bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of surface geometry on light exposure, photoacclimation and photosynthetic energy acquisition in zooxanthellate corals
Authors: López-Londoño Tomás , Enríquez Susana , Iglesias-Prieto Roberto 
Published: July 2023

AbstractSymbiotic corals display a great array of morphologies, each of which has unique effects on light interception and the photosynthetic performance ofin hospitezooxanthellae. Changes in light availability elicit photoacclimation responses to optimize the energy balances in primary producers, extensively documented for corals exposed to contrasting light regimes along depth gradients. Yet, response variation driven by coral colony geometry and its energetic implications on colonies with contrasting morphologies remain largely unknown. In this study, we assessed the effect of the inclination angle of coral surface on light availability, short- and long-term photoacclimation responses, and potential photosynthetic usable energy. Increasing surface inclination angle resulted in an order of magnitude reduction of light availability, following a linear relationship explained by the cosine law and relative changes in the direct and diffuse components of irradiance. The light gradient induced by surface geometry triggered photoacclimation responses comparable to those observed along depth gradients: changes in the quantum yield of photosystem II, photosynthetic parameters, and optical properties and pigmentation of the coral tissue. Differences in light availability and photoacclimation driven by surface inclination led to contrasting energetic performance. Horizontally and vertically oriented coral surfaces experienced the largest reductions in photosynthetic usable energy as a result of excessive irradiance and light-limiting conditions, respectively. This pattern is predicted to change with depth or local water optical properties. Our study concludes that colony geometry plays an essential role in shaping the energy balance and determining the light niche of zooxanthellate corals.
Neurotrophin-3 from the dentate gyrus supports postsynaptic sites of mossy fiber-CA3 synapses and contextual memory
Authors: Tan Ji-Wei , Xu Haifei , Liao Guey-Ying , An Juan Ji , Xu Baoji 
Published: July 2023

AbstractAt the center of the hippocampal tri-synaptic loop are synapses formed between mossy fiber (MF) terminals from granule cells in the dentate gyrus (DG) and proximal dendrites of CA3 pyramidal neurons. However, the molecular mechanism regulating the development and function of these synapses is poorly understood. In this study, we showed that neurotrophin-3 (NT3) was expressed in nearly all mature granule cells but not CA3 cells. We selectively deleted the NT3-encodingNtf3gene in the DG during the 1sttwo postnatal weeks to generate aNtf3conditional knockout (Ntf3-cKO). Ntf3-cKO mice had normal hippocampal cytoarchitecture but displayed elevated anxiety level and impairments in contextual memory, spatial reference memory and nest building. As MF-CA3 synapses are essential for encoding of contextual memory, we examined synaptic transmission at these synapses using ex vivo electrophysiological recordings. We found that Ntf3-cKO mice showed impaired basal synaptic transmission due to deficits in excitatory postsynaptic currents mediated by AMPA receptors but normal presynaptic function and intrinsic excitability of CA3 pyramidal neurons. Consistent with this selective postsynaptic deficit, Ntf3-cKO mice had fewer and smaller thorny excrescences on proximal apical dendrites of CA3 neurons and lower GluR1 levels in the stratum lucidum area where MF-CA3 synapses reside but normal MF terminals, compared with control mice. Thus, our study indicates that NT3 expressed in the dentate gyrus is crucial for the postsynaptic structure and function of MF-CA3 synapses and hippocampal-dependent memory.
Urine proteomic signatures of histological class, activity, chronicity, and treatment response in lupus nephritis
Authors: Fava Andrea , Buyon Jill , Magder Laurence , Hodgin Jeff , Rosenberg Avi , Demeke Dawit S. , Rao Deepak A. , Arazi Arnon , Celia Alessandra Ida , Putterman Chaim , Anolik Jennifer H. , Barnas Jennifer , Dall’Era Maria , Wofsy David , Furie Richard , Kamen Diane , Kalunian Kenneth , James Judith A. , Guthridge Joel , Atta Mohamed G. , Trujillo Jose Monroy , Fine Derek , Clancy Robert , Belmont H. Michael , Izmirly Peter , Apruzzese William , Goldman Daniel , Berthier Celine C. , Hoover Paul , Hacohen Nir , Raychaudhuri Soumya , Davidson Anne , Diamond Betty ,   Accelerating Medicines Partnership in RA/SLE network, Petri Michelle 
Published: July 2023

