bluuebunny/crossref_metadata_2025_split huggingface dataset:
Population-specific effects of ocean acidification in the Olympia oyster
Authors: Spencer Laura H , Silliman Katherine , Roberts Steven 
Published: September 2023

AbstractPopulations of marine species that respond differently to ocean acidification offer natural reservoirs of biodiversity that can be leveraged for conservation efforts and to sustain marine food systems. The molecular and physiological traits associated with tolerance to acidification must first be identified. This study leveraged oysters from three phenotypically distinct populations of the Olympia oyster,Ostrea lurida, but that were bred and reared in common conditions for four years. We assessed their growth, reproductive development, and transcriptional response to acidification within and across generations. Responses reveal energetic trade-offs that reflect unique physiotypes previously observed among populations. The population with the slowest growth but high survival rates, oysters from Dabob Bay, mounted the largest transcriptional response to acidification without effects to growth and reproduction. A moderate response was observed in the population with fastest growth rate but lowest fecundity (Fidalgo Bay). Oyster Bay, the population with highest fecundity but lowest survival rates, did not respond at the transcript level. Oyster Bay was also the only population for which acidification negatively affected growth and reproductive development. While exposure to acidification did not affect gene expression in the next generation’s larval stage, it did result in larger larvae in the Oyster Bay population, which could partially alleviate negative effects of acidification in the wild for that population. Given the distinct transcriptional response of the Dabob Bay population to acidification and its high survival rates in previous studies, we then identified genes that were uniquely expressed in Dabob Bay oysters compared to the other populations. Genes involved in antibacterial and antiviral processes, metabolism, growth, and reproduction were uniquely expressed in Dabob Bay, and many similar functions were identified in both adults and larvae, which provides insight into the mechanisms behind a stress-tolerant oyster population. The population-specific physiotypes and responses to acidification illustrate the diversity of physiological strategies inO. luridathat balance the energetic demands of growth, reproduction, cellular maintenance, and offspring viability. Taken together this study reveals that there are distinct physiotypes among marine invertebrate populations on small geographic scales with implications for species resilience to acidification and other environmental stressors.
Highly localized chemical sampling at sub-second temporal resolution enabled with a silicon nanodialysis platform at exceedingly slow flows
Authors: Park Insu , Kim Sungho , Brenden Christopher Kenji , Shi Weihua , Iyer Hrishikesh , Bashir Rashid , Vlasov Yurii 
Published: September 2023

AbstractMicrodialysis (MD) is a versatile and powerful technique for chemical profiling of biological tissues and is widely used for quantification of neurotransmitters, neuropeptides, metabolites, biomarkers, and drugs in the central nervous system as well as in dermatology, ophthalmology, and in pain research. However, MD performance is severely limited by fundamental tradeoffs between chemical sensitivity, spatial resolution, and temporal response. Here, by using wafer-scale silicon microfabrication, we develop and demonstrate a nanodialysis (ND) sampling probe that enables highly localized chemical sampling with 100μm spatial resolution and sub-second temporal resolution at high recovery rates. These performance metrics, which are 100X-1000X superior to existing MD approaches, are enabled by a 100X reduction of the microfluidic channel cross-section, a corresponding drastic 100X reduction of flow rates to exceedingly slow few nL/min flows, and integration of a nanometer-thin nanoporous membrane with high transport flux into the probe sampling area. Miniaturized ND probes may allow for the minimally invasive and highly localized sampling and chemical profiling in live biological tissues with unprecedented spatio-temporal resolution for clinical, biomedical, and pharmaceutical applications.
Longevity interventions in Titan mice attenuate frailty and senescence accumulation
Authors: Gille Benedikt , Müller-Eigner Annika , Gottschalk Shari , Wytrwat Erika , Langhammer Martina , Peleg Shahaf 
Published: September 2023

