bluuebunny/crossref_metadata_2025_split huggingface dataset:
Myxococcus xanthus fruiting body morphology is important for spore recovery after exposure to environmental stress
Authors: Lall Dave , Glaser Maike M. , Higgs Penelope I. 
Published: May 2023

ABSTRACTEnvironmental microorganisms have evolved a variety of strategies to survive fluctuations in environmental conditions, including production of biofilms and differentiation into spores.Myxococcus xanthusare ubiquitous soil bacteria that produce starvation-induced multicellular fruiting bodies filled with environmentally resistant spores (a specialized biofilm). Fruiting bodies are thought to facilitate theM. xanthussocial life cycle by ensuring spores can germinateen masseinto a productive feeding community. Isolated spores have been shown to be more resistant than vegetative cells to heat, ultraviolet radiation, and desiccation, but it is unknown whether assembly of spores into a fruiting body provides additional protection from environmental insults. We developed a high-throughput method to compare the recovery (outgrowth) of distinct cell types (vegetative cells, free spores, and intact fruiting bodies) after exposure to ultraviolet radiation or desiccation. Our data indicate haystack-shaped fruiting bodies protect spores from extended UV radiation but do not provide additional protection from desiccation. Perturbation of fruiting body morphology strongly impedes recovery from both UV exposure and desiccation. These results hint that the distinctive fruiting bodies produced by different myxobacterial species may have evolved to optimize their persistence in distinct ecological niches.IMPORTANCEThe myxobacteria are environmentally ubiquitous social bacteria that influence the local microbial community composition. Understanding how these bacteria are affected by environmental insults is important in predicting how microbial biogeochemical cycling is affected by climate change. When starved, myxobacteria produce multicellular fruiting bodies filled with spores. As spores are resistant to a variety of environmental insults, it has long been held that the fruiting body evolved to ensure group germination into a productive feeding community. Using the model myxobacterium,Myxococcus xanthus, we demonstrate that the haystack-shaped fruiting body morphology enables significantly more resistance to UV exposure than the free spores. In contrast, fruiting bodies are slightly detrimental to recovery from extended desiccation, an effect that is strongly exaggerated if fruiting body morphology is perturbed. These results suggest the variety of fruiting body morphologies observed in the myxobacteria may dictate their relative resistance to changing climate conditions.
Flagellin is essential for initial attachment to mucosal surfacesby Clostridioides difficile
Authors: Sidner Ben , Lerma Armando , Biswas Baishakhi , Ronish Leslie A. , McCullough Hugh , Auchtung Jennifer M. , Piepenbrink Kurt H. 
Published: May 2023

AbstractMucins are glycoproteins which can be found in host cell membranes and as a gelatinous surface formed from secreted mucins. Mucosal surfaces in mammals form a barrier to invasive microbes, particularly bacteria, but are a point of attachment for others.Clostridioides difficileis anaerobic bacterium which colonizes the mammalian GI tract and is a common cause of acute GI inflammation leading to a variety of negative outcomes. AlthoughC. difficiletoxicity stems from secreted toxins, colonization is a prerequisite forC. difficiledisease. WhileC. difficileis known to associate with the mucus layer and underlying epithelium, the mechanisms underlying these interactions that facilitate colonization are less well-understood. To understand the molecular mechanisms by whichC. difficileinteracts with mucins, we usedex vivomucosal surfaces to test the ability ofC. difficileto bind to mucins from different mammalian tissues. We found significant differences inC. difficileadhesion based upon the source of mucins, with highest levels of binding observed to mucins purified from the human colonic adenocarcinoma line LS174T and lowest levels of binding to porcine gastric mucin. We also observed that defects in adhesion by mutants deficient in flagella, but not type IV pili. These results imply that interactions between host mucins andC. difficileflagella facilitate the initial host attachment ofC. difficileto host cells and secreted mucus.
The regulation of Insulin/IGF-1 signaling by miR-142-3p associated with human longevity
Authors: Wang Xifan , Jung Hwa Jin , Milholland Brandon , Cui Jinhua , Tazearslan Cagdas , Atzmon Gil , Wang Xizhe , Yang Jiping , Guo Qinghua , Barzilai Nir , Robbins Paul D. , Suh Yousin 
Published: May 2023

