bluuebunny/crossref_metadata_2025_split huggingface dataset:
SIRT6 facilitates directional telomere movement upon oxidative damage
Authors: Gao Ying , Tan Jun , Jin Jingyi , Ma Hongqiang , Chen Xiukai , Leger Brittany , Xu Jianquan , Spagnol Stephen T. , Dahl Kris Noel , Levine Arthur S. , Liu Yang , Lan Li 
Published: March 2018

AbstractOxidative damage to telomeres leads to telomere attrition and genomic instability, resulting in poor cell viability. Telomere dynamics contribute to the maintenance of telomere integrity; however, whether oxidative damage induces telomere movement and how telomere mobility is regulated remain poorly understood. Here, we show that oxidative damage at telomeres triggers directional telomere movement. The presence of the human Sir2 homolog, Sirtuin 6 (SIRT6) is required for oxidative damage-induced telomeric movement. SIRT6 knock out (KO) cells show neither damage-induced telomere movement nor chromatin decondensation at damaged telomeres; both are observed in wild type (WT) cells. A deacetylation mutant of SIRT6 increases damage-induced telomeric movement in SIRT6 KO cells as well as WT SIRT6. SIRT6 recruits the chromatin-remodeling protein SNF2H to damaged telomeres, which appears to promote chromatin decondensation independent of its deacetylase activity. Together, our results suggest that SIRT6 plays a role in the regulation of telomere movement upon oxidative damage, shedding new light onto the function of SIRT6 in telomere maintenance.
High-resolution GPS tracking reveals sex differences in migratory behaviour and stopover habitat use in the Lesser Black-backed Gull Larus fuscus
Authors: Baert Jan M. , Stienen Eric W. M. , Heylen Brigitte C. , Kavelaars Marwa M. , Buijs Roland-Jan , Shamoun-Baranes Judy , Lens Luc , Müller Wendt 
Published: March 2018

AbstractSex-, size- or age-dependent variation in migration strategies in birds is generally expected to reflect differences in competitive abilities. Theoretical and empirical studies thereby focus on differences in wintering areas, by which individuals may benefit from avoiding food competition during winter or ensuring an early return and access to prime nesting sites in spring. Here, we use GPS tracking to assess sex- and size-related variation in the spatial behaviour of adult Lesser Black-backed Gulls (Larus fuscus) throughout their annual cycle. We did not find sex- or size-dependent differences in wintering area or the timing of spring migration. Instead, sexual differences occurred prior to, and during, autumn migration, when females strongly focussed on agricultural areas. Females exhibited a more protracted autumn migration strategy, hence spent more time on stopover sites and arrived 15 days later at their wintering areas, than males. This shift in habitat use and protracted autumn migration coincided with the timing of moult, which overlaps with chick rearing and migration. Our results suggest that this overlap between energy-demanding activities may lead females to perform a more prolonged autumn migration, which results in spatiotemporal differences in foraging habitat use between the sexes.
Systemic IGF-1 gene delivery by rAAV9 improves spontaneous autoimmune peripheral polyneuropathy (SAPP)
Authors: Gao Tong , Bogdanova Nataliia , Ghauri Sameera , Zhang Gang , Lin Jianxin , Sheikh Kazim 
Published: March 2018

AbstractSpontaneous autoimmune peripheral polyneuropathy (SAPP) is a mouse model of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) in non-obese diabetic (NOD) mice null for costimulatory molecule, B7-2 gene (B7-2−/−). SAPP is a chronic progressive and multifocal inflammatory and demyelinating polyneuropathy of spontaneous onset with secondary axonal degeneration. Insulin-like growth factor 1(IGF-1) is a pleiotropic factor with neuroprotective, regenerative, and anti-inflammatory effects with extensive experience in its preclinical and clinical use. Systemic delivery of recombinant adeno-associated virus serotype 9 (rAAV9) provides robust and widespread gene transfer to central and peripheral nervous systems making it suitable for gene delivery in neurological diseases. A significant proportion of patients with inflammatory neuropathies like CIDP do not respond to current clinical therapies and there is a need for new treatments. In this study, we examined the efficacy IGF-1 gene therapy by systemic delivery with rAAV9 in SAPP model. The rAAV9 construct also contained a reporter gene to monitor the surrogate expression of IGF-1. We found significant improvement in neuropathic disease after systemic delivery of rAAV9/IGF-1 gene at presymptomatic and symptomatic stages of SAPP model. These findings support that IGF-1 treatment (including gene therapy) is a viable therapeutic option in immune neuropathies such as CIDP.
SFTS phlebovirus promotes LC3-II accumulation and nonstructural protein of SFTS phlebovirus co-localizes with autophagy proteins
Authors: Sun Yue , Liu Miao-miao , Lei Xiao-ying , Yu Xue-jie 
Published: March 2018

