bluuebunny/crossref_metadata_2025_split huggingface dataset:
Plasmodium vivaxFrom Duffy-Negative and Duffy-Positive Individuals Share Similar Gene Pools in East Africa
Authors: Kepple Daniel , Hubbard Alfred , Ali Musab M , Abargero Beka R , Lopez Karen , Pestana Kareen , Janies Daniel A , Yan Guiyun , Hamid Muzamil Mahdi , Yewhalaw Delenasaw , Lo Eugenia 
Published: January 2021

AbstractPlasmodium vivax malaria was thought to be rare in Africa, but an increasing number of P. vivax cases reported across Africa and in Duffy-negative individuals challenges this dogma. The genetic characteristics of P. vivax in Duffy-negative infections, the transmission of P. vivax in East Africa, and the impact of environments on transmission remain largely unknown. This study examined genetic and transmission features of P. vivax from 107 Duffy-negative and 305 Duffy-positive individuals in Ethiopia and Sudan. No clear genetic differentiation was found in P. vivax between the 2 Duffy groups, indicating between-host transmission. P. vivax from Ethiopia and Sudan showed similar genetic clusters, except samples from Khartoum, possibly due to distance and road density that inhibited parasite gene flow. This study is the first to show that P. vivax can transmit to and from Duffy-negative individuals and provides critical insights into the spread of P. vivax in sub-Saharan Africa.
Interferon regulatory factor 6 correlates with the progression of non-small cell lung cancer and can be regulated by miR-320
Authors: Liu Yunpeng , Shao Guoguang , Yang Zhiguang , Lin Xingyu , Liu Xing , Qian Benxin , Liu Zihao 
Published: January 2021

Abstract

Objectives
The expression of interferon regulatory factor 6 (IRF6) has been reported in several cancer types, but its roles underlying the progression of lung cancer have not been detailedly investigated.

Methods
The pairs of lung cancer tissues and para-carcinoma tissues and The Cancer Genome Atlas database were collected to detect IRF6 expression. Cell counting kit-8, transwell and terminal-deoxynucleoitidyl transferase-mediated nick end labelling assays were used to evaluate cell proliferation, migration and apoptosis.

Key findings
A significant up-regulation of IRF6 in both lung adenocarcinoma and lung squamous cell carcinoma tissues compared with normal non-tumor tissues. Subsequently, Immunostaining also revealed that canceration of lung tissues predisposed to evoke IRF6 expression. In vitro experiments revealed the antitumour effects, including growth and migration inhibition, of IRF6 siRNA transfection. Considering miR-320 as an endogenous inhibitor to IRF6, miR-320 mimics transfection led to the inhibition of proliferation and migration of lung cancer cells. However, overexpressed IRF6 neutralized the antineoplastic activities of miR-320 in lung cancer cells.

Conclusions
The miR-320/IRF6 signalling axis was implicated in pulmonary canceration. miR-320 as an endogenous inhibitor of IRF6 provided a novel therapeutic strategy for the treatment of lung cancer.
1,3,5,6-tetrahydroxyxanthone promotes diuresis, renal protection and antiurolithic properties in normotensive and hypertensive rats
Authors: Mariano Luísa Nathália Bolda , Boeing Thaise , Cechinel Filho Valdir , Niero Rivaldo , Mota da Silva Luisa , de Souza Priscila 
Published: January 2021

Abstract

Objectives
This study investigated the prolonged diuretic and renal effects of 1,3,5,6- tetrahydroxyxanthone (THX) in rats.

Methods
Normotensive (NTR) and hypertensive rats (SHR) received orally the treatment with THX, hydrochlorothiazide or vehicle (VEH). Urine volume, urinary, plasma and kidney parameters were evaluated daily or at the end of 7 days of the experiment.

Key findings
The urinary volume of both NTR and SHR were significantly augmented with the THX treatment, an effect associated with increased levels of urinary Na+ and K+, besides a Ca2+-sparing effect. As well, THX decreased the quantity of monohydrate crystals in urines from NTR and SHR when compared with VEH-group. Regarding the renal analyses, the glutathione levels and the activities of superoxide dismutase, glutathione S-transferase and myeloperoxidase in kidney homogenates of the SHR group were decreased. In contrast, the generation of lipid hydroperoxides (LOOH) and catalase activity was significantly increased. THX reduced the content of LOOH and increased nitrite levels in kidney homogenates obtained from SHR. Additionally, THX also augmented the levels of nitrite in the plasma from the SHR group.

