bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cavernous Angioma Symptomatic Hemorrhage (CASH) Trial Readiness II: Imaging Biomarkers and Trial Modeling
Authors: Hage Stephanie , Kinkade Serena , Girard Romuald , Flemming Kelly D. , Kim Helen , Torbey Michel T. , Huang Judy , Huston John , Shu Yunhong , Selwyn Reed G. , Hart Blaine L. , Mabray Marc C. , Feghali James , Sair Haris I. , Narvid Jared , Lupo Janine M. , Lee Justine , Stadnik Agnieszka , Alcazar Roberto , Shenkar Robert , Hobson Nicholas , DeBiasse Dorothy , Lane Karen , McBee Nichole , Treine Kevin , Ostapkovich Noeleen , Wang Ying , Thompson Richard E. , Mendoza-Puccini Carolina , Koenig James , Carroll Timothy , Hanley Daniel F. , Awad Issam A. 
Published: June 2023

AbstractBackgroundQuantitative susceptibility mapping (QSM) and dynamic contrast enhanced quantitative perfusion (DCEQP) MRI sequences assessing iron deposition and vascular permeability were previously correlated with new hemorrhage in cavernous angiomas. We assessed their prospective changes in cavernous angiomas with symptomatic hemorrhage (CASH) in a multisite trial readiness project (clinicaltrials.govNCT03652181).MethodsPatients with CASH in the prior year, without prior or planned lesion resection or irradiation were enrolled. Mean QSM and DCEQP of CASH lesion were acquired at baseline, and at 1- and 2-year follow-ups. Sensitivity and specificity of biomarker changes were analyzed in relation to predefined lesional symptomatic hemorrhage (SH) or asymptomatic change (AC). Sample size calculations for hypothesized therapeutic effects were conducted.ResultsWe logged 143 QSM and 130 DCEQP paired annual assessments. Annual QSM change was greater in cases with SH than in cases without SH (p= 0.019). Annual QSM increase by ≥ 6% occurred in 7 of 7 cases (100%) with recurrent SH and in 7 of 10 cases (70%) with AC during the same epoch, and 3.82 times more frequently than clinical events. DCEQP change had lower sensitivity for SH and AC than QSM change, and greater variance. A trial with smallest sample size would detect a 30% difference in QSM annual change in 34 or 42 subjects (one and two-tailed, respectively), power 0.8, alpha 0.05.ConclusionsAssessment of QSM change is feasible and sensitive to recurrent bleeding in CASH. Evaluation of an intervention on QSM percent change may be used as a time-averaged difference between 2 arms using a repeated measures analysis. DCEQP change is associated with lesser sensitivity and higher variability than QSM. These results are the basis of an application for certification by the U.S. F.D.A. of QSM as a biomarker of drug effect in CASH.
Inhibition of BCR::ABL1 tyrosine kinase activity Aids in the Generation of Stable Chronic Myeloid Leukemia Induced Pluripotent Stem Cells
Authors: Bama Benjamin Esther Sathya , Babu Dinesh , Joshi Gaurav , Rajamani Bharathi M , Nandy Krittika , Rani Sonam , Anandan Senthamizhselvi , Premkumar Chitra , Maddali Madhavi , Abraham Aby , Velayudhan Shaji R , Balasubramanian Poonkuzhali 
Published: June 2023

