bluuebunny/crossref_metadata_2025_split huggingface dataset:
Unravelling the paradox in physically dormant species: elucidating the onset of dormancy after dispersal and dormancy-cycling
Authors: Jaganathan Ganesh K 
Published: June 2022

Abstract

Background
For species that produce seeds with a water-impermeable coat, i.e. physical dormancy (PY), it has been widely recognized that (1) seeds shed at a permeable state cannot become impermeable after dispersal; and (2) dormancy-cycling, i.e. a permeable ↔ impermeable transition, does not occur. Given a tight relationship between moisture content and onset of seed-coat impermeability, seeds maturing at low relative humidity (RH) and occurring in a high-temperature environment are inferred to produce impermeable coats, and ex situ drying of permeable seeds can lead to the onset of impermeability.

Scope and conclusion
It is proposed here that permeable seeds dispersed at low RH and in high-temperature soils might become impermeable due to continuous drying. Similarly, seeds with shallow PY dormancy (with higher moisture content immediately after becoming impermeable) can cycle back to a permeable state or absolute PY (complete dry state) when RH increases or decreases, respectively. A conceptual model is developed to propose that seeds from several genera of 19 angiosperm families at the time of natural dispersal can be (1) impermeable (dormant), i.e. primary dormancy; (2) impermeable (dormant) and become permeable (non-dormant) and then enter a dormant state in the soil, often referred to as secondary dormancy; (3) permeable (non-dormant) and become impermeable (dormant) in the soil, i.e. enforced dormancy; or (4) dormant or non-dormant, but cycle between permeable and non-permeable states depending on the soil conditions, i.e. dormancy-cycling, which is different from sensitivity-cycling occurring during dormancy break. It is suggested that this phenomenon could influence the dormancy-breaking pattern, but detailed studies of this are lacking.
Effects of operational sex ratio and male density on size-dependent mating in Minshan’s toads, Bufo minshanicus, on the Tibetan Plateau of China
Authors: Yu Tonglei , Green David M , Deng Yaohui , Han Yanting 
Published: June 2022

Abstract
In many animal species, an increase in the operational sex ratio (OSR), density or a combination of both should lead to more intensive competition among individuals of the more abundant sex. To test this, we examined pairing patterns of Minshan’s toad (Bufo minshanicus) from six populations between 2008 and 2015 along the eastern Tibetan Plateau in south-west China. OSRs in breeding aggregations of Minshan’s toad are normally male biased and males actively compete with each other for acquisition and retention of mates. We found evidence that deviations from random mating by size varied between populations and between years according to the magnitude of the OSR and male density. Larger males were generally more successful in pairing than smaller males when the OSR was slightly male biased and male density was high. However, the resulting size-disproportionate mating was more evident when OSR was closer to 1.99, indicating a positive correlation with the intensity of aggressive scramble competition. Thus, the intensity of male-male competition may partly explain variation in size-disproportionate mating among populations.
Local fitness and epistatic effects lead to distinct patterns of linkage disequilibrium in protein-coding genes
Authors: Ragsdale Aaron P 
Published: June 2022

Abstract
Selected mutations interfere and interact with evolutionary processes at nearby loci, distorting allele frequency trajectories and creating correlations between pairs of mutations. Recent studies have used patterns of linkage disequilibrium between selected variants to test for selective interference and epistatic interactions, with some disagreement over interpreting observations from data. Interpretation is hindered by a lack of analytic or even numerical expectations for patterns of variation between pairs of loci under the combined effects of selection, dominance, epistasis, and demography. Here, I develop a numerical approach to compute the expected two-locus sampling distribution under diploid selection with arbitrary epistasis and dominance, recombination, and variable population size. I use this to explore how epistasis and dominance affect expected signed linkage disequilibrium, including for nonsteady-state demography relevant to human populations. Using whole-genome sequencing data from humans, I explore genome-wide patterns of linkage disequilibrium within protein-coding genes. I show that positive linkage disequilibrium between missense mutations within genes is driven by strong positive allele-frequency correlations between mutations that fall within the same annotated conserved domain, pointing to compensatory mutations or antagonistic epistasis as the prevailing mode of interaction within conserved genic elements. Linkage disequilibrium between missense mutations is reduced outside of conserved domains, as expected under Hill–Robertson interference. This variation in both mutational fitness effects and selective interactions within protein-coding genes calls for more refined inferences of the joint distribution of fitness and interactive effects, and the methods presented here should prove useful in that pursuit.
Accounting for Errors in Data Improves Divergence Time Estimates in Single-cell Cancer Evolution
Authors: Chen Kylie , Moravec Jiří C , Gavryushkin Alex , Welch David , Drummond Alexei J 
Published: June 2022

