bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evolution of Functional Diversity in the Holozoan Tyrosine Kinome
Authors: Yeung Wayland , Kwon Annie , Taujale Rahil , Bunn Claire , Venkat Aarya , Kannan Natarajan 
Published: September 2021

Abstract
The emergence of multicellularity is strongly correlated with the expansion of tyrosine kinases, a conserved family of signaling enzymes that regulates pathways essential for cell-to-cell communication. Although tyrosine kinases have been classified from several model organisms, a molecular-level understanding of tyrosine kinase evolution across all holozoans is currently lacking. Using a hierarchical sequence constraint-based classification of diverse holozoan tyrosine kinases, we construct a new phylogenetic tree that identifies two ancient clades of cytoplasmic and receptor tyrosine kinases separated by the presence of an extended insert segment in the kinase domain connecting the D and E-helices. Present in nearly all receptor tyrosine kinases, this fast-evolving insertion imparts diverse functionalities, such as post-translational modification sites and regulatory interactions. Eph and EGFR receptor tyrosine kinases are two exceptions which lack this insert, each forming an independent lineage characterized by unique functional features. We also identify common constraints shared across multiple tyrosine kinase families which warrant the designation of three new subgroups: Src module (SrcM), insulin receptor kinase-like (IRKL), and fibroblast, platelet-derived, vascular, and growth factor receptors (FPVR). Subgroup-specific constraints reflect shared autoinhibitory interactions involved in kinase conformational regulation. Conservation analyses describe how diverse tyrosine kinase signaling functions arose through the addition of family-specific motifs upon subgroup-specific features and coevolving protein domains. We propose the oldest tyrosine kinases, IRKL, SrcM, and Csk, originated from unicellular premetazoans and were coopted for complex multicellular functions. The increased frequency of oncogenic variants in more recent tyrosine kinases suggests that lineage-specific functionalities are selectively altered in human cancers.
The proteomes of endometrial stromal cell-derived extracellular vesicles following a decidualizing stimulus define the cells’ potential for decidualization success
Authors: Gurung Shanti , Greening David W , Rai Alin , Poh Qi Hui , Evans Jemma , Salamonsen Lois A 
Published: September 2021

Abstract
Adequate endometrial stromal cell (ESC) decidualization is vital for endometrial health. Given the importance of extracellular vesicles (EVs) in intercellular communication, we investigated how their protein landscape is reprogrammed and dysregulated during decidual response. Small EVs (sEVs) from human ESC-conditioned media at Day-2 and -14 following decidual stimuli were grouped as well- (WD) or poorly decidualized (PD) based on their prolactin secretion and subjected to mass spectrometry-based quantitative proteomics. On Day 2, in PD- versus WD-ESC-sEVs, 17 sEV- proteins were down-regulated (C5, C6; complement/coagulation cascades, and SERPING1, HRG; platelet degranulation and fibrinolysis) and 39 up-regulated (FLNA, COL1A1; focal adhesion, ENO1, PKM; glycolysis/gluconeogenesis, and RAP1B, MSN; leukocyte transendothelial migration). On Day 14, in PD- versus WD-ESC-sEVs, FLNA was down-regulated while 21 proteins were up-regulated involved in complement/coagulation cascades (C3, C6), platelet degranulation (SERPINA4, ITIH4), B-cell receptor signalling and innate immune response (immunoglobulins). Changes from Days 2 to 14 suggested a subsequent response in PD-ESC-sEVs with 89 differentially expressed proteins mostly involved in complement and coagulation cascades (C3, C6, C5), but no change in WD-ESC-sEVs ESC. Poor decidualization was also associated with loss of crucial sEV-proteins for cell adhesion and invasion (ITGA5, PFN1), glycolysis (ALDOA, PGK1) and cytoskeletal reorganization (VCL, RAC1). Overall, this study indicates varied ESC response even prior to decidualization and provides insight into sEVs-proteomes as a benchmark of well-decidualized ESC. It shows distinct variation in sEV-protein composition depending on the ESC decidual response that is critical for embryo implantation, enabling and limiting trophoblast invasion during placentation and sensing a healthy embryo.
A mouse testis serine protease, TESP1, as the potential SPINK3 receptor protein on mouse sperm acrosome
Authors: Ramachandran Shiyam Sundar , Balu Rubhadevi , Vilwanathan Ravikumar , Jeyaraman Jeyakanthan , Paramasivam Sudhakar Gandhi 
Published: September 2021