Conclusions
Therefore, THX can be highlighted as a natural diuretic agent with renal protective properties and antiurolithic action.
Morphology of relaxed and merging galaxy clusters: analytical models for monolithic Minkowski functionals
Authors: Schimd C , Sereno M 
Published: January 2021

ABSTRACT
Galaxy clusters exhibit a rich morphology during the early and intermediate stages of mass assembly, especially beyond their boundary. A classification scheme based on shapefinders deduced from the Minkowski functionals is examined to fully account for the morphological diversity of galaxy clusters, including relaxed and merging clusters, clusters fed by filamentary structures, and cluster-pair bridges. These configurations are conveniently treated with idealized geometric models and analytical formulas, some of which are novel. Examples from CLASH and LC2 clusters and observed cluster-pair bridges are discussed.
Analysis of Polycerate Mutants Reveals the Evolutionary Co-option of HOXD1 for Horn Patterning in Bovidae
Authors: Allais-Bonnet Aurélie , Hintermann Aurélie , Deloche Marie-Christine , Cornette Raphaël , Bardou Philippe , Naval-Sanchez Marina , Pinton Alain , Haruda Ashleigh , Grohs Cécile , Zakany Jozsef , Bigi Daniele , Medugorac Ivica , Putelat Olivier , Greyvenstein Ockert , Hadfield Tracy , Jemaa Slim Ben , Bunevski Gjoko , Menzi Fiona , Hirter Nathalie , Paris Julia M , Hedges John , Palhiere Isabelle , Rupp Rachel , Lenstra Johannes A , Gidney Louisa , Lesur Joséphine , Schafberg Renate , Stache Michael , Wandhammer Marie-Dominique , Arbogast Rose-Marie , Guintard Claude , Blin Amandine , Boukadiri Abdelhak , Rivière Julie , Esquerré Diane , Donnadieu Cécile , Danchin-Burge Coralie , Reich Coralie M , Riley David G , Marle-Koster Este van , Cockett Noelle , Hayes Benjamin J , Drögemüller Cord , Kijas James , Pailhoux Eric , Tosser-Klopp Gwenola , Duboule Denis , Capitan Aurélien 
Published: January 2021

Abstract
In the course of evolution, pecorans (i.e., higher ruminants) developed a remarkable diversity of osseous cranial appendages, collectively referred to as “headgear,” which likely share the same origin and genetic basis. However, the nature and function of the genetic determinants underlying their number and position remain elusive. Jacob and other rare populations of sheep and goats are characterized by polyceraty, the presence of more than two horns. Here, we characterize distinct POLYCERATE alleles in each species, both associated with defective HOXD1 function. We show that haploinsufficiency at this locus results in the splitting of horn bud primordia, likely following the abnormal extension of an initial morphogenetic field. These results highlight the key role played by this gene in headgear patterning and illustrate the evolutionary co-option of a gene involved in the early development of bilateria to properly fix the position and number of these distinctive organs of Bovidae.
Genomic Insights into the Origin and Evolution of Molluscan Red-Bloodedness in the Blood ClamTegillarca granosa
Authors: Bao Yongbo , Zeng Qifan , Wang Jing , Zhang Zelei , Zhang Yang , Wang Sufang , Wong Nai-Kei , Yuan Wenbin , Huang Yiyi , Zhang Weifeng , Liu Jing , Lv Liyuan , Xue Qinggang , Zha Shanjie , Peng Zhilan , Yao Hanhan , Bao Zhenmin , Wang Shi , Lin Zhihua 
Published: January 2021

AbstractBlood clams differ from their molluscan kins by exhibiting a unique red-blood (RB) phenotype; however, the genetic basis and biochemical machinery subserving this evolutionary innovation remain unclear. As a fundamental step toward resolving this mystery, we presented the first chromosome-level genome and comprehensive transcriptomes of the blood clam Tegillarca granosa for an integrated genomic, evolutionary, and functional analyses of clam RB phenotype. We identified blood clam-specific and expanded gene families, as well as gene pathways that are of RB relevant. Clam-specific RB-related hemoglobins (Hbs) showed close phylogenetic relationships with myoglobins (Mbs) of blood clam and other molluscs without the RB phenotype, indicating that clam-specific Hbs were likely evolutionarily derived from the Mb lineage. Strikingly, similar to vertebrate Hbs, blood clam Hbs were present in a form of gene cluster. Despite the convergent evolution of Hb clusters in blood clam and vertebrates, their Hb clusters may have originated from a single ancestral Mb-like gene as evidenced by gene phylogeny and synteny analysis. A full suite of enzyme-encoding genes for heme synthesis was identified in blood clam, with prominent expression in hemolymph and resembling those in vertebrates, suggesting a convergence of both RB-related Hb and heme functions in vertebrates and blood clam. RNA interference experiments confirmed the functional roles of Hbs and key enzyme of heme synthesis in the maintenance of clam RB phenotype. The high-quality genome assembly and comprehensive transcriptomes presented herein serve new genomic resources for the super-diverse phylum Mollusca, and provide deep insights into the origin and evolution of invertebrate RB.
Hsp70 acts as a fine-switch that controls E3 ligase CHIP-mediated TAp63 and ΔNp63 ubiquitination and degradation
Authors: Wu H Helena , Wang Benfan , Armstrong Stephen R , Abuetabh Yasser , Leng Sarah , Roa Wilson H Y , Atfi Azeddine , Marchese Adriano , Wilson Beverly , Sergi Consolato , Flores Elsa R , Eisenstat David D , Leng Roger P 
Published: January 2021

