A Positively Selected MAGEE2 LoF Allele Is Associated with Sexual Dimorphism in Human Brain Size and Shows Similar Phenotypes in Magee2 Null Mice.

A nonsense allele at rs1343879 in human MAGEE2 on chromosome X has previously been reported as a strong candidate for positive selection in East Asia. This premature stop codon causing ∼80% protein truncation is characterized by a striking geographical pattern of high population differentiation: common in Asia and the Americas (up to 84% in the 1000 Genomes Project East Asians) but rare elsewhere. Here, we generated a Magee2 mouse knockout mimicking the human loss-of-function mutation to study its functional consequences. The Magee2 null mice did not exhibit gross abnormalities apart from enlarged brain structures (13% increased total brain area, P = 0.0022) in hemizygous males. The area of the granular retrosplenial cortex responsible for memory, navigation, and spatial information processing was the most severely affected, exhibiting an enlargement of 34% (P = 3.4×10-6). The brain size in homozygous females showed the opposite trend of reduced brain size, although this did not reach statistical significance. With these insights, we performed human association analyses between brain size measurements and rs1343879 genotypes in 141 Chinese volunteers with brain MRI scans, replicating the sexual dimorphism seen in the knockout mouse model. The derived stop gain allele was significantly associated with a larger volume of gray matter in males (P = 0.00094), and smaller volumes of gray (P = 0.00021) and white (P = 0.0015) matter in females. It is unclear whether or not the observed neuroanatomical phenotypes affect behavior or cognition, but it might have been the driving force underlying the positive selection in humans.

Delirium Screening in Neurocritical Care and Stroke Unit Patients: A Pilot Study on the Influence of Neurological Deficits on CAM-ICU and ICDSC Outcome.

BACKGROUND/OBJECTIVE: Delirium is a common complication in critically ill patients with a negative impact on hospital length of stay, morbidity, and mortality. Little is known on how neurological deficits affect the outcome of commonly used delirium screening tools such as the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU) and the Intensive Care Delirium Screening Checklist (ICDSC) in neurocritical care patients. METHODS: Over a period of 1 month, all patients admitted to a neurocritical care and stroke unit at a single academic center were prospectively screened for delirium using both CAM-ICU and ICDSC. Tool-based delirium screening was compared with delirium evaluation by the treating clinical team. Additionally, ICD-10 delirium criteria were assessed. RESULTS: One hundred twenty-three patients with a total of 644 daily screenings were included. Twenty-three patients (18.7%) were diagnosed with delirium according to the clinical evaluation. Delirium incidence amounted to 23.6% (CAM-ICU) and 26.8% (ICDSC). Sensitivity and specificity of both screening tools were 66.9% and 93.3% for CAM-ICU and 69.9% and 93.9% for ICDSC, respectively. Patients identified with delirium by either CAM-ICU or ICDSC presented a higher proportion of neurological deficits such as impaired consciousness, expressive aphasia, impaired language comprehension, and hemineglect. Subsequently, generalized estimating equations identified a significant association between impaired consciousness (as indexed by Richmond Agitation and Sedation Scale) and a positive delirium assessment with both CAM-ICU and ICDSC, while impaired language comprehension and hemineglect were only associated with a positive CAM-ICU result. CONCLUSIONS: A positive delirium screening with both CAM-ICU and ICDSC in neurocritical care and stroke unit patients was found to be significantly associated with the presence of neurological deficits. These findings underline the need for a more specific delirium screening tool in neurocritical care patients.

Induced parental care in a poison frog: a tadpole cross-fostering experiment.

