bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dendritic cell-mediated responses to secretedCryptosporidiumeffectors are required for parasite-specific CD8+T cell responses
Authors: Haskins Breanne E. , Gullicksrud Jodi A. , Wallbank Bethan A. , Dumaine Jennifer E. , Guérin Amandine , Cohn Ian S. , O’Dea Keenan M. , Pardy Ryan D. , Merolle Maria I. , Shallberg Lindsey A. , Hunter Emma N. , Byerly Jessica H. , Smith Eleanor J. , Buenconsejo Gracyn Y. , McLeod Briana I. , Christian David A. , Striepen Boris , Hunter Christopher A. 
Published: August 2023

AbstractCryptosporidiumcauses debilitating diarrheal disease in patients with primary and acquired defects in T cell function. However, it has been a challenge to understand how this infection generates T cell responses and how they mediate parasite control. Here,Cryptosporidiumwas engineered to express a parasite effector protein (MEDLE-2) that contains the MHC-I restricted SIINFEKL epitope which is recognized by TCR transgenic OT-I CD8+T cells. These modified parasites induced expansion of endogenous SIINFEKL-specific and OT-I CD8+T cells that were a source of IFN-γ that could restrict growth ofCryptosporidium. This T cell response was dependent on the translocation of the effector and similar results were observed with another secreted parasite effector (ROP1). Although infection and these translocated effector proteins are restricted to intestinal epithelial cells (IEC), type I dendritic cells (cDC1) were required to generate CD8+T cell responses to these model antigens. These data sets highlightCryptosporidiumeffectors as targets of the immune system and suggest that crosstalk between enterocytes and cDC1s is crucial for CD8+T cell responses toCryptosporidium.
A future food boom rescues the negative effects of cumulative early-life adversity on adult lifespan in a small mammal
Authors: Petrullo Lauren , Delaney David , Boutin Stan , Lane Jeffrey E. , McAdam Andrew G. , Dantzer Ben 
Published: August 2023

ABSTRACTAdverse early-life conditions, even when transient, can have long-lasting effects on individual phenotypes and reduce lifespan across species. If these effects can be mitigated. by a high quality later-life environment, then differences in future resource access may explain variation in vulnerability and resilience to early-life adversity. Using 32 years of data on 1,000+ wild North American red squirrels, we tested the hypothesis that the negative effects of early-life adversity on lifespan can be buffered by later-life food abundance. We found that although cumulative early-life adversity was negatively associated with adult lifespan, this relationship was modified by future food abundance. Squirrels that experienced a naturally-occurring future food boom in the second year of life did not suffer reduced longevity despite early-life adversity. Experimental supplementation with additional food did not replicate this effect, though it did increase adult lifespan overall. Our results suggest a non-deterministic role for early-life conditions on later-life phenotypes, and highlight the importance of contextualizing the influence of harsh early-life conditions over an animal’s entire life course.
In vitro investigation of antibacterial activity of Gum Arabic prepared by two different processing methods against Enterococcus faecalis
Authors: Elmubarak Nuha , Ibrahim Yahia , Gareeballah Abbas , Sanhouri Nada 
Published: August 2023

AbstractBackgroundEntrococcus faecalis is a known cause of endodontic treatment failure. Synthetic drugs have been preferred for decades, but recently, many plants have been reported for their antibacterial activity.AimTo investigate the antibacterial effect of Gum Arabic (GA) processed with two different processing methods against Enterococcus faecalis.MethodAntibacterial susceptibility tests against Enterococcus faecalis (ATCC 29212) were performed for 200mg/ml ethanolic extracts of spray-dried and mechanically ground GA using Agar disc diffusion. Sodium Hypochlorite (1%), Chlorhexidine (0.2%), and Antibiotic multi-disc were used as positive controls, and ethanol (20%) as a negative. The inhibition zones diameters were measured.Serial dilutions of both types of Gum Arabic (100, 50, 25, 12.5 mg/ml) were tested for their antibacterial activity.ResultsIn Concentration 200 mg/ml, spray-dried GA displayed a significantly greater inhibition zone against E. faecalis than mechanically ground(P=0.02).Both types of Gum Arabic exhibited lower antibacterial activity than chlorhexidine (0.2%). However, only mechanically ground GA showed significant result(P=0.005).Spray-dried GA showed significantly higher antibacterial activity against than Tetracycline 300mcg(P=0.005).The antibacterial activity of spray-dried GA exceeded that of mechanically ground in all concentrations of serial dilutions, except for 12.5mg/ml, both are similar.Conclusionprocessing method of Gum Arabic affects its antibacterial potency against E. faecalis. In high concentrations, spray-dried GA is active antibacterial, while mechanically ground is non-active.Decreasing the concentration of mechanically ground GA increases its inhibitory effect, but the opposite effect was observed with spray-dried GA.
Mapping Human Tissues with Highly Multiplexed RNA in situ Hybridization
Authors: Kalhor Kian , Chen Chien-Ju , Lee Ho Suk , Cai Matthew , Nafisi Mahsa , Que Richard , Palmer Carter , Yuan Yixu , Zhang Yida , Song Jinghui , Knoten Amanda , Lake Blue B. , Gaut Joseph P. , Keene Dirk , Lein Ed , Kharchenko Peter V. , Chun Jerold , Jain Sanjay , Fan Jian-Bing , Zhang Kun 
Published: August 2023

