bluuebunny/crossref_metadata_2025 huggingface dataset:
Increased troponin I is associated with fatal outcome in acquired thrombotic thrombocytopenic purpura
Authors: Brazelton Jason , Oster Robert A. , McCleskey Brandi , Fuller Jessica , Adamski Jill , Marques Marisa B.
Published: September 2016

Thrombotic thrombocytopenic purpura (TTP) has >90% mortality without therapeutic plasma exchange (TPE). Despite TPE, approximately 10% of patients still die, presumably from cardiac ischemia. We sought clinical or laboratory parameters associated with death by reviewing the records of all patients hospitalized with acquired TTP in our institution for 10 years, and collect demographics and results for hemoglobin, platelet count, creatinine, lactate dehydrogenase, transaminases, total bilirubin, creatinine kinase (CK), CK‐MB, and troponin I. Sixty‐eight patients were admitted 88 times, and 11 died. Survivors and non‐survivors were similar in terms of sex, ethnicity, thrombocytopenia, and degree of anemia at presentation, while the latter were older, had worse renal function and higher CK, CK‐MB, and troponin I (univariate analysis). However, only troponin I remained significant on multivariate analyses. We propose that patients with TTP should be monitored with troponin I to detect significant myocardial ischemia that could predict death despite TPE.
Genetic disruption of the KLF1 gene to overexpress the γ‐globin gene using the CRISPR/Cas9 system
Authors: Shariati Laleh , Khanahmad Hossein , Salehi Mansoor , Hejazi Zahra , Rahimmanesh Ilnaz , Tabatabaiefar Mohammad Amin , Modarressi Mohammad Hossein
Published: September 2016

Background

β‐thalassemia comprises a major group of human genetic disorders involving a decrease in or an end to the normal synthesis of the β‐globin chains of hemoglobin. KLF1 is a key regulatory molecule involved in the γ‐ to β‐globin gene switching process directly inducing the expression of the β‐globin gene and indirectly repressing γ‐globin. The present study aimed to investigate the ability of an engineered CRISPR/Cas9 system with respect to disrupting the KLF1 gene to inhibit the γ‐ to β‐hemoglobin switching process in K562 cells.

Methods

We targeted three sites on the KLF1 gene, two of which are upstream of codon 288 in exon 2 and the other site being in exon 3.

Results

The average indel percentage in the cells transfected with CRISPR a, b and c was approximately 24%. Relative quantification was performed for the assessment of γ‐globin expression. The levels of γ‐globin mRNA on day 5 of differentiation were 8.1‐, 7.7‐ and 1.8‐fold in the cells treated with CRISPR/Cas9 a, b and c, respectively,compared to untreated cells. The measurement of HbF expression levels confirmed the same results.

Conclusions

The findings obtained in the present study support the induction of an indel mutation in the KLF1 gene leading to a null allele. As a result, the effect of KLF1 on the expression of BCL11A is decreased and its inhibitory effect on γ‐globin gene expression is removed. Application of CRISPR technology to induce an indel in the KLF1 gene in adult erythroid progenitors may provide a method for activating fetal hemoglobin expression in individuals with β‐thalassemia or sickle cell disease.
Synthesis and Anti‐influenza Virus Activity of Novel bis(4H‐chromene‐3‐carbonitrile) Derivatives
Authors: Abdella Amna M. , Moatasim Yassmin , Ali Mohamed A. , Elwahy Ahmed H. M. , Abdelhamid Ismail A.
Published: September 2016

An efficient and convenient method for the synthesis of bis(4H‐chromene‐3‐carbonitrile) derivatives by one‐pot, multicomponent reaction of bis‐aldehydes, malononitrile, and dimedone in the presence of a catalytic amount of piperidine is reported. Bis(2‐benzylidene‐1H‐indene)‐1,3‐(2H)‐dione derivatives were obtained as the main products as a result of reaction of the bis(arylidenemalononitriles) with indandione. The anti‐influenza H5N1 virus activities of the newly prepared bis‐chromene derivatives are also investigated.
Carbon screen‐printed electrodes on ceramic substrates for label‐free molecular detection of antibiotic resistance
Authors: Obaje Eleojo A. , Cummins Gerard , Schulze Holger , Mahmood Salman , Desmulliez Marc P.Y. , Bachmann Till T.
Published: September 2016

The growing threat posed by antimicrobial resistance on the healthcare and economic well‐being of mankind is pushing the need to develop novel and improved diagnostic platforms for its rapid detection at point of care, facilitating better patient management strategies during antibiotic therapy. In this paper, we present the manufacturing and characterisation of a low‐cost carbon screen‐printed electrochemical sensor on a ceramic substrate. Using label‐free electrochemical impedance spectroscopy, the sensor is demonstrated for the detection of blaNDM, which is one of the main antimicrobial resistance factors in carbapenem‐resistant Enterobacteriaceae. The electrochemical performance of the newly fabricated sensor was initially investigated in relation to the function of its underlying composite materials, evaluating the choice of carbon and dielectric pastes by characterising properties like surface roughness, wetting and susceptibility of unspecific DNA binding. Subsequently, the sensor was used in an electrochemical impedance spectroscopy assay for the sensitive and specific detection of synthetic blaNDM targets achieving a detection limit of 200 nM. The sensor properties and performance demonstrated in this study proved the suitability of the new electrode materials and manufacturing for further point‐of‐care test development as an inexpensive and effective alternative to gold electrodes sensor.
Neuropeptides shaping the central nervous system development: Spatiotemporal actions of VIP and PACAP through complementary signaling pathways
Authors: Maduna Tando , Lelievre Vincent
Published: September 2016

