bluuebunny/crossref_metadata_2025 huggingface dataset:
Structural insights of resveratrol with its binding partners in the toll‐like receptor 4 pathway
Authors: Saqib Uzma , Faisal Syed M. , Saluja Rohit , Baig Mirza S.
Published: September 2018

The benefits associated with resveratrol (Resv; 3,4′,5‐trihydroxy‐trans‐stilbene) are known for a long time. The therapeutic properties of Resv are observed in diseases like cancer, neurological disorders, atherosclerosis, aging, inflammation, etc. Multiple studies suggest that the beneficial properties of Resv are due to its binding to targets in multiple pathways. The same has been reflected in inflammation, where Resv has been shown to inhibit nuclear factor κ light‐chain enhancer of activated B cells in the toll‐like receptor 4 (TLR4) pathway. There are multiple cellular targets which bind to Resv, however the mode and the key interactions involved remain elusive for many of them. In the current work, we have investigated the structural insights of Resv with three of its binding partners involved in the inflammatory TLR4 signaling pathway. Through a structure‐based modelling and molecular dynamics study, we have unraveled the molecular and atomic interactions involved in the Resv‐binary complexes of inhibitor of κB kinase, cyclooxygeanse‐2, and tank‐binding kinase I, all three of which are key players in TLR4 inflammatory signaling. This study is the latest addition to the investigations of the structural partners of Resv and its molecular interactions.
Novel mechanisms of regulation of the expression and transcriptional activity of hepatocyte nuclear factor 4α
Authors: Guo Shangdong , Lu Hong
Published: September 2018

Hepatocyte nuclear factor 4α (HNF4α) is a master regulator of development and function of digestive tissues. The HNF4A gene uses two separate promoters P1 and P2, with P1 products predominant in adult liver, whereas P2 products prevalent in fetal liver, pancreas, and liver/colon cancer. To date, the mechanisms for the regulation of
HNF4A and the dynamic switch of P1‐HNF4α and P2‐HNF4α during ontogenesis and carcinogenesis are still obscure. Our study validated the previously reported self‐stimulation of P1‐HNF4α but invalidated the reported synergism between HNF4α and HNF1α.
HNF4A‐AS1, a long noncoding RNA, is localized between the P2 and P1 promoters of
HNF4A. We identified critical roles of P1‐HNF4α in regulating the expression of
HNF4A‐AS1 and its mouse ortholog
Hnf4a‐os. Paired box 6 (PAX6), a master regulator of pancreas development overexpressed in colon cancer, cooperated with HNF1α to induce P2‐HNF4α but antagonized HNF4α in
HNF4A‐AS1 expression. Thus, PAX6 may be important in determining ontogenic and carcinogenic changes of P2‐HNF4α and
HNF4A‐AS1 in the pancreas and intestine. We also interrogated transactivation activities on multiple gene targets by multiple known and novel HNF4α mutants identified in patients with maturity onset diabetes of the young 1 (MODY1) and liver cancer. Particularly, HNF4α‐D78A and HNF4α‐G79S, two mutants found in liver cancer with mutations in DNA‐binding domain, displayed highly gene‐specific transactivation activities. Interestingly, HNF4α‐Q277X, a MODY1 truncation mutant, antagonized the transactivation activities of HNF1α and farnesoid X receptor, key regulators of insulin secretion. Taken together, our study provides novel mechanistic insights regarding the transcriptional regulation and transactivation activity of HNF4α in digestive tissues.
Tributyltin oxide exposure impairs mouse oocyte maturation and its possible mechanisms
Authors: Yang Lei‐Lei , Cui Ying‐Xue , Ma Jun‐Yu , Ge Zhao‐Jia , Shen Wei , Yin Shen
Published: September 2018

Tributyltin oxide (TBTO) has been widely used as marine antifouling composition, preservative, biocide, and a stabilizer in plastic industry. Previous studies have indicated that TBTO can cause immunotoxicity as an environmental pollutant. However, little is known about its reproductive toxicity, especially on female oocyte maturation and the underlying mechanisms. In this study, mouse oocytes were cultured with different concentrations of TBTO in vitro, and several crucial events during meiotic maturation were evaluated. We found that the first polar body extrusion rate was significantly reduced, which reflected the disruption of meiotic maturation. The rate of abnormal spindle organization increased significantly, accompanied with a higher rate of chromosome misalignment. In addition, TBTO treatment increased reactive oxygen species generation markedly, which also accelerated the early‐stage apoptosis. Moreover, heterogeneous mitochondrial distribution, mitochondrial dysfunction, and higher rate of aneuploidy were detected, which consequently disrupted in vitro fertilization. In conclusion, our results indicated that TBTO exposure could impair mouse oocyte maturation by affecting spindle organization, chromosome alignment, mitochondria functions, oxidative stress, and apoptosis.
MAPK/ERK pathway inhibition is a promising treatment target for adrenocortical tumors
Authors: Pereira Sofia S , Monteiro Mariana P , Costa Madalena M , Ferreira Jorge , Alves Marco G , Oliveira Pedro F , Jarak Ivana , Pignatelli Duarte
Published: September 2018

