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Abstract Obesity exacerbates tissue degeneration and compromises the integrity and reparative potential of mesenchymal stem/stromal cells (MSCs), but the underlying mechanisms have not been sufficiently elucidated. Mitochondria modulate the viability, plasticity, proliferative capacity, and differentiation potential of MSCs. We hypothesized that alterations in the 5-hydroxymethylcytosine (5hmC) profile of mitochondria-related genes may mediate obesity-driven dysfunction of human adipose-derived MSCs. MSCs were harvested from abdominal subcutaneous fat of obese and age/sex-matched non-obese subjects (n = 5 each). The 5hmC profile and expression of nuclear-encoded mitochondrial genes were examined by hydroxymethylated DNA immunoprecipitation sequencing (h MeDIP-seq) and mRNA-seq, respectively. MSC mitochondrial structure (electron microscopy) and function, metabolomics, proliferation, and neurogenic differentiation were evaluated in vitro, before and after epigenetic modulation. hMeDIP-seq identified 99 peaks of hyper-hydroxymethylation and 150 peaks of hypo-hydroxymethylation in nuclear-encoded mitochondrial genes from Obese- versus Non-obese-MSCs. Integrated hMeDIP-seq/mRNA-seq analysis identified a select group of overlapping (altered levels of both 5hmC and mRNA) nuclear-encoded mitochondrial genes involved in ATP production, redox activity, cell proliferation, migration, fatty acid metabolism, and neuronal development. Furthermore, Obese-MSCs exhibited decreased mitochondrial matrix density, membrane potential, and levels of fatty acid metabolites, increased superoxide production, and impaired neuronal differentiation, which improved with epigenetic modulation. Obesity elicits epigenetic changes in mitochondria-related genes in human adipose-derived MSCs, accompanied by structural and functional changes in their mitochondria and impaired fatty acid metabolism and neurogenic differentiation capacity. These observations may assist in developing novel therapies to preserve the potential of MSCs for tissue repair and regeneration in obese individuals.

OBJECTIVES Programmatic assessment approaches can be extended to the design of allied health professions training, to enhance the learning of trainees. The Australasian College of Physical Scientists and Engineers in Medicine worked with assessment specialists at the Australian Council for Educational Research and Amplexa Consulting, to revise their medical physics and radiopharmaceutical science training programs. One of the central aims of the revisions was to produce a training program that provides standardized training support to their registrars throughout the 3 years, better supporting their registrars to successfully complete the program in the time frame through providing timely and constructive feedback on the registrar's progression. METHODS We used the principles of programmatic assessment to revise the assessment methods and progression decisions in the three training programs. RESULTS We revised the 3-year training programs for diagnostic imaging medical physics, radiation oncology medical physics and radiopharmaceutical science in Australia and New Zealand, incorporating clear stages of training and associated progression points. CONCLUSIONS We discuss the advantages and difficulties that have arisen with this implementation. We found 5 key elements necessary for implementing programmatic assessment in these specialized contexts: embracing blurred boundaries between assessment of and for learning, adapting the approach to each specialized context, change management, engaging subject matter experts, and clear communication to registrars/trainees.

BackgroundFirearms used in pediatric firearm deaths are most often obtained from the child’s home, making secure firearm storage initiatives imperative in prevention efforts. Evidence-based home visiting (EBHV) programs are implemented with over 277,000 families annually, providing an opportunity for secure firearm storage counseling. The purpose of this study was to assess EBHV providers’ experiences with firearm screening (“assessment”), secure storage counseling, and their perceptions for related training needs.MethodsProviders in the U.S. from SafeCare®, an EBHV program often implemented with families experiencing increased risk of child neglect and physical or emotional abuse, were invited to participate in a survey to examine firearm assessment and attitudes toward and experiences with firearm safety counseling. Survey items were primarily Likert scale ratings to indicate level of agreement, with some open-ended follow-up questions. Descriptive statistics (i.e., frequencies and percentages) were used to report item-level agreement. A post hoc analysis was conducted using Spearman correlation to examine the association between assessment and counseling and provider-level factors.ResultsSixty-three SafeCare providers consented to and completed the survey items. Almost three-quarters (74.6%) agreed/strongly agreed that they assess in-home firearm availability. However, 66.7% agreed/strongly agreed that they have not been adequately trained to discuss firearm safety topics. A substantial proportion (80.6%) indicated they would counsel more if materials and training on this topic were available. Response variability emerged by level of urbanicity. A post hoc analysis found that providers’ self-reported frequency of assessment and counseling were associated with their comfort level discussing firearm safety and whether or not they had worked with families impacted by firearm injury.ConclusionSafeCare providers report a need for materials and training on secure firearm storage, and a willingness to provide more counseling with proper training to the families they serve. Findings illuminate the need for secure storage initiatives for EBHV programs, which have broad service reach to a substantial number of at-risk U.S. families annually.

