Biology subjects

Roth, E.

Publications and source records attributed to Roth, E..

9 recordsLinked to original sources

bioRxiv2026

IgA plasma cells co-secrete monomeric and dimeric IgA

Dimeric immunoglobulin A (dIgA) is generated from IgA monomers (mIgA) via JCHAIN-dependent polymerization. DIgA is transported across epithelial barriers by the poly Ig receptor (PIGR) and confers mucosal protection, while serum contains substantial amounts of IgA monomers. Distinct plasma cell subsets have been proposed to produce either monomeric or dimeric IgA, with bone marrow plasma cells as a primary source of mIgA. Here, we addressed whether IgA plasma cell populations segregate based on mIgA or dIgA production. Flow cytometric analysis of antibody-secreting cells from bone marrow, lymphoid and mucosal tissues revealed universal intracellular JCHAIN expression across isotypes and failed to identify a discrete JCHAIN-negative IgA plasma cell population. To detect polymeric IgA, we generated a recombinant soluble PIGR that selectively bound JCHAIN-containing dIgA in Western blot, ELISA, and flow cytometry. Soluble PIGR binding was detected in all IgA plasma cells irrespective of tissue origin, arguing against a dedicated mIgA-producing plasma cell subset incapable of dIgA formation. Ex vivo cultures and single-cell DropMap secretion assays demonstrated that bone marrow and lamina propria IgA antibody-secreting cells co-secrete mIgA and dIgA. These findings suggest that dIgA assembly and secretion are general properties of IgA plasma cells and disfavor a dedicated mIgA-producing population. HighlightsO_LIAll plasma cells express JCHAIN protein C_LIO_LIRecombinant poly Ig receptor detects dimeric IgA in all IgA plasma cells C_LIO_LIBone marrow plasma cells secrete dimeric IgA C_LIO_LIIgA plasma cells co-secrete mono- and dimeric IgA C_LI

immunology↗

bioRxiv2025

Connections in the Dark: Social-Ecological Networks as a Promising Tool for Bat Conservation and One Health

Bats provide vital ecosystem services, including pest suppression and crop pollination. However, the increasing proximity of bats and humans is a growing conservation and public health concern with negative consequences for both sides. Mitigating these consequences requires integrative approaches like network science and the emerging field of social-ecological networks (SENs), which offer powerful tools to map and analyse complex social and ecological dynamics. Here, we synthesize how network approaches have been applied to bat research and conservation. Specifically, we: (i) assess the use of both ecological and social network analyses to study bats; (ii) identify network tools well-suited for SEN-based bat research; (iii) present a case study illustrating how SEN applications in bat research can inform conservation and One Health efforts; and, lastly, (iv) discuss key challenges and opportunities in using SENs to investigate the human-bat interface. Our review unveils a rise in network-based bat research from 2006 to 2020, followed by a post-pandemic decline. Nevertheless, across the 127 studies mapped by our review, only one applied an SEN lens. Finally, we suggest how applying some underexplored SEN tools to bat research could lead to novel perspectives, aiming to promote integrated strategies for the coexistence of bats and humans.

ecology↗

bioRxiv2025

Rat Hindlimb Amputation Model Shows Analgesia and Sexually Dimorphic Cold Hypersensitivity with Immediate Targeted Muscle Reinnervation