Unraveling molecular mechanisms that regulate tumor development and proliferation is of the utmost importance in the quest to decrease the high mortality rate of adrenocortical carcinomas (ACC). Our aim was to evaluate the role of two of the mitogen‐activated protein kinase (MAPK) signaling pathways (extracellular signal‐regulated protein kinases [ERKs 1/2] and p38) in the adrenocortical tumorigenesis, as well as the therapeutic potential of MAPK/ERK inhibition. ERKs 1/2 and p38 activation were evaluated in incidentalomas (INC; n = 10), benign Cushing's syndrome (BCS; n = 12), malignant Cushing's syndrome (MCS; n = 6) and normal adrenal glands (NAG; 8). ACC cell line (H295R) was used to evaluate the ability of PD184352 (0.1, 1, and 10 µM), a specific MEK‐MAPK‐ERK pathway inhibitor, to modulate cell proliferation, viability, metabolism, and steroidogenesis. ERKs 1/2 activation was significantly higher in MCS (2.83 ± 0.17) compared with NAG (1.00 ± 0.19 “arbitrary units”), INC (1.20 ± 0.13) and BCS (2.09 ± 0.09). Phospho‐p38 expression was absent in all the MCS analyzed. MAPK/ERK kinase (MEK) inhibition with PD184352 significantly decreased proliferation as well as steroidogenesis and also increased the redox state of the H295R cells. This data suggests that MEK‐MAPK‐ERK signaling has a role in adrenocortical tumorigenesis that could be potentially used as a diagnostic marker for malignancy and targeted treatment in ACC.
Negative regulation of the RLR‐mediated IFN signaling pathway by duck ubiquitin‐specific protease 18 (USP18)
Authors: Gu Tiantian , Lu Lu , An Chen , Zhang Yu , Wu Xinsheng , Xu Qi , Chen Guohong
Published: September 2018

Ubiquitin‐specific protease 18 (USP18) plays an important role in regulating type I interferon (IFN) signaling in innate immunity, and has a crucial impact on the IFN therapeutic effect. Although significant progress has been made in elucidating USP18 function in mammals, the role of USP18 in ducks (duUSP18) remains poorly understood. In this study, we cloned the USP18 gene from white crested ducks by reverse transcription polymerase chain reaction (RT‐PCR) and rapid amplification of complementary DNA (cDNA) ends. We determined that duUSP18 cDNA contains a 52‐bp 5′UTR, a 1,131‐bp open reading frame and a 356‐bp 3′UTR, and encodes a 376‐amino acid protein. Multiple sequence alignments showed that duUSP18 shares high similarity with USP18 from other vertebrates. Overexpression of duUSP18 inhibited nuclear factor‐κB (NF‐κB) and interferon regulatory factor 1 (IRF1) activity, and reduced IFN‐β production following 5′ triphosphate double‐stranded RNA (5′ppp dsRNA) or lipopolysaccharide (LPS) stimulation. duUSP18 knockdown significantly activated 5′ppp dsRNA‐induced and LPS‐induced NF‐κB and IRF1 activation, and induced IFN‐β expression in duck embryo fibroblasts. Furthermore, Quantitative real‐time PCR (qRT‐PCR) revealed that overexpression or knockdown of duUSP18 could alter the expression of genes related to the RLR‐mediated IFN signaling pathway following the treatment with 5′ppp dsRNA. In addition, site‐directed mutation analysis revealed that cysteine 66 (C66), histidine 313 (H313), and histidine 321 (H321) of duUSP18 were critical for inhibiting IFN‐β activity. Taken together, these results suggest that duck USP18 plays an important role in innate immune responses against double‐stranded RNA viruses in the RLR‐mediated IFN signaling pathway, and that further studies are warranted to elucidate its underlying mechanisms, which could provide molecular insights into the effect of the treatment of duck diseases.
Streptozotocin‐induced type II diabetic rat administered with nonobesogenic high‐fat diet is highly susceptible to myocardial ischemia–reperfusion injury: An insight into the function of mitochondria
Authors: Ansari Mahalakshmi , Gopalakrishnan Senthilkumar , Kurian Gino A.
Published: September 2018

Rationale

Our recent study suggested that ischemia–reperfusion (I/R) induced oxidative stress was minimal in the rat heart during initial stage of diabetes and the one that progressed to diabetic cardiomyopathy (DCM), despite having higher infarct and low cardiac performance. Mitochondrial dysfunction is an important mediator for adverse outcome in rat heart affected with diabetes, which is also a potential contributor for the cardiac reperfusion injury.

Objective

The current study aims to evaluate the susceptibility of diabetes heart with or without myopathy to I/R injury and its influence on cardiac mitochondrial function.

Methods and Results

Male Wistar rats (3 weeks old) were fed with high‐fat diet for 8 weeks followed by diabetes mellitus (DM) induction via streptozotocin (35 mg/kg body weight) and maintained for further 4 weeks. The animal displayed cardiomyopathy characteristics like hypertrophy, fibrosis, and insulin resistance‐termed diabetic cardiomyopathy (DCM). To study the specific effect of DCM on I/R, we included diabetic rats without cardiomyopathy. Induction of I/R in different groups suggested higher vulnerability to injury in DCM rat hearts than DM and normal (measured via hemodynamics, triphenyltetrazolium chloride stain, and apoptotic markers). Mitochondrial function at the subpopulation level was evaluated with respect to adenosine triphosphate (ATP) concentration, membrane potential, swelling behavior, and oxidative stress, wherein the results confirmed I/R‐induced mitochondrial dysfunction. Unlike normal heart, DM, and DCM heart challenged to I/R exhibited altered ATP producing capacity among subsarcolemmal and interfibrillar mitochondria.

