Biology subjects

Bauer, A.

Publications and source records attributed to Bauer, A..

At least 19 recordsLinked to original sources

bioRxiv2026

PREDICTING HISTORIC, CONTEMPORARY, AND FUTURE DISTRIBUTIONS OF CULEX CORONATOR FOLLOWING RAPID RANGE EXPANSION

Invasive mosquito species pose substantial risks to human and animal health. Since 2004, Culex coronator, a mosquito vector species of public health concern, has shown rapid range expansion within the United States, spreading from a historically limited distribution in southern Texas to across the Gulf Coast region and into eastern and mid-Atlantic states. However, changes in environmental suitability associated with this expansion across historical, contemporary, and future climate conditions have not been evaluated. Here, we used species distribution models (SDMs) to compare predictions of abiotic suitability for Cx. coronator under historic (1960-1989) and recent (2000-2024) climate conditions calibrated on the historical range in the United States. We also created a contemporary SDM based on occurrence records prior to and following species range expansion (1960-2024), and further, to predict potential distributions under current and future climate conditions. Models calibrated on the historical range predicted only modest changes in suitability along the Gulf Coast region and failed to identify large areas of the humid subtropical eastern United States that are now occupied. In contrast, the contemporary model predicted widespread suitability across much of the southern and eastern United States. Future projections under the mid-range SSP3 scenario predicted increasing suitability at higher latitudes and elevations. Across all models, suitability was consistently low in arid and semi-arid regions, including along the historical western range limit, suggesting that moisture availability may constrain Cx. coronator distributions. Together, these results highlight the need to incorporate updated occurrence records when modeling invasive mosquito species to strengthen surveillance and control strategies.

ecology↗

bioRxiv2026

Deep learning enables direct HLA typing from immunopeptidomics data

The immune system eliminates malignant and infected cells through T-cell-mediated recognition of peptides presented by human leukocyte antigen molecules. Mass spectrometry-based immunopeptidomics enables unbiased identification of naturally presented HLA-restricted peptides and has become central to the development of T-cell-based immunotherapies. However, immunopeptidomics data reflects the combined peptide presentation of multiple HLA alleles, and determining which allotypes are represented in this multi-allelic complexity remains an unmet computational challenge. Here, we introduce immunotype, a deep learning-based ensemble predictor for HLA class I allotyping directly from immunopeptidomics data. Immunotype integrates peptide and HLA protein sequence information through transformer encoders and a graph neural network, complemented by a curated mono-allelic reference of known peptide-HLA binding preferences. Immunotype achieves an overall accuracy of 87.2% at protein-level resolution across diverse tissues and thereby enables rapid, cost-effective HLA typing of large-scale immunopeptidomics datasets.

bioinformatics↗

bioRxiv2025

APETALA2 controls seed growth by regulating outer integument mechanical identity during seed coat differentiation

Organ morphogenesis requires differentiating cells to acquire mechanical properties that precisely regulate growth. In Arabidopsis thaliana, seed size and shape are largely controlled by the outer integument of the seed coat, whose two layers develop distinct mechanical behaviors critical for growth regulation. Here, we show that the cell identity factor APETALA2 (AP2) both promotes and restricts seed growth by coordinating the post-fertilization differentiation of these layers into distinct seed coat tissues. AP2 drives layer-specific remodeling of cell wall composition, notably affecting pectin and xyloglucan, thereby establishing contrasting mechanical properties between the two layers. Unexpectedly, these changes in wall composition and mechanics do not alter mechanosensitive responses, revealing a surprising uncoupling between cell wall remodeling and mechanotransduction. Our findings identify AP2 as a key coordinator of tissue-specific mechanical differentiation during organ morphogenesis.

plant biology↗

bioRxiv2024

Multiplex genome editing eliminates the Warburg Effect without impacting growth rate in mammalian cells

