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Instruments for air quality observations on geostationary satellites provide multiple observations per day and allow for the analysis of the diurnal variation in important air pollutants such as nitrogen dioxide (NO2). The South Korean instrument GEMS (Geostationary Environmental Monitoring Spectrometer), launched in February 2020, is the first geostationary instrument that is able to observe the diurnal variation in NO2. The measurements have a spatial resolution of 3.5 km × 8 km and cover a large part of Asia. This study compares 1 year of tropospheric NO2 vertical column density (VCD) observations from the operational GEMS L2 product, the scientific GEMS IUP-UB (Institute of Environmental Physics at the University of Bremen) product, the operational TROPOspheric Monitoring Instrument (TROPOMI) product, and ground-based differential optical absorption spectroscopy (DOAS) measurements in South Korea. The GEMS L2 tropospheric NO2 VCDs overestimate the ground-based tropospheric NO2 VCDs with a median relative difference of +61 % and a correlation coefficient of 0.76. The median relative difference is −2 % for the GEMS IUP-UB product and −16 % for the TROPOMI product, with correlation coefficients of 0.83 and 0.89, respectively. The scatter in the GEMS products can be reduced when observations are limited to the TROPOMI overpass time. Diurnal variations in tropospheric NO2 VCDs differ by the pollution level of the analyzed site but with good agreement between the GEMS IUP-UB and ground-based observations. Low-pollution sites show weak or almost no diurnal variation. In summer, the polluted sites show a minimum around noon, indicating the large influence of photochemical loss. Most variation is seen in spring and autumn, with increasing NO2 in the morning, a maximum close to noon, and a decrease towards the afternoon. Winter observations show rather flat or slightly decreasing NO2 throughout the day. Winter observations under low-wind-speed conditions at high-pollution sites show enhancements of NO2 throughout the day. This indicates that under calm conditions, dilution and the less effective chemical loss in winter do not balance the accumulating emissions. Diurnal variation observed at a low-pollution site follows seasonal wind patterns. A weekday–weekend effect analysis shows good agreement between the different products. However, the GEMS L2 product, while agreeing with the other data sets on weekdays, shows significantly less reduction on weekends. The influence of the stratospheric contribution and the surface reflectivity product on the satellite tropospheric NO2 VCD products is investigated. While the TM5 model's stratospheric VCDs, used in the TROPOMI product, are too high, resulting in tropospheric NO2 VCDs that are too low and even negative, when used in the GEMS IUP-UB retrieval, the GEMS L2 stratospheric VCD is too low. Surface reflectivity comparisons indicate that the GEMS L2 reflectivity makes a large contribution to the observed overestimation and scatter.

Abstract Familial Platelet Disorder with associated Myeloid Malignancy (FPDMM, FPD/AML, RUNX1‐FPD), caused by monoallelic deleterious germline RUNX1 variants, is characterized by bleeding diathesis and predisposition for hematologic malignancies, particularly myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). Clinical data on FPDMM‐associated AML (FPDMM‐AML) are limited, complicating evidence‐based clinical decision‐making. Here, we present retrospective genetic and clinical data of the largest cohort of FPDMM patients reported to date. We describe 159 European patients (from 94 families) of whom 134 were evaluable for the development of malignant disease. Sixty developed a hematologic malignancy (44.8%), most frequently AML (36/134, 26.9%) or MDS (18/134, 13.4%). Somatic alterations of RUNX1 by gene mutation (48%) and chromosome 21 aberrations (14.3%) were the most common somatic genetic aberrations in FPDMM‐AML, followed by FLT3‐ITD mutations (24.1%). Somatic RUNX1 and FLT3‐ITD mutations were not detected in FPDMM‐associated MDS, suggesting important contributions to leukemic transformation. Remission‐induction chemotherapy resulted in complete remission in 80% of FPDMM‐AML patients with a 5‐year overall survival (OS) of 50.4%. Survival outcome was non‐inferior compared to a large cohort of newly diagnosed adult RUNX1‐mutated AML (5‐year OS 36.6%, p = 0.5), with relatively infrequent concurrent adverse risk somatic aberrations (ASXL1 mutation, monosomal karyotype, monosomy 5/del 5q) in FPDMM‐AML. Collectively, data support the notion that step‐wise leukemic evolution in FPDMM is associated with distinct genetic events and indicate that a substantial subset of FPDMM‐AML patients achieves prolonged survival with conventional AML treatment, including allogeneic stem cell transplant. These findings are anticipated to inform personalized clinical decision‐making in this rare disorder.

