bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transcriptomic changes predict metabolic alterations in LC3 associated phagocytosis in aged mice
Authors: Dhingra Anuradha , Tobias John W , Philp Nancy J , Boesze-Battaglia Kathleen 
Published: March 2023

AbstractLC3b (Map1lc3b) plays an essential role in canonical autophagy and is one of several components of the autophagy machinery that mediates non-canonical autophagic functions. Phagosomes are often associated with lipidated LC3b, to pro-mote phagosome maturation in a process called LC3-associated phagocytosis (LAP). Specialized phagocytes such as mammary epithelial cells, retinal pigment epithelial (RPE) cells, and sertoli cells utilize LAP for optimal degradation of phagocytosed material, including debris. In the visual system, LAP is critical to maintain retinal function, lipid homeostasis and neuroprotection. In a mouse model of retinal lipid steatosis - mice lacking LC3b (LC3b-/-), we observed increased lipid deposition, metabolic dysregulation and enhanced inflammation. Herein we present a non-biased approach to determine if loss of LAP mediated processes modulate the expression of various genes related to metabolic homeostasis, lipid handling, and inflammation. A comparison of the RPE transcriptome of WT andLC3b-/-mice revealed 1533 DEGs, with ~73% upregulated and 27% down-regulated. Enriched gene ontology (GO) terms included inflammatory response (upregulated DEGs), fatty acid metabolism and vascular transport (downregulated DEGs). Gene set enrichment analysis (GSEA) identified 34 pathways; 28 were upregulated (dominated by inflammation/related pathways) and 6 were downregulated (dominated by metabolic pathways). Analysis of additional gene families identified significant differences for genes in the solute carrier family, RPE signature genes, and genes with potential role in age-related macular degeneration. These data indicate that loss of LC3b induces robust changes in the RPE transcriptome contributing to lipid dysregulation and metabolic imbalance, RPE atrophy, inflammation, and disease pathophysiology.
Manuscript: Detecting differences in Size Spectra
Authors: Pomeranz Justin , Junker James R. , Gjoni Vojsava , Wesner Jeff S. 
Published: March 2023

AbstractThe distribution of body size in communities is remarkably consistent across habitats and taxa and can be represented by size spectra, which are described by a power law. The focus of size spectra analysis is to estimate the exponent (λ) of the power law.Many methods have been proposed for estimatingλmost of which involve binning the data, summing abundance within bins, and then fitting a ordinary least squares (OLS) regression in log-log space. However, recent work has shown that binning procedures may return biased estimates of size spectra exponents compared to procedures that directly estimateλusing maximum likelihood estimation (MLE). Despite this variability in estimates, it is unclear if the relative change across environmental gradients is consistent across methodologies. Here, we used simulation to compare the ability of two binning methods (NAS, ELBn) and MLE to 1) recapture known values ofλ, and 2) recapture parameters in a linear regression measuring the change inλacross a hypothetical environmental gradient. We also compared the methods using two previously published body size datasets across a pollution gradient and a temperature gradientMaximum likelihood methods always performed better than common binning methods, which demonstrated consistent bias depending on the simulated values ofλ. This bias carried over to the regressions, which were more accurate whenλwas estimated using MLE compared to the binning procedures. Additionally, the variance in estimates using MLE methods is markedly reduced when compared to binning methods.The uncertainty and variation in estimates when using binning methods is often greater than or equal to the variation previously published in experimental and observational studies, bringing into question the effect size of previously published results. However, while the methods produced different slope estimates from previously published datasets, they were in qualitative agreement on the sign of those slopes (i.e., all negative or all positive). Our results provide further support for the direct estimation ofλusing MLE (or similar procedures) over the more common methods of binning.
Population-level annotation of lncRNA transcription in Arabidopsis reveals extensive variation associated with transposable element-like silencing
Authors: Kornienko Aleksandra E. , Nizhynska Viktoria , Morales Almudena Molla , Pisupati Rahul , Nordborg Magnus 
Published: March 2023

