bluuebunny/crossref_metadata_2025 huggingface dataset:
Elevational diversity gradients of Tibetan loaches: The relative roles of ecological and evolutionary processes
Authors: Feng Chenguang , Wu Yongjie , Tian Fei , Tong Chao , Tang Yongtao , Zhang Renyi , Li Guogang , Zhao Kai
Published: October 2017

It is widely believed that species richness patterns (SRPs) are shaped by both ecological and evolutionary processes. However, the relative roles of these processes remain unclear, especially for aquatic organisms. In this study, we integrated ecological and evolutionary measures to tease apart the relative influences of these factors on theSRPof Tibetan loaches along an extensive elevational gradient. We found that the Tibetan loaches displayed a richness pattern that peaked at midelevations. The mean annual temperature (MAT), mid‐domain effect (MDE), and summed age of colonization (SAC, complex of colonization age and colonization frequency) were the main drivers, accounting for 85%, 51%, and 88% of the variations in theSRP, respectively. The three predictors had very high combined effects (MAT‐MDE‐SAC,MAT‐SAC, andMDE‐SACwere 44%, 38%, and 6%, respectively). Our analyses suggested that energy input, time‐for‐speciation, and species dispersal may directly guide theSRPor mediate it by geometric constraints. Conclusively, theSRPof the Tibetan loaches with elevation is the outcome of interactions between biogeographical processes and regional ecological conditions.
Rarefaction and extrapolation of species richness using an area‐based Fisher's logseries
Authors: Chen Youhua , Shen Tsung‐Jen
Published: October 2017

Fisher's logseries is widely used to characterize species abundance pattern, and some previous studies used it to predict species richness. However, this model, derived from the negative binomial model, degenerates at the zero‐abundance point (i.e., its probability mass fully concentrates at zero abundance, leading to an odd situation that no species can occur in the studied sample). Moreover, it is not directly related to the sampling area size. In this sense, the original Fisher's alpha (correspondingly, species richness) is incomparable among ecological communities with varying area sizes. To overcome these limitations, we developed a novel area‐based logseries model that can account for the compounding effect of the sampling area. The new model can be used to conduct area‐based rarefaction and extrapolation of species richness, with the advantage of accurately predicting species richness in a large region that has an area size being hundreds or thousands of times larger than that of a locally observed sample, provided that data follow the proposed model. The power of our proposed model has been validated by extensive numerical simulations and empirically tested through tree species richness extrapolation and interpolation in Brazilian Atlantic forests. Our parametric model is data parsimonious as it is still applicable when only the information on species number, community size, or the numbers of singleton and doubleton species in the local sample is available. Notably, in comparison with the original Fisher's method, our area‐based model can provide asymptotically unbiased variance estimation (therefore correct 95% confidence interval) for species richness. In conclusion, the proposed area‐based Fisher's logseries model can be of broad applications with clear and proper statistical background. Particularly, it is very suitable for being applied to hyperdiverse ecological assemblages in which nonparametric richness estimators were found to greatly underestimate species richness.
Effects of macronutrient intake on the lifespan and fecundity of the marula fruit fly, Ceratitis cosyra (Tephritidae): Extreme lifespan in a host specialist
Authors: Malod Kevin , Archer C. Ruth , Hunt John , Nicolson Susan W. , Weldon Christopher W.
Published: October 2017

In insects, lifespan and reproduction are strongly associated with nutrition. The ratio and amount of nutrients individuals consume affect their life expectancy and reproductive investment. The geometric framework (GF) enables us to explore how animals regulate their intake of multiple nutrients simultaneously and determine how these nutrients interact to affect life‐history traits of interest. Studies using the GF on host‐generalist tephritid flies have highlighted trade‐offs between longevity and reproductive effort in females, mediated by the protein‐to‐carbohydrate (P:C) ratio that individuals consume. Here, we tested how P and C intake affect lifespan (LS) in both sexes, and female lifetime (LEP), and daily (DEP) egg production, in Ceratitis cosyra, a host‐specialist tephritid fly. We then determined the P:C ratio that C. cosyra defends when offered a choice of foods. Female LS was optimized at a 0:1 P:C ratio, whereas to maximize their fecundity, females needed to consume a higher P:C ratio (LEP = 1:6 P:C; DEP = 1:2.5 P:C). In males, LS was also optimized at a low P:C ratio of 1:10. However, when given the opportunity to regulate their intake, both sexes actively defended a 1:3 P:C ratio, which is closer to the target for DEP than either LS or LEP. Our results show that female C. cosyra experienced a moderate trade‐off between LS and fecundity. Moreover, the diets that maximized expression of LEP and DEP were of lower P:C ratio than those required for optimal expression of these traits in host‐generalist tephritids or other generalist insects.
Synthesis of Celecoxib, Mavacoxib, SC‐560, Fluxapyroxad, and Bixafen Enabled by Continuous Flow Reaction Modules
Authors: Britton Joshua , Jamison Timothy F.
Published: October 2017

