Obsessive-Compulsive Behavior Isn't Necessarily a Bad Thing.

It is difficult to believe that in about 1960 practically nothing was known about the thymus and some of its products, T cells bearing αß receptors for antigen. Thus I was lucky to join the field of T cell biology almost at its beginning, when knowledge about the cells was just getting off the ground and there was so much to discover. This article describes findings about these cells made by others and myself that led us all from ignorance, via complete confusion, to our current state of knowledge. I believe I was fortunate to practice science in very supportive institutions and with very collaborative colleagues in two countries that both encourage independent research by independent scientists, while simultaneously ignoring or somehow being able to avoid some of the difficulties of being a woman in what was, at the time, a male-dominated profession.

The power of hope.

My patient was in his late 20s and dying of an advanced sarcoma. He came to our institution seeking a miracle-a cure for his incurable cancer. Despite second and third opinions, he never relinquished his hope that science would cure him. In this story, I explore how hope allowed my patient, and others like him, to reclaim their narratives and maintain their personhood in the face of serious illness.

We like neurons.

Charleese Williams is the winner of the 2021 Rising Black Scientists Award for an undergraduate scholar. For this award, we asked emerging Black scientists to tell us about the experiences that sparked their interest in the life sciences, their vision and goals, and how they want to contribute to a more inclusive scientific community. This is her story.

Science as a tool for justice.

Elle Lett is the winner of the 2021 Rising Black Scientists Award for a post-graduate scholar. For this award, we asked emerging Black scientists to tell us about the experiences that sparked their interest in the life sciences, their vision and goals, and how they want to contribute to a more inclusive scientific community. This is her story.

Interdisciplinary approaches are fundamental to decode the biology of adversity.

The COVID-19 pandemic has highlighted structural inequalities and racism promoting health disparities among communities of color. Taking cardiovascular disease as an example, we provide a framework for multidisciplinary efforts leveraging translational and epidemiologic approaches to decode the biological impacts of inequalities and racism and develop targeted interventions that promote health equity.

Infodemics: A new challenge for public health.

The COVID-19 information epidemic, or "infodemic," demonstrates how unlimited access to information may confuse and influence behaviors during a health emergency. However, the study of infodemics is relatively new, and little is known about their relationship with epidemics management. Here, we discuss unresolved issues and propose research directions to enhance preparedness for future health crises.

Race Matters.

Despite their initial high interest in science, students who belong to excluded racial and ethnic groups leave science at unacceptably high rates. "Fixing the student" approaches are not sufficient at stemming the loss. It is time to change the culture of science by putting inclusive diversity at the center.

Lifted Up from Lockdown.

The pandemic has impacted every scientist differently. Many negative impacts are frequently discussed. Here we highlight unexpected positives that we have found and hope will persist: improved access to experts; deeper and broader human engagement among colleagues, collaborators, and competitors; and significant democratization of research.

Restoring the Sense of Touch Using a Sensorimotor Demultiplexing Neural Interface.

Paralyzed muscles can be reanimated following spinal cord injury (SCI) using a brain-computer interface (BCI) to enhance motor function alone. Importantly, the sense of touch is a key component of motor function. Here, we demonstrate that a human participant with a clinically complete SCI can use a BCI to simultaneously reanimate both motor function and the sense of touch, leveraging residual touch signaling from his own hand. In the primary motor cortex (M1), residual subperceptual hand touch signals are simultaneously demultiplexed from ongoing efferent motor intention, enabling intracortically controlled closed-loop sensory feedback. Using the closed-loop demultiplexing BCI almost fully restored the ability to detect object touch and significantly improved several sensorimotor functions. Afferent grip-intensity levels are also decoded from M1, enabling grip reanimation regulated by touch signaling. These results demonstrate that subperceptual neural signals can be decoded from the cortex and transformed into conscious perception, significantly augmenting function.

The neuroimmunology of social-stress-induced sensitization.

Myriad clinical findings provide links between chronic stressors, inflammation, and mood disorders. Furthermore, traumatic or chronic exposure to psychological stressors may promote stress sensitization, in which individuals have long-term complications, including increased vulnerability to subsequent stressors. Post-traumatic stress disorder (PTSD) is a clinically relevant example of stress sensitization. PTSD alters neuronal circuitry and mood; however, the mechanisms underlying long-term stress sensitization within this disorder are unclear. Rodent models of chronic social defeat recapitulate several key physiological, immunological, and behavioral responses associated with psychological stress in humans. Repeated social defeat (RSD) uniquely promotes the convergence of neuronal, central inflammatory (microglial), and peripheral immune (monocyte) pathways, leading to prolonged anxiety, social withdrawal, and cognitive impairment. Moreover, RSD promotes stress sensitization, in which mice are highly sensitive to subthreshold stress exposure and recurrence of anxiety weeks after the cessation of stress. Therefore, the purpose of this Review is to discuss the influence of social-defeat stress on the immune system that may underlie stress sensitization within three key cellular compartments: neurons, microglia, and monocytes. Delineating the mechanisms of stress sensitization is critical in understanding and treating conditions such as PTSD.