AbstractLong non-coding RNAs (lncRNAs) are understudied and underannotated in plants. In mammals, lncRNA loci are nearly as ubiquitous as protein-coding genes, and their expression is highly variable between individuals of the same species. UsingArabidopsis thalianaas a model, we aimed to understand the true scope of lncRNA transcription across plants from different regions and study its natural variation. We used transcriptome deep sequencing datasets spanning hundreds of natural accessions and several developmental stages to create a population-wide annotation of lncRNAs, revealing thousands of previously unannotated lncRNA loci. While lncRNA transcription is ubiquitous in the genome, most loci appear to be actively silenced and their expression is extremely variable between natural accessions. This high expression variability is largely caused by the high variability of repressive chromatin levels at lncRNA loci. High variability was particularly common for intergenic lncRNAs (lincRNAs), where pieces of transposable elements (TEs) present in 50% of these lincRNA loci are associated with increased silencing and variation, and such lncRNAs tend to be targeted by the TE silencing machinery. We create a population-wide lncRNA annotation inA. thalianaand improve our understanding of plant lncRNA genome biology, raising fundamental questions about what causes transcription and silencing across the genome.One-sentence summarylncRNA loci are plentiful in theA. thalianagenome, but their expression is extremely variable and largely repressed, with TE pieces enriched in intergenic lncRNAs aiding variability and silencing.
Damage-induced basal epithelial cell migration modulates the spatial organization of redox signaling and sensory neuron regeneration
Authors: Fister Alexandra M. , Horn Adam , Lasarev Michael , Huttenlocher Anna 
Published: March 2023

SummaryEpithelial damage leads to early reactive oxygen species (ROS) signaling, which regulates sensory neuron regeneration and tissue repair. How the initial type of tissue injury influences early damage signaling and regenerative growth of sensory axons remains unclear. Previously we reported that thermal injury triggers distinct early tissue responses in larval zebrafish. Here, we found that thermal but not mechanical injury impairs sensory axon regeneration and function. Real-time imaging revealed an immediate tissue response to thermal injury characterized by the rapid Arp2/3-dependent migration of keratinocytes, which was associated with tissue-scale ROS production and sustained sensory axon damage. Isotonic treatment was sufficient to limit keratinocyte movement, spatially restrict ROS production and rescue sensory neuron function. These results suggest that early keratinocyte dynamics regulate the spatial and temporal pattern of long-term signaling in the wound microenvironment during tissue repair.
N-WASP-dependent branched actin polymerization attenuates B-cell receptor signaling by increasing the molecular density of receptor clusters
Authors: Bhanja Anshuman , Seeley-Fallen Margaret K. , Lazzaro Michelle , Upadhyaya Arpita , Song Wenxia 
Published: March 2023

AbstractAntigen-induced B-cell receptor (BCR) signaling is critical for initiating and regulating B-cell activation. The actin cytoskeleton plays essential roles in BCR signaling. Upon encountering cell-surface antigens, actin-driven B-cell spreading amplifies signaling, while B-cell contraction following spreading leads to signal attenuation. However, the mechanism by which actin dynamics switch BCR signaling from amplification to attenuation is unknown. Here, we show that Arp2/3-mediated branched actin polymerization is required for B-cell contraction. Contracting B-cells generate centripetally moving actin foci from lamellipodial F-actin networks in the B-cell plasma membrane region contacting antigen-presenting surfaces. Actin polymerization driven by N-WASP, but not WASP, initiates these actin foci and facilitates non-muscle myosin II recruitment to the contact zone, creating actomyosin ring-like structures. Furthermore, B-cell contraction increases BCR molecular density in individual clusters, leading to decreased BCR phosphorylation. Increased BCR molecular density reduced levels of the stimulatory kinase Syk, the inhibitory phosphatase SHIP-1, and their phosphorylated forms in individual BCR clusters. These results suggest that N-WASP-activated Arp2/3, coordinating with myosin, generates centripetally moving foci and contractile actomyosin ring-like structures from lamellipodial networks, enabling contraction. B-cell contraction attenuates BCR signaling by pushing out both stimulatory kinases and inhibitory phosphatases from BCR clusters, providing novel insights into actin-facilitated signal attenuation.
Hippocampal sharp wave-ripple dynamics in NREM sleep encode motivation for anticipated physical activity
Authors: Buhler Chelsea M. , Basso Julia C. , English Daniel Fine 
Published: March 2023

