bluuebunny/crossref_metadata_2025 huggingface dataset:
Causality and Pleiotropy in the Association Between Bullying Victimization in Adolescence and Depressive Episodes in Adulthood
Authors: Kretschmer Tina , Tropf Felix C. , Niezink Nynke M. D.
Published: January 2018

Children and adolescents who are victims or perpetrators of bullying victimization are at elevated risk for maladjustment problems, concurrently and in the long run. Previous studies suggest that this correlation is partly explained by genetic influence. However, whether the genetic correlation is independent of a causal effect of victimization on maladjustment remains unclear. Using data from 2,510 females from the TwinsUK registry, we applied an innovative extension of the Cholesky decomposition to investigate to what extent the association between victimization in adolescence and self-reported depressive episodes in adulthood is caused by shared genetic effects (pleiotropy), and to what extent it is due to a phenotypic causal relationship. We find that around 60% of the association between victimization and self-reported depressive episodes is due to a causal effect of victimization on depressive episodes, and 40% is due to pleiotropic effects. These findings underline the importance of integrating genetic information into social science research and demonstrate a neat strategy to elucidate causal mechanisms in the absence of experimental designs.
Development and validation of the Patient Benefit Index for peripheral arterial disease
Authors: Zander Nicole , Demirel Ebru-Berrin , Augustin Matthias , Sommer Rachel , Debus Eike Sebastian , Breuer Peter , Blome Christine
Published: January 2018

Abstract. Background: The aim of this study was to develop and validate a specific Patient Benefit Index (PBI) version for the treatment of peripheral arterial disease (PAD). Patients and methods: A non-interventional longitudinal development study was conducted. The first phase comprised a qualitative pre-study with n = 50 patients, in which the PBI was adapted for peripheral arterial disease. The resulting Patient Benefit Index for peripheral arterial disease (PBI-PAD) was validated in the second phase at two points of measurement. The total PBI-PAD score was calculated by weighting item-wise the achievement of treatment goals with the initially assessed needs. Feasibility, internal consistency, and construct validity were analysed and the generic three level version of the EuroQol five-dimensional questionnaire (EQ-5D-3L) and the disease-specific instrument Vascular Quality of Life Questionnaire (VascuQoL) were used for convergent validation. Results: In the pre-study, the PBI-PAD, consisting of 12 items, was developed. N = 103 patients participated in the main study. At T2, data were available for n = 57 patients. Mean age was 71.0 years ± 9.1 and 66.7 % of the participants were male. The amount of missing values of the PBI-PAD score was low (< 4.0 %) and no relevant floor effects were observed. Both parts of the PBI (needs at T1 and benefits at T2) were internally consistent with Cronbach’s alpha > 0.7. PBI-PAD total score correlated significantly with the T2-T1-differences of the EuroQol-visual analogue scale (EQ VAS) (r = 0.4, p = 0.007) and the Vascular Quality of Life Questionnaire (r = 0.5, p < 0.001). Conclusions: The PBI-PAD is a feasible, internally consistent, and valid instrument to assess patient-relevant benefits in PAD patients receiving minimally invasive treatment or surgical procedures. It can be recommended for use in routine care as well as in clinical studies.
Repräsentanz von Pflegewissenschaftlerinnen und Pflegewissenschaftlern aus dem deutschsprachigen Raum in Zeitschriften mit hohem Impact Factor
Authors: Hirt Julian , Buhtz Christian , Mersdorf Benedikt , Meyer Gabriele
Published: January 2018

Zusammenfassung.Hintergrund: Die Häufigkeit pflegewissenschaftlicher Beiträge aus dem deutschsprachigen Raum in Zeitschriften mit hohem Impact Factor gibt Hinweise auf die Teilhabe der Disziplin am internationalen Diskurs. Bisherige Analysen beschränken sich auf pflegewissenschaftliche Zeitschriften. Diese konstatieren eine Unterrepräsentanz experimenteller Studien und klinischer Themen. Ziel: Identifikation und Analyse der Publikationen von im deutschsprachigen Raum ansässigen Pflegewissenschaftlerinnen/Pflegewissenschaftlern in internationalen pflegerelevanten High Impact Journals. Methode: Mittels Journal Citation Reports wurden pflegerelevante Zeitschriftenkategorien identifiziert, in denen die nach dem 5-Jahres-Impact-Factor höchsten 10 % der Zeitschriften der Jahre 2010 bis 2014 ausgewählt wurden. Der Einschluss der Publikationen und die Datenextraktion erfolgten durch zwei unabhängige Personen. Ergebnisse: Durchsucht wurden 106939 Publikationen aus 126 Zeitschriften. Eingeschlossen wurden 100 Publikationen, an denen 114 Pflegewissenschaftler/-innen aus dem deutschsprachigen Raum insgesamt 229 Mal beteiligt sind. Insgesamt 42 % sind Beobachtungsstudien, 11 % sind experimentelle Studien. Die berichteten Themen sind mehrheitlich klinisch orientiert (55 %). Über 50 % sind in den letzten zwei Jahren publiziert worden. Schlussfolgerungen: Das pflegewissenschaftliche Publikationsaufkommen aus dem deutschsprachigen Raum in High Impact Journals ist gering. Eine Zunahme über den Beobachtungszeitraum ist zu verzeichnen. Im Gegensatz zu früheren Analysen zeigt sich ein höherer Anteil klinischer Forschung.
Precambrian origins of the TNFR superfamily
Authors: Quistad S D , Traylor-Knowles N
Published: January 2018

