bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genome-wide transcriptome analysis reveals the diversity and function of long non-coding RNAs in dinoflagellates
Authors: Chen Yibi , Dougan Katherine E. , Nguyen Quan , Bhattacharya Debashish , Chan Cheong Xin 
Published: June 2023

AbstractDinoflagellates are a diverse group of phytoplankton, ranging from harmful bloom-forming microalgae to photosymbionts that are critical for sustaining coral reefs. Genome and transcriptome data from dinoflagellates are revealing extensive genomic divergence and lineage-specific innovation of gene functions. However, most studies thus far have focused on protein-coding genes; long non-coding RNAs (lncRNAs), known to regulate gene expression in eukaryotes, are largely unexplored. Here, using both genome and transcriptome data, we identified a combined total of 48,039 polyadenylated lncRNAs in the genomes of three dinoflagellate species: the coral symbionts ofCladocopium proliferumandDurusdinium trenchii, and the bloom-formingProrocentrum cordatum. These putative lncRNAs are shorter, and have fewer introns and lower G+C-content when compared to protein-coding sequences. Although 37,768 (78.6%) lncRNAs shared no significant similarity with one another, we classified all lncRNAs based on conserved sequence motifs (k-mers) into distinct clusters following properties of potential protein-binding and/or subcellular localisation. Interestingly, 3708 (7.7%) lncRNAs were differentially expressed in response to heat stress, lifestyle, and/or growth phases, and they shared co-expression patterns with protein-coding genes. Based on inferred triplex interactions between lncRNA and upstream (putative promoter) regions of protein-coding genes, we identified a combined 19,460 putative gene targets for 3,721 lncRNAs; 907 genes exhibit differential expression under heat stress. These results reveal for the first time the functional diversity of lncRNAs in dinoflagellates, and demonstrate how lncRNAs, often overlooked in transcriptome data, could regulate gene expression as a molecular response to heat stress in these ecologically important organisms.
Experimental safety testing confirms that the NSAID nimesulide is toxic toGypsvultures in India
Authors: Mathesh Karikalan , Manickam Kesavan , Mallord John W. , Mahendran K. , Asok Kumar M. , Saikia Debasish , Chandra Mohan S. , Beena V , Sree Lakshmi P. , Prakash Nikita , Shringarpure Rohan , Pawde Abhijit , Green Rhys E. , Prakash Vibhu 
Published: June 2023

AbstractPopulation declines ofGypsvultures throughout South Asia were caused by unintentional poisoning by the NSAID diclofenac, which was subsequently banned. However, other vulture-toxic NSAIDs are available, including nimesulide, which, in experiments carried out in South Africa, was shown to be toxic toGypsvultures. We report on safety-testing of nimesulide carried out on Himalayan GriffonsG. himalayensis. We gave two vultures a dose of nimesulide by oral gavage at the maximum level of exposure, with two controls dosed with benzyl alcohol. In the two tested birds, plasma nimesulide concentrations peaked after six hours, while serum uric acid concentrations increased steadily up until 24 hours post-treatment, after which both birds died, displaying severe visceral gout. The control birds showed no adverse clinical or biochemical signs. We confirm that nimesulide is toxic toGypsvultures. Veterinary use of nimesulide should be banned in allGypsvulture range countries in the region.
Phosphorylation and O-GlcNAcylation at the same α-synuclein site generate distinct fibril structures
Authors: Hu Jinjian , Xia Wencheng , Zeng Shuyi , Lim Yeh-Jun , Tao Youqi , Sun Yunpeng , Zhao Lang , Wang Haosen , Li Dan , Liu Cong , Li Yan-Mei 
Published: June 2023

