bluuebunny/crossref_metadata_2025_split huggingface dataset:
Microbial aromatic amino acid metabolism is modifiable in fermented food matrices to promote bioactivity
Authors: Kasperek Mikaela C. , Galeas Adriana Velasquez , Caetano-Silva Maria Elisa , Xie Zifan , Ulanov Alexander V. , La Frano Michael R. , Devkota Suzanne , Miller Michael , Allen Jacob M. 
Published: December 2023

AbstractIngestion of fermented foods impacts human immune function, yet the bioactive food components underlying these effects are not understood. Here, we interrogated whether fermented food bioactivity could be traced to a class of microbial metabolites derived from aromatic amino acids (ArAA), termed aryl-lactates. Using targeted metabolomics, we established that the aryl-lactates phenyllactic acid (PLA), 4-hydroxyphenyllactic acid (4-HPLA), and indole-3-lactic acid (ILA), are present in varying concentrations across a wide range of commercially available fermented foods, including many vegetable and dairy ferments. After pinpointing fermented food-associated lactic acid bacteria (LAB) that produce high levels of aryl-lactates (e.g.,Lactiplantibacillus plantarum), we utilized our knowledge of LAB metabolism to identify fermentation conditions (added cultures [e.g.,L. plantarum] and metabolic co-factors [e.g., aryl-pyruvates]) to increase aryl-lactate production in food matrices up to 5×103fold vs. standard fermentation conditions. Next, usingex vivoreporter assays, we found that a variety of food matrix conditions optimized for aryl-lactate production exhibited enhanced agonist activity for the human aryl-hydrocarbon receptor (AhR) as compared to standard fermentation conditions and/or commercial brands. Moreover, we determined that strategies to enhance aryl-lactates effectively maintained food matrix AhR bioactivity across 4 weeks of storage. Reduced microbial-induced AhR activity has emerged as a hallmark of many chronic inflammatory diseases, thus we envision strategies to enhance microbially produced aryl-lactates and thus AhR bioactivity of fermented foods can be leveraged to improve human health.
Heterogeneous distribution of kinesin-streptavidin complexes revealed by Mass Photometry
Authors: Xu Jing , Brown Nathaniel J. S. , Seol Yeonee , Neuman Keir C. 
Published: December 2023

AbstractKinesin-streptavidin complexes are widely used in microtubule-based active-matter studies. The stoichiometry of the complexes is empirically tuned but experimentally challenging to determine. Here, mass photometry measurements reveal heterogenous distributions of kinesin-streptavidin complexes. Our binding model indicates that heterogeneity arises from both the kinesin-streptavidin mixing ratio and the kinesin-biotinylation efficiency.
Role of theosaAgene inAspergillus fumigatusdevelopment, secondary metabolism and virulence
Authors: Dabholkar Apoorva , Pandit Sandesh , Devkota Ritu , Dhingra Sourabh , Lorber Sophie , Puel Olivier , Calvo Ana M. 
Published: December 2023

AbstractAspergillus fumigatusis the leading cause of aspergillosis, associated with high mortality rates, particularly in immunocompromised individuals. In search of novel genetic targets against aspergillosis, we studied the WOPR transcription factor OsaA. Deletion of theosaAgene resulted in colony growth reduction. Conidiation is also influenced byosaA; bothosaAdeletion and overexpression resulted in a decrease in spore production. Wild-type expression levels ofosaAare necessary for expression of the conidiation regulatory genesbrlA,abaAandwetA. In addition,osaAis necessary for normal cell wall integrity. Furthermore, deletion ofosaAresulted in a reduction in the ability ofA. fumigatusto adhere to surfaces, decreased thermotolerance, as well as increased sensitivity to oxidative stress. Metabolomics analysis indicated thatosaAdeletion or overexpression led to alterations in the production of multiple secondary metabolites, including gliotoxin. This was accompanied by changes in the expression of genes in the corresponding secondary metabolite gene clusters. These effects could be, at least in part, due to the observed reduction in the expression levels of theveAandlaeAglobal regulators when theosaAlocus was altered. Importantly, our study shows thatosaAis indispensable for virulence in both the neutropenic and corticosteroid-immunosuppressed mouse models.
Behavioral relevance of category selectivity revealed by human ECoG data
Authors: Hashemi Seyedamin , Ebadi Seyed Ali , Jahromy Fatemeh Zareayan , Treue Stefan , Kreiman Gabriel , Esghaei Moein 
Published: December 2023