The evolution of the tumor necrosis factor/tumor necrosis factor receptor superfamily (TNF/TNFR) is complicated and not well understood. To date, most TNFR studies have focused on vertebrate models leaving the role of TNFRs in invertebrates largely unexplored. The evolution of important cellular processes including stress response, apoptosis, development, and inflammation will be better understood by examining the TNF/TNFR superfamily in ancient invertebrate phyla. How widespread is this gene family within the evolutionary tree of life and is there evidence for similar function in invertebrates? A first step is to identify the presence or absence of these genes within basal metazoan taxa using the signature cysteine-rich domain (CRD) of the TNFR superfamily. In this perspective, we will start by examining what is currently known about the function of TNFRs in invertebrates. Then, we will assess the role of TNFRs in apoptosis and explore the origins of the domains found in TNFRs including the death domain (DD) and CRD. Finally, we will examine the phylogenetic relationship between TNFRs containing DDs identified to date. From these data, we propose a model for a Precambrian origin of TNFRs and their functional role in apoptosis.
WAH-1/AIF regulates mitochondrial oxidative phosphorylation in the nematode Caenorhabditis elegans
Authors: Troulinaki Kostoula , Büttner Sven , Marsal Cots Anaïs , Maida Simona , Meyer Katharina , Bertan Fabio , Gioran Anna , Piazzesi Antonia , Fornarelli Alessandra , Nicotera Pierluigi , Bano Daniele
Published: January 2018

Impaired mitochondrial energy metabolism contributes to a wide range of pathologic conditions, including neurodegenerative diseases. Mitochondrial apoptosis-inducing factor (AIF) is required for the correct maintenance of mitochondrial electron transport chain. An emerging body of clinical evidence indicates that several mutations in the AIFM1 gene are causally linked to severe forms of mitochondrial disorders. Here we investigate the consequence of WAH-1/AIF deficiency in the survival of the nematode Caenorhabditis elegans. Moreover, we assess the survival of C. elegans strains expressing a disease-associated WAH-1/AIF variant. We demonstrate that wah-1 downregulation compromises the function of the oxidative phosphorylation system and reduces C. elegans lifespan. Notably, the loss of respiratory subunits induces a nuclear-encoded mitochondrial stress response independently of an evident increase of oxidative stress. Overall, our data pinpoint an evolutionarily conserved role of WAH-1/AIF in the maintenance of proper mitochondrial activity.
Improved security bound for the round-robin-differential-phase-shift quantum key distribution
Authors: Yin Zhen-Qiang , Wang Shuang , Chen Wei , Han Yun-Guang , Wang Rong , Guo Guang-Can , Han Zheng-Fu
Published: January 2018

The round-robin-differential-phase-shift (RRDPS) quantum key distribution (QKD) protocol has attracted intensive study due to its distinct security characteristics; e.g., information leakage is bounded without learning the error rate of key bits. Nevertheless, its practicality and performance are still not satisfactory. Here, by observing the phase randomization of the encoding states and its connection with eavesdropper’s attack, we develop an improved bound on information leakage. Interestingly, our theory is especially useful for implementations with short trains of pulses, and running without monitoring signal disturbance is still available. As a result, the practicality and performance of RRDPS are improved. Furthermore, we realize a proof-of-principle experiment with up to 140 km of fiber, which has been the longest achievable distance of RRDPS until now, whereas the original theory predicted that no secret key could be generated in our experiment. Our results will help in bringing practical RRDPS closer to practical implementations.
Platinum-bearing chromite layers are caused by pressure reduction during magma ascent
Authors: Latypov Rais , Costin Gelu , Chistyakova Sofya , Hunt Emma J. , Mukherjee Ria , Naldrett Tony
Published: January 2018

Platinum-bearing chromitites in mafic-ultramafic intrusions such as the Bushveld Complex are key repositories of strategically important metals for human society. Basaltic melts saturated in chromite alone are crucial to their generation, but the origin of such melts is controversial. One concept holds that they are produced by processes operating within the magma chamber, whereas another argues that melts entering the chamber were already saturated in chromite. Here we address the problem by examining the pressure-related changes in the topology of a Mg2SiO4–CaAl2Si2O8–SiO2–MgCr2O4 quaternary system and by thermodynamic modelling of crystallisation sequences of basaltic melts at 1–10 kbar pressures. We show that basaltic melts located adjacent to a so-called chromite topological trough in deep-seated reservoirs become saturated in chromite alone upon their ascent towards the Earth’s surface and subsequent cooling in shallow-level chambers. Large volumes of these chromite-only-saturated melts replenishing these chambers are responsible for monomineralic layers of massive chromitites with associated platinum-group elements.
A peculiar low-luminosity short gamma-ray burst from a double neutron star merger progenitor
Authors: Zhang B.-B. , Zhang B. , Sun H. , Lei W.-H. , Gao H. , Li Y. , Shao L. , Zhao Y. , Hu Y.-D. , Lü H.-J. , Wu X.-F. , Fan X.-L. , Wang G. , Castro-Tirado A. J. , Zhang S. , Yu B.-Y. , Cao Y.-Y. , Liang E.-W.
Published: January 2018

Double neutron star (DNS) merger events are promising candidates of short gamma-ray burst (sGRB) progenitors as well as high-frequency gravitational wave (GW) emitters. On August 17, 2017, such a coinciding event was detected by both the LIGO-Virgo gravitational wave detector network as GW170817 and Gamma-Ray Monitor on board NASA’s Fermi Space Telescope as GRB 170817A. Here, we show that the fluence and spectral peak energy of this sGRB fall into the lower portion of the distributions of known sGRBs. Its peak isotropic luminosity is abnormally low. The estimated event rate density above this luminosity is at least $$190_{ - 160}^{ + 440}$$
19