Multi‐step continuous flow synthesis enables a parallel approach to obtain agrochemicals and pharmaceuticals containing 3‐fluoroalkyl pyrazole cores. In this system, fluorinated amines are transformed into pyrazole cores through a telescoped in situ generation and consumption of diazoalkanes. Once synthesized, additional continuous flow and batch reactions add complexity to the pyrazole core via C–N arylation and methylation, TMS cleavage, and amidation. Using this modular assembly line approach, Bixafen and Fluxapyroxad were synthesized in 38 % yield over four continuous flow steps in an overall reaction time of 56 min. Finally, coupling selected continuous flow processes with an offline (batch) Ullmann coupling afforded Celecoxib, Mavacoxib, and SC‐560 in 33–54 % yield over two to three steps.
Domino Reactions of Chromone‐3‐carboxylic Acids with Aminoheterocycles: Synthesis of Heteroannulated Pyrido[2,3‐c]coumarins and their Optical and Biological Activity
Authors: Miliutina Mariia , Janke Julia , Chirkina Elena , Hassan Sidra , Ejaz Syeda Abida , Khan Shafi Ullah , Iqbal Jamshed , Friedrich Aleksej , Lochbrunner Stefan , Ivanov Anton , Villinger Alexander , Lecka Joanna , Sévigny Jean , Langer Peter
Published: October 2017

A series of new heteroannulated pyrido[2,3‐c]coumarins have been prepared by the domino reactions of chromone‐3‐carboxylic acid derivatives with electron‐rich binucleophilic aminoheterocycles. The products contain the core structures of coumarin, pyridine, and an annulated five‐membered heterocyclic system, namely pyrazole, pyrrole, or isoazole. The fluorescence of the products was investigated. The products inhibit ecto‐5′‐nucleotidase (e5′NT) enzymatic activity.
Delay Discounting of Reward and Impulsivity in Eating Disorders: From Anorexia Nervosa to Binge Eating Disorder
Authors: Steward Trevor , Mestre‐Bach Gemma , Vintró‐Alcaraz Cristina , Agüera Zaida , Jiménez‐Murcia Susana , Granero Roser , Fernández‐Aranda Fernando
Published: October 2017

Evidence points to eating disorder patients displaying altered rates of delay discounting (one's degree of preference for immediate rewards over larger delayed rewards). Anorexia nervosa (AN) patients are believed to have an increased capacity to delay reward, which reflects their ability to override the drive to eat. Contrarily, binge eating disorder (BED) patients are associated with a reduced predisposition to delay gratification. Here, we investigated monetary delay discounting and impulsivity in 80 adult women with EDs (56 AN and 24 BED), diagnosed according to Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition criteria, and 80 healthy controls. AN‐restrictive (AN‐R) subtype patients showed less steep discounting rates than BED and AN‐bingeing/purging subtype patients. Compared with healthy controls and AN‐R patients, BED and AN‐bingeing/purging patients presented higher delay discounting and positive and negative urgency levels. Our findings suggest that restriction in AN‐R patients is associated with disproportionate self‐control, whereas bingeing behaviours could be more driven by emotional states and impulsivity traits. Copyright © 2017 John Wiley & Sons, Ltd and Eating Disorders Association.
Catechol‐O‐Methyltransferase (COMT) Val158Met Polymorphism and Eating Disorders: Data From a New Biobank and Meta‐Analysis of Previously Published Studies
Authors: Collantoni Enrico , Solmi Marco , Gallicchio Davide , Santonastaso Paolo , Meneguzzo Paolo , Carvalho Andrè F. , Stubbs Brendon , Clementi Maurizio , Pinato Claudia , Forzan Monica , Cassina Matteo , Fontana Francesca , Piva Ivana , Siani Roberta , Salvo Pierandrea , Tenconi Elena , Veronese Nicola , Correll Christoph U. , Favaro Angela
Published: October 2017

Objectives

We investigated whether catechol‐O‐methyltransferase (COMT) Val158Met polymorphism is associated with eating disorders (EDs).

Methods

We conducted a systematic literature search of studies published until 15 January 2017 and added data from the Italian ‘Biobanca Veneta per i Disturbi Alimentari’ biobank, performing a meta‐analysis comparing COMT Val158Met genotype and allele frequencies in EDs and anorexia nervosa (AN) or bulimia nervosa (BN) patients versus controls.

Results

Ten studies plus Biobanca Veneta per i Disturbi Alimentari (ED: n = 920, controls: n = 261 controls) with 3541 ED patients (AN = 2388; BN = 233) and 3684 controls were included. There were no significant group differences in COMT Val158Met alleles and genotype frequencies between patients and controls, for all EDs pooled together [range of odds ratios (ORs): 0.96–1.04, p‐values: 0.46–0.97, I2 = 0%] and when analysing separately patients with AN (ORs: 0.94–1.04, p‐values: 0.31–0.61, I2 = 0%) or BN (ORs: 0.80–1.09, p‐values: 0.28–0.64, I2 = 0–44%).

Conclusions

Meta‐analysing data results from 11 studies and 7225 subjects show that COMT Val158Met polymorphism is not associated with EDs. Copyright © 2017 John Wiley & Sons, Ltd and Eating Disorders Association.
Meta-analysis of pesticide sorption in subsoil
Authors: Jarvis Nicholas
Published: October 2017