Pituitary adenylate cyclase–activating polypeptide (PACAP) and vasoactive intestinal peptide (VIP) are neuropeptides with wide, complementary, and overlapping distributions in the central and peripheral nervous systems, where they exert important regulatory roles in many physiological processes. VIP and PACAP display a large range of biological cellular targets and functions in the adult nervous system including regulation of neurotransmission and neuroendocrine secretion and neuroprotective and neuroimmune responses. As the main focus of the present review, VIP and PACAP also have been long implicated in nervous system development and maturation through their interaction with the seven transmembrane domain G protein–coupled receptors, PAC1, VPAC1, and VPAC2, initiating multiple signaling pathways. Compared with PAC1, which solely binds PACAP with very high affinity, VPACs exhibit high affinities for both VIP and PACAP but differ from each other because of their pharmacological profile for both natural accessory peptides and synthetic or chimeric molecules, with agonistic and antagonistic properties. Complementary to initial pharmacological studies, transgenic animals lacking these neuropeptides or their receptors have been used to further characterize the neuroanatomical, electrophysiological, and behavioral roles of PACAP and VIP in the developing central nervous system. In this review, we recapitulate the critical steps and processes guiding/driving neurodevelopment in vertebrates and superimposing the potential contribution of PACAP and VIP receptors on the given timeline. We also describe how alterations in VIP/PACAP signaling may contribute to both (neuro)developmental and adult pathologies and suggest that tuning of VIP/PACAP signaling in a spatiotemporal manner may represent a novel avenue for preventive therapies of neurological and psychiatric disorders. © 2016 Wiley Periodicals, Inc.
Effects of melatonin on severe crush spinal cord injury–induced reactive astrocyte and scar formation
Authors: Krityakiarana Warin , Sompup Kamonrapat , Jongkamonwiwat Nopporn , Mukda Sujira , Pinilla Fernando Gomez , Govitrapong Piyarat , Phansuwan‐Pujito Pansiri
Published: September 2016

The present work aimed at analyzing the effects of melatonin on scar formation after spinal cord injury (SCI). Upregulation of reactive astrocyte under SCI pathological conditions has been presented in several studies. It has been proved that the crucial factor in triggering this upregulation is proinflammatory cytokines. Moreover, scar formation is an important barrier to axonal regeneration through the lesion area. Melatonin plays an important role in reducing inflammation, but its effects on scar formation in the injured spinal cord remain unknown. Hence, we used the model of severe crush injury in mice to investigate the effects of melatonin on scar formation. Mice were randomly separated into four groups; SCI, SCI+Melatonin 1 (single dose), SCI+Melatonin 14 (14 daily doses), and control. Melatonin was administered by intraperitoneal injection (10 mg/kg) after injury. Immunohistochemical analysis, Western blot, and behavioral evaluation were used to explore the effects of melatonin after SCI for 14 days. The melatonin‐treated mice presented higher expression of neuronal markers (P < 0.001). Remarkably, the inflammatory response appeared to be greatly reduced in the SCI+Melatonin 14 group (P < 0.001), which also displayed less scar formation (P < 0.05). These findings suggest that melatonin inhibits scar formation by acting on inflammatory cytokines after SCI. Overall, our results suggest that melatonin is a promising treatment strategy after SCI that deserves further investigation. © 2016 Wiley Periodicals, Inc.
Measuring Stakeholder Perspectives on Environmental and Community Stability in a Tourism‐Dependent Economy
Authors: Carr Liam M. , Liu Daniel Y.
Published: September 2016

Tourism is promoted as an environmentally beneficial activity for Caribbean economies. Yet degradation still occurs and more integrated policy approaches are needed. Using Q‐methodology within a social‐ecological system (SES) framework, we quantified the importance of various policy issues to stakeholders in Providenciales, Turks and Caicos Islands, where tourism produces 77% of its GDP. Stakeholders agree Providenciales' economy benefits from a healthy marine environment, but disagree over which SES drivers are functionally important. Our results show that Q‐methodology is a robust tool for informing the policy‐making process and quantifying stakeholder views in a tourism‐dependent economy. Copyright © 2016 John Wiley & Sons, Ltd.
Behavioral connectivity among bighorn sheep suggests potential for disease spread
Authors: Borg Nathan J. , Mitchell Michael S. , Lukacs Paul M. , Mack Curt M. , Waits Lisette P. , Krausman Paul R.
Published: September 2016

Connectivity is important for population persistence and can reduce the potential for inbreeding depression. Connectivity between populations can also facilitate disease transmission; respiratory diseases are one of the most important factors affecting populations of bighorn sheep (Ovis canadensis). The mechanisms of connectivity in populations of bighorn sheep likely have implications for spread of disease, but the behaviors leading to connectivity between bighorn sheep groups are not well understood. From 2007–2012, we radio‐collared and monitored 56 bighorn sheep in the Salmon River canyon in central Idaho. We used cluster analysis to define social groups of bighorn sheep and then estimated connectivity between these groups using a multi‐state mark‐recapture model. Social groups of bighorn sheep were spatially segregated and linearly distributed along the Salmon River canyon. Monthly probabilities of movement between adjacent male and female groups ranged from 0.08 (±0.004 SE) to 0.76 (±0.068) for males and 0.05 (±0.132) to 0.24 (±0.034) for females. Movements of males were extensive and probabilities of movement were considerably higher during the rut. Probabilities of movement for females were typically smaller than those of males and did not change seasonally. Whereas adjacent groups of bighorn sheep along the Salmon River canyon were well connected, connectivity between groups north and south of the Salmon River was limited. The novel application of a multi‐state model to a population of bighorn sheep allowed us to estimate the probability of movement between adjacent social groups and approximate the level of connectivity across the population. Our results suggest high movement rates of males during the rut are the most likely to result in transmission of pathogens among both male and female groups. Potential for disease spread among female groups was smaller but non‐trivial. Land managers can plan grazing of domestic sheep for spring and summer months when males are relatively inactive. Removal or quarantine of social groups may reduce probability of disease transmission in populations of bighorn sheep consisting of linearly distributed social groups. © 2016 The Wildlife Society.
Stable benefits of bilateral over unilateral cochlear implantation after two years: A randomized controlled trial
Authors: van Zon Alice , Smulders Yvette E. , Stegeman Inge , Ramakers Geerte G. J. , Kraaijenga Veronique J. C. , Koenraads Simone P. C. , Zanten Gijsbert A. Van , Rinia Albert B. , Stokroos Robert J. , Free Rolien H. , Frijns Johan H. M. , Huinck Wendy J. , Mylanus Emmanuel A. M. , Tange Rinze A. , Smit Adriana L. , Thomeer Hans G. X. M. , Topsakal Vedat , Grolman Wilko
Published: September 2016

