bluuebunny/crossref_metadata_2025_split huggingface dataset:
Low Electric Treatment activates Rho GTPase via Heat Shock Protein 90 and Protein Kinase C for Intracellular Delivery of siRNA
Authors: Hasan Mahadi , Hama Susumu , Kogure Kentaro 
Published: March 2019

AbstractLow electric treatment (LET) promotes intracellular delivery of naked siRNA by altering cellular physiology. However, which signaling molecules and cellular events contribute to LET-mediated siRNA uptake are unclear. Here, we used isobaric tags in relative and absolute quantification (iTRAQ) proteomic analysis to identify changes in the levels of phosphorylated proteins that occur during cellular uptake of siRNA promoted by LET. iTRAQ analysis revealed that heat shock protein 90 (Hsp90)α and myristoylated alanine-rich C-kinase substrate (Marcks) were highly phosphorylated following LET of NIH 3T3 cells, but not untreated cells. Furthermore, the levels of phosphorylated Hsp90α and protein kinase C (PKC)γ were increased by LET both with siRNA and liposomes having various physicochemical properties used as model macromolecules, suggesting that PKCγ activated partly by Ca2+ influx as well as Hsp90 chaperone function were involved in LET-mediated cellular siRNA uptake. Furthermore, LET with siRNA induced activation of Rho GTPase via Hsp90 and PKC, which could contribute to cellular siRNA uptake accompanied by actin cytoskeleton remodeling. Collectively, our results suggested that LET-induced Rho GTPase activation via Hsp90 and PKC would participate in actin-dependent cellular uptake of siRNA.
G protein-coupled and ATP-sensitive inwardly rectifying potassium ion channels are essential for HIV entry
Authors: Dubey Ravi C. , Mishra Nawneet , Gaur Ritu 
Published: March 2019

AbstractThe high genetic diversity of Human Immunodeficiency virus (HIV), has hindered the development of effective vaccines or antiviral drugs against it. Hence, there is a continuous need for identification of new antiviral targets. HIV exploits specific host proteins also known as HIV-dependency factors during its replication inside the cell. Potassium channels play a crucial role in the life cycle of several viruses by modulating ion homeostasis, cell signaling, cell cycle, and cell death. In this study, using pharmacological tools, we have identified that HIV utilizes distinct cellular potassium channels at various steps in its life cycle. Members of inwardly rectifying potassium (Kir) channel family, G protein-coupled (GIRK), and ATP-sensitive (KATP) are involved in HIV entry. Blocking these channels using specific inhibitors reduces HIV entry. Another member, Kir 1.1 plays a role post entry as inhibiting this channel inhibits virus production and release. These inhibitors are not toxic to the cells at the concentration used in the study. We have further identified the possible mechanism through which these potassium channels regulate HIV entry by using a slow-response potential-sensitive probe DIBAC4(3) and have observed that blocking these potassium channels inhibits membrane depolarization which then inhibits HIV entry and virus release as well. These results demonstrate for the first time, the important role of Kir channel members in HIV-1 infection and suggest that these K+ channels could serve as a safe therapeutic target for treatment of HIV/AIDS.
Solution structures and biophysical analysis of full-length group A PAKs reveal they are monomeric and auto-inhibited in cis
Authors: Sorrell Fiona J. , Kilian Lena Marie , Elkins Jonathan M. 
Published: March 2019

Abstract
The group A p21-activated kinases (PAKs) exist in an auto-inhibited form until activated by GTPase binding and auto-phosphorylation. In the auto-inhibited form, a regulatory domain binds to the kinase domain (KD) blocking the binding of substrates, and CDC42 or Rac binding to the regulatory domain relieves this auto-inhibition allowing auto-phosphorylation on the KD activation loop. We have determined the crystal structure of the PAK3 catalytic domain and by small angle X-ray scattering, the solution-phase structures of full-length inactive PAK1 and PAK3. The structures reveal a compact but elongated molecular shape that demonstrates that, together with multiple independent biophysical measurements and in contrast with previous assumptions, group A PAKs are monomeric both before and after activation, consistent with an activation mechanism of cis-auto-inhibition and initial cis-auto-phosphorylation, followed by transient dimerisation to allow trans-auto-phosphorylation for full activation, yielding a monomeric active PAK protein.
Increased risk of hepatitis B virus infection amongst individuals with diabetes mellitus
Authors: Zhang Xuan , Zhu Xia , Ji Yulin , Li Hong , Hou Fengsu , Xiao Chuan , Yuan Ping 
Published: March 2019

