedIn post
With over a decade of experience in media strategy and consumer-driven planning
she brings strong expertise across categories including e-commerce
Tomar was Senior Business Director at Havas Media Group
Shauna Bannon will face off with Puja Tomar at UFC London on Saturday
The opening line has Bannon coming in at -170 while Tomar is coming in at +142
Shauna "Mama B" Bannon steps into the cage holding a record of 6-1-0
The 31-year-old records a weight of 115 lbs and measures 5'5"
Puja "Cyclone" Tomar measures in at 5'4" and is weighing in at 115 lbs
The southpaw fighter comes into this bout with a mark of 9-4-0
Shauna Bannon is landing 4.37 per min and Puja Tomar is connecting on 6.33 significant strikes per min
Bannon is landing 41% of the significant strikes she attempts while Tomar connects on 47%
"Mama B" absorbs 3.77 significant strikes per minute and "Cyclone" absorbs 5.60
Bannon also stops 42% of the significant strikes her opponents throw at her and Tomar is able to deflect 44% of the strikes thrown her way
Shauna Bannon is the more apt grappler as she takes her opponents to the canvas 0.70 times per 15 min
Bannon is getting her opponent to the mat on 15% of her tries and thwarting 42% of all takedowns attempted by her opposition
Tomar is taking her opponents to the canvas on 15% of the takedowns she attempts and stopping 85% of the attempts against her
Bannon is the more capable fighter by trying 0.6 submissions per 15 min while Tomar attempts 0.4 submissions per 3 rds
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Shauna Bannon fought Alice Ardelean and took home the victory by way of split decision in round 3
Ardelean ended up landing 80 of 139 total strikes that she threw in that fight
Bannon ended the night having landed 151 of 252 total strikes
She ended up landing 42 of 84 significant strikes aimed at the head
Bannon landed 45% of her significant strikes by sticking 77 of 169
In regard to the placement of these significant strikes
87% of the significant strikes landed by Ardelean and 94% of them connected on by Bannon were tallied at distance
she went up against Rayanne dos Santos and wound up taking home the win via split decision in round 3
Santos ended up landing 94% of the significant strikes she took from distance and Tomar ended up connecting on 98% of the significant strikes she took from distance
Tomar landed 47% of her significant strikes attempted by connecting on 95 of 199
She landed 29 of 112 significant strikes directed at the head
Santos landed 84 of 150 significant strikes in that battle
she connected on 47 of 92 aimed at the head
In terms of total strikes that she let go in that contest
Santos landed 86 of 152 while Tomar ended up connecting on 99 of 203 total strikes
One more match to look forward to is when Leon Edwards squares up against Sean Brady
Edwards walks into the cage with a mark of 22-4-0 (1 NC)
The 33-year-old steps on the scale at 170 lbs and measures 6'2"
Brady stands 5'10" and tips the scales at 170 lbs
The orthodox fighter will be looking to add a win to his career record of 17-1-0
Leon Edwards gets a takedown 1.25 times per 3 rounds while Sean Brady is able to score a takedown 3.49 times per 15 min
Edwards connects on 2.68 strikes/min and is landing 53% of the strikes that he attempts
who is connecting on 55% of the strikes he has tried and connects on 4.09 per minute
An additional fight that you're going to want to see is when Carlos Ulberg is set to face off against Jan Blachowicz
Blachowicz walks into the Octagon with a record of 29-10-1
The 42-year-old weighs 205 lbs and stands in at 6'2"
The orthodox fighter has a reach of 78"
Ulberg comes in at 6'4" and records a weight of 205 lbs
The orthodox fighter steps into the Octagon holding a mark of 12-1-0
Jan Blachowicz is able to curb 68% of his opponents' takedown attempts and is getting his opponent to the mat on 50% of the times he tries
Ulberg is taking his opponents down on 75% of the attempts he tries and is able to deflect 83% of the takedowns his opponents try
Blachowicz takes 2.91 strikes per minute and he dishes out 3.41 per minute
is taking 4.27 strikes per min and dishes out 7.20 per min
Who will win tonight's UFC match against the spread
Guy Bruhn's Pick: Take Puja Tomar (+142)
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Those three words have followed Puja Tomar throughout her career in combat sports
where she will become the first woman from her country to compete in the UFC when she meets Rayanne dos Santos in Louisville
who has always been in her corner and always wanted her to take this as far as she could go
Saturday's Full Fight Card Preview
“My mom has always been very excited for every one of my MMA fights
and one day she asked me which one is the biggest one,” said Tomar from her training camp in Bali
and one day I'm going to UFC.’ And when I told her that now I'm in UFC
she was crying and she's so excited and so happy.”
This one is bigger because the 30-year-old native of Muzaffarnagar isn’t just representing herself and her family; she’s representing a nation that hasn’t exactly been a hotbed for the sport over the years
And consider that Tomar is the first woman from India in a promotion that has had women fighting in the Octagon since 2013
MORE LOUISVILLE: Rising Fighters | Dom Reyes Interview | Thiago Moisés Interview
“Everybody in India is very excited for me because I’m the first Indian female fighter in UFC and for India, the people are stoked because a girl hasn’t represented India on this platform.”
View this post on Instagram A post shared by UFC India (@ufcindia)
Anshul Jubli and Bharat Kandare have represented India on the world stage in the UFC
but the ladies haven’t had their shot until now
a Wushu fighter who arrives with an 8-4 record that includes six knockouts and a four-fight winning streak
has the opportunity to open the door for her peers back home
TUF 32: Episode 1 Recap | How To Watch
“I'm thinking now it's going to be Indian all the way up because before it wasn’t growing
female fighters and male fighters are waiting for this
There will be some who tune in on Saturday and think Tomar fell out of the sky and into the Octagon
one that started when a 12-year-old Tomar lost her father and started training to protect her family
I didn't know what the UFC was,” she recalled
“I just wanted to protect my family after my father passed away
So I started to learn karate and kickboxing
I think I can make my career in martial arts.”
FONTAINEBLEAU LAS VEGAS TO HOST POWER SLAP 8 DURING INTERNATIONAL FIGHT WEEK JUNE 27
just kick and punch and come back home.’”
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NEW DELHI: The Enforcement Directorate (ED) has carried out searches in Delhi, Jaipur and Mumbai in a cryptocurrency fraud, in which an Indian national – Chirag Tomar, 31, has been sentenced to serve five years in prison in the US, the agency said on Monday.
A file photo of the Enforcement Directorate Delhi Zonal Office on Jawaharlal Nehru Marg in New Delhi (Hindustan Times/Amal KS) A US district judge in Charlotte (North Carolina), in October 2024 sentenced Tomar for stealing more than $20 million from hundreds of victims through the use of fake or spoofed websites that mimicked cryptocurrency exchange website Coinbase.
Tomar, according to the US attorney’s office statement in October 2024, used the victims’ funds to pay for his lavish lifestyle, including purchase of rare watches such as Audemars Piguet and luxury vehicles such as Lamborghinis and Porsches, and to make trips to Dubai, Thailand and elsewhere.
On December 20, 2023, Tomar was arrested at the Atlanta airport upon entering the United States. On May 20, 2024, Tomar pleaded guilty to wire fraud conspiracy.
After his sentencing in the US, ED launched a probe under the foreign exchange management act (FEMA) in the matter.
The federal agency has estimated that crypto worth ₹600 crore was converted at various Indian crypto exchanges and subsequently transferred by the accused.
On February 20, ED carried out searches at Delhi, Jaipur (Rajasthan) and Mumbai (Maharashtra) under FEMA.
“The case pertains to conversion of crypto currency worth around ₹600 crore at various Indian crypto exchanges and subsequent transfer of the funds to the beneficiaries,” ED said in its statement.
It added that trusted websites were spoofed in such a way that when the website would be searched, the spoofed website would appear at the top. “The spoofed website appeared exactly similar to the trusted website except the contact details,” ED said.
“When users entered the login credentials, the spoofed website would show it wrong. Therefore, the users would contact the number given in the spoofed website which would eventually connect them to the designated call centre managed by Chirag Tomar,” it added.
Once the fraudsters gained access to the victims’ accounts, they quickly transferred the victims’ cryptocurrency holdings to crypto currency wallets under their control. “The stolen crypto currency would then be sold on a website named-- localbitcoins.com-- and converted into Indian rupee at Indian crypto exchanges,” ED said.
Subsequently, the money was “transferred in the bank accounts of Chirag Tomar and his family members.”
ED has traced ₹15 crore received by Tomar and his family.
It said, “several bank accounts pertaining to the Tomar family have been frozen during the searches including deposits of ₹2.18 crore kept in them”.
Besides, ED found that a similar modus of selling doubtful crypto on local bitcoins and its conversion to Indian rupee on Indian crypto exchanges was unearthed during the search operation.