AbstractAutophagy is essential for eukaryotic cell homeostasis and can perform both anti-viral and pro-viral roles depending on the kinds of viruses, cell types and cell environment. Severe fever with thrombocytopenia syndrome phlebovirus (SFTSV) is a newly discovered tick-borne virus in the Phenuiviridae family that causes a severe hemorrhagic fever disease in East Asia. In this study we determined interactions between SFTSV and autophagy. Our results showed that LC3-II (microtubule associated protein 1 light chain 3-II) protein accumulated from 4 h to 24 h after SFTSV infection compared to mock-infected Vero cells, and the use of E64d and pepstatin A did not affect the expression of LC3-II protein, which indicated that the increased LC3-II may be the result of inhibition of autophagic degradation caused by SFTSV infection. However, knockdown of LC3B promotes SFTSV replication, which indicated a negative role of LC3B protein in SFTSV replication. We also detected co-localization of SFTSV non-structure (NSs) protein with LC3B, p62 and Lamp2b respectively in SFTSV infected Vero cells, which indicated the possibility of selective autophagy or chaperone-mediated autophagy involving in SFTSV infection. Our results indicated that SFTSV infection promotes LC3 accumulation and several proteins of the autophagy pathway co-localize with NSs protein during SFTSV infection.
Comparative genome-wide analysis of extracellular small RNAs from the mucormycosis pathogen Rhizopus delemar
Authors: Liu Muxing , Bruni Gillian O. , Taylor Christopher M. , Zhang Zhengguang , Wang Ping 
Published: March 2018

AbstractRhizopus delemar is an emerging fungal pathogen causing devastating mucormycosis in immunocompromised individuals. The organism remains understudied and there are urgent needs for new methods of rapid disease diagnosis for timely therapy. Extracellular vesicles with encapsulated RNAs have recently been discovered to have great potential applications for disease diagnoses and treatments. To explore the utilization of ex-RNA in studies of mucormycosis, we have performed RNA-Seq of ex-sRNAs from two clinical strains of R. delemar. Approximately 3.3 and 3.2 million clean reads were obtained from FGSC-9543 and CDC-8219 strains, respectively. The median sequence length of the sRNAs was 22 nts, with a minimum of 18 and a maximum of 30 nts. Further annotation identified 560 and 526 miRNAs from FGSC-9543 and CDC-8219 strains, respectively. miRNA target prediction and analysis of GO and KEGG pathways have revealed that the regulation of metabolism, secondary metabolite biosynthesis, and two-component system signaling are important during growth. We have also validated RNA-Seq by qRT-PCR and Northern blotting analysis of randomly selected miRNAs. Our results show that R. delemar has a rich reservoir of secreted ex-sRNAs and our studies could facilitate the development of improved diagnostic methods as well as elucidating virulence mechanisms for R. delemar infection.
Epigenetic Transgenerational Inheritance of Altered Sperm Histone Retention Sites
Authors: Ben Maamar Millissia , Sadler-Riggleman Ingrid , Beck Daniel , Skinner Michael K. 
Published: March 2018

AbstractA variety of environmental toxicants and factors have been shown to induce the epigenetic transgenerational inheritance of disease and phenotypic variation. Epigenetic alterations in the germline (sperm or egg) are required to transmit transgenerational phenotypes. The current study was designed to investigate the potential role of histones in sperm to help mediate the epigenetic transgenerational inheritance. The agricultural fungicide vinclozolin and the pesticide DDT (dichlorodiphenyltrichloroethane) were independently used to promote the epigenetic transgenerational inheritance of disease. Purified cauda epididymal sperm were collected from the transgenerational F3 generation control and exposure lineage male rats for histone analysis. A reproducible core of histone H3 retention sites was observed using an H3 chromatin immunoprecipitation (ChIP-Seq) analysis in control lineage sperm. Interestingly, the same core group of H3 retention sites plus additional differential histone retention sites (DHRs) were observed in the F3 generation exposure lineage sperm. Although new histone H3 retention sites were observed, negligible change in histone modification (methylation of H3K27me3) was observed between the control and exposure lineages. Observations demonstrate that in addition to alterations in sperm DNA methylation and ncRNA previously identified, the induction of differential histone retention sites (DHRs) also appear to be involved in environmentally induced epigenetic transgenerational inheritance.
Using human brain activity to guide machine learning
Authors: Fong Ruth C. , Scheirer Walter J. , Cox David D. 
Published: March 2018

