bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dependence of Intravoxel Incoherent Motion diffusion MR thresholdb-value selection for separating perfusion and diffusion compartments and liver fibrosis diagnostic performance
Authors: Li Yao , Lu Pu-Xuan , Huang Hua , Leung Jason , Chen Weitian , Wang Yi-Xiang 
Published: July 2017

AbstractPurposeTo explore how the selection of thresholdb-value impacts Intravoxel Incoherent Motion (IVIM) diffusion parameters of PF (f), Dslow(D),and Dfast(D*) values and their performance for liver fibrosis detection.Materials and MethodsFifteen healthy volunteers and 33 hepatitis-b patients were included. With a 1.5 T MR scanner and respiration gating, IVIM data was acquired with 10b-values of 10,20,40,60,80,100,150, 200, 400, and 800 s/mm2. Signal measurement was performed on right liver. Segmented-unconstrained analysis was used to compute IVIM parameters, and six thresholdb-values between 40 and 200 s/mm2were compared. PF, Dslow, and Dfast values were placed along thex-axis,y-axis, andz-axis, and a plane was defined to separate volunteers from patients.ResultsHigher thresholdb-values were associated with higher PF measurement; while lower thresholdb-values led to higher Dslow and Dfast measurements. The dependence of PF, Dslow, and Dfast on thresholdb-value differed between healthy livers and fibrotic livers; with the healthy livers showing a higher dependence. Thresholdb-value=60 s/mm2showed the largest mean distance between healthy liver datapoints vs. fibrotic liver datapoints in 3-dimensional space.ConclusionFor segmented-unconstrained analysis, the selection of thresholdb-value=60 s/mm2improves IVIM diffusion differentiation between healthy livers and fibrotic livers.
A mathematical model relates intracellular TLR4 oscillations to sepsis progression
Authors: Stan Razvan C. , Soriano Francisco G. , de Camargo Maristela M. 
Published: July 2017

AbstractOscillations drive many biological processes and their modulation is determinant for various pathologies. In sepsis syndrome, Toll-like receptor 4 (TLR4) is a key sensor for signaling the presence of Gram-negative bacteria. Its expression and activity, along with its intracellular trafficking rates shift the equilibrium between the pro‐ and anti-inflammatory downstream signaling cascades, leading to either the physiological resolution of the bacterial stimulation or to sepsis. We hypothesize that the initialtlr4expression in patients diagnosed with sepsis and TLR4 dynamic concentration changes on the cell membrane or intracellularly, dictates how the sepsis syndrome is initiated. Using a set of three differential equations, we defined the TLR4 flux between relevant cell organelles. We obtained three different regions in the phase space: 1. a limit-cycle describing unstimulated physiological oscillations, 2. a fixed-point attractor resulting from moderate LPS stimulation that is resolved and 3. a double-attractor resulting from sustained LPS stimulation that leads to sepsis. We tested the models against hospital data of sepsis patients and we correctly evaluate the clinical outcome of these patients.
A phylogenetic and evolutionary analysis of antimycin biosynthesis
Authors: Joynt Rebecca , Seipke Ryan F. 
Published: July 2017

AbstractStreptomycesspecies and otherActinobacteriaare ubiquitous in diverse environments worldwide and are the source of, or inspiration for, the majority of pharmaceuticals. The genomic era has enhanced biosynthetic understanding of these valuable chemical entities and has also provided a window into the diversity and distribution of natural product biosynthetic gene clusters. Antimycin is an inhibitor of mitochondrial cytochrome c reductase and more recently was shown to inhibit Bcl-2/Bcl-XLsrelated anti-apoptotic proteins commonly overproduced by cancerous cells. Here we identify 65 putative antimycin biosynthetic gene clusters (BGCs) in publicly available genome sequences ofActinobacteriaand classify them based on the presence or absence of cluster-situated genesantPandantQ,which encode a kynureninase and phosphopantetheinyl transferase (PPTase), respectively. The majority of BGCs possess either bothantPandantQ(L-form) or neither (S-form), while a minority of them lack eitherantPorantQ(IQor IPform, respectively). We also evaluate the biogeographical distribution and phylogenetic relationships of antimycin producers and BGCs. We show that antimycin BGCs occur on five of the seven continents and are frequently isolated from plants and other higher organisms. We also provide evidence for two distinct phylogenetic clades of antimycin producers and gene clusters, which delineate S-form from L- and I-form BGCs. Finally, our findings suggest that the ancestral antimycin producer harboured an L-form gene cluster which was primarily propagated by vertical transmission and subsequently diversified into S-, IQand IPform biosynthetic pathways.
Cytosolic proteins can exploit membrane localization to trigger functional assembly
Authors: Yogurtcu Osman N. , Johnson Margaret E. 
Published: July 2017