ObjectiveAge-related hippocampal atrophy is associated with memory loss in older adults, and certain hippocampal subfields are more vulnerable to age-related atrophy than others. Cardiorespiratory fitness (CRF) may be an important protective factor for preserving hippocampal volume, but little is known about how CRF relates to the volume of specific hippocampal subfields, and whether associations between CRF and hippocampal subfield volumes are related to episodic memory performance. To address these gaps, the current study evaluates the associations among baseline CRF, hippocampal subfield volumes, and episodic memory performance in cognitively unimpaired older adults from the Investigating Gains in Neurocognition Trial of Exercise (IGNITE) (NCT02875301).MethodsParticipants (N = 601, ages 65–80, 72% female) completed assessments including a graded exercise test measuring peak oxygen comsumption (VO2peak) to assess CRF, cognitive testing, and high-resolution magnetic resonance imaging of the hippocampus processed with Automated Segmentation of Hippocampal Subfields (ASHS). Separate linear regression models examined whether CRF was associated with hippocampal subfield volumes and whether those assocations were moderated by age or sex. Mediation models examined whether hippocampal volumes statistically mediated the relationship between CRF and episodic memory performance. Covariates included age, sex, years of education, body mass index, estimated intracranial volume, and study site.ResultsHigher CRF was significantly associated with greater total left (B = 5.82, p = 0.039) and total right (B = 7.64, p = 0.006) hippocampal volume, as well as greater left CA2 (B = 0.14, p = 0.022) and dentate gyrus (DG; B = 2.34, p = 0.031) volume, and greater right CA1 (B = 3.99, p = 0.011), CA2 (B = 0.15, p = 0.002), and subiculum (B = 1.56, p = 0.004) volume. Sex significantly moderated left DG volume (B = −4.26, p = 0.017), such that the association was positive and significant only for males. Total left hippocampal volume [indirect effect = 0.002, 95% CI (0.0002, 0.00), p = 0.027] and right subiculum volume [indirect effect = 0.002, 95% CI (0.0007, 0.01), p = 0.006] statistically mediated the relationship between CRF and episodic memory performance.DiscussionWhile higher CRF was significantly associated with greater total hippocampal volume, CRF was not associated with all underlying subfield volumes. Our results further demonstrate the relevance of the associations between CRF and hippocampal volume for episodic memory performance. Finally, our results suggest that the regionally-specific effects of aging and Alzheimer’s disease on hippocampal subfields could be mitigated by maintaining higher CRF in older adulthood.

Background/aimsAge-related cognitive decline is a pervasive problem in our aging population. To date, no pharmacological treatments to halt or reverse cognitive decline are available. Behavioral interventions, such as physical exercise and Mindfulness-Based Stress Reduction, may reduce or reverse cognitive decline, but rigorously designed randomized controlled trials are needed to test the efficacy of such interventions.MethodsHere, we describe the design of the Mindfulness, Education, and Exercise study, an 18-month randomized controlled trial that will assess the effect of two interventions-mindfulness training plus moderate-to-vigorous intensity exercise or moderate-to-vigorous intensity exercise alone-compared with a health education control group on cognitive function in older adults. An extensive battery of biobehavioral assessments will be used to understand the mechanisms of cognitive remediation, by using structural and resting state functional magnetic resonance imaging, insulin sensitivity, inflammation, and metabolic and behavioral assessments.ResultsWe provide the results from a preliminary study (n = 29) of non-randomized pilot participants who received both the exercise and Mindfulness-Based Stress Reduction interventions. We also provide details on the recruitment and baseline characteristics of the randomized controlled trial sample (n = 585).ConclusionWhen complete, the Mindfulness, Education, and Exercise study will inform the research community on the efficacy of these widely available interventions improve cognitive functioning in older adults.

The sleep–wake cycle is a highly regulated behavior in which a circadian clock times sleep and waking, whereas a homeostatic process controls sleep need. Both the clock and the sleep homeostat interact, but to what extent they influence each other is not understood. There is evidence that clock genes, in particular Period2 (Per2), might be implicated in the sleep homeostatic process. Sleep regulation depends also on the proper functioning of neurons and astroglial cells, two cell-types in the brain that are metabolically dependent on each other. In order to investigate clock-driven contributions to sleep regulation we non-invasively measured sleep of mice that lack the Per2 gene either in astroglia, neurons, or all body cells. We observed that mice lacking Per2 in all body cells (Per2Brdm and TPer2 animals) display earlier onset of sleep after sleep deprivation (SD), whereas neuronal and astroglial Per2 knock-out animals (NPer2 and GPer2, respectively) were normal in that respect. It appears that systemic (whole body) Per2 expression is important for physiological sleep architecture expressed by number and length of sleep bouts, whereas neuronal and astroglial Per2 weakly impacts night-time sleep amount. Our results suggest that Per2 contributes to the timing of the regulatory homeostatic sleep response by delaying sleep onset after SD and attenuating the early night rebound response.