ABSTRACTα-Synuclein (α-syn) forms amyloid fibrils that are critical in the progression of Parkinson’s disease (PD) and serves as the pathological hallmark of PD. Different posttranslational modifications (PTMs) have been identified at multiple sites of α-syn, influencing its conformation, aggregation and function. Here, we investigate how disease-related phosphorylation and O-GlcNAcylation at the same α-syn site (S87) affect fibril structure and neuropathology. Using semi-synthesis, we obtained homogenous α-syn monomer with site-specific phosphorylation (pS87) and O-GlcNAcylation (gS87) at S87, respectively. Cryo-EM analysis revealed that pS87 and gS87 α-syn form two novel but distinct fibril structures. The GlcNAc situated at S87 establishes interactions with K80 and E61, inducing a unique iron-like fold with the GlcNAc molecule on the iron handle. While, phosphorylation at the same site prevents a lengthy C-terminal region including residues 73-140 from incorporating into the fibril core due to electrostatic repulsion. Instead, the N-terminal half (1-72) shapes a novel arch-like fibril structure. We further show that both pS87 and gS87 α-syn fibrils display reduced neurotoxicity and propagation activity compared with unmodified α-syn fibril. Our findings demonstrate that different PTMs at the same site can produce distinct fibril structures, which emphasizes the precise regulation of PTMs to amyloid fibril formation and pathology.
Visual features are processed before navigational affordances in the human brain
Authors: Dwivedi Kshitij , Sadiya Sari , Balode Marta P. , Roig Gemma , Cichy Radoslaw M. 
Published: June 2023

ABSTRACTTo navigate through their immediate environment humans process scene information rapidly. How does the cascade of neural processing elicited by scene viewing to facilitate navigational planning unfold over time? To investigate, we recorded human brain responses to visual scenes with electroencephalography (EEG) and related those to computational models that operationalize three aspects of scene processing (2D, 3D, and semantic information), as well as to a behavioral model capturing navigational affordances. We found a temporal processing hierarchy: navigational affordance is processed later than the other scene features (2D, 3D, and semantic) investigated. This reveals the temporal order with which the human brain computes complex scene information and suggests that the brain leverages these pieces of information to plan navigation.
The formation of KV2.1 macro-clusters is required for sex-specific differences in L-type CaV1.2 clustering and function in arterial myocytes
Authors: Matsumoto Collin , O’Dwyer Samantha C. , Manning Declan , Hernandez-Hernandez Gonzalo , Rhana Paula , Fong Zhihui , Sato Daisuke , Clancy Colleen E. , Vierra Nicholas C. , Trimmer James S. , Santana L. Fernando 
Published: June 2023

AbstractIn arterial myocytes, the canonical function of voltage-gated CaV1.2 and KV2.1 channels is to induce myocyte contraction and relaxation through their responses to membrane depolarization, respectively. Paradoxically, KV2.1 also plays a sex-specific role by promoting the clustering and activity of CaV1.2 channels. However, the impact of KV2.1 protein organization on CaV1.2 function remains poorly understood. We discovered that KV2.1 forms micro-clusters, which can transform into large macro-clusters when a critical clustering site (S590) in the channel is phosphorylated in arterial myocytes. Notably, female myocytes exhibit greater phosphorylation of S590, and macro-cluster formation compared to males. Contrary to current models, the activity of KV2.1 channels seems unrelated to density or macro-clustering in arterial myocytes. Disrupting the KV2.1 clustering site (KV2.1S590A) eliminated KV2.1 macro-clustering and sex-specific differences in CaV1.2 cluster size and activity. We propose that the degree of KV2.1 clustering tunes CaV1.2 channel function in a sex-specific manner in arterial myocytes.
Implementing a framework of carbon and nitrogen feedback responses into a plant resource allocation model
Authors: Holland Bethany L , Monk Nicholas A M , Clayton Richard H , Osborne Colin P 
Published: June 2023

AbstractThe allocation of resources to roots and shoots can greatly alter total plant mass. Allocation is thought to be the consequence of growth processes (i.e uptake rates, transport rates, growth rates) and the communication between them via signalling mechanisms. Feedbacks that alter growth processes are induced in nature by changes in the internal pools of carbon and nitrogen, but how these function together to define allocation remains unclear.We introduce a framework model of internal feedback responses to changes in plant carbon and nitrogen concentrations. We evaluate how well the model responds to changes in carbon and nitrogen availability by simulating external environmental perturbations that influence the uptake of resources.The model reflects experimental results when looking at the effect of atmosphericCO2and soil nitrogen concentrations on total plant mass and replicates observed responses to leaf defoliation events. Overall this shows that a combination of known signalling mechanisms are sufficient to reproduce experimentally observed responses to external resource availability.Model simulations highlight key areas of uncertainty where more empirical data is needed. In particular, quantitative data is needed to establish the strengths and rates at which feedback responses to carbon and nitrogen substrate concentrations alter growth and uptake rates.
Evaluating Study Design Rigor in Preclinical Cardiovascular Research: A Replication Study
Authors: Jimenez Isaiah C. , Montenegro Gabrielle C. , Zahiri Keyana , Patel Damini , Mueller Adrienne 
Published: June 2023