Objectives/Hypothesis

To investigate hearing capabilities and self‐reported benefits of simultaneous bilateral cochlear implantation (BiCI) compared with unilateral cochlear implantation (UCI) after a 2‐year follow‐up and to evaluate the learning effect of cochlear implantees over time.

Study Design

Multicenter randomized controlled trial.

Methods

Thirty‐eight postlingually deafened adults were included in this study and randomly allocated to either UCI or simultaneous BiCI. Our primary outcome was speech intelligibility in noise, with speech and noise coming from straight ahead (Utrecht–Sentence Test with Adaptive Randomized Roving levels). Secondary outcomes were speech intelligibility in noise with spatially separated sources, speech intelligibility in silence (Dutch phoneme test), localization capabilities and self‐reported benefits assessed with different quality of hearing and quality of life (QoL) questionnaires. This article describes the results after 2 years of follow‐up.

Results

We found comparable results for the UCI and simultaneous BiCI group, when speech and noise were both presented from straight ahead. Patients in the BiCI group performed significantly better than patients in the UCI group, when speech and noise came from different directions (P = .01). Furthermore, their localization capabilities were significantly better. These results were consistent with patients' self‐reported hearing capabilities, but not with the questionnaires regarding QoL. We found no significant differences on any of the subjective and objective reported outcomes between the 1‐year and 2‐year follow‐up.

Conclusions

This study demonstrates important benefits of simultaneous BiCI compared with UCI that remain stable over time. Bilaterally implanted patients benefit significantly in difficult everyday listening situations such as when speech and noise come from different directions. Furthermore, bilaterally implanted patients are able to localize sounds, which is impossible for unilaterally implanted patients.

Level of Evidence

1b Laryngoscope, 127:1161–1168, 2017
Risk of tinnitus in patients with sleep apnea: A nationwide, population‐based, case‐control study
Authors: Koo Malcolm , Hwang Juen‐Haur
Published: September 2016

Objective

To investigate the risk of tinnitus in patients with sleep disturbance or sleep apnea.

Study Design

Case control study.

Methods

We identified 21,798 middle‐aged and elderly patients with otolaryngologist‐diagnosed tinnitus between January 1, 2000, and December 31, 2012, from the Longitudinal Health Insurance Database 2000 of the Taiwan National Health Insurance Research Database. A total of 108,990 controls were also identified from the same database based on frequency‐matching on 10‐year age interval, sex, and year of index date of the cases. Diagnoses of sleep disturbance (International Classification of Diseases, 9th Revision, Clinical Modification [ICD‐9‐CM] codes 780.50, 780.52, 307.4) and sleep apnea (ICD‐9‐CM codes 780.51, 780.53, 780.57) in the cases and controls prior to the index date were assessed. The risks of tinnitus in patients with sleep disturbance and sleep apnea were separately evaluated with multivariate logistic regression analyses.

Results

The mean age of the total 130,788 patients was 59.8 years, and 47% of them were males. The risk of tinnitus was higher in patients with sleep disturbance compared to those without the condition (adjusted odds ratio [OR] = 1.13, 95% confidence interval [CI] [95% CI] = 1.11–1.17), and the risk of tinnitus was higher in patients with sleep apnea compared to those without the condition (adjusted OR = 1.36, 95% CI = 1.16–1.60).

Conclusion

In this population‐based, case‐control study, the risk of tinnitus was found to be significantly higher among middle‐aged and elderly Taiwanese patients with sleep disturbances, especially with sleep apnea.

Level of Evidence

3b. Laryngoscope, 127:2171–2175, 2017
Synthesis of Unsaturated Nonionic Poly(ester‐sulfones) via Acyclic Diene Metathesis (ADMET) Polymerization and Anode‐Selective Electrophoretic Deposition
Authors: Kawarazaki Isamu , Takasu Akinori
Published: September 2016

Nonionic aliphatic polymers containing ester and sulfonyl moieties, [poly(ester‐sulfones)s] were found to undergo anode‐selective electrophoresis under electrophoretic deposition conditions. Herein are reported the syntheses of unsaturated nonionic polyesters containing sulfide linkages and double bonds on the polymer backbone via acyclic diene metathesis polymerization using a Grubbs' catalyst. Subsequent oxone oxidation was carried out, affording the corresponding poly(ester‐sulfone), followed by electrophoretic deposition of the unsaturated poly(ester‐sulfone) onto stainless steel. Subsequent UV‐irradiation cured the deposited film, improving the peeling strength of the coating.