Objective: To investigate medication factors and patient characteristics associated with readmissions following alcohol-related hospitalizations. Patients and Methods: Adult patients admitted from September 1, 2016, through August 31, 2019, who had an alcohol-related hospitalization were identified through electronic health records. Patient characteristics and medications of interest administered during hospitalization or prescribed at discharge were identified. Medications of interest included US Food and Drug Administration–approved medications for alcohol use disorder, benzodiazepines, barbiturates, gabapentin, opioids, and muscle relaxants. The primary outcome was to identify medications and patient factors associated with 30-day alcohol-related readmission. Secondary outcomes included medications and patient characteristics associated with multiple alcohol-related readmissions within a year from the index admission (ie, two or more readmissions) and factors associated with 30-day all-cause readmission. Results: Characteristics of the 932 patients included in this study associated with a 30-day alcohol-related readmission included younger age, severity of alcohol withdrawal, history of psychiatric disorder, marital status, and the number of prior alcohol-related admission in the previous year. Benzodiazepine or barbiturate use during hospitalization or upon discharge was associated with 30-day alcohol-related readmission (P=.006). Gabapentin administration during hospitalization or upon discharge was not associated with 30-day alcohol-related readmission (P=.079). Conclusion: The findings reinforce current literature identifying patient-specific factors associated with 30-day readmissions. Gabapentin use was not associated with readmissions; however, there was an association with benzodiazepine/barbiturate use.

ABSTRACT: Increased consumer concern for animal welfare has led some poultry producers to alter their stunning methods from electrical to controlled atmosphere stunning. The potential for different impacts on meat quality between commercially applied controlled atmosphere stunning (CAS) and electrical stunning (ES) using current US parameters needs further evaluation. Three trials were conducted in a commercial broiler processing facility that uses separate processing lines for ES and CAS. Blood glucose concentrations were measured from broilers stunned by either CAS or ES at: 1) lairage, 2) pre-stunning, and 3) post-stunning, using a glucose monitor. Occurrence of visible wing damage was evaluated post-defeathering and breast fillet meat quality was evaluated through measurement of pH, color, and drip loss at deboning and after 24 h. Data were analyzed using GLM or chi-square with a significance at P ≤ 0.05 and means were separated by Tukey's HSD. Blood glucose concentrations (mg/dL) from CAS and ES birds were not different at lairage (284, 272, P = 0.2646) or immediately prior to stunning (274, 283, P = 0.6425). Following stunning and neck cut, circulating blood glucose from birds stunned by CAS was higher than ES (418, 259, P < 0.0001). CAS carcasses had more visible wing damage than ES carcasses (3.6%, 2.2%, P < 0.0001). Breast fillet pH was lower, L* was higher, and a* was lower at debone for CAS fillets (5.81, 54.65, 1.96) compared to ES fillets (5.92, 53.15, 2.31, P < 0.0001, P = 0.0005, P = 0.0303). Drip loss did not differ between breast fillets from CAS or ES broilers (4.83, 4.84; P = 0.0859). The implications of increased blood glucose concentration post-CAS are unknown and require further evaluation. However, the increase in visible wing damage observed post-defeathering from CAS carcasses indicated a need for equipment parameter adjustments during the process from stunning through defeathering when using CAS for broiler stunning. Although differences were observed in breast fillet attributes at deboning, these differences would have minimal practical application and were no longer present at 24 h. Overall, use of CAS in a commercial facility resulted in differences in subsequent product quality when compared to ES.

