Dopamine Gut Brain Vagus Nerve Reward Addiction

Gut-Brain Vagus Nerve Rewrites Dopamine Science, Challenging Brain-Only Addition Models

Dopamine, the neurotransmitter that shapes motivation, pleasure, mood and learning, has gained unexpected celebrity in recent years, becoming a buzzword for the fleeting highs of social media, comfort food and impulse shopping. This popularity has reinforced the idea that dopamine operates solely within the brain, where it is best known for its role in the mesolimbic pathway—a reward circuit linking the Ventral Tegmental Area (VTA) with the Nucleus Accumbens (NAc), amygdala and hippocampus.

However, new research published in Science Advances challenges this narrow view. The study reveals that the vagus nerve, which forms a vital communication bridge between the brain and the gut, also plays a crucial role in regulating motivation and reward-related behaviour.

The Gut-Brain-Vagal Axis Explained

The vagus nerve serves as the primary communication highway of the gut-brain axis, a sophisticated network that links peripheral organs to the brain. Through this pathway, the body continuously sends internal signals related to mood, digestion, inflammation and stress, shaping how the brain interprets physical states.

Explaining their findings, the study's authors highlight the gut as a central coordinator of this body-brain dialogue. They note that metabolically active organs, particularly the gut, influence brain function through hormonal signals, metabolites produced by gut microbes and a complex web of local and long-distance neural connections.

While previous research has largely focused on brain-centered models of reward, some studies have shown that gut-to-brain signaling via the vagus nerve can influence dopamine activity linked to food and eating behaviour. Until now, however, it remained unclear whether these gut-driven signals also affect other dopamine-fueled addictions.

Disrupted Vagal Signaling Alters Dopamine Activity

To investigate how strongly the gut-brain-vagal axis influences dopamine-driven reward, researchers carried out a series of experiments using mice. In some trials, the vagus nerve was surgically severed through a Subdiaphragmatic Vagotomy (SDV), allowing scientists to compare food-and drug-related reward behaviours between SDV mice and unaltered, or "Sham", mice. Dopamine activity inside the brain was tracked in real time using fiber photometry, alongside molecular testing and electrophysiological measurements.

The findings revealed that the gut-brain vagal axis plays a critical role in both food-and drug-induced reward. When offered foods typically considered addictive, SDV mice ate more slowly and consumed les overall, while unaltered mice showed a rapid rise in intake over a ten-day period.

Behavioural Changes in Food Motivation

The researchers observed heightened excitement in sham mice, a response that was notably absent in SDV mice. Using their experimental model alongside telemetric monitoring of movement, they found that sham mice showed increased activity both before eating—reflecting food anticipation — and during consumption itself.

By contrast, SDV mice displayed markedly reduced movement during both phases. Crucially, this difference was not linked to any underlying mobility problems, as sham and SDV mice showed comparable activity levels during the dark, foraging period and under normal baseline conditions.

Drug Experiments Reveal Similar Patterns

Comparable patterns emerged in drug-related experiments involving substances such as cocaine, morphine and amphetamines. SDV mice showed diminished locomotor responses to both morphine and cocaine, suggesting the vagus nerve plays a role in shaping dopamine signaling or its integration in the brain. Amphetamines, however, produced no consistent differences and showed dose-dependent effects in conditioning tests.

The researchers report that while sham mice developed a clear preference for cocaine, SDV mice showed no such conditioning. The response to amphetamine, however, varied with dose. At 2 mg/kg, both SDV and sham mice displayed positive conditioning.

At a lower dose of 1 mg/kg, the picture changed. SDV mice showed a reduced conditioning response compared with controls, indicating that the neural adaptations linked to SDV may be masked when dopamine levels rise sufficiently at higher doses.

Dopamine Signaling Inside the Brain

Further in vivo experiments revealed that an intact vagus nerve is essential for:

• Normal dopamine neuron firing
• Dopamine-driven molecular changes
• Structural plasticity within the brain's reward circuits

Using fiber photometry, the researchers found that severing the vagus nerve delayed dopamine signaling in the nucleus accumbens and reduced dopamine responses during food anticipation, eating and following drug exposure.