Physical activity (PA) in the form of aerobic exercise (AE) preserves and improves neurocognitive function across the lifespan. However, a mechanistic understanding of the pathways by which aerobic exercise impacts brain health is still lacking, particularly with respect to stress-related pathways. One mechanistic hypothesis is that AE improves neurocognitive health in part by modifying circulating levels of stress-related hormones and signaling factors associated with the hypothalamic-pituitary-adrenal (HPA) axis and autonomic nervous system (ANS), as commonly measured by the biomarkers cortisol (CORT) and salivary α-amylase (sAA). Thus, this hypothesis predicts that changes in stress biomarkers, such as CORT and sAA, are possible explanatory pathways mediating the positive effects of AE on neurocognitive health. In the present review article, we provide a summary of available studies examining the possibility that exercise-induced changes to stress biomarkers could partly account for exercise-related improvements in neurocognitive health. Our review indicates that despite the intuitive appeal of this hypothesis, there is insufficient evidence available to conclude that chronic and habitual AE affects neurocognitive health by altering stress biomarker pathways. The cross-sectional nature of the majority of reviewed studies highlights the need for well-controlled studies to adequately test this hypothesis.

A variety of empirical papers document the coexistence of exclusive and nonexclusive contracts within a given market across a multitude of industries. However, the theoretical literature has not been able to generate a differentiable model with the coexistence of these contracts. I rectify the gap in the literature by developing a theoretical model of two-sided matching, in which principals and agents choose between exclusive and nonexclusive contracts with cost-of-effort inefficiencies. I find that the coexistence of contracts relies on cost-sharing between principals, relative bargaining power, and an endogenous outside option. I also find that the pattern of contracts is monotonic with respect to the type distributions of principals and agents.

Abstract Methods relying on diagnostic codes to identify suicidal ideation and suicide attempt in Electronic Health Records (EHRs) at scale are suboptimal because suicide-related outcomes are heavily under-coded. We propose to improve the ascertainment of suicidal outcomes using natural language processing (NLP). We developed information retrieval methodologies to search over 200 million notes from the Vanderbilt EHR. Suicide query terms were extracted using word2vec. A weakly supervised approach was designed to label cases of suicidal outcomes. The NLP validation of the top 200 retrieved patients showed high performance for suicidal ideation (area under the receiver operator curve [AUROC]: 98.6, 95% confidence interval [CI] 97.1–99.5) and suicide attempt (AUROC: 97.3, 95% CI 95.2–98.7). Case extraction produced the best performance when combining NLP and diagnostic codes and when accounting for negated suicide expressions in notes. Overall, we demonstrated that scalable and accurate NLP methods can be developed to identify suicidal behavior in EHRs to enhance prevention efforts, predictive models, and precision medicine.

