bluuebunny/crossref_metadata_2025_split huggingface dataset:
N‐terminal diproline and charge group effects on the stabilization of helical conformation in alanine‐based short peptides: CD studies with water and methanol as solvent
Authors: Goyal Bhupesh , Srivastava Kinshuk Raj , Durani Susheel 
Published: April 2017

Protein folding problem remains a formidable challenge as main chain, side chain and solvent interactions remain entangled and have been difficult to resolve. Alanine‐based short peptides are promising models to dissect protein folding initiation and propagation structurally as well as energetically. The effect of N‐terminal diproline and charged side chains is assessed on the stabilization of helical conformation in alanine‐based short peptides using circular dichroism (CD) with water and methanol as solvent. A1 (Ac–Pro–Pro–Ala–Lys–Ala–Lys–Ala–Lys–Ala–NH2) is designed to assess the effect of N‐terminal homochiral diproline and lysine side chains to induce helical conformation. A2 (Ac–Pro–Pro–Glu–Glu–Ala–Ala–Lys–Lys–Ala–NH2) and A3 (Ac–dPro–Pro–Glu–Glu–Ala–Ala–Lys–Lys–Ala–NH2) with N‐terminal homochiral and heterochiral diproline, respectively, are designed to assess the effect of Glu...Lys (i, i + 4) salt bridge interactions on the stabilization of helical conformation. The CD spectra of A1, A2 and A3 in water manifest different amplitudes of the observed polyproline II (PPII) signals, which indicate different conformational distributions of the polypeptide structure. The strong effect of solvent substitution from water to methanol is observed for the peptides, and CD spectra in methanol evidence A2 and A3 as helical folds. Temperature‐dependent CD spectra of A1 and A2 in water depict an isodichroic point reflecting coexistence of two conformations, PPII and β‐strand conformation, which is consistent with the previous studies. The results illuminate the effect of N‐terminal diproline and charged side chains in dictating the preferences for extended‐β, semi‐extended PPII and helical conformation in alanine‐based short peptides. The results of the present study will enhance our understanding on stabilization of helical conformation in short peptides and hence aid in the design of novel peptides with helical structures. Copyright © 2017 European Peptide Society and John Wiley & Sons, Ltd.
Nonconvex spectral optimization algorithms for reduced‐order LPV‐LFT controllers
Authors: Shi Ye , Tuan Hoang D. , Apkarian Pierre 
Published: April 2017

SummaryA novel sequential semi‐definite programming method is developed for optimization subject to rank constraints on matrix‐valued nonlinear functions of matrix decision variables, which arise in reduced‐order linear parameter varying‐linear fractional transformational control synthesis. The global convergence of the method is easily proven without any step size control. An intensive simulation shows the clear advantage of the proposed method over the state‐of‐the‐art nonlinear matrix inequality solvers. Copyright © 2017 John Wiley & Sons, Ltd.
Littoral benthic macroinvertebrate response to water‐level fluctuations in three reservoirs of the Willamette River Basin, Oregon
Authors: Whitmore M. M. , Murphy C. A. , Johnson B. , Arismendi I. , Johnson S. L. 
Published: April 2017

AbstractHigh‐head dams throughout the Willamette River Basin, Oregon create deep reservoirs that undergo inter‐seasonal and intra‐seasonal water‐level fluctuations (WLFs). The magnitude of WLFs is dependent on competing objectives of flood control, recreation, and water releases to maintain downstream habitat and facilitate migration of Endangered Species Act–listed salmonids. These reservoirs are drawn down to minimum conservation pool in winter, refilled to full pool by late spring and undergo variable WLFs, typically between 4 and 15 m, throughout summer. Here, we investigate the impact of seasonal WLFs on the density, biomass, and species composition of littoral benthic macroinvertebrates at Fall Creek, Hills Creek, and Lookout Point reservoirs. We sampled the submerged littoral zone during spring and summer using an adapted quadrat sampling method and assessed differences in species assemblages using a non‐parametric multivariate statistical technique. Descriptors of variation in substrate, WLF, temperature, and depth were incorporated to identify environmental variables associated with variation in assemblage composition. We hypothesized that density and biomass would decrease and assemblage composition would shift between seasons in response to WLFs. We found statistically significant differences in assemblage composition between seasons and among reservoirs, but density and biomass did not respond similarly. Observed variation in assemblages was associated with surface water temperature, water depth, substrate, and WLF. None of these variables alone explained observed variation. We provide evidence that seasonal WLFs influence macroinvertebrate assemblage composition and alter habitat characteristics. Our procedure effectively quantifies changes in species assemblages in impounded systems with low densities and dynamic littoral zones and can inform water management decisions with relatively modest costs.
The Effectiveness of Prophylactic Modified Neck Dissection for Reducing the Development of Lymph Node Recurrence of Papillary Thyroid Carcinoma
Authors: Ito Yasuhiro , Miyauchi Akira , Kudo Takumi , Kihara Minoru , Fukushima Mitsuhiro , Miya Akihiro 
Published: April 2017