Abstract
Serine protease inhibitor Kazal type 3 (SPINK3) from mouse seminal vesicles is a Kazal-type trypsin inhibitor. It has been shown to bind to the sperm acrosome and modify sperm activity by influencing the sub-cellular Ca2+ influx. Previously, SPINK3 was reported to suppress in vitro sperm capacitation. However, under natural coitus, SPINK3 is removed from the mouse acrosome in the female reproductive tract, leading to successful fertilisation. Identification of the SPINK3 binding partner becomes essential to develop a contraceptive that works by prolonging the binding of SPINK3 to the sperm acrosome. We identified the SPINK3 receptor by using recombinant SPINK3 (rSPINK3). Testicular serine protease 1 (TESP1) was identified as the receptor for SPINK3 by 2D gel electrophoresis coupled with western blot analysis. To authenticate TESP1 as the receptor for SPINK3, sperm cells were incubated with TESP1 peptide antibody followed by determining the intracellular [Ca2+]i concentration by flow cytometry using Fluo-3 AM as a calcium probe. Furthermore, the 3D structures of SPINK3 and TESP1 were predicted by homology modelling (Schrodinger suite) using the crystal structure of pancreatic secretory trypsin inhibitor (PDB ID—1TGS) and human prostasin (PDB ID—3DFJ) as templates. The modelled protein structures were validated and subjected to molecular dynamics simulation (MDS) using GROMACS v5.0.5. Protein–protein docking was performed using HDOCK and the complex was validated by MDS. The results predicted that SPINK3 and TESP1 had strong binding affinity, with a dock score of −430.70 and 14 hydrogen bonds as key active site residues. If the binding affinity between SPINK3 and TESP1 could be increased, the SPINK3-TESP1 association will be prolonged, which will be helpful in the development of a male contraceptive.
RNA-based cooperative protein labeling that permits direct monitoring of the intracellular concentration change of an endogenous protein
Authors: Pe Kathleen Beverly Alog , Yatsuzuka Kenji , Hakariya Hayase , Kida Tomoki , Katsuda Yousuke , Fukuda Masatora , Sato Shin-ichi 
Published: September 2021

AbstractImaging the dynamics of proteins in living cells is a powerful means for understanding cellular functions at a deeper level. Here, we report a versatile method for spatiotemporal imaging of specific endogenous proteins in living mammalian cells. The method employs a bifunctional aptamer capable of selective protein recognition and fluorescent probe-binding, which is induced only when the aptamer specifically binds to its target protein. An aptamer for β-actin protein preferentially recognizes its monomer forms over filamentous forms, resulting in selective G-actin staining in both fixed and living cells. Through actin-drug treatment, the method permitted direct monitoring of the intracellular concentration change of endogenous G-actin. This protein-labeling method, which is highly selective and non-covalent, provides rich insights into the study of spatiotemporal protein dynamics in living cells.
Fusarium BP1 is a reader of H3K27 methylation
Authors: Tang Guangfei , Yuan Jianlong , Wang Jing , Zhang Yi-Zhe , Xie Si-Si , Wang Hongkai , Tao Zeng , Liu Huiquan , Kistler H Corby , Zhao Youfu , Duan Cheng-Guo , Liu Wende , Ma Zhonghua , Chen Yun 
Published: September 2021

Abstract
Histone H3 lysine 27 methylation catalyzed by polycomb repressive complex 2 (PRC2) is conserved from fungi to humans and represses gene transcription. However, the mechanism for recognition of methylated H3K27 remains unclear, especially in fungi. Here, we found that the bromo-adjacent homology (BAH)-plant homeodomain (PHD) domain containing protein BAH–PHD protein 1 (BP1) is a reader of H3K27 methylation in the cereal fungal pathogen Fusarium graminearum. BP1 interacts with the core PRC2 component Suz12 and directly binds methylated H3K27. BP1 is distributed in a subset of genomic regions marked by H3K27me3 and co-represses gene transcription. The BP1 deletion mutant shows identical phenotypes on mycelial growth and virulence, as well as similar expression profiles of secondary metabolite genes to the strain lacking the H3K27 methyltransferase Kmt6. More importantly, BP1 can directly bind DNA through its PHD finger, which might increase nucleosome residence and subsequently reinforce transcriptional repression in H3K27me3-marked target regions. A phylogenetic analysis showed that BP1 orthologs are mainly conserved in fungi. Overall, our findings provide novel insights into the mechanism by which PRC2 mediates gene repression in fungi, which is distinct from the PRC1-PRC2 system in plants and mammals.
Massive lithospheric delamination in southeastern Tibet facilitating continental extrusion
Authors: Feng Jikun , Yao Huajian , Chen Ling , Wang Weitao 
Published: September 2021