AbstractSingle-cell sequencing provides a new way to explore the evolutionary history of cells. Compared to traditional bulk sequencing, where a population of heterogeneous cells is pooled to form a single observation, single-cell sequencing isolates and amplifies genetic material from individual cells, thereby preserving the information about the origin of the sequences. However, single-cell data are more error-prone than bulk sequencing data due to the limited genomic material available per cell. Here, we present error and mutation models for evolutionary inference of single-cell data within a mature and extensible Bayesian framework, BEAST2. Our framework enables integration with biologically informative models such as relaxed molecular clocks and population dynamic models. Our simulations show that modeling errors increase the accuracy of relative divergence times and substitution parameters. We reconstruct the phylogenetic history of a colorectal cancer patient and a healthy patient from single-cell DNA sequencing data. We find that the estimated times of terminal splitting events are shifted forward in time compared to models which ignore errors. We observed that not accounting for errors can overestimate the phylogenetic diversity in single-cell DNA sequencing data. We estimate that 30–50% of the apparent diversity can be attributed to error. Our work enables a full Bayesian approach capable of accounting for errors in the data within the integrative Bayesian software framework BEAST2.
Recent progress on the treatment of type 1 autoimmune pancreatitis and IgG4-related disease
Authors: Okazaki Kazuichi , Ikeura Tsukasa , Uchida Kazushige 
Published: June 2022

ABSTRACTIgG4-related disease (IgG4-RD) is a fibroinflammatory disorder recognized as a novel clinical entity with either synchronous or metachronous multiorgan involvement. Autoimmune pancreatitis (AIP) is classified into two types: type 1 AIP as a pancreatic manifestation of IgG4-RD and type 2 AIP with granulocytic epithelial lesion and occasional association with ulcerative colitis. Although the pathogenic mechanism still remains unclear, possible multipathogenic factors such as genetic factors, disease-specific or related antigens, and abnormal innate or adaptive immunity may be involved in the development of IgG4-RD. Many immunocytes including M2 macrophages, plasmablasts, B cells, and T-cells (Th2-CD4+T, follicular helper T-cells, and CD4+SLAMF7+cytotoxic T-cells) play important roles in the pathogenesis. Conventional induction and maintenance therapies with glucocorticoid or rituximab are recommended in all symptomatic patients with active IgG4-RD. In those at risk for irreversible damage in any organs, this should be done urgently, regardless of symptoms. As no randomized clinical trials other than glucocorticoid maintenance therapy for type 1 AIP have been performed, the comprehensive management for IgG4-RD has not been established yet. Targeted treatment approaches against the plasmablast to B cell lineage and the CD4+ SLAMF7+ cytotoxic T-cell seem to be promising for the future-directed treatment.
TEB/POLQ plays dual roles in protecting Arabidopsis from NO-induced DNA damage
Authors: Lv Qiang , Han Shuang , Wang Lei , Xia Jinchan , Li Peng , Hu Ruoyang , Wang Jinzheng , Gao Lei , Chen Yuli , Wang Yu , Du Jing , Bao Fang , Hu Yong , Xu Xingzhi , Xiao Wei , He Yikun 
Published: June 2022

Abstract
Nitric oxide (NO) is a key player in numerous physiological processes. Excessive NO induces DNA damage, but how plants respond to this damage remains unclear. We screened and identified an Arabidopsis NO hypersensitive mutant and found it to be allelic to TEBICHI/POLQ, encoding DNA polymerase θ. The teb mutant plants were preferentially sensitive to NO- and its derivative peroxynitrite-induced DNA damage and subsequent double-strand breaks (DSBs). Inactivation of TEB caused the accumulation of spontaneous DSBs largely attributed to endogenous NO and was synergistic to DSB repair pathway mutations with respect to growth. These effects were manifested in the presence of NO-inducing agents and relieved by NO scavengers. NO induced G2/M cell cycle arrest in the teb mutant, indicative of stalled replication forks. Genetic analyses indicate that Polθ is required for translesion DNA synthesis across NO-induced lesions, but not oxidation-induced lesions. Whole-genome sequencing revealed that Polθ bypasses NO-induced base adducts in an error-free manner and generates mutations characteristic of Polθ-mediated end joining. Our experimental data collectively suggests that Polθ plays dual roles in protecting plants from NO-induced DNA damage. Since Polθ is conserved in higher eukaryotes, mammalian Polθ may also be required for balancing NO physiological signaling and genotoxicity.
The cotranscriptional folding landscape for two cyclic di-nucleotide-sensing riboswitches with highly homologous aptamer domains acting either as ON- or OFF-switches
Authors: Landgraf Tom , Völklein Albrecht Eduard , Fürtig Boris , Schwalbe Harald 
Published: June 2022