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Here we used two distinct paradigms of preconception acute high-fat diet to dissect epididymal versus testicular contributions to the sperm sncRNA pool and offspring health
are sensitive to the environment and identify mitochondrial tRNAs (mt-tRNAs) and their fragments (mt-tsRNAs) as sperm-borne factors
mt-tsRNAs in spermatozoa correlate with body mass index
and paternal overweight at conception doubles offspring obesity risk and compromises metabolic health
Sperm sncRNA sequencing of mice mutant for genes involved in mitochondrial function
and metabolic phenotyping of their wild-type offspring
suggest that the upregulation of mt-tsRNAs is downstream of mitochondrial dysfunction
Single-embryo transcriptomics of genetically hybrid two-cell embryos demonstrated sperm-to-oocyte transfer of mt-tRNAs at fertilization and suggested their involvement in the control of early-embryo transcription
Our study supports the importance of paternal health at conception for offspring metabolism
shows that mt-tRNAs are diet-induced and sperm-borne and demonstrates
father-to-offspring transfer of sperm mitochondrial RNAs at fertilization
These studies do not account for spermatogenesis timing; report combined testicular and epididymal effects on the sperm epigenome; and are not suitable to study susceptibility windows and identify environmental sensors in the male reproductive tract
we have shown that sperm mt-tsRNAs are associated with body mass index (BMI) and that paternal BMI at conception is an independent determinant of offspring metabolic health
the findings of our study strengthen the relevance of paternal health at conception for offspring metabolism
show that mt-tRNAs (and their fragments) are diet-induced and sperm-borne
Glucose tolerance of unexposed male offspring (F1) of HFD-exposed bucks
Bottom: frequency distribution analysis to identify tolerant and intolerant animals
n = 60 male mice across 4 cohorts with 5 litters each and 3 males per litter (eLFD and eHFD bucks); n = 10–15 (sLFD and sHFD bucks) including 1 cohort with 5 litters and 3 males per litter
Glucose tolerance (c; mean ± s.e.m.) and insulin sensitivity (d; mean ± s.e.m.) of male offspring (F1) of HFD-exposed bucks
Data represent a re-phenotyping of the animals in c carried out 8 weeks after the first phenotyping
Significance calculated by a two-way (c; n in graph) or one-way (d; n as in c) analysis of variance (ANOVA; ***P < 10−4)
PCA plot (e) and functional enrichment analysis (KEGG (Kyoto Encyclopedia of Genes and Genomes); f) of peripheral tissue RNA-seq data from HFDt and HFDi F1 animals
Left: overlap between genes differentially expressed in tissues from HFDi mice and their human orthologues associated with childhood obesity
Right: functional enrichment analysis (KEGG) of the overlapping genes (n = 693) pre-classified as protective and risk genes for childhood obesity on the basis of the β-score for BMI-SDS
Scatter plot of children’s body weight trajectories as a function of paternal BMI at conception in families with mothers who were lean (red line; r = 0.2611; P value < 10−4) or overweight (blue line; r = 0.3467; P value < 10−4) at conception
Significant association calculated by linear regression analysis
measured as ISIMatsuda (top) or homeostatic model assessment for insulin resistance (HOMA-IR; bottom) indices in children as a function of parental weight status at conception
n lean–lean = 106; overweight–lean = 184; lean–overweight = 114; overweight–overweight = 415
Data represented as mean ± s.e.m. Significance calculated by two-way ANOVA (details in the graph)
Source Data
These results strengthen the importance of paternal preconceptional body weight for offspring metabolic health in mice and humans
the phenotypic discrepancy between offspring sired by mice exposed to 2 weeks of HFD (eHFD) and offspring sired by those then allowed to recover on chow diet for 4 weeks (sHFD) not only shows that this diet-based model is fully reversible but also suggests that epididymal spermatozoa can be directly susceptible to environmental cues
Uniform manifold approximation and projection (UMAP) representation of mtDNA transcription during spermatogenesis from testis single-cell RNA-seq data
In conjunction with the offspring phenotypes (Fig. 1 and Extended Data Fig. 2)
these findings support a primary role of the epididymis in the response to the acute HFD challenge and suggest a role for sperm sncRNAs as dynamic molecular signals
Although obtained from a small human cohort
these findings reinforce the idea that mt-sncRNAs can have important functions in response to acute metabolic challenges in mice and humans
Density plot (d) and heat map (e) representation of the quantified heteroplasmy at the 416 SNPs mapped between BL6 and ST mitochondrial genomes
Relative heteroplasmy enrichment of the highlighted mt-tRNAs against LFD embryos
Biotype-specific heteroplasmy enrichment (over LFD) in male and female HFD embryos (HFD_B shown on the x axis; data represented as mean ± s.e.m.)
HFD_female = 3.5× compared to the respective LFD)
With the caveat that other sperm RNAs can also be paternally inherited
these findings demonstrate—in a physiological setting—sperm-to-oocyte transfer of mtRNAs at fertilization
The male-specific and 30%-penetrant offspring phenotype makes the preferential transfer of sperm mt-tRNAs to the HFD_A subpopulation of male embryos (Fig. 3g) intriguing.
Bar plot representation of the relative (WT versus control) glucose intolerance (measured as AUCipGTT) in WT offspring of fathers heterozygous for genes important for mitochondrial structure and function
Black arrows indicate genes for which cryopreserved heterozygous sperm samples were analysed
Distribution of sncRNA biotypes in cauda spermatozoa from the indicated mutant mice (n = 10 mice per gene)
Heat map representation of the relative abundance of 5′ n-tsRNAs and 5′ mt-tsRNAs in mutant spermatozoa
LFD and HFD samples are cryopreserved and resequenced to serve as reference and technical controls
From these results, we reason that the upregulation of mt-tRNAs (and their 5′ fragments) in cauda spermatozoa is a compensatory response to the diet-induced mitochondrial dysfunction (Extended Data Fig. 8e)
supporting the proposal that mitochondrial dysfunction triggers the observed intergenerational paternal effects
Despite the lack of zygotic microinjections data demonstrating that mt-tsRNAs are sufficient to transfer the metabolic phenotypes
and therefore with the standing caveat that other sncRNAs (and epigenetic factors) can contribute to the observed paternal effects; the robustness
the dynamic and the reversibility of the mt-tRNA signature makes these sperm-borne RNAs suitable candidates for new strategies to monitor preconception lifestyle interventions aimed at preventing the spread of metabolic disorders through paternal epigenetic inheritance
C57BL/6N male and female mice were purchased from Charles River Laboratories Germany
All animals were fed ad libitum and housed at constant temperature (22 ± 1 °C) and controlled humidity in ventilated cages on a 12 h:12 h light/dark cycle
6-week-old male mice were randomly assigned to two groups fed for 2 weeks with purified HFD (rodent diet with 60 kcal% from fat; Research Diet D12492i) or LFD control diet (rodent diet with 10 kcal% from fat; Research Diet D12450B) and subsequently mated with a single unexposed
6-week-old male mice were randomly assigned to two groups fed for 2 weeks with purified HFD (rodent diet with 60 kcal% from fat; Research Diet D12492i) or LFD control diet (rodent diet with 10 kcal% from fat; Research Diet D12450B)
mated with a single unexposed virgin female (to empty the epididymis) and moved back to a standard chow diet for 4 weeks
These animals were subsequently mated with a single
virgin and aged-matched female to generate the offspring cohort
both males and females were fed ad libitum on a standard chow diet
males were removed from the cage after delivery and the mothers were maintained individually throughout newborn nursing and lactation
Litter size was adjusted to 6–8 whenever the number of pups was higher
Offspring from LFD or HFD males and WT unexposed females were named F1
F1 animals were weaned at 21 days post-partum and kept on ad libitum chow diet for their entire life
All animal experiments have been carried out according to the European Union directive 2010/63/EU and were approved by the responsible authorities of the government of Upper Bavaria
under licence number ROB-55.2-2532.Vet_02-17-33
Body weight and relative lean and fat mass were measured in exposed F0 animals before and after the dietary challenge
as well as in chow-fed F1 animals bi-weekly from 4 to 14 weeks of age
Body composition was determined by nuclear magnetic resonance spectroscopy with a Minispec NMR analyser (Brucker Optics)
according to the manufacturer’s instructions
ipGTTs were conducted on 8- or 12-week-old F0 mice and 16- and 24-week-old F1 mice after an overnight fasting period of 16 h (from 6 pm to 10 am)
A ratio of 2 g of glucose per kilogram of fasting body weight was injected
Blood glucose levels were determined before and after the injection at 15
60 and 120 min using the Roche AccuChek Aviva blood glucose meter
Plasma samples were separated from the whole blood
collected in EDTA-coated microvettes (Sarstedt) at time 0
and snap-frozen in liquid nitrogen for further analyses
Insulin tolerance tests were carried out on 25-week-old F1 mice after 6 h fasting (from 6 am to 12 pm)
Mice were injected with 0.5 U insulin per kilogram of body weight
Blood glucose was measured before the intraperitoneal injection and at 15
Testis from 8-week-old mice exposed to 2 weeks of LFD- or HFD-feeding were dissected and processed for histology (n = 5 mice per diet)
and purification of round spermatids for RNA and sncRNA-seq (n = 3 mice per diet) or further processed for single-cell RNA-seq (n = 3 mice per diet)
Testis sections were fixed for 48 h in 10% formalin
cleared in xylene and embedded in paraffin
4-μm sections were stained with haematoxylin and eosin
1.5-μm sections were dewaxed by standard techniques
Heat treatment was carried out for antigen retrieval in sodium citrate buffer
Endogenous peroxidase activity was quenched with 3% H2O2 in methanol at room temperature for 5 min
Incubation with primary antibodies was carried out overnight at 4 °C in blocking buffer (TBS–Tween 1%)
and chromogenic reactions were carried out
Staining was carried out using the automatic Discovery XT (Ventana Systems) stainer
Sections were subjected to EDTA-based antigen retrieval for 20 min and protein block (Dako
Sections were then examined under an Olympus microscope
The primary antibody was TRA98 (Abcam Ab82527; 1:1,000); secondary antibody was rabbit anti-rat IgG H&L (HRP; Abcam Ab6734; 1:1,000)
The diameters of 60–70 seminiferous tubuli were measured from cross-sectional areas of TRA98-stained testes and expressed as the average of the horizontal and vertical diameters
the cauda and the vas deferens were cut into small pieces
placed in 500 μl Donners medium (25 mM NaHCO3
1 mM sodium pyruvate and 0.53% (vol/vol) sodium dl-lactate in Donners stock; Donners stock: 135 mM NaCl
filtered through a 0.22-μM filter and stored at room temperature)
1.5 ml of supernatant (composed mainly of motile sperm) was transferred into a new 1.5-ml tube
A 1 ml volume of supernatant was then collected
The supernatant was discarded and the pellet was resuspended in a cell lysis buffer (SDS 0.01%
dissolved in RNAse-free water) and incubated on ice for 30 min
Samples were then centrifuged at 4,800 r.p.m.