Abstract
There have been reports of hepatitis B outbreaks amongst diabetics in long-term care facilities, suggesting that risk of hepatitis B virus (HBV) infection is higher in this population. However, the magnitude of the risk and the incidence of HBV infection amongst the general diabetic population in China remains unknown. Data from a cohort study conducted in Mianyang City, Sichuan Province, China, were retrospectively analyzed in order to address this question. Demographic information was collected using a custom-designed questionnaire, and blood samples were tested for HBV using ELISA. We used multivariate logistic regression to explore the relationship between HBV infection and diabetes, while adjusting for age, sex, region, medical insurance, exposure history, and HBV vaccination. During 2013–2014, a total of 189766 adults were surveyed, of which 7382 were newly infected with HBV, corresponding to an incidence of 3.89%. In this study population, there were 4982 diabetic patients and 182710 non-diabetic individuals. Amongst those with diabetes, 265 (5.32%) were newly infected with HBV. In contrast, 7038 (3.85%) in the non-diabetic population were newly infected with HBV. The relative risk (RR) of HBV infection was 43% higher amongst those diagnosed with diabetes than amongst those not diagnosed (RR 1.43, 95% confidence interval (CI) 1.26–1.63). These results suggest that the risk of HBV infection is higher amongst individuals diagnosed with diabetes mellitus in Mianyang City, Sichuan Province, China. Hepatitis B vaccination and continuous infection control practices may help to reduce HBV infection in diabetic patients, and should be considered for diabetes management.
The Wound Healing Properties of Betulin from Birch Bark from Bench to Bedside
Authors: Scheffler Armin 
Published: March 2019

AbstractWith central European approval in January 2016 for a betulin-oleogel (Episalvan), used to accelerate wound closure in partial thickness wounds, the herbal active ingredient triterpene dry extract (betulin), from birch bark, was introduced into therapy for the first time. Clinical evidence of accelerated wound healing was provided in a new study design by means of intraindividual comparison of split-thickness skin graft donor wounds and burn wounds. Clinical results of a phase II study evidencing accelerated wound healing in the rare disease epidermolysis bullosa are also available, and a pivotal multi-centre phase III study is currently being conducted. The mode of action affects all three phases of wound healing (inflammation, migration, and differentiation), and it has been possible, in some cases, to shed light on this down to the molecular level. After temporary stimulation of the inflammatory phase, the keratinocytes migrate more rapidly to the wound closure and, finally, epidermal differentiation is stimulated. With this project, we have shown that scientifically founded new developments in phytotherapy are possible in Europe. The active ingredient is new and its indication is for the first time clearly proven in studies. Betulin-oleogel is the first drug of its indication and is patented until 2030. In addition, it is the first phytotherapeutic agent in surgery, and thus opens up a new therapeutic area for phytotherapy. The birch bark contains about 22% betulin in its cork tissue, meaning that the active ingredient is sustainably available from Northern Europeʼs wood-processing industry on a scale of several 100,000 t/a.
Synthetic Approaches to Chiral Non-C
2-symmetric N-Heterocyclic Carbene Precursors
Authors: Czerwiński Paweł , Michalak Michał 
Published: March 2019

N-Heterocyclic carbenes and their metal complexes have found applications in many organic transformations. Apart from the privileged C
2-symmetry present in modern enantioselective catalysis, ligands bearing C
1-symmetry have witnessed growing attention due to the better control of process stereoselectivity in many cases. The present review summarizes, for the first time, the seminal synthetic efforts for the preparation of N-heterocyclic carbene precursors exhibiting C
1-symmetry. The well-established methods will be discussed in the light of recent achievements, giving a direct opportunity for comparison of the existing methods, and simultaneously a chance to find the best synthetic pathway for the ideal chiral ligand.1	Introduction2	Five-Membered Rings2.1	Five-Membered Saturated (Imidazolinium) Ring2.1.1	Amino Alcohol Derivatives2.1.2	Amino Acid Derivatives2.1.3	Amine and Diamine Derivatives2.2	Five-Membered Unsaturated Ring2.2.1	Cyclization Strategy2.2.2	Functionalization of the Existing N-Imidazole Ring3	Triazolium Salts3.1	Substitution in Oxadiazolium Salts3.2	Lactam-Derived Triazolium NHC (The Leeper and Knight Methodology)3.3	Monoterpenoid-Derived NHC Triazolium Salts3.4	Modifications of the Existing Triazole Ring4	Thiazole-Derived Salts4.1	Cyclization of a Thiazolium Ring4.2	Modifications of the Existing Thiazole Ring5	Summary and Outlook
Language socialization across borders
Authors: Arnold Lynnette 
Published: March 2019