AbstractInduced pluripotent stem cells (iPSCs) generated from patients with chronic myeloid leukemia (CML) have the potential for disease modeling to study disease pathogenesis and screening therapeutic interventions. In this study, we aimed to generate iPSCs from CD34+hematopoietic progenitors of CML patients with varying responses to tyrosine kinase inhibitor (TKI) therapy. The generated CML-CD34-iPSC colonies displayed atypical “dome-shaped” morphology and underwent spontaneous differentiation in a few days. However, supplementation with imatinib (IM), the most widely used TKI to treat CML patients, in the culture medium improved the stability and maintenance of all isolated CML-CD34-iPSC colonies, allowing them to be maintained for more than 20 passages without significant differentiation. In contrast to previous studies, our results indicate that suppressing the BCR::ABL1 oncogenic pathway is essential for efficiently generating stable CML-iPSC colonies. Furthermore, we successfully differentiated these iPSCs to CD34+hematopoietic progenitors both in the presence and absence of IM. This robust protocol for generating CML-iPSCs provides a valuable resource for disease modelling. The generated iPSCs will be a valuable tool for investigating CML pathophysiology, drug resistance mechanisms, and drug screening to identify novel and effective therapies for this disease.
Meaning-making behavior in a small-brained hominin,Homo naledi, from the late Pleistocene: contexts and evolutionary implications
Authors: Fuentes Agustin , Kissel Marc , Spikins Penny , Molopyane Keneiloe , Hawks John , Berger Lee R. 
Published: June 2023

AbstractExplorations in the Dinaledi Subsystem of the Rising Star cave system have yielded some of the earliest evidence of a mortuary practice in hominins. Because the evidence is attributable to the small-brainedHomo naledi, these analyses call into question several assumptions about behavioral and cognitive evolution in Pleistocene hominins. The evidence from the Dinaledi Subsystem, and at other locations across the Rising Star cave system may widen the phylogenetic breadth of mortuary, and possibly funerary, behaviors. These discoveries may also associate the creation of meaning making and increased behavioral complexity with a small-brained hominin species, challenging certain assertions about the role of encephalization and cognition in hominin and human evolution. We suggest that the hominin socio-cognitive niche is more diverse than previously thought. If true, technological, meaning-making activities, and cognitive advances in human evolution are not associated solely with the evolution of larger brained members of the genusHomo.One-Sentence SummaryEvidence for complex behaviors associated with a small-brained hominin suggest that large brains are not solely responsible for the manifestation of human-like behavioral complexity.
Isolation by environment is more important than isolation by distance along a tropical gradient in direct developing frogs
Authors: Percino-Daniel Ruth , Jones Kara S. , Maigret Thomas A. , Weisrock David W. , Piñero Daniel 
Published: June 2023

AbstractAbiotic factors are important for defining population structure and limiting gene flow, especially in ectotherm species, the challenge is to identify which ones are the most important and can produce a pattern of isolation by environment. Our study aim is to quantify the extent to which divergence is driven by abiotic factors such as temperature, precipitation and elevation. To do so, we used a direct-developing frog species,Craugastor lokithat occurs along a steep elevation gradient. Using restriction-site associated DNA sequencing (RADseq) from individuals collected from 100 m to 2250 m of elevation at 13 localities at Sierra Madre de Chiapas in southern Mexico we described population structure using a variety of model-based clustering and landscape genomics approaches. We found that populations sampled at higher elevation correspond probably to an undescribed new species ofCraugastor, and that populations fromCraugastor lokibetween 120 m and 1500 m are clustered in two different genetic groups: a Pacific slope group and a Central Depression slope group. We found signatures of isolation by environment more important that isolation by distance in contributing to genetic divergence in this group of frogs at a fine scale. The environmental variables such as: mean temperature of wettest and warmest quarter, annual mean temperature, and seasonality in temperature and precipitation play an important role on population differentiation. Our results underscore the importance of abiotic factors as drivers and highlight the use of different approaches to illuminate fine scale population divergence given the complexity of disentangling the contribution of both patterns of isolation.
DGRPool: A web tool leveraging harmonizedDrosophilaGenetic Reference Panel phenotyping data for the study of complex traits
Authors: Gardeux Vincent , Bevers Roel P.J. , David Fabrice P.A. , Rosschaert Emily , Rochepeau Romain , Deplancke Bart 
Published: June 2023