ABSTRACTBackgroundMethodological rigor remains a priority in preclinical cardiovascular research to ensure experimental reproducibility and high-quality research. Limited reproducibility diminishes the translation of preclinical discoveries into medical practice. In addition, lack of reproducibility fosters uncertainty in the public’s acceptance of reported research results.MethodsWe evaluated the reporting of methodological practices in preclinical cardiovascular research studies published in leading scientific journals by screening articles for the inclusion of the following study design elements (SDEs): considering sex as a biological variable, randomization, blinding, and sample size power estimation. We screened for these SDEs across articles regarding preclinical cardiovascular research studies published between 2011 and 2021. We replicated and extended a study published in 2017 by Ramirez et al. We hypothesized a higher SDE inclusion across preclinical studies over time, that preclinical studies that include human and animal substudies within the same study will exhibit greater SDE inclusion than animal-only preclinical studies, and that a difference exists in SDE usage between large and small animal models.ResultsSDE inclusion was low; with 15.2% of animal-only studies including both sexes as a biological variable, 30.4% including randomization, 32.1% including blinding, and 8.2% including sample size estimation. The incorporation of SDEs did not significantly increase over the ten-year timeframe in the screened articles. Randomization and sample size estimation differed significantly between animal and human substudies (corrected p=1.85e-05 and corrected p=3.81e-07, respectively.)ConclusionsEvidence of methodological rigor varies depending on the study type and model organisms used. From 2011-2021, SDE reporting within preclinical studies has not increased, suggesting more work is needed to foster the inclusion of rigorous study design elements in cardiovascular research.
Genomic insights into southern white rhinoceros (Ceratotherium simum simum) reproduction: revealing granulosa cell gene expression
Authors: Ruggeri Elena , Klohonatz Kristin , Sirard Marc-André , Durrant Barbara , Coleman Stephen 
Published: June 2023

AbstractIn vivo-collected granulosa cells (GC) from the southern white rhinoceros (SWR) provide a non-invasive assessment of the developmental status of oocytes prior toin vitroculture, which could aid in the development of assisted reproductive technologies (ART). Our study aimed to investigate gene expression in SWR granulosa cells, collectedin vivoand gain preliminary insight into the transcriptional activity occurring within the cells during various stages of oocyte development. It was hypothesized there would be similarities between the SWR GC transcriptome and cattle and humans, two species for which well-annotated genomes are available and ART are commonly used. GC were collected from SWR following ovum pickup (OPU) and pooled from all aspirated follicles. Total RNA was isolated, libraries prepared, and sequencing performed using an Illumina NextSeq 500. Reads were aligned and annotated to CerSimCot1.0. Databases for cattle and human were acquired for comparison. This study identified 37,407 transcripts present in GC of SWR. It was determined that cattle and human transcriptomes are valuable resources with a homology of 45% with the SWR. In conclusion, these data provide preliminary, novel insights into the transcriptional activity of GC in the SWR that can be used to enhance ART in this species.
Dying of thirst: Osmoregulation by a hawkmoth pollinator in response to variability in ambient humidity and nectar availability
Authors: Dahake Ajinkya , Persaud Steven , Jones Marnesha N. , Goyret Joaquin , Davidowitz Goggy , Raguso Robert A. 
Published: June 2023