AbstractIn situ transcriptomic techniques promise a holistic view of tissue organization and cell-cell interactions. Recently there has been a surge of multiplexed RNA in situ techniques but their application to human tissues and clinical biopsies has been limited due to their large size, general lower tissue quality and high background autofluorescence. Here we report DART-FISH, a versatile padlock probe-based technology capable of profiling hundreds to thousands of genes in centimeter-sized human tissue sections at cellular resolution. We introduced an omni-cell type cytoplasmic stain, dubbed RiboSoma that substantially improves the segmentation of cell bodies. We developed a computational decoding-by-deconvolution workflow to extract gene spots even in the presence of optical crowding. Our enzyme-free isothermal decoding procedure allowed us to image 121 genes in a large section from the human neocortex in less than 10 hours, where we successfully recapitulated the cytoarchitecture of 20 neuronal and non-neuronal subclasses. Additionally, we demonstrated the detection of transcripts as short as 461 nucleotides, including neuropeptides and discovered new cortical layer markers. We further performed in situ mapping of 300 genes on a diseased human kidney, profiled >20 healthy and pathological cell states, and identified diseased niches enriched in transcriptionally altered epithelial cells and myofibroblasts.
Neural Networks Are Tuned Near Criticality During a Cognitive Task and Distanced from Criticality In a Psychopharmacological Model of Alzheimer’s Disease
Authors: Habibollahi Forough , Sun Dechuan , Burkitt Anthony N. , French Chris 
Published: August 2023

ABSTRACTDynamical systems exhibit transitions between ordered and disordered states and “criticality” occurs when the system lies at the borderline between these states at which the input is neither strongly damped nor excessively amplified. Impairments in brain function such as dementia or epilepsy could arise from failure of adaptive criticality, and deviation from criticality may be a potential biomarker for cognition-related neurological and psychiatric impairments. Miniscope wide-field calcium imaging of several hundred hippocampal CA1 neurons in freely-behaving mice was studied during rest, a cognitive task of novel object recognition (NOR), and novel object recognition following scopolamine administration that greatly impairs spatial memory encoding. We find that while hippocampal networks exhibit characteristics of a near-critical system at rest, the network activity shifts significantly closer to a critical state when the mice engaged in the NOR task. The dynamics shift away from criticality with impairment of novel object performance due to scopolamine-induced memory impairment. These results support the concept that hippocampal neural networks move closer to criticality when successfully processing increased cognitive load, taking advantage of maximal dynamical range, information content, and transmission that occur in critical regimes.
Distinct Microstructural Heterogeneities Underpin Specific Micromechanical Properties in Human ACL Femoral and Tibial Entheses
Authors: Fang Jinghua , Wang Xiaozhao , Lai Huinan , Li Wenyue , Pan Zongyou , Mao Renwei , Yan Yiyang , Xie Chang , Lin Junxin , Sun Wei , Li Rui , Wang Jiajie , Dai Jiacheng , Xu Kaiwang , Yu Xinning , Xu Tengjing , Duan Wangping , Qian Jin , Ouyang Hongwei , Dai Xuesong 
Published: August 2023

