bluuebunny/crossref_metadata_2025_split huggingface dataset:
Glioblastoma states are defined by cohabitating cellular populations with progression-, imaging- and sex-distinct patterns
Authors: Bond Kamila M. , Curtin Lee , Hawkins-Daarud Andrea , Urcuyo Javier C. , De Leon Gustavo , Sereduk Christopher , Singleton Kyle W. , Langworthy Jazlynn M. , Jackson Pamela R. , Krishna Chandan , Zimmerman Richard S. , Patra Devi Prasad , Bendok Bernard R. , Smith Kris , Nakaji Peter , Donev Kliment , Baxter Leslie , Mrugała Maciej M. , Al-Dalahmah Osama , Hu Leland S. , Tran Nhan L. , Rubin Joshua B. , Canoll Peter , Swanson Kristin R. 
Published: March 2022

AbstractGlioblastomas (GBMs) are biologically heterogeneous within and between patients. Many previous attempts to characterize this heterogeneity have classified tumors according to their omics similarities. These discrete classifications have predominantly focused on characterizing malignant cells, neglecting the immune and other cell populations that are known to be present. We leverage a manifold learning algorithm to define a low-dimensional transcriptional continuum along which heterogeneous GBM samples organize. This reveals three polarized states: invasive, immune/inflammatory, and proliferative. The location of each sample along this continuum correlates with the abundance of eighteen malignant, immune, and other cell populations. We connect these cell abundances with magnetic resonance imaging and find that the relationship between contrast enhancement and tumor composition varies with patient sex and treatment status. These findings suggest that GBM transcriptional biology is a predictably constrained continuum that contains a limited spectrum of viable cell cohabitation ecologies. Since the relationships between this ecological continuum and imaging vary with patient sex and tumor treatment status, studies that integrate imaging features with tumor biology should incorporate these variables in their design.
On-farm Implementation of Midseason Drainage to Decrease Greenhouse Gas Emissions and Grain Arsenic Concentration in Rice Systems
Authors: Perry Henry , Carrijo Daniela R. , Duncan Aria H. , Fendorf Scott , Linquist Bruce 
Published: March 2022

AbstractRice (Oryza sativa L.) is an important staple crop throughout much of the world, however, it is also a significant source of agricultural methane (CH4) emissions and exposure to arsenic (As). Introduction of soil aerobic events through practices such as alternate wetting and drying or midseason drainage, in flooded rice systems can significantly decrease grain As concentration and seasonal CH4 emissions. Previous on small research plots research has shown that a single midseason drain accomplishes these goals without yield reduction, but the degree of benefit depends on soil-drying severity. A midseason drain also has the potential to fit in well within current management practices of California rice systems, however, it has not been tested across a wide range of soil types or at a scale that farmers typically manage in this region. Therefore, in this three-year study, we aimed to determine if the results from previous small plot research are similar to what can be expected on-farm. At seven on-farm trials we implemented a single midseason drain and compared the grain yields, GHG emissions, and As concentration to the traditional farmer practice (FP) practiced in an adjacent part of the field. Soil moisture parameters [perched water table, volumetric water content, gravimetric water content (GWC), and soil water potential], CH4 and nitrous oxide (N2O) emissions, grain As and cadmium concentration, and grain yield were quantified. Across site-years, midseason drainage reduced seasonal CH4 emissions by 20-77%, compared to the FP control with the magnitude of reduction related to the soil-drying severity. For every 1% reduction in soil GWC during the drainage period, CH4 emissions were reduced by approximately 3.2%, compared to 2.5% in previous on-station research using small plots. Midseason drainage increased N2O emissions (average = 0.248 kg N2O-N ha-1) compared to the control but this accounted for only 3% of the seasonal global warming potential across all drainage treatments. Drainage also decreased grain As concentration by approximately 20%, on average, but was not related to the degree of soil-drying. Importantly, midseason drainage had no significant impact on grain yields. Overall, these results confirm findings from previous on-station research, indicating that midseason drainage may be a viable on-farm management practice for GHG mitigation and for reducing grain As concentration in flooded rice fields with limited risk of yield reduction.
Microbial Energy Metabolism Fuels a CSF2-dependent Intestinal Macrophage Niche within Tertiary Lymphoid Organs
Authors: Chiaranunt Pailin , Burrows Kyle , Ngai Louis , Cao Eric Y , Tai Siu Ling , Liang Helen , Hamidzada Homaira , Wong Anthony , Kuypers Meggie , Despot Tijana , Momen Abdul , Lim Sung Min , Malleavey Thierry , Conway Tyrrell , Imamura Hiromi , Epelman Slava , Mortha Arthur 
Published: March 2022