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Directional Mechanochromic Luminescent Behavior in Liquid Crystalline Composite Polymeric Films
Authors: Kondo Mizuho , Nakanishi Takao , Matsushita Takumi , Kawatsuki Nobuhiro
Published: September 2016

The doping of a liquid crystalline (LC) photoemissive compound into a LC polymethacrylate with photoemissive side groups induces repeatable changes in the photoemission wavelength upon mechanical grinding and thermal annealing. The color changes observed in a handwritten pattern demonstrate the successful induction of anisotropic photoemission behavior in a LC composite polymeric film parallel to the grinding direction. The LC characteristics of the composite films play an important role in the directional selectivity of the polarized mechanoinduced color change.

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Using Nucleobase Pairing as Supermolecule Linker to Assemble the Bionic Copolymer Nanoparticles with Small Size
Authors: Zhao Xuefei , Deng Hongzhang , Feng Hailiang , Zhang Jianhua , Dong Anjie , Deng Liandong
Published: September 2016

The specificity hydrogen bonds of nucleobase pairs are the main linker in DNA and RNA. Compared with conventional covalent‐linking polymer to prepare nanoparticles (NPs), nucleobase pairs as supermolecule linker to assemble the bionic copolymer NPs may be an innovative way. Adenine (A) modified poly(ε‐caprolactone) and thymine (T) modified poly(ethylene glycol) are prepared to assemble multiple hydrogen bonds linked NPs in situ. The introduction of multiple hydrogen bonds into NPs results in a unique method to prepare NPs replacing the conventional assemble method. These NPs exhibit narrow size distribution with the average diameter of 45 nm under pH 7.4. The chemical shift of T NH proton moves from 11.30 to 11.05 ppm with increasing temperature from 25 to 80 °C, and the same phenomenon also appears in A NH2 proton resonance, which demonstrate the existence of hydrogen bonds. The low cytotoxicity of NPs is confirmed by MTT assay using MCF7 tumor cells. Collectively, the novel method opens the possibilities to combine bionics in assembling small size nanoparticles.

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Ultrasonic Cavitation Induced Shape‐Memory Effect in Porous Polymer Networks
Authors: Zhang Pengfei , Behl Marc , Peng Xingzhou , Razzaq Muhammad Yasar , Lendlein Andreas
Published: September 2016

Inspired by the application of ultrasonic cavitation based mechanical force (CMF) to open small channels in natural soft materials (skin or tissue), it is explored whether an artificial polymer network can be created, in which shape‐changes can be induced by CMF. This concept comprises an interconnected macroporous rhodium‐phosphine (Rh‐P) coordination polymer network, in which a CMF can reversibly dissociate the Rh‐P microphases. In this way, the ligand exchange of Rh‐P coordination bonds in the polymer network is accelerated, resulting in a topological rearrangement of molecular switches. This rearrangement of molecular switches enables the polymer network to release internal tension under ultrasound exposure, resulting in a CMF‐induced shape‐memory capability. The interconnected macroporous structure with thin pore walls is essential for allowing the CMF to effectively permeate throughout the polymer network. Potential applications of this CMF‐induced shape‐memory polymer can be mechanosensors or ultrasound controlled switches.

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Comb‐Like Poly(Ether‐Sulfone) Membranes Derived from Planar 6,12‐Diaryl‐5,11‐Dihydroindolo[3,2‐b]Carbazole Monomer for Alkaline Fuel Cells
Authors: Zuo Peipei , Su Yumiao , Li Wenmu
Published: September 2016

Highly conductive anion exchange membranes (AEMs), along with the ability to suppress swelling, are critical but challenging requirements for alkaline fuel cell applications. To achieve this criterion, a series of poly(ether sulfone)s (PESFs) with flexible alkyl imidazolium pendants attached directly on large planar 6,12‐bis(4‐hydroxyphenyl)‐5,11‐dihydroindolo[3,2‐b]carbazole (DCP) units is reported. The planar DCP units stabilize the hydrophobic phase through strong π‐π interactions and also facilitate the formation of ionic conducting channels through self assembly of hydrophilic pendants. The AEM prepared here, based on rational design, has a relatively low ion exchange capacity (IEC) of 1.86 × 10–3 mol g–1 and exhibits high hydroxide ion (OH–) conductivity of 101 × 10–3 S cm–1, a low swelling ratio of 9.3% and a water uptake of 39.6%. Furthermore, the AEMs reported in this paper have excellent stability in 1 m NaOH solution at 80 °C over 500 h. Therefore, the synthesized polymers offer a new insight into the design of high performance materials for AEMs.

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Analysis of unsteady stagnation‐point flow over a shrinking sheet and solving the equation with rational Chebyshev functions
Authors: Foroutan Mohammadreza , Ebadian Ali , Najafzadeh Shahram
Published: September 2016

This paper investigates the nonlinear boundary value problem, resulting from the exact reduction of the Navier–Stokes equations for unsteady laminar boundary layer flow caused by a stretching surface in a quiescent viscous incompressible fluid. We prove existence of solutions for all values of the relevant parameters and provide unique results in the case of a monotonic solution. The results are obtained using a topological shooting argument, which varies a parameter related to the axial shear stress. To solve this equation, a numerical method is proposed based on a rational Chebyshev functions spectral method. Using the operational matrices of derivative, we reduced the problem to a set of algebraic equations. We also compare this work with some other numerical results and present a solution that proves to be highly accurate. Copyright © 2016 John Wiley & Sons, Ltd.
Dynamical properties of a non‐autonomous bouncing ball model forced by non‐harmonic excitation
Authors: Lampart Marek , Zapoměl Jaroslav
Published: September 2016

