bluuebunny/crossref_metadata_2025_split huggingface dataset:
The pho1;2a’-m1.1 allele of Phosphate1 conditions mis-regulation of the phosphorus starvation response in maize (Zea mays ssp. mays L.)
Authors: Alonso-Nieves Ana Laura , Salazar-Vidal M. Nancy , Torres-Rodríguez J. Vladimir , Chávez Montes Ricardo A. , Pérez-Vázquez Leonardo M. , Massange-Sánchez Julio A. , Gillmor C. Stewart , Sawers Ruairidh J. H. 
Published: March 2022

ABSTRACTPHO1 proteins play a central role in plant inorganic phosphorus translocation and sensing. The maize (Zea mays ssp. mays) genome encodes two co-orthologs of the Arabidopsis PHO1 gene, designated ZmPho1;2a and ZmPho1;2b. Here, we report the characterization of the transposon-footprint allele Zmpho1;2a’-m1.1, which we refer to hereafter as pho1;2a. The pho1;2a allele is a stable derivative formed by excision of an Activator element from the ZmPho1;2a gene. The pho1;2a allele contains an 8 bp insertion at the point of excision that disrupts the reading frame and is predicted to generate a premature translational stop. We show that the pho1;2a allele is linked to a dosage-dependent reduction in transcript accumulation and a mild reduction in seedling growth that is enhanced under nutrient deficient conditions. Characterization of the shoot and root transcriptomes of seedlings segregating the pho1;2a mutation under different nutrient conditions revealed pho1;2a to have a dominant effect on patterns of transcript accumulation. Gene set enrichment analysis of the transcripts mis-regulated in pho1;2a mutants suggests that Pho1;2a functions in the fine-tuning of the transcriptional phosphate starvation response. We discuss our results with reference to possible genetic redundancy among maize Pho1 genes and in the context of reports linking functional variation in Pho1;2a to agronomically important traits.
Pulvinar Slits: Cellulose-deficient and De-Methyl-Esterified Homogalacturonan-Rich Structures in a Legume Motor Cell
Authors: Takahara Masahiro , Tsugawa Satoru , Sakamoto Shingo , Demura Taku , Nakata Miyuki T 
Published: March 2022

AbstractThe cortical motor cells (CMCs) in a legume pulvinus execute the reversible deformation in leaf movement that is driven by changes in turgor pressure. In contrast to the underlying osmotic regulation proper, the cell wall structure of CMCs that contributes to the movement has yet to be characterized in detail. Here, we report that the cell wall of CMCs has circumferential slits with low levels of cellulose deposition. This structure is unique and distinct from that of any other primary cell walls reported so far; thus, we named them “pulvinar slits.” Notably, we predominantly detected de-methyl-esterified homogalacturonan inside pulvinar slits, with a low deposition of highly methyl-esterified homogalacturonan, as with cellulose. In addition, Fourier-transform infrared spectroscopy analysis indicated that the cell wall composition of pulvini is different from that of other axial organs, such as petioles or stems. Moreover, monosaccharide analysis showed that pulvini are pectin-rich organs like developing stems and that the amount of galacturonic acid in pulvini is greater than in developing stems. Computer modeling suggested that pulvinar slits facilitate anisotropic extension in the direction perpendicular to the slits in the presence of turgor pressure. When tissue slices of CMCs were transferred to different extracellular osmotic conditions, pulvinar slits altered their opening width, indicating their deformability. In this study, we thus characterized a distinctive cell wall structure of CMCs, adding new knowledge to repetitive and reversible organ deformation as well as the structural diversity and function of the plant cell wall.
Robustness of field studies evaluating biodiversity responses to invasive species management in New Zealand
Authors: Allen Robert B. , Forsyth David M. , MacKenzie Darryl I. , Peltzer Duane A. 
Published: March 2022