AbstractAimThe most frequent recurrence site of papillary thyroid carcinoma (PTC) is the cervical lymph nodes. The introduction of an electric linear probe for use with ultrasonography in 1996 improved preoperative lateral neck evaluations. Before 2006, however, our hospital routinely performed prophylactic modified neck dissection (p‐MND) for N0 or N1a PTCs >1 cm to prevent node recurrence. In 2006, we changed our policy and the indications for p‐MND to PTCs >3 cm and/or with significant extrathyroid extension. Here, we retrospectively compared lymph node recurrence‐free survival between PTCs with/without p‐MND.MethodsWe examined the cases of N0 or N1 and M0 PTC patients who underwent initial surgery in 1992–2012. To compare lymph node recurrence‐free survival between patients who did/did not undergo p‐MND, we divided these patients into three groups (excluding those whose surgery was in 2006): the 2045 patients whose surgery was performed in 1992–1996 (Group 1), the 2989 with surgery between 1997 (post‐introduction of ultrasound electric linear probes) and 2005 (Group 2), and the 5332 operated on in 2007–2012 (Group 3).ResultsThe p‐MND performance rate of Group 3 (9%) was much lower than that of Group 1 (80%), but the lymph node recurrence‐free survival of the former was significantly better, probably due to differences in clinical features and neck evaluations by ultrasound between the two groups. Our analysis of the patients aged <75 years with 1.1–4‐cm PTCs in Groups 2 and 3 showed that p‐MND did not improve lymph node recurrence‐free survival. p‐MND did significantly improve lymph node recurrence‐free survival for the extrathyroid extension‐positive 3.1–4‐cm PTCs, but not for the other subsets.ConclusionsAbolishing routine p‐MND for PTCs in 2006 did not decrease lymph node recurrence‐free survival, probably due to improved ultrasound preoperative neck evaluations and clinical feature changes. Selective p‐MND for high‐risk cases improved lymph node recurrence‐free survival.
Clinical setting-based smoking cessation programme and the quality of life in people living with HIV in Austria and Germany
Authors: Grabovac Igor , Brath Helmut , Schalk Horst , Degen Olaf , Dorner Thomas E. 
Published: April 2017

AbstractPurposeTo report on the global quality of life (QOL) in people living with HIV (PLWHIV) and how a smoking cessation intervention influences the changes in QOL.MethodsParticipants were asked to fill out a questionnaire during visits to their HIV outpatient clinic consisting of sociodemographic information, general health data and the WHOQOL HIV-Bref. Exhaled carbon monoxide measurements were used to confirm the smoking status, based on which participants classified as smokers received a short 5 min structured intervention and were offered participation in a full smoking cessation programme consisting of five sessions. Follow-up was done 8 months after the baseline.ResultsOverall 447 (mean age = 45.5) participants took part with 221 being classified as smokers. A total of 165 (74.6%) participants received a short intervention and 63 (29.4%) agreed to participate in the full program. At baseline, differences in QoL were observed, where smokers had lower QoL in domains of physical (M = 16.1 vs. 15.3,p = 0.009) and psychological (M = 15.3 vs. 14.6,p = 0.021) well-being, independency level (M = 16.1 vs. 15.2,p = 0.003) and environment (M = 16.5 vs. 16.0,p = 0.036). At study end, 27 (12.2%) participants quit smoking; 12 (19.0%) participants of the full programme and 15 (14.7%) that received the short intervention. There were no significant differences in QoL between those that continued to smoke and quitters at follow-up.ConclusionQuality of life results may be used to better understand the underlying motivation of PLWHIV who start cessation programs. In order to reduce the high prevalence and health burden that smoking causes in PLWHIV, it is necessary to introduce effective interventions that can be used in the clinical settings.
Hydrocarbon composition and structural parameters of resins and asphaltenes of naphthenic oils of northern West Siberia
Authors: Pevneva G.S. , Fursenko E.A. , Voronetskaya N.G. , Mozhayskaya M.V. , Golovko A.K. , Nesterov I.I. , Kashirtsev V.A. , Shevchenko N.P. 
Published: April 2017