The main aim of the paper is to research dynamic properties of a mechanical system consisting of a ball jumping between a movable baseplate and a fixed upper stop. The model is constructed with one degree of freedom in the mechanical oscillating part. The ball movement is generated by the gravity force and non‐harmonic oscillation of the baseplate in the vertical direction. The impact forces acting between the ball and plate and the stop are described by the nonlinear Hertz contact law. The ball motion is then governed by a set of two nonlinear ordinary differential equations. To perform their solving, the Runge–Kutta method of the fourth order with adaptable time step was applied. As the main result, it is shown that the systems exhibit regular, irregular, and chaotic pattern for different choices of parameters using the newly introduced 0–1 test for chaos, detecting bifurcation diagram, and researching Fourier spectra. Copyright © 2016 John Wiley & Sons, Ltd.
Repeated blood flow restriction induces muscle fiber hypertrophy
Authors: Sudo Mizuki , Ando Soichi , Kano Yutaka
Published: September 2016

Introduction

We recently developed an animal model to investigate the effects of eccentric contraction (ECC) and blood flow restriction (BFR) on muscle tissue at the cellular level. This study clarified the effects of repeated BFR, ECC, and BFR combined with ECC (BFR+ECC) on muscle fiber hypertrophy.

Methods

Male Wistar rats were assigned to 3 groups: BFR, ECC, and BFR+ECC. The contralateral leg in the BFR group served as a control (CONT). Muscle fiber cross‐sectional area (CSA) of the tibialis anterior was determined after the respective treatments for 6 weeks.

Results

CSA was greater in the BFR+ECC group than in the CONT (P < 0.01) and ECC (P < 0.05) groups. CSA was greater in the BFR group than that in the CONT group (P < 0.05).

Cnclusions

These results suggest that repeated BFR alone as well as BFR+ECC induces muscle fiber hypertrophy at the cellular level. Muscle Nerve 55: 274–276, 2017
Novel mutation in CNTNAP1 results in congenital hypomyelinating neuropathy
Authors: Mehta Paulomi , Küspert Melanie , Bale Tejus , Brownstein Catherine A. , Towne Meghan C. , De Girolami Umberto , Shi Jiahai , Beggs Alan H. , Darras Basil T. , Wegner Michael , Piao Xianhua , Agrawal Pankaj B.
Published: September 2016

Introduction

Congenital hypomyelinating neuropathy (CHN) is a rare congenital neuropathy that presents in the neonatal period and has been linked previously to mutations in several genes associated with myelination. A recent study has linked 4 homozygous frameshift mutations in the contactin‐associated protein 1 (CNTNAP1) gene with this condition.

Methods

We report a neonate with CHN who was found to have absent sensory nerve and compound muscle action potentials and hypomyelination on nerve biopsy.

Results

On whole exome sequencing, we identified a novel CNTNAP1 homozygous missense mutation (p.Arg388Pro) in the proband, and both parents were carriers. Molecular modeling suggests that this variant disrupts a β‐strand to cause an unstable structure and likely significant changes in protein function.

Conclusions

This report links a missense CNTNAP1 variant to the disease phenotype previously associated only with frameshift mutations. Muscle Nerve 55: 761–765, 2017
Muscle MRI of classic infantile pompe patients: Fatty substitution and edema‐like changes
Authors: Pichiecchio Anna , Rossi Marta , Cinnante Claudia , Colafati Giovanna Stefania , De Icco Roberto , Parini Rossella , Menni Francesca , Furlan Francesca , Burlina Alberto , Sacchini Michele , Donati Maria Alice , Fecarotta Simona , Casa Roberto Della , Deodato Federica , Taurisano Roberta , Di Rocco Maja
Published: September 2016

Introduction

The aim of this study was to evaluate the muscle MRI pattern of 9 patients (median age: 6.5 ± 2.74 years) affected by classic infantile‐onset Pompe disease who were treated with enzyme replacement therapy.

Methods

We performed and qualitatively scored T1‐weighted (T1‐w) sequences of the facial, shoulder girdle, paravertebral, and lower limb muscles and short‐tau inversion recovery (STIR) sequences of the lower limbs using the Mercuri and Morrow scales, respectively.

Results

On T1‐w images, mild (grade 1) or moderate (grade 2) involvement was found in the tongue in 6 of 6 patients and in the adductor magnus muscle in 6 of 9. STIR hyperintensity was detected in all areas examined and was categorized as limited to mild in 5 of 8 patients.

Conclusions

On T1‐w sequences, mild/moderate adipose substitution in the adductor magnus and tongue muscles was documented. STIR edema‐like alterations of thigh and calf muscles are novel findings. Correlations with biopsy findings and clinical parameters are needed to fully understand these findings. Muscle Nerve 55: 841–848, 2017
Total and regional adiposity measured by dual‐energy X‐ray absorptiometry and mortality in NHANES 1999‐2006
Authors: Zong Geng , Zhang Zefeng , Yang Quanhe , Wu Hongyu , Hu Frank B. , Sun Qi
Published: September 2016

Objective

Associations of overall and regional body fat measured by dual‐energy X‐ray absorptiometry with total and cause‐specific mortality in the National Health and Nutrition Examination Survey (NHANES) 1999‐2006 were investigated.

Methods

This study included 9,471 participants (≥20 years) free of major chronic diseases at baseline. Death information was obtained from the National Death Index (mean follow‐up duration: 8.8 years).