AbstractSignificant left-lateral movement along the Ailao Shan-Red River fault accommodated a substantial amount of the late Eocene to early Miocene India-Asia convergence. However, the activation of this critical strike-slip fault remains poorly understood. Here, we show key seismic evidence for the occurrence of massive lithospheric delamination in southeastern Tibet. Our novel observation of reflected body waves (e.g. P410P and P660P) retrieved from ambient noise interferometry sheds new light on the massive foundered lithosphere currently near the bottom of the mantle transition zone beneath southeastern Tibet. By integrating the novel seismic and pre-existing geochemical observations, we highlight a linkage between massive lithospheric delamination shortly after the onset of hard collision and activation of continental extrusion along the Ailao Shan-Red River fault. This information provides critical insight into the early-stage evolution of the India-Asia collision in southeastern Tibet, which has significant implications for continental collision and its intracontinental response.
The relationship between deprivation and frailty trajectories over 1 year and at the end of life: a case–control study
Authors: Stow Daniel , Hanratty Barbara , Matthews Fiona E 
Published: September 2021

Abstract

Background
We investigated the association between area-level, multi-domain deprivation and frailty trajectories in the last year of life and over 1 year in a matched non-end-of-life sample.

Methods
A 1-year longitudinal case–control study using primary care electronic health records from 20 460 people age ≥ 75. Cases (died 1 January 2015 to 1 January 2016) were 1:1 matched to controls by age, sex and practice location. Monthly interval frailty measured using a 36-item electronic frailty index (eFI: range 0–1, lower scores mean less frailty). Deprivation measured using Index of Multiple Deprivation (IMD) quintiles. We used latent growth curves to model the relationship between IMD and eFI trajectory.

Results
Living in a less deprived area was associated with faster increase in eFI for cases (0.005% per month, 95%confidence interval [CI]: 0.001, 0.010), but not controls, and was associated with lower eFI at study baseline in cases (−0.29% per IMD quintile, 95%CI −0.45, −0.13) and controls (−0.35% per quintile, 95%CI −0.51, −0.20).

Conclusions
Overall, greater area-level deprivation is associated with higher levels of frailty, but people who survive to ≥75 have similar 1-year frailty trajectories, regardless of area-level deprivation. Interventions to reduce frailty should target younger age groups, especially those living in the most deprived areas.
Varieties of functional income inequality in Latin America: Chile and Mexico compared
Authors: Gouzoulis Giorgos , Constantine Collin 
Published: September 2021

Abstract
Contributing to a better understanding of the varying inequality patterns within Latin America, this article examines the drivers of the private sector labour shares of Chile and Mexico between 1980 and 2011. Over this period, Chile’s labour share has declined, similar to many advanced economies, while Mexico’s labour share has remained relatively stable. Our historical and econometric analysis suggests that in Chile high private indebtedness has undermined wage demands and induced wage cuts, while policies of small government have also contributed to the decline in its wage share. Chile’s natural resource exports have benefited from Latin America’s commodity boom and exhibited some limited positive effects on its wage share. Contrariwise, we find that Mexico, as a more capital-intensive economy, has experienced significant substitution effects, which have undermined its wage share. Yet, high government spending has counterbalanced the negative effects of globalization. These comparative results challenge popular narratives around hyper-globalization and policy homogenization.
Host Adaptation Through Hybridization: Genome Analysis of Triticale Powdery Mildew Reveals Unique Combination of Lineage-Specific Effectors
Authors: Müller Marion C. , Kunz Lukas , Graf Johannes , Schudel Seraina , Keller Beat 
Published: September 2021

