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Abstract Toll-like receptor 7 (Tlr7) deficiency-accelerated severe COVID-19 is associated with reduced production of interferons (IFNs). However, the underlying mechanisms remain elusive. To address these questions, we utilize Tlr7 and Irf7 deficiency mice, single-cell RNA analysis together with bone marrow transplantation approaches. We demonstrate that at the early phase of infection, SARS-CoV-2 causes the upregulation of Tlr7, Irf7, and IFN pathways in the lungs of the infected mice. The deficiency of Tlr7 and Irf7 globally and/or in immune cells in mice increases the severity of COVID-19 via impaired IFN activation in both immune and/or non-immune cells, leading to increased lung viral loads. These effects are associated with reduced IFN alpha and gamma levels in the circulation. The deficiency of Tlr7 tends to cause the reduced production and nuclear translocation of interferon regulatory factor 7 (IRF7) in the lungs of the infected mice, indicative of reduced IRF7 activation. Despite higher amounts of lung viral antigen, Tlr7 or Irf7 deficiency resulted in substantially reduced production of antibodies against SARS-CoV-2, thereby delaying the viral clearance. These results highlight the importance of the activation of TLR7 and IRF7 leading to IFN production on the development of innate and adaptive immunity against COVID-19.

Abstract Hyperglycemia, and exacerbation of pre-existing deficits in glucose metabolism, are manifestations of the post-acute sequelae of SARS-CoV-2. Our understanding of metabolic decline after acute COVID-19 remains unclear due to the lack of animal models. Here, we report a non-human primate model of metabolic post-acute sequelae of SARS-CoV-2 using SARS-CoV-2 infected African green monkeys. Using this model, we identify a dysregulated blood chemokine signature during acute COVID-19 that correlates with elevated and persistent hyperglycemia four months post-infection. Hyperglycemia also correlates with liver glycogen levels, but there is no evidence of substantial long-term SARS-CoV-2 replication in the liver and pancreas. Finally, we report a favorable glycemic effect of the SARS-CoV-2 mRNA vaccine, administered on day 4 post-infection. Together, these data suggest that the African green monkey model exhibits important similarities to humans and can be utilized to assess therapeutic candidates to combat COVID-related metabolic defects.

Objective: This study evaluated a media literacy education program designed for sexual health promotion, "Media Aware," in southeastern universities. Participants: Participants included college students from four universities in the southeastern United States (n = 457). Methods: "Media Aware" was implemented on college campuses either in a group setting, one-on-one setting, at a student event, or online only. "Media Aware" contains four sections on sexual health promotion including on how media messages influence sexual health, gender stereotypes and representations of romantic relationships, sexual violence, substance use, consent, sexual risk behaviors, contraception, STIs, and partner communication. Results: Results indicated significant changes in intention to visit a healthcare provider for sexual health services, intention to use condoms and other forms of birth control, and awareness of Long Acting Reversible Contraceptives after participation in "Media Aware." Conclusion: Future research should explore how to extend program impacts and use an experimental study design to assess between group differences.

Abstract An influenza vaccine approach that overcomes the problem of viral sequence diversity and provides long-lived heterosubtypic protection is urgently needed to protect against pandemic influenza viruses. Here, to determine if lung-resident effector memory T cells induced by cytomegalovirus (CMV)-vectored vaccines expressing conserved internal influenza antigens could protect against lethal influenza challenge, we immunize Mauritian cynomolgus macaques (MCM) with cynomolgus CMV (CyCMV) vaccines expressing H1N1 1918 influenza M1, NP, and PB1 antigens (CyCMV/Flu), and challenge with heterologous, aerosolized avian H5N1 influenza. All six unvaccinated MCM died by seven days post infection with acute respiratory distress, while 54.5% (6/11) CyCMV/Flu-vaccinated MCM survived. Survival correlates with the magnitude of lung-resident influenza-specific CD4 + T cells prior to challenge. These data demonstrate that CD4 + T cells targeting conserved internal influenza proteins can protect against highly pathogenic heterologous influenza challenge and support further exploration of effector memory T cell-based vaccines for universal influenza vaccine development.

Abstract MVA-based monovalent eastern equine encephalitis virus (MVA-BN-EEEV) and multivalent western, eastern, and Venezuelan equine encephalitis virus (MVA-BN-WEV) vaccines were evaluated in the cynomolgus macaque aerosol model of EEEV infection. Macaques vaccinated with two doses of 5 × 108 infectious units of the MVA-BN-EEEV or MVA-BN-WEV vaccine by the intramuscular route rapidly developed robust levels of neutralizing antibodies to EEEV that persisted at high levels until challenge at day 84 via small particle aerosol delivery with a target inhaled dose of 107 PFU of EEEV FL93-939. Robust protection was observed, with 7/8 animals receiving MVA-BN-EEEV and 100% (8/8) animals receiving MVA-BN-WEV surviving while only 2/8 mock vaccinated controls survived lethal challenge. Complete protection from viremia was afforded by both vaccines, with near complete protection from vRNA loads in tissues and any pathologic evidence of central nervous system damage. Overall, the results indicate both vaccines are effective in eliciting an immune response that is consistent with protection from aerosolized EEEV-induced disease.