resuspended in 500 μl of TRIzol reagent (Thermo Fisher) and stored at −80 °C until further processing
Total RNA was prepared using the RNAeasy Mini Kit (QIAGEN 74104) or the miRNeasy Micro Kit (QIAGEN 1071023) according to the manufacturer’s instructions
A 10–15-μl aliquot of PBS-washed motile spermatozoa was used to microscopically check somatic cell contamination (only samples with no visible somatic cells were considered for downstream applications) and for functional analyses
motility and progressive motility have been calculated using an automated computer-assisted semen analysis (Hamilton Thorn IVOS II) according to the manufacturer’s instructions
Oocyte isolation and IVF were conducted following standardized procedures of the INFRAFRONTIER consortium as previously described21
male gamete donors were euthanized at 8 weeks of age
Mature sperm cells were obtained from cauda epididymis as described above
WT unexposed female oocyte donors were euthanized the same day at 10–11 weeks of age
after superovulation induced with 7.5 U of pregnant mare serum gonadotropin and 7.5 U of human chorionic gonadotropin before being killed for oocyte collection
The sperm and the oocytes were co-cultured for 4–6 h
the oocytes were transferred and incubated in high-calcium human tubal fluid (HTF) culture medium at 37 °C and 5% CO2
First-cleavage (zygote to two-cell embryo) rate and rate of blastocyst development were measured to assess embryonic development and complement sperm functional analysis in determining the effects of HFD on male reproductive fitness
Morulae were microscopically checked and individually picked after incubating fertilized oocytes in high-calcium HTF for 72 h
A 10–50 ng quantity of total RNA from round spermatids (50 ng; n = 3 per group) and cauda spermatozoa (10 ng; n = 3 per group) from mice fed on HFD or LFD for 2 weeks or cauda spermatozoa from mice fed on HFD or LFD for 2 weeks
mated and allowed to recover on chow diet for 4 weeks (10 ng; n = 3 per group) was used for sncRNA library preparation
Libraries were prepared using the NEBNext Multiplex Small RNA Library Prep Set for Illumina (NEB E7560S) with 5′ and 3′ adaptors diluted 1:5 and 15 PCR amplification cycles
Libraries were verified using a 2100 Bioanalyzer (Agilent) and paired-end (read length = 150 base pairs (bp)) sequenced with the Illumina NovaSeq 6000 platform
Although allowing robust detection of all sncRNA biotypes
this library preparation method does not efficiently capture highly modified sncRNAs
rRNA from National Center for Biotechnology Information (NCBI) Nucleotide
The raw count tables generated by SPORTS were annotated to small RNA biotypes
Averages were aggregated across biotypes (rsRNA
piRNA and so on) using the default annotations in SPORTS result output files
The downstream analysis was carried out as previously described66 with few modifications
counts were converted into reads per million (RPM)
The fragments with at least 0.01 RPM in all of the samples and lengths between 16 and 45 nucleotides were retained for further analysis
edgeR was used to identify differentially expressed fragments
All of the analyses were carried out using different packages in R version 4.1.2 and Bioconductor version 3.14
cauda spermatozoa and morula library construction and sequencing were outsourced to IGA Technology Services
Libraries were constructed using the Nextera Library Prep Kit (Illumina) according to the manufacturer’s instructions and sequenced on an Illumina HiSeq 2500 at 75-bp paired-ended (round spermatids and morula) or single-ended (cauda spermatozoa)
with a minimum output of 40 million reads per sample
muscle and epididymal white adipose tissue total RNA was prepared using TRIzol reagent (Thermo Fisher) according to the manufacturer’s instructions
RNA concentration and integrity were controlled on a Bioanalyzer system (Agilent) and only RNA samples with RIN values > 7 were used for downstream applications
Sequencing libraries were prepared by using the Quantseq 3′ mRNA-Seq mRNA Library Prep Kit FWD for Illumina (Lexogen) with i7 indexes (Lexogen) according to the manufacturer’s instructions
Libraries were sequenced on an Illumina HiSeq 2500 at 50-bp single-ended
with a minimum output of 40–50 million reads per sample
A total of 60 female mice of the strain C57BL/6N-mtST (nuclear DNA: C57BL/6N; mtDNA: ST, GenBank accession number KC663621) of the age of 3 to 16 weeks were used
Mice were specific pathogen free according to FELASA recommendations and maintained in a barrier rodent facility
Groups of 3 to 4 females were housed in type IIL IVC cages (Blue Line
The cages were lined with 120 g bedding (Lignocel Select
Rettenmaier) and enriched with nesting material (PurZellin
Paul Hartmann) (photoperiod 12 h:12 h light/dark)
Ssniff Spezialdiaeten) and tap water in 250-ml bottles were available ad libitum
These experiments were carried out at the University of Vienna (Austria) and all of the experimental procedures were discussed and approved by the Ethics and Welfare Committee of the University of Veterinary Medicine
Vienna and the national authority (Austrian Federal Ministry of Education
Science and Research) according to section 26ff of the Animal Experiments Act
Tierversuchsgesetz 2012–TVG 2012 under licence number 2021-0.731.149
snap-frozen in liquid nitrogen and stored at −80 °C
Libraries were verified using a 2100 Bioanalyzer (Agilent)
pooled and paired-end sequenced on an Illumina NovaSeq 6000 platform (read length = 150 bp)
Plotted are the driver GO terms from the ‘Molecular function’ and ‘Biological processes’ categories
For Seurat-based clustering of the single embryos
the counts data matrix from featureCounts was used as input to the Seurat package to treat the individual sample as a single cell
The Seurat NormalizeData function was used to normalize counts
The highly variable genes were identified using the FindVariableFeatures function
The Seurat object was subsequently scaled using ScaleData and PCA was carried out using RunPCA
The FindNeighbors function was used to construct the nearest-neighbour graph with a dimensionality reduction of 1:15
Clusters were then identified using the FindClusters function with the resolution parameter of 0.8
To account for the partial penetrance of the reported phenotypes
we should have profiled sncRNAs in single embryos
according to the genetic distance between the ST and the BL6 mtDNAs (which we used to calculate the heteroplasmy)
only 5′ fragments of mt-Tp would be reliably detectable (which has an SNP at the 5′ and 3′ of the mature tRNA sequence)
our data do not show transfer of mt-tsRNAs while demonstrating inheritance of paternal mature mt-tRNAs
we used anthropometric data of the most recent visit of the child
The polygenic effect on BMI-SDS of children was subtracted by linear mixed model analysis using the R package GenABEL
We then tested the effects of parent BMI on BMI-SDS of children by linear regression analysis adjusting for age and sex
Total RNA was extracted from spermatozoa with the TRIzol–chloroform phase separation method followed by precipitation and wash steps with 100% and 70% ethanol
RNA quality control was carried out with Agilent Bioanalyzer and only the samples with a RIN value of between 2 and 4.5 and no evident intact ribosomal RNA peaks were further processed
Sequencing libraries were prepared using NEBNext Small RNA Library Prep Set for Illumina (New England Biolabs) with 100–120 ng RNA as a total input
whereas reverse transcription primer was applied undiluted
Amplified libraries were cleaned with Monarch PCR & DNA Cleanup Kit (New England Biolabs) and size selected with AMPure XP (Beckman Coulter) using 1.0× and 3.7× beads for long-fragment removal and target-size retention
Pooled libraries were sequenced on a NovaSeq 6000
100 cycles (Illumina) at an average depth of 53.18 million reads per sample
a generalized linear model-based algorithm estimated the association of each sequence with the BMI across samples and output log2[FC] reflecting change in sequence expression level per unit of increment of BMI
Benjamini–Hochberg Padj < 0.1 served as a measure of significance for each result
Pearson-based correlation analysis between donors’ BMI and sperm sncRNA biotypes (variance-stabilizing transformation-normalized expression) has been carried out with GraphPad Prism 8 using default parameters
The following string represents the code used for the continuous DESeq2 analysis of human sperm sncRNA-seq data: dd_obj <- DESeqDataSetFromMatrix(countData = [your sequence count matrix]
colData = [data frame with sample ID and BMI values]
we used the IMPC dataset to study the (epi)genetic
intergenerational consequences of paternal manipulation of genes involved in mitochondrial structure and function
we compared a battery of 11 numerical metabolic phenotypes (fat/body weight; initial response to intraperitoneal glucose load; AUCipGTT; total food intake; respiratory exchange ratio; total cholesterol; HDL cholesterol; triglycerides; fasting blood glucose; albumin; alkaline phosphatase) in two populations of isogenic WT C57BL/6N mice generated from a pure WT lineage (control) or from heterozygous matings (WT—parental information (father × mother): het_×_het; het_×_WT; WT_×_het)
The data matrix was then scaled and the prcomp function in R was used to determine the principal components of the dataset
To quantify the difference between the genes on the basis of phenotypes
we use the Pearson correlation method using the get_dist function from the factoextra R package
These correlation coefficients were calculated to identify similarity patterns in gene–phenotype pairs and visualized in a heat map generated by using the ComplexHeatmap package from R
Cluster-specific phenotypes were visualized in a heat map including the 11 phenotypes
as well as sex- and parent-of-origin-specific information
Ranked AUCipGTT (expressed as log2[FC(WT versus control)]) was plotted as a horizontal bar plot using GraphPad Prism 9
Cryopreserved sperm samples containing a pool of purified cauda spermatozoa from 10 heterozygous mice were obtained from EMMA56
Genes were selected for availability with the exception of Tsfm (Ts translation elongation factor
which represents a suitable negative control for initial mechanistic dissection
Individual straws were thawed directly in TRIzol and RNA was extracted with the miRNeasy Micro Kit (QIAGEN 1071023) according to the manufacturer’s instructions