Understanding the external stimuli and natural contexts that elicit complex behaviours, such as parental care, is key in linking behavioural mechanisms to their real-life function. Poison frogs provide obligate parental care by shuttling their tadpoles from terrestrial clutches to aquatic nurseries, but little is known about the proximate mechanisms that control these behaviours. In this study, we used Allobates femoralis, a poison frog with predominantly male parental care, to investigate whether tadpole transport can be induced in both sexes by transferring unrelated tadpoles to the backs of adults in the field. Specifically, we asked whether the presence of tadpoles on an adult's back can override the decision-making rules preceding tadpole pick-up and induce the recall of spatial memory necessary for finding tadpole deposition sites. We used telemetry to facilitate accurate tracking of individual frogs and spatial analysis to compare movement trajectories. All tested individuals transported their foster-tadpoles to water pools outside their home area. Contrary to our expectation, we found no sex difference in the likelihood to transport or in the spatial accuracy of finding tadpole deposition sites. We reveal that a stereotypical cascade of parental behaviours that naturally involves sex-specific offspring recognition strategies and the use of spatial memory can be manipulated by experimental placement of unrelated tadpoles on adult frogs. As individuals remained inside their home area when only the jelly from tadpole-containing clutches was brushed on the back, we speculate that tactile rather than chemical stimuli trigger these parental behaviours.

Objective markers for sleep propensity: comparison between the Multiple Sleep Latency Test and the Vigilance Algorithm Leipzig.

The regulation of wakefulness is important for high-order organisms. Its dysregulation is involved in the pathomechanism of several psychiatric disorders. Thus, a tool for its objective but little time-consuming assessment would be of importance. The Vigilance Algorithm Leipzig allows the objective measurement of sleep propensity, based on a single resting state electroencephalogram. To compare the Vigilance Algorithm Leipzig with the standard for objective assessment of excessive daytime sleepiness, a four-trial Multiple Sleep Latency Test in 25 healthy subjects was conducted. Between the first two trials, a 15-min, 25-channel resting electroencephalogram was recorded, and Vigilance Algorithm Leipzig was used to classify the sleep propensity (i.e., type of vigilance regulation) of each subject. The results of both methods showed significant correlations with the Epworth Sleepiness Scale (ρ = -0.70; ρ = 0.45, respectively) and correlated with each other (ρ = -0.54). Subjects with a stable electroencephalogram-vigilance regulation yielded significant increased sleep latencies compared with an unstable regulation (multiple sleep latency 898.5 s versus 549.9 s; P = 0.03). Further, Vigilance Algorithm Leipzig classifications allowed the identification of subjects with average sleep latencies <6 min with a sensitivity of 100% and a specificity of 77%. Thus, Vigilance Algorithm Leipzig provides similar information on wakefulness regulation in comparison to the much more cost- and time-consuming Multiple Sleep Latency Test. Due to its high sensitivity and specificity for large sleep propensity, Vigilance Algorithm Leipzig could be an effective and reliable alternative to the Multiple Sleep Latency Test, for example for screening purposes in large cohorts, where objective information about wakefulness regulation is needed.

Subjective and objective olfactory abnormalities in Crohn's disease.

The pathogenesis of Crohn's disease (CD) is still unknown, but the involvement of the olfactory system in CD appears possible. No study to date has systematically assessed the olfactory function in CD patients. We investigated the olfactory function in CD patients in active (n = 31) and inactive disease (n = 27) and in a control group of age- and sex-matched healthy subjects (n = 35). Subjective olfactory testing was applied using the Sniffin' Sticks test. For olfactory testing, olfactory event-related potentials (OERPs) were obtained with a 4-channel olfactometer using phenyl ethyl alcohol (PEA) and hydrogen sulfide (H(2)S). Carbon dioxide (CO(2)) was employed as control stimulus, and chemosomatosensory event-related potentials (CSSERPs) were registered. Results of the Sniffin' Sticks test revealed significantly different olfactory hedonic judgment with increased olfactory hedonic estimates for pleasant odorants in CD patients in active disease compared with healthy subjects. A statistical trend was found toward lower olfactory thresholds in CD patients. In objective olfactory testing, CD patients showed lower amplitudes of OERPs and CSSERPs. Additionally, OERPs showed significantly shorter N1- and P2 latencies following stimulation of the right nostril with H(2)S in CD patients in inactive disease compared with controls. Our study demonstrates specific abnormalities of olfactory perception in CD patients.

Disease-specific molecular events in cortical multiple sclerosis lesions.