Models used to assess leaching risks generally use organic carbon partition coefficient (kOC) values derived from batch experiments on topsoil samples to estimate pesticide sorption in subsoils of much smaller organic carbon contents. This can introduce significant errors in leaching risk calculations, because inorganic sorbents can play an important role for sorption in subsoil. The objectives of the present study were therefore to summarize the available literature data on pesticide sorption in subsoils and to test whether a simple alternative model could improve on the standard kOC approach used in risk assessment models for pesticide leaching. This model describes the sorption constant as a power law function of the organic carbon content. A database with the results of batch sorption experiments was collated from published studies that emphasized measurements in subsoils. This database contains 1029 data entries from 36 published studies with data for 29 active substances (11 nonionic compounds, 10 weak acids, 6 weak bases, one cation, and one zwitterion). The results show that whereas the constant kOC model proved to be an adequate model for 17 of the 63 individual datasets, the power law model gave acceptable fits (p < 0.05) for 60 of these cases. The exponent in the power law model varied over a wide range, from slightly negative to near unity. It also differed significantly (p = 0.015) for ionized and nonionized compounds, with median values of 0.25 and 0.55, respectively. It is concluded that the power law model could be used to parameterize subsoil sorption in regulatory leaching models, because it has widespread applicability and is simple enough for this purpose. Suitable ways of incorporating this approach in risk assessment procedures are discussed. Environ Toxicol Chem 2018;37:755–761. © 2017 SETAC
Clinical features and biological implications of different U2AF1 mutation types in myelodysplastic syndromes
Authors: Li Bing , Liu Jinqin , Jia Yujiao , Wang Jingya , Xu Zefeng , Qin Tiejun , Shi Zhongxun , Song Zhen , Peng Shuailing , Huang Huijun , Fang Liwei , Zhang Hongli , Pan Lijuan , Hu Naibo , Qu Shiqiang , Zhang Yue , Wu Jian , Liu Na , Ru Kun , Huang Gang , Xiao Zhijian
Published: October 2017

U2AF1 mutations (U2AF1MT) occur commonly in myelodysplastic syndromes (MDS) without ring sideroblasts. The aim of this study was to investigate the clinical and biological implications of different U2AF1 mutation types in MDS. We performed targeted gene sequencing in a cohort of 511 MDS patients. Eighty‐six patients (17%) were found to have U2AF1MT, which occurred more common in younger patients (P = .001) and represented ancestral lesions in a substantial proportion (71%) of cases. ASXL1MT and isolated +8 were significantly enriched in U2AF1MT‐positive cases, whereas TP53MT, SF3B1MT, and complex karyotypes were inversely associated with U2AF1MT. U2AFS34 subjects were enriched for isolated +8 and were inversely associated with complex karyotypes. U2AF1MT was significantly associated with anemia, thrombocytopenia, and poor survival in both lower‐risk and higher‐risk MDS. U2AF1S34 subjects had more frequently platelet levels of <50 × 109/L (P = .043) and U2AF1Q157/U2AF1R156 subjects had more frequently hemoglobin concentrations at <80 g/L (P = .008) and more often overt fibrosis (P = .049). In conclusion, our study indicates that U2AF1MT is one of the earliest genetic events in MDS patients and that different types of U2AF1MT have distinct clinical and biological characteristics.
An investigation of regional cerebral blood flow and tissue structure changes after acute administration of antipsychotics in healthy male volunteers
Authors: Hawkins Peter C.T. , Wood Tobias C. , Vernon Anthony C. , Bertolino Alessandro , Sambataro Fabio , Dukart Juergen , Merlo‐Pich Emilio , Risterucci Celine , Silber‐Baumann Hanna , Walsh Eamonn , Mazibuko Ndabezinhle , Zelaya Fernando O. , Mehta Mitul A.
Published: October 2017

Chronic administration of antipsychotic drugs has been linked to structural brain changes observed in patients with schizophrenia. Recent MRI studies have shown rapid changes in regional brain volume following just a single dose of these drugs. However, it is not clear if these changes represent real volume changes or are artefacts (“apparent” volume changes) due to drug‐induced physiological changes, such as increased cerebral blood flow (CBF). To address this, we examined the effects of a single, clinical dose of three commonly prescribed antipsychotics on quantitative measures of T1 and regional blood flow of the healthy human brain. Males (n = 42) were randomly assigned to one of two parallel groups in a double‐blind, placebo‐controlled, randomized, three‐period cross‐over study design. One group received a single oral dose of either 0.5 or 2 mg of risperidone or placebo during each visit. The other received olanzapine (7.5 mg), haloperidol (3 mg), or placebo. MR measures of quantitative T1, CBF, and T1‐weighted images were acquired at the estimated peak plasma concentration of the drug. All three drugs caused localized increases in striatal blood flow, although drug and region specific effects were also apparent. In contrast, all assessments of T1 and brain volume remained stable across sessions, even in those areas experiencing large changes in CBF. This illustrates that a single clinically relevant oral dose of an antipsychotic has no detectable acute effect on T1 in healthy volunteers. We further provide a methodology for applying quantitative imaging methods to assess the acute effects of other compounds on structural MRI metrics. Hum Brain Mapp 39:319–331, 2018. © 2017 Wiley Periodicals, Inc.
Functional subdivisions within the human intraparietal sulcus are involved in visuospatial transformation in a non‐context‐dependent manner
Authors: Papadopoulos Alexandra , Sforazzini Francesco , Egan Gary , Jamadar Sharna
Published: October 2017