Clostridium thermocellum is a desirable biocatalyst for biohydrogen production, with a native ability to simultaneously saccharify cellulose and to metabolize released cellodextrins for hydrogen production. During fermentation with C. thermocellum, partial pressures of two gases - CO2 and H2 - are critical drivers of overall reaction kinetics. Biohydrogen production is enhanced by maintaining a low hydrogen partial pressure, while high concentrations of dissolved CO2 promote microbial biomass synthesis. Our study evaluates the inherent trade-offs between hydrogen stripping and inorganic carbon supply for optimized biohydrogen synthesis. We find that nitrogen sparging at low flow rates increases hydrogen production when compared with an equivalent nitrogen overlay, but that high rates of nitrogen sparging inhibit cell growth and hydrogen production. Decreasing dissolved hydrogen partial pressure via nitrogen sparging also lowers the production of reduced metabolites, including lactate and ethanol. To address potential stripping of inorganic carbon from the production medium, we supplemented CO2 to the sparging gas and co-optimized for gas flow rate and for the CO2 fraction of the sparging gas. Total hydrogen production increased from 50 mmol∙L−1 in the base condition, when the bioreactor was sparged with 0.1 LPM of pure nitrogen, to 181.3 mmol∙L−1 when sparged with 1.3 LPM of 33 % CO2, demonstrating that biohydrogen production is highly sensitive to both parameters. Fine sensitivity of biohydrogen production to sparging conditions highlights the critical importance of bioreactor design and operation to achieve maximum H2 removal without compromising inorganic carbon supply to bacterial central metabolism.

The well-being of wildlife populations, ecosystem health, and human health are interlinked, and preserving wildlife is crucial for sustaining healthy ecosystems. Wildlife numbers, and in particular avian populations, have steeply declined over the past century, associated with anthropogenic factors originating from industry, urbanization, changing land use, habitat loss, pollution, emerging diseases, and climate change. All these factors combine to exert increasing stress and impair health for both humans and wildlife, with diminished metabolic, immune, and reproductive function, deteriorating overall health, and reduced longevity. The “toxic aging coin” suggests that these stressors may have dual impacts on aging–they can accelerate the aging process, and older individuals may struggle to cope with pollutants compared to younger ones. These responses are reflected in the health and productivity of individuals, and at a larger scale, the health and ability of populations to withstand disturbances. To understand the potential risk to health over the lifespan, it is important to articulate some of these global challenges and consider both their impacts on aging populations and on the aging process. In this review, we use the toxic aging coin and One Health conceptual frameworks to examine the interconnected health of humans, wildlife, and ecosystems. This exploration aims to develop proactive approaches for optimizing wildlife and human health.

Pecan (Carya illinoensis), an economically important deciduous tree, bears commercially valuable nutritional nuts. Spring freezes in April can severely injure pecan buds, decreasing bloom, and fruit set. This study determined how low temperatures affect pecan buds/flowers at different growth stages in several pecan scion/rootstock combinations. This study focused on three pecan scion/rootstock combinations: Pawnee/Peruque (PP), Kanza/Giles (KG), and Maramec/Colby (MC), grown at the Cimarron Valley Research Station, Perkins, Oklahoma. Branches at three different growth stages, i.e., outer bud scale shed, one week after bud break, and early bloom stages were collected from PP, MC, and KG. Branches were held in a Conviron E8 freezing unit at 4 temperatures (-2, 0, 2, and 4°C) for 4 and 8 hours; A total of 8 treatments. One sample set was kept as an untreated control. After 2–3 weeks, branch samples from all the temperature treatments were observed and categorized into two groups. Group one with number of branches had healthy buds/formation of healthy leaves/flowers and group two with number of dead branches. The carbohydrate content reserved from dormant was analyzed using an Anthrone reagent. Visual observations and carbohydrate analyses revealed differences in damage and carbohydrate content among the scion/rootstock combinations, low-temperature treatments, and growth stages. The MC combination had minimum visual damage to leaves, buds, and flowers and significantly lower soluble sugars and starch in bark phloem as well as significantly lower soluble sugars in woody tissue xylem. The KG combination had maximum visual damage and significantly higher soluble sugars and starches in the bark, and soluble sugars in the woody tissues. These results indicate the MC combination is more tolerant to spring freeze damage at all three growth stages compared to the other two pecan scion/rootstock combinations. The results also demonstrate the MC combination is using more non-structural carbohydrates, soluble sugars and starches, suggesting this is a possible mechanism in its freeze tolerance.

Abstract SARS-CoV-2 infection can cause persistent respiratory sequelae. However, the underlying mechanisms remain unclear. Here we report that sub-lethally infected K18-human ACE2 mice show patchy pneumonia associated with histiocytic inflammation and collagen deposition at 21 and 45 days post infection (DPI). Transcriptomic analyses revealed that compared to influenza-infected mice, SARS-CoV-2-infected mice had reduced interferon-gamma/alpha responses at 4 DPI and failed to induce keratin 5 (Krt5) at 6 DPI in lung, a marker of nascent pulmonary progenitor cells. Histologically, influenza- but not SARS-CoV-2-infected mice showed extensive Krt5+ “pods” structure co-stained with stem cell markers Trp63/NGFR proliferated in the pulmonary consolidation area at both 7 and 14 DPI, with regression at 21 DPI. These Krt5+ “pods” structures were not observed in the lungs of SARS-CoV-2-infected humans or nonhuman primates. These results suggest that SARS-CoV-2 infection fails to induce nascent Krt5+ cell proliferation in consolidated regions, leading to incomplete repair of the injured lung.