0

-
160

+
440

 Gpc−3 yr−1, which is close to but still below the DNS merger event rate density. This event likely originates from a structured jet viewed from a large viewing angle. There are similar faint soft GRBs in the Fermi archival data, a small fraction of which might belong to this new population of nearby, low-luminosity sGRBs.
Bacterial capture efficiency in fluid bloodstream improved by bendable nanowires
Authors: Liu Lizhi , Chen Sheng , Xue Zhenjie , Zhang Zhen , Qiao Xuezhi , Nie Zongxiu , Han Dong , Wang Jianlong , Wang Tie
Published: January 2018

Bacterial infectious diseases, such as sepsis, can lead to impaired function in the lungs, kidneys, and other vital organs. Although established technologies have been designed for the extracorporeal removal of bacteria, a high flow velocity of the true bloodstream might result in low capture efficiency and prevent the realization of their full clinical potential. Here, we develop a dialyzer made by three-dimensional carbon foam pre-grafted with nanowires to isolate bacteria from unprocessed blood. The tip region of polycrystalline nanowires is bent readily to form three-dimensional nanoclaws when dragged by the molecular force of ligand-receptor, because of a decreasing Young’s moduli from the bottom to the tip. The bacterial capture efficiency was improved from ~10% on carbon foam and ~40% on unbendable single-crystalline nanowires/carbon foam to 97% on bendable polycrystalline nanowires/carbon foam in a fluid bloodstream of 10 cm s−1 velocity.
Disrupted Resting State Network of Fibromyalgia in Theta frequency
Authors: Choe Mi Kyung , Lim Manyoel , Kim June Sic , Lee Dong Soo , Chung Chun Kee
Published: January 2018

Fibromyalgia (FM), chronic widespread pain, exhibits spontaneous pain without external stimuli and is associated with altered brain activities during resting state. To understand the topological features of brain network in FM, we employed persistent homology which is a multiple scale network modeling framework not requiring thresholding. Spontaneous magnetoencephalography (MEG) activity was recorded in 19 healthy controls (HCs) and 18 FM patients. Barcode, single linkage dendrogram and single linkage matrix were generated based on the proposed modeling framework. In theta band, the slope of decrease in the number of connected components in barcodes showed steeper in HC, suggesting FM patients had decreased global connectivity. FM patients had reduced connectivity within default mode network, between middle/inferior temporal gyrus and visual cortex. The longer pain duration was correlated with reduced connectivity between inferior temporal gyrus and visual cortex. Our findings demonstrated that the aberrant resting state network could be associated with dysfunction of sensory processing in chronic pain. The spontaneous nature of FM pain may accrue to disruption of resting state network.
Effects of pulsing of light on the dentinogenesis of dental pulp stem cells in vitro
Authors: Kim Hong Bae , Baik Ku Youn , Seonwoo Hoon , Jang Kyoung-Je , Lee Myung Chul , Choung Pill-Hoon , Chung Jong Hoon
Published: January 2018

Low power light (LPL) treatment has been widely used in various clinical trials, which has been known to reduce pain and inflammation and to promote wound healing. LPL was also shown to enhance differentiation of stem cells into specific lineages. However, most studies have used high power light in mW order, and there was lack of studies about the effects of very low power light in μW. In this study, we applied 810 nm LPL of 128 μW/cm2 energy density in vitro. Upon this value, continuous wave (CW) irradiation did not induce any significant changes for differentiation of human dental pulp stem cells (hDPSCs). However, the membrane hyperpolarization, alkaline phosphatase activity, and intracellular oxidative stress were largely enhanced in the pulsed wave (PW) with 30% of duty cycle and 300–3000 Hz frequencies-LPL in which LED driver work in the form of square wave. After 21 days of daily LPL treatment, Western blot revealed the dentinogenesis in this condition in vitro. This study demonstrates that the very low power light at 810 nm enhanced significant differentiation of hDPSCs in the PW mode and there were duty cycle dependency as well as pulsing frequency dependency in the efficiency.
Detection of 16S rRNA and KPC Genes from Complex Matrix Utilizing a Molecular Inversion Probe Assay for Next-Generation Sequencing
Authors: Stefan Christopher P. , Hall Adrienne T. , Minogue Timothy D.
Published: January 2018

Targeted sequencing promises to bring next-generation sequencing (NGS) into routine clinical use for infectious disease diagnostics. In this context, upfront processing techniques, including pathogen signature enrichment, must amplify multiple targets of interest for NGS to be relevant when applied to patient samples with limited volumes. Here, we demonstrate an optimized molecular inversion probe (MIP) assay targeting multiple variable regions within the 16S ribosomal gene for the identification of biothreat and ESKAPE pathogens in a process that significantly reduces complexity, labor, and processing time. Probes targeting the Klebsiella pneumoniae carbapenemase (KPC) antibiotic resistance (AR) gene were also included to demonstrate the ability to concurrently identify etiologic agent and ascertain valuable secondary genetic information. Our assay captured gene sequences in 100% of mock clinical samples prepared from flagged positive blood culture bottles. Using a simplified processing and adjudication method for mapped sequencing reads, genus and species level concordance was 100% and 80%, respectively. In addition, sensitivity and specificity for KPC gene detection was 100%. Our MIP assay produced sequenceable amplicons for the identification of etiologic agents and the detection of AR genes directly from blood culture bottles in a simplified single tube assay.
Work Function Variations in Twisted Graphene Layers
Authors: Robinson Jeremy T. , Culbertson James , Berg Morgann , Ohta Taisuke
Published: January 2018

