bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tbx2aModulates Switching ofRH2andLWSOpsin Gene Expression
Authors: Sandkam Benjamin A , Campello Laura , O’Brien Conor , Nandamuri Sri Pratima , Gammerdinger William J , Conte Matthew A , Swaroop Anand , Carleton Karen L 
Published: March 2020

AbstractSensory systems are tuned by selection to maximize organismal fitness in particular environments. This tuning has implications for intraspecies communication, the maintenance of species boundaries, and speciation. Tuning of color vision largely depends on the sequence of the expressed opsin proteins. To improve tuning of visual sensitivities to shifts in habitat or foraging ecology over the course of development, many organisms change which opsins are expressed. Changes in this developmental sequence (heterochronic shifts) can create differences in visual sensitivity among closely related species. The genetic mechanisms by which these developmental shifts occur are poorly understood. Here, we use quantitative trait locus analyses, genome sequencing, and gene expression studies in African cichlid fishes to identify a role for the transcription factor Tbx2a in driving a switch between long wavelength sensitive (LWS) and Rhodopsin-like (RH2) opsin expression. We identify binding sites for Tbx2a in the LWS promoter and the highly conserved locus control region of RH2 which concurrently promote LWS expression while repressing RH2 expression. We also present evidence that a single change in Tbx2a regulatory sequence has led to a species difference in visual tuning, providing the first mechanistic model for the evolution of rapid switches in sensory tuning. This difference in visual tuning likely has important roles in evolution as it corresponds to differences in diet, microhabitat choice, and male nuptial coloration.
Relative Model Fit Does Not Predict Topological Accuracy in Single-Gene Protein Phylogenetics
Authors: Spielman Stephanie J 
Published: March 2020

Abstract
It is regarded as best practice in phylogenetic reconstruction to perform relative model selection to determine an appropriate evolutionary model for the data. This procedure ranks a set of candidate models according to their goodness of fit to the data, commonly using an information theoretic criterion. Users then specify the best-ranking model for inference. Although it is often assumed that better-fitting models translate to increase accuracy, recent studies have shown that the specific model employed may not substantially affect inferences. We examine whether there is a systematic relationship between relative model fit and topological inference accuracy in protein phylogenetics, using simulations and real sequences. Simulations employed site-heterogeneous mechanistic codon models that are distinct from protein-level phylogenetic inference models, allowing us to investigate how protein models performs when they are misspecified to the data, as will be the case for any real sequence analysis. We broadly find that phylogenies inferred across models with vastly different fits to the data produce highly consistent topologies. We additionally find that all models infer similar proportions of false-positive splits, raising the possibility that all available models of protein evolution are similarly misspecified. Moreover, we find that the parameter-rich GTR (general time reversible) model, whose amino acid exchangeabilities are free parameters, performs similarly to models with fixed exchangeabilities, although the inference precision associated with GTR models was not examined. We conclude that, although relative model selection may not hinder phylogenetic analysis on protein data, it may not offer specific predictable improvements and is not a reliable proxy for accuracy.
Dynamic Evolution of Euchromatic Satellites on the X Chromosome in Drosophila melanogaster and the simulans Clade
Authors: Sproul John S , Khost Danielle E , Eickbush Danna G , Negm Sherif , Wei Xiaolu , Wong Isaac , Larracuente Amanda M 
Published: March 2020

AbstractSatellite DNAs (satDNAs) are among the most dynamically evolving components of eukaryotic genomes and play important roles in genome regulation, genome evolution, and speciation. Despite their abundance and functional impact, we know little about the evolutionary dynamics and molecular mechanisms that shape satDNA distributions in genomes. Here, we use high-quality genome assemblies to study the evolutionary dynamics of two complex satDNAs, Rsp-like and 1.688 g/cm3, in Drosophila melanogaster and its three nearest relatives in the simulans clade. We show that large blocks of these repeats are highly dynamic in the heterochromatin, where their genomic location varies across species. We discovered that small blocks of satDNA that are abundant in X chromosome euchromatin are similarly dynamic, with repeats changing in abundance, location, and composition among species. We detail the proliferation of a rare satellite (Rsp-like) across the X chromosome in D. simulans and D. mauritiana. Rsp-like spread by inserting into existing clusters of the older, more abundant 1.688 satellite, in events likely facilitated by microhomology-mediated repair pathways. We show that Rsp-like is abundant on extrachromosomal circular DNA in D. simulans, which may have contributed to its dynamic evolution. Intralocus satDNA expansions via unequal exchange and the movement of higher order repeats also contribute to the fluidity of the repeat landscape. We find evidence that euchromatic satDNA repeats experience cycles of proliferation and diversification somewhat analogous to bursts of transposable element proliferation. Our study lays a foundation for mechanistic studies of satDNA proliferation and the functional and evolutionary consequences of satDNA movement.
Alterations of endometrial epithelial–mesenchymal transition and MAPK signalling components in women with PCOS are partially modulated by metformin in vitro
Authors: Hu Min , Zhang Yuehui , Li Xin , Cui Peng , Li Juan , Brännström Mats , Shao Linus R , Billig Håkan 
Published: March 2020