Three online courses at the authors' institution have successfully used an extensive guest lecturer format (N = 22-30) for almost 10 years. The course design facilitates networking within the relatively small but diverse and global field of aquatic animal health. In this study of students' learning experiences, students perceived the courses as valuable and provided ample positive feedback in appreciation of the inclusion of many diverse guest speakers. Moreover, only minimal course design modifications were identified to improve upon learner satisfaction and academic success.

Abstract Introduction Choosing the right contraception can be a daunting process and it is important that people feel in control of their bodies during this decision‐making process. Materials and Methods This study investigates who college‐aged students talk to about their hormonal contraceptive choice and how that impacts their feeling of control during their decision‐making process. Results The study found participants spoke to a variety of sources about this decision, like their healthcare providers when they wanted a clinical point of view, their mothers when they wanted a more personal and caring point a view, their overall social networks when they wanted multiple point of views, and some participants ultimately felt the most control when just referring to themselves and their own feelings. Conclusions More research can be done on how specific beliefs among figures in college‐aged students' lives impact these contraceptive discussions, the choices they feel they can make, and how in control of themselves they feel.

The significance of urban landscapes in safeguarding biodiversity is often disregarded, even though a considerable amount of conservation focus is directed toward biodiversity hotspots where urban land conversion is happening at the fastest pace. Maintaining biodiversity in urban areas not only benefits the environment, but along with social, economic, and technological factors can increase the stability of urban systems to disturbance, a concept known as “urban resilience”. In this synthesis paper, we explore the ecological dimension of urban resilience and specifically focus on avian biodiversity because birds are easy to observe, relatively abundant, and can serve as an indicator of the overall health of urban environments. We first examine the concept of ecological resilience and discuss the role of environmental stressors associated with urbanization in the ongoing avian biodiversity crisis. We then provide an overview of characteristics of the urban environment that may promote ecological resilience in birds, and associations between social and economic factors and urban ecological resilience. Finally, we provide recommendations on future research regarding strategies to improve urban ecological resilience and thus, urban resilience as a whole, at the intersections of urban ecology, ecosystem ecology, environmental justice, and urban planning. Since 68% of the world’s population is projected to live in urban areas by 2050, it is imperative that scientists, urban planners, civil engineers, architects, and others consider urban ecological resilience as a dimension of both environmental health and the resilience of cities to future natural and anthropogenic stressors.

Zika virus (ZIKV) is unique among mosquito-borne flaviviruses in that it is also vertically and sexually transmitted by humans. The male reproductive tract is thought to be a ZIKV reservoir; however, the reported magnitude and duration of viral persistence in male genital tissues vary widely in humans and non-human primate models. ZIKV tissue and cellular tropism and potential effects on male fertility also remain unclear. The objective of this study was to resolve these questions by analyzing archived genital tissues from 51 ZIKV-inoculated male macaques and correlating data on plasma viral kinetics, tissue tropism, and ZIKV-induced pathological changes in the reproductive tract. We hypothesized that ZIKV would persist in the male macaque genital tract for longer than there was detectable viremia, where it would localize to germ and epithelial cells and associate with lesions. We detected ZIKV RNA and infectious virus in testis, epididymis, seminal vesicle, and prostate gland. In contrast to prepubertal males, sexually mature macaques were significantly more likely to harbor persistent ZIKV RNA or infectious virus somewhere in the genital tract, with detection as late as 60 days post-inoculation. ZIKV RNA localized primarily to testicular stem cells/sperm precursors and epithelial cells, including Sertoli cells, epididymal duct epithelium, and glandular epithelia of the seminal vesicle and prostate gland. ZIKV infection was associated with microscopic evidence of inflammation in the epididymis and prostate gland of sexually mature males, pathologies that were absent in uninfected controls, which could have significant effects on male fertility. The findings from this study increase our understanding of persistent ZIKV infection which can inform risk of sexual transmission during assisted reproductive therapies as well as potential impacts on male fertility.

BackgroundAcute myeloid leukemia (AML) is fatal in elderly patients who are unfit for standard induction chemotherapy. The objective of this study was to evaluate the survival benefit of administering sapacitabine, an oral nucleoside analogue, in alternating cycles with decitabine, a low-intensity therapy, to elderly patients with newly diagnosed AML.MethodsThis randomized, open-label, phase 3 study (SEAMLESS) was conducted at 87 sites in 11 countries. Patients aged ≥70 years who were not candidates for or chose not to receive standard induction chemotherapy were randomized 1:1 to arm A (decitabine in alternating cycles with sapacitabine) received 1-hour intravenous infusions of decitabine 20 mg/m2 once daily for 5 consecutive days every 8 weeks (first cycle and subsequent odd cycles) and sapacitabine 300 mg twice daily on 3 consecutive days per week for 2 weeks every 8 weeks (second cycle and subsequent even cycles) or to control arm C who received 1-hour infusions of decitabine 20 mg/m2 once daily for 5 consecutive days every 4 weeks. Prior hypomethylating agent therapy for preexisting myelodysplastic syndromes or myeloproliferative neoplasms was an exclusion criterion. Randomization was stratified by antecedent myelodysplastic syndromes or myeloproliferative neoplasms, white blood cell count (