A 10 ng quantity of total RNA was used for sncRNA library preparation
Libraries were verified using a 2100 Bioanalyzer (Agilent) and paired-end (read length = 150 bp) sequenced with the Illumina NovaSeq 6000 platform
All figures and statistical analyses (as needed and appropriate) were generated using GraphPad Prism 8 or 9. Statistical significance was tested by Student’s t-test, or ANOVA as appropriate. Correlation analyses were used to test for linear regression. Odds ratios have been calculated using MedCalc (https://www.medcalc.org/calc/odds_ratio.php)
and a two-tailed P value < 0.05 was considered to indicate statistical significance unless otherwise specified in the text
Further information on research design is available in the Nature Portfolio Reporting Summary linked to this article
All of the raw sequencing data have been deposited at the NCBI Gene Expression Omnibus under accession number GSE239815. Processed sequencing data and anonymized human data will be provided by the corresponding author upon reasonable request. Source data are provided with this paper
Sperm RNA payload: implications for intergenerational epigenetic inheritance
Exercise alters mouse sperm small noncoding RNAs and induces a transgenerational modification of male offspring conditioned fear and anxiety
Elevated paternal glucocorticoid exposure alters the small noncoding RNA profile in sperm and modifies anxiety and depressive phenotypes in the offspring
Biogenesis and function of tRNA fragments during sperm maturation and fertilization in mammals
Sperm tsRNAs contribute to intergenerational inheritance of an acquired metabolic disorder
Implication of sperm RNAs in transgenerational inheritance of the effects of early trauma in mice
RNA-mediated epigenetic heredity requires the cytosine methyltransferase Dnmt2
Developmental windows of susceptibility for epigenetic inheritance through the male germline
Reproductive biology: delivering spermatozoan RNA to the oocyte
Small RNAs gained during epididymal transit of sperm are essential for embryonic development in mice
sncRNAs in epididymosomes: the contribution to embryonic development and offspring health
Characterisation of mouse epididymosomes reveals a complex profile of microRNAs and a potential mechanism for modification of the sperm epigenome
Small RNAs are trafficked from the epididymis to developing mammalian sperm
The contribution of epididymosomes to the sperm small RNA profile
Small RNA shuffling between murine sperm and their cytoplasmic droplets during epididymal maturation
IV Inheritance of paternal lifestyles and exposures through sperm DNA methylation
Histone H3 lysine 4 trimethylation in sperm is transmitted to the embryo and associated with diet-induced phenotypes in the offspring
Sperm histone H3 lysine 4 tri-methylation serves as a metabolic sensor of paternal obesity and is associated with the inheritance of metabolic dysfunction
Inheritable testicular metabolic memory of high-fat diet causes transgenerational sperm defects in mice
Epigenetic germline inheritance of diet-induced obesity and insulin resistance
Long non-coding RNAs could act as vectors for paternal heredity of high fat diet-induced obesity
Diet-induced paternal obesity impairs cognitive function in offspring by mediating epigenetic modifications in spermatozoa
Diet-induced paternal obesity in the absence of diabetes diminishes the reproductive health of two subsequent generations of mice
Dnmt2 mediates intergenerational transmission of paternally acquired metabolic disorders through sperm small non-coding RNAs
Rhox13 is required for a quantitatively normal first wave of spermatogenesis in mice
Mitochondrial gene expression in male germ cells of the mouse
Epigenetic inheritance of acquired traits through sperm RNAs and sperm RNA modifications
The International Mouse Phenotyping Consortium: comprehensive knockout phenotyping underpinning the study of human disease
Evidence of early alterations in adipose tissue biology and function and its association with obesity-related inflammation and insulin resistance in children
Intergenerational transmission of overweight among Finnish adolescents and their parents: a 16-year follow-up study
The LIFE Child study: a population-based perinatal and pediatric cohort in Germany
The LIFE child study: a life course approach to disease and health
Muniyappa, R., Madan, R. & Varghese, R. T. Assessing Insulin Sensitivity and Resistance in Human. Endotext [Internet] https://www.ncbi.nlm.nih.gov/books/NBK278954/ (updated 9 August 2021)
Human sperm displays rapid responses to diet
Dietary sugar shifts mitochondrial metabolism and small RNA biogenesis in sperm
Obesity and bariatric surgery drive epigenetic variation of spermatozoa in humans
The microRNA signature of mouse spermatozoa is substantially modified during epididymal maturation
Mitochondrial regulation in spermatogenesis
Effects of a high-fat diet on rat epididymis
MtDNA segregation in heteroplasmic tissues is common in vivo and modulated by haplotype differences and developmental stage
Metabolism of the preimplantation embryo: 40 years on
Oxidative phosphorylation-dependent and -independent oxygen consumption by individual preimplantation mouse embryos
Pre-implantation mouse embryos cultured in vitro under different oxygen concentrations show altered ultrastructures
Oxygen concentration alters mitochondrial structure and function in in vitro fertilized preimplantation mouse embryos
Feuer, S. et al. Transcriptional signatures throughout development: the effects of mouse embryo manipulation in vitro. Reproduction https://doi.org/10.1530/REP-16-0473 (2017)
Paternal diet-induced obesity retards early mouse embryo development
mitochondrial activity and pregnancy health
Mitochondrial TCA cycle metabolites control physiology and disease
Drougard, A. et al. A rapid microglial metabolic response controls metabolism and improves memory. Preprint at bioRxiv https://doi.org/10.1101/2023.04.03.535373 (2023)
Mitochondrial dysfunction in white adipose tissue
Obesity-induced oxidative stress and mitochondrial dysfunction negatively affect sperm quality
Dynamic regulation of mitochondrial transcription as a mechanism of cellular adaptation
Mitochondria: their role in spermatozoa and in male infertility
Genetics of mitochondrial dysfunction and infertility
Elimination of paternal mitochondria in mouse embryos occurs through autophagic degradation dependent on PARKIN and MUL1
Single-cell RNA-seq analysis of mouse preimplantation embryos by third-generation sequencing
Reporting animal research: explanation and elaboration for the ARRIVE guidelines 2.0
Da Ros, M., Lehtiniemi, T., Olotu, O., Meikar, O. & Kotaja, N. Enrichment of pachytene spermatocytes and spermatids from mouse testes using standard laboratory equipment. J. Vis. Exp. https://doi.org/10.3791/60271 (2019)
Repressive and active histone methylation mark distinct promoters in human and mouse spermatozoa
Integrated analysis of multimodal single-cell data
sensitive and accurate integration of single-cell data with Harmony
A comprehensive roadmap of murine spermatogenesis defined by single-cell RNA-seq
SPORTS1.0: a tool for annotating and profiling non-coding RNAs optimized for rRNA- and tRNA-derived small RNAs
Data quality aware analysis of differential expression in RNA-seq with NOISeq R/Bioc package
ClustVis: a web tool for visualizing clustering of multivariate data using principal component analysis and heatmap
Enrichr: interactive and collaborative HTML5 gene list enrichment analysis tool
g:Profiler: a web server for functional enrichment analysis and conversions of gene lists (2019 update)
Full-length RNA-seq from single cells using Smart-seq2
g:Profiler-interoperable web service for functional enrichment analysis and gene identifier mapping (2023 update)
Cell competition acts as a purifying selection to eliminate cells with mitochondrial defects during early mouse development
Transcriptome analyses of adipose tissue samples identify EGFL6 as a candidate gene involved in obesity-related adipose tissue dysfunction in children
An estimator for pairwise relatedness using molecular markers
The preparation of human spermatozoal RNA for clinical analysis
Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2
MissForest-non-parametric missing value imputation for mixed-type data
Download references
for technical support with the IVF and embryo culture experiments; J
semen analysis and sperm purification in Turku; the animal caretakers of the German Mouse Clinic; R
the IMPC Data Wrangler and the IMPC consortium for granting us access to the systemic phenotypic data of the entire WT mouse population; and the members of the Environmental Epigenetics group at the Helmholtz Munich for constant brainstorming and for proofreading and providing feedback on the manuscript
This work has been supported by grants from the German Diabetes Research Center (DZD Next Grant 2019)
the Minerva Association (ARCHES Prize 2016)
the Helmholtz Association (Helmholtz ERC Recognition Award) and the Fritz-Thyssen Stiftung (no
10.19.2.027MN) to R.T.; grants from the Sigrid Juselius Foundation
the Pediatric Research Foundation and Turku University Hospital to J.T
and N.K.; grants from the Novo Nordisk Foundation and the Jalmari and Rauha Ahokas Foundation to N.K.; grants from the German Research Foundation (DFG) for the Clinical Research Center ‘Obesity Mechanisms’ SFB1052/CRC1052 (no
Körner; and grants from the Christian-Hagedorn project funding by the German Diabetes Society to A
Open access funding provided by Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt (GmbH)
German Research Center for Environmental Health (GmbH)
Department of Biological Sciences and Pathobiology
University of Natural Resources and Life Sciences
Integrative Physiology and Pharmacology Unit
University of Turku and Turku University Hospital
Center for Pediatric Research Leipzig (CPL)
LIFE Leipzig Research Center for Civilization Diseases
Helmholtz Institute for Metabolic Obesity and Vascular Research (HI-MAG)
Helmholtz Zentrum München at the University of Leipzig and University Hospital Leipzig
Single-embryo library preparation and analysis: M.G.-V
Human cohorts—Leipzig Childhood Obesity cohort
Life Child cohort and Leipzig Adipose Tissue Childhood cohort: W.K.
Human adipocyte gene expression analysis: A
Human spermatozoa sncRNA-seq and analysis: L.M
Testes single-cell RNA-seq and analysis: M.G.-V
Total RNA and sncRNA-seq data generation and analysis: M.G.-V.