SummaryMaintaining intestinal macrophage (MP) heterogeneity is critical to ensure tissue homeostasis and host defense. The gut microbiota and host factors are thought to synergistically shape colonic MP development, although there remains a fundamental gap in our understanding of the details of such collaboration. Here, we report tertiary lymphoid organs (TLOs), enriched in group 3 innate lymphoid cells (ILC3s), as a microbiota-operated intestinal niche for the development of monocyte-derived MPs. ILC3-derived colony stimulating factor 2 (CSF2) serves as a developmental and functional determinant for MPs and required microbe-derived extracellular adenosine 5’-triphosphate (ATP) as a trigger. Microbial communities rich in extracellular ATP promoted MP turnover via ILC3 activity in an NLRP3-dependent fashion. Single cell RNA-sequencing of MPs revealed unique TLO-associated, CSF2-dependent MP populations critical for anti-microbial defense against enteric infection. Collectively, these findings describe a fundamental framework that constitutes an intestinal MP niche fueled by microbial energy metabolism.
Thiazides induce glucose intolerance through inhibition of mitochondrial carbonic anhydrase 5b in β-cells
Authors: Kucharczyk Patrycja , Albano Giuseppe , Deisl Christine , Wueest Stephan , Konrad Daniel , Fuster Daniel G. 
Published: March 2022

AbstractThiazides are associated with glucose intolerance and new onset diabetes mellitus, but the molecular mechanisms remain elusive. The aim of this study was to decipher the molecular basis of thiazide-induced glucose intolerance. In mice, hydrochlorothiazide induced a pathological glucose tolerance, characterized by reduced first phase insulin secretion but normal insulin sensitivity. In vitro, thiazides inhibited glucose-and sulfonylurea-stimulated insulin secretion in islets and the murine β-cell line Min6 at pharmacologically relevant concentrations. Inhibition of insulin secretion by thiazides was CO2/HCO3--dependent, not additive to unselective carbonic anhydrase (CA) inhibition with acetazolamide and independent of extracellular potassium. In contrast, insulin secretion was unaltered in islets of mice lacking the known molecular thiazide targets NCC (SLC12A3) or NDCBE (SLC4A8). CA expression profiling with subsequent knock-down of individual CA isoforms suggested mitochondrial CA5b as molecular target. In support of these findings, thiazides significantly attenuated Krebs cycle anaplerosis through reduction of mitochondrial oxalacetate synthesis. CA5b KO mice were resistant to thiazide-induced glucose intolerance, and insulin secretion of islets isolated from CA5b KO mice was unaffected by thiazides.In summary, our study reveals attenuated insulin secretion due to inhibition of the mitochondrial CA5b isoform in β-cells as molecular mechanism of thiazide-induced glucose intolerance.
Designing Cost-Effective, Open-Source, Multi-Head Bioprinters via Conversion of Hobby-Grade 3D Printers
Authors: Chimene David , Deo Kaivalya A. , Thomas Jeremy , Gaharwar Akhilesh K. 
Published: March 2022