Conclusion

The above results suggest that mitochondrial changes associated with diabetes and cardiomyopathy significantly contribute to the adverse outcome of I/R injury.
Matrix metalloproteinase‐13 is a target gene of high‐mobility group box‐containing protein 1 in modulating oral cancer cell invasion
Authors: Chan Chien‐Yi , Lin Tzu‐Yuan , Sheu Jim Jinn‐Chyuan , Wu Wen‐Chieh , Huang Chun‐Yin
Published: September 2018

Transcription factor high‐mobility group box‐containing protein 1 (HBP1) may function as a tumor suppressor in various types of cancer. In a previous study, we demonstrated that HBP1 suppressed cell invasion in oral cancer. To further understand the underlying mechanism, the current study is aimed at investigating how HBP1 exerts its antimetastatic potential in oral cancer. In a cell model, ectopic expression of HBP1 potently suppressed epithelial–mesenchymal transition, cellular migration, and invasion; conversely, HBP1 knockdown promoted these malignant phenotypes. The matrix metalloproteinase (MMP) family is highly implicated in tumor metastasis. Therefore, we examined the effect of HBP1 on the activation of the MMP members, MMP‐2, ‐9, and ‐13 that are highly associated with the aggressiveness of oral cancer. Ectopic expression of HBP1 resulted in a mild reduction in the expression and activity of MMP‐2 and ‐9, yet it had a potent inhibitory effect on MMP‐13. In contrast, HBP1 knockdown strongly enhanced the activation of MMP‐13. Further, we demonstrated that MMP‐13 is a target of HBP1 transcription repression as evidenced by the identification of an HBP1 binding site in the cis proximal region of the MMP‐13 promoter. More important, MMP‐13 knockdown significantly alleviated HBP1 small interfering RNA‐mediated promotion in cell invasion. Analysis of oral tumor specimens revealed that the low HBP1 (<0.3‐fold)/high MMP‐13 (>3‐fold) status was associated with metastatic potential. All told, our study provides evidence supporting the idea that the HBP1–MMP‐13 axis is a key regulator of the aggressiveness in oral cancer.
Upregulation of long noncoding RNA MEG3 inhibits the osteogenic differentiation of periodontal ligament cells
Authors: Liu Yi , Zeng Xuemin , Miao Jie , Liu Chunpeng , Wei Fulan , Liu Dongxu , Zheng Zhong , Ting Kang , Wang Chunling , Guo Jie
Published: September 2018

Objective

This study aims to discuss long noncoding RNA (lncRNA) maternally expressed gene 3 (MEG3) function of regulating osteogenesis in human periodontal ligament cells (hPDLCs).

Methods

First, use of a mineralizing solution induced osteogenic differentiation of hPDLCs to establish a differentiated cell model. Through microarray analysis, we selected a lncRNA MEG3 with marked changes between differentiated and undifferentiated cells. The quantitative polymerase chain reaction was used to detect the
MEG3 content and an enzyme‐linked immunosorbent assay was used to detect changes in related proteins. Cell viability was determined by the 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide assay and apoptosis was measured by flow cytometry. Alizarin red staining was also used to evaluate cells’ osteogenic level. Finally, RNA‐binding protein immunoprecipitation assays were conducted to further clarify the endogenous relationship between
MEG3 and bone morphogenetic protein 2 (
BMP2) in hPDLCs.

Results

MEG3 was downregulated in osteogenic differentiation hPDLCs induced by mineralizing solution. Overexpression of
MEG3 inhibited cell viability and increased cell apoptosis.
MEG3 overexpression can reverse osteogenic differentiation induced by mineralizing solution.
MEG3 can suppress
BMP2 through interaction with heterogeneous nuclear ribonucleoprotein I.

Conclusion

Upregulation of MEG3 inhibits the osteogenic differentiation of periodontal ligament cells by downregulating
BMP2 expression.
Structural basis of urea‐induced unfolding of Fasciola gigantica glutathione S‐transferase
Authors: Kalita Jupitara , Shukla Rohit , Tripathi Timir
Published: September 2018

Glutathione S‐transferases (GSTs) are enzymes that are involved in the detoxification of harmful electrophilic endogenous and exogenous compounds by conjugating with glutathione (GSH). The liver fluke GSTs have multifunctional roles in the host–parasite interaction, such as general detoxification and bile acid sequestration to synthase activity. The GSTs have been highlighted as vaccine candidates towards parasitic flukes. In this study, we have thoroughly examined the urea‐induced unfolding of a mu‐class Fasciola gigantica GST1
(FgGST1) using spectroscopic techniques and molecular dynamic simulations. FgGST1 is a highly cooperative molecule, because during urea‐induced equilibrium unfolding, a concurrent unfolding of the protein without stabilization of any folded intermediate was observed. The protein was stabilized with conformational free energy of about ~12.36 kcal/mol. The protein loses its activity with increasing urea concentration, as the GSH molecule is not able to bind to the protein. We also studied the fluorescence quenching of Trp residues and the obtained
K
SV data that provided additional information on the unfolding of FgGST1. Molecular dynamic trajectories simulated in different urea concentrations and temperatures indicated that urea destabilizes FgGST1 structure by weakening hydrophobic interactions and the hydrogen bond network. We observed a precise correlation between the in vitro and in silico studies.
Circulating miR‐22‐5p and miR‐122‐5p are promising novel biomarkers for diagnosis of acute myocardial infarction
Authors: Wang Yu , Chang Wenguang , Zhang Yuan , Zhang Lei , Ding Han , Qi Hongzhao , Xue Sheng , Yu Hua , Hu Longgang , Liu Dacheng , Zhu Wenjie , Wang Yin , Li Peifeng
Published: September 2018

Background/Aims

This study sought to evaluate the potential of circulating microRNAs (miRNAs) as novel indicators for acute myocardial infarction (AMI).