Abstract
Growing evidence suggests that epithelial–mesenchymal transition (EMT) and its regulator mitogen-activated protein kinase (MAPK) contribute to endometria-related reproductive disorders. However, the regulation of EMT and MAPK signalling components in the endometrium from polycystic ovary syndrome (PCOS) patients has not been systematically investigated and remains elusive. In humans, how metformin induces molecular alterations in the endometrial tissues under PCOS conditions is not completely clear. Here, we recruited 7 non-PCOS patients during the proliferative phase (nPCOS), 7 non-PCOS patients with endometrial hyperplasia (nPCOSEH), 14 PCOS patients during the proliferative phase (PCOS) and 3 PCOS patients with endometrial hyperplasia (PCOSEH). Our studies demonstrated that compared with nPCOS, PCOS patients showed decreased Claudin 1 and increased Vimentin and Slug proteins. Similar to increased Slug protein, nPCOSEH and PCOSEH patients showed increased N-cadherin protein. Western blot and immunostaining revealed increased epithelial phosphorylated Cytokeratin 8 (p-CK 8) expression and an increased p-CK 8:CK 8 ratio in PCOS, nPCOSEH and PCOSEH patients compared to nPCOS patients. Although nPCOSEH and PCOSEH patients showed increased p-ERK1/2 and/or p38 protein levels, the significant increase in p-ERK1/2 expression and p-ERK1/2:ERK1/2 ratio was only found in PCOS patients compared to nPCOS patients. A significant induction of the membrane ERβ immunostaining was observed in the epithelial cells of PCOS and PCOSEH patients compared to nPCOS and nPCOSEH patients. While in vitro treatment with metformin alone increased Snail and decreased Claudin 1, N-cadherin and α-SMA proteins, concomitant treatment with metformin and E2 increased the expression of CK 8 and Snail proteins and decreased the expression of Claudin 1, ZO-1, Slug and α-SMA proteins. Our findings suggest that the EMT contributes to the switch from a healthy state to a PCOS state in the endometrium, which might subsequently drive endometrial injury and dysfunction. We also provide evidence that metformin differentially modulates EMT protein expression in PCOS patients depending on oestrogenic stimulation.
Mechanistic insights from structure of Mycobacterium smegmatis topoisomerase I with ssDNA bound to both N- and C-terminal domains
Authors: Cao Nan , Tan Kemin , Zuo Xiaobing , Annamalai Thirunavukkarasu , Tse-Dinh Yuk-Ching 
Published: March 2020

AbstractType IA topoisomerases interact with G-strand and T-strand ssDNA to regulate DNA topology. However, simultaneous binding of two ssDNA segments to a type IA topoisomerase has not been observed previously. We report here the crystal structure of a type IA topoisomerase with ssDNA segments bound in opposite polarity to the N- and C-terminal domains. Titration of small ssDNA oligonucleotides to Mycobacterium smegmatis topoisomerase I with progressive C-terminal deletions showed that the C-terminal region has higher affinity for ssDNA than the N-terminal active site. This allows the C-terminal domains to capture one strand of underwound negatively supercoiled DNA substrate first and position the N-terminal domains to bind and cleave the opposite strand in the relaxation reaction. Efficiency of negative supercoiling relaxation increases with the number of domains that bind ssDNA primarily with conserved aromatic residues and possibly with assistance from polar/basic residues. A comparison of bacterial topoisomerase I structures showed that a conserved transesterification unit (N-terminal toroid structure) for cutting and rejoining of a ssDNA strand can be combined with two different types of C-terminal ssDNA binding domains to form diverse bacterial topoisomerase I enzymes that are highly efficient in their physiological role of preventing excess negative supercoiling in the genome.
Rapid and assured genetic engineering methods applied to Acinetobacter baylyi ADP1 genome streamlining
Authors: Suárez Gabriel A , Dugan Kyle R , Renda Brian A , Leonard Sean P , Gangavarapu Lakshmi Suryateja , Barrick Jeffrey E 
Published: March 2020