Abstract
The composition of saturated and aromatic hydrocarbons and the structural-group characteristics of resins and asphaltenes in four oils of northern West Siberia have been studied. As follows from the distribution of hydrocarbons, the Cenomanian oils (pools in the beds PK and K2c) of the Russkoe, Barsukovskoe, and Pangodinskoe fields are naphthenic and the Pangodinskoe oil sample from the Lower Cretaceous pool (bed BN9) is methanoic. The hydrocarbon composition pattern of the saturated fraction and the characteristics of the heterocyclic components of these oils point to their formation from dispersed organic matter of mixed genesis in the oil window. Hence, the oil source rocks are localized at depths much greater than the present-day level of the oil pools. Secondary (cryptohypergene) alterations (oxidation and biodegradation) in the shallow-depth oils determined their current predominantly naphthenic composition and considerably hamper reconstruction of the types of initial dispersed organic matter. We assume that the mixed genetic type of the studied oils is not only due to their heterogeneous source but also due to the reorganization of primary oil pools at the Cenozoic stage of tectogenesis. The Cenomanian Russkoe and Pangodinskoe naphthenic oils are saturated with adamantoids, which can be selectively accumulated during biodegradation.
BROKEN-HEART, COMMON LIFE, HETEROGENEITY: ANALYZING THE SPOUSAL MORTALITY DEPENDENCE
Authors: Lu Yang 
Published: April 2017

AbstractUsing data on joint annuities, we conduct an analysis of the inter-couple lifetime dependence. We estimate a mixed proportional hazards model with treatment effects, which disentangles the broken-heart syndrome from the spurious risk dependence induced by unobserved heterogeneities. We use a flexible semi-parametric distribution for the unobserved heterogeneities to allow for either positive or negative spurious risk dependence. We find that the effect of losing one's spouse is asymmetric for the two sexes. Moreover, although the broken-heart syndrome explains a large portion of the dependency, there is evidence of positive spurious risk dependence. These findings have important implications for the pricing of joint insurance products. Failure to take into account either of these two effects leads to pricing error that can be either positive or negative, depending on the characteristics of the couple.
Biological activity of tumor-treating fields in preclinical glioma models
Authors: Silginer Manuela , Weller Michael , Stupp Roger , Roth Patrick 
Published: April 2017

AbstractGlioblastoma is the most common and aggressive form of intrinsic brain tumor with a very poor prognosis. Thus, novel therapeutic approaches are urgently needed. Tumor-treating fields (TTFields) may represent such a novel treatment option. The aim of this study was to investigate the effects of TTFields on glioma cells, as well as the functional characterization of the underlying mechanisms. Here, we assessed the anti-glioma activity of TTFields in several preclinical models. Applying TTFields resulted in the induction of cell death in a frequency- and intensity-dependent manner in long-term glioma cell lines, as well as glioma-initiating cells. Cell death occurred in the absence of caspase activation, but involved autophagy and necroptosis. Severe alterations in cell cycle progression and aberrant mitotic features, such as poly- and micronucleation, preceded the induction of cell death. Furthermore, exposure to TTFields led to reduced migration and invasion, which are both biological hallmarks of glioma cells. The combination of TTFields with irradiation or the alkylating agent, temozolomide (TMZ), resulted in additive or synergistic effects, and the O6-methyl-guanine DNA methyltransferase status did not influence the efficacy of TTFields. Importantly, TMZ-resistant glioma cells were responsive to TTFields application, highlighting the clinical potential of this therapeutic approach. In summary, our results indicate that TTFields induce autophagy, as well as necroptosis and hamper the migration and invasiveness of glioma cells. These findings may allow for a more detailed clinical evaluation of TTFields beyond the clinical data available so far.
FRET biosensor uncovers cAMP nano-domains at β-adrenergic targets that dictate precise tuning of cardiac contractility
Authors: Surdo Nicoletta C. , Berrera Marco , Koschinski Andreas , Brescia Marcella , Machado Matias R. , Carr Carolyn , Wright Peter , Gorelik Julia , Morotti Stefano , Grandi Eleonora , Bers Donald M. , Pantano Sergio , Zaccolo Manuela 
Published: April 2017

