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White dwarfs are some of the most versatile tools in the universe. Their ages can provide a lower limit to the age of the universe, and their masses and structure can inform us about the inner workings of the stars they came from. Asteroseismic studies of pulsating white dwarfs have greatly increased our knowledge about the masses of the atmospheric layers, which are crucial to determine the cooling rate of white dwarfs. Knowing the cooling rate will tell us much about the age of the white dwarf and in turn, the age of the universe. In this study, we present the first time-series photometry of pulsating white dwarf candidates in the open star cluster Messier 67. By looking at an ensemble of white dwarfs in an old, open cluster such as Messier 67, we can begin to constrain which properties of stars affect the thicknesses of the atmospheric layers. Standard stellar evolutionary theory suggests the atmospheric structure of each white dwarf in the sample should be identical, as they came from nearly identical progenitor stars; this prediction has yet to be tested. This sample of spectroscopically confirmed white dwarfs comes from a previous study of the white dwarf population in Messier 67. Six hours of time-series photometry are analyzed for pulsation-driven luminosity changes. We find one definite pulsator that is not a cluster member and evidence of variability in three additional white dwarfs that are cluster members. If these additional white dwarfs can be confirmed to be variable, then they can be subject to the time-intensive follow-up observations necessary to search for differences in their atmospheric structures.

Schneider et al. (2020) presented the discovery of WISEA J041451.67-585456.7 and WISEA J181006.18-101000.5, which appear to be the first examples of extreme T-type subdwarfs (esdTs; metallicity <= -1 dex, T_eff <= 1400 K). Here we present new discoveries and follow-up of three T-type subdwarf candidates, with an eye toward expanding the sample of such objects with very low metallicity and extraordinarily high kinematics, properties that suggest membership in the Galactic halo. Keck/NIRES near-infrared spectroscopy of WISEA J155349.96+693355.2, a fast-moving object discovered by the Backyard Worlds: Planet 9 citizen science project, confirms that it is a mid-T subdwarf. With H_W2 = 22.3 mag, WISEA J155349.96+693355.2 has the largest W2 reduced proper motion among all spectroscopically confirmed L and T subdwarfs, suggesting that it may be kinematically extreme. Nevertheless, our modeling of the WISEA J155349.96+693355.2 near-infrared spectrum indicates that its metallicity is only mildly subsolar. In analyzing the J155349.96+693355.2 spectrum, we present a new grid of low-temperature, low-metallicity model atmosphere spectra. We also present the discoveries of two new esdT candidates, CWISE J073844.52-664334.6 and CWISE J221706.28-145437.6, based on their large motions and colors similar to those of the two known esdT objects. Finding more esdT examples is a critical step toward mapping out the spectral sequence and observational properties of this newly identified population.

We report the identification of 89 new systems containing ultracool dwarf companions to main sequence stars and white dwarfs, using the citizen science project Backyard Worlds: Planet 9 and cross-reference between Gaia and CatWISE2020. Thirty-two of these companions and thirty-three host stars were followed up with spectroscopic observations, with companion spectral types ranging from M7-T9 and host spectral types ranging from G2-M9. These systems exhibit diverse characteristics, from young to old ages, blue to very red spectral morphologies, potential membership to known young moving groups, and evidence of spectral binarity in 9 companions. Twenty of the host stars in our sample show evidence for higher order multiplicity, with an additional 11 host stars being resolved binaries themselves. We compare this sample's characteristics with those of the known stellar binary and exoplanet populations, and find our sample begins to fill in the gap between directly imaged exoplanets and stellary binaries on mass ratio-binding energy plots. With this study, we increase the population of ultracool dwarf companions to FGK stars by \\(\\)42\\%, and more than triple the known population of ultracool dwarf companions with separations larger than 1,000 au, providing excellent targets for future atmospheric retrievals.

We present Spitzer follow-up imaging of 95 candidate extremely cold brown dwarfs discovered by the Backyard Worlds: Planet 9 citizen science project, which uses visually perceived motion in multi-epoch WISE images to identify previously unrecognized substellar neighbors to the Sun. We measure Spitzer [3.6]-[4.5] color to phototype our brown dwarf candidates, with an emphasis on pinpointing the coldest and closest Y dwarfs within our sample. The combination of WISE and Spitzer astrometry provides quantitative confirmation of the transverse motion of 75 of our discoveries. Nine of our motion-confirmed objects have best-fit linear motions larger than 1\"/yr; our fastest-moving discovery is WISEA J155349.96+693355.2 (total motion ~2.15\"/yr), a possible T type subdwarf. We also report a newly discovered wide-separation (~400 AU) T8 comoving companion to the white dwarf LSPM J0055+5948 (the fourth such system to be found), plus a candidate late T companion to the white dwarf LSR J0002+6357 at 5.5' projected separation (~8,700 AU if associated). Among our motion-confirmed targets, five have Spitzer colors most consistent with spectral type Y. Four of these five have exceptionally red Spitzer colors suggesting types of Y1 or later, adding considerably to the small sample of known objects in this especially valuable low-temperature regime. Our Y dwarf candidates begin bridging the gap between the bulk of the Y dwarf population and the coldest known brown dwarf.