Object‐based visuospatial transformation is important for the ability to interact with the world and the people and objects within it. In this preliminary investigation, we hypothesized that object‐based visuospatial transformation is a unitary process invoked regardless of current context and is localized to the intraparietal sulcus. Participants (n = 14) performed both antisaccade and mental rotation tasks while scanned using fMRI. A statistical conjunction confirmed that both tasks activated the intraparietal sulcus. Statistical parametric anatomical mapping determined that the statistical conjunction was localized to intraparietal sulcus subregions hIP2 and hIP3. A Gaussian naïve Bayes classifier confirmed that the conjunction in region hIP3 was indistinguishable between tasks. The results provide evidence that object‐based visuospatial transformation is a domain‐general process that is invoked regardless of current context. Our results are consistent with the modular model of the posterior parietal cortex and the distinct cytoarchitectonic, structural, and functional connectivity profiles of the subregions in the intraparietal sulcus. Hum Brain Mapp 39:354–368, 2018. © 2017 Wiley Periodicals, Inc.
Affective creativity meets classic creativity in the scanner
Authors: Perchtold Corinna M. , Papousek Ilona , Koschutnig Karl , Rominger Christian , Weber Hannelore , Weiss Elisabeth M. , Fink Andreas
Published: October 2017

The investigation of neurocognitive processes underlying more real‐life creative behavior is among the greatest challenges in creativity research. In this fMRI study, we addressed this issue by investigating functional patterns of brain activity while participants were required to be creative in an affective context. Affective creativity was assessed in terms of individual's inventiveness in generating alternative appraisals for anger‐evoking events, which has recently emerged as a new ability concept in cognitive reappraisal research. In addition, a classic divergent thinking task was administered. Both creativity tasks yielded strong activation in left prefrontal regions, indicating their shared cognitive processing demands like the inhibition of prepotent responses, shifting between different perspectives and controlled memory retrieval. Regarding task‐specific differences, classic creative ideation activated a characteristic divergent thinking network comprising the left supramarginal, inferior temporal, and inferior frontal gyri. Affective creativity on the other hand specifically recruited the right superior frontal gyrus, presumably involved in the postretrieval monitoring of reappraisal success, and core hubs of the default‐mode network, which are also implicated in social cognition. As a whole, by taking creativity research to the realm of emotion, this study advances our understanding of how more real‐life creativity is rooted in the brain. Hum Brain Mapp 39:393–406, 2018. © 2017 Wiley Periodicals, Inc.
Case definitions for inclusion and analysis of endpoints in clinical trials for nonalcoholic steatohepatitis through the lens of regulatory science
Authors: Siddiqui Mohammad Shadab , Harrison Stephen A. , Abdelmalek Manal F. , Anstee Quentin M. , Bedossa Pierre , Castera Laurent , Dimick‐Santos Lara , Friedman Scott L. , Greene Katherine , Kleiner David E. , Megnien Sophie , Neuschwander‐Tetri Brent A. , Ratziu Vlad , Schabel Elmer , Miller Veronica , Sanyal Arun J. ,   on behalf of the Liver Forum Case Definitions Working Group
Published: October 2017

Nonalcoholic steatohepatitis (NASH) is an important cause of liver‐related morbidity and mortality. There are no approved therapies, and the results of clinical trials have been difficult to compare due to inconsistent definitions of relevant disease parameters in patients with NASH. The natural course of the disease has not been rigorously characterized, particularly with respect to the contributions of underlying obesity, type 2 diabetes, and other comorbidities and the treatments provided for these comorbidities. Efforts to perform analyses of pooled data are limited by heterogeneous case definitions used across studies to define disease states. There remains a major unmet need in the field to develop standardized definitions for populations for interventional trials. Such definitions are expected to impact how endpoints for clinical trials are constructed. The Liver Forum is a multistakeholder effort including US and European regulatory agencies, academic investigators, professional and patient representative organizations, and industry to catalyze therapeutic development for NASH by developing potential solutions to barriers to development. The Case Definitions Working Group was established by The Liver Forum to evaluate the validity of case definitions for populations to be included in clinical trials for NASH from a regulatory science perspective. Based on such analyses, specific recommendations are provided noting the strengths and weaknesses of the case definitions along with knowledge gaps that require additional study. (Hepatology 2018;67:2001‐2012)
Label‐free imaging of redox status and collagen deposition showing metabolic differences in the heart
Authors: Morrison Janna L. , Sorvina Alexandra , Darby Jack R.T. , Bader Christie A. , Lock Mitchell C. , Seed Mike , Kuchel Tim , Plush Sally E. , Brooks Douglas A.
Published: October 2017

The heart has high metabolic demand to maintain function. The primary source of energy supply to support correct contractile muscle function differs between a fetus and an adult. In fetal life, ATP is primarily generated by glycolysis and lactate oxidation, whereas following birth, there is a shift towards a reliance on mitochondrial metabolism and fatty acid oxidation. This change in metabolic status is an adaptation to different fuel availability, oxygenation and growth patterns. In this study, we have employed 2‐photon excitation fluorescence microscopy to define the relationship between two critical metabolic cofactors nicotinamide adenine dinucleotide(P)H and flavin adenine dinucleotide, effectively utilizing a redox ratio to differentiate between the metabolic status in fetal (proliferative) and adult (quiescent/hypertrophic) hearts. Two‐photon imaging was also used to visually confirm the known increase in collagen deposition in the adult heart. The changes observed were consistent with a hypertrophic growth profile and greater availability of fatty acids in the adult heart, compared to the proliferative fetal heart. Two‐photon excitation fluorescence microscopy is therefore a convenient imaging technology that enables the monitoring of striated muscle architecture and the metabolic status of heart tissue. This imaging technology can potentially be employed to visualize cardiac and other muscle pathologies.
From mutational inactivation to aberrant gain‐of‐function: Unraveling the structural basis of mutant p53 oncogenic transition
Authors: Olotu Fisayo A. , Soliman Mahmoud E.S.
Published: October 2017

