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Abstract Intracortical microelectrodes (IMEs) are devices designed to be implanted into the cerebral cortex for various neuroscience and neuro-engineering applications. A critical feature of IMEs is their ability to detect neural activity from individual neurons. Currently, IMEs are limited by chronic failure, largely considered to be caused by the prolonged neuroinflammatory response to the implanted devices. Over the past few years, the characterization of the neuroinflammatory response has grown in sophistication, with the most recent advances focusing on mRNA expression following IME implantation. While gene expression studies increase our broad understanding of the relationship between IMEs and cortical tissue, advanced proteomic techniques have not been reported. Proteomic evaluation is necessary to describe the diverse changes in protein expression specific to neuroinflammation, neurodegeneration, or tissue and cellular viability, which could lead to the further development of targeted intervention strategies designed to improve IME functionality. In this study, we have characterized the expression of 62 proteins within 180 μm of the IME implant site at 4-, 8-, and 16-weeks post-implantation. We identified potential targets for immunotherapies, as well as key pathways that contribute to neuronal dieback around the IME implant.

Genetic resources are the foundation of American agriculture’s ongoing success—the diversity, security, health, and genetic integrity of these resources must be safeguarded. However, in contrast to other crops, protecting, managing, and using collections of woody landscape plant genetic resources present significant challenges. These include conservation of at-risk populations that have high genetic diversity, evaluation of taxa with an unknown potential to invade, and management of large specimens that have long generation times and often recalcitrant or difficult-to-store seeds. The wide diversity of taxa and the limited number of specialist curators and scholars present further challenges. Thus, effective collection, preservation, evaluation, and distribution of woody landscape plant germplasm require substantial and specialized resources. The most fundamental challenge is simple: too many built landscapes have low taxonomic diversity and are often dominated by a single taxon, or monoculture. In turn, these taxonomically and genetically depauperate landscapes are vulnerable to a host of biotic and abiotic threats and are less likely to provide ecosystem and societal services for which they were designed. To develop more resilient landscapes, there is an urgent need to expand taxonomic diversity, which requires the horticultural community to effectively acquire, curate, evaluate, distribute, and use diverse woody landscape plant genetic resources. The role of the US Department of Agriculture-Agricultural Research Service (USDA-ARS) National Plant Germplasm System (NPGS) Woody Landscape Plant Crop Germplasm Committee (WLPCGC) is to identify vulnerabilities and threats that compromise WLP crops in the United States and make recommendations for prioritization of germplasm acquisition, evaluation, research, and management priorities through regular interaction with stakeholders. Due to the breadth of genera and shifting plant genetic resource needs of the nursery industry, it is impractical to list specific threatened or priority genera in a broadly applicable crop vulnerability statement. Instead, the WLPCGC has identified themes of threats and vulnerabilities providing a foundation upon which to support prioritization as threats to specific genera emerge.

Abstract Excitons in two-dimensional (2D) semiconductors have offered an attractive platform for optoelectronic and valleytronic devices. Further realizations of correlated phases of excitons promise device concepts not possible in the single particle picture. Here we report tunable exciton “spin” orders in WSe2/WS2 moiré superlattices. We find evidence of an in-plane (xy) order of exciton “spin”—here, valley pseudospin—around exciton filling v ex = 1, which strongly suppresses the out-of-plane “spin” polarization. Upon increasing v ex or applying a small magnetic field of ~10 mT, it transitions into an out-of-plane ferromagnetic (FM-z) spin order that spontaneously enhances the “spin” polarization, i.e., the circular helicity of emission light is higher than the excitation. The phase diagram is qualitatively captured by a spin-1/2 Bose–Hubbard model and is distinct from the fermion case. Our study paves the way for engineering exotic phases of matter from correlated spinor bosons, opening the door to a host of unconventional quantum devices.

The nursery industry produces and sells plants for landscape and environmental purposes and represents a major sector within the US agricultural industry. In recent years, the nursery industry has undergone rapid growth as a result of various factors, including increased demand from housing development and pandemic-fueled interest in home horticulture. As with any industry, the nursery industry must adapt to changes in societal trends to sustain growth. In the wake of unprecedented societal and supply chain issues stemming from the global coronavirus disease 2019 pandemic, the American Society for Horticultural Science Nursery Crops Professional Interest Group gathered experts in various disciplines to provide their opinions and insights into the future of the nursery industry, focusing specifically on the changes and challenges the nursery industry will face in the coming decade. Nursery crop specialists spanning the United States identified three primary areas that will steer the future momentum of the nursery industry: consumer trends, natural resources, and labor. Six experts were selected to represent these areas in a workshop held Jul 2022 at the American Society for Horticultural Science Annual Conference in Chicago, IL, USA. This article was developed to disseminate to the greater scientific community the discussions held and insight shared during that workshop.

Background: Prostatic urethral lift, or UroLift, has gained popularity as a treatment for lower urinary tract symptoms associated with benign prostatic hyperplasia (BPH). Surgical reintervention rates are a reliable indicator for treatment durability. Objective: The objective of this study was to utilize TriNetX, a third-party database, to investigate the incidence of surgical reintervention following UroLift, transurethral resection of the prostate (TURP), and photoselective vaporization of the prostate (PVP) procedures for BPH from 2015 to 2018. Design, setting, and participants: Male patients aged 18–100 yr diagnosed with BPH were identified in the TriNetX Diamond Network database between January 2015 and December 2018. Cohorts of individuals undergoing their first UroLift procedure were built using Current Procedural Terminology and International Classification of Diseases 10th Revision codes. TURP and PVP cohorts were built as comparison groups. The cohorts were then queried for subsequent BPH-related procedures. Outcome measurements and statistical analysis: Reprocedure rates were assessed and descriptive statistics were used. Results and limitations: The mean age at first-time UroLift was 70.1 ± 9.4 yr (n = 14 343). Cumulative reprocedure rates collected after first-time UroLift included 1 yr after UroLift (5.1%, n = 14 343) and 4 yr after UroLift (16.1%, n = 710), with an average annual increase of +3.6% per year following 1 yr after the procedure. Comparatively, TURP (n = 22 071) and PVP (n = 14 110) had 4-yr reprocedure rates of 7.5% and 7.8%, respectively, during the same timeframe. Limitations include a lack of clinical data and loss of follow-up data outside the Diamond Network. Conclusions: The reprocedure rate of UroLift at 4 yr is double the rate of TURP and PVP. In appropriately selected patients, UroLift might be a suitable option for those who desire symptomatic relief from BPH with minimal erectile and ejaculatory side effects. However, the risk of secondary surgical intervention should be considered when considering BPH treatments. Patient summary: We compared the reintervention rates of prostatic urethral lift (PUL), transurethral resection of the prostate (TURP), and photoselective vaporization of the prostate (PVP) using the TriNetX database, and have found that the highest reintervention rates were for PUL of 16% at 4 yr of follow-up, compared with about 8% for those who had TURP and PVP. Interestingly, the most common reintervention was the same operation at 1 yr. This has important implications when counseling patients about the durability of these various outlet procedures for BPH.