Cortical lesions constitute an important part of multiple sclerosis pathology. Although inflammation appears to play a role in their formation, the mechanisms leading to demyelination and neurodegeneration are poorly understood. We aimed to identify some of these mechanisms by combining gene expression studies with neuropathological analysis. In our study, we showed that the combination of inflammation, plaque-like primary demyelination and neurodegeneration in the cortex is specific for multiple sclerosis and is not seen in other chronic inflammatory diseases mediated by CD8-positive T cells (Rasmussen's encephalitis), B cells (B cell lymphoma) or complex chronic inflammation (tuberculous meningitis, luetic meningitis or chronic purulent meningitis). In addition, we performed genome-wide microarray analysis comparing micro-dissected active cortical multiple sclerosis lesions with those of tuberculous meningitis (inflammatory control), Alzheimer's disease (neurodegenerative control) and with cortices of age-matched controls. More than 80% of the identified multiple sclerosis-specific genes were related to T cell-mediated inflammation, microglia activation, oxidative injury, DNA damage and repair, remyelination and regenerative processes. Finally, we confirmed by immunohistochemistry that oxidative damage in cortical multiple sclerosis lesions is associated with oligodendrocyte and neuronal injury, the latter also affecting axons and dendrites. Our study provides new insights into the complex mechanisms of neurodegeneration and regeneration in the cortex of patients with multiple sclerosis.

NADPH oxidase expression in active multiple sclerosis lesions in relation to oxidative tissue damage and mitochondrial injury.

Multiple sclerosis is a chronic inflammatory disease of the central nervous system, associated with demyelination and neurodegeneration. The mechanisms of tissue injury are poorly understood, but recent data suggest that mitochondrial injury may play an important role in this process. Mitochondrial injury can be triggered by reactive oxygen and nitric oxide species, and we recently provided evidence for oxidative damage of oligodendrocytes and dystrophic axons in early stages of active multiple sclerosis lesions. In this study, we identified potential sources of reactive oxygen and nitrogen species through gene expression in carefully staged and dissected lesion areas and by immunohistochemical analysis of protein expression. Genome-wide microarrays confirmed mitochondrial injury in active multiple sclerosis lesions, which may serve as an important source of reactive oxygen species. In addition, we found differences in the gene expression levels of various nicotinamide adenine dinucleotide phosphate oxidase subunits between initial multiple sclerosis lesions and control white matter. These results were confirmed at the protein level by means of immunohistochemistry, showing upregulation of the subunits gp91phox, p22phox, p47phox, nicotinamide adenine dinucleotide phosphate oxidase 1 and nicotinamide adenine dinucleotide phosphate oxidase organizer 1 in activated microglia in classical active as well as slowly expanding lesions. The subunits gp91phox and p22phox were constitutively expressed in microglia and were upregulated in the initial lesion. In contrast, p47phox, nicotinamide adenine dinucleotide phosphate oxidase 1 and nicotinamide adenine dinucleotide phosphate oxidase organizer 1 expression were more restricted to the zone of initial damage or to lesions from patients with acute or early relapsing/remitting multiple sclerosis. Double labelling showed co-expression of the nicotinamide adenine dinucleotide phosphate oxidase subunits in activated microglia and infiltrated macrophages, suggesting the assembly of functional complexes. Our data suggest that the inflammation-associated oxidative burst in activated microglia and macrophages plays an important role in demyelination and free radical-mediated tissue injury in the pathogenesis of multiple sclerosis.

Multisystem inflammatory syndrome in adults with cardiac engagement: a case report and literature review.

Background: Following infection with severe acute respiratory syndrome coronavirus, a post-infectious multisystem inflammatory syndrome in adults (MIS-A) has been identified. It affects multiple organ systems and can lead to multi-organic failure. Case summary: This case report describes a patient with MIS-A with significant cardiac involvement including peri-myocarditis, pulmonary hypertension, right-sided heart failure, tricuspid regurgitation, and cardiogenic shock. After being diagnosed and treated correctly for MIS-A, the patient recovered completely, without any cardiac sequelae. Discussion: The hyperinflammation in MIS-A can have cardiac engagement. Although more research is required to further clarify the underlying mechanisms, prompt diagnosis and anti-inflammatory treatment are crucial for better outcomes and cardiac recovery.

Home security cameras as a tool for behavior observations and science equity.