Various evidence has revealed that mutations in p53 exert activities that go beyond simply inactivation of wildtype functions but rather elicits downstream interactions that promote malignancy described as mutant p53 gain‐of‐function (GOF). Here we report the first account of the dynamics of mutation‐induced structural transition of native p53 to an aberrant gain‐of‐function state, studying the wildtype (WT) and high incidence contact (R273C) and structural (R175H) mutant p53 (mutp53) through molecular dynamics simulation. Result analysis revealed that both mutants exhibited structural distortion and reduced flexibility, indicative of rigidity and kinetic stability. In addition, surface analysis revealed an increase in the accessible surface area in the p53 mutants. This suggests that the GOF transition involves protein unfolding and exposure of buried hydrophobic surface essential for interaction with HSF‐1 oncogenic partner and wildtype p63, and p73 homologs. Further validation revealed binding cavities, similar in the mutants but dissimilar to the WT. Taken together, this study complements experimental findings and reveals the interplay between mutation‐induced structural distortion, loss of flexibility, rigidity, enhanced stability, protein unfolding and ultimately, exposure of binding surfaces as conformational attributes that characterize mutP53 structure‐GOF activities. This insight is, therefore, of great importance as it opens up a novel therapeutic approach toward the structure based targeting of mutP53 oncogenic involvement beyond wildtype inactivation. Furthermore, “exposed” binding site information obtained from this study can be explored for structure‐based design of substances best described as “destabilizers” to disrupt the GOF interaction of mutp53.
GCNF regulates OCT4 expression through its interactions with nuclear receptor binding elements in NCCIT cells
Authors: Park Sung‐Won , Do Hyun‐Jin , Choi Wonbin , Kim Jin‐Hoi , Song Hyuk , Seo Han Geuk , Kim Jae‐Hwan
Published: October 2017

We demonstrate that OCT4 expression is regulated by germ cell nuclear factor (GCNF) via its interactions with three nuclear receptor (NR) binding sites within OCT4 promoter conserved regions (CRs) in human embryonic carcinoma (EC) NCCIT cells. OCT4 expression is gradually reduced during the retinoic acid‐induced differentiation, while GCNF temporarily increased after 2 days and then significantly decreased. In addition, OCT4 expression is significantly reduced by overexpression of exogenous GCNF, but increased by GCNF shRNA‐mediated knockdown. The transcriptional activity of OCT4 is significantly inhibited by dose‐dependent overexpression of GCNF. While mutants at each of the NR binding sites retain the repressive effects of GCNF on OCT4 promoter activity, the repressive effect was completely eliminated in the reporter construct with all binding sites mutated even in the presence of GCNF. Furthermore, the transcriptional activity of native minimal promoter (CR1‐Luc) containing the first NR binding site was significantly reduced by GCNF overexpression, while the mutant retained basal activity to some extent. Next, an exogenous minimal ti promoter‐inserted CR2 reporter construct containing the second and third NR binding sites (CR2‐ti‐Luc) was co‐transfected with GCNF expression vector. The transcriptional activity of CR2‐ti‐Luc was significantly decreased by GCNF overexpression, while mutation of both binding sites retained the transcriptional activity of the reporter construct. Binding assays confirmed the direct interaction of GCNF with all three NR binding sites cooperatively. Taken together, GCNF acts as a transcriptional repressor in the regulation of OCT4 gene expression through cooperative interaction with three NR binding elements in pluripotent NCCIT cells.
S14G‐humanin alleviates insulin resistance and increases autophagy in neurons of APP/PS1 transgenic mouse
Authors: Han Kun , Jia Ning , Zhong Yi , Shang Xiuli
Published: October 2017

Alzheimer's disease (AD) is a progressive neurodegenerative disease characterized by Aβ plaque deposition in the brain, which is related to the disorder of autophagosome maturation, transport, and formation of autolysosome. Notably, abnormal insulin signaling is connected with cognitive dysfunction in AD. In this study, using APP/PS1 transgenic mice as AD model, we investigated the mechanism by which S14G‐humanin (HNG) improved autophagy and insulin signaling in AD brain. Immunohistochemistry was used to determine the levels of mTOR and Aβ deposition, and Western blot analysis was used to determine IRS‐1, IRS‐1 pSEr636, ULK1, p62, LC3 I/LC3 II protein levels. Our results demonstrated that HNG could improve the learning ability and memory in APP/PS1 transgenic mice, possibly through decreasing IRS‐1 Ser636 phosphorylation and mTOR protein expression in the hippocampus, thus improving insulin resistance in the brain. In addition, HNG increased ULK1 expression, decreased p62 and LC3 I/LC3 II protein levels, thus enhancing autophagy and decreasing Aβ deposition in the brain. Taken together, our results suggest that through the regulation of IRS‐1/mTOR insulin signaling in the hippocampus, HNG increases the activity of autophagy and decreases Aβ deposition in the brain, and improves learning ability and memory of AD mice.
A longitudinal investigation of the psychological health of United States Air Force base communities
Authors: Lorber Michael F. , Heyman Richard E. , Slep Amy M. Smith
Published: October 2017