AbstractMicroRNAs (miRNAs) have been demonstrated to modulate life span in the invertebratesC. elegansandDrosophilaby targeting conserved pathways of aging, such as insulin/IGF-1 signaling (IIS). However, a role for miRNAs in modulating human longevity has not been fully explored. Here we investigated novel roles of miRNAs as a major epigenetic component of exceptional longevity in humans. By profiling the miRNAs in B-cells from Ashkenazi Jewish centenarians and 70-year-old controls without a longevity history, we found that the majority of differentially expressed miRNAs were upregulated in centenarians and predicted to modulate the IIS pathway. Notably, decreased IIS activity was found in B cells from centenarians who harbored these upregulated miRNAs. miR-142-3p, the top upregulated miRNA, was verified to dampen the IIS pathway by targeting multiple genes includingGNB2, AKT1S1, RHEBandFURIN. Overexpression of miR-142-3p improved the stress resistance under genotoxicity and induced the impairment of cell cycle progression in IMR90 cells. Furthermore, mice injected with a miR-142-3p mimic showed reduced IIS signaling and improved longevity-associated phenotypes including enhanced stress resistance, improved diet/aging-induced glucose intolerance, and longevity-associated change of metabolic profile. These data suggest that miR-142-3p is involved in human longevity through regulating IIS-mediated pro-longevity effects. This study provides strong support for the use of miR-142-3p as a novel therapeutic to promote longevity or prevent aging/aging-related diseases in human.
Allele-specific epigenetic regulation ofFURINexpression at a coronary artery disease susceptibility locus
Authors: Yang Wei , Cao Junjun , McVey David G. , Ye Shu 
Published: May 2023

AbstractBackgroundGenome-wide association studies have revealed an association between the genetic variant rs17514846 on chromosome 15q26.1 and coronary artery disease susceptibility. Studies have shown that rs17514846 influences the expression of the FES Upstream Region (FURIN) gene located at this locus in monocytes. We investigated the mechanism through which rs17514846 modulatesFURINexpression.Methods and ResultsAn analysis of isogenic monocytic cell lines with either the rs17514846 C/C or A/A genotype showed that the cells of the A/A genotype expressed higher levels ofFURINthan cells of the C/C genotype. A pyrosequencing methylation analysis showed that the cytosine (in a CpG motif) at the rs17514846 position on the C allele was methylated. Treatment with the DNA methylation inhibitor 5-aza-2’-deoxycytidine increasedFURINexpression. A bioinformatic analysis indicated that the rs17514846 site might interact with the transcription factor MeCP2 that often functions as a gene repressor by binding to methylated CpG sites. An electrophoretic mobility super-shift assay with a probe corresponding to the DNA sequence at and around the rs17514846 position of the C allele detected two DNA-protein complex bands, which were altered by the addition of an anti-MeCP2 antibody in the assay, whilst these DNA-protein complexes were barely detectable with a probe for the A allele. A chromatin immunoprecipitation assay showed an enrichment of the DNA sequence containing the rs17514846 site in chromatin precipitates pulled down by an anti-MeCP2 antibody. siRNA-mediated knockdown of MeCP2 caused an increase inFURINexpression. Furthermore, MeCP2 knockdown increased monocyte migration and proliferation, and this effect was diminished by a FURIN inhibitor.ConclusionsThe results of our study suggest that DNA methylation inhibitsFURINexpression and that the coronary artery disease predisposing variant rs17514846 modulatesFURINexpression and monocyte migration via an allele-specific effect on DNA methylation.
Species composition of Culicidae (Diptera) in Bromeliads in rural and urban areas of Londrina, Brazil
Authors: Silva Bianca Piraccini , Arcos Adriano Nobre , Ferreira Francisco Augusto da Silva , Medri Cristiano , Zequi João Antonio Cyrino 
Published: May 2023

