bluuebunny/crossref_metadata_2025_split huggingface dataset:
Targeting RLIP with CRISPR/Cas9 controls tumor growth
Authors: Singhal Jyotsana , Chikara Shireen , Horne David , Awasthi Sanjay , Salgia Ravi , Singhal Sharad S 
Published: May 2020

AbstractBreast cancer (BC) remains one of the major causes of cancer deaths in women. Over half of all BCs carry genetic defects in the gene encoding p53, a powerful tumor suppressor. P53 is known as the ‘guardian of the genome’ because it is essential for regulating cell division and preventing tumor formation. Ral-interacting protein (RLIP) is a modular protein capable of participating in many cellular functions. Blocking this stress-responsive protein, which is overexpressed during malignancy, enables BC cells to overcome the deleterious effects of p53 loss more effectively. In the clustered regularly interspaced short palindromic repeats/CRISPR-associated protein (CRISPR/Cas9) system, a single-guide RNA (sgRNA) recognizes a specific DNA sequence and directs the endonuclease Cas9 to make a double-strand break, which enables editing of targeted genes. Here, we harnessed CRISPR/Cas9 technology to target the RLIP gene in BC cells. We screened sgRNAs using a reporter system and lentivirally delivered them, along with Cas9, to BC cells for validation. We then assessed the survival, proliferation, and tumorigenicity of BC cells in vitro and the growth of tumors in vivo after CRISPR-mediated knockdown of RLIP. Doxycycline-inducible expression of Cas9 in BC cells transduced with lentiviral vectors encoding the sgRNAs disrupted the RLIP gene, leading to inhibition of BC cell proliferation both in vitro and in vivo, with resected tumors showing reduced levels of the survival and proliferation markers Ki67, RLIP, pAkt, and survivin, the cell cycle protein CDK4, and the mesenchymal marker vimentin, as well as elevated levels of the differentiation protein E-cadherin and pro-apoptotic protein Bim. Inducible Cas9/sgRNA-transduced BC cells without doxycycline treatment did not exhibit altered cell survival or proliferation in vitro or in vivo. Our study provides proof-of-concept that the CRISPR/Cas9 system can be utilized to target RLIP in vitro and in vivo.
COVID-19: The New Caledonia Experience
Authors: Kerbaj Jad , Cazorla Cecile , De Greslan Thierry , Serie Mathieu , Gourinat Ann-Claire , Marot Benoit 
Published: May 2020

AbstractNew Caledonia is a French territory in the South Pacific Ocean. While COVID-19 is expanding over the world, the situation on our island seems controlled with a total of 18 documented cases. We report the measures implemented on our island that probably helped contain the epidemic spread.
Chromosomal-Level Genome Assembly of the Sea Urchin Lytechinus variegatus Substantially Improves Functional Genomic Analyses
Authors: Davidson Phillip L , Guo Haobing , Wang Lingyu , Berrio Alejandro , Zhang He , Chang Yue , Soborowski Andrew L , McClay David R , Fan Guangyi , Wray Gregory A 
Published: May 2020

Abstract
Lytechinus variegatus is a camarodont sea urchin found widely throughout the western Atlantic Ocean in a variety of shallow-water marine habitats. Its distribution, abundance, and amenability to developmental perturbation make it a popular model for ecologists and developmental biologists. Here, we present a chromosomal-level genome assembly of L. variegatus generated from a combination of PacBio long reads, 10× Genomics sequencing, and HiC chromatin interaction sequencing. We show L. variegatus has 19 chromosomes with an assembly size of 870.4 Mb. The contiguity and completeness of this assembly are reflected by a scaffold length N50 of 45.5 Mb and BUSCO completeness score of 95.5%. Ab initio and transcript-informed gene modeling and annotation identified 27,232 genes with an average gene length of 12.6 kb, comprising an estimated 39.5% of the genome. Repetitive regions, on the other hand, make up 45.4% of the genome. Physical mapping of well-studied developmental genes onto each chromosome reveals nonrandom spatial distribution of distinct genes and gene families, which provides insight into how certain gene families may have evolved and are transcriptionally regulated in this species. Lastly, aligning RNA-seq and ATAC-seq data onto this assembly demonstrates the value of highly contiguous, complete genome assemblies for functional genomics analyses that is unattainable with fragmented, incomplete assemblies. This genome will be of great value to the scientific community as a resource for genome evolution, developmental, and ecological studies of this species and the Echinodermata.
Viviparous Reptile Regarded to Have Temperature-Dependent Sex Determination Has Old XY Chromosomes
Authors: Cornejo-Páramo Paola , Dissanayake Duminda S B , Lira-Noriega Andrés , Martínez-Pacheco Mónica L , Acosta Armando , Ramírez-Suástegui Ciro , Méndez-de-la-Cruz Fausto R , Székely Tamás , Urrutia Araxi O , Georges Arthur , Cortez Diego 
Published: May 2020