Reliably capturing transient animal behavior in the field and laboratory remains a logistical and financial challenge, especially for small ectotherms. Here, we present a camera system that is affordable, accessible, and suitable to monitor small, cold-blooded animals historically overlooked by commercial camera traps, such as small amphibians. The system is weather-resistant, can operate offline or online, and allows collection of time-sensitive behavioral data in laboratory and field conditions with continuous data storage for up to four weeks. The lightweight camera can also utilize phone notifications over Wi-Fi so that observers can be alerted when animals enter a space of interest, enabling sample collection at proper time periods. We present our findings, both technological and scientific, in an effort to elevate tools that enable researchers to maximize use of their research budgets. We discuss the relative affordability of our system for researchers in South America, which is home to the largest population of ectotherm diversity.

Dissecting the autism-associated 16p11.2 locus identifies multiple drivers in neuroanatomical phenotypes and unveils a male-specific role for the major vault protein.

BACKGROUND: Using mouse genetic studies and systematic assessments of brain neuroanatomical phenotypes, we set out to identify which of the 30 genes causes brain defects at the autism-associated 16p11.2 locus. RESULTS: We show that multiple genes mapping to this region interact to regulate brain anatomy, with female mice exhibiting far fewer brain neuroanatomical phenotypes. In male mice, among the 13 genes associated with neuroanatomical defects (Mvp, Ppp4c, Zg16, Taok2, Slx1b, Maz, Fam57b, Bola2, Tbx6, Qprt, Spn, Hirip3, and Doc2a), Mvp is the top driver implicated in phenotypes pertaining to brain, cortex, hippocampus, ventricles, and corpus callosum sizes. The major vault protein (MVP), the main component of the vault organelle, is a conserved protein found in eukaryotic cells, yet its function is not understood. Here, we find MVP expression highly specific to the limbic system and show that Mvp regulates neuronal morphology, postnatally and specifically in males. We also recapitulate a previously reported genetic interaction and show that Mvp+/-;Mapk3+/- mice exhibit behavioral deficits, notably decreased anxiety-like traits detected in the elevated plus maze and open field paradigms. CONCLUSIONS: Our study highlights multiple gene drivers in neuroanatomical phenotypes, interacting with each other through complex relationships. It also provides the first evidence for the involvement of the major vault protein in the regulation of brain size and neuroanatomy, specifically in male mice.

Binding and sequestration of poison frog alkaloids by a plasma globulin.

Alkaloids are important bioactive molecules throughout the natural world, and in many animals they serve as a source of chemical defense against predation. Dendrobatid poison frogs bioaccumulate alkaloids from their diet to make themselves toxic or unpalatable to predators. Despite the proposed roles of plasma proteins as mediators of alkaloid trafficking and bioavailability, the responsible proteins have not been identified. We use chemical approaches to show that a ~50 kDa plasma protein is the principal alkaloid-binding molecule in blood of poison frogs. Proteomic and biochemical studies establish this plasma protein to be a liver-derived alkaloid-binding globulin (ABG) that is a member of the serine-protease inhibitor (serpin) family. In addition to alkaloid-binding activity, ABG sequesters and regulates the bioavailability of 'free' plasma alkaloids in vitro. Unexpectedly, ABG is not related to saxiphilin, albumin, or other known vitamin carriers, but instead exhibits sequence and structural homology to mammalian hormone carriers and amphibian biliverdin-binding proteins. ABG represents a new small molecule binding functionality in serpin proteins, a novel mechanism of plasma alkaloid transport in poison frogs, and more broadly points toward serpins acting as tunable scaffolds for small molecule binding and transport across different organisms.

Oxidative damage in multiple sclerosis lesions.