Despite these changes, dopamine function was not entirely lost. Movement-related processes remained intact, although overall activity was diminished, with dopamine neurons firing less frequently and receiving weaker excitatory input.

Implications for Addiction Treatment in Humans

The findings strengthen the case that the gut, acting through the vagus nerve, plays a direct and vital role in shaping reward and motivation. However, treatment for addiction that rely on reducing vagal signaling remain a distant prospect.

Surgically severing the vagus nerve, as done in the mouse experiments, is neither practical nor desirable in humans and could carry significant side effects. The researchers also caution that the gut may adapt over time, developing compensatory mechanisms to offset the loss of signaling.

As a result, further research is essential. The team suggests future studies should focus on more precise genetic or vital techniques to isolate specific vagal circuits, or explore alternative ways of modulating vagal activity. With further refinement, such approaches could one day contribute to treatments for eating disorders and addition.

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Key Takeaways for Readers

• Dopamine is influenced not only by the brain but also by gut-brain signaling.
• The vagus nerve plays a critical role in food and drug reward behaviour.
• Disrupting vagal signaling alters dopamine activity without eliminating movement.
• Future addiction treatments may target gut-brain communication rather than the brain alone.

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Earliest Genetic Diagnosis Prehistoric DNA Romito

Ancient DNA Reveals Rare Genetic Growth Disorder in 12,000-Year-Old Mother and Daughter

Researcher Identify Rare Inherited Growth Disorder in a Prehistoric Mother and Daughter

Researchers from the University of Vienna, working alongside Liège University Hospital Center, have identified genetic mutations associated with a rare inherited growth disorder in two prehistoric people dating back over 12,000 years. Through the analysis of ancient DNA alongside modern clinical genetic techniques, the team diagnosed the condition in a mother and daughter interred together in southern Italy. Their study, published in the New England Journal of Medicine, highlights the growing power of paleogenomics to reveal both ancient population histories and rare genetic conditions.

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Grotta del Romito burial revisited

The discovery follows a renewed investigation of a famous Upper Palaeolithic burial site uncovered in 1963 at Grotta del Romito. For decades, researchers have debated the meaning of the burial and the unusual skeletal traits observed, with lingering uncertainty surrounding the pair's relationship and the biological cause of their reduced height.

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A Remarkable Double Burial Raises Long-Standing Questions

The Romito Burial Explained

The two individuals were buried together in a striking embrace. The younger figure, known as "Romito 2", an adolescent with markedly shortened limbs and long believed to be male, was found resting in the arms of "Romito 1", previously identified as an adult woman. Careful examination revealed no evidence of injury or violent death.

Romito 2 is estimated to have stood around 110 cm tall, a stature consistent with a rare skeletal condition known as acromesomelic dysplasia, although this diagnosis could not be confirmed from bone evidence alone. Romito 1 was also notably short for the era, measuring approximately 145 centimeters.

For decades, scholars have debated:

• The biological sex of both individuals
• Their familial relationship
• Whether a shared medical condition explained their reduced height

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Ancient DNA Unlocks Family relationship and Genetic Cause

To resolve these questions, researchers extracted ancient DNA from the petrous portion of the temporal bone in both individuals, an area known for exceptional genetic preservation. The analysis confirmed a first-degree biological relationship.

The team then examined genes linked to skeletal development, comparing the detected variants with modern clinical databases. This interdisciplinary investigation brought together:

• Paleogenomics
• Clinical genetics
• Physical anthropology

The research involved experts from the University of Vienna alongside collaborators in Italy, Portugal and Belgium.

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Genetics and inherited conditions

Earliest Genetic Diagnosis Ever Identified in Humans

The genetic analysis revealed that both individuals were female and closely related at the first-degree level, most likely a mother and her daughter.

In the younger individual, Romito 2, researchers identified a homozygous mutation in the NPR2 gene, a gene known to play a crucial role in skeletal development.