AbstractWild-type murine models for aging research have lifespans of several years, which results in long experimental duration and late output. Here we explore the short-lived non-inbred Titan mouse as a mouse model to test longevity interventions. We show that Titan mice exhibit increased frailty and cellular senescence at an early age. Dietary intervention attenuates the frailty progression of Titan mice. Additionally, cyclic administration of the senolytic drug Navitoclax at early age increases the lifespan and reduces cellular senescence. Our data suggests that Titan mice can serve as a cost-effective and timely model for longevity interventions in mammals.
Contrasting Effects of SARS-CoV-2 Vaccination vs. Infection on Antibody and TCR Repertoires
Authors: Braun Jasper , Hill Elliot D. , Contreras Elisa , Yasuda Michie , Morgan Alexandra , Ditelberg Sarah , Winter Ethan , Callahan Cody , Mazzoni Gabrielle , Kirmaier Andrea , Mirebrahim Hamid , Asgharian Hosseinali , Telman Dilduz , Collier Ai-Ris Y. , Barouch Dan H. , Riedel Stefan , Dutta Sanjucta , Rubelt Florian , Arnaout Ramy 
Published: September 2023

AbstractAntibodies and helper T cells play important roles in SARS-CoV-2 infection and vaccination. We sequenced B– and T-cell receptor repertoires (BCR/TCR) from the blood of 251 infectees, vaccinees, and controls to investigate whether features of these repertoires could predict subjects’ SARS-CoV-2 neutralizing antibody titer (NAbs), as measured by enzyme-linked immunosorbent assay (ELISA). We sequenced recombined immunoglobulin heavy-chain (IGH), TCRβ (TRB), and TCRδ (TRD) genes in parallel from all subjects, including select B– and T-cell subsets in most cases, with a focus on their hypervariable CDR3 regions, and correlated this AIRRseq data with demographics and clinical findings from subjects’ electronic health records. We found that age affected NAb levels in vaccinees but not infectees. Intriguingly, we found that vaccination, but not infection, has a substantial effect on non-productively recombined IGHs, suggesting a vaccine effect that precedes clonal selection. We found that repertoires’ binding capacity to known SARS-CoV-2-specific CD4+ TRBs performs as well as the best hand-tuned fuzzy matching at predicting a protective level of NAbs, while also being more robust to repertoire sample size and not requiring hand-tuning. The overall conclusion from this large, unbiased, clinically well annotated dataset is that B– and T-cell adaptive responses to SARS-CoV-2 infection and vaccination are surprising, subtle, and diffuse. We discuss methodological and statistical challenges faced in attempting to define and quantify such strong-but-diffuse repertoire signatures and present tools and strategies for addressing these challenges.
Transcriptional modulation during photomorphogenesis in rice seedlings
Authors: Gupta Parul , Jaiswal Pankaj 
Published: September 2023

ABSTRACTLight is one of the most important factors regulating plant gene expression patterns, metabolism, physiology, growth, and development. To explore how light may induce or alter transcript splicing, we conducted RNA-Seq-based transcriptome analyses by comparing the samples harvested as etiolated seedlings grown under continuous dark conditions vs. the light-treated green seedlings. We identified 14,766 differentially expressed genes, of which 4369 genes showed alternative splicing. We observed that genes mapped to the plastid-localized methyl-erythritol-phosphate (MEP) pathway were light-upregulated compared to the cytosolic mevalonate (MVA) pathway genes. Many of these genes also undergo splicing. These pathways provide crucial metabolite precursors for the biosynthesis of secondary metabolic compounds needed for chloroplast biogenesis, the establishment of successful photosynthetic apparatus, and photomorphogenesis. In the chromosome-wide survey of the light-induced transcriptome, we observed intron retention as the most predominant splicing event. In addition, we identified 1709 novel lncRNA transcripts in our transcriptome data.
γδ T cells respond directly and selectively to the skin commensal yeastMalasseziafor IL-17-dependent fungal control
Authors: Ruchti Fiorella , Tuor Meret , Mathew Liya , McCarthy Neil E , LeibundGut-Landmann Salomé 
Published: September 2023