Methods

Plasma samples were collected from each participant, and total RNA was extracted. Quantitative real‐time polymerase chain reaction were used to investigate the expression of circulating miRNAs. We measured circulating levels of six individual miRNAs, which are known to be relevant to AMI, in the plasma samples from 66 AMI patients and 70 non‐AMI healthy comparisons.

Results

Five small RNAs were specifically expressed in AMI patients, plasma miR‐122‐5p levels is significantly elevated (p < 0.0001) in AMI patients, while plasma miR‐22‐5p (
p < 0.05) levels were significantly decreased. In addition, significant correlations between miR‐22‐5p and miR‐122‐5p (
R = 0.773), miR‐122‐5p and creatine kinase isoenzyme (CK‐MB;
R = 0.6296) were detected. Further, receiver operating characteristic (ROC) analysis indicated that miR‐22‐5p showed considerable diagnostic efficiency for predicting AMI (area under the curve [AUC] = 0.975). Combining miR‐22‐5p and miR‐122‐5p in a panel increased the sensitivity (98.6%) of distinguishing between patients with AMI and healthy comparisons.

Conclusion

Circulating miR‐22‐5p and miR‐122‐5p could be considered promising novel diagnostic biomarkers for AMI.
No Clinical Impact of CYP3A5 Gene Polymorphisms on the Pharmacokinetics and/or Efficacy of Maraviroc in Healthy Volunteers and HIV‐1–Infected Subjects
Authors: Vourvahis Manoli , McFadyen Lynn , Nepal Sunil , Valluri Srinivas Rao , Fang Annie , Fate Gwendolyn D. , Wood Linda S. , Marshall Jean‐Claude , Chan Phylinda L. S. , Nedderman Angus , Haynes Julian , Savage Mark E. , Clark Andrew , Smith Kimberly Y. , Heera Jayvant
Published: September 2018

Maraviroc is a C‐C chemokine receptor type‐5 antagonist approved for the treatment of HIV‐1. Previous studies show that cytochrome P450 3A5 (CYP3A5) plays a role in maraviroc metabolism. CYP3A5 is subject to a genetic polymorphism. The presence of 2 functional alleles (CYP3A5*1/*1) confers the extensive metabolism phenotype, which is rare in whites but common in blacks. The effect of CYP3A5 genotype on maraviroc and/or metabolite pharmacokinetics was evaluated in 2 clinical studies: a post hoc analysis from a phase 2b/3 study (NCT00098293) conducted in 494 HIV‐1–infected subjects (study 1) in which the impact on maraviroc efficacy in 303 subjects was also assessed, and a study conducted in 47 healthy volunteers (study 2). In study 2 (NCT02625207), extensive metabolizers had 26% to 37% lower mean area under the concentration‐time curve compared with poor metabolizers (no CYP3A5*1 alleles). This effect diminished to 17% in the presence of potent CYP3A inhibition. The effect of CYP3A5 genotype was greatest in the formation of the metabolite (1S,2S)‐2‐hydroxymaraviroc. In study 1, the CYP3A5*1/*1 genotype unexpectedly had higher maraviroc area under the curve predictions (20%) compared with those with no CYP3A5*1 alleles. The reason for this disparity remains unclear. The proportions of subjects with viral loads <50 and <400 copies/mL for maraviroc were comparable among all 3 CYP3A5 genotypes. In both studies maraviroc exposures were in the range of near‐maximal viral inhibition in the majority of subjects. These results demonstrate that although CYP3A5 contributes to the metabolism of maraviroc, CYP3A5 genotype does not affect the clinical response to maraviroc in combination treatment of HIV‐1 infection at approved doses.
Environmentally induced phenotypic plasticity explains hatching synchrony in the freshwater turtleChrysemys picta
Authors: McGlashan Jessica K. , Thompson Michael B. , Janzen Fredric J. , Spencer Ricky‐John
Published: September 2018

Environmentally cued hatching allows embryos to alter the time of hatching in relation to environment through phenotypic plasticity. Spatially variable temperatures within shallow nests of many freshwater turtles cause asynchronous development of embryos within clutches, yet neonates still hatch synchronously either by hatching early or via metabolic compensation. Metabolic compensation and changes in circadian rhythms presumably enable embryos to adjust their developmental rates to catch up to more advanced embryos within the nest. Hatchlings of the North American freshwater turtleChrysemys pictausually overwinter within the nest and emerge the following spring, but still hatch synchronously via hatching early. Here, we used rates of oxygen consumption and heart rate profiles to investigate the metabolic rates of clutches ofC. pictadeveloping in conditions that result in asynchronous development to determine if compensatory changes in metabolism occur during incubation. Embryos hatched synchronously and displayed circadian rhythms throughout incubation, but exhibited no evidence of metabolic compensation. Phenotypic traits of hatchlings, including body size and righting performance, were also not affected by asynchronous development. We conclude that less developed embryos ofC. pictahatch synchronously with their clutch‐mates by hatching early, which does not appear to inflict a fitness cost to individuals. The ultimate mechanism for synchronous hatching inC. pictacould be for hatchlings to ensure an optimal overwintering position within the center of the nest. Consequently, immediate fitness costs will not hinder hatchling survival. The geographic location, as well as environmental and genetic factors unique to populations, can all influence hatching behavior in turtles through phenotypic plasticity. Hence, synchronous hatching is an adaptive bet‐hedging strategy in turtles, but the mechanisms to achieve it are diverse.
IL-20 receptor cytokines in autoimmune diseases
Authors: Chen Jun , Caspi Rachel R , Chong Wai Po
Published: September 2018