Abstract
The water skinks Eulamprus tympanum and Eulamprus heatwolei show thermally induced sex determination where elevated temperatures give rise to male offspring. Paradoxically, Eulamprus species reproduce in temperatures of 12–15 °C making them outliers when compared with reptiles that use temperature as a cue for sex determination. Moreover, these two species are among the very few viviparous reptiles reported to have thermally induced sex determination. Thus, we tested whether these skinks possess undetected sex chromosomes with thermal override. We produced transcriptome and genome data for E. heatwolei. We found that E. heatwolei presents XY chromosomes that include 14 gametologs with regulatory functions. The Y chromosomal region is 79–116 Myr old and shared between water and spotted skinks. Our work provides clear evidence that climate could be useful to predict the type of sex determination systems in reptiles and it also indicates that viviparity is strictly associated with sex chromosomes.
Co-development of Couples’ Life Satisfaction in Transition to Retirement: A Longitudinal Dyadic Perspective
Authors: Weber Elisa , Hülür Gizem 
Published: May 2020

AbstractObjectivesRetirement is one of the major life course transitions in old age. Evidence suggests that exiting work life is associated with notable changes in life satisfaction, which are heterogeneous across individuals. Effects of retirement transitions on life satisfaction have been understudied in couples. We examined change in life satisfaction with retirement for retirees and their spouses/partners, the extent to which change in life satisfaction was heterogeneous and correlated within couples, and associations with health status and social participation.MethodWe used data from the German Socioeconomic Panel obtained in the years 1984 to 2016 (n = 2,117 couples; 74% male retirees; age at retirement: M = 61 years, SD = 3 years, range = 55 to 70 years; 98% married or in a registered relationship). We examined health and social participation of retirees and their partners as predictor variables and controlled for age, gender, education, partner employment, household income, and region in Germany (former East vs West). Data were analyzed with dyadic multilevel two-phase growth curve models.ResultsOn average, both retirees and partners reported increasing life satisfaction at retirement. Change in life satisfaction was heterogeneous across individuals and highly correlated within couples. Health and social participation were associated with levels of, but not with change in life satisfaction with retirement in retirees and partners.DiscussionRetirement is not a uniform period of transition, but is shaped by the multidimensional context in which life unfolds. Moreover, life satisfaction can be shaped in response to life transitions experienced by close others.
Self-Perceptions of Aging: Factorial Structure and Invariance by Gender
Authors: Turner Shelbie G , Hooker Karen , Geldhof G John 
Published: May 2020

Abstract

Background and Objectives
Self-perceptions of aging (SPA)—the appraisals people place on their own aging processes—predict well-being in later life. Researchers are increasingly hypothesizing that the overarching construct of SPA is comprised of two factors—positive SPA and negative SPA—and that SPA are gendered. The purpose of this study was to empirically test the hypothesized two-factor structure of SPA and to analyze how the two-factor structure varies between men and women.

Research Design and Methods
Data come from the 2012 wave of the Health and Retirement Study (N = 7,029; Mage = 68.08), which includes an 8-item SPA scale. We used confirmatory factor analysis (CFA) to assess (i) the positive SPA and negative SPA two-factor solution for the 8-item scale and (ii) whether the two-factor solution had configural, strong, or weak invariance across men and women.

Results
CFAs indicated a two-factor latent structure of the 8-item scale, with SPA being comprised of both a positive SPA factor and a negative SPA factor. The latent structure was the same for both men and women.