This findings confirmed a diagnosis of acromesomelic dysplasia, Maroteaux type — a very rare inherited condition marked by:

• Extreme short stature
• Pronounced limb shortening

Genetic evidence from Romito 1 showed that she carried a single altered copy of the same gene, a variant typically associated with a milder reduction in height.

Rare Diseases Have Roots in Human History

Ron Pinhasi of the University of Vienna, who co-led the research, says the use of ancient DNA is transforming how scientists interpret the past.

"By analyzing genetic material from prehistoric individuals, we can now pinpoint specific mutations," he explains. "This allows us to trace how far back rare genetic conditions extend and may even reveal variants that have never been documented before."

Daniel Fernandes of the University of Coimbra, the study's lead author, adds that confirming both individuals as female and closely related reframes the burial as a rare familial genetic case.

"The milder short stature of the older woman is consistent with a heterozygous mutation," he says, "demonstrating how the same gene could affect members of a prehistoric family in different ways."

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Clinical Insights From Prehistoric Genetics

From a clinical perspective, the findings underline the long history of rare diseases. Adrian Daly of Li ège University Hospital Center, a co-leader of the study, notes:

"Rare genetic disorders are not a modern development. They have existed throughout human history and understanding their past can help us recognize and interpret these conditions today."

Evidence of Compassion and Long-Term Social Care

Despite profound physical limitations, Romito 2 lived into adolescence or possible adulthood, pointing to long-term care within her community.

Alfredo Coppa of Sapienza University of Rome, a co-leader of the study, says her survival would almost certainly have depended on sustained support.

"We believe she was cared for by her group over many years, receiving assistance with food and movement in what would have been a demanding environment," he explains.

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Toxic Masculinity Manosphere Study Male Idenity

Is All Masculinity Toxic? New Study Break Down Five Male Identity Types

A growing online subculture known as the "manosphere" has emerged across forums and social media, promoting a hardline view of masculinity rooted in dominance, misogyny and hostility towards feminism—traits widely described as toxic.

Researchers Flag Lack of Clear Evidence

Amid rising concern over the influence of such movements, researchers noted a striking lack of solid evidence clearly defining or measuring what toxic masculinity actually looks like.

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Large-Scale Study of Masculinity in New Zealand

To address this gap, the team analyzed nationwide data from a representative sample of 15,808 heterosexual men in New Zealand, aged between 18 and 99. They assessed levels of gender identification alongside attitudes including sexism, sexual prejudice, narcissism and support for social dominance, identifying five distinct profiles. The largest group, representing 35.4% of participants, showed largely non-toxic patterns.

Gender Identity Not Strongly Linked to Toxic Behaviour

One of the study's more unexpected conclusions was that a strong sense of gender identity was not closely linked to toxic behaviour. Even among men whose views aligned with patterns associated with toxic masculinity, being male played only a slightly greater role in their self-identity than it did for others.

The researchers stress that identifying strongly as "manly" does not, in itself, make someone toxic. The findings were published in Psychology of Men & Masculinities.

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Is All Masculinity Toxic?

Origins of the Term

The term toxic masculinity was first introduced in 1990 by psychologist Shepherd Bliss as part of the mythopoetic men's movement. He used it to describe behaviours that harm women, children and other men, pointing to a damaging aspect of male psychology. Since the rise of the Metoo movement, the meaning of the term has broadened significantly.

How the Meaning of Toxic Masculinity Has Expanded

Today, it is often used as an umbrella label covering issues ranging from explicit misogyny and rape culture to limits on women's reproductive rights, mansplaining and men's avoidance of domestic labour.

Concerns Over Vague Use of the Term

Despite its widespread use in public debate—and more than 10,000 academic articles published since 2020 —many studies fail to measure toxic masculinity empirically. Instead, the term is frequently employed as a general expression of disapproval.

Researchers warn that treating masculinity as inherently toxic may be counterproductive, particularly at a time when many men face serious challenges around health and wellbeing.

