bluuebunny/crossref_metadata_2025_split huggingface dataset:
RYR1 causing distal myopathy
Authors: Laughlin Ruple S. , Niu Zhiyv , Wieben Eric , Milone Margherita 
Published: October 2017

AbstractBackgroundCongenital myopathies due to ryanodine receptor (RYR1) mutations are increasingly identified and correlate with a wide range of phenotypes, most commonly that of malignant hyperthermia susceptibility and central cores on muscle biopsy with rare reports of distal muscle weakness, but in the setting of early onset global weakness.MethodsWe report a case of a patient presenting with childhood onset hand stiffness and adult onset progressive hand weakness and jaw contractures discovered to have two variants in the RYR1 gene.ResultsThe patient manifested with distal upper limb weakness which progressed to involve the distal lower limb, proximal upper limb, as well as the face in addition to limited jaw opening. Creatine kinase was mildly elevated with EMG findings supporting a myopathy. Muscle biopsy showed features consistent with centronuclear myopathy. Whole exome sequencing revealed a novel heterozygous pathogenic variant in RYR1 (c.12315_12328delAGAAATCCAGTTCC, p.Glu4106Alafs*8), and a heterozygous missense variant (c.10648C>T, p.Arg3550Trp) of unknown significance in compound heterozygous state.ConclusionWe expand the spectrum of RYR1‐related myopathy with the description of a novel phenotype in an adult patient presenting with hand weakness and suggest considering RYR1 analysis in the diagnosis of distal myopathies.
RJSplot: Interactive Graphs with R
Authors: Barrios David , Prieto Carlos 
Published: October 2017

AbstractData visualization techniques provide new methods for the generation of interactive graphs. These graphs allow a better exploration and interpretation of data but their creation requires advanced knowledge of graphical libraries. Recent packages have enabled the integration of interactive graphs in R. However, R provides limited graphical packages that allow the generation of interactive graphs for computational biology applications. The present project has joined the analytical power of R with the interactive graphical features of JavaScript in a new R package (RJSplot). It enables the easy generation of interactive graphs in R, provides new visualization capabilities, and contributes to the advance of computational biology analytical methods. At present, 16 interactive graphics are available in RJSplot, such as the genome viewer, Manhattan plots, 3D plots, heatmaps, dendrograms, networks, and so on. The RJSplot package is freely available online at http://rjsplot.net.
Dietary Flavone Tectochrysin Exerts Anti‐Inflammatory Action by Directly Inhibiting MEK1/2 in LPS‐Primed Macrophages
Authors: Hou Rui , Han Yixin , Fei Qiaoling , Gao Yuan , Qi Ruijuan , Cai Runlan , Qi Yun 
Published: October 2017

ScopeIn this study, we investigate the underlying molecular mechanism of the effect of tectochrysin on LPS‐primed macrophages.Methods and resultsAs measured by western blot, RT‐PCR, and ELISA, tectochrysin inhibits extracellular signal‐related kinase 1/2 (ERK1/2) phosphorylation and sequentially suppressed downstream inducible nitric oxide synthase (iNOS), tumor necrosis factor‐α (TNF‐α), and IL‐6 transcription as well as the NO, TNF‐α, and IL‐6 in supernatant, but it does not affect extracellular signal‐regulated kinase (MEK) phosphorylation levels. An enzyme reaction study shows that tectochrysin exerted an inhibitory effect on ERK1/2 phosphorylation by inactivating phosphorylated MEK1/2. Moreover, tectochrysin decreases arginase II expression in LPS‐primed RAW264.7 macrophages via reduction of NO production. Tectochrysin also suppresses inflammatory mediator release in peritoneal lavage fluid and in the serum of LPS‐induced endotoxemia mice.ConclusionOur data indicate that by directly inactivating p‐MEK1/2, tectochrysin decreases the phosphorylation level of ERK and subsequently suppresses activator protein‐1 (AP‐1) activation to reduce pro‐inflammatory mediator production, suggesting that tectochrysin has great potential for use in a nutritional preventive strategy against inflammation‐related diseases.
Is Palmitoleic Acid a Plausible Nonpharmacological Strategy to Prevent or Control Chronic Metabolic and Inflammatory Disorders?
Authors: de Souza Camila O. , Vannice Gretchen K. , Rosa Neto José C. , Calder Philip C. 
Published: October 2017