ABSTRACTCell division, endocytosis, and viral budding would not function without the localization and assembly of protein complexes on membranes. What is poorly appreciated, however, is that by localizing to membranes, proteins search in a reduced space that effectively drives up concentration. Here we derive an accurate and practical analytical theory to quantify the significance of this dimensionality reduction in regulating protein assembly on membranes. We define a simple metric, an effective equilibrium constant, that allows for quantitative comparison of protein-protein interactions with and without membrane present. To test the importance of membrane localization for driving protein assembly, we collected the protein-protein and protein-lipid affinities, protein and lipid concentrations, and volume-to-surface-area ratios for 46 interactions between 37 membrane-targeting proteins in human and yeast cells. We find that many of the protein-protein interactions between pairs of proteins involved in clathrin-mediated endocytosis in human and yeast cells can experience enormous increases in effective protein-protein affinity (10-1000 fold) due to membrane localization. Localization of binding partners thus triggers robust protein complexation, suggesting that it can play an important role in controlling the timing of endocytic protein coat formation. Our analysis shows that several other proteins involved in membrane remodeling at various organelles have similar potential to exploit localization. The theory highlights the master role of phosphoinositide lipid concentration, the volume-to-surface-area ratio, and the ratio of 3D to 2D equilibrium constants in triggering (or preventing) constitutive assembly on membranes. Our simple model provides a novel quantitative framework for interpreting or designingin vitroexperiments of protein complexation influenced by membrane binding.
Physical activity unveils the relationship between mitochondrial energetics, muscle quality and physical function in older adults
Authors: Distefano Giovanna , Standley Robert A. , Zhang Xiaolei , Carnero Elvis A. , Yi Fanchao , Cornnell Heather H. , Coen Paul M. 
Published: July 2017

ABSTRACTBackgroundThe concept of mitochondrial dysfunction in aging muscle is highly controversial. In addition, emerging evidence suggests that reduced muscle oxidative capacity and efficiency underlie the etiology of mobility loss in older adults. Here, we hypothesized that studying well phenotyped older cohorts across a wide range of physical activity would unveil a range of mitochondrial function in skeletal muscle and in turn allow us to more clearly examine the impact of ageper seon mitochondrial energetics. This also enabled us to more clearly define the relationships between mitochondrial energetics and muscle lipid content with clinically relevant assessments of muscle and physical function.MethodsThirty-nine volunteers were recruited to the following study groups; Young Active (YA, n=2F/8M, age=31.2±5.4 yrs.). Older Active (OA, n=2F/8M, age=67.5±2.7 yrs.) and Older Sedentary (OS, n=8F/11M, age=70.7±4.7 yrs.). Participants completed a graded exercise test to determine fitness (VO2peak), a submaximal exercise test to determine exercise efficiency, and daily physical activity (PA) was recorded using a tri-axial armband accelerometer. Mitochondrial energetics were determined by 1) 31P magnetic resonance spectroscopy and 2) respirometry of fiber bundles from vastus lateralis biopsies. Quadriceps function was assessed by isokinetic dynamometry and physical function by the short physical performance battery (SPPB) and stair climb test.ResultsDaily PA energy expenditure was significantly lower in OS, compared to YA and OA groups. Despite fitness being higher in YA compared to OA and OS, mitochondrial respiration, ATPMax, P/O ratio and exercise efficiency were similar in YA and OA groups and were significantly lower in OS. P/O ratio was correlated with exercise efficiency. Time to complete the stair climb and repeated chair stand tests was significantly greater for OS. Interestingly, ATPMax was related to muscle contractile performance and physical function.ConclusionsOlder adults who maintain a high amount of physical activity have better mitochondrial capacity, similar to highly active younger adults, and this is related to their better muscle quality, exercise efficiency and physical performance. This suggests that mitochondria could be an important therapeutic target for sedentary aging associated conditions including sarcopenia, dynapenia and loss of physical function.
Characterization of a set of abdominal neuroendocrine cells that regulate stress physiology using colocalized diuretic peptides inDrosophila
Authors: Zandawala Meet , Marley Richard , Davies Shireen A. , Nässel Dick R. 
Published: July 2017