Autoimmune disorders are complex diseases of unclear etiology, although evidence suggests that the convergence of genetic susceptibility and environmental factors are critical. In type 1 diabetes (T1D), enterovirus infection and disruption of the intestinal microbiota are two environmental factors that have been independently associated with T1D onset in both humans and animal models. However, the possible interaction between viral infection and the intestinal microbiota remains unknown. Here, we demonstrate that Coxsackievirus B4 (CVB4), an enterovirus that accelerates T1D onset in non-obese diabetic (NOD) mice, induced restructuring of the intestinal microbiome prior to T1D onset. Microbiome restructuring was associated with an eroded mucosal barrier, bacterial translocation to the pancreatic lymph node, and increased circulating and intestinal commensal-reactive antibodies. The CVB4-induced change in community composition was strikingly similar to that of uninfected NOD mice that spontaneously developed diabetes, implying a mutual “diabetogenic” microbiome. Notably, members of the Bifidobacteria and Akkermansia genera emerged as conspicuous members of this diabetogenic microbiome, implicating these taxa, among others, in diabetes onset. Further, fecal microbiome transfer (FMT) of the diabetogenic microbiota from CVB4-infected mice enhanced T1D susceptibility and led to diminished expression of the short chain fatty acid receptor GPR43 and fewer IL-10-expressing regulatory CD4+ T cells in the intestine of naïve NOD recipients. These findings support an overlap in known environmental risk factors of T1D, and suggest that microbiome disruption and impaired intestinal homeostasis contribute to CVB-enhanced autoreactivity and T1D.

Elevation gradients within forested wetlands have long been recognized for their role in defining species composition through factors such as hydrology and soil characteristics. Greentree reservoirs (GTRs) are levee-impounded tracts of bottomland hardwood forest flooded throughout the winter months to provide habitat for overwintering waterfowl. Artificial flooding of GTRs alters the forest composition due to flood frequency, depth, and duration in combination with slight changes in topography. To evaluate the effect of elevation gradients, soil properties, and management techniques in the overstory species composition and red oak (Quercus spp.) species abundance, we inventoried 662 plots across 12 independent GTRs in eastern Arkansas. In the lower elevations ranging from 50.98 to 54.99 ​m above sea level, the importance value index (IVI) was highest for nuttall oak (Quercus texana) and overcup oak (Quercus lyrata), whereas IVI shifted to cherrybark oak (Quercus pagoda) in the higher elevations ranging from 54.99 to 58.00 ​m. Alpha diversity did not differ by elevation gradient, soil property, or management technique within GTRs. Beta diversity, using non-metric multi-dimensional scaling (NMDS) analysis, indicated site-specific variability significantly correlated with the environmental predictors, including elevation (R2 = ​0.57), easting (R2 = ​0.47), soil texture (R2 = ​0.21), and pH (R2 = ​0.12). Red oak species-specific mixed-effects modeling of abundance response using Poisson distribution suggested an inverse correlation of nuttall oak and a direct correlation of cherrybark oak abundance with elevation. However, willow oak (Quercus phellos) abundance was not significantly affected by elevation but was by silt loam soil texture and restoration management techniques. These findings will aid management efforts to reduce the dominance of less desirable species that are prominent under specific environmental conditions and promote the dominance of more desirable species. Ultimately GTR sustainability is increasingly important amid the unpredictable impacts of climate change on the preferred red oak species that are economically, ecologically, and environmentally valuable to the sustaining economy of the local community and managing habitats for wildlife.

Food resources are assumed to limit waterfowl populations in the Mississippi Alluvial Valley, thus bioenergetic models are used for spatial allocation of food resources to provide adequate energy to support regional waterfowl population objectives. Changes in population abundance and distributions of midcontinent greater white-fronted geese Anser albifrons have implications for region-specific conservation planning of energetic resources for wintering waterfowl. This research aimed to quantify timing of arrival of greater white-fronted geese to wintering areas and quantify foraging behaviors. These data can help refine bioenergetics models and facilitate future waterfowl habitat planning efforts in the region. Bioenergetics models account for energetic demands of wintering geese by assuming they forage in flooded habitats 25% of the time across a 110-day winter planning period. Although this assumption has gone untested, our estimate of time spent foraging in flooded habitats (27.4% ± 5.8%) confirms the current model parameter of 25% of the time. However, we suggest that this is not the best parameter to use in bioenergetics models as greater white-fronted geese in our study foraged in dry habitats (72.6% ± 5.8%) more often than in flooded habitats. In addition, selection for rice fields in heavily weighted toward early winter (November; β = 2.85), and use declined 70% as winter progressed (February; β = 0.89), likely due to depletion of available rice grain, hunting pressure, and the physiological need to switch from a greater carbohydrate diet to a nitrogen-rich diet. In addition, white-fronted geese arrived to wintering areas earlier than current models accounted for with a mean arrival date of 30 October (± 2.5 days) to the Mississippi Alluvial Valley. We suggest early arrival to the wintering area and greater selection for dry rice fields during early winter indicates exploitative competition by white-fronted geese for shared food resources that may not be adequately accounted for in current bioenergetics models. We suggest current models underestimated energetic demands and the competitive nature of early migratory greater white-fronted geese.