AbstractAlthough dietary fatty acids can modulate metabolic and immune responses, the effects of palmitoleic acid (16:1n‐7) remain unclear. Since this monounsaturated fatty acid is described as a lipokine, studies with cell culture and rodent models have suggested it enhances whole body insulin sensitivity, stimulates insulin secretion by β cells, increases hepatic fatty acid oxidation, improves the blood lipid profile, and alters macrophage differentiation. However, human studies report elevated blood levels of palmitoleic acid in people with obesity and metabolic syndrome. These findings might be reflection of the level or activity of stearoyl‐CoA desaturase‐1, which synthesizes palmitoleate and is enhanced in liver and adipose tissue of obese patients. The aim of this review is to describe the immune–metabolic effects of palmitoleic acid observed in cell culture, animal models, and humans to answer the question of whether palmitoleic acid is a plausible nonpharmacological strategy to prevent, control, or ameliorate chronic metabolic and inflammatory disorders. Despite the beneficial effects observed in cell culture and in animal studies, there are insufficient human intervention studies to fully understand the physiological effects of palmitoleic acid. Therefore, more human‐based research is needed to identify whether palmitoleic acid meets the promising therapeutic potential suggested by the preclinical research.
Plasma Cholesteryl Ester Fatty Acids do not Mediate the Association of Ethnicity with Type 2 Diabetes: Results From the HELIUS Study
Authors: Muilwijk Mirthe , Celis‐Morales Carlos , Nicolaou Mary , Snijder Marieke B. , Gill Jason M.R. , van Valkengoed Irene G.M. 
Published: October 2017

ScopeEthnic minority groups have a higher risk of type 2 diabetes (T2D) than the host population. Our aim is to identify whether plasma cholesteryl ester fatty acids (CEFA) mediate the ethnic differences in type 2 diabetes.Methods and resultsWe included 202 Dutch, 206 South‐Asian Surinamese, 205 African Surinamese, 215 Turkish, and 213 Moroccan origin participants of the HELIUS study (Amsterdam, the Netherlands). Logistic regression is used to determine the associations between plasma CEFA and T2D. Mediation analysis is used to identify whether CEFA contributed to the association between ethnicity and T2D. We adjusted for ethnicity, age, sex, smoking, physical activity, and BMI. Associations between plasma CEFA and T2D were similar across all ethnic groups. Although differences in plasma CEFA across ethnic groups were observed, CEFA did not mediate the differences in T2D prevalence between ethnic groups.ConclusionAlthough ethnic differences in plasma CEFA are found and CEFA are associated with T2D, CEFA does not contribute to the difference in T2D prevalence between ethnic groups. If confirmed, this implies that maintenance of the more beneficial CEFA profiles in the non‐Dutch ethnic groups may be encouraged to prevent an even higher prevalence of T2D in these groups.
Early Supplementation of d‐Cysteine or l‐Cysteine Prevents Hypertension and Kidney Damage in Spontaneously Hypertensive Rats Exposed to High‐Salt Intake
Authors: Hsu Chien‐Ning , Lin Yu‐Ju , Lu Pei‐Chen , Tain You‐Lin 
Published: October 2017

ScopeWe investigate whether early supplementation of precursors of hydrogen sulfide (H2S), d‐ or l‐cysteine can prevent hypertension and kidney damage in spontaneously hypertensive rats (SHR) treated with high‐salt.Methods and ResultsWe examine 12‐week‐old male SHRs from four groups: SHR, high salt SHR (SHRs received 1% NaCl in drinking water for 8 weeks), high salt SHR+d (SHRs received high salt and d‐cysteine), and high salt SHR+l (SHRs received high salt and l‐cysteine). d‐ or l‐cysteine was supplemented at 8 mmol kg−1 body weight/day between 4 and 6 weeks of ages. High salt intake exacerbate hypertension and kidney damage in SHRs, which is prevented by d‐ or l‐cysteine supplementation. d‐ or l‐Cysteine supplementation reduce the degree of high salt‐induced oxidative stress damage. Renal 3‐mercaptopyruvate sulphurtransferase (3MST) protein levels and activity are reduced by d‐ or l‐cysteine supplementation. Additionally, d‐ or l‐Cysteine supplementation reduce renal angiotensin I and angiotensin II concentrations, decrease mRNA expression of Ren, and increase protein levels of type 2 angiotensin II receptor.ConclusionEarly supplementation of d‐ or l‐cysteine before hypertension becomes evident and may protect against hypertension and kidney damage in adult SHRs exposed to high salt consumption via regulation of oxidative stress, renin‐angiotensin system, and H2S‐generating pathways.
Nerve ultrasound reliability of upper limbs: Effects of examiner training
Authors: Garcia‐Santibanez Rocio , Dietz Alexander R. , Bucelli Robert C. , Zaidman Craig M. 
Published: October 2017

ABSTRACTIntroduction: Duration of training to reliably measure nerve cross‐sectional area with ultrasound is unknown. Methods: A retrospective review was performed of ultrasound data, acquired and recorded by 2 examiners—an expert and either a trainee with 2 months (novice) or a trainee with 12 months (experienced) of experience. Data on median, ulnar, and radial nerves were reviewed for 42 patients. Results: Interrater reliability was good and varied most with nerve site but little with experience. Coefficient of variation (CoV) range was 9.33%–22.5%. Intraclass correlation coefficient (ICC) was good to excellent (0.65–95) except ulnar nerve‐wrist/forearm and radial nerve‐humerus (ICC = 0.39–0.59). Interrater differences did not vary with nerve size or body mass index. Expert–novice and expert–experienced interrater differences and CoV were similar. The ulnar nerve‐wrist expert–novice interrater difference decreased with time (rs = −0.68, P = 0.001). Discussion: A trainee with at least 2 months of experience can reliably measure upper limb nerves. Reliability varies by nerve and location and slightly improves with time. Muscle Nerve 57: 189–192, 2018
Low conversion rate of ocular to generalized myasthenia gravis in Singapore
Authors: Teo Kelvin Y. , Tow Sharon L. , Haaland Benjamin , Gosavi Tushar D. , Jing‐Liang LOO , Yew Long LO , Milea Dan 
Published: October 2017

ABSTRACTIntroduction: Ocular myasthenia gravis (OMG) is a common condition of the neuromuscular junction that may convert to generalized myasthenia gravis (GMG). Our aim in this study was to determine the conversion rate and predictive factors for generalization in OMG, in an Asian population. Methods: The investigation consisted of a retrospective study of OMG patients with a minimum 2 years of follow‐up. Results: Among 191 patients with OMG, 155 had the minimum 2‐year follow‐up. The conversion rate at median follow‐up (40.8 months) was 10.6% (95% confidence interval 7.9%–13.3%), and at the 2‐year follow‐up it was 7.7% (95% confidence interval 5.6%–9.8%). At baseline, the predictive factors for generalization were positive acetylcholine receptor antibodies (hazard ratio 3.71, P = 0.024), positive repetitive nerve stimulation (RNS) studies (hazard ratio 4.42, P = 0.003), and presence of radiologically presumed or pathologically confirmed thymoma (hazard ratio 3.10, P = 0.013). Discussion: The conversion rate of OMG to GMG in Asian patients is low, as predicted by presence of acetylcholine receptor antibodies, presence of thymoma, and positive RNS studies. Muscle Nerve 57: 756–760, 2018
Sampling and energy evaluation challenges in ligand binding protein design
Authors: Dou Jiayi , Doyle Lindsey , Jr. Greisen Per , Schena Alberto , Park Hahnbeom , Johnsson Kai , Stoddard Barry L. , Baker David 
Published: October 2017

AbstractThe steroid hormone 17α‐hydroxylprogesterone (17‐OHP) is a biomarker for congenital adrenal hyperplasia and hence there is considerable interest in development of sensors for this compound. We used computational protein design to generate protein models with binding sites for 17‐OHP containing an extended, nonpolar, shape‐complementary binding pocket for the four‐ring core of the compound, and hydrogen bonding residues at the base of the pocket to interact with carbonyl and hydroxyl groups at the more polar end of the ligand. Eight of 16 designed proteins experimentally tested bind 17‐OHP with micromolar affinity. A co‐crystal structure of one of the designs revealed that 17‐OHP is rotated 180° around a pseudo‐two‐fold axis in the compound and displays multiple binding modes within the pocket, while still interacting with all of the designed residues in the engineered site. Subsequent rounds of mutagenesis and binding selection improved the ligand affinity to nanomolar range, while appearing to constrain the ligand to a single bound conformation that maintains the same “flipped” orientation relative to the original design. We trace the discrepancy in the design calculations to two sources: first, a failure to model subtle backbone changes which alter the distribution of sidechain rotameric states and second, an underestimation of the energetic cost of desolvating the carbonyl and hydroxyl groups of the ligand. The difference between design model and crystal structure thus arises from both sampling limitations and energy function inaccuracies that are exacerbated by the near two‐fold symmetry of the molecule.
Protein–protein interactions leave evolutionary footprints: High molecular coevolution at the core of interfaces
Authors: Teppa Elin , Zea Diego Javier , Marino‐Buslje Cristina 
Published: October 2017

AbstractProtein–protein interactions are essential to all aspects of life. Specific interactions result from evolutionary pressure at the interacting interfaces of partner proteins. However, evolutionary pressure is not homogeneous within the interface: for instance, each residue does not contribute equally to the binding energy of the complex. To understand functional differences between residues within the interface, we analyzed their properties in the core and rim regions. Here, we characterized protein interfaces with two evolutionary measures, conservation and coevolution, using a comprehensive dataset of 896 protein complexes. These scores can detect different selection pressures at a given position in a multiple sequence alignment. We also analyzed how the number of interactions in which a residue is involved influences those evolutionary signals. We found that the coevolutionary signal is higher in the interface core than in the interface rim region. Additionally, the difference in coevolution between core and rim regions is comparable to the known difference in conservation between those regions. Considering proteins with multiple interactions, we found that conservation and coevolution increase with the number of different interfaces in which a residue is involved, suggesting that more constraints (i.e., a residue that must satisfy a greater number of interactions) allow fewer sequence changes at those positions, resulting in higher conservation and coevolution values. These findings shed light on the evolution of protein interfaces and provide information useful for identifying protein interfaces and predicting protein–protein interactions.
Coffee inhibition of CYP3A4 in vitro was not translated to a grapefruit‐like pharmacokinetic interaction clinically
Authors: Dresser George K. , Urquhart Brad L. , Proniuk Julianne , Tieu Alvin , Freeman David J. , Arnold John Malcolm , Bailey David G. 
Published: October 2017

AbstractGrapefruit can augment oral medication bioavailability through irreversible (mechanism‐based) inhibition of intestinal CYP3A4. Supplementary data from our recent coffee–drug interaction clinical study showed some subjects had higher area under the plasma drug concentration ‐ time curve (AUC) and plasma peak drug concentration (Cmax) of the CYP3A4 probe felodipine compared to aqueous control. It was hypothesized that coffee might interact like grapefruit in responsive individuals. Beans from six geographical locations were consistently brewed into coffee that was separated chromatographically to a methanolic fraction for in vitro inhibition testing of CYP3A4 metabolism of felodipine at 1% coffee strength. The effect of simultaneous incubation and 10‐min preincubation with coffee fractions determined whether coffee had direct and mechanism‐based inhibitory activity. A subsequent five‐way randomized balanced controlled crossover clinical study evaluated the clinical pharmacokinetic interaction with single‐dose felodipine. Grapefruit juice, water, or three of the in vitro tested coffees were ingested at 300 mL alone 1 h before and then with felodipine. In vitro, all six coffees decreased felodipine metabolism for both simultaneous and preincubation exposure compared to corresponding control. Five coffees demonstrated mechanism‐based inhibition. Grapefruit increased felodipine AUC0–8 (25 vs. 13 ng.h/mL, P < 0.001) and Cmax (5.8 vs. 2.7 ng/mL, P < 0.001) and decreased dehydrofelodipine/felodipine AUC0–8 ratio (0.84 vs. 1.29, P < 0.001), while the three coffees caused no change in these parameters compared to water. Despite high in vitro potency of CYP3A4 inhibition, the coffees did not cause a clinical pharmacokinetic interaction possibly from insufficient amount of inhibitor(s) in coffee reaching intestinal CYP3A4 during the absorption phase of felodipine. The results of this study highlight the need for follow‐up clinical testing when in vitro results indicate the possibility of an interaction.
Long-Term Recovery After Endothelial Colony-Forming Cells or Human Umbilical Cord Blood Cells Administration in a Rat Model of Neonatal Hypoxic-Ischemic Encephalopathy
Authors: Grandvuillemin Isabelle , Garrigue Philippe , Ramdani Alaa , Boubred Farid , Simeoni Umberto , Dignat-George Françoise , Sabatier Florence , Guillet Benjamin 
Published: October 2017

AbstractNeonatal hypoxic-ischemic encephalopathy (NHIE) is a dramatic perinatal complication, associated with poor neurological prognosis despite neuroprotection by therapeutic hypothermia, in the absence of an available curative therapy. We evaluated and compared ready-to-use human umbilical cord blood cells (HUCBC) and bankable but allogeneic endothelial progenitors (ECFC) as cell therapy candidate for NHIE. We compared benefits of HUCBC and ECFC transplantation 48 hours after injury in male rat NHIE model, based on the Rice-Vannucci approach. Based on behavioral tests, immune-histological assessment and metabolic imaging of brain perfusion using single photon emission computed tomography (SPECT), HUCBC, or ECFC administration provided equally early and sustained functional benefits, up to 8 weeks after injury. These results were associated with total normalization of injured hemisphere cerebral blood flow assessed by SPECT/CT imaging. In conclusion, even if ECFC represent an efficient candidate, HUCBC autologous criteria and easier availability make them the ideal candidate for hypoxic-ischemic cell therapy.
Ni2P@Carbon Core–Shell Nanoparticle‐Arched 3D Interconnected Graphene Aerogel Architectures as Anodes for High‐Performance Sodium‐Ion Batteries
Authors: Miao Xianguang , Yin Ruiyang , Ge Xiaoli , Li Zhaoqiang , Yin Longwei 
Published: October 2017

AbstractTo alleviate large volume change and improve poor electrochemical reaction kinetics of metal phosphide anode for sodium‐ion batteries, for the first time, an unique Ni2P@carbon/graphene aerogel (GA) 3D interconnected porous architecture is synthesized through a solvothermal reaction and in situ phosphorization process, where core–shell Ni2P@C nanoparticles are homogenously embedded in GA nanosheets. The synergistic effect between components endows Ni2P@C/GA electrode with high structural stability and electrochemical activity, leading to excellent electrochemical performance, retaining a specific capacity of 124.5 mA h g−1 at a current density of 1 A g−1 over 2000 cycles. The robust 3D GA matrix with abundant open pores and large surface area can provide unblocked channels for electrolyte storage and Na+ transfer and make fully close contact between the electrode and electrolyte. The carbon layers and 3D GA together build a 3D conductive matrix, which not only tolerates the volume expansion as well as prevents the aggregation and pulverization of Ni2P nanoparticles during Na+ insertion/extraction processes, but also provides a 3D conductive highway for rapid charge transfer processes. The present strategy for phosphides via in situ phosphization route and coupling phosphides with 3D GA can be extended to other novel electrodes for high‐performance energy storage devices.
Post‐buckling strength of plate girders subjected to shear – experimental verification
Authors: Hansen Thomas 
Published: October 2017

AbstractThis paper describes a calculation method for steel plate girders with transverse web stiffeners subjected to shear. It may be used to predict the failure load or, as a design method, to determine the optimal number of internal web stiffeners. The method is based on the theory of plasticity. Many other theories have been developed, but the method presented here differs from these theories by incorporating the strength of the transverse stiffeners and by assuming that the tensile bands may pass the transverse stiffeners – an effect often observed in tests. Other methods have only dealt with a single web field between two stiffeners.The load‐carrying capacity may be predicted by applying both the lower‐bound and upper‐bound theorems. The upper‐bound solutions show very good correlation with existing tests. The emphasis is placed on the presentation of the tests conducted at the Technical University of Denmark. The test programme comprised six full‐scale plate girder specimens. Agreement between the theory and the tests is very good.
Selection Considerations for your Optimum Leak Testing Method and Process
Authors: Morris Dave , Seibert Dennis 
Published: October 2017

SummaryLeak testing with air or tracer gas has made significant progress in the last decade with respect to technology, improved sensitivity and shorter cycle times. The motivation was driven by stricter environmental regulations and cost pressure. The article gives an overview of different leak testing methods. Furthermore a question guideline for the selection of the optimal leak detection method for different applications is introduced.