Secretin: An Old Hormone with a Burning Secret.

Most theories of meal-induced thermogenesis involve a gut-brain-brown adipose tissue axis driving sympathetic nervous system-mediated thermogenesis. Li et al. demonstrate that secretin released by the gut after a meal binds to abundant receptors in brown adipose tissue to stimulate thermogenesis, inhibiting food intake and thereby suggesting a novel role for secretin regulating satiety.

Visualizing hypothalamic network dynamics for appetitive and consummatory behaviors.

Optimally orchestrating complex behavioral states, such as the pursuit and consumption of food, is critical for an organism's survival. The lateral hypothalamus (LH) is a neuroanatomical region essential for appetitive and consummatory behaviors, but whether individual neurons within the LH differentially contribute to these interconnected processes is unknown. Here, we show that selective optogenetic stimulation of a molecularly defined subset of LH GABAergic (Vgat-expressing) neurons enhances both appetitive and consummatory behaviors, whereas genetic ablation of these neurons reduced these phenotypes. Furthermore, this targeted LH subpopulation is distinct from cells containing the feeding-related neuropeptides, melanin-concentrating hormone (MCH), and orexin (Orx). Employing in vivo calcium imaging in freely behaving mice to record activity dynamics from hundreds of cells, we identified individual LH GABAergic neurons that preferentially encode aspects of either appetitive or consummatory behaviors, but rarely both. These tightly regulated, yet highly intertwined, behavioral processes are thus dissociable at the cellular level.

Clinical targeting of HIV capsid protein with a long-acting small molecule.

Oral antiretroviral agents provide life-saving treatments for millions of people living with HIV, and can prevent new infections via pre-exposure prophylaxis1-5. However, some people living with HIV who are heavily treatment-experienced have limited or no treatment options, owing to multidrug resistance6. In addition, suboptimal adherence to oral daily regimens can negatively affect the outcome of treatment-which contributes to virologic failure, resistance generation and viral transmission-as well as of pre-exposure prophylaxis, leading to new infections1,2,4,7-9. Long-acting agents from new antiretroviral classes can provide much-needed treatment options for people living with HIV who are heavily treatment-experienced, and additionally can improve adherence10. Here we describe GS-6207, a small molecule that disrupts the functions of HIV capsid protein and is amenable to long-acting therapy owing to its high potency, low in vivo systemic clearance and slow release kinetics from the subcutaneous injection site. Drawing on X-ray crystallographic information, we designed GS-6207 to bind tightly at a conserved interface between capsid protein monomers, where it interferes with capsid-protein-mediated interactions between proteins that are essential for multiple phases of the viral replication cycle. GS-6207 exhibits antiviral activity at picomolar concentrations against all subtypes of HIV-1 that we tested, and shows high synergy and no cross-resistance with approved antiretroviral drugs. In phase-1 clinical studies, monotherapy with a single subcutaneous dose of GS-6207 (450 mg) resulted in a mean log10-transformed reduction of plasma viral load of 2.2 after 9 days, and showed sustained plasma exposure at antivirally active concentrations for more than 6 months. These results provide clinical validation for therapies that target the functions of HIV capsid protein, and demonstrate the potential of GS-6207 as a long-acting agent to treat or prevent infection with HIV.

Author Correction: Increasing CO2 threatens human nutrition.

An Amendment to this paper has been published and can be accessed via a link at the top of the paper.

Adherence, clinical benefits, and adverse effects of endocrine therapies among women with nonmetastatic breast cancer in developing countries: A systematic review and meta-analysis.

BACKGROUND: Despite significant advances in breast cancer control and survival with endocrine therapies (ETs), treatment utilization and outcomes in developing countries have not been adequately explored. This review evaluated ET adherence, potential benefits, and harms in populations across developing countries. METHODS: A literature search was conducted through August 2023 in five databases: PubMed, Cochrane Library, Web of Science, Global Health, and WHO Global Index Medicus. Retrieved records were screened to identify observational research presenting at least one outcome in women with nonmetastatic breast cancer in developing countries who received ET (tamoxifen or aromatase inhibitors). A random effects model was used to compute the rates of adherence, discontinuation, adverse events (AEs), disease progression, and death. RESULTS: A total of 104 studies met the inclusion criteria. Risk of bias was low in most studies, and a large portion of the patients involved Asians. The overall heterogeneity between studies was partially attributed to variations in study design or outcome measurement method. Results showed a pooled adherence rate of 75% (95% confidence interval [CI], 67%-81%) and a discontinuation rate of 16% (95% CI, 10%-25%). Treatment side effects and young age consistently emerged as significant predictors of nonadherence. A wide range of AEs was identified in our analysis. The estimated average rates of cancer recurrence and mortality at 5-years were 16% and 8%, respectively. CONCLUSIONS: The findings of this study underscore suboptimal ET use in developing countries and provide comprehensive insights into treatment experiences in the real-world setting. Targeted strategies are warranted to enhance adherence and subsequently optimize treatment benefits.

