bluuebunny/crossref_metadata_2025_split huggingface dataset:
Disrupted topological organization of structural and functional brain connectomes in clinically isolated syndrome and multiple sclerosis
Authors: Shu Ni , Duan Yunyun , Xia Mingrui , Schoonheim Menno M. , Huang Jing , Ren Zhuoqiong , Sun Zheng , Ye Jing , Dong Huiqing , Shi Fu-Dong , Barkhof Frederik , Li Kuncheng , Liu Yaou 
Published: July 2016

AbstractThe brain connectome of multiple sclerosis (MS) has been investigated by several previous studies; however, it is still unknown how the network changes in clinically isolated syndrome (CIS), the earliest stage of MS, and how network alterations on a functional level relate to the structural level in MS disease. Here, we investigated the topological alterations of both the structural and functional connectomes in 41 CIS and 32 MS patients, compared to 35 healthy controls, by combining diffusion tensor imaging and resting-state functional MRI with graph analysis approaches. We found that the structural connectome showed a deviation from the optimal pattern as early as the CIS stage, while the functional connectome only showed local changes in MS patients, not in CIS. When comparing two patient groups, the changes appear more severe in MS. Importantly, the disruptions of structural and functional connectomes in patients occurred in the same direction and locally correlated in sensorimotor component. Finally, the extent of structural network changes was correlated with several clinical variables in MS patients. Together, the results suggested early disruption of the structural brain connectome in CIS patients and provided a new perspective for investigating the relationship of the structural and functional alterations in MS.
Biochemical and proteomic characterization of retrovirus Gag based microparticles carrying melanoma antigens
Authors: Kurg Reet , Reinsalu Olavi , Jagur Sergei , Õunap Kadri , Võsa Liisi , Kasvandik Sergo , Padari Kärt , Gildemann Kiira , Ustav Mart 
Published: July 2016

AbstractExtracellular vesicles are membraneous particles released by a variety of cells into the extracellular microenvironment. Retroviruses utilize the cellular vesiculation pathway for virus budding/assembly and the retrovirus Gag protein induces the spontaneous formation of microvesicles or virus-like particles (VLPs) when expressed in the mammalian cells. In this study, five different melanoma antigens, MAGEA4, MAGEA10, MART1, TRP1 and MCAM, were incorporated into the VLPs and their localization within the particles was determined. Our data show that the MAGEA4 and MAGEA10 proteins as well as MCAM are expressed on the surface of VLPs. The compartmentalization of exogenously expressed cancer antigens within the VLPs did not depend on the localization of the protein within the cell. Comparison of the protein content of VLPs by LC-MS/MS-based label-free quantitative proteomics showed that VLPs carrying different cancer antigens are very similar to each other, but differ to some extent from VLPs without recombinant antigen. We suggest that retrovirus Gag based virus-like particles carrying recombinant antigens have a potential to be used in cancer immunotherapy.
Risk Factors and Outcomes of Nontuberculous Mycobacterial Disease among Rheumatoid Arthritis Patients: A Case-Control study in a TB Endemic Area
Authors: Liao Tsai-Ling , Lin Chin-Fu , Chen Yi-Ming , Liu Hung-Jen , Chen Der-Yuan 
Published: July 2016

AbstractIncreasing evidence indicates that the risk of nontuberculous mycobacteria (NTM) disease is elevated in patients with rheumatoid arthritis (RA). However, the risk factors and outcomes for NTM disease among RA patients remain unclear. We conducted a case-control study and estimated odds ratios (ORs) for RA patients with NTM disease according to comorbidities and anti-rheumatic medications by using conditional logistic regression. Prior tuberculosis history (adjusted OR (aOR) =5.58, p < 0.001), hypertension (aOR = 2.55, p = 0.013), diabetes mellitus (aOR = 3.31, p = 0.005), interstitial lung disease (aOR = 8.22, p < 0.001), chronic obstructive pulmonary disease (aOR = 8.59, p < 0.001) and exposure to oral corticosteroids in a dose-dependent manner (5− < 10 mg/day aOR = 2.51, Ptrend = 0.007) were associated with a significantly increased risk of NTM disease in RA patients. The predominant species causing NTM disease in RA patients was Mycobacterium intracellulare (46.0%). Most NTM isolates were resistant to the majority of the antibiotics that are currently available, which maybe caused treatment failure; hospitalization and mortality are increased. To prevent and treat NTM disease efficiently, we suggested that it is important to monitor the development of NTM disease in RA patients receiving therapy with corticosteroids, particularly in those with predisposing factors.
Modelling the sensitivity of life history traits to climate change in a temporary pool crustacean
Authors: Pinceel Tom , Vanschoenwinkel Bram , Brendonck Luc , Buschke Falko 
Published: July 2016

