bluuebunny/crossref_metadata_2025_split huggingface dataset:
SUMOylation of YTHDF2 promotes mRNA degradation and cancer progression by increasing its binding affinity with m6A-modified mRNAs
Authors: Hou Guofang , Zhao Xian , Li Lian , Yang Qianqian , Liu Xiaojia , Huang Caihu , Lu Runhui , Chen Ran , Wang Yanli , Jiang Bin , Yu Jianxiu 
Published: January 2021

Abstract
N 6-Methyladenosine (m6A) is the most abundant modification within diverse RNAs including mRNAs and lncRNAs and is regulated by a reversible process with important biological functions. Human YTH domain family 2 (YTHDF2) selectively recognized m6A-RNAs to regulate degradation. However, the possible regulation of YTHDF2 by protein post-translational modification remains unknown. Here, we show that YTHDF2 is SUMOylated in vivo and in vitro at the major site of K571, which can be induced by hypoxia while reduced by oxidative stress and SUMOylation inhibitors. SUMOylation of YTHDF2 has little impact on its ubiquitination and localization, but significantly increases its binding affinity of m6A-modified mRNAs and subsequently results in deregulated gene expressions which accounts for cancer progression. Moreover, Disease-free survival analysis of patients with lung adenocarcinoma derived from TCGA dataset reveals that higher expression of YTHDF2 together with higher expression of SUMO1 predicts poor prognosis. Our works uncover a new regulatory mechanism for YTHDF2 recognition of m6A-RNAs and highlight the importance of YTHDF2 SUMOylation in post-transcriptional gene expression regulation and cancer progression.
Analysing the yeast complexome—the Complex Portal rising to the challenge
Authors: Meldal Birgit H M , Pons Carles , Perfetto Livia , Del-Toro Noemi , Wong Edith , Aloy Patrick , Hermjakob Henning , Orchard Sandra , Porras Pablo 
Published: January 2021

Abstract
The EMBL-EBI Complex Portal is a knowledgebase of macromolecular complexes providing persistent stable identifiers. Entries are linked to literature evidence and provide details of complex membership, function, structure and complex-specific Gene Ontology annotations. Data are freely available and downloadable in HUPO-PSI community standards and missing entries can be requested for curation. In collaboration with Saccharomyces Genome Database and UniProt, the yeast complexome, a compendium of all known heteromeric assemblies from the model organism Saccharomyces cerevisiae, was curated. This expansion of knowledge and scope has led to a 50% increase in curated complexes compared to the previously published dataset, CYC2008. The yeast complexome is used as a reference resource for the analysis of complexes from large-scale experiments. Our analysis showed that genes coding for proteins in complexes tend to have more genetic interactions, are co-expressed with more genes, are more multifunctional, localize more often in the nucleus, and are more often involved in nucleic acid-related metabolic processes and processes where large machineries are the predominant functional drivers. A comparison to genetic interactions showed that about 40% of expanded co-complex pairs also have genetic interactions, suggesting strong functional links between complex members.
Binding of phosphorothioate oligonucleotides with RNase H1 can cause conformational changes in the protein and alter the interactions of RNase H1 with other proteins
Authors: Zhang Lingdi , Vickers Timothy A , Sun Hong , Liang Xue-hai , Crooke Stanley T 
Published: January 2021

Abstract
We recently found that toxic PS-ASOs can cause P54nrb and PSF nucleolar mislocalization in an RNase H1-dependent manner. To better understand the underlying mechanisms of these observations, here we utilize different biochemical approaches to demonstrate that PS-ASO binding can alter the conformations of the bound proteins, as illustrated using recombinant RNase H1, P54nrb, PSF proteins and various isolated domains. While, in general, binding of PS-ASOs or ASO/RNA duplexes stabilizes the conformations of these proteins, PS-ASO binding may also cause the unfolding of RNase H1, including both the hybrid binding domain and the catalytic domain. The extent of conformational change correlates with the binding affinity of PS-ASOs to the proteins. Consequently, PS-ASO binding to RNase H1 induces the interaction of RNase H1 with P54nrb or PSF in a 2′-modification and sequence dependent manner, and toxic PS-ASOs tend to induce more interactions than non-toxic PS-ASOs. PS-ASO binding also enhances the interaction between P54nrb and PSF. However, the interaction between RNase H1 and P32 protein can be disrupted upon binding of PS-ASOs. Together, these results suggest that stronger binding of PS-ASOs can cause greater conformational changes of the bound proteins, subsequently affecting protein–protein interactions. These observations thus provide deeper understanding of the molecular basis of PS-ASO-induced protein mislocalization or degradation observed in cells and advance our understanding of why some PS-ASOs are cytotoxic.
Sex difference in ambulatory blood pressure control associates with risk of ESKD and death in CKD patients receiving stable nephrology care
Authors: Minutolo Roberto , Gabbai Francis B , Agarwal Rajiv , Garofalo Carlo , Borrelli Silvio , Chiodini Paolo , Signoriello Simona , Paoletti Ernesto , Ravera Maura , Bellizzi Vincenzo , Conte Giuseppe , De Nicola Luca 
Published: January 2021

