bluuebunny/crossref_metadata_2025_split huggingface dataset:
Addition of Epigallocatechin Gallate 400 mg to Sofosbuvir 400 mg + Daclatisvir 60 mg With or Without Ribavirin in Treatment of Patients with Chronic Hepatitis C Improves the Safety Profile: A Pilot Study
Authors: Shiha Gamal , Soliman Reham , Elbasiony Mohamed , Darwish Noureldien H. E. , Mousa Shaker A. 
Published: September 2019

AbstractEmergence of new molecules acting directly on the hepatitic C virus (HCV) has improved treatment outcomes. However, there is a risk of selecting viral escape mutants, so a new combination is needed using different inhibitors that target different steps of the HCV infectious cycle. Novel single tablet formulations were developed: Dactavira, composed of sofosbuvir (SOF) 400 mg/daclatisvir (DCV) 60 mg/epigallocatechin gallate (EGCG) 400 mg without ribavirin (RBV); and Dactavira plus, which includes RBV 800 mg. A randomized, open-label study was carried out on treatment-naïve non-cirrhotic (Group A, n = 50) and treatment-naïve cirrhotic (Group B, n = 22) patients with genotype 4 HCV infection. Group A was randomly assigned to receive a single daily fixed-dose (Dactavira, n = 25) or the standard of care [SOF 400 mg/DCV 60 mg] (n = 25) daily for 12 weeks. Group B was randomly assigned to receive a single daily fixed-dose (Dactavira plus, n = 11) or the standard of care + RBV 800 mg (n = 11) daily for 12 weeks. Patients receiving Dactavira or Dactavira plus had a significantly more rapid rate of viral load decline as compared to patients receiving the standard of care therapy. Sustained virological response for 12 weeks for Dactavira or Dactavira plus showed no statistically significant difference when compared to the standard of care. Also, they did not affect normal hemoglobin levels (p < 0.001) versus the standard of care. The incorporated EGCG interferes with the viral entry mechanisms, as reported by several investigators, and in turn enhances efficacy and prevents relapse as compared to the standard of care. Also, its antihemeolytic and antifibrotic activities may improve the safety and tolerability of the therapy.
Visual and somatosensory information contribute to distortions of the body model
Authors: Peviani Valeria , Melloni Lucia , Bottini Gabriella 
Published: September 2019

AbstractDistorted representations of the body are observed in healthy individuals as well as in neurological and psychiatric disorders. Distortions of the body model have been attributed to the somatotopic cerebral representation. Recently, it has been demonstrated that visual biases also contribute to those distortions. To better understand the sources of such distortions, we compared the metric representations across five body parts affording different degrees of tactile sensitivity and visual accessibility. We evaluated their perceived dimensions using a Line Length Judgment task. We found that most body parts were underestimated in their dimensions. The estimation error relative to their length was predicted by their tactile acuity, supporting the influence of the cortical somatotopy on the body model. However, tactile acuity did not explain the distortions observed for the width. Visual accessibility in turn does appear to mediate body distortions, as we observed that the dimensions of the dorsal portion of the neck were the only ones accurately perceived. Coherent with the multisensory nature of body representations, we argue that the perceived dimensions of body parts are estimated by integrating visual and somatosensory information, each weighted differently, based on their availability for a given body part and a given spatial dimension.
Fragment-based discovery of the first nonpeptidyl inhibitor of an S46 family peptidase
Authors: Sakamoto Yasumitsu , Suzuki Yoshiyuki , Nakamura Akihiro , Watanabe Yurie , Sekiya Mizuki , Roppongi Saori , Kushibiki Chisato , Iizuka Ippei , Tani Osamu , Sakashita Hitoshi , Inaka Koji , Tanaka Hiroaki , Yamada Mitsugu , Ohta Kazunori , Honma Nobuyuki , Shida Yosuke , Ogasawara Wataru , Nakanishi-Matsui Mayumi , Nonaka Takamasa , Gouda Hiroaki , Tanaka Nobutada 
Published: September 2019