AbstractGenome-wide association studies have advanced our understanding of complex traits, but studying how a GWAS variant can affect a specific trait in the human population remains challenging due to environmental variability.Drosophila melanogasteris in this regard an excellent model organism for studying the relationship between genetic and phenotypic variation due to its simple handling, standardized growth conditions, low cost, and short lifespan. TheDrosophilaGenetic Reference Panel (DGRP) in particular has been a valuable tool for studying complex traits, but proper harmonization and indexing of DGRP phenotyping data is necessary to fully capitalize on this resource. To address this, we created a web tool calledDGRPool(dgrpool.epfl.ch), which aggregates phenotyping data of 1034 phenotypes across 135 DGRP studies in a common environment. DGRPool enables users to download data and run various tools such as genome-wide (GWAS) and phenome-wide (PheWAS) association studies. As a proof-of-concept, DGRPool was used to study the longevity phenotype and uncovered both established and unexpected correlations with other phenotypes such as locomotor activity, starvation resistance, desiccation survival, and oxidative stress resistance. DGRPool has the potential to facilitate new genetic and molecular insights of complex traits inDrosophilaand serve as a valuable, interactive tool for the scientific community.
Attention Modulates Human Visual Responses to Objects by Tuning Sharpening
Authors: Doostani Narges , Hossein-Zadeh Gholam-Ali , Cichy Radoslaw Martin , Vaziri-Pashkam Maryam 
Published: June 2023

AbstractVisual stimuli compete with each other for cortical processing and attention biases this competition in favor of the attended stimulus. How does the relationship between the stimuli affect the strength of this attentional bias? Here, we used functional MRI to explore the effect of target-distractor similarity in neural representation on attentional modulation in the human visual cortex using univariate and multivariate pattern analyses. Using stimuli from four object categories (human bodies, cats, cars and houses), we investigated attentional effects in the primary visual area V1, the object-selective regions LO and pFs, the body-selective region EBA, and the scene-selective region PPA. We demonstrated that the strength of the attentional bias towards the target is not fixed but decreases with increasing target-distractor similarity. Simulations provided evidence that this result pattern is explained by tuning sharpening rather than an increase in gain. Our findings provide a mechanistic explanation for behavioral effects of target-distractor similarity on attentional biases and suggest tuning sharpening as the underlying mechanism in object-based attention.
But, what are the cells doing? Image Analysis pipeline to follow single cells in the zebrafish embryo
Authors: Bercowsky-Rama Arianne , Venzin Olivier F. , Rohde Laurel A. , Chiaruttini Nicolas , Oates Andrew C. 
Published: June 2023

AbstractMicroscopy has rapidly evolved at pace with live markers, enabling ever higher spatiotemporal resolution of multicellular dynamics within larger fields of view. Consequently, we are now in the era of widespread production of terabyte (TB)-sized time-lapse movies of experimental model systems, including developing embryos and organoids. Working with these large datasets has presented a new set of hurdles, particularly due to the lack of standardized open-source pipelines for acquiring, handling and analyzing the data. Moreover, although long-term tracking of a cell throughout an entire process, for example vertebrate organogenesis, is key to revealing the underlying cellular dynamics, this has proven largely elusive. To specifically address the question “But, what are the cells doing?”, we created an image analysis pipeline optimized to track single cells in light-sheet acquired datasets (1 TB sized time-lapse, 8h of imaging, 30 min gene expression cycle, cell movement speed (1µm /1 minute), 200-400 µm tissue depth). Our modular pipeline optimizes and connects the following: image acquisition parameters to improve tracking feasibility; hardware specifications; data handling and compression tools; pre-processing steps; state-of-the-art cell tracking tools (Mastodon, MaMuT) and a novel open-source/ python-based tool (Paleontologist) to analyze and visualize spatiotemporal dynamics of the tracked cells. Importantly, our pipeline is adaptable to a variety of experimental systems and accessible to researchers regardless of expertise in coding and image analysis.One-sentence SummaryUser-friendly cell-tracking pipeline that connects image acquisition in multicellular systems through to data analysis of cellular dynamics.
QTL Mapping of Seed Fe Concentration in an Interspecific RIL Population Derived fromLens culinaris×Lens ervoides
Authors: Podder Rajib , Gela Tadesse S. , Bett Kirstin E. , Vandenberg Albert 
Published: June 2023