BackgroundRhesus monkeys (Macaca mulatta) exhibit pronounced individual differences in social traits as measured by the macaque Social Responsiveness Scale-Revised. The macaque Social Responsiveness Scale was previously adapted from the Social Responsiveness Scale, an instrument designed to assess social and autistic trait variation in humans. To better understand potential biological underpinnings of this behavioral variation, we evaluated the trait-like consistency of several biological measures previously implicated in autism (e.g., arginine vasopressin, oxytocin, and their receptors, as well as ERK1/2, PTEN, and AKT(1-3) from the RAS-MAPK and PI3K-AKT pathways). We also tested which biological measures predicted macaque Social Responsiveness Scale-Revised scores.MethodsCerebrospinal fluid and blood samples were collected from N = 76 male monkeys, which, as a sample, showed a continuous distribution on the macaque Social Responsiveness Scale-Revised. In a subset of these subjects (n = 43), samples were collected thrice over a 10-month period. The following statistical tests were used: "Case 2A" intra-class correlation coefficients of consistency, principal component analysis, and general linear modeling.ResultsAll biological measures (except AKT) showed significant test-retest reliability within individuals across time points. We next performed principal component analysis on data from monkeys with complete biological measurement sets at the first time point (n = 57), to explore potential correlations between the reliable biological measures and their relationship to macaque Social Responsiveness Scale-Revised score; a three-component solution was found. Follow-up analyses revealed that cerebrospinal fluid arginine vasopressin concentration, but no other biological measure, robustly predicted individual differences in macaque Social Responsiveness Scale-Revised scores, such that monkeys with the lowest cerebrospinal fluid arginine vasopressin concentration exhibited the greatest social impairment. Finally, we confirmed that this result held in the larger study sample (in which cerebrospinal fluid arginine vasopressin values were available from n = 75 of the subjects).ConclusionsThese findings indicate that cerebrospinal fluid arginine vasopressin concentration is a stable trait-like measure and that it is linked to quantitative social trait variation in male rhesus monkeys.

The effects of immunodeficiency associated with chronic HIV infection on COVID-19 disease and viral persistence have not been directly addressed in a controlled setting. In this pilot study, we exposed two pigtail macaques (PTMs) chronically infected with SIVmac239, exhibiting from very low to no CD4 T cells across all compartments, to SARS-CoV-2. We monitored the disease progression, viral replication, and evolution, and compared these outcomes with SIV-naïve PTMs infected with SARS-CoV-2. No overt signs of COVID-19 disease were observed in either animal, and the SARS-CoV-2 viral kinetics and evolution in the SIVmac239 PTMs were indistinguishable from those in the SIV-naïve PTMs in all sampled mucosal sites. However, the single-cell RNA sequencing of bronchoalveolar lavage cells revealed an infiltration of functionally inert monocytes after SARS-CoV-2 infection. Critically, neither of the SIV-infected PTMs mounted detectable anti-SARS-CoV-2 T-cell responses nor anti-SARS-CoV-2 binding or neutralizing antibodies. Thus, HIV-induced immunodeficiency alone may not be sufficient to drive the emergence of novel viral variants but may remove the ability of infected individuals to mount adaptive immune responses against SARS-CoV-2.

Human immunodeficiency virus (HIV) and malaria, caused by infection with Plasmodium spp., are endemic in similar geographical locations. As a result, there is high potential for HIV/Plasmodium co-infection, which increases the pathology of both diseases. However, the immunological mechanisms underlying the exacerbated disease pathology observed in co-infected individuals are poorly understood. Moreover, there is limited data available on the impact of Plasmodium co-infection on antiretroviral (ART)-treated HIV infection. Here, we used the rhesus macaque (RM) model to conduct a pilot study to establish a model of Plasmodium fragile co-infection during ART-treated simian immunodeficiency virus (SIV) infection, and to begin to characterize the immunopathogenic effect of co-infection in the context of ART. We observed that P. fragile co-infection resulted in parasitemia and anemia, as well as persistently detectable viral loads (VLs) and decreased absolute CD4+ T-cell counts despite daily ART treatment. Notably, P. fragile co-infection was associated with increased levels of inflammatory cytokines, including monocyte chemoattractant protein 1 (MCP-1). P. fragile co-infection was also associated with increased levels of neutrophil elastase, a plasma marker of neutrophil extracellular trap (NET) formation, but significant decreases in markers of neutrophil degranulation, potentially indicating a shift in the neutrophil functionality during co-infection. Finally, we characterized the levels of plasma markers of gastrointestinal (GI) barrier permeability and microbial translocation and observed significant correlations between indicators of GI dysfunction, clinical markers of SIV and Plasmodium infection, and neutrophil frequency and function. Taken together, these pilot data verify the utility of using the RM model to examine ART-treated SIV/P. fragile co-infection, and indicate that neutrophil-driven inflammation and GI dysfunction may underlie heightened SIV/P. fragile co-infection pathogenesis.