AbstractAntimicrobial resistance is a global public threat and raises the need for development of new antibiotics with a novel mode of action. The dipeptidyl peptidase 11 from Porphyromonas gingivalis (PgDPP11) belongs to a new class of serine peptidases, family S46. Because S46 peptidases are not found in mammals, these enzymes are attractive targets for novel antibiotics. However, potent and selective inhibitors of these peptidases have not been developed to date. In this study, a high-resolution crystal structure analysis of PgDPP11 using a space-grown crystal enabled us to identify the binding of citrate ion, which could be regarded as a lead fragment mimicking the binding of a substrate peptide with acidic amino acids, in the S1 subsite. The citrate-based pharmacophore was utilized for in silico inhibitor screening. The screening resulted in an active compound SH-5, the first nonpeptidyl inhibitor of S46 peptidases. SH-5 and a lipophilic analog of SH-5 showed a dose-dependent inhibitory effect against the growth of P. gingivalis. The binding mode of SH-5 was confirmed by crystal structure analysis. Thus, these compounds could be lead structures for the development of selective inhibitors of PgDPP11.
Photopharmacologic Vision Restoration Reduces Pathological Rhythmic Field Potentials in Blind Mouse Retina
Authors: Hüll Katharina , Benster Tyler , Manookin Michael B. , Trauner Dirk , Van Gelder Russell N. , Laprell Laura 
Published: September 2019

AbstractPhotopharmacology has yielded compounds that have potential to restore impaired visual responses resulting from outer retinal degeneration diseases such as retinitis pigmentosa. Here we evaluate two photoswitchable azobenzene ion channel blockers, DAQ and DAA for vision restoration. DAQ exerts its effect primarily on RGCs, whereas DAA induces light-dependent spiking primarily through amacrine cell activation. Degeneration-induced local field potentials remain a major challenge common to all vision restoration approaches. These 5–10 Hz rhythmic potentials increase the background firing rate of retinal ganglion cells (RGCs) and overlay the stimulated response, thereby reducing signal-to-noise ratio. Along with the bipolar cell-selective photoswitch DAD and second-generation RGC-targeting photoswitch PhENAQ, we investigated the effects of DAA and DAQ on rhythmic local field potentials (LFPs) occurring in the degenerating retina. We found that photoswitches targeting neurons upstream of RGCs, DAA (amacrine cells) and DAD (bipolar cells) suppress the frequency of LFPs, while DAQ and PhENAQ (RGCs) had negligible effects on frequency or spectral power of LFPs. Taken together, these results demonstrate remarkable diversity of cell-type specificity of photoswitchable channel blockers in the retina and suggest that specific compounds may counter rhythmic LFPs to produce superior signal-to-noise characteristics in vision restoration.
Association between the relative abundance of gastric microbiota and the risk of gastric cancer: a case-control study
Authors: Gunathilake Madhawa Neranjan , Lee Jeonghee , Choi Il Ju , Kim Young-Il , Ahn Yongju , Park Chanhyeok , Kim Jeongseon 
Published: September 2019

AbstractThe human gut hosts a diverse community of bacteria referred to as the gut microbiome. We investigated the association between the relative abundance of gastric microbiota and gastric cancer (GC) risk in a Korean population. The study participants included 268 GC patients and 288 controls. DNA was extracted from gastric biopsies, and 16S rRNA gene analysis was performed. Unconditional logistic regression models were used to observe the associations. Of the participants, those who had the highest level (highest tertile) of relative Helicobacter pylori and Propionibacterium acnes abundances showed a significantly higher risk for GC after adjusting for potential confounding variables (odds ratio (OR) = 1.86, 95% confidence interval (CI) = 1.17–2.97, p for trend = 0.017 and OR = 4.77, 95% CI = 2.94–7.74, p for trend <0.001, respectively). Subjects who carried Prevotella copri had a significantly higher risk of GC than noncarriers (OR = 2.54, 95% CI = 1.42–4.55, p for trend = 0.002). There was a lower risk of GC in subjects carrying Lactococcus lactis than in noncarriers (OR = 0.21, 95% CI = 0.10–0.44, p for trend <0.001). H. pylori, P. acnes and P. copri are strong risk factors, whereas L. lactis is a protective factor, for GC development in Koreans. Further microbiome studies are warranted to verify the findings of the current study.
Heparanase-2 protects from LPS-mediated endothelial injury by inhibiting TLR4 signalling
Authors: Kiyan Yulia , Tkachuk Sergey , Kurselis Kestutis , Shushakova Nelli , Stahl Klaus , Dawodu Damilola , Kiyan Roman , Chichkov Boris , Haller Hermann 
Published: September 2019