AbstractBiofortification of lentil (Lens culinarisMedik.) was investigated to potentially increase bioavailable iron (Fe) in the human diet. This study assessed the genetic variation for seed Fe concentration (SFeC) and identified the genomic regions associated with SFeC in an interspecific mapping population derived from crossing betweenL. culinariscv. ‘Eston’ andL. ervoidesaccession IG 72815. A total of 134 RILs were evaluated in three environments. The SFeC data for individual environments and best linear unbiased prediction (BLUP) of the SFeC across environments were used for QTL analysis. The seeds of the RILs exhibited variation for SFeC from 47.0 to 102.9 mg kg-1and several RILs showed transgressive segregation for SFeC. QTL analysis identified two QTLs on chromosomes 2 and 6 that accounted for 11.9-14.0% and 12.5-20.5%, respectively, of the total phenotypic variation for SFeC. The SNP markers linked to the identified QTLs may prove useful for increasing SFeC via marker-assisted selection. RILs with high SFeC can be incorporated into the lentil breeding program to broaden the genetic base of the breeding pool and/or used for the development of genetic resources for future genomic studies.
Initiation of B-type starch granules in wheat endosperm requires the plastidial α-glucan phosphorylase PHS1
Authors: Kamble Nitin Uttam , Makhamadnojov Farrukh , Fahy Brendan , Martins Carlo , Saalbach Gerhard , Seung David 
Published: June 2023

AbstractPHS1 is a plastidial α-glucan phosphorylase that can elongate and degrade maltooligosaccharides (MOS), but its exact physiological role in plants is poorly understood. Here, we discover a specialised role of PHS1 in establishing the unique bimodal characteristic of starch granules in the wheat endosperm. Wheat endosperm contains large A-type granules that initiate at early grain development, and small B-type granules that initiate in later grain development. We demonstrate that PHS1 interacts with BGC1 – a carbohydrate-binding protein essential for normal B-type granule initiation. Mutants of tetraploid durum wheat deficient in all homeologs of PHS1 had normal A-type granules, but fewer and larger B-type granules. Grain size and starch content were not affected by the mutations. Further, by assessing granule numbers during grain development in thephs1mutant, and using a double mutant defective in both PHS1 and BGC1, we demonstrate that PHS1 is exclusively involved in B-type granule initiation. The total starch content and number of starch granules per chloroplast in leaves were not affected by loss of PHS1, suggesting that its role in granule initiation in wheat is limited to the endosperm. We therefore propose that the initiation of A- and B-type granules occur via distinct biochemical mechanisms, where PHS1 plays an exclusive role in B-type granule initiation.
Quantifying the impact of sample, instrument, and data processing on biological signatures detected with Raman spectroscopy
Authors: Wiemann Jasmina , Heck Philipp R. 
Published: June 2023

AbstractRaman spectroscopy is a popular tool for characterizing complex biological materials and their geological remains1-10. Ordination methods, such as Principal Component Analysis (PCA), rely on spectral variance to create a compositional space1, the ChemoSpace, grouping samples based on spectroscopic manifestations that reflect different biological properties or geological processes1-7. PCA allows to reduce the dimensionality of complex spectroscopic data and facilitates the extraction of relevant informative features into data formats suitable for downstream statistical analyses, thus representing an essential first step in the development of diagnostic biosignatures. However, there is presently no systematic survey of the impact of sample, instrument, and spectral processing on the occupation of the ChemoSpace. Here the influence of sample count, signal-to-noise ratios, spectrometer decalibration, baseline subtraction routines, and spectral normalization on ChemoSpace grouping is investigated using synthetic spectra. Increase in sample size improves the dissociation of sample groups in the ChemoSpace, however, a stable pattern in occupation can be achieved with less than 10 samples per group. Systemic noise of different amplitude and frequency, features that can be introduced by instrument or sample11,12, are eliminated by PCA even when spectra of differing signal-to-noise ratios are compared. Routine offsets (± 1 cm−1) in spectrometer calibration contribute to less than 0.1% of the total spectral variance captured in the ChemoSpace, and do not obscure biological information. Standard adaptive baselining, together with normalization, increase spectral comparability and facilitate the extraction of informative features. The ChemoSpace approach to biosignatures represents a powerful tool for exploring, denoising, and integrating molecular biological information from modern and ancient organismal samples.
The demographic history of the wild crop relativeBrachypodium distachyonis shaped by distinct past and present ecological niches
Authors: Minadakis Nikolaos , Williams Hefin , Horvath Robert , Caković Danka , Stritt Christoph , Thieme Michael , Bourgeois Yann , Roulin Anne C. 
Published: June 2023