Abstract

Background
It is unknown whether faster progression of chronic kidney disease (CKD) in men than in women relates to differences in ambulatory blood pressure (ABP) levels.

Methods
We prospectively evaluated 906 hypertensive CKD patients (553 men) regularly followed in renal clinics to compare men versus women in terms of ABP control [daytime &lt;135/85 and nighttime blood pressure (BP) &lt;120/70 mmHg] and risk of all-cause mortality and end-stage kidney disease (ESKD).

Results
Age, estimated glomerular filtration rate and use of renin–angiotensin system inhibitors were similar in men and women, while proteinuria was lower in women [0.30 g/24 h interquartile range (IQR) 0.10–1.00 versus 0.42 g/24 h, IQR 0.10–1.28, P = 0.025]. No sex-difference was detected in office BP levels; conversely, daytime and nighttime BP were higher in men (134 ± 17/78 ± 11 and 127 ± 19/70 ± 11 mmHg) than in women (131 ± 16/75 ± 11, P = 0.005/P &lt; 0.001 and 123 ± 20/67 ± 12, P = 0.006/P &lt; 0.001), with ABP goal achieved more frequently in women (39.1% versus 25.1%, P &lt; 0.001). During a median follow-up of 10.7 years, 275 patients reached ESKD (60.7% men) and 245 died (62.4% men). Risks of ESKD and mortality (hazard ratio and 95% confidence interval), adjusted for demographic and clinical variables, were higher in men (1.34, 1.02–1.76 and 1.36, 1.02–1.83, respectively). Adjustment for office BP at goal did not modify this association. In contrast, adjustment for ABP at goal attenuated the increased risk in men for ESKD (1.29, 0.98–1.70) and death (1.31, 0.98–1.77). In the fully adjusted model, ABP at goal was associated with reduced risk of ESKD (0.49, 0.34–0.70) and death (0.59, 0.43–0.80). No interaction between sex and ABP at goal on the risk of ESKD and death was found, suggesting that ABP-driven risks are consistent in males and females.

Conclusions
Our study highlights that higher ABP significantly contributes to higher risks of ESKD and mortality in men.
Textural and Geochemical Evidence for Multiple, Sheet-like Magma Pulses in the Limeira Intrusion, Paraná Magmatic Province, Brazil
Authors: Lino Lucas Martins , Vlach Silvio Roberto Farias 
Published: January 2021

AbstractQuantitative petrographic, structural, and textural parameters are integrated with geological, geochemical, and Sr-isotope data to examine the emplacement, growth processes, and magmatic evolution of the high-Ti tholeiitic Limeira Intrusion, in the Paraná Magmatic Province of SE Brazil. Our data strongly support a multiple-stage evolution, owing to the nested emplacement of distinct crystal-bearing magma pulses that probably evolved independently, except at their boundaries. A stage of cooling and crystallization between magma injections results in a stepwise T–t path, leading to variations in the plagioclase residence times and effective growth rates inwards, also occasioning sudden changes in crystal shape and size at the boundaries of each magma pulse. The time delay between pulses allows preservation of internal ‘chilled margins’ and the development of near-rigid surfaces at their contacts, increasing the alignment and clustering of crystals during magma replenishment. Isotopic and textural data demonstrate a complex assembly history, in which the appearance of mixed plagioclase populations between magma pulses coincides with the onset of initial Sr isotope ratio increase, which can be attributed to a locally enhanced cooling rate, and the extraction of residual melts from the previous crystallizing batches and mixing with the younger pulses. Typical C- and S-shaped MgO (wt%) compositional profiles within individual pulses indicate that the first one probably evolved by in situ fractional crystallization followed by melt migration inward, whereas the younger ones have contributions from both compaction of the lowermost crystallization front and compositional convection. Mafic globular structures are found at the boundaries of magma pulses and constituting the mafic-rich layers in layered rocks. They are interpreted as evidence for chemical disequilibrium, arguably associated with the trigger of silicate liquid immiscibility. The upwards compositional convection of the silica-rich residual liquid and the accumulation of the Fe–Ti–P-rich crystalbearing end-member in the bottom of the latest magma pulses might represent the most significant mechanism of differentiation in the Limeira Intrusion.
Association of AM-PAC “6-Clicks” Basic Mobility and Daily Activity Scores With Discharge Destination
Authors: Warren Meghan , Knecht Jeff , Verheijde Joseph , Tompkins James 
Published: January 2021

Abstract

Objective
The objective was to use the Activity Measure for Post-Acute Care “6-Clicks” scores at initial physical therapist and/or occupational therapist evaluation to assess (1) predictive ability for community versus institutional discharge, and (2) association with discharge destination (home/self-care [HOME], home health [HHA], skilled nursing facility [SNF], and inpatient rehabilitation facility [IRF]).

Methods
In this retrospective cohort study, initial “6-Clicks” Basic Mobility and/or Daily Activity t scores and discharge destination were obtained from electronic health records of 17,546 inpatient admissions receiving physical therapy/occupational therapy at an academic hospital between October 1, 2015 and August 31, 2018. For objective (1), postacute discharge destination was dichotomized to community (HOME and HHA) and institution (SNF and IRF). Receiver operator characteristic curves determined the most predictive Basic Mobility and Daily Activity scores for discharge destination. For objective (2), adjusted odds ratios (OR) from multinomial logistic regression assessed association between discharge destination (HOME, HHA, SNF, IRF) and cut-point scores for Basic Mobility (≤40.78 vs &gt;40.78) and Daily Activity (≤40.22 vs &gt;40.22), accounting for patient and clinical characteristics.

Results
Area under the curve for Basic Mobility was 0.80 (95% CI = 0.80–0.81) and Daily Activity was 0.81 (95% CI = 0.80–0.82). The best cut-point for Basic Mobility was 40.78 (raw score = 16; sensitivity = 0.71 and specificity = 0.74) and for Daily Activity was 40.22 (raw score = 19; sensitivity = 0.68 and specificity = 0.79). Basic Mobility and Daily Activity were significantly associated with discharge destination, with those above the cut-point resulting in increased odds of discharge HOME. The Basic Mobility scores ≤40.78 had higher odds of discharge to HHA (OR = 1.7 [95% CI = 1.5–1.9]), SNF (OR = 7.8 [95% CI = 6.8–8.9]), and IRF (OR = 7.5 [95% CI = 6.3–9.1]), and the Daily Activity scores ≤40.22 had higher odds of discharge to HHA (OR = 1.8 [95% CI = 1.7–2.0]), SNF (OR = 8.9 [95% CI = 7.9–10.0]), and IRF (OR = 11.4 [95% CI = 9.7–13.5]).

Conclusion
6-Clicks at physical therapist/occupational therapist initial evaluation demonstrated good prediction for discharge decisions. Higher scores were associated with discharge to HOME; lower scores reflected discharge to settings with increased support levels.

Impact
Initial Basic Mobility and Daily Activity scores are valuable clinical tools in the determination of discharge destination.
Priorities of Hybrid Clinician-Managers: A Qualitative Study of How Managers Balance Clinical Quality Among Competing Responsibilities
Authors: Hoekstra Christopher J , Ash Joan S , Steckler Nicole A , Becton James R , Sanders Benjamin W , Mishra Meenakshi , Gorman Paul N 
Published: January 2021

Abstract

Objective
Oversight of clinical quality is only one of physical therapy managers’ multiple responsibilities. With the move to value-based care, organizations need sound management to navigate this evolving reimbursement landscape. Previous research has not explored how competing priorities affect physical therapy managers’ oversight of clinical quality. The purpose of this study was to create a preliminary model of the competing priorities, motivations, and responsibilities of managers while overseeing clinical quality.

Methods
This qualitative study used the Rapid Qualitative Inquiry method. A purposive sample of 40 physical therapy managers and corporate leaders was recruited. A research team performed semi-structured interviews and observations in outpatient practices. The team used a grounded theory-based immersion/crystallization analysis approach. Identified themes delineated the competing priorities and workflows these managers use in their administrative duties.

Results
Six primary themes were identified that illustrate how managers: (1) balance managerial and professional priorities; (2) are susceptible to stakeholder influences; (3) experience internal conflict; (4) struggle to measure and define quality objectively; (5) are influenced by the culture and structure of their respective organizations; and (6) have professional needs apart from the needs of their clinics.

Conclusion
Generally, managers’ focus on clinical quality is notably less comprehensive than their focus on clinical operations. Additionally, the complex role of hybrid clinician-manager leaves limited time beyond direct patient care for administrative duties. Managers in organizations that hold them accountable to quality-based metrics have more systematic clinical quality oversight processes.

Impact
This study gives physical therapy organizations a framework of factors that can be influenced to better facilitate managers’ effective oversight of clinical quality. Organizations offering support for those managerial responsibilities will be well positioned to thrive in the new fee-for-value care structure.
A distinguishing profile of chemokines, cytokines and biomarkers in the saliva of children with Sjögren’s syndrome
Authors: Gomez Hernandez M Paula , Starman Emily E , Davis Andrew B , Withanage Miyuraj Harishchandra Hikkaduwa , Zeng Erliang , Lieberman Scott M , Brogden Kim A , Lanzel Emily A 
Published: January 2021

Abstract

Objective
SS is an autoimmune disease most commonly diagnosed in adults but can occur in children. Our objective was to assess the presence of chemokines, cytokines and biomarkers (CCBMs) in saliva from these children that were associated with lymphocyte and mononuclear cell functions.

Methods
Saliva was collected from 11 children diagnosed with SS prior to age 18 years and 16 normal healthy children. A total of 105 CCBMs were detected in multiplex microparticle-based immunoassays. ANOVA and t test (0.05 level) were used to detect differences. Ingenuity Pathway Analysis (IPA) was used to assess whether elevated CCBMs were in annotations associated with immune system diseases and select leukocyte activities and functions. Machine learning methods were used to evaluate the predictive power of these CCBMs for SS and were measured by receiver operating characteristic (ROC) curve and area under curve (AUC).

Results
Of the 105 CCBMs detected, 43 (40.9%) differed in children with SS from those in healthy study controls (P &lt; 0.05) and could differentiate the two groups (P &lt; 0.05). Elevated CCBMs in IPA annotations were associated with autoimmune diseases and with leukocyte chemotaxis, migration, proliferation, and regulation of T cell activation. The best AUC value in ROC analysis was 0.93, indicating that there are small numbers of CCBMs that may be useful for diagnosis of SS.

Conclusion
While 35 of these 43 CCBMs have been previously reported in SS, 8 CCBMs had not. Additional studies focusing on these CCBMs may provide further insight into disease pathogenesis and may contribute to diagnosis of SS in children.
Racial Segregation under Slavery
Authors: Ruef Martin 
Published: January 2021

Abstract
Social demographers and historians have devoted extensive research to patterns of racial segregation that emerged under Jim Crow and during the post-Civil Rights era but have paid less attention to the role of slavery in shaping the residential distribution of Black populations in the United States. One guiding assumption has been that slavery rendered racial segregation to be both unnecessary and impractical. In this study, I argue that apart from the master–slave relationship, slavery relentlessly produced racial segregation during the antebellum period through the residential isolation of slaves and free people of color. To explain this pattern, I draw on racial threat theory to test hypotheses regarding interracial economic competition and fear of slave mobilization using data from the 1850 Census, as well as an architectural survey of antebellum sites. Findings suggest that the residential segregation of free people of color increased with their local prevalence, whereas the segregation of slaves increased with the prevalence of the slave population. These patterns continue to hold after controlling for interracial competition over land or jobs and past slave rebellions or conspiracies.
Distributional characterizations and testing for differences of relatedness and inbreeding of a subpopulation of American Hereford bulls
Authors: Simmons M A , Riggs P K , Sanders S , Herring A D , Sanders J O , Riley D G 
Published: January 2021