Abstract Investigations were conducted to develop a general protocol for the isolation and in vitro culture of ovary‐derived cells from black crappie, Pomoxis nigromaculatus, and white crappie, P. annularis. Five digestive enzymes: 500 U/mL collagenase type I, 500 U/mL collagenase type IV, 0.05% trypsin‐EDTA, 0.25% trypsin‐EDTA, and 1X TrypLE™ Express were evaluated for live cell isolation. The isolated cells were cultured in 10 or 20% fetal bovine serum (FBS) in L‐15 growth media. In addition, four incubation temperatures (15°C, 20°C, 25°C, and 30°C) were also evaluated. The number of live cells obtained from the 0.25% trypsin and TrypLE™ Express treatments was significantly higher than other treatments. No difference in cell growth was observed between the two FBS treatments. Cells isolated using TrypLE™ Express and 0.25% trypsin reached 80% to 90% confluency in 12.5 cm2 cell culture flasks within 5 days of inoculation at 20 and 25°C. At 15°C, 10 days were required to reach 80%–90% confluency. Morphologically, cells incubated at 15°C, 20°C, and 25°C appeared healthier than cells incubated at 30°C, where irregular cell shape and substrate detachment were observed. We concluded TrypLE™ Express and 0.25% trypsin were optimal for cell dissociation and isolation of crappie ovarian cells. An incubation temperature of 20°C–25°C was favorable for cell culture in L‐15 media supplemented with either 10% or 20% FBS.

Oligodendrocyte-lineage cells are central nervous system (CNS) glia that perform multiple functions including the selective myelination of some but not all axons. During myelination, synaptic vesicle release from axons promotes sheath stabilization and growth on a subset of neuron subtypes. In comparison, it is unknown if pre-myelinating oligodendrocyte process extensions selectively interact with specific neural circuits or axon subtypes, and whether the formation and stabilization of these neuron–glia interactions involves synaptic vesicle release. In this study, we used fluorescent reporters in the larval zebrafish model to track pre-myelinating oligodendrocyte process extensions interacting with spinal axons utilizing in vivo imaging. Monitoring motile oligodendrocyte processes and their interactions with individually labeled axons revealed that synaptic vesicle release regulates the behavior of subsets of process extensions. Specifically, blocking synaptic vesicle release decreased the longevity of oligodendrocyte process extensions interacting with reticulospinal axons. Furthermore, blocking synaptic vesicle release increased the frequency that new interactions formed and retracted. In contrast, tracking the movements of all process extensions of singly-labeled oligodendrocytes revealed that synaptic vesicle release does not regulate overall process motility or exploratory behavior. Blocking synaptic vesicle release influenced the density of oligodendrocyte process extensions interacting with reticulospinal and serotonergic axons, but not commissural interneuron or dopaminergic axons. Taken together, these data indicate that alterations to synaptic vesicle release cause changes to oligodendrocyte-axon interactions that are neuron subtype specific.

Long-term immunity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) requires the identification of T-cell epitopes affecting host immunogenicity. In this computational study, we explored the CD8+ epitope diversity estimated in 27 of the most common HLA-A and HLA-B alleles, representing most of the United States population. Analysis of 16 SARS-CoV-2 variants [B.1, Alpha (B.1.1.7), five Delta (AY.100, AY.25, AY.3, AY.3.1, AY.44), and nine Omicron (BA.1, BA.1.1, BA.2, BA.4, BA.5, BQ.1, BQ.1.1, XBB.1, XBB.1.5)] in analyzed MHC class I alleles revealed that SARS-CoV-2 CD8+ epitope conservation was estimated at 87.6%–96.5% in spike (S), 92.5%–99.6% in membrane (M), and 94.6%–99% in nucleocapsid (N). As the virus mutated, an increasing proportion of S epitopes experienced reduced predicted binding affinity: 70% of Omicron BQ.1-XBB.1.5 S epitopes experienced decreased predicted binding, as compared with ~3% and ~15% in the earlier strains Delta AY.100–AY.44 and Omicron BA.1–BA.5, respectively. Additionally, we identified several novel candidate HLA alleles that may be more susceptible to severe disease, notably HLA-A*32:01, HLA-A*26:01, and HLA-B*53:01, and relatively protected from disease, such as HLA-A*31:01, HLA-B*40:01, HLA-B*44:03, and HLA-B*57:01. Our findings support the hypothesis that viral genetic variation affecting CD8 T-cell epitope immunogenicity contributes to determining the clinical severity of acute COVID-19. Achieving long-term COVID-19 immunity will require an understanding of the relationship between T cells, SARS-CoV-2 variants, and host MHC class I genetics. This project is one of the first to explore the SARS-CoV-2 CD8+ epitope diversity that putatively impacts much of the United States population.

Locus coeruleus (LC) projections to the hippocampus play a critical role in learning and memory. However, the precise timing of LC-hippocampus communication during learning and which LC-derived neurotransmitters are important for memory formation in the hippocampus are currently unknown. Although the LC is typically thought to modulate neural activity via the release of norepinephrine, several recent studies have suggested that it may also release dopamine into the hippocampus and other cortical regions. In some cases, it appears that dopamine release from LC into the hippocampus may be more important for memory than norepinephrine. Here, we extend these data by characterizing the phasic responses of the LC and its projections to the dorsal hippocampus during trace fear conditioning in mice. We find that the LC and its projections to the hippocampus respond to task-relevant stimuli and that amplifying these responses with optogenetic stimulation can enhance long-term memory formation. We also demonstrate that LC activity increases both norepinephrine and dopamine content in the dorsal hippocampus and that the timing of hippocampal dopamine release during trace fear conditioning is similar to the timing of LC activity. Finally, we show that hippocampal dopamine is important for trace fear memory formation, while norepinephrine is not.

Ungulates commonly select habitat with higher forage biomass and or nutritional quality to improve body condition and fitness. However, predation risk can alter ungulate habitat selection and foraging behavior and may affect their nutritional condition. Ungulates often choose areas with lower predation risk, sometimes sacrificing higher quality forage. This forage–predation risk trade-off can be important for life history strategies and influences individual nutritional condition and population vital rates. We used GPS collar data from adult female mule deer (Odocoileus hemionus) and mountain lions (Puma concolor) to model mule deer habitat selection in relation to forage conditions, stalking cover and predation risk from mountain lions to determine if a forage-predation risk trade-off existed for mule deer in central New Mexico. We also examined mountain lion kill sites and mule deer foraging locations to assess trade-offs at a finer scale. Forage biomass and protein content were inversely correlated with horizontal visibility, hence associated with higher stalking cover for mountain lions, suggesting a forage-predation risk trade-off for mule deer. Mule deer habitat selection was influenced by forage biomass and protein content at the landscape and within home range spatial scales, with forage protein being related to habitat selection during spring and summer and forage biomass during winter. However, mule deer selection for areas with better foraging conditions was constrained by landscape-scale encounter risk for mountain lions, such that increasing encounter risk was associated with diminished selection for areas with better foraging conditions. Mule deer also selected for areas with higher visibility when mountain lion predation risk was higher. Mountain lion kill sites were best explained by decreasing horizontal visibility and available forage protein, suggesting that deer may be selecting for forage quality at the cost of predation risk. A site was 1.5 times more likely to be a kill site with each 1-meter decrease in visibility (i.e., increased stalking cover). Mule deer selection of foraging sites was related to increased forage biomass, further supporting the potential for a trade-off scenario. Mule deer utilized spatio-temporal strategies and risk-conditional behavior to reduce predation risk, and at times selected suboptimal foraging areas with lower predation risk.