Results

A total of 682 participants died after 12 months since baseline, with 206 and 170 deaths attributed to cardiovascular diseases (CVD) and cancer, respectively. The second quartile of fat mass percentages (FM%) was used as the reference to account for potential nonlinearity. In the multivariate‐adjusted model, participants in the highest quartile of total FM% had increased total mortality; hazard ratio (HR; 95% confidence interval, 95% CI) was 1.48 (1.07‐2.04; P < 0.05). Higher total and trunk FM%, but not leg FM%, were significantly associated with an increased CVD mortality; HRs (95% CIs) in the highest quartiles of total, trunk, and leg FM% were 2.24 (1.17‐4.31), 1.93 (1.02‐3.66), and 1.50 (0.77‐2.94), respectively.

Conclusions

Higher total body fat was associated with increased total mortality in U.S. adults. Higher total and trunk fat contents were also associated with increased CVD mortality, although fat accumulation in the lower body was not an independent predictor of mortality.
Nuclear phosphoproteome analysis of 3T3‐L1 preadipocyte differentiation reveals system‐wide phosphorylation of transcriptional regulators
Authors: Rabiee Atefeh , Schwämmle Veit , Sidoli Simone , Dai Jie , Rogowska‐Wrzesinska Adelina , Mandrup Susanne , Jensen Ole N.
Published: September 2016

Adipocytes (fat cells) are important endocrine and metabolic cells critical for systemic insulin sensitivity. Both adipose excess and insufficiency are associated with adverse metabolic function. Adipogenesis is the process whereby preadipocyte precursor cells differentiate into lipid‐laden mature adipocytes. This process is driven by a network of transcriptional regulators (TRs). We hypothesized that protein PTMs, in particular phosphorylation, play a major role in activating and propagating signals within TR networks upon induction of adipogenesis by extracellular stimulus. We applied MS‐based quantitative proteomics and phosphoproteomics to monitor the alteration of nuclear proteins during the early stages (4 h) of preadipocyte differentiation. We identified a total of 4072 proteins including 2434 phosphorylated proteins, a majority of which were assigned as regulators of gene expression. Our results demonstrate that adipogenic stimuli increase the nuclear abundance and/or the phosphorylation levels of proteins involved in gene expression, cell organization, and oxidation–reduction pathways. Furthermore, proteins acting as negative modulators involved in negative regulation of gene expression, insulin stimulated glucose uptake, and cytoskeletal organization showed a decrease in their nuclear abundance and/or phosphorylation levels during the first 4 h of adipogenesis. Among 288 identified TRs, 49 were regulated within 4 h of adipogenic stimulation including several known and many novel potential adipogenic regulators. We created a kinase–substrate database for 3T3‐L1 preadipocytes by investigating the relationship between protein kinases and protein phosphorylation sites identified in our dataset. A majority of the putative protein kinases belong to the cyclin‐dependent kinase family and the mitogen‐activated protein kinase family including P38 and c‐Jun N‐terminal kinases, suggesting that these kinases act as orchestrators of early adipogenesis.
Proteomic and phosphoproteomic analyses of yeast reveal the global cellular response to sphingolipid depletion
Authors: Fröhlich Florian , Olson Daniel K. , Christiano Romain , Farese Robert V. , Walther Tobias C.
Published: September 2016

Sphingolipids are essential components of eukaryotic cells with important functions in membrane biology and cellular signaling. Their levels are tightly controlled and coordinated with the abundance of other membrane lipids. How sphingolipid homeostasis is achieved is not yet well understood. Studies performed primarily in yeast showed that the phosphorylation states of several enzymes and regulators of sphingolipid synthesis are important, although a global understanding for such regulation is lacking. Here, we used high‐resolution MS‐based proteomics and phosphoproteomics to analyze the cellular response to sphingolipid synthesis inhibition. Our dataset reveals that changes in protein phosphorylation, rather than protein abundance, dominate the response to blocking sphingolipid synthesis. We identified Ypk signaling as a pathway likely to be activated under these conditions, and we identified potential Ypk1 target proteins. Our data provide a rich resource for on‐going mechanistic studies of key elements of the cellular response to the depletion of sphingolipid levels and the maintenance of sphingolipid homeostasis. All MS data have been deposited in the ProteomeXchange with identifier PXD003854 (http://proteomecentral.proteomexchange.org/dataset/PXD003854).
5′‐N‐ethylcarboxamidoadenosine is not a paralog‐specific Hsp90 inhibitor
Authors: Liu Shanshan , Street Timothy O.
Published: September 2016

The molecular chaperone Hsp90 facilitates the folding and modulates activation of diverse substrate proteins. Unlike other heat shock proteins such as Hsp60 and Hsp70, Hsp90 plays critical regulatory roles by maintaining active states of kinases, many of which are overactive in cancer cells. Four Hsp90 paralogs are expressed in eukaryotic cells: Hsp90α/β (in the cytosol), Grp94 (in the endoplasmic reticulum), Trap1 (in mitochondria). Although numerous Hsp90 inhibitors are being tested in cancer clinical trials, little is known about why different Hsp90 inhibitors show specificity among Hsp90 paralogs. The paralog specificity of Hsp90 inhibitors is likely fundamental to inhibitor efficacy and side effects. In hopes of gaining insight into this issue we examined NECA (5′‐N‐ethylcarboxamidoadenosine), which has been claimed to be an example of a highly specific ligand that binds to one paralog, Grp94, but not cytosolic Hsp90. To our surprise we find that NECA inhibits many different Hsp90 proteins (Grp94, Hsp90α, Trap1, yeast Hsp82, bacterial HtpG). NMR experiments demonstrate that NECA can bind to the N‐terminal domains of Grp94 and Hsp82. We use ATPase competition experiments to quantify the inhibitory power of NECA for different Hsp90 proteins. This scale: Hsp82 > Hsp90α > HtpG ≈ Grp94 > Trap1, ranks Grp94 as less sensitive to NECA inhibition. Because NECA is primarily used as an adenosine receptor agonist, our results also suggest that cell biological experiments utilizing NECA may have confounding effects from cytosolic Hsp90 inhibition.
Cu(In,Ga)Se2 solar cells with improved current based on surface treated stoichiometric absorbers
Authors: Choubrac Léo , Bertram Tobias , Elanzeery Hossam , Siebentritt Susanne
Published: September 2016