The plight of wild birds is becoming critical due to exposure to environmental contaminants. Although laboratory studies have provided insights into the developmental effects of chemical exposures, less is known about the adverse effects of environmental chemicals in developing wild birds. Early life stages are critical windows during which long-term organization of physiological, behavioral, and neurological systems can occur. Thus, contaminant exposure at early life stages can directly influence survival and reproductive success, with consequences for population stability and resilience in wild species. This review synthesizes existing knowledge regarding both short- and long-term effects of early-life exposure to widespread contaminants in birds. We focus especially on wild birds and on contaminants of concern within the Gulf of Mexico as an example of a habitat under anthropogenic stress from exposure to a complex mixture of chemicals and changing land uses that exacerbate existing vulnerabilities of wildlife in this region. Chemical contaminants for discussion in this review are based on avian mortality records from the Wildlife Health Information Sharing Partnership (WHISPers) database and on additional review of the literature regarding avian contaminants of concern for the northern Gulf of Mexico, and include oil and associated polycyclic aromatic hydrocarbons, dioxin and dioxin-like compounds, flame retardants, pesticides, heavy metals, and plastics. We provide an overview of effects in bird species at both the pre-hatching and post-hatching early life stages, discuss differences in sensitivities by route of exposure, life stage, and life history, and provide recommendations for future research. We find that additional research is needed on altricial species, post-hatching early-life exposure, long-term effects, and on ecologically relevant contaminant concentrations and routes of exposure. Given the increasing frequency and intensity of anthropogenic stressors encountered by wild animals, understanding both lethal and sublethal impacts of contaminants on the health of individuals and populations will be critical to inform restoration, management, and mitigation efforts.

The extraordinary disruption since the onset of the COVID-19 pandemic prompted the need to better understand changes in people’s activity and mobility patterns. Reduced leisure activity space and differing risk profiles due to public health interventions changed people’s ability to participate in different discretionary activity types. Using survey samples collected in 2019 and 2020, this paper conducted comprehensive statistical tests for temporal stability and gender difference of leisure variety and its contributing factors such as social capital, mobility, personalities, and demographics on leisure variety. Model inference shows an average 37% reduction in leisure variety in 2020, ceteris paribus. Individuals with more social capital, particularly instrumental capital, have substantial and significantly higher leisure activity variety, and the effect size remains temporally stable before and during the pandemic. This result suggests social capital robustly impacts activity variety even under drastic changes and restrictions. Openness to experience remains temporally stable and consistent between genders, but age, household size, and extraversion are among the factors that exhibit temporal instability.

People with autism spectrum disorder (ASD) exhibit a variety of medical morbidities at significantly higher rates than the general population. Using an established monkey model of naturally occurring low sociality, we investigated whether low-social monkeys show an increased burden of medical morbidities compared to their high-social counterparts. We systematically reviewed the medical records of N = 152 (n = 73 low-social; n = 79 high-social) rhesus macaques (Macaca mulatta) to assess the number of traumatic injury, gastrointestinal, and inflammatory events, as well as the presence of rare medical conditions. Subjects' nonsocial scores, determined by the frequency they were observed in a nonsocial state (i.e., alone), and macaque Social Responsiveness Scale-Revised (mSRS-R) scores were also used to test whether individual differences in social functioning were related to medical morbidity burden. Medical morbidity type significantly differed by group, such that low-social monkeys incurred higher rates of traumatic injury compared to high-social monkeys. Nonsocial scores and mSRS-R scores also significantly and positively predicted traumatic injury rates, indicating that monkeys with the greatest social impairment were most impacted on this health measure. These findings from low-social monkeys are consistent with well-documented evidence that people with ASD incur a greater number of traumatic injuries and receive more peer bullying than their neurotypical peers, and add to growing evidence for the face validity of this primate model. LAY SUMMARY: People with autism exhibit multiple medical problems at higher rates than the general population. We conducted a comprehensive medical record review of monkeys that naturally exhibit differences in sociality and found that low-social monkeys are more susceptible to traumatic injuries than high-social monkeys. These results are consistent with reports that people with autism also incur greater traumatic injury and peer bullying and add to growing evidence for the validity of this monkey model.

Most primate species are highly social. Yet, within species, pronounced individual differences in social functioning are evident. In humans, the Social Responsiveness Scale (SRS) measures variation in social functioning. The SRS provides a quantitative measure of social functioning in natural social settings and can be used as a screening tool for autistic traits. The SRS was previously adapted for use in chimpanzees and recently refined for rhesus macaques, resulting in the macaque Social Responsiveness Scale-Revised (mSRS-R). Here, we performed an exploratory factor analysis on the mSRS-R in a large sample of male rhesus macaques (N = 233). We investigated the relationships of the resulting mSRS-R factors to quantitative social behavior (alone, proximity, contact, groom, and play) and to previously-established personality dimensions (Sociability, Confidence, Irritability, and Equability). Factor analysis yielded three mSRS-R factors: Poor Social Motivation, Poor Social Attractiveness, and Inappropriate Behavior. mSRS-R factors mapped closely to social behavior and personality dimensions in rhesus macaques, providing support for this instrument's convergent and discriminant validity. Animals with higher Poor Social Motivation were more likely to be observed alone and less likely to be observed in contact and grooming with conspecifics. Animals with higher Poor Social Attractiveness were less likely to be observed playing but more likely to be observed grooming with conspecifics. Inappropriate Behavior did not predict any behavioral measure. Finally, animals with higher Poor Social Motivation and higher Poor Social Attractiveness had less sociable personalities, whereas animals with more Inappropriate Behavior were more confident and more irritable. These findings suggest that the mSRS-R is a promising, psychometrically robust tool that can be deployed to better understand the psychological factors contributing to individual differences in macaque social functioning and, with relevant species-specific modification, the SRS may hold promise for investigating variation in social functioning across diverse primate taxa.

Burkholderia thailandensis, an opportunistic pathogen found in the environment, is a bacterium closely related to B. pseudomallei, the cause of melioidosis. Human B. thailandensis infections are uncommon. We isolated B. thailandensis from water in Texas and Puerto Rico and soil in Mississippi in the United States, demonstrating a potential public health risk.

Objective: The purpose of this study was to compare knowledge about human papillomavirus (HPV) and HPV vaccine, college student's beliefs toward HPV, and HPV vaccine uptake between US and international college students studying in the US. Participants: The study was conducted using a sample (N = 588) of college students from a university in the South Central US. Methods: Study measures was derived from previously validated measures. Data were collected via an online survey using Qualtrics. Results: Significant differences were found in HPV awareness, HPV vaccine awareness, and HPV vaccine uptake between US and international college students. Conclusion: This study showed existing disparities between US and international college students regarding HPV and HPV vaccine awareness, and HPV vaccine uptake. College health centers can play a crucial role in raising awareness of HPV and HPV vaccination rates by organizing various intervention programs to reduce these disparities.

This study investigates the roles of T, B, and Natural Killer (NK) cells in the pathogenesis of severe COVID-19, utilizing mouse-adapted SARS-CoV-2-MA30 (MA30). To evaluate this MA30 mouse model, we characterized MA30-infected C57BL/6 mice (B6) and compared them with SARS-CoV-2-WA1 (an original SARS-CoV-2 strain) infected K18-human ACE2 (K18-hACE2) mice. We found that the infected B6 mice developed severe peribronchial inflammation and rapid severe pulmonary edema, but less lung interstitial inflammation than the infected K18-hACE2 mice. These pathological findings recapitulate some pathological changes seen in severe COVID-19 patients. Using this MA30-infected mouse model, we further demonstrate that T and/or B cells are essential in mounting an effective immune response against SARS-CoV-2. This was evident as Rag2−/− showed heightened vulnerability to infection and inhibited viral clearance. Conversely, the depletion of NK cells did not significantly alter the disease course in Rag2−/− mice, underscoring the minimal role of NK cells in the acute phase of MA30-induced disease. Together, our results indicate that T and/or B cells, but not NK cells, mitigate MA30-induced disease in mice and the infected mouse model can be used for dissecting the pathogenesis and immunology of severe COVID-19.

Pecan [Carya illinoinensis (Wangenh.) K. Koch] is a member of the Juglandaceae family. During spring, pecan trees break their bud dormancy and produce new leaves and flowers. Carbohydrates stored in roots and shoots are thought to support the bloom and early vegetative growth during this time until new leaves start the full photosynthetic activity. Spring freeze is known for its damaging effects on pecan bud and flower growth and development. Pecan shoots with leaves and flowers from five scion–rootstock combinations were collected hours before and after a recent spring freeze (below 0 °C for 6 hours, 21 Apr 2021, Perkins, OK, USA). Morphologies of the leaf, bud, and catkin were visually observed, and the morphologies of the anther and pollen in paraffin sections were investigated by light microscopy. Soluble sugar and starch from bark and wood were analyzed using the anthrone reagent method. The Kanza–Mount showed the maximum damage to terminal leaves, buds, and catkins, whereas Maramec–Colby had the minimum damage only to leaves. Pollen grains were shrunk and reduced in number in the anthers in the protandrous Pawnee scions, whereas no pollen damage was observed in the protogynous Kanza scion. Furthermore, bark soluble sugar levels increased in all the scion–rootstock combinations after the freeze, which may indicate a physiological response to the cold stress. Overall, the extent of spring freeze damage of pecans is affected by the growth stage, types of scion and rootstock, and the scion–rootstock interactions. Furthermore, in addition to low temperature, scion–rootstock interactions also affected the starch and soluble sugar contents in wood and bark tissues.

Naturally low-social rhesus macaques exhibit social impairments with direct relevance to autism spectrum disorder (ASD). To more efficiently identify low-social individuals in a large colony, we exploited, refined, and psychometrically assessed the macaque Social Responsiveness Scale (mSRS), an instrument previously derived from the human ASD screening tool. We performed quantitative social behavior assessments and mSRS ratings on a total of N = 349 rhesus macaques (Macaca mulatta) housed in large, outdoor corrals. In one cohort (N = 116), we conducted inter-rater and test-retest reliabilities, and in a second cohort (N = 233), we evaluated the convergent construct and predictive validity of the mSRS-Revised (mSRS-R). Only 17 of the original 36 items demonstrated inter-rater and test-retest reliability, resulting in the 17-item mSRS-R. The mSRS-R showed strong validity: mSRS-R scores robustly predicted monkeys' social behavior frequencies in home corrals. Monkeys that scored 1.5 standard deviations from the mean on nonsocial behavior likewise exhibited significantly more autistic-like traits, and mSRS-R scores predicted individuals' social classification (low-social vs. high-social) with 96% accuracy (likelihood ratio chi-square = 25.07; P

The dynamics of γδ T cell frequencies and functions through the course of SARS-CoV-2 infection in rhesus macaques and African green monkeys reveals that Vδ1 γδ T cells are involved in the early immune response to SARS-CoV-2 infection.

