Shifts in population density centers of a hibernating mammal driven by conflicting effects of climate change and disease.

Populations wax and wane over time in response to an organism's interactions with abiotic and biotic forces. Numerous studies demonstrate that fluctuations in local populations can lead to shifts in relative population densities across the geographic range of a species over time. Fewer studies attempt to disentangle the causes of such shifts.

A nondepleting anti-CD19 antibody impairs B cell function and inhibits autoimmune diseases.

B cells contribute to multiple aspects of autoimmune disorders, and B cell-targeting therapies, including B cell depletion, have been proven to be efficacious in treatment of multiple autoimmune diseases. However, the development of novel therapies targeting B cells with higher efficacy and a nondepleting mechanism of action is highly desirable. Here we describe a nondepleting, high-affinity anti-human CD19 antibody LY3541860 that exhibits potent B cell inhibitory activities.

Hydrogen-Deuterium Exchange Epitope Mapping of Glycosylated Epitopes Enabled by Online Immobilized Glycosidase.

Hydrogen-deuterium exchange coupled with mass spectrometry (HDX-MS) is widely used for monoclonal antibody (mAb) epitope mapping, which aids in the development of therapeutic mAbs and vaccines, as well as enables the understanding of viral immune evasion. Numerous mAbs are known to recognize N-glycosylated epitopes and to bind in close proximity to an -glycan site; however, glycosylated protein sites are typically obscured from HDX detection as a result of the inherent heterogeneity of glycans. To overcome this limitation, we covalently immobilized the glycosidase PNGase Dj on a solid resin and incorporated it into an online HDX-MS workflow for post-HDX deglycosylation.

The labels and models used to describe problematic substance use impact discrete elements of stigma: A registered report.

Objectives: Problematic substance use is one of the most stigmatized health conditions leading research to examine how the labels and models used to describe it influence public stigma. Two recent studies examine whether beliefs in a disease model of addiction influence public stigma but result in equivocal findings-in line with the mixed-blessings model, Kelly et al. (2021) found that while the label "chronically relapsing brain disease" reduced blame attribution, it decreased prognostic optimism and increased perceived danger and need for continued care; however, Rundle et al.

Plant pathogens provide clues to the potential origin of bat white-nose syndrome .

White-nose syndrome has killed millions of bats, yet both the origins and infection strategy of the causative fungus, , remain elusive. We provide evidence for a novel hypothesis that emerged from plant-associated fungi and retained invasion strategies affiliated with fungal pathogens of plants. We demonstrate that invades bat skin in successive biotrophic and necrotrophic stages (hemibiotrophic infection), a mechanism previously only described in plant fungal pathogens.

Experimental inoculation trial to determine the effects of temperature and humidity on White-nose Syndrome in hibernating bats.

Disease results from interactions among the host, pathogen, and environment. Inoculation trials can quantify interactions among these players and explain aspects of disease ecology to inform management in variable and dynamic natural environments. White-nose Syndrome, a disease caused by the fungal pathogen, Pseudogymnoascus destructans (Pd), has caused severe population declines of several bat species in North America.

Body Temperature Frequency Distributions: A Tool for Assessing Thermal Performance in Endotherms?

There is increasing recognition that rather than being fully homeothermic, most endotherms display some degree of flexibility in body temperature. However, the degree to which this occurs varies widely from the relatively strict homeothermy in species, such as humans to the dramatic seasonal hibernation seen in Holarctic ground squirrels, to many points in between. To date, attempts to analyse this variability within the framework generated by the study of thermal performance curves have been lacking.

Heterothermy as a mechanism to offset energetic costs of environmental and homeostatic perturbations.

Environmental and biotic pressures impose homeostatic costs on all organisms. The energetic costs of maintaining high body temperatures (T) render endotherms sensitive to pressures that increase foraging costs. In response, some mammals become more heterothermic to conserve energy.

Hidden in plain sight: Working class and low-income atheists.

The current study sought to qualitatively examine the role of social class in the development of atheist identity, the experience of atheism-related minority stress, and relationships between atheists. Using a critical phenomenological design, we captured the experiences of 15 working-class and the low-income U.S.

Temperature alone is insufficient to understand hibernation energetics.

Energy conservation has long been a focal point in hibernation research. A long-standing assumption is that ambient temperature (Ta) largely defines the rate of energy expenditure because of well-known relationships between Ta, metabolic rate and frequency of arousal from torpor. Body condition and humidity also affect energy expenditure but are usually considered secondary factors.

High Body Temperature is an Unlikely Cause of High Viral Tolerance in Bats.

The global SARS-CoV-2 pandemic and the role of bats in zoonotic spillover have renewed interest in the flight-as-fever hypothesis, which posits that high body temperatures experienced by bats during flight contribute to their high viral tolerance. We argue that flight-as-fever is unlikely to explain why bats harbor more viruses than other mammals on the basis of two lines of reasoning. First, flight temperatures reported in the literature overestimate true flight temperatures because of methodologic limitations.

Discovery and characterization of a neutralizing pan-ELR+CXC chemokine monoclonal antibody.

CXCR1 and CXCR2 signaling play a critical role in neutrophil migration, angiogenesis, and tumorigenesis and are therefore an attractive signaling axis to target in a variety of indications. In human, a total of seven chemokines signal through these receptors and comprise the ELRCXC chemokine family, so named because of the conserved ELRCXC N-terminal motif. To fully antagonize CXCR1 and CXCR2 signaling, an effective therapeutic should block either both receptors or all seven ligands, yet neither approach has been fully realized clinically.

Validation of a de-immunization strategy for monoclonal antibodies using cynomolgus macaque as a surrogate for human.