AbstractTemporary pool inhabitants face altered inundation regimes under climate change. While their exposure to these changes has received considerable attention, few studies have investigated their sensitivity or adaptability. Here, we use zooplankton as a model to explore how decreasing hydroperiods affect extinction risks and assess whether changes in life history traits could promote persistence. For this, we construct a three-stage matrix population model parameterised with realistic life-history values for the fairy shrimp Branchipodopsis wolfi from pools with varying hydroperiods. Our results suggest that extinction risks increase drastically once the median hydroperiod drops below a critical threshold. Although changes in life-history parameters could potentially compensate for this risk, the relative importance of each trait for population growth depends on the median hydroperiod. For example, survival of dormant eggs seemed to be most important when hydroperiods were short while the survival of freshly laid eggs and adult individuals were more important in longer-lived pools. Overall, this study demonstrates that zooplankton species are sensitive to climate change and that the adaptive capacity of organisms from temporary pools with dissimilar hydrology hinges on selection of different life history traits.
Quantification of intracellular payload release from polymersome nanoparticles
Authors: Scarpa Edoardo , Bailey Joanne L. , Janeczek Agnieszka A. , Stumpf Patrick S. , Johnston Alexander H. , Oreffo Richard O. C. , Woo Yin L. , Cheong Ying C. , Evans Nicholas D. , Newman Tracey A. 
Published: July 2016

AbstractPolymersome nanoparticles (PMs) are attractive candidates for spatio-temporal controlled delivery of therapeutic agents. Although many studies have addressed cellular uptake of solid nanoparticles, there is very little data available on intracellular release of molecules encapsulated in membranous carriers, such as polymersomes. Here, we addressed this by developing a quantitative assay based on the hydrophilic dye, fluorescein. Fluorescein was encapsulated stably in PMs of mean diameter 85 nm, with minimal leakage after sustained dialysis. No fluorescence was detectable from fluorescein PMs, indicating quenching. Following incubation of L929 cells with fluorescein PMs, there was a gradual increase in intracellular fluorescence, indicating PM disruption and cytosolic release of fluorescein. By combining absorbance measurements with flow cytometry, we quantified the real-time intracellular release of a fluorescein at a single-cell resolution. We found that 173 ± 38 polymersomes released their payload per cell, with significant heterogeneity in uptake, despite controlled synchronisation of cell cycle. This novel method for quantification of the release of compounds from nanoparticles provides fundamental information on cellular uptake of nanoparticle-encapsulated compounds. It also illustrates the stochastic nature of population distribution in homogeneous cell populations, a factor that must be taken into account in clinical use of this technology.
Murine matrix metalloproteinase-20 overexpression stimulates cell invasion into the enamel layer via enhanced Wnt signaling
Authors: Shin Masashi , Suzuki Maiko , Guan Xiaomu , Smith Charles E. , Bartlett John D. 
Published: July 2016