Objective: Age-related hippocampal atrophy is associated with memory loss in older adults, and certain hippocampal subfields are more vulnerable to age-related atrophy than others. Cardiorespiratory fitness (CRF) may be an important protective factor for preserving hippocampal volume, but little is known about how CRF relates to the volume of specific hippocampal subfields, and whether associations between CRF and hippocampal subfield volumes are related to episodic memory performance. To address these gaps, the current study evaluates the associations among baseline CRF, hippocampal subfield volumes, and episodic memory performance in cognitively unimpaired older adults from the Investigating Gains in Neurocognition Trial of Exercise (IGNITE) (NCT02875301). Methods: Participants (N = 601, ages 65–80, 72% female) completed assessments including a graded exercise test measuring peak oxygen comsumption (VO2peak) to assess CRF, cognitive testing, and high-resolution magnetic resonance imaging of the hippocampus processed with Automated Segmentation of Hippocampal Subfields (ASHS). Separate linear regression models examined whether CRF was associated with hippocampal subfield volumes and whether those assocations were moderated by age or sex. Mediation models examined whether hippocampal volumes statistically mediated the relationship between CRF and episodic memory performance. Covariates included age, sex, years of education, body mass index, estimated intracranial volume, and study site. Results: Higher CRF was significantly associated with greater total left (B = 5.82, p = 0.039) and total right (B = 7.64, p = 0.006) hippocampal volume, as well as greater left CA2 (B = 0.14, p = 0.022) and dentate gyrus (DG; B = 2.34, p = 0.031) volume, and greater right CA1 (B = 3.99, p = 0.011), CA2 (B = 0.15, p = 0.002), and subiculum (B = 1.56, p = 0.004) volume. Sex significantly moderated left DG volume (B = −4.26, p = 0.017), such that the association was positive and significant only for males. Total left hippocampal volume [indirect effect = 0.002, 95% CI (0.0002, 0.00), p = 0.027] and right subiculum volume [indirect effect = 0.002, 95% CI (0.0007, 0.01), p = 0.006] statistically mediated the relationship between CRF and episodic memory performance. Discussion: While higher CRF was significantly associated with greater total hippocampal volume, CRF was not associated with all underlying subfield volumes. Our results further demonstrate the relevance of the associations between CRF and hippocampal volume for episodic memory performance. Finally, our results suggest that the regionally-specific effects of aging and Alzheimer's disease on hippocampal subfields could be mitigated by maintaining higher CRF in older adulthood. [ABSTRACT FROM AUTHOR]

Circadian rhythms are self-sustained oscillators with a period of 24 h that is based on the output of transcriptional and post-translational feedback loops. Phosphorylation is considered one of the most important post-translational modifications affecting rhythmicity from cyanobacteria to mammals. For example, the lack of cyclin-dependent kinase 5 (CDK5) shortened the period length of the circadian oscillator in the Suprachiasmatic Nuclei (SCN) of mice via the destabilization of the PERIOD 2 (PER2) protein. Here, we show that CDK5 kinase activity and its interaction with clock components, including PER2 and CLOCK, varied over time in mouse embryonic fibroblast cells. Furthermore, the deletion of Cdk5 from cells resulted in a prolonged period and shifted the transcription of clock-controlled genes by about 2 to 4 h with a simple delay of chromatin binding of ARNTL (BMAL1) CLOCK. Taken together, our data indicate that CDK5 is critically involved in regulating the circadian clock in vitro at the molecular level.

Farmers, veterinarians and other animal health managers in the livestock sector are currently missing sufficient information on prevalence and burden of contagious endemic animal diseases. They need adequate tools for risk assessment and prioritization of control measures for these diseases. The DECIDE project develops data-driven decision-support tools, which present (i) robust and early signals of disease emergence and options for diagnostic confirmation; and (ii) options for controlling the disease along with their implications in terms of disease spread, economic burden and animal welfare. DECIDE focuses on respiratory and gastro-intestinal syndromes in the three most important terrestrial livestock species (pigs, poultry, cattle) and on reduced growth and mortality in two of the most important aquaculture species (salmon and trout). For each of these, we (i) identify the stakeholder needs; (ii) determine the burden of disease and costs of control measures; (iii) develop data sharing frameworks based on federated data access and meta-information sharing; (iv) build multivariate and multi-level models for creating early warning systems; and (v) rank interventions based on multiple criteria. Together, all of this forms decision-support tools to be integrated in existing farm management systems wherever possible and to be evaluated in several pilot implementations in farms across Europe. The results of DECIDE lead to improved use of surveillance data and evidence-based decisions on disease control. Improved disease control is essential for a sustainable food chain in Europe with increased animal health and welfare and that protects human health.

Abstract Light affects many physiological processes in mammals such as entrainment of the circadian clock, regulation of mood, and relaxation of blood vessels. At the molecular level, a stimulus such as light initiates a cascade of kinases that phosphorylate CREB at various sites, including serine 133 (S133). This modification leads CREB to recruit the co-factor CRCT1 and the histone acetyltransferase CBP to stimulate the transcription of genes containing a CRE element in their promoters, such as Period 1 (Per1). However, the details of this pathway are poorly understood. Here we provide evidence that PER2 acts as a co-factor of CREB to facilitate the formation of a transactivation complex on the CRE element of the Per1 gene regulatory region in response to light or forskolin. Using in vitro and in vivo approaches, we show that PER2 modulates the interaction between CREB and its co-regulator CRTC1 to support complex formation only after a light or forskolin stimulus. Furthermore, the absence of PER2 abolished the interaction between the histone acetyltransferase CBP and CREB. This process was accompanied by a reduction of histone H3 acetylation and decreased recruitment of RNA Pol II to the Per1 gene. Collectively, our data show that PER2 supports the stimulus-dependent induction of the Per1 gene via modulation of the CREB/CRTC1/CBP complex.