IntroductionTargeted muscle reinnervation (TMR) has been used clinically to reduce pain in amputees but the mechanisms producing analgesia are unknown. Here we employ rat hindlimb amputation as an appropriate model to evaluate algogenic processes affected by TMR, performed at the time of amputation in subjects of both sex. MethodsAdult male and female Sprague-Dawley rats were assigned to amputation-only or amputation + immediate TMR (iTMR). Reflexive pain behaviors (von Frey, pin, and cold hypersensitivity testing) and spontaneous pain behaviors (guarding, flinching, anhedonia from loss of sucrose preference) were assessed. Retrograde labeling distinguished sensory and motor neurons and identified nerve coaptation sites. ResultsiTMR reduced hyperalgesia and anhedonia that followed amputation. By 4 weeks, pin testing showed reduced pain responses in iTMR rats (25%) versus amputation-only (51%, p=0.01). Sucrose preference testing revealed reduced anhedonia in iTMR rats (76% vs. 43%, p=0.01). Response to cold diminished in male iTMR rats (49% vs. 100% in amputation-only males, p<0.001), but not in females. Histology showed neuroma formation in controls but not after iTMR. Both sensory and motor fibers entered the motor branch after iTMR. ConclusionsThese findings show iTMR prevents neuroma formation and provides analgesia after amputation and, while its effect on cold hypersensitivity is sexually dimorphic. This supports further investigation into TMR analgesic mechanisms, the utility of the hindlimb amputation model, and the need for sex-specific evaluations. PerspectiveUsing a rat hindlimb amputation model to evaluate iTMR, we demonstrate its potential to mitigate neuropathic pain and neuroma formation and reveal sex-specific responses to cold hypersensitivity. These findings indicate the potential clinical utility of iTMR in improving pain outcomes, potentially providing more tailored approaches to pain management in amputees.

animal behavior and cognition↗

bioRxiv2022

Fractions strategy differences in those born extremely preterm

IntroductionTo investigate the effects of different strategies and cognitive load we explored brain hemodynamic responses associated with the use of different strategies to solve subtraction of fractions. We focused on those born extremely preterm (EPT; <28 weeks gestation) as they are known to have cognitive challenges and struggle with mathematics. We also included a group of full-term (FT) peers for comparison. MethodsFunctional MRI was acquired while the participants mentally solved fraction equations using either a strategy based on improper or mixed fractions. Different fraction item types were given, which affected respective required cognitive loads per strategy. Diffusion and T1-weighted structural images were also acquired. ResultsThe EPT and FT groups differed in terms of task-related hemodynamic responses. Functional group differences were greatest when strategies were applied to item types that result in high cognitive load. Other findings showed reduced white and grey matter volume and reduced white matter connectivity in widespread areas in the EPT group compared to the FT group. ConclusionThe understanding of function and structure presented here may help inform pedagogical practices by allowing for tailoring of mathematical education through identifying suitable strategy adoption that depends on item type, to circumvent weaknesses in cognitive skills.

neuroscience↗

bioRxiv2022

The microRNA processing subunit DGCR8 is required for a T cell-dependent germinal center response

We have previously shown that the microRNA (miRNA) processor complex consisting of the RNAse Drosha and the DiGeorge Critical Region (DGCR) 8 protein is essential for central B cell maturation. To determine whether miRNA processing is required to initiate T cell-mediated antibody responses, we deleted DGCR8 in maturing B-2 cells by crossing a mouse with loxP-flanked DGCR8 alleles with a CD23-Cre mouse. As expected, non-immunized mice showed reduced numbers of mature B-2 cells and IgG-secreting cells and diminished serum IgG titers. In accordance, germinal centers and antigen-specific IgG-secreting cells were absent in mice immunized with T cell-dependent antigens. Therefore, DGCR8 is required to mount an efficient T cell-dependent antibody response. However, DGCR8 deletion in B-1 cells was incomplete, which explains relatively unaffected B-1 cell numbers and adequate IgM and IgA titers in DGCR8-knock out mice and suggests that this mouse model could be used to analyze B-1 responses in the absence of functional B-2 cells.

immunology↗

bioRxiv2022

IRF4 deficiency vulnerates B cell progeny for leukemogenesis via somatically acquired Jak3 mutations conferring IL-7 hypersensitivity