People living with multiple sclerosis (MS) experience episodic CNS white matter lesions instigated by autoreactive T cells. With age, patients with MS show evidence of gray matter demyelination and experience devastating nonremitting symptomology. What drives progression is unclear and studying this has been hampered by the lack of suitable animal models. Here, we show that passive experimental autoimmune encephalomyelitis (EAE) induced by an adoptive transfer of young Th17 cells induced a nonremitting clinical phenotype that was associated with persistent leptomeningeal inflammation and cortical pathology in old, but not young, SJL/J mice. Although the quantity and quality of T cells did not differ in the brains of old versus young EAE mice, an increase in neutrophils and a decrease in B cells were observed in the brains of old mice. Neutrophils were also found in the leptomeninges of a subset of progressive MS patient brains that showed evidence of leptomeningeal inflammation and subpial cortical demyelination. Taken together, our data show that while Th17 cells initiate CNS inflammation, subsequent clinical symptoms and gray matter pathology are dictated by age and associated with other immune cells, such as neutrophils.

ABSTRACT: The presence of Salmonella in air of poultry houses has been previously confirmed. Therefore, it is important to investigate the entry of Salmonella into broilers through air. The present study aimed to evaluate different levels of Salmonella Enteritidis aerosol inoculations in broiler chicks for colonization of ceca, trachea, and liver/spleen and persistence over time. In 3 independent trials, 112 one-day-old birds were randomly divided into 4 groups (n = 28/group). On d 1 of age, one group was exposed to an aerosol of sterile saline and the remaining three groups were exposed to an aerosol generated from one of 3 doses (103, 106, or 109 CFU/mL) of S. Enteritidis inoculum. Aerosol exposure time was 30 min/group and was performed using a nebulizer. On d 3, 7, 14, and 21 of age, ceca, trachea, and liver/spleen were aseptically removed. Ceca were cultured for Salmonella counts (log10 CFU/g) and all tissues were cultured for Salmonella prevalence. All tissues from the control group were Salmonella negative for all sampling days. On sampling d 3 and 7, ceca Salmonella counts were highest (5.14 and 5.11, respectively) when challenged with 109 Salmonella (P ≤ 0.0281). Ceca Salmonella counts increased from d 3 (2.43) to d 7 (4.43), then remained constant when challenged at 103 Salmonella, and counts decreased over time for all other groups. Tissue Salmonella prevalence increased with increasing challenge levels at all sampling timepoints (P ≤ 0.0213). Salmonella prevalence was low (0/18 to 4/18) and did not change over time following 103 Salmonella challenge (P ≥ 0.2394). Prevalence decreased over time in ceca and trachea following 106 and 109 Salmonella challenge (P ≤ 0.0483). Liver/spleen Salmonella prevalence increased from d 3 (13/18) to d 14 (18/18) and then decreased at d 21 (10/18) in birds exposed to an aerosol of 109 Salmonella but remained constant over time for rest of the Salmonella inoculated groups. Overall, this study demonstrated the Salmonella colonization and persistence in different tissues in broilers following exposure to aerosolized Salmonella.