ABSTRACTThe anterior cruciate ligament (ACL) is anchored to the femur and tibia by a specialized interface tissue called the enthesis, which transfers forces in multiple directions and magnitudes without accruing fatigue damage during loading cycles over a lifetime. However, the precise structural and mechanical characteristics of the ACL femoral enthesis (FE) and tibial enthesis (TE) and their intricate interplay are unknown. In this study, we identified two ultrathin-graded mineralization regions in the FE (∼21 μm) and TE (∼14 μm), both of which exhibited distinct biomolecular compositions and mineral assembly patterns. FE interface exhibited progressively maturing hydroxyapatites (HAps), whereas minerals at the TE interface region changed from an amorphous phase (ACP) to HAps with increasing crystallinity. The LC-MS/MS results revealed that MGP protein uniquely enriched at the TE interface may be favorable for stabilizing ACP, while CLEC11A enriched at the FE interface could facilitate osteogenesis of the interface. The finite element analysis results indicated that the FE model was more resistant to shearing, while the TE model facilitated tensile resistance. It suggested that the great discrepancy in biomolecular expression and the corresponding mineral assembling heterogeneities together contributed to the superior mechanical properties of both the FE and TE models. These findings provide new perspectives regarding the management of ACL injury and the development of high-performance interface materials.
Human intestinal organoid-derived PDGFRα+ mesenchymal stroma empowers LGR4+ epithelial stem cells
Authors: JunLong Chen , Horiuchi Shinichiro , Kuramochi So , Kawasaki Tomoyuki , Kawasumi Hayato , Akiyama Saeko , Arai Tomoki , Morinaga Kenichi , Kimura Tohru , Kiyono Tohru , Akutsu Hidenori , Ishida Seiichi , Umezawa Akihiro 
Published: August 2023

AbstractThe columnar epithelial cells comprising the intestinal tract, stomach, and uterus can be cultured in vitro as organoids or in adherent culture. However, the proliferation of these columnar epithelial cells in adherent culture is limited. Likewise, human pluripotent stem cell (hPSC)-derived intestinal epithelial cells do not show extensive or clonal propagation in vitro. In this study, we induced proliferation of hPSC-derived small intestinal epithelium for a longer time by utilizing mesenchymal stromal cells derived from self-organized intestinal organoids as feeders. The proliferating cells exhibited columnar form, microvilli and glycocalyx formation, and cell polarity, as well as expression of drug-metabolizing enzymes and transporters. It is noteworthy that small intestinal epithelial stem cells cannot be cultured in adherent culture alone, and the stromal cells cannot be replaced by other feeders. Organoid-derived mesenchymal stromal cells resemble the trophocytes essential for maintaining small intestinal epithelial stem cells, and play a crucial role in adherent culture. The high proliferative expansion, productivity, and functionality of hPSC-derived small intestinal epithelial stem cells could have potential applications in pharmacokinetic and toxicity studies and regenerative medicine.
Syntaxin clusters and cholesterol affect the mobility of Syntaxin1a
Authors: Weisgerber Alan W. , Otruba Zdeněk , Knowles Michelle K 
Published: August 2023

ABSTRACTSyntaxin1a (Syx1a) is essential for stimulated exocytosis in neuroendocrine cells. The vesicle docking process involves the formation of nanoscale Syx1a domains on the plasma membrane and the Syx1a clusters disintegrate during the fusion process. Syx1a nanodomains are both static yet empty and refill; the process by which these clusters maintain this balance is unclear. In this work, the dynamics of the Syx1a molecules is elucidated relative to the cluster position through a labeling strategy that allows both the bulk position of the Syx clusters to be visualized concurrent with the trajectories of single Syx1a molecules on the surface of PC12 cells. Single Syx1a molecules were tracked in time relative to cluster positions to decipher how Syx1a moves within a cluster and when clusters are not present. Syx1a is mobile on the plasma membrane, more mobile at the center of clusters, and less mobile near the edges of clusters; this depends on the presence of the N-terminal Habc domain and cholesterol, which are essential for proper exocytosis. Simulations of the dynamics observed at clusters support a model where clusters are maintained by a large cage (r= 100 nm) within which Syx1a remains highly mobile within the cluster (r= 50 nm). The depletion of cholesterol dramatically reduces the mobility of Syx1a within clusters and less so over the rest of the plasma membrane. This suggests that fluidity of Syx1a supramolecular clusters is needed for function.STATEMENT OF SIGNIFICANCESyntaxin1a (Syx1a) is essential for exocytosis where the vesicle docking process involves the formation of nanoscale Syx1a domains on the plasma membrane. Syx1a nanodomains are both static yet empty and refill; the process by which these clusters maintain this balance is unclear. In this work, the dynamics of the Syx1a molecules was elucidated relative to the cluster position on the surface of PC12 cells. Single molecules were tracked relative to clusters and Syx1a is mobile on the plasma membrane, more so within a cluster and less mobile near the edges of clusters. This depends on the presence of the N-terminal domain and cholesterol, which are essential for proper exocytosis. This suggests that fluidity of Syx1a clusters is needed for function.
Climate change should drive mammal defaunation in tropical dry forests
Authors: Moura Mario R. , Oliveira Gibran A. , Paglia Adriano P. , Pires Mathias M. , Santos Bráulio A. 
Published: August 2023

ABSTRACTHuman-induced climate change has intensified negative impacts on socioeconomic factors, the environment, and biodiversity, including changes in rainfall patterns and an increase in global average temperatures. Drylands are particularly at risk, with projections suggesting they will become hotter, drier, and less suitable for a significant portion of their species, potentially leading to mammal defaunation. We use ecological niche modelling and community ecology biodiversity metrics to examine potential geographical range shifts of non-volant mammal species in the largest Neotropical dryland, the Caatinga, and evaluate impacts of climate change on mammal assemblages. According to projections, 85% of the mammal species will lose suitable habitats, with one quarter of species projected to completely lose suitable habitats by 2060. This will result in a decrease in species richness for more than 90% of assemblages and an increase in compositional similarity to nearby assemblages (i.e., reduction in spatial beta diversity) for 70% of the assemblages. Small-sized mammals will be the most impacted and lose most of their suitable habitats, especially in highlands. The scenario is even worse in the eastern half of Caatinga where habitat destruction already prevails, compounding the threats faced by species there. While species-specific responses can vary with respect to dispersal, behaviour, and energy requirements, our findings indicate that climate change can drive mammal assemblages to biotic homogenisation and species loss, with drastic changes in assemblage trophic structure. For successful long-term socioenvironmental policy and conservation planning, it is critical that findings from biodiversity forecasts are considered.
BMP7 promotes cardiomyocyte regeneration
Authors: Bongiovanni Chiara , Bueno-Levy Hanna , Pena Denise Posadas , Bono Irene Del , Redaelli Simone , Bergen Max , Pra Silvia Da , Sacchi Francesca , Miano Carmen , Boriati Stefano , Pontis Francesca , Romaniello Donatella , Mazzeschi Martina , Petraroia Ilaria , Tassinari Riccardo , Kellerer Laura , Lauriola Mattia , Ventura Carlo , Heermann Stephan , Weidinger Gilbert , Tzahor Eldad , D’Uva Gabriele 
Published: August 2023

AbstractZebrafish has a remarkable and lifelong ability for cardiac regeneration after severe damage, whereas mammals lose their innate capacity for heart regeneration during early postnatal development. This study aimed to investigate whether the decreased production of growth factors during postnatal mammalian development contributes to the exit of cardiomyocytes from the cell cycle and the reduction in cardiac regenerative ability.We identified growth factors with declining expression levels during early postnatal life in the mouse model and assessed the pro-proliferative ability of these factors on neonatal murine primary cardiomyocytesin vitro. Our findings confirmed the previously reported pro-proliferative effects of NRG1, IL1b, RANKL, IGF2 and IL6, while also identifying novel potential pro-regenerative growth factors. Among them, BMP7 exhibited the most pronounced efficacy.Bmp7 knockdown interfered with the proliferation of neonatal mouse cardiomyocytes in culture and adult bmp7 mutant zebrafish displayed reduced cardiomyocyte proliferation during heart regeneration, indicating that Bmp7 is crucial for cardiomyocyte proliferation in the regenerative stages of mouse and zebrafish hearts. Conversely,bmp7overexpression was sufficient to boost cardiomyocyte cycling in regenerating zebrafish hearts, while BMP7 administration stimulated mouse cardiomyocyte cycling at postnatal-day-7, when cardiomyocytes ceased to proliferate, and enhanced cardiomyocyte regenerationin vivoin adult mice following myocardial infarction.Mechanistically, BMP7-induced proliferation was mediated by type I BMP receptors BMPR1A and ACVR1, and type II receptors ACVR2A and BMPR2. Downstream signalling involved SMAD5, ERK and AKT.In conclusion, the administration of BMP7 holds promise as a strategy to stimulate heart regeneration following cardiac injury.
Multi-omics analysis reveals critical cis-regulatory roles of transposable elements in livestock genomes
Authors: Wang Chao , Lei Bowen , Bao Yongzhou , Wang Zhen , Chen Choulin , Zhang Yuanyuan , Qin Shenghua , Sun Tao , Tang Zhonglin , Liu Yuwen 
Published: August 2023

