bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cooperative activities of dICA69N-BARand dCIP4F-BARdomain proteins regulate membrane tubule organizationin vivo
Authors: Mallik Bhagaban , Bhat Sajad , Kumar Vimlesh 
Published: August 2023

AbstractIntracellular membrane tubules play a crucial role in diverse cellular processes, and their regulation is facilitated by Bin-Amphiphysin-Rvs (BAR) domain-containing proteins. This study investigates the roles of dICA69N-BARand dCIP4F-BARin vivo, focusing on their impact onin vivotubule organization. Through cell culture and immunofluorescence staining, we observed co-localization of endogenous dICA69 with dCIP4-induced membrane tubules, indicating their potential recruitment for tubule formation and maintenance. Additionally, dCIP4-positive tubules exhibit enrichment of actin regulatory proteins such as Wasp, SCAR, Arp2, Arp3, and Syndapin. Overexpressing dICA69N-BARin S2R+ cells reveals distinct punctate patterns in the perinuclear region. An earlier study indicated that F-BAR proteins spontaneously segregate from the N-BAR domain-containing proteins during membrane tubule formation. In contrast, our observation supports a model in which different BAR-domain family members can associate with the same tubule and cooperate to fine-tune the tubule width. Moreover, our analysis highlights how dCIP4F-BARfacilitates the redistribution of dICA69N-BARpunctae, leading to altered patterns within the cells. These cooperative activities of dICA69N-BARand dCIP4F-BARare vital for the precise organization of intracellular tubules. Understanding the underlying mechanisms governing this cooperation provides valuable insights into cellular dynamics and the organization of membrane tubules. The implications extend to various physiological and pathological conditions related to intracellular membrane dynamics.
Unveiling nesting strategies: Investigating visual concealment and nest-site selection in Yellow-wattled Lapwings,Vanellus malabaricus(Boddaert, 1783)
Authors: Jagati Vishwa , Ramaswami Geetha , Datta-Roy Aniruddha 
Published: August 2023

ABSTRACTGround-nesting birds such as Yellow-wattled Lapwing,Vanellus malabaricus(Boddaert, 1783) employ several nesting and behavioral strategies to mitigate nest predation, which greatly influences their reproductive success and survival. Yet the breeding ecology of Yellow-wattled Lapwing has received relatively little research attention despite the species’ widespread presence in the Indian subcontinent. The objective of this study was to investigate the significance and impact of two visual concealment strategies commonly utilized by open ground-nesting birds: visual concealment through vegetative characteristics and camouflage using Yellow-wattled Lapwing as the model organism. We also assessed the nest-site selection of Yellow-wattled Lapwings in relation to vegetation cover and food availability, as well as their choice of nest substrate by using behavioral sampling, quadrat sampling, and digital image analysis techniques. We found that variation in hatching success could not be attributed to the analyzed camouflage mechanisms (disruptive markings and pattern complexity matching). Furthermore, the nesting pairs exhibited a preference for areas with high vegetation cover and low food availability while selecting nesting sites. We also showed that this species might exhibit an active behavioral preference for selecting nest substrates. It is important to note that this study was conducted during a single nesting season for the Yellow-wattled Lapwings, and further temporal replicates are necessary to validate and establish the findings over the long term.
Phylogenomic analyses support a new infrageneric classification ofPourthiaea(Maleae, Rosaceae) using multiple inference methods and extensive taxon sampling
Authors: Liu Guang-Ning , Ma Dai-Kun , Zhang Yu , Hodel Richard G.J. , Xie Si-Yu , Wang Hui , Jin Ze-Tao , Li Fu-Xing , Jin Shui-Hu , Zhao Liang , Xu Chao , Wei Yu , Liu Bin-Bin 
Published: August 2023