IL-19, IL-20, and IL-24 are the members of IL-10 family. They are also known as IL-20 receptor (IL-20R) cytokines as they all signal through the IL-20RA/IL-20RB receptor complex; IL-20 and IL-24 (but not IL-19) also signal through the IL-20RB/IL22RA1 receptor complex. Despite their protein structure homology and shared use of receptor complexes, they display distinct biological functions in immune regulation, tissue homeostasis, host defense, and oncogenesis. IL-20R cytokines can be expressed by both immune cells and epithelial cells, and are important for their interaction. In general, these cytokines are considered to be associated with pathogenesis of chronic inflammation and autoimmune diseases, including psoriasis, rheumatoid arthritis, and inflammatory bowel disease. However, a number of studies also highlighted their suppressive functions in regulating both innate and adaptive T cell responses and other immune cells, suggesting that the role of IL-20R cytokines in autoimmunity may be complex. In this review, we will discuss the immunobiological functions of IL-20R cytokines and how they are involved in regulating autoimmune diseases.

This review outlines the current view of the biological effects of IL-20 receptor cytokines and the roles of these cytokines in autoimmune diseases.
Functional anatomy of the male reproductive system of the American lobster (Homarus americanus)
Authors: Comeau Michel , Benhalima Kadra
Published: September 2018

Despite supporting a valuable fishery, the reproductive system of the male American lobster (Homarus americanus) is poorly understood. The elongated H‐shaped testis is responsible for spermatogenesis and is composed of follicles, a common collecting duct with interlaced scattered striated muscles, and a serosa as an external wall. Sertoli cells are associated with the spermatogenesis that produces spermatozoa, which are transferred to the collecting duct through a temporary passageway. Spermatogenesis is asynchronous between follicles and occurs on a continuous basis. The anterior and posterior lobes of the testes are independent and connect to the vasa deferentia through the Y‐shaped collecting tubules that have a different cell anatomy and function than the two organs they connect. The vas deferens is divided into four regions. Spermatophores, produced in the proximal vas deferens, are packets of spermatozoa encapsulated in a single layer—the spermatophoric wall, which is composed of mucopolysaccharide acid. Large dense ovoid granules and the seminal fluid, composed of acidic sulfated mucosubstances, are secreted in the median vas deferens. Spermatophores within these secreted substances (i.e., semen) are stored in the distal vas deferens that, with the spermiduct (last region of the vas deferens), is responsible for the extrusion of the semen by striated muscle contractions. Smooth muscles suggest a peristaltic movement of the spermatophores within the vas deferens. Finally, the gonopores and the first pair of pleopods (i.e., gonopod) move the semen to the female seminal receptacle during copulation.
Respiratory viral infections in infants with possible sepsis
Authors: Aykac Kubra , Karadag‐Oncel Eda , Tanır Basaranoglu Sevgen , Alp Alpaslan , Cengiz Ali Bulent , Ceyhan Mehmet , Kara Ates
Published: September 2018

Background

Knowledge of infections leading to sepsis is needed to develop comprehensive infection prevention and sepsis, as well as early recognition and treatment strategies.The aim of this study was to investigate the etiology of sepsis and evaluate the proportion of respiratory viral pathogens in infants under two years of age with possible sepsis.

Methods

The prospective study was performed in two years. Multiplex reverse transcriptase polymerase chain reaction (RT‐PCR) was performed to detect viral pathogens. All patients who were included in this study had sepsis symptoms as defined by the Surviving Sepsis Campaign.

Results

We compared 90 patients with sepsis into three groups as patients (n = 33) who had only viral positivity in nasopharyngeal swab, patients (17) had proven bacterial infection with or without viral infection, and patients (40) without the pathogen detection. Human rhinovirus (16.7%) and influenza (7.8%) were the most commonly seen viruses. A cough was more common in the viral infection group than other groups (
P = 0.02) and median thrombocyte count was lower in the bacterial infection group than the others (
P = 0.01). Patients having bacterial sepsis had the longest duration of hospitalization than the other groups (
P = 0.04). During winter and spring seaons, patients with sepsis had more viral infection; however, in summer and autumn period, patients were mostly in a state that we could not prove infection agents (
P = 0.02).

Conclusions

Our results suggest that respiratory tract viruses may play an important role in patients with sepsis and they should be kept in mind, especially during winter and spring seasons. In overall infection, viral respiratory viruses as a single pathogen with a detection rate of 36.6% in sepsis etiology.
Characteristics of extreme precipitation over eastern Asia and its possible connections with Asian summer monsoon activity
Authors: Cui Danyang , Wang Chenghai , Santisirisomboon Jerasorn
Published: September 2018

Frequently occurring extreme precipitation events have caused severe disasters over the years, especially in monsoon regions such as Southeast Asia and East China (SAEC). Understanding the characteristics of extreme precipitation in SAEC on annual and monthly scales is essential for improving predictions extreme precipitation events. In this study, the temporal and spatial distribution characteristics of extreme precipitation events in the summer half‐year (May to September) are analysed from 1986 to 2015 over SAEC, based on the threshold of extreme precipitation defined with a percentile method and the daily precipitation data from 190 meteorological stations. The results indicate that the precipitation in annual and summer half‐year over the SAEC are mainly attributed to extreme precipitation events. The frequency and amount of extreme precipitation are significant in South China and Southeast Asia, the Yangtze River region, and North China; specifically, the duration of high extreme precipitation events are longer in South China and Southeast Asia compared to those in other areas. The frequency and amount of extreme precipitation increased in South China, Southeast Asia and North China while have a decreasing trend in Yangtze River basin. Further investigation of the possible relationship between summer extreme precipitation events and the activity of the Asian summer monsoon (ASM) indicate that, the movements of extreme precipitation are consistent with the northward advance and southward withdrawal of summer monsoon and are commonly located in the vicinity of the front of the ASM. This phenomenon suggests that summer extreme precipitation events over SAEC are closely connected with ASM activity and may be the products of ASM.
The longest one‐man weather chronicle (1721–1786) by Gottfried Reyger for Gdańsk, Poland as a source for improved understanding of past climate variability
Authors: Filipiak Janusz , Przybylak Rajmund , Oliński Piotr
Published: September 2018