ABSTRACTStable microbial colonization of the skin depends on tight control by the host immune system. The lipid-dependent yeastMalasseziatypically colonizes skin as a harmless commensal and is subject to host type 17 immunosurveillance, but this fungus has also been associated with diverse skin pathologies in both humans and animals. Using a murine model ofMalasseziaexposure, we show that Vγ4+dermal γδ T cells expand rapidly and are the major source of IL-17A mediating fungal control in colonized skin. A pool of memory-likeMalassezia-responsive Vγ4+T cells persisted in the skin, were enriched in draining lymph nodes even after fungal clearance, and were protective upon fungal re-exposure up to several weeks later. Induction of γδT17 immunity depended on IL-23 and IL-1 family cytokine signalling, whereas Toll-like and C-type lectin receptors were dispensable. Furthermore, Vγ4+T cells fromMalassezia-exposed hosts were able to respond directly and selectively toMalassezia-derived ligands, independently of antigen-presenting host cells. Reactivity of human γδ T cells againstMalasseziaspp. confirmed the relevance of this fungus-specific response across different host species. The fungal moieties detected were shared across diverse species of theMalasseziagenus, but not conserved in other Basidiomycota or Ascomycota. These data provide novel mechanistic insight into the induction and maintenance of type 17 immunosurveillance of skin commensal colonization that has significant implications for cutaneous health.AUTHOR SUMMARYMalasseziais the most abundant fungus living on our skin and is usually harmless, but this microbe has also been shown to play a role in pathological conditions such as eczema and dermatitis. Here, we investigated how a population of Vγ4+γδ T cells protect mouse skin against fungal overgrowth. While generally considered part of the innate immune system, we found that γδ T cells were maintained long afterMalasseziawas cleared from the skin of experimentally-infected animals. These cells displayed memory-like features and were highly efficient at fighting the fungus after a secondary challenge. We observed that classic fungal pattern recognition receptors were not involved, and that antigen-presenting cells were not required to generateMalassezia-protective γδ T cells. Finally, we confirmed that γδ T cells can recogniseMalassezia, both in mice and human hosts. The fungal structure that triggers these responses was highly specific toMalasseziaand was not conserved among other fungi. Our results highlight for the first time an important role for γδ T cells in preventing uncontrolled growth of the most abundant skin fungus. These findings have implications for severalMalassezia-associated pathologies including eczema, dermatitis, and potentially even cancer.
No single PCR test is sufficient to determine parvovirus IHHNV presence in or impact on farmed shrimp production
Authors: Sritunyalucksana Kallaya , Sanguanrut Piyachat , Srisala Jiraporn , Thawonsuwan Jumroensri , Saleetid Nattakan , Vanichviriyakit Rapeepun , Chotwiwatthanakun Charoonroj , Flegel Timothy W. , Taengchaiyaphum Suparat 
Published: September 2023

ABSTRACTThe main purpose of this report is to provide hard evidence that the shrimp parvovirus IHHNV has not resulted “in significant consequences e.g. production losses, morbidity or mortality at a zone or country level” in Thailand since at least 2010. It also reveals that no single PCR test is sufficient to identify IHHNV-infected shrimp. It presents historical evidence and new evidence from 11 commercial ponds cultivating the giant tiger shrimpPenaeus monodonin Thailand. These ponds were selected because they were the ponds that gave positive PCR test results for IHHNV using 2 methods recommended for IHHNV diagnosis by WOAH. However, an additional in-house “IHHNV Long-Amp method” (IHHNV-LA) was also used to amplify 90% of the 4 kb IHHNV genome sequence, and it also gave false-positive test results with 2 of the 11 ponds. Further tests using normal histopathological analysis for the presence of pathognomonic Cowdry A type inclusions (CAI),in situhybridization (ISH) and immunohistochemistry (IHC) could confirm IHHNV infections in only 2 of the 4 ponds PCR-positive using all 3 PCR methods. In addition, positive detection of CAI alone was equivalent to ISH or IHC in confirming IHHNV infection after a positive test with any of the PCR methods used. In summary, the recommended WOAH PCR methods gave false positive test results for IHHNV infection with 9/11 ponds (82%). All 11 ponds gave profitable harvests despite the confirmation of IHHNV in 2 ponds, where it was accompanied by various additional pathogens. Unfortunately, according to current practice, positive PCR test results with the WOAH methods alone sometimes leads to rejection of traded shrimp products without assurance that the test results are not false positive results that may arise from endogenous viral elements (EVE).
Bet hedging in a unicellular microalga
Authors: Tang Si , Liu Yaqing , Hammerschmidt Katrin , Zhu Jianming , Cheng Xueyu , Liu Lu , Zhou Jin , Cai Zhonghua 
Published: September 2023

