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Abstract Background Erythropoietin (EPO) improves cognition of human subjects in the clinical setting by as yet unknown mechanisms. We developed a mouse model of robust cognitive improvement by EPO to obtain the first clues of how EPO influences cognition, and how it may act on hippocampal neurons to modulate plasticity. Results We show here that a 3-week treatment of young mice with EPO enhances long-term potentiation (LTP), a cellular correlate of learning processes in the CA1 region of the hippocampus. This treatment concomitantly alters short-term synaptic plasticity and synaptic transmission, shifting the balance of excitatory and inhibitory activity. These effects are accompanied by an improvement of hippocampus dependent memory, persisting for 3 weeks after termination of EPO injections, and are independent of changes in hematocrit. Networks of EPO-treated primary hippocampal neurons develop lower overall spiking activity but enhanced bursting in discrete neuronal assemblies. At the level of developing single neurons, EPO treatment reduces the typical increase in excitatory synaptic transmission without changing the number of synaptic boutons, consistent with prolonged functional silencing of synapses. Conclusion We conclude that EPO improves hippocampus dependent memory by modulating plasticity, synaptic connectivity and activity of memory-related neuronal networks. These mechanisms of action of EPO have to be further exploited for treating neuropsychiatric diseases.

A key feature of advanced brain aging includes structural defects of intracortical myelin that are associated with secondary neuroinflammation. A similar pathology is seen in specific myelin mutant mice that model ‘advanced brain aging’ and exhibit a range of behavioral abnormalities. However, the cognitive assessment of these mutants is problematic because myelin-dependent motor-sensory functions are required for quantitative behavioral readouts. To better understand the role of cortical myelin integrity for higher brain functions, we generated mice lacking Plp1, encoding the major integral myelin membrane protein, selectively in ventricular zone stem cells of the mouse forebrain. In contrast to conventional Plp1 null mutants, subtle myelin defects were restricted to the cortex, hippocampus, and underlying callosal tracts. Moreover, forebrain-specific Plp1 mutants exhibited no defects of basic motor-sensory performance at any age tested. Surprisingly, several behavioral alterations reported for conventional Plp1 null mice (Gould et al., 2018) were absent and even social interactions appeared normal. However, with novel behavioral paradigms, we determined catatonia-like symptoms and isolated executive dysfunction in both genders. This suggests that loss of myelin integrity has an impact on cortical connectivity and underlies specific defects of executive function. These observations are likewise relevant for human neuropsychiatric conditions and other myelin-related diseases.

Skilled, ethical use of social media can advance social justice, impact policy, engage and educate the community, and elevate social workers. To assure that MSW students develop these skills, we created an assignment that required students to use a professional social media profile to advocate for a cause or policy based on findings from a needs and strengths assessment conducted as a group project. We used class discussion, readings, and online tutorials to support students' learning. We conducted a pretest-posttest evaluation and found a statistically significant increase in competency and knowledge of written and unwritten rules of each platform. Our recommendations for implementing the assignment include encouraging students to develop a professional presence on the platform earlier and requiring tutorials.

Evaluating populational trends of health condition has become an important topic for marine mammal populations under the Marine Strategy Framework Directive (MSFD). In the Baltic Sea, under the recommendation of Helsinki Commission (HELCOM), efforts have been undertaken to use blubber thickness as an indicator of energy reserves in marine mammals. Current values lack geographical representation from the entire Baltic Sea area and a large dataset is only available for grey seals (Halichoerus grypus) from Sweden and Finland. Knowledge on variation of blubber thickness related to geography throughout the Baltic Sea is important for its usage as an indicator. Such evaluation can provide important information about the energy reserves, and hence, food availability. It is expected that methodological standardization under HELCOM should include relevant datasets with good geographical coverage that can also account for natural variability in the resident marine mammal populations. In this study, seasonal and temporal trends of blubber thickness were evaluated for three marine mammal species—harbor seal (Phoca vitulina), grey seal (Halichoerus grypus) and harbor porpoise (Phocoena phocoena)—resident in the southern Baltic Sea collected and investigated under stranding networks. Additionally, the effects of age, season and sex were analyzed. Seasonal variation of blubber thickness was evident for all species, with harbor seals presenting more pronounced effects in adults and grey seals and harbor porpoises presenting more pronounced effects in juveniles. For harbor seals and porpoises, fluctuations were present over the years included in the analysis. In the seal species, blubber thickness values were generally higher in males. In harbor seals and porpoises, blubber thickness values differed between the age classes: while adult harbor seals displayed thicker blubber layers than juveniles, the opposite was observed for harbor porpoises. Furthermore, while an important initial screening tool, blubber thickness assessment cannot be considered a valid methodology for overall health assessment in marine mammals and should be complemented with data on specific health parameters developed for each species.