AbstractCompartmentalized cAMP/PKA signalling is now recognized as important for physiology and pathophysiology, yet a detailed understanding of the properties, regulation and function of local cAMP/PKA signals is lacking. Here we present a fluorescence resonance energy transfer (FRET)-based sensor, CUTie, which detects compartmentalized cAMP with unprecedented accuracy. CUTie, targeted to specific multiprotein complexes at discrete plasmalemmal, sarcoplasmic reticular and myofilament sites, reveals differential kinetics and amplitudes of localized cAMP signals. This nanoscopic heterogeneity of cAMP signals is necessary to optimize cardiac contractility upon adrenergic activation. At low adrenergic levels, and those mimicking heart failure, differential local cAMP responses are exacerbated, with near abolition of cAMP signalling at certain locations. This work provides tools and fundamental mechanistic insights into subcellular adrenergic signalling in normal and pathological cardiac function.
Structural investigations on orotate phosphoribosyltransferase from Mycobacterium tuberculosis, a key enzyme of the de novo pyrimidine biosynthesis
Authors: Donini Stefano , Ferraris Davide M. , Miggiano Riccardo , Massarotti Alberto , Rizzi Menico 
Published: April 2017

AbstractThe Mycobacterium tuberculosis orotate phosphoribosyltransferase (MtOPRT) catalyses the conversion of α-D-5-phosphoribosyl-1-pyrophosphate (PRPP) and orotate (OA) in pyrophosphate and orotidine 5′-monophosphate (OMP), in presence of Mg2+. This enzyme is the only responsible for the synthesis of orotidine 5′-monophosphate, a key precursor in the de novo pyrimidine biosynthesis pathway, making MtOPRT an attractive drug target for the development of antitubercular agents. We report the crystal structures of MtOPRT in complex with PRPP (2.25 Å resolution), inorganic phosphate (1.90 Å resolution) and the exogenous compound Fe(III) dicitrate (2.40 Å resolution). The overall structure of the mycobacterial enzyme is highly similar to those described for other OPRTases, with the “flexible loop” assuming a well define conformation and making specific contacts with the Fe(III)-dicitrate complex. The structures here reported add to the knowledge of a potential drug target for tuberculosis, and will provide a useful tool for the structure-based drug design of potent enzyme inhibitors.
A Systems Pharmacology Approach to Determine Active Compounds and Action Mechanisms of Xipayi KuiJie’an enema for Treatment of Ulcerative colitis
Authors: Yu Wei , Li Zhihong , Long Fei , Chen Wen , Geng Yurong , Xie Zhiyong , Yao Meicun , Han Bo , Liu Teigang 
Published: April 2017

AbstractXipayi Kui Jie’an (KJA), a type of traditional Uygur medicine (TUM), has shown promising therapeutic effects in Ulcerative colitis (UC). Owing to the complexity of TUM, the pharmacological mechanism of KJA remains vague. Therefore, the identification of complex molecular mechanisms is a major challenge and a new method is urgently needed to address this problem. In this study, we established a feasible pharmacological model based on systems pharmacology to identify potential compounds and targets. We also applied compound-target and target-diseases network analysis to evaluate the action mechanisms. According to the predicted results, 12 active compounds were selected and these compounds were also identified by HPLC-ESI-MS/MS analysis. The main components were tannins, this result is consistent with the prediction. The active compounds interacted with 22 targets. Two targets including PTGS2 and PPARG were demonstrated to be the main targets associated with UC. Systematic analysis of the constructed networks revealed that these targets were mainly involved in NF-κB signaling pathway. Furthermore, KJA could also regulate the CD4 + CD25 + Foxp3 + Treg cells. In conclusion, this systems pharmacology-based approach not only explained that KJA could alleviate the UC by regulating its candidate targets, but also gave new insights into the potential novel therapeutic strategies for UC.
Trends in the pervasiveness of type 2 diabetes, impaired fasting glucose and co-morbidities during an 8-year-follow-up of nationwide Korean population
Authors: Noh Junghyun , Han Kyung-Do , Ko Seung-Hyun , Ko Kyung Soo , Park Cheol-Young 
Published: April 2017