The Warburg effect is ubiquitous in proliferative mammalian cells, including cancer cells, but poses challenges for biopharmaceutical production, as lactate accumulation inhibits cell growth and protein production. Previous efforts to eliminate lactate production via knockout have failed in mammalian bioprocessing since lactate dehydrogenase has proven essential. However, here we eliminated the Warburg effect in Chinese hamster ovary (CHO) and HEK293 cells by simultaneously knocking out lactate dehydrogenase and regulators involved in a negative feedback loop that typically inhibits pyruvate conversion to acetyl-CoA. In contrast to long-standing assumptions about the role of aerobic glycolysis, Warburg-null cells maintain wildtype growth rate while producing negligible lactate. Further characterization of Warburg-null CHO cells showed a compensatory increase in oxygen consumption, a near total reliance on oxidative metabolism, and higher cell densities in fed-batch cell culture. These cells remained amenable for production of diverse biotherapeutic proteins, reaching industrially relevant titers and maintaining product glycosylation. Thus, the ability to eliminate the Warburg effect is an important development for biotherapeutic production and provides a tool for investigating a near-universal metabolic phenomenon.

bioengineering↗

bioRxiv2024

Plectin-mediated cytoskeletal crosstalk as a target for inhibition of hepatocellular carcinoma growth and metastasis.

The most common primary malignancy of the liver, hepatocellular carcinoma (HCC), is a heterogeneous tumor entity with high metastatic potential and complex pathophysiology. Increasing evidence suggests that tissue mechanics plays a critical role in tumor onset and progression. Here we show that plectin, a major cytoskeletal crosslinker protein, plays a crucial role in mechanical homeostasis and mechanosensitive oncogenic signaling that drives hepatocarcinogenesis. Our expression analyses revealed elevated plectin levels in liver tumors, which correlated with poor prognosis for HCC patients. Using autochthonous and orthotopic mouse models we demonstrated that genetic and pharmacological inactivation of plectin potently suppressed the initiation and growth of HCC. Moreover, plectin targeting potently inhibited the invasion potential of human HCC cells and reduced their metastatic outgrowth in the lung. Proteomic and phosphoproteomic profiling linked plectin-dependent disruption of cytoskeletal networks to attenuation of oncogenic FAK, MAPK/Erk, and PI3K/AKT signatures. Importantly, by combining cell line-based and murine HCC models, we show that plectin inhibitor plecstatin-1 (PST) is well-tolerated and potently inhibits HCC progression. In conclusion, our study demonstrates that plectin-controlled cytoarchitecture is a key determinant of HCC development and suggests that pharmacologically induced disruption of mechanical homeostasis may represent a new therapeutic strategy for HCC treatment.

cancer biology↗

bioRxiv2023

Spatiotemporally distinct responses to mechanical forces shape the developing seed of Arabidopsis

Organ morphogenesis depends on mechanical interactions between cells and tissues. These interactions generate forces that can be sensed by cells and affect key cellular processes. However, how mechanical forces contribute, together with biochemical signals, to the shaping of complex organs is still unclear. We address this question using the seed of Arabidopsis as a model system. We show that seeds first experience a phase of high anisotropic growth that is dependent on the response of cortical microtubule (CMT) to forces, which guide cellulose deposition according to shape-driven stresses in the outermost layer of the seed coat. However, at later stages of development, we show that seed growth is isotropic and depend on the properties of an inner layer of the seed coat that stiffens its walls in response to tension but has isotropic material properties. Finally, we show that the transition from anisotropic to isotropic growth is due to dampening of CMT responses to shape-driven stresses. Altogether, our work support that spatiotemporally distinct mechanical responses control the shape of developing seeds in Arabidopsis.

plant biology↗

bioRxiv2023

Repeated Caffeine Intake Suppresses Cerebral Grey Matter Responses to Chronic Sleep Restriction in an A1 Adenosine Receptor-Dependent Manner.