Cu(In,Ga)Se2 (CIGS) solar cells based on Cu‐rich instead of Cu‐poor absorbers are investigated. Despite superior bulk transport properties and lower defect density, Cu‐rich CIGS performances are strongly reduced due to unfavorable features at the grain boundaries and CIGS/CdS interface. A very thin (<10 nm) gallium post‐deposition treatment followed by an annealing step is used to solve these issues. Such a treatment is found to efficiently passivate the grain boundaries when performed under low‐selenium flux, resulting in an improved short‐circuit current compared to Cu‐poor references. Under higher selenium flux, the grain boundaries are no more passivated, but the CIGS/CdS interface can be strongly improved, leading to an open‐circuit voltage approaching that of Cu‐poor. Succession of both treatments if finally performed, improves efficiency from 7.5 to 14.4%, with higher short‐circuit current (+6%) compared to Cu‐poor reference. These results show that the short‐circuit current of CIGS solar cells can be improved by an adequate metal‐chalcogen treatment of Cu‐rich absorbers, and paves the way for efficiency enhancement.
Impact of the morphology and composition on the dealloying process of co‐sputtered silver–aluminum alloy thin films
Authors: Chauvin Adrien , Txia Cha Heu Willigis , Tessier Pierre‐Yves , El Mel Abdel‐Aziz
Published: September 2016

Dealloying has been widely employed lately for the fabrication of nanoporous metals. However, in case of thin films, the impact of the initial morphology on the final porosity is still not well understood. In this work, we report on the influence of the initial morphology of silver–aluminum (Ag–Al) thin films on the dealloying process in hydrochloric acid. The films deposition was performed by a DC co‐sputtering process of silver and aluminum targets in a cofocal geometry using pure argon plasma; by tuning the deposition conditions such as the electrical powers applied to the targets and the deposition temperature, films with various compositions and morphologies can be obtained. The dealloying is then carried out using a free corrosion process applied in diluted (2 wt.%) hydrochloric acid in order to leach preferentially aluminum leaving behind a nanoporous skeleton of silver. We show that the dealloying process becomes faster when decreasing the initial silver content within the films. We further demonstrate that the dealloying kinetic is also dependent on the initial morphology of the Ag–Al films: it increases when decreasing the size of the columns forming the Ag–Al films.

Top‐view SEM image of Ag–Al alloy thin film with 23 at.% of initial Ag content dealloyed for 5 min in 2 wt.% hydrochloric acid.
Implementation quality of family literacy programmes: a review of literature
Authors: de la Rie S. , van Steensel R.C.M. , van Gelderen A.J.S.
Published: September 2016

Raising the literacy levels of young children is a major concern in many countries for which various programmes have been suggested. One of these is family literacy programmes. In previous meta‐analyses wide variability in effects has been found and it has been suggested that this is partly caused by variability in implementation quality. This review aims to look at the implementation quality of family literacy programmes and its relationship with programme effectiveness. A search in relevant databases resulted in 46 studies. We found substantial, but variable information on implementation quality. Almost all studies provided information on parents’ quantitative engagement in programmes, but fewer studies reported about characteristics of parent training, quality of engagement and transfer to daily life. Overall, the included studies that did provide information showed frequent use of intervention strategies and degree of participation was generally high. Parents increased their use of the learned techniques and engaged in more literacy activities outside programme time. However, few of the included studies analysed the relationship between implementation quality and programme effects and these studies provided mixed results, making it difficult to draw conclusions. Of critical note is the poor quality of the selected studies. Many had serious methodological flaws. Some of the measures used are not necessarily reliable indicators of implementation quality and results were at times presented with little precision. More robust evaluations of the effects of implementation quality are therefore needed.
Rationale Design, Synthesis And In Vitro Anticancer Activity of New 2,5‐Disubstituted‐1,3,4‐Oxadiazole Analogues
Authors: Ahsan Mohamed Jawed
Published: September 2016

Two new series of oxadiazole analogues (4a–e and 4f–j) were designed based on heterocyclic (1,3,4‐oxadiazole) linked aryl core of IMC‐038525 (tubulin polymerization inhibitor), NSC 784595, and NSC 784597. All the synthesized compounds were synthesized and characterized by IR, NMR, and mass spectral data and the purity of compounds was checked by elemental analysis. Eight compounds were evaluated for their in vitro anticancer activity on 9 different panels of 60 cell lines (60 NCI cancer cell lines) according to the National Cancer Institute (NCI) screening protocol and percent growth (GP) and percent growth inhibition (% GI) was calculated at 10 μM drug concentration. N‐{[5‐(4‐Chlorophenyl)‐1,3,4‐oxadiazol‐2‐yl]methyl}‐4‐methoxyaniline (4 g) showed maximum anticancer activity at 10 μM, and showed maximum sensitivity towards SNB‐75, MDA‐MB‐231/ATCC, T‐47D, 786–0, MCF7, EKVX, PC‐3, HS 578T, MOLT‐4, HCT‐116, HCT‐15, SR, COLO‐205, A549/ATCC, SF‐295, SNB‐19 and RPMI‐8226 with % GIs of 65.48, 60.21, 56.38, 50.36, 49.15, 47.36, 45.16, 41.37, 41.20, 40.02, 38.67, 37.39, 36.61, 34.64, 34.21, 33.77, and 32.92 respectively. Furthermore the compound 4 g showed superior anticancer activity than that of the standard drug Imatinib on 50 human cancer cell lines. The oxadiazoles containing methylene (‐CH2‐) linkage showed comparatively higher anticancer activity.
Vinyl Esters as Acetaldehyde Surrogates: Potential Utility in Some Common Multicomponent Sequences
Authors: Kumar Manoj , Bagchi Sourav , Sharma Anuj
Published: September 2016