The immunogenicity of biotherapeutics presents a major challenge during the clinical development of new protein drugs including monoclonal antibodies. To address this, multiple humanization and de-immunization techniques that employ in silico algorithms and in vitro test systems have been proposed and implemented. However, the success of these approaches has been variable and to date, the ability of these techniques to predict immunogenicity has not been systematically tested in humans or other primates.

An oversimplification of physiological principles leads to flawed macroecological analyses.

Macrophysiological analyses are useful to predict current and future range limits and improve our understanding of endotherm macroecology, but such analyses too often rely on oversimplifications of endothermic thermoregulatory and energetic physiology, which lessens their applicability. We detail some of the major issues with macrophysiological analyses based on the classic Scholander-Irving model of endotherm energetics in the hope that it will encourage other research teams to more appropriately integrate physiology into macroecological analyses.

An experimental test of the allotonic frequency hypothesis to isolate the effects of light pollution on bat prey selection.

Artificial lights may be altering interactions between bats and moth prey. According to the allotonic frequency hypothesis (AFH), eared moths are generally unavailable as prey for syntonic bats (i.e.

Testing the "Fasting While Foraging" Hypothesis: Effects of Recent Feeding on Plasma Metabolite Concentrations in Little Brown Bats ().

Plasma metabolite concentrations can be used to understand nutritional status and foraging behavior across ecological contexts including prehibernation fattening, migration refueling, and variation in foraging habitat quality. Generally, high plasma concentrations of the ketone β-hydroxybutyrate, a product of fat catabolism, indicate fasting, while triglycerides indicate recent feeding and fat accumulation. In recent studies of insectivorous bats, triglyceride concentration increased after feeding as expected, but β-hydroxybutyrate also unexpectedly increased rather than decreased.

A Brief Introduction to Methods for Describing Body Temperature in Endotherms.

Researchers commonly measure body, orifice, or skin temperature (collectively referred to as body temperature [] herein) of endothermic animals in biomedical, physiological, evolutionary, and ecological studies. However, comparing among species or placing a single study in context is challenging because there is no single, standard method to describe and synthesize data of endotherms. A variety of metrics are available, and each has strengths and weaknesses appropriate for answering different types of questions.

Community Physiological Ecology.

The effects of animal homeostatic function on ecological interactions have not been well-integrated into community ecology. Animals mediate environmental change and stressors through homeostatic shifts in physiology and behavior, which likely shape ecological interactions and plant communities. Animal responses to stressors can alter their habitat use, selective foraging, and stoichiometry, which can in turn affect trophic interactions, plant growth, reproduction, and dispersal.

Illuminating the physiological implications of artificial light on an insectivorous bat community.

Global light pollution threatens to disturb numerous wildlife species, but impacts of artificial light will likely vary among species within a community. Thus, artificial lights may change the environment in such a way as to create winners and losers as some species benefit while others do not. Insectivorous bats are nocturnal and a good model to test for differential effects of light pollution on a single community.

Engineered FcRn Binding Fusion Peptides Significantly Enhance the Half-Life of a Fab Domain in Cynomolgus Monkeys.

There is a rapidly growing reinvigoration of the investigation of small proteins, cyclic peptides, and mAb derived domains as biotherapies. The drugability of these structures are challenged by fast peripheral clearance properties that can reduce their potential to be realized as medicines. Engineering strategies have been of limited value because mechanistically the half-life benefit is manifested by increasing the molecular weight and/or the hydrodyanimc radius which slows the molecule's renal elimination, but can result in the inherent loss of activity and target accessibility.

Emerging threat of the 21st century lightscape to global biodiversity.

Over the last century the temporal and spatial distribution of light on Earth has been drastically altered by human activity. Despite mounting evidence of detrimental effects of light pollution on organisms and their trophic interactions, the extent to which light pollution threatens biodiversity on a global scale remains unclear. We assessed the spatial extent and magnitude of light encroachment by measuring change in the extent of light using satellite imagery from 1992 to 2012 relative to species richness for terrestrial and freshwater mammals, birds, reptiles, and amphibians.

Does student debt affect dental students' and dentists' stress levels?

Introduction Many studies have shown financial worries and debt to induce stress in individuals, this combined with the existing stress of being a dentist raises the question of how student debt affects students' and dentists' stress levels.Objectives Determine whether student debt has had any noticeable effect on student stress levels; investigate whether student debt has any effect on dentists' career choice; investigate whether the increase in tuition fees has influenced the number of applicants to study dentistry at the University of Birmingham.Method Anonymous questionnaires were completed by 70 4th year and 38 5th year BDS and 22 Dental Core Trainees (DCTs).

Exogenous stress hormones alter energetic and nutrient costs of development and metamorphosis.

Variation in environmental conditions during larval life stages can shape development during critical windows and have lasting effects on the adult organism. Changes in larval developmental rates in response to environmental conditions, for example, can trade off with growth to determine body size and condition at metamorphosis, which can affect adult survival and fecundity. However, it is unclear how use of energy and nutrients shape trade-offs across life-stage transitions because no studies have quantified these costs of larval development and metamorphosis.

Polymer-mediated flocculation of transient CHO cultures as a simple, high throughput method to facilitate antibody discovery.

Most biopharmaceutical drugs, especially monoclonal antibodies (mAbs), bispecific antibodies (BsAbs) and Fc-fusion proteins, are expressed using Chinese Hamster Ovary (CHO) cell lines. CHO cells typically yield high product titers and high product quality. Unfortunately, CHO cell lines also generate high molecular weight (HMW) aggregates of the desired product during cell culture along with CHO host cell protein (HCP) and CHO DNA.