In the paper we focus on the notes of botanist and meteorologist Gottfried Reyger on the weather conditions in Gdańsk, Poland. In our estimation, this chronicle, covering the period from December 1721 to June 1786 (the longest weather chronicle recorded by a single person), is a reliable source of information with the potential to contribute to the understanding of climate variability in 18th‐century Gdańsk, the significant old Hanseatic city in northern Poland. The temperature and precipitation series for the period 1721–1786 were indexed against contemporary conditions using the calculated percentages of cold, normal and warm decades. The climate in the 18th century in Gdańsk was colder than nowadays; the springs were much cooler, as were the winters, while the summers were warmer. A few relatively cold periods and several warm periods were identified. The first half of the analysed period was very humid, whereas the second was quite dry. The reconstructed indexed data series were compared to annual and seasonal mean values of air temperature and precipitation derived from regular instrumental observations made in Gdańsk since 1739. The linear regression method was applied to calibrate the reconstructed index series against anomalies from the 1961–1990 average. The correlation coefficient, standard error of estimate and the root‐mean‐square error statistics were used to diagnose the quality of calibration and verification. The highest correlation between the temperature indices and the observational series was found for winter. The reconstructed series for precipitation has a smaller variability than in reality. The reconstructed values for the years prior to 1739 indicate cold years for 1725–1732 and a wet period in the 1730s.
Rapid, simultaneous, and in situ authentication and quality assessment of intact bell peppers using near‐infrared spectroscopy technology
Authors: Sánchez María‐Teresa , Torres Irina , de la Haba María‐José , Chamorro Ana , Garrido‐Varo Ana , Pérez‐Marín Dolores
Published: September 2018

BACKGROUND

The ability of near‐infrared (NIR) spectroscopy to authenticate individual bell peppers as a function of the growing system (outdoor or greenhouse) was tested using partial least squares discriminant analysis. Bell peppers grown outdoors (130 samples) or in a greenhouse (264 samples) during the 2015 and 2016 seasons were selected for this purpose and analysed using a portable, handheld, microelectromechanical system (MEMS) instrument MicroPhazir (spectral range 1600–2400 nm), working in reflectance. Subsequently, the potential of NIR spectroscopy as a non‐destructive sensor for in situ quality (dry matter and soluble solid content) measurements, was investigated.

RESULTS

The models correctly classified 89.73% and 88.00% of the samples by growing system, when trained with unbalanced and balanced sets respectively, mainly due to the differences in physical–chemical attributes between bell peppers cultivated in the two growing systems. Separate classification models for bell peppers grouped by ripeness (judged by the colour), allowed the classification of 88.28–91.37% of the samples correctly. The standard error of cross‐validation values for the quantitative models were 0.66% fresh weight and 0.75 °Brix for dry matter and soluble solid content, respectively.

CONCLUSIONS

The results showed that NIR spectroscopy can be used successfully for predicting the growing systems used in bell pepper production, which is of particular value to guarantee the authentication of outdoor‐grown peppers. Additionally, the results showed that NIR spectroscopy can be used simultaneously as a rapid preliminary screening technique to measure quality. © 2018 Society of Chemical Industry
Carotenoids retention in biofortified yellow cassava processed with traditional African methods
Authors: Taleon Victor , Sumbu Dan , Muzhingi Tawanda , Bidiaka Sylvain
Published: September 2018

BACKGROUND

Biofortified yellow cassava is being cultivated in countries with high cassava consumption to improve its population's vitamin A status. The carotenoid retention in biofortified cassava when processed as boiled, fufu, and chikwangue was evaluated in this study. Commercial biofortified varieties Kindisa and Vuvu and the experimental genotypes MVZ2011B/360 and MVZ2012/044 were used. Fresh cassava roots were processed as boiled, fufu, and chikwangue. Provitamin A carotenoids (pVACs) content of fresh and processed cassava was measured by high‐performance liquid chromatography, and total carotenoids was measured by spectrophotometer.

RESULTS

pVACs content of fresh peeled cassava was 1.79–6.65 µg g−1 on a fresh weight basis, whereas in boiled cassava, fufu, and chikwangue the pVACs content was 1.71–6.91 µg g−1, 0.04–0.37 µg g−1, and 0.52–1.75 µg g−1 respectively. True retention of carotenoids after cooking was 93.2–96.8%, 0.8–3.1%, and 4.0–18.1% for boiled cassava, fufu, and chikwangue respectively. Significant total carotenoids loss was observed during storage.