Analyses of publicly available sncRNA-seq data: A.T
IVF experiments and sperm analysis Germany: R.G
Organization of the technical work in the German Mouse Clinic: V.G.-D
The authors declare no competing interests
reviewer(s) for their contribution to the peer review of this work
Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations
(k) Representative marker genes for the different germ cell populations
body composition (a-right) and glucose tolerance (b) in mice exposed to two weeks of LFD or HFD feeding
(mean ± SEM – significance calculated by two-tailed t-test (a; N = 18/diet – p-value = 0.0003 BW
and <10−4 Fat mass) or two-way ANOVA (b; N = 10-11/diet – p-value < 10−4)) (c-d) Effect of four weeks recovery on chow diet on diet-induced body weight (c-left)
body composition (c-right) and glucose tolerance (d)
N = 8/diet (mean ± SEM – significance calculated by two-tailed t-test (c – p-value = 0.03 BW
and 0.008 Fat mass) or two-way ANOVA (d – p-value = 0.006))
(e-f) Body weight (e) and Fat mass (f) development in male offspring of LFD and HFD-exposed bucks and bucks allowed to recover for four weeks on chow diet (N = 60 male mice across 4 cohorts with 5 litters each and 3 males/litter (eLFD and eHFD); N = 10–15 (sLFD and sHFD) including one cohort with 5 litters and 3 males/litter – significance calculated with Mann-Whitney test to compare ranks for weight and fat-mass gain)
(g) Frequency of HFDi offspring across four different F0-F1 cohorts
Fat mass (i) and glucose tolerance (j) in female offspring of LFD and HFD-exposed bucks and bucks allowed to recover for four weeks on chow diet
(N = 60 female mice across 4 cohorts with 5 litters each and 3 female/litter (eLFD and eHFD); N = 10–15 (sLFD and sHFD) including one cohort with 5 litters and 2-3 females/litter – significance calculated with Mann-Whitney test to compare ranks for weight and fat-mass gain)
(k) Differentially Expressed Genes (male HFDi vs HFDt) in peripheral tissues
(l) Childhood obesity risk (top) and protective (bottom) genes differentially expressed in HFDi tissues
(a-b) Control linear regression analysis (r2 and p-value in the respective panels) for associations between (a) maternal and paternal BMIs at conception and (b) maternal and offspring BMI (dotted lines indicate the 95% confidence intervals of the regression line)
(c) Frequency of overweight and obesity in offspring stratified by paternal BMI groups in families with lean mothers (analysis detailed in the methods section; results in the figure)
(d-e) Control linear regression analysis (r2 and p-value in the respective panels) for associations between ISI-MATSUDA (d) and HOMA-IR (e) insulin sensitivity indices and paternal BMI at conception (dotted lines indicate the 95% confidence intervals of the regression line)
(l) Biotype-specific differential expression analysis of round spermatids sncRNAs from LFD and HFD-fed mice
(a) Distribution of sncRNA biotypes in human spermatozoa purified from ejaculates
left) biotypes distribution in single donors stratified per BMI; (up
right) average biotypes distribution in lean (BMI < 24) and owt (BMI > 24) donors
left) relative abundance of n- and mt-tsRNAs in single donors stratified per BMI; (down
right) average relative abundance of n- and mt-tsRNAs in lean and owt donors
(b-d) Pearson-based co-correlation matrix of sncRNA biotypes and BMI (b) and scatter plot representation for mt-tsRNAs (c) and n-tsRNAs (d) Exact p-values for c and d indicated in the figure
(e) Biotype-specific differential expression analysis of human sperm sncRNAs
(f) Heatmap representation of the Continuous Differential Expression analysis results for n- and mt-tsRNAs
(g) Dot plot showing the upregulation of n-tRNA-GlyGCC_5_end in spermatozoa from owt donors
(a-c) MA plot representation of differentially expressed genes in HFD_A vs HFD_B (a), HFD_B vs LFD (b) and HFD vs LFD Female (c) embryos. (d) Heatmap representation of the genes used for the PCA plot in Fig. 4e
(e) Scheme of the working hypothesis by which exposure of male mice to two weeks of HFD induces mild mitochondrial dysfunction
which leads to a compensatory up-regulation of mt-DNA transcription in spermatozoa
transfer of mt-tRNAs from sperm-to-oocytes at fertilisation and reprogramming of offspring glucose metabolism
(f) Heatmap representation of the IMPC metabolic phenotypes analysed in the WT offspring of IMPC-selected genes mutants with indication of offspring gender and parental effects (Het_x_Wt = paternal effect)
(g-i) Heatmap representation of the tsRNA expression (g) and the relative abundance of 3’ (h) and CCA (i) fragments in mutant spermatozoa
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Monuments and cultural spaces in Tomar registered more than half a million tourists in 2024
the Tomar (Santarém) City Council reported on the visitors it received last year
“in visits to museum facilities and monuments managed by the municipality”
there was an “increase of around 7% in entries compared to the previous year”
195,540 visitors were registered in the cultural facilities managed by the municipality of Tomar
an event that takes place every four years
there were 182,126 visitors and in 2022 134,071 were registered
Of the 195,540 visitors to Tomar's municipally managed cultural facilities in 2024
112,408 were Portuguese (57.49%) and 83,132 were foreigners (42.51%)
21.52% came from the United States of America
Tomar City Council indicates that the number of visitors in 2024 is “very significant” and reveals how the city has seen “increased tourist demand regardless of the Convent of Christ”
the values of which are not included in this calculation
is not under the supervision of the municipality
Lusa contacted the management of the Convent of Christ
managed by Museus e Monumentos de Portugal
with an official source from the monument indicating that the figures for 2024 have not yet been released by the authority
but “exceed the 311,879 visitors registered in 2023”
Among the cultural facilities managed by the municipality of Tomar
the Synagogue was once again the most visited monument
The Synagogue's Interpretive Center also maintained this trend
of which 15,336 were from outside the country
The second most popular place was the Chapel of Santa Iria
which registered a total of 31,261 visitors
with the vast majority (20,942) being Portuguese tourists
which houses the Tomarense Foundry and Power Plant Museum Centers
with the “Fábrica das Artes | Tomar” project
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Myrriah Tomar’s contributions to state economic development recognized
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associate engineer and AI research analyst at Exelaration
shares how she pivoted from mechanical engineering to software engineering on this episode of Diverse: a SWE podcast
Hear practical steps that engineers can take to enter the software field
how women in STEM can position themselves to succeed in the world of AI
and Tomar’s reflections on moving to the U.S
Prachi Tomar is a certified Agilist with a mechanical engineering background
excelling as a software engineer and technical trainer
she has advanced into AI and machine learning
focusing on data analysis and neural networks
Her adeptness in Agile and Scrum methodologies enables her to simplify complex technical and AI concepts
aligning software solutions with client objectives to deliver high business value
Prachi’s experience spans delivering impactful workshops
and developing cutting-edge software solutions
blending engineering expertise with innovative problem-solving
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You can hear her on “Sam & Dames” in the afternoon from 3-7PM on Toronto’s #1 Hit Music Station
hosting and producing the podcast “Lessons to My Younger Self,” or sharing a video that leads to a personal invite from Oprah Winfrey
Sam is also a certified mindfulness meditation teacher and is thrilled to be able to share tools to help cultivate presence
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It’s up-to-date information and news about the Society and how our members are making a difference everyday
What do you think of Unnati Tomar accusing Digvijay Rathee of adultery?ADVT
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what was the key part of IIM Bangalore’s MBA programming that led you to choose this business school and why was it so important to you
IIM Bangalore offers the maximum number of electives across any Business school in the country
and Himalayan Mountain Challenge will help me charter my own learning experience
I have been actively involved in sports and IIM Bangalore has the best sports facility across any IIM
What has been your favorite course or extracurricular activity at IIM Bangalore
What has been the most important lesson that you have learned from it
One of my favorite courses at IIMB has been Competition and Strategy by Prof R Srinivasan
It not only helped me get familiar with different Strategy frameworks and provided exposure to different industries but also it forced tertiary-level and outside-the-box thinking through first principles approach
Another course that I really enjoyed is Professor Chetan Subramanian’s Macroeconomics
coupled with boundless enthusiasm and thought-provoking discussions
turned Monday afternoons into eagerly-anticipated learning experiences
The course’s exploration of Aggregate Demand and Aggregate Supply models
These concepts were presented with remarkable clarity
making complex economic relationships feel intuitive
What makes Bengaluru such a great place to earn your MBA
Bangalore has a robust startup ecosystem and strong industry connections
allowing us to engage frequently with industry leaders and gain valuable insights from their experiences
we have interacted with industry leaders like Rahm Shastry
Executive Chairman of DriveU; Akhil Sharma
Director of Product RazorPay; and Chris Dickens
All these interactions have been instrumental in solidifying our understanding of business
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I led an 8-member team to establish India’s first online platform for buying and selling Active Pharmaceutical Ingredients (APIs)
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* Competing against the brightest minds in the country
I received a Merit scholarship worth 6L for being in the top 1% of the candidates during the IIM Bangalore admission process
* To better hone my people management skills
I took up additional responsibility of International Immersion Committee which is responsible for both internal and external stakeholder coordination for all 82 students travelling to ESCP
* Notwithstanding the packed MBA curriculum
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Frisbee and Hockey during intra-college events
It has been instrumental in building cordial relationships with not only my own batchmates but also the PGPs