Health and wellbeing perspectives

Traits Used to Measure Problematic Masculinity

To address this gap, the researchers examined how widespread different forms of problematic masculinity are by analyzing eight core traits and beliefs:

• Centrality of gender identity
• Sexual prejudice
• Disagreeableness
• Narcissism
• Hostile sexism
• Benevolent sexism
• Opposition to domestic violence prevention
• Support for social dominance

Data Source and Analytical Approach

The team drew on data from the long-running New Zealand Attitudes and Values Study (NZAVS) and applied latent profile analysis, a statistical technique used to identify distinct groups within large datasets. this approach revealed five separate masculinity profiles.

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Five Distinct Masculinity Profiles Identified

The analysis showed:

• 35.4% fell into an atoxic category, showing consistently low levels across all harmful indicators
• 53.8% were grouped into two moderate profiles, with generally low-to-moderate scores that differed mainly in levels of sexual prejudice
• 7.6% fit a benevolent toxic profile, marked by high benevolent sexism alongside elevated sexual prejudice
• 3.2% fell into a hostile toxic category, marked by high levels of sexism, narcissism and opposition to efforts aimed at preventing domestic violence

Masculinity and Harm Are Not the Same

The findings further showed that a strong identification with being "manly" did not automatically signal problematic masculinity.

Researchers stressed the importance of distinguishing harmful expressions of masculinity from healthy and positive ones, noting that future studies using more diverse samples could help shape targeted interventions for different toxic masculinity profiles.

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Jelly Like Artificial Nerve Senses Human pain

Scientists Develop Jelly-Like Artificial Nerve That Can Sense Pain Like Humans

Artificial Nociceptors Inspired by the Human Body

Scattered throughout the human body are microscopic sensors known as nociceptors, which detect potentially harmful stimuli and relay warning signals to the brain and spinal cord, helping to prevent injury and tissue damage.

Breakthrough in Artificial Pain-Sensing Technology

In a recent breakthrough, researchers at Northeast Normal University in China developed a soft, jelly-like artificial pain-sensing nerve pathway using a memristor — a tiny electronic component capable of regulating electrical flow while retaining a memory of past currents.

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How the Artificial Pain Sensor Works

Thanks to a property known as quantized conductance, in which electrical signals move in discrete steps rather than a continuous flow, the artificial receptor was able to register four graded pain responses, closely mirroring the human experience:

• No pain
• Mild pain
• Moderate pain
• Severe pain

Self-Healing and Bio-Inspired Capabilities

The bio-inspired receptor also demonstrated self-healing capabilities, showing an ability to repair physical damage and gradually diminish pain signals over time.

Researchers believe that replicating the body's natural pain-sensing mechanisms could open new frontiers in neuroprosthetics and enable more intuitive interactions between humans and machines.

The study has been published in the journal Advanced Functional Materials.

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Get That Senses Pain at Different Levels

Limits of Earlier Artificial Nociceptors

Artificial nociceptors have been the subject of scientific research for many years. Early efforts relied on conventional semiconductor technology, but this approach required complex, bulky circuitry to replicate even the most basic human pain responses.

Role of Memristors in Pain Detection

The emergence of memristors marked a turning point, shifting attention away from traditional semiconductors towards compact, two-terminal devices well suited to brain-inspired computing. Using their unique switching behaviour, scientists have created artificial pain sensors that intensify their response to repeated stimulation, without becoming desensitized over time as natural pain receptors do.

Despite this progress, many existing artificial nociceptors still struggle to replicate graded pain levels and self-healing abilities, both of which are essential for realistic pain perception and recovery.

Testing Pain Sensitivity and Human-Like Responses

In this study, researchers achieved greater precision in pain sensing by combining two types of gelatin film:

• A 10 wt.% formulation for pressure detection
• A 1 wt.% formulation for the memristor

When linked in series, these components formed an artificial nerve pathway.

Pressure Testing and Pain Response Levels

To test its sensitivity, the team applied mechanical pressures ranging from 9 to 45 kPa (kilopascal), successfully identifying four distinct response levels, from no pain through to severe pain.

Demonstrating Self-Healing Ability

They also assessed the system's self-healing ability by introducing cuts up to 50.7 micrometers wide into the gelatin sensors. After heating the material to 60°C for 20 minutes, the damage vanished and the electrical performance returned to its original state.