Abstract
The major clinical problem in human cancer is metastasis. Metastases are the cause of 90% of human cancer deaths. TAp63 is a critical suppressor of tumorigenesis and metastasis. ΔNp63 acts as a dominant-negative inhibitor to block the function of p53 and TAp63. Although several ubiquitin E3 ligases have been reported to regulate p63 stability, the mechanism of p63 regulation remains partially understood. Herein, we show that CHIP, an E3 ligase with a U-box domain, physically interacts with p63 and promotes p63 degradation. Notably, Hsp70 depletion by siRNA stabilizes TAp63 in H1299 cells and destabilizes ΔNp63 in SCC9 cells. Loss of Hsp70 results in a reduction in the TAp63-CHIP interaction in H1299 cells and an increase in the interaction between ΔNp63 and CHIP in SCC9 cells. Our results reveal that Hsp70 acts as a molecular switch to control CHIP-mediated ubiquitination and degradation of p63 isoforms. Furthermore, regulation of p63 by the Hsp70-CHIP axis contributes to the migration and invasion of tumor cells. Hence, our findings demonstrate that Hsp70 is a crucial regulator of CHIP-mediated ubiquitination and degradation of p63 isoforms and identify a new pathway for maintaining TAp63 or ΔNp63 stability in cancers.
Dynamics of Ku and bacterial non-homologous end-joining characterized using single DNA molecule analysis
Authors: Öz Robin , Wang Jing L , Guerois Raphael , Goyal Gaurav , KK Sriram , Ropars Virginie , Sharma Rajhans , Koca Firat , Charbonnier Jean-Baptiste , Modesti Mauro , Strick Terence R , Westerlund Fredrik 
Published: January 2021

AbstractWe use single-molecule techniques to characterize the dynamics of prokaryotic DNA repair by non-homologous end-joining (NHEJ), a system comprised only of the dimeric Ku and Ligase D (LigD). The Ku homodimer alone forms a ∼2 s synapsis between blunt DNA ends that is increased to ∼18 s upon addition of LigD, in a manner dependent on the C-terminal arms of Ku. The synapsis lifetime increases drastically for 4 nt complementary DNA overhangs, independently of the C-terminal arms of Ku. These observations are in contrast to human Ku, which is unable to bridge either of the two DNA substrates. We also demonstrate that bacterial Ku binds the DNA ends in a cooperative manner for synapsis initiation and remains stably bound at DNA junctions for several hours after ligation is completed, indicating that a system for removal of the proteins is active in vivo. Together these experiments shed light on the dynamics of bacterial NHEJ in DNA end recognition and processing. We speculate on the evolutionary similarities between bacterial and eukaryotic NHEJ and discuss how an increased understanding of bacterial NHEJ can open the door for future antibiotic therapies targeting this mechanism.
Shared Environmental Influences on Electronic Cigarette Use Among Adolescent and Young Adult Females
Authors: Bares Cristina , Lopez-Quintero Catalina 
Published: January 2021

Abstract

Introduction
Electronic cigarettes are now the most commonly used form of tobacco product among youth in the United States. Current evidence suggests that although e-cigarettes are perceived as less harmful and preferred over combustible cigarettes by adolescents, adolescents who try e-cigarettes are at greater risk of transitioning to combustible cigarettes. The genetic and environmental contributions to liability for e-cigarette use have not yet been examined using a behavioral genetic design.

Methods
Behavioral genetic models of lifetime and current e-cigarette use and friends who use e-cigarettes were examined among female monozygotic and dizygotic twins.