AbstractMachine learning is a field of computer science that builds algorithms that learn. In many cases, machine learning algorithms are used to recreate a human ability like adding a caption to a photo, driving a car, or playing a game. While the human brain has long served as a source ofinspirationfor machine learning, little effort has been made to directly use data collected from working brains as aguidefor machine learning algorithms. Here we demonstrate a new paradigm of “neurally-weighted” machine learning, which takes fMRI measurements of human brain activity from subjects viewing images, and infuses these data into the training process of an object recognition learning algorithm to make it more consistent with the human brain. After training, these neurally-weighted classifiers are able to classify images without requiring any additional neural data. We show that our neural-weighting approach can lead to large performance gains when used with traditional machine vision features, as well as to significant improvements with already high-performing convolutional neural network features. The effectiveness of this approach points to a path forward for a new class of hybrid machine learning algorithms which take both inspiration and direct constraints from neuronal data.
Activation of Eosinophils and Mast Cells in Functional Dyspepsia: an Ultrastructural Evaluation
Authors: Vanheel Hanne , Vicario Maria , Boesmans Werend , Vanuytsel Tim , Salvo-Romero Eloisa , Tack Jan , Farré Ricard 
Published: March 2018

AbstractWe recently identified mucosal mast cell and eosinophil hyperplasia in association with a duodenal impaired barrier function in functional dyspepsia (FD). We aimed to further describe the implication of these immune cells by assessing their activation state at the ultrastructural level and by evaluating the association between impaired epithelial integrity and immune activation. Duodenal biopsies were obtained from 24 FD patients and 37 healthy controls. The ultrastructure of mast cells and eosinophils was analyzed by transmission electron microscopy. Transepithelial electrical resistance and paracellular permeability were measured to evaluate epithelial barrier function. The type of degranulation in eosinophils and mast cells was piecemeal. Eosinophils displayed higher degree of degranulation in FD patients than in controls (p < 0.0001). Quantification revealed a decreased granular density in eosinophils of FD patients (p < 0.0001). The degree of degranulation in mast cells was similar in both groups. However, a more heterogeneous profile was found in the FD group (p < 0.0001). No association between epithelial integrity and the number and activation state of mucosal eosinophils and mast cells was found. We demonstrated ultrastructural changes in degranulation state of eosinophils and mast cells, suggesting that eosinophil and mast cell activation play a role in the pathophysiology of FD.
Characterization of Split Fluorescent Protein Variants and Quantitative Analyses of Their Self-Assembly Process
Authors: Köker Tuğba , Fernandez Anthony , Pinaud Fabien 
Published: March 2018

AbstractMany biotechniques use complementary split-fluorescent protein (sFPs) fragments to visualize protein-protein interactions, image cells by ensemble or single molecule fluorescence microscopy, or assemble nanomaterials and protein superstructures. Yet, the reassembly mechanisms of sFPs, including fragment binding rates, folding, chromophore maturation and overall photophysics remain poorly characterized. Here, we evolved asymmetric and self-complementing green, yellow and cyan sFPs together with their full-length equivalents (flFPs) and described their biochemical and photophysical propertiesin vitroand in cells. While re-assembled sFPs have spectral properties similar to flFPs, they display slightly reduced quantum yields and fluorescence lifetimes due to a less sturdy β-barrel structure. The complementation of recombinant sFPs expressedin vitrofollows a conformational selection mechanism whereby the larger sFP fragments exist in a monomer-dimer equilibrium and only monomers are competent for fluorescence complementation. This bimolecular fragment interaction involves a slow and irreversible binding step, followed by chromophore maturation at a rate similar to that of flFPs. When expressed as fusion tags in cells, sFPs behave as monomers directly activated with synthetic complementary fragments. This study resulted in the development of sFP color variants having improved maturation kinetics, brightness, and photophysics for fluorescence microscopy imaging of cellular processes, including single molecule detection.
Evaluation of Screened Lignin-degrading Fungi for the Biological Pretreatment of Corn Stover
Authors: Su Yingjie , Yu Xiaoxiao , Sun Yang , Wang Gang , Chen Huan , Chen Guang 
Published: March 2018