Successful Testing in a Living Nervous System

The artificial pain sensor was linked to the sciatic nerve of an anaesthetized mouse. When pressure was applied, the device generated electrical signals that triggered muscle contractions, closely replicating a natural withdrawal response.

Implications for Human-Machine Interaction

The findings suggest that soft, jelly-like materials designed to imitate pain receptors could transform human-machine interfaces and support the development of more effective rehabilitation technologies for people recovering from injury.

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Acetaminophen Pregnancy Autism ADHD Lancet Study

Major Study Finds No Link Between Acetaminophen Use in Pregnancy and Autism or ADHD

Largest Review to Date Addresses Long-Standing Safety Concerns

A major new study has found no evidence that taking acetaminophen during pregnancy increases the likelihood of autism, ADHD or intellectual disability in children. Published in The Lancet Obstetrics, Gynecology & Women's Health, the research was led by scientists from City St George's, University of London.

Why the Study Was Conducted

The researchers examined data from 43 earlier studies in a detailed systematic review and meta-analysis, aiming to settle long-running questions about the drug's safety during pregnancy. The review was prompted by public concern after claims made in September 2025 suggested acetaminophen could harm children's neurodevelopment.

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Earlier Claims and Scientific Concerns

While some earlier studies hinted at slight associations with autism, the new analysis found these claims were often based on flawed evidence. Many failed to control for bias, used incomplete data or overlooked sibling comparisons — an essential step in separating drug effects from family-related influences.

How the Research Was Conducted

Review of High-Quality Studies

The researchers examined 43 of the highest-quality studies, using the most robust research methods available, to compare pregnancies in which mothers took acetaminophen with those in which the drug was not used.

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Sibling-Comparison Analysis Explained

They combined findings from sibling-comparison studies, analyzing families where one child was exposed to acetaminophen in the womb and another was not. This powerful approach helps account for shared genetics, home environment and long-standing parental factors that standard observational studies often miss.

Large-Scale Data Strengthens Findings

In total, the sibling data covered:

• 262,852 children assessed for autism
• 335, 255 children assessed for ADHD
• 406, 681 children assessed for intellectual disability

The analysis confirmed that prenatal acetaminophen use was not associated with an increased risk of any of these conditions.

Expert Opinion: Acetaminophen Remains First-Line Treatment

Professor Asma Khalil, professor of obstetrics and maternal-fetal medicine at City St George's, University of London and the study's lead author, said the findings point away from acetaminophen as the cause of earlier reported risks. Instead, she explained, those links are more likely due to genetic predisposition or other maternal factors, such as fever or underlying pain.

"The message is clear," she said. "Acetaminophen remains a safe option in pregnancy when taken as recommended. It is the first-line treatment we advise for pregnant women experiencing pain or fever, and they should feel confident that they still have a safe way to manage their symptoms."

Pregnancy and maternal health resources

Quality Assessment and Long-Term Consistency

All studies were assessed using the Quality in Prognosis Studies (QUIPS) tool, which evaluates multiple aspects of study design to determine the risk of bias. Crucially, the lack of any association between prenatal acetaminophen use and autism, ADHD or intellectual disability remained consistent in the highest-quality studies and in those with follow-up periods exceeding five years.

Study Limitations Acknowledged

Researchers noted that the study was limited by gaps in the available data, which made it impossible to analyze smaller subgroups in sibling-comparison research. Too few studies provided information on:

• Trimester-specific use
• Sex of the child
• Frequency of acetaminophen intake

Medical Guidance and Public Health Implications

Even so, the findings align closely with recommendations from major medical bodies worldwide. The team hopes the strength of this comprehensive review will dispel ongoing concerns, warning that avoiding acetaminophen for significant pain or fever can expose both pregnant women and their babies to known dangers, particularly untreated maternal fever.

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Bat Borne Orthoreovirus Bangladesh

Bat-Borne Orthoreovirus Linked to Mysterious Respiratory and Brain Illness in Bangladesh

Infections disease specialists have traced a mysterious illness affecting five patients in Bangladesh to Pteropine orthoreoviruses (PRVs)—a newly emerging group of bat-borne pathogens. One of the patients later died after suffering from unexplained complications, raising fresh concerns over hidden viral threats.