AbstractThe endothelial glycocalyx and its regulated shedding are important to vascular health. Endo-β-D-glucuronidase heparanase-1 (HPSE1) is the only enzyme that can shed heparan sulfate. However, the mechanisms are not well understood. We show that HPSE1 activity aggravated Toll-like receptor 4 (TLR4)-mediated response of endothelial cells to LPS. On the contrary, overexpression of its endogenous inhibitor, heparanase-2 (HPSE2) was protective. The microfluidic chip flow model confirmed that HPSE2 prevented heparan sulfate shedding by HPSE1. Furthermore, heparan sulfate did not interfere with cluster of differentiation-14 (CD14)-dependent LPS binding, but instead reduced the presentation of the LPS to TLR4. HPSE2 reduced LPS-mediated TLR4 activation, subsequent cell signalling, and cytokine expression. HPSE2-overexpressing endothelial cells remained protected against LPS-mediated loss of cell-cell contacts.In vivo, expression of HPSE2 in plasma and kidney medullary capillaries was decreased in mouse sepsis model. We next applied purified HPSE2 in mice and observed decreases in TNFα and IL-6 plasma concentrations after intravenous LPS injections. Our data demonstrate the important role of heparan sulfate and the glycocalyx in endothelial cell activation and suggest a protective role of HPSE2 in microvascular inflammation. HPSE2 offers new options for protection against HPSE1-mediated endothelial damage and preventing microvascular disease.
Identification of differentially expressed genes and fusion genes associated with malignant progression of spinal cord gliomas by transcriptome analysis
Authors: Liu Dong-kang , Wang Jin , Guo Yi , Sun Zhen-xing , Wang Gui-huai 
Published: September 2019

AbstractGlioma, the most common histological subtype of primary spinal cord tumors, is considered as a rare central nervous system neoplasm. In this study, 9 glioma samples (4 of grade II and 5 of grade IV with H3K27M positive) were analyzed to examine the molecular mechanisms underlying the malignant progression of gliomas, transcriptome sequencing. Differentially expressed genes (DEGs) in grade IV vs. grade II were analyzed by using the Limma package in R. Enrichment analysis was performed for the individual DEGs through VennPlex software and the Database for Annotation. Gene mutations and fusions were analyzed using the Genome Analysis Toolkit and STAR-Fusion. A total of 416 DEGs were identified in grade IV vs. grade II. Functional analysis of the DEGs showed that GALR1 and GRM5 of neuroactive ligand-receptor interactions signaling pathways may be relaed to malignant progression of gliomas. Further systematic transcriptional profiling identified 11 in-frame/frameshift gene fusions in the tumors. Notably, one novel gene fusions, GATSL2-GTF2I was detected in all of the grade II samples. In summary, the molecular alterations observed in glioma progression may improve the characterization of different human spinal cord glioma grades. The transcriptome analysis of intramedullary spinal cord glioma will provide a new candidate gene list for further mechanism research.
Two-dimensional boron nitride as a sulfur fixer for high performance rechargeable aluminum-sulfur batteries
Authors: Zhang Kaiqiang , Lee Tae Hyung , Cha Joo Hwan , Varma Rajender S. , Choi Ji-Won , Jang Ho Won , Shokouhimehr Mohammadreza 
Published: September 2019