AbstractOver the past decade, additive manufacturing has resulted in significant advances towards fabricating anatomic-size, patient-specific scaffolds for tissue models and regenerative medicine. This can be attributed to the development of advanced bioinks capable of precise deposition of cells and biomaterials. The combination of additive manufacturing with advanced bioinks is enabling researchers to fabricate intricate tissue scaffolds that recreate the complex spatial distributions of cells and bioactive cues found in the human body. However, the expansion of this promising technique has been hampered by the high cost of commercially available bioprinters and proprietary software. In contrast, conventional 3D printing has become increasingly popular with home hobbyists and caused an explosion of both low-cost thermoplastic 3D printers and open source software to control the printer. In this work, we bring these benefits into the field of bioprinting by converting widely available and cost-effective 3D printers into fully functional, open source, and customizable multi-head bioprinters. We demonstrate the practicality of this approach by designing bioprinters customized with multiple extruders, automatic bed leveling, and temperature controls for approximately $400. These bioprinters were then used for in vitro and ex vivo bioprinting to demonstrate their utility for tissue engineering.
Repositioning linifanib as a potent anti-necroptosis agent for sepsis
Authors: Yang Kai , Li Min , Yu Liang , He Xiaoyan 
Published: March 2022

AbstractBackgroundSepsis is a systemic inflammatory syndrome (SIRS) caused by acute microbial infection with high mortality rate. The role of tumour necrosis factor α (TNF-α)-induced necroptosis in promoting the pathophysiology of sepsis has been identified. Effective prevention of necroptosis is expected to improve the prognosis of sepsis patients.MethodsWe conducted bioinformatics prediction of candidate drugs by analyzing differentially expressed genes of sepsis patients extracted from GEO database, combining library of integrated network-based cellular signatures (LINCS) L1000 perturbation database. Biological experiments based on TNF-α-induced necroptosis in cellular and mouse model were performed to verify the protection of candidate drugs from SIRS. Cell viability was measured by CellTiter-Glo luminescent ATP assay. Effects of linifanib on necroptosis were investigated by western blotting, immunoprecipitation, and in vitro RIPK1 kinase assay. Survival curve analysis of SIRS mice treated by linifanib was performed.ResultsA total of 16 candidate drugs was screened out through bioinformatics analysis. Our experiments demonstrated that linifanib effectively protected cells from necroptosis and rescued the death of SIRS mice from shock induced by TNF-α. In vitro, linifanib directly suppressed RIPK1 kinase activity. In vivo, linifanib effectively reduced the overexpressed level of IL-6, a good marker of severity during severe sepsis, in the lung of SIRS mice.ConclusionWe provide preclinical evidence for the potential clinical utility of linifanib in sepsis. Study of drug repositioning using bioinformatical predictions combined with experimental validations provides novel strategies for the development of sepsis drug.
Genome-wide signatures of geographic expansion and breeding process in soybean
Authors: Li Ying-hui , Qin Chao , Wang Li , Jiao Chengzhi , Hong Huilong , Tian Yu , Li Yanfei , Xing Guangnan , Wang Jun , Gu Yongzhe , Gao Xingpeng , Li Delin , Li Hongyu , Liu Zhangxiong , Jing Xin , Feng Beibei , Zhao Tao , Guan Rongxia , Guo Yong , Liu Jun , Yan Zhe , Zhang Lijuan , Ge Tianli , Li Xiangkong , Wang Xiaobo , Qiu Hongmei , Zhang Wanhai , Luan Xiaoyan , Han Yingpeng , Han Dezhi , Chang Ruzhen , Guo Yalong , Reif Jochen C. , Jackson Scott A. , Liu Bin , Tian Shilin , Qiu Li-juan 
Published: March 2022

AbstractThe clarification of genomic signatures left during evolutionary histories of crops is crucial for breeding varieties adapting to changing climate. Soybean, a leguminous crop, provides both plant oil and protein. Here, we analyzed genome sequences of 2,214 soybeans and proposed its evolutionary route, which includes four geographic paths, expansion of annual wild soybean (Glycine soja Sieb. & Zucc.) from Southern China, domestication in Central China, expansion of landrace (G. max (L.) Merr.), and local breeding. We observed that local adaptation of the wild and cultivated soybeans was largely independent, and that genetic introgression was mostly derived from sympatric rather than allopatric wild populations during the range expansion of soybean landraces. Range expansion and breeding processes were accompanied with positive selection of flowering-time genes including GmSPA3c as validated by knock-out mutants. Our study shed lights on the evolutionary history of soybean and provides valuable genetic resources for future breeding.TeaserThe expansion and selection history of soybean
Stress-induced transcriptional readthrough into neighboring genes is linked to intron retention
Authors: Hadar Shani , Meller Anatoly , Shalgi Reut 
Published: March 2022