Abstract
Riboswitches are gene regulatory elements located in untranslated mRNA regions. They bind inducer molecules with high affinity and specificity. Cyclic-di-nucleotide-sensing riboswitches are major regulators of genes for the environment, membranes and motility (GEMM) of bacteria. Up to now, structural probing assays or crystal structures have provided insight into the interaction between cyclic-di-nucleotides and their corresponding riboswitches. ITC analysis, NMR analysis and computational modeling allowed us to gain a detailed understanding of the gene regulation mechanisms for the Cd1 (Clostridium difficile) and for the pilM (Geobacter metallireducens) riboswitches and their respective di-nucleotides c-di-GMP and c-GAMP. Binding capability showed a 25 nucleotide (nt) long window for pilM and a 61 nt window for Cd1. Within this window, binding affinities ranged from 35 μM to 0.25 μM spanning two orders of magnitude for Cd1 and pilM showing a strong dependence on competing riboswitch folds. Experimental results were incorporated into a Markov simulation to further our understanding of the transcriptional folding pathways of riboswitches. Our model showed the ability to predict riboswitch gene regulation and its dependence on transcription speed, pausing and ligand concentration.
A novel, essentialtrans-splicing protein connects the nematode SL1 snRNP to the CBC-ARS2 complex
Authors: Fasimoye Rotimi Yemi , Spencer Rosie Elizabeth Barker , Soto-Martin Eva , Eijlers Peter , Elmassoudi Haitem , Brivio Sarah , Mangana Carolina , Sabele Viktorija , Rechtorikova Radoslava , Wenzel Marius , Connolly Bernadette , Pettitt Jonathan , Müller Berndt 
Published: June 2022

AbstractSpliced leader trans-splicing is essential for gene expression in many eukaryotes. To elucidate the molecular mechanism of this process, we characterise the molecules associated with the Caenorhabditis elegans major spliced leader snRNP (SL1 snRNP), which donates the spliced leader that replaces the 5′ untranslated region of most pre-mRNAs. Using a GFP-tagged version of the SL1 snRNP protein SNA-1 created by CRISPR-mediated genome engineering, we immunoprecipitate and identify RNAs and protein components by RIP-Seq and mass spectrometry. This reveals the composition of the SL1 snRNP and identifies associations with spliceosome components PRP-8 and PRP-19. Significantly, we identify a novel, nematode-specific protein required for SL1 trans-splicing, which we designate SNA-3. SNA-3 is an essential, nuclear protein with three NADAR domains whose function is unknown. Mutation of key residues in NADAR domains inactivates the protein, indicating that domain function is required for activity. SNA-3 interacts with the CBC-ARS2 complex and other factors involved in RNA metabolism, including SUT-1 protein, through RNA or protein-mediated contacts revealed by yeast two-hybrid assays, localisation studies and immunoprecipitations. Our data are compatible with a role for SNA-3 in coordinating trans-splicing with target pre-mRNA transcription or in the processing of the Y-branch product of the trans-splicing reaction.
From bench to bedside: Improving the clinical safety of GalNAc–siRNA conjugates using seed-pairing destabilization
Authors: Schlegel Mark K , Janas Maja M , Jiang Yongfeng , Barry Joseph D , Davis Wendell , Agarwal Saket , Berman Daniel , Brown Christopher R , Castoreno Adam , LeBlanc Sarah , Liebow Abigail , Mayo Tara , Milstein Stuart , Nguyen Tuyen , Shulga-Morskaya Svetlana , Hyde Sarah , Schofield Sally , Szeto John , Woods Lauren Blair , Yilmaz Vedat O , Manoharan Muthiah , Egli Martin , Charissé Klaus , Sepp-Lorenzino Laura , Haslett Patrick , Fitzgerald Kevin , Jadhav Vasant , Maier Martin A 
Published: June 2022