The longitudinal course of the psychological health (PH) of United States Air Force (USAF) base communities in relation to risk and demographic factors was studied over a 5‐year period. PH (clinically significant hazardous drinking, prescription drug misuse, depressive symptoms, suicidal thoughts and behaviors, intimate partner violence [IPV] and child abuse) and risk (personal and family adjustment, workplace adjustment, broader community adjustment) and demographic factors (age and gender distribution) were operationalized at the aggregate level for bases (N = 77) as measured in three large scale surveys of USAF active duty members. Bases whose members collectively exhibited greater levels of risk collectively experienced greater initial problems with alcohol and drug use, depression, suicidality, and physical IPV. Hazardous drinking more quickly increased at bases whose members were younger and more male, and at those with poorer initial aggregate personal adjustment and workplace adjustment. The challenges of studying the community‐level course of PH are highlighted.
Clinical and prognostic value of the C‐Met/HGF signaling pathway in cervical cancer
Authors: Boromand Nadia , Hasanzadeh Malihe , ShahidSales Soodabeh , Farazestanian Marjaneh , Gharib Masoumeh , Fiuji Hamid , Behboodi Negin , Ghobadi Niloofar , Hassanian Seyed Mahdi , Ferns Gordon A. , Avan Amir
Published: October 2017

Aberrant activation of the HGF/c‐Met signalling pathway is reported to be associated with cell proliferation, progression, and metastasis features of several tumor types, including cervical cancer, suggesting that it may be of potential value as a novel therapeutic target. Furthermore, HPV‐positive patients had a higher serum level of HGF or c‐Met protein, compared with HPV‐negative patients. c‐Met or HGF overexpression in lesions of cervical cancer is reported to be related to a poorer prognosis, and hence this may be of value as a prognostic and predictive biomarker. Several approaches have been developed for targeting HGF and/or c‐Met. One of these is crizotinib (a dual c‐Met/ALK inhibitor). This has been approved by FDA for the treatment of lung‐cancer. Further investigations are required to evaluate and optimize the use of c‐Met inhibitors in cervical cancer or parallel targeting signalling pathway associated/activated via MET/HGF pathway. The main aim of current review was to give an overview of the potential of the c‐Met/HGF pathway as a prognostic, or predictive biomarker in cervical cancer.
Fatty acid synthase knockout impairs early embryonic development via induction of endoplasmic reticulum stress in pigs
Authors: Guo Jing , Niu Ying‐Jie , Shin Kyung‐Tae , Kwon Jeong‐Woo , Kim Nam‐Hyung , Cui Xiang‐Shun
Published: October 2017

Fatty acid synthase (FAS) is an important enzyme involved in the de novo synthesis of long‐chain fatty acids. During development, the function of FAS in growth is greater than that in energy storage pathways; therefore, we hypothesized that knockout of FAS would affect early embryonic development owing to the induction of endoplasmic reticulum (ER) stress. In the present study, the function of FAS was studied using the CRISPR (clustered regularly interspaced short palindromic repeats)/ CRISPR‐associated protein 9 (Cas9) system. Cas9 and single‐guide RNA (sgRNA) were injected into parthenotes to decrease the number of FAS‐positive embryos. The efficiency of knockout was assayed by DNA sequencing. We found that FAS knockout caused excessive production of reactive oxygen species (ROS). Excess ROS induced ER stress, resulting in activation of the adaptive unfolded protein response (UPR). FAS knockout caused splicing of the X‐box binding protein 1 gene (XBP1) and expression of spliced XBP1 mRNA. In addition, FAS knockout caused phosphorylation of PKR‐like ER kinase (PERK), and an increase in the mRNA expression of the ER stress‐regulated genes, activating transcription factor 4 (ATF4), and C/EBP homologous protein (CHOP). Finally, Ca2+ was released from the ER and taken up by the mitochondria. As the ER stress became intolerable, apoptosis was initiated. These results demonstrate that FAS knockout induced ROS generation, which mediated the activation of UPR via the ER stress, ultimately leading to apoptosis induction.
Involvement of dying beta cell originated messenger molecules in differentiation of pancreatic mesenchymal stem cells under glucotoxic and glucolipotoxic conditions
Authors: Gezginci‐Oktayoglu Selda , Onay‐Ucar Evren , Sancar‐Bas Serap , Karatug‐Kacar Ayse , Arda Emine S. N. , Bolkent Sehnaz
Published: October 2017

Beta cell mass regulation represents a critical issue for understanding and treatment of diabetes. The most important process in the development of diabetes is beta cell death, generally induced by glucotoxicity or glucolipotoxicity, and the regeneration mechanism of new beta cells that will replace dead beta cells is still not fully understood. The aim of this study was to investigate the generation mechanism of new beta cells by considering the compensation phase of type 2 diabetes mellitus. In this study, pancreatic islet derived mesenchymal stem cells (PI‐MSCs) were isolated from adult rats and characterized. Then, beta cells isolated from rats were co‐cultured with PI‐MSCs and they were exposed to glucotoxicity, lipotoxicity and glucolipotoxicity conditions for 72 hr. As the results apoptotic and necrotic cell death were increased in both PI‐MSCs and beta cells especially by the exposure of glucotoxic and glucolipotoxic conditions to the co‐culture systems. Glucotoxicity induced‐differentiated beta cells were functional due to their capability of insulin secretion in response to rising glucose concentrations. Moreover, beta cell proliferation was induced in the glucotoxicity‐treated co‐culture system whereas suppressed in lipotoxicity or glucolipotoxicity‐treated co‐culture systems. In addition, 11 novel proteins, that may release from dead beta cells and have the ability to stimulate PI‐MSCs in the direction of differentiation, were determined in media of glucotoxicity or glucolipotoxicity‐treated co‐culture systems. In conclusion, these molecules were considered as important for understanding cellular mechanism of beta cell differentiation and diabetes. Thus, they may be potential targets for diagnosis and cellular or therapeutic treatment of diabetes.
Recovery of butanol from Clostridium beijerinckii P260 fermentation broth by supercritical CO2 extraction
Authors: Qureshi Nasib , Eller Fred
Published: October 2017