ABSTRACTBromeliaceae, has 82 genera and 3,719 species found throughout the Neotropical region, from the southern United States to central Argentina and Chile. These plants are present in environments with different characteristics and have high endemism in the Atlantic Forest in Brazil. Tank bromeliads stand out for their morphology, which forms permanent water-accumulating compartments called phytotelmata, rich in organic detritus and living organisms. Culicidae use phytotelma as a breeding ground, and some species of Wyeomyia are highly dependent on these tanks. Research on the importance of bromeliads as water reservoirs that may favor the reproduction of mosquitoes that carry pathogens are controversial. Some studies indicate that these plants are potential breeding grounds forAedes, while others suggest that they are not preferential foci for synanthropic mosquitoes, as is the case forA. aegypti. This work aimed at verifying the presence ofAedesand other Culicidae in native bromeliads in natural habitat and under ornamental cultivation in an urban environment, comparing the incidence of larvae in these possible breeding sites and contrasting with the luminosity and accumulated water volumes. Differences in species composition were observed between rural and urban environments. In the rural environment, four species of Culicidae were collected, the most abundant beingWyeomyia galvaoi-19 specimens, followed byCulex(Microculex)imitator- five specimens, whileAedes aegyptiandToxorhynchitessp 1, were the least abundant, with two individuals each. In the urban environment, five species were found, with greater abundance ofAedes aegypti(461 individuals), followed byAedes albopictus(45),Toxorhynchitessp. 01 (3),Wyeomyiasp1 (02), andWyeomyia galvaoi(01) In addition, these phytotelma showed great diversity of other organisms, such as: mites, nematodes, protists, rotifers, ostracods, and insect larvae of the Chironomidae, Syrphidae and Tachinidae families. The study concluded that the incidence of mosquito larvae in native bromeliads is low, and that luminosity and accumulated water volumes can influence the presence of larvae. The authors emphasize that the importance of bromeliads in mosquito reproduction may vary according to several factors.
Multiplexed volumetric CLEM enabled by antibody derivatives provides new insights into the cytology of the mouse cerebellar cortex
Authors: Han Xiaomeng , Lu Xiaotang , Li Peter H. , Wang Shuohong , Schalek Richard , Meirovitch Yaron , Lin Zudi , Adhinarta Jason , Berger Daniel , Wu Yuelong , Fang Tao , Meral Elif Sevde , Asraf Shadnan , Ploegh Hidde , Pfister Hanspeter , Wei Donglai , Jain Viren , Trimmer James S. , Lichtman Jeff W. 
Published: May 2023

AbstractMapping neuronal networks that underlie behavior has become a central focus in neuroscience. While serial section electron microscopy (ssEM) can reveal the fine structure of neuronal networks (connectomics), it does not provide the molecular information that helps identify cell types or their functional properties. Volumetric correlated light and electron microscopy (vCLEM) combines ssEM and volumetric fluorescence microscopy to incorporate molecular labeling into ssEM datasets. We developed an approach that uses small fluorescent single-chain variable fragment (scFv) immuno-probes to perform multiplexed detergent-free immuno-labeling and ssEM on the same samples. We generated eight such fluorescent scFvs that targeted useful markers for brain studies (green fluorescent protein, glial fibrillary acidic protein, calbindin, parvalbumin, voltage-gated potassium channel subfamily A member 2, vesicular glutamate transporter 1, postsynaptic density protein 95, and neuropeptide Y). To test the vCLEM approach, six different fluorescent probes were imaged in a sample of the cortex of a cerebellar lobule (Crus 1), using confocal microscopy with spectral unmixing, followed by ssEM imaging of the same sample. The results show excellent ultrastructure with superimposition of the multiple fluorescence channels. Using this approach we could document a poorly described cell type in the cerebellum, two types of mossy fiber terminals, and the subcellular localization of one type of ion channel. Because scFvs can be derived from existing monoclonal antibodies, hundreds of such probes can be generated to enable molecular overlays for connectomic studies.
Enhancer status in the primitive endoderm supports unrestricted lineage plasticity in regulative development
Authors: Linneberg-Agerholm Madeleine , Sell Annika Charlotte , Redo-Riveiro Alba , Proks Martin , Knudsen Teresa E. , Perera Marta , Brickman Joshua M. 
Published: May 2023

AbstractMammalian blastocyst formation involves the specification of trophectoderm followed by the differentiation of the inner cell mass into either epiblast or primitive endoderm. During this time, the embryo maintains a window of plasticity and can redirect its cellular fate when challenged experimentally. In this context, we found that the primitive endoderm alone was sufficient to regenerate a complete blastocyst and continue normal postimplantation development to term. We identify anin vitropopulation similar to the early primitive endodermin vivo, that exhibits the same embryonic and extra-embryonic potency, forming three dimensional embryoid structures. Commitment in early primitive endoderm is suppressed by JAK/STAT signalling, collaborating with OCT4 to safeguard enhancer status enabling multi-lineage differentiation. Our observations support the notion that transcription factor persistence underlies plasticity in regulative development and highlights the importance of primitive endoderm in perturbed development.
SRC-1 controls growth cone polarity and protrusion with the UNC-6/Netrin receptor UNC-5 inCaenorhabditis elegans
Authors: Mahadik Snehal S. , Burt Emily K. , Lundquist Erik A. 
Published: May 2023

