Biology subjects

Sommer, J.

Publications and source records attributed to Sommer, J..

10 recordsLinked to original sources

bioRxiv2026

Cell-envelope conduits enable transfer of megabase-sized double-stranded DNA between cells of the nosocomial pathogen Acinetobacter baumannii

Horizontal gene transfer in Acinetobacter baumannii has been attributed to conjugative pili, transduction, and natural transformation. Here, we describe a previously unrecognized type of chromosomal DNA exchange mediated by cell-envelope conduits that establish direct cytoplasmic continuity between neighboring A. baumannii cells. Cryo-electron tomography reveals that these conduits, which were found in multiple clinical isolates, comprise an outer membrane, a peptidoglycan layer, and an inner membrane. The ~65 nm-thick conduits contain two ~2 nm-thick filaments, which super-resolution microscopy identifies as DNA. Interstrain horizontal gene transfer assays coupled with whole-genome sequencing demonstrate the transfer and homologous recombination of chromosomal segments up to 1.1 Mbp, corresponding to as much as 27% of the A. baumannii genome. Together, these findings provide direct structural and functional evidence for a conduit-mediated large-scale chromosomal DNA exchange, thus expanding the known repertoire of horizontal gene transfer strategies that may contribute to the remarkable genomic plasticity of A. baumannii.

microbiology↗

bioRxiv2026

Machine learning-guided discovery of a conserved plasmid proteomic signature enables MALDI-TOF MS detection of pOXA-48-carrying Enterobacterales

OXA-48 carbapenemases are among the most widespread and important resistance mechanisms in Enterobacterales. Yet detecting carbapenemases by conventional workflows necessitates additional testing, thus delaying optimization of therapy and implementation of infection control measures. Here, we present a machine learning approach that identifies the conserved pOXA-48 plasmid directly from routine MALDI-TOF spectra acquired for species identification. The model detects pOXA-48 carriers with an AUROC of 0.96-0.98 across two independent hospital cohorts and instrument platforms, indicating near-perfect discrimination. Using bottom-up proteomics, plasmid conjugation, and plasmid curing, we link the discriminative MALDI-TOF spectral features to proteins encoded on pOXA-48, with DUF1496 domain-containing protein producing the most discriminative spectral feature. Our approach reframes the resistance prediction task from inferring a resistance phenotype to detecting a conserved plasmid through its expressed proteomic signature and has the potential to enable rapid MALDI-TOF MS-based diagnostics for a wide range of plasmid-based resistance determinants.

microbiology↗

bioRxiv2025

OXA-1207, a new OXA-48-type carbapenem-hydrolysing class D beta lactamase from Escherichia coli

1.We present the characterisation of OXA-1207, a novel, plasmid-encoded OXA-48-like carbapenemase identified in two unrelated Escherichia coli (sequence type (ST) ST405 and ST4405) isolates from hospital patients in Germany. OXA-1207 is closely related to OXA-181, differing by two amino acid substitutions (214G and 244W). The blaOXA-1207 gene was located on a self-transmissible IncFIC plasmids (pOXA-1207) featuring a conserved backbone and the novel {Delta}Tn6361 transposon structure, which derived from IncX3 plasmids carrying blaOXA-181. Notably, pOXA-1207 exhibited an exceptionally high conjugation frequency (mean 1.2 x 10-1) to E. coli, surpassing the typical rates reported for widely distributed OXA-48 plasmids. Analysis of public genomic datasets identified 40 E. coli isolates carrying blaOXA-1207, belonging to diverse high-risk clonal lineages (ST167, ST405 and ST410). The isolates originated from multiple continents, indicating global dissemination. These findings highlight OXA-1207 as an emerging and concerning resistance determinant with enhanced transmissibility and emphasise the need for continued molecular surveillance of OXA-48-like carbapenemases.

microbiology↗

bioRxiv2024

The aging-induced long non-coding RNA MIRIAL controls endothelial cell and mitochondrial function