Identifying ways to support children of parents with substance use disorder is a critical public health issue. This study focused on the parent-child relationship as a critical catalyst in child resilience. Using data from a longitudinal cohort study, the aims of this study were to: (1 ) examine the agreement between parent and child reports of parenting behaviors and (2 ) describe the association between agreement and child mental health. Participants were 50 parent-child dyads that included parents enrolled in an adult drug court and their children, aged 8–18. Overall, agreement (i.e., concordance) between parent and child reports of parenting was slight to fair. Parents reported their parenting behaviors to be slightly more positive than how children rated the same behaviors in the areas of: involvement, 0.53 (SD = 0.80); positive parenting, 0.66 (SD = 0.87), and monitoring behaviors, 0.46 (SD = 0.90). Parents also rated themselves, in comparison to their children's reports, as using less inconsistent discipline, −0.33 (SD = 1.00), and less corporal punishment, 0.13 (SD = 1.01). Agreement was related to some, but not all, child mental health outcomes. When parents rating their parenting as more positive than their child reported, that had a negative effect on child self-esteem and personal adjustment. Contrary to hypotheses, we did not find a significant relationship between positive parenting and internalizing problems. Findings have implications for obtaining parent and child reports of parenting within the drug court system, and for identifying children at higher risk for externalizing problems.

As the pressure to address the climate crisis builds, scientists must walk the line between research and activism. This was apparent at the 2019 United Nations (UN) Framework Convention on Climate Change – Conference of the Parties (UNFCCC – COP), the largest annual meeting to address the climate crisis via supranational policymaking. COP has convened annually since 1995 in effort to establish international agreements for the reduction of greenhouse gas emissions, and in 2015, was the launch pad for the UN Paris Climate Agreement (PCA). Here, we present our collective perspective as early-career researchers on COP, an institution that we believe plays a critical role in the future of our oceans. Given the current pledges from signatories to the PCA, Earth is expected to warm ∼3°C by 2100, with the majority of anthropogenic heat content stored throughout the ocean. For this reason, among others, we feel it is crucial for ocean scientists to have a baseline understanding of the negotiations unfolding at COP and within the UNFCCC. We also provide evidence that certain features/structures of COP formalize colonial hierarchies, marginalize certain groups, and threaten to perpetuate the drivers of the environmental crises we all face. Thus, we urge that the future of such gatherings include purposeful and self-reflective acts of restructuring the space they occupy, the solutions they advocate, and the ways in which power is distributed amongst participants. We balance our critique with examples of how this has already been successful at COP, particularly with respect to organizing around ocean-climate issues.

Abstract Observational networks enhance real‐time situational awareness for emergency and water resource management during extreme weather events. We present examples of how a diverse, multitiered observational network in California provided insights into hydrometeorological processes and impacts during a 3‐day atmospheric river storm centered on 14 February 2019. This network, which has been developed over the past two decades, aims to improve understanding and mitigation of effects from extreme storms influencing water resources and natural hazards. We combine atmospheric reanalysis output and additional observations to show how the network allows: (1) the validation of record cool season precipitable water observations over southern California; (2) the identification of phenomena that produce natural hazards and present difficulties for short‐term weather forecast models, such as extreme precipitation amounts and snow level variability; (3) the use of soil moisture data to improve hydrologic model forecast skill in northern California's Russian River basin; and (4) the combination of meteorological data with seismic observations to identify when a large avalanche occurred on Mount Shasta. This case study highlights the value of investments in diverse observational assets and the importance of continued support and synthesis of these networks to characterize climatological context and advance understanding of processes modulating extreme weather.

Using the nationally representative sample from the United States in the 2012 Programme for International Student Assessment (N = 7,429 students from 240 schools), the present study examined the effects of student help-seeking behaviors on eight measures of student mathematics achievement. To account for the multilevel structure of the data with students nested within schools (i.e., students attending different schools), a two-level hierarchical linear model was used in the data analysis. Student help-seeking behaviors showed statistically significant positive effects on all eight measures of mathematics achievement, even after controlling for student characteristics and school characteristics. Furthermore, for all eight measures of mathematics achievement, the positive effects of student help-seeking behaviors on student mathematics achievement are independent of which schools students attend.