The origin of squamates revealed by a Middle Triassic lizard from the Italian Alps.

Modern squamates (lizards, snakes and amphisbaenians) are the world's most diverse group of tetrapods along with birds 1 and have a long evolutionary history, with the oldest known fossils dating from the Middle Jurassic period-168 million years ago2-4. The evolutionary origin of squamates is contentious because of several issues: (1) a fossil gap of approximately 70 million years exists between the oldest known fossils and their estimated origin5-7; (2) limited sampling of squamates in reptile phylogenies; and (3) conflicts between morphological and molecular hypotheses regarding the origin of crown squamates6,8,9. Here we shed light on these problems by using high-resolution microfocus X-ray computed tomography data from the articulated fossil reptile Megachirella wachtleri (Middle Triassic period, Italian Alps 10 ). We also present a phylogenetic dataset, combining fossils and extant taxa, and morphological and molecular data. We analysed this dataset under different optimality criteria to assess diapsid reptile relationships and the origins of squamates. Our results re-shape the diapsid phylogeny and present evidence that M. wachtleri is the oldest known stem squamate. Megachirella is 75 million years older than the previously known oldest squamate fossils, partially filling the fossil gap in the origin of lizards, and indicates a more gradual acquisition of squamatan features in diapsid evolution than previously thought. For the first time, to our knowledge, morphological and molecular data are in agreement regarding early squamate evolution, with geckoes-and not iguanians-as the earliest crown clade squamates. Divergence time estimates using relaxed combined morphological and molecular clocks show that lepidosaurs and most other diapsids originated before the Permian/Triassic extinction event, indicating that the Triassic was a period of radiation, not origin, for several diapsid lineages.

Role of platelet count in a murine stasis model of deep vein thrombosis.

Platelets are core components of thrombi but their effect on thrombus burden during deep vein thrombosis (DVT) has not been fully characterized. We examined the role of thrombopoietin-altered platelet count on thrombus burden in a murine stasis model of DVT. To modulate platelet count compared to baseline, CD1 mice were pretreated with thrombopoietin antisense oligonucleotide (THPO-ASO, 56% decrease), thrombopoietin mimetic (TPO-mimetic, 36% increase), or saline (within 1%). Thrombi and vein walls were examined on postoperative days (POD) 3 and 7. Thrombus weights on POD 3 were not different between treatment groups (p = .84). The mean thrombus weights on POD 7 were significantly increased in the TPO-mimetic cohort compared to the THPO-ASO (p = .005) and the saline (p = .012) cohorts. Histological grading at POD 3 revealed a significantly increased smooth muscle cell presence in the thrombi and CD31 positive channeling in the vein wall of the TPO-mimetic cohort compared to the saline and THPO-ASO cohorts (p < .05). No differences were observed in histology on POD 7. Thrombopoietin-induced increased platelet count increased thrombus weight on POD 7 indicating platelet count may regulate thrombus burden during early resolution of venous thrombi in this murine stasis model of DVT.

Deep vein thrombosis (DVT) is a pathology in which blood clots form in the deep veins of our body. Usually occurring in the legs, these clots can be dangerous if they dislodge and travel to the heart and are pumped into the lungs. Often these clots do not travel and heal where they formed. However, as the body heals the clot it may also cause damage to the vein wall and predispose the patient to future clots, i.e., the biggest risk factor for a second clot is the first clot. DVT can also cause symptoms of pain, swelling, and redness in the long-term, leading to post-thrombotic syndrome where the initial symptoms of the clot persist for a long time. All blood clots have common components of red blood cells, white blood cells, platelets, and fibrin in varying concentrations. Humans maintain a platelet count between 150 and 400 thousand platelets per microliter of our blood. However, diseases like cancer or medications like chemotherapy can cause a change in our body's platelet count. The effect of a changing platelet count on the size (clot burden) of DVT clot and how platelet count could affect DVT as the clot heals is not fully understood. Studying this might help us develop better targets and treat patients with a wide range of platelet counts who experience DVT. In this study, we intentionally decreased, left unchanged, and increased platelet counts in mice and then created a DVT to study what the effect of low, normal, and high platelet counts, respectively, would be on the clot burden. We observed that mice with higher platelet counts had a higher clot burden during the early part of the healing process of the clot. Within this study, we can conclude that higher platelet counts may lead to higher clot burden in DVT which furthers our understanding of how platelet count affects clot burden during DVT.