AbstractLupus nephritis (LN) is a pathologically heterogenous autoimmune disease linked to end-stage kidney disease and mortality. Better therapeutic strategies are needed as only 30-40% of patients completely respond to treatment. Noninvasive biomarkers of intrarenal inflammation may guide more precise approaches. Because urine collects the byproducts of kidney inflammation, we studied the urine proteomic profiles of 225 LN patients (573 samples) in the longitudinal Accelerating Medicines Partnership (AMP) in RA/SLE cohort. Urinary biomarkers of monocyte/neutrophil degranulation (i.e., PRTN3, S100A8, azurocidin, catalase, cathepsins, MMP8), macrophage activation (i.e., CD163, CD206, galectin-1), wound healing/matrix degradation (i.e., nidogen-1, decorin), and IL-16 characterized the aggressive proliferative LN classes and significantly correlated with histological activity. A decline of these biomarkers after 3 months of treatment predicted the 1-year response more robustly than proteinuria, the standard of care (AUC: CD206 0.92, EGFR 0.9, CD163 0.89, proteinuria 0.8, p<0.01). Candidate biomarkers were validated and provide new potentially treatable targets. We propose these biomarkers of intrarenal immunological activity as noninvasive tools to diagnose LN, guide treatment, and as surrogate endpoints for clinical trials. These findings provide new insights into the processes involved in LN activity. This dataset (matching other AMP omics) is a public resource to generate and test hypotheses and validate biomarkers.
Intranasal lavage with hypochlorous acid safely reduces the symptoms in the ambulatory patient with COVID-19
Authors: Abner Monique Lisa 
Published: July 2023

ABSTRACTOBJECTIVEThis study was designed to investigate intranasal lavage with a hypochlorous acid solution in the reduction of symptoms in the ambulatory COVID-19 patient.STUDY DESIGNStudy approval granted by the Institutional Review Board of Reading Hospital (IRB 036-20), with informed consent obtained from all adult participants(age>18 years).SETTINGAll enrollees, taken from the same ambulatory testing facility, received nasopharyngeal swabs for COVID-19 testing by reverse transcription polymerase chain (RT-PCR) or the COVID-19 antigen specific test (Binax NOW, Abbott Lab)METHODSConvenience sampling methodology was utilized. Each enrollee was provided with the study devices which included a Nasaflo Neti Pot (NeilMed Pharmaceutical, Inc.), and the hypochlorous acid solution (Vashe Wound Solution, Urgo Medical North America, LLC). Participants were instructed to irrigate each nostril with 120 cc (four ounces) of the solution for ten consecutive days, and record the presence or absence of symptoms in a scripted diary log.RESULTSThe study included 88 patients of which 74 (84.1%) completed the ten days of nasal lavage. All data analysis was conducted using SPSS version 25.0.Chi square test of association found no significant difference related to gender, age group race, ethnicity, residence, or living arrangements (all p-values > 0.05). There were no statistical differences in any of the co-morbid conditions. Mild adverse reactions included burning, epistaxis, and oral metallic taste. No enrollees required mechanical ventilation. There were no deaths.CONCLUSIONThis study suggests the feasibility and safety of using intranasal lavage with a hypochlorous acid solution in relieving symptoms in the ambulatory Covid-19 patient.
Phylogenetic diversity and functional potential of large and cell-associated viruses in the Bay of Bengal
Authors: Minch Benjamin , Akter Salma , Weinheimer Alaina , Rahman M Shaminur , Parvez Md Anowar Khasru , Rahman Sabita Rezwana , Ahmed Md Firoz , Moniruzzaman Mohammad 
Published: July 2023