Meningeal γδ T cells regulate anxiety-like behavior via IL-17a signaling in neurons.

Interleukin (IL)-17a has been highly conserved during evolution of the vertebrate immune system and widely studied in contexts of infection and autoimmunity. Studies suggest that IL-17a promotes behavioral changes in experimental models of autism and aggregation behavior in worms. Here, through a cellular and molecular characterization of meningeal γδ17 T cells, we defined the nearest central nervous system-associated source of IL-17a under homeostasis. Meningeal γδ T cells express high levels of the chemokine receptor CXCR6 and seed meninges shortly after birth. Physiological release of IL-17a by these cells was correlated with anxiety-like behavior in mice and was partially dependent on T cell receptor engagement and commensal-derived signals. IL-17a receptor was expressed in cortical glutamatergic neurons under steady state and its genetic deletion decreased anxiety-like behavior in mice. Our findings suggest that IL-17a production by meningeal γδ17 T cells represents an evolutionary bridge between this conserved anti-pathogen molecule and survival behavioral traits in vertebrates.

How Instructions, Learning, and Expectations Shape Pain and Neurobiological Responses.

Treatment outcomes are strongly influenced by expectations, as evidenced by the placebo effect. Meta-analyses of clinical trials reveal that placebo effects are strongest in pain, indicating that psychosocial factors directly influence pain. In this review, I focus on the neural and psychological mechanisms by which instructions, learning, and expectations shape subjective pain. I address new experimental designs that help researchers tease apart the impact of these distinct processes and evaluate the evidence regarding the neural mechanisms by which these cognitive factors shape subjective pain. Studies reveal that expectations modulate pain through parallel circuits that include both pain-specific and domain-general circuits such as those involved in affect and learning. I then review how expectations, learning, and verbal instructions impact clinical outcomes, including placebo analgesia and responses to pharmacological treatments, and discuss implications for future work.

A Cortical Circuit for Sexually Dimorphic Oxytocin-Dependent Anxiety Behaviors.

The frequency of human social and emotional disorders varies significantly between males and females. We have recently reported that oxytocin receptor interneurons (OxtrINs) modulate female sociosexual behavior. Here, we show that, in male mice, OxtrINs regulate anxiety-related behaviors. We demonstrate that corticotropin-releasing-hormone-binding protein (CRHBP), an antagonist of the stress hormone CRH, is specifically expressed in OxtrINs. Production of CRHBP blocks the CRH-induced potentiation of postsynaptic layer 2/3 pyramidal cell activity of male, but not female, mice, thus producing an anxiolytic effect. Our data identify OxtrINs as critical for modulation of social and emotional behaviors in both females and males and reveal a molecular mechanism that acts on local medial prefrontal cortex (mPFC) circuits to coordinate responses to OXT and CRH. They suggest that additional studies of the impact of the OXT/OXTR and CRHBP/CRH pathways in males and females will be important in development of gender-specific therapies.

Navigating COVID-19: Starting a lab during the pandemic.

For new principal investigators, the first years are key to getting a laboratory off the ground and running. COVID-19 has changed the world, bringing on unforeseen difficulties and challenges at every level. We asked these investigators to share their experiences in navigating the unique environment since the start of the pandemic-what has changed in their vision for their laboratory, how they have adapted, and what advice they can share with others in a similar situation.

Monkeys in a prisoner's dilemma.

Haroush and Williams trained pairs of monkeys to play in a prisoner's dilemma game, a model of social interactions. Recording from the dorsal anterior cingulate cortex (dACC), they find neurons whose activity reflects the anticipation of the opponent's yet unknown choice, which may be important in guiding animals' performance in the game.

Neuronal prediction of opponent's behavior during cooperative social interchange in primates.

A cornerstone of successful social interchange is the ability to anticipate each other's intentions or actions. While generating these internal predictions is essential for constructive social behavior, their single neuronal basis and causal underpinnings are unknown. Here, we discover specific neurons in the primate dorsal anterior cingulate that selectively predict an opponent's yet unknown decision to invest in their common good or defect and distinct neurons that encode the monkey's own current decision based on prior outcomes. Mixed population predictions of the other was remarkably near optimal compared to behavioral decoders. Moreover, disrupting cingulate activity selectively biased mutually beneficial interactions between the monkeys but, surprisingly, had no influence on their decisions when no net-positive outcome was possible. These findings identify a group of other-predictive neurons in the primate anterior cingulate essential for enacting cooperative interactions and may pave a way toward the targeted treatment of social behavioral disorders.