White matter hyperintensities and the surrounding normal appearing white matter are associated with water channel disruption in the oldest old.

INTRODUCTION: Age-related magnetic resonance imaging (MRI) T2 white matter hyperintensities (WMHs) are common and associated with neurological decline. We investigated the histopathological underpinnings of MRI WMH and surrounding normal appearing white matter (NAWM), with a focus on astroglial phenotypes. METHODS: Brain samples from 51 oldest old Oregon Alzheimer's Disease Research Center participants who came to autopsy underwent post mortem (PM) 7 tesla MRI with targeted histopathological sampling of WMHs and NAWM. Stained slides were digitized and quantified. Mixed-effects models determined differences in molecular characteristics between WMHs and the NAWM and across NAWM. RESULTS: PM MRI-targeted WMHs are characterized by demyelination, microglial activation, and prominent astrocytic alterations, including disrupted aquaporin (AQP) expression. Similar changes occur within the surrounding NAWM in a pattern of decreasing severity with increased distance from WMHs. DISCUSSION: Decreased AQP expression within WMH and proximal NAWM suggest an overwhelmed system wherein water homeostasis is no longer maintained, contributing to WM damage in older individuals. HIGHLIGHTS: Post mortem magnetic resonance imaging (MRI) was used to characterize the pathology of white matter hyperintensities (WMHs) and surrounding normal appearing white matter (NAWM). Stained immunohistochemical (IHC) slides from targeted WMH and NAWM samples were digitized and quantified. WMHs and NAWM were associated with inflammation, demyelination, and gliosis. WMHs and NAWM astrocytic changes included decreased AQP1 and AQP4 expression. Abnormal NAWM pathology diminished in severity with increasing distance from WMH.

Community pharmacists' naloxone counseling: A theory-informed qualitative study.

BACKGROUND: Opioid-related overdose (ORO) deaths have reached a record high in the United States. Naloxone is an opioid antagonist that can rapidly reverse an opioid overdose. Pharmacists are in an ideal position to provide naloxone and related counseling, given their accessibility and expertise. However, minimal research is available on community pharmacists' naloxone counseling. OBJECTIVES: The aim of this study was to investigate Georgia community pharmacists' naloxone counseling as well as explore their attitudes, subjective norms, and perceived behavioral control toward counseling. METHODS: Semi-structured telephone interviews were conducted to elicit pharmacists' beliefs and practices regarding naloxone counseling. The interviews were guided by open-ended questions based on the theory of planned behavior (TPB). Thematic analysis was performed to identify the modal salient beliefs expressed by the pharmacists. The Consolidated Criteria for Reporting Qualitative Research was used to report the study findings. RESULTS: A total of 12 community pharmacists participated. Pharmacists held mixed attitudes toward naloxone counseling. While they recognized it as a vital part of their profession to prevent ORO deaths, they also expressed concerns about offending patients. Regarding normative beliefs, pharmacists identified several groups, including regulatory agencies (e.g., Board of Pharmacy, CDC), managers, news/media, patients, and doctors, influencing their provision of naloxone counseling. Facilitators to counseling included receiving naloxone training and having access to counseling guidelines and resources. Reimbursement issues, high costs of naloxone, and lack of patient awareness were the most commonly cited barriers. Pharmacists reported participating in counseling and providing information on identifying signs of opioid overdose and administering naloxone. CONCLUSIONS: The TPB is a useful framework for understanding community pharmacists' beliefs and practices regarding naloxone counseling. Capitalizing on facilitators and targeting barriers related to pharmacists' reimbursement issues, high costs of naloxone, and increasing patients' awareness of naloxone use and benefits may enhance pharmacists' naloxone counseling.