AbstractClimate-induced alterations in flowering phenology can lead to a temporal mismatch between pollinators and the availability of floral resources. Such asynchrony may be especially impactful in desert ecosystems, where flowering time and pollinator emergence are particularly sensitive to rainfall. To investigate the osmoregulation of a desert-living hawkmoth pollinatorManduca sexta, we sampled hemolymph osmolality of over 1000 lab-grown moths held at 20%, 50%, and 80% ambient humidity. Under starvation, the hemolymph osmolality of moths remained within a healthy range from days 1-3, regardless of ambient humidity. However, osmolality levels increase steeply from a baseline of 360-370 mmol/kg to 550 mmol/kg after 4-5 days in low and intermediate humidity and after 5 days in high humidity. Starved moths exposed to low humidity conditions died within 5 days, whereas those in high humidity conditions lived twice as long. Moths fed either syntheticDatura wrightiinectar, syntheticAgave palmerinectar, or water, maintained osmolality within a healthy baseline range of 350-400 mmol/kg. The same was true for moths that fed on authentic floral nectars. However, moths consumed higher amounts of synthetic nectar, likely due to the non-sugar nectar constituents in the authentic nectar. Finally, simulating a 4-day mismatch between pollinator emergence and nectar availability, we found that a single nectar meal can osmotically rescue moths in dry ambient conditions. Our findings indicate that hemolymph osmolality provides a rapid and accurate biomarker for assessing both the health and relative hydration state of insect pollinators.
Phylogenetic placement ofCeratophyllum submersumbased on a complete plastome sequence derived from nanopore long read sequencing data
Authors: Meckoni Samuel Nestor , Nass Benneth , Pucker Boas 
Published: June 2023

AbstractObjectiveEutrophication poses a mounting concern in today’s world.Ceratophyllum submersumL. is one of many plants capable of living in eutrophic conditions, therefore it could play a critical role in addressing the problem of eutrophication. This study aimed to take a first genomic look atC. submersum.ResultsSequencing of gDNA fromC. submersumyielded enough reads to assemble a plastome. Subsequent annotation and phylogenetic analysis validated existing information regarding angiosperm relationships and the positioning of Ceratophylalles in a wider phylogenetic context.
Pixel-wise programmability enables dynamic high-SNR cameras for high-speed microscopy
Authors: Zhang Jie , Newman Jonathan , Wang Zeguan , Qian Yong , Feliciano-Ramos Pedro , Guo Wei , Honda Takato , Chen Zhe Sage , Linghu Changyang , Etienne-Cummings Ralph , Fossum Eric , Boyden Edward , Wilson Matthew 
Published: June 2023

AbstractHigh-speed wide-field fluorescence microscopy has the potential to capture biological processes with exceptional spatiotemporal resolution. However, conventional cameras suffer from low signal-to-noise ratio at high frame rates, limiting their ability to detect faint fluorescent events. Here, we introduce an image sensor where each pixel has individually programmable sampling speed and phase, so that pixels can be arranged to simultaneously sample at high speed with a high signal-to-noise ratio. In high-speed voltage imaging experiments, our image sensor significantly increases the output signal-to-noise ratio compared to a low-noise scientific CMOS camera (∼2-3 folds). This signal-to-noise ratio gain enables the detection of weak neuronal action potentials and subthreshold activities missed by the standard scientific CMOS cameras. Our camera with flexible pixel exposure configurations offers versatile sampling strategies to improve signal quality in various experimental conditions.
Competitive specific anchorage of molecules onto surfaces: quantitative control of grafting densities and contamination by free anchors
Authors: Kirichuk Oksana , Srimasorn Sumitra , Zhang Xiaoli , Roberts Abigail R. E. , Coche-Guerente Liliane , Kwok Jessica C. F. , Bureau Lionel , Débarre Delphine , Richter Ralf P. 
Published: June 2023