AbstractIn the Polarity/Protusion model of growth cone migration away from the guidance cue UNC-6/Netrin, the UNC-5 receptor polarizes the VD growth cone such that filopodial protrusions are biased to the dorsal leading edge of the growth cone. UNC-5 also inhibits growth cone protrusion ventrally based upon this polarity. The SRC-1 tyrosine kinase has been previously shown to physically interact with and phosphorylate UNC-5, and to act with UNC-5 in axon guidance and cell migration. Here, the role of SRC-1 in VD growth cone polarity and protrusion is investigated. A precise deletion ofsrc-1was generated, and mutants displayed unpolarized growth cones with increased size, similar tounc-5mutants. Transgenic expression ofsrc-1(+)in VD/DD neurons resulted in smaller growth cones, and rescued growth cone polarity defects ofsrc-1mutants, indicating cell-autonomous function. Transgenic expression of a putative kinase-deadsrc-1(D831A)mutant caused a phenotype similar tosrc-1loss-of-function, suggesting that this is a dominant negative mutation. The D381A mutation was introduced into the endogenoussrc-1gene by genome editing, which also had a dominant-negative effect. Genetic interactions ofsrc-1andunc-5suggest they act in the same pathway on growth cone polarity and protrusion, but might have overlapping, parallel functions in other aspects of axon guidance.src-1function was not required for the effects of activatedmyr::unc-5, suggesting that SRC-1 might be involved in UNC-5 dimerization and activation by UNC-6, of whichmyr::unc-5is independent. In sum, these results show that SRC-1 acts with UNC-5 in growth cone polarity and inhibition of protrusion.
Distinct brain network features predict internalizing and externalizing traits in children and adults
Authors: Qu Yueyue Lydia , Chen Jianzhong , Tam Angela , Ooi Leon Qi Rong , Dhamala Elvisha , Cocuzza Carrisa , Lawhead Connor , Yeo B. T. Thomas , Holmes Avram J. 
Published: May 2023

AbstractInternalizing and externalizing traits are two distinct classes of behaviors in psychiatry. However, whether shared or unique brain network features predict internalizing and externalizing behaviors in children and adults remain poorly understood. Using a sample of 2262 children from the Adolescent Brain Cognitive Development (ABCD) study and 752 adults from the Human Connectome Project (HCP), we show that network features predicting internalizing and externalizing behavior are, at least in part, dissociable in children, but not in adults. In ABCD children, traits within internalizing and externalizing behavioral categories are predicted by more similar network features concatenated across task and resting states than those between different categories. We did not observe this pattern in HCP adults. Distinct network features predict internalizing and externalizing behaviors in ABCD children and HCP adults. These data reveal shared and unique brain network features accounting for individual variation within broad internalizing and externalizing categories across developmental stages.
Transcriptome mining of RNA viruses (familyTotiviridae) inEimeria necatrixandEimeria stiedai
Authors: Nibert Max L. , Xie Yue , Xiao Jie , Gao Yang , Liu Dandan , Yang Guangyou , Tao Jianping 
Published: May 2023

ABSTRACTCoccidian protozoa from the genusEimeriaare widespread parasites of vertebrates, causing serious disease (coccidiosis) and economic loss most notably in poultry. Several species ofEimeriaare themselves infected with small RNA viruses assigned to the familyTotiviridae. In this study, the sequences of two such viruses were newly determined, one of which represents the first complete protein-coding sequence of a virus fromE. necatrix, an important pathogen of chickens, and the other of which is fromE. stiedai, an important pathogen of rabbits. Sequence features of the newly identified viruses, compared with those of ones reported previously, provide several insights. Phylogenetic analyses suggest that these eimerian viruses constitute a well-demarcated clade, probably deserving of recognition as a distinct genus.
Comprehensive structural and interactome analysis reveals novel interactions and protein binding sites in miR-675: a non-coding RNA critically involved in multiple diseases
Authors: Dey Abhishek 
Published: May 2023