AbstractThe biological pretreatment of lignocellulosic biomass is a low-cost and eco-friendly method for facilitating enzymatic hydrolysis. In this study, strains with lignin depletion capability were screened using a high-throughput screening method. Sixty-three strains were screened out and Myrothecium verrucaria secreted three lignin-degrading enzymes simultaneously during the bio-pretreatment process. The activity levels of laccase, lignin peroxidase and manganese peroxidase were 6.61, 0.78 and 1.31 U g−1 dry biomass. The content of lignin in corn stover decreased by 42.30% after bio-pretreatment, and the conversion rate increased by 123.84% during the subsequent saccharification process in comparison with the untreated corn stover. Furthermore, the effects of bio-pretreatment on the structure of corn stover were presented using a scanning electron microscope (SEM), Brunauer-Emmet-Teller (BET), X-ray diffractometer (XRD) and Fourier transform infrared spectroscopy (FTIR). The results showed that M.V. is a promising lignin-degrading fungus. This research demonstrated an efficient pretreatment approach for enhancing the enzymatic saccharification of corn stover.
Low testosterone in ApoE/LDL receptor double-knockout mice is associated with rarefied testicular capillaries together with fewer and smaller Leydig cells
Authors: Steinfeld Kai , Beyer Daniela , Mühlfeld Christian , Mietens Andrea , Eichner Gerrit , Altinkilic Bora , Kampschulte Marian , Jiang Qingkui , Krombach Gabriele A. , Linn Thomas , Weidner Wolfgang , Middendorff Ralf 
Published: March 2018

AbstractThe testis as a site for atherosclerotic changes has so far attracted little attention. We used the apolipoprotein E (ApoE)/low density lipoprotein (LDL) receptor deficient mouse model (KO) for atherosclerosis (20, 40, 60 and 87-week-old) to investigate whether Leydig cells or the capillary network are responsible for reduced serum testosterone levels previously observed in extreme ages of this model. In KO mice, overall testosterone levels were reduced whereas the adrenal gland-specific corticosterone was increased excluding a general defect of steroid hormone production. In addition to micro-CT investigations for bigger vessels, stereology revealed a reduction of capillary length, volume and surface area suggesting capillary rarefaction as a factor for diminished testosterone. Stereological analyses of interstitial cells demonstrated significantly reduced Leydig cell numbers and size. These structural changes in the testis occurred on an inflammatory background revealed by qPCR. Reduced litter size of the KO mice suggests hypo- or infertility as a consequence of the testicular defects. Our data suggest reduced testosterone levels in this atherosclerosis model might be explained by both, rarefication of the capillary network and reduced Leydig cell number and size. Thus, this study calls for specific treatment of male infertility induced by microvascular damage through hypercholesterolemia and atherosclerosis.
Multistep transition of diamond to warm dense matter state revealed by femtosecond X-ray diffraction
Authors: Medvedev Nikita , Ziaja Beata 
Published: March 2018

AbstractDiamond bulk irradiated with a free-electron laser pulse of 6100 eV photon energy, 5 fs duration, at the ~19–25 eV/atom absorbed doses, is studied theoretically on its way to warm dense matter state. Simulations with our hybrid code XTANT show disordering on sub-100 fs timescale, with the diffraction peak (220) vanishing faster than the peak (111). The warm dense matter formation proceeds as a nonthermal damage of diamond with the band gap collapse triggering atomic disordering. Short-living graphite-like state is identified during a few femtoseconds between the disappearance of (220) peak and the disappearance of (111) peak. The results obtained are compared with the data from the recent experiment at SACLA, showing qualitative agreement. Challenges remaining for the accurate modeling of the transition of solids to warm dense matter state and proposals for supplementary measurements are discussed in detail.
RETRACTED ARTICLE: Differences in cognitive functions between cytomegalovirus-infected and cytomegalovirus-free university students: a case control study
Authors: Chvátalová Veronika , Šebánková Blanka , Hrbáčková Hana , Tureček Petr , Flegr Jaroslav 
Published: March 2018