Abstract Introduction Amblyopia therapy appears to be most effective in children under the age of 7 years, but results from randomized control trials (RCTs) have shown that occlusion therapy and/or atropine penalization therapy may improve visual acuity in an older age group. Which of these two therapies is the most effective with fewer adverse effects in an older age group has not yet been agreed upon. Methods We systematically searched the literature for RCTs that compared atropine penalization therapy and occlusion therapy in terms of their visual acuity outcomes and adverse events and performed a meta-analysis on the visual acuity data obtained. The adverse effects reported and their implications for clinical practice are discussed. Results Two RCTs were identified, with the authors of both concluding that there was no detectable difference between the two therapies for the age groups they studied. The mean difference between atropine penalization and occlusion therapies was calculated to be − 0.01 logMAR (95% confidence interval − 0.07 to 0.03 logMAR) in favor of occlusion therapy, and no statistical difference between the two groups was detected (P = 0.45). Neither study detected a marked difference in terms of reported adverse effects from the two interventions. Conclusion Based on the results of our meta-analysis we conclude that there is no difference in visual acuity outcomes between atropine penalization therapy and occlusion therapy after 17 to 24 weeks of treatment in children aged 7–12 years. Further evidence to determine the efficacy of amblyopia therapy for an older patient population is required before studies comparing atropine penalization and occlusion therapy in patients older than 12 years can be performed. Atropine penalization therapy may cause more frequent minor adverse effects, such as light sensitivity, but in the clinical setting this needs to be balanced with the potential practical benefits of twice-weekly eye drops versus daily occlusion. Funding The funding for this study was provided by the National Institute for Health Research (NIHR) and Health Education England (HEE). Plain Language Summary A plain language summary is available for this article.

Mammalian evolution has occurred in the presence of mutualistic, commensal, and pathogenic micro- and macro-organisms for millennia. The presence of these organisms during mammalian evolution has allowed for intimate crosstalk between these colonizing species and the host immune system. In this review, we introduce the concept of the ‘multibiome’ to holistically refer to the biodiverse collection of bacteria, viruses, fungi and multicellular helminthic worms colonizing the mammalian intestine. Furthermore, we discuss new insights into multibiome-host interactions in the context of host-protective immunity and immune-mediated diseases, including inflammatory bowel disease and multiple sclerosis. Finally, we provide reasons to account for the multibiome in experimental design, analysis and in therapeutic applications.

Efficient coding suggests that adapting gain to match the varying stimulus statistics should help in optimizing behaviour. Here the authors show that adaptation in motion sensitive neurons maximizes information and improves movement accuracy in pursuit eye movements.

Background: Children are a vulnerable population following a natural disaster, due to their age and dependence on adults. The primary presenting problem children report after disasters is posttraumatic stress symptoms (PTSS). Prior research suggests that PTSS is inversely related to social support, which is often disrupted after a disaster. Objective: This study examined the relationship between social support (from parents, teachers, and peers) and PTSS in children affected by Hurricane Katrina. The research contributes to the literature by examining the mechanisms that drive this relationship over time. Methods: In this study, 426 children were followed over four timepoints, beginning 3–7 months after Hurricane Katrina and concluding 25–27 months post-hurricane. Three path models analysed the relationship between social support (from parents, teachers, and peers, measured by the Social Support Scale for Children) and PTSS (measured by the UCLA PTSD Reaction Index). Covariates included child age, minority status, gender, perceived life threat, and actual life threat. Nonsignificant paths were trimmed from the final models. Global fit indices were examined to determine model fit. Results: In the parent and peer social support models, PTSS exhibited statistically significant effects on social support from one wave to the next. In the teacher model, this was only true between Waves 2 and 3. Social support showed a statistically significant effect on PTSS between Wave 2 and Wave 3 in the peer model (standardized estimate = −0.26, p

Behavioral states marked by varying levels of arousal and attention modulate some properties of cortical responses (e.g. average firing rates or pairwise correlations), yet it is not fully understood what drives these response changes and how they might affect downstream stimulus decoding. Here we show that changes in state modulate the tuning of response variance-to-mean ratios (Fano factors) in a fashion that is neither predicted by a Poisson spiking model nor changes in the mean firing rate, with a substantial effect on stimulus discriminability. We recorded motion-sensitive neurons in middle temporal cortex (MT) in two states: alert fixation and light, opioid anesthesia. Anesthesia tended to lower average spike counts, without decreasing trial-to-trial variability compared to the alert state. Under anesthesia, within-trial fluctuations in excitability were correlated over longer time scales compared to the alert state, creating supra-Poisson Fano factors. In contrast, alert-state MT neurons have higher mean firing rates and largely sub-Poisson variability that is stimulus-dependent and cannot be explained by firing rate differences alone. The absence of such stimulus-induced variability tuning in the anesthetized state suggests different sources of variability between states. A simple model explains state-dependent shifts in the distribution of observed Fano factors via a suppression in the variance of gain fluctuations in the alert state. A population model with stimulus-induced variability tuning and behaviorally constrained information-limiting correlations explores the potential enhancement in stimulus discriminability by the cortical population in the alert state.