Searching for food follows a well-organized decision process in mammals to take up food only if necessary. Moreover, scavenging is preferred during their activity phase. Various time-dependent regulatory processes have been identified originating from the suprachiasmatic nuclei (SCN), which convert external light information into synchronizing output signals. However, a direct impact of the SCN on the timing of normal food searching has not yet been found. Here, we revisited the function of the SCN to affect when mice look for food. We found that this process was independent of light but modified by the palatability of the food source. Surprisingly, reducing the output from the SCN, in particular from the vasopressin releasing neurons, reduced the amount of scavenging during the early activity phase. The SCN appeared to transmit a signal to the paraventricular nuclei (PVN) via GABA receptor A1. Finally, the interaction of SCN and PVN was verified by retrograde transport-mediated complementation. None of the genetic manipulations affected the uptake of more palatable food. The data indicate that the PVN are sufficient to produce blunted food searching rhythms and are responsive to hedonistic feeding. Nevertheless, the search for normal food during the early activity phase is significantly enhanced by the SCN.

Abstract The circadian clock regulates many biochemical and physiological pathways, and lack of clock genes, such as Period (Per) 2, affects not only circadian activity rhythms, but can also modulate feeding and mood-related behaviors. However, it is not known how cell-type specific expression of Per2 contributes to these behaviors. In this study, we find that Per2 in glial cells is important for balancing mood-related behaviors, without affecting circadian activity parameters. Genetic and adeno-associated virus-mediated deletion of Per2 in glial cells of mice leads to reduced despair and anxiety. This is paralleled by an increase of the GABA transporter 2 (Gat2/Slc6a13) and Dopamine receptor D3 (Drd3) mRNA, and a reduction of glutamate levels in the nucleus accumbens (NAc). Interestingly, neuronal Per2 knock-out also reduces despair, but does not influence anxiety. The change in mood-related behavior is not a result of a defective molecular clock, as glial Bmal1 deletion has no effect on neither despair nor anxiety. Exclusive deletion of Per2 in glia of the NAc reduced despair, but had no influence on anxiety. Our data provide strong evidence for an important role of glial Per2 in regulating mood-related behavior.

Instruments for air quality observations on geostationary satellites provide multiple observations per day and allow for the analysis of the diurnal variation in important air pollutants such as nitrogen dioxide (NO2). The South Korean instrument GEMS (Geostationary Environmental Monitoring Spectrometer), launched in February 2020, is the first geostationary instrument that is able to observe the diurnal variation in NO2. The measurements have a spatial resolution of 3.5 km × 8 km and cover a large part of Asia. This study compares 1 year of tropospheric NO2 vertical column density (VCD) observations from the operational GEMS L2 product, the scientific GEMS IUP-UB (Institute of Environmental Physics at the University of Bremen) product, the operational TROPOspheric Monitoring Instrument (TROPOMI) product, and ground-based differential optical absorption spectroscopy (DOAS) measurements in South Korea. The GEMS L2 tropospheric NO2 VCDs overestimate the ground-based tropospheric NO2 VCDs with a median relative difference of + 61 % and a correlation coefficient of 0.76. The median relative difference is - 2 % for the GEMS IUP-UB product and - 16 % for the TROPOMI product, with correlation coefficients of 0.83 and 0.89, respectively. The scatter in the GEMS products can be reduced when observations are limited to the TROPOMI overpass time. Diurnal variations in tropospheric NO2 VCDs differ by the pollution level of the analyzed site but with good agreement between the GEMS IUP-UB and ground-based observations. Low-pollution sites show weak or almost no diurnal variation. In summer, the polluted sites show a minimum around noon, indicating the large influence of photochemical loss. Most variation is seen in spring and autumn, with increasing NO2 in the morning, a maximum close to noon, and a decrease towards the afternoon. Winter observations show rather flat or slightly decreasing NO2 throughout the day. Winter observations under low-wind-speed conditions at high-pollution sites show enhancements of NO2 throughout the day. This indicates that under calm conditions, dilution and the less effective chemical loss in winter do not balance the accumulating emissions. Diurnal variation observed at a low-pollution site follows seasonal wind patterns. A weekday–weekend effect analysis shows good agreement between the different products. However, the GEMS L2 product, while agreeing with the other data sets on weekdays, shows significantly less reduction on weekends. The influence of the stratospheric contribution and the surface reflectivity product on the satellite tropospheric NO2 VCD products is investigated. While the TM5 model's stratospheric VCDs, used in the TROPOMI product, are too high, resulting in tropospheric NO2 VCDs that are too low and even negative, when used in the GEMS IUP-UB retrieval, the GEMS L2 stratospheric VCD is too low. Surface reflectivity comparisons indicate that the GEMS L2 reflectivity makes a large contribution to the observed overestimation and scatter. [ABSTRACT FROM AUTHOR]