AbstractThe Bay of Bengal (BoB), the largest bay in the world, provides valuable ecosystem services such as fishing and recreation to millions of people living along its coast and has a significant economic value. The BoB is impacted by various environmental factors such as seasonal monsoons and multiple freshwater inputs, and this region is particularly vulnerable to sea-level rise and increased frequency of devastating cyclones that are predicted to be exacerbated due to global climate change. These factors are also compounded by anthropogenic influences from tourism and development, making it an important ecosystem to understand and study from a global change perspective. Despite its importance, microbial diversity and ecology have remained largely understudied in this region. In this study, we describe the diversity and putative functional importance of large and cell-associated (that is, originating from the cellular size fraction) viruses from two coastal sites in the BoB, with an emphasis on giant viruses and large phages. Sites chosen for this study include Cox’s Bazar, a populated beach with multiple freshwater inputs, and Saint Martin Island, a resort island that has considerably less human influence compared to Cox’s Bazar. Through metagenomic sequencing, we were able to identify a more abundant and more diverse viral community at Cox’s Bazar consisting of many viruses that are indicators of freshwater intrusion and runoff. Overall, 1962 putative phage genome bins were obtained ranging from 10 - 655 kilobase pairs (kbp) in sizes. Of these genomes, 16 from Saint Martin were found to be larger than 100kbp which we deemed “large” phages, and we were able to reconstruct a phylogeny of these large phages using the TerL gene as a marker. This phylogeny revealed clades enriched in large phages and a high diversity of large phage candidates in the Bay of Bengal coast. Protein annotation analysis showed a wide variety of functionality from both sites with more auxiliary metabolic genes (AMGs) found in the Cox’s Bazar viral community. Five giant virus (Phylum Nucleocytoviricota) genomes were also reconstructed from Cox’s Bazar and identified as belonging to the orders Imitervirales and Pandoravirales. These genomes ranged from 83 - 876 kbp in size and contained a wide range of encoded functionalities. To the best of our knowledge, our study represents the first insights on the phylogenetic and functional diversity of viruses in the Bay of Bengal. These results thus provide an important foundation for further studies on the impact of host-virus interactions on biogeochemical cycles and microbial food web in this understudied marine environment.
Intestinal LKB1 loss drives a pre-malignant program along the serrated cancer pathway
Authors: Plugge S.F. , Ma H. , van der Vaart J.Y. , Sprangers J. , Morsink F.H.M. , Xanthakis D. , Jamieson C. , Keijzer A.R. , Margaritis T. , Candelli T. , Straver R. , de Ridder J. , Holstege F.C.P. , de Leng W.W.J. , Offerhaus G.J.A. , Merenda A. , Maurice M.M. 
Published: July 2023

AbstractBackground & AimsHeterozygous inactivating mutations of Liver Kinase B1 (LKB1) are causative to the Peutz-Jeghers syndrome (PJS), a hereditary disease characterized by gastrointestinal polyposis and increased cancer susceptibility. While LKB1 loss-induced polyp formation has been ascribed to non-epithelial tissues, how LKB1 deficiency increases cancer risk of patients by altering the phenotypical landscape and hierarchical organization of epithelial tissues remains poorly understood.MethodsUsing CRISPR/Cas9, we generated heterozygous and homozygous Lkb1-deficient mouse small intestinal organoids. These organoids were characterized by a combined approach that integrates imaging, bulk and single-cell RNA sequencing and growth assays. Our findings were validated in human PJS-derived tissues using immunohistochemistry and linked to colorectal cancer profiles using the TCGA cancer database.ResultsOur results reveal that heterozygous Lkb1 loss is sufficient to push cells into a premalignant transcriptional program associated with serrated colorectal cancer, which is further amplified by loss-of-heterozygosity. This altered epithelial growth state associates with persistent features of regeneration and enhanced EGFR ligand and receptor expression, conferring niche-independent growth properties to Lkb1-deficient organoids. Moreover, LKB1 loss-of-function mutations co-occur with serrated colorectal cancer driver mutations for which synergistic cooperation was experimentally confirmed for Kras mutation and Lkb1-deficiency by assessing growth properties and transcriptomes.ConclusionsHeterozygous loss of LKB1 pushes intestinal cells into a chronic regenerative state which is amplified upon loss-of-heterozygosity. Lkb1-deficiency thereby establishes fertile ground for serrated colorectal cancer formation in the intestine, explaining the increased cancer risk observed in PJS.
The role of the unicellular bottleneck and organism size in mediating cooperation and conflict among cells at the onset of multicellularity
Authors: Ackermann Sydney , Osmond Matthew 
Published: July 2023