AbstractClosely related to economically important crops, the grassBrachypodium distachyonhas been originally established as a pivotal species for grass genomics but more recently flourished as a model for developmental biology. Grasses encompass more than 10,000 species and cover more than 40% of the world land area from tropical to temperate regions. Given that grasses also supply about a fifth of the world’s dietary protein as cereal grains, unlocking the sources of phenotypic variation inB. distachyonis hence of prime interest in fundamental and applied research in agronomy, ecology and evolution. We present here theB. distachyondiversity panel, which encompasses 332 fully sequenced accessions covering the whole species distribution from Spain to Iraq. By combining population genetics, niche modeling and landscape genomics, we suggest thatB. distachyonrecolonized Europe and the Middle East following the last glacial maximum. Consequently, the species faced new environmental conditions which led to clear associations between bioclimatic variables and genetic factors as well as footprints of positive selection in the genome. Altogether, this genomic resource offers a powerful alternative toArabidopsis thalianato investigate the genetic bases of adaptation and phenotypic plasticity in plants and more specifically in monocots.
Single-cell lineage tracing reveals hierarchy and mechanism of adipocyte precursor maturation
Authors: Rivera-Gonzalez Guillermo C. , Butka Emily G. , Gonzalez Carolynn E. , Kong Wenjun , Jindal Kunal , Morris Samantha A. 
Published: June 2023

AbstractWhite adipose tissue is crucial in various physiological processes. In response to high caloric intake, adipose tissue may expand by generating new adipocytes. Adipocyte precursor cells (progenitors and preadipocytes) are essential for generating mature adipocytes, and single-cell RNA sequencing provides new means to identify these populations. Here, we characterized adipocyte precursor populations in the skin, an adipose depot with rapid and robust generation of mature adipocytes. We identified a new population of immature preadipocytes, revealed a biased differentiation potential of progenitor cells, and identified Sox9 as a critical factor in driving progenitors toward adipose commitment, the first known mechanism of progenitor differentiation. These findings shed light on the specific dynamics and molecular mechanisms underlying rapid adipogenesis in the skin.
Investigating the impact of paternal aging on murine sperm miRNA profiles and their potential link to autism spectrum disorder
Authors: Miyahara Kazusa , Tatehana Misako , Kikkawa Takako , Osumi Noriko 
Published: June 2023

AbstractPaternal aging has consistently been linked to an increased risk of neurodevelopmental disorders, including autism spectrum disorder (ASD), in offspring. Recent evidence has highlighted the involvement of epigenetic factors. In this study, we aimed to investigate age-related alterations in microRNA (miRNA) profiles of mouse sperm and analyze target genes regulated by differentially expressed miRNAs (DEmiRNAs). Microarray analyses were conducted on sperm samples from mice at different ages: 3 months (3 M), over 12 M, and beyond 20 M. We identified 26 miRNAs with differential expression between the 3 M and 20 M mice, 34 miRNAs between the 12 M and 20 M mice, and 2 miRNAs between the 3 M and 12 M mice. The target genes regulated by these miRNAs were significantly associated with apoptosis/ferroptosis pathways and the nervous system. We revealed alterations in sperm miRNA profiles due to aging and suggest that the target genes regulated by these DEmiRNAs are associated with apoptosis and the nervous system, implying a potential link between paternal aging and an increased risk of neurodevelopmental disorders such as ASD. The observed age-related changes in sperm miRNA profiles have the potential to impact sperm quality and subsequently affect offspring development.