Background The small GTPase RhoA (Ras homolog gene family, member A) regulates a variety of cellular processes, including cell motility, proliferation, survival, and permeability. In addition, there are reports indicating that RhoA‐ROCK (rho associated coiled‐coil containing protein kinase) activation is essential for VEGF (vascular endothelial growth factor)‐mediated angiogenesis, whereas other work suggests VEGF‐antagonistic effects of the RhoA‐ROCK axis. Methods and Results To elucidate this issue, we examined human umbilical vein endothelial cells and human coronary artery endothelial cells after stable overexpression (lentiviral transduction) of constitutively active (G14V/Q63L), dominant‐negative (T19N), or wild‐type RhoA using a series of in vitro angiogenesis assays (proliferation, migration, tube formation, angiogenic sprouting, endothelial cell viability) and a human umbilical vein endothelial cells xenograft assay in immune‐incompetent NOD scid gamma mice in vivo. Here, we report that expression of active and wild‐type RhoA but not dominant‐negative RhoA significantly inhibited endothelial cell proliferation, migration, tube formation, and angiogenic sprouting in vitro. Moreover, active RhoA increased endothelial cell death in vitro and decreased human umbilical vein endothelial cell‐related angiogenesis in vivo. Inhibition of RhoA by C3 transferase antagonized the inhibitory effects of RhoA and strongly enhanced VEGF‐induced angiogenic sprouting in control‐treated cells. In contrast, inhibition of RhoA effectors ROCK1/2 and LIMK1/2 (LIM domain kinase 1/2) did not significantly affect RhoA‐related effects, but increased angiogenic sprouting and migration of control‐treated cells. In agreement with these data, VEGF did not activate RhoA in human umbilical vein endothelial cells as measured by a Förster resonance energy transfer–based biosensor. Furthermore, global transcriptome and subsequent bioinformatic gene ontology enrichment analyses revealed that constitutively active RhoA induced a differentially expressed gene pattern that was enriched for gene ontology biological process terms associated with mitotic nuclear division, cell proliferation, cell motility, and cell adhesion, which included a significant decrease in VEGFR‐2 (vascular endothelial growth factor receptor 2) and NOS3 (nitric oxide synthase 3) expression. Conclusions Our data demonstrate that increased RhoA activity has the potential to trigger endothelial dysfunction and antiangiogenic effects independently of its well‐characterized downstream effectors ROCK and LIMK.

Recent technological advances have multiplied the variety of biologgers used in wildlife research, particularly with small-bodied animals. Passive integrated transponders (PIT) have been used for decades to log visits of tagged animals at reader-equipped artificial feeders or roost boxes. More recently, novel miniaturized sensor nodes can collect data on social encounters among tagged individuals in any location. Combining these systems allows researchers to gather high-resolution tracking data on certain individuals from their long-term PIT-tagged animal populations. However, there can be a risk of interference among tracking systems. Here we tested whether placing an additional biologging sensor on top of a PIT tag might attenuate the magnetic field reaching the PIT tag and, in turn, hamper reading success of the radio-frequency identification (RFID) reader. We also evaluated data transmission by a digital sensor node in the presence of a magnetic field created by the RFID antenna. The combination of this RFID system and wireless biologging sensors works without error, suggesting that the simultaneous use of PIT tags and other digital biologgers, e.g., miniaturized GPS-loggers, should also work together properly when communication channels do not overlap. The combination of long-term monitoring with PIT tags and short-term tracking with biologging sensor nodes creates exciting new opportunities to gather rich social data when individuals are not present at RFID reader stations.