Post-January 6th deplatforming reduced the reach of misinformation on Twitter.

The social media platforms of the twenty-first century have an enormous role in regulating speech in the USA and worldwide1. However, there has been little research on platform-wide interventions on speech2,3. Here we evaluate the effect of the decision by Twitter to suddenly deplatform 70,000 misinformation traffickers in response to the violence at the US Capitol on 6 January 2021 (a series of events commonly known as and referred to here as 'January 6th'). Using a panel of more than 500,000 active Twitter users4,5 and natural experimental designs6,7, we evaluate the effects of this intervention on the circulation of misinformation on Twitter. We show that the intervention reduced circulation of misinformation by the deplatformed users as well as by those who followed the deplatformed users, though we cannot identify the magnitude of the causal estimates owing to the co-occurrence of the deplatforming intervention with the events surrounding January 6th. We also find that many of the misinformation traffickers who were not deplatformed left Twitter following the intervention. The results inform the historical record surrounding the insurrection, a momentous event in US history, and indicate the capacity of social media platforms to control the circulation of misinformation, and more generally to regulate public discourse.

Hybrid working from home improves retention without damaging performance.

Working from home has become standard for employees with a university degree. The most common scheme, which has been adopted by around 100 million employees in Europe and North America, is a hybrid schedule, in which individuals spend a mix of days at home and at work each week1,2. However, the effects of hybrid working on employees and firms have been debated, and some executives argue that it damages productivity, innovation and career development3-5. Here we ran a six-month randomized control trial investigating the effects of hybrid working from home on 1,612 employees in a Chinese technology company in 2021-2022. We found that hybrid working improved job satisfaction and reduced quit rates by one-third. The reduction in quit rates was significant for non-managers, female employees and those with long commutes. Null equivalence tests showed that hybrid working did not affect performance grades over the next two years of reviews. We found no evidence for a difference in promotions over the next two years overall, or for any major employee subgroup. Finally, null equivalence tests showed that hybrid working had no effect on the lines of code written by computer-engineer employees. We also found that the 395 managers in the experiment revised their surveyed views about the effect of hybrid working on productivity, from a perceived negative effect (-2.6% on average) before the experiment to a perceived positive one (+1.0%) after the experiment. These results indicate that a hybrid schedule with two days a week working from home does not damage performance.

Online images amplify gender bias.

Each year, people spend less time reading and more time viewing images1, which are proliferating online2-4. Images from platforms such as Google and Wikipedia are downloaded by millions every day2,5,6, and millions more are interacting through social media, such as Instagram and TikTok, that primarily consist of exchanging visual content. In parallel, news agencies and digital advertisers are increasingly capturing attention online through the use of images7,8, which people process more quickly, implicitly and memorably than text9-12. Here we show that the rise of images online significantly exacerbates gender bias, both in its statistical prevalence and its psychological impact. We examine the gender associations of 3,495 social categories (such as 'nurse' or 'banker') in more than one million images from Google, Wikipedia and Internet Movie Database (IMDb), and in billions of words from these platforms. We find that gender bias is consistently more prevalent in images than text for both female- and male-typed categories. We also show that the documented underrepresentation of women online13-18 is substantially worse in images than in text, public opinion and US census data. Finally, we conducted a nationally representative, preregistered experiment that shows that googling for images rather than textual descriptions of occupations amplifies gender bias in participants' beliefs. Addressing the societal effect of this large-scale shift towards visual communication will be essential for developing a fair and inclusive future for the internet.

Artificial intelligence and illusions of understanding in scientific research.

Scientists are enthusiastically imagining ways in which artificial intelligence (AI) tools might improve research. Why are AI tools so attractive and what are the risks of implementing them across the research pipeline? Here we develop a taxonomy of scientists' visions for AI, observing that their appeal comes from promises to improve productivity and objectivity by overcoming human shortcomings. But proposed AI solutions can also exploit our cognitive limitations, making us vulnerable to illusions of understanding in which we believe we understand more about the world than we actually do. Such illusions obscure the scientific community's ability to see the formation of scientific monocultures, in which some types of methods, questions and viewpoints come to dominate alternative approaches, making science less innovative and more vulnerable to errors. The proliferation of AI tools in science risks introducing a phase of scientific enquiry in which we produce more but understand less. By analysing the appeal of these tools, we provide a framework for advancing discussions of responsible knowledge production in the age of AI.