AbstractIn this comprehensive study, we conducted extensive taxon sampling and performed phylogenomic analyses based on plastome and nuclear ribosomal DNA (nrDNA) datasets. We employed multiple inference methods, including concatenated and coalescent-based strategies, to generate an accurate phylogeny of the woody Rosaceae genusPourthiaea. The nrDNA phylogeny ofPourthiaeastrongly supported three major clades, which were consistent with morphology. However, the plastid tree provided an alternative phylogenetic topology, indicating cytonuclear discordance. Frequent hybridizations between and among the species ofPourthiaeacould explain the cytonuclear discordance. Considering the evidence from morphology and phylogenomic data, we propose a new infrageneric classification forPourthiaea, consisting of three sections:P.sect.Pourthiaea,P.sect.AmphidoxaeB.B.Liu, andP.sect.ImpressivenaeB.B.Liu.
A Pooled Cell Painting CRISPR Screening Platform Enables de novo Inference of Gene Function by Self-supervised Deep Learning
Authors: Sivanandan Srinivasan , Leitmann Bobby , Lubeck Eric , Sultan Mohammad Muneeb , Stanitsas Panagiotis , Ranu Navpreet , Ewer Alexis , Mancuso Jordan E. , Phillips Zachary F , Kim Albert , Bisognano John W. , Cesarek John , Ruggiu Fiorella , Feldman David , Koller Daphne , Sharon Eilon , Kaykas Ajamete , Salick Max R. , Chu Ci 
Published: August 2023

AbstractPooled CRISPR screening has emerged as a powerful method of mapping gene functions thanks to its scalability, affordability, and robustness against well or plate-specific confounders present in array-based screening1–6. Most pooled CRISPR screens assay for low dimensional phenotypes (e.g. fitness, fluorescent markers). Higher-dimensional assays such as perturb-seq are available but costly and only applicable to transcriptomics readouts7–11. Recently, pooled optical screening, which combines pooled CRISPR screening and microscopy-based assays, has been demonstrated in the studies of the NFkB pathway, essential human genes, cytoskeletal organization and antiviral response12–15. While the pooled optical screening methodology is scalable and information-rich, the applications thus far employ hypothesis-specific assays. Here, we enable hypothesis-free reverse genetic screening for generic morphological phenotypes by re-engineering the Cell Painting16technique to provide compatibility with pooled optical screening. We validated this technique using well-defined morphological genesets (124 genes), compared classical image analysis and self-supervised learning methods using a mechanism-of-action (MoA) library (300 genes), and performed discovery screening with a druggable genome library (1640 genes)17. Across these three experiments we show that the combination of rich morphological data and deep learning allows gene networks to emerge without the need for target-specific biomarkers, leading to better discovery of gene functions.
High quality genome assemblies reveal evolutionary dynamics of repetitive DNA and structural rearrangements in theDrosophila virilissub-group
Authors: Flynn Jullien M. , Ahmed-Braimah Yasir H. , Long Manyuan , Wing Rod A. , Clark Andrew G. 
Published: August 2023

ABSTRACTHigh-quality genome assemblies across a range of non-traditional model organisms can accelerate the discovery of novel aspects of genome evolution. TheDrosophila virilisgroup has several attributes that distinguish it from more highly studied species in theDrosophilagenus, such as an unusual abundance of repetitive elements and extensive karyotype evolution, in addition to being an attractive model for speciation genetics. Here we used long-read sequencing to assemble five genomes of three virilis group species and characterized sequence and structural divergence and repetitive DNA evolution. We find that our contiguous genome assemblies allow characterization of chromosomal arrangements with ease and can facilitate analysis of inversion breakpoints. We also leverage a small panel of resequenced strains to explore the genomic pattern of divergence and polymorphism in this species and show that known demographic histories largely predicts the extent of genome-wide segregating polymorphism. We further find that a neo-X chromosome inD. americanadisplays X-like levels of nucleotide diversity. We also found that unusual repetitive elements were responsible for much of the divergence in genome composition among species. Helitron-derived tandem repeats tripled in abundance on the Y chromosome inD. americanacompared toD. novamexicana, accounting for most of the difference in repeat content between these sister species. Repeats with characteristics of both transposable elements and satellite DNAs expanded by three-fold, mostly in euchromatin, in bothD. americanaandD. novamexicanacompared toD. virilis. Our results represent a major advance in our understanding of genome biology in this emerging model clade.Significance statementTheDrosophila virilissub-group is an emerging model with an enticing combination of attributes, including abundant and diverse repetitive DNA content, structural rearrangements, and hybridization capability. The lack of high-quality genome assemblies for this group have prevented detailed understanding of genome evolution. Here, we present five new long-read genome assemblies of three virilis sub-group species along with analyses of structural variants, polymorphisms, repetitive DNAs, and Y chromosome genes and repeats. We find that the expansion and mobilization of non-canonical repetitive elements accounts for most of the divergence in assembled genome sequence between these species, with an especially striking takeover of the Y chromosome by a single type of element in one of the three species. Overall, our study positions the virilis sub-group as a model for a variety of future studies.
Genomic signatures of adaptation to abiotic stress from a geographically diverse collection of chile peppers (Capsicum spp.) from Mexico
Authors: Bernau Vivian , Kantar Michael , Jardon Barbolla Lev , McCoy Jack , Mercer Kristin L. , McHale Leah K. 
Published: August 2023