Summary: Motor neuron (MN) demise is a hallmark of several neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS). Post-transcriptional gene regulation can control RNA’s fate, and defects in RNA processing are critical determinants of MN degeneration. N6-methyladenosine (m6A) is a post-transcriptional RNA modification that controls diverse aspects of RNA metabolism. To assess the m6A requirement in MNs, we depleted the m6A methyltransferase-like 3 (METTL3) in cells and mice. METTL3 depletion in embryonic stem cell-derived MNs has profound and selective effects on survival and neurite outgrowth. Mice with cholinergic neuron-specific METTL3 depletion display a progressive decline in motor behavior, accompanied by MN loss and muscle denervation, culminating in paralysis and death. Reader proteins convey m6A effects, and their silencing phenocopies METTL3 depletion. Among the m6A targets, we identified transactive response DNA-binding protein 43 (TDP-43) and discovered that its expression is under epitranscriptomic control. Thus, impaired m6A signaling disrupts MN homeostasis and triggers neurodegeneration conceivably through TDP-43 deregulation.

Introduction: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and acute pulmonary embolism (APE) present a diagnostic challenge in the emergency department (ED) setting. We aimed to identify key clinical characteristics and D-dimer thresholds associated with APE in SARS-CoV-2 positive ED patients. Methods: We performed a multicenter, retrospective cohort study for adult patients who were diagnosed with coronavirus 2019 (COVID-19) and had computed tomography pulmonary angiogram (CTPA) performed between March 17, 2020–January 31, 2021. We performed univariate analysis to determine numeric medians, chi-square values for association between clinical characteristic and positive CTPA. Logistic regression was used to determine the odds of a clinical characteristic being associated with a diagnosis of APE. Results: Of 408 patients who underwent CTPA, 29 (7.1%) were ultimately found to have APE. In multivariable analysis, patients with a body mass index greater than 32 (odds ratio [OR] 4.4, 95% confidence interval [CI] 1.0 -19.3), a heart rate greater than 90 beats per minute (bpm) (OR 5.0, 95% CI 1.0-24.9), and a D-dimer greater than 1,500 micrograms per liter (μg/L) (OR 5.6, 95% CI 1.6-20.2) were significantly associated with pulmonary embolism. In our population that received a D-dimer and was SARS-CoV-2 positive, limiting CTPA to patients with a heart rate over 90 or a D-dimer value over 1500 μg/L would reduce testing 27.2% and not miss APE. Conclusion: In patients with acute COVID-19 infections, D-dimer at standard cutoffs was not usable. Limiting CTPA using a combination of heart rate greater than 90 bpm or D-dimer greater than 1,500 μg/L would significantly decrease imaging in this population.

Abstract Background and Aim The DanEoE is a previously described population‐ and register‐based cohort of 236 adult patients with eosinophilic esophagitis (EoE) in a well‐defined Danish region with a population of 580 000 and free medical treatment. The aim of the study was to compare the phenotype and treatment response between EoE patients with complications to patients without complications at diagnosis. Methods A retrospective cross‐sectional study of the DanEoE cohort's 236 adult EoE patients diagnosed between 2007 and 2017 in the North Denmark Region. Patients were divided into a group who had had complications (dilated or food bolus obstruction [FBO]) before or at the diagnosis, and a group without. Results At the diagnostic endoscopy, 61% had never had a complication, and 39% had either had FBO (n = 77) or been dilated (n = 15). The complicated group had the same mean age at symptom debut (37 [SD = 16] vs 37 [SD = 17] years, P = 1.0), but were diagnosed significantly later with a resulting longer diagnostic delay (13 [SD = 13] vs 7.9 [SD = 11] years, P = 0.01). Almost half of all patients were never treated to symptomatic remission (uncomplicated 40%, complicated 49%). The histological remission was not secured in the majority (uncomplicated 68%, complicated 70%). Despite this,

Abstract Lissencephaly-1 (LIS1) is associated with neurodevelopmental diseases and is known to regulate the molecular motor cytoplasmic dynein activity. Here we show that LIS1 is essential for the viability of mouse embryonic stem cells (mESCs), and it governs the physical properties of these cells. LIS1 dosage substantially affects gene expression, and we uncovered an unexpected interaction of LIS1 with RNA and RNA-binding proteins, most prominently the Argonaute complex. We demonstrate that LIS1 overexpression partially rescued the extracellular matrix (ECM) expression and mechanosensitive genes conferring stiffness to Argonaute null mESCs. Collectively, our data transforms the current perspective on the roles of LIS1 in post-transcriptional regulation underlying development and mechanosensitive processes.

Introduction The aetiology of bacterial vaginosis (BV), a biofilm-associated vaginal infection, remains unknown. Epidemiologic data suggest that it is sexually transmitted. BV is characterised by loss of lactic acid-producing lactobacilli and an increase in facultative and strict anaerobic bacteria. Gardnerella spp are present in 95%–100% of cases; Gardnerella vaginalis has been found to be more virulent than other BV-associated bacteria (BVAB) in vitro. However, G. vaginalis is found in women with normal vaginal microbiota and colonisation is not sufficient for BV development. We hypothesise that Gardnerella spp initiate BV biofilm formation, but incident BV (iBV) requires incorporation of other key BVAB (ie, Prevotella bivia, Fannyhessea vaginae) into the biofilm that alter the transcriptome of the polymicrobial consortium. This study will investigate the sequence of microbiologic events preceding iBV.Methods and analysis This study will enrol 150 women aged 18–45 years with normal vaginal microbiota and no sexually transmitted infections at a sexual health research clinic in Birmingham, Alabama. Women will self-collect twice daily vaginal specimens up to 60 days. A combination of 16S rRNA gene sequencing, qPCR for Gardnerella spp, P. bivia and F. vaginae, and broad range 16S rRNA gene qPCR will be performed on twice daily vaginal specimens from women with iBV (Nugent score 7–10 on at least 2 consecutive days) and controls (with comparable age, race, contraceptive method and menstrual cycle days) maintaining normal vaginal microbiota to investigate changes in the vaginal microbiota over time for women with iBV. Participants will complete daily diaries on multiple factors including sexual activity.Ethics and dissemination This protocol is approved by the University of Alabama at Birmingham Institutional Review Board (IRB-300004547) and written informed consent will be obtained from all participants. Findings will be presented at scientific conferences and published in peer-reviewed journals as well as disseminated to providers and patients in communities of interest.

BackgroundTransgender men (TGM) are underrepresented in genital microbiome research. Our prospective study in Birmingham, AL investigated genital microbiota changes over time in TGM initiating testosterone, including the development of incident bacterial vaginosis (iBV). Here, we present lessons learned from recruitment challenges encountered during the conduct of this study.MethodsInclusion criteria were assigned female sex at birth, TGM or non-binary identity, age ≥18 years, interested in injectable testosterone but willing to wait 7 days after enrollment before starting, and engaged with a testosterone-prescribing provider. Exclusion criteria were recent antibiotic use, HIV/STI infection, current vaginal infection, pregnancy, or past 6 months testosterone use. Recruitment initiatives included community advertisements via flyers, social media posts, and referrals from local gender health clinics.ResultsBetween February 2022 and October 2023, 61 individuals contacted the study, 17 (27.9%) completed an in-person screening visit, and 10 (58.8%) of those screened were enrolled. The primary reasons for individuals failing study screening were having limited access to testosterone-prescribing providers, already being on testosterone, being unwilling to wait 7 days to initiate testosterone therapy, or desiring the use of topical testosterone. Engagement of non-White TGM was also minimal.ConclusionDespite robust study inquiry by TGM, screening and enrollment challenges were faced including engagement by TGM not yet in care and specific study eligibility criteria. Excitement among TGM for research representation should be leveraged in future work by engaging transgender community stakeholders at the inception of study development, particularly regarding feasibility of study inclusion and exclusion criteria, as well as recruitment of TGM of color. These results also highlight the need for more clinical resources for prescribing gender-affirming hormone therapy, especially in the Southeastern US.