AbstractObject recognition is a crucial brain function that involves a complex interplay between various brain regions. However, the behavioral relevance of functional interactions between these regions remains largely unexplored. In this study, we examined the functional interactions between different brain regions during object recognition using intracranial electrocorticography (ECoG) recordings in subjects diagnosed with pharmacologically intractable epilepsy. We computed the phase locking value (PLV) between different brain areas and its category selectivity, and assessed its behavioral relevance by comparing correctly and incorrectly performed trials. Our results revealed that phase locking between brain regions varies across different object categories and that this variability significantly influences the perceptual behavior of subjects. Importantly, we found that the behavioral relevance of these interactions is spatially organized, with long-range (global) connections being more behaviorally relevant for the frontal lobe and local connections being more crucial for the occipital lobe. These findings underscore the unique roles of different brain areas in object recognition and pave the way for more nuanced explorations of the interplay between brain regions in object recognition and other cognitive functions.
CEP41, a ciliopathy-linked centrosomal protein, regulates microtubule assembly and cell proliferation
Authors: Prassanawar Shweta Shyam , Sarkar Tuhin , Panda Dulal 
Published: December 2023

AbstractCentrosomal proteins play pivotal roles in orchestrating microtubule dynamics, and their dysregulation leads to disorders, including cancer and ciliopathies. Understanding the multifaceted roles of centrosomal proteins is vital to comprehend their involvement in disease development. Here, we report novel cellular functions of CEP41, a centrosomal and ciliary protein implicated in Joubert syndrome. We show that CEP41 is an essential microtubule-associated protein with microtubule-stabilizing activity. Purified CEP41 binds to preformed microtubules, promotes microtubule nucleation, and suppresses microtubule disassembly. When overexpressed in cultured cells, CEP41 localizes to microtubules and promotes microtubule bundling. Conversely, shRNA-mediated knockdown of CEP41 disrupts the interphase microtubule network and delays microtubule reassembly, emphasizing its role in microtubule organization. Further, we demonstrate that CEP41’s association with microtubules relies on its conserved rhodanese homology domain (RHOD) and the N-terminal region. Interestingly, a disease-causing mutation in the RHOD domain impairs CEP41-microtubule interaction. Moreover, depletion of CEP41 inhibits cell proliferation and disrupts cell cycle progression, suggesting its potential involvement in cell cycle regulation. These insights into the cellular functions of CEP41 hold promise for unraveling the impact of its mutations in ciliopathies.SummaryA novel role of CEP41 as a microtubule-associated protein that promotes microtubule assembly and regulates cell cycle progression could offer insights into the development of ciliopathies.
Scaling of ventral hippocampal activity during anxiety
Authors: Cerquetella Carlo , Gontier Camille , Forro Thomas , Pfister Jean-Pascal , Ciocchi Stéphane 
Published: December 2023

AbstractThe hippocampus supports a multiplicity of functions, with the dorsal region contributing to spatial representations and memory, and the ventral hippocampus (vH) being primarily involved in emotional processing. While spatial encoding has been extensively investigated, how the vH activity is tuned to emotional states, e.g. to different anxiety levels, is not well understood. We developed an adjustable linear track maze (aLTM) for mice with which we could induce a scaling of behavioral anxiety levels within the same spatial environment. Usingin vivosingle-unit recordings, optogenetic manipulations and the application of a convolutional classifier, we examined the changes and causal effects of vH activity at different anxiety levels. We found that anxiogenic experiences activated the vH and that this activity scaled with increasing anxiety levels. We identified two processes that contributed to this scaling of anxiety-related activity: increased tuning and successive remapping of neurons to the anxiogenic compartment. Moreover, optogenetic inhibition of the vH reduced anxiety across different levels, while anxiety-related activity scaling could be decoded using a convolutional classifier. Collectively, our findings position the vH as a critical limbic region that functions as an ‘anxiometer’ by scaling its activity based on perceived anxiety levels. Our discoveries go beyond the traditional theory of cognitive maps in the hippocampus underlying spatial navigation and memory, by identifying hippocampal mechanisms selectively regulating anxiety.
A Fully-Automated Senescence Test (FAST) for the high-throughput quantification of senescence-associated markers
Authors: Neri Francesco , Takajjart Selma N. , Lerner Chad A. , Desprez Pierre-Yves , Schilling Birgit , Campisi Judith , Gerencser Akos A. 
Published: December 2023