ABSTRACTPhysical activity is an integral part of every mammal’s daily life, and as a driver of Darwinian fitness, required coordinated evolution of the body and brain. The decision to engage in physical activity is driven either by survival needs or by motivation for the rewarding qualities of physical activity itself. Rodents exhibit innate and learned motivation for voluntary wheel running, and over time run longer and farther, reflecting increased incentive salience and motivation for this consummatory behavior. Dynamic coordination of neural and somatic physiology are necessary to ensure the ability to perform behaviors that are motivationally variable. Hippocampal sharp wave-ripples (SWRs) have evolved both cognitive and metabolic functions, which in modern mammals may facilitate body-brain coordination. To determine if SWRs encode aspects of exercise motivation we monitored hippocampal CA1 SWRs and running behaviors in adult mice, while manipulating the incentive salience of the running experience. During non-REM (NREM) sleep, the duration of SWRs before (but not after) running positively correlated with future running duration, and larger pyramidal cell assemblies were activated in longer SWRs, suggesting that the CA1 network encodes exercise motivation at the level of neuronal spiking dynamics. Inter-Ripple-intervals (IRI) before but not after running were negatively correlated with running duration, reflecting more SWR bursting, which increases with learning. In contrast, SWR rates before and after running were positively correlated with running duration, potentially reflecting a tuning of metabolic demand for that day’s anticipated and actual energy expenditure rather than motivation. These results suggest a novel role for CA1 in exercise behaviors and specifically that cell assembly activity during SWRs encodes motivation for anticipated physical activity.SIGNIFICANCE STATEMENTDarwinian fitness is increased by body-brain coordination through internally generated motivation, though neural substrates are poorly understood. Specific hippocampal rhythms (i.e., CA1 SWRs), which have a well-established role in reward learning, action planning and memory consolidation, have also been shown to modulate systemic [glucose]. Using a mouse model of voluntary physical activity that requires body-brain coordination, we monitored SWR dynamics when animals were highly motivated and anticipated rewarding exercise (i.e., when body-brain coordination is of heightened importance). We found that during non-REM sleep before exercise, SWR dynamics (which reflect cognitive and metabolic functions) were correlated with future time spent exercising. This suggests that SWRs support cognitive and metabolic facets that motivate behavior by coordinating the body and brain.
Reciprocal discoidin domain receptor signaling strengthens integrin adhesion to connect adjacent tissues
Authors: Park Kieop , Jayadev Ranjay , Payne Sara G. , Kenny-Ganzert Isabel W. , Chi Qiuyi , Costa Daniel S. , Ramos-Lewis William , Thendral Siddharthan Balachandar , Sherwood David R. 
Published: March 2023

AbstractSeparate tissues connect through adjoining basement membranes to carry out molecular barrier, exchange, and organ support functions. Cell adhesion at these connections must be robust and balanced to withstand independent tissue movement. Yet, how cells achieve synchronized adhesion to connect tissues is unknown. Here, we have investigated this question using theC. elegansutse-seam tissue connection that supports the uterus during egg-laying. Through genetics, quantitative fluorescence, and cell specific molecular disruption, we show that type IV collagen, which fastens the linkage, also activates the collagen receptor discoidin domain receptor 2 (DDR-2) in both the utse and seam. RNAi depletion, genome editing, and photobleaching experiments revealed that DDR-2 signals through LET-60/Ras to coordinately strengthen an integrin adhesion in the utse and seam that stabilizes their connection. These results uncover a synchronizing mechanism for robust adhesion during tissue connection, where collagen both affixes the linkage and signals to both tissues to bolster their adhesion.
Dopamine receptor D2 confers colonization resistance via gut microbial metabolites
Authors: Scott Samantha A. , Fu Jingjing , Chang Pamela V. 
Published: March 2023