AbstractBeta distributions are characterized by two determining parameters and a parameter space from 0 to 1, and may be useful for examining population genetic parameters such as the relationship or inbreeding coefficients. Often subpopulations exist within breeds that are congregated around particular lineages of cattle or ancestors that breeders value. These subpopulations are more related to each other than to the majority of other animals; they may have higher inbreeding as well. Value may be added to these subpopulations because of their relatedness with important or renowned ancestors. The objectives of this work were to compare the relatedness and inbreeding of a group of 26 modern bulls from a subpopulation of the American Hereford breed relative to 1) 30 males with the most descendants present in the pedigree, 2) 15 renowned American Hereford bulls considered important individuals in the breed’s history, and 3) 19 prominent subpopulation male ancestors. Conformance of the mean relationship coefficients of the bulls with the three groups and the mean inbreeding coefficient with all pedigree animals to beta distributions was assessed by 1) visually determining the parameters of the beta distributions based on the entire pedigree, 2) testing the mean relationship coefficient or inbreeding coefficient of the group of subpopulation bulls for its positional inclusion in those distributions, and 3) bootstrap sampling methodology. The mean relationship coefficients of the 26 Trask bulls with the 30 bulls with the most descendants, the 15 renowned ancestors, and the 19 Trask male ancestors were 0.15, 0.132, and 0.208, respectively. Testing of these means in beta distributions indicated that the group of 26 Trask bulls were no more related to the three groups of bulls than all of the animals in the pedigree (0.06 &lt; P &lt; 0.25). Bootstrap sampling indicated that the 26 bulls were more related to the three groups of male ancestors than the remainder of the animals in the pedigree (P &lt; 0.0001). The mean inbreeding coefficient of the 26 bulls (0.13) did not differ from the overall inbreeding coefficient (0.056) when tested using a beta distribution; however, bootstrap sampling indicated otherwise (P &lt; 0.0001). Results may indicate the inadequacy of visually parameterizing a beta distribution. Quantification of pedigree relatedness of a group of animals to key ancestors, especially with no DNA available, may add value to that group and individuals.
Genetic changes in beef cow traits following selection for calving ease
Authors: Bennett Gary L , Thallman Richard M , Snelling Warren M , Keele John W , Freetly Harvey C , Kuehn Larry A 
Published: January 2021

Abstract
One approach to reducing calving difficulty is to select heifers with higher breeding value for calving ease. Calving ease is often associated with lower birth weight and that may result in other possible effects on lifetime productivity. Females from experimental select and control calving ease lines within each of the seven populations were compared. Random samples of 720 heifers from lines selected for better calving ease breeding values and 190 heifers from control lines selected for average birth weights were followed through four parities. Select and control lines within the same population were selected to achieve similar yearling weight breeding values. Weights of sampled heifers in select lines were 2.6 kg (P &lt; 0.01) lighter at birth but not different from control lines at weaning. Select lines had significantly shorter hip height, lighter mature weight, and greater calving success at second parity. Their calves were born significantly earlier with lighter weights and less assistance. Significant interactions with parity showed fewer calves assisted and greater calf survival to weaning as heifers but negligible differences with control lines in later parities. Steer progeny sampled from these dams in select lines (n = 204) were not different from steers in control lines (n = 91) for hot carcass weight but had significantly greater fat depth. Two production systems were compared considering the seven populations as replicates. The systems differed in selection history of females (select and control lines) and the use of bulls within their lines as young cows, but used the same bulls in both lines as older cows. Cows were culled after single unsuccessful breeding and kept for up to four parities. Select line cows tended (P ≤ 0.10) to wean more calves and stay in the herd longer. They were assisted significantly fewer times at calving and had greater calf weight gain to weaning when evaluated over their herd life. Mature weights were lighter in select lines, but marketable cow weight from the systems was nearly identical. Control lines did have more marketable young cow weight and select lines older cow weight. Weaned calf weight per heifer starting the system was significantly greater for the select heifer system due to greater survival of calves from heifers and greater calving success at second parity. No important unfavorable effects of genetic differences in calving ease were identified in this experiment.