Biology subjects

Bach, H.

Publications and source records attributed to Bach, H..

7 recordsLinked to original sources

bioRxiv2026

Diagnostic Value of Antibody Responses to Mycobacterium avium subsp. paratuberculosis-Derived Proteins PtpA and PtpB in Rheumatoid Arthritis

Evidence suggests that Mycobacterium avium subspecies paratuberculosis (MAP) may contribute to autoimmune diseases such as rheumatoid arthritis (RA), partly through effector proteins--particularly the tyrosine phosphatases PtpA and PtpB--that modulate macrophage signaling and promote bacterial persistence. This study evaluated whether serum antibodies against these proteins serve as biomarkers of RA. Humoral responses to PtpA and PtpB were quantified in Mexican RA patients (n = 100) and healthy controls (n = 100) using in-house ELISAs. Associations with disease activity (DAS28), ROC performance, and logistic regression models were assessed. Results showed that anti-PtpB antibody levels were significantly higher in patients with RA than in healthy controls (median OD 0.185 vs. 0.080; p < 0.0001) and had moderate discriminative capacity (AUC = 0.762). Anti-PtpB reactivity increased with higher disease activity and showed a significant positive association with DAS28 (p < 0.05). In addition, there was a functional disability measured by HAQ (p < 0.001), as well as moderate correlations with erythrocyte sedimentation rate and rheumatoid factor. A combined logistic regression model integrating both antibodies markedly improved diagnostic accuracy (AUC = 0.934), achieving high sensitivity (90%) and specificity (89%). These findings support a potential role of MAP in RA immunopathogenesis and indicate that combined quantification of anti-PtpA and anti-PtpB antibodies captures complementary and non-redundant immunological information. This combined serological approach may enhance RA diagnosis and provide clinically relevant insights into disease activity and severity.

microbiology↗

bioRxiv2025

The SARS-CoV-2 nonstructural protein 15 collapses the host cytoskeleton by interacting with the host keratin type II cytoskeletal 1

COVID-19, the deadliest recorded pandemic of the 21st century, was caused by a novel coronavirus, SARS-CoV-2. To explore why this coronavirus was significantly more pathogenic than its predecessors, more information is needed about the functions of the viral proteins that contributed to this uptick in virulence. This study explored how one of these viral proteins, the nonstructural protein 15 (NSP15), interacts with the host. Our findings revealed a novel protein-protein interaction between NSP15 and the host keratin type II cytoskeletal 1 in Vero E6 cells, as determined by mass spectrometry, and subsequently validated by immunoprecipitation. We observed that when NSP15 was delivered into Vero E6 cells, the fibrous network of keratin intermediate filaments was disrupted, and the nuclear structure was lost. This disruption of the keratin cytoskeleton was then shown to cause a statistically significant reduction in cell viability of Vero E6 cells. These results indicate that the presence of NSP15 in host cells leads to a collapse of the keratin cytoskeleton. This cytoskeletal collapse could be a mechanism the virus employs to escape the infected host cell via cell lysis, once significant amounts of viral protein and progeny have accumulated.

microbiology↗

bioRxiv2025

Transient Early Postnatal Neuronal Hyperexcitation Results in Lasting Social Preference Deficits

Perturbations during critical periods of neurodevelopment are implicated in the etiology of autism spectrum disorder (ASD), a condition marked by considerable heterogeneity and prevalent comorbidities. One such comorbidity is epilepsy, with approximately 30% of children with ASD experiencing seizures and a similar proportion of children with epilepsy displaying ASD-like symptoms. Both conditions have been associated with disruptions in the brains excitation-to-inhibition (E/I) balance. Although early-life seizures in rodents have been linked to social impairments, direct causal evidence connecting E/I imbalance, interneuron development, and social behavior remains limited. To address this gap, we induced transient, brain-wide hyperexcitation in neonatal mice using pentylenetetrazol (PTZ), a GABA_A receptor antagonist. We administered both convulsive and subconvulsive doses and assessed long-term effects on social behavior, cortical E/I balance, and parvalbumin (PV) interneuron development. PTZ-treated groups displayed impaired social preference as measured in the 3-chamber test and increased PV interneuron density within the medial prefrontal cortex. These findings highlight a critical developmental window during which E/I imbalance leads to social deficits characteristic of ASD and epilepsy. They also reveal dose-dependent neurobiological changes, underscoring the importance of early-life neural activity in shaping social circuitry.