The neuromodulators dopamine (DA) and serotonin (5-hydroxytryptamine; 5HT) powerfully regulate associative learning 1 , 2 , 3 , 4 , 5 , 6 , 7 – 8 . Similarities in the activity and connectivity of these neuromodulatory systems have inspired competing models of how DA and 5HT interact to drive the formation of new associations 9 , 10 , 11 , 12 , 13 – 14 . However, these hypotheses have not been tested directly because it has not been possible to interrogate and manipulate multiple neuromodulatory systems in a single subject. Here we establish a mouse model that enables simultaneous genetic access to the brain’s DA and 5HT neurons. Anterograde tracing revealed the nucleus accumbens (NAc) to be a putative hotspot for the integration of convergent DA and 5HT signals. Simultaneous recording of DA and 5HT axon activity, together with genetically encoded DA and 5HT sensor recordings, revealed that rewards increase DA signalling and decrease 5HT signalling in the NAc. Optogenetically dampening DA or 5HT reward responses individually produced modest behavioural deficits in an appetitive conditioning task, while blunting both signals together profoundly disrupted learning and reinforcement. Optogenetically reproducing DA and 5HT reward responses together was sufficient to drive the acquisition of new associations and supported reinforcement more potently than either manipulation did alone. Together, these results demonstrate that striatal DA and 5HT signals shape learning by exerting opponent control of reinforcement. A double-transgenic mouse model that enables monitoring or manipulation of dopamine and serotonin simultaneously in the brain’s nucleus accumbens shows that these neuromodulators have opponent roles in reward learning.

Most animals and humans are inherently social, enabling group dynamics to promote survival. Despite their importance, how the brain calibrates appropriate social behaviors to maximize survival and benefits remains incompletely understood. Distributed networks of neural circuits mediate complex behavioral states, including social behaviors. The striatum has long-known to be a structure essential for motivation and goal-directed behavior. The striatum is massive: it extends far along the anterior-posterior axis and can be divided into ventral, dorsal, and posterior domains. While it is well-appreciated that these striatal domains control motivated behaviors through coordinated functions, such that ventral striatum (e.g., nucleus accumbens) governs motivation and rewards processing, dorsal striatum mediates motor planning and action selection, and the posterior striatum (i.e., tail of the striatum) integrates sensory inputs, much less is understood about how they modulate social interactions. This mini review discusses the current understanding of what aspects of social behavior are controlled by each striatal subregion. We focus on key studies that highlight prominent neuromodulators, such as dopamine, serotonin, and neuropeptides, and their roles in social behaviors. We propose a framework in which striatal subregions calibrate social interaction through coordinated activities that mediate distinct aspects of the social interaction, similar to general motivation. A deeper understanding of how distributed striatal circuits modulate social behavior will help inform the development of therapeutic approaches for social dysfunction in various psychiatric states.

This study investigates correlates of anti-S1 antibody response following COVID-19 vaccination in a U.S. population-based meta-cohort of adults participating in longstanding NIH-funded cohort studies. Anti-S1 antibodies were measured from dried blood spots collected between February 2021-August 2022 using Luminex-based microsphere immunoassays. Of 6245 participants, mean age was 73 years (range, 21-100), 58% were female, and 76% were non-Hispanic White. Nearly 52% of participants received the BNT162b2 vaccine and 48% received the mRNA-1273 vaccine. Lower anti-S1 antibody levels are associated with age of 65 years or older, male sex, higher body mass index, smoking, diabetes, COPD and receipt of BNT16b2 vaccine (vs mRNA-1273). Participants with a prior infection, particularly those with a history of hospitalized illness, have higher anti-S1 antibody levels. These results suggest that adults with certain socio-demographic and clinical characteristics may have less robust antibody responses to COVID-19 vaccination and could be prioritized for more frequent re-vaccination. The antibody response to COVID-19 vaccines varies among individuals. Here the authors find that older age, male sex, smoking, higher BMI, vaccine type, and certain comorbidities are associated with lower anti-S1 antibody levels after COVID-19 vaccinations, indicating that certain groups might benefit from higher frequency or doses of vaccination.