AbstractEvolutionary transitions in individuality introduce new levels of selection and thus enable discordant selection, threatening the stability of the transition. Cheating is such a problem for multicellularity. So why have so many transitions to multicellularity persisted? One possibility is that the unicellular propagule maintains cooperation among cells by purging cheaters. The evolution of propagule size has been modeled previously, but in the absence of competition between individuals, which may often select for larger propagules. How does the nature of competition between individuals affect the optimal propagule size in the presence of cheating? Here we take a model of early multicellularity, add phenotypic switching between cheating and cooperative phenotypes, and simulate size-dependent competition on a lattice, which allows us to tune the strength of interspecific vs. intraspecific competition via dispersal. As expected, cheating favors strategies with unicellular propagules while size-dependent competition favors strategies with few large propagules (binary fragmentation). How these opposing forces resolve depends on dispersal. Local dispersal, which intensifies intraspecific competition, favors binary fragmentation, which reduces intraspecific competition for space, with one unicellular propagule. Global dispersal instead favours multiple fission when cheating is common. We also find that selfishness promotes smaller body size, despite direct opposing selection from competition. Our results shed light on the evolution of multicellular life cycles and the prevalence of a unicellular stage in the multicellular life cycle across the tree of life.Author summaryA multicellular organism is a group of cooperating cells. But wherever there is cooperation there is the temptation to cheat. Having offspring that start as a single cell (a unicellular bottleneck) has been hypothesized as an adaptation to purge lineages of cheating cells. We model the evolution of offspring size but add competition between individuals, which may select against small unicellular offspring. We find that having some unicellular offspring is still a successful strategy, but how many depends on the nature of competition.
DeepDynaForecast: Phylogenetic-informed graph deep learning for epidemic transmission dynamic prediction
Authors: Sun Chaoyue , Fang Ruogu , Salemi Marco , Prosperi Mattia , Magalis Brittany Rife 
Published: July 2023

In the midst of an outbreak or sustained epidemic, reliable prediction of transmission risks and patterns of spread is critical to inform public health programs. Projections of growth or decline among specific risk groups can aid in optimizing interventions, particularly when resources are limited. Phylogenetic trees have been widely used in the detection of transmission chains and high-risk populations. Moreover, tree topology and the incorporation of population parameters (phylodynamics) can be useful to reconstruct the evolutionary dynamics of an epidemic across space and time among individuals. We now demonstrate the utility of phylodynamic trees for infection forecasting in addition to backtracking, developing a phylogeny-based deep learning system, calledDeepDynaForecast. Our approach leverages a primal-dual graph learning structure with shortcut multi-layer aggregation, and it is suited for the early identification and prediction of transmission dynamics in emerging high-risk groups. We demonstrate the accuracy ofDeepDynaForecastusing simulated outbreak data and the utility of the learned model using empirical, large-scale data from the human immunodeficiency virus epidemic in Florida between 2012 and 2020. Our framework is available as open-source software (MIT license) at:https://github.com/lab-smile/DeepDynaForcast.Author SummaryDuring an outbreak or sustained epidemic, accurate prediction of patterns in transmission risk can reliably inform public health strategies. Projections indicating growth or decline of transmission for specific risk groups can significantly enhance the optimization of interventions, especially when resources are limited. To address this, we presentDeepDynaForecast, a cutting-edge deep learning algorithm designed for forecasting pathogen transmission dynamics. Uniquely,DeepDynaForecastwas trained on in-depth simulation data and used more information from the phylogenetic tree of pathogen sequence data than any other algorithm in the field to date, allowing classification of samples according to their dynamics (growth, static, or decline) with incredible accuracy. We evaluated the model’s performance using both simulated outbreak data and empirical, large-scale data from the HIV epidemic in Florida between 2012 and 2020. We concludeDeepDynaForecastrepresents a significant advancement in genomics-mediated pathogen transmission characterization and has the potential to catalyze new research directions within virology, molecular biology, and public health.
Reliable interpretability of biology-inspired deep neural networks
Authors: Esser-Skala Wolfgang , Fortelny Nikolaus 
Published: July 2023

AbstractDeep neural networks display impressive performance but suffer from limited interpretability. Biology-inspired deep learning, where the architecture of the computational graph is based on biological knowledge, enables unique interpretability where real-world concepts are encoded in hidden nodes, which can be ranked by importance and thereby interpreted. In such models trained on single-cell transcriptomes, we previously demonstrated that node-level interpretations lack robustness upon repeated training and are influenced by biases in biological knowledge. Similar studies are missing for related models. Here, we test and extend our methodology for reliable interpretability in P-NET, a biology-inspired model trained on patient mutation data. We observe variability of interpretations and susceptibility to knowledge biases, and identify the network properties that drive interpretation biases. We further present an approach to control the robustness and biases of interpretations, which leads to more specific interpretations. In summary, our study reveals the broad importance of methods to ensure robust and bias-aware interpretability in biology-inspired deep learning.
EHMT2/G9a-Inhibition Reprograms Cancer-Associated Fibroblasts (CAFs) to a More Differentiated, Less Proliferative and Invasive State
Authors: Wu Nila C , Quevedo Rene , Nurse Michelle , Hezaveh Kebria , Liu Haijiao , Sun Fumao , Muffat Julien , Sun Yu , Simmons Craig A , McGaha Tracy L , Prinos Panagiotis , Arrowsmith Cheryl H , Ailles Laurie , D’Arcangelo Elisa , McGuigan Alison P 
Published: July 2023