AbstractMultiple neuropeptides are known to regulate water and ion balance inDrosophila melanogaster. Several of these peptides also have other functions in physiology and behavior. Examples are corticotropin-releasing factor-like diuretic hormone (diuretic hormone 44; DH44) and leucokinin (LK), both of which induce fluid secretion by Malpighian tubules (MTs), but also regulate stress responses, feeding, circadian activity and other behaviors. Here, we investigated the functional relations between the LK and DH44 signaling systems. DH44 and LK peptides are only colocalized in a set of abdominal neurosecretory cells (ABLKs). Targeted knockdown of each of these peptides in ABLKs leads to increased resistance to desiccation, starvation and ionic stress. Food ingestion is diminished by knockdown of DH44, but not LK, and water retention is increased by LK knockdown only. Thus, the two colocalized peptides display similar systemic actions, but differ with respect to regulation of feeding and body water retention. We also demonstrated that DH44 and LK have additive effects on fluid secretion by MTs. It is likely that the colocalized peptides are coreleased from ABLKs into the circulation and act on the tubules where they target different cell types and signaling systems to regulate diuresis and stress tolerance. Additional targets seem to be specific for each of the two peptides and subserve regulation of feeding and water retention. Our data suggest that the ABLKs and hormonal actions are sufficient for many of the known DH44 and LK functions, and that the remaining neurons in the CNS play other functional roles.
Contrasting responses of phosphatase kinetic parameters to nitrogen and phosphorus additions in forest soils
Authors: Zhang Xinyu , Yang Yang , Zhang Chuang , Niu Shuli , Yang Hao , Yu Guirui , Wang Huimin , Blagodatskaya Evgenia , Kuzyakov Yakov , Tian Dashuan , Tang Yuqian , Liu Shuang , Sun Xiaomin 
Published: July 2017

Abstract

Global changes include increasing nitrogen (N) and phosphorus (P) deposition, which affect microbial nutrient demand and biogeochemical cycles. The responses of P‐mineralizing enzymes to these global change components are poorly defined and are not specified in forest soils differing in P content.

We chose one site in a P‐rich and two sites in P‐poor forests and established sixteen 20 × 20 m plots at each site. Control, either N only, P only, or combined N and P, were randomly distributed through each forest site with four replicates. We investigated the effects of N and P additions over 4 years on the phosphomonoesterase potential activity (Vmax), its half‐saturation constant (Km) and its catalytic efficiency (Vmax/Km).

Without N and P additions, the enzyme kinetic parameters Vmax, Km and Vmax/Km were higher in P‐rich than in P‐poor forest soils. These parameters increased with soil pH, SOC, TN and TP contents increased.

Remarkably, P additions caused the Vmax and Km to increase in P‐rich soils, but had no effect on Vmax/Km. P additions to P‐poor soils resulted in a decrease in the Vmax/Km via the inhibitory effects of inorganic P on the Vmax. N additions had no effect on the Vmax/Km in P‐rich and P‐poor soils because of the similar increases in the Vmax and Km. The effects of combined N and P and P only additions to P‐poor soils on the Vmax and Km were similar, but were stronger than the effects of N only or P only additions on the P‐rich soils.

Phosphatase kinetic parameters were positively related to the availability of N and P in P‐rich soils, but inorganic P inhibited phosphatase activity and caused a decrease in the catalytic efficiency in P‐poor soils. More microbial community groups could contribute to the secretion of a broader spectrum of iso‐enzymes under combined additions of N and P in P‐rich soils. We conclude contrast responses of phosphatase kinetics to P and N inputs in P‐rich and P‐poor forest soils, while long‐term N deposition might mitigate P limitation by increasing phosphatase secretion.

