bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genome assembly and annotation of the red flour beetle (Tribolium castaneum)from India
Authors: Singhal Shivansh , Choudhary Chhavi , Basu Dipendra Nath , Seal Srijan , Khan Imroze , Shukla Jayendra Nath , Agashe Deepa 
Published: May 2024

ABSTRACTThe largest insect order, Coleoptera, includes several economically important beetles that also serve as major model species for biological research. Perhaps foremost among these is the red flour beetle, a global pest of stored grains and flour whose genome was sequenced in 2008. However, the currently available reference genome (Tcas5.2) is incomplete, fragmented and contains many gaps, and the Y chromosome is not assembled. Here we present inTcas1, an updated genome assembly and annotation ofT. castaneumcollected from India, assembled using both short and long read sequencing, and annotated using two transcriptome datasets. We report that inTcas1 has fewer gaps, less fragmentation, and many new genes and new isoforms of previously annotated genes. This new resource provides a useful update, comparison, and reference for new beetle genome assemblies. The first Y chromosome assembly for this species also provides critical data to study the evolution of insect sex chromosomes and sex determination systems.SIGNIFICANCEWe present here an improvedT. castaneumgenome assembly (inTcas1) for beetles sampled from India, including the first Y chromosome of this important pest and laboratory model species. The new genome should facilitate more comprehensive analysis of Coleoptera genome and transcriptome datasets, especially beetle populations from Asia – the previously available genome, Tcas5.2, was assembled using the GA2 strain from USA. The updated genome should also facilitate analyses of genome evolution, including sex determination and sex chromosome dynamics; and the new gene annotations can expand the genetic toolkit for this beetle.
PRR adjuvants restrain high stability peptides presentation on APCs
Authors: Li Bin , Zhang Jin , He Taojun , Yuan Hanmei , Wu Hui , Wang Peng , Wu Chao 
Published: May 2024

AbstractAdjuvants can affect APCs function and boost adaptive immune responses post-vaccination. However, whether they modulate the specificity of immune responses, particularly immunodominant epitope responses, and the mechanisms of regulating antigen processing and presentation remain poorly defined. Here, using overlapping synthetic peptides, we screened the dominant epitopes of Th1 responses in mice post-vaccination with different adjuvants and found that the adjuvants altered the antigen-specific CD4+T-cell immunodominant epitope hierarchy. MHC-II immunopeptidomes demonstrated that the peptide repertoires presented by APCs were significantly altered by the adjuvants. Unexpectedly, no novel peptide presentation was detected after adjuvant treatment, whereas peptides with high binding stability for MHC-II presented in the control group were missing after adjuvant stimulation, particularly in the MPLA- and CpG-stimulated groups. The low-stability peptide present in the adjuvant groups effectively elicited robust T-cell responses and formed immune memory. Collectively, our results suggest that adjuvants (MPLA and CpG) inhibit high-stability peptide presentation instead of revealing cryptic epitopes, which may alter the specificity of CD4+T-cell-dominant epitope responses. The capacity of adjuvants to modify peptide–MHC (pMHC) stability and antigen-specific T-cell immunodominant epitope responses has fundamental implications for the selection of suitable adjuvants in the vaccine design process and epitope vaccine development.
Pangenomic analysis ofHelcococcus ovisreveals widespread tetracycline resistance and a novel bacterial species,Helcococcus bovis
Authors: Cunha Federico , Zhai Yuting , Casaro Segundo , Jones Kristi L. , Hernandez Modesto , Bisinotto Rafael S. , Kariyawasam Subhashinie , Brown Mary B. , Phillips Ashley , Jeong Kwangcheol C. , Galvão Klibs N. 
Published: May 2024