Abstract/Summary Paragraph:The gut microbiome plays major roles in modulating host physiology. One such function is colonization resistance, or the ability of the microbial collective to protect the host against enteric pathogens1–3, including enterohemorrhagicEscherichia coli(EHEC) serotype O157:H7, an attaching and effacing (AE) food-borne pathogen that causes severe gastroenteritis, enterocolitis, bloody diarrhea, and acute renal failure (hemolytic uremic syndrome)4,5. Although gut microbes can provide colonization resistance by outcompeting some pathogens or modulating host defense provided by the gut barrier and intestinal immune cells, this phenomenon remains poorly understood. Emerging evidence suggests that small-molecule metabolites produced by the gut microbiota may mediate this process6. Here, we show that tryptophan (Trp)-derived metabolites produced by the gut bacteria protect the host againstCitrobacter rodentium, a murine AE pathogen widely used as a model for EHEC infection7,8, by activation of the host neurotransmitter dopamine receptor D2 (DRD2) within the intestinal epithelium. We further find that these Trp metabolites act through DRD2 to decrease expression of a host actin regulatory protein involved inC. rodentiumand EHEC attachment to the gut epithelium via formation of actin pedestals. Previously identified mechanisms of colonization resistance either directly affect the pathogen by competitive exclusion or indirectly by modulation of host defense mechanisms9,10, so our results delineate a noncanonical colonization resistance pathway against AE pathogens featuring an unconventional role for DRD2 outside the nervous system in controlling actin cytoskeletal organization within the gut epithelium. Our findings may inspire prophylactic and therapeutic approaches for improving gut health and treating gastrointestinal infections, which afflict millions globally.
Gut microbial community in proboscis monkeys (Nasalis larvatus): implications for effects of geographical and social factors
Authors: Jose Lilian , Lee Wanyi , Hanya Goro , Tuuga Augustine , Goossens Benoit , Tangah Joseph , Matsuda Ikki , Kumar Vijay Subbiah 
Published: March 2023

AbstractRecent technological advances have enabled comprehensive analyses of the previously uncharacterized microbial community in the gastrointestinal tracts of numerous animal species; however, the gut microbiota of several species, such as the endangered proboscis monkey (Nasalis larvatus) examined in this study, remains poorly understood. Our study sought to establish the first comprehensive data on the gut microbiota of free-ranging foregut-fermenting proboscis monkeys and to determine how their microbiota are affected locally by environmental factor, i.e. geographical distance, and social factor, i.e. number of adult females within harem groups and number of adults and subadults within non-harem groups, in a riparian forest in Sabah, Malaysian Borneo. Using 16S rRNA gene sequencing of 264 faecal samples collected from free-ranging proboscis monkeys, we demonstrated the trend that their microbial community composition is not particularly distinctive compared to other foregut and hindgut fermenting primates. The microbial alpha diversity was higher in larger groups and individuals inhabiting diverse vegetation (i.e. presumed to have a diverse diet). For microbial beta diversity, some measures were significant, showing higher values with larger geographical distances between samples. These results suggest that social factors such as increased interindividual interactions, which can occur with larger groups, as well as physical distances between individuals or differences in dietary patterns, may affect the gut microbial communities.
Gestational exposure to unmethylated CpG oligonucleotides dysregulates placental molecular clock network and fetoplacental growth dynamics, and disrupts maternal blood pressure circadian rhythms in rats
Authors: Bradshaw Jessica L. , Cushen Spencer C. , Ricci Contessa A. , Tucker Selina M. , Gardner Jennifer J. , Little Joel T. , Osikoya Oluwatobiloba , Goulopoulou Styliani 
Published: March 2023