AimsVascular aging is characterized by the progressive deterioration of endothelial function. Long non-coding RNAs (lncRNAs) are critical regulators of gene expression and protein function. However, their involvement in aging-related dysregulation of endothelial cell function remains largely unknown. Here, we aim to characterize the aging-regulated lncRNA MIRIAL in endothelial cells. Methods + ResultsWe identified Mirial as an aging-induced lncRNA in RNA-sequencing data of mouse cardiac endothelial cells. In human umbilical vein endothelial cells (HUVECs), gapmer-mediated knockdown of MIRIAL led to decreases in proliferation, migration and basal angiogenic sprouting. Additionally, MIRIAL knockdown led to increased mitochondrial mass, spare respiratory capacity, and vascular endothelial growth factor (VEGF)-stimulated sprouting. Mechanistically, we demonstrate that MIRIAL forms an RNA{middle dot}DNA:DNA triple helix (triplex) with a regulatory region of the quiescence-promoting Forkhead Box O1 (FOXO1) gene, thus inducing its expression. The formation of this triplex involves an Alu element within the MIRIAL transcript, representing a previously undescribed mechanism of action for a lncRNA. Further, we generated a global Mirial knockout mouse line of. Angiogenic sprouting of aortic rings from Mirial knockout mice was reduced under basal conditions, but increased after VEGF administration, validating the in vitro angiogenic phenotype. Importantly, cardiac contractile function after acute myocardial infarction is severely reduced in Mirial knockout mice, as compared to wild-type littermates. ConclusionsThe lncRNA MIRIAL is an aging-induced regulator of endothelial quiescence and metabolism. Translational PerspectiveLncRNAs often exhibit cell-type or tissue-specific expression and regulation, rendering them potentially druggable targets requiring lower doses and having fewer side effects compared to protein targets. Our current research highlights, that loss of Mirial correlates with adverse outcomes post-acute myocardial infarction in a murine model. Dysregulation of MIRIAL in various human pathological conditions, such as ischemic heart disease, abdominal aortic aneurysm, cancer, and aging, indicates its potential as a diagnostic marker. Mechanistically, MIRIAL regulates endothelial quiescence by modulating FOXO1 expression, suggesting it as a promising therapeutic target to counteract the age-related decline in endothelial cell function.

cell biology↗

bioRxiv2024

Behavioral state influences encoding mechanisms of color and odor integration in a model insect, the bumblebee Bombus impatiens.

Bumblebees rely on diverse sensory information to locate flowers while foraging. The majority of research exploring the relationship between visual and olfactory floral cues is performed at local spatial scales and applicable to understanding floral selection. Floral-cue use during search remains underexplored. This study investigates how the bumblebee Bombus impatiens uses visual versus olfactory information from flowers across behavioral states and spatial scales. At local spatial scales, non-flying animals in an associative learning paradigm will generalize to either unimodal attribute of a learned color + odor cue with equal likelihood. However, bumblebees flying in a wind tunnel shift cue-use strategy depending on the spatiotemporal scale of cue encounter. When both color and odor cues mimic local/ within patch spatial scale, bumblebees weigh color information of a learned floral-cue more heavily. When cues mimic an intermediate/ between patch spatial scale, bumblebees weigh color and odor information equally, and show the highest response to fully intact multimodal cues. Thus the spatiotemporal scale of sensory information influences how bumblebees utilize multimodal floral cues. Statements and DeclarationsThis work was internally funded by Muhlenberg College. The authors have no competing interests

animal behavior and cognition↗

bioRxiv2023

Reprogramming method does not impact the neuronal differentiation potential of 16p11.2 deletion patient iPSCs

A major impediment to the actualization of the induced pluripotent stem cell (iPSC)-based personalized medicine revolution is the lack of widely accepted standard operating procedures (SOPs) across different groups and institutions. The various methods employed can include choice of starting materials, reprogramming agents, and culture conditions, with each of these factors hypothesized to influence the reprogramming efficiency and transcriptional identity of iPSCs. As such, we systematically compared iPSC reprogramming procedures using cells derived from the somatic cells of three patients with 16p11.2 deletion syndrome (16p11.2del) and found remarkable similarity among the different methods. FACS analysis revealed that regardless of somatic cell type (fibroblast, lymphocyte, erythroblast), route of reprogramming factor introduction (mRNA, Sendai virus, episome), donor sex, or facility (Rutgers, NYSCF), 16p11.2del patient iPSCs were viable as high purity cultures expressing pluripotency marker proteins. This observation was supported at the transcript level by qPCR analysis, which demonstrated the ability for the iPSCs to differentiate into all three embryonic germ cell lineages after 12 days in culture as embryoid bodies. NGN2-mediated differentiation of these iPSCs produced functional neurons that formed active synaptic networks as revealed by multi-electrode array (MEA) recordings. Importantly, no group-wise comparisons among the reprogramming methods yielded consistent statistically significant differences, indicating that these procedures are equally capable of producing pluripotent stem cells that can efficiently differentiate into mature, functional neurons. This work highlights the utility of these reprogramming methods and supports the use of differentially reprogrammed iPSCs for direct comparative studies of human neurodevelopment.

developmental biology↗

bioRxiv2022

Parity modulates impact of BMI and Gestational Weight Gain on gut microbiota in human pregnancy