By combining optical imaging, Raman spectroscopy, kelvin probe force microscopy (KFPM), and photoemission electron microscopy (PEEM), we show that graphene’s layer orientation, as well as layer thickness, measurably changes the surface potential (Φ). Detailed mapping of variable-thickness, rotationally-faulted graphene films allows us to correlate Φ with specific morphological features. Using KPFM and PEEM we measure ΔΦ up to 39 mV for layers with different twist angles, while ΔΦ ranges from 36–129 mV for different layer thicknesses. The surface potential between different twist angles or layer thicknesses is measured at the KPFM instrument resolution of ≤ 200 nm. The PEEM measured work function of 4.4 eV for graphene is consistent with doping levels on the order of 1012cm−2. We find that Φ scales linearly with Raman G-peak wavenumber shift (slope = 22.2 mV/cm−1) for all layers and twist angles, which is consistent with doping-dependent changes to graphene’s Fermi energy in the ‘high’ doping limit. Our results here emphasize that layer orientation is equally important as layer thickness when designing multilayer two-dimensional systems where surface potential is considered.
“Gilbert’s-like” syndrome as part of a spectrum of persistent unconjugated hyperbilirubinemia in post-chronic hepatitis patients
Authors: Ye Jin , Cui Lianlian , Zhou Yingqiao , Huang Ying , Banafa Omar , Hou Xiaohua , Ding Zhen , Lin Rong
Published: January 2018

Gilbert’s syndrome (GS) patients present with remittent unconjugated hyperbilirubinemia. In this study, we investigated the correlation between polymorphisms in the gene encoding UDP-glucuronosyltransferase, UGT1A1, and the development of unconjugated hyperbilirubinemia in clinical GS and post-hepatitis hyperbilirubinemia. Blood samples were collected from 285 patients, including 85 patients who were clinically diagnosed with GS, 70 patients who had indirect hyperbilirubinemia during the recovery period of chronic liver diseases, 109 patients with normal hepatic function and 21 chronic active hepatitis patients. All samples were tested for the presence of the *28/*6 UGT1A1 genotype by pyrosequencing. Compared with the GS-control group, a significant difference in variations of the UGT1A1*28/*6 allele gene was found in GS patients. The post-hepatitis group showed a significant difference in the UGT1A1*28/*6 allele gene frequency distribution relative to that in the hepatitis control group. There were no significant differences between the GS group and post-hepatitis group in the distribution of the UGT1A1*28/*6 allele gene frequency and UGT1A1 diplotypes. UGT1A1*28/*6 gene polymorphisms in patients who had indirect hyperbilirubinemia while recovering from chronic liver diseases presented similar patterns as those seen for GS patients. These findings suggest that a “Gilbert’s-like” syndrome might be part of the spectrum of persistent unconjugated hyperbilirubinemia in post-chronic hepatitis patients.
Expression and specificity of a chitin deacetylase from the nematophagous fungus Pochonia chlamydosporia potentially involved in pathogenicity
Authors: Aranda-Martinez Almudena , Grifoll-Romero Laia , Aragunde Hugo , Sancho-Vaello Enea , Biarnés Xevi , Lopez-Llorca Luis Vicente , Planas Antoni
Published: January 2018

Chitin deacetylases (CDAs) act on chitin polymers and low molecular weight oligomers producing chitosans and chitosan oligosaccharides. Structurally-defined, partially deacetylated chitooligosaccharides produced by enzymatic methods are of current interest as bioactive molecules for a variety of applications. AmongPochonia chlamydosporia(Pc) annotated CDAs, genepc_2566was predicted to encode for an extracellular CE4 deacetylase with two CBM18 chitin binding modules. Chitosan formation during nematode egg infection by this nematophagous fungus suggests a role for their CDAs in pathogenicity. TheP. chlamydosporiaCDA catalytic domain (PcCDA) was expressed inE. coliBL21, recovered from inclusion bodies, and purified by affinity chromatography. It displays deacetylase activity on chitooligosaccharides with a degree of polymerization (DP) larger than 3, generating mono- and di-deacetylated products with a pattern different from those of closely related fungal CDAs. This is the first report of a CDA from a nematophagous fungus. On a DP5 substrate,PcCDA gave a single mono-deacetylated product in the penultimate position from the non-reducing end (ADAAA) which was then transformed into a di-deacetylated product (ADDAA). This novel deacetylation pattern expands our toolbox of specific CDAs for biotechnological applications, and will provide further insights into the determinants of substrate specificity in this family of enzymes.
Axial elongation measured by long scan depth optical coherence tomography during pilocarpine-induced accommodation in intraocular lens-implanted eyes
Authors: Shao Yilei , Jiang Qiuruo , Hu Di , Zhang Lingmin , Shen Meixiao , Huang Shenghai , Leng Lin , Yuan Yimin , Chen Qi , Zhu Dexi , Wang Jianhua , Lu Fan
Published: January 2018

We used an ultra-long scan depth optical coherence tomography (UL-OCT) system to investigate changes in axial biometry of pseudophakic eyes during pilocarpine- induced accommodation. The right eyes from 25 healthy subjects (age range 49 to 84 years) with an intraocular lens (IOL) were imaged twice in the non-accommodative and the accommodative states. A custom-built UL-OCT instrument imaged the whole eye. Then accommodation was induced by two drops of 0.5% pilocarpine hydrochloride separated by a 5-minute interval. Following the same protocol, images were acquired again 30 minutes after the first drop. The central corneal thickness (CCT), anterior chamber depth (ACD), IOL thickness (IOLT), and vitreous length (VL) were obtained using custom automated software. The axial length (AL) was calculated by summing the CCT, ACD, IOLT, and VL. With accommodation, ACD increased by +0.08 ± 0.09 mm, while the VL decreased by −0.04 ± 0.09 mm (paired t-test each, P<0.05). CCT and IOLT remained constant during accommodation (P > 0.05). The non-accommodative AL was 23.47 ± 0.93 mm, and it increased by +0.04 ± 0.04 mm after accommodation (P<0.01). The AL increased and the IOL moved backward during pilocarpine-induced accommodation in pseudophakic eyes.
Grey matter OPCs are less mature and less sensitive to IFNγ than white matter OPCs: consequences for remyelination
Authors: Lentferink Dennis H. , Jongsma Jacomien M. , Werkman Inge , Baron Wia
Published: January 2018

Multiple sclerosis (MS) is a chronic inflammatory disease characterized by the formation of demyelinated lesions in the central nervous system. At later stages of the disease repair in the form of remyelination often fails, which leads to axonal degeneration and neurological disability. For the regeneration of myelin, oligodendrocyte progenitor cells (OPCs) have to migrate, proliferate and differentiate into remyelinating oligodendrocytes. Remyelination occurs faster and is more extensive in grey matter (GM) lesions than in white matter (WM) lesions. Here, we examined differences in neonatal OPCs from GM (gmOPCs) and WM (wmOPCs), both intrinsically and in response to environmental (injury) signals. We show that gmOPCs are less mature than wmOPCs, both on morphological and on gene-expression level. Additionally, gmOPCs proliferate more and differentiate slower than wmOPCs. When exposed to astrocyte-secreted signals wmOPC, but not gmOPC, migration decreases. In addition, wmOPCs are more sensitive to the detrimental effects of IFNγ treatment on proliferation, differentiation, and process arborisation, which is potentiated by TNFα. Our results demonstrate that OPCs from GM and WM differ both intrinsically and in response to their environment, which may contribute to the difference in remyelination efficiency between GM and WM MS lesions.
Strong constraint on modelled global carbon uptake using solar-induced chlorophyll fluorescence data
Authors: MacBean Natasha , Maignan Fabienne , Bacour Cédric , Lewis Philip , Peylin Philippe , Guanter Luis , Köhler Philipp , Gómez-Dans Jose , Disney Mathias
Published: January 2018

Accurate terrestrial biosphere model (TBM) simulations of gross carbon uptake (gross primary productivity – GPP) are essential for reliable future terrestrial carbon sink projections. However, uncertainties in TBM GPP estimates remain. Newly-available satellite-derived sun-induced chlorophyll fluorescence (SIF) data offer a promising direction for addressing this issue by constraining regional-to-global scale modelled GPP. Here, we use monthly 0.5° GOME-2 SIF data from 2007 to 2011 to optimise GPP parameters of the ORCHIDEE TBM. The optimisation reduces GPP magnitude across all vegetation types except C4 plants. Global mean annual GPP therefore decreases from 194 ± 57 PgCyr−1 to 166 ± 10 PgCyr−1, bringing the model more in line with an up-scaled flux tower estimate of 133 PgCyr−1. Strongest reductions in GPP are seen in boreal forests: the result is a shift in global GPP distribution, with a ~50% increase in the tropical to boreal productivity ratio. The optimisation resulted in a greater reduction in GPP than similar ORCHIDEE parameter optimisation studies using satellite-derived NDVI from MODIS and eddy covariance measurements of net CO2 fluxes from the FLUXNET network. Our study shows that SIF data will be instrumental in constraining TBM GPP estimates, with a consequent improvement in global carbon cycle projections.
Genome-wide associations identify novel candidate loci associated with genetic susceptibility to tuberculosis in wild boar
Authors: Queirós João , Alves Paulo Célio , Vicente Joaquín , Gortázar Christian , de la Fuente José
Published: January 2018

Tuberculosis (TB) affects a wide range of host species worldwide. Understanding host-pathogen co-evolution remains a global challenge owing to complex interactions among host genetic factors, pathogen traits and environmental conditions. We used an endemic wild boar population that had undergone a huge increase in Mycobacterium bovis infection prevalence, from 45% in 2002/06 to 83% in 2009/12, to understand the effects of host genetics on host TB outcomes and disease dynamics. Host genomic variation was characterized using a high-density single nucleotide polymorphism (SNP) array, while host TB phenotype was assessed using both gross pathology and mycobacterial culture. Two complementary genome-wide association (GWAS) analyses were conducted: (i) infected-uninfected; and (ii) 2002/06–2009/12. The SNPs with the highest allelic frequency differences between time-periods and TB outcomes were identified and validated in a large dataset. In addition, we quantified the expression levels of some of their closest genes. These analyses highlighted various SNPs (i.e. rs81465339, rs81394585, rs81423166) and some of the closest genes (i.e. LOC102164072, BDNF/NT-3, NTRK2, CDH8, IGSF21) as candidates for host genetic susceptibility. In addition to TB-driven selection, our findings outline the putative role of demographic events in shaping genomic variation in natural populations and how population crashes and drift may impact host genetic susceptibility to TB over time.
A Systematic Machine Learning Based Approach for the Diagnosis of Non-Alcoholic Fatty Liver Disease Risk and Progression
Authors: Perveen Sajida , Shahbaz Muhammad , Keshavjee Karim , Guergachi Aziz
Published: January 2018

Prevention and diagnosis of NAFLD is an ongoing area of interest in the healthcare community. Screening is complicated by the fact that the accuracy of noninvasive testing lacks specificity and sensitivity to make and stage the diagnosis. Currently no non-invasive ATP III criteria based prediction method is available to diagnose NAFLD risk. Firstly, the objective of this research is to develop machine learning based method in order to identify individuals at an increased risk of developing NAFLD using risk factors of ATP III clinical criteria updated in 2005 for Metabolic Syndrome (MetS). Secondly, to validate the relative ability of quantitative score defined by Italian Association for the Study of the Liver (IASF) and guideline explicitly defined for the Canadian population based on triglyceride thresholds to predict NAFLD risk. We proposed a Decision Tree based method to evaluate the risk of developing NAFLD and its progression in the Canadian population, using Electronic Medical Records (EMRs) by exploring novel risk factors for NAFLD. Our results show proposed method could potentially help physicians make more informed choices about their management of patients with NAFLD. Employing the proposed application in ordinary medical checkup is expected to lessen healthcare expenditures compared with administering additional complicated test.
Small-molecule flunarizine increases SMN protein in nuclear Cajal bodies and motor function in a mouse model of spinal muscular atrophy
Authors: Sapaly Delphine , Dos Santos Matthieu , Delers Perrine , Biondi Olivier , Quérol Gwendoline , Houdebine Léo , Khoobarry Kevinee , Girardet François , Burlet Philippe , Armand Anne-Sophie , Chanoine Christophe , Bureau Jean-François , Charbonnier Frédéric , Lefebvre Suzie
Published: January 2018

The hereditary neurodegenerative disorder spinal muscular atrophy (SMA) is characterized by the loss of spinal cord motor neurons and skeletal muscle atrophy. SMA is caused by mutations of the survival motor neuron (SMN) gene leading to a decrease in SMN protein levels. The SMN deficiency alters nuclear body formation and whether it can contribute to the disease remains unclear. Here we screen a series of small-molecules on SMA patient fibroblasts and identify flunarizine that accumulates SMN into Cajal bodies, the nuclear bodies important for the spliceosomal small nuclear RNA (snRNA)-ribonucleoprotein biogenesis. Using histochemistry, real-time RT-PCR and behavioural analyses in a mouse model of SMA, we show that along with the accumulation of SMN into Cajal bodies of spinal cord motor neurons, flunarizine treatment modulates the relative abundance of specific spliceosomal snRNAs in a tissue-dependent manner and can improve the synaptic connections and survival of spinal cord motor neurons. The treatment also protects skeletal muscles from cell death and atrophy, raises the neuromuscular junction maturation and prolongs life span by as much as 40 percent (p < 0.001). Our findings provide a functional link between flunarizine and SMA pathology, highlighting the potential benefits of flunarizine in a novel therapeutic perspective against neurodegenerative diseases.
Expression of steroidogenic enzymes and metabolism of steroids in COS-7 cells known as non-steroidogenic cells
Authors: Nozaki Mitsuki , Haraguchi Shogo , Miyazaki Takuro , Shigeta Daichi , Kano Noriko , Lei Xiao-Feng , Kim-Kaneyama Joo-ri , Minakata Hiroyuki , Miyazaki Akira , Tsutsui Kazuyoshi
Published: January 2018

The COS-7 (CV-1 inOrigin withSV40 genes) cells are known as non-steroidogenic cells because they are derived from kidney cells and the kidney is defined as a non-steroidogenic organ. Therefore, COS-7 cells are used for transfection experiments to analyze the actions of functional molecules including steroids. However, a preliminary study suggested that COS-7 cells metabolize [3H]testosterone to [3H]androstenedione. These results suggest that COS-7 cells are able to metabolize steroids. Therefore, the present study investigated the expression of steroidogenic enzymes and the metabolism of steroids in COS-7 cells. RT-PCR analyses demonstrated the expressions of several kinds of steroidogenic enzymes, such as cytochrome P450 side-chain cleavage enzyme, 3β-hydroxysteroid dehydrogenase/Δ5-Δ4isomerase, cytochrome P450 7α-hydroxylase, cytochrome P450 17α-hydroxylase/17,20-lyase, 17β-hydroxysteroid dehydrogenase, 5α-reductase, cytochrome P450 21-hydroxylase, cytochrome P450 11β-hydroxylase, and cytochrome P450 aromatase in COS-7 cells. In addition, steroidogenic enzymes 3β-HSD, P4507α, 5α-reductase, P450c17, P450c21, P450c11β, and 17β-HSD actively metabolized various steroids in cultured COS-7 cells. Finally, we demonstrated that 17β-HSD activity toward androstenedione formation was greater than other steroidogenic enzyme activities. Our results provide new evidence that COS-7 cells express a series of steroidogenic enzyme mRNAs and actively metabolize a variety of steroids.
CT pulmonary angiography in patients with acute or chronic renal insufficiency: Evaluation of a low dose contrast material protocol
Authors: Meyer Mathias , Haubenreisser Holger , Schabel Christoph , Leidecker Christianne , Schmidt Bernhard , Schoenberg Stefan O. , Henzler Thomas
Published: January 2018

Adverse effects of intravenous contrast media (CM) in patients with renal risk factors and acute kidney injury are still controversially discussed. The aim of this study was to investigate whether dual-energy (DE) pulmonary CT angiography (CTPA) in combination with a noise optimized virtual monoenergetic imaging algorithm allows for a reduction of CM. This IRB-approved study comprised 150 patients with suspected pulmonary embolism (78 male; mean age 65 ± 17years). 50 patients with acute/chronic renal failure were examined on a 3rd generation dual-source CT with an optimized DE CTPA protocol and a low CM injection protocol (5.4 g iodine). 100 further patients were either examined with a standard CTPA protocol or a standard DE CTPA (32 g iodine). For the DE CTPA virtual monoenergetic spectral datasets (40–100 keV) were reconstructed. Main pulmonary arteries at 50 keV and peripheral pulmonary arteries at 40 keV datasets provided the highest contrast-to-noise-ratio (CNR) for both the standard DE CTPA and the optimized protocol, with significantly higher CNR values for the standard DE CTPA protocol (p < 0.05). No pulmonary embolism was missed on the optimized CM protocol. DE CTPA utilizing image reconstruction at 40/50 keV allowed for a reduction of 84% in iodine load while maintaining CNR, which is especially important in patients with acute/chronic renal failure.
Non-invasive detection of divergent metabolic signals in insulin deficiency vs. insulin resistance in vivo
Authors: Morze Cornelius von , Allu Prasanna K. R. , Chang Gene Y. , Marco-Rius Irene , Milshteyn Eugene , Wang Zhen J. , Ohliger Michael A. , Gleason Catherine E. , Kurhanewicz John , Vigneron Daniel B. , Pearce David
Published: January 2018

The type 2 diabetic phenotype results from mixed effects of insulin deficiency and insulin resistance, but the relative contributions of these two distinct factors remain poorly characterized, as do the respective roles of the gluconeogenic organs. The purpose of this study was to investigate localized in vivo metabolic changes in liver and kidneys of contrasting models of diabetes mellitus (DM): streptozotocin (STZ)-treated wild-type Zucker rats (T1DM) and Zucker diabetic fatty (ZDF) rats (T2DM). Intermediary metabolism was probed using hyperpolarized (HP) [1-13C]pyruvate MRI of the liver and kidneys. These data were correlated with gene expression data for key mediators, assessed using rtPCR. Increased HP [1-13C]lactate was detected in both models, in association with elevated gluconeogenesis as reflected by increased expression of phosphoenolpyruvate carboxykinase. In contrast, HP [1-13C]alanine diverged between the two models, increasing in ZDF rats, while decreasing in the STZ-treated rats. The differences in liver alanine paralleled differences in key lipogenic mediators. Thus, HP [1-13C]alanine is a marker that can identify phenotypic differences in kidneys and liver of rats with T1DM vs. T2DM, non-invasively in vivo. This approach could provide a powerful diagnostic tool for characterizing tissue metabolic defects and responses to treatment in diabetic patients with ambiguous systemic manifestations.
Toxicity assessment of chlorpyrifos-degrading fungal bio-composites and their environmental risks
Authors: Liu Jie , Zhang Xiaoying , Yang Mengran , Hu Meiying , Zhong Guohua
Published: January 2018

Bioremediation techniques coupling with functional microorganisms have emerged as the most promising approaches for in-situ elimination of pesticide residue. However, the environmental safety of bio-products based on microorganisms or engineered enzymes was rarely known. Here, we described the toxicity assessment of two previously fabricated fungal bio-composites which were used for the biodegradation of chlorpyrifos, to clarify their potential risks on the environment and non-target organisms. Firstly, the acute and chronic toxicity of prepared bio-composites were evaluated using mice and rabbits, indicating neither acute nor chronic effect was induced via short-term or continuous exposure. Then, the acute mortality on zebrafish was investigated, which implied the application of fungal bio-composites had no lethal risk on aquatic organisms. Meanwhile, the assessment on soil organic matters suggested that no threat was posed to soil quality. Finally, by monitoring, the germination of cabbage was not affected by the exposure to two bio-products. Therefore, the application of fungal bio-composites for chlorpyrifos elimination cannot induce toxic risk to the environment and non-target organisms, which insured the safety of these engineered bio-products for realistic management of pesticide residue, and provided new insights for further development of bioremediation techniques based on functional microorganisms.
Targeted Knockdown of Overexpressed VEGFA or VEGF164 in Müller cells maintains retinal function by triggering different signaling mechanisms
Authors: Becker Silke , Wang Haibo , Simmons Aaron B. , Suwanmanee Thipparat , Stoddard Gregory J. , Kafri Tal , Hartnett M. Elizabeth
Published: January 2018

Oxygen-induced retinopathy (OIR) upregulates Müller cell vascular endothelial growth factor A (VEGFA) that causes intravitreal neovascularization similar to severe retinopathy of prematurity (ROP). Safety concerns exist with anti-VEGF treatment for ROP. We evaluated long-term knockdown of Müller cell-VEGFA with short-hairpin RNAs to VEGFA or VEGF164 via subretinal lentivirus delivery (L-VEGFAshRNA, L-VEGF164shRNA) on retinal structure and function in a rat OIR model. Lectin-stained retinal flat mounts analyzed for areas of avascular/total retina (AVA) and intravitreal neovascular/total retina (IVNV) showed initial significantly reduced IVNV by L-VEGFAshRNA and L-VEGF164shRNA compared to control, luciferase-shRNA lentivirus, without late recurrence. Spectral-domain optical coherence tomography (OCT) and immunohistochemical sections (IHC) demonstrated changes in retinal layer thicknesses in L-VEGFAshRNA or L-VEGF164shRNA  compared to control. Ganzfeld electroretinograms were increased in L-VEGFAshRNA or L-VEGF164shRNA compared to control. Erythropoietin (EPO), brain-derived neurotrophic factor, glial-derived neurotrophic factor, nerve growth factor, neurotrophin-3 (NT-3) mRNAs were increased in L-VEGFAshRNA, but not L-VEGF164shRNA retinas. In cultured rat Müller cells, knockdown of VEGF upregulated NT-3 and EPO, whereas treatment with EPO activated neuroprotective signaling. Methods to reduce IVNV by selective knockdown of VEGFA, and particularly VEGF164, in Müller cells may have fewer deleterious effects than nonselective VEGFA inhibition to all cells in the retina.
New Sequencing technologies help revealing unexpected mutations in Autosomal Dominant Hypercholesterolemia
Authors: Elbitar Sandy , Susan-Resiga Delia , Ghaleb Youmna , El Khoury Petra , Peloso Gina , Stitziel Nathan , Rabès Jean-Pierre , Carreau Valérie , Hamelin Josée , Ben-Djoudi-Ouadda Ali , Bruckert Eric , Boileau Catherine , Seidah Nabil G. , Varret Mathilde , Abifadel Marianne
Published: January 2018