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My favorite hangout place outside the campus is Uru Brewery given the proximity to the campus
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Get done with your GMAT well in advance and give sufficient time to the application and essay writing process
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IIMB appreciates genuine individuals with diverse viewpoints and experiences
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Volume 15 - 2021 | https://doi.org/10.3389/fnbeh.2021.710725
Chronic and acute stress differentially affect behavior as well as the structural integrity of the hippocampus
a key brain region involved in cognition and memory
it remains unclear if and how the facilitatory effects of acute stress on hippocampal information coding are disrupted as the stress becomes chronic
we compared the impact of acute and chronic stress on neural activity in the CA1 subregion of male mice subjected to a chronic immobilization stress (CIS) paradigm
We observed that following first exposure to stress (acute stress)
the spatial information encoded in the hippocampus sharpened
and the neurons became increasingly tuned to the underlying theta oscillations in the local field potential (LFP)
following repeated exposure to the same stress (chronic stress)
spatial tuning was poorer and the power of both the slow-gamma (30–50 Hz) and fast-gamma (55–90 Hz) oscillations
which correlate with excitatory inputs into the region
These results support the idea that acute and chronic stress differentially affect neural computations carried out by hippocampal circuits and suggest that acute stress may improve cognitive processing
the impact of acute stress on the neural computations carried out by hippocampal circuits in the intact brain remains unclear
it is likely that both acute and chronic stress may impact these oscillatory patterns in unique ways
we examined alterations in both rate and temporal coding of CA1 pyramidal cells
as well as changes in the hippocampal oscillatory activity
All experiments were performed using male C57BL/6J mice. A total of five mice, aged between 3 and 6 months, were used for this study. The data related to the physiology during the stress exposure from these mice was previously reported (Tomar et al., 2021)
Mice were maintained on a 12-h light-dark cycle with ad libitum access to food and water
All procedures were approved by the RIKEN Institutional Animal Care and Use Committee and complied with the National Institutes of Health guide for the care and use of laboratory animals (NIH Publications No
All efforts were made to minimize animal suffering and to reduce the number of animals used
all mice experienced a familiar track twice
the first before (PRE) and second after the stress exposure (POST)
on the first day (Acute) and the last day (Chronic) of a CIS paradigm thus providing us with four conditions: (i) PRE-Acute; (ii) POST-Acute; (iii) PRE-Chronic; and (iv) POST-Chronic
Each track (RUN) epoch was bracketed by Rest-state (REST) epochs and each epoch was ~ 30 min
Impact of stress on CA1 place cell activity
(A) Schematic representation of the chronic immobilization stress (CIS) protocol and experimental design
(B) Percentage of pyramidal cells active during exploration (RUN) compared to quiet wakefulness/sleep (REST) period
(C) Pre-stress mean firing rates between REST and RUN on day-1 and day-10 [LMMs: main effect of day
p = 7.708 × 10−15; interaction
(D) Pre-stress place field size density distribution differs between day-1 and day-10 (PRE-Acute (n = 95) vs
display a decrease in field size on day-1 (PRE-Acute 13.89 ± 1.46 vs
(E) Pre-stress sparsity of place fields does not differ between day-1 and day-10 (PRE-Acute (n = 95) vs
display a decrease in sparsity-index on day-1 (PRE-Acute
(F) Pre-stress information content (bits/spike) of place fields does not differ between day-1 and day-10 [PRE-Acute (n = 95) vs
display a significant increase on day-1 (PRE-Acute
All box plots represent interquartile range (IQR
median is the thick line in the box and whiskers extend to 1.5 times the IQR
The black and red dotted lines on density plots display median values
Mice were anesthetized using Avertin (2,2,2-tribromoethanol; Sigma-Aldrich
i.p.) and were surgically implanted with a microdrive (manufactured with the assistance of the Advanced Manufacturing Support Team
The microdrive housed eight independently movable tetrodes (14 μm diameter
nichrome) and was placed above the right dorsal hippocampus (coordinates from Bregma: AP −1.8 mm; ML + (1.2 mm)
tetrodes were gold plated to lower impedance down to a range of 100–250 kΩ
Tetrodes were gradually lowered over the course of several days
such that by the start of the experiment they reached the CA1 stratum pyramidale
Data were acquired using a 32-channel Digital Lynx 4S acquisition system (Neuralynx
Signals were sampled at 32,556 Hz and spike waveforms were filtered between 600 Hz and 6 kHz
Skull screws located above the cerebellum served as a ground
and a tetrode positioned in the superficial layers of the neocortex
when all tetrodes reached the CA1 stratum pyramidale
evident by multiple large amplitude spikes and SPW-Rs
the mice were located in a small circular sleep box (15-cm diameter)
mice underwent terminal anesthesia (Avertin)
for 8 s) was administered through each electrode to mark their locations
Transcardial perfusion was carried out using saline followed by 4% paraformaldehyde (PFA) followed by a further 24-h fixation in 4% PFA
Brains were sliced using a vibratome (Leica) to prepare coronal slices (50 μm thick) and inspected by standard light microscopy to confirm electrode placement
where Pspk(i) is the probability of spiking in bin “i” and “Pocc(i)” is the occupancy probability in bin “i”
The “Pspk” and “Pocc” values were computed from the rate and occupancy maps respectively
The Power Spectral Density (PSD) during exploratory behavior was calculated by using Welch’s averaged modified periodogram method with a 2,048-sample (1.26 s) window size
50% overlap and 4,096 FFT points (2.52 s) resulting in a time-varying spectrogram
The PSD curves corresponding to time bins when the animal’s velocity was above 6 cm/s were averaged yielding a single PSD curve for each of the four experimental conditions
In order to account for power fluctuations caused by differences in position/impedance of the electrodes and make PSD values comparable across mice
we normalized each PSD curve by its own mean power within the 0–3 Hz band
Instantaneous running speed curves were obtained by element-wise division of relative changes in the animal’s position between video frames by correspondent inter-frame timestamps
The resulting signal was then smoothed with a 2.5-SD gaussian kernel
all the spikes fired by the cell when the animal was running along the track were binned
using the camera’s frame rate (1/30 s as the bin size
yielding an instantaneous firing rate curve
Instantaneous running speed values were then binned using logarithmically distributed velocity values
The resulting index matrix (second return value of the MATLAB histc() function) was then used to calculate the mean firing rate of the cell within each running speed bin
Modulation of LFP power in gamma frequency bands by the animal’s running speed was assessed by first down-sampling the LFP signal to 400 Hz and up-sampling the previously calculated instantaneous velocity curve using linear interpolation method to the same sampling frequency value as the down-sampled LFP
The resulting LFP signal was then filtered in the target frequency bands (slow and fast gamma) and converted into instantaneous power values by calculating the absolute value of the Hilbert transform of the filtered LFP trace
The up-sampled running speed curve was then binned using the same logarithmically distributed velocity values
and corresponding mean fast and slow gamma power was calculated by using the method described above for each velocity bin
Gamma/spikes modulation was computed in a similar manner; the calculation was performed using LFP traces filtered in slow gamma (30–50 Hz) and fast gamma (55–90 Hz) frequency bands
Due to the transient nature of gamma oscillations
additional gamma “bursts” detection was performed by calculating time periods when instantaneous power (absolute value of Hilbert transform) of gamma-band filtered LFP trace exceeded various threshold values (in Standard Deviations
All statistical analyses were performed in R software (3.3.2)
The normality of distributions was not assumed
so comparisons were made using non-parametric statistics
while for cells matched between two epochs
Wilcoxon signed-rank tests were used to test the equality of medians
stats package) followed by Tukey’s honestly significant difference (HSD) test (TukeyHSD function
stats package) was used to test for differences between treatments
Overall differences in place cell properties were assessed using linear mixed effects models (LMMs)
where mouse identity was specified as a random factor and day and behavior state were specified as fixed factors
The output of the lmer function was summarized as an ANOVA table (anova function
comparisons for power distributions across various frequency bands in LFP signals were assessed using LMMs
where mouse identity was specified as a random factor and frequency bands as categorical variables were specified as fixed factors
Correlation between parameters was calculated using Pearson’s correlation coefficient analysis (base package)
The dependence of a parameter on another was calculated by employing standardized major axis (SMA) regression (sma function
Comparisons between regression lines were made by likelihood ratio tests (sma function
the Kolmogorov-Smirnov test was employed (ks.test
statistical analyses were performed on 10° binned data however for visualization purposes data is presented in 30° bins
Boxplots represent Interquartile Range (IQR
the median is the thick line housed in the box and whiskers extend to 1.5 times the IQR
No data points were removed as outliers either for making boxplots or for statistical analysis
the significance threshold for all tests was set at p < 0.05 and p-values are shown as follows: *p < 0.05; **p < 0.01; ***p < 0.001
thus providing us with four conditions: (i) PRE-Acute; (ii) POST-Acute; (iii) PRE-Chronic; and (iv) POST-Chronic
Our recordings from the dorsal CA1 region of the hippocampus (Supplementary Figure 1A) during baseline activity state (REST) yielded a total of 180 pyramidal cells on day-1 (Acute) and 166 pyramidal cells on day-10 (Chronic). No major differences in firing rates was observed, although bursting activity showed a small, but significant, increase at the chronic time point (Table 1)
we assessed the impact of stress on mouse behavior during track exploration (RUN) by employing ANOVA statistics where the “main effect of day” signifies the comparisons made between day-1 and day-10 (i.e.