AbstractCancer-associated fibroblasts (CAFs) have previously been shown to play a pivotal role in multiple cancer dynamics, including mediating tumor cell invasion: their pro-invasive secretory profile and ability to remodel the extracellular matrix (ECM) architecture particularly promote tumor progression through tumor cell invasion into surrounding tissue areas and beyond. Given that reduced CAF abundance in tumors correlates with improved outcomes in various cancers, we set out to identify epigenetic targets involved in CAF activation in the tumor-stromal margin to reduce overall tumor aggressiveness. Using the GLAnCE (Gels for Live Analysis of Compartmentalized Environments) co-culture platform, we performed an image-based, phenotypic screen and identified EHMT2 (also known as G9a), an epigenetic enzyme that targets the methylation of histone 3 lysine 9 (H3K9), as the most potent modulator of CAF abundance and CAF-mediated tumor cell invasion. Transcriptomic and functional analysis of EHMT2-inhibited CAFs revealed the involvement of EHMT2 in driving CAFs towards a pro-invasive phenotype. Further, EHMT2 signaling mediated CAF hyperproliferation, a feature that is typically associated with activated fibroblasts present in tumors, but the molecular basis for which has not thus far been identified. This study suggests a role for EHMT2 as a regulator of CAF hyperproliferation within the tumor mass, which in turn magnifies CAF-induced pro-invasive effects on tumor cells.
Persistent effects of intramammary ceftiofur treatment on the gut microbiome and antibiotic resistance in dairy cattle
Authors: Vasco Karla A. , Carbonell Samantha , Sloup Rebekah E. , Bowcutt Bailey , Colwell Rita R. , Graubics Karlis , Erskine Ronald , Norby Bo , Ruegg Pamela L. , Zhang Lixin , Manning Shannon D. 
Published: July 2023

ABSTRACTIntramammary (IMM) ceftiofur treatment is commonly used in dairy farms to prevent mastitis, though its impact on the cattle gut microbiome and selection of antibiotic-resistant bacteria has not been elucidated. Herein, we enrolled 40 healthy dairy cows after lactation: 20 were treated with IMM ceftiofur (Spectramast®DC) and a non-antibiotic internal teat sealant (bismuth subnitrate) and 20 (controls) received only bismuth subnitrate. Fecal samples were collected before (day −1) and after treatment (weeks 1, 2, 3, 5, 7, and 9) for bacterial quantification and metagenomic next-generation sequencing. Overall, 90% and 24% of the 278 samples had Gram-negative bacteria with resistance to ampicillin and ceftiofur, respectively. Most of the cows treated with ceftiofur did not have an increase in the number of resistant bacteria; however, a subset (25%) shed higher levels of ceftiofur-resistant bacteria for up to 2 weeks post-treatment. At week 5, the antibiotic-treated cows had lower microbiome abundance and richness, whereas a greater abundance of genes encoding extended-spectrum β-lactamases (ESBLs), CfxA, ACI-1, and CMY, was observed at weeks 1, 5 and 9. Moreover, the contig and network analyses detected associations between β-lactam resistance genes and phages, mobile genetic elements, and specific genera. Commensal bacterial populations belonging to Bacteroidetes most often possessed ESBL genes followed by members of Enterobacteriaceae. This study highlights variable, persistent effects of IMM ceftiofur treatment on the gut microbiome and resistome in dairy cattle. Antibiotic-treated cattle had an increased abundance of specific taxa and genes encoding ESBL production that persisted for 9 weeks, while fecal shedding of ESBL-producing Enterobacteriaceae varied across animals. Together, these findings highlight the need for additional studies that identify factors linked to shedding levels and the dissemination and persistence of resistance determinants on dairy farms in different geographic locations.