Autosomal dominant hypercholesterolemia (ADH) is characterized by elevated LDL-C levels leading to coronary heart disease. Four genes are implicated in ADH: LDLR, APOB, PCSK9 and APOE. Our aim was to identify new mutations in known genes, or in new genes implicated in ADH. Thirteen French families with ADH were recruited and studied by exome sequencing after exclusion, in their probands, of mutations in the LDLR, PCSK9 and APOE genes and fragments of exons 26 and 29 of APOB gene. We identified in one family a p.Arg50Gln mutation in the APOB gene, which occurs in a region not usually associated with ADH. Segregation and in-silico analysis suggested that this mutation is disease causing in the family. We identified in another family with the p.Ala3396Thr mutation of APOB, one patient with a severe phenotype carrying also a mutation in PCSK9: p.Arg96Cys. This is the first compound heterozygote reported with a mutation in APOB and PCSK9. Functional studies proved that the p.Arg96Cys mutation leads to increased LDL receptor degradation. This work shows that Next-Generation Sequencing (exome, genome or targeted sequencing) are powerful tools to find new mutations and identify compound heterozygotes, which will lead to better diagnosis and treatment of ADH.
Differential abundance and transcription of 14-3-3 proteins during vegetative growth and sexual reproduction in budding yeast
Authors: Kumar Ravinder
Published: January 2018

14-3-3 is a family of relatively low molecular weight, acidic, dimeric proteins, conserved from yeast to metazoans including humans. Apart from their role in diverse cellular processes, these proteins are also known for their role in several clinical implications. Present proteomic and biochemical comparison showed increased abundance and differential phosphorylation of these proteins in meiotic cells. Double deletion of bmh1−/−bmh2−/− leads to complete absence of sporulation with cells arrested at G1/S phase while further incubation of cells in sporulating media leads to cell death. In silico analysis showed the presence of 14-3-3 interacting motifs in bonafide members of kinetochore complex (KC) and spindle pole body (SPB), while present cell biological data pointed towards the possible role of yeast Bmh1/2 in regulating the behaviour of KC and SPB. We further showed the involvement of 14-3-3 in segregation of genetic material and expression of human 14-3-3β/α was able to complement the function of endogenous 14-3-3 protein even in the complex cellular process like meiosis. Our present data also established haplosufficient nature of BMH1/2. We further showed that proteins synthesized during mitotic growth enter meiotic cells without de novo synthesis except for meiotic-specific proteins required for induction and meiotic progression in Saccharomyces cerevisiae.
Historical ecology reveals landscape transformation coincident with cultural development in central Italy since the Roman Period
Authors: Mensing Scott A. , Schoolman Edward M. , Tunno Irene , Noble Paula J. , Sagnotti Leonardo , Florindo Fabio , Piovesan Gianluca
Published: January 2018

Knowledge of the direct role humans have had in changing the landscape requires the perspective of historical and archaeological sources, as well as climatic and ecologic processes, when interpreting paleoecological records. People directly impact land at the local scale and land use decisions are strongly influenced by local sociopolitical priorities that change through time. A complete picture of the potential drivers of past environmental change must include a detailed and integrated analysis of evolving sociopolitical priorities, climatic change and ecological processes. However, there are surprisingly few localities that possess high-quality historical, archeological and high-resolution paleoecologic datasets. We present a high resolution 2700-year pollen record from central Italy and interpret it in relation to archival documents and archaeological data to reconstruct the relationship between changing sociopolitical conditions, and their effect on the landscape. We found that: (1) abrupt environmental change was more closely linked to sociopolitical and demographic transformation than climate change; (2) landscape changes reflected the new sociopolitical priorities and persisted until the sociopolitical conditions shifted; (3) reorganization of new plant communities was very rapid, on the order of decades not centuries; and (4) legacies of forest management adopted by earlier societies continue to influence ecosystem services today.
Quantifying the influence of temperature on hand, foot and mouth disease incidence in Wuhan, Central China
Authors: Huang Jiao , Chen Shi , Wu Yang , Tong Yeqing , Wang Lei , Zhu Min , Hu Shuhua , Guan Xuhua , Wei Sheng
Published: January 2018

Hand, foot and mouth disease (HFMD) is a substantial burden throughout Asia, but the effects of temperature pattern on HFMD risk are inconsistent. To quantify the effect of temperature on HFMD incidence, Wuhan was chosen as the study site because of its high temperature variability and high HFMD incidence. Daily series of HFMD counts and meteorological variables during 2010–2015 were obtained. Distributed lag non-linear models were applied to characterize the temperature-HFMD relationship and to assess its variability across different ages, genders, and types of child care. Totally, 80,219 patients of 0–5 years experienced HFMD in 2010–2015 in Wuhan. The cumulative relative risk of HFMD increased linearly with temperature over 7 days (lag0–7), while it presented as an approximately inverted V-shape over 14 days (lag0–14). The cumulative relative risk at lag0–14 peaked at 26.4 °C with value of 2.78 (95%CI: 2.08–3.72) compared with the 5thpercentile temperature (1.7 °C). Subgroup analyses revealed that children attended daycare were more vulnerable to temperature variation than those cared for at home. This study suggests that public health actions should take into consideration local weather conditions and demographic characteristics.