AbstractBacterial infections and impaired mitochondrial DNA dynamics are associated with adverse pregnancy outcomes. Unmethylated cytosine-guanine dinucleotide (CpG) motifs are common in bacterial and mitochondrial DNA and act as potent immunostimulators. Here, we tested the hypothesis that exposure to CpG oligonucleotides (ODN) during pregnancy would disrupt blood pressure circadian rhythms and the placental molecular clock machinery, mediating aberrant fetoplacental growth dynamics. Rats were repeatedly treated with CpG ODN in the 3rdtrimester (gestational day, GD, 14, 16, 18) and euthanized on GD20 (near term) or with a single dose of CpG ODN and euthanized 4 hours after treatment on GD14. Hemodynamic circadian rhythms were analyzed via Lomb-Scargle periodogram analysis on 24-h raw data collected continuously via radiotelemetry. Ap-value ≥ 0.05 indicates the absence of a circadian rhythm. Following the first treatment with CpG ODN, maternal systolic and diastolic blood pressure circadian rhythms were lost (p≥ 0.05). Blood pressure circadian rhythm was restored by GD16 and remained unaffected after the second treatment with CpG ODN (p< 0.0001). Diastolic blood pressure circadian rhythm was again lost after the last treatment on GD18 (p≥ 0.05). CpG ODN increased placental expression ofPer2andPer3andTnfα(p≤ 0.05) and affected fetoplacental growth dynamics, such as reduced fetal and placental weights were disproportionately associated with increases in the number of resorptions in ODN-treated dams compared to controls. In conclusion, gestational exposure to unmethylated CpG DNA dysregulates placental molecular clock network and fetoplacental growth dynamics and disrupts blood pressure circadian rhythms.
A laser capture microdissection transcriptome ofM. truncatularoots responding to rhizobia reveals spatiotemporal tissue expression patterns of genes involved in nodule signaling and organogenesis
Authors: Schnabel Elise , Thomas Jacklyn , El-Hawaz Rabia , Gao Yueyao , Poehlman William , Chavan Suchitra , Pasha Asher , Esteban Eddi , Provart Nicholas , Feltus F. Alex , Frugoli Julia 
Published: March 2023

AbstractWe report a public resource for examining the spatiotemporal RNA expression of 54,893M. truncatulagenes during the first 72 hours of response to rhizobial inoculation. Using a methodology that allows synchronous inoculation and growth of over 100 plants in a single media container, we harvested the same segment of each root responding to rhizobia in the initial inoculation over a time course, collected individual tissues from these segments with laser capture microdissection, and created and sequenced RNA libraries generated from these tissues. We demonstrate the utility of the resource by examining the expression patterns of a set of genes induced very early in nodule signaling, as well as two gene families (CLE peptides and nodule specific PLAT-domain proteins) and show that despite similar whole root expression patterns, there are tissue differences in expression between the genes. Using a rhizobial response data set generated from transcriptomics on intact root segments, we also examined differential temporal expression patterns and determined that, after nodule tissue, the epidermis and cortical cells contained the most temporally patterned genes. We circumscribed gene lists for each time and tissue examined and developed an expression pattern visualization tool. Finally, we explored transcriptomic differences between the inner cortical cells that become nodules and those that do not, confirming that the expression of ACC synthases distinguishes inner cortical cells that become nodules and provide and describe potential downstream genes involved in early nodule cell division.
Cas12a/Cpf1 knock-in mice enable efficient multiplexed immune cell engineering
Authors: Dong Matthew B. , Tang Kaiyuan , Zhou Xiaoyu , Shen Johanna , Chen Krista , Kim Hyunu R. , Zhou Jerry , Cao Hanbing , Vandenbulcke Erica , Zhang Yueqi , Chow Ryan D. , Du Andrew , Suzuki Kazushi , Fang Shao-Yu , Majety Medha , Dai Xiaoyun , Chen Sidi 
Published: March 2023

SummaryCas9 transgenic animals have drastically accelerated the discovery of novel immune modulators. But due to its inability to process its own CRISPR RNAs (crRNAs), simultaneous multiplexed gene perturbations using Cas9 remains limited, especially by pseudoviral vectors. Cas12a/Cpf1, however, can process concatenated crRNA arrays for this purpose. Here, we created conditional and constitutive LbCas12a knock-in transgenic mice. With these mice, we demonstrated efficient multiplexed gene editing and surface protein knockdown within individual primary immune cells. We showed genome editing across multiple types of primary immune cells including CD4 and CD8 T cells, B cells, and bone-marrow derived dendritic cells. These transgenic animals, along with the accompanying viral vectors, together provide a versatile toolkit for a broad range ofex vivoandin vivogene editing applications, including fundamental immunological discovery and immune gene engineering.