bluuebunny/crossref_metadata_2025_split huggingface dataset:
Increased GABAB receptor signaling in a rat model for schizophrenia
Authors: Selten Martijn M. , Meyer Francisca , Ba Wei , Vallès Astrid , Maas Dorien A. , Negwer Moritz , Eijsink Vivian D. , van Vugt Ruben W. M. , van Hulten Josephus A. , van Bakel Nick H. M. , Roosen Joey , van der Linden Robert J. , Schubert Dirk , Verheij Michel M. M. , Kasri Nael Nadif , Martens Gerard J. M. 
Published: September 2016

AbstractSchizophrenia is a complex disorder that affects cognitive function and has been linked, both in patients and animal models, to dysfunction of the GABAergic system. However, the pathophysiological consequences of this dysfunction are not well understood. Here, we examined the GABAergic system in an animal model displaying schizophrenia-relevant features, the apomorphine-susceptible (APO-SUS) rat and its phenotypic counterpart, the apomorphine-unsusceptible (APO-UNSUS) rat at postnatal day 20–22. We found changes in the expression of the GABA-synthesizing enzyme GAD67 specifically in the prelimbic- but not the infralimbic region of the medial prefrontal cortex (mPFC), indicative of reduced inhibitory function in this region in APO-SUS rats. While we did not observe changes in basal synaptic transmission onto LII/III pyramidal cells in the mPFC of APO-SUS compared to APO-UNSUS rats, we report reduced paired-pulse ratios at longer inter-stimulus intervals. The GABAB receptor antagonist CGP 55845 abolished this reduction, indicating that the decreased paired-pulse ratio was caused by increased GABAB signaling. Consistently, we find an increased expression of the GABAB1 receptor subunit in APO-SUS rats. Our data provide physiological evidence for increased presynaptic GABAB signaling in the mPFC of APO-SUS rats, further supporting an important role for the GABAergic system in the pathophysiology of schizophrenia.
Adhesive ligand tether length affects the size and length of focal adhesions and influences cell spreading and attachment
Authors: Attwood Simon J. , Cortes Ernesto , Haining Alexander William M. , Robinson Benjamin , Li Danyang , Gautrot Julien , del Río Hernández Armando 
Published: September 2016

AbstractCells are known to respond to physical cues from their microenvironment such as matrix rigidity. Discrete adhesive ligands within flexible strands of fibronectin connect cell surface integrins to the broader extracellular matrix and are thought to mediate mechanosensing through the cytoskeleton-integrin-ECM linkage. We set out to determine if adhesive ligand tether length is another physical cue that cells can sense. Substrates were covalently modified with adhesive arginylglycylaspartic acid (RGD) ligands coupled with short (9.5 nm), medium (38.2 nm) and long (318 nm) length inert polyethylene glycol tethers. The size and length of focal adhesions of human foreskin fibroblasts gradually decreased from short to long tethers. Furthermore, we found cell adhesion varies in a linker length dependent manner with a remarkable 75% reduction in the density of cells on the surface and a 50% reduction in cell area between the shortest and longest linkers. We also report the interplay between RGD ligand concentration and tether length in determining cellular spread area. Our findings show that without varying substrate rigidity or ligand density, tether length alone can modulate cellular behaviour.
BEN domain protein Elba2 can functionally substitute for linker histone H1 in Drosophila in vivo
Authors: Xu Na , Lu Xingwu , Kavi Harsh , Emelyanov Alexander V. , Bernardo Travis J. , Vershilova Elena , Skoultchi Arthur I. , Fyodorov Dmitry V. 
Published: September 2016

AbstractMetazoan linker histones are essential for development and play crucial roles in organization of chromatin, modification of epigenetic states and regulation of genetic activity. Vertebrates express multiple linker histone H1 isoforms, which may function redundantly. In contrast, H1 isoforms are not present in Dipterans, including D. melanogaster, except for an embryo-specific, distantly related dBigH1. Here we show that Drosophila BEN domain protein Elba2, which is expressed in early embryos and was hypothesized to have insulator-specific functions, can compensate for the loss of H1 in vivo. Although the Elba2 gene is not essential, its mutation causes a disruption of normal internucleosomal spacing of chromatin and reduced nuclear compaction in syncytial embryos. Elba2 protein is distributed ubiquitously in polytene chromosomes and strongly colocalizes with H1. In H1-depleted animals, ectopic expression of Elba2 rescues the increased lethality and ameliorates abnormalities of chromosome architecture and heterochromatin functions. We also demonstrate that ectopic expression of BigH1 similarly complements the deficiency of H1 protein. Thus, in organisms that do not express redundant H1 isoforms, the structural and biological functions performed by canonical linker histones in later development, may be shared in early embryos by weakly homologous proteins, such as BigH1, or even unrelated, non-homologous proteins, such as Elba2.
Colluvium supply in humid regions limits the frequency of storm-triggered landslides
Authors: Parker Robert N. , Hales Tristram C. , Mudd Simon M. , Grieve Stuart W. D. , Constantine José A. 
Published: September 2016

AbstractShallow landslides, triggered by extreme rainfall, are a significant hazard in mountainous landscapes. The hazard posed by shallow landslides depends on the availability and strength of colluvial material in landslide source areas and the frequency and intensity of extreme rainfall events. Here we investigate how the time taken to accumulate colluvium affects landslide triggering rate in the Southern Appalachian Mountains, USA and how this may affect future landslide hazards. We calculated the failure potential of 283 hollows by comparing colluvium depths to the minimum (critical) soil depth required for landslide initiation in each hollow. Our data show that most hollow soil depths are close to their critical depth, with 62% of hollows having soils that are too thin to fail. Our results, supported by numerical modeling, reveal that landslide frequency in many humid landscapes may be insensitive to projected changes in the frequency of intense rainfall events.
Proteome Profiling of Urinary Exosomes Identifies Alpha 1-Antitrypsin and H2B1K as Diagnostic and Prognostic Biomarkers for Urothelial Carcinoma
Authors: Lin Shih-Yi , Chang Chao-Hsiang , Wu His-Chin , Lin Ching-Chan , Chang Kai-Po , Yang Chi-Rei , Huang Chi-Ping , Hsu Wu-Huei , Chang Chiz-Tzung , Chen Chao-Jung 
Published: September 2016

AbstractMALDI-TOF spectrometry has not been used for urinary exosome analysis. We used it for determining UC biomarkers. From 2012 to 2015, we enrolled 129 consecutive patients with UC and 62 participants without UC. Exosomes from their urine were isolated, and analyzed through MALDI-TOF spectrometry. Immunohistochemical (IHC) analysis of another 122 UC and 26 non-UC tissues was conducted to verify the discovered biomarkers. Two peaks at m/z 5593 (fragmented peptide of alpha-1-antitrypsin; sensitivity, 50.4%; specificity, 96.9%) and m/z 5947 (fragmented peptide of histone H2B1K sensitivity, 62.0%; specificity, 92.3%) were identified as UC diagnosis exosome biomarkers. UC patients with detectable histone H2B1K showed 2.29- and 3.11-fold increased risks of recurrence and progression, respectively, compared with those with nondetectable histone H2B1K. Verification results of IHC staining revealed significantly higher expression of alpha 1-antitrypsin (p = 0.038) and H2B1K (p = 0.005) in UC tissues than in normal tissues. The expression of alpha 1-antitrypsin and H2B1K in UC tissues was significantly correlated with UC grades (p < 0.05). Urinary exosome proteins alpha 1-antitrypsin and histone H2B1K, which are identified through MALDI-TOF analysis, could facilitate rapid diagnosis and prognosis of UC.
Non-specific alarm calls trigger mobbing behavior in Hainan gibbons (Nomascus hainanus)
Authors: Deng Huaiqing , Gao Kai , Zhou Jiang 
Published: September 2016

AbstractAlarm calls are important defensive behaviors. Here, we report the acoustic spectrum characteristics of alarm calls produced by Hainan gibbons (Nomascus hainanus) inhabiting Bawangling National Nature Reserve in Hainan, China. Analysis of call data collected from 2002–2014 shows that alarm calls are emitted by all family group members, except infants. Alarm behavior included simple short alarming calls (7–10 min) followed by longer variable-frequency mobbing calls lasting 5–12 min. The duration of individual alarming and mobbing calls was 0.078 ± 0.014 s and 0.154 ± 0.041 s at frequency ranges of 520–1000 Hz and 690–3920 Hz, respectively. Alarming call duration was positively associated with group size. The alarm calls can trigger mobbing behavior in Hainan gibbons; this is a defense way of social animals and first report among the primates’ species. The system of vocal alarm behavior described in this critically endangered species is simple and effective.
Bithionol blocks pathogenicity of bacterial toxins, ricin and Zika virus
Authors: Leonardi William , Zilbermintz Leeor , Cheng Luisa W. , Zozaya Josue , Tran Sharon H. , Elliott Jeffrey H. , Polukhina Kseniya , Manasherob Robert , Li Amy , Chi Xiaoli , Gharaibeh Dima , Kenny Tara , Zamani Rouzbeh , Soloveva Veronica , Haddow Andrew D. , Nasar Farooq , Bavari Sina , Bassik Michael C. , Cohen Stanley N. , Levitin Anastasia , Martchenko Mikhail 
Published: September 2016

AbstractDiverse pathogenic agents often utilize overlapping host networks and hub proteins within these networks represent attractive targets for broad-spectrum drugs. Using bacterial toxins, we describe a new approach for discovering broad-spectrum therapies capable of inhibiting host proteins that mediate multiple pathogenic pathways. This approach can be widely used, as it combines genetic-based target identification with cell survival-based and protein function-based multiplex drug screens and concurrently discovers therapeutic compounds and their protein targets. Using B-lymphoblastoid cells derived from the HapMap Project cohort of persons of African, European and Asian ancestry we identified host caspases as hub proteins that mediate the lethality of multiple pathogenic agents. We discovered that an approved drug, Bithionol, inhibits host caspases and also reduces the detrimental effects of anthrax lethal toxin, diphtheria toxin, cholera toxin, Pseudomonas aeruginosa exotoxin A, Botulinum neurotoxin, ricin and Zika virus. Our study reveals the practicality of identifying host proteins that mediate multiple disease pathways and discovering broad-spectrum therapies that target these hub proteins.
SMC4, which is essentially involved in lung development, is associated with lung adenocarcinoma progression
Authors: Zhang Chengli , Kuang Manchao , Li Meng , Feng Lin , Zhang Kaitai , Cheng Shujun 
Published: September 2016

AbstractStructural maintenance of chromosome 4 (SMC4) is a core subunit of condensin complexes that mainly contributes to chromosome condensation and segregation. Our previous study demonstrated that the gene expression profile during lung development is of great values for the study of lung cancer. In this study, we identified SMC4 through co-expression network analysis and clique percolation clustering using genes that constant changes during four stages of lung development. Gene ontology and KEGG pathway enrichment analysis demonstrated that SMC4 is closely related to cell cycle, cell adhesion and RNA processing in lung development and carcinogenesis. Moreover, SMC4 is overexpressed in lung adenocarcinoma tissues and acts as an independent prognostic factor. SMC4 knockdown significantly inhibits the proliferation and invasion of A549 cells. Furthermore, we found that SMC4 interacts with DDX46 (DEAD-box helicase 46). In conclusion, the pivotal role of SMC4 in lung development and carcinogenesis suggests that genes with a similar expression pattern to SMC4 in lung development may also contribute to lung cancer progression. The identification of genes that are essentially involved in development through a comparative study between development and cancer may be a practical strategy for discovering potential biomarkers and illuminating the mechanisms of carcinogenesis.
Optimization of Treatment Geometry to Reduce Normal Brain Dose in Radiosurgery of Multiple Brain Metastases with Single–Isocenter Volumetric Modulated Arc Therapy
Authors: Wu Qixue , Snyder Karen Chin , Liu Chang , Huang Yimei , Zhao Bo , Chetty Indrin J. , Wen Ning 
Published: September 2016

AbstractTreatment of patients with multiple brain metastases using a single-isocenter volumetric modulated arc therapy (VMAT) has been shown to decrease treatment time with the tradeoff of larger low dose to the normal brain tissue. We have developed an efficient Projection Summing Optimization Algorithm to optimize the treatment geometry in order to reduce dose to normal brain tissue for radiosurgery of multiple metastases with single-isocenter VMAT. The algorithm: (a) measures coordinates of outer boundary points of each lesion to be treated using the Eclipse Scripting Application Programming Interface, (b) determines the rotations of couch, collimator and gantry using three matrices about the cardinal axes, (c) projects the outer boundary points of the lesion on to Beam Eye View projection plane, (d) optimizes couch and collimator angles by selecting the least total unblocked area for each specific treatment arc and (e) generates a treatment plan with the optimized angles. The results showed significant reduction in the mean dose and low dose volume to normal brain, while maintaining the similar treatment plan qualities on the thirteen patients treated previously. The algorithm has the flexibility with regard to the beam arrangements and can be integrated in the treatment planning system for clinical application directly.
Gamma-H2AX upregulation caused by Wip1 deficiency increases depression-related cellular senescence in hippocampus
Authors: He Zhi-Yong , Wang Wen-Yue , Hu Wei-Yan , Yang Lu , Li Yan , Zhang Wei-Yuan , Yang Ya-Shu , Liu Si-Cheng , Zhang Feng-Lan , Mei Rong , Xing Da , Xiao Zhi-Cheng , Zhang Ming 
Published: September 2016

AbstractThe PP2C family member Wild-type p53-induced phosphatase 1 (Wip1) critically regulates DNA damage response (DDR) under stressful situations. In the present study, we investigated whether Wip1 expression was involved in the regulation of DDR-induced and depression-related cellular senescence in mouse hippocampus. We found that Wip1 gene knockout (KO) mice showed aberrant elevation of hippocampal cellular senescence and of γ-H2AX activity, which is known as a biomarker of DDR and cellular senescence, indicating that the lack of Wip1-mediated γ-H2AX dephosphorylation facilitates cellular senescence in hippocampus. Administration of the antidepressant fluoxetine had no significant effects on the increased depression-like behaviors, enriched cellular senescence and aberrantly upregulated hippocampal γ-H2AX activity in Wip1 KO mice. After wildtype C57BL/6 mice were exposed to the procedure of chronic unpredictable mild stress (CUMS), cellular senescence and γ-H2AX activity in hippocampus were also elevated, accompanied by the suppression of Wip1 expression in hippocampus when compared to the control group without CUMS experience. These CUMS-induced symptoms were effectively prevented following fluoxetine administration in wildtype C57BL/6 mice, with the normalization of depression-like behaviors. Our data demonstrate that Wip1-mediated γ-H2AX dephosphorylation may play an important role in the occurrence of depression-related cellular senescence.
Differential roles of NF-Y transcription factor in ER chaperone expression and neuronal maintenance in the CNS
Authors: Yamanaka Tomoyuki , Tosaki Asako , Miyazaki Haruko , Kurosawa Masaru , Koike Masato , Uchiyama Yasuo , Maity Sankar N. , Misawa Hidemi , Takahashi Ryosuke , Shimogori Tomomi , Hattori Nobutaka , Nukina Nobuyuki 
Published: September 2016

AbstractThe mammalian central nervous system (CNS) contains various types of neurons with different neuronal functions. In contrast to established roles of cell type-specific transcription factors on neuronal specification and maintenance, whether ubiquitous transcription factors have conserved or differential neuronal function remains uncertain. Here, we revealed that inactivation of a ubiquitous factor NF-Y in different sets of neurons resulted in cell type-specific neuropathologies and gene downregulation in mouse CNS. In striatal and cerebellar neurons, NF-Y inactivation led to ubiquitin/p62 pathologies with downregulation of an endoplasmic reticulum (ER) chaperone Grp94, as we previously observed by NF-Y deletion in cortical neurons. In contrast, NF-Y inactivation in motor neurons induced neuronal loss without obvious protein deposition. Detailed analysis clarified downregulation of another ER chaperone Grp78 in addition to Grp94 in motor neurons and knockdown of both ER chaperones in motor neurons recapitulated the pathology observed after NF-Y inactivation. Finally, additional downregulation of Grp78 in striatal neurons suppressed ubiquitin accumulation induced by NF-Y inactivation, implying that selective ER chaperone downregulation mediates different neuropathologies. Our data suggest distinct roles of NF-Y in protein homeostasis and neuronal maintenance in the CNS by differential regulation of ER chaperone expression.
A general solution for opening double-stranded DNA for isothermal amplification
Authors: Chen Gangyi , Dong Juan , Yuan Yi , Li Na , Huang Xin , Cui Xin , Tang Zhuo 
Published: September 2016

AbstractNucleic acid amplification is the core technology of molecular biology and genetic
engineering. Various isothermal amplification techniques have been developed as
alternatives to polymerase chain reaction (PCR). However, most of these
methods can only detect single stranded nucleic acid. Herein, we put forward a
simple solution for opening double-stranded DNA for isothermal detection methods.
The strategy employs recombination protein from E. coli (RecA) to form
nucleoprotein complex with single-stranded DNA, which could scan double-stranded
template for homologous sites. Then, the nucleoprotein can invade the
double-stranded template to form heteroduplex in the presence of ATP, resulting in
the strand exchange. The ATP regeneration system could be eliminated by using high
concentration of ATP, and the 3′-OH terminal of the invasion strand can
be recognized by other DNA modifying enzymes such as DNA polymerase or DNA ligase.
Moreover, dATP was found to be a better cofactor for RecA, which make the
system more compatible to DNA polymerase. The method described here is a general
solution to open dsDNA, serving as a platform to develop more isothermal nucleic
acids detection methods for real DNA samples based on it.
Catalysis at the nanoscale may change selectivity
Authors: Costentin Cyrille , Savéant Jean-Michel 
Published: September 2016

Significance
The benefits of passing from massive catalytic electrodes to a set of nanoparticles of the same material is an issue of considerable current interest. This process relates to the domain of fuels cells and, more generally, to contemporary energy challenges. When several products are concurrently formed, the question arises regarding the possible effect of such nanoscaling on product selectivity. It is tempting to view these effects as relevant to the exclusive domain of purely chemical factors, such as creation of surface defects triggered by nanoparticle deposition. Although such factors might be important in some circumstances, it is shown that product selectivity may well result from the coupling of competitive chemical steps with short-distance transport of the reactants.
Sex Ratios and Average Sperm per Female Blue Crab Callinectes sapidus in Six Tributaries of Chesapeake Bay
Authors: Rains Sarah A. M. , Wilberg Michael J. , Miller Thomas J. 
Published: September 2016

Abstract
Sperm limitation has been a concern for several crustacean species around the world. It may be of particular concern for blue crabs Callinectes sapidus in Chesapeake Bay due to the species’ reproductive biology and the sex-specific fishery regulations in place. Our objectives were to characterize the differences in sperm counts in mated females from six tributaries of the Chesapeake Bay and to determine whether sperm quantity was affected by the ratio of males to females in each system. Mature females were sampled 1–4 times in each tributary on a biweekly schedule from September to November 2011. We quantified sperm storage for each crab by microscopic examination and compared the sperm counts of females among river systems with the adult male : female sex ratios using ANOVA and linear regression. Total sperm quantity per female varied 16-fold (0.9–13.0 × 108) among tributaries. The sex ratio was also variable among tributaries. Total sperm quantity per female was not significantly related to sex ratio, tributary, or month but was negatively related to the development stage of the spermathecae. Estimated sperm : egg ratios varied from 153:1 to 2:1 but were always higher than 1:1. Our results suggest that sperm quantities are not affected by male : female sex ratios and that sperm limitation caused by low sex ratios is likely not a concern in tributaries similar to those in our study.
Received April 3, 2015; accepted June 24, 2016
Processing Mechanisms in Hearing-Impaired Listeners: Evidence from Reaction Times and Sentence Interpretation
Authors: Carroll Rebecca , Uslar Verena , Brand Thomas , Ruigendijk Esther 
Published: September 2016

Objective:
The authors aimed to determine whether hearing impairment affects sentence comprehension beyond phoneme or word recognition (i.e., on the sentence level), and to distinguish grammatically induced processing difficulties in structurally complex sentences from perceptual difficulties associated with listening to degraded speech. Effects of hearing impairment or speech in noise were expected to reflect hearer-specific speech recognition difficulties. Any additional processing time caused by the sustained perceptual challenges across the sentence may either be independent of or interact with top-down processing mechanisms associated with grammatical sentence structure.

Design:
Forty-nine participants listened to canonical subject-initial or noncanonical object-initial sentences that were presented either in quiet or in noise. Twenty-four participants had mild-to-moderate hearing impairment and received hearing-loss-specific amplification. Twenty-five participants were age-matched peers with normal hearing status. Reaction times were measured on-line at syntactically critical processing points as well as two control points to capture differences in processing mechanisms. An off-line comprehension task served as an additional indicator of sentence (mis)interpretation, and enforced syntactic processing.

Results:
The authors found general effects of hearing impairment and speech in noise that negatively affected perceptual processing, and an effect of word order, where complex grammar locally caused processing difficulties for the noncanonical sentence structure. Listeners with hearing impairment were hardly affected by noise at the beginning of the sentence, but were affected markedly toward the end of the sentence, indicating a sustained perceptual effect of speech recognition. Comprehension of sentences with noncanonical word order was negatively affected by degraded signals even after sentence presentation.

Conclusion:
Hearing impairment adds perceptual processing load during sentence processing, but affects grammatical processing beyond the word level to the same degree as in normal hearing, with minor differences in processing mechanisms. The data contribute to our understanding of individual differences in speech perception and language understanding. The authors interpret their results within the ease of language understanding model.