AbstractMatrix metalloproteinase-20 (MMP20) is expressed by ameloblasts in developing teeth and MMP20 mutations cause enamel malformation. We established a stably transfected Tet-Off Mmp20-inducible ameloblast-lineage cell line and found that MMP20 expression promoted cell invasion. Previously, we engineered transgenic mice (Tg) that drive Mmp20 expression and showed that Mmp20+/+Tg mice had soft enamel. Here we asked if Mmp20 overexpression disrupts ameloblast function. Incisors from Mmp20+/+ mice expressing the Mmp20 Tg had a striking cell infiltrate which nearly replaced the entire enamel layer. A thin layer of enamel-like material remained over the dentin and at the outer tooth surface, but between these regions were invading fibroblasts and epithelial cells that surrounded ectopic bone-like calcifications. Mmp20+/+Tg mice had decreased enamel organ cadherin levels compared to the Mmp20 ablated and WT mice and, instead of predominantly locating adjacent to the ameloblast cell membrane, β-catenin was predominantly present within the nuclei of invading cells. Our data suggest that increased cadherin cleavage by transgenic MMP20 in the WT background releases excess β-catenin, which translocates to ameloblast nuclei to promote cell migration/invasion. Therefore, we conclude that MMP20 plays a role in normal ameloblast migration through tightly controlled Wnt signaling and that MMP20 overexpression disrupts this process.
Host protective ASP-based vaccine against the parasitic nematode Ostertagia ostertagi triggers NK cell activation and mixed IgG1-IgG2 response
Authors: González-Hernández Ana , Van Coppernolle Stefanie , Borloo Jimmy , Van Meulder Frederik , Paerewijck Oonagh , Peelaers Iris , Leclercq Georges , Claerebout Edwin , Geldhof Peter 
Published: July 2016

AbstractThe mucus-dwelling parasite Ostertagia ostertagi is one of the most important gastrointestinal nematodes in cattle. Our group has previously demonstrated the protective capacity of a vaccine against this parasite based on a native activation-associated secreted protein ASP1 (nASP) in combination with the saponin adjuvant QuilA. The aim of the current study was to analyse the effect of both antigen and adjuvant on the cellular and humoral vaccine-induced immune responses by comparing the native ASP to a recombinant version expressed in Pichia pastoris (pASP) and replacing QuilA by Al(OH)3. Immunization of cattle with the protective nASP+QuilA vaccine was associated with antigen-induced proliferation of natural killer (NK) cells combined with IFN-γ secretion and the induction of a mixed IgG1/IgG2 antibody response. ASP-specific activation and proliferation of NK cells was also observed in mice following the same vaccination regime. Replacing QuilA by Al(OH)3 or nASP by pASP significantly decreased the capacity of the vaccines to trigger both NK cell activation and antibody responses and failed to induce protection against a challenge infection. Reduction of the structurally anchoring disulphide bonds of the nASP completely abolished its ability to induce NK cell activation and antibody responses, highlighting the importance of protein conformation for the immunostimulatory activity.
Deciduous trees are a large and overlooked sink for snowmelt water in the boreal forest
Authors: Young-Robertson Jessica M. , Bolton W. Robert , Bhatt Uma S. , Cristóbal Jordi , Thoman Richard 
Published: July 2016

AbstractThe terrestrial water cycle contains large uncertainties that impact our understanding of water budgets and climate dynamics. Water storage is a key uncertainty in the boreal water budget, with tree water storage often ignored. The goal of this study is to quantify tree water content during the snowmelt and growing season periods for Alaskan and western Canadian boreal forests. Deciduous trees reached saturation between snowmelt and leaf-out, taking up 21–25% of the available snowmelt water, while coniferous trees removed <1%. We found that deciduous trees removed 17.8–20.9 billion m3 of snowmelt water, which is equivalent to 8.7–10.2% of the Yukon River’s annual discharge. Deciduous trees transpired 2–12% (0.4–2.2 billion m3) of the absorbed snowmelt water immediately after leaf-out, increasing favorable conditions for atmospheric convection, and an additional 10–30% (2.0–5.2 billion m3) between leaf-out and mid-summer. By 2100, boreal deciduous tree area is expected to increase by 1–15%, potentially resulting in an additional 0.3–3 billion m3 of snowmelt water removed from the soil per year. This study is the first to show that deciduous tree water uptake of snowmelt water represents a large but overlooked aspect of the water balance in boreal watersheds.
Circulating cell-free mature microRNAs and their target gene prediction in bovine metritis
Authors: Kasimanickam Vanmathy , Kastelic John 
Published: July 2016