AbstractCellular senescence is a major driver of aging and age-related diseases. Quantification of senescent cells remains challenging due to the lack of senescence-specific markers and generalist, unbiased methodology. Here, we describe the Fully-Automated Senescence Test (FAST), an image-based method for the high-throughput, single-cell assessment of senescence in cultured cells. FAST quantifies three of the most widely adopted senescence-associated markers for each cell imaged: senescence-associated β-galactosidase activity (SA-β-Gal) using X-Gal, proliferation arrest via lack of 5-ethynyl-2’-deoxyuridine (EdU) incorporation, and enlarged morphology via increased nuclear area. The presented workflow entails microplate image acquisition, image processing, data analysis, and graphing. Standardization was achieved by i) quantifying colorimetric SA-β-Gal via optical density; ii) implementing staining background controls; iii) automating image acquisition, image processing, and data analysis. In addition to the automated threshold-based scoring, a multivariate machine learning approach is provided. We show that FAST accurately quantifies senescence burden and is agnostic to cell type and microscope setup. Moreover, it effectively mitigates false-positive senescence marker staining, a common issue arising from culturing conditions. Using FAST, we compared X-Gal with fluorescent C12FDG live-cell SA-β-Gal staining on the single-cell level. We observed only a modest correlation between the two, indicating that those stains are not trivially interchangeable. Finally, we provide proof of concept that our method is suitable for screening compounds that modify senescence burden. This method will be broadly useful to the aging field by enabling rapid, unbiased, and user-friendly quantification of senescence burden in culture, as well as facilitating large-scale experiments that were previously impractical.
Computational identification of key transcription factors for embryonic and postnatalSox2+dental epithelial stem cell
Authors: Shao Fan , Van Otterloo Eric , Cao Huojun 
Published: December 2023

ABSTRACTWhile many reptiles can replace their tooth throughout life, human loss the tooth replacement capability after formation of the permanent teeth. It was thought that the difference in tooth regeneration capability depends on the persistence of a specialized dental epithelial structure, the dental lamina that contains dental epithelial stem cells (DESC). Currently, we know very little about DESC such as what genes are expressed or its chromatin accessibility profile. Multiple markers of DESC have been proposed such asSox2andLgr5. Few single cell RNA-seq experiments have been performed previously, but no obvious DESC cluster was identified in these scRNA-seq datasets, possible due to that the expression level of DESC markers such asSox2andLgr5is too low or the percentage of DESC is too low in whole tooth. We utilize a mouse lineSox2-GFPto enrichSox2+DESC and use Smart-Seq2 protocol and ATAC-seq protocol to generate transcriptome profile and chromatin accessibility profile of P2Sox2+DESC. Additionally, we generate transcriptome profile and chromatin accessibility profile of E11.5 Sox2+ dental lamina cells. With transcriptome profile and chromatin accessibility profile, we systematically identify potential key transcription factors for E11.5Sox2+cells and P2Sox2+cells. We identified transcription factors includingPitx2, Id3, Pitx1, Tbx1, Trp63, Nkx2-3, Grhl3, Dlx2, Runx1, Nfix, Zfp536, etc potentially formed the core transcriptional regulatory networks ofSox2+DESC in both embryonic and postnatal stages.
Optimization-Based Synthesis with Directed Cell Migration
Authors: Havenhill Eric C. , Ghosh Soham 
Published: December 2023

ABSTRACTCollective behavior of biological agents such as herds of organisms and cells is a fundamental feature in the systems biology and in the emergence of new phenomena in the biological environ-ment. Collective cell migration under a physical or chemical cue is an example of this fundamental phenomenon where individual cell migration is driven by the collective behavior of the neighboring cells and vice versa. The goal of this research is to discover the mathematical rules of collective cell migration using experimental data and testing the predictive nature of the models in independent experimental data. Such insight is made possible in this work with the hybrid use of dynamic mode decomposition (DMD) [1] and optimal control theory. Both single and multi-cellular systems are simulated, including obstacle courses, using this framework. The results of this work show how cells collectively behave during their migration and also, opens the possibility of designing robotic cells for possible therapeutic purpose where the cell trajectory can be controlled.
Neutrophil extracellular traps drive lupus flares with acute skin and kidney inflammation triggered by ultraviolet irradiation
Authors: Lyu Xing , Li Minghui , Zhang Ping L. , Wei Wei , Werth Victoria P. , Liu Ming-Lin 
Published: December 2023