Discussion and Implications
Results suggest that SPA is a broader construct made up of positive and negative latent factors. Researchers should consider separating the SPA by positive and negative factors to analyze how each factor uniquely shapes health. Moreover, the two-factor solution was equivalent across men and women, possibly because of the generalized nature of the 8-item scale. Researchers can use the 8-item scale similarly for men and women and should continue to elucidate possible gender differences in SPA.
The Tudor-domain protein TDRD7, mutated in congenital cataract, controls the heat shock protein HSPB1 (HSP27) and lens fiber cell morphology
Authors: Barnum Carrie E , Al Saai Salma , Patel Shaili D , Cheng Catherine , Anand Deepti , Xu Xiaolu , Dash Soma , Siddam Archana D , Glazewski Lisa , Paglione Emily , Polson Shawn W , Chuma Shinichiro , Mason Robert W , Wei Shuo , Batish Mona , Fowler Velia M , Lachke Salil A 
Published: May 2020

AbstractMutations of the RNA granule component TDRD7 (OMIM: 611258) cause pediatric cataract. We applied an integrated approach to uncover the molecular pathology of cataract in Tdrd7−/− mice. Early postnatal Tdrd7−/− animals precipitously develop cataract suggesting a global-level breakdown/misregulation of key cellular processes. High-throughput RNA sequencing integrated with iSyTE-bioinformatics analysis identified the molecular chaperone and cytoskeletal modulator, HSPB1, among high-priority downregulated candidates in Tdrd7−/− lens. A protein fluorescence two-dimensional difference in-gel electrophoresis (2D-DIGE)-coupled mass spectrometry screen also identified HSPB1 downregulation, offering independent support for its importance to Tdrd7−/− cataractogenesis. Lens fiber cells normally undergo nuclear degradation for transparency, posing a challenge: how is their cell morphology, also critical for transparency, controlled post-nuclear degradation? HSPB1 functions in cytoskeletal maintenance, and its reduction in Tdrd7−/− lens precedes cataract, suggesting cytoskeletal defects may contribute to Tdrd7−/− cataract. In agreement, scanning electron microscopy (SEM) revealed abnormal fiber cell morphology in Tdrd7−/− lenses. Further, abnormal phalloidin and wheat germ agglutinin (WGA) staining of Tdrd7−/− fiber cells, particularly those exhibiting nuclear degradation, reveals distinct regulatory mechanisms control F-actin cytoskeletal and/or membrane maintenance in post-organelle degradation maturation stage fiber cells. Indeed, RNA immunoprecipitation identified Hspb1 mRNA in wild-type lens lysate TDRD7-pulldowns, and single-molecule RNA imaging showed co-localization of TDRD7 protein with cytoplasmic Hspb1 mRNA in differentiating fiber cells, suggesting that TDRD7–ribonucleoprotein complexes may be involved in optimal buildup of key factors. Finally, Hspb1 knockdown in Xenopus causes eye/lens defects. Together, these data uncover TDRD7’s novel upstream role in elevation of stress-responsive chaperones for cytoskeletal maintenance in post-nuclear degradation lens fiber cells, perturbation of which causes early-onset cataracts.
Repeated implantation failure (RIF): an iatrogenic meaningless definition that generates unnecessary and costly use of add-on procedures
Authors: Ben Rafael Zion 
Published: May 2020

Abstract
This opinion paper addresses the literature regarding repeated implantation failure (RIF) in IVF embryo transfer programmes. We provide several lines of discussion as to why such diagnosis might be wrong, why it should not be a call for action or a reason to change the course of treatment, and how RIF biases the quality of the publications and leads to the use of unnecessary and costly adjuvant procedures beyond basic IVF. We argue that these costly add-on procedures are being offered to patients in this highly privatized sector to prevent them from quitting the programme and as a by-product to increase the clinic income. The patients, on the other hand, often equate lucrative hi-tech procedures with possible success and request them despite the lack of proof of the efficacy of most of the procedures.
CpG Methylation inTGFβ1andIL-6Genes as Surrogate Biomarkers for Diagnosis of IBD in Children
Authors: Samarani Suzanne , Dupont-Lucas Claire , Marcil Valerie , Mack David , Israel David , Deslandres Colette , Jantchou Prevost , Ahmad Ali , Amre Devendra 
Published: May 2020