AbstractThe prevalence and incidence of type 2 diabetes, impaired fasting glucose, and co-morbidities from 2006 to 2013 in the population aged ≥30 years were estimated using the Korean NHIS database. The prevalence of type 2 diabetes increased 0.2–0.5% annually, from 5.6% in 2006 to 8% in 2013. The prevalence of type 2 diabetes was higher in men than in women and increased with age. The incidence of type 2 diabetes was 0.81% in 2013 and was 1.4 times higher in men than in women and increased with age. An overall decrease in the incidence rate occurred from 2006 to 2013(from 0.95 to 0.81%), which was mirrored in all age groups except the 30–39-year-old group. The prevalence of IFG was 25% in 2013. The prevalence of hypertension(62.5 vs 16.9%) and dyslipidemia(49.5 vs 9.7%) were more prevalent in patients with type 2 diabetes compared to non-diabetic cases. This study shows that type 2 diabetes is both common and increasing and that one-quarter of the Korean adult population has IFG. We also confirmed that the prevalence of hypertension and dyslipidemia are 3.7-fold and 5.1-fold higher, respectively, in diabetic patients than in non-diabetic adults.
SUV39H1 Reduction Is Implicated in Abnormal Inflammation in COPD
Authors: Chen Tzu-Tao , Wu Sheng-Ming , Ho Shu-Chuan , Chuang Hsiao-Chi , Liu Chien-Ying , Chan Yao-Fei , Kuo Lu-Wei , Feng Po-Hao , Liu Wen-Te , Chen Kuan-Yuan , Hsiao Ta-Chih , Juang Jer-Nan , Lee Kang-Yun 
Published: April 2017

AbstractChronic obstructive pulmonary disease(COPD) is characterized by enhanced chronic inflammation in the airways, lung parenchyma, and circulation. We investigated whether SUV39H1, a histone methyltransferase, is causatively implicated in the abnormal inflammation observed in COPD. The SUV39H1 and H3K9me3 levels were reduced in peripheral blood mononuclear cells(PBMCs), primary human small airway epithelial cells(HSAEpCs) and lung tissues from COPD patients, which were correlated with poor lung function and the serum IL-8 and IL-6 levels. A specific SUV39H1 inhibitor, chaetocin, induced a distinct COPD panel of inflammatory cytokines in normal PBMCs. Mechanistically, chaetocin reduced the SUV39H1 and H3K9me3 levels in the native IL-8 promoter in normal HSAEpCs, which mimicked unstimulated COPD HSAEpCs and led to decreased HP-1α levels and increased RNA polymerase II levels. SUV39H1 knockdown reproduced the pattern of COPD inflammation, whereas SUV39H1 overexpression in COPD HSAEpCs rescued the H3K9me3 levels and suppressed inflammation. In COPD mice, chaetocin further repressed the SUV39H1/H3K9me3 levels and enhanced inflammation. SUV39H1 epigenetically controls a distinct panel of pro-inflammatory cytokines. Its reduction in COPD leads to a loss of the repressive chromatin mark H3K9me3 and confers an abnormal inflammatory response to stimulators. SUV39H1 and its regulatory pathways are potential therapeutic targets for COPD.
Saffron Flower Extract Promotes Scratch Wound Closure of Keratinocytes and Enhances VEGF Production
Authors: Verjee Sheela , Garo Eliane , Pelaez Sarah , Fertig Orlando , Hamburger Matthias , Butterweck Veronika 
Published: April 2017

AbstractDuring saffron (Crocus sativus) spice production, large amounts of floral biowaste are generated. It was the aim of this study to develop a value-added product from saffron floral biowaste to be used as a natural cosmetic ingredient. HPLC-PDA-MS analysis of saffron flower extracts revealed the presence of flavonols with the highest amounts in the acetone extract. Kaempferol-3-O-sophoroside was identified as the main flavonoid in the acetone extract (saffron flower acetone extract). Saffron flower acetone extract and kaempferol-3-O-sophoroside were tested in HaCaT cells for potential effects on cell migration, proliferation, and for anti-inflammatory properties. Saffron flower acetone extract concentration dependently (50–200 µg/mL) augmented cell proliferation, as indicated by an increased BrdU-incorporation, while kaempferol-3-O-sophoroside (1–50 µM) had no effect. Furthermore, treatment of HaCaT cells with saffron flower acetone extract, but not with kaempferol-3-O-sophoroside, concentration-dependently increased vascular endothelial growth factor secretion (control 49.72 pg/mL vs. saffron flower acetone extract at 200 µg/mL 218.60 pg/mL). Cell migration was determined using time-lapse microscopy and a modification of the scratch-wound assay in which saffron flower acetone extract significantly improved wound closure compared to the untreated control. Overproduction of the proinflammatory cytokines interleukin-8 and interleukin-6 in HaCaT cells was induced by TNF-α. Kaempferol-3-O-sophoroside (10–50 µM), but not saffron flower acetone extract, inhibited TNF-α-induced IL-8 secretion. The effect was comparable to 10 µM hydrocortisone (positive control). Interestingly, saffron flower acetone extract further increased IL-6 levels in TNF-α-treated HaCaT cells in a concentration-dependent manner. In summary, the pronounced wound healing properties of saffron flower acetone extract present a promising application for the cosmetic industry.