AbstractHelcococcus ovis(H. ovis) is an opportunistic bacterial pathogen of a wide range of animal hosts including domestic ruminants, swine, avians, and humans. In this study, we sequenced the genomes of 35Helcococcus sp.clinical isolates from the uterus of dairy cows and explored their antimicrobial resistance and biochemical phenotypes. Phylogenetic and average nucleotide identity analyses placed fourHelcococcusisolates within a cryptic clade-representing an undescribed species, for which we propose the nameHelcococcus bovissp. nov. We applied whole genome comparative analyses to explore the pangenome, resistome, virulome, and taxonomic diversity of the remaining 31H. ovisisolates. H. oviswas more often isolated from cows with metritis, however, there was no associations betweenH. ovisgene clusters and uterine infection. The phylogenetic distribution of high-virulence determinants ofH. ovisis consistent with convergent gene loss in the species. The majority ofH. ovisstrains (30/31) contain mobile tetracycline resistance genes, leading to higher minimum inhibitory concentrations of tetracyclines in vitro. In summary, this study showed that the presence ofH. ovisis associated with uterine infection in dairy cows, that mobile genetic element-mediated tetracycline resistance is widespread inH. ovis, and that there is evidence of co-occurring virulence factors across clades suggesting convergent gene loss in the species. Finally, we introduced a novelHelcococcusspecies closely related toH. ovis, calledH. bovissp. nov.HighlightsThe presence ofHelcococcus ovisis associated with uterine infection in dairy cowsMobile genetic element-mediated tetracycline resistance is widespread inH. ovisCo-occurring virulence factors across clades suggest convergent gene loss in the speciesHelcococcus bovisis a novel species closely related toHelcococcus ovis
Context-dependent neural preparation for information relevance vs. probability
Authors: Peñalver José M.G. , González-García Carlos , Palenciano Ana F. , López-García David , Ruz María 
Published: May 2024

AbstractPreparation is a top-down phenomenon known to improve performance across different situations. In light of recent electrophysiological findings that suggest that anticipatory neural preactivations linked to preparation are context-specific and do not generalize across domains, in the current study we used fMRI to investigate the brain regions involved in these differential patterns. We applied multivariate decoding to data obtained in a paradigm where, in different blocks, cues provided information about the relevance or probability of incoming target stimuli. Results showed that the anticipated stimulus category was pre-activated in both conditions, mostly in different brain regions within the ventral visual cortex and with differential overlap with actual target perception. Crucially, there was scarce cross-classification across attention and expectation contexts except on a patch of the fusiform gyrus, indicating mostly differential neural coding of anticipated contents in relevance and probability scenarios. Finally, a model-based fMRI-EEG fusion showed that these regions differentially code for specific conditions during preparation, as well as specifically preparing for category anticipation in a ramping-up manner. Overall, our results stress the specificity of anticipatory neural processing depending on its informative role while highlighting a key hub of commonality in the fusiform gyrus.
Impaired Functional Connectivity of Cortico-Amygdala Pathway Can Drive Social Behavior Deficits in Synucleinopathies
Authors: Zhou Wei , Daniels Samuel , Singh Vijay , Menard Marissa , Escobar Galvis Martha L , Chu Hong-Yuan 
Published: May 2024

AbstractThe small molecule protein α-synuclein forms insoluble aggregates in a group of neurological disorders, including Parkinson’s disease and dementia with Lewy bodies (DLB), which are collectively called synucleinopathies. In PD and DLB, the amygdala has been identified as a particularly susceptible region in the brain for the deposition of Lewy-like α-synuclein aggregates. Though α-synuclein aggregation is closely associated with neurodegeneration, there is a poor correlation between neurodegeneration in the amygdala and the clinical features of PD/DLB. We hypothesize that, prior to neurodegeneration, α-synuclein aggregation disrupts functional cortical modulation of the amygdala circuits, leading to emotion dysregulation in synucleinopathies. In the present study, we combined electrophysiology, optogenetics, mouse model of synucleinopathies, and behavioral analysis to test this hypothesis. Using an α-synuclein preformed fibrils (PFFs)-based mouse model of synucleinopathies, we reported dynamic changes in the levels of α-synuclein pathology in the basolateral amygdala (BLA). Such dynamic changes of pathology associated with a decreased cortico-BLA connection strength prior to a significant loss of cortical axon terminals. In parallel to the reduced cortico-BLA connection, PFFs-injected mice manifested impaired social preference behavior. The impaired sociability of PFFs-injected mice could be rescued by chemogenetic stimulation of cortico-BLA inputs. Altogether, we presented a series of evidence to delineate key circuit events associated with α-synuclein pathology development in the amygdala circuits. The present work highlights the necessity of a thorough investigation of functional consequences of α-synuclein aggregation to advance our understand of pathophysiology of synucleinopathies and development of effective therapies.
The variability of multidimensional diffusion-relaxation MRI estimates in the human brain
Authors: Manninen Eppu , Bao Shunxing , Landman Bennett A. , Yang Yihong , Topgaard Daniel , Benjamini Dan 
Published: May 2024