AbstractBackgroundDiagnostic markers for distinguishing between Crohn disease (CD) and ulcerative colitis (UC) remain elusive. We studied whether methylation marks across the promoters of the transforming growth factor beta 1 (TGFβ1) and interleukin-6 genes have diagnostic utility.MethodsA case-control study was carried out. Cases were treatment-naïve, diagnosed before age 20, and recruited from 3 pediatric gastroenterology clinics across Canada. Control patients did not have inflammatory bowel disease and were recruited from orthopedic clinics within the same hospitals as the gastroenterology clinics. Patient DNA from peripheral blood was processed to identify methylation sites (CpG) across the promoter regions of the TGFβ1 and interleukin-6 genes. After initial nonparametric univariate analyses, multivariate logistic regression models were fit. Models with the best fit (Akaike information criteria) and strongest discriminatory capabilities (area under the curve [AUC]) were identified, and P values were adjusted for multiple comparisons using the false discovery rate method.ResultsA total of 67 CD, 31 UC, and 43 control patients were included. The age distribution of the 3 groups was similar. Most CD patients had ileocolonic disease (44.8%) and inflammatory disease (88.1%). Most UC patients had extensive (71%) and moderate disease (51.6%). Logistic regression analysis revealed the following: 14 TGFβ1 CpG sites discriminated between CD and control patients (AUC = 0.94), 9 TGFβ1 CpG sites discriminated between UC and control patients (AUC = 0.99), 3 TGFβ1 CpG sites discriminated between CD and UC (AUC = 0.81), and 6 TGFβ1 CpG sites distinguished colonic CD from UC (AUC = 0.91).ConclusionsWe found that CpG methylation in the promoter of the TGFβ1 gene has high discriminative power for identifying CD and UC and could serve as an important diagnostic marker.
Early childhood growth trajectory and later cognitive ability: evidence from a large prospective birth cohort of healthy term-born children
Authors: Ahmed Asma , Kramer Michael S , Bernard Jonathan Y , Perez Trejo Maria Esther , Martin Richard M , Oken Emily , Yang Seungmi 
Published: May 2020

Abstract

Background
Most studies of associations between child growth and cognitive ability were based on size at one or two ages and a single measure of cognition. We aimed to characterize different aspects of early growth and their associations with cognitive outcomes in childhood through adolescence.

Methods
In a sample of 12 368 Belarusian children born at term, we examined associations of length/height and weight trajectories over the first 6.5 years of life with cognitive ability at 6.5 and 16 years and its change over time. We estimated growth trajectories using two random-effects models—the SuperImposition by Translation and Rotation to model overall patterns of growth and the Jenss-Bayley to distinguish growth in infancy from post infancy. Cognitive ability was measured using the Wechsler Abbreviated Scales of Intelligence at 6.5 years and the computerized NeuroTrax test at 16 years.

Results
Higher length/height between birth and 6.5 years was associated with higher cognitive scores at 6.5 and 16 years {2.7 points [95% confidence interval (CI): 2.1, 3.2] and 2.5 points [95% CI: 1.9, 3.0], respectively, per standard deviation [SD] increase}. A 1-SD delay in the childhood height-growth spurt was negatively associated with cognitive scores [–2.4 (95% CI: –3.0, –1.8) at age 6.5; –2.2 (95% CI: –2.7, –1.6) at 16 years]. Birth size and post-infancy growth velocity were positively associated with cognitive scores at both ages. Height trajectories were not associated with the change in cognitive score. Similar results were observed for weight trajectories.

Conclusions
Among term infants, the overall size, timing of the childhood growth spurt, size at birth and post-infancy growth velocity were all associated with cognitive ability at early-school age and adolescence.
Blow-up of error estimates in time-fractional initial-boundary value problems
Authors: Chen Hu , Stynes Martin 
Published: May 2020

Abstract
Time-fractional initial-boundary value problems of the form $D_t^\alpha u-p \varDelta u +cu=f$ are considered, where $D_t^\alpha u$ is a Caputo fractional derivative of order $\alpha \in (0,1)$ and the spatial domain lies in $\mathbb{R}^d$ for some $d\in \{1,2,3\}$. As $\alpha \to 1^-$ we prove that the solution $u$ converges, uniformly on the space-time domain, to the solution of the classical parabolic initial-boundary value problem where $D_t^\alpha u$ is replaced by $\partial u/\partial t$. Nevertheless, most of the rigorous analyses of numerical methods for this time-fractional problem have error bounds that blow up as $\alpha \to 1^-$, as we demonstrate. We show that in some cases these analyses can be modified to obtain robust error bounds that do not blow up as $\alpha \to 1^-$.
Danger-associated metabolic modifications during bacterial infection of macrophages
Authors: Dramé Mariatou , Buchrieser Carmen , Escoll Pedro 
Published: May 2020