after a single exposure and repeated stress) while the “main effect of session” means comparisons made before and after exposure to stress
We observed no discernible change in behavior as the total number of laps traveled by mice did not differ between sessions across days (2-way repeated measures ANOVA: main effect of day
distance traveled on the track did not differ between days and sessions (2-way repeated measures ANOVA: main effect of day
These data demonstrated that neither acute nor chronic stress strongly affected mouse locomotor behavior
Pyramidal cell properties during baseline activity and exploratory states on day-1 and day-10
with no discernible effect of repeated stress exposure (averaged firing; LMMs: main effect of day
pyramidal cells increased their discharge rate during spatial coding and neither acute nor chronic stress affected this property of pyramidal cells
We then performed detailed analysis of place cell properties. Place field size, defined as the proportion of the track that a place cell was active on, showed a main effect of day (Figure 1D; size; LMMs: main effect of day
density distribution of field size during PRE-stress sessions changed after repeated stress such that compared to day-1
a greater fraction of cells had larger place fields [day-1 (n = 95 cells) vs
that were active during both PRE and POST stress sessions
displayed a decrease in field size after stress exposure on day-1 (PRE-Acute
N = 5 mice) but not on day-10 (PRE-Chronic
place fields decreased in size after the acute stress
but expanded after repeated exposure to stress
This was further confirmed as place cells active on the track before and after the exposure to stress also showed a significant increase in information content on day-1 (PRE-Acute
we noticed a clear pattern of increase in firing rate as the speed increased [2-way mixed ANOVA: main effect of speed
p = 3.546 × 10−10; interaction
the above data indicate that smaller place fields and enhanced spatial tuning
was not caused by altered speed or relationship between firing rate and speed
as no effect of day or session was observed (theta; 2-way repeated measures ANOVA: day
Impact of stress on CA1 oscillatory activity
(A) Representative examples of unfiltered (top) and filtered (bottom) local field potentials (LFPs) during track exploration for theta
(B) Power spectral density (PSD) curves of CA1 LFPs during linear track exploration (RUN) show no significant differences for theta (6–12 Hz; Theta
Fast-gamma (55–90 Hz) showed an effect of day but not of session (FG
right inset; 2-way repeated measure ANOVA: main effect of day
Slow-gamma (30–50 Hz) showed an effect of day but not of session (SG
2-way repeated measure ANOVA: main effect of day
(C) Relationship between FG power and running speed on the track (FG; 2-way repeated measure ANOVA : main effect of speed
(D) Representative examples of modulation of gamma amplitude by theta phase in dorsal CA1 pyramidal cell layer before (top) and after (bottom) stress exposure on day-1 (left) and day-10 (right)
The colorbar represents the z-scored gamma power in arbitrary units (a.u.) for both left and right-side graphs
(E) Theta-FG phase-amplitude coupling (top) did not differ across days and sessions (2-way repeated measures ANOVA: day
theta-SG coupling (bottom) was not affected by either acute or chronic stress (2-way repeated measures ANOVA: day
the increase in slow gamma power as the speed increased was subtler (SG; 2-way repeated measure ANOVA: main effect of speed
Further no significant difference was observed either between theta-fast gamma coupling (theta-FG; 2-way repeated measures ANOVA: day
N = 5 mice) or theta-slow gamma coupling (theta-SG; 2-way repeated measures ANOVA: day
LFP power analysis indicated that while the first exposure to stress did not alter theta and gamma oscillatory activity
repeated stress led to suppression of SG and FG power
but had no impact on CFC between theta and gamma
N = 5 mice); post hoc Tukey’s test
Distribution of place cells phase-locked to theta and gamma oscillations on day-1 and day-10
Impact of stress on phase-locking properties of CA1 place cells to theta and gamma oscillations
(A) The spiking probability plotted as a function of the phase of theta for significantly theta-modulated place cell populations (Rayleigh p < 0.05)
Population spiking probability is elevated around the trough and ascending phase of theta (0/360° set for theta peak
(B) The strength of theta-phase locking (Modulation index
MI) is altered by stress [LMMs: main effect of day
(C) The spiking probability plotted as a function of the phase of fast-gamma (FG) for significantly FG-modulated place cell populations (Rayleigh p < 0.05) is elevated around the trough and descending phase of FG (0/360° set for FG peak
180° for FG trough) but stress did not affect this phase relationship: (FG
(D) The strength of FG phase-locking (MI) remains unaltered by stress (FG; LMMs: main effect of day
(E) The spiking probability plotted as a function of the phase of slow-gamma (SG) for significantly SG-modulated place cell populations (Rayleigh p < 0.05)
Population spiking probability is elevated around the descending phase of SG (0/360° set for SG peak
(F) The strength of SG-phase locking (MI) was not significantly altered by stress (SG; LMMs: main effect of day
Boxplots represent interquartile range (IQR
median is the thick line in the box and whiskers extend to 1.5 times the IQR.
while first exposure to stress increased the strength of theta phase-locking demonstrating the facilitatory effects of acute stress on temporal coding
chronic stress disrupted temporal coding as the mean phase and the strength of phase-locking of place cells to slow-gamma oscillations was altered on day-10
these results indicate that acute stress has a facilitatory impact on hippocampal information coding
Future studies are needed to further investigate the role of SAM-activated neuromodulation on CA1 spatial coding
Our observation of decreased slow and fast gamma power following chronic
but not acute stress reflects the poor functional connectivity in hippocampal-entorhinal circuits in chronically stressed subjects
functional connectivity was not altered after acute stress
as place maps were more informative of animal’s location in space
are contributed by CIS-induced weakening of inhibition
Future studies will have to assess the differential contributions of chronic stress-induced altered inhibition
synaptic plasticity and dendritic atrophy to altered place cell activity
gamma oscillations and phase-locking phenotypes observed in this study
Since this study only employed immobilization stress
it is not yet clear if the changes observed in this study would be elicited by other models of stress
future studies employing two or more different animal models of chronic stress are needed to clarify if only the immobilization-related physical model of stress or any stress could differentially alter spatial coding and gamma oscillations when applied either once or repeatedly
our results of altered oscillatory and place cell activity have implications for neural computations across various memory-related circuits connected to the hippocampus
our results of acute stress-induced increased information content of place cells and strengthening of phase-locking to theta oscillations further support the idea that acute stress facilitates hippocampal neural computations
we propose that acute and chronic stress differentially
influence hippocampal information processing
The raw data supporting the conclusions of this article will be made available by the authors
The animal study was reviewed and approved by RIKEN Institutional Animal Care and Use Committee
AT and TM wrote the manuscript with inputs from DP
All authors contributed to the article and approved the submitted version
This work was supported by Grant-in-Aid for Scientific Research from MEXT (19H05646; TM)
Grant-in-Aid for Scientific Research on Innovative Areas from MEXT (19H05233; TM)
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 thank all members of the CBP laboratory for their support
RIKEN Center for Advanced Photonics for their assistance in microdrive production and Lalitha Krishnan for assistance with figure generation
The Supplementary Material for this article can be found online at: https://www.frontiersin.org/articles/10.3389/fnbeh.2021.710725/full#supplementary-material
SUPPLEMENTARY FIGURE 1 | The impact of stress on the relationship between CA1 place cell spiking vs
(A) Coronal section of the hippocampus showing the tetrode locations (black arrows) at the CA1 pyramidal layer
(B) Dependence of firing rate on the speed was affected by stress (2-way mixed ANOVA: main effect of speed
place cells displayed lower firing over the range of speed bins examined (PRE-Acute (n = 95) cells vs
the firing rate of place cells increased over the range of speed bins examined (PRE-Acute (n = 95 cells) vs
PRE-Chronic (n = 101 cells) p < 0.003
post hoc Tukey’s test) and this relationship further increased after experiencing the stress on day-10 (PRE-Chronic (n = 101 cells)
Circular histograms display the preferred phase of all place cells during theta (C)
The thick line in each circular histogram depicts averaged phase across all cells
CA2 neuronal activity controls hippocampal low gamma and ripple oscillations
Chronic unpredictable stress impairs long-term potentiation in rat hippocampal CA1 area and dentate gyrus in vitro
Fast synaptic inhibition promotes synchronized gamma oscillations in hippocampal interneuron networks
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Polygalov D and McHugh TJ (2021) Differential Impact of Acute and Chronic Stress on CA1 Spatial Coding and Gamma Oscillations
Received: 17 May 2021; Accepted: 28 June 2021; Published: 20 July 2021
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*Correspondence: Anupratap Tomar, YW51cHJhdGFwLnRvbWFyQGJyaXN0b2wuYWMudWs=; Thomas J. McHugh, dGhvbWFzLm1jaHVnaEByaWtlbi5qcA==
† Present address: Anupratap Tomar
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The excitement around the release of the much-awaited Bhool Bhulaiyaa 3 is growing as we near the release date of November 1st
Adding the the bollytizzy and now becoming a viral sensation is the song ‘Ami Je Tomar 3.0’
While Ami Je Tomar has been a classic song of the franchise since the first installment
this time it arrives with an entirely new energy
‘Ami Je Tomar 3.0’ features a face-off between the OG Manjulika
As they take over the scene with their electrifying performances the amalgamation of Kathak by Madhuri and Bharatnatyam by Vidya in a royal form creates an iconic dance sequence
to embody the legacy of ‘Ami Je Tomar’ is a dream
we’re bringing this classical masterpiece back to your screens.”
‘Ami Je Tomar 3.0’ is sung absolutely brilliantly by Shreya Ghoshal
The new version of the song is reprised by Amaal Mallik
Acclaimed choreographer Chinni Prakash has expertly crafted a mesmerizing blend of these classical dance forms
The song was released first and was a hit before the video even dropped
Adding in the visuals of watching Vidya and Madhuri dance and it has become viral over all the platforms and fans are shouting more
Choreographer Chinni Prakash in an interview with TOI explained
That was the original plan according to the script
Madhuri also became part of the song and it became a jugalbandi
Vidya’s solo was going to be in the first half
it was decided that it would be a jugalbandi
“Bazmee told me there would be a dance with the two because there was a misunderstanding between the two sisters and they don’t get along
He wanted a performance where each lady tried to show that she was a better dancer than the other through her expressions.The body language is very important in jugalbandi.”
Both of them behaved like students who hadn’t done any song before
They hand themselves over to you completely
Talking about working with Vidya and Madhuri
“They have done a fantastic and extraordinary job
Those five days (when the song was shot with Vidya Balan and Madhuri Dixit were very special
Everybody was happy and we just watched them
This film will be remembered for a long time.”
Also at the song launch event Vidya and Madhuri danced a 52-second sneak peek. Check out this amazing behind the scenes
A post shared by Vidya Balan (@balanvidya)
With Kartik Aaryan reprising his role as Rooh Baba from the superhit Bhool Bhulaiyaa 2
Directed by Anees Bazmee and initiated by Bhushan Kumar
this highly anticipated release is set to carry forward the legacy of Bollywood’s beloved horror-comedy franchise
Get ready for a Diwali filled with spooky fun and laughter
Bhool Bhulaiyaa 3 gears up for a grand release this Diwali on November 1
Puja Tomar beat Rayanne Amanda with a split decision Saturday to open the preliminary card at UFC on ESPN 57 at KFC Yum
Take a look inside the fight with Puja Tomar
who became the first Indian woman to win in the UFC
Result: Puja Tomar def. Rayanne Amanda via split decision (30-27, 27-30, 29-28)
Key stats: Tomar stuffed all three of Amanda's takedown attempts
"My coach was a little bit angry because his game plan was (better)
I feel like my striking was better than her."