Abstract
Recent scholarship on language use has developed a resurgent interest in the complex interrelationship of language and materiality; given its longstanding investigation of both non-verbal communication and political economy, language socialization research is well-positioned to make important contributions to this investigation of language materiality. This paper advances such a project by demonstrating how the discursive processes of language socialization make the material affectively meaningful. Through an exploration of prompting interactions in cross-border conversations within transnational Salvadoran families, the paper elucidates how processes of material-affective semiosis produce subject positions that are made normative for some individuals, in this case, differentiating between migrant and non-migrant kin. Drawing out the role of materiality in such processes thus reveals how language socialization functions as a scale-making resource that turns the inequalities of transnational migration into constitutive features of family life.
A patch to the possibility part of Gödel’s Ontological Proof
Authors: Gustafsson Johan E 
Published: March 2019

AbstractKurt Gödel’s version of the Ontological Proof derives rather than assumes the crucial (yet controversial) Possibility Claim, that is, the claim that it is possible that something God-like exists. Gödel’s derivation starts off with a proof of the Possible Instantiation of the Positive, that is, the principle that, if a property is positive, it is possible that there exists something that has that property. I argue that Gödel’s proof of this principle relies on some implausible axiological assumptions. Nevertheless, I present a proof of the Possible Instantiation of the Positive, which only relies on plausible axiological principles. Nonetheless, Gödel’s derivation of the Possibility Claim also needs a substantial axiological assumption, which is still open to doubt.
DEFOR: depth- and frequency-based somatic copy number alteration detector
Authors: Zhang He , Zhan Xiaowei , Brugarolas James , Xie Yang 
Published: March 2019

Abstract

Motivation
Detection of somatic copy number alterations (SCNAs) using high-throughput sequencing has become popular because of rapid developments in sequencing technology. Existing methods do not perform well in calling SCNAs for the unstable tumor genomes.

Results
We developed a new method, DEFOR, to detect SCNAs in tumor samples from exome-sequencing data. The evaluation showed that DEFOR has a higher accuracy for SCNA detection from exome sequencing compared with the five existing tools. This advantage is especially apparent in unstable tumor genomes with a large proportion of SCNAs.

Availability and implementation
DEFOR is available at https://github.com/drzh/defor.

Supplementary information
Supplementary data are available at Bioinformatics online.
Stable H3K4me3 is associated with transcription initiation during early embryo development
Authors: Huang Xin , Gao Xudong , Li Wanying , Jiang Shuai , Li Ruijiang , Hong Hao , Zhao Chenghui , Zhou Pingkun , Chen Hebing , Bo Xiaochen , Li Hao 
Published: March 2019

Abstract

Motivation
During development of the mammalian embryo, histone modification H3K4me3 plays an important role in regulating gene expression and exhibits extensive reprograming on the parental genomes. In addition to these dramatic epigenetic changes, certain unchanging regulatory elements are also essential for embryonic development.

Results
Using large-scale H3K4me3 chromatin immunoprecipitation sequencing data, we identified a form of H3K4me3 that was present during all eight stages of the mouse embryo before implantation. This ‘stable H3K4me3’ was highly accessible and much longer than normal H3K4me3. Moreover, most of the stable H3K4me3 was in the promoter region and was enriched in higher chromatin architecture. Using in-depth analysis, we demonstrated that stable H3K4me3 was related to higher gene expression levels and transcriptional initiation during embryonic development. Furthermore, stable H3K4me3 was much more active in blood tumor cells than in normal blood cells, suggesting a potential mechanism of cancer progression.