Abstract
In this review, we propose that certain modifications in cellular metabolism might function as danger signals triggering inflammasome-mediated immune responses. We propose to call them danger-associated metabolic modifications (DAMMs). As intracellular bacteria can actively modulate macrophage metabolism for their benefit, infected host cells might sense bacteria-induced metabolic alterations and activate immune reactions. Here we report the known metabolic interactions that occur during infection of macrophages by intracellular bacteria and discuss the possible emergence of DAMMs upon bacteria-induced alterations of cellular metabolism.
How did a Quality Premium financial incentive influence antibiotic prescribing in primary care? Views of Clinical Commissioning Group and general practice professionals
Authors: Borek Aleksandra J , Anthierens Sibyl , Allison Rosalie , McNulty Cliodna A M , Lecky Donna M , Costelloe Ceire , Holmes Alison , Butler Christopher C , Walker A Sarah , Tonkin-Crine Sarah 
Published: May 2020

AbstractBackgroundThe Quality Premium (QP) was introduced for Clinical Commissioning Groups (CCGs) in England to optimize antibiotic prescribing, but it remains unclear how it was implemented.ObjectivesTo understand responses to the QP and how it was perceived to influence antibiotic prescribing.MethodsSemi-structured telephone interviews were conducted with 22 CCG and 19 general practice professionals. Interviews were analysed thematically.ResultsThe findings were organized into four categories. (i) Communication: this was perceived as unstructured and infrequent, and CCG professionals were unsure whether they received QP funding. (ii) Implementation: this was influenced by available local resources and competing priorities, with multifaceted and tailored strategies seen as most helpful for engaging general practices. Many antimicrobial stewardship (AMS) strategies were implemented independently from the QP, motivated by quality improvement. (iii) Mechanisms: the QP raised the priority of AMS nationally and locally, and provided prescribing targets to aim for and benchmark against, but money was not seen as reinvested into AMS. (iv) Impact and sustainability: the QP was perceived as successful, but targets were considered challenging for a minority of CCGs and practices due to contextual factors (e.g. deprivation, understaffing). CCG professionals were concerned with potential discontinuation of the QP and prescribing rates levelling off.ConclusionsCCG and practice professionals expressed positive views of the QP and associated prescribing targets and feedback. The QP helped influence change mainly by raising the priority of AMS and defining change targets rather than providing additional funding. To maximize impact, behavioural mechanisms of financial incentives should be considered pre-implementation.
CpxR regulates the colistin susceptibility of Salmonella Typhimurium by a multitarget mechanism
Authors: Zhai Ya-Jun , Sun Hua-Run , Luo Xing-Wei , Liu Jian-Hua , Pan Yu-Shan , Wu Hua , Yuan Li , Liang Jun , He Dan-Dan , Hu Gong-Zheng 
Published: May 2020

Abstract

Background
The two-component signalling systems PmrAB and PhoPQ of Salmonella have been extensively studied with regard to colistin resistance. We previously showed that overexpressed CpxR could significantly increase the colistin susceptibility (16-fold compared with the WT strain) of Salmonella enterica serovar Typhimurium (Salmonella Typhimurium) through PmrAB and PhoPQ.

Objectives
To identify the potential target genes of CpxR in PmrAB- and PhoPQ-related signalling pathways.

Methods
His6-CpxR was prokaryotically expressed and purified by Ni-NTA resin affinity chromatography. β-Galactosidase activity assays were conducted to investigate whether CpxR could regulate the promoters of colistin resistance-related genes (CRRGs). Electrophoretic mobility shift assays (EMSAs) were used to further detect His6-CpxR complexes with promoters of CRRGs.

Results
We demonstrated for the first time (to the best of our knowledge) that CpxR and the AcrAB–TolC efflux pump have reciprocal effects on CRRG transcription. Additionally, CpxR could regulate the colistin susceptibility of Salmonella Typhimurium by binding directly to the promoters of phoPQ, pmrC, pmrH and pmrD at the CpxR box-like sequences or indirectly through other regulators including pmrAB and mgrB.

Conclusions
CpxR could regulate the colistin susceptibility of Salmonella Typhimurium by a multitarget mechanism.