Pregnancy requires maternal adaptations to support fetal growth: whether these adaptations include temporal shifts in the gut microbiome is still unclear. We investigated the maternal gut microbiome longitudinally over the course of pregnancy and the impact of pre-pregnancy BMI (pBMI) and GWG. We also determined whether parity modulated observed associations. We show that the gut microbiota of participants with higher pBMI changed less over the course of pregnancy in primiparous, but not multiparous participants. This suggests that previous pregnancies may have persistent impacts on maternal adaptations to pregnancy. This ecological memory appears to be passed to the next generation, as parity modulated the impact of maternal GWG on the infant gut microbiome. This work supports a role for the gut microbiome in maternal adaptations to pregnancy and highlights the need for longitudinal sampling and accounting for parity as key considerations for studies of the microbiome in pregnancy and infants.

microbiology↗

bioRxiv2022

Mapping the landscape of genetic dependencies in chordoma

Identifying the spectrum of genes required for cancer cell survival can reveal essential cancer circuitry and therapeutic targets, but such a map remains incomplete for many cancer types. We applied genome-scale CRISPR-Cas9 loss-of-function screens to map the landscape of selectively essential genes in chordoma, a bone cancer with few validated targets. This approach confirmed a known chordoma dependency, TBXT (T; brachyury), and identified a range of additional dependencies, including PTPN11, ADAR, PRKRA, LUC7L2, SRRM2, SLC2A1, SLC7A5, FANCM, and THAP1. CDK6, SOX9, and EGFR, genes previously implicated in chordoma biology, were also recovered. We found genomic and transcriptomic features that predict specific dependencies, including interferon-stimulated gene expression, which correlates with ADAR dependence and is elevated in chordoma. Validating the therapeutic relevance of dependencies, small-molecule inhibitors of SHP2, encoded by PTPN11, had potent preclinical efficacy against chordoma. Our results generate an emerging map of chordoma dependencies to enable biological and therapeutic hypotheses.

cancer biology↗

bioRxiv2019

The Ontogenetic Development of Hemispheric Lateralization During Face Processing: A Functional Magnetic Resonance Imaging Pilot Study in 7- to 9-Year-old Children

Face processing is mediated by a distributed neural network commonly divided into a \"core system\" and an \"extended system\". The core system consists of several, typically right-lateralized brain regions in the occipito-temporal cortex, including the occipital face area (OFA), the fusiform face area (FFA) and the posterior superior temporal sulcus (pSTS). It was recently proposed that the face processing network is initially bilateral and becomes right-specialized in the course of the development of reading abilities due to the competition between language-related regions in the left occipito-temporal cortex (e.g., the visual word form area) and the FFA for common neural resources.\n\nThe goal of the present pilot study was to prepare the basis for a larger follow-up study assessing the ontogenetic development of the lateralization of the face processing network. More specifically, we aimed on the one hand to establish a functional magnetic resonance imaging (fMRI) paradigm suitable for assessing activation in the core system of face processing in young children at the single subject level, and on the other hand to calculate the necessary group size for the planned follow-up study.\n\nTwelve children aged 7-9 years, and ten adults were measured with a face localizer task that was specifically adapted for children. Our results showed that it is possible to localize the core systems brain regions in children even at the single subject level. We further found a (albeit non-significant) trend for increased right-hemispheric lateralization of all three regions in adults compared to children, with the largest effect for the FFA (estimated effect size d=0.78, indicating medium to large effects). Using these results as basis for an informed power analysis, we estimated that an adequately powered (sensitivity 0.8) follow-up study testing developmental changes of FFA lateralization would require the inclusion of 18 children and 26 adults.

neuroscience↗

bioRxiv2019

LAB-QA2GO: A free, easy-to-use toolbox for the quality assessment of magnetic resonance imaging data

Image characteristics of magnetic resonance imaging (MRI) data (e.g. signal-to-noise ratio, SNR) may change over the course of a study. To monitor these changes a quality assurance (QA) protocol is necessary. QA can be realized both by performing regular phantom measurements and by controlling the human MRI datasets (e.g. noise detection in structural or movement parameters in functional datasets). Several QA tools for the assessment of MRI data quality have been developed. Many of them are freely available. This allows in principle the flexible set-up of a QA protocol specifically adapted to the aims of ones own study. However, setup and maintenance of these tools bind time, in particular since the installation and operation often require a fair amount of technical knowledge. In this article we present a light-weighted virtual machine, named LAB-QA2GO, which provides scripts for fully automated QA analyses of phantom and human datasets. This virtual machine is ready for analysis by starting it the first time. With minimal configuration in the guided web-interface the first analysis can start within 10 minutes, while adapting to local phantoms and needs is easily possible. The usability and scope of LAB-QA2GO is illustrated using a data set from the QA protocol of our lab. With LAB-QA2GO we hope to provide an easy-to-use toolbox that is able to calculate QA statistics without high effort.

neuroscience↗