bluuebunny/crossref_metadata_2025_split huggingface dataset:
Empirical comparison of reduced representation bisulfite sequencing and Infinium BeadChip reproducibility and coverage of DNA methylation in humans
Authors: Carmona Juan J. , Accomando William P. , Binder Alexandra M. , Hutchinson John N. , Pantano Lorena , Izzi Benedetta , Just Allan C. , Lin Xihong , Schwartz Joel , Vokonas Pantel S. , Amr Sami S. , Baccarelli Andrea A. , Michels Karin B. 
Published: April 2017

AbstractWe empirically examined the strengths and weaknesses of two human genome-wide DNA methylation platforms: rapid multiplexed reduced representation bisulfite sequencing and Illumina’s Infinium BeadChip. Rapid multiplexed reduced representation bisulfite sequencing required less input DNA, offered more flexibility in coverage, and interrogated more CpG loci at a higher regional density. The Infinium covered slightly more protein coding, cancer-associated and mitochondrial-related genes, both platforms covered all known imprinting clusters, and rapid multiplexed reduced representation bisulfite sequencing covered more microRNA genes than the HumanMethylation450, but fewer than the MethylationEPIC. Rapid multiplexed reduced representation bisulfite sequencing did not always interrogate exactly the same CpG loci, but genomic tiling improved overlap between different libraries. Reproducibility of rapid multiplexed reduced representation bisulfite sequencing and concordance between the platforms increased with CpG density. Only rapid multiplexed reduced representation bisulfite sequencing could genotype samples and measure allele-specific methylation, and we confirmed that Infinium measurements are influenced by nearby single-nucleotide polymorphisms. The respective strengths and weaknesses of these two genome-wide DNA methylation platforms need to be considered when conducting human epigenetic studies.
Heroin-HIV-1 (H2) vaccine: induction of dual immunologic effects with a heroin hapten-conjugate and an HIV-1 envelope V2 peptide with liposomal lipid A as an adjuvant
Authors: Torres Oscar B. , Matyas Gary R. , Rao Mangala , Peachman Kristina K. , Jalah Rashmi , Beck Zoltan , Michael Nelson L. , Rice Kenner C. , Jacobson Arthur E. , Alving Carl R. 
Published: April 2017

AbstractA synthetic heroin analog (MorHap) and a synthetic 42 amino acid V2 loop peptide from A/E strain of HIV-1 gp120 envelope protein that was previously used in a successful phase III vaccine trial were constructed as antigens together with liposomes containing monophosphoryl lipid A as an adjuvant, to explore the feasibility of producing a dual use vaccine both for treatment of heroin addiction and prevention of HIV-1 infection among injection drug users. The V2 peptide was tethered by a palmitoyl fatty acyl tail embedded in the liposomal lipid bilayer, and the heroin analog was conjugated to tetanus toxoid as a carrier protein that was mixed with the adjuvant. Upon comparison of a linear V2 peptide with a cyclic peptide, differences were found in the secondary configurations by circular dichroism, with the tethered cyclic peptide (palm-cyclic peptide) entirely in a random coil, and the tethered linear V2 peptide (palm-linear V2 peptide) entirely in a beta-sheet. Upon immunization of mice, palm-cyclic peptide induced anti-cyclic peptide endpoint titers >106and was considered to be a better immunogen overall than palm-linear V2 peptide for inducing antibodies to gp120 and gp70-V1V2. The antibodies also inhibited the binding of V2 peptide to the HIV-1 α4β7integrin receptor. Antibody titers to MorHap, even with the presence of injected cyclic peptide, were very high, and resulted in inhibition of the hyper-locomotion and antinociception effects of injected heroin. From these initial experiments, we conclude that with a potent adjuvant and mostly synthetic constituents, a vaccine directed to heroin and HIV-1 (H2 vaccine) could be a feasible objective.
Therapeutic vaccines for allergic disease
Authors: Gutowska-Owsiak Danuta , Ogg Graham S. 
Published: April 2017

AbstractAllergic diseases are highly prevalent worldwide and affect all age groups, contributing to a high personal and socioeconomic burden. Treatment with an “allergy vaccine” or allergen immunotherapy aims to provide long-lasting benefits by inducing unresponsiveness to the relevant antigen. The consequences of the therapy are considered disease modifying and range from dampening of the immediate immune responses to the reduction of secondary tissue remodeling. Furthermore, allergen immunotherapy interventions have a potential to slow or cease the development of additional allergic manifestations with a long-term overall effect on morbidity and quality of life. Here, we review proposed mechanisms underlying the therapeutic effects of immunotherapy for allergic diseases. Further, we discuss both standard and novel approaches and possible future directions in the development of allergen immunotherapy.
A tongue for all seasons: extreme phenotypic flexibility in salamandrid newts
Authors: Heiss Egon , Handschuh Stephan , Aerts Peter , Van Wassenbergh Sam 
Published: April 2017

AbstractMany organisms faced with seasonally fluctuating abiotic and biotic conditions respond by altering their phenotype to account for the demands of environmental changes. Here we discovered that newts, which switch seasonally between an aquatic and terrestrial lifestyle, grow a complex adhesive system on their tongue pad consisting of slender lingual papillae and mucus-producing cells to increase the efficiency of prey capture as they move from water onto land. The adhesive system is reduced again as newts switch back to their aquatic stage, where they use suction to capture prey. As suction performance is also enhanced seasonally by reshaping of the mouth due to the growth of labial lobes, our results show that newts are exceptional in exhibiting phenotypic flexibility in two alternating components (i.e. tongue pad and labial lobes) within a single functional system, and suggest that this form of phenotypic flexibility demands complex genetic regulation.
Joint-based description of protein structure: its application to the geometric characterization of membrane proteins
Authors: Thangappan Jayaraman , Wu Sangwook , Lee Sun-Gu 
Published: April 2017

AbstractA macroscopic description of a protein structure allows an understanding of the protein conformations in a more simplistic manner. Here, a new macroscopic approach that utilizes the joints of the protein secondary structures as a basic descriptor for the protein structure is proposed and applied to study the arrangement of secondary structures in helical membrane proteins. Two types of dihedral angle, Ω and λ, were defined based on the joint points of the transmembrane (TM) helices and loops, and employed to analyze 103 non-homologous membrane proteins with 3 to 14 TM helices. The Ω-λ plot, which is a distribution plot of the dihedral angles of the joint points, identified the allowed and disallowed regions of helical arrangement. Analyses of consecutive dihedral angle patterns indicated that there are preferred patterns in the helical alignment and extension of TM proteins, and helical extension pattern in TM proteins is varied as the size of TM proteins increases. Finally, we could identify some symmetric protein pairs in TM proteins under the joint-based coordinate and 3-dimensional coordinates. The joint-based approach is expected to help better understand and model the overall conformational features of complicated large-scale proteins, such as membrane proteins.
Endogenous Two-Photon Excited Fluorescence Imaging Characterizes Neuron and Astrocyte Metabolic Responses to Manganese Toxicity
Authors: Stuntz Emily , Gong Yusi , Sood Disha , Liaudanskaya Volha , Pouli Dimitra , Quinn Kyle P. , Alonzo Carlo , Liu Zhiyi , Kaplan David L. , Georgakoudi Irene 
Published: April 2017

AbstractAs neurodegenerative conditions are increasingly linked to mitochondrial dysfunction, methods for studying brain cell metabolism at high spatial resolution are needed to elucidate neurodegeneration mechanisms. Two-photon excited fluorescence (TPEF) imaging is a non-destructive, high-resolution technique for studying cell metabolism via endogenous fluorescence of reduced nicotinamide adenine dinucleotide (phosphate) (NAD(P)H) and flavin adenine dinucleotide (FAD). We employed TPEF to study the metabolism of primary rat astrocyte and neuronal cultures under normal growth conditions and in response to manganese (Mn) treatment. Histograms of pixel-wise optical redox ratio, defined as FAD/(FAD + NAD(P)H), revealed three distinct redox distributions and significant differences in their relative weights between astrocytes and neurons. When treated with Mn, both cell types exhibited redox ratio shifts consistent with increased oxidative stress. However, the manner in which the redox distributions was affected was distinct for the two cell types. Furthermore, NAD(P)H fluorescence lifetime imaging revealed an increase in bound NAD(P)H fraction upon Mn treatment for neurons, consistent with enhanced apoptosis. Astrocytes showed a decrease in bound fraction, possibly due to a shift towards glycolytic metabolism in response to impaired respiration. These results exhibit TPEF’s utility for characterizing detailed metabolic changes of different brain cell types in response to neurotoxins.
Closed-loop deep brain stimulation by pulsatile delayed feedback with increased gap between pulse phases
Authors: Popovych Oleksandr V. , Lysyansky Borys , Tass Peter A. 
Published: April 2017

AbstractComputationally it was shown that desynchronizing delayed feedback stimulation methods are effective closed-loop techniques for the control of synchronization in ensembles of interacting oscillators. We here computationally design stimulation signals for electrical stimulation of neuronal tissue that preserve the desynchronizing delayed feedback characteristics and comply with mandatory charge deposit-related safety requirements. For this, the amplitude of the high-frequency (HF) train of biphasic charge-balanced pulses used by the standard HF deep brain stimulation (DBS) is modulated by the smooth feedback signals. In this way we combine the desynchronizing delayed feedback approach with the HF DBS technique. We show that such a pulsatile delayed feedback stimulation can effectively and robustly desynchronize a network of model neurons comprising subthalamic nucleus and globus pallidus external and suggest this approach for desynchronizing closed-loop DBS. Intriguingly, an interphase gap introduced between the recharging phases of the charge-balanced biphasic pulses can significantly improve the stimulation-induced desynchronization and reduce the amount of the administered stimulation. In view of the recent experimental and clinical studies indicating a superiority of the closed-loop DBS to open-loop HF DBS, our results may contribute to a further development of effective stimulation methods for the treatment of neurological disorders characterized by abnormal neuronal synchronization.
Birth weight changes in a major city under rapid socioeconomic transition in China
Authors: He Jian-Rong , Li Wei-Dong , Lu Min-Shan , Guo Yong , Chan Fan-Fan , Lu Jin-Hua , Zhang Li-Fang , Shen Song-Ying , Xia Xiao-Yan , Wang Ping , Mo Wei-Jian , Lam Kin Bong Hubert , Hirst Jane E. , Xia Hui-Min , Qiu Xiu 
Published: April 2017

AbstractEstimates of trends in birth weight may be useful in evaluating population health. We aimed to determine whether temporal changes in birth weight have occurred amongst 2.3 million neonates born in Guangzhou, China, during 2001–2015 and investigate the socioeconomic determinants of any changes. Trends in mean birth weight and annualized changes with the associated 95% confidence intervals (CIs) in the incidence of small for gestational age (SGA) and large for gestational age (LGA), defined as birth weight <10th or >90th centile respectively for gestational age and sex, were examined using linear and Poisson regression models. We found that mean birth weight declined by 1.07 grams/year from 2001 to 2015. After adjustment for gestational length, the decline in birth weight was attenuated (0.37 grams/year). The incidence of both SGA and LGA significantly decreased during the study period (annual decrease of 1.6% [95% CI, 1.5% to 1.7%] for SGA, 1.6% [95% CI, 1.5% to 1.8%] for LGA). We found a narrowing of disparities in SGA and LGA incidence across different maternal educational levels and residence location. Our results demonstrate that there has been an increase in the proportion of neonates born in the healthy birth weight range in Guangzhou.
Decreasing temperature enhances the formation of sixfold hydrogen bonded rings in water-rich water-methanol mixtures
Authors: Bakó Imre , Pusztai László , Temleitner László 
Published: April 2017

AbstractThe evolution of the structure of liquid water-methanol mixtures as a function of temperature has been studied by molecular dynamics simulations, with a focus on hydrogen bonding. The combination of the OPLS-AA (all atom) potential model of methanol and the widely used SPC/E water model has provided excellent agreement with measured X-ray diffraction data over the temperature range between 298 and 213 K, for mixtures with methanol molar fractions of 0.2, 0.3 and 0.4. Hydrogen bonds (HB-s) have been identified via a combined geometric/energetic, as well as via a purely geometric definition. The number of recognizable hydrogen bonded ring structures in some cases doubles while lowering the temperature from 298 to 213 K; the number of sixfold rings increases most significantly. An evolution towards the structure of hexagonal ice, that contains only sixfold hydrogen bonded rings, has thus been detected on cooling water-methanol mixtures.
Severe hearing loss and outer hair cell death in homozygous Foxo3 knockout mice after moderate noise exposure
Authors: Gilels Felicia , Paquette Stephen T. , Beaulac Holly J. , Bullen Anwen , White Patricia M. 
Published: April 2017

AbstractNoise induced hearing loss (NIHL) is a disease that affects millions of Americans. Identifying genetic pathways that influence recovery from noise exposure is an important step forward in understanding NIHL. The transcription factor Foxo3 integrates the cellular response to oxidative stress and plays a role in extending lifespan in many organisms, including humans. Here we show that Foxo3 is required for auditory function after noise exposure in a mouse model system, measured by ABR. Absent Foxo3, outer hair cells are lost throughout the middle and higher frequencies. SEM reveals persistent damage to some surviving outer hair cell stereocilia. However, DPOAE analysis reveals that some function is preserved in low frequency outer hair cells, despite concomitant profound hearing loss. Inner hair cells, auditory synapses and spiral ganglion neurons are all present after noise exposure in the Foxo3KO/KO fourteen days post noise (DPN). We also report anti-Foxo3 immunofluorescence in adult human outer hair cells. Taken together, these data implicate Foxo3 and its transcriptional targets in outer hair cell survival after noise damage. An additional role for Foxo3 in preserving hearing is likely, as low frequency auditory function is absent in noise exposed Foxo3KO/KOs even though all cells and structures are present.
Effects of porosity on dynamic indentation resistance of silica nanofoam
Authors: Zhao Cang , Zhong Ying , Qiao Yu 
Published: April 2017

AbstractThe dynamic indentation behaviors of monolithic silica nanofoams of various porosities are investigated. When the pore size is on the nm scale, as the porosity increases, despite the decrease in mass density, the resistance offered by silica nanofoam to dynamic indentation is maintained at a high level, higher than the resistance of solid silica or regular porous silica. This phenomenon is related to the fast collapse of nanocells, which produces a locally hardened region and significantly increases the volume of material involved in impact energy dissipation.
Genome-wide identification, characterization of the MADS-box gene family in Chinese jujube and their involvement in flower development
Authors: Zhang Liman , Zhao Jin , Feng Chunfang , Liu Mengjun , Wang Jiurui , Hu Yafei 
Published: April 2017

AbstractMADS-box genes encode transcription factors that are involved in plant development control (particularly in floral organogenesis) and signal transduction pathways, though a comprehensive analysis of MADS-box family proteins in Chinese jujube (Ziziphus jujuba Mill.) is still missing. Here, we report a genome-wide analysis of the MADS-box gene family in Chinese jujube. Based on phylogenetic analyses, 52 jujube MADS-box genes were classified into 25 MIKCC-type, 3 MIKC*-type, 16 Mα, 5 Mβ and 3 Mγ genes. 37 genes were randomly distributed across all 12 putative chromosomes. We found that the type II genes are more complex than the type I genes and that tandem duplications have occurred in three groups of MADS-box genes. Meanwhile, some gene pairs in the same clade displayed similar or distinct expression profiles, suggesting possible functional redundancy or divergence. MIKCC-type genes exhibited typical temporal and spatial expression patterns in the four whorls of floral tissues. The expressions of B, C/D and E-type genes were significantly suppressed in phyllody as compared to flower, providing valuable evidence for their involvement in flower development. This study is the first comprehensive analysis of the MADS-box family in jujube, and provides valuable information for elucidating molecular regulation mechanism of jujube flower development.
White spot syndrome virus VP28 specific double-stranded RNA provides protection through a highly focused siRNA population
Authors: Nilsen Pål , Karlsen Marius , Sritunyalucksana Kallaya , Thitamadee Siripong 
Published: April 2017

AbstractSeveral studies have demonstrated that injection of double-stranded RNAs (dsRNA) homologous to mRNA for the white spot syndrome virus (WSSV) viral protein 28 (VP28) can induce protection in shrimp against WSSV through RNA interference (RNAi). In comparison to shrimp injected with either PBS or a green fluorescent protein (GFP) nonspecific dsRNA, we obtained nearly complete protection against WSSV infection in shrimp injected with VP28 dsRNA. Upregulation of host genes associated with small RNA silencing was measured 48 hours post treatment in groups injected with dsRNA, and although the VP28-treated group remained moderately upregulated after challenge with WSSV, many-fold higher induction was observed in both control groups reflecting the ongoing viral infection. RNA sequencing of VP28-treated shrimp demonstrated a siRNA population dominated by high levels of 22 nt long molecules narrowly targeting the VP28 mRNA both before and after challenge with WSSV. Conversely, while no siRNAs targeting WSSV were detected before challenge, a broad response of 22 nt siRNAs mapping across the entire WSSV genome were found in both control groups after challenge. These results give detailed insight to how dsRNA targeting VP28 function to induce protection against WSSV, by generating a highly focused population of 22 nt long siRNA molecules.
Involvement of gonadotropin-inhibitory hormone in pubertal disorders induced by thyroid status
Authors: Kiyohara Mika , Son You Lee , Tsutsui Kazuyoshi 
Published: April 2017

AbstractThyroid disorders cause abnormal puberty, indicating interactions between the hypothalamus-pituitary-thyroid (HPT) and hypothalamus-pituitary-gonadal (HPG) axes, which are important in pubertal development. The hypothalamic gonadotropin-inhibitory hormone (GnIH) was shown to be decreased in the early prepubertal stage, suggesting the role of GnIH on pubertal onset. Here, we investigated whether thyroid dysfunction affects pubertal onset in female mice via GnIH regulation. Hypothyroidism showed delayed pubertal onset with increased GnIH expression and reduced pituitary-gonadal activity. Remarkably, knockout of GnIH prevented the effect of hypothyroidism to delay the pubertal onset, resulting in indistinguishable pubertal timing in GnIH-knockout female mice between control and hypothyroidism-induced group, indicating that increased GnIH expression induced by hypothyroidism may lead to delayed puberty. In contrast, hyperthyroidism led to a decrease in GnIH expression, however pubertal onset was normal, implying further reduction of the inhibitory GnIH had little effect on the phenotypical change. Critically, thyroid hormone suppressed GnIH expression in hypothalamic explants and GnIH neurons expressed thyroid hormone receptors to convey the thyroid status. Moreover, the thyroid status highly regulated the chromatin modifications of GnIH promoter, H3acetylation and H3K9tri-methylation. These findings indicate a novel function of GnIH to mediate HPT-HPG interactions that contribute to proper pubertal development.
A role of human RNase P subunits, Rpp29 and Rpp21, in homology directed-repair of double-strand breaks
Authors: Abu-Zhayia Enas R. , Khoury-Haddad Hanan , Guttmann-Raviv Noga , Serruya Raphael , Jarrous Nayef , Ayoub Nabieh 
Published: April 2017

AbstractDNA damage response (DDR) is needed to repair damaged DNA for genomic integrity preservation. Defective DDR causes accumulation of deleterious mutations and DNA lesions that can lead to genomic instabilities and carcinogenesis. Identifying new players in the DDR, therefore, is essential to advance the understanding of the molecular mechanisms by which cells keep their genetic material intact. Here, we show that the core protein subunits Rpp29 and Rpp21 of human RNase P complex are implicated in DDR. We demonstrate that Rpp29 and Rpp21 depletion impairs double-strand break (DSB) repair by homology-directed repair (HDR), but has no deleterious effect on the integrity of non-homologous end joining. We also demonstrate that Rpp29 and Rpp21, but not Rpp14, Rpp25 and Rpp38, are rapidly and transiently recruited to laser-microirradiated sites. Rpp29 and Rpp21 bind poly ADP-ribose moieties and are recruited to DNA damage sites in a PARP1-dependent manner. Remarkably, depletion of the catalytic H1 RNA subunit diminishes their recruitment to laser-microirradiated regions. Moreover, RNase P activity is augmented after DNA damage in a PARP1-dependent manner. Altogether, our results describe a previously unrecognized function of the RNase P subunits, Rpp29 and Rpp21, in fine-tuning HDR of DSBs.