Abstract Up to one person in a population of 10,000 is diagnosed once in lifetime with an encephalitis, in 50–70% of unknown origin. Recognized causes amount to 20–50% viral infections. Approximately one third of affected subjects develops moderate and severe subsequent damage. Several neurotropic viruses can directly infect pyramidal neurons and induce neuronal death in cortex and hippocampus. The resulting encephalitic syndromes are frequently associated with cognitive deterioration and dementia, but involve numerous parallel and downstream cellular and molecular events that make the interpretation of direct consequences of sudden pyramidal neuronal loss difficult. This, however, would be pivotal for understanding how neuroinflammatory processes initiate the development of neurodegeneration, and thus for targeted prophylactic and therapeutic interventions. Here we utilized adult male NexCreERT2xRosa26-eGFP-DTA (= ‘DTA’) mice for the induction of a sterile encephalitis by diphtheria toxin-mediated ablation of cortical and hippocampal pyramidal neurons which also recruits immune cells into gray matter. We report multifaceted aftereffects of this defined process, including the expected pathology of classical hippocampal behaviors, evaluated in Morris water maze, but also of (pre)frontal circuit function, assessed by prepulse inhibition. Importantly, we modelled in encephalitis mice novel translationally relevant sequelae, namely altered social interaction/cognition, accompanied by compromised thermoreaction to social stimuli as convenient readout of parallel autonomic nervous system (dys)function. High resolution magnetic resonance imaging disclosed distinct abnormalities in brain dimensions, including cortical and hippocampal layering, as well as of cerebral blood flow and volume. Fluorescent tracer injection, immunohistochemistry and brain flow cytometry revealed persistent blood–brain-barrier perturbance and chronic brain inflammation. Surprisingly, blood flow cytometry showed no abnormalities in circulating major immune cell subsets and plasma high-mobility group box 1 (HMGB1) as proinflammatory marker remained unchanged. The present experimental work, analyzing multidimensional outcomes of direct pyramidal neuronal loss, will open new avenues for urgently needed encephalitis research.

Abstract Objective To investigate national trends of SBS diagnosis codes and how trends varied among patient and hospital characteristics. Methods We examined possible SBS, confirmed SBS, and non-SBS abuse diagnosis codes among children age three and younger who were hospitalized for abuse between 1998 and 2014 using a secondary analysis of the National Inpatient Sample, the largest US all-payer inpatient care database (N = 66,854). A baseline category logit model was used based on a quasi-likelihood approach (QIC) with an independent working correlation structure. Results The rate (per 100,000 census population of children age 3 and younger) of confirmed and possible SBS diagnosis codes was 5.4 (± 0.3) between 1998 and 2014, whereas the rate of non-SBS abuse was 19.6 (± 1.0). The rate of confirmed SBS diagnosis codes increased from 3.8 (± 0.3) in 1998 to 5.1 (± 0.9) in 2005, and decreased to 1.3 (± 0.2) in 2014. Possible SBS diagnosis codes were 0.6 (± 0.2) in 1998, increasing to 2.4 (± 0.4) in 2014. Confirmed SBS diagnosis codes have declined since 2002, while possible SBS diagnosis codes have increased. All abuse types were more frequent among infants, males, children from low-income homes, and urban teaching hospitals. Conclusions We investigated seventeen-year trends of SBS diagnosis codes among young children hospitalized for abuse. The discrepancy between trends in possible and confirmed SBS diagnosis codes suggests differences in norms for utilizing SBS diagnosis codes, which has implications for which hospital admissions are coded as AHT. Future research should investigate processes for using SBS diagnosis codes and whether all codes associated with abusive head injuries in young children are classified as AHT. Our findings also highlight the relativity defining and applying SBS diagnosis codes to children admitted to the hospital for shaking injuries. Medical professionals find utility in using SBS diagnosis codes, though may be more apt to apply codes related to possible SBS diagnosis codes in children presenting with abusive head injuries. Clarifying norms for SBS diagnosis codes and refining definitions for AHT diagnosis will ensure that young children presenting with, and coded for, abusive head injuries are included in overall counts of AHT based on secondary data of diagnosis codes. This baseline data, an essential component of child abuse surveillance, will enable ongoing efforts to track, prevent, and reduce child abuse.