Bacterial vaginosis (BV), a dysbiosis of the vaginal microbiota, is a common coinfection with Chlamydia trachomatis (Ct), and BV-associated bacteria (BVAB) and their products have been implicated in aiding Ct evade natural immunity. Here, we determined if a non-optimal vaginal microbiota was associated with a higher genital Ct burden and if metronidazole, a standard treatment for BV, would reduce Ct burden or aid in natural clearance of Ct infection. Cervicovaginal samples were collected from women at enrollment and, if testing positive for Ct infection, at a follow-up visit approximately one week later. Cervical Ct burden was assessed by inclusion forming units (IFU) and Ct genome copy number (GCN), and 16S rRNA gene sequencing was used to determine the composition of the vaginal microbiota. We observed a six-log spectrum of IFU and an eight-log spectrum of GCN in our study participants at their enrollment visit, but BV, as indicated by Amsel’s criteria, Nugent scoring, or VALENCIA community state typing, did not predict infectious and total Ct burden, although IFU : GCN increased with Amsel and Nugent scores and in BV-like community state types. Ct burden was, however, associated with the abundance of bacterial species in the vaginal microbiota, negatively with Lactobacillus crispatus and positively with Prevotella bivia. Women diagnosed with BV were treated with metronidazole, and Ct burden was significantly reduced in those who resolved BV with treatment. A subset of women naturally cleared Ct infection in the interim, typified by low Ct burden at enrollment and resolution of BV. Abundance of many BVAB decreased, and Lactobacillus increased, in response to metronidazole treatment, but no changes in abundances of specific vaginal bacteria were unique to women who spontaneously cleared Ct infection.

AbstractPer- and polyfluoroalkyl substances (PFASs) are used in a multitude of processes and products, including nonstick coatings, food wrappers, and fire-fighting foams. These chemicals are environmentally-persistent, ubiquitous, and can be detected in the serum of 98% of Americans. Despite evidence that PFASs alter adaptive immunity, few studies have investigated their effects on innate immunity. The report here presents results of studies that investigated the impact of nine environmentally-relevant PFASs [e.g. perfluorooctanoic acid (PFOA), perfluorooctane sulfonic acid potassium salt (PFOS-K), perfluorononanoic acid (PFNA), perfluorohexanoic acid (PFHxA), perfluorohexane sulfonic acid (PFHxS), perfluorobutane sulfonic acid (PFBS), ammonium perfluoro(2-methyl-3-oxahexanoate) (GenX), 7H-perfluoro-4-methyl-3,6-dioxa-octane sulfonic acid (Nafion byproduct 2), and perfluoromethoxyacetic acid sodium salt (PFMOAA-Na)] on one component of the innate immune response, the neutrophil respiratory burst. The respiratory burst is a key innate immune process by which microbicidal reactive oxygen species (ROS) are rapidly induced by neutrophils in response to pathogens; defects in the respiratory burst can increase susceptibility to infection. The study here utilized larval zebrafish, a human neutrophil-like cell line, and primary human neutrophils to ascertain whether PFAS exposure inhibits ROS production in the respiratory burst. It was observed that exposure to PFHxA and GenX suppresses the respiratory burst in zebrafish larvae and a human neutrophil-like cell line. GenX also suppressed the respiratory burst in primary human neutrophils. This report is the first to demonstrate that these PFASs suppress neutrophil function and support the utility of employing zebrafish larvae and a human cell line as screening tools to identify chemicals that may suppress human immune function.

Abstract Much of our understanding of cell and tissue development, structure, and function stems from fluorescence microscopy. The acquisition of colorful and glowing images engages and excites users ranging from seasoned microscopists to STEM students. Fluorescence microscopes range in cost from several thousand to several hundred thousand US dollars. Therefore, the use of fluorescence microscopy is typically limited to well-funded institutions and biotechnology companies, research core facilities, and medical laboratories, but is financially impractical at many universities and colleges, primary and secondary schools (K-12), and in science outreach settings. In this study, we developed and characterized components that when used in combination with a smartphone or tablet, perform fluorescence microscopy at a cost of less than $50 US dollars per unit. We re-purposed recreational LED flashlights and theater stage lighting filters to enable viewing of green and red fluorophores including EGFP, DsRed, mRFP, and mCherry on a simple-to-build frame made of wood and plexiglass. These devices, which we refer to as glowscopes, were capable of 10 µm resolution, imaging fluorescence in live specimens, and were compatible with all smartphone and tablet models we tested. In comparison to scientific-grade fluorescence microscopes, glowscopes may have limitations to sensitivity needed to detect dim fluorescence and the inability to resolve subcellular structures. We demonstrate capability of viewing fluorescence within zebrafish embryos, including heart rate, rhythmicity, and regional anatomy of the central nervous system. Due to the low cost of individual glowscope units, we anticipate this device can help to equip K-12, undergraduate, and science outreach classrooms with fleets of fluorescence microscopes that can engage students with hands-on learning activities.

Female genital tract infections (FGTIs) include vaginal infections (e.g., bacterial vaginosis [BV]), endometritis, pelvic inflammatory disease [PID], and chorioamnionitis [amniotic fluid infection]. They commonly occur in women of reproductive age and are strongly associated with multiple adverse health outcomes including increased risk of HIV/sexually transmitted infection acquisition and transmission, infertility, and adverse birth outcomes such as preterm birth. These FGTIs are characterized by a disruption of the cervicovaginal microbiota which largely affects host immunity through the loss of protective, lactic acid-producing Lactobacillus spp. and the overgrowth of facultative and strict anaerobic bacteria. Prevotella species (spp.), anaerobic Gram-negative rods, are implicated in the pathogenesis of multiple bacterial FGTIs. Specifically, P. bivia, P. amnii, and P. timonensis have unique virulence factors in this setting, including resistance to antibiotics commonly used in treatment. Additionally, evidence suggests that the presence of Prevotella spp. in untreated BV cases can lead to infections of the upper female genital tract by ascension into the uterus. This narrative review aims to explore the most common Prevotella spp. in FGTIs, highlight their important role in the pathogenesis of FGTIs, and propose future research in this area.