AbstractUterine infections in dairy cows are common after calving, reduce fertility and cause substantial economic losses. Conventional diagnosis (based on clinical signs) and treatment can be challenging. Serum microRNA (miRNA) profiles serve as non-invasive biomarkers in several pathological conditions including inflammatory diseases. The objective was to identify differentially expressed serum miRNAs in cows with metritis and normal uterus (four cows per group), integrate miRNAs to their target genes and categorize target genes for biological processes involved in bacterial infection and inflammatory responses. Out of 84 bovine-specific, prioritized miRNAs analyzed, 30 were differentially expressed between metritis and normal cows (p ≤ 0.05, fold regulation ≥2 magnitudes). Bta-miR-15b, bta-miR-17-3p, bta-miR-16b, bta-miR-148a, bta-miR-26b, bta-miR-101 and bta-miR-29b were highly up-regulated whereas bta-miR-148b, bta-miR-199a-3p, bta-miR-122, bta-miR-200b and bta-miR-10a were highly down-regulated in cows with metritis compared to cows with normal uterus. Highly scored target genes of up-regulated and down-regulated miRNAs were categorized for various biological processes, including biological regulation, cellular process, developmental process, metabolic process, localization, multicellular organismal process, response to stimulus, immune system process, cellular components organization, apoptotic process, biological adhesion, developmental process and locomotion that are critical to combat bacterial infections and provoke inflammatory responses.
The HSA21 gene EURL/C21ORF91 controls neurogenesis within the cerebral cortex and is implicated in the pathogenesis of Down Syndrome
Authors: Li Shan Shan , Qu Zhengdong , Haas Matilda , Ngo Linh , Heo You Jeong , Kang Hyo Jung , Britto Joanne Maria , Cullen Hayley Daniella , Vanyai Hannah Kate , Tan Seong-Seng , Chan-Ling Tailoi , Gunnersen Jenny Margaret , Heng Julian Ik-Tsen 
Published: July 2016

AbstractCopy number variations to chromosome 21 (HSA21) cause intellectual disability and Down Syndrome, but our understanding of the HSA21 genetic factors which contribute to fetal brain development remains incomplete. Here, we focussed on the neurodevelopmental functions for EURL (also known as C21ORF91, Refseq Gene ID:54149), a protein-coding gene at the centromeric boundary of the Down Syndrome Critical Region (DSCR) of HSA21. We report that EURL is expressed during human and mouse cerebral cortex development, and we report that alterations to EURL mRNA levels within the human brain underlie Down Syndrome. Our gene perturbation studies in mice demonstrate that disruptions to Eurl impair progenitor proliferation and neuronal differentiation. Also, we find that disruptions to Eurl impair the long-term positioning and dendritic spine densities of cortical projection neurons. We provide evidence that EURL interacts with the coiled-coil domain-containing protein CCDC85B so as to modulate β-catenin levels in cells. Further, we utilised a fluorescent reporter (8xTOPFLASHd2EGFP) to demonstrate that disruptions to Eurl alter β-catenin signalling in vitro as well as in vivo. Together, these studies highlight EURL as an important new player in neuronal development that is likely to impact on the neuropathogenesis of HSA21-related disorders including Down Syndrome.
Delineation of autoantibody repertoire through differential proteogenomics in hepatitis C virus-induced cryoglobulinemia
Authors: Ogishi Masato , Yotsuyanagi Hiroshi , Moriya Kyoji , Koike Kazuhiko 
Published: July 2016

AbstractAntibodies cross-reactive to pathogens and autoantigens are considered pivotal in both infection control and accompanying autoimmunity. However, the pathogenic roles of autoantibodies largely remain elusive without a priori knowledge of disease-specific autoantigens. Here, through a novel quantitative proteogenomics approach, we demonstrated a successful identification of immunoglobulin variable heavy chain (VH) sequences highly enriched in pathological immune complex from clinical specimens obtained from a patient with hepatitis C virus-induced cryoglobulinemia (HCV-CG). Reconstructed single-domain antibodies were reactive to both HCV antigens and potentially liver-derived human proteins. Moreover, over the course of antiviral therapy, a substantial “de-evolution” of a distinct sub-repertoire was discovered, to which proteomically identified cryoprecipitation-prone autoantibodies belonged. This sub-repertoire was characterized by IGHJ6*03-derived, long, hydrophobic complementarity determining region (CDR-H3). This study provides a proof-of-concept of de novo mining of autoantibodies and corresponding autoantigen candidates in a disease-specific context in human, thus facilitating future reverse-translational research for the discovery of novel biomarkers and the development of antigen-specific immunotherapy against various autoantibody-related disorders.
X-ray detection with zinc-blende (cubic) GaN Schottky diodes
Authors: Gohil T. , Whale J. , Lioliou G. , Novikov S. V. , Foxon C. T. , Kent A. J. , Barnett A. M. 
Published: July 2016