[This corrects the article DOI: 10.1371/journal.ppat.1005684.].

In order for a virus to persist, there must be a balance between viral replication and immune clearance. It is commonly believed that adaptive immunity drives clearance of viral infections and, thus, dysfunction or viral evasion of adaptive immunity is required for a virus to persist. Type I interferons (IFNs) play pleiotropic roles in the antiviral response, including through innate control of viral replication. Murine norovirus (MNoV) replicates in dendritic cells (DCs) and type I IFN signaling in DCs is important for early control of MNoV replication. We show here that the non-persistent MNoV strain CW3 persists systemically when CD11c positive DCs are unable to respond to type I IFN. Persistence in this setting is associated with increased early viral titers, maintenance of DC numbers, increased expression of DC activation markers and an increase in CD8 T cell and antibody responses. Furthermore, CD8 T cell function is maintained during the persistent phase of infection and adaptive immune cells from persistently infected mice are functional when transferred to Rag1-/- recipients. Finally, increased early replication and persistence are also observed in mixed bone marrow chimeras where only half of the CD11c positive DCs are unable to respond to type I IFN. These findings demonstrate that increased early viral replication due to a cell-intrinsic innate immune deficiency is sufficient for persistence and a functional adaptive immune response is not sufficient for viral clearance.

Background. Mobile communication technologies provide novel opportunities to support clinic-based health initiatives. Adoption of technologies for daily use and for health communication can differ between communities, depending upon demographic and cultural characteristics. Design and methods. A survey was administered in adolescent primary care and subspecialty clinics to assess parent-adolescent preferences in use of mobile technologies and social media to support provider-patient communication in an urban Latino community. Results. Of 130 respondents (65 parent-adolescent pairs), approximately half frequently sent and received text messages but lacked agreement regarding the other’s text messaging use. In contrast, adolescents only rarely used email compared to parents (15.4% versus 37.5%, P=0.006). Of social media, FacebookTM/MySpaceTM was most frequently used by parents and youth (60% and 55.4%, P=0.59); however, most lacked interest in using social media for health communication. Parents reported more interest than adolescents in receiving email (73.4% versus 35.9%, Pversus 33.9%, P=0.005) for health, but had more concerns about privacy issues (26.2% versus 9.2%, P=0.01). Respondents who were American born (aOR 5.7, 95%CI 1.2-28.5) or regularly used Instant Messaging or FacebookTM/MySpaceTM (aOR 4.6, 95%CI 1.4-14.7) were more likely to be interested in using social media for health communication. Conclusions. These findings underscore the importance of targeted assessment for planning the utilization of communication technologies and social media in clinical care or research for underserved youth.

Plant roots generate electrical currents and associated electrical fields as a consequence of electrogenic ion transport at the root surface. Here we demonstrate that the attraction of swimming zoospores of oomycete plant pathogens to plant roots is mediated in part by electrotaxis in natural root-generated electric fields. The zones of accumulation of anode- or cathode-seeking zoospores adjacent to intact and wounded root surfaces correlated with their in vitro electrotactic behavior. Manipulation of the root electrical field was reflected in changes in the pattern of zoospore accumulation and imposed focal electrical fields were capable of overriding endogenous signals at the root surface. The overall pattern of zoospore accumulation around roots was not affected by the presence of amino acids at concentrations expected within the rhizosphere, although higher concentrations induced encystment and reduced root targeting. The data suggest that electrical signals can augment or override chemical ones in mediating short-range tactic responses of oomycete zoospores at root surfaces.

Chikungunya virus (CHIKV) is a mosquito-borne alphavirus best known for causing fever, rash, arthralgia, and occasional neurologic disease. By using real-time reverse transcription–PCR, we detected CHIKV in plasma samples of 8 (14%) of 58 children with suspected central nervous system infection in Bellary, India. CHIKV was also detected in the cerebrospinal fluid of 3 children.