The decline in the population of ring-necked pheasants (Phasianus colchicus) in northwestern Germany since 2007 raises questions about the underlying causes. We therefore studied the growth and immune status of ring-necked pheasant chicks dependent on different feed composition. Here, 490 ring-necked pheasant chicks were raised in five groups up to nine weeks. While control groups C1 and C2 received sufficient crude protein (28%) and energy (12.5 MJ/Kg feed) according to current standards, group C2 was treated with cyclosporine eight hours prior to phythemagglutination (PHA) testing, serving as a positive immune suppressed control. Group V1 was fed with reduced protein (20%) but optimal energy content (12.5 MJ/Kg feed), group V2 was fed with sufficient protein (28%) and reduced energy content (10 MJ/kg feed) whereas group V3 was fed reduced crude protein (20%) and reduced energy content (10MJ/kg feed). On all chicks, health status was checked each week, and 20 birds of each group were weighed randomly per week. PHA-testing was performed on 12 birds of each group to study the in vivo non-specific activation of lymphocytes at week 2, 4, 6, 7, 8 and 9. In addition, hemolysis-hemagglutination-assay (HHA) was performed on each of the PHA-tested chicks, which were subsequently euthanized and dissected. Histopathologic examinations of 5 birds that were randomly chosen were performed. The PHA-test results demonstrate significant differences between control (C1, C2) and experimental groups (V1-V3) in several developmental stages. According to the HHA results, weekly testing detected a significant increase of titres per week in all groups without significant differences. Here, only hemagglutination and no lysis of samples was observed. It seems appropriate to conclude that during their first weeks of life, protein content is of higher importance in ring-necked pheasant chicks than energy intake. In particular T-cell response is significantly reduced, which indicate a weaker immune system resulting in a higher risk for clinical diseases. Therefore, we assume that protein i.e. insect availability is a highly important co-factor in the free-ranging population dynamics, and is linked to declines of the northwestern German population.

Emerging infectious diseases have been especially devastating to amphibians, the most endangered class of vertebrates. For amphibians, the greatest disease threat is chytridiomycosis, caused by one of two chytridiomycete fungal pathogens Batrachochytrium dendrobatidis (Bd) and Batrachochytrium salamandrivorans (Bsal). Research over the last two decades has shown that susceptibility to this disease varies greatly with respect to a suite of host and pathogen factors such as phylogeny, geography (including abiotic factors), host community composition, and historical exposure to pathogens; yet, despite a growing body of research, a comprehensive understanding of global chytridiomycosis incidence remains elusive. In a large collaborative effort, Bd-Maps was launched in 2007 to increase multidisciplinary investigations and understanding using compiled global Bd occurrence data (Bsal was not discovered until 2013). As its database functions aged and became unsustainable, we sought to address critical needs utilizing new technologies to meet the challenges of aggregating data to facilitate research on both Bd and Bsal. Here, we introduce an advanced central online repository to archive, aggregate, and share Bd and Bsal data collected from around the world. The Amphibian Disease Portal (https://amphibiandisease.org) addresses several critical community needs while also helping to build basic biological knowledge of chytridiomycosis. This portal could be useful for other amphibian diseases and could also be replicated for uses with other wildlife diseases. We show how the Amphibian Disease Portal provides: (1) a new repository for the legacy Bd-Maps data; (2) a repository for sample-level data to archive datasets and host published data with permanent DOIs; (3) a flexible framework to adapt to advances in field, laboratory, and informatics technologies; and (4) a global aggregation of Bd and Bsal infection data to enable and accelerate research and conservation. The new framework for this project is built using biodiversity informatics best practices and metadata standards to ensure scientific reproducibility and linkages across other biological and biodiversity repositories.