Anti-inflammatory actions of ß-funaltrexamine in a mouse model of lipopolysaccharide-induced inflammation.

Neuroinflammation is involved in a wide range of brain disorders, thus there is great interest in identifying novel anti-inflammatory agents to include in therapeutic strategies. Our previous in vitro studies revealed that beta-funaltrexamine (ß-FNA), a well-characterized selective mu-opioid receptor (MOR) antagonist, inhibits inflammatory signaling in human astroglial cells, albeit through an apparent MOR-independent mechanism. We also previously determined that lipopolysaccharide (LPS)-induced sickness behavior and neuroinflammation in mice are prevented by pretreatment with ß-FNA. Herein we investigated the temporal importance of ß-FNA treatment in this pre-clinical model of LPS-induced neuroinflammation. Adult, male C57BL/6J mice were administered an i.p. injection of LPS followed by treatment (i.p. injection) with ß-FNA immediately or 4 h post-LPS. Sickness behavior was assessed using an open-field test, followed by assessment of inflammatory signaling in the brain, spleen, and plasma. Levels of inflammatory chemokines/cytokines (interferon γ-induced protein, CXCL10; monocyte chemotactic protein 1, CCL2; and interleukin-6, IL-6) in tissues were measured using an enzyme-linked immunosorbent assay and nuclear factor-kappa B (NFκB), p38 mitogen activated kinase (p38 MAPK), and glial fibrillary acidic protein (GFAP) expression were measured by western blot. LPS-induced sickness behavior and chemokine expression were inhibited more effectively when ß-FNA treatment occurred immediately after LPS administration, as opposed to 4 h post-LPS; and ß-FNA-mediated effects were time-dependent as evidenced by inhibition at 24 h, but not at 8 h. The inhibitory effects of ß-FNA on chemokine expression were more evident in the brain versus the spleen or plasma. LPS-induced NFκB-p65 and p38 MAPK expression in the brain and spleen were inhibited at 8 and 24 h post-LPS. These findings extend our understanding of the anti-inflammatory effects of ß-FNA and warrant further investigation into its therapeutic potential.

The Genome-Wide Binding Profile for Human RE1 Silencing Transcription Factor Unveils a Unique Genetic Circuitry in Hippocampus.

Early studies in mouse neurodevelopment led to the discovery of the RE1 Silencing Transcription Factor (REST) and its role as a master repressor of neuronal gene expression. Recently, REST was reported to also repress neuronal genes in the human adult brain. These genes were found to be involved in pro-apoptotic pathways; and their repression, associated with increased REST levels during aging, were found to be neuroprotective and conserved across species. However, direct genome-wide REST binding profiles for REST in adult brain have not been identified for any species. Here, we apply this approach to mouse and human hippocampus. We find an expansion of REST binding sites in the human hippocampus that are lacking in both mouse hippocampus and other human non-neuronal cell types. The unique human REST binding sites are associated with genes involved in innate immunity processes and inflammation signaling which, on the basis of histology and recent public transcriptomic analyses, suggest that these new target genes are repressed in glia. We propose that the increases in REST expression in mid-adulthood presage the beginning of brain aging, and that human REST function has evolved to protect the longevity and function of both neurons and glia in human brain.SIGNIFICANCE STATEMENT The RE1 Silencing Transcription Factor (REST) repressor has served historically as a model for gene regulation during mouse neurogenesis. Recent studies of REST have also suggested a conserved role for REST repressor function across lower species during aging. However, direct genome-wide studies for REST have been lacking for human brain. Here, we perform the first genome-wide analysis of REST binding in both human and mouse hippocampus. The majority of REST-occupied genes in human hippocampus are distinct from those in mouse. Further, the REST-associated genes unique to human hippocampus represent a new set related to innate immunity and inflammation, where their gene dysregulation has been implicated in aging-related neuropathology, such as Alzheimer's disease.

Health and Health Care Among Transgender Adults in the United States.

Transgender (trans) communities in the USA and globally have long organized for health and social equity but have only recently gained increased visibility within public health. In this review, we synthesize evidence demonstrating that trans adults in the USA are affected by disparities in physical and mental health and in access to health care, relative to cisgender (nontrans) persons. We draw on theory and data to situate these disparities in their social contexts, explicating the roles of gender affirmation, multilevel and intersectional stigmas, and public policies in reproducing or ameliorating trans health disparities. Until recently, trans health disparities were largely made invisible by exclusionary data collection practices. We highlight the importance of, and methodological considerations for, collecting inclusive sex and gender data. Moving forward, we recommend routine collection of gender identity data, an emphasis on intervention research to achieve trans health equity, public policy advocacy, and investment in supporting gender-diverse public health leadership.