Abstract
Preclinical mechanistic studies have pointed towards RNA interference-mediated off-target effects as a major driver of hepatotoxicity for GalNAc–siRNA conjugates. Here, we demonstrate that a single glycol nucleic acid or 2′–5′-RNA modification can substantially reduce small interfering RNA (siRNA) seed-mediated binding to off-target transcripts while maintaining on-target activity. In siRNAs with established hepatotoxicity driven by off-target effects, these novel designs with seed-pairing destabilization, termed enhanced stabilization chemistry plus (ESC+), demonstrated a substantially improved therapeutic window in rats. In contrast, siRNAs thermally destabilized to a similar extent by the incorporation of multiple DNA nucleotides in the seed region showed little to no improvement in rat safety suggesting that factors in addition to global thermodynamics play a role in off-target mitigation. We utilized the ESC+ strategy to improve the safety of ALN-HBV, which exhibited dose-dependent, transient and asymptomatic alanine aminotransferase elevations in healthy volunteers. The redesigned ALN-HBV02 (VIR-2218) showed improved specificity with comparable on-target activity and the program was reintroduced into clinical development.
Novel cancer gene discovery using a forward genetic screen in RCAS-PDGFB-driven gliomas
Authors: Weishaupt Holger , Čančer Matko , Rosén Gabriela , Holmberg Karl O , Häggqvist Susana , Bunikis Ignas , Jiang Yiwen , Sreedharan Smitha , Gyllensten Ulf , Becher Oren J , Uhrbom Lene , Ameur Adam , Swartling Fredrik J 
Published: June 2022

AbstractBackgroundMalignant gliomas, the most common malignant brain tumors in adults, represent a heterogeneous group of diseases with poor prognosis. Retroviruses can cause permanent genetic alterations that modify genes close to the viral integration site.MethodsHere we describe the use of a high-throughput pipeline coupled to the commonly used tissue-specific retroviral RCAS-TVA mouse tumor model system. Utilizing next-generation sequencing, we show that retroviral integration sites can be reproducibly detected in malignant stem cell lines generated from RCAS-PDGFB-driven glioma biopsies.ResultsA large fraction of common integration sites contained genes that have been dysregulated or misexpressed in glioma. Others overlapped with loci identified in previous glioma-related forward genetic screens, but several novel putative cancer-causing genes were also found. Integrating retroviral tagging and clinical data, Ppfibp1 was highlighted as a frequently tagged novel glioma-causing gene. Retroviral integrations into the locus resulted in Ppfibp1 upregulation, and Ppfibp1-tagged cells generated tumors with shorter latency on orthotopic transplantation. In human gliomas, increased PPFIBP1 expression was significantly linked to poor prognosis and PDGF treatment resistance.ConclusionsAltogether, the current study has demonstrated a novel approach to tagging glioma genes via forward genetics, validating previous results, and identifying PPFIBP1 as a putative oncogene in gliomagenesis.
The current state of glioma data registries
Authors: Yearley Alexander G , Iorgulescu Julian Bryan , Chiocca Ennio Antonio , Peruzzi Pier Paolo , Smith Timothy R , Reardon David A , Mooney Michael A 
Published: June 2022

Abstract

Background
The landscape of glioma research has evolved in the past 20 years to include numerous large, multi-institutional, database efforts compiling either clinical data on glioma patients, molecular data on glioma specimens, or a combination of both. While these strategies can provide a wealth of information for glioma research, obtaining information regarding data availability and access specifications can be challenging.

Methods
We reviewed the literature for ongoing clinical, molecular, and combined database efforts related to glioma research to provide researchers with a curated overview of the current state of glioma database resources.

Results
We identified and reviewed a total of 20 databases with data collection spanning from 1975 to 2022. Surveyed databases included both low- and high-grade gliomas, and data elements included over 100 clinical variables and 12 molecular data types. Select database strengths included large sample sizes and a wide variety of variables available, while limitations of some databases included complex data access requirements and a lack of glioma-specific variables.