Abstract
One goal of synthetic biology is to improve the efficiency and predictability of living cells by removing extraneous genes from their genomes. We demonstrate improved methods for engineering the genome of the metabolically versatile and naturally transformable bacterium Acinetobacter baylyi ADP1 and apply them to a genome streamlining project. In Golden Transformation, linear DNA fragments constructed by Golden Gate Assembly are directly added to cells to create targeted deletions, edits, or additions to the chromosome. We tested the dispensability of 55 regions of the ADP1 chromosome using Golden Transformation. The 18 successful multiple-gene deletions ranged in size from 21 to 183 kb and collectively accounted for 23.4% of its genome. The success of each multiple-gene deletion attempt could only be partially predicted on the basis of an existing collection of viable ADP1 single-gene deletion strains and a new transposon insertion sequencing (Tn-Seq) dataset that we generated. We further show that ADP1’s native CRISPR/Cas locus is active and can be retargeted using Golden Transformation. We reprogrammed it to create a CRISPR-Lock, which validates that a gene has been successfully removed from the chromosome and prevents it from being reacquired. These methods can be used together to implement combinatorial routes to further genome streamlining and for more rapid and assured metabolic engineering of this versatile chassis organism.
Chronic hypoxia exacerbates diabetic glomerulosclerosis through mesangiolysis and podocyte injury in db/db mice
Authors: Takahashi Naoki , Yoshida Haruyoshi , Kimura Hideki , Kamiyama Kazuko , Kurose Tomomi , Sugimoto Hidehiro , Imura Toshio , Yokoi Seiji , Mikami Daisuke , Kasuno Kenji , Kurosawa Hiroyuki , Hirayama Yoshiaki , Naiki Hironobu , Hara Masanori , Iwano Masayuki 
Published: March 2020

Abstract

Background
Chronic hypoxia may play a pivotal role in the development of diabetic nephropathy (DN). However, the precise mechanisms underlying progressive hypoxia-induced glomerular injury remain unclear.

Methods
We housed db/db mice in a hypoxia chamber (12% O2) for up to 16 weeks beginning at 8 weeks of age. Various urine, serum and kidney abnormalities and glomerular messenger RNA (mRNA) expression were compared with those in age-matched db/db mice housed under normoxia.

Results
Levels of urinary albumin and podocalyxin (PCX) were significantly higher in hypoxic mice early during hypoxia. Ultracentrifugation of urine samples revealed that podocytes in the hypoxic mice shed PCX-positive microparticles into the urine. After 16 weeks of hypoxia, the mice also had higher hematocrits with lower serum glucose and various degrees of mesangiolytic glomerulosclerosis with microaneurysms and the infrequent occurrence of nodular lesions. Immunohistologically, hypoxic mice showed significantly decreased endothelial cell densities early during hypoxia and decreased podocyte densities later. In both hypoxic and normoxic mice, glomerular macrophage and transforming growth factor-β1 (TGF-β1) staining significantly increased with aging, without changes in vascular endothelial growth factor or endothelial nitric oxide synthase (eNOS). Glomerular mRNA expression of monocyte chemoattractant protein-1, eNOS and TGF-β1 was significantly enhanced in the hypoxic mice.

Conclusions
These results indicate that chronic hypoxia induces advanced glomerulosclerosis with accelerated albuminuria triggered by mesangiolysis and podocyte injury in a murine model of DN.
Effects of bariatric surgery on kidney diseases, cardiovascular diseases, mortality and severe hypoglycaemia among patients with Type 2 diabetes mellitus
Authors: Wong Carlos K H , Wu Tingting , Wong Simon K H , Law Betty T T , Grieve Eleanor , Ng Enders K W , Wu Olivia , Lam Cindy L K 
Published: March 2020

Abstract

Background
Bariatric surgery has been widely indicated for the management of obesity and related comorbidities. However, there are uncertainties pertaining to the risks of post-bariatric severe hypoglycaemia (SH), cardiovascular diseases (CVDs), end-stage kidney diseases (ESKDs) and all-cause mortality in obese patients with Type 2 diabetes mellitus (T2DM), especially among Asian populations.