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Evidence of an abnormal epithelial barrier in active, untreated and corticosteroid‐treated eosinophilic esophagitis
Authors: Simon D. , Page B. , Vogel M. , Bussmann C. , Blanchard C. , Straumann A. , Simon H.‐U. 
Published: July 2017

AbstractBackgroundEosinophilic esophagitis (EoE) is a chronic, immune/antigen‐mediated disease characterized by symptoms related to esophageal dysfunction and an eosinophil‐predominant inflammation. This study has aimed to investigate whether the recently observed sensitization to Candida albicans in patients with EoE is owing to pre‐existing disease and its underlying abnormal epithelial barrier or, alternatively, is linked to corticosteroid (CS) therapy.MethodsMedical histories, as well as serum and tissue samples of 60 patients with EoE (15 CS naive, 45 with current or previous CS therapy) and 20 controls, stored in the Swiss Eosinophilic Esophagitis Database (SEED) and Biobank, were analyzed. We applied ImmunoCAP to measure IgE levels and immunofluorescence techniques to examine epithelial barrier components.ResultsPatients with EoE had higher total IgE levels and were more frequently sensitized to C. albicans than controls. In EoE tissue specimens, increased numbers of eosinophils and mast cells, a higher expression levels of thymic stromal lymphopoietin (TSLP), cathelicidin, proteases, that is, the kallikreins (KLK)‐5 and KLK‐7, were observed as compared with controls, while reduced expression of lympho‐epithelial Kazal‐type‐related inhibitor (LEKTI), filaggrin, E‐cadherin, claudin, occludin, desmoglein‐1 was found, independent of CS therapy. In CS‐treated EoE, significantly lower numbers of CD1a+ cells and cathelicidin expression were noted as compared to CS‐naive EoE.ConclusionThis study provides further evidence that EoE is associated with an abnormal epithelial barrier and postulates that CS therapy, by reducing innate immune mechanisms, may promote C. albicans colonization and likely subsequent sensitization.
Therapeutic effect of capsaicin nasal treatment in patients with mixed rhinitis unresponsive to intranasal steroids
Authors: Van Gerven L. , Steelant B. , Alpizar Y. A. , Talavera K. , Hellings P. W. 
Published: July 2017

AbstractLiterature is convincing regarding the efficacy of capsaicin nasal treatment in idiopathic rhinitis (IR). However, up to 50% of IR patients do not meet the strict inclusion criteria of the trials conducted so far. As a consequence, the efficacy of capsaicin is unknown in a significant number of IR patients that do not meet the strict inclusion/exclusion criteria (J Allergy Clin Immunol. 2014;133:1332, J Allergy Clin Immunol. 2017; [Epub ahead of print]). “Mixed rhinitis” (MR) patients have more than one major etiologic factor involved in the mucosal pathology. We have no idea about the efficacy of capsaicin nasal spray in these patients nor about the time interval to seek a second application. We report here that capsaicin nasal spray is effective in a broader group of IR than the purely selected ones described before, that subjective nasal hyper‐reactivity is a good predictor of positive outcome, and that the time interval for seeking a second treatment is likely to be shorter in MR patients than in the strictly selected IR patients.
Lactobacillus reuteri DSM 17938 and a placebo both significantly reduced symptoms in children with functional abdominal pain
Authors: Maragkoudaki M , Chouliaras G , Orel R , Horvath A , Szajewska H , Papadopoulou A 
Published: July 2017

AbstractAimLactobacillus reuteri is a Gram‐positive bacterium that naturally inhabits the human intestinal tract. This study assessed how effectively the probiotic L. reuteri DSM 17938 managed childhood functional abdominal pain (FAP).MethodsWe recruited 54 children with a mean age 9.1 ± 3.8 years, who were diagnosed with FAP in the outpatient clinics of three university hospitals in Greece, Slovenia and Poland, according to the Rome III criteria, from January 2013 to December 2015. They were randomly assigned to receive either 2 × 108 colony‐forming units of L. reuteri (n = 27) or a placebo (n = 27) for four weeks.ResultsBoth L. reuteri and the placebo significantly reduced the frequency and intensity of abdominal pain episodes at four and eight weeks compared to baseline (all p < 0.001). L. reuteri decreased the use of pain relieving drugs at four weeks and the number of child school and adult work absences at four and eight weeks, unlike the placebo, which achieved nonsignificant results. However, the difference between the groups did not reach significance. No side effects were recorded.ConclusionBoth L. reuteri and the placebo were effective in alleviating pain in children with FAP, but only L. reuteri improved the child's and family's normal activities.
A longitudinal study of cognitive and educational outcomes of those born small for gestational age
Authors: Yu Bing , Garcy Anthony M. 
Published: July 2017

