bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

AbstractAccurate 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

AbstractTuberculosis (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

AbstractPrevention 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

AbstractThe 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

AbstractThe 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

AbstractAdverse 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

AbstractThe 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

AbstractBioremediation 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

AbstractOxygen-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

AbstractAutosomal 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

Abstract14-3-3 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

AbstractKnowledge 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

AbstractHand, 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.
Genetic interaction involving photoperiod-responsive Hd1 promotes early flowering under long-day conditions in rice
Authors: Subudhi Prasanta K. , De Leon Teresa B. , Tapia Ronald , Chai Chenglin , Karan Ratna , Ontoy John , Singh Pradeep K. 
Published: January 2018

AbstractAlthough flowering in rice has been extensively investigated, few studies focused on genetic interactions. Flowering evaluation of two recombinant inbred line (RIL) populations involving photo-insensitive rice cultivars, Bengal and Cypress, and a weedy rice accession, PSRR-1, under natural long-day (LD) conditions, revealed six to ten quantitative trait loci (QTLs) and a major QTL interaction. In addition to the validation of several previously cloned genes using an introgression lines (IL) population of PSRR-1, a few novel QTLs were also discovered. Analysis of the marker profiles of the advanced backcross lines revealed that Hd1 allele of PSRR-1 was responsible for the photoperiodic response in the near-isogenic lines (NILs) developed in both cultivar backgrounds. Based on the phenotypic and genotypic data of the NILs, and NIL mapping population and the transcript abundance of key flowering pathway genes, we conclude that Hd1 and its interaction with a novel gene other than Ghd7 play an important role in controlling flowering under LD conditions. Our study demonstrates the important role of genetic interaction that regulates flowering time in rice and the need for further investigation to exploit it for breeding adaptable rice varieties.