Category: Trauma; Basic Sciences/Biologics Introduction/Purpose: A variable pitch locking screw is intended to provide interfragmentary compression combined with fixed angle stability of locking plate constructs. The objective of this study was to compare variable pitch locking screws with standard locking screws in bicortical fixation scenarios in cadaver bone, by assessing: (1) interfragmentary compression and plate-bone compression; and (2) construct biomechanical stability. Methods: Nine matched pairs of fresh-frozen cadaveric specimens were used to compare variable pitch locking screws and standard locking screws. First, interfragmentary compression and plate-bone compression associated with insertion of single bicortical screws at increasing levels of torque were measured in distal tibiae having a simulated longitudinal fracture. Second, fibulae were osteotomized to create a stable fracture pattern, fixed with five-screw plated constructs, and tested in either cyclic axial and torsional loading or four-point bending. Results: Interfragmentary and plate-bone compression forces were significantly higher with variable pitch locking screws compared to standard locking screws (p =0.002 & p=0.028, respectively). The amount of compression was variable across specimens. In cyclic loading of fibula constructs, no significant differences were detected in construct axial displacement or angular displacement. In four-point bending, no differences were detected in maximum force or bending stiffness. Conclusion: Variable pitch locking screws can produce high interfragmentary compression between cortices, along with moderate plate-bone compression. In a stable bicortical fixation scenario under external loading, construct stability was similar to normal locking screws.

Objective HLA‐DR–expressing fibroblast‐like synoviocytes (FLS) are a prominent cell type in synovial tissue in chronic inflammatory forms of arthritis. FLS‐derived extracellular matrix (ECM) proteins, including fibronectin‐1 (FN1), contain immunogenic CD4+ T cell epitopes in patients with postinfectious Lyme arthritis (LA). However, the role of FLS in presentation of these T cell epitopes remains uncertain. Methods Primary LA FLS and primary murine FLS stimulated with interferon gamma (IFNγ), Borrelia burgdorferi, and/or B burgdorferi peptidoglycan (PG) were assessed for properties associated with antigen presentation. HLA‐DR–presented peptides from stimulated LA FLS were identified by immunopeptidomics analysis. OT‐II T cells were co‐cultured with stimulated murine FLS in the presence of cognate ovalbumin antigen to determine the potential of FLS to act as inducible antigen presenting cells (APCs). Results FLS expressed HLA‐DR molecules within inflamed synovial tissue and tendons from patients with postinfectious LA in situ. Major histocompatibility complex (MHC) class II and co‐stimulatory molecules were expressed by FLS following in vitro stimulation with IFNγ and B burgdorferi and presented both foreign and self‐MHC‐II peptides, including an immunogenic T cell epitope derived from Lyme autoantigen FN1. Stimulated FLS induced proliferation of naive OT‐II CD4+ T cells that were dependent on OT‐II antigen and CD40. Stimulation with B burgdorferi PG enhanced FLS‐mediated T cell activation. Conclusion MHC‐II+ FLS are inducible APCs that can induce CD4+ T cell activation in an antigen‐ and CD40‐dependent manner. Activated FLS can also present ECM‐derived Lyme autoantigens, implicating FLS in amplifying tissue‐localized autoimmunity in LA.

Despite the availability of effective vaccines and a recent decrease in annual deaths, COVID-19 remains a leading cause of death. Serological studies provide insights into host immunobiology of adaptive immune response to infection, which holds promise for identifying high-risk individuals for adverse COVID-19 outcomes. We investigated correlates of anti-nucleocapsid antibody responses following SARS-CoV-2 infection in a US population-based meta-cohort of adults participating in longstanding National Institutes of Health–funded cohort studies. Anti-nucleocapsid antibodies were measured from dried blood spots collected between February 2021 and February 2023. Among 1419 Collaborative Cohort of Cohorts for COVID-19 Research participants with prior SARS-CoV-2 infection, the mean age (standard deviation) was 65.8 (12.1), 61% were women, and 42.8% self-reported membership in a race/ethnicity minority group. The proportion of participants reactive to nucleocapsid peaked at 69% by 4 months after infection and waned to only 44% ≥12 months after infection. Higher anti-nucleocapsid antibody response was associated with older age, Hispanic or American Indian Alaskan Native (vs White) race/ethnicity, lower income, lower education, former smoking, and higher anti-spike antibody levels. Asian race (vs White) and vaccination (even after infection) were associated with lower nucleocapsid reactivity. Neither vaccine manufacturer nor common cardiometabolic comorbidities were not associated with anti-nucleocapsid response. These findings inform the underlying immunobiology of adaptive immune response to infection, as well as the potential utility of anti-nucleocapsid antibody response for clinical practice and COVID-19 serosurveillance.