Phosphorus (P) fertilizers applied to container-grown nursery crops readily leach through pine bark-based substrates and can subsequently runoff and contribute to surface water contamination. The objectives of this research were to determine the effect of adding a layer of FeSO4·7H2O-amended pine bark (FSB) to the bottoms of nursery containers on P leaching characteristics. Phosphorus and iron (Fe) leaching in response to FSB layer height (4 or 7.5 cm), FeSO4·7H2O rate (0.3, 0.6, or 1.2 kg·m−3 Fe), and form (i.e., granular versus liquid) used to formulate the FSB layer, and the inclusion of dolomite in the FSB layer were also investigated. Greenhouse studies lasting 15 and 19 weeks were conducted, in which 2.5 L nursery containers containing the FSB layer treatments below non-amended pine bark substrate were fertilized with 199 or 117 mg P from a soluble or controlled-release fertilizer, respectively. Leachate resulting from daily irrigation was collected and analyzed for P and Fe weekly. All FSB treatments leached less P than the control (non-amended pine bark only), with P reductions ranging from 22% (4 cm FSB with 0.3 kg·m−3 Fe) to 73% (7.5 cm FSB with 1.2 kg·m−3 Fe). Phosphorus leaching decreased linearly with an increase in Fe rate or layer height. The amount of Fe that leached from containers with FSB was 4·7H2O with or without dolomite were equally effective at reducing P leaching. Adding 0.6 kg·m−3 Fe to the bottom 500 cm3 of pine bark increased P adsorption by 0.053 mg·cm−3 P, which equates to 17.9 mg P adsorbed per gram of FeSO4·7H2O added. Results from this research suggest that including an FSB layer in the bottom of nursery containers is an effective strategy for reducing P runoff from container-based nursery production sites.

In the original publication [...]

The lysosome in animal cells or the vacuole in plant and yeast cells serve as storage and/or recycling depots and their delimiting membranes host signaling events critical for starvation-induced cellular self-eating or macroautophagy/autophagy. Initiation of autophagy occurs when the Atg1 complex is formed and this process requires the inactivation of the target of rapamycin complex 1 (TORC1), a master regulator of cell growth and metabolism in all eukaryotes. In budding yeast, TORC1 localizes to two independent pools around the vacuolar membrane and in signaling endosomes juxtaposed to the vacuole. These pools are thought to exist independently of nutrient availability and target unique substrates using regulatory elements that are not well understood. One key upstream regulator of TORC1 is the SEA complex (GATOR complex in humans). The SEA complex is a multimeric eight-protein complex (Iml1/Sea1, Rtc1/Sea2, Mtc5/Sea3, Sea4, Seh1, Sec13, Npr2, Npr3) with both inhibiting and activating TORC1 domains, that resides on the vacuolar membrane. However, despite the discovery of the SEA complex over a decade ago, it is still not well understood. In our recent manuscript, we identified a genetic and functional connection between a novel yeast sorting nexin, Vps501, and the SEA complex. Abbreviations ORF: open reading frame; PX: Phox homology; SEACIT: sea complex inhibitory domain; SNX: Sorting nexin; TORC1: target of rapamycin complex 1

Introduction: Undiagnosed congenital heart disease and management of pediatric cardiogenic shock presents a diagnostic challenge for the emergency clinician. These diagnoses are rare and require a high index of suspicion given the overlap with more common pediatric pathology. Point-of-care ultrasound can assist in differentiating these presentations. We present a case of neonatal cardiogenic shock secondary to a previously undiagnosed congenital heart disease, specifically Shone complex, detected using point-of-care ultrasound. Case Report: A six-week-old female presented with severe respiratory distress and was found to be in cardiogenic shock secondary to a previously undiagnosed congenital heart defect. Conclusion: Initial diagnosis of congenital heart disease is uncommon in the emergency department, but it should be recognized by clinicians given the high associated morbidity and mortality. Point-of-care ultrasound is a powerful tool to assist in evaluating for cardiac abnormalities as an etiology for undifferentiated shock in the pediatric population.

Bacterial vaginosis (BV) is the most common vaginal dysbiosis. In this condition, a polymicrobial biofilm develops on vaginal epithelial cells. Accurately quantifying the bacterial burden of the BV biofilm is necessary to further our understanding of BV pathogenesis. Historically, the standard for calculating total bacterial burden of the BV biofilm has been based on quantifying Escherichia coli 16S rRNA gene copy number. However, E. coli is improper for measuring the bacterial burden of this unique micro-environment. Here, we propose a novel qPCR standard to quantify bacterial burden in vaginal microbial communities, from an optimal state to a mature BV biofilm. These standards consist of different combinations of vaginal bacteria including three common BV-associated bacteria (BVAB) Gardnerella spp. (G), Prevotella spp. (P), and Fannyhessea spp. (F) and commensal Lactobacillus spp. (L) using the 16S rRNA gene (G:P:F:L, G:P:F, G:P:L and 1G:9L). We compared these standards to the traditional E. coli (E) reference standard using known quantities of mock vaginal communities and 16 vaginal samples from women. The E standard significantly underestimated the copy numbers of the mock communities, and this underestimation was significantly greater at lower copy numbers of these communities. The G:P:L standard was the most accurate across all mock communities and when compared to other mixed vaginal standards. Mixed vaginal standards were further validated with vaginal samples. This new G:P:L standard can be used in BV pathogenesis research to enhance reproducibility and reliability in quantitative measurements of BVAB, spanning from the optimal to non-optimal (including BV) vaginal microbiota.

Freshwater ecosystems provide vital services, yet are facing increasing risks from global change. In particular, lake thermal dynamics have been altered around the world as a result of climate change, necessitating a predictive understanding of how climate will continue to alter lakes in the future as well as the associated uncertainty in these predictions. Numerous sources of uncertainty affect projections of future lake conditions but few are quantified, limiting the use of lake modeling projections as management tools. To quantify and evaluate the effects of two potentially important sources of uncertainty, lake model selection uncertainty and climate model selection uncertainty, we developed ensemble projections of lake thermal dynamics for a dimictic lake in New Hampshire, USA (Lake Sunapee). Our ensemble projections used four different climate models as inputs to five vertical one-dimensional (1-D) hydrodynamic lake models under three different climate change scenarios to simulate thermal metrics from 2006 to 2099. We found that almost all the lake thermal metrics modeled (surface water temperature, bottom water temperature, Schmidt stability, stratification duration, and ice cover, but not thermocline depth) are projected to change over the next century. Importantly, we found that the dominant source of uncertainty varied among the thermal metrics, as thermal metrics associated with the surface waters (surface water temperature, total ice duration) were driven primarily by climate model selection uncertainty, while metrics associated with deeper depths (bottom water temperature, stratification duration) were dominated by lake model selection uncertainty. Consequently, our results indicate that researchers generating projections of lake bottom water metrics should prioritize including multiple lake models for best capturing projection uncertainty, while those focusing on lake surface metrics should prioritize including multiple climate models. Overall, our ensemble modeling study reveals important information on how climate change will affect lake thermal properties, and also provides some of the first analyses on how climate model selection uncertainty and lake model selection uncertainty interact to affect projections of future lake dynamics.

Rare-earth ion-doped crystals are of great interest for quantum memories, a central component in future quantum repeaters. To assess the promise of 1 $\%$ Tm ^3+ -doped yttrium gallium garnet (Tm:YGG), we report measurements of optical coherence and energy-level lifetimes of its ^3 H $_6~\leftrightarrow~^3$ H _4 transition at a temperature of around 500 mK and various magnetic fields. Using spectral hole burning (SHB), we find hyperfine ground-level (Zeeman level) lifetimes of several minutes at magnetic fields of less than 1000 G. We also measure coherence time exceeding one millisecond using two-pulse photon echoes. Three-pulse photon echo and SHB measurements reveal that due to spectral diffusion, the effective coherence time reduces to a few µ s over a timescale of around two hundred seconds. Finally, temporal and frequency-multiplexed storage of optical pulses using the atomic frequency comb protocol is demonstrated. Our results suggest Tm:YGG to be promising for multiplexed photonic quantum memory for quantum repeaters.

Exoplanet systems are thought to evolve on secular timescales over billions of years. This evolution is impossible to directly observe on human timescales in most individual systems. While the availability of accurate and precise age inferences for individual exoplanet host stars with ages τ in the interval 1 Gyr ≲ τ ≲ 10 Gyr would constrain this evolution, accurate and precise age inferences are difficult to obtain for isolated field dwarfs like the host stars of most exoplanets. The Galactic velocity dispersion of a thin-disk stellar population monotonically grows with time, and the relationship between age and velocity dispersion in a given Galactic location can be calibrated by a stellar population for which accurate and precise age inferences are possible. Using a sample of subgiants with precise age inferences, we calibrate the age–velocity dispersion relation in the Kepler field. Applying this relation to the Kepler field’s planet populations, we find that Kepler-discovered systems plausibly in second-order mean-motion resonances have 1 Gyr ≲ τ ≲ 2 Gyr. The same is true for systems plausibly in first-order mean-motion resonances, but only for systems likely affected by tidal dissipation inside their innermost planets. These observations suggest that many planetary systems diffuse away from initially resonant configurations on secular timescales. Our calibrated relation also indicates that ultra-short-period (USP) planet systems have typical ages in the interval 5 Gyr ≲ τ ≲ 6 Gyr. We propose that USP planets tidally migrated from initial periods in the range 1 day ≲ P ≲ 2 days to their observed locations at P < 1 day over billions of years and trillions of cycles of secular eccentricity excitation and inside-planet damping.

Before the launch of the Kepler Space Telescope, models of low-mass planet formation predicted that convergent type I migration would often produce systems of low-mass planets in low-order mean-motion resonances. Instead, Kepler discovered that systems of small planets frequently have period ratios larger than those associated with mean-motion resonances and rarely have period ratios smaller than those associated with mean-motion resonances. Both short-timescale processes related to the formation or early evolution of planetary systems and long-timescale secular processes have been proposed as explanations for these observations. Using a thin disk stellar population’s Galactic velocity dispersion as a relative age proxy, we find that Kepler-discovered multiple-planet systems with at least one planet pair near a period ratio suggestive of a second-order mean-motion resonance have a colder Galactic velocity dispersion and are therefore younger than both single-transiting and multiple-planet systems that lack planet pairs consistent with mean-motion resonances. We argue that a nontidal secular process with a characteristic timescale no less than a few hundred Myr is responsible for moving systems of low-mass planets away from second-order mean-motion resonances. Among systems with at least one planet pair near a period ratio suggestive of a first-order mean-motion resonance, only the population of systems likely affected by tidal dissipation inside their innermost planets has a small Galactic velocity dispersion and is therefore young. We predict that period ratios suggestive of mean-motion resonances are more common in young systems with 10 Myr ≲ τ ≲ 100 Myr and become less common as planetary systems age.

Abstract We construct supersymmetric AdS 3 solutions of D = 11 supergravity, dual to d = 2, N $$ \mathcal{N} $$ = (0, 2) SCFTs, that are associated with M5-branes wrapping two different four-dimensional orbifolds. In one case the orbifold is a spindle fibred over another spindle, while in the other it is a spindle fibred over a Riemann surface with genus g > 1. We show that the central charges of the d = 2 SCFTs calculated from the gravity solutions agree with field theory computations using anomaly polynomials. The new D = 11 solutions are obtained after constructing a new consistent Kaluza-Klein truncation of maximal D = 7 gauged supergravity reduced on a spindle down to D = 5 minimal gauged supergravity.

BackgroundHyponatremia and hypernatremia, as conventionally defined (145 mEq/L, respectively), are associated with increased perioperative morbidity and mortality. However, the effects of subtle deviations in serum sodium concentration within the normal range are not well-characterized. ObjectiveThe purpose of this analysis is to determine the association between borderline hyponatremia (135-137 mEq/L) and hypernatremia (143-145 mEq/L) on perioperative morbidity and mortality. MethodsA retrospective cohort study was performed using data from the American College of Surgeons National Surgical Quality Improvement Program database. This database is a repository of surgical outcome data collected from over 600 hospitals across the United States. The National Surgical Quality Improvement Program database was queried to extract all patients undergoing elective, noncardiac surgery from 2015 to 2019. The primary predictor variable was preoperative serum sodium concentration, measured less than 5 days before the index surgery. The 2 primary outcomes were the odds of morbidity and mortality occurring within 30 days of surgery. The risk of both outcomes in relation to preoperative serum sodium concentration was modeled using weighted generalized additive models to minimize the effect of selection bias while controlling for covariates. ResultsIn the overall cohort, 1,003,956 of 4,551,726 available patients had a serum sodium concentration drawn within 5 days of their index surgery. The odds of morbidity and mortality across sodium levels of 130-150 mEq/L relative to a sodium level of 140 mEq/L followed a nonnormally distributed U-shaped curve. The mean serum sodium concentration in the study population was 139 mEq/L. All continuous covariates were significantly associated with both morbidity and mortality (P

BackgroundSquamous cell carcinoma of the anus (SCCA) is a rare gastrointestinal cancer. Factors associated with progression of HPV infection to anal dysplasia and cancer are unclear and screening guidelines and approaches for anal dysplasia are less clear than for cervical dysplasia. One potential contributing factor is the anorectal microbiome. In this study, we aimed to identify differences in anal microbiome composition in the settings of HPV infection, anal dysplasia, and anal cancer in this rare disease.MethodsPatients were enrolled in two prospective studies. Patients with anal dysplasia were part of a cross-sectional cohort that enrolled women with high-grade lower genital tract dysplasia. Anorectal tumor swabs were prospectively collected from patients with biopsy-confirmed locally advanced SCCA prior to receiving standard-of-care chemoradiotherapy (CRT). Patients with high-grade lower genital tract dysplasia without anal dysplasia were considered high-risk (HR Normal). 16S V4 rRNA Microbiome sequencing was performed for anal swabs. Alpha and Beta Diversity and composition were compared for HR Normal, anal dysplasia, and anal cancer.Results60 patients with high-grade lower genital tract dysplasia were initially enrolled. Seven patients had concurrent anal dysplasia and 44 patients were considered HR Normal. Anorectal swabs from 21 patients with localized SCCA were included, sequenced, and analyzed in the study. Analysis of weighted and unweighted UniFrac distances demonstrated significant differences in microbial community composition between anal cancer and HR normal (p=0.018). LEfSe identified that all three groups exhibited differential enrichment of specific taxa. Peptoniphilus (p=0.028), Fusobacteria (p=0.0295), Porphyromonas (p=0.034), and Prevotella (p=0.029) were enriched in anal cancer specimens when compared to HR normal.ConclusionAlthough alpha diversity was similar between HR Normal, dysplasia and cancer patients, composition differed significantly between the three groups. Increased anorectal Peptoniphilus, Fusobacteria, Porphyromonas, and Prevotella abundance were associated with anal cancer. These organisms have been reported in various gastrointestinal cancers with roles in facilitating the proinflammatory microenvironment and neoplasia progression. Future work should investigate a potential role of microbiome analysis in screening for anal dysplasia and investigation into potential mechanisms of how these microbial imbalances influence the immune system and anal carcinogenesis.