AbstractUnderstanding how organisms adapt to unpredictable future environments is a fundamental goal in biology, which becomes even more urgent in an era of rapid climate change. One evolutionary adaptation to randomly fluctuating environments is bet hedging, a strategy that successfully facilitates reproduction and population persistence and has been widely reported from microbes to humans. Empirical evidence for its presence in microalga, one of Earth’s most important primary producers and carbon sinks, is lacking. Here, we report a bet-hedging strategy in the unicellular microalgaHaematococcus pluvialis.In a series of experiments, we show that an isogenicH. pluvialispopulation reversibly diversifies into hetero-phenotypic mobile and non-mobile subunits, independent of environmental conditions. Mobile cells grow faster but are more susceptible to external stressors, while non-mobile cells hardly grow but are more stress-resistant. This is attributed to dramatic shifts from growth-promoting activities (cell division, photosynthesis) to resilience-promoting cellular metabolic processes, including cell enlargement and aggregation, and accumulation of antioxidant and energy-storaging compounds. Our results provide experimental evidence for bet hedging in microalga, which has implications for their potential to adapt to current and predicted future conditions, and thus for the conservation of ecosystem functions.
Development and Characterization of Co-crystals Assisted withIn-silicoScreening for Solubility and Permeability Enhancement of Curcumin
Authors: Singh Meera , Takawale Shweta , Patil Rajesh , Chaudhari Somdatta , Pathan Aarifkhan , Sangshetti Jaiprakash , Moin Abu Tayab , Zubair Talha , Uddin Mohammad Helal 
Published: September 2023

AbstractDespite being a promising phytochemical, Curcumin’s potential applications are limited due to its classification in BCS class IV, which is associated with low water solubility and permeability. Enhancing the bioavailability of BCS class IV drugs presents a significant challenge, but crystal chemistry provides a hopeful avenue for overcoming this hurdle. In this research, co-crystals of Curcumin were developed to improve both solubility and permeability. Unlike traditional methods that require extensive trial-based lab work and time-consuming screening of co-formers, the use of molecular docking inIn-silicoco-former screening offers a scientific and rational approach to selecting suitable partners. In this study, two distinct co-crystals were synthesized using a solvent evaporation technique with methanol as the solvent, employing a 1:1 molar ratio. L-proline and piperine were chosen as co-formers to enhance solubility and permeability, respectively. The co-crystals underwent optimization and characterization through Design of Experiments (DOE). Comparing the dissolution study results for the same curcumin concentration, the cumulative drug release (CDR) after 8 hours was 20% for pure curcumin and an impressive 71% for curcumin-L-proline co-crystals. The permeability study, conducted over four hours using the everted gut sac method in phosphate buffer pH 6.8, revealed curcumin’s permeability to be less than 0.05 mg/mL, while curcumin-piperine co-crystals exhibited a five-fold increase (0.2545 mg/mL) in permeability. The co-crystals formed through a molecular ratio of 1:1 for curcumin-L-proline to enhance solubility and 1:1 for curcumin-piperine to enhance permeability, both demonstrated positive outcomes with support from optimization analysis, FTIR, DSC, SEM, PXRD analysis, and dissolution studies.
Mycotools: An Automated and Scalable Platform for Comparative Genomics
Authors: Konkel Zachary , Slot Jason C. 
Published: September 2023

ABSTRACTComparative genomics comprises analyses that investigate the genetic basis of organismal biology and ecology, which have also been applied to high throughput trait screening for applied purposes. The number of fungal genomes deposited in publicly available databases are currently in exponential growth. Due to the limited cutting-edge software availability and size or efficiency constraints of web-based analyses, comparative genomics research is often conducted on local computing environments. There is thus a need for an efficient standardized framework for locally assimilating, curating, and interfacing with genomic data. We present Mycotools as a comparative genomics database software suite that automatically curates, updates, and standardizes local comparative genomics. Mycotools incorporates novel analysis pipelines that are built on a suite of modules that streamline routine-to-complex comparative genomic tasks. The Mycotools software suite serves as a foundation for accessible and reproducible large-scale comparative genomics on local compute systems.
The Immune-Evasive Proline 283 Substitution in Influenza Nucleoprotein Increases Aggregation Propensity Without Altering the Native Structure
Authors: Yoon Jimin , Zhang Yu Meng , Her Cheenou , Grant Robert A. , Ponomarenko Anna M. , Ackermann Bryce E. , Debelouchina Galia T. , Shoulders Matthew D. 
Published: September 2023