The processes leading from disturbed B cell development to adult B cell progenitor acute lymphoblastic leukemia (BCP-ALL) are poorly understood. Here, we describe Irf4-/- mice as prone to developing BCP-ALL with age. Irf4-/- preB-I cells exhibited impaired differentiation but enhanced proliferation in response to IL-7, along with reduced retention in the IL-7 providing bone marrow niche due to decreased CXCL12 responsiveness. Thus selected, preB-I cells acquired Jak3 mutations, probably following irregular AID activity, resulting in malignant transformation. We demonstrate heightened IL-7 sensitivity due to Jak3 mutants, devise a model to explain it and describe structural and functional similarities to Jak2 mutations often occurring in human Ph-like ALL. Finally, targeting JAK signaling with Ruxolitinib in vivo prolonged survival of mice bearing established Irf4-/- leukemia. Intriguingly, organ infiltration including leukemic meningeosis was selectively reduced without affecting blood blast counts. In this work, we present spontaneous leukemogenesis following IRF4 deficiency with potential implications for high-risk BCP-ALL in adult humans.

cancer biology↗

bioRxiv2021

A pair of non-competing neutralizing human monoclonal antibodies protecting from disease in a SARS-CoV-2 infection model

TRIANNI mice carry an entire set of human immunoglobulin V region gene segments and are a powerful tool to rapidly generate human monoclonal antibodies. After immunizing these mice against the spike protein of SARS-CoV-2, we identified 29 hybridoma antibodies that reacted with the SARS-CoV-2 spike protein. Nine antibodies neutralized SARS-CoV-2 infection at IC50 values in the subnanomolar range. ELISA-binding studies and DNA sequence analyses revealed one cluster of clonally related neutralizing antibodies that target the receptor-binding domain and compete with the cellular receptor hACE2. A second cluster of neutralizing antibodies binds to the N-terminal domain of the spike protein without competing with the binding of hACE2 or cluster 1 antibodies. SARS-CoV-2 mutants selected for resistance to an antibody from one cluster are still neutralized by an antibody from the other cluster. Antibodies from both clusters markedly reduced viral spread in mice transgenic for human ACE2 and protected the animals from SARS-CoV-2 induced weight loss. Thus, we report two clusters of potent non-competing SARS-CoV-2 neutralizing antibodies providing potential candidates for therapy and prophylaxis of COVID-19. The study further supports the use of transgenic animals with human immunoglobulin gene repertoires in pandemic preparedness initiatives.

immunology↗

bioRxiv2020

Effect of Handedness on Learned Controllers and Sensorimotor Noise During Trajectory-Tracking

In human-in-the-loop control systems, operators can learn to manually control dynamic machines with either hand using a combination of reactive (feedback) and predictive (feed-forward) control. This paper studies the effect of handedness on learned controllers and performance during a trajectory-tracking task. In an experiment with 18 participants, subjects perform an assay of unimanual trajectory-tracking and disturbance-rejection tasks through second-order machine dynamics, first with one hand then the other. To assess how hand preference (or dominance) affects learned controllers, we extend, validate, and apply a non-parametric modeling method to estimate the concurrent feedback and feedforward controllers. We find that performance improves because feedback adapts, regardless of the hand used. We do not detect statistically significant differences in performance or learned controllers between hands. Adaptation to reject disturbances arising exogenously (i.e. applied by the experimenter) and endogenously (i.e. generated by sensorimotor noise) explains observed performance improvements.

neuroscience↗

bioRxiv2017

mTORC1 in AGRP neurons integrates exteroceptive and interoceptive food-related cues in the modulation of adaptive energy expenditure in mice

Energy dissipation through interscapular brown adipose tissue (iBAT) thermogenesis is an important contributor to adaptive energy expenditure. However, it remains unresolved how acute and chronic changes in energy availability are detected by the brain to adjust iBAT activity and maintain energy homeostasis. Here we provide evidence that AGRP inhibitory tone to iBAT represents an energy-sparing circuit that integrates environmental food cues and internal signals of energy availability. We establish a role for the nutrient-sensing mTORC1 signaling pathway within AGRP neurons in the detection of environmental food cues and internal signals of energy availability, and in the bi-directional control of iBAT thermogenesis during nutrient deficiency and excess. Collectively, our findings provide insights into how mTORC1 signaling within AGRP neurons surveys energy availability to engage iBAT thermogenesis, and identify AGRP neurons as a neuronal substrate for the coordination of energy intake and adaptive expenditure under varying physiological and environmental contexts.

neuroscience↗