Evidence has shown that both sleep loss and daily caffeine intake can induce changes in grey matter (GM). Caffeine is frequently used to combat sleepiness and impaired performance caused by insufficient sleep. It is unclear 1) whether daily use of caffeine could prevent or exacerbate the GM alterations induced by chronic sleep restriction, and 2) whether the potential impact on GM plasticity depends on individual differences in the availability of adenosine receptors, which are involved in mediating effects of caffeine on sleep and waking function. In this double-blind, randomized, controlled study, 36 healthy adults (aged 28.9 {+/-} 5.2 y/o; 15 females; habitual daily caffeine intake < 450 mg; 29 homozygous C/C allele carriers of the A2A adenosine receptor (A2AR) gene variant rs5751876 of ADORA2A) underwent a 9-day laboratory visit consisting of one adaption day, 2 baseline days (BL), 5-day sleep restriction (CSR, 5 h time-in-bed), and a recovery day (REC) after an 8-h sleep opportunity. Nineteen participants received 300 mg caffeine in coffee through the 5 days of CSR (CAFF group), while 17 matched participants received decaffeinated coffee (DECAF group). We measured the GM morphology on the 2nd BL Day, 5th CSR Day, and REC Day. Moreover, we used [18F]-CPFPX PET to quantify the baseline availability of A1 adenosine receptors (A1R) and their relation to GM plasticity. The voxel-wise multimodal whole-brain analysis on T1-weighted images controlled for variances of cerebral blood flow indicated a significant interaction between caffeine and CSR in four brain regions: 1) right temporal-occipital region, 2) right thalamus, 3) left dorsolateral, and 4) dorsomedial prefrontal region. The post-hoc analyses indicated increased GM intensity in the DECAF group in all four regions but decreased GM in the thalamus as well as dorsolateral and dorsomedial prefrontal regions in the CAFF group after sleep restriction. Furthermore, lower baseline subcortical A1R availability predicted larger reduction in the CAFF group after CSR of all brain regions except for the caffeine-associated thalamic reduction. In conclusion, our data suggest an adaptive upregulation in GM after 5-day CSR, while concomitant use of caffeine instead leads to a GM reduction. The lack of consistent association with individual A1R availability may suggest that CSR and caffeine affect GM plasticity predominantly by a different mechanism. Future studies on the role of adenosine A2A receptors (ADORA2A) in CSR-induced GM plasticity are warranted.

neuroscience↗

bioRxiv2023

Fiber alignment in 3D collagen networks as a biophysical marker for cell contractility

Cells cultured in 3D fibrous biopolymer matrices exert traction forces on their environment that induce deformations and remodeling of the fiber network. By measuring these deformations, the traction forces can be reconstructed if the mechanical properties of the matrix and the force-free matrix configuration are known. These requirements severely limit the applicability of traction force reconstruction in practice. In this study, we test whether force-induced matrix remodeling can instead be used as a proxy for cellular traction forces. We measure the traction forces of hepatic stellate cells and different glioblastoma cell lines and quantify matrix remodeling by measuring the fiber orientation and fiber density around these cells. In agreement with simulated fiber networks, we demonstrate that changes in local fiber orientation and density are directly related to cell forces. By resolving Rho-kinase (ROCK) Inhibitor-induced changes of traction forces and fiber alignment and density in hepatic stellate cells, we show that the method is suitable for drug screening assays. We conclude that differences in local fiber orientation and density, which are easily measurable, can be used as a qualitative proxy for changes in traction forces. The method is available as an open-source Python package with a graphical user interface.

biophysics↗

bioRxiv2023

Time-course of antipredator behavioral changes induced by the helminth Pomphorhynchus laevis in its intermediate host Gammarus pulex: the switch in manipulation according to parasite developmental stage differs between behaviors