Effects of routine treatment with nonsteroidal anti-inflammatory drugs at calving and when lame on the future probability of lameness and culling in dairy cows: A randomized controlled trial.

Claw horn lesions (CHL) are reported as the most common cause of lameness in intensive dairy systems. Despite their prevalence, the underlying pathological mechanisms and preventive strategies for CHL remain poorly understood. Recent advances have pointed to the role of inflammation in disease aetiopathogenesis. Moderating inflammation from first calving may lead to long-term benefits and a viable intervention for treating and preventing disease. We conducted a 34-mo randomized controlled trial to investigate the effects of routine treatment with the nonsteroidal anti-inflammatory drug ketoprofen at calving and during treatment for lameness, on the future probability of lameness and culling, caused by exposure to normal farm conditions. A cohort of dairy heifers were recruited from a single, commercial dairy herd between January 8, 2018, and June 22, 2020, and randomly allocated to one of 4 treatment groups before first calving. The lactating herd was lameness scored every 2 wk on a 0 to 3 scale, to identify animals that became lame (single score ≥2a) and hence required treatment. Animals in group 1 received a therapeutic trim and a hoof block on the sound claw (if deemed necessary) every time they were treated for lameness. Animals in group 2 received the same treatment as group 1 with the addition of a 3-d course of ketoprofen (single dose daily) every time they were treated for lameness. Animals in group 3 received the same treatment as group 2 with the addition of a 3-d course of ketoprofen (single dose daily) starting 24 to 36 h after each calving. Animals in group 4 received a 3-d course of ketoprofen (single dose daily) every time they were identified with lameness. No therapeutic trim was administered to this group, unless they were identified as severely lame (a single score ≥3a). Animals were followed for the duration of the study (ending October 23, 2020). Probability of lameness was assessed by a lameness outcome score collected every 14 d. Data on culling was extracted from farm records. One hundred thirty-two animals were recruited to each group, with data from 438 animals included in the final analysis (111 in group 1, 117 in group 2, 100 in group 3, and 110 in group 4). Mixed effect logistic regression models were used to evaluate the effect of treatment group on the ongoing probability of lameness. Compared with the control group (group 1), animals in group 3 were less likely to become lame (odds ratio: 0.66) and severely lame (odds ratio: 0.28). A Cox proportional hazards survival model was used to investigate the effect of treatment group on time to culling. Compared with group 1, animals in groups 2 and 3 were at reduced risk of culling (hazard ratios: 0.55 and 0.56, respectively). The lameness effect size we identified was large and indicated that treating a cohort of animals with the group 3 protocol, would lead to an absolute reduction in population lameness prevalence of approximately 10% and severe lameness prevalence of 3%, compared with animals treated in accordance with conventional best practice (group 1).

The Fractal Dimension Suggests Two Chromatin Configurations in Small Cell Neuroendocrine Lung Cancer and Is an Independent Unfavorable Prognostic Factor for Overall Survival.

Experimental studies have shown that in small cell neuroendocrine lung carcinomas (SCLC) global opening of the chromatin structure is associated with a higher transcription activity and increase of tumor aggressiveness and metastasis. The study of the fractal characteristics (FD) of nuclear chromatin has been widely used to describe the cell nuclear texture and its changes correspond to changes in nuclear metabolic and transcription activity. Hence, we investigated whether the nuclear fractal dimension could be a prognostic factor in SCLC. Hematoxylin-eosin stained brush cytology slides from 49 patients with SCLC were retrieved from our files. The chromatin (FD) was calculated in digitalized and interactively segmented nuclei using a differential box-counting method. The 3,575 nuclei studied showed a bimodal distribution (peaks at FD1 = 2.115 and FD2 = 2.180). The 75 percentile of the FD was an independent unfavorable prognostic factor for overall survival when tested together with ECOG (Eastern Cooperative Oncology Group) performance status, tumor extension, and therapy in a multivariate Cox regression. Our study corroborates the concept of two main chromatin configurations in small cell neuroendocrine carcinomas and that globally more open chromatin indicates a higher risk of metastasis and therefore a shorter survival of the patient.

Two-Photon Excitation Spectra of Various Fluorescent Proteins within a Broad Excitation Range.

Two-photon excitation fluorescence laser-scanning microscopy is the preferred method for studying dynamic processes in living organ models or even in living organisms. Thanks to near-infrared and infrared excitation, it is possible to penetrate deep into the tissue, reaching areas of interest relevant to life sciences and biomedicine. In those imaging experiments, two-photon excitation spectra are needed to select the optimal laser wavelength to excite as many fluorophores as possible simultaneously in the sample under consideration. The more fluorophores that can be excited, and the more cell populations that can be studied, the better access to their arrangement and interaction can be reached in complex systems such as immunological organs. However, for many fluorophores, the two-photon excitation properties are poorly predicted from the single-photon spectra and are not yet available, in the literature or databases. Here, we present the broad excitation range (760 nm to 1300 nm) of photon-flux-normalized two-photon spectra of several fluorescent proteins in their cellular environment. This includes the following fluorescent proteins spanning from the cyan to the infrared part of the spectrum: mCerulean3, mTurquoise2, mT-Sapphire, Clover, mKusabiraOrange2, mOrange2, LSS-mOrange, mRuby2, mBeRFP, mCardinal, iRFP670, NirFP, and iRFP720.

Aggregated Alpha-Synuclein Inclusions within the Nucleus Predict Impending Neuronal Cell Death in a Mouse Model of Parkinsonism.

Alpha-synuclein (aSyn) is a 14 kD protein encoded by the SNCA gene that is expressed in vertebrates and normally localizes to presynaptic terminals and the nucleus. aSyn forms pathological intracellular aggregates that typify a group of important neurodegenerative diseases called synucleinopathies. Previous work in human tissue and model systems indicates that some of these aggregates can be intranuclear, but the significance of aSyn aggregation within the nucleus is not clear. We used a mouse model that develops aggregated aSyn nuclear inclusions. Using aSyn preformed fibril injections in GFP-tagged aSyn transgenic mice, we were able to induce the formation of nuclear aSyn inclusions and study their properties in fixed tissue and in vivo using multiphoton microscopy. In addition, we analyzed human synucleinopathy patient tissue to better understand this pathology. Our data demonstrate that nuclear aSyn inclusions may form through the transmission of aSyn between neurons, and these intranuclear aggregates bear the hallmarks of cytoplasmic Lewy pathology. Neuronal nuclear aSyn inclusions can form rod-like structures that do not contain actin, excluding them from being previously described nuclear actin rods. Longitudinal, in vivo multiphoton imaging indicates that certain morphologies of neuronal nuclear aSyn inclusions predict cell death within 14 days. Human multiple system atrophy cases contain neurons and glia with similar nuclear inclusions, but we were unable to detect such inclusions in Lewy body dementia cases. This study suggests that the dysregulation of a nuclear aSyn function associated with nuclear inclusion formation could play a role in the forms of neurodegeneration associated with synucleinopathy.

Social Stimuli Induce Activation of Oxytocin Neurons Within the Paraventricular Nucleus of the Hypothalamus to Promote Social Behavior in Male Mice.

Oxytocin (OT) is critical for the expression of social behavior across a wide array of species; however, the role of this system in the encoding of socially relevant information is not well understood. In the present study, we show that chemogenetic activation of OT neurons within the paraventricular nucleus of the hypothalamus (PVH) of male mice (OT-Ires-Cre) enhanced social investigation during a social choice test, while chemogenetic inhibition of these neurons abolished typical social preferences. These data suggest that activation of the OT system is necessary to direct behavior preferentially toward social stimuli. To determine whether the presence of a social stimulus is sufficient to induce activation of PVH-OT neurons, we performed the first definitive recording of OT neurons in awake mice using two-photon calcium imaging. These recordings demonstrate that social stimuli activate PVH-OT neurons and that these neurons differentially encode social and nonsocial stimuli, suggesting that PVH-OT neurons may act to convey social salience of environmental stimuli. Finally, an attenuation of social salience is associated with social disorders, such as autism. We therefore also examined possible OT system dysfunction in a mouse model of autism, Shank3b knock-out (KO) mice. Male Shank3b KO mice showed a marked reduction in PVH-OT neuron number and administration of an OT receptor agonist improved social deficits. Overall, these data suggest that the presence of a social stimulus induces activation of the PVH-OT neurons to promote adaptive social behavior responses.SIGNIFICANCE STATEMENT Although the oxytocin (OT) system is well known to regulate a diverse array of social behaviors, the mechanism in which OT acts to promote the appropriate social response is poorly understood. One hypothesis is that the presence of social conspecifics activates the OT system to generate an adaptive social response. Here, we selectively recorded from OT neurons in the paraventricular hypothalamic nucleus (PVH) to show that social stimulus exposure indeed induces activation of the OT system. We also show that activation of the OT system is necessary to promote social behavior and that mice with abnormal social behavior have reduced numbers of PVH-OT neurons. Finally, aberrant social behavior in these mice was rescued by administration of an OT receptor agonist.