Multiple sclerosis is a chronic inflammatory disease of the central nervous system, associated with demyelination and neurodegeneration. The mechanisms of tissue injury are currently poorly understood, but recent data suggest that mitochondrial injury may play an important role in this process. Since mitochondrial injury can be triggered by reactive oxygen and nitric oxide species, we analysed by immunocytochemistry the presence and cellular location of oxidized lipids and oxidized DNA in lesions and in normal-appearing white matter of 30 patients with multiple sclerosis and 24 control patients without neurological disease or brain lesions. As reported before in biochemical studies, oxidized lipids and DNA were highly enriched in active multiple sclerosis plaques, predominantly in areas that are defined as initial or 'prephagocytic' lesions. Oxidized DNA was mainly seen in oligodendrocyte nuclei, which in part showed signs of apoptosis. In addition, a small number of reactive astrocytes revealed nuclear expression of 8-hydroxy-d-guanosine. Similarly, lipid peroxidation-derived structures (malondialdehyde and oxidized phospholipid epitopes) were seen in the cytoplasm of oligodendrocytes and some astrocytes. In addition, oxidized phospholipids were massively accumulated in a fraction of axonal spheroids with disturbed fast axonal transport as well as in neurons within grey matter lesions. Neurons stained for oxidized phospholipids frequently revealed signs of degeneration with fragmentation of their dendritic processes. The extent of lipid and DNA oxidation correlated significantly with inflammation, determined by the number of CD3 positive T cells and human leucocyte antigen-D expressing macrophages and microglia in the lesions. Our data suggest profound oxidative injury of oligodendrocytes and neurons to be associated with active demyelination and axonal or neuronal injury in multiple sclerosis.

Contrasting parental roles shape sex differences in poison frog space use but not navigational performance.

Sex differences in vertebrate spatial abilities are typically interpreted under the adaptive specialization hypothesis, which posits that male reproductive success is linked to larger home ranges and better navigational skills. The androgen spillover hypothesis counters that enhanced male spatial performance may be a byproduct of higher androgen levels. Animal groups that include species where females are expected to outperform males based on life-history traits are key for disentangling these hypotheses. We investigated the association between sex differences in reproductive strategies, spatial behavior, and androgen levels in three species of poison frogs. We tracked individuals in natural environments to show that contrasting parental sex roles shape sex differences in space use, where the sex performing parental duties shows wider-ranging movements. We then translocated frogs from their home areas to test their navigational performance and found that the caring sex outperformed the non-caring sex only in one out of three species. In addition, males across species displayed more explorative behavior than females and androgen levels correlated with explorative behavior and homing accuracy. Overall, we reveal that poison frog reproductive strategies shape movement patterns but not necessarily navigational performance. Together this work suggests that prevailing adaptive hypotheses provide an incomplete explanation of sex differences in spatial abilities.

Pathogenic T cell responses against aquaporin 4.

Inflammatory lesions in the central nervous system of patients with neuromyelitis optica are characterized by infiltration of T cells and deposition of aquaporin-4-specific antibodies and complement on astrocytes at the glia limitans. Although the contribution of aquaporin-4-specific autoantibodies to the disease process has been recently elucidated, a potential role of aquaporin-4-specific T cells in lesion formation is unresolved. To address this issue, we raised aquaporin-4-specific T cell lines in Lewis rats and characterized their pathogenic potential in the presence and absence of aquaporin-4-specific autoantibodies of neuromyelitis optica patients. We show that aquaporin-4-specific T cells induce brain inflammation with particular targeting of the astrocytic glia limitans and permit the entry of pathogenic anti-aquaporin-4-specific antibodies to induce NMO-like lesions in spinal cord and brain. In addition, transfer of aquaporin-4-specific T cells provoked mild (subclinical) myositis and interstitial nephritis. We further show that the expression of the conformational epitope, recognized by NMO patient-derived aquaporin-4-specific antibodies is induced in kidney cells by the pro-inflammatory cytokine gamma-interferon. Our data provide further support for the view that NMO lesions may be induced by a complex interplay of T cell mediated and humoral immune responses against aquaporin-4.

Physical Activity, Loneliness, and Meaning of Friendship in Young Individuals - A Mixed-Methods Investigation Prior to and During the COVID-19 Pandemic With Three Cross-Sectional Studies.