Many trophically transmitted parasites with complex life cycles manipulate their intermediate hosts antipredatory defenses in ways facilitating their transmission to final host by predation. Some parasites also protect the intermediate host from predation when noninfective during its ontogeny. The acanthocephalan Pomphorynchus laevis, a fish intestinal helminth, infecting freshwater gammarid amphipods as intermediate hosts, is using such a strategy of protection-then-exposure to predation by the definitive host. However, the whole time-course of this sequence of behavioral switch is not yet known, and only one antipredator behavior has been studied to date. Here we show that the protective part of this manipulation begins quite late during the parasite ontogeny, suggesting that the advantages overpass the costs induced by this protective manipulation only at this stage. We confirmed that the refuge use behavior is showing a switch in the few days following the stage mature for the definitive host (switching from overuse to underuse). However, such a switch was not observed for the gammarids activity rate, a behavior also known to make the host less conspicuous to predators when weak. While we predicted a low activity during early development stages, then a switch to high activity, we observed general decrease in activity during the parasite ontogeny. The possible causes for this discrepancy between behaviors are discussed. All these behavioral changes were observed mostly when animals were tested in water scented by potential predators (here brown trout), suggesting condition-dependent manipulation.

zoology↗

bioRxiv2023

A genetic variation in the adenosine A2A receptor gene contributes to variability in oscillatory alpha power in wake and sleep EEG and A1 adenosine receptor availability in the human brain

The EEG alpha rhythm (8-13 Hz) is one of the most salient human brain activity rhythms. Spectral power in the alpha range in wakefulness and sleep varies among individuals based on genetical predisposition, yet knowledge about the underlying genes is scarce. The EEG alpha oscillations are related to cerebral energy metabolism and modulated by the level of attention and vigilance. The neuromodulator adenosine is directly linked to energy metabolism as product of adenosine tri-phosphate (ATP) breakdown and acts as a sleep promoting molecule by activitating A1 and A2A adenosine receptors. We quantified EEG oscillatory alpha power in wakefulness and sleep, as well as A1 adenosine receptor availability by positron emission tomography with 18F-CPFPX, in a large sample of healthy volunteers carrying different alleles of gene variant rs5751876 of ADORA2A encoding A2A adenosine receptors. Oscillatory alpha power was higher in homozygous C-allele carriers (n = 27, 11 females) compared to heterozygous and homozygous carriers of the T-allele (n(C/T) = 23, n(T/T) = 5, 13 females) (F(18,37) = 2.35, p = 0.014, Wilks {Lambda} = 0.467). Across considered brain regions an effect of ADORA2A genotype on A1 adenosine receptor binding potential was found (F(18,40) = 2.62, p = 0.006, Wilks {Lambda} = 0.459) and after correction for multiple testing this effect was shown to be significant for circumscribed occipital region of calcarine fissures. A correlation between individual differences in oscillatory alpha power and adenosine receptor availability was found for the subgroup of female participants only. In conclusion: a genetic variation in the adenosinergic system affects individual alpha power, although a direct modulatory effect via the A1AR has been demonstrated for females only.

neuroscience↗

bioRxiv2023

Prdm16 mutation determines sex-specific cardiac metabolism and identifies two novel cardiac metabolic regulators

