bluuebunny/crossref_metadata_2025 huggingface dataset:
Employing BINOL‐Phosphoroselenoyl Chloride for Selective Inositol Phosphorylation and Synthesis of Glycosyl Inositol Phospholipid from Entamoeba histolytica
Authors: Aiba Toshihiko , Suehara Sae , Choy Siew‐Ling , Maekawa Yuuki , Lotter Hannelore , Murai Toshiaki , Inuki Shinsuke , Fukase Koichi , Fujimoto Yukari
Published: April 2017

The chemical synthesis of glycosyl inositol phospholipids from Entamoeba histolytica is reported. The key feature of this synthesis is a regioselective phosphorylation reaction that occurs through desymmetrization of a myo‐inositol derivative with phosphoroselenoyl chloride. A new protecting‐group strategy was developed that utilizes allyl and alloc groups to synthesize complex glycolipids bearing unsaturated lipids. These developments provided an efficient synthetic route for various complex inositol phospholipids and their analogues. Furthermore, the binding affinity of the synthetic inositol phospholipids with mouse CD1d molecules has been evaluated, as well as the immunostimulatory activity.
Outer‐Sphere Reactivity Shift of Secondary Phosphine Oxide‐Based Nickel Complexes: From Ethylene Hydrophosphinylation to Oligomerization
Authors: Lhermet Rudy , Moser Emile , Jeanneau Erwann , Olivier‐Bourbigou Hélène , Breuil Pierre‐Alain R.
Published: April 2017

A new dimension for secondary phosphine oxide (SPOs) ligands is described in this article. Demonstrated on original π‐allylic nickel structures, these self‐assembled complexes trigger catalytic hydrophosphinylation reactions. Addition of a Lewis acid B(C6F5)3 switches the reactivity towards migratory insertion and thus ethylene oligomerization through an unprecedented outer‐sphere interaction with the coordinated SPO ligand. NMR experiments and X‐ray analyses allowed for the observation of the formation of zwitterionic active species as well as their degradation pathway.
Role of the Methoxy Groups in Cryptophanes for Complexation of Xenon: Conformational Selection Evidence from 129Xe‐1H NMR SPINOE Experiments
Authors: Berthault Patrick , Boutin Céline , Léonce Estelle , Jeanneau Erwann , Brotin Thierry
Published: April 2017

We report the laser‐polarized 129Xe and 1H NMR spectra of a series of cryptophane derivatives that differ only by the number of methoxy groups attached on their benzene rings and the syn or anti arrangement of the linkers (compounds 6 a–s, 9 a–s, 12 a–s). All these compounds bind xenon even though the characteristic signal of the gas encapsulated in the cavity of the cage‐molecule cannot always be detected. Interestingly, the exchange dynamics of xenon strongly depends on the degree of substitution and is different from that of the cryptophane derivatives studied previously. In solution, the 1H NMR spectra of these derivatives show the presence of different conformations in a slow exchange regime that can be explained by a decrease of the flexibility of their skeleton. Thanks to 129Xe‐1H dipolar cross‐relaxation (SPINOE) spectra, we demonstrate that a single conformation present in solution can bind xenon.
Quantitative High‐Throughput Screening Using a Coincidence Reporter Biocircuit
Authors: Schuck Brittany W. , MacArthur Ryan , Inglese James
Published: April 2017

Reporter‐biased artifacts—i.e., compounds that interact directly with the reporter enzyme used in a high‐throughput screening (HTS) assay and not the biological process or pharmacology being interrogated—are now widely recognized to reduce the efficiency and quality of HTS used for chemical probe and therapeutic development. Furthermore, narrow or single‐concentration HTS perpetuates false negatives during primary screening campaigns. Titration‐based HTS, or quantitative HTS (qHTS), and coincidence reporter technology can be employed to reduce false negatives and false positives, respectively, thereby increasing the quality and efficiency of primary screening efforts, where the number of compounds investigated can range from tens of thousands to millions. The three protocols described here allow for generation of a coincidence reporter (CR) biocircuit to interrogate a biological or pharmacological question of interest, generation of a stable cell line expressing the CR biocircuit, and qHTS using the CR biocircuit to efficiently identify high‐quality biologically active small molecules. © 2017 by John Wiley & Sons, Inc.
Cooperative breeding shapes post‐fledging survival in an Afrotropical forest bird
Authors: Van de Loock Dries , Strubbe Diederik , De Neve Liesbeth , Githiru Mwangi , Matthysen Erik , Lens Luc
Published: April 2017

For avian group living to be evolutionary stable, multiple fitness benefits are expected. Yet, the difficulty of tracking fledglings, and thus estimating their survival rates, limits our knowledge on how such benefits may manifest postfledging. We radio‐tagged breeding females of the Afrotropical cooperatively breeding Placid greenbul (Phyllastrephus placidus)during nesting. Tracking these females after fledging permitted us to locate juvenile birds, their parents, and any helpers present and to build individual fledgling resighting datasets without incurring mortality costs or causing premature fledging due to handling or transmitter effects. A Bayesian framework was used to infer age‐specific mortality rates in relation to group size, fledging date, maternal condition, and nestling condition. Postfledging survival was positively related to group size, with fledglings raised in groups with four helpers showing nearly 30% higher survival until independence compared with pair‐only offspring, independent of fledging date, maternal condition or nestling condition. Our results demonstrate the importance of studying the early dependency period just after fledging when assessing presumed benefits of cooperative breeding. While studying small, mobile organisms after they leave the nest remains highly challenging, we argue that the telemetric approach proposed here may be a broadly applicable method to obtain unbiased estimates of postfledging survival.
Immune checkpoints and their inhibition in cancer and infectious diseases
Authors: Dyck Lydia , Mills Kingston H.G.
Published: April 2017

The development of chronic infections and cancer is facilitated by a variety of immune subversion mechanisms, such as the production of anti‐inflammatory cytokines, induction of regulatory T (Treg) cells, and expression of immune checkpoint molecules, including CTLA‐4 and PD‐1. CTLA‐4, expressed on T cells, interacts with CD80/CD86, thereby limiting T‐cell activation and leading to anergy. PD‐1 is predominantly expressed on T cells and its interaction with PD‐L1 and PD‐L2 expressed on antigen‐presenting cells (APCs) and tumors sends a negative signal to T cells, which can lead to T‐cell exhaustion. Given their role in suppressing effector T‐cell responses, immune checkpoints are being targeted for the treatment of cancer. Indeed, antibodies binding to CTLA‐4, PD‐1, or PD‐L1 have shown remarkable efficacy, especially in combination therapies, for a number of cancers and have been licensed for the treatment of melanoma, nonsmall cell lung cancer, and renal and bladder cancers. Moreover, immune checkpoint inhibitors have been shown to enhance ex vivo effector T‐cell responses from patients with chronic viral, bacterial, or parasitic infection, including HIV, tuberculosis, and malaria. Although the data from clinical trials in infectious diseases are still sparse, these inhibitors have great potential for treating chronic infections, especially when combined with therapeutic vaccines.
Fluorine at the C5 Position of 2′‐Deoxyuridine Enhances Repair of a O4‐Methyl Adduct by O6‐Alkylguanine DNA Alkyltransferases
Authors: Sacre Lauralicia , Wilds Christopher J.
Published: April 2017

Alkylation damage at the O6‐ and O4‐atoms of 2′‐deoxyguanosine (dG) and thymidine (T), respectively, can be removed by O6‐alkylguanine‐DNA alkyltransferases (AGTs). Previous studies have shown that human AGT (hAGT) repairs small adducts poorly at the O4‐atom of T, in comparison to the E. coli variants (OGT and Ada‐C). The C5 methyl group of the thymine nucleobase is suspected to contribute to hAGT repair proficiency possibly due to steric effects in the protein active site. In the present study, repair of oligonucleotides containing a 5‐fluoro‐O4‐methyl‐2′‐deoxyuridine (dFU‐Me) insert by hAGT, E. coli AGT variants (OGT and Ada‐C) and a chimeric hAGT/OGT protein was evaluated. All AGT variants, particularly hAGT and the hAGT/OGT chimera, demonstrated improved proficiency at removing the O4‐methyl group from substrates containing dFU‐Me, relative to the thymidine and 2′‐deoxyuridine counterparts.
Design of photovoltaics for modules with 50% efficiency
Authors: Warmann Emily C. , Flowers Cristofer , Lloyd John , Eisler Carissa N. , Escarra Matthew D. , Atwater Harry A.
Published: April 2017

We describe a spectrum splitting solar module design approach using ensembles of 2–20 subcells with bandgaps optimized for the AM1.5D spectrum. Device physics calculations and experimental data determine radiative efficiency parameters for III‐V compound semiconductor subcells and enable modification of conventional detailed balance calculations to predict module efficiency while retaining computational speed for a wide search of the design space. Accounting for nonideal absorption and recombination rates due to realistic material imperfections allows us to identify the minimum subcell quantity, quality, electrical connection configuration, and concentration required for 50% module efficiency with realistic optical losses and modeled contact resistance losses. We predict a module efficiency of 50% or greater will be possible with 7–10 electrically independent subcells in a spectral splitting optic at 300–500 suns concentration, assuming a 90% optical efficiency and 98% electrical efficiency, provided the subcells can achieve an average external radiative efficiency of 3–5% and a short circuit current that is at least 90% of the ideal. In examining spectrum splitting solar cells with both series‐connected and electrically independent subcells, we identify a new design trade‐off independent of the challenges of fabricating optimal bandgap combinations. Series‐connected ensembles, having a single set of electrical contacts, are less sensitive to lumped series resistance losses than ensembles where each subcells are contacted independently. By contrast, ensembles with electrically independent subcells can achieve lower radiative losses when the subcells are designed for good optical confinement. Distributing electrically independent subcells in a concentrating receiver module allows flexibility in subcell selection and fabrication, and can achieve ultra‐high efficiency with conventional III‐V cell technology.
ETV6/RUNX1‐like acute lymphoblastic leukemia: A novel B‐cell precursor leukemia subtype associated with the CD27/CD44 immunophenotype
Authors: Zaliova Marketa , Kotrova Michaela , Bresolin Silvia , Stuchly Jan , Stary Jan , Hrusak Ondrej , te Kronnie Geertruy , Trka Jan , Zuna Jan , Vaskova Martina
Published: April 2017

We have shown previously that ETV6/RUNX1‐positive acute lymphoblastic leukemia (ALL) is distinguishable from other ALL subtypes by CD27pos/CD44low‐neg immunophenotype. During diagnostic immunophenotyping of 573 childhood B‐cell precursor ALL (BCP‐ALL), we identified eight cases with this immunophenotype among “B‐other ALL” (BCP‐ALL cases negative for routinely tested chromosomal/genetic aberrations). We aimed to elucidate whether these cases belong to the recently described ETV6/RUNX1‐like ALL defined by the ETV6/RUNX1‐specific gene expression profile (GEP), harboring concurrent ETV6 and IKZF1 lesions. We performed comprehensive genomic analysis using single nucleotide polymorphism arrays, whole exome and transcriptome sequencing and GEP on microarrays. In unsupervised hierarchical clustering based on GEP, five out of seven analyzed CD27pos/CD44low‐neg B‐other cases clustered with ETV6/RUNX1‐positive ALL and were thus classified as ETV6/RUNX1‐like ALL. The two cases clustering outside ETV6/RUNX1‐positive ALL harbored a P2RY8/CRLF2 fusion with activating JAK2 mutations and a TCF3/ZNF384 fusion, respectively, assigning them to other ALL subtypes. All five ETV6/RUNX1‐like cases harbored ETV6 deletions; uniform intragenic ARPP21 deletions and various IKZF1 lesions were each found in three ETV6/RUNX1‐like cases. The frequency of ETV6 and ARPP21 deletions was significantly higher in ETV6/RUNX1‐like ALL compared with a reference cohort of 42 B‐other ALL. In conclusion, we show that ETV6/RUNX1‐like ALL is associated with CD27pos/CD44low‐neg immunophenotype and identify ARPP21 deletions to contribute to its specific genomic profile enriched for ETV6 and IKZF1 lesions. In conjunction with previously published data, our study identifies the ETV6 lesion as the only common genetic aberration and thus the most likely key driver of ETV6/RUNX1‐like ALL.
Abdominal obesity and white matter microstructure in midlife
Authors: Birdsill Alex Cole , Oleson Stephanie , Kaur Sonya , Pasha Evan , Ireton Adele , Tanaka Hirofumi , Haley Andreana
Published: April 2017

The aging U.S. population and the recent rise in the prevalence of obesity are two phenomena of great importance to public health. In addition, research suggests that midlife body mass index (BMI) is a risk factor for dementia, a particularly costly disease, in later life. BMI could influence brain health by adversely impacting cerebral white matter. Recently, greater BMI has been associated with lower white matter fractional anisotropy (FA), an index of tissue microstructure, as measured by diffusion‐tensor imaging in midlife. The aim of this study was to investigate the role of abdominal obesity, the most metabolically active adipose tissue compartment, and white matter microstructure in midlife. Community dwelling participants (N = 168) between the ages of 40–62 underwent MRI scanning at 3T and a general health assessment. Inferences were made on whole brain white matter tracts using full‐tensor, high‐dimension normalization, and tract‐based spatial statistics. Higher waist circumference was associated with higher FA, indicating more directional diffusion in several white matter tracts controlling for age, sex, triglycerides, systolic blood pressure, fasting glucose, and HDL‐cholesterol. Post hoc analysis revealed that greater waist circumference was associated with lower axial diffusivity, indicating lower parallel diffusion; lower radial diffusivity, indicating lower perpendicular diffusion; and lower mean diffusivity, indicating restricted diffusion. This is the first study to report a positive relationship between obesity and FA, indicating a more complicated view of this relationship in the aging brain. Hum Brain Mapp 38:3337–3344, 2017. © 2017 Wiley Periodicals, Inc.
White matter developmental trajectories associated with persistence and recovery of childhood stuttering
Authors: Chow Ho Ming , Chang Soo‐Eun
Published: April 2017

Stuttering affects the fundamental human ability of fluent speech production, and can have a significant negative impact on an individual's psychosocial development. While the disorder affects about 5% of all preschool children, approximately 80% of them recover naturally within a few years of stuttering onset. The pathophysiology and neuroanatomical development trajectories associated with persistence and recovery of stuttering are still largely unknown. Here, the first mixed longitudinal diffusion tensor imaging (DTI) study of childhood stuttering has been reported. A total of 195 high quality DTI scans from 35 children who stutter (CWS) and 43 controls between 3 and 12 years of age were acquired, with an average of three scans per child, each collected approximately a year apart. Fractional anisotropy (FA), a measure reflecting white matter structural coherence, was analyzed voxel‐wise to examine group and age‐related differences using a linear mixed‐effects (LME) model. Results showed that CWS exhibited decreased FA relative to controls in the left arcuate fasciculus, underlying the inferior parietal and posterior temporal areas, and the mid body of corpus callosum. Further, white matter developmental trajectories reflecting growth rate of these tract regions differentiated children with persistent stuttering from those who recovered from stuttering. Specifically, a reduction in FA growth rate (i.e., slower FA growth with age) in persistent children relative to fluent controls in the left arcuate fasciculus and corpus callosum was found, which was not evident in recovered children. These findings provide first glimpses into the possible neural mechanisms of onset, persistence, and recovery of childhood stuttering. Hum Brain Mapp 38:3345–3359, 2017. © 2017 Wiley Periodicals, Inc.
Toward an electrophysiological “sweet spot” for deep brain stimulation in the subthalamic nucleus
Authors: Horn Andreas , Neumann Wolf‐Julian , Degen Katharina , Schneider Gerd‐Helge , Kühn Andrea A.
Published: April 2017

Enhanced beta‐band activity recorded in patients suffering from Parkinson‘s Disease (PD) has been described as a potential physiomarker for disease severity. Beta power is suppressed by Levodopa intake and STN deep brain stimulation (DBS) and correlates with disease severity across patients. The aim of the present study was to explore the promising signature of the physiomarker in the spatial domain. Based on local field potential data acquired from 54 patients undergoing STN‐DBS, power values within alpha, beta, low beta, and high beta bands were calculated. Values were projected into common stereotactic space after DBS lead localization. Recorded beta power values were significantly higher at posterior and dorsal lead positions, as well as in active compared with inactive pairs. The peak of activity in the beta band was situated within the sensorimotor functional zone of the nucleus. In contrast, higher alpha activity was found in a more ventromedial region, potentially corresponding to associative or premotor functional zones of the STN. Beta‐ and alpha‐power peaks were then used as seeds in a fiber tracking experiment. Here, the beta‐site received more input from primary motor cortex whereas the alpha‐site was more strongly connected to premotor and prefrontal areas. The results summarize predominant spatial locations of frequency signatures recorded in STN‐DBS patients in a probabilistic fashion. The site of predominant beta‐activity may serve as an electrophysiologically determined target for optimal outcome in STN‐DBS for PD in the future. Hum Brain Mapp 38:3377–3390, 2017. © 2017 Wiley Periodicals, Inc.
Brain structure and verbal function across adulthood while controlling for cerebrovascular risks
Authors: Sanfratello L. , Lundy S.L. , Qualls C. , Knoefel J.E. , Adair J.C. , Caprihan A. , Stephen J.M. , Aine C.J.
Published: April 2017

The development and decline of brain structure and function throughout adulthood is a complex issue, with cognitive aging trajectories influenced by a host of factors including cerebrovascular risk. Neuroimaging studies of age‐related cognitive decline typically reveal a linear decrease in gray matter (GM) volume/density in frontal regions across adulthood. However, white matter (WM) tracts mature later than GM, particularly in regions necessary for executive functions and memory. Therefore, it was predicted that a middle‐aged group (MC: 35–45 years) would perform best on a verbal working memory task and reveal greater regional WM integrity, compared with both young (YC: 18–25 years) and elder groups (EC: 60+ years). Diffusion tensor imaging (DTI) and magnetoencephalography (MEG) were obtained from 80 healthy participants. Objective measures of cerebrovascular risk and cognition were also obtained. As predicted, MC revealed best verbal working memory accuracy overall indicating some maturation of brain function between YC and MC. However, contrary to the prediction fractional anisotropy values (FA), a measure of WM integrity, were not greater in MC (i.e., there were no significant differences in FA between YC and MC but both groups showed greater FA than EC). An overall multivariate model for MEG ROIs showed greater peak amplitudes for MC and YC, compared with EC. Subclinical cerebrovascular risk factors (systolic blood pressure and blood glucose) were negatively associated with FA in frontal callosal, limbic, and thalamic radiation regions which correlated with executive dysfunction and slower processing speed, suggesting their contribution to age‐related cognitive decline.Hum Brain Mapp 38:3472–3490, 2017. ©2017 Wiley Periodicals, Inc.
Default mode and task‐positive networks connectivity during the N‐Back task in remitted depressed patients with or without emotional residual symptoms
Authors: Delaveau Pauline , Arruda Sanchez Tiago , Steffen Ricardo , Deschet Karine , Jabourian Maritza , Perlbarg Vincent , Gasparetto Emerson Leandro , Dubal Stéphanie , Costa e Silva Jorge , Fossati Philippe
Published: April 2017

Clinical remission of depression may be associated with emotional residual symptoms. We studied the association of emotional blunting, rumination with neural networks dynamics in remitted depressed patients and cognitive performance during an N‐Back task. Twenty‐six outpatients in remission of depression (Hamilton Depressive rating scale score <7) performed an N‐Back task during fMRI assessment. All patients had been treated by paroxetine for a minimum of 4 months. Two subgroups of patients [Nonemotionally blunted (NEB) = 14 and emotionally blunted (EB) = 12] were determined. To identify functional network maps across participants, the Network Detection using Independent Component Analysis approach was employed. Within and between Task Positive Network (TPN) and Default Mode Network (DMN) connectivity were assessed and related to variability of performance on the N‐Back task and rumination. EB and NEB patients were not different for the level of accurate responses at the N‐Back. However over the entire working memory task, the negative correlation between DMN and TPN was significantly lower in the EB than NEB group and was differently related to cognitive performance and rumination. The stronger the negative correlation between DMN and TPN was, the less variable the reaction time during 3‐Back task in NEB patients. Moreover the greater the negative correlation between DMN and TPN was, the lower the rumination score in EB patients. Emotional blunting may be associated with compromised monitoring of rumination and cognitive functioning in remitted depressed patients through altered cooperation between DMN and TPN. The study suggests clinical remission in depression is associated with biological heterogeneity. Hum Brain Mapp 38:3491–3501, 2017. © 2017 Wiley Periodicals, Inc.
Association between hyperinsulinemia and increased risk of cancer death in nonobese and obese people: A population‐based observational study
Authors: Tsujimoto Tetsuro , Kajio Hiroshi , Sugiyama Takehiro
Published: April 2017

Obesity, metabolic syndrome and type 2 diabetes are associated with cancer‐related mortality. We assessed whether hyperinsulinemia is a risk factor for cancer death in nonobese people without diabetes. We conducted a prospective cohort study using data from the National Health and Nutrition Examination Survey 1999–2010 and followed up the participants until December 31, 2011. For the primary analysis of cancer mortality, we used Cox proportional hazard models to estimate hazard ratios (HRs) in the participants with hyperinsulinemia and those without. Hyperinsulinemia was defined as a fasting insulin level of ≥10 μU/mL. To identify causes of deaths, the International Classification of Diseases, Tenth Revision codes were used. This study included 9,778 participants aged 20 years or older without diabetes or a history of cancer: 6,718 nonobese participants (2,057 with hyperinsulinemia [30.6%]) and 3,060 obese participants (2,303 with hyperinsulinemia [75.3%]). A total of 99.9% completed follow‐up. Among all study participants, cancer mortality was significantly higher in those with hyperinsulinemia than in those without hyperinsulinemia (adjusted HR 2.04, 95% CI 1.24–3.34, p = 0.005). Similarly, among nonobese participants, multivariable analysis showed that cancer mortality was significantly higher in those with hyperinsulinemia than in those without (adjusted HR 1.89, 95% CI 1.07–3.35, p = 0.02). Considering that nonobese people with hyperinsulinemia were at higher risk of cancer mortality than those without hyperinsulinemia, improvement of hyperinsulinemia may be an important approach for preventing cancer regardless of the presence or absence of obesity.
Role of the Lysosomal Membrane Protein, CLN3, in the Regulation of Cathepsin D Activity
Authors: Cárcel‐Trullols Jaime , Kovács Attila D. , Pearce David A.
Published: April 2017

Among Neuronal Ceroid Lipofuscinoses (NCLs), which are childhood fatal neurodegenerative disorders, the juvenile onset form (JNCL) is the most common. JNCL is caused by recessive mutations in the CLN3 gene. CLN3 encodes a lysosomal/endosomal transmembrane protein but its precise function is not completely known. We have previously reported that in baby hamster kidney (BHK) cells stably expressing myc‐tagged human CLN3 (myc‐CLN3), hyperosmotic conditions drastically increased myc‐CLN3 mRNA and protein expression. In the present study, we analyzed the consequences of hyperosmolarity, and increased CLN3 expression on cathepsin D (CTSD) activity and prosaposin processing using BHK cells transiently or stably expressing myc‐CLN3. We found that hyperosmolarity increased lysotracker staining of lysosomes, and elevated the levels of myc‐CLN3 and lysosome‐associated membrane protein‐1 (LAMP1). Hyperosmolarity, independently of the expression level of myc‐CLN3, decreased the levels of PSAP and saposin D, which are protein cofactors in sphingolipid metabolism. The lysosomal enzyme cathepsin D (CTSD) mediates the proteolytic cleavage of PSAP precursor into saposins A‐D. Myc‐CLN3 colocalized with CTSD and activity of CTSD decreased as myc‐CLN3 expression increased, and clearly decreased under hyperosmotic conditions. Nevertheless, levels of CTSD measured by Western blotting were not altered under any studied condition. Our results suggest a direct involvement of CLN3 in the regulation of CTSD activity. J. Cell. Biochem. 118: 3883–3890, 2017. © 2017 Wiley Periodicals, Inc.
Cucurbitacin B Protects Against Pressure Overload Induced Cardiac Hypertrophy
Authors: Xiao Yang , Yang Zheng , Wu Qing‐Qing , Jiang Xiao‐Han , Yuan Yuan , Chang Wei , Bian Zhou Yan , Zhu Jin Xiu , Tang Qi‐Zhu
Published: April 2017

Lack of effective anti‐cardiac hypertrophy drugs creates a major cause for the increasing prevalence of heart failure. In the present study, we determined the anti‐hypertrophy and anti‐fibrosis potential of a natural plant triterpenoid, Cucurbitacin B both in vitro and in vivo. Aortic banding (AB) was performed to induce cardiac hypertrophy. After 1 week of surgery, mice were receive cucurbitacin B treatment (Gavage, 0.2 mg/kg body weight/2 day). After 4 weeks of AB, cucurbitacin B demonstrated a strong anti‐hypertrophy and ‐fibrosis ability as evidenced by decreased of heart weight, myocardial cell cross‐sectional area and interstitial fibrosis, ameliorated of systolic and diastolic abnormalities, normalized in gene expression of hypertrophic and fibrotic markers, reserved microvascular density in pressure overload induced hypertrophic mice. Cucurbitacin B also showed significant hypertrophy inhibitory effect in phenylephrine stimulated cardiomyocytes. The Cucurbitacin B‐mediated mitigated cardiac hypertrophy was attributable to the increasing level of autophagy, which was associated with the blockade of Akt/mTOR/FoxO3a signal pathway, validated by SC79, MK2206, and 3‐MA, the Akt agonist, inhibitor and autophagy inhibitor in vitro. The overexpression of constitutively active Akt completely abolished the Cucurbitacin B‐mediated protection of cardiac hypertrophy in human cardiomyocytes AC16. Collectively, our findings suggest that cucurbitacin B protects against cardiac hypertrophy through increasing the autophagy level in cardiomyocytes, which is associated with the inhibition of Akt/mTOR/FoxO3a signal axis. J. Cell. Biochem. 118: 3899–3910, 2017. © 2017 Wiley Periodicals, Inc.
Molecular Imaging and Oral Cancer Diagnosis and Therapy
Authors: Keshavarzi Maryam , Darijani Mansoreh , Momeni Fatemeh , Moradi Pouya , Ebrahimnejad Hamed , Masoudifar Aria , Mirzaei Hamed
Published: April 2017

Oral cancer is known as one of relatively common type of cancer worldwide. Despite the easy access of the oral cavity to examination, oral tumors are diagnosed in more advanced stages of the disease. Imaging techniques have been recently emerged as non‐invasive approaches to detect molecular and cellular changes in living cells and organisms. These techniques such as computed tomography (CT), magnetic resonance imaging (MRI), and positron emission tomography (PET) could help physicians to screen patients with oral tumors particularly oral squamous cell carcinoma (OSCC) in early stage of the disease. In this review, we discuss that early detection and diagnosis of oral tumors through using more robust and precise imaging techniques and a variety of cellular/molecular biomarkers not only could lead to more effective and less aggressive form of treatment for the disease but also could improve survival rates and lower treatment costs. J. Cell. Biochem. 118: 3055–3060, 2017. © 2017 Wiley Periodicals, Inc.
Conformational changes of ubiquitin under high pressure conditions: A pressure simulated tempering molecular dynamics study
Authors: Mori Yoshiharu , Okamoto Yuko
Published: April 2017

Molecular dynamics simulations for the system of ubiquitin were performed with pressure simulated tempering to study pressure‐induced conformational changes of ubiquitin. The pressure dependence of ubiquitin was analyzed in a wide range of pressure from atmospheric pressure (0.1 MPa) to 1.0 GPa. The fluctuation of the distance between amino‐acid residues and the distribution of a largely fluctuating distance were calculated. The large fluctuation of the L8‐E34 distance induced by pressure means that the conformation of ubiquitin changes under high pressure conditions. There were more water molecules near the largely fluctuating region at high pressure than at low pressure. The pressure dependence of interaction energies among ubiquitin and water was also calculated to investigate the role of water for the pressure‐induced conformational changes of ubiquitin. The protein–water interaction is important when the conformation of ubiquitin changes at high pressure. © 2017 Wiley Periodicals, Inc.
[Cu6(NGuaS)6]2+ and its oxidized and reduced derivatives: Confining electrons on a torus
Authors: Witte Matthias , Rohrmüller Martin , Gerstmann Uwe , Henkel Gerald , Schmidt Wolf Gero , Herres‐Pawlis Sonja
Published: April 2017

The hexanuclear thioguanidine mixed‐valent copper complex cation [Cu6(NGuaS)6]+2 (NGuaS = o‐SC6H4NC(NMe2)2) and its oxidized/reduced states are theoretically analyzed by means of density functional theory (DFT) (TPSSh + D3BJ/def2‐TZV (p)). A detailed bonding analysis using overlap populations is performed. We find that a delocalized Cu‐based ring orbital serves as an acceptor for donated S p electrons. The formed fully delocalized orbitals give rise to a confined electron cloud within the Cu6S6 cage which becomes larger on reduction. The resulting strong electrostatic repulsion might prevent the fully reduced state. Experimental UV/Vis spectra are explained using time‐dependent density functional theory (TD‐DFT) and analyzed with a natural transition orbital analysis. The spectra are dominated by MLCTs within the Cu6S6 core over a wide range but LMCTs are also found. The experimental redshift of the reduced low energy absorption band can be explained by the clustering of the frontier orbitals. © 2017 Wiley Periodicals, Inc.
Exploring the Influence of Attitude and Stigma on Participation of African American and Latino Populations in Mental Health Services
Authors: Fripp Jessica A. , Carlson Ryan G.
Published: April 2017

Various factors, including mistrust and disparities, prevent people of color from taking advantage of mental health services. Previous research has focused on mistrust, disparities, and stigma. However, little is understood about how one's attitude affects participation in mental health. The authors surveyed 129 African American and Latino community participants to examine the relationships among attitudes, stigma, and help‐seeking behavior. Linear regression analyses revealed that attitude is a unique predictor in one's decision to seek counseling and is influenced by the presence of stigma.

Varios factores, entre los que se incluyen la falta de confianza y las disparidades, impiden que las personas de color aprovechen los servicios de salud mental. Las investigaciones hasta ahora se han centrado en la falta de confianza, las disparidades y los estigmas. Sin embargo, falta mucho para comprender cómo la actitud de una persona afecta a su participación en la salud mental. Los autores entrevistaron a 129 participantes de comunidades afroamericanas y latinas para examinar las relaciones entre actitudes, estigmas y la búsqueda de ayuda. Los análisis de regresión lineal revelaron que la actitud es un indicador único en la decisión de un individuo de buscar servicios de consejería, y está influida por la presencia de estigmas.
Efficacy and safety of nucleoside‐sparing regimen based on raltegravir and ritonavir‐boosted darunavir in HIV‐1‐infected treatment‐experienced patients
Authors: Jabłonowska Elżbieta , Pulik Piotr , Kalinowska Anna , Gąsiorowski Jacek , Parczewski Miłosz , Bociąga‐Jasik Monika , Pulik Łukasz , Siwak Ewa , Wójcik Kamila
Published: April 2017

Aim

To assess the efficacy and tolerability of dual therapy containing raltegravir (RAL) and ritonavir boosted darunavir (DRV/r) in HIV‐1‐infected treatment‐experienced patients.

Method

Retrospective analysis of 81 HIV‐1‐infected treatment‐experienced patients (56 male and 25 female, 5 Polish centers) who switched to RAL/DRV/r.

Results

The main reasons for the introduction of dual therapy were renal dysfunction (16/81 patients—19.8%) and virologic failure on previous regimens (15/81 patients—18.5%). At 48 weeks the treatment was continued in 58/81 (71.6% of patients). In three patients the therapy was discontinued because of virologic failure. However, no mutations to DRV or integrase inhibitors (InI) were detected. At 48 weeks of treatment CD4+ lymphocyte count increased statistically significantly (median 121 cells/μL) P < 0.005. The main reasons for the discontinuation of therapy were treatment simplification (11/23—47.8% patients), adverse events (7/23 patients 30.4%), virologic failure (3/23 patients 13.0%). All patients who switched to RAL/DRV/r therapy because of prior renal impairment were maintained on the treatment for 48 weeks. In this group, before the introduction of dual therapy eGFR (estimated glomerular filtration rate) <60 mL/min/1.72 m2 was reported in nine patients and after 48 weeks in four patients (56.3% vs 25%) (P > 0.05). We found a statistically significant decrease in the prevalence of proteinuria or eGFR <60 mL/min/1.72 m2 (93.8% vs 37.5%; P = 0.004 before and after the introduction of dual therapy, respectively).

Conclusions

Dual therapy was effective and safe for the vast majority of antiretroviral‐experienced subjects. Such therapy can be recommended especially for patients with renal impairment or NRTIs intolerance.
Molecular analysis of Hepatitis B virus sub‐genotypes and incidence of preS1/preS2 region mutations in HBV‐infected Egyptian patients from Mansoura
Authors: El‐Mowafy Mohammed , Elgaml Abdelaziz , El‐Mesery Mohamed , Elegezy Mohamed
Published: April 2017

Hepatitis B virus (HBV) is one of the major causes of viral hepatitis worldwide. Despite the prevalence of HBV infection in Egypt, few studies have focused on sub‐genotyping of the virus. Moreover, no studies are available regarding the mutational analysis of the preS1/preS2 region of the viral genome, or its impact on hepatocellular carcinoma (HCC) development in Egypt. In this study, we have analyzed the sub‐genotypes and incidence of mutations in the preS1/preS2 region of HBV present in HBV‐infected patients, from Mansoura city (located in the center of Nile Delta region of Egypt), via partial sequencing of this specific region. Moreover, we have investigated the impact of these mutations on HCC development by measuring serum alpha fetoprotein (AFP) level and abdominal ultrasound examination of the HBV‐infected patients. According to our results, all samples were genotype D in which sub‐genotype D1 was predominant. In addition, the results revealed mutations in the preS1/preS2 region, which could result in either immature preS1 protein or completely inhibit the translation of the preS2 protein. However, there was no incidence of HCC development in patients infected with mutated HBV in the preS1/preS2 region. In summary, for the first time our work has proved the predominance of sub‐genotype D1 among HBV‐infected Egyptian patients in Mansoura city, Nile Delta region, Egypt, and incidence of mutations in the preS1/preS2 region of HBV genome. This current study opens up research opportunities to discuss the impact of HBV mutations on the development of HCC in Egypt.
Recommendations for Writing Case Study Articles for Publication in the Journal of College Counseling
Authors: Scholl Mark B.
Published: April 2017

The author presents recommendations for writing case studies for publication in the Journal of College Counseling. Recommendations fall into 2 categories: (a) ethical considerations and (b) criteria essential to methodological rigor (e.g., Hyett, Kenny, & Dickson‐Swift, ). The article is intended to guide and encourage prospective case study authors.
Early local delivery of vancomycin suppresses ectopic bone formation in a rat model of trauma‐induced heterotopic ossification
Authors: Seavey Jonathan G. , Wheatley Benjamin M. , Pavey Gabriel J. , Tomasino Allison M. , Hanson Margaret A. , Sanders Erin M. , Dey Devaveena , Moss Kaitlyn L. , Potter Benjamin K. , Forsberg Jonathan A. , Qureshi Ammar T. , Davis Thomas A.
Published: April 2017

Heterotopic ossification (HO) is a debilitating sequela of high‐energy injuries. It frequently requires surgical excision once symptomatic and there is no practical prophylaxis for combat‐injured patients. In this study, we examined the effect of local vancomycin powder on HO formation in a small animal model of blast‐related, post‐traumatic HO. Male Sprague‐Dawley rats were subjected to a polytraumatic extremity injury and amputation with or without methicillin‐resistant Staphylococcus aureus infection. Animals were randomized to receive a single local application of vancomycin (20 mg/kg) at the time of injury (POD‐0, n = 34) or on postoperative day‐3 (POD‐3, n = 11). Quantitative volumetric measurement of ectopic bone was calculated at 12‐weeks post‐injury by micro‐CT. Bone marrow and muscle tissues were also collected to determine the bacterial burden. Blood for serum cytokine analysis was collected at baseline and post‐injury. Vancomycin treatment on POD‐0 suppressed HO formation by 86% and prevented bone marrow and soft tissue infections. We concurrently observed a marked reduction histologically in nonviable tissue, chronic inflammatory cell infiltrates, bone infection, fibrous tissue, and areas of bone necrosis within this same cohort. Delayed treatment was significantly less efficacious. Neither treatment had a marked effect on the production of pro‐inflammatory cytokines. Our study demonstrates that local vancomycin treatment at the time of injury significantly reduces HO formation in both the presence and absence of infection, with decreased efficacy if not given early. These findings further support the concept that the therapeutic window for prophylaxis is narrow, highlighting the need to develop early treatment strategies for clinical management. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:2397–2406, 2017.
Preparation and bioavailability of calcium‐chelating peptide complex from tilapia skin hydrolysates
Authors: Chen Jun , Qiu Xujian , Hao Gengxin , Zhang Meng , Weng Wuyin
Published: April 2017

BACKGROUND

With the continuous improvement in material life, the generation of fish by‐products and the market demand for calcium supplements have been increasing in China. Therefore a calcium‐chelating peptide complex (CPC) from tilapia skins was prepared and its effect on calcium (Ca)‐deficient mice was investigated.

RESULTS

The molecular weight distribution of CPC mainly ranged from 2000 to 180 Da, and its contents of complete amino acids and free amino acids were 85.30 and 8.67% (w/w) respectively. Scanning electron microscopy images and Fourier transform infrared data revealed that Ca crystals were bound with gelatin hydrolysates via interaction between Ca ions and NH/CN groups. When Ca‐deficient mice were fed CPC and CaCO3 respectively for 4 weeks, no significant differences in serum biochemistry or bone mineral density were found. However, the length, weight, Ca content and hydroxyproline content of the femur, Ca absorption and body weight gain of mice fed CPC were significantly higher than those of mice fed CaCO3.

CONCLUSION

It is concluded that the prepared CPC could promote bone formation via better bioavailability of Ca and an increase in bone collagen. © 2017 Society of Chemical Industry
The ORAC Assay: Mathematical Analysis of the Rate Equations and Some Practical Considerations
Authors: Arellano Juan B. , Mellado‐Ortega Elena , Naqvi K. Razi
Published: April 2017

ORAC (oxygen radical absorbance capacity), a method widely used for measuring the total antioxidant capacity of biological samples, can also be used for the determination of the relative reactivity of an antioxidant compound (XH) by examining the dependence of the rate of consumption of the probe (PH) on the concentration of XH; initial conditions are chosen in such a way that the rate of consumption of the starting reactants may be assumed to follow a drastically simplified kinetic scheme, and the steady‐state approximation for the concentration of the azo compound peroxyl (ROO•) radical is invoked to simplify the analysis. Here we first attempted to find an analytical solution to the coupled first‐order ordinary differential equations (ODEs) of the minimal ORAC kinetic system, applying Lie symmetry group theory without any precondition. However, the Lie symmetry transformations applied to the Chini equation, which appeared after mathematical transformations, showed that the form of the coefficients of the Chini equation precluded the analytical solution of the minimal ORAC kinetic system through symmetry reduction. Consequently, an approximate analytical solution was sought, valid for the case when the bimolecular rate constant of XH with ROO• (i.e., kx) was much larger than that of PH with ROO• (i.e., kp). Using numerical solutions of the original set of ODEs of the ORAC kinetic system, the quality of the approximate solution was inspected under conditions that correspond to those employed in several ORAC methods together with a low initial concentration of the azo compound radical initiator. The simulations allowed us to conclude that the approximate analytical solution of the ODEs of the minimal ORAC kinetic system was not entirely devoid of academic interest, but its applicability was restricted to conditions where both kx ≫ kp and the initial concentration of XH was higher than that of PH.
Synthesis and Validation of Functional Nanogels as pH‐Sensors in the Hair Follicle
Authors: Dimde Mathias , Sahle Fitsum Feleke , Wycisk Virginia , Steinhilber Dirk , Camacho Luis Cuellar , Licha Kai , Lademann Jürgen , Haag Rainer
Published: April 2017

In the present study, a pH responsive dendritic polyglycerol nanogel (dPG‐NG) is developed to measure the pH values inside the hair follicle (HF) using an ex vivo porcine ear model. The macromolecular precursors are labeled with a pH sensitive indodicarbocyanine dye (pH‐IDCC) and a control dye (indocarbocyanine dye: ICC) and crosslinked via a mild and surfactant‐free Thiol–Michael reaction using an inverse nanoprecipitation method. With this method, it is possible to prepare tailor‐made particles in the range of 100 nm to 1 µm with a narrow polydispersity. The dPG‐NGs are characterized using dynamic light scattering, nanoparticle tracking analysis, and atomic force microscopy. Systematic analysis of confocal microscope images of histological sections of the skin enables accurate determination of the pH gradient inside the HF. The results show that these novel pH‐nanosensors deeply penetrate the skin via the follicular pathway and the pH of the pig hair follicles increase from 6.5 at the surface of the skin to 7.4 in deeper areas of the HF. The pH‐nanosensor shows no toxicity potentials.

image
Dextran Nanoparticles Cross‐Linked in Aqueous and Aqueous/Alcoholic Media
Authors: Iakobson Olga D. , Dobrodumov Anatoly V. , Saprykina Natalia N. , Shevchenko Natalia N.
Published: April 2017

The attractiveness of the dextran nanoparticle application in medicine and pharmacology results from biocompatibility, biodegradability, and nontoxicity of the polymer. However, it still remains a challenge to prepare such nanoparticles in an aqueous medium due to dextran hydrophilicity. Here, the technique of dextran nanoparticle synthesis with the average diameter of 140–450 nm in aqueous and aqueous/ethanolic media is described. The chemical structure of cross‐linker used for the dextran nanoparticle stabilization is demonstrated to influence the dextran nanoparticle diameter, size distribution, and ζ‐potential. As shown the regulation of the nanoparticle diameter and ζ‐potential is possible through the surfactants and/or dextran nonsolvent (ethanol) addition into the reaction medium. Due to the additional steric stabilization, the dextran nanoparticles of minimum diameter are formed in the presence of ionic surfactants in the aqueous/ethanolic medium. The nanoparticle shape and diameter are analyzed by dynamic light scattering, transmission electron microscopy, and scanning electron microscopy; the composition is investigated by 1H NMR spectroscopy.

image
Degeneration of rapid eye movement sleep circuitry underlies rapid eye movement sleep behavior disorder
Authors: McKenna Dillon , Peever John
Published: April 2017

During healthy rapid eye movement sleep, skeletal muscles are actively forced into a state of motor paralysis. However, in rapid eye movement sleep behavior disorder—a relatively common neurological disorder—this natural process is lost. A lack of motor paralysis (atonia) in rapid eye movement sleep behavior disorder allows individuals to actively move, which at times can be excessive and violent. At first glance this may sound harmless, but it is not because rapid eye movement sleep behavior disorder patients frequently injure themselves or the person they sleep with. It is hypothesized that the degeneration or dysfunction of the brain stem circuits that control rapid eye movement sleep paralysis is an underlying cause of rapid eye movement sleep behavior disorder. The link between brain stem degeneration and rapid eye movement sleep behavior disorder stems from the fact that rapid eye movement sleep behavior disorder precedes, in the majority (∼80%) of cases, the development of synucleinopathies such as Parkinson's disease, dementia with Lewy bodies, and multiple system atrophy, which are known to initially cause degeneration in the caudal brain stem structures where rapid eye movement sleep circuits are located. Furthermore, basic science and clinical evidence demonstrate that lesions within the rapid eye movement sleep circuits can induce rapid eye movement sleep‐specific motor deficits that are virtually identical to those observed in rapid eye movement sleep behavior disorder. This review examines the evidence that rapid eye movement sleep behavior disorder is caused by synucleinopathic neurodegeneration of the core brain stem circuits that control healthy rapid eye movement sleep and concludes that rapid eye movement sleep behavior disorder is not a separate clinical entity from synucleinopathies but, rather, it is the earliest symptom of these disorders. © 2017 International Parkinson and Movement Disorder Society