The amphibian chytrid fungus Batrachochytrium dendrobatidis (Bd) is a skin pathogen that can cause the emerging infectious disease chytridiomycosis in susceptible species. It has been considered one of the most severe threats to amphibian biodiversity. We aimed to provide an updated compilation of global Bd occurrences by host taxon and geography, and with the larger global Bd dataset we reanalyzed Bd associations with environmental metrics at the world and regional scales. We also compared our Bd data compilation with a recent independent assessment to provide a more comprehensive count of species and countries with Bd occurrences. Bd has been detected in 1,375 of 2,525 (55%) species sampled, more than doubling known species infections since 2013. Bd occurrence is known from 93 of 134 (69%) countries at this writing; this compares to known occurrences in 56 of 82 (68%) countries in 2013. Climate-niche space is highly associated with Bd detection, with different climate metrics emerging as key predictors of Bd occurrence at regional scales; this warrants further assessment relative to climate-change projections. The accretion of Bd occurrence reports points to the common aims of worldwide investigators to understand the conservation concerns for amphibian biodiversity in the face of potential disease threat. Renewed calls for better mitigation of amphibian disease threats resonate across continents with amphibians, especially outside Asia. As Bd appears to be able to infect about half of amphibian taxa and sites, there is considerable room for biosecurity actions to forestall its spread using both bottom-up community-run efforts and top-down national-to-international policies. Conservation safeguards for sensitive species and biodiversity refugia are continuing priorities.

Abstract Background The European brown hare (Lepus europaeus) typically resides in open habitats in agriculturally dominated landscapes in Europe. Over recent decades, a widely observed population decline occurred, which was attributed to agricultural intensification. However, with political incentives for specific crops, especially maize for energy production, the habitat went through massive changes. Thus, there is the need to identify parameters that characterize a suitable habitat for the brown hare in today’s agricultural lands. Results We modelled European brown hare densities spatially and temporally explicit over 10 years (2005–2014) across an entire federal state. The generalized additive mixed model confirms a constant decline of the European brown hare population in Lower Saxony. Municipalities with a high proportion of grassland and precipitation totaling up to 900 mm are more favored. Woodland showed an approximately linear negative effect. The most important agricultural crop groups such as winter grains and winter oilseed rape showed overall positive effects on hare densities. However, the effect of maize was unimodal, with a positive effect of medium proportions, but a negative effect of very high proportions. The effect of sugar beet was relatively weak but negative. Brown hares were also more abundant in municipalities with a higher density of vixen with litter and municipalities with a high proportion of wildflower strips showed higher brown hare abundance. Conclusion Lower Saxony is a diverse federal state with grassland dominated areas in the northwest, more woodland in the east, but intensive arable land in most remaining areas. The European brown hare—a species with a wide ecological potency—shows preferences to both grassland and the most typical arable crop groups such as winter grains and winter oilseed rape. The substantial increase in maize production within the time frame was likely unfavourable and may be one reason for the decline. Nonetheless, political tools such as the agri-environmental scheme “wildflower strips” were beneficial for the brown hare abundance and may be an option to reverse the decline seen over the 10 years.

AbstractPublic library staff increasingly assist patrons with psychosocial needs (e.g. food or housing insecurity). To address growing demands for psychosocial support, libraries are engaging in social work (SW) collaborations; however, successful collaborations depend on library staff’s openness to intervention. This quantitative study examines the relationship between burnout and openness to SW collaboration, and whether resilience and empowerment protect against burnout. Results show that career resilience mediates the relationship between psychological empowerment and burnout. Burnout was not associated with openness to SW collaboration. Findings suggest resilience plays a role in preventing burnout, and that library staff are open to SW collaborations. [ABSTRACT FROM AUTHOR]