BackgroundMutation of the PRDM16 gene has been associated with human cardiomyopathy. The PRDM16 protein is a transcriptional regulator affecting cardiac development via Tbx5 and Hand1 regulating myocardial structure. Biallelic Prdm16 inactivation induces severe cardiac dysfunction with postnatal lethality and hypertrophy in mice. Early pathological events upon Prdm16 inactivation have not been explored. MethodsThis study performed in depth pathophysiological and molecular analysis of male and female Prdm16csp1/wt mice carrying systemic, monoallelic Prdm16 gene inactivation. We systematically assessed early molecular changes with transcriptomics, proteomics, and metabolomics. Kinetic modelling of the cardiac metabolism was undertaken in silico with CARDIOKIN. ResultsPrdm16csp1/wt mice are viable up to 8 months, develop hypoplastic hearts, and diminished systolic performance that is more pronounced in female mice. Prdm16csp1/wt hearts demonstrate moderate alterations of specific transcripts and protein levels with consistent upregulation of pyridine nucleotide-disulphide oxidoreductase domain 2 (Pyroxd2) and the transcriptional regulator pre B-cell leukemia transcription factor interacting protein 1 (Pbxip1). The strongest concordant transcriptional upregulation was detected for Prdm16 itself probably by an autoregulatory mechanism. Prdm16csp1/wt cardiac tissue showed reduction of metabolites associated with amino acid as well as glycerol metabolism, glycolysis, and tricarboxylic acid cycle. Global lipid metabolism was also affected with accumulation of triacylglycerides detected in male Prdm16csp1/wt hearts. In addition, Prdm16csp1/wt cardiac tissue revealed diminished glutathione (GSH) and increased inosine monophosphate (IMP) levels indicating oxidative stress and a dysregulated energetics, respectively. Metabolic modelling in silico suggested lowered fatty acid utilization in male and reduced glucose utilization in female Prdm16csp1/wt cardiac tissue. ConclusionsMonoallelic Prdm16 mutation restricts cardiac performance in Prdm16csp1/wt mice. Metabolic alterations precede transcriptional dysregulation in Prdm16csp1/wt cardiac tissue. Female Prdm16csp1/wt mice develop a more pronounced phenotype indicating a sexual dimorphism at this early pathological window. This study suggests that metabolic dysregulation is an early event in PRDM16 associated cardiac pathology. Novelty and SignificanceO_ST_ABSWhat Is Known?C_ST_ABS- Mutation of the PRDM16 gene has been associated with human cardiomyopathy. - Biallelic inactivation of Prdm16 in mice induces severe cardiac dysfunction with early postnatal lethality. - Prdm16 cooperates with transcription factors such as Tbx5 and Hand1 to activate transcriptional programs that define the development of the compacted myocardium. What New Information Does This Article Contribute?- Systemic, monoallelic inactivation in Prdm16csp1/wt mice induces cardiac dysfunction with normal survival. - Metabolic alterations are the leading pathophysiological consequences and induce cardiac hypoplasia. On the molecular level this is associated with upregulation of metabolic regulators Pyroxd2 and Pbxip1. - Metabolic response after Prdm16 inactivation occurs in a sex specific manner.

pathology↗

bioRxiv2022

Adaptation of a transmitted/founder simian-human immunodeficiency virus for enhanced replication in rhesus macaques

Transmitted/founder (TF) simian-human immunodeficiency viruses (SHIVs) express HIV-1 envelopes modified at position 375 to efficiently infect rhesus macaques while preserving authentic HIV-1 Env biology. TF SHIV.C.CH505 is an extensively characterized virus shown to recapitulate key features of HIV-1 immunobiology, including CCR5-tropism, a tier 2 neutralization profile, reproducible early viral kinetics, and authentic immune responses. SHIV.C.CH505 is used frequently in nonhuman primate studies of HIV, but viral loads after months of infection are variable and typically lower than those in people living with HIV. We hypothesized that additional mutations besides {Delta}375 might further enhance virus fitness without compromising essential components of CH505 Env biology. From sequence analysis of SHIV.C.CH505-infected macaques across multiple experiments, we identified a signature of envelope mutations associated with higher viremia. We then used short-term in vivo mutational selection and competition to identify a minimally adapted SHIV.C.CH505 with just five amino acid changes that substantially improve virus replication fitness in macaques. Next, we validated the performance of the adapted SHIV in vitro and in vivo and identified the mechanistic contributions of selected mutations. In vitro, the adapted SHIV shows improved virus entry, enhanced replication on primary rhesus cells, and preserved neutralization profiles. In vivo, the minimally adapted virus rapidly outcompetes the parental SHIV with an estimated growth advantage of 0.14 days-1 and persists through suppressive antiretroviral therapy to rebound at treatment interruption. Here, we report the successful generation of a well-characterized, minimally adapted virus, termed SHIV.C.CH505.v2, with enhanced replication fitness and preserved native Env properties that can serve as a new reagent for NHP studies of HIV-1 transmission, pathogenesis, and cure. Author SummaryThe power of the nonhuman primate model of HIV to predict outcomes in people living with HIV (PLWH) depends on authentic virus-host interactions. In pursuit of viruses that generate infection that mirrors the effects of HIV-1 in PLWH, we developed a minimally adapted version of a commonly used virus, SHIV.C.CH505, which has better fitness than the parental virus while retaining important biological properties. First, we studied virus sequences from SHIV.C.CH505-infected rhesus macaques to identify a signature of mutations common to animals with higher viral loads. We then tested viruses containing the various mutations in the lab and in animals to determine the most fit version and to identify the contribution of each mutation. Ultimately, we identified a minimally adapted version of SHIV.C.CH505 with just 5 amino acid substitutions that enhances virus replication and preserves CH505 envelope properties, including sensitivity to clinically relevant broadly neutralizing antibodies. This new virus, called SHIV.C.CH505.v2 replicates well in macaques over time and persists through antiretroviral therapy. SHIV.C.CH505.v2 could be an important component of nonhuman primate studies of HIV prevention, therapy, and cure.