Meaningful social interactions and regular physical activity are inversely associated with loneliness. Using a mixed-methods research design employing quantitative and qualitative research approaches, this research aimed to explore loneliness, physical activity, friendship, and experiences relating to the COVID-19 pandemic both prior to and during the pandemic. Quantitative data of (1) n = 363 first-year university students assessed in 2018/2019 and of (2) n = 175 individuals aged 18-29 years assessed in 2020 were gathered using independent self-administered online surveys. In addition, (3) n = 4 students were recruited for semi-structured, qualitative interviews in 2020 during the onset phase of the COVID-19 pandemic. Correlation and regression analyses as well as analyses of variance were conducted. Thematic analysis as a qualitative method was used to explore the role physical activity, friendship, and social interactions played in loneliness, particularly in times of social isolation and social distancing. Results revealed associations of varying strength between physical activity and loneliness in 2018/2019 (r = -0.09, p ≤ 0.05) and 2020 (r = -0.20, p < 0.01). In 2020, n = 73 (41.7%) participants felt that their loneliness had increased since the COVID-19 social and physical distancing guidelines were introduced, but this was not associated with a perceived change in physical activity (r = -0.05, p > 0.05). Analyses of qualitative data revealed three main themes: (1) the lack of deep friendships at university, (2) the positive perceived impact of team sports on feelings of loneliness, and (3) the need for real connection in times of crisis. Thus, with regard to feelings of loneliness during the pandemic, being physically active seems to be a small but potentially relevant factor among young individuals. The qualitative study suggests that first-year university students might buffer the lack of deep friendships and meaningful interactions by building social bonds in team sports. In times of physical distancing, young individuals vulnerable to loneliness may therefore require special support such as doing sports with physical distance and perceiving connected with their team for instance by digital devices and emotional coping.

Pool choice in a vertical landscape: Tadpole-rearing site flexibility in phytotelm-breeding frogs.

Many species of Neotropical frogs have evolved to deposit their tadpoles in small water bodies inside plant structures called phytotelmata. These pools are small enough to exclude large predators but have limited nutrients and high desiccation risk. Here, we explore phytotelm use by three common Neotropical species: Osteocephalus oophagus, an arboreal frog that periodically feeds eggs to its tadpoles; Dendrobates tinctorius, a tadpole-transporting poison frog with cannibalistic tadpoles; and Allobates femoralis, a terrestrial tadpole-transporting poison frog with omnivorous tadpoles. We found that D. tinctorius occupies pools across the chemical and vertical gradient, whereas A. femoralis and O. oophagus appear to have narrower deposition options that are restricted primarily by pool height, water capacity, alkalinity, and salinity. Dendrobates tinctorius tadpoles are particularly flexible and can survive in a wide range of chemical, physical, and biological conditions, whereas O. oophagus seems to prefer small, clear pools and A. femoralis occupies medium-sized pools with abundant leaf litter and low salinity. Together, these results show the possible niche partitioning of phytotelmata among frogs and provide insight into stressors and resilience of phytotelm breeders.

Inflammation induced by innate immunity in the central nervous system leads to primary astrocyte dysfunction followed by demyelination.

Primary loss and dysfunction of astrocytes may trigger demyelination, as seen in neuromyelitis optica, an inflammatory disease of the central nervous system. In most patients affected by this disease, injury to astrocytes is initiated by the action of autoantibodies targeting aquaporin 4 (AQP-4), a water channel on astrocytes. We show here that damage of astrocytes and subsequent demyelination can also occur in the absence of autoantibody-mediated mechanisms. Following injection of lipopolysaccharide into the white matter initial microglia activation is followed by a functional disturbance of astrocytes, mainly reflected by retraction of astrocytic foot processes at the glia limitans and loss of AQP-4 and connexins, which are involved in the formation of gap junctions between astrocytes and oligodendrocytes. Demyelination and oligodendrocyte degeneration in this model follows astrocyte pathology. Similar structural abnormalities were also seen in a subset of active lesions in multiple sclerosis. Our studies suggest that astrocyte injury may be an important early step in the cascade of lesion formation in brain inflammation.

Reproductive behavior drives female space use in a sedentary Neotropical frog.