Mounting evidence indicates that SARS-CoV-2 can infect multiple systemic tissues, but few studies have evaluated SARS-CoV-2 RNA dynamics in multiple specimen types due to their reduced accessibility and diminished performance of RT-qPCR with non-respiratory specimens. Here, we employed an ultrasensitive CRISPR-RT–PCR assay to analyze longitudinal mucosal (nasal, buccal, pharyngeal, and rectal), plasma, and breath samples from SARS-CoV-2-infected non-human primates (NHPs) to detect dynamic changes in SARS-CoV-2 RNA level and distribution among these specimens. We observed that CRISPR-RT–PCR results consistently detected SARS-CoV-2 RNA in all sample types at most time points post-infection, and that SARS-CoV-2 infection dose and administration route did not markedly affect the CRISPR-RT–PCR signal detected in most specimen types. However, consistent RT-qPCR positive results were restricted to nasal, pharyngeal, and rectal swab samples, and tended to decrease earlier than CRISPR-RT–PCR results, reflecting lower assay sensitivity. SARS-CoV-2 RNA was detectable in both pulmonary and extrapulmonary specimens from early to late infection by CRISPR-RT–PCR, albeit with different abundance and kinetics, with SARS-CoV-2 RNA increases detected in plasma and rectal samples trailing those detected in upper respiratory tract samples. CRISPR-RT–PCR assays for SARS-CoV-2 RNA in non-respiratory specimens may thus permit direct diagnosis of suspected COVID-19 cases missed by RT–PCR, while tracking SARS-CoV-2 RNA in minimally invasive alternate specimens may better evaluate the progression and resolution of SARS-CoV-2 infections.

Experimental evidence has implicated multiple neurotransmitter systems in either the direct or indirect modulation of cortical arousal and attention circuitry. In this review, we selectively focus on three such systems: 1) norepinephrine (NE)-containing neurons of the locus coeruleus (LC), 2) acetylcholine (ACh)-containing neurons of the basal forebrain (BF), and 3) parvalbumin (PV)-containing gamma-aminobutyric acid neurons of the BF. Whereas BF-PV neurons serve as a rapid and transient arousal system, LC-NE and BF-ACh neuromodulation are typically activated on slower but longer-lasting timescales. Recent findings suggest that the BF-PV system serves to rapidly respond to even subtle sensory stimuli with a microarousal. We posit that salient sensory stimuli, such as those that are threatening or predict the need for a response, will quickly activate the BF-PV system and subsequently activate both the BF-ACh and LC-NE systems if the circumstances require longer periods of arousal and vigilance. We suggest that NE and ACh have overlapping psychological functions with the main difference being the precise internal/environmental sensory situations/contexts that recruit each neurotransmitter system – a goal for future research to determine. Implications of dysfunction of each of these three attentional systems for our understanding of neuropsychiatric conditions are considered. Finally, the contemporary availability of research tools to selectively manipulate and measure the activity of these distinctive neuronal populations promises to answer longstanding questions, such as how various arousal systems influence downstream decision-making and motor responding.

Assessing stress in wild populations is important in many ecological and conservation contexts because the physiological responses of individuals to stressors can be used to identify at-risk populations and the ability to respond appropriately to stressors is related to individual quality and fitness. Yet, one of the great challenges in ecophysiology is linking physiological measures in wild animal populations with changes in individual fitness. Here, we examined two indices of stress, namely, circulating baseline corticosterone concentration ([Cort]) and the heterophil:lymphocyte (H/L) ratio, in a long-lived seabird, the Nazca booby (Sula granti) and their relationship with current individual state and subsequent survival and residual and lifetime reproductive success. [Cort] was related to sex, age, and current reproductive effort in in that males, older birds, and birds currently engaged in a breeding attempt birds had higher [Cort]. [Cort] was negatively associated with survival to the next breeding season. The H/L ratio was not associated with the current state of birds but predicted cohort-specific long-term survival. Lifespan and reproductive performance are correlated in Nazca boobies; therefore, our results suggest that the H/L ratio may be useful as an indicator of overall fitness, while [Cort] can be used to predict current or near-term fitness in this species. We further propose the H/L [or neutrophil/lymphocyte (N/L)] Ratio-Fitness Hypothesis, which posits that this ratio is repeatable within individuals and are negatively associated with fitness. This hypothesis needs to be tested in Nazca boobies and other species, and when supported by empirical evidence, then these ratios could be a powerful monitoring tool for assessing population health or identifying at-risk populations.

ABSTRACT Rational engineering of gas-fermenting bacteria for high yields of bioproducts is vital for a sustainable bioeconomy. It will allow the microbial chassis to renewably valorize natural resources from carbon oxides, hydrogen, and/or lignocellulosic feedstocks more efficiently. To date, rational design of gas-fermenting bacteria such as changing the expression levels of individual enzymes to obtain the desired pathway flux is challenging, because pathway design must follow a verifiable metabolic blueprint indicating where interventions should be executed. Based on recent advances in constraint-based thermodynamic and kinetic models, we identify key enzymes in the gas-fermenting acetogen Clostridium ljungdahlii that correlate with the production of isopropanol. To this extent, we integrated a metabolic model in comparison with proteomics measurements and quantified the uncertainty for a variety of pathway targets needed to improve the bioproduction of isopropanol. Based on in silico thermodynamic optimization, minimal protein requirement analysis, and ensemble modeling-based robustness analysis, we identified the top two significant flux control sites, i.e., acetoacetyl-coenzyme A (CoA) transferase (AACT) and acetoacetate decarboxylase (AADC), overexpression of which could lead to increased isopropanol production. Our predictions directed iterative pathway construction, which enabled a 2.8-fold increase in isopropanol production compared to the initial version. The engineered strain was further tested under gas-fermenting mixotrophic conditions, where more than 4 g/L isopropanol was produced when CO, CO2, and fructose were provided as the substrates. In a bioreactor environment sparging with CO, CO2, and H2 only, the strain produced 2.4 g/L isopropanol. Our work highlighted that the gas-fermenting chasses can be fine-tuned for high-yield bioproduction by directed and elaborative pathway engineering. IMPORTANCE Highly efficient bioproduction from gaseous substrates (e.g., hydrogen and carbon oxides) will require systematic optimization of the host microbes. To date, the rational redesign of gas-fermenting bacteria is still in its infancy, due in part to the lack of quantitative and precise metabolic knowledge that can direct strain engineering. Here, we provide a case study by engineering isopropanol production in gas-fermenting Clostridium ljungdahlii. We demonstrate that a modeling approach based on the thermodynamic and kinetic analysis at the pathway level can provide actionable insights into strain engineering for optimal bioproduction. This approach may pave the way for iterative microbe redesign for the conversion of renewable gaseous feedstocks.