AbstractExtreme environmental variability requires the identification of genetic diversity that can help crops withstand difficult abiotic conditions. Understanding the genetic basis of adaptation to abiotic stress can provide tools for adapting agriculture to changing climates. Crop landraces and their wild ancestors from centers of domestication have often evolved across diverse environmental conditions and provide a unique opportunity to locate loci harboring alleles that could contribute to abiotic stress tolerance, among other traits. We collected chile peppers (Capsicumspp.) from farmers in southern Mexico along environmental transects crossing temperature, precipitation, and elevational gradients. Using 32,623 filtered SNPs generated from genotyping-by-sequencing (GBS), we conducted an environmental association analysis (EAA) combined with two outlier analyses, FSTand spatial ancestry analyses to detect priority candidate loci associated with climate and soil phenotypes relevant to drought tolerance. Even though cultivated species may be shielded from some environmental selection by management practices (e.g., irrigation), we found fifteen priority loci whose genetic variation covaried with environmental variation in our EAA and were also allele frequency outliers (i.e., Fst and/or SPA). Thirty-three percent of the priority loci were validated with phenotype in response to water deficit. The haplotype blocks associated with these loci identify unique genetic variants worthy of conservation and harbor genes with abiotic stress-related functions. This work provides valuable information to explore quantitative trait loci (QTLs) underlying abiotic stress tolerance in chile pepper and is a new resource for improving plant breeding around the world.Article SummaryThe extreme environmental variability faced by crops requires the identification of potentially adaptive loci for abiotic stressors. We conducted an environmental association analysis (EAA) environments using chile peppers collected in southern Mexico along environmental transects crossing temperature, precipitation, and elevational gradients. We combined EAA with outlier analyses FSTand spatial ancestry analysis to detect priority candidate loci associated with climate and soil phenotypes relevant to drought tolerance that may putatively contribute to abiotic stress adaptation.
Reduced brain glutathione levels during normal aging are associated with visuospatial memory
Authors: Hu Xin , Pan Keyu , Zhao Min , Lv Jiali , Wang Jing , Zhang Xiaofeng , Liu Yuxi , Song Yulu , Gudmundson Aaron T. , Edden Richard A.E. , Ren Fuxin , Zhang Tao , Gao Fei 
Published: August 2023

AbstractDuring aging, the brain is subject to greater oxidative stress (OS), which is thought to play a critical role in cognitive impairment. Glutathione (GSH), as a major antioxidant in the brain, can be used to combatting OS. However, how brain GSH levels vary with age and their associations with cognitive function remain unclear. In this study, we combined point-resolved spectroscopy and edited spectroscopy sequences to investigate GSH levels in the anterior cingulate cortex (ACC), posterior cingulate cortex (PCC), and occipital cortex (OC) of 276 healthy participants (166 females, age range 20–70 years) and examined their relationships with age and cognitive function. The results revealed decreased GSH levels with age in the PCC among all participants. Notably, the timecourse of GSH level changes in the PCC and ACC differed between males and females. Additionally, positive correlations were observed between GSH levels in the PCC and OC and visuospatial memory. Taken together, these findings enhance our understanding of the brain GSH timecourse during normal aging and associations with sex and memory, which is an essential first step for understanding the neurochemical underpinnings of OS-related diseases.
F-box protein FBXB-65 regulates anterograde transport of UNC-104 through modification near the PH domain
Authors: Sabharwal Vidur , Boyanapalli Sri Padma Priya , Shee Amir , Nonet Michael L. , Nandi Amitabha , Chaudhuri Debasish , Koushika Sandhya P. 
Published: August 2023