We previously introduced the brain erythropoietin (EPO) circle as a model to explain the adaptive ‘brain hardware upgrade’ and enhanced performance. In this fundamental circle, brain cells, challenged by motor-cognitive tasks, experience functional hypoxia, triggering the expression of EPO among other genes. We attested hypoxic cells by a transgenic reporter approach under the ubiquitous CAG promoter, with Hif-1α oxygen-dependent degradation-domain (ODD) fused to CreERT2-recombinase. To specifically focus on the functional hypoxia of excitatory pyramidal neurons, here, we generated CaMKIIα-CreERT2-ODD::R26R-tdTomato mice. Behavioral challenges, light-sheet microscopy, immunohistochemistry, single-cell mRNA-seq, and neuronal cultures under normoxia or hypoxia served to portray these mice. Upon complex running wheel performance as the motor-cognitive task, a distinct increase in functional hypoxic neurons was assessed immunohistochemically and confirmed three-dimensionally. In contrast, fear conditioning as hippocampal stimulus was likely too short-lived to provoke neuronal hypoxia. Transcriptome data of hippocampus under normoxia versus inspiratory hypoxia revealed increases in CA1 CaMKIIα-neurons with an immature signature, characterized by the expression of Dcx, Tbr1, CaMKIIα, Tle4, and Zbtb20, and consistent with accelerated differentiation. The hypoxia reporter response was reproduced in vitro upon neuronal maturation. To conclude, task-associated activity triggers neuronal functional hypoxia as a local and brain-wide reaction mediating adaptive neuroplasticity. Hypoxia-induced genes such as EPO drive neuronal differentiation, brain maturation, and improved performance.

Mutations in PARK15, which encodes for the F‐box protein FBXO7 have been associated with Parkinsonian Pyramidal syndrome, a rare and complex movement disorder with Parkinsonian symptoms, pyramidal tract signs and juvenile onset. Our previous study showed that systemic loss of Fbxo7 in mice causes motor defects and premature death. We have also demonstrated that FBXO7 has a crucial role in neurons as the specific deletion in tyrosine hydroxylase‐positive or glutamatergic forebrain neurons leads to late‐onset or early‐onset motor dysfunction, respectively. In this study, we examined NEX‐Cre;Fbxo7fl/fl mice, in which Fbxo7 was specifically deleted in glutamatergic projection neurons. The effects of FBXO7 deficiency on striatal integrity were investigated with HPLC and histological analyses. NEX‐Cre;Fbxo7fl/fl mice revealed an increase in striatal dopamine concentrations, changes in the glutamatergic, GABAergic and dopaminergic pathways, astrogliosis and microgliosis and little or no neuronal loss in the striatum. To determine the effects on the integrity of the synapse, we purified synaptic membranes, subjected them to quantitative mass spectrometry analysis and found alterations in the complement system, endocytosis and exocytosis pathways. These neuropathological changes coincide with alterations in spontaneous home cage behavior. Taken together, our findings suggest that FBXO7 is crucial for corticostriatal projections and the synaptic integrity of the striatum, and consequently for proper motor control. [ABSTRACT FROM AUTHOR]

Abstract Anxiety disorders and substance abuse, including benzodiazepine use disorder, frequently occur together. Unfortunately, treatment of anxiety disorders still includes benzodiazepines, and patients with an existing comorbid benzodiazepine use disorder or a genetic susceptibility for benzodiazepine use disorder may be at risk of adverse treatment outcomes. The identification of genetic predictors for anxiety disorders, and especially for benzodiazepine use disorder, could aid the selection of the best treatment option and improve clinical outcomes. The brain-specific angiogenesis inhibitor I-associated protein 3 (Baiap3) is a member of the mammalian uncoordinated 13 (Munc13) protein family of synaptic regulators of neurotransmitter exocytosis, with a striking expression pattern in amygdalae, hypothalamus and periaqueductal gray. Deletion of Baiap3 in mice leads to enhanced seizure propensity and increased anxiety, with the latter being more pronounced in female than in male animals. We hypothesized that genetic variation in human BAIAP3 may also be associated with anxiety. By using a phenotype-based genetic association study, we identified two human BAIAP3 single-nucleotide polymorphism risk genotypes (AA for rs2235632, TT for rs1132358) that show a significant association with anxiety in women and, surprisingly, with benzodiazepine abuse in men. Returning to mice, we found that male, but not female, Baiap3 knockout (KO) mice develop tolerance to diazepam more quickly than control animals. Analysis of cultured Baiap3 KO hypothalamus slices revealed an increase in basal network activity and an altered response to diazepam withdrawal. Thus, Baiap3/BAIAP3 is gender specifically associated with anxiety and benzodiazepine use disorder, and the analysis of Baiap3/BAIAP3-related functions may help elucidate mechanisms underlying the development of both disorders.