AbstractAluminum-ion batteries (AIBs) are regarded as promising candidates for post-lithium-ion batteries due to their lack of flammability and electrochemical performance comparable to other metal-ion batteries. The lack of suitable cathode materials, however, has hindered the development of high-performing AIBs. Sulfur is a cost-efficient material, having distinguished electrochemical properties, and is considered an attractive cathode material for AIBs. Several pioneering reports have shown that aluminum-sulfur batteries (ASBs) exhibit superior electrochemical capacity over other cathode materials for AIBs. However, a rapid decay in the capacity is a huge barrier for their practical applications. Here, we have demonstrated systematically for the first time that the two-dimensional layered materials (e.g. MoS2, WS2, and BN) can serve as fixers of S and sulfide compounds during repeated charge/discharge processes; BN/S/C displays the highest capacity of 532 mAh g−1 (at a current density of 100 mA g−1) compared with the current state-of-the-art cathode material for AIBs. Further, we could improve the life-span of ASBs to an unprecedented 300 cycles with a high Coulombic efficiency of 94.3%; discharge plateaus at ~1.15 V vs. AlCl4−/Al was clearly observed during repeated charge/discharge cycling. We believe that this work opens up a new method for achieving high-performing ASBs.
Seasonality of riverine macroplastic transport
Authors: van Emmerik Tim , Strady Emilie , Kieu-Le Thuy-Chung , Nguyen Luan , Gratiot Nicolas 
Published: September 2019

AbstractMarine plastic pollution is an increasing environmental threat. Although it is assumed that most marine plastics are transported from land to the ocean through rivers, only limited data on riverine plastic transport exists. Recently, new methods have been introduced to characterize riverine plastics consistently through time and space. For example, combining visual counting observations and plastic debris sampling can provide order of magnitude estimations of plastic transport through a river. In this paper, we present findings from multi-season measurement campaign in the Saigon River, Vietnam. For the first time, we demonstrate that macroplastic transport exhibits strong temporal variation. The monthly averaged plastic transport changes up to a factor five within the measurement period. As it is unclear what drives the variation in plastic transport, relations between rainfall, river discharge, presence of organic material and plastic transport have been explored. Furthermore, we present new findings on the cross-sectional and vertical distribution of riverine plastic transport. With this paper we present new insights in the origin and fate of riverine plastic transport, emphasizing the severity of the emerging thread of plastic pollution on riverine ecosystems.
Segregation and potential functional impact of a rare stop-gain PABPC4L variant in familial atypical Parkinsonism
Authors: Aslam Muhammad , Ullah Anwar , Paramasivam Nagarajan , Kandasamy Nirosiya , Naureen Saima , Badshah Mazhar , Khan Kafaitullah , Wajid Muhammad , Abbasi Rashda , Eils Roland , Brockmann Marc A. , Schlesner Matthias , Ahmad Nafees , von Engelhardt Jakob 
Published: September 2019

AbstractAtypical parkinsonian disorders (APDs) comprise a group of neurodegenerative diseases with heterogeneous clinical and pathological features. Most APDs are sporadic, but rare familial forms have also been reported. Epidemiological and post-mortem studies associated APDs with oxidative stress and cellular protein aggregates. Identifying molecular mechanisms that translate stress into toxic protein aggregation and neurodegeneration in APDs is an active area of research. Recently, ribonucleic acid (RNA) stress granule (SG) pathways were discussed to be pathogenically relevant in several neurodegenerative disorders including APDs. Using whole genome sequencing, mRNA expression analysis, transfection assays and cell imaging, we investigated the genetic and molecular basis of a familial neurodegenerative atypical parkinsonian disorder. We investigated a family with six living members in two generations exhibiting clinical symptoms consistent with atypical parkinsonism. Two affected family members suffered from parkinsonism that was associated with ataxia. Magnetic resonance imaging (MRI) of these patients showed brainstem and cerebellar atrophy. Whole genome sequencing identified a heterozygous stop-gain variant (c.C811T; p.R271X) in the Poly(A) binding protein, cytoplasmic 4-like (PABPC4L) gene, which co-segregated with the disease in the family. In situ hybridization showed that the murine pabpc4l is expressed in several brain regions and in particular in the cerebellum and brainstem. To determine the functional impact of the stop-gain variant in the PABPC4L gene, we investigated the subcellular localization of PABPC4L in heterologous cells. Wild-type PABPC4L protein localized predominantly to the cell nucleus, in contrast to the truncated protein encoded by the stop-gain variant p.R271X, which was found homogeneously throughout the cell. Interestingly, the wild-type, but not the truncated protein localized to RasGAP SH3 domain Binding Protein (G3BP)-labeled cytoplasmic granules in response to oxidative stress induction. This suggests that the PABPC4L variant alters intracellular distribution and possibly the stress granule associated function of the protein, which may underlie APD in this family. In conclusion, we present genetic and molecular evidence supporting the role of a stop-gain PABPC4L variant in a rare familial APD. Our data shows that the variant results in cellular mislocalization and inability of the protein to associate with stress granules.
Glaucony authigenesis, maturity and alteration in the Weddell Sea: An indicator of paleoenvironmental conditions before the onset of Antarctic glaciation
Authors: López-Quirós Adrián , Escutia Carlota , Sánchez-Navas Antonio , Nieto Fernando , Garcia-Casco Antonio , Martín-Algarra Agustín , Evangelinos Dimitris , Salabarnada Ariadna 
Published: September 2019