The emergence of new fungal pathogens through hybridization represents a serious challenge for agriculture. Hybridization between the wheat mildew (Blumeria graminis f. sp. tritici) and rye mildew (B. graminis f. sp. secalis) pathogens has led to the emergence of a new mildew form (B. graminis f. sp. triticale) growing on triticale, a man-made amphiploid crop derived from crossing rye and wheat, which was originally resistant to the powdery mildew disease. The identification of the genetic basis of host adaptation in triticale mildew has been hampered by the lack of a reference genome. Here, we report the 141.4-Mb reference assembly of triticale mildew isolate THUN-12 derived from long-read sequencing and genetic map-based scaffolding. All 11 triticale mildew chromosomes were assembled from telomere-to-telomere and revealed that 19.7% of the hybrid genome was inherited from the rye mildew parental lineage. We identified lineage-specific regions in the hybrid, inherited from the rye or wheat mildew parental lineages, that harbor numerous bona fide candidate effectors. We propose that the combination of lineage-specific effectors in the hybrid genome is crucial for host adaptation, allowing the fungus to simultaneously circumvent the immune systems contributed by wheat and rye in the triticale crop. In line with this, we demonstrate the functional transfer of the SvrPm3 effector from wheat to triticale mildew, a virulence effector that specifically suppresses resistance of the wheat Pm3 allelic series. This transfer is the likely underlying cause for the observed poor effectiveness of several Pm3 alleles against triticale mildew and exemplifies the negative implications of pathogen hybridizations on resistance breeding.[Formula: see text] Copyright © 2021 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license .
Outcomes of the First Pregnancy After Fertility-Sparing Surgery for Early-Stage Cervical Cancer
Authors: Nitecki Roni , Floyd Jessica , Lamiman Kelly , Clapp Mark A. , Fu Shuangshuang , Jorgensen Kirsten , Melamed Alexander , Brady Paula C. , Kaimal Anjali , del Carmen Marcela G. , Woodard Terri L. , Meyer Larissa A. , Giordano Sharon H. , Ramirez Pedro T. , Rauh-Hain J. Alejandro 
Published: September 2021

OBJECTIVE:
To evaluate outcomes of the first pregnancy after fertility-sparing surgery in patients with early-stage cervical cancer.

METHODS:
We performed a population-based study of women aged 18–45 years with a history of stage I cervical cancer reported to the 2000–2012 California Cancer Registry. Data were linked to the OSHPD (California Office of Statewide Health Planning and Development) birth and discharge data sets. We included patients with cervical cancer who conceived at least 3 months after a fertility-sparing surgery, which included cervical conization or loop electrosurgical excision procedure. Those undergoing trachelectomy were excluded. The primary outcome was preterm birth. Secondary outcomes included growth restriction, neonatal morbidity, stillbirth, cesarean delivery, and severe maternal morbidity. We used propensity scores to match similar women from two groups in a 1:2 ratio of case group participants to control group participants: population individuals without cancer and individuals with cervical cancer (women who delivered before their cervical cancer diagnosis). Wald statistics and logistic regressions were used to evaluate outcomes.

RESULTS:
Of 4,087 patients with cervical cancer, 118 (2.9%) conceived after fertility-sparing surgery, and 107 met inclusion criteria and were matched to control group participants. Squamous cell carcinoma was the most common histology (63.2%), followed by adenocarcinoma (30.8%). Patients in the case group had higher odds of preterm birth before 37 weeks of gestation compared with both control groups (21.5% vs 9.3%, odds ratio [OR] 2.7, 95% CI 1.4–5.1; 21.5% vs 12.7%, OR 1.9, 95% CI 1.0–3.6), but not preterm birth before 32 weeks. Neonatal morbidity was more common among the patients in the case group relative to those in the cervical cancer control group (15.9% vs 6.9%, OR 2.5, 95% CI 1.2–5.5). There were no differences in rates of growth restriction, stillbirth, cesarean delivery, and maternal morbidity.

CONCLUSION:
In a population-based cohort, patients who conceived after surgery for cervical cancer had higher odds of preterm delivery compared with control groups.
Causes of Maternal Mortality in Rwanda, 2017–2019
Authors: Rulisa Stephen , Ntihinyurwa Polyphile , Ntirushwa David , Wong Andrew , Olufolabi Adeyemi 
Published: September 2021

OBJECTIVE:
To assess the causes of maternal mortality at a referral hospital in Rwanda.