CONCLUSION

The results indicated that biofortified boiled cassava could be an effective food product to improve pVACs intake in areas where vitamin A deficiency exists, and processing of chikwangue and fufu should be improved before promoting biofortified cassava in vitamin‐A‐deficient areas with high cassava consumption. © 2018 The Authors. Journal of the Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.
Aortic Versus Dual Perfusion for Retrieval of the Liver After Brain Death: A National Registry Analysis
Authors: Hameed Ahmer M. , Pang Tony , Yoon Peter , Balderson Glenda , De Roo Ronald , Yuen Lawrence , Lam Vincent , Laurence Jerome , Crawford Michael , D. M. Allen Richard , Hawthorne Wayne J. , Pleass Henry C.
Published: September 2018

There is lack of consensus in the literature regarding the comparative efficacy of in situ aortic‐only compared with dual (aortic and portal venous) perfusion for retrieval and transplantation of the liver. Recipient outcomes from the Australia/New Zealand Liver Transplant Registry (2007‐2016), including patient and graft survival and causes of graft loss, were stratified by perfusion route. Subgroup analyses were conducted for higher‐risk donors. A total of 1382 liver transplantation recipients were analyzed (957 aortic‐only; 425 dual perfusion). There were no significant differences in 5‐year graft and patient survivals between the aortic‐only and dual cohorts (80.1% versus 84.6% and 82.6% versus 87.8%, respectively) or in the odds ratios of primary nonfunction, thrombotic graft loss, or graft loss secondary to biliary complications or acute rejection. When analyzing only higher‐risk donors (n = 369), multivariate graft survival was significantly less in the aortic‐only cohort (hazard ratio, 0.49; 95% confidence interval, 0.26‐0.92). Overall, there was a trend toward improved outcomes when dual perfusion was used, which became significant when considering higher‐risk donors alone. Inferences into the ideal perfusion technique in multiorgan procurement will require further investigation by way of a randomized controlled trial, and outcomes after the transplantation of other organs will also need to be considered.
Chemical space of Escherichia coli dihydrofolate reductase inhibitors: New approaches for discovering novel drugs for old bugs
Authors: Srinivasan* Bharath , Tonddast‐Navaei Sam , Roy Ambrish , Zhou Hongyi , Skolnick Jeffrey
Published: September 2018

Escherichia coli Dihydrofolate reductase is an important enzyme that is essential for the survival of the Gram‐negative microorganism. Inhibitors designed against this enzyme have demonstrated application as antibiotics. However, either because of poor bioavailability of the small‐molecules resulting from their inability to cross the double membrane in Gram‐negative bacteria or because the microorganism develops resistance to the antibiotics by mutating the DHFR target, discovery of new antibiotics against the enzyme is mandatory to overcome drug‐resistance. This review summarizes the field of DHFR inhibition with special focus on recent efforts to effectively interface computational and experimental efforts to discover novel classes of inhibitors that target allosteric and active‐sites in drug‐resistant variants of EcDHFR.
Stabilization of an axially moving viscoelastic string under a spatiotemporally varying tension
Authors: Kelleche Abdelkarim , Saedpanah Fardin
Published: September 2018

In this paper, we consider a system modeling an axially moving viscoelastic string under a spatiotemporally varying tension. A mechanism consisted of a hydraulic touch‐roll actuator pointed at the right boundary to suppress the transverse vibrations. We adopt the multiplier method to design a boundary control law and to prove an exponential stability result. However, this result is obtained provided that the lower bound of the tension in the string is larger than its time derivative. The effectiveness of the proposed control law is demonstrated via simulations.
Proton pump inhibitors are not associated with inflammatory myopathies: A case control study
Authors: Khoo Thomas , Caughey Gillian E. , Hill Catherine , Limaye Vidya
Published: September 2018

Introduction: A rare association of proton pump inhibitor (PPI) use with the development of inflammatory myopathies (IM) has been reported, but, unlike with statin medications, there is limited data supporting or refuting this observation. Methods: A case‐control study was conducted on patients with IM. Clinical information, medications, and demographics were recorded. Controls were matched 3:1 for age and gender. Results: Two hundred twenty‐one cases of IM were identified. No association of PPI use with IM was observed when compared with controls (odds ratio 1.04 [95% confidence interval 0.68–1.58]) and similar results were observed after adjusting for diabetes, cardiovascular disease, and statin exposure (adjusted odds ratio 1.084 [95% confidence interval 0.69–1.70]). There was no association of any histologic subtype of IM with PPI exposure. Discussion: Our findings do not support an association of PPI exposure with IM. Co‐prescription of PPI with other medications was not considered and could be further investigated with larger cohorts. Muscle Nerve 58:855–857, 2018
GNE myopathy in the bedouin population of Kuwait: Genetics, prevalence, and clinical description
Authors: Alrohaif Hadil , Pogoryelova Oksana , Al‐Ajmi Abdullah , Aljeryan Lulwa A. , Alrashidi Nuwayer H. , Alefasi Sara A. , Urtizberea Andoni , Lochmüller Hanns , Bastaki Laila
Published: September 2018

Introduction: GNE myopathy is a rare recessive myopathy caused by mutations in the GNE gene. It is mainly a distal myopathy with relative sparing of the quadriceps muscle. Methods: Patients with distal myopathies from Kuwait were examined and tested for the Middle Eastern GNE gene founder mutation, p.M743T. Patients were further studied for disease‐associated features. Results: GNE myopathy was confirmed in 14 of the 37 patients (37.8%) screened. All cases were caused by the p.M743T mutation. Age of onset and time from disease onset to loss of ambulation were variable. Both wasted and hypertrophied calf muscles were noted. Severely affected quadriceps were present in 1 patient, and ptosis, ophthalmoplegia, and tongue wasting in another. Discussion: The scope of the p.M743T mutation now includes the Arabian Peninsula. Variations in age of onset, disease progression, and distribution in patients harboring the same mutation suggest the role of other genetic‐ and environment‐modifying factors. Muscle Nerve 58: 700–707, 2018
Stable isotope analysis of human bone hydroxyapatite and collagen for the reconstruction of dietary patterns of hunter‐gatherers from Jomon populations
Authors: Kusaka Soichiro
Published: September 2018