ObjectiveOverweight and obesity [body mass index (BMI) ≥ 25 kg/m2] are associated with poorer prognosis among women with breast cancer, and weight gain is common during treatment. Symptoms of depression and anxiety are also highly prevalent in women with breast cancer and may be exacerbated by post-diagnosis weight gain. Altered brain function may underlie psychological distress. Thus, this secondary analysis examined the relationship between BMI, psychological health, and resting state functional connectivity (rsFC) among women with breast cancer.MethodsThe sample included 34 post-menopausal women newly diagnosed with Stage 0-IIa breast cancer (Mage = 63.59 ± 5.73) who were enrolled in a 6-month randomized controlled trial of aerobic exercise vs. usual care. At baseline prior to randomization, whole-brain analyses were conducted to evaluate the relationship between BMI and seed-to-voxel rsFC of the hippocampus and amygdala. Connectivity values from significant clusters were then extracted and examined as predictors of self-reported depression and anxiety.ResultsMean BMI was in the obese range (M = 31.83 ± 6.62). For both seeds examined, higher BMI was associated with lower rsFC with regions of prefrontal cortex (PFC), including ventrolateral PFC (vlPFC), dorsolateral PFC, and superior frontal gyrus (z range = 2.85–4.26). Hippocampal connectivity with the vlPFC was negatively correlated with self-reported anxiety (β = 0.47, p < 0.01).ConclusionHigher BMI was associated with lower hippocampal and amygdala connectivity to regions of PFC implicated in cognitive control and emotion regulation. BMI-related differences in hippocampal and amygdala connectivity following a recent breast cancer diagnosis may relate to future worsening of psychological functioning during treatment and remission. Additional longitudinal research exploring this hypothesis is warranted.

Autoimmune diseases (AIDs) are the consequence of a breach in immune tolerance, leading to the inability to sufficiently differentiate between self and non-self. Immune reactions that are targeted towards self-antigens can ultimately lead to the destruction of the host’s cells and the development of autoimmune diseases. Although autoimmune disorders are comparatively rare, the worldwide incidence and prevalence is increasing, and they have major adverse implications for mortality and morbidity. Genetic and environmental factors are thought to be the major factors contributing to the development of autoimmunity. Viral infections are one of the environmental triggers that can lead to autoimmunity. Current research suggests that several mechanisms, such as molecular mimicry, epitope spreading, and bystander activation, can cause viral-induced autoimmunity. Here we describe the latest insights into the pathomechanisms of viral-induced autoimmune diseases and discuss recent findings on COVID-19 infections and the development of AIDs.

Rapid advancements in biologging technology have led to unprecedented insights into animal behaviour, but testing the effects of biologgers on tagged animals is necessary for both scientific and ethical reasons. Here, we measured how quickly 13 wild-caught and captively isolated common vampire bats (Desmodus rotundus) habituated to mock proximity sensors glued to their dorsal fur. To assess habituation, we scored video-recorded behaviours every minute from 18.00 to 06.00 for 3 days, then compared the rates of grooming directed to the sensor tag versus to their own body. During the first hour, the mean tag-grooming rate declined dramatically from 53% of sampled time (95% CI = 36–65%, n = 6) to 16% (8–24%, n = 9), and down to 4% by hour 5 (1–6%, n = 13), while grooming of the bat's own body did not decline. When tags are firmly attached, isolated individual vampire bats mostly habituate within an hour of tag attachment. In two cases, however, tags became loose before falling off causing the bats to dishabituate. For tags glued to fur, behavioural data are likely to be impacted immediately after the tag is attached and when it is loose before it falls off.

Stable social bonds in group-living animals can provide greater access to food. A striking example is that female vampire bats often regurgitate blood to socially bonded kin and nonkin that failed in their nightly hunt. Food-sharing relationships form via preferred associations and social grooming within roosts. However, it remains unclear whether these cooperative relationships extend beyond the roost. To evaluate if long-term cooperative relationships in vampire bats play a role in foraging, we tested if foraging encounters measured by proximity sensors could be explained by wild roosting proximity, kinship, or rates of co-feeding, social grooming, and food sharing during 21 months in captivity. We assessed evidence for 6 hypothetical scenarios of social foraging, ranging from individual to collective hunting. We found that closely bonded female vampire bats departed their roost separately, but often reunited far outside the roost. Repeating foraging encounters were predicted by within-roost association and histories of cooperation in captivity, even when accounting for kinship. Foraging bats demonstrated both affiliative and competitive interactions with different social calls linked to each interaction type. We suggest that social foraging could have implications for social evolution if "local" within-roost cooperation and "global" outside-roost competition enhances fitness interdependence between frequent roostmates.