This marks the first recorded instance of a bat-origin orthoreovirus, a double-stranded RNA virus, being linked to acute respiratory disease and encephalitis in humans in Bangladesh. The research has been published in the journal Emerging Infectious Diseases.

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Raw Date-Palm Sap Identified as a Common Exposure

Investigators found that all five patients had recently consumed raw date-palm sap, a seasonal delicacy that bats frequently feed on during winter. The sap has already been identified as a transmission route for Nipah virus in the country.

Bats are recognized as natural hosts for a wide range of zoonotic viruses, including rabies, Nipah, Hendra, Marburg and SARS-1.

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Scientists Warn of Broader Zoonotic Spillover Risks

"Our research shows that the danger of zoonotic spillover linked to the consumption of raw date-palm sap goes well beyond Nipah virus," said Dr Nischay Mishra, Associate Professor of Epidemiology at the Center for Infection and Immunity, Columbia University Mailman School of Public Health, and the study's senior author.

He stressed the urgent need for broad-spectrum surveillance systems to detect and reduce public health threats posed by newly emerging bat-borne viruses.

Patients Initially Suspected of Nipah Virus Infection

The five patients, who hospitalized between 2022 and 2023, were initially suspected of having Nipah virus infection. However, laboratory tests repeatedly returned negative results, despite the patients displaying similar symptoms such as:

• Fever
• Vomiting
• Headaches
• Fatigue
• Excessive salivation
• Serious respiratory complications
• Neurological complications

Human Health and infectious disease insights

Advanced Viral Sequencing Reveals the Culprit

In the latest study, scientists carried out high-throughput, agnostic viral sequencing using the CII's VirCapSeq-VERT platform. Biological samples were analyzed from the five confirmed cases, alongside samples from more than 130 patients who had shown Nipah-like symptoms between 2006 and 2022.

The work formed part of a long-running Nipah virus surveillance programme led by:

• Bangladesh's Institute of Epidemiology, Disease Control and Research (IEDCR)
• The International Centre for Diarrhoeal Disease Research, Bangladesh (ICDDR,B)
• The US Centres for Disease Control and Prevention (CDC)

How VirCapSeq-VERT Detects Emerging Viruses

Dr Nishchay Mishra and his team employed VirCapSeq-VERT, a technology developed at the Centre for Infection and Immunity, to rapidly detect all known vertebrate-origin viral infections.

The system matches the sensitivity of gold-standard PCR testing, while allowing thousands of viruses to be screened simultaneously and delivering near-complete viral genome sequences.

Live Infectious Virus Confirmed in the Laboratory

Researchers also confirmed the presence of live, infectious virus through laboratory culture. All five patients suffered severe illness, although PRV infections reported in neighbouring countries have typically been milder, raising concerns that less serious cases in Bangladesh may be going undetected.

"This represents a new zoonotic spillover risk, causing respiratory and neurological complications following the consumption of raw date-palm sap, alongside the well-known threat of Nipah virus," said Dr Tahmina Shirin, Director of the Institute of Epidemiology, Disease Control and Research (IEDCR) and the National Influenza Centre (NIC) in Bangladesh.

Bats Near Patient Homes Identified as Likely Source

In more recent work, Mishra and his colleagues traced the source of infection by identifying genetically similar Pteropine orthoreoviruses in bats captured near the homes of the five patients in the Padma River Basin.

These findings, though yet to be published, strengthen the suspected animal-to-human link.

"This research offers vital evidence connecting bat reservoirs to human infection," said Ariful Islam, a bat-borne disease ecologist and epidemiologist at Charles Sturt University in Australia and co-first author of the study.

"We are now investigating how spillover occurs from bats to humans and domestic animals, and examining the wider ecology of emerging bat-borne viruses in communities along the Padma River Basin."