Soybean BARCSoySNP6K: An assay for soybean genetics and breeding research.

The limited number of recombinant events in recombinant inbred lines suggests that for a biparental population with a limited number of recombinant inbred lines, it is unnecessary to genotype the lines with many markers. For genomic prediction and selection, previous studies have demonstrated that only 1000-2000 genome-wide common markers across all lines/accessions are needed to reach maximum efficiency of genomic prediction in populations. Evaluation of too many markers will not only increase the cost but also generate redundant information. We developed a soybean (Glycine max) assay, BARCSoySNP6K, containing 6000 markers, which were carefully chosen from the SoySNP50K assay based on their position in the soybean genome and haplotype block, polymorphism among accessions and genotyping quality. The assay includes 5000 single nucleotide polymorphisms (SNPs) from euchromatic and 1000 from heterochromatic regions. The percentage of SNPs with minor allele frequency >0.10 was 95% and 91% in the euchromatic and heterochromatic regions, respectively. Analysis of progeny from two large families genotyped with SoySNP50K versus BARCSoySNP6K showed that the position of the common markers and number of unique bins along linkage maps were consistent based on the SNPs genotyped with the two assays; however, the rate of redundant markers was dramatically reduced with the BARCSoySNP6K. The BARCSoySNP6K assay is proven as an excellent tool for detecting quantitative trait loci, genomic selection and assessing genetic relationships. The assay is commercialized by Illumina Inc. and being used by soybean breeders and geneticists and the list of SNPs in the assay is an ideal resource for SNP genotyping by targeted amplicon sequencing.

de Gennes Narrowing and Relationship between Structure and Dynamics in Self-Organized Ion-Beam Nanopatterning.

Investigating the relationship between structure and dynamical processes is a central goal in condensed matter physics. Perhaps the most noted relationship between the two is the phenomenon of de Gennes narrowing, in which relaxation times in liquids are proportional to the scattering structure factor. Here, a similar relationship is discovered during the self-organized ion-beam nanopatterning of silicon using coherent x-ray scattering. However, in contrast to the exponential relaxation of fluctuations in classic de Gennes narrowing, the dynamic surface exhibits a wide range of behaviors as a function of the length scale, with a compressed exponential relaxation at lengths corresponding to the dominant structural motif-self-organized nanoscale ripples. These behaviors are reproduced in simulations of a nonlinear model describing the surface evolution. We suggest that the compressed exponential behavior observed here is due to the morphological persistence of the self-organized surface ripple patterns which form and evolve during ion-beam nanopatterning.

Structural Transphobia, Homophobia, and Biphobia in Public Health Practice: The Example of COVID-19 Surveillance.

Public health surveillance can have profound impacts on the health of populations, with COVID-19 surveillance offering an illuminating example. Surveillance surrounding COVID-19 testing, confirmed cases, and deaths has provided essential information to public health professionals about how to minimize morbidity and mortality. In the United States, surveillance has also pointed out how populations, on the basis of geography, age, and race and ethnicity, are being impacted disproportionately, allowing targeted intervention and evaluation. However, COVID-19 surveillance has also highlighted how the public health surveillance system fails some communities, including sexual and gender minorities. This failure has come about because of the haphazard and disorganized way disease reporting data are collected, analyzed, and reported in the United States, and the structural homophobia, transphobia, and biphobia acting within these systems. We provide recommendations for addressing these concerns after examining experiences collecting race data in COVID-19 surveillance and attempts in Pennsylvania and California to incorporate sexual orientation and gender identity variables into their pandemic surveillance efforts.