AbstractDiffusion-relaxation correlation multidimensional MRI (MD-MRI) replaces voxel-averaged diffusion tensor quantities and R1and R2relaxation rates with their multidimensional distributions, enabling the selective extraction and mapping of specific diffusion-relaxation spectral ranges that correspond to different cellular features. This approach has the potential of achieving high sensitivity and specificity in detecting subtle changes that would otherwise be averaged out. Here, the whole brain characterization of MD-MRI distributions and derived parameters is presented and the intrascanner test–retest reliability, repeatability, and reproducibility are evaluated to promote the further development of these quantities as neuroimaging biomarkers. We compared white matter tracts and cortical and subcortical gray matter regions, revealing notable variations in their diffusion-relaxation profiles, indicative of unique microscopic morphological characteristics. We found that the reliability and repeatability of MD-MRI-derived diffusion and relaxation mean parameters were comparable to values expected in conventional diffusion tensor imaging and relaxometry studies. Importantly, the estimated signal fractions of intra-voxel spectral components in the MD-MRI distribution, corresponding to white matter, gray matter, and cerebrospinal fluid, were found to be reproducible. This underscores the viability of employing a spectral analysis approach to MD-MRI data. Our results show that a clinically feasible MD-MRI protocol can reliably deliver information of the rich structural and chemical variety that exists within each imaging voxel, creating potential for new MRI biomarkers with enhanced sensitivity and specificity.
Endogenous opioid dynamics in the dorsal striatum sculpt neural activity to control goal-directed action
Authors: Gowrishankar Raajaram , Hjort Madelyn , Elerding Abigail J , Shirley Sofia E , Van Tilburg Josie , Marcus David J , Senthilkumar Pranav , Abrera Khalid A , Sumarli Dustin , Motovilov Kat , Lau Valerie , Gordon-Fennell Adam A , Zhou Zhe C , Dong Chunyang , Tian Lin , Stuber Garret D , Bruchas Michael R. 
Published: May 2024

AbstractEndogenous neuropeptides are uniquely poised to regulate neuronal activity and behavior across multiple timescales. Traditional studies ascribing neuropeptide contributions to behavior lack spatiotemporal precision. The endogenous opioid dynorphin is highly enriched in the dorsal striatum, known to be critical for regulating goal-directed behavior. However, the locus, the precise timescale, or functional role of endogenous dyn-KOR signaling on goal-directed behavior is unknown. Here, we report that local, time-locked dynorphin release from the dorsomedial striatum is necessary and sufficient for goal-directed behavior using a suite of high resolution modern approaches includingin vivotwo-photon imaging, neuropeptide biosensor detection, conditional deletions and time-locked optogenetic manipulations. We discovered that glutamatergic axon terminals from the basolateral amygdala evoke striatal dynorphin release, resulting in retrograde presynaptic GPCR inhibition during behavior. Collectively, our findings isolate a causal role for endogenous neuropeptide release at rapid timescales, and subsequent GPCR activity for tuning and promoting fundamental goal-directed behaviors.
Kif1a and intact microtubules maintain synaptic-vesicle populations at ribbon synapses in zebrafish hair cells
Authors: David Sandeep , Pinter Katherine , Nguyen Keziah-Khue , Lee David S. , Lei Zhengchang , Sokolova Yuliya , Sheets Lavinia , Kindt Katie S. 
Published: May 2024