AbstractAxonal transport is essential for cargo movement between the neuronal cell body and synapses. UNC-104/KIF1A, a Kinesin-3 motor inC. elegansthat anterogradely transports precursors of synaptic vesicles (pre-SVs), is known to be degraded at synapses through the ubiquitin pathway. Knockdown of the E1 ubiquitin-activating enzyme,uba-1, leads to increased accumulation of UNC-104 at neuronal ends and at synapses of touch receptor neurons (TRNs). Loss of the F-box protein FBXB-65, a putative E3 ligase, leads to UNC-104 accumulation at distal ends of neurons, alters net anterograde movement of UNC-104, and the intensity of moving UNC-104 puncta likely bound to cargo without changes in synaptic UNC-104 levels. Using a theoretical model, we analyze the steady state distribution of the anterogradely moving UNC-104 motor. A good agreement between the model and the experimental distributions leads to a crucial hypothesis that UNC-104 may exhibit cooperative binding with moving motor puncta likely associated with cargo, which is regulated byfbxb-65. FBXB-65 regulates the modification of UNC-104 motor in a region besides the cargo binding PH-domain. Bothfbxb-65and UNC-104 motor independent of FBXB-65 regulate the extent of cargo transport in the axon and transport behaviour of cargo at branch points. Our study shows that modification of UNC-104 near its cargo-binding domain may regulate number of motors on the cargo surface and this regulation can fine-tune cargo transport to its destination, the synapse.
RasGEFX triggers spontaneous Ras excitation with RasGEFB/M/U for random cell migration
Authors: Iwamoto Koji , Matsuoka Satomi , Ueda Masahiro 
Published: August 2023

SUMMARYExcitable systems of eukaryotic chemotaxis can generate asymmetric signals of Ras-GTP-enriched domains spontaneously to drive random cell migration without guidance cues. The molecules responsible for the spontaneous signal generation remain elusive. Here, we characterized RasGEFs encoded inDictyostelium discoideumby the live-cell imaging of the Ras dynamics and hierarchical clustering, finding that RasGEFX triggers symmetry breaking to generate a Ras-GTP-enriched domain and is essential for random migration in combination with RasGEFB/M/U but dispensable for chemotaxis. Among RasGEFs, RasGEFX and RasGEFB co-localize with Ras-GTP on oscillatory waves propagating along the membrane and regulate the temporal periods and spatial sizes, respectively, of the waves and thus the cytoskeletal dynamics differently. RasGEFU localized uniformly on the membrane and regulated cell adhesion. These findings provide mechanistic insights into the internal signal generation that operates independently of external chemotaxis signaling and suggest a coordinated control of the cytoskeletal dynamics by multiple RasGEFs for spontaneous motility.
A PD-1-ST2 axis controls Th2 effector function in tissue via a metabolic checkpoint
Authors: Heieis Graham A. , Everts Bart , Roberts Craig W. , Maizels Rick M. , Perona-Wright Georgia 
Published: August 2023

AbstractType 2 immune responses characterise both helminth infections and atopic disease such as allergy or asthma, but a better understanding of the mechanisms that regulate these responses is key to improving therapeutic and vaccination strategies. Immuno-metabolic studies over the last two decades have suggested T cell activation broadly requires rapid increases in glycolysis and oxidative phosphorylation. In contrast, we show that CD4+T helper 2 (Th2) cells activatedin vivo, using models of helminth infection, do not acquire a glycolytic metabolism. Instead, we show that Th2 cells solely increase their oxidative metabolism, associated with increased fatty acid uptake. Rather than contributing directly to effector function, our data reveal that Th2 cells switch to fatty acid oxidation downstream of PD-1 signalling to promote expression of the IL-33 receptor (ST2). These data provide insight into the spatial regulation of T cell metabolism, and suggest that PD-1 blockade therapies may be effective in Th2 disorders.
Global and local adaptation to aridity in a desert plantGymnocarpos przewalskii
Authors: Fu Ruirui , Zhu Yuxiang , Liu Ying , Yang Zhaoping , Lu Ruisen , Qiu Yingxiong , Lascoux Martin , Li Pan , Chen Jun 
Published: August 2023