IL-7 is a critical cytokine for lymphocyte development. Recent work has highlighted critical roles for IL-7 signaling in mature T cell homeostasis and function, but its role in B cells is less well characterized. Using a knock-in mouse possessing a Tyr to Phe mutation at position 449 (IL-7Rα(449F/449F) mice) within the cytoplasmic SH2-binding motif of IL-7Rα, we evaluated the role of IL-7Rα Y449 motif in spleen B cells. IL-7Rα(449F/449F) mice had reduced numbers and increased death of follicular B cells compared to WT, but had significantly more follicular cells than IL-7Rα(-/-). The death of IL-7Rα(449F/449F) follicular cells was not due to a failure to respond to BAFF or lower levels of BAFF, a critical B cell survival factor. Marginal zone B cells were unaffected by the IL-7Rα(449F/449F) mutation. Any role for TSLP was ruled out, as TSLPR(-/-) mice had an identical B cell phenotype to wild-type mice. Bone marrow chimeras and the absence of IL-7Rα on B cells suggested that IL-7 did not directly regulate mature B cells, but that an IL-7-responsive cell was influencing B cells. IL-7 was also critical at the checkpoint between the T1 and T2 stages in the spleen. IL-7Rα(-/-) mice fail to develop T2 cells, but IL-7Rα(449F/449F) show a reduction compared to WT but not complete absence of T2 cells. We also tested the functional responses of IL-7Rα(449F/449F) to antigens and infection and found no difference in antibody responses to T-dependent or T-independent antigens, or to Influenza/A. IL-7 was important for generation of antibody responses to the intestinal worm H. polygyrus and for naive levels of IgA. Taken together, this suggests that IL-7 regulates follicular B cell numbers and survival in a cell-extrinsic manner, via a bone-marrow derived cell, but is not critical for antibody production outside the gut.

Synaptic transmission involves the calcium-dependent release of neurotransmitter from synaptic vesicles. Genetically encoded optical probes emitting different wavelengths of fluorescent light in response to neuronal activity offer a powerful approach to understand the spatial and temporal relationship of calcium dynamics to the release of neurotransmitter in defined neuronal populations. To simultaneously image synaptic vesicle recycling and changes in cytosolic calcium, we developed a red-shifted reporter of vesicle recycling based on a vesicular glutamate transporter, VGLUT1-mOrange2 (VGLUT1-mOr2), and a presynaptically-localized green calcium indicator, synaptophysin-GCaMP3 (SyGCaMP3) with a large dynamic range. The fluorescence of VGLUT1-mOr2 is quenched by the low pH of synaptic vesicles. Exocytosis upon electrical stimulation exposes the luminal mOr2 to the neutral extracellular pH and relieves fluorescence quenching. Re-acidification of the vesicle upon endocytosis again reduces fluorescence intensity. Changes in fluorescence intensity thus monitor synaptic vesicle exo- and endocytosis, as demonstrated previously for the green VGLUT1-pHluorin. To monitor changes in calcium, we fused the synaptic vesicle protein synaptophysin to the recently improved calcium indicator GCaMP3. SyGCaMP3 is targeted to presynaptic varicosities, and exhibits changes in fluorescence in response to electrical stimulation consistent with changes in calcium concentration. Using real-time imaging of both reporters expressed in the same synapses, we determine the time course of changes in VGLUT1 recycling in relation to changes in presynaptic calcium concentration. Inhibition of P/Q- and N-type calcium channels reduces calcium levels, as well as the rate of synaptic vesicle exocytosis and the fraction of vesicles released.

We investigate the operation of a load current multiplier (LCM) on a pulse-forming-line nanosecond pulse-power generator. Potential benefits of using the LCM technique on such generators are studied analytically for a simplified case. A concrete LCM design on the Zebra accelerator (1.9 Ohm, ∼1 MA, 100 ns) is described. This design is demonstrated experimentally with high-voltage power pulses having a rise time of dozens of nanoseconds. Higher currents and magnetic energies were observed in constant-inductance solid-state loads when a better generator-to-load energy coupling was achieved. The load current on Zebra was increased from the nominal 0.8–0.9 MA up to about 1.6 MA. This result was obtained without modifying the generator energetics or architecture and it is in good agreement with the presented numerical simulations. Validation of the LCM technique at a nanosecond time scale is of importance for the high-energy-density physics research.