Supplementary information
Supplementary data are available at Bioinformatics online.
Single-Cell and Neuronal Network Alterations in an In Vitro Model of Fragile X Syndrome
Authors: Moskalyuk Anastasiya , Van De Vijver Sebastiaan , Verstraelen Peter , De Vos Winnok H , Kooy R Frank , Giugliano Michele 
Published: March 2019

Abstract
The Fragile X mental retardation protein (FMRP) is involved in many cellular processes and it regulates synaptic and network development in neurons. Its absence is known to lead to intellectual disability, with a wide range of comorbidities including autism. Over the past decades, FMRP research focused on abnormalities both in glutamatergic and GABAergic signaling, and an altered balance between excitation and inhibition has been hypothesized to underlie the clinical consequences of absence of the protein. Using Fmrp knockout mice, we studied an in vitro model of cortical microcircuitry and observed that the loss of FMRP largely affected the electrophysiological correlates of network development and maturation but caused less alterations in single-cell phenotypes. The loss of FMRP also caused a structural increase in the number of excitatory synaptic terminals. Using a mathematical model, we demonstrated that the combination of an increased excitation and reduced inhibition describes best our experimental observations during the ex vivo formation of the network connections.
To discard or not to discard: transplantation and the art of scoring
Authors: Stallone Giovanni , Grandaliano Giuseppe 
Published: March 2019

AbstractThe growing gap between inadequate supply and constantly high demand for kidney transplantation observed in the last two decades led to exploring the possibility of using organs from older donors with an increasing number of comorbidities. The main issue in this scenario is to identify transplantable organs and to allocate them to the most suitable recipients. A great number of clinical investigations proposed several acceptance/allocation criteria to reduce the discard rate of these kidneys and to improve their outcome, including histological features at the time of transplant. Despite the widespread use of several histological scoring systems, there is no consensus on their value in predicting allograft survival and there is established evidence that histological analysis is the most common reason to discard expanded criteria donor kidneys. To overcome this issue, a clinical scoring system, the Kidney Donor Profile Index (KDPI), was developed on the basis of easily accessible donor features. The KDPI score, adopted in the new US allocation procedure, has good reproducibility but presents several limitations, as suggested also in this issue of Clinical Kidney Journal. This observation should stimulate the search for novel scores combining clinical, histological and molecular features in an attempt to improve the decision process.
Utility of routine oral contrast study for detecting postesophagectomy anastomotic leak – a systematic review and meta-analysis
Authors: Yonis G , Cabalag C S , Link E , Duong C P 
Published: March 2019

SUMMARY
Oral contrast studies are used to detect anastomotic leak (AL) postesophagectomy. However, recent evidence suggests oral contrast studies have low sensitivity in detecting ALs, and their false positive results can lead to unnecessary prolonged hospital stay. The objective of this study was to determine if oral contrast studies should be used routinely post-esophagectomy for cancer. A systematic literature search was conducted for studies published between January 1990 and June 2018. Data extracted for analyses included type of esophagectomy, operative morbidity (such as AL and pneumonia), mortality rates, timing of contrast study, and type of oral contrast used. The sensitivity, specificity, and positive and negative predictive values of routine oral contrast studies to detect AL were calculated using the aforementioned variables. Two hundred and forty-seven studies were reviewed with 16 studies included in the meta-analysis. Postoperative oral contrast study was performed in 94.0% of cases between day 5 and 7. The rates of early and delayed leaks were 2.4% (1.8%–3.3%) and 2.8% (1.8%–4.4%), respectively. Routine contrast studies have a sensitivity and specificity of 0.44 (0.32–0.57) and 0.98 (0.95–0.99), respectively. Analysis of covariates revealed that sensitivity is reduced in centers with a higher volume of cases (greater than 15 per year: 0.50 [0.34–0.75; p = 0.0008]) and specificity was higher in centers with a lower leak rate. Given its poor sensitivity and inability to detect early/delayed AL, oral contrast study should be used selectively with endoscopy and/or computerized tomography scan to assess surgical anastomoses following esophagectomy.
Brazilian-adapted soybean Bradyrhizobium strains uncover IS elements with potential impact on biological nitrogen fixation
Authors: Barros-Carvalho Gesiele Almeida , Hungria Mariangela , Lopes Fabrício Martins , Van Sluys Marie-Anne 
Published: March 2019