neuroscience↗

bioRxiv2025

Calbindin Stratifies Midbrain Dopaminergic Neurons Governing Distinct Aspects of Locomotion

Despite advances in delineating the molecular diversity and projection patterns of midbrain dopaminergic (DA) neurons, their specific contributions to locomotion and motor learning remain poorly defined. Here, we applied intersectional ablation and chemogenetic approaches to dissect the distinct roles of calbindin-expressing (CALB1+) and non-expressing (CALB1-) DA neurons in locomotion. Using newly engineered intersectional constructs, we ablated CALB1+ or CALB1- DA neurons in the mouse midbrain. Loss of either subtype led to pronounced deficits in the initiation and vigor of voluntary movements, as demonstrated by a reduction in peak speed, acceleration and deceleration of locomotor bouts. Notably, only CALB1- ablation disrupted locomotor learning. Beyond these functional effects, we observed that selective ablation of CALB1 DA neurons induced local microglial activation and was followed by a non-cell-autonomous loss of CALB1- DA neurons, suggesting that CALB1- neurons are more vulnerable to inflammation triggered by CALB1 neuron loss. We then confirmed these findings by performing acute inhibition of either population using inhibitory DREADD hM4Di. CALB1- DA neurons inhibition impaired the initial acquisition of locomotor learning, whereas inhibition of CALB1+ DA neurons disrupted the retention of acquired motor skills from previous days. Moreover, inhibition of CALB1+ DA neurons further impaired the initiation and amplitude of voluntary movements, as well as the velocity and acceleration/deceleration of locomotor bouts. Together, these findings provide causal evidence for functional specialization among molecularly distinct midbrain DA subtypes and reveal new aspects of mesostriatal circuit organization underlying locomotion and motor memory.

neuroscience↗

bioRxiv2022

Co-occurrence patterns and habitat selection of the mountain hare, European hare, and European rabbit in urban areas of Sweden

Assessing the underlying mechanisms of co-occurrence patterns can be challenging as biotic and abiotic causations are hard to disentangle. To date, few studies have investigated co-occurrence patterns within urban areas that constitute novel habitat to numerous wildlife species. Moreover, as urban areas expand and are increasingly used as habitat by wildlife, there is a need for a better understanding of urban ecology to facilitate human-wildlife coexistence. Here, we investigated co-occurrence patterns and habitat selection of the European hare (Lepus europaeus), mountain hare (L. timidus), and European rabbit (Oryctolagus cuniculus) inside urban areas of Sweden, using joint species distribution models and generalized linear mixed models based on citizen science observations. All three species were observed within urban areas, but European hares and rabbits appear to be more successful urban colonizers compared to mountain hares. Overall, our findings suggested that urban occurrence by all three lagomorphs was related to suitable conditions within the distribution of each species (e.g. climate and elevation), rather than by the presence of other lagomorph species or specific land cover types within urban areas. On a finer spatial scale, our findings suggested facilitation of European hares by rabbits, though the mechanism for this remains unclear. European hares and rabbits generally selected for green urban areas and mountain hares for residential gardens, which likely constitute suitable foraging sites. Our findings contribute to the understanding of urban ecology and provide valuable insight for management measures of the three lagomorphs in urban areas of Sweden.