Familial myeloid malignancies have recently been classified as separate disease entities. Here, using whole-exome sequencing of affected pedigrees - the authors highlight genetic variants associated with these conditions.

Abstract Background Bats are among the most successful desert mammals. Yet, our understanding of their spatio-temporal dynamics in habitat use associated with the seasonal oscillation of resources is still limited. In this study, we have employed state-of-the-art lightweight GPS loggers to track the yellow-winged bat Lavia frons in a desert in northern Kenya to investigate how seasonality in a desert affects the a) spatial and b) temporal dimensions of movements in a low-mobility bat. Methods Bats were tracked during April–May 2017 (rainy season) and January–February 2018 (dry season) using 1-g GPS loggers. Spatial and temporal dimensions of movements were quantified, respectively, as the home range and nightly activity patterns. We tested for differences between seasons to assess responses to seasonal drought. In addition, we quantified home range overlap between neighbouring individuals to investigate whether tracking data will be in accordance with previous reports on territoriality and social monogamy in L. frons. Results We obtained data for 22 bats, 13 during the rainy and 9 during the dry season. Home ranges averaged 5.46 ± 11.04 ha and bats travelled a minimum distance of 99.69 ± 123.42 m/hour. During the dry season, home ranges were larger than in the rainy season, and bats exhibited high activity during most of the night. No apparent association with free water was identified during the dry season. The observed spatial organisation of home ranges supports previous observations that L. frons partitions the space into territories throughout the year. Conclusions Our results suggest that, in low-mobility bats, a potential way to cope with seasonally harsh conditions and resource scarcity in deserts is to cover larger areas and increase time active, suggesting lower cost-efficiency of the foraging activity. Climate change may pose additional pressures on L. frons and other low-mobility species by further reducing food abundances.

Light at night has strong effects on physiology and behavior of mammals. It affects mood in humans, which is exploited as light therapy, and has been shown to reset the circadian clock in the suprachiasmatic nuclei (SCN). This resetting is paramount to align physiological and biochemical timing to the environmental light-dark cycle. Here we provide evidence that light at zeitgeber time (ZT) 22 affects mood-related behaviors also in mice by activating the clock gene Period1 (Per1) in the lateral habenula (LHb), a brain region known to modulate mood-related behaviors. We show that complete deletion of Per1 in mice led to depressive-like behavior and loss of the beneficial effects of light on this behavior. In contrast, specific deletion of Per1 in the region of the LHb did not affect mood-related behavior, but suppressed the beneficial effects of light. RNA sequence analysis in the mesolimbic dopaminergic system revealed profound changes of gene expression after a light pulse at ZT22. In the nucleus accumbens (NAc), sensory perception of smell and G-protein coupled receptor signaling were affected the most. Interestingly, most of these genes were not affected in Per1 knock-out animals, indicating that induction of Per1 by light serves as a filter for light-mediated gene expression in the brain. Taken together we show that light affects mood-related behavior in mice at least in part via induction of Per1 in the LHb with consequences on mood-related behavior and signaling mechanisms in the mesolimbic dopaminergic system.

Individuals carrying a pathogenic germline variant in the breast cancer predisposition gene BRCA1 (gBRCA1+) are prone to developing breast cancer. Apart from its well-known role in DNA repair, BRCA1 has been shown to powerfully impact cellular metabolism. While, in general, metabolic reprogramming was named a hallmark of cancer, disrupted metabolism has also been suggested to drive cancer cell evolution and malignant transformation by critically altering microenvironmental tissue integrity. Systemic metabolic effects induced by germline variants in cancer predisposition genes have been demonstrated before. Whether or not systemic metabolic alterations exist in gBRCA1+ individuals independent of cancer incidence has not been investigated yet. We therefore profiled the plasma metabolome of 72 gBRCA1+ women and 72 age-matched female controls, none of whom (carriers and non-carriers) had a prior cancer diagnosis and all of whom were cancer-free during the follow-up period. We detected one single metabolite, pyruvate, and two metabolite ratios involving pyruvate, lactate, and a metabolite of yet unknown structure, significantly altered between the two cohorts. A machine learning signature of metabolite ratios was able to correctly distinguish between gBRCA1+ and controls in ~82%. The results of this study point to innate systemic metabolic differences in gBRCA1+ women independent of cancer incidence and raise the question as to whether or not constitutional alterations in energy metabolism may be involved in the etiology of BRCA1-associated breast cancer.