AbstractSensory hair cells of the inner ear utilize specialized ribbon synapses to transmit sensory stimuli to the central nervous system. This sensory transmission necessitates rapid and sustained neurotransmitter release, which relies on a large pool of synaptic vesicles at the hair-cell presynapse. Work in neurons has shown that kinesin motor proteins traffic synaptic material along microtubules to the presynapse, but how new synaptic material reaches the presynapse in hair cells is not known. We show that the kinesin motor protein Kif1a and an intact microtubule network are necessary to enrich synaptic vesicles at the presynapse in hair cells. We use genetics and pharmacology to disrupt Kif1a function and impair microtubule networks in hair cells of the zebrafish lateral-line system. We find that these manipulations decrease synaptic-vesicle populations at the presynapse in hair cells. Using electron microscopy, along within vivocalcium imaging and electrophysiology, we show that a diminished supply of synaptic vesicles adversely affects ribbon-synapse function.Kif1amutants exhibit dramatic reductions in spontaneous vesicle release and evoked postsynaptic calcium responses. Additionally, we find thatkif1amutants exhibit impaired rheotaxis, a behavior reliant on the ability of hair cells in the lateral line to respond to sustained flow stimuli. Overall, our results demonstrate that Kif1a-based microtubule transport is critical to enrich synaptic vesicles at the active zone in hair cells, a process that is vital for proper ribbon-synapse function.Key points:Kif1a mRNAs are present in zebrafish hair cellsLoss of Kif1a disrupts the enrichment of synaptic vesicles at ribbon synapsesDisruption of microtubules depletes synaptic vesicles at ribbon synapsesKif1a mutants have impaired ribbon-synapse and sensory-system function
Bisphenol TMC disturbs mitochondrial activity and biogenesis, reducing lifespan and healthspan in the nematodeCaenorhabditis elegans
Authors: Rathor Laxmi , Lee Ho Jeong , McElroy Taylor , Beck Steven , Bailey Julia , Wohlgemuth Stephanie , Kim Sung-Hwan , Heo Jeong-doo , Xiao Rui , Han Sung Min , Hyun Moonjung 
Published: May 2024

AbstractRising concerns about Bisphenol A (BPA) toxicity have prompted the search for safer alternatives. However, concerns persist regarding the safety of replacements like bisphenol TMC (BPTMC), a rapidly emerging BPA substitute. Utilizing thein vivomodel organismCaenorhabditis elegans(C. elegans), whose shared genes mirror human biology, we aim to unveil the potential toxicity of BPTMC on a live animal.C. elegansexposed to 1 mM BPTMC exhibited developmental delays, reduced reproduction, and diminished longevity. Furthermore, an investigation into mortality at various animal stages, oxidative stress, and thermal stress revealed additional compromised toxicity. Notably, exposure to BPTMC resulted in mitochondrial abnormalities, including reduced oxygen consumption, lowered mitochondrial membrane potential, and decreased ATP levels. Additionally, BPTMC increased ROS levels but decreased mitochondrial population. Transcriptome analysis revealed that BPTMC induces alterations in the expression of genes associated with mitochondrial biogenesis. Our findings raise crucial concerns about BPTMC as a safe BPA alternative. The observed widespread toxicity across key life stages suggests a need for further investigation into the potential toxicity of BPTMC on human health and environmental consequences.
Unraveling the impact of hyperleptinemia on female reproduction: Insights from transgenic pig model
Authors: Jamal Muhammad , Cheng Yixiao , Jiao Deling , Cheng Wen , Di Zou M , Wang Xia , Wei Taiyun , Guo Jianxiong , Xu Kaixiang , Zhao Heng , Pu Shaoxia , Yang Chang , Qing Yubo , Jia Baoyu , Li Honghui , Zhao Rusong , Zhao Hong-Ye , Wei Hong-Jiang 
Published: May 2024

AbstractBackgroundInfertility is a growing global health concern affecting millions of couples worldwide. Among several factors, an extreme body weight adversely affects reproductive functions. Leptin is a well-known adipokine that serves as an endocrine signal between adiposity and fertility. However, the exact mechanisms underlying the effects of high leptin on female reproduction remain unclear.MethodsTransgenic pig overexpressing leptin (11) were produced by back cross and screened for leptin overexpression, and the growth curve, fat deposition, reproductive performance, apoptosis, serum hormones and cholesterol production, RNA sequencing, and single nucleus RNA sequencing of the leptin-overexpressed pigs and control group were evaluated.ResultsTransgenic pig overexpressing leptin (11) were obtained, which exhibited significantly reduced body weight, body size, and back fat thickness. These pigs manifested late onset of puberty (327±48.5 vs 150±6.5 days), irregular estrous behavior characterized by increased inter-estrous interval (28.1±4.2 vs 21.3 ± 0.9 days), and more numbers of mating until pregnancy (at least 3 times). This reproductive impairment in leptin pigs was related to hormonal imbalances characterized by increased levels of FSH, LH, prolactin, E2, P4, and TSH, altered steroidogenesis such as increased levels of serum CE along with steroidogenic markers (STAR, CYP19A), and ovarian dysfunctions manifested by neutrophilic infiltration and low expression of caspase-3 positive cells on leptin pigs ovary. Meanwhile, bulk RNA sequencing of the ovaries also revealed neutrophilic infiltration followed by upregulation of inflammation-related genes. Further, leptin overexpression triggered immune response, suppressed follicle development and luteinization, imposing metabolism dysfunction and hormone imbalance in the ovary by single-nucleus RNA sequencing (snRNA-seq).ConclusionLow body weight in leptin overexpression pigs adversely affects reproductive performance, causing delayed puberty, irregular estrous cycles, and reduced breeding efficiency. This is linked to metabolic imbalances, increased immune response, and altered ovarian functions. This study provided a theoretical basis for the complex mechanisms underlying leptin, and infertility by employing leptin-overexpressed female pigs.
Genetically Encoded and Modular SubCellular Organelle Probes (GEM-SCOPe) reveal lysosomal and mitochondrial dysfunction driven byPRKNknockout
Authors: Goldman Camille , Kareva Tatyana , Sarrafha Lily , Schuldt Braxton R. , Sahasrabudhe Abhishek , Ahfeldt Tim , Blanchard Joel W. 
Published: May 2024