ecology↗

bioRxiv2018

Targeting the CALCB/RAMP1-axis inhibits growth of Ewing sarcoma

Ewing sarcoma (EwS) is an aggressive cancer caused by chromosomal translocations generating fusions of the EWSR1 gene with ETS transcription factors (in 85% FLI1). EWSR1-FLI1 induces gene expression via binding to enhancer-like GGAA-microsatellites, whose activity increases with the number of consecutive GGAA-repeats.\n\nHerein, we investigate the role of the secretory neuropeptide CALCB (calcitonin related polypeptide {beta}) in EwS, which signals via the CGRP-(calcitonin gene-related peptide) receptor complex, containing RAMP1 (receptor activity modifying protein 1) as crucial part for receptor specificity. Analysis of 2,678 gene expression microarrays comprising 50 tumor entities and 71 normal tissue types revealed that CALCB is specifically and highly overexpressed in EwS. Time-course knockdown experiments showed that CALCB expression is tightly linked to that of EWSR1-FLI1. Consistently, gene set enrichment analyses of genes whose expression in primary EwS is correlated to that of CALCB indicated that it is co-expressed with other EWSR1-FLI1 target genes and associated with signatures involved in stemness and proliferation. Chromatin immunoprecipitation followed by sequencing (ChIP-seq) data for EWSR1-FLI1 and histone marks from EwS cells demonstrated that EWSR1-FLI1 binds to a GGAA-microsatellite close to CALCB, which exhibits characteristics of an active enhancer. Reporter assays confirmed the strong EWSR1-FLI1- and length-dependent enhancer activity of this GGAA-microsatellite. Mass-spectrometry analyses of supernatants of EwS cell cultures demonstrated that CALCB is secreted by EwS cells. While short-term RNA interference-mediated CALCB knockdown had no effect on proliferation and clonogenic growth of EwS cells in vitro, its long-term knockdown decreased EwS growth in vitro and in vivo. Similarly, knockdown of RAMP1 reduced clonogenic/spheroidal growth and tumorigenicity, and small-molecule inhibitors directed against the CGRP-receptor comprising RAMP1 reduced growth of EwS.\n\nCollectively, our findings suggest that CALCB is a direct EWSR1-FLI1 target and that targeting the CALCB/RAMP1-axis may offer a new therapeutic strategy for inhibition of EwS growth.

cancer biology↗

bioRxiv2018

The monothiol glutaredoxin Grx4 interacts with the Cryptococcus iron regulator Cir1 and regulates iron homeostasis and virulence in the Cryptococcus neoformans

The acquisition of iron and the maintenance of iron homeostasis are important aspects of the virulence in the pathogenic fungus Cryptococcus neoformans. In this study, we identified the monothiol glutaredoxin Grx4 as a binding partner of Cir1, a master regulator of iron-responsive genes and virulence factor elaboration in C. neoformans. Monothiol glutaredoxins are important regulators of iron homeostasis because of their conserved roles in [2Fe-2S] cluster sensing and trafficking. We confirmed that Grx4 binds Cir1 and demonstrated that iron repletion promotes the relocalization of Grx4 from the nucleus to the cytoplasm. Nuclear retention is partially dependent on Cir1 and also influenced by treatment with the proteasome inhibitor bortezomib. Cir1 remains in the nucleus in both iron replete and iron limiting conditions. We also found that a grx4{Delta} mutant displayed iron-related phenotypes similar to those of a cir1{Delta} mutant, including poor growth upon iron deprivation. Importantly, a grx4{Delta} mutant was avirulent in mice, a phenotype consistent with observed defects in the key virulence determinants, capsule and melanin, and poor growth at 37{degrees}C. A comparative transcriptome analysis of a grx4{Delta} mutant and the WT strain in low iron and iron-replete conditions confirmed a central role for Grx4 in iron homeostasis. Dysregulation of iron-related metabolism was consistent with grx4{Delta} mutant phenotypes related to oxidative stress, mitochondrial function, and DNA repair. Overall, the phenotypes of the grx4{Delta} mutant and the RNA-Seq analysis support the hypothesis that Grx4 functions as a sensor of iron levels, in part through an interaction with Cir1, to extensively regulate iron homeostasis and contribute to virulence.

microbiology↗