AbstractAs a major source of genetic and regulatory variation in their host genome, transposable elements (TEs) have gained a growing interest in research on humans and model organisms. In this species, integrative analysis of multi-omics data has shed light on the regulatory functions of TEs. However, there remains a notable gap in our understanding of TEs in domesticated animals. we annotated TEs in the genomes of pigs, cattle, and chickens, respectively, and systematically compared the genome distributions and amplification patterns of TEs across these three species. Furthermore, by integrating multi-tissue RNA-seq, ATAC-seq, and histone modification ChIP-seq data, we explored the expression atlas of TEs and their contribution to cis-regulatory elements (CREs) in different tissues of the three species. Most importantly, we developed a novel computational framework that revealed TE-mediated gene regulatory networks (TE-GRNs) underlying tissue-related biological processes. To demonstrate the power of this approach, we applied our framework to analyze liver tissues across the three different species. Overall, our research provides novel insights into the regulatory functions of TEs in livestock animals and highlights a computational framework to uncover TE-GRNs in various biological contexts.
Pneumonic plague protection induced by a monophosphoryl lipid A decoratedYersiniaouter-membrane-vesicle vaccine
Authors: Majumder Saugata , Das Shreya , Li Peng , Yang Nicole , Dellario Hazel , Sui Haixin , Guan Ziqiang , Sun Wei 
Published: August 2023

AbstractA newly constructedYersinia pseudotuberculosismutant (YptbS46) carrying thelpxEinsertion andpmrF-Jdeletion exclusively synthesized an adjuvant form of lipid A, monophosphoryl lipid A (MPLA). Outer membrane vesicles (OMVs) isolated from YptbS46 harboring anlcrVexpression plasmid, pSMV13, were designated OMV46-LcrV, which contained MPLA and high amounts of LcrV and displayed low activation of Toll-like receptor 4 (TLR4).Similar to the previous OMV44-LcrV, intramuscular prime-boost immunization with 30 µg of OMV46-LcrV exhibited substantially reduced reactogenicity and conferred complete protection to mice against a high-dose of respiratoryY. pestischallenge. OMV46-LcrV immunization induced robust adaptive responses in both lung mucosal and systemic compartments and orchestrated innate immunity in the lung, which were correlated with rapid bacterial clearance and unremarkable lung damage duringY. pestischallenge. Additionally, OMV46-LcrV immunization conferred long-term protection. Moreover, immunization with reduced doses of OMV46-LcrV exhibited further lower reactogenicity and still provided great protection against pneumonic plague. Our studies strongly demonstrate the feasibility of OMV46-LcrV as a new type of plague vaccine candidate.
Comparative analysis of the molecular starvation response of Southern Ocean copepods
Authors: Berger Cory A. , Steinberg Deborah K. , Copeman Louise A. , Tarrant Ann M. 
Published: August 2023

AbstractLarge lipid-storing copepods dominate mesozooplankton biomass in the polar oceans and form a critical link between primary production and higher trophic levels. The ecological success of these species depends on their ability to survive periods of food deprivation in a highly seasonal environment, but the molecular changes that mediate starvation tolerance in these taxa are unknown. We conducted starvation experiments for two dominant Southern Ocean copepods,Calanoides acutusandCalanus propinquus, allowing us to compare the molecular starvation response between species. These species differ in life history, diet, and metabolic traits, and expressed overlapping but distinct transcriptomic responses to starvation. Most starvation-response genes were species-specific, but we identified a conserved core set of starvation-response genes related to RNA and protein metabolism. We used phylotranscriptomics to place these results in the context of copepod evolution and found that starvation-response genes are under strong purifying selection at the sequence level and stabilizing selection at the expression level, consistent with their role in mediating essential biological functions. Selection on starvation-response genes was especially strong in our focal lipid-storing lineage relative to other copepod taxa, underscoring the significance of starvation tolerance for these species. We also found that certain key lipid enzymes (elongases and desaturases) have experienced diversification and positive selection in lipid-storing lineages, reflecting the unique lipid storage needs of these animals. Our results shed light on the molecular adaptations of high-latitude zooplankton to variable food conditions, and suggest that starvation-response genes are under particularly strong sequence and expression constraints.