SummaryExposure to certain stresses leads to readthrough transcription. Here we found that readthrough transcription often proceeds into the proximal gene downstream, in a phenomenon termed “read-in”. Using polyA-selected RNA-seq data from mouse fibroblasts, we identified widespread read-in in heat shock, oxidative and osmotic stress conditions. We found that read-in genes share distinctive genomic characteristics; they are extremely short, and highly GC rich. Furthermore, using ribosome footprint profiling we found that translation of read-in genes is significantly reduced. Strikingly, read-in genes show extremely high levels of intron retention during stress, mostly in their first intron, which is not explained by features usually associated with intron retention, such as short introns and high GC content. Finally, we found that first introns in read-in genes have weaker splice sites. Our data portray a relationship between read-in and intron retention, suggesting it may have co-evolved to facilitate reduced translation of read-in genes during stress.
The actin assembly requirements of the formin Fus1 to build the fusion focus
Authors: Billault-Chaumartin Ingrid , Michon Laetitia , Anderson Caitlin A , Yde Sarah E , Suarez Cristian , Iwaszkiewicz Justyna , Zoete Vincent , Kovar David R , Martin Sophie G 
Published: March 2022

AbstractFormins form the largest family of actin filament nucleators and elongators, involved in the assembly of diverse actin structures. Actin filament nucleation and elongation activities reside in the formin homology 1 (FH1) and FH2 domains, common to all formins. However, the rate of these reactions varies between formins by at least 20-fold. Typically, each cell expresses several distinct formins, each contributing to the assembly of one or several actin structures, raising the question of what confers each formin its specificity. Here, using the formin Fus1 in the fission yeast Schizosaccharomyces pombe, we systematically probed the importance of formin nucleation and elongation rates for function in vivo. Fus1 assembles the actin fusion focus, an aster-like structure of actin filaments at the contact site between gametes, necessary for the process of cell fusion to form the zygote during sexual reproduction. By constructing chimeric formins with combinations of FH1 and FH2 domains previously characterized in vitro, we establish that changes in formin nucleation and elongation rates have direct consequences on the architecture of the fusion focus, and that Fus1 native high nucleation and low elongation rates are optimal for fusion focus assembly. We further describe a point mutant in the Fus1 FH2 domain that preserves native nucleation and elongation rates in vitro but alters function in vivo, indicating an additional property of the FH2 domain. Thus, rates of actin assembly are tailored for assembly of specific actin structures.
Suboptimal foraging decisions and involvement of the ventral tegmental area in human opioid addiction
Authors: Raio Candace M. , Biernacki Kathryn , Kapoor Ananya , Wengler Kenneth , Bonagura Darla , Xue Joany , Constantino Sara M. , Horga Guillermo , Konova Anna B. 
Published: March 2022