Stable isotope analysis on human skeletal remains is a powerful tool to reconstruct prehistoric human diet. A previous study used carbon and nitrogen isotope analyses of bone collagen to reveal that the incorporation of marine resources was significant in the diet of people in the Jomon period. It was found that carbon and nitrogen isotope ratios in bone collagen reflect those of protein sources in the diet during adulthood, whereas the incorporation of terrestrial plants could not be evaluated. In this study, we assessed the consumption of terrestrial plants during adulthood by analysing the carbon isotope ratios in bone hydroxyapatite, which reflect the respective values in the whole diet (carbohydrates, lipids, and proteins). We studied 55 human skeletal remains from the Yoshigo and Inariyama shell mounds of the Tokai region in Japan. The carbon isotope ratios in bone hydroxyapatite from these samples were analysed to evaluate the dietary dependence on marine and terrestrial resources. We discovered that the carbon isotope ratios in the bone hydroxyapatite were as low as those in terrestrial mammals, thereby indicating that C3 plants and terrestrial mammals were the main sources of dietary energy for the Jomon people. This result suggests that the dietary incorporation of terrestrial resources was recorded in the bone hydroxyapatite. Finally, the difference between the carbon isotope ratios of the bone hydroxyapatite and collagen was correlated to the nitrogen isotope ratios of the bone collagen, thereby suggesting the large dietary variation among individuals. This study highlighted the utility of carbon isotope analysis of bone hydroxyapatite and bone collagen from human skeletal remains in the investigation of the prehistoric diet of Jomon populations.
Evolution of the biocontrol active substances in the framework of the European Pesticide Regulation (EC) No. 1107/2009
Authors: Robin Diane C , Marchand Patrice A
Published: September 2018

BACKGROUND

The use of biocontrol agents (BCA) is growing strongly with a market of €1.9 billion worldwide and €542 million in Europe, and an estimated annual growth of between 15% and 20%. Biocontrol substances use natural mechanisms as part of integrated pest management. With the exception of macro‐organisms, substances or products comprising microorganisms, semiochemicals and natural substances depend on plant protection Regulation (EC) No. 1107/2009.

RESULTS

When this regulation came into force, a number of BCA had already been approved. The total number of BCA rose during the period 2011–2018 to ∼ 60 substances in line with global growth in approved substances. This growth was not smooth or equal between biocontrol categories; the microorganisms category increased the most, with a doubling of the number of approved substances in use, followed by natural substances and semiochemicals.

CONCLUSION

This positive development has been influenced by many factors such as scientific advances and environmental characteristics. However, some obstacles remain that limit the development of BCA (market size, variability in effectiveness, etc.). Regulatory measures could be a key to enhancing the development of biocontrol registrations. © 2018 Society of Chemical Industry
Investigation of serum amino acids involved in gallic acid detoxification of formaldehyde by liquid chromatography/tandem mass spectrometry and neutral loss scan
Authors: Jiang Hai‐peng , Cai Nian , Ju Xiu‐lian , Huang Juan , Wang Xian
Published: September 2018

Rationale

Gallic acid is one of the most common polyphenols in natural products and human diet. The consumption of gallic acid reduces the incidence of cardiovascular diseases, chronic metabolic disorders and cancers. Most previous publications focused on the antioxidative or prooxidative properties of gallic acid. In the present work, gallic acid as a trapping agent of blood formaldehyde was investigated by liquid chromatography/tandem mass spectrometry (LC/MS/MS) and neutral loss scan.

Methods

Serum samples incubated with gallic acid were subjected to LC/MS/MS analysis using an LTQ XL ion trap mass spectrometer. The adduct ions of gallic acid‐formaldehyde‐amino acids were explored by investigation of their fragmentation patterns and neutral loss scan experiments.

Results

A series of Mannich adducts (namely, gallic acid‐formaldehyde‐alanine, gallic acid‐formaldehyde‐proline, gallic acid‐formaldehyde‐leucine or gallic acid‐formaldehyde‐isoleucine and gallic acid‐formaldehyde‐phenylalanine) were identified as metabolites by neutral loss scan experiments.

Conclusions

This work demonstrated that serum amino acids are involved in gallic acid detoxification of formaldehyde. Because excessive formaldehyde in blood is implicated in a variety of disease pathologies, detoxification of formaldehyde, especially endogenous formaldehyde, may be another health beneficial effect of gallic acid. It also suggested that more attention should be paid to Mannich‐type metabolites of polyphenol‐formaldehyde‐amino acids in research into the pharmacokinetics and bioavailability of polyphenols.
Recent Progress on Black Phosphorus‐Based Materials for Photocatalytic Water Splitting
Authors: Yan Junqing , Verma Priyanka , Kuwahara Yasutaka , Mori Kohsuke , Yamashita Hiromi
Published: September 2018

Employing photocatalytic technology for efficient water splitting to hydrogen evolution is a sustainable and renewable solution for energy and environmental issues. Large‐scale utilization of solar hydrogen requires the appropriate usage of photocatalysts with high efficiency and their easy integration into solar devices. Recently, 2D materials have been widely studied because of their potential utility in device fabrication. Black phosphorus (BP) is a newly developed 2D direct bandgap semiconductor with an impressive tunable bandgap and fast carrier migration characteristics. In this review, the optical and electronic characteristics of 2D phosphorene‐based materials are mainly discussed in terms of water splitting reaction. Density functional theory calculations are first summarized, followed by brief discussions on the direct application of BP in photocatalytic water splitting based on recent reports. This review might assist researchers to design new materials for photocatalytic water splitting.