AbstractThe formation of surfaces decorated with biomacromolecules such as proteins, glycans or nucleic acids with well-controlled orientations and densities is of critical importance for the design ofin vitromodels,e.g., synthetic cell membranes, and interaction assays. To this effect, ligand molecules are often functionalized with an anchor that specifically binds to a surface with a high density of binding sites, providing control over the presentation of the molecules. Here, we present a method to robustly and quantitatively control the surface density of one or several types of anchor-bearing molecules by tuning the relative concentrations of target molecules and free anchors in the incubation solution. We provide a theoretical background that relates incubation concentrations to the final surface density of the molecules of interest, and present effective guidelines towards optimizing incubation conditions for the quantitative control of surface densities. Focussing on the biotin anchor, a commonly used anchor for interaction studies, as a salient example, we experimentally demonstrate surface density control over a wide range of densities and target molecule sizes. Conversely, we show how the method can be adapted to quality control the purity of end-grafted biopolymers such as biotinylated glycosaminoglycans by quantifying the amount of residual free biotin reactant in the sample solution.
Efficacy of the oral nucleoside prodrug GS-5245 (Obeldesivir) against SARS-CoV-2 and coronaviruses with pandemic potential
Authors: Martinez David R. , Moreira Fernando R. , Zweigart Mark R. , Gully Kendra L. , Cruz Gabriela De la , Brown Ariane J. , Adams Lily E. , Catanzaro Nicholas , Yount Boyd , Baric Thomas J. , Mallory Michael L. , Conrad Helen , May Samantha R. , Dong Stephanie , Scobey D. Trevor , Montgomery Stephanie A. , Perry Jason , Babusis Darius , Barrett Kimberly T. , Nguyen Anh-Hoa , Nguyen Anh-Quan , Kalla Rao , Bannister Roy , Bilello John P. , Feng Joy Y. , Cihlar Tomas , Baric Ralph S. , Mackman Richard L. , Schäfer Alexandra , Sheahan Timothy P. 
Published: June 2023

AbstractDespite the wide availability of several safe and effective vaccines that can prevent severe COVID-19 disease, the emergence of SARS-CoV-2 variants of concern (VOC) that can partially evade vaccine immunity remains a global health concern. In addition, the emergence of highly mutated and neutralization-resistant SARS-CoV-2 VOCs such as BA.1 and BA.5 that can partially or fully evade (1) many therapeutic monoclonal antibodies in clinical use underlines the need for additional effective treatment strategies. Here, we characterize the antiviral activity of GS-5245, Obeldesivir (ODV), an oral prodrug of the parent nucleoside GS-441524, which targets the highly conserved RNA-dependent viral RNA polymerase (RdRp). Importantly, we show that GS-5245 is broadly potent in vitro against alphacoronavirus HCoV-NL63, severe acute respiratory syndrome coronavirus (SARS-CoV), SARS-CoV-related Bat-CoV RsSHC014, Middle East Respiratory Syndrome coronavirus (MERS-CoV), SARS-CoV-2 WA/1, and the highly transmissible SARS-CoV-2 BA.1 Omicron variant in vitro and highly effective as antiviral therapy in mouse models of SARS-CoV, SARS-CoV-2 (WA/1), MERS-CoV and Bat-CoV RsSHC014 pathogenesis. In all these models of divergent coronaviruses, we observed protection and/or significant reduction of disease metrics such as weight loss, lung viral replication, acute lung injury, and degradation in pulmonary function in GS-5245-treated mice compared to vehicle controls. Finally, we demonstrate that GS-5245 in combination with the main protease (Mpro) inhibitor nirmatrelvir had increased efficacy in vivo against SARS-CoV-2 compared to each single agent. Altogether, our data supports the continuing clinical evaluation of GS-5245 in humans infected with COVID-19, including as part of a combination antiviral therapy, especially in populations with the most urgent need for more efficacious and durable interventions.
Identifying molecular targets of a colloidal nanosilver formulation (Silversol®) in multidrug resistantPseudomonas aeruginosa
Authors: Gajera Gemini , Thakkar Nidhi , Godse Chhaya , DeSouza Anselm , Mehta Dilip , Kothari Vijay 
Published: June 2023

AbstractP. aeruginosais a notorious pathogen. A multi-drug resistant strain of this bacterium was challenged with a colloidal nano-silver formulation- Silversol®. Its minimum inhibitory concentration againstP. aeruginosawas found to be 1.5 ppm, and at sub-MIC of 1 ppm, it was able to alter quorum-sensing regulated pigmentation, exopolysaccharide synthesis and biofilm formation, antibiotic susceptibility, protein synthesis and export, nitrogen metabolism, and siderophore production in this pathogen. Transcriptome analysis of the silver-exposedP. aeruginosaindicated generation of nitrosative stress and disturbance of iron homeostasis to be the major mechanisms associated with anti-Pseudomonas activity of Silversol®. Network analysis of the differentially expressed genes in silver-treated bacterium identified ten genes as the potential molecular targets: norB, norD, nirS, nirF, nirM, nirQ, nosZ, nosY, narK1, and norE (all associated with nitrogen metabolism or denitrification). Three of them (norB, narK1, and norE) were also validated through RT-PCR.