ABSTRACTSunlight triggers lupus flares causing both local skin and systemic inflammation, including lupus nephritis, through poorly understood mechanisms. To address this knowledge gap, we found that UVB irradiation of asymptomatic, young female lupus-prone mice induced skin and kidney inflammation with proteinuria, accompanied by neutrophil infiltration and neutrophil extracellular trap (NET) formation. Furthermore, UVB irradiation induced co-expression of CXCR4 and cytokines/C3 by neutrophilsin vitroandin vivo,in the skin and kidneys of lupus-prone mice, indicating their transmigratory and pro-inflammatory potentials. A causality study demonstrated that inhibiting CXCR4 attenuated renal neutrophil infiltration, accumulation of NETs, NET-associated cytokines/C3, and proteinuria in UVB-irradiated lupus-prone mice. Remarkably, inhibiting NETosis through a novel strategy targeting nuclear envelope integrity reduced deposition of NET-associated cytokines/C3 in skin and kidneys, attenuating proteinuria in UVB-irradiated MRL/lpr·lmnB1Tgmice. Our investigation unveils a new mechanism by which neutrophil NETs drive the early onset of lupus flares triggered by UVB-irradiation. Targeting neutrophil transmigration and NETosis could be promising therapeutic strategies.
The Neuroprotective Effect of Short-chain Fatty Acids Against Hypoxia-reperfusion Injury
Authors: Harijan Anjit K. , Kalaiarasan Retnamony , Ghosh Amit Kumar , Jain Ruchi P. , Bera Amal Kanti 
Published: December 2023

AbstractGut microbe-derived short-chain fatty acids (SCFAs) are known to have a profound impact on various brain functions, including cognition, mood, and overall neurological health. However, their role, if any, in protecting against hypoxic injury and ischemic stroke has not been extensively studied. In this study, we investigated the effects of two major SCFAs abundant in the gut, propionate (P) and butyrate (B), on hypoxia-reperfusion injury using a neuronal cell line and a zebrafish model. Neuro 2a (N2a) cells treated with P and B exhibited reduced levels of mitochondrial and cytosolic reactive oxygen species (ROS), diminished loss of mitochondrial membrane potential, suppressed caspase activation, and lower rates of cell death when exposed to CoCl2-induced hypoxia, compared to the control group. Furthermore, adult zebrafish fed with SCFAs-supplemented feeds showed less susceptibility to hypoxic conditions compared to the control group, as indicated by multiple behavioral measures. Histological analysis of TTC-stained brain sections revealed lesser damage in the SCFAs-fed group. We also found that FABP7 (also known as BLBP), a neuroprotective fatty acid binding protein, was upregulated in the brains of the SCFAs-fed group. Additionally, when FABP7 was overexpressed in N2a cells, it protected the cells from hypoxia-reperfusion injury. Overall, our data clearly demonstrates a neuroprotective role of P and B against hypoxic brain injury and suggests the potential of dietary supplementation with SCFAs to mitigate stroke-induced brain damage.HighlightsShort-chain fatty acid (SCFA) Propionate (P) and Butyrate (B) protect N2a cells from hypoxia-reperfusion.Zebrafish, when fed an SCFA-supplemented diet, are more resilient to hypoxia-reperfusion.SCFAs in the diet boost brain expression of FABP7 (fatty acid binding protein).FABP7 overexpression in N2a cells provides protection against hypoxia-reperfusion.SCFAs reduce reactive oxygen species (ROS) levels and increase FABP7, contributing to neuroprotection.
Novel nitrifying symbiont lineages are vertically inherited and widespread in marine sponges
Authors: Glasl Bettina , Luter Heidi M. , Damjanovic Katarina , Kitzinger Katharina , Mueller Anna J. , Mahler Leonie , Engelberts Joan Pamela , Rix Laura , Osvatic Jay T. , Hausmann Bela , Séneca Joana , Daims Holger , Pjevac Petra , Wagner Michael 
Published: December 2023