AbstractNucleoprotein (NP) is a key structural protein of influenza ribonucleoprotein complexes and is central to viral RNA packing and trafficking. In human cells, the interferon induced Myxovirus resistance protein 1 (MxA) binds to NP and restricts influenza replication. This selection pressure has caused NP to evolve a few critical MxA-resistant mutations, particularly the highly conserved Pro283 substitution. Previous work showed that this essential Pro283 substitution impairs influenza growth, and the fitness defect becomes particularly prominent at febrile temperature (39 °C) when host chaperones are depleted. Here, we biophysically characterize Pro283 NP and Ser283 NP to test if the fitness defect is owing to Pro283 substitution introducing folding defects. We show that the Pro283 substitution changes the folding pathway of NP without altering the native structure, making NP more aggregation prone during folding. These findings suggest that influenza has evolved to hijack host chaperones to promote the folding of otherwise biophysically incompetent viral proteins that enable innate immune system escape.TeaserPro283 substitution in flu nucleoprotein introduces folding defects, and makes influenza uniquely dependent on host chaperones.
MUSTANG: MUlti-sample Spatial Transcriptomics data ANalysis with cross-sample transcriptional similarity Guidance
Authors: Niyakan Seyednami , Sheng Jianting , Cao Yuliang , Zhang Xiang , Xu Zhan , Wu Ling , Wong Stephen T.C. , Qian Xiaoning 
Published: September 2023

AbstractSpatially resolved transcriptomics has revolutionized genome-scale transcriptomic profiling by providing high-resolution characterization of transcriptional patterns. We here present our spatial transcriptomics analysis framework,MUSTANG(MUlti-sampleSpatialTranscriptomics dataANalysis with cross-sample transcriptional similarityGuidance), which is capable of performing multi-sample spatial transcriptomics spot cellular deconvolution by allowing both cross-sample expression based similarity information sharing as well as spatial correlation in gene expression patterns within samples. Experiments on two real-world spatial transcriptomics datasets demonstrate the effectiveness ofMUSTANGin revealing biological insights inherent in cellular characterization of tissue samples under the study. MUSTANG is publicly available at athttps://github.com/namini94/MUSTANG
Next-generation sequencing-based liquid biopsy can be used for detection of residual disease and cancer recurrence monitoring in dogs
Authors: McCleary-Wheeler Angela L. , Fiaux Patrick C. , Ruiz-Perez Carlos A. , McLennan Lisa M. , Tynan John A. , Hicks Susan C. , Rafalko Jill M. , Grosu Daniel S. , Chibuk Jason , O’Kell Allison L. , Cohen Todd A. , Flesner Brian K. , Chorny Ilya , Tsui Dana W.Y. , Kruglyak Kristina M. , Flory Andi 
Published: September 2023

AbstractObjectiveThe purpose of this study was to evaluate the performance of a next-generation sequencing-based liquid biopsy test for cancer monitoring in dogs.SamplesPre- and post-operative blood samples were collected prospectively from dogs with confirmed cancer diagnoses originally enrolled in the CANcer Detection in Dogs (CANDiD) study. A subset of these dogs also had longitudinal blood samples collected for recurrence monitoring.MethodsAll patients had a pre-operative blood sample collected (after diagnosis but prior to surgical intervention) in which a cancer signal was detected, and had at least one post-operative sample collected. Clinical data were collected for all patients and used to assign a clinical disease status for each follow-up visit.ResultsFollowing excisional surgery, in the absence of clinical residual disease at the post-operative visit, patients withCancer Signal Detectedresults at that visit were 1.95-times as likely to have clinical recurrence within 6 months compared to patients withCancer Signal Not Detectedresults. In the subset of patients with longitudinal liquid biopsy samples that had clinical recurrence documented during the study period, 73% (8/11; 95% CI: 39 – 93%) of patients hadCancer Signal Detectedin blood prior to or concomitant with clinical recurrence; in the 6 patients where molecular recurrence was detected prior to clinical recurrence, the median lead time was 168 days (range: 47 – 238).Clinical RelevanceNext-generation sequencing-based liquid biopsy is a non-invasive tool for cancer monitoring in dogs that can be used as an adjunct to current standard-of-care clinical assessment methods.