AbstractCytomegalovirus (CMV) is the herpetic virus, which infects 45–100% people worldwide. Many reports suggest that CMV could impair cognitive functions of infected subjects. Here we searched for indices of effects of CMV on infected subjects’ intelligence and knowledge. The Intelligence Structure Test I-S-T 2000 R was used to compare IQ of 148 CMV-infected and 135 CMV-free university students. Infected students expressed higher intelligence. Paradoxically, their IQ decreased with decreasing concentration of anti-CMV antibodies, which can be used, statistically, as a proxy of the time passed from the moment of infection in young subjects when the age of subjects is statistically controlled. The paradox of seemingly higher intelligence of CMV infected subjects could be explained by the presence of the subpopulation of about 5–10% CMV-positive individuals in the population of “CMV-negative students”. These false negative subjects had probably not only the oldest infections and therefore the lowest concentration of anamnestic antibodies, but also the lowest intelligence among the infected students. Prevalence of CMV infection in all countries is very high, approaching sometimes 90%. Therefore, the total impact of CMV on human intelligence may be large.
Renal Prognosis and Related Risk Factors for Henoch-Schönlein Purpura Nephritis: A Chinese Adult Patient Cohort
Authors: Huang Xiao , Wu Xiaomei , Le Weibo , Hao Yaxin , Wu Jing , Zeng Caihong , Liu Zhihong , Tang Zheng 
Published: March 2018

AbstractThis study investigated the clinicopathological characteristics of Henoch-Schönlein purpura nephritis (HSPN) in Chinese adult patients and analyzed the renal outcomes and prognostic risk factors for progression to end-stage renal disease (ESRD). Adult patients who had biopsy-proven HSPN were studied. Their clinicopathological data, renal prognoses and related risk factors were assessed. A total of 698 patients were studied, including 363 men (52.0%) and 335 women (48.0%). Most of the patients had hematuria (85.8%) and/or proteinuria (82.1%). During a median follow-up of 54.0 months, 32 patients (4.6%) progressed to ESRD. The 5- and 10-year cumulative renal survival rates from ESRD were 96.4% and 88.6%, respectively. Baseline urinary protein, renal insufficiency, glomerular sclerosis and tubular atrophy/interstitial fibrosis were independent predictors of renal outcomes. Both the time-average mean arterial pressure and proteinuria during follow-up also influenced the renal prognosis. The patients with a time-average proteinuria <0.4 g/day had the lowest rates of ESRD or a 50% decline in renal function. In conclusion, identifying of clinical and histological prognostic factors may permit the prediction of renal outcomes. The optimal goal of therapy for HSPN patients may be to lower proteinuria to <0.4 g/day and control hypertension to achieve an ideal renal outcome.
Diagnostic accuracy of liver stiffness measurement in chronic hepatitis B patients with normal or mildly elevated alanine transaminase levels
Authors: Li Qiang , Chen Liang , Zhou Yu 
Published: March 2018

AbstractWe aimed to evaluate the diagnostic accuracy of liver stiffness measurement (LSM) in 188 chronic hepatitis B (CHB) patients with alanine transaminase (ALT) ≤ twice the upper limit of normal (ULN). Liver fibrosis was staged using METAVIR scoring system. Define significant fibrosis as F2-F4, severe fibrosis as F3-F4, and cirrhosis as F4. To predict F2-F4, the AUROC of LSM was higher than that of APRI (0.86 vs 0.73, p = 0.001) and FIB-4 (0.86 vs 0.61, p < 0.001). To predict F4, the AUROC of LSM was also higher than that of APRI (0.93 vs 0.77, p = 0.012) and FIB-4 (0.93 vs 0.64, p < 0.001). Patients with ALT levels 1–2 ULN had higher cut-off values than patients with normal ALT levels for the diagnosis of F2-F4 (6.5 vs 6 kPa) and F4 (10.2 vs 7.8 kPa). Using cut-off values regardless of ALT levels, the diagnostic accuracy of LSM was 81% for F2-F4, and 89% for F4. Applying ALT-stratified cut-off values, the diagnostic accuracy of LSM was 82% for F2-F4, and 86% for F4. In conclusion, LSM is a reliable noninvasive test for the diagnosis of liver fibrosis. Applying ALT-stratified cut-off values did not enhance diagnostic accuracy of LSM in CHB patients with ALT ≤ 2 ULN.