METHODS:
A secondary data analysis of 217 women with recorded maternal mortality from 2017 to 2019 was conducted among 11,308 total maternal admissions. Demographics, diagnosis, management, referring hospital source, and outcomes were recorded.

RESULTS:
The mean (±SD) age of maternal death was 30.7±7.2 years (range 16–57 years). The overall maternal mortality rate was 1.99%, with yearly rates of 2.45%, 2.53%, and 1.84% in 2017, 2018, and 2019, respectively. A significant seasonal variation was noted. Sepsis was the most common cause of maternal death (50%), followed by hemorrhage (19%) and hypertensive disorders (15%). Causes of maternal deaths included preeclampsia (13%) and abortion (8%). Furthermore, 82% of all the deaths were referrals from smaller community hospitals.

CONCLUSION:
Maternal death due to sepsis remain a major cause of maternal deaths in Rwanda. Infection prevention and the early diagnosis and management of sepsis must be a priority in reducing maternal mortality.
Associations Between Maternal Depression, Antidepressant Use During Pregnancy, and Adverse Pregnancy Outcomes
Authors: Vlenterie Richelle , van Gelder Marleen M. H. J. , Anderson H. Ross , Andersson Liselott , Broekman Birit F. P. , Dubnov-Raz Gal , El Marroun Hanan , Ferreira Ema , Fransson Emma , van der Heijden Frank M. M. A. , Holzman Claudia B. , Kim J. Jo , Khashan Ali S. , Kirkwood Betty R. , Kuijpers Harold J. H. , Lahti-Pulkkinen Marius , Mason Dan , Misra Dawn , Niemi Maria , Nordeng Hedvig M. E. , Peacock Janet L. , Pickett Kate E. , Prady Stephanie L. , Premji Shahirose S. , Räikkönen Katri , Rubertsson Christine , Sahingoz Mine , Shaikh Kiran , Silver Richard K. , Slaughter-Acey Jaime , Soremekun Seyi , Stein Dan J. , Sundström-Poromaa Inger , Sutter-Dallay Anne-Laure , Tiemeier Henning , Uguz Faruk , Varela Pinelopi , Vrijkotte Tanja G.M. , Winterfeld Ursula , Zar Heather J. , Zervas Iannis M. , Prins Judith B. , Pop-Purceleanu Monica , Roeleveld Nel 
Published: September 2021

OBJECTIVE:
To evaluate the associations of depressive symptoms and antidepressant use during pregnancy with the risks of preterm birth, low birth weight, small for gestational age (SGA), and low Apgar scores.

DATA SOURCES:
MEDLINE, EMBASE, ClinicalTrials.gov, and PsycINFO up to June 2016.

METHODS OF STUDY SELECTION:
Data were sought from studies examining associations of depression, depressive symptoms, or use of antidepressants during pregnancy with gestational age, birth weight, SGA, or Apgar scores. Authors shared the raw data of their studies for incorporation into this individual participant data meta-analysis.

TABULATION, INTEGRATION, AND RESULTS:
We performed one-stage random-effects meta-analyses to estimate odds ratios (ORs) with 95% CIs. The 215 eligible articles resulted in 402,375 women derived from 27 study databases. Increased risks were observed for preterm birth among women with a clinical diagnosis of depression during pregnancy irrespective of antidepressant use (OR 1.6, 95% CI 1.2–2.1) and among women with depression who did not use antidepressants (OR 2.2, 95% CI 1.7–3.0), as well as for low Apgar scores in the former (OR 1.5, 95% CI 1.3–1.7), but not the latter group. Selective serotonin reuptake inhibitor (SSRI) use was associated with preterm birth among women who used antidepressants with or without restriction to women with depressive symptoms or a diagnosis of depression (OR 1.6, 95% CI 1.0–2.5 and OR 1.9, 95% CI 1.2–2.8, respectively), as well as with low Apgar scores among women in the latter group (OR 1.7, 95% CI 1.1–2.8).

CONCLUSION:
Depressive symptoms or a clinical diagnosis of depression during pregnancy are associated with preterm birth and low Apgar scores, even without exposure to antidepressants. However, SSRIs may be independently associated with preterm birth and low Apgar scores.

SYSTEMATIC REVIEW REGISTRATION:
PROSPERO, CRD42016035711.