BACKGROUND

Butanol is a superior biofuel to ethanol because of its blend properties and higher energy density. However, its recovery by distillation from the fermentation broth is energy intensive. For this reason, butanol recovery by supercritical CO2 extraction from simulated and actual fermentation broths was studied. Recovery of butanol by this technique has numerous advantages including being environmentally favorable, avoiding use of costly chemicals or membranes, and compatible with the microbial culture.

RESULTS

For the model solution extraction process, feed contained 7.00, 12.00, and 1.00 g L−1 acetone, butanol, ethanol (ABE), respectively, to mimic the actual concentrations obtained in the fermentation broth. In the extract phase, butanol concentration obtained ranged from 460.4 to 573.2 g L−1 with butanol selectivities ranging from 128 to 204.8. ABE recovery was also successfully demonstrated using actual fermentation broth of C. beijerinckii P260.

CONCLUSION

Supercritical CO2 extraction was successfully used for recovery of all three (ABE) components. Fermentation broth raffinate (feed depleted in ABE after recovery) was also reused for a second fermentation thus allowing process water recycle. Published 2017. This article is a U.S. Government work and is in the public domain in the USA.
Simulation of graphitic contacts to p‐type Si using a metal‐resistor‐semiconductor (M‐R‐S) model implemented in TCAD
Authors: Alnassar M.S.N. , Luong S. , Tran H.N. , Partridge J.G. , Holland A.S.
Published: October 2017

In this paper, we describe simulations of highly rectifying carbon/p‐Si junctions using Sentaurus TCAD from Synopsys. 2‐D and 3‐D models were constructed and optimized to fit I‐V characteristics measured from these junctions. The TCAD models included a resistive interface layer, previously observed experimentally. From the model, the interface resistance was determined to be 0.04 Ω·cm2, and the work function of the graphitic contacts was determined to be 4.43 eV. The latter is the work function at the interface, which cannot be measured experimentally. Schottky barrier lowering was implemented in the model to provide agreement with the measurements. The modeling provided information that could not be obtained from measurements and suggested a path to improved devices.
Differentiation of MSC and annulus fibrosus cells on genetically engineered silk fleece‐membrane‐composites enriched for GDF‐6 or TGF‐β3
Authors: Frauchiger Daniela A. , Heeb Silvan R. , May Rahel D. , Wöltje Michael , Benneker Lorin M. , Gantenbein Benjamin
Published: October 2017

Intervertebral disc (IVD) repair is a high‐priority topic in our active and increasingly ageing society. Since a high number of people are affected by low back pain treatment options that are able to restore the biological function of the IVD are highly warranted. Here, we investigated whether the feasibility of genetically engineered (GE)‐silk from Bombyx mori containing specific growth factors to precondition human bone‐marrow derived mesenchymal stem cells (hMSC) or to activate differentiated human annulus fibrosus cells (hAFC) prior transplantation or for direct repair on the IVD. Here, we tested the hypothesis that GE‐silk fleece can thrive human hMSC towards an IVD‐like phenotype. We aimed to demonstrate a possible translational application of good manufacturing practice (GMP)‐compliant GE‐silk scaffolds in IVD repair and regeneration. GE‐silk with growth and differentiation factor 6 (GDF‐6‐silk) or transforming growth factor β3 (TGF‐β3, TGF‐β3‐silk) and untreated silk (cSilk) were investigated by DNA content, cell activity assay and glycosaminoglycan (GAG) content and their differentiation potential by qPCR analysis. We found that all silk types demonstrated a very high biocompatibility for both cell types, that is, hMSC and hAFC, as revealed by cell activity, and DNA proliferation assay. Further, analyzing qPCR of marker genes revealed a trend to differentiation toward an NP‐like phenotype looking at the Aggrecan/Collagen 2 ratio which was around 10:1. Our results support the conclusion that our GE‐silk scaffold treatment approach can thrive hMSC towards a more IVD‐like phenotype or can maintain the phenotype of native hAFC. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:1324–1333, 2018.
Effects of thermal drying on phosphorus availability from iron‐precipitated sewage sludge
Authors: Lemming Camilla , Scheutz Charlotte , Bruun Sander , Jensen Lars Stoumann , Magid Jakob
Published: October 2017