Methods
A retrospective population-based cohort of 1702 obese T2DM patients who were free of CVD and ESKD were assembled based on the 2006–17 Hospital Authority database. One-to-five propensity-score matching was used to balance baseline covariates between patients in bariatric surgery and control groups. Incidence rates (IRs) of SH, CVD, Stage 4/5 chronic kidney diseases (CKD), ESKD and all-cause mortality events for two groups were calculated. Hazard ratios (HR) for SH, CVD and Stage 4/5 CKD events were assessed using Cox-proportional hazard models. Changes in estimated glomerular filtration rate (eGFR) and urine albumin–creatinine ratio (UACR) were measured up to 60 months.

Results
Over a mean follow-up period of 32 months with 5725 person-years, cumulative incidences of mortality, CVD, Stage 4/5 CKD, ESKD and SH were 0, 0.036, 0.050, 0.017 and 0.020, respectively. The surgery group had a significant reduction in risk of CVD events (HR = 0.464, P = 0.015) and no occurrence of mortality events. However, there were no significant differences in risks of SH [HR = 0.469, 95% confidence interval (CI): 0.204–1.081], Stage 4/5 CKD (HR =0.896, 95% CI: 0.519–1.545) and ESKD (HR = 0.666, 95% CI: 0.264–1.683) between two groups, although IRs were lower in the surgery group. Surgical patients had significantly higher eGFR within 12 months and had significantly lower UACR until 48 months.

Conclusions
Among obese T2DM patients, bariatric surgery lowered the risk of CVD and mortality, and was beneficial towards the kidney outcomes.
Deep-learning-based information mining from ocean remote-sensing imagery
Authors: Li Xiaofeng , Liu Bin , Zheng Gang , Ren Yibin , Zhang Shuangshang , Liu Yingjie , Gao Le , Liu Yuhai , Zhang Bin , Wang Fan 
Published: March 2020

AbstractWith the continuous development of space and sensor technologies during the last 40 years, ocean remote sensing has entered into the big-data era with typical five-V (volume, variety, value, velocity and veracity) characteristics. Ocean remote-sensing data archives reach several tens of petabytes and massive satellite data are acquired worldwide daily. To precisely, efficiently and intelligently mine the useful information submerged in such ocean remote-sensing data sets is a big challenge. Deep learning—a powerful technology recently emerging in the machine-learning field—has demonstrated its more significant superiority over traditional physical- or statistical-based algorithms for image-information extraction in many industrial-field applications and starts to draw interest in ocean remote-sensing applications. In this review paper, we first systematically reviewed two deep-learning frameworks that carry out ocean remote-sensing-image classifications and then presented eight typical applications in ocean internal-wave/eddy/oil-spill/coastal-inundation/sea-ice/green-algae/ship/coral-reef mapping from different types of ocean remote-sensing imagery to show how effective these deep-learning frameworks are. Researchers can also readily modify these existing frameworks for information mining of other kinds of remote-sensing imagery.
Classification–coordination–collaboration: a systems approach for advancing Sustainable Development Goals
Authors: Fu Bojie , Zhang Junze , Wang Shuai , Zhao Wenwu 
Published: March 2020

Summary
It is an urgent task to advance Sustainable Development Goals (SDGs) on different scales in the world. We propose a systems approach to combat this issue, namely `classification–coordination–collaboration'. This approach allows SDGs to realize key breakthroughs over the short-term while achieving sweeping progress over the long run.
For whom and under what circumstances do nutrition-education cooking interventions work: a realist synthesis
Authors: Maugeri Isabella P , Brimblecombe Julie , Choi Tammie S T , Kleve Sue , Palermo Claire 
Published: March 2020

Abstract

Objective
To explore for whom and under what circumstances nutrition-education cooking interventions affect nutrition outcomes in adults.

Methods
A realist synthesis was undertaken. The CINAHL, Ovid Medline, Scopus, and Web of Science databases were searched for literature published between 1980 and 2019, using the terms “cook” and “intervention” and their synonyms; 5759 articles were identified. Grey literature was sourced for further additional program context. A total of 23 articles (n = 11 programs) met inclusion criteria for analysis. Program data were coded in duplicate for context, outcome, and mechanism configurations, and used to build a refined program theory.

Results
Nutrition-education cooking interventions targeted at low-socioeconomic-status and marginalized populations produced a range of positive nutrition outcomes. Outcomes were observed when the program involved hands-on cooking and a skilled facilitator coupled with individual self-efficacy, knowledge gain, family support, and an expectation of positive health outcomes.