A novel function for the L1 cell adhesion molecule, which binds the actin adaptor protein Ankyrin was identified in constraining dendritic spine density on pyramidal neurons in the mouse neocortex. In an L1-null mouse mutant increased spine density was observed on apical but not basal dendrites of pyramidal neurons in diverse cortical areas (prefrontal cortex layer 2/3, motor cortex layer 5, visual cortex layer 4. The Ankyrin binding motif (FIGQY) in the L1 cytoplasmic domain was critical for spine regulation, as demonstrated by increased spine density and altered spine morphology in the prefrontal cortex of a mouse knock-in mutant (L1YH) harboring a tyrosine (Y) to histidine (H) mutation in the FIGQY motif, which disrupted L1-Ankyrin association. This mutation is a known variant in the human L1 syndrome of intellectual disability. L1 was localized by immunofluorescence staining to spine heads and dendrites of cortical pyramidal neurons. L1 coimmunoprecipitated with Ankyrin B (220 kDa isoform) from lysates of wild type but not L1YH forebrain. This study provides insight into the molecular mechanism of spine regulation and underscores the potential for this adhesion molecule to regulate cognitive and other L1-related functions that are abnormal in the L1 syndrome.

Introduction: This mixed-method study analyzes the self-archiving behaviors and underlying motivations of researchers at an institution very recently recategorized by the Carnegie Classification system from “Doctoral– High Research Activity (R2)” to “Doctoral–Very High Research Activity (R1).” Methods: A quantitative analysis of data provided by CHORUS, a multi-institutional open access (OA) infrastructure project designed to minimize the administrative costs of complying with federal public access mandates, was followed by semi-structured qualitative interviews with researchers to determine the underlying motivations for self-archiving research papers resulting from federal grant support. Results: Fifty-one authors with federal research funding published 71 journal articles; 139 OA versions of these 71 articles were intentionally made available by researchers across nine types of platforms, including and in addition to those provided by publishers. Interviews with 11 investigators revealed motivators such as a dedication to public access to knowledge, learned behaviors in specific disciplines, and enlightened self-interest. Challenges included concern regarding confidentiality, confusion about intellectual property and funder requirements, administrative overhead, and integrity of the scholarly record. Discussion: Despite concerns and a lack of an OA mandate and other drivers more commonly present at larger, more research-intensive universities, several researchers interviewed actively engaged in self-archiving article versions, not always with clear motivations. These findings have implications for both scholarly communications and collection development services. Conclusion: These quantitative and qualitative data informed the creation of three distinct personas intended to help librarians at similar universities design services in a manner that aligns with investigator motivations.

Access to healthcare is a Social Determinant of Health that is associated with public health outcomes and barriers to access disproportionately affect African American adults. This study used a health and financial literacy approach to qualitatively assess how African American adults access healthcare and potential barriers faced (n = 20). Results indicated a wide range of experiences generally split between positive and negative experiences in access to healthcare. Specific themes that emerged included scheduling issues and appointment availability, expense of care, lack of transparency in insurance coverage, the need for more primary care clinics and enhanced community outreach and education on how to access healthcare. This research identifies a need for increased education surrounding health insurance coverage and an identified need for more local physicians or ease of scheduling. All participants in this study stated they were covered by health insurance of some form. Future research should examine these issues in the context of socioeconomic and insurance status.

IntroductionSARS-CoV-2 is a respiratory pathogen currently causing a worldwide pandemic, with resulting pathology of differing severity in humans, from mild illness to severe disease and death. The rhesus macaque model of COVID-19 was utilized to evaluate the added benefit of prophylactic administration of human post-SARS-CoV-2 infection convalescent plasma (CP) on disease progression and severity.MethodsA pharmacokinetic (PK) study using CP in rhesus monkeys preceded the challenge study and revealed the optimal time of tissue distribution for maximal effect. Thereafter, CP was administered prophylactically three days prior to mucosal SARS-CoV-2 viral challenge.ResultsResults show similar viral kinetics in mucosal sites over the course of infection independent of administration of CP or normal plasma, or historic controls with no plasma. No changes were noted upon necropsy via histopathology, although there were differences in levels of vRNA in tissues, with both normal and CP seemingly blunting viral loads.DiscussionResults indicate that prophylactic administration with mid-titer CP is not effective in reducing disease severity of SARS-CoV-2 infection in the rhesus COVID-19 disease model.