Technology Already Proven in Other Major Outbreak Investigations

In earlier work, Mishra and his colleagues used the same technology to:

• Uncover a previously unrecognized viral threat in transplant patients
• Identify neurological complications in an infant and COVID-19
• Trace an enterovirus infection responsible for a rare neurological disorder
• Determine the origins of chikungunya in Brazil

Beyond its use in research settings, VirCapSeq-VERT has now secured regulatory approval for clinical application.

Study Authorship

The study was co-first authored by Sharmin Sultana, Assistant Professor of Virology and Senior Scientific Officer at Bangladesh's Institute of Epidemiology, Disease Control and Research (IEDCR).

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Human Brain Prefrontal Cortex Development Macaques

Why the Human Brain Develops Differently From Other Primates, New Research Reveals

The Human Brain's Unique Developmental Journey

The human brain stands as one of nature's most remarkable achievements, enabling advanced behaviours and cognitive skills that are not found in any other species. For generations, scientists have sought to uncover what sets the human brain apart and how it evolves throughout a person's lifetime.

In recent years, breakthroughs in technology and experimental methods have transformed neuroscience, allowing researchers to map brain structure and function with unprecedented precision. These advances are offering valuable insights into the biological roots of neuropsychiatric and neurodevelopmental conditions.

Comparing Human and Macaque Brain Development

A research team from Beijing Normal University, the Changping Laboratory and partner institutions has now compared the developmental trajectories of the human and macaque brains using cutting-edge genetic and molecular techniques. Their findings, published in Nature Neuroscience, reveal notable differences between the species, particularly showing that the human prefrontal cortex develops at a slower pace than that of macaques.

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Decoding Prefrontal Cortex Development at Cellular Level

Decoding how the human prefrontal cortex (PFC) develops at the cellular and molecular level is key to understanding both human intelligence and vulnerability to neurological and neuropsychiatric conditions, the researchers explained.

Jiyao Zhang, Mayuqing Li and their team reported the creation of a unique comparative resource that captures gene activity, chromatin structure and spatial transcriptomic patterns in the postnatal PFC of humans and macaques, analyzed one cell at a time.

Mapping Brain Development at a Single-Cell Level

The study involved high-resolution mapping of brain development using tissue samples collected from the prefrontal cortex of humans and macaques at different postnatal stages. Human tissue was sourced from paediatric epilepsy patients undergoing medically necessary brain surgery.

The research team examined gene activity within individual cells extracted from the collected tissue, alongside chromatin accessibility, which indicates how open or closed DNA is inside each cell. Using spatial transcriptomics, they also charted gene expression across entire brain sections and identified the various cell types present.

According to the authors, these integrated analyses revealed species-specific developmental pathways for different cell populations, pinpointing critical periods and gene regulatory networks involved in synapse formation, synaptic pruning and gliogenesis.

Environmental science & evolution context

Human-Specific Brain Development Mechanisms Identified

The findings showed that the human prefrontal cortex develops over a longer timeframe than that of macaques. In addition, glial progenitor cells —steam-like cells that later give rise to specialized glial types—were found to proliferate more extensively in humans.

The researchers reported that they had identified regulatory mechanisms linked to the extended development of the human prefrontal cortex compared with that of macaques. They found that glial progenitor cells in humans display a greater capacity for proliferation, accompanied by distinctive gene expression patterns.

The study also pinpointed specific cell types and development lineages that appear most vulnerable to neurodevelopmental and neuropsychiatric disorders, with particular emphasis on transcription factors showing human-specific expression.

Insights That Could Deepen Understanding of Human Cognition

Zhang, Li and their colleagues uncovered a series of important findings that offer deeper insight into well-known functional differences between human brains and those of other primates. The team identified transcription factors that influence human brain development but appear absent in macaques, while also highlighting specific cell types in human tissue that are commonly affected in patients with certain neurological disorders.

"Our findings reveal human-specific regulatory programmes that extend postnatal cortical maturation through coordinated neuronal and glial development, with clear implications for cognition and neurodevelopmental disorders," the researchers wrote.

Looking ahead, these results could improve understanding of how the human brain matures and which molecular pathways are disrupted in neurodevelopmental and neuropsychiatric conditions, potentially opening the door to new preventive or therapeutic approaches.

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