Introduction The effect of testosterone (T) therapy on the vaginal microbiota of transgender men (TGM) is not well characterised, although one cross-sectional study comparing the vaginal microbiota of cisgender women to TGM on T≥1 year found that, in 71% of the TGM, the vaginal microbiota was less likely to be Lactobacillus-dominated and more likely to be enriched with >30 other bacterial species, many associated with bacterial vaginosis (BV). This prospective study aims to investigate changes in the composition of the vaginal microbiota over time in TGM who retain their natal genitalia (ie, vagina) and initiate T. In addition, we will identify changes in the vaginal microbiota preceding incident BV (iBV) in this cohort while investigating behavioural factors, along with hormonal shifts, which may be associated with iBV.Methods and analysis T-naïve TGM who have not undergone gender-affirming genital surgery with normal baseline vaginal microbiota (ie, no Amsel criteria, normal Nugent Score with no Gardnerella vaginalis morphotypes) will self-collect daily vaginal specimens for 7 days prior to initiating T and for 90 days thereafter. These specimens will be used for vaginal Gram stain, 16S rRNA gene sequencing and shotgun metagenomic sequencing to characterise shifts in the vaginal microbiota over time, including development of iBV. Participants will complete daily diaries on douching, menses and behavioural factors including sexual activity during the study.Ethics and dissemination This protocol is approved through the single Institutional Review Board mechanism by the University of Alabama at Birmingham. External relying sites are the Louisiana State University Health Sciences Center, New Orleans Human Research Protection Program and the Indiana University Human Research Protection Program. Study findings will be presented at scientific conferences and peer-reviewed journals as well as shared with community advisory boards at participating gender health clinics and community-based organisations servicing transgender people.Registration details Protocol # IRB-300008073.

Abstract Background Quantitative whole-body PET/MRI relies on accurate patient-specific MRI-based attenuation correction (AC) of PET, which is a non-trivial challenge, especially for the anatomically complex head and neck region. We used a deep learning model developed for dose planning in radiation oncology to derive MRI-based attenuation maps of head and neck cancer patients and evaluated its performance on PET AC. Methods Eleven head and neck cancer patients, referred for radiotherapy, underwent CT followed by PET/MRI with acquisition of Dixon MRI. Both scans were performed in radiotherapy position. PET AC was performed with three different patient-specific attenuation maps derived from: (1) Dixon MRI using a deep learning network (PETDeep). (2) Dixon MRI using the vendor-provided atlas-based method (PETAtlas). (3) CT, serving as reference (PETCT). We analyzed the effect of the MRI-based AC methods on PET quantification by assessing the average voxelwise error within the entire body, and the error as a function of distance to bone/air. The error in mean uptake within anatomical regions of interest and the tumor was also assessed. Results The average (± standard deviation) PET voxel error was 0.0 ± 11.4% for PETDeep and −1.3 ± 21.8% for PETAtlas. The error in mean PET uptake in bone/air was much lower for PETDeep (−4%/12%) than for PETAtlas (−15%/84%) and PETDeep also demonstrated a more rapidly decreasing error with distance to bone/air affecting only the immediate surroundings (less than 1 cm). The regions with the largest error in mean uptake were those containing bone (mandible) and air (larynx) for both methods, and the error in tumor mean uptake was −0.6 ± 2.0% for PETDeep and −3.5 ± 4.6% for PETAtlas. Conclusion The deep learning network for deriving MRI-based attenuation maps of head and neck cancer patients demonstrated accurate AC and exceeded the performance of the vendor-provided atlas-based method both overall, on a lesion-level, and in vicinity of challenging regions such as bone and air.

Naturally occurring body movements and collective neural activity both exhibit complex dynamics, often with scale-free, fractal spatiotemporal structure. Scale-free dynamics of both brain and behavior are important because each is associated with functional benefits to the organism. Despite their similarities, scale-free brain activity and scale-free behavior have been studied separately, without a unified explanation. Here, we show that scale-free dynamics of mouse behavior and neurons in the visual cortex are strongly related. Surprisingly, the scale-free neural activity is limited to specific subsets of neurons, and these scale-free subsets exhibit stochastic winner-take-all competition with other neural subsets. This observation is inconsistent with prevailing theories of scale-free dynamics in neural systems, which stem from the criticality hypothesis. We develop a computational model which incorporates known cell-type-specific circuit structure, explaining our findings with a new type of critical dynamics. Our results establish neural underpinnings of scale-free behavior and clear behavioral relevance of scale-free neural activity.

BackgroundHypertension represents one of the major risk factors for cardiovascular morbidity and mortality globally. Early detection and treatment of this condition is vital to prevent complications. However, hypertension often goes undetected, and even if detected, not every patient receives adequate treatment. Identifying simple and effective interventions is therefore crucial to fight this problem and allow more patients to receive the treatment they need. Therefore, we aim at investigating the impact of a population-based blood pressure (BP) screening and the subsequent "low-threshold" information treatment on long-term cardiovascular disease (CVD) morbidity and mortality.Methods and findingsWe examined the impact of a BP screening embedded in a population-based cohort study in Germany and subsequent personalized "light touch" information treatment, including a hypertension diagnosis and a recommendation to seek medical attention. We pooled four waves of the KORA study, carried out between 1984 and 1996 (N = 14,592). Using a sharp multivariate regression discontinuity (RD) design, we estimated the impact of the information treatment on CVD mortality and morbidity over 16.9 years. Additionally, we investigated potential intermediate outcomes, such as hypertension awareness, BP, and behavior after 7 years. No evidence of effect of BP screening was observed on CVD mortality (hazard ratio (HR) = 1.172 [95% confidence interval (CI): 0.725, 1.896]) or on any (fatal or nonfatal) long-term CVD event (HR = 1.022 [0.636, 1.641]) for individuals just above (versus below) the threshold for hypertension. Stratification for previous self-reported diagnosis of hypertension at baseline did not reveal any differential effect. The intermediate outcomes, including awareness of hypertension, were also unaffected by the information treatment. However, these results should be interpreted with caution since the analysis might not be sufficiently powered to detect a potential intervention effect.ConclusionsThe study does not provide evidence of an effect of the assessed BP screening and subsequent information treatment on BP, health behavior, or long-term CVD mortality and morbidity. Future studies should consider larger datasets to detect possible effects and a shorter follow-up for the intermediate outcomes (i.e., BP and behavior) to detect short-, medium-, and long-term effects of the intervention along the causal pathway.

Monkeypox (MPX) is a viral zoonotic disease that was endemic to Central and West Africa. However, during the first half of 2022, MPX spread to almost 60 countries all over the world. Smallpox vaccines are about 85% effective in preventing MPX infections. Our objective is to determine whether the vaccines should be mandated or whether voluntary use of the vaccine could be enough to stop the MPX outbreak. We incorporate a standard SVEIR compartmental model of MPX transmission into a game-theoretical framework. We study a vaccination game in which individuals decide whether or not to vaccinate by assessing their benefits and costs. We solve the game for Nash equilibria, i.e., the vaccination rates the individuals would likely adopt without any outside intervention. We show that, without vaccination, MPX can become endemic in previously non-endemic regions, including the United States. We also show that to "not vaccinate" is often an optimal solution from the individual's perspective. Moreover, we demonstrate that, for some parameter values, there are multiple equilibria of the vaccination game, and they exhibit a backward bifurcation. Thus, without centrally mandated minimal vaccination rates, the population could easily revert to no vaccination scenario.