AbstractAmmonia-oxidising archaea and nitrite-oxidising bacteria are common members of marine sponge microbiomes. They derive energy for carbon fixation and growth from nitrification - the oxidation of ammonia to nitrite and further to nitrate - and are proposed to play essential roles in the carbon and nitrogen cycling of sponge holobionts. In this study, we characterise two novel nitrifying symbiont lineages, ‘Ca. Nitrosokoinonia’ and ‘Ca. Nitrosymbion’ in the marine spongeCoscinoderma matthewsiusing a combination of molecular tools, single-cell imaging techniques, and physiological rate measurements. Both represent a new genus in the ammonia-oxidising archaeal classNitrososphaeriaand the nitrite-oxidising bacterial orderNitrospirales, respectively. Furthermore, we show that larvae of this viviparous sponge are densely colonised by representatives of ‘Ca. Nitrosokoinonia’ and ‘Ca. Nitrosymbion’ indicating vertical transmission. In adults, the representatives of both symbiont genera are located extracellularly in the mesohyl. Comparative metagenome analyses and physiological data suggest that ammonia-oxidising archaeal symbionts of the genusCa. Nitrosokoinonia strongly rely on endogenously produced nitrogenous compounds (i.e., ammonium, urea, nitriles/cyanides, and creatinine) rather than on exogenous ammonium sources taken up by the sponge. Additionally, the nitrite-oxidising bacterial symbiontsCa. Nitrosymbion may reciprocally support the ammonia-oxidisers with ammonia via the utilisation of sponge-derived urea and cyanate. Interestingly, comparative analyses of published environmental 16S rRNA amplicon data revealed that ‘Ca. Nitrosokoinonia’ and ‘Ca. Nitrosymbion’ are widely distributed and predominantly associated with marine sponges and corals, suggesting a broad relevance of our findings.
Influence of different landscape configurations on insect pollinators of important horticultural crops in a western Himalayan landscape
Authors: Khan Susmita , Sinha Bitapi , Uniyal V.P. 
Published: December 2023

AbstractPollinators play critical roles in ecosystem stability and agricultural productivity, and their decline has become a global concern. One of the main reasons for pollinators decline is changing landscape configuration. We conducted this study in Kullu Valley, Himachal Pradesh, India to evaluate varied landscape configuration impacts on the diversity, richness, and abundance of insect pollinators in apple and plum orchards. Five different landscape configurations were considered for the study. The survey spanned 28 orchards across the valley during the blooming periods of 2021 and 2022. Standard sampling protocols were used to collect the pollinator specimen. We recorded a total of 107 insect species across 67 genera, 29 families and five orders (Hymenoptera, Lepidoptera, Diptera, Coleoptera, and Thysanoptera) from different orchards. Hymenoptera and Diptera were the most abundant pollinators in the study area. Pollinator richness and diversity were higher in orchards located within 1-km of natural forests and in lower elevations (>1500 meters). Orchards near large settlements, agricultural lands and complete modernised management practice showed comparative less pollinator diversity and abundance. This study demonstrates the influence of diverse land-use practices on pollinators on a landscape scale and provides insights for developing effective conservation strategies in the Himalaya.
The intracellular C-terminus confers compartment-specific targeting of voltage-gated Ca2+channels
Authors: Chin Morven , Kaeser Pascal S. 
Published: December 2023

AbstractTo achieve the functional polarization that underlies brain computation, neurons sort protein material into distinct compartments. Ion channel composition, for example, differs between axons and dendrites, but the molecular determinants for their polarized trafficking remain obscure. Here, we identify the mechanisms that target voltage-gated Ca2+channels (CaVs) to distinct subcellular compartments. In hippocampal neurons, CaV2s trigger neurotransmitter release at the presynaptic active zone, and CaV1s localize somatodendritically. After knockout of all three CaV2s, expression of CaV2.1, but not of CaV1.3, restores neurotransmitter release. Chimeric CaV1.3 channels with CaV2.1 intracellular C-termini localize to the active zone, mediate synaptic vesicle exocytosis, and render release fully sensitive to blockade of CaV1 channels. This dominant targeting function of the CaV2.1 C-terminus requires an EF hand in its proximal segment, and replacement of the CaV2.1 C-terminus with that of CaV1.3 abolishes CaV2.1 active zone localization. We conclude that the intracellular C-termini mediate compartment-specific CaVtargeting.