Results
A total of 41 female twin pairs (65.9% monozygotic twins; age = 19.7, SD = 1.6) with complete data on the study variables were included in the present analyses. The majority of the sample (68.1%) had at least some friends who use e-cigarettes. Additive genetic effects on e-cigarette use were not present, but the shared environment explained 98.7% of the variance in lifetime e-cigarette use, 96.6% in current e-cigarette use, and 94.9% in affiliation with friends who use e-cigarettes.

Conclusion
This first study on the behavioral genetics of e-cigarette use among adolescents and young adults suggest that environmental factors shared by twins within a family seem to play a predominant role in the initial stages of e-cigarette use, a finding that is consistent with what has been found for tobacco. The findings emphasize the importance of continuing population-based tobacco control interventions to reduce the burden of e-cigarette use among adolescents.

Implications
The shared environment significantly influences the initiation and regular use of electronic cigarettes and affiliation with friends who use electronic cigarettes among adolescent and young adult females. These findings underscore the importance of formulating preventive interventions that mitigate the social effects of familial influences on e-cigarette use through social skills training, education on harms of e-cigarettes for young people, or altering social norms regarding initiation of novel tobacco products.
Use of various immunotherapies for refractory ulcerative colitis in a person living with HIV: a case report
Authors: Costiniuk Cecilia T , Bessissow Talat , Isnard Stéphane , Routy Jean-Pierre 
Published: January 2021

ABSTRACT
Cancer therapies include several immune checkpoint or anticytokine therapies whereas ulcerative colitis treatments consist of anticytokine therapies. The development of tolerance and immunogical effects of these agents in people living with HIV are not well assessed as these persons are often excluded from clinical trials. Herein, we report a case of a Caucasian woman who received multiple sequential immunotherapies for severe ulcerative colitis. Due to steroid-refractory disease, receipt of maximal doses of mesalamine and initial repeated decline of surgical intervention, she went on to receive biologic immune inhibitors like tumor necrosis fator-α blockers infliximab and adalimumab, the α4β7integrin blocker vedolizumab, anti-interleukin 12/23 blocker ustekinumab and Janus Kinase inihibitor tofacitinib without achieving remission. Only minor infectious complications were encountered and no significant changes in CD4 count nor CD4/CD8 ratio occurred. This case provides support for the safety and tolerability of the above immunotherapies in people living with HIV with suppressed viral load on antiretroviral therapy.
Time-course observation of the reconstruction of stem cell niche in the intact root
Authors: Xu Meizhi , Gu Xu , Yu Qiaozhi , Liu Yuting , Bian Xinxin , Wang Renyin , Yang Meina , Wu Shuang 
Published: January 2021

AbstractThe stem cell niche (SCN) is critical in maintaining continuous postembryonic growth of the plant root. During their growth in soil, plant roots are often challenged by various biotic or abiotic stresses, resulting in damage to the SCN. This can be repaired by the reconstruction of a functional SCN. Previous studies examining the SCN’s reconstruction often introduce physical damage including laser ablation or surgical excision. In this study, we performed a time-course observation of the SCN reconstruction in pWOX5:icals3m roots, an inducible system that causes non-invasive SCN differentiation upon induction of estradiol on Arabidopsis (Arabidopsis thaliana) root. We found a stage-dependent reconstruction of SCN in pWOX5:icals3m roots, with division-driven anatomic reorganization in the early stage of the SCN recovery, and cell fate specification of new SCN in later stages. During the recovery of the SCN, the local accumulation of auxin was coincident with the cell division pattern, exhibiting a spatial shift in the root tip. In the early stage, division mostly occurred in the neighboring stele to the SCN position, while division in endodermal layers seemed to contribute more in the later stages, when the SCN was specified. The precise re-positioning of SCN seemed to be determined by mutual antagonism between auxin and cytokinin, a conserved mechanism that also regulates damage-induced root regeneration. Our results thus provide time-course information about the reconstruction of SCN in intact Arabidopsis roots, which highlights the stage-dependent re-patterning in response to differentiated quiescent center.
Fever as a predictor of adverse outcomes in COVID-19
Authors: Chew N W , Ngiam J N , Tham S M , Lim Z Y , Li T Y W , Cen S , Yap E S , Tambyah P A , Santosa A , Cross G B , Sia C -H 
Published: January 2021

Summary

Background/Introduction
There are little data on outcomes of COVID-19 patients with the presence of fever compared to the presence of symptoms.

Aim
We examined the associations between symptomology, presence of fever and outcomes of a COVID-19 cohort.