Limited applicability of acetaldehyde in many multicomponent sequences widely restrict its utility in synthetic chemistry, diversity oriented synthesis and drug discovery efforts. Present report evaluates the potential scope of vinyl esters as acetaldehyde surrogates in some common multicomponent reactions (MCRs). Reactions were quite successful with cyclic 1,3‐diketones and methyl substituted acridione, thioxanthendione, bis(hydroxycyclohex‐2‐enone), tetrahydroquinazolindione derivatives were obtained in moderate to good yield. With substrates like aniline and 2‐naphthol, vinyl esters simply acted as acylating agent in place of desired acetaldehyde equivalents.
In(OTf)3‐HBF4 Assisted Multicomponent Approach for One‐Pot Synthesis of Pyrazolopyridinone Fused Imidazopyridines
Authors: Devi Nisha , Singh Dharmender , Sunkaria Ramesh K. , Malakar Chandi C. , Mehra Saloni , Rawal Ravindra K. , Singh Virender
Published: September 2016

An efficient methodolgy has been developed towards the one‐pot synthesis of pyrazolopyridinone fused imidazopyridines from 4‐formyl‐1H‐pyrazole‐3‐carboxylates, pyridin‐2‐amines and tert‐butyl isonitrile as the starting materials. The transformation has been accomplished by using In(OTf)3 assisted Groebke‐Blackburn‐Bienayme (GBB) multicomponent approach to yield the N‐fused imidazo[1,2‐a]pyridine scaffolds which were further served in‐situ HBF4 mediated dealkylation and tandem intramolecular condensation. The current protocol paves the way for the synthesis of biologically interesting molecular frameworks and has advantages in terms of low catalyst loading with appreciable atom economy and easy‐to‐perform reaction conditions with straightforward purification procedure. Importantly, this efficient catalytic system offers a lot of future scope for variety of organic transformations in other MCRs.
Bifunctional Demulsifier of ODTS Modified Magnetite/Reduced Graphene Oxide Nanocomposites for Oil–water Separation
Authors: Ma Shenghua , Wang Yinan , Wang Xuejing , Li Qingchuan , Tong Shanshan , Han Xiaojun
Published: September 2016

A bifunctional demulsifier of ODTS modified magnetite/reduced graphene oxide (MRGO@ODTS) was synthesized and demonstrated to demulsify effectively both water‐in‐oil (W/O) and oil‐in‐water (O/W) emulsions, benefitting from its surfactant property. The demulsifier was fully characterized with TEM, XRD, FTIR, TGA, and magnetometer instruments, which confirmed the evenly Fe3O4 nanoparticle modified RGO sheet structure of MRGO@ODTS demulsifier. The demulsification efficiency can reach 96.8 ± 2.9 % for W/O emulsion and 97.9 ± 2.1 % for O/W emulsion with 25 g L−1 and 75 g L−1 demulsifier, respectively. Another important feature of MRGO@ODTS is responsive to magnetic field, and consequently reusable. The recyclability tests of MRGO@ODTS show there is no obvious decline of demulsification efficiency within ten cycles. The demusification ability of MRGO@ODTS is more effective for W/O emulsions than that for O/W emulsions. The possible demulsification mechanism was also proposed. The bifunctional demulsifier may find great potential in oil‐water separation in industry.
Embedded Iron Nanoparticles in Carbon Nanogranules for Direct Synthesis of Lower Olefins
Authors: Ghosh Indrajit K. , Ali Asgar , Dukare Appasaheb , Kumar Umesh , Bordoloi Ankur
Published: September 2016

Iron nanoparticles in carbon nanogranules have been in‐situ generated during the synthesis of lower olefins from Syngas. Very uniformly distributed these carbon embedded iron nanoparticles are found to be very selective for the direct F−T synthesis of lower olefins. The iron incorporated carbon nanogranules were synthesized from refinery heavy residue/vacuum residue and ferrocene. The iron nanoparticles are sTable and do not undergo major sintering during the activity run. The HRTEM images show well dispersion of iron nanoparticles during reduction to reaction processes.
Synthesis of Δ3‐1,3,4‐Telluradiazolines by Reaction of Fenchone Hydrazone with Tellurium Tetrachloride: Mechanistic Insight into Twofold Extrusion
Authors: Okuma Kentaro , Yahata Shuhei , Munakata Kazunori , Nagahora Noriyoshi , Shioji Kosei , Ishikawa Ryuta , Yamada Yuji
Published: September 2016

The reaction of (‐)‐fenchone hydrazone with TeCl4 and DBU gave two isomers of Δ3‐1,3,4‐telluradiazoline (syn‐ and anti‐forms). Thermolysis of isolated anti‐Δ3‐1,3,4‐telluradiazoline gave chiral (E)‐1,1’,3,3,3’,3’‐hexamethyl‐2,2’‐binorbornylidene with perfect stereoselectivity in 93 % yield, which clearly showed that the reaction proceeded through a twofold extrusion process. On the other hand, thermolysis of an anti‐selenium derivative gave a mixture of E‐ and Z‐alkenes along with selenofenchone, suggesting that 1,3‐dipolar retrocyclization proceeded along with twofold extrusion.