AbstractAddiction is marked by a tendency to exploit sources of reward despite diminishing returns. This behavior is aptly captured by animal patch-foraging models that have recently been extended to humans. Dopamine and norepinephrine centrally mediate addictive behavior and activity in both catecholaminergic systems is proposed to reflect the computations necessary for optimal foraging. However, the specific neural bases of excessive foraging and their role in human addiction are largely unknown. To address this gap, we studied the behavior of people with and without opioid use disorder (OUD) on a patch-foraging task in which they made serial decisions to “harvest” a depleting resource (“patch”) for reward or incur a varying cost to “travel” to a replenished patch. In a subset of participants, we used high-resolution neuromelanin-sensitive MRI to image neuromelanin concentration, a proxy for long-term catecholaminergic function, in distinct dopaminergic nuclei (ventral tegmental area, substantia nigra subregions) and the noradrenergic locus coeruleus. While all participants were sensitive to the long-run reward rates of different patch-foraging environments, OUD participants stayed in reward patches longer than optimal—markedly overharvesting a source of reward despite its declining value—and this correlated with more chronic drug use. Overharvesting was selectively associated with lower neuromelanin signal in the ventral tegmental area but not other dopaminergic nuclei, nor the locus coeruleus. Our findings suggest that foraging decisions relevant to addiction involve a ventral-tegmental-area circuit that may signal reward rates in dynamic environments and implicate this circuit in maladaptive reward pursuit in human addiction to opioids.Significance statementPatch-foraging provides a potentially important translational framework for understanding addictive behavior by revealing how maladaptive reward pursuit emerges in more ecologically valid decision contexts. Here, we show that the tendency to exploit sources of reward despite diminishing returns is associated with chronic drug use in people with opioid use disorder, a particularly devastating form of addiction. We further use neuromelanin-sensitive MRI, a neuroimaging measure of the long-term function of dopamine neurons, to reveal that variation in ventral tegmental area neuromelanin signal selectively underlies individual differences in this overharvesting bias. These findings establish a role for specific dopaminergic circuits in patch-foraging decisions and advance understanding of the neurobiology of human addiction to opioids that has so far eluded the field.
Comparative assessment of computed tomography and magnetic resonance imaging of the spider morph of Python regius and wild type Python regius to evaluate the morphological correlate of the wobble syndrome
Authors: Schrenk Fabian , Starck Matthias , Kiefer Ingmar , Flegel Thomas , Tebrün Wiebke , Pees Michael 
Published: March 2022

AbstractThere is general awareness of artificial selection and its potential implications on health and welfare of animals. Despite growing popularity and increasing numbers of breeds of atypical colour and pattern variants in reptiles, only few studies have investigated the appearance and cause of various diseases associated with colour morphs. Ball pythons (Python regius) are among the most frequently bred reptiles and breeders selected for a multitude of different colour and pattern morphs. Among those colour variants, the spider morph of the ball python is frequently associated with the wobble syndrome. The aim of this study was to determine, whether a morphological variant can be found and brought in association with the clinical occurrence of the wobble syndrome in spider ball pythons, using MRI and CT-imaging as intra-vitam diagnostic methods. Data from eight ball pythons including five spider ball pythons and three wild type ball pythons was assessed and evaluated comparatively. We were able to identify distinctive structural differences in inner ear morphology in spider ball pythons highly probable to relate to the wobble syndrome. To our knowledge, these anomalies are described for the first time and represent a basis for further anatomical and genetic studies and discussions regarding animal welfare in reptile breeding.
Complex developmental and transcriptional dynamics underlie pollinator-driven evolutionary transitions in nectar spur morphology in Aquilegia (columbine)
Authors: Edwards Molly B. , Ballerini Evangeline S. , Kramer Elena M. 
Published: March 2022

ABSTRACTPremiseDetermining the developmental programs underlying morphological variation is key to elucidating the evolutionary processes that generated the stunning biodiversity of the angiosperms. Here, we characterize the developmental and transcriptional dynamics of the elaborate petal nectar spur of Aquilegia (columbine) in species with contrasting pollination syndromes and spur morphologies.MethodsWe collected petal epidermal cell number and length data across four Aquilegia species, two with the short, curved nectar spurs of the bee-pollination syndrome, and two with the long, straight spurs of the hummingbird syndrome. We also performed RNA-seq on A. brevistyla (bee) and A. canadensis (hummingbird) distal and proximal spur compartments at multiple developmental stages. Finally, we intersected these datasets with a previous QTL mapping study on spur length and shape to identify new candidate loci.ResultsThe differential growth between the proximal and distal surfaces of curved spurs is primarily driven by differential cell division. However, independent transitions to straight spurs in the hummingbird syndrome have evolved by increasing differential cell elongation between spur surfaces. The RNA-seq data reveal these tissues to be transcriptionally distinct, and point to auxin signaling as being involved with the differential cell elongation responsible for the evolution of straight spurs. We identify several promising candidate genes for future study.ConclusionsOur study, taken together with previous work in Aquilegia, reveals the complexity of the developmental mechanisms underlying trait variation in this system. The framework we have establish here will lead to exciting future work examining candidate genes and processes involved in the rapid radiation of the genus.