AbstractAimThis study examined the long‐term cognitive and educational outcomes of being born small for gestational age (SGA) and assessed whether the family's attitude towards education modified the effect of being born SGA on educational attainment.MethodsWe used anonymised data on 9598 individuals from the Stockholm Birth Cohort. This study focused on babies born in 1953 in the Stockholm metropolitan area, who were followed up for 50 years, and included educational data at the age of 13 and 48. Ordinary least squares regression analyses, modification analyses and logistic regression analyses were conducted.ResultsThe findings suggested that individuals who were born SGA (n = 798) had lower mean verbal, spatial and numerical test scores than those born appropriate for gestational age (AGA) (n = 7364) and large for gestational age (n = 1436). The SGA/AGA differences were small, but statistically significant, and the effects of being born SGA on the test scores was modified by the family's attitude towards education. The findings also suggested that attaining higher education was largely, but not entirely, explained by the family's attitude towards education.ConclusionThe detrimental effects of being born SGA were limited on cognitive and educational outcomes, but may have been reduced by positive family attitudes.
Long‐term outcomes and transmission rates in hepatitis C virus‐positive donor to hepatitis C virus‐negative kidney transplant recipients: Analysis of United States national data
Authors: Gupta Gaurav , Kang Le , Yu Jonathan W. , Limkemann Ashley J. , Garcia Victoria , Bandyopadhyay Dipankar , Kumar Dhiren , Fattah Hasan , Levy Marlon , Cotterell Adrian H. , Sharma Amit , Bhati Chandra , Reichman Trevor , King Anne L. , Sterling Richard 
Published: July 2017

AbstractThe use of kidneys from hepatitis C virus (HCV)‐positive (D+) deceased donors for HCV‐negative recipients (R−) might increase the donor pool. We analyzed the national Organ Procurement and Transplant Network (OPTN) registry from 1994 to 2014 to compare the outcomes of HCV D+/R− (n = 421) to propensity‐matched HCV‐negative donor (D−)/R− kidney transplants, as well as with waitlisted patients who never received a transplant, in a 1:5 ratio (n = 2105, per matched group). Both 5‐year graft survival (44% vs 66%; P < .001) and patient survival (57% vs 79%; P < .001) were inferior for D+/R− group compared to D−/R−. Nevertheless, 5‐year patient survival from the time of wait listing was superior for D+/R− when compared to waitlisted controls (68% vs 43%; P < .001). Of the 126 D+/R− with available post‐transplant HCV testing, HCV seroconversion was confirmed in 62 (49%), likely donor‐derived. Five‐year outcomes were similar between D+/R− that seroconverted vs D+/R− that did not (n = 64). Our analysis shows inferior outcomes for D+/R− patients although detailed data on pretransplant risk factors was not available. Limited data suggest that HCV transmission occurred in half of HCV D+/R− patients, although this might not have been the primary factor contributing to the poor observed outcomes.
Influence of kidney offer acceptance behavior on metrics of allocation efficiency
Authors: Wey Andrew , Salkowski Nicholas , Kasiske Bertram L. , Israni Ajay K. , Snyder Jon J. 
Published: July 2017

AbstractWe investigated associations of deceased donor kidney offer acceptance with likelihood of the kidney being discarded, cold ischemia time at transplant (CIT), and likelihood of the kidney being exported outside the donation service area (DSA). We used kidney offers from donors in the Scientific Registry of Transplant Recipients July 1, 2015‐June 30, 2016, and a stratified logistic regression to estimate odds ratios of acceptance for candidates wait‐listed in aDSA. We estimated associations between these ratios and likelihood of discard or export andCITat transplant. Approximately 0.50 kidneys were discarded per donor; lowerDSA‐specific offer acceptance ratios were associated with more discards (R=−0.20;P=0.006). For a median donor, theDSAwith the highest acceptance ratio would place 0.12 more kidneys per donor than theDSAwith the lowest ratio. Low acceptance ratios were associated with higherCIT(R=−0.23;P<0.001). For the median donor,CITwas 2.9 hours shorter for theDSAwith the highest versus lowest acceptance ratio. Low acceptance ratios were associated with more exports (R=−0.43;P<0.001); the probability was 15% higher for a median donor in theDSAwith the lowest versus highest acceptance ratio. Improving lower‐than‐expected offer acceptance would likely reduce discards,CIT, and exports.