AbstractIn order to thrive and survive plant species need to combine stability in the long term and rapid response to environmental challenges in the short term. The former would be reflected by global adaptation across species and the latter by pronounced local adaptation among populations of the same species. It remains unclear how much overlap is to be expected between the parts of the genome associated to these two contrasted adaptation processes. In the present study, we generated a high-quality genome and re-sequenced 177 individuals forGymnocarpos przewalskii, an important desert plant species from North-West China, to detect local adaptation. To test for global adaptation to aridity at the molecular level we compared genomic data of 15 species that vary in their ability to withstand drought. A total of 118 genes were involved in global adaptation to aridity. Sixty-fiveG. przewalskiigenes were shared across all xerophytic species, of which sixty-three were under stabilizing selection and two under directional selection. While 20% ofG. przewalskiigenome showed signatures of local adaptation to aridity during population divergence, only 13 of those genes were also under global adaptation. Hence, our results suggest that long-term stability is crucial for adaptation to extreme environmental stress but is only maintained in a small group of highly pleiotropic genes while a rapid response to recent changes elicits a genome-wide response, including gene family expansion. The overlap between the two evolutionary mechanisms appears limited.
Orphan quality control by an SCF ubiquitin ligase directed to pervasive C-degrons
Authors: Kong Ka-Yiu Edwin , Shankar Susmitha , Rühle Frank , Khmelinskii Anton 
Published: August 2023

SummarySelective protein degradation typically involves substrate recognition via short linear motifs known as degrons. Various degrons can be found at protein termini from bacteria to mammals. While N-degrons have been extensively studied, our understanding of C-degrons is still limited. Towards a comprehensive understanding of eukaryotic C-degron pathways, we performed an unbiased survey of C-degrons in budding yeast. We identified over 5000 potential C-degrons by stability profiling of random peptide libraries and of the yeast C-terminome. Combining machine learning, high-throughput mutagenesis and genetic screens revealed that the SCF ubiquitin ligase targets ∼40% of degrons using a single F-box substrate receptor Das1. Although sequence-specific, Das1 is highly promiscuous, recognizing a variety of C-degron motifs. By screening for endogenous substrates, we implicate SCFDas1in degradation of orphan protein complex subunits. Altogether, this work provides a comprehensive view of a eukaryotic C-degronome and uncovers how an SCF/C-degron pathway of broad specificity contributes to proteostasis.
Sensory representations and pupil-indexed listening effort provide complementary contributions to multi-talker speech intelligibility
Authors: McHaney Jacie R. , Hancock Kenneth E. , Polley Daniel B. , Parthasarathy Aravindakshan 
Published: August 2023

AbstractOptimal speech perception in noise requires successful separation of the target speech stream from multiple competing background speech streams. The ability to segregate these competing speech streams depends on the fidelity of bottom-up neural representations of sensory information in the auditory system and top-down influences of effortful listening. Here, we use objective neurophysiological measures of bottom-up temporal processing using envelope-following responses (EFRs) to amplitude modulated tones and investigate their interactions with pupil-indexed listening effort, as it relates to performance on the Quick speech in noise (QuickSIN) test in young adult listeners with clinically normal hearing thresholds. We developed an approach using ear-canal electrodes and adjusting electrode montages for modulation rate ranges, which extended the rage of reliable EFR measurements as high as 1024Hz. Pupillary responses revealed changes in listening effort at the two most difficult signal-to-noise ratios (SNR), but behavioral deficits at the hardest SNR only. Neither pupil-indexed listening effort nor the slope of the EFR decay function independently related to QuickSIN performance. However, a linear model using the combination of EFRs and pupil metrics significantly explained variance in QuickSIN performance. These results suggest a synergistic interaction between bottom-up sensory coding and top-down measures of listening effort as it relates to speech perception in noise. These findings can inform the development of next-generation tests for hearing deficits in listeners with normal-hearing thresholds that incorporates a multi-dimensional approach to understanding speech intelligibility deficits.