AbstractThree types of glaucony grains were identified in the late Eocene (~35.5–34.1 Ma) sediments from Ocean Drilling Program (ODP) Hole 696B in the northwestern Weddell Sea (Antarctica). The grains are K2O-rich (~7 wt%) and formed by smectite-poor interstratified ~10 Å glauconite-smectite with flaky/rosette-shaped surface nanostructures. Two glaucony types reflect an evolved (types 1 and 2 glaucony; less mature to mature) stage and long term glauconitization, attesting to the glaucony grains being formedin situ, whereas the third type (type 3 glaucony) shows evidences of alteration and reworking from nearby areas. Conditions for the glaucony authigenesis occurred in an open-shelf environment deeper than 50 m, under sub-oxic conditions near the sediment-water interface. These environmental conditions were triggered by low sedimentation rates and recurrent winnowing action by bottom-currents, leading to stratigraphic condensation. The condensed glaucony-bearing section provides an overview of continuous sea-level rise conditions pre-dating the onset of Antarctic glaciation during the Eocene-Oligocene transition. Sediment burial, drop of O2levels, and ongoing reducing (postoxic to sulphidic) conditions at Hole 696B, resulting in iron-sulphide precipitation, were a key limiting factor for the glauconitization by sequestration of Fe2+.
Hexokinase is necessary for glucose-mediated photosynthesis repression and lipid accumulation in a green alga
Authors: Roth Melissa S. , Westcott Daniel J. , Iwai Masakazu , Niyogi Krishna K. 
Published: September 2019

AbstractGlobal primary production is driven largely by oxygenic photosynthesis, with algae as major contributors. The green alga Chromochloris zofingiensis reversibly switches off photosynthesis in the presence of glucose in the light and augments production of biofuel precursors (triacylglycerols) and the high-value antioxidant astaxanthin. Here we used forward genetics to reveal that this photosynthetic and metabolic switch is mediated by the glycolytic enzyme hexokinase (CzHXK1). In contrast to wild-type, glucose-treated hxk1 mutants do not shut off photosynthesis or accumulate astaxanthin, triacylglycerols, or cytoplasmic lipid droplets. We show that CzHXK1 is critical for the regulation of genes related to photosynthesis, ketocarotenoid synthesis and fatty acid biosynthesis. Sugars play fundamental regulatory roles in gene expression, physiology, metabolism, and growth in plants and animals, and we introduce a relatively simple, emerging model system to investigate conserved eukaryotic sugar sensing and signaling at the base of the green lineage.
Auxiliary-assisted chemical ubiquitylation of NEMO and linear extension by HOIP
Authors: Burlina Fabienne , Abdel-Aal Abu-Baker M. , Raz Richard , Pinzuti Irene , Papageorgiou George , Li Jiejin , Antrobus Robin , Martin Stephen R. , Kunzelmann Simone , Stieglitz Benjamin , Offer John 
Published: September 2019

AbstractThe ubiquitylation of NF-κB essential modulator (NEMO) is part of the intracellular immune signalling pathway. Monoubiquitylated NEMO is required for exploring the mechanism of NEMO linear ubiquitylation by LUBAC (linear ubiquitin chain assembly complex), but is not accessible by biological techniques. