bluuebunny/crossref_metadata_2025 huggingface dataset:
Three brothers with a nonsense mutation in KAT6A caused by parental germline mosaicism
Authors: Satoh Chisei , Maekawa Ryuta , Kinoshita Akira , Mishima Hiroyuki , Doi Michiko , Miyazaki Mutsuko , Fukuda Masafumi , Takahashi Haruo , Kondoh Tatsuro , Yoshiura Koh-ichiro
Published: November 2017

Mutations in KAT6A, encoding a member of the MYST family of histone acetyl-transferases, were recently reported in patients with a neurodevelopmental disorder (OMIM: #616268, autosomal dominant mental retardation-32). In this report, we describe three siblings with intellectual disability (ID) or global developmental delay and a KAT6A heterozygous nonsense mutation, i.e., c.3070C>T (p.R1024*, ENST00000406337; chr8:41795056G>A on hg19). This mutation was identified by whole-exome sequencing of all three siblings but not in a healthy sibling. The mutation was not detected in the peripheral blood of their parents, suggesting the existence of parental germline mosaicism. The primary symptoms of our patients included severe to profound ID or global developmental delay, including speech delay with craniofacial dysmorphism; these symptoms are consistent with symptoms previously described for patients with KAT6A mutations. Although several features are common among patients with KAT6A mutations, the features are relatively nonspecific, making it difficult to establish a clinical entity based on clinical findings alone. To the best of our knowledge, this is the first report of cases with a KAT6A mutation in an Asian population and these cases represent the first reported instances of germline mosaicism of this disease.
Spinal arteriovenous fistula coexisting within a spinal lipoma: report of two cases
Authors: Horiuchi Yosuke , Iwanami Akio , Akiyama Takenori , Hikata Tomohiro , Watanabe Kota , Yagi Mitsuru , Fujita Nobuyuki , Okada Eijiro , Nagoshi Narihito , Tsuji Osahiko , Ishii Ken , Yoshida Kazunari , Nakamura Masaya , Matsumoto Morio
Published: November 2017

Introduction

Spinal lipoma and spinal arteriovenous fistula (sAVF) are different pathologies and their co-existence is extremely rare. Here we reported two cases of adult-onset sAVF occurring within a spinal lipoma and with review the literature in an attempt to identify the mechanisim of and optimal treatment of this condition.

Case presentation

Case 1 was a 51-year-old man who was treated by embolization of the feeding artery and ligation of the draining vein. Case 2 was a 53-year-old man who was treated by embolization and resection of the tumor containing the shunt zone. In both cases, symptoms improved after surgery. However, in Case 1, angiography at 1 month after the surgery revealed recurrence of the arteriovenous shunt.

Discussion

A literature search revealed only nine other similar case reports. All cases, including ours occurred in adults. In almost all cases, the shunt was located within the spinal lipoma. Pathologic examination revealed venous hypertension, but no evidence of congenital vascular malformation. Given that lipomas release angiogenic factors, the presence of a spinal lipoma may indicate its involvement in the development of acquired sAVF. Our two cases might represent a new subtype of sAVF. Based on our experiences, we recommend resection of the tumor containing the shunt for the management of sAVF.
Oscillators that sync and swarm
Authors: O’Keeffe Kevin P. , Hong Hyunsuk , Strogatz Steven H.
Published: November 2017

Synchronization occurs in many natural and technological systems, from cardiac pacemaker cells to coupled lasers. In the synchronized state, the individual cells or lasers coordinate the timing of their oscillations, but they do not move through space. A complementary form of self-organization occurs among swarming insects, flocking birds, or schooling fish; now the individuals move through space, but without conspicuously altering their internal states. Here we explore systems in which both synchronization and swarming occur together. Specifically, we consider oscillators whose phase dynamics and spatial dynamics are coupled. We call them swarmalators, to highlight their dual character. A case study of a generalized Kuramoto model predicts five collective states as possible long-term modes of organization. These states may be observable in groups of sperm, Japanese tree frogs, colloidal suspensions of magnetic particles, and other biological and physical systems in which self-assembly and synchronization interact.
Emergent patterns of collective cell migration under tubular confinement
Authors: Xi Wang , Sonam Surabhi , Beng Saw Thuan , Ladoux Benoit , Teck Lim Chwee
Published: November 2017

Collective epithelial behaviors are essential for the development of lumens in organs. However, conventional assays of planar systems fail to replicate cell cohorts of tubular structures that advance in concerted ways on out-of-plane curved and confined surfaces, such as ductal elongation in vivo. Here, we mimic such coordinated tissue migration by forming lumens of epithelial cell sheets inside microtubes of 1–10 cell lengths in diameter. We show that these cell tubes reproduce the physiological apical–basal polarity, and have actin alignment, cell orientation, tissue organization, and migration modes that depend on the extent of tubular confinement and/or curvature. In contrast to flat constraint, the cell sheets in a highly constricted smaller microtube demonstrate slow motion with periodic relaxation, but fast overall movement in large microtubes. Altogether, our findings provide insights into the emerging migratory modes for epithelial migration and growth under tubular confinement, which are reminiscent of the in vivo scenario.
DJ-1 controls bone homeostasis through the regulation of osteoclast differentiation
Authors: Kim Hyuk Soon , Nam Seung Taek , Mun Se Hwan , Lee Sun-Kyeong , Kim Hyun Woo , Park Young Hwan , Kim Bokyung , Won Kyung-Jong , Kim Hae-Rim , Park Yeong-Min , Kim Hyung Sik , Beaven Michael A. , Kim Young Mi , Choi Wahn Soo
Published: November 2017

Receptor activator of NF-kB ligand (RANKL) generates intracellular reactive oxygen species (ROS), which increase RANKL-mediated signaling in osteoclast (OC) precursor bone marrow macrophages (BMMs). Here we show that a ROS scavenging protein DJ-1 negatively regulates RANKL-driven OC differentiation, also called osteoclastogenesis. DJ-1 ablation in mice leads to a decreased bone volume and an increase in OC numbers. In vitro, the activation of RANK-dependent signals is enhanced in DJ-1-deficient BMMs as compared to wild-type BMMs. DJ-1 suppresses the activation of both RANK-TRAF6 and RANK-FcRγ/Syk signaling pathways because of activation of Src homology region 2 domain-containing phosphatase-1, which is inhibited by ROS. Ablation of DJ-1 in mouse models of arthritis and RANKL-induced bone disease leads to an increase in the number of OCs, and exacerbation of bone damage. Overall, our results suggest that DJ-1 plays a role in bone homeostasis in normal physiology and in bone-associated pathology by negatively regulating osteoclastogenesis.
Unique transcriptome signatures and GM-CSF expression in lymphocytes from patients with spondyloarthritis
Authors: Al-Mossawi M. H. , Chen L. , Fang H. , Ridley A. , de Wit J. , Yager N. , Hammitzsch A. , Pulyakhina I. , Fairfax B. P. , Simone D. , Yi Yao , Bandyopadhyay S. , Doig K. , Gundle R , Kendrick B. , Powrie F. , Knight J. C. , Bowness P.
Published: November 2017

Spondyloarthritis encompasses a group of common inflammatory diseases thought to be driven by IL-17A-secreting type-17 lymphocytes. Here we show increased numbers of GM-CSF-producing CD4 and CD8 lymphocytes in the blood and joints of patients with spondyloarthritis, and increased numbers of IL-17A+GM-CSF+ double-producing CD4, CD8, γδ and NK cells. GM-CSF production in CD4 T cells occurs both independently and in combination with classical Th1 and Th17 cytokines. Type 3 innate lymphoid cells producing predominantly GM-CSF are expanded in synovial tissues from patients with spondyloarthritis. GM-CSF+CD4+ cells, isolated using a triple cytokine capture approach, have a specific transcriptional signature. Both GM-CSF+ and IL-17A+GM-CSF+ double-producing CD4 T cells express increased levels of GPR65, a proton-sensing receptor associated with spondyloarthritis in genome-wide association studies and pathogenicity in murine inflammatory disease models. Silencing GPR65 in primary CD4 T cells reduces GM-CSF production. GM-CSF and GPR65 may thus serve as targets for therapeutic intervention of spondyloarthritis.
Quantitative analysis of protein-protein interactions and post-translational modifications in rare immune populations
Authors: Avin Ayelet , Levy Maayan , Porat Ziv , Abramson Jakub
Published: November 2017

In spite of recent advances in proteomics, quantitative analyses of protein–protein interactions (PPIs) or post-translational modifications (PTMs) in rare cell populations remain challenging. This is in particular true for analyses of rare immune and/or stem cell populations that are directly isolated from humans or animal models, and which are often characterized by multiple surface markers. To overcome these limitations, here we have developed proximity ligation imaging cytometry (PLIC), a protocol for proteomic analysis of rare cells. Specifically, by employing PLIC on medullary thymic epithelial cells (mTECs), which serve as a paradigm for a rare immune population, we demonstrate that PLIC overcomes the inherent limitations of conventional proteomic approaches and enables a high-resolution detection and quantification of PPIs and PTMs at a single cell level.
Genome-wide mapping of genetic determinants influencing DNA methylation and gene expression in human hippocampus
Authors: Schulz Herbert , Ruppert Ann-Kathrin , Herms Stefan , Wolf Christiane , Mirza-Schreiber Nazanin , Stegle Oliver , Czamara Darina , Forstner Andreas J. , Sivalingam Sugirthan , Schoch Susanne , Moebus Susanne , Pütz Benno , Hillmer Axel , Fricker Nadine , Vatter Hartmut , Müller-Myhsok Bertram , Nöthen Markus M. , Becker Albert J. , Hoffmann Per , Sander Thomas , Cichon Sven
Published: November 2017

Emerging evidence emphasizes the strong impact of regulatory genomic elements in neurodevelopmental processes and the complex pathways of brain disorders. The present genome-wide quantitative trait loci analyses explore the cis-regulatory effects of single-nucleotide polymorphisms (SNPs) on DNA methylation (meQTL) and gene expression (eQTL) in 110 human hippocampal biopsies. We identify cis-meQTLs at 14,118 CpG methylation sites and cis-eQTLs for 302 3′-mRNA transcripts of 288 genes. Hippocampal cis-meQTL-CpGs are enriched in flanking regions of active promoters, CpG island shores, binding sites of the transcription factor CTCF and brain eQTLs. Cis-acting SNPs of hippocampal meQTLs and eQTLs significantly overlap schizophrenia-associated SNPs. Correlations of CpG methylation and RNA expression are found for 34 genes. Our comprehensive maps of cis-acting hippocampal meQTLs and eQTLs provide a link between disease-associated SNPs and the regulatory genome that will improve the functional interpretation of non-coding genetic variants in the molecular genetic dissection of brain disorders.
Millisecond dynamics of BTK reveal kinome-wide conformational plasticity within the apo kinase domain
Authors: Sultan Mohammad M. , Denny Rajiah Aldrin , Unwalla Ray , Lovering Frank , Pande Vijay S.
Published: November 2017

Bruton tyrosine kinase (BTK) is a key enzyme in B-cell development whose improper regulation causes severe immunodeficiency diseases. Design of selective BTK therapeutics would benefit from improved, in-silico structural modeling of the kinase’s solution ensemble. However, this remains challenging due to the immense computational cost of sampling events on biological timescales. In this work, we combine multi-millisecond molecular dynamics (MD) simulations with Markov state models (MSMs) to report on the thermodynamics, kinetics, and accessible states of BTK’s kinase domain. Our conformational landscape links the active state to several inactive states, connected via a structurally diverse intermediate. Our calculations predict a kinome-wide conformational plasticity, and indicate the presence of several new potentially druggable BTK states. We further find that the population of these states and the kinetics of their inter-conversion are modulated by protonation of an aspartate residue, establishing the power of MD & MSMs in predicting effects of chemical perturbations.
Biogenic selenium and its hepatoprotective activity
Authors: Li Baozhen , Li Dan , Jing Weixin , Fan Jinhua , Dahms Hans-Uwe , Lee Shao-Chin , Wang Lan
Published: November 2017

Elemental selenium nanoparticles (SeNPs) have multiple biological activities. In this study, we investigated the protective effects of biogenic SeNPs (BioSeNPs) on CCl4-induced liver damage in mice. The results showed that: (i) when compared to sodium selenite (SS), BioSeNPs has a similar tissue distribution after intragastrical administration to mice; (ii) BioSeNPs and SS showed comparable efficacy in increasing the activities of glutathione peroxidase and thioredoxin reductase in liver cell lines, mice blood and liver; (iii) pretreatment with BioSeNPs inhibiting the elevation of activities of various enzymes significantly which included aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, lactate dehydrogenase and liver lipid peroxide (p < 0.05 or p < 0.01) in CCl4-treated mice; (iv) activities of antioxidant enzymes (superoxide dismutase, catalase, and glutathione peroxidase) were significantly increased (p < 0.05 or p < 0.01) after a pretreatment with BioSeNPs in CCl4-treated mice; (v) histopathological damages in the liver from CCl4-treated mice were ameliorated by a pretreatment with BioSeNPs. In conclusion, these results have shown that BioSeNPs is able to protect the liver from CCl4-induced hepatic damage via increasing the antioxidant capacity and inhibiting oxidative damage. BioSeNPs may have the potential to be used as a trace element food supplement inducing antioxidant bioactivities.
People with higher interoceptive sensitivity are more altruistic, but improving interoception does not increase altruism
Authors: Piech Richard M. , Strelchuk Daniela , Knights Jake , Hjälmheden Jonathan V. , Olofsson Jonas K. , Aspell Jane E.
Published: November 2017

People consistently show preferences and behaviors that benefit others at a cost to themselves, a phenomenon termed altruism. We investigated if perception of one’s body signals – interoception - may be underlying such behaviors. We tested if participants’ sensitivity to their own heartbeat predicted their decision on a choice between self-interest and altruism, and if improving this sensitivity through training would make participants more altruistic. Across these two experiments, interoceptive sensitivity predicted altruism measured through monetary generosity. Improving interoceptive sensitivity did, however, not lead to more altruistic behaviour. We conclude that there is a unique link between interoception and altruistic behaviour, likely established over an individual’s history of altruistic acts, and the body responses they elicit. The findings suggest that humans might literally ‘listen to their heart’ to guide their altruistic behavior.
Publisher Correction: Membrane association of the bacterial riboregulator Hfq and functional perspectives
Authors: Malabirade Antoine , Morgado-Brajones Javier , Trépout Sylvain , Wien Frank , Marquez Ileana , Seguin Jérôme , Marco Sergio , Velez Marisela , Arluison Véronique
Published: November 2017

A correction to this article has been published and is linked from the HTML version of this paper. The error has been fixed in the paper.
Human ATG3 binding to lipid bilayers: role of lipid geometry, and electric charge
Authors: Hervás Javier H. , Landajuela Ane , Antón Zuriñe , Shnyrova Anna V. , Goñi Felix M. , Alonso Alicia
Published: November 2017

Specific protein-lipid interactions lead to a gradual recruitment of AuTophaGy-related (ATG) proteins to the nascent membrane during autophagosome (AP) formation. ATG3, a key protein in the movement of LC3 towards the isolation membrane, has been proposed to facilitate LC3/GABARAP lipidation in highly curved membranes. In this work we have performed a biophysical study of human ATG3 interaction with membranes containing phosphatidylethanolamine, phosphatidylcholine and anionic phospholipids. We have found that ATG3 interacts more strongly with negatively-charged phospholipid vesicles or nanotubes than with electrically neutral model membranes, cone-shaped anionic phospholipids (cardiolipin and phosphatidic acid) being particularly active in promoting binding. Moreover, an increase in membrane curvature facilitates ATG3 recruitment to membranes although addition of anionic lipid molecules makes the curvature factor relatively less important. The predicted N-terminus amphipathic α-helix of ATG3 would be responsible for membrane curvature detection, the positive residues Lys 9 and 11 being essential in the recognition of phospholipid negative moieties. We have also observed membrane aggregation induced by ATG3 in vitro, which could point to a more complex function of this protein in AP biogenesis. Moreover, in vitro GABARAP lipidation assays suggest that ATG3-membrane interaction could facilitate the lipidation of ATG8 homologues.
In vivo characterization of the electrophysiological and astrocytic responses to a silicon neuroprobe implanted in the mouse neocortex
Authors: Mols Katrien , Musa Silke , Nuttin Bart , Lagae Liesbet , Bonin Vincent
Published: November 2017

Silicon neuroprobes hold great potential for studies of large-scale neural activity and brain computer interfaces, but data on brain response in chronic implants is limited. Here we explored with in vivo cellular imaging the response to multisite silicon probes for neural recordings. We tested a chronic implant for mice consisting of a CMOS-compatible silicon probe rigidly implanted in the cortex under a cranial imaging window. Multiunit recordings of cortical neurons with the implant showed no degradation of electrophysiological signals weeks after implantation (mean spike and noise amplitudes of 186 ± 42 µVpp and 16 ± 3.2 µVrms, respectively, n = 5 mice). Two-photon imaging through the cranial window allowed longitudinal monitoring of fluorescently-labeled astrocytes from the second week post implantation for 8 weeks (n = 3 mice). The imaging showed a local increase in astrocyte-related fluorescence that remained stable from the second to the tenth week post implantation. These results demonstrate that, in a standard electrophysiology protocol in mice, rigidly implanted silicon probes can provide good short to medium term chronic recording performance with a limited astrocyte inflammatory response. The precise factors influencing the response to silicon probe implants remain to be elucidated.
The maternal genetic make-up of the Iberian Peninsula between the Neolithic and the Early Bronze Age
Authors: Szécsényi-Nagy Anna , Roth Christina , Brandt Guido , Rihuete-Herrada Cristina , Tejedor-Rodríguez Cristina , Held Petra , García-Martínez-de-Lagrán Íñigo , Arcusa Magallón Héctor , Zesch Stephanie , Knipper Corina , Bánffy Eszter , Friederich Susanne , Meller Harald , Bueno Ramírez Primitiva , Barroso Bermejo Rosa , de Balbín Behrmann Rodrigo , Herrero-Corral Ana M. , Flores Fernández Raúl , Alonso Fernández Carmen , Jiménez Echevarria Javier , Rindlisbacher Laura , Oliart Camila , Fregeiro María-Inés , Soriano Ignacio , Vicente Oriol , Micó Rafael , Lull Vicente , Soler Díaz Jorge , López Padilla Juan Antonio , Roca de Togores Muñoz Consuelo , Hernández Pérez Mauro S. , Jover Maestre Francisco Javier , Lomba Maurandi Joaquín , Avilés Fernández Azucena , Lillios Katina T. , Silva Ana Maria , Magalhães Ramalho Miguel , Oosterbeek Luiz Miguel , Cunha Claudia , Waterman Anna J. , Roig Buxó Jordi , Martínez Andrés , Ponce Martínez Juana , Hunt Ortiz Mark , Mejías-García Juan Carlos , Pecero Espín Juan Carlos , Cruz-Auñón Briones Rosario , Tomé Tiago , Carmona Ballestero Eduardo , Cardoso João Luís , Araújo Ana Cristina , Liesau von Lettow-Vorbeck Corina , Blasco Bosqued Concepción , Ríos Mendoza Patricia , Pujante Ana , Royo-Guillén José I. , Esquembre Beviá Marco Aurelio , Dos Santos Goncalves Victor Manuel , Parreira Rui , Morán Hernández Elena , Méndez Izquierdo Elena , Vega y Miguel Jorge , Menduiña García Roberto , Martínez Calvo Victoria , López Jiménez Oscar , Krause Johannes , Pichler Sandra L. , Garrido-Pena Rafael , Kunst Michael , Risch Roberto , Rojo-Guerra Manuel A. , Haak Wolfgang , Alt Kurt W.
Published: November 2017

Agriculture first reached the Iberian Peninsula around 5700 BCE. However, little is known about the genetic structure and changes of prehistoric populations in different geographic areas of Iberia. In our study, we focus on the maternal genetic makeup of the Neolithic (~ 5500–3000 BCE), Chalcolithic (~ 3000–2200 BCE) and Early Bronze Age (~ 2200–1500 BCE). We report ancient mitochondrial DNA results of 213 individuals (151 HVS-I sequences) from the northeast, central, southeast and southwest regions and thus on the largest archaeogenetic dataset from the Peninsula to date. Similar to other parts of Europe, we observe a discontinuity between hunter-gatherers and the first farmers of the Neolithic. During the subsequent periods, we detect regional continuity of Early Neolithic lineages across Iberia, however the genetic contribution of hunter-gatherers is generally higher than in other parts of Europe and varies regionally. In contrast to ancient DNA findings from Central Europe, we do not observe a major turnover in the mtDNA record of the Iberian Late Chalcolithic and Early Bronze Age, suggesting that the population history of the Iberian Peninsula is distinct in character.
Hypercholesterolemia Enhances T Cell Receptor Signaling and Increases the Regulatory T Cell Population
Authors: Mailer Reiner K. W. , Gisterå Anton , Polyzos Konstantinos A. , Ketelhuth Daniel F. J. , Hansson Göran K.
Published: November 2017

Hypercholesterolemia promotes the inflammation against lipoproteins in atherosclerosis. Development of atherosclerosis is affected by the balance between pro-inflammatory effector T cells and anti-inflammatory regulatory T (Treg) cells. However, phenotype and function of T cell subpopulations in hypercholesterolemia remain to be investigated. Here, we found that cholesterol-containing diet increased the expression of the Treg cell lineage-defining transcription factor FoxP3 among thymocytes and splenocytes. Hypercholesterolemia elevated the FoxP3 expression level and population size of peripheral Treg cells, but did not prevent enhanced proliferation of stimulated T cells. Moreover, cholesterol supplementation in diet as well as in cell culture medium promoted T cell antigen receptor (TCR) signaling in CD4+ T cells. Our results demonstrate that hypercholesterolemia enhances TCR stimulation, Treg cell development as well as T cell proliferation. Thus, our findings may help to understand why hypercholesterolemia correlates with altered CD4+ T cell responses.
Robust Segmentation of the Full Cerebral Vasculature in 4D CT of Suspected Stroke Patients
Authors: Meijs Midas , Patel Ajay , van de Leemput Sil C. , Prokop Mathias , van Dijk Ewoud J. , de Leeuw Frank-Erik , Meijer Frederick J. A. , van Ginneken Bram , Manniesing Rashindra
Published: November 2017

A robust method is presented for the segmentation of the full cerebral vasculature in 4-dimensional (4D) computed tomography (CT). The method consists of candidate vessel selection, feature extraction, random forest classification and postprocessing. Image features include among others the weighted temporal variance image and parameters, including entropy, of an intensity histogram in a local region at different scales. These histogram parameters revealed to be a strong feature in the detection of vessels regardless of shape and size. The method was trained and tested on a large database of 264 patients with suspicion of acute ischemia who underwent 4D CT in our hospital in the period January 2014 to December 2015. Five subvolumes representing different regions of the cerebral vasculature were annotated in each image in the training set by medical assistants. The evaluation was done on 242 patients. A total of 16 (<8%) patients showed severe under or over segmentation and were reported as failures. One out of five subvolumes was randomly annotated in 159 patients and was used for quantitative evaluation. Quantitative evaluation showed a Dice coefficient of 0.91 ± 0.07 and a modified Hausdorff distance of 0.23 ± 0.22 mm. Therefore, robust vessel segmentation in 4D CT is feasible with good accuracy.
Structural and functional differences in gut microbiome composition in patients undergoing haemodialysis or peritoneal dialysis
Authors: Stadlbauer Vanessa , Horvath Angela , Ribitsch Werner , Schmerböck Bianca , Schilcher Gernot , Lemesch Sandra , Stiegler Philipp , Rosenkranz Alexander R. , Fickert Peter , Leber Bettina
Published: November 2017

Complications of end-stage renal disease (ESRD) are critically related to inflammation. The gut microbiome is a key driver of inflammation. Since dialysis modalities may differently influence the gut microbiome, we aimed to compare the effects of haemodialysis (HD) and peritoneal dialysis (PD) on patients’ gut microbiome composition and function. We therefore studied faecal microbiome composition and function as well as inflammation and gut permeability in 30 patients with ESRD (15 HD, 15 PD) and compared to 21 healthy controls. We found an increase in potentially pathogenic species and a decrease in beneficial species in patients on HD and to a lesser extend in patients on PD when compared to controls. These changes in taxonomic composition also resulted in differences in predicted metagenome functions of the faecal microbiome. In HD but not in PD, changes in microbiome composition were associated with an increase in c-reactive protein (CRP) but not with intestinal inflammation or gut permeability. In conclusion microbiome composition in ESRD differs from healthy controls but also between modes of dialysis. These differences are associated with systemic inflammation and cannot completely be explained by dialysis vintage. The mode of renal replacement therapy seems to be an important driver of dysbiosis in ESRD.
Exploring the alpha desynchronization hypothesis in resting state networks with intracranial electroencephalography and wiring cost estimates
Authors: Gómez-Ramírez Jaime , Freedman Shelagh , Mateos Diego , Pérez Velázquez José Luis , Valiante Taufik A.
Published: November 2017

This paper addresses a fundamental question, are eyes closed and eyes open resting states equivalent baseline conditions, or do they have consistently different electrophysiological signatures? We compare the functional connectivity patterns in an eyes closed resting state with an eyes open resting state to investigate the alpha desynchronization hypothesis. The change in functional connectivity from eyes closed to eyes open, is here, for the first time, studied with intracranial recordings. We perform network connectivity analysis in iEEG and we find that phase-based connectivity is sensitive to the transition from eyes closed to eyes open only in interhemispheral and frontal electrodes. Power based connectivity, on the other hand, consistently discriminates between the two conditions in temporal and interhemispheral electrodes. Additionally, we provide a calculation for the wiring cost, defined in terms of the connectivity between electrodes weighted by distance. We find that the wiring cost variation from eyes closed to eyes open is sensitive to the eyes closed and eyes open conditions. We extend the standard network-based approach using the filtration method from algebraic topology which does not rely on the threshold selection problem. Both the wiring cost measure defined here and this novel methodology provide a new avenue for understanding the electrophysiology of resting state.
A Novel Medium for Enhancing Callus Growth of Hazel (Corylus avellana L.)
Authors: Salehi Mina , Moieni Ahmad , Safaie Naser
Published: November 2017

Paclitaxel is a powerful antimitotic agent with excellent activity against a range of cancers. Hazel has been described as a paclitaxel-producing species among angiosperms. Fast-growing callus is a prerequisite for the success of callus production and then paclitaxel production. Therefore, optimizing the medium culture for enhancing callus growth is a crucial step for paclitaxel production. In this research, Murashige and Skoog (1962) (MS) medium was optimized for improving callus growth of hazel (Corylus avellana L.). The M10 medium (MS medium with pH 6.0 and supplemented with 1000 mg l−1 spirulina powder, 1000 mg l−1 casein hydrolysate and 3 g l−1 gelrite) significantly improved hazel callus growth. This modified MS medium increased callus fresh weight (55.8%) as compared to the control. M10 medium increased fatty acids yield of callus (66.7%) as compared to the control. Liquid M10 medium maintained growth over a longer period of time and also increased slightly, the paclitaxel production as compared to the control. This novel medium is promising for facilitating the mass production of hazel callus as a source of valuable metabolites including paclitaxel, linoleic and oleic acids.
Crystal structure of the N-terminal domain of human CDC73 and its implications for the hyperparathyroidism-jaw tumor (HPT-JT) syndrome
Authors: Sun Wei , Kuang Xiao-Lin , Liu Yan-Ping , Tian Li-Fei , Yan Xiao-Xue , Xu Wenqing
Published: November 2017

CDC73/Parafibromin is a critical component of the Paf1 complex (PAF1C), which is involved in transcriptional elongation and histone modifications. Mutations of the human CDC73/HRPT2 gene are associated with hyperparathyroidism-jaw tumor (HPT-JT) syndrome, an autosomal dominant disorder. CDC73/parafibromin was initially recognized as a tumor suppressor by inhibiting cell proliferation via repression of cyclin D1 and c-myc genes. In recent years, it has also shown oncogenic features by activating the canonical Wnt/β-catenin signal pathway. Here, through limited proteolysis analysis, we demonstrate that the evolutionarily conserved human CDC73 N-terminal 111 residues form a globularly folded domain (hCDC73-NTD). We have determined a crystal structure of hCDC73-NTD at 1.02 Å resolution, which reveals a novel protein fold. CDC73-NTD contains an extended hydrophobic groove on its surface that may be important for its function. Most pathogenic CDC73 missense mutations associated with the HPT-JT syndrome are located in the region encoding CDC73-NTD. Our crystal and biochemical data indicate that most CDC73 missense mutations disrupt the folding of the hydrophobic core of hCDC73-NTD, while others such as the K34Q mutant reduce its thermostability. Overall, our results provide a solid structural basis for understanding the structure and function of CDC73 and its association with the HPT-JT syndrome and other diseases.
Sex-specific association between asthma and hypertension in nationally representative young Korean adults
Authors: Lee Hong Seok , Park Yong-Moon , Han Kyungdo , Pekler Gerald , Lee Seong-Su , Yoo Soonjib , Kim Sung Rae
Published: November 2017

It has been reported that people with asthma have an increased risk of hypertension. However, little is known about the specific relationship between asthma and hypertension in young adults. Among subjects who participated in the Korea National Health and Nutrition Examination Survey conducted in 2008–2013, a total of 10,138 young adults (4,226 men and 5,912 women) aged 19–39 years were analyzed. Multiple logistic regression analysis was used to estimate adjusted odds ratios (ORs) and 95% confidence intervals (CIs). The prevalence of ever asthma was 11.1% in men and 8.4% in women. The mean diastolic blood pressure (DBP) was lower in men with asthma than in men without asthma (p = 0.03), whereas the mean DBP was higher in women with asthma than in women without asthma (p = 0.04). Having asthma was inversely associated with hypertension in men (OR: 0.62, 95% CI: 0.41–0.91). In contrast, having asthma was positively associated with hypertension in women (OR: 2.19, 95% CI: 1.19–4.02). Our results suggest that asthma pathophysiology might be differentially associated with hypertension in young adults depending on sex.
Differential overexpression of SERPINA3 in human prion diseases
Authors: Vanni S. , Moda F. , Zattoni M. , Bistaffa E. , De Cecco E. , Rossi M. , Giaccone G. , Tagliavini F. , Haïk S. , Deslys J. P. , Zanusso G. , Ironside J. W. , Ferrer I. , Kovacs G. G. , Legname G.
Published: November 2017

Prion diseases are fatal neurodegenerative disorders with sporadic, genetic or acquired etiologies. The molecular alterations leading to the onset and the spreading of these diseases are still unknown. In a previous work we identified a five-gene signature able to distinguish intracranially BSE-infected macaques from healthy ones, with SERPINA3 showing the most prominent dysregulation. We analyzed 128 suitable frontal cortex samples, from prion-affected patients (variant Creutzfeldt-Jakob disease (vCJD) n = 20, iatrogenic CJD (iCJD) n = 11, sporadic CJD (sCJD) n = 23, familial CJD (gCJD) n = 17, fatal familial insomnia (FFI) n = 9, Gerstmann–Sträussler–Scheinker syndrome (GSS)) n = 4), patients with Alzheimer disease (AD, n = 14) and age-matched controls (n = 30). Real Time-quantitative PCR was performed for SERPINA3 transcript, and ACTB, RPL19, GAPDH and B2M were used as reference genes. We report SERPINA3 to be strongly up-regulated in the brain of all human prion diseases, with only a mild up-regulation in AD. We show that this striking up-regulation, both at the mRNA and at the protein level, is present in all types of human prion diseases analyzed, although to a different extent for each specific disorder. Our data suggest that SERPINA3 may be involved in the pathogenesis and the progression of prion diseases, representing a valid tool for distinguishing different forms of these disorders in humans.
Impact of deforestation and climate on the Amazon Basin’s above-ground biomass during 1993–2012
Authors: Exbrayat Jean-François , Liu Yi Y. , Williams Mathew
Published: November 2017

Since the 1960s, large-scale deforestation in the Amazon Basin has contributed to rising global CO2 concentrations and to climate change. Recent advances in satellite observations enable estimates of gross losses of above-ground biomass (AGB) stocks due to deforestation. However, because of simultaneous regrowth, the net contribution of deforestation emissions to rising atmospheric CO2 concentrations is poorly quantified. Climate change may also reduce the potential for forest regeneration in previously disturbed regions. Here, we address these points of uncertainty with a machine-learning approach that combines satellite observations of AGB with climate data across the Amazon Basin to reconstruct annual maps of potential AGB during 1993–2012, the above-ground C storage potential of the undisturbed landscape. We derive a 2.2 Pg C loss of AGB over the study period, and, for the regions where these losses occur, we estimate a 0.7 Pg C reduction in potential AGB. Thus, climate change has led to a decline of ~1/3 in the capacity of these disturbed forests to recover and recapture the C lost in disturbances during 1993–2012. Our approach further shows that annual variations in land use change mask the natural relationship between the El Niño/Southern Oscillation and AGB stocks in disturbed regions.
Spatial distribution of tree species in evergreen-deciduous broadleaf karst forests in southwest China
Authors: Du Hu , Hu Fang , Zeng Fuping , Wang Kelin , Peng Wanxia , Zhang Hao , Zeng Zhaoxia , Zhang Fang , Song Tongqing
Published: November 2017

Understanding the spatial distribution of tree species in subtropical evergreen-deciduous broadleaf karst forest is fundamental to studying species coexistence and karst species diversity. Here, complete spatial randomness and heterogeneous Poisson process models were used to analyze the spatial distribution patterns of 146 species with at least one individual per ha in a 25-ha plot in southwest China. We used canonical correspondence analysis (CCA) and the torus-translation test (TTT) to explain the distributions of observed species. Our results show that an aggregated distribution was the dominant pattern in Mulun karst forests; the percentage and intensity of aggregated decreased with increasing spatial scale, abundance, mean diameter at breast height (DBH), and maximum DBH. Rare species were more aggregated than intermediately abundant and abundant species. However, functional traits (e.g., growth form and phenological guild) had no significant effects on the distributions of species. The CCA revealed that the four analyzed topographic variables (elevation, slope, aspect, and convexity) had significant influences on species distributions. The TTT showed that not all species have habitat preferences and that 68.5% (100 out of 146 species) show a strongly positive or negative association with at least one habitat. Most species were inclined to grow on slopes and hilltops.
Sociospatial structure explains marked variation in brucellosis seroprevalence in an Alpine ibex population
Authors: Marchand Pascal , Freycon Pauline , Herbaux Jean-Philippe , Game Yvette , Toïgo Carole , Gilot-Fromont Emmanuelle , Rossi Sophie , Hars Jean
Published: November 2017

In a context of (re)emerging infectious diseases with wildlife reservoirs, understanding how animal ecology shapes epidemiology is a key issue, particularly in wild ungulates that share pathogens with domestic herbivores and have similar food requirements. For the first time in Europe, brucellosis (Brucella melitensis), a virulent zoonosis, persisted in an Alpine ibex (Capra ibex) population and was transmitted to cattle and humans. To better understand disease dynamics, we investigated the relationships between the spatial ecology of ibex and the epidemiology of brucellosis. Combining home range overlap between 37 GPS-collared individuals and visual observations of 148 visually-marked individuals monitored during the 2013–2016 period, we showed that females were spatially segregated in at least 4 units all year round, whereas males were more prone to move between female units, in particular during the rutting period. In addition to ibex age, the spatial structure in females largely contributed to variation in seroprevalence in the whole population. These results suggest that non-sexual routes are the most likely pathways of intraspecific transmission, crucial information for management. Accounting for wildlife spatial ecology was hence decisive in improving our ability to better understand this health challenge involving a wildlife reservoir.
Genomic mosaicism in paternal sperm and multiple parental tissues in a Dravet syndrome cohort
Authors: Yang Xiaoxu , Liu Aijie , Xu Xiaojing , Yang Xiaoling , Zeng Qi , Ye Adam Yongxin , Yu Zhe , Wang Sheng , Huang August Yue , Wu Xiru , Wu Qixi , Wei Liping , Zhang Yuehua
Published: November 2017

Genomic mosaicism in parental gametes and peripheral tissues is an important consideration for genetic counseling. We studied a Chinese cohort affected by a severe epileptic disorder, Dravet syndrome (DS). There were 56 fathers who donated semen and 15 parents who donated multiple peripheral tissue samples. We used an ultra-sensitive quantification method, micro-droplet digital PCR (mDDPCR), to detect parental mosaicism of the proband’s pathogenic mutation in SCN1A, the causal gene of DS in 112 families. Ten of the 56 paternal sperm samples were found to exhibit mosaicism of the proband’s mutations, with mutant allelic fractions (MAFs) ranging from 0.03% to 39.04%. MAFs in the mosaic fathers’ sperm were significantly higher than those in their blood (p = 0.00098), even after conditional probability correction (p’ = 0.033). In three mosaic fathers, ultra-low fractions of mosaicism (MAF < 1%) were detected in the sperm samples. In 44 of 45 cases, mosaicism was also observed in other parental peripheral tissues. Hierarchical clustering showed that MAFs measured in the paternal sperm, hair follicles and urine samples were clustered closest together. Milder epileptic phenotypes were more likely to be observed in mosaic parents (p = 3.006e-06). Our study provides new insights for genetic counseling.
Assessment of Genetic Diversity and Population Structure in Iranian Cannabis Germplasm
Authors: Soorni Aboozar , Fatahi Reza , Haak David C. , Salami Seyed Alireza , Bombarely Aureliano
Published: November 2017

Cannabis sativa has a complex history reflected in both selection on naturally occurring compounds and historical trade routes among humans. Iran is a rich resource of natural populationswhich hold the promise to characterize historical patterns of population structure and genetic diversity within Cannabis. Recent advances in high-throughput DNA sequencing technologies have dramatically increased our ability to produce information to the point that it is now feasible to inexpensively obtain population level genotype information at a large scale. In the present investigation, we have explored the use of Genotyping-By-Sequencing (GBS) in Iranian cannabis. We genotyped 98 cannabis samples 36 from Iranian locations and 26 accessions from two germplasm collections. In total, 24,710 high-quality Single Nucleotide Polymorphisms (SNP) were identified. Clustering analysis by Principal Component Analysis (PCA) identified two genetic clusters among Iranian populations and fineSTRUCTURE analysis identified 19 populations with some geographic partitioning. We defined Iranian cannabis in two main groups using the results of the PCA and discovered some strong signal to define some locations as population according to fineSTRUCTURE analyses. However, single nucleotide variant analysis uncovered a relatively moderate level of variation among Iranian cannabis.
Mild heat induces a distinct “eustress” response in Chinese Hamster Ovary cells but does not induce heat shock protein synthesis
Authors: Peksel Begüm , Gombos Imre , Péter Mária , Vigh László , Tiszlavicz Ádám , Brameshuber Mario , Balogh Gábor , Schütz Gerhard J. , Horváth Ibolya , Vigh László , Török Zsolt
Published: November 2017

The current research on cellular heat stress management focuses on the roles of heat shock proteins (HSPs) and the proteostasis network under severe stress conditions. The mild, fever-type stress and the maintenance of membrane homeostasis are less well understood. Herein, we characterized the acute effect of mild, fever-range heat shock on membrane organization, and HSP synthesis and localization in two mammalian cell lines, to delineate the role of membranes in the sensing and adaptation to heat. A multidisciplinary approach combining ultrasensitive fluorescence microscopy and lipidomics revealed the molecular details of novel cellular “eustress”, when cells adapt to mild heat by maintaining membrane homeostasis, activating lipid remodeling, and redistributing chaperone proteins. Notably, this leads to acquired thermotolerance in the complete absence of the induction of HSPs. At higher temperatures, additional defense mechanisms are activated, including elevated expression of molecular chaperones, contributing to an extended stress memory and acquired thermotolerance.
Understanding the anticorrosive protective mechanisms of modified epoxy coatings with improved barrier, active and self-healing functionalities: EIS and spectroscopic techniques
Authors: Njoku Demian I. , Cui Miaomiao , Xiao Haigang , Shang Baihui , Li Ying
Published: November 2017

The present investigation adopted long-term in-situ electrochemical and spectroscopic approaches to study the combined active, self-healing and passive protective mechanisms of a new class of innovative anti-corrosive coatings based on epoxy doped with clay nanotubes impregnated with active species for the protection of carbon steel in 3.5% NaCl solution. The suitability of the as-received clay nanotubes to encapsulate the active agents was confirmed by different spectroscopic measurements. Tube end stopper with Ferric ion and polymer encapsulation with chitosan cross-linked with glutaraldehyde were adopted to tunnel the release of the active agents loaded into the nanotubes. The improved passive barrier performances of the various innovative coatings were revealed by the electrochemical impedance spectroscopic, while their active feedback and self-healing abilities were revealed by the optical and spectroscopic techniques. The optical/spectroscopic techniques revealed the degree of pit formation at the steel/coating interface and the iron rust formation around the artificially marked defects, including the ability of the marked defects to self-heal over exposure times. Adhesion and impacts tests were adopted to compare the physical/mechanical properties of the various coatings. The results afforded insights into the effects of exposure time on the protective and failure behaviours of both the reference and modified coatings.
The psoriasis-associated IL-17A induces and cooperates with IL-36 cytokines to control keratinocyte differentiation and function
Authors: Pfaff Carolina M. , Marquardt Yvonne , Fietkau Katharina , Baron Jens M. , Lüscher Bernhard
Published: November 2017

Psoriasis is a TH17-driven inflammatory disease affecting a significant proportion of the world population. The molecular consequences of IL-17 signaling in the skin are only partially understood. Therefore, we evaluated the IL-17A effects on organotypic 3-dimensional skin models and observed that IL-17A interfered with keratinocyte differentiation. In agreement with this phenotype, IL-17A repressed the expression of many genes encoding structural proteins. Moreover, genes encoding anti-microbial peptides were induced, resulting in a strengthening of the chemical barrier. Finally, we observed enhanced expression of the three IL-36 cytokines IL-36α, β and γ. We found that IL-36γ was secreted from keratinocytes in an inactive form and that neutrophilic proteases, including elastase, were capable of activating this cytokine. Functionally and similar to IL-17A, truncated IL-36 cytokines interfered with keratinocyte differentiation in 3D models. The molecular analysis revealed strong cooperative effects of IL-17A and IL-36 cytokines in regulating target genes, which was dependent on the proteolytic activation of the latter. Together these findings suggest an amplification cycle that can be initiated by IL-17A, involving IL-36 cytokines and immune cell derived proteases and resulting in active IL-36 cytokines which synergize with IL-17A. This amplification cycle might be relevant for a persistent psoriatic phenotype.
The phase diagram and stability of trapped D-dimensional spin-orbit coupled Bose-Einstein condensate
Authors: Yu Zi-Fa , Xue Ju-Kui
Published: November 2017

By variational analysis and direct numerical simulation, we study the phase transition and stability of a trapped D-dimensional Bose-Einstein condensate with spin-orbit coupling. The complete phase and stability diagrams of the system are presented in full parameter space, while the collapse dynamics induced by the mean-filed attraction and the mechanism for stabilizing the collapse by spin-orbit coupling are illustrated explicitly. Particularly, a full and deep understanding of the dependence of phase transition and stability mechanism on geometric dimensionality and external trap potential is revealed. It is shown that the spin-orbit coupling can modify the dispersion relations, which can balance the mean-filed attractive interaction and result in a spin polarized or overlapped state to stabilize the collapse, then changes the collapsing threshold dependent on the geometric dimensionality and external trap potential. Moreover, from 2D to 3D system, the mean-field attraction for inducing the collapse is reduced and the collapse speed is enhanced, namely, the collapse can be more easily stabilized in 2D system. That is, the collapse can be manipulated by adjusting the spin-orbit coupling, Raman coupling, geometric dimensionality and the external trap potential, which can provide a possible way for elaborating the collapse dynamics experimentally.