Summary: Biomass conversion to fuels and chemicals is crucial to decarbonization, but choosing an advantageous upgrading pathway out of many options is challenging. Rigorously evaluating all candidate pathways (process simulation, product property testing) requires a prohibitive amount of research effort; even simple upgrading schemes have hundreds of possible permutations. We present a method enabling high-throughput screening by approximating upgrading unit operations and drop-in compatibility of products (e.g., fuel properties) and apply it to volatile fatty acid (VFA) conversion to liquid transportation fuels via a MATLAB script, VFA Upgrading to Liquid Transportation fUels Refinery Estimation (VULTURE). VULTURE selects upgrading configurations that maximize fuel blend bio-derived content. We validate VULTURE’s approximations through surrogate fuel property testing and process simulation. Techno-economic and life cycle analyses suggest that VFA upgrading processes down-selected by VULTURE are profitable and have low carbon intensities, demonstrating the potential for the strategy to accelerate process development timelines at decreased costs.

The amount of phosphorus (P) conventionally recommended and applied to container nursery crops commonly exceeds plant requirements, resulting in unused P leaching from containers and potentially contributing to surface water impairment. An experiment was replicated in the Middle Atlantic Coastal Plain (MACP) and Ridge and Valley ecoregions of Virginia to compare the effect of a low-P controlled-release fertilizer (CRF, 0.9% or 1.4% P depending on species) vs. a conventional CRF formulation (control, 1.7% P) on plant shoot growth, crop quality, and substrate nutrient concentrations of four species: ‘Natchez’ crape myrtle (Lagerstroemia indica × Lagerstroemia fauriei), ‘Roblec’ Encore azalea (Rhododendron hybrid), ‘Radrazz’ Knock Out rose (Rosa hybrid), and ‘Green Giant’ arborvitae (Thuja plicata × Thuja standishii). In both ecoregions, the low-P CRF resulted in 9% to 26% lower shoot dry weight in all four species compared with those given the conventional formulation, but quality ratings for two economically important species, ‘Radrazz’ Knock Out rose and ‘Green Giant’ arborvitae, were similar between treatments. When fertilized with the low-P CRF, ‘Roblec’ Encore azalea and ‘Natchez’ crape myrtle in both ecoregions, and ‘Green Giant’ arborvitae in the MACP ecoregion had ∼56% to 75% lower substrate pore-water P concentrations than those that received the control CRF. Nitrate-nitrogen (N) concentrations in substrate pore water at week 5 were more than six times greater in control-fertilized plants than in those that received a low-P CRF, which may have been a result of the greater urea-N content or the heterogeneous nature of the low-P CRFs. Lower water-extractable pore-water P and N indicate less environmental risk and potentially increased crop efficiency. Our results suggest low-P CRFs can be used to produce certain economically important ornamental nursery crops successfully without sacrificing quality; however, early adopters will need to evaluate the effect of low-P CRFs on crop quality of specific species before implementing on a large scale.

In a recent numerical study by Haldar et al. [Phys. Rev. X 11, 031062] it was shown that signatures of proximate quantum critical points can be observed at early and intermediate times after certain quantum quenches. Said work focused mainly on the case of the axial next-nearest neighbour Ising (ANNNI) model. Here we construct a simple time-dependent mean-field theory that allows us to obtain a quantitatively accurate description of these quenches at short times, which for reasons we explain remains a fair approximation at late times (with some caveats). Our approach provides a simple framework for understanding the reported numerical results as well as fundamental limitations on detecting quantum critical points through quench dynamics. We moreover explain the origin of the peculiar oscillatory behaviour seen in various observables as arising from the formation of a long-lived bound state.

Abstract Developmental and epileptic encephalopathies (DEE) are a group of disorders associated with intractable seizures, brain development, and functional abnormalities, and in some cases, premature death. Pathogenic human germline biallelic mutations in tumor suppressor WW domain‐containing oxidoreductase (WWOX) are associated with a relatively mild autosomal recessive spinocerebellar ataxia‐12 (SCAR12) and a more severe early infantile WWOX‐related epileptic encephalopathy (WOREE). In this study, we generated an in vitro model for DEEs, using the devastating WOREE syndrome as a prototype, by establishing brain organoids from CRISPR‐engineered human ES cells and from patient‐derived iPSCs. Using these models, we discovered dramatic cellular and molecular CNS abnormalities, including neural population changes, cortical differentiation malfunctions, and Wnt pathway and DNA damage response impairment. Furthermore, we provide a proof of concept that ectopic WWOX expression could potentially rescue these phenotypes. Our findings underscore the utility of modeling childhood epileptic encephalopathies using brain organoids and their use as a unique platform to test possible therapeutic intervention strategies.

Voice transformation, for example, from a male speaker to a female speaker, is achieved here using a two-level dynamic warping algorithm in conjunction with an artificial neural network. An outer warping process which temporally aligns blocks of speech (dynamic time warp, DTW) invokes an inner warping process, which spectrally aligns based on magnitude spectra (dynamic frequency warp, DFW). The mapping function produced by inner dynamic frequency warp is used to move spectral information from a source speaker to a target speaker. Artifacts arising from this amplitude spectral mapping are reduced by reconstructing phase information. Information obtained by this process is used to train an artificial neural network to produce spectral warping information based on spectral input data. The performance of the speech mapping compared using Mel-Cepstral Distortion (MCD) with previous voice transformation research, and it is shown to perform better than other methods, based on their reported MCD scores.

The evolution of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in the emergence of several variants of concern (VOC) with increased immune evasion and transmissibility. This has motivated studies to assess protection conferred by earlier strains following infection or vaccination to each new VOC. We hypothesized that while NAbs play a major role in protection against infection and disease, a heterologous reinfection or challenge may gain a foothold in the upper respiratory tract (URT) and result in a self-limited viral infection accompanied by an inflammatory response. To test this hypothesis, we infected K18-hACE2 mice with SARS-CoV-2 USA-WA1/2020 (WA1) and, after 24 days, challenged with WA1, Alpha, or Delta. While NAb titers against each virus were similar across all cohorts prior to challenge, the mice challenged with Alpha and Delta showed weight loss and upregulation of proinflammatory cytokines in the URT and lower RT (LRT). Mice challenged with WA1 showed complete protection. We noted increased levels of viral RNA transcripts only in the URT of mice challenged with Alpha and Delta. In conclusion, our results suggested self-limiting breakthrough infections of Alpha or Delta in the URT, which correlated with clinical signs and a significant inflammatory response in mice.

Summary: Antibody-mediated immunity is initiated by B cell differentiation into multiple cell subsets, including plasmablast, memory, and germinal center (GC) cells. B cell differentiation trajectories are determined by transcription factors, yet very few mechanisms that specifically determine early B cell fates have been described. Here, we report a post-transcriptional mechanism that suppresses the plasmablast genetic program and promotes GC B cell fate commitment. Single-cell RNA-sequencing analysis reveals that antigen-specific B cell precursors at the pre-GC stage upregulate YTHDF2, which enhances the decay of methylated transcripts. Ythdf2-deficient B cells exhibit intact proliferation and activation, whereas differentiation into GC B cells is blocked. Mechanistically, B cells require YTHDF2 to attenuate the plasmablast genetic program during GC seeding, and transcripts of key plasmablast-regulating genes are methylated and bound by YTHDF2. Collectively, this study reveals how post-transcriptional suppression of gene expression directs appropriate B cell fate commitment during initiation of the adaptive immune response.