Conclusions
This review highlights current databases and registries and their potential utility in clinical and genomic glioma research. While many high-quality resources exist, the fluid nature of glioma taxonomy makes it difficult to isolate a large cohort of patients with a pathologically confirmed diagnosis. Large, well-defined, and publicly available glioma datasets have the potential to expand the reach of glioma research and drive the field forward.
Restricting Tobacco Retail Outlets Around Middle and High Schools as a Way to Reduce Tobacco Marketing Disparities: A Simulation Study
Authors: Obinwa Udoka , Pasch Keryn E , Jetelina Katelyn K , Ranjit Nalini , Perez Adriana , Perry Cheryl L , Harrell Melissa 
Published: June 2022

AbstractIntroductionCommunities with more people of color and economically disadvantaged residents are disproportionately exposed to tobacco marketing from tobacco companies. This study examined if banning tobacco retail outlets (TROs) within 1000 ft of schools would reduce these marketing disparities through a greater reduction in the amount of tobacco advertising around schools in these communities.MethodsData from objectively audited advertisement data from 106 convenience stores and gas stations around 42 middle and high schools located in the four major metropolitan areas of Texas were linked with schools’ enrollment data. ArcGIS (Aeronautical Reconnaissance Coverage Geographic Information System) was used to simulate a 1000-ft ban of tobacco sales around the schools. Independent sample T-tests and Mann–Whitney U tests were used to test mean differences where appropriate.ResultsSchools with a higher enrollment of Hispanic/Latino (mean = 171.6, SD = 96.9) and economically disadvantaged students (mean = 168.9, SD = 102.3) were surrounded with significantly greater advertising at TROs than schools with lower enrollment of these groups (mean = 82.8, SD = 49.1 and mean = 89.2, SD = 50.6, respectively). A simulated 1000 ft ban of TROs around schools led to greater advertising reduction around schools with a higher enrollment of Hispanic/Latino students (13.3%–29.4% reductions) in comparison to schools with lower Hispanic/Latino student enrollment. However, the more economically disadvantaged schools had a smaller reduction in the number of advertisements (5.9%–21.9% reductions) in comparison to schools with less economically disadvantaged students.ConclusionThe implementation of a ban of tobacco sales at TROs within 1000 ft of schools is one policy approach to reduce youth exposure to tobacco marketing, particularly among students of color.Study ImplicationTobacco retail outlets (TROs) around schools with a higher enrollment of Hispanic/Latino and economically disadvantaged students had significantly more tobacco advertisements in comparison to schools with lower enrollment of these student groups. A simulated ban of TROs within 1000 ft of schools led to greater advertising reduction around schools with a higher enrollment of Hispanic/Latino students. For schools with more economically disadvantaged students, the ban led to a smaller reduction in advertisements in comparison to schools with less economically disadvantaged students. This proposed place-based strategy could be a successful means to reduce tobacco advertising and marketing disparity among communities of color.
Role of serine/threonine protein kinase STN7 in the formation of two distinct photosystem I supercomplexes in Physcomitrium patens
Authors: Gerotto Caterina , Trotta Andrea , Bajwa Azfar Ali , Morosinotto Tomas , Aro Eva-Mari 
Published: June 2022

Abstract
Reversible thylakoid protein phosphorylation provides most flowering plants with dynamic acclimation to short-term changes in environmental light conditions. Here, through generating Serine/Threonine protein kinase 7 (STN7)-depleted mutants in the moss Physcomitrella (Physcomitrium patens), we identified phosphorylation targets of STN7 kinase and their roles in short- and long-term acclimation of the moss to changing light conditions. Biochemical and mass spectrometry analyses revealed STN7-dependent phosphorylation of N-terminal Thr in specific Light-Harvesting Complex II (LHCII) trimer subunits (LHCBM2 and LHCBM4/8) and provided evidence that phospho-LHCBM accumulation is responsible for the assembly of two distinct Photosystem I (PSI) supercomplexes (SCs), both of which are largely absent in STN7-depleted mutants. Besides the canonical state transition complex (PSI-LHCI-LHCII), we isolated the larger moss-specific PSI-Large (PSI-LHCI-LHCB9-LHCII) from stroma-exposed thylakoids. Unlike PSI-LHCI-LHCII, PSI-Large did not demonstrate short-term dynamics for balancing the distribution of excitation energy between PSII and PSI. Instead, PSI-Large contributed to a more stable increase in PSI antenna size in Physcomitrella, except under prolonged high irradiance. Additionally, the STN7-depleted mutants revealed altered light-dependent phosphorylation of a monomeric antenna protein, LHCB6, whose phosphorylation displayed a complex regulation by multiple kinases. Collectively, the unique phosphorylation plasticity and dynamics of Physcomitrella monomeric LHCB6 and trimeric LHCBM isoforms, together with the presence of PSI SCs with different antenna sizes and responsiveness to light changes, reflect the evolutionary position of mosses between green algae and vascular plants, yet with clear moss-specific features emphasizing their adaptation to terrestrial low-light environments.