"This win is for all Indian fans and all Indian fighters
'I have to win.' To walk out with my Indian song and Indian flag
but I'm going to improve myself and I'm going to be all the way up (in the rankings)."
check out the video of the full post-fight interview above
For more on the card, visit MMA Junkie's event hub for UFC on ESPN 57
UFC on ESPN 57: Best photos from Louisville
UFC on ESPN 57: Official scorecards from Louisville
Home » Movies » Movie News » Vidya Balan And Madhuri Dixit In Ami Je Tomar 3.0
Biggest Day Of My Career Says Amaal Mallik
Amaal took to his X profile to share his excitement
reflecting on the intense creative process that went into recreating this beloved classic
zero rest and lots of creative back and forth has resulted in this rebirth of #AmiJeTomar & #MereDholna
The first one sung by the OG @shreyaghoshal
Featuring the legendary ladies @vidya_balan @MadhuriDixit
The song features the original vocals of Shreya Ghoshal
making this release even more special for fans of the franchise
Directed by Anees Bazmee and written by Aakash Kaushik
Bhool Bhulaiyaa 3 is produced by T-Series Films and Cine1 Studios
This film marks the third installment in the popular Bhool Bhulaiyaa franchise
following Bhool Bhulaiyaa (2007) and Bhool Bhulaiyaa 2 (2022)
The star-studded cast includes: Kartik Aaryan
Bhool Bhulaiyaa 3 is set to release on November 1
making it a highly anticipated event for fans of the franchise and music lovers alike
With Amaal Mallik at the helm of this musical revival
Ami Je Tomar 3.0 is expected to resonate with audiences and capture the magic of the original while introducing a new generation to this timeless classic
Be sure to catch the song and the film when it releases
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Yuvika Chaudhary and Prince Narula are one of the much-loved couples in the television world
their friendship evolved into something deeper
the duo welcomed their baby girl into their lives
Shauna Bannon showed her submission skills—and some incredible toughness—in her latest win
A UFC London preliminary bout saw Bannon rocked badly by a Puja Tomar head kick
but she managed to recover and score an armbar submission moments later
Watch the strawweight’s comeback finish below
Shaun Bannon survives the head kick and taps out Puja Tomar at #UFCLondon! pic.twitter.com/4SgrQ5NRiI
Bannon was likely ahead on the scorecards after one round, making the most of her reach advantage with long-range side kicks that had Tomar confused as to how to approach. In Round 2, Tomar still struggled to close the distance, but found an opening for a kick of her own that caught Bannon clean on the side of her head.
The shot dropped Bannon and Tomar followed with ground-and-pound, with referee Lukasz Bosacki moving in to take a close look at the action. He allowed the fight to continue and Bannon regained her bearings. Bannon then went to attack Tomar’s arm and despite valiant defense from the Indian fighter, Bannon sharply adjusted and finished the armbar at the 3:22 mark of the second round.
Bannon (7-1) improved to 2-1 in the UFC with her first-ever submission, while Tomar (9-5) falls to 1-1 after tapping out for the first time in her pro career.
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"You need a lot of good friends here because you can't open up
Har aadmi kabhi na kabhi kamzor feel karta hai (Every person feels weak at times)," he said
Dhulia also emphasized having a true friend to confide in during tough times
his movie Paan Singh Tomar bagged the National Film Award for Best Feature Film
The film featured Irrfan Khan and Nawazuddin Siddiqui
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Home | Sports | Puja Tomar makes history as first Indian UFC fighter to win inside the Octagon
just made history as the first ever Indian fighter to secure a win inside the UFC octagon
Tomar secured a split-decision victory against the Brazilian Rayanne dos Santos in the UFC’s strawweight division (52kg)
Puja Tomar made history last night as the first fighter from India to earn a victory in the UFC! ???#UFCLouisville pic.twitter.com/kPg4tLHXYn
— UFC (@ufc) June 9, 2024
Bearing the nickname ‘The Cyclone’, the 30 year old Indian native signed with the UFC last October, and though many Indians have competed in the octagon, Tomar is the first to secure a victory in the UFC.
Being a five time national wushu champion with a background in Tae Kwondo and karate, Tomar is clearly a striker, but reflected that she needs to work on her takedown defense in order to compete with the best in the world on the UFC stage. “I felt pressured in the second round, and need to improve a lot on my takedowns,” the fighter admitted. Still, claiming victory by any means necessary is no small feat against the most dangerous humans on the planet.
A post shared by UFC India (@ufcindia)
“women will never fight in the UFC,” only to now have some of the organisation’s most decorated and talked about athletes being females
The UFC’s female strawweight division features some of the most ferocious fighters in any organisation
and Tomar undoubtedly has her work cut out for her should her ascent continue
is the UFC’s first champion from Asia
and one can only imagine Tomar will now be gunning for her title
But as Weili’s opponents have discovered in the past
taking on the Chinese champion is a viciously unrewarding task
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Puja Tomar has rewritten the narrative of Indian women in combat sports
Puja's journey to becoming the first Indian woman to secure a UFC contract is an inspiration
Puja faced societal and economic hurdles but she was raised as "The Cyclone"
Puja won a tough match against Brazilian MMA fighter Rayanne dos Santos
"Puja Tomar is a pioneer for women's MMA in India," said Kevin Chang
UFC Senior Vice President and Head of Asia
Her journey from Budhana village to the global stage of UFC is an inspiration
but for anyone who is fighting and striving to break free from societal constraints and pursue their dreams
Puja Tomar made history last night as the first fighter from India to earn a victory in the UFC! ???#UFCLouisville pic.twitter.com/kPg4tLHXYn
Here are five lessons we can learn from Puja's Journey:
society criticized her parents for not having a son
It is a motivation for lakhs of women who face the same patriarchal problems still today
"My MMA journey was not easy; this win is for my mother
She has fought with the world for me," Puja shared post-match Her success shows that with support and determination
Puja lost her father at the tender age of just 7 years old
which filled her with anger and disappointment with life
instead of letting these feelings hold her back
she used them to fuel her training and took up martial arts
She worked very hard and the rest is history
"I want to show the world that Indian fighters are not losers
Puja's story illustrates how turning life problems into motivation to bring changes can lead to great achievements
Puja is known for her relentless hard work and never-give-up attitude
I need to improve on a lot of skills like takedowns," she shared earlier
Her dedication shows the importance of understanding mistakes and doing hard work towards them
Puja shared her experience during the match
it shows her toughness and preparedness for the match
"I walked out to my Indian song with the Indian flag
Her story serves as an inspiration to many
illustrating that no obstacle is too great to overcome with the right mindset
Embracing Continuous Learning and Improvement
she emphasized her focus on what she can improve and do great in future matches
I'm going to improve myself and I'm going all the way up," she shared
Her commitment to learning and getting better highlights the importance of always striving for improvement
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Ex flames Unnati Tomar and Digvijay Singh Rathee's breakup has now taken an ugly turn after the actress
in a recent live video accused Digvijay of cheating on her with not one but multiple women
she went to meet Digvijay at his residence
but the Bigg Boss 18 fame refused to even open the door for her
She states that Digvijay has been accusing her of cheating as she spoke to her 'ex boyfriend,' however
he is the one who has slept with multiple women
''Just because ladki agar apne ex se baat kar rahi hai kyunke wo nahi hai sahi situation mein toh wo cheating ho gayi aur tum ladkiyon ke sath jaa kar so rahe ho
this reaction of Unnati came after Digvijay
in a recent interview claimed that Unnati was 'cheating on him.' In an interview with Filmy Gyaan
the Bigg Boss 18 fame stated that she 'refused' for him to touch her mobile phone and that when he checked her phone after she fell asleep
He reveals blocking her after finding things out
indirectly speaking about a 'Splitsvilla contestan's booty call' has been doing rounds on the internet
Netizens are now associating the same with Digvijay
Next Read: Anshula Kapoor Recalls Boney Kapoor And Mona Kapoor's Ugly Divorce: 'No One Knew What To Say..'ADVT
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Rahul Bhat plays DSP Tomar in Netflix's new series Black Warrant
a gripping neo-noir thriller directed by Anurag Kashyap
became the talk of the Cannes Film Festival in 2023
Rahul's portrayal of the tormented and morally complex ex-cop resonated deeply with audiences
showcasing a level of craftsmanship that only an actor of his caliber could deliver
Rahul’s foray into the world of serious cinema truly began with Anurag Kashyap’s Ugly (2013)
The hard-hitting psychological thriller unraveled a gut-wrenching tale of loss and human frailty
Rahul played a struggling actor caught in a web of deceit and desperation
His raw and intense performance was a masterclass in authenticity
Rahul Bhat won hearts in his role as a Pakistani diplomat and Firdaus’ (Katrina Kaif) fiancé in Abhishek Kapoor's Fitoor
Rahul's magnetic appearance on screen was not only impactful but also left a lasting impression in the limited screen time he got
A remake of the 2018 Spanish film ‘Mirage’
the Hindi version helmed by Anurag Kashyap delves into the life of a young woman who gets the power to manipulate time
Rahul’s impactful performance in ‘Dobaara’ garnered him critical appreciation
Union Leader (2017) is a hard-hitting movie that explores the life of a chemical factory supervisor who tries to help his fellow workers by raising his voice against the toxic conditions at the factory
Rahul carefully depicts the vulnerabilities of a common man in this emotional thriller
a supervisor at a chromium sulfate factory of Apollo Chemicals in Gujarat
Rahul ticked off every actor’s dream role by playing Dev in director Sudhir Mishra’s romantic political thriller
The film is a modern adaptation of Sarat Chandra Chattopadhyay’s celebrated novel ‘Devdas’
Rahul Bhat highlighted a unique spectrum of emotions in the film as Dev Pratap Chauhan
Rahul Bhat highlighted the life of a common man in Umesh Shukla’s ‘Chakki’
The film revolves around Vijay whose life takes an unexpected turn when his flour mill’s electricity bill goes exorbitantly high