ABSTRACTBradyrhizobium diazoefficiens CPAC 7 and Bradyrhizobium japonicum CPAC 15 are broadly used in commercial inoculants in Brazil, contributing to most of the nitrogen required by the soybean crop. These strains differ in their symbiotic properties: CPAC 7 is more efficient in fixing nitrogen, whereas CPAC 15 is more competitive. Comparative genomics revealed many transposases close to genes associated with symbiosis in the symbiotic island of these strains. Given the importance that insertion sequences (IS) elements have to bacterial genomes, we focused on identifying the local impact of these elements in the genomes of these and other related Bradyrhizobium strains to further understand their phenotypic differences. Analyses were performed using bioinformatics approaches. We found IS elements disrupting and inserted at regulatory regions of genes involved in symbiosis. Further comparative analyses with 21 Bradyrhizobium genomes revealed insertional polymorphism with distinguishing patterns between B. diazoefficiens and B. japonicum lineages. Finally, 13 of these potentially impacted genes are differentially expressed under symbiotic conditions in B. diazoefficiens USDA 110. Thus, IS elements are associated with the diversity of Bradyrhizobium, possibly by providing mechanisms for natural variation of symbiotic effectiveness.
Population bottlenecks have shaped the genetic variation of Ailanthus altissima (Mill.) Swingle in an area of early introduction
Authors: Neophytou Charalambos , Pötzelsberger Elisabeth , Curto Manuel , Meimberg Harald , Hasenauer Hubert 
Published: March 2019

AbstractAilanthus altissima is a common tree species of the European non-native flora. In Eastern Austria, Ailanthus has both a long tradition, dating back to the late 18th century, and a high frequency of occurrence. Here, we apply molecular markers from the nuclear and chloroplast DNA in order to study the origin, as well as the clonal and genetic structure of the species in forest stands of this region. Our results indicate a single area of origin for all our study populations from the north-eastern part of the native range, in agreement with historical reports. Within populations, vegetative reproduction has resulted in extensive clonal structures at some sites. Long presence and repeated vegetative recruitment might have led to expansion of clones in areas of early introduction. In addition, limited mate availability may also have promoted vegetative reproduction. Tests for recent bottlenecks were significant in almost all stands, possibly reflecting founder effects since the introduction of Ailanthus in our study area. Among populations, we found a very pronounced and significant genetic structure, which did not follow a spatial pattern. We argue that founder effects due to population establishment with a low number of propagules – whether naturally or artificially – have caused genetic drift and a structured gene pool. The lack of spatial pattern or isolation-by-distance suggests that seed transfer by humans might have been a major factor shaping the genetic variation of Ailanthus in Eastern Austria.
End-of-Life Healthcare Utilization of Older Mexican Americans With and Without a Diagnosis of Alzheimer’s Disease and Related Dementias
Authors: Nguyen Christine , Downer Brian , Chou Lin-Na , Kuo Yong-Fang , Raji Mukaila 
Published: March 2019

Abstract

Background
Little is known about the patterns of end-of-life health care for older Mexican Americans with or without a diagnosis of Alzheimer’s disease and related dementias (ADRD). Our objective was to investigate the frequency of acute hospital admissions, intensive care unit use, and ventilator use during the last 30 days of life for deceased older Mexican American Medicare beneficiaries with and without an ADRD diagnosis.

Methods
We used Medicare claims data linked with survey information from 1,090 participants (mean age of death 85.1 years) of the Hispanic Established Populations for the Epidemiologic Studies of the Elderly. Multivariable logistic regression models were used to estimate the odds for hospitalization, intensive care unit use, and ventilator use in the last 30 days of life for decedents with ADRD than those without ADRD. Generalized linear models were used to estimate the risk ratio (RR) for length of stay in hospital.

Results
Within the last 30 days of life, 64.5% decedents had an acute hospitalization (59.1% ADRD, 68.3% no ADRD), 33.9% had an intensive care unit stay (31.3% ADRD, 35.8% no ADRD), and 17.2% used a ventilator (14.9% ADRD, 18.8% no ADRD). ADRD was associated with significantly lower hospitalizations (odds ratio [OR] = 0.67, 95% confidence interval [CI] = 0.50–0.89) and shorter length of stay in hospital (RR = 0.77, 95% CI = 0.65–0.90).

Conclusion
Hospitalization, intensive care unit stay, and ventilator use are common at the end of life for older Mexican Americans. The lower hospitalization and shorter length of stay in hospital of decedents with ADRD indicate a modest reduction in acute care use. Future research should investigate the impact of end-of-life planning on acute-care use and quality of life in terminally ill Mexican American older adults.