Thermal drying of sewage sludge implies sanitation and improves practical handling options of the sludge prior to land application. However, it may also affect its value as a fertilizer. The objective of this study was to assess whether thermal drying of sewage sludge, as well as drying temperature, affects plant P availability after application to soil. The experiment included dewatered sewage sludge (20% DM) and thermally dried sewage sludge (95% DM) collected at a Danish wastewater treatment plant, as well as laboratory oven‐dried (70, 130, 190, and 250°C; DM > 95%) subsamples of the dewatered sludge, and a triple superphosphate as a reference. Plant P availability was studied in a 197 d soil incubation experiment, with sampling for Diffusive Gradients in Thin films (DGT) and water extractable P (WEP) analyses over time, and in a pot experiment with spring barley (Hordeum vulgare L.). In both experiments, thermal drying reduced P availability, as shown by 37 and 23% lower DGT and WEP values, respectively, and a 16% lower P uptake by barley in the pot experiment. The specific drying temperature did not appear to have much effect. Overall, our results suggest that thermal drying of iron‐precipitated sewage sludge is not an optimal treatment option if the aim is to optimize plant P availability.
Soil phosphorus dynamics along a loess–limestone transect in Mihla, Thuringia (Germany)
Authors: Weihrauch Christoph , Opp Christian
Published: October 2017

The distribution of phosphorus (P) along a loess–limestone soil transect were investigated to delineate the spatial variation of the nutrient vertically in the soil profiles and laterally in the landscape. We hypothesized that spatial P patterns result from translocation caused by P mobilization, although P fixation would be expected along the slope. To depict this, three P fractions clearly differing in solubility were determined. Soil samples were treated with 0.1 M hydrochloric acid (HCl), with 12.1 M HCl, and with aqua regia (AR). In the profiles the spatial P distribution slightly corresponds to the occurrence of different bedrocks and substrata. Thus, a native “P loading” might not primarily explain the spatial P patterns. Especially the strong enrichment of the toeslope with easily soluble P indicates P translocation and prior mobilization. The enrichment is detectable throughout the profiles. Thus, superficial translocation (e.g., erosion) cannot sufficiently explain that pattern. Instead, underground processes must be the cause for this. They cause relatively high vertical and lateral variation in the spatial P distribution, e.g., within soil horizons and substratum layers. Hence, mixed sampling of soil sections might not produce data accurate enough for some kinds of P research and for P management. Also, the lateral P distribution should be detected more precisely prior to fertilization of agricultural land.
Practical guidance for using multiple data sources in systematic reviews and meta‐analyses (with examples from the MUDS study)
Authors: Mayo‐Wilson Evan , Li Tianjing , Fusco Nicole , Dickersin Kay ,   for the MUDS investigators
Published: October 2017

Data for individual trials included in systematic reviews may be available in multiple sources. For example, a single trial might be reported in 2 journal articles and 3 conference abstracts. Because of differences across sources, source selection can influence the results of systematic reviews. We used our experience in the Multiple Data Sources in Systematic Reviews (MUDS) study, and evidence from previous studies, to develop practical guidance for using multiple data sources in systematic reviews.

We recommend the following: (1) Specify which sources you will use. Before beginning a systematic review, consider which sources are likely to contain the most useful data. Try to identify all relevant reports and to extract information from the most reliable sources. (2) Link individual trials with multiple sources. Write to authors to determine which sources are likely related to the same trials. Use a modified Preferred Reporting Items for Systematic Reviews and Meta‐analyses (PRISMA) flowchart to document both the selection of trials and the selection of sources. (3) Follow a prespecified protocol for extracting trial characteristics from multiple sources. Identify differences among sources, and contact study authors to resolve differences if possible. (4) Prespecify outcomes and results to examine in the review and meta‐analysis. In your protocol, describe how you will handle multiple outcomes within each domain of interest. Look for outcomes using all eligible sources. (5) Identify which data sources were included in the review. Consider whether the results might have been influenced by data sources used. (6) To reduce bias, and to reduce research waste, share the data used in your review.
Simultaneous analysis by Quadrupole‐Orbitrap mass spectrometry and UHPLC‐MS/MS for the determination of sedative‐hypnotics and sleep inducers in adulterated products
Authors: Lee Ji Hyun , Park Han Na , Choi Ji Yeon , Kim Nam Sook , Park Hyung‐Joon , Park Seong Soo , Baek Sun Young
Published: October 2017

Adulterated products are continuously detected in society and cause problems. In this study, we developed and validated a method for determining synthetic sedative‐hypnotics and sleep inducers, including barbital, benzodiazepam, zolpidem, and first‐generation antihistamines, in adulterated products using Quadrupole‐Orbitrap mass spectrometry and ultrahigh performance liquid chromatography with tandem mass spectrometry. In Quadrupole‐Orbitrap mass spectrometry analysis, target compounds were confirmed using a combination of retention time, mass tolerance, mass accuracy, and fragment ions. For quantification, several validation parameters were employed using ultrahigh performance liquid chromatography with tandem mass spectrometry. The limit of detection and limit of quantitation was 0.05–53 and 0.17–177 ng/mL, respectively. The correlation coefficient for linearity was more than 0.995. The intra‐ and interassay accuracies were 86–110 and 84–111%, respectively. Their precision values were evaluated as within 4.0 (intraday) and 10.7% (interday). Mean recoveries of target compounds in adulterated products ranged from 85 to 116%. The relative standard deviation of stability was less than 10.7% at 4°C for 48 h. The 144 adulterated products obtained over 3 years (2014–2016) from online and in‐person vendors were tested using established methods. After rapidly screening with Quadrupole‐Orbitrap mass spectrometry, the detected samples were quantified using ultrahigh performance liquid chromatography with tandem mass spectrometry. Two of them were adulterated with phenobarbital.