AbstractmiR-675 is a microRNA expressed from exon 1 of H19 long non-coding RNA. H19 lncRNA is temporally expressed in humans and atypical expression of miR-675 has been linked with several diseases and disorders. To execute its function inside the cell, miR-675 is folded into a particular conformation which aids in its interaction with several other biological molecules. However, the exact folding dynamics of miR-675 and its complete interaction map are currently unknown. Moreover, how H19 lncRNA and miR-675 crosstalk and modulate each other’s activities is also unclear. Detailed structural analysis of miR-675 in this study determines its conformation and identifies novel protein binding sites on miR-675 which can make it an excellent therapeutic target against numerous diseases. Mapping of the interactome identified some of known and unknown interactors of miR-675 which aid in expanding our repertoire of miR-675 involved pathways in the cell. This analysis also identified some of the previously unknown and yet to be characterised proteins as probable interactors of miR-675. Structural and base pair conservation analysis between H19 lncRNA and miR-675 results in structural transformations in miR-675 thus describing the earlier unknown mechanism of interaction between these two molecules. Comprehensively, this study details the conformation of miR-675, its interacting biological partners and explains its relationship with H19 lncRNA which can be interpreted to understand the role of miR-675 in the development and progression of various diseases.
Self-driving laboratories to autonomously navigate the protein fitness landscape
Authors: Rapp Jacob T. , Bremer Bennett J. , Romero Philip A. 
Published: May 2023

AbstractProtein engineering has nearly limitless applications across chemistry, energy, and medicine, but creating new proteins with improved or novel functions remains slow, labor-intensive, and inefficient. In this work, we present theSelf-driving Autonomous Machines for Protein Landscape Exploration(SAMPLE) platform for fully autonomous protein engineering. SAMPLE is driven by an intelligent agent that learns protein sequence-function relationships, designs new proteins, and sends designs to a fully automated robotic system that experimentally tests designed proteins and provides feedback to improve the agent’s understanding of the system. We deployed four SAMPLE agents with the goal of engineering glycoside hydrolase enzymes with enhanced thermal tolerance. Despite showing individual differences in their search behavior, all four agents quickly converged on thermostable enzymes that were at least 12 °C more stable than the starting sequences. Self-driving laboratories automate and accelerate the scientific discovery process and hold great potential for the fields of protein engineering and synthetic biology.
Epitranscriptomics m6A analyses reveal distinct m6A marks under tumor necrosis factor α (TNF-α)-induced apoptotic conditions in HeLa cells
Authors: Akçaöz-Alasar Azime , Tüncel Özge , Sağlam Buket , Gazaloğlu Yasemin , Atbinek Melis , Cagiral Umut , Iscan Evin , Ozhan Gunes , Akgül Bünyamin 
Published: May 2023

AbstractTNF-α is a ligand that induces both intrinsic and extrinsic apoptotic pathways in HeLa cells by modulating complex gene regulatory mechanisms. However, the full spectrum of TNF-α-modulated epitranscriptomic m6A marks is unknown. We employed a genomewide approach to examine the extent of m6A RNA modifications under TNF-α-modulated apoptotic conditions in HeLa cells. miCLIP-seq analyses revealed a plethora of m6A marks on 632 target mRNAs with an enrichment on 99 mRNAs associated with apoptosis. Interestingly, the m6A RNA modification patterns were quite different under cisplatin- and TNF-α-mediated apoptotic conditions. We then examined the abundance and translational efficiencies of several mRNAs under METTL3 knockdown and/or TNF-α treatment conditions. Our analyses showed changes in the translational efficiency ofTP53INP1mRNA based on the polysome profile analyses. Additionally, TP53INP1 protein amount was modulated by METTL3 knockdown upon TNF-α treatment but not CP treatment, suggesting the existence of a pathway-specific METTL3-TP53INP1 axis. Congruently, METLL3 knockdown sensitized HeLa cells to TNF-α-mediated apoptosis, which was also validated in a zebrafish larval xenograft model. These results suggest that apoptotic pathway-specific m6A methylation marks exist in cells and TNF-α-METTL3-TP53INP1 axis modulates TNF-α-mediated apoptosis in HeLa cells.