AbstractThe room temperature X-ray responses as functions of time of two n type cubic GaN Schottky diodes (200 μm and 400 μm diameters) are reported. The current densities as functions of time for both diodes showed fast turn-on transients and increases in current density when illuminated with X-ray photons of energy up to 35 keV. The diodes were also electrically characterized: capacitance, implied depletion width and dark current measurements as functions of applied bias at room temperature are presented. At −5 V reverse bias, the capacitances of the diodes were measured to be (84.05 ± 0.01) pF and (121.67 ± 0.02) pF, respectively. At −5 V reverse bias, the dark current densities of the diodes were measured to be (347.2 ± 0.4) mA cm−2 and (189.0 ± 0.2) mA cm−2, respectively. The Schottky barrier heights of the devices (0.52 ± 0.07) eV and (0.63 ± 0.09) eV, respectively, were extracted from the forward dark current characteristics.
Viral Evolution and Cytotoxic T Cell Restricted Selection in Acute Infant HIV-1 Infection
Authors: Garcia-Knight Miguel A. , Slyker Jennifer , Payne Barbara Lohman , Pond Sergei L. Kosakovsky , de Silva Thushan I. , Chohan Bhavna , Khasimwa Brian , Mbori-Ngacha Dorothy , John-Stewart Grace , Rowland-Jones Sarah L. , Esbjörnsson Joakim 
Published: July 2016

AbstractAntiretroviral therapy-naive HIV-1 infected infants experience poor viral containment and rapid disease progression compared to adults. Viral factors (e.g. transmitted cytotoxic T- lymphocyte (CTL) escape mutations) or infant factors (e.g. reduced CTL functional capacity) may explain this observation. We assessed CTL functionality by analysing selection in CTL-targeted HIV-1 epitopes following perinatal infection. HIV-1 gag, pol and nef sequences were generated from a historical repository of longitudinal specimens from 19 vertically infected infants. Evolutionary rate and selection were estimated for each gene and in CTL-restricted and non-restricted epitopes. Evolutionary rate was higher in nef and gag vs. pol, and lower in infants with non-severe immunosuppression vs. severe immunosuppression across gag and nef. Selection pressure was stronger in infants with non-severe immunosuppression vs. severe immunosuppression across gag. The analysis also showed that infants with non-severe immunosuppression had stronger selection in CTL-restricted vs. non-restricted epitopes in gag and nef. Evidence of stronger CTL selection was absent in infants with severe immunosuppression. These data indicate that infant CTLs can exert selection pressure on gag and nef epitopes in early infection and that stronger selection across CTL epitopes is associated with favourable clinical outcomes. These results have implications for the development of paediatric HIV-1 vaccines.
Decadal variability of tropical tropopause temperature and its relationship to the Pacific Decadal Oscillation
Authors: Wang Wuke , Matthes Katja , Omrani Nour-Eddine , Latif Mojib 
Published: July 2016

AbstractTropopause temperatures (TPTs) control the amount of stratospheric water vapour, which influences chemistry, radiation and circulation in the stratosphere and is also an important driver of surface climate. Decadal variability and long-term trends in tropical TPTs as well as stratospheric water vapour are largely unknown. Here, we present for the first time evidence, from reanalysis and state-of-the-art climate model simulations, of a link between decadal variability in tropical TPTs and the Pacific Decadal Oscillation (PDO). The negative phase of the PDO is associated with anomalously cold sea surface temperatures (SSTs) in the tropical east and central Pacific, which enhance the zonal SST gradient across the equatorial Pacific. The latter drives a stronger Walker Circulation and a weaker Hadley Circulation, which leads to less convection and subsequently a warmer tropopause over the central equatorial Pacific. Over the North Pacific, positive sea level pressure anomalies occur, which damp vertical wave propagation into the stratosphere. This in turn slows the Brewer-Dobson circulation and hence warms the tropical tropopause, enabling more water vapour to enter the stratosphere. The reverse chain of events holds for the positive phase of the PDO. Such ocean-troposphere-stratosphere interactions may provide an important feedback on the Earth’s global surface temperature.