microbiology↗

bioRxiv2022

Dynamic traction force measurements of migrating immune cells in 3D matrices

Immune cells such as natural killer (NK) cells migrate with high speeds of several {micro}m/min through dense tissue, but the traction forces are unknown. We present a method to measure dynamic traction forces of fast migrating cells in non-linear biopolymer matrices. The method accounts for the mechanical non-linearity of the 3D tissue matrix and can be applied to time series of confocal or bright-field image stacks. The method is highly sensitive over a large range of forces and object sizes, from [~]1 nN for axon growth cones up to [~]10 {micro}N for mouse intestinal organoids. We find that NK cells display bursts of large traction forces that increase with matrix stiffness and facilitate migration through tight constrictions.

biophysics↗

bioRxiv2022

Viscoelastic properties of suspended cells measured with shear flow deformation cytometry

Numerous cell functions are accompanied by phenotypic changes in viscoelastic properties, and measuring them can help elucidate higher-level cellular functions in health and disease. We present a high-throughput, simple and low-cost microfluidic method for quantitatively measuring the elastic (storage) and viscous (loss) modulus of individual cells. Cells are suspended in a high-viscosity fluid and are pumped with high pressure through a 5.8 cm long and 200 {micro}m wide microfluidic channel. The fluid shear stress induces large, near ellipsoidal cell deformations. In addition, the flow profile in the channel causes the cells to rotate in a tank-treading manner. From the cell deformation and tank treading frequency, we extract the frequency-dependent viscoelastic cell properties based on a theoretical framework developed by R. Roscoe1 that describes the deformation of a viscoelastic sphere in a viscous fluid under steady laminar flow. We confirm the accuracy of the method using atomic force microscopy-calibrated polyacrylamide beads and cells. Our measurements demonstrate that suspended cells exhibit power-law, soft glassy rheological behavior that is cell cycle-dependent and mediated by the physical interplay between the actin filament and intermediate filament networks.

biophysics↗

bioRxiv2021

Identification, Characterization and Synthesis of Natural Parasitic Cysteine Protease Inhibitors -- More Potent Falcitidin Analogs

Protease inhibitors represent a promising therapeutic option for the treatment of parasitic diseases such as malaria and human African trypanosomiasis. Falcitidin was the first member of a new class of inhibitors of falcipain-2, a cysteine protease of the malaria parasite Plasmodium falciparum. Using a metabolomics dataset of 25 Chitinophaga strains for molecular networking enabled identification of over 30 natural analogs of falcitidin. Based on MS/MS spectra, they vary in their amino acid chain length, sequence, acyl residue, and C-terminal functionalization; therefore, they were grouped into the four falcitidin peptide families A-D. The isolation, characterization and absolute structure elucidation of two falcitidin-related pentapeptide aldehyde analogs by extensive MS/MS spectrometry and NMR spectroscopy in combination with advanced Marfeys analysis was in agreement with the in silico analysis of the corresponding biosynthetic gene cluster. Total synthesis of chosen pentapeptide analogs followed by in vitro testing against a panel of proteases revealed selective parasitic cysteine protease inhibition and additionally low-micromolar inhibition of -chymotrypsin. The pentapeptides investigated here showed superior inhibitory activity compared to falcitidin.