Conclusion
These findings highlight key program components to achieve improvements in nutrition and important recommendations for nutrition-education cooking interventions.
Genetic Manipulation of Transcriptional Regulators Alters Nicotine Biosynthesis in Tobacco
Authors: Hayashi Shunya , Watanabe Mutsumi , Kobayashi Makoto , Tohge Takayuki , Hashimoto Takashi , Shoji Tsubasa 
Published: March 2020

Abstract
The toxic alkaloid nicotine is produced in the roots of Nicotiana species and primarily accumulates in leaves as a specialized metabolite. A series of metabolic and transport genes involved in the nicotine pathway are coordinately upregulated by a pair of jasmonate-responsive AP2/ERF-family transcription factors, NtERF189 and NtERF199, in the roots of Nicotiana tabacum (tobacco). In this study, we explored the potential of manipulating the expression of these transcriptional regulators to alter nicotine biosynthesis in tobacco. The transient overexpression of NtERF189 led to alkaloid production in the leaves of Nicotiana benthamiana and Nicotiana alata. This ectopic production was further enhanced by co-overexpressing a gene encoding a basic helix-loop-helix-family MYC2 transcription factor. Constitutive and leaf-specific overexpression of NtERF189 increased the accumulation of foliar alkaloids in transgenic tobacco plants but negatively affected plant growth. By contrast, in a knockout mutant of NtERF189 and NtERF199 obtained through CRISPR/Cas9-based genome editing, alkaloid levels were drastically reduced without causing major growth defects. Metabolite profiling revealed the impact of manipulating the nicotine pathway on a wide range of nitrogen- and carbon-containing metabolites. Our findings provide insights into the biotechnological applications of engineering metabolic pathways by targeting transcription factors.
Negligible risk of the COVID-19 resurgence caused by work resuming in China (outside Hubei): a statistical probability study
Authors: Zhao Kedong , Long Cheng , Wang Yan , Zeng Tieyong , Fu Xinmiao 
Published: March 2020

Abstract
The COVID-19 outbreak in China appears to reach the late stage since late March 2020, and a stepwise restoration of economic operations is implemented. Risk assessment for such economic restoration is of significance. Here, we estimated the probability of COVID-19 resurgence caused by work resuming in typical provinces/cities and found that such probability is very limited (&lt;5% for all the regions except Beijing). Our work may inform provincial governments to make risk level-based, differentiated control measures.
Circular RNA sequencing indicates circ-IQGAP2 and circ-ZC3H6 as noninvasive biomarkers of primary Sjögren’s syndrome
Authors: Li Fengxia , Liu Zhenwei , Zhang Bing , Jiang Shan , Wang Qiongdan , Du Lifeng , Xue Huangqi , Zhang Yu , Jin Mengmeng , Zhu Xiaochun , Brown Matthew A , Wu Jinyu , Wang Xiaobing 
Published: March 2020

Abstract

Objectives
This study aims to characterize the expression profiles of circRNAs in primary Sjogren’s Syndrome (pSS) and examine the potential of noninvasive circular RNAs (circRNAs) as biomarkers of pSS.

Methods
We performed RNA sequencing of minor salivary gland (MSG) biopsies from four pSS and four non-pSS individuals (subjects undergoing MSG biopsies but not meeting 2012 or 2016 ACR classification criteria for SS). Differentially expressed circRNAs were identified by DESeq2, and confirmed by quantitative real-time PCR in the MSGs as well as in plasma exosomes in 37 pSS and 14 non-pSS subjects. Discriminatory capacity testing using receiver operating characteristic analysis was used to evaluate the performance of circRNAs as diagnostic biomarkers for pSS.

Results
Circ-IQGAP2 and circ-ZC3H6 had significantly upregulated expression in the MSGs of pSS patients, and this elevated expression was confirmed by quantitative real-time PCR of plasma exosome RNA. The expression of these circRNAs also showed significant correlation with both clinical features, serum IgG level and MSG focus scores. Receiver operating characteristic analysis showed that the indices comprised of both the two circRNAs and clinical features were better able to distinguish pSS from non-pSS subjects with high mean areas under the curve of 0.93 in the MSGs and 0.92 in the plasma exosomes.

Conclusion
This study indicated the potential roles of circ-IQGAP2 and circ-ZC3H6 as noninvasive biomarkers for the diagnosis of pSS.