Longer-range movements of anuran amphibians such as mass migrations and habitat invasion have received a lot of attention, but fine-scale spatial behavior remains largely understudied. This gap is especially striking for species that show long-term site fidelity and display their whole behavioral repertoire in a small area. Studying fine-scale movement with conventional capture-mark-recapture techniques is difficult in inconspicuous amphibians: individuals are hard to find, repeated captures might affect their behavior and the number of data points is too low to allow a detailed interpretation of individual space use and time budgeting. In this study, we overcame these limitations by equipping females of the Brilliant-Thighed Poison Frog (Allobates femoralis) with a tag allowing frequent monitoring of their location and behavior. Neotropical poison frogs are well known for their complex behavior and diverse reproductive and parental care strategies. Although the ecology and behavior of the polygamous leaf-litter frog Allobates femoralis is well studied, little is known about the fine-scale space use of the non-territorial females who do not engage in acoustic and visual displays. We tracked 17 females for 6 to 17 days using a harmonic direction finder to provide the first precise analysis of female space use in this species. Females moved on average 1 m per hour and the fastest movement, over 20 m per hour, was related to a subsequent mating event. Traveled distances and activity patterns on days of courtship and mating differed considerably from days without reproduction. Frogs moved more on days with lower temperature and more precipitation, but mating seemed to be the main trigger for female movement. We observed 21 courtships of 12 tagged females. For seven females, we observed two consecutive mating events. Estimated home ranges after 14 days varied considerably between individuals and courtship and mating associated space use made up for ∼30% of the home range. Allobates femoralis females spent large parts of their time in one to three small centers of use. Females did not adjust their time or space use to the density of males in their surroundings and did not show wide-ranging exploratory behavior. Our study demonstrates how tracking combined with detailed behavioral observations can reveal the patterns and drivers of fine-scale spatial behavior in sedentary species.

[Effect of different pain management protocols on the health status of German Holstein heifer calves undergoing hot iron disbudding]. / Einfluss der thermischen Enthornung mit unterschiedlichem Schmerzmanagement auf die Gesundheit von Kälbern.

OBJECTIVE: Hot iron disbudding of calves is a stressful and painful procedure. Previous parts of an ongoing comprehensive study on disbudding in dairy calves dealt with various types of pain management and the direct effects of the procedure on physiological, biochemical and behavioral processes. The goal of this study part was to investigate the effects of the disbudding procedure per se, pain management and the age of the calf at the time of disbudding on the health status of the calf. MATERIALS AND METHODS: A total of 337 German Holstein heifer calves were used for this prospective, randomized and triple-blinded study. The calves were disbudded at 4-10 days or at 15-28 days of age. Each calf was randomly assigned to one of 9 treatment groups, which differed with respect to pain management (sedation, local anesthesia, nonsteroidal antiinflammatory drugs, placebo). All but the sham-disbudded calves underwent hot iron disbudding and all calves were monitored clinically before and until 4 weeks after the procedure. The findings were analyzed using valuation scores and a threshold model of the SAS software. RESULTS: Disbudding exhibited adverse effects on respiratory health. Calves undergoing sham disbudding experienced the lowest incidence of respiratory disease and calves that did not receive any anesthesia or pain medication displayed the highest frequency. All treatments showed mitigating effects on the incidence of respiratory tract diseases, however the effects varied with the type of pain management. Fever was less common in calves that were disbudded early in life than calves that underwent disbudding at an older age. CONCLUSION: Disbudding of young calves poses a risk to respiratory health. If breeding of polled offspring is not possible or when farming of horned cattle is not feasible, the risk of respiratory disease induced by disbudding can be minimized by adequate pain management. Disbudding of very young calves is feasible and recommended. CLINICAL RELEVANCE: The present study underlines the importance of optimal pain management during disbudding of dairy calves.

The "window of susceptibility" for inflammation in the immature central nervous system is characterized by a leaky blood-brain barrier and the local expression of inflammatory chemokines.

Early in postnatal development, the immature central nervous system (CNS) is more susceptible to inflammation than its adult counterpart. We show here that this "window of susceptibility" is characterized by the presence of leaky vessels in the CNS, and by a global chemokine expression profile which is clearly distinct from the one observed in the adult CNS and has three important characteristics. First, it contains chemokines with known roles in the differentiation and maturation of glia and neurons. Secondly, these chemokines have been described before in inflammatory lesions of the CNS, where they are important for the recruitment of monocytes and T cells. Lastly, the chemokine profile is shaped by pathological changes like oligodendrocyte stress and attempts of myelin repair. Changes in the chemokine expression profile along with a leaky blood-brain barrier pave the ground for an accelerated development of CNS inflammation.