Design and Methods
Between 23 January and 30 April 2020, 554 COVID-19 patients were admitted to a tertiary hospital in Singapore. They were allocated into four groups based on symptomology and fever—Group 1: asymptomatic and afebrile, Group 2: symptomatic but afebrile, Group 3: febrile but asymptomatic and Group 4: symptomatic and febrile. The primary outcomes were intensive care unit (ICU) admissions and mortality. The composite end-point included ICU admissions, mortality or any COVID-19 related end-organ involvement.

Results
There were differences in ferritin (P=0.003), C-reactive protein (CRP) levels (P&lt;0.001) and lymphopenia (P=0.033) across all groups, with the most favourable biochemical profile in Group 1, and the least in Group 4. Symptomatic groups (Groups 2 and 4) had higher ICU admissions (1.9% and 6.0%, respectively, P=0.003) than asymptomatic groups (Groups 1 and 3). Composite end-point was highest in Group 4 (24.0%), followed by Group 3 (8.6%), Group 2 (4.8%) and Group 1 (2.4%) (P&lt;0.001). The presence of fever (OR 4.096, 95% CI 1.737–9.656, P=0.001) was associated with the composite end-point after adjusting for age, pulse rate, comorbidities, lymphocyte, ferritin and CRP. Presence of symptoms was not associated with the composite end-point.

Discussion/Conclusion
In this COVID-19 cohort, presence of fever was a predictor of adverse outcomes. This has implications on the management of febrile but asymptomatic COVID-19 patients.
Disease activity and its predictors in early inflammatory arthritis: findings from a national cohort
Authors: Yates Mark , Ledingham Joanna M , Hatcher Paul Amlani , Adas Maryam , Hewitt Sasha , Bartlett-Pestell Sam , Rampes Sanketh , Norton Sam , Galloway James B 
Published: January 2021

AbstractObjectivesWe set out to characterize patient factors that predict disease activity during the first year of treatment for early inflammatory arthritis (EIA).MethodsWe used an observational cohort study design, extracting data from a national clinical audit. All NHS organizations providing secondary rheumatology care in England and Wales were eligible to take part, with recruitment from 215/218 (99%) clinical commissioning groups (CCGs)/Health Boards. Participants were &gt;16 years old and newly diagnosed with RA pattern EIA between May 2018 and May 2019. Demographic details collected at baseline included age, gender, ethnicity, work status and postcode, which was converted to an area level measure of socioeconomic position (SEP). Disease activity scores (DAS28) were collected at baseline, three and 12 months follow-up.ResultsA total of 7455 participants were included in analyses. Significant levels of CCG/Health board variation could not be robustly identified from mixed effects modelling. Gender and SEP were predictors of low disease activity at baseline, three and 12 months follow-up. Mapping of margins identified a gradient for SEP, whereby those with higher degrees of deprivation had higher disease activity. Black, Asian and Minority Ethnic patients had lower odds of remission at three months follow-up.ConclusionPatient factors (gender, SEP, ethnicity) predict disease activity. The rheumatology community should galvanise to improve access to services for all members of society. More data are required to characterize area level variation in disease activity.
Splint Padding Thickness: Temperature Effects and X-ray Visualization
Authors: Everson Peter J. , Sura Tej , Udawatta Thiran , Nicolaou Daemeon , Watson John Tracy 
Published: January 2021

Objectives:
The purpose of this study was to determine if the thickness of splint padding could be determined on X-rays, and whether increasing layers of splint padding have an effect on temperature at the skin after placement.

Methods:
Both in vitro and in vivo testing was performed. Ten cadaveric lower extremities were used. A thermocouple was placed on the posterior calf for temperature determination. Cadavers were used with short leg posterior splints with sidebars placed using various thicknesses of padding: (1) 2 layers of Webril, (2) 4 layers of Webril, (3) 2 × 2 padding (Webril followed by kerlix, then repeated), and (4) bulky cotton padding. A splint with no padding was used as a control. Lateral X-rays of the ankle were obtained. The padding thickness was measured. The change in temperature at the level of the skin was measured throughout the process. The test was then repeated in vivo to correlate the cadaver findings with a live subject.

Results:
The mean thickness of the 5 padding types could be reliably determined on X-ray. Our cadaver temperature data shows that all padding thickness tested decreased temperature change after plaster curing, with no significant difference between wraps. Live subject testing showed similarities between the 2-layer Webril and 2 × 2 padding, and between the 4-layer Webril and bulky padding.

Conclusions:
Padding thickness can be consistently determined on X-ray. We determined that at least 2 layers of Webril significantly decrease temperature change at the level of the skin caused by plaster curing. Two layers of Webril can be identified on X-ray by measuring at least 1 mm of padding.