SummaryCellular processes including lysosomal and mitochondrial dysfunction are implicated in the development of many diseases. Quantitative visualization of mitochondria and lysosoesl is crucial to understand how these organelles are dysregulated during disease. To address a gap in live-imaging tools, we developed GEM-SCOPe (Genetically Encoded and Modular SubCellular Organelle Probes), a modular toolbox of fluorescent markers designed to inform on localization, distribution, turnover, and oxidative stress of specific organelles. We expressed GEM-SCOPe in differentiated astrocytes and neurons from a human pluripotent stem cellPRKN-knockout model of Parkinson’s disease and identified disease-associated changes in proliferation, lysosomal distribution, mitochondrial transport and turnover, and reactive oxygen species. We demonstrate GEM-SCOPe is a powerful panel that provide critical insight into the subcellular mechanisms underlying Parkinson’s disease in human cells. GEM-SCOPe can be expanded upon and applied to a diversity of cellular models to glean an understanding of the mechanisms that promote disease onset and progression.
Realisation of a key step in the evolution of C4photosynthesis in rice by genome editing
Authors: Jethva Jay , Hahn Florian , Giuliani Rita , Peeters Niels , Cousins Asaph , Kelly Steven 
Published: May 2024

AbstractC4photosynthesis is a repeatedly evolved adaptation to photosynthesis that functions to reduce energy loss from photorespiration. The recurrent evolution of this adaptation is achieved through changes in the expression and localisation of several enzymes and transporters that are conventionally used in non-photosynthetic metabolism. These alterations result in the establishment of a biochemical CO2pump that increases the concentration of CO2around rubisco in a cellular environment where rubisco is protected from oxygen thus preventing the occurrence of photorespiration. A key step in the evolution of C4photosynthesis is the change in subcellular localisation of carbonic anhydrase (CA) activity from the mesophyll cell chloroplast to the cytosol, where it catalyzes the first biochemical step of the C4pathway. Here, we achieve this key step in C4evolution in the C3plantOryza sativa(rice) using genome editing. We show that editing the chloroplast transit peptide of the primary CA isoform in the leaf results in relocalisation of leaf CA activity from the chloroplast to the cytosol. Through analysis of fluorescence induction kinetics in these CA relocalisation lines we uncover a role a new role for chloroplast CA in photosynthetic induction. We also reveal that relocalisation of CA activity to the cytosol causes no detectable perturbation to plant growth or leaf-level CO2assimilation. Collectively, this work uncovers a novel role for chloroplast CA in C3plants, and demonstrates that it is possible to achieve a key step in the evolution of C4photosynthesis by genome editing.Significance statementC4photosynthesis is a highly efficient adaptation to photosynthesis that fuels the world’s most productive crop plants. It evolved from conventional C3photosynthesis through a series of changes in leaf biochemistry and anatomy. Here we achieve a key evolutionary step on the path to C4photosynthesis in rice using genome editing. Specifically, we alter the primary location of carbonic anhydrase activity in the rice leaf from the chloroplast to the cytosol. In doing so, we uncover a novel role for carbonic anhydrase in facilitating the rapid induction kinetics of photosystem II, and initiate a new era of C4engineering using precision breeding techniques.