microbiology↗

bioRxiv2021

Primary glia cells from bank vole propagate multiple rodent-adapted scrapie prions

Since the beginning prion research has been largely dependent on animal models for deciphering the disease, drug development or prion detection and quantification. Thereby, ethical as well as cost and labour-saving aspects call for alternatives in vitro. Cell models can replace or at least complement animal studies, but their number is still limited and the application usually restricted to certain strains and host species due to often strong transmission barriers. Bank voles promise to be an exception as they or materials prepared from them are uniquely susceptible to prions from various species in vivo, in vitro and in cell-free applications. Here we present a mainly astrocyte-based primary glia cell assay from bank vole, which is infectible with scrapie strains from bank vole, mouse and hamster. Stable propagation of bank vole-adapted RML, murine 22L and RML, and hamster 263K scrapie is detectable from 20 or 30 days post exposure onwards. Thereby, the infected bank vole glia cells show similar or even faster prion propagation than likewise infected glia cells of the corresponding murine or hamster hosts. We propose that our bank vole glia cell assay could be a versatile tool for studying and comparing multiple prion strains with different species backgrounds in a single cell assay.

neuroscience↗

bioRxiv2021

Genomic and chemical decryption of the Bacteroidetes phylum for its potential to biosynthesize natural products

With progress in genome sequencing and data sharing, 1000s of bacterial genomes are publicly available. Genome mining - using bioinformatics tools in terms of biosynthetic gene cluster (BGC) identification, analysis and rating - has become a key technology to explore the capabilities for natural product (NP) biosynthesis. Comprehensively, analyzing the genetic potential of the phylum Bacteroidetes revealed Chitinophaga as the most talented genus in terms of BGC abundance and diversity. Guided by the computational predictions, we conducted a metabolomics and bioactivity driven NP discovery program on 25 Chitinophaga strains. High numbers of peerless strain-specific metabolite buckets confirmed the upfront predicted biosynthetic potential and revealed a tremendous uncharted chemical space. Sourcing this dataset, we isolated the new iron chelating nonribosomally-synthesized cyclic tetradeca- and pentadecalipodepsipeptide antibiotics chitinopeptins with activity against Candida, produced by C. eiseniae DSM 22224 and C. flava KCTC 62435, respectively. TeaserCombination of omics-technologies revealed taxonomical hotspots for specialized metabolites within Bacteroidetes.

microbiology↗

bioRxiv2021

NECAB2 orchestrates an endosomal pathway of mitochondrial quality control at striatal synapses

Synaptic signaling depends on ATP generated by mitochondria. Due to extensive connectivity, the striatum is especially vulnerable to mitochondrial dysfunction and thus requires efficient mitochondrial quality control and repair. We found that global knockout of the neuronal calcium-binding protein 2 (NECAB2) in the mouse causes loss of striatal synapses and behavioral phenotypes related to striatal dysfunction such as reduced motivation and altered sensory gating. Striatal mitochondria from Necab2 knockout mice are more abundant and smaller. They are characterized by increased respiration and superoxide production resulting in oxidative stress. This accumulation of dysfunctional mitochondria is caused by a defective assembly of mitochondria with early endosomes in a pathway that involves the small GTPase Rab5 and its guanine nucleotide exchange factor Alsin/ALS2. NECAB2 therefore participates in an endosomal pathway of mitochondrial stress response and repair important for striatal function.

neuroscience↗