AbstractBenefits of invasive species management for terrestrial biodiversity are widely expected and promoted in New Zealand. Evidence for this is presented in policy and scientific reviews of the literature, but the robustness and repeatability of the underpinning evidence-base remains poorly understood. We evaluated the design of field-based studies assessing biodiversity responses to invasive species management in 155 peer-reviewed articles published across 46 journals from 2010 - 2019. Each study was assessed against nine principles of experimental design, covering robustness of sampling and avoidance of bias. These principles are important in New Zealand to detect treatment effects from environmental variability driven by underlying gradients such as soil fertility, climate and disturbance. Fifty two percent of studies defined a sampling universe and 68% of studies specified the treatment. Whereas, 54%, 74%, and 50% of studies did not utilise replication, representatively sample the universe, or quantify invasive species, respectively. Ninety five percent of studies quantified biodiversity responses, although a high proportion of these did not representatively sample replicates. Initial conditions and accounting for effects of experimental implementation were not utilised in 57% and 84% of studies respectively. No studies avoided observer/analyst bias using blinding methods, despite this being widely adopted in other fields. Ordinal logistic regression showed these principles varied in how robustly they were applied among categories of biodiversity responses and invasive species. Our findings suggest that greater attention to experimental design principles is desirable: supported by researchers, funding agencies, reviewers, and journal editors. Greater resources is not necessarily a solution to these design issues. Undertaking fewer studies, that are individually more expensive because they better adhere to experimental design principles, is one alternative. Our intent in this article is to improve the robustness of future field studies for at least some principles. Robust designs have enduring value, reduce uncertainty and increase our understanding of when, where and how often the impacts of invasive species on biodiversity are indeed reversible.
SARS-CoV-2 reinfections during the first three major COVID-19 waves in Bulgaria
Authors: Marinov Georgi K. , Mladenov Mladen , Rangachev Antoni , Alexiev Ivailo 
Published: March 2022

AbstractBackgroundThe COVID-19 pandemic has had a devastating impact on the world over the past two years (2020-2021). One of the key questions about its future trajectory is the protection from subsequent infections and disease conferred by a previous infection, as the SARS-CoV-2 virus belongs to the coronaviruses, a group of viruses the members of which are known for their ability to reinfect convalescent individuals. Bulgaria, with high rates of previous infections combined with low vaccination rates and an elderly population, presents a somewhat unique context to study this question.MethodsWe use detailed governmental data on registered COVID-19 cases to evaluate the incidence and outcomes of COVID-19 reinfections in Bulgaria in the period between March 2020 and early December 2021.ResultsFor the period analyzed, a total of 4,106 cases of individuals infected more than once were observed, including 31 cases of three infections and one of four infections. The number of reinfections increased dramatically during the Delta variant-driven wave of the pandemic towards the end of 2021. We observe a moderate reduction of severe outcomes (hospitalization and death) in reinfections relative to primary infections, and a more substantial reduction of severe outcomes in breakthrough infections in vaccinated individuals.ConclusionsIn the available datasets from Bulgaria, prior infection appears to provide some protection from severe outcomes, but to a lower degree than the reduction in severity of breakthrough infections in the vaccinated compared to primary infections in the unvaccinated.
Seasonality in living kidney donation in the United States from 1995-2019
Authors: Arking Andrew , Kaddu Gabriella , Segev Dorry L. , Garonzik-Wang Jacqueline , Muzaale Abimereki D. , Ammary Fawaz Al 
Published: March 2022

ABSTRACTFor nearly two decades, the annual number of US living kidney donors has been characterized by worrying patterns of decline and no factors have been identified to explain and reverse these patterns. Evidence suggests that there is seasonality in living kidney donation; herein we investigate whether potentially modifiable social, economic, and structural issues might explain this seasonality. Using donor-registry data from the Scientific Registry of Transplant Recipients, we described this seasonality in living kidney donation and used Poisson regression stratified by both donor–recipient biological relationship and estimated household income tertile to quantify these trends. In every decade from 1980-2020, there was a summer-only surge in living kidney donations (13%-25% for biologically related donors and 10%-17% for unrelated donors). This summer-only surge was evident for the months of June, July, and August when compared with January for each given year and statistically significant in some groups (range of incidence rate ratio [IRR] for related donors: 1.05-1.34; IRR for unrelated donors: 1.08-1.19). We observed this summer-only surge across all three income tertiles ($73,544+, $52,635- $73,544, and <$52,635) and regardless of donor-recipient relationship. Seasonal variation in donation is associated with structural factors, which may serve as potential targets for interventions to increase donation.
Clinical improvement of DM1 patients reflected by reversal of disease-induced gene expression in blood
Authors: van Cruchten Remco T.P. , van As Daniël , Glennon Jeffrey C. , van Engelen Baziel G.M. , ’t Hoen Peter A. C. ,   the OPTIMISTIC consortium,   the ReCognitION consortium
Published: March 2022

AbstractMyotonic dystrophy type 1 (DM1) is an incurable multisystem disease caused by a CTG-repeat expansion in the DM1 protein kinase (DMPK) gene. The OPTIMISTIC clinical trial demonstrated positive and heterogenous effects of cognitive behavioral therapy (CBT) on the capacity for activity and social participations in DM1 patients. Here, we performed mRNA sequencing of full blood for 27 patients of the OPTIMISTIC cohort before and after the CBT intervention. We identified 608 genes for which their expression was significantly associated with the disease causing CTG-repeat expansion, as well as 1176 genes significantly associated with the average clinical response towards the intervention. Remarkably, all 97 genes significantly associated with both returned to more normal levels in patients who benefited most from CBT. This trend was consistent with the difference observed between DM1 patients and controls in an earlier study of blood mRNA expression levels, singling these genes out as candidate biomarkers for therapy response. Together these results highlight the ability to find disease relevant information in full blood of DM1 patients, opening new avenues to monitor therapy effects.
The Microbiome in Adult Acute Appendicitis
Authors: Lee Mei Sze , Sulit Arielle , Frizelle Frank , Purcell Rachel 
Published: March 2022

AbstractAcute appendicitis is a common acute surgical emergency; however, the pathogenesis of adult appendicitis remains poorly understood. The microbiome is increasingly thought to play a key role in inflammatory disease of the bowel and similarly, may play a role in appendicitis.AimThis study aimed to characterize the microbiome of adult acute appendicitis in a prospective cohort.MethodWe recruited 60 adults with acute appendicitis and 20 healthy controls. Rectal swabs were taken from each patient. After DNA extraction, 16S rRNA amplicon sequencing was carried out for analysis of diversity and taxonomic abundance.ResultsPhylogenetic sequencing of the samples indicated that there is a difference between the microbial composition of those with acute appendicitis and healthy controls, with a statistically significant decrease in alpha diversity in rectal swabs of appendicitis patients compared to healthy controls. At the genus level, we saw an increased abundance of potential pathogens, e.g. Parvimonas and Acinetobacter, and a decrease in commensal taxa such as Faecalibacterium, Blautia and Lachnospiraceae in appendicitis patients compared to healthy controls.ConclusionAn imbalance in the gut microbiome may contribute to the pathogenesis of adult acute appendicitis.
Comparison of radiation dose and cancer risk between conventional polychromatic imaging and gemstone spectral imaging in computed tomography (CT) examination: a phantom study
Authors: Wu Yuliang , Li Songyang , Fang Tianqi , Deng Wei , Liu Guoqing , Wu Jiabao , Chen Xianjie , Chen Hanwei , Ma Jinting , Huang Bingsheng 
Published: March 2022

AbstractThis study aims to measure the radiation doses and estimate the associated lifetime attributable risks (LARs) of cancer incidence resulted from gemstone spectral imaging (GSI) and conventional polychromatic imaging (CPI) in computed tomography (CT) examinations. Organ doses were measured using an adult phantom and thermoluminescent dosimeters. Four scans, including head CT, thorax CT, abdomen CT and pelvis CT, were performed on the phantom. LARs of cancer incidence were estimated for Chinese population and US population. The effective doses of thorax CT was the highest. With CPI, it was 7.94 mSv for females, and 7.74 mSv for males. With GSI, it was 6.81 mSv for females, and 7.69 mSv for males. With GSI, the corresponding LARs for males and females aged 20-70 years were less than 0.062% and 0.154%, respectively. With CPI, these values were less than 0.074% and less than 0.171%, respectively. The LARs decreased in both US population and Chinese population when exposed age increased, with thorax scan causing the highest risk. GSI does not increased radiation exposure or cancer risk compared to CPI. These findings may allow the application of GSI in patients referred for CT.
Immortal time bias in older vs younger age groups: a simulation study with application to a population-based cohort of patients with colon cancer
Authors: Pilleron Sophie , Maringe Camille , Morris Eva JA , Leyrat Clémence 
Published: March 2022

AbstractBackgroundIn observational studies, the risk of immortal time bias (ITB) increases with the likelihood of early death, itself increasing with age. We investigated how age impacts the magnitude of ITB when estimating the effect of surgery on one-year overall survival (OS) in patients with stage IV colon cancer aged 50-74 and 75-99 in England.MethodUsing simulations, we compared estimates from a time-fixed exposure model to three methods addressing ITB: time-varying exposure, delayed entry, and landmark methods. We then estimated the effect of surgery on one-year OS using a national population-based cohort of patients derived from the CORECT-R resource.ResultsIn simulations, the magnitude of ITB was larger among older patients when their probability of early death increased or treatment was delayed. The bias was corrected using the methods addressing ITB. When applied to CORECT-R data, these methods yielded smaller effects than the time-fixed exposure approach but effects were similar in both age groups.ConclusionITB must be addressed in all longitudinal studies, particularly, when investigating the effect of an exposure on an outcome in different groups of people (e.g., age groups) with different distributions of exposure and outcomes.
Different structural variant prediction tools yield considerably different results in Caenorhabditis elegans
Authors: Lesack Kyle , Mariene Grace M. , Andersen Erik C. , Wasmuth James D. 
Published: March 2022

ABSTRACTThe accurate characterization of structural variation is crucial for our understanding of how large chromosomal alterations affect phenotypic differences and contribute to genome evolution. Whole-genome sequencing is a popular approach for identifying structural variants, but the accuracy of popular tools remains unclear due to the limitations of existing benchmarks. Moreover, the performance of these tools for predicting variants in non-human genomes is less certain, as most tools were developed and benchmarked using data from the human genome.To address this problem, multiple short- and long-read tools were benchmarked using real and simulated Caenorhabditis elegans whole-genome sequence data. To evaluate the use of long-read data for the validation of short-read predictions, the agreement between predictions from a short-read ensemble learning method and long-read tools were compared. The results obtained from simulated data indicate that the best performing tool is contingent on the type and size of the variant, as well as the sequencing depth of coverage. These results also highlight the need for reference datasets generated from real data that can be used as ‘ground truth’ in benchmarks.
Comparing the potential of microglia preparations generated using different human iPSC-based differentiation methods to model microglia-mediated mechanisms of amyotrophic lateral sclerosis pathophysiology
Authors: Tang Ye Man , Pulimood Nisha S. , Stifani Stefano 
Published: March 2022

AbstractMicroglia are the resident immune cells of nervous system. In healthy conditions, microglia actively patrol neural tissues in a homeostatic state, which can rapidly change to an activated state in response to local injury/disease. Dysregulated microglia activation is a hallmark of disorders and diseases of the nervous system, including motor neuron diseases such as amyotrophic lateral sclerosis (ALS). The elucidation of the roles of microglia in human biology and disease has recently benefitted from the development of human induced pluripotent stem cell (iPSC)-based approaches to generate microglia-like cells. Microglia represent a heterogeneous group of cells with spatial diversity in both health and disease. This situation poses a considerable challenge along the path towards establishing the most pathologically-relevant human iPSC-derived microglia preparations to investigate the complex roles of microglia in ALS and other neurological diseases. The success of these approaches must account for microglia diversity in different regions of the brain and spinal cord. In this study, we compared the transcriptomes of human iPSC-derived microglia generated using different methods to determine whether or not separate strategies can be used to generate microglia with distinct transcriptional signatures in vitro. We show that microglia derived using two different methods display distinct in vitro maturation characteristics. We also reveal that different derivation methods give rise to preparations comprising human microglia with distinct transcriptomic signatures resembling the gene profiles of specific microglia subpopulations in vivo. These findings suggest that a careful, and coordinated, implementation of multiple microglia differentiation methods from human iPSCs can be an effective approach towards the goal of generating multiple microglia subtypes that will offer enhanced model systems to account for microglia heterogeneity in vivo. Spatially-defined human iPSC-derived microglia would represent an enhanced tool to study the multiple levels of involvement of microglia in mechanisms of motor neuron degeneration in ALS, as well as other neurological diseases and disorders.
THE STABILIZATAION OF C-MYC BY THE NOVEL CELL CYCLE REGULATOR, SPY1, DECREASES EFFICACY OF BREAST CANCER TREATMENTS
Authors: Ferraiuolo Rosa-Maria , Fifield Bre-Anne , Hamm Caroline , Porter Lisa Ann 
Published: March 2022

AbstractPurposec-Myc is frequently upregulated in breast cancers, however, targeting c-Myc has proven to be a challenge. Targeting of downstream mediators of c-Myc, such as the ‘cyclin-like’ cell cycle regulator Spy1, may be a viable therapeutic option in a subset of breast cancer subtypes.MethodsMouse mammary tumour cells isolated from MMTV-Myc mice and human breast cancer cell lines were used to manipulate Spy1 levels followed by tamoxifen or chemotherapeutic treatment with a variety of endpoints. Patient samples from TNBC patients were obtained and constructed into a TMA and stained for c-Myc and Spy1 protein levels.ResultsOver time, MMTV-Myc cells show a decreased response to tamoxifen treatment with increasing levels of Spy1 in the tamoxifen-resistant cells. shRNA against Spy1 re-establishes tamoxifen sensitivity. Spy1 was found to be highly elevated in human TNBC cell and patient samples, correlating to c-Myc protein levels. c-Myc was found to be stabilized by Spy1 and knocking down Spy1 in TNBC cells shows a significant increase in response to chemotherapy treatments.ConclusionsUnderstanding the interplay between protein expression level and response to treatment is a critical factor in developing novel treatment options for breast cancer patients. These data have shown a connection between Spy1 and c-Myc protein levels in more aggressive breast cancer cells and patient samples. Furthermore, targeting c-Myc has proven difficult, these data suggest targeting Spy1 even when c-Myc is elevated can confer an advantage to current chemotherapies.
Opiate responses are controlled by interactions ofOprm1andFgf12loci in rodents: Correspondence to human GWAS findings
Authors: Lemen Paige M. , Zuo Yanning , Hatoum Alexander S. , Dickson Price E. , Mittleman Guy , Agrawal Arpana , Reiner Benjamin C. , Berrettini Wade , Ashbrook David G. , Gunturkun Mustafa Hakan , Mulligan Megan K. , Williams Robert W , Telese Francesca , Chen Hao 
Published: March 2022

AbstractWe mapped high-precision time-series data (15 min bins for 3 hours) generated for ~ 700 adult BXD mice across 105 morphine- and naloxone-related traits using new sequence-derived marker maps and a linear-mixed model. We confirm a previously mapped sex-independent effect of initial locomotor responses to morphine (50 mg/kg ip) that maps precisely toOprm1on chromosome (Chr) 10, with the linkage score reaching −log10P of ~12.4 (with a high B allele) at 75 min and exhausted by 160 min. We detected a new modulator of opiate locomotor activation in both sexes on Chr 16, with a peak linkage that climbs from 105 through to 180 min after injection. This locus includes one compelling candidate—fibroblast growth factor 12 (Fgf12). We also detected a strong, but transient epistatic interaction between these two loci. Single nuclei transcriptomic analyses in rats demonstrates that expression ofOprm1andFgf12mRNA covary in one specific subtype ofDrd1medium spiny neurons. Our Bayesian network analysis identified that a cascade of MAP kinases—Mapk8ip2, Map3k11, andMap3k12—are part of theOprm1–Fgf12network. This is the first demonstration of a time-dependent epistatic interaction modulating drug response in mammals with interesting mechanistic implications. Analysis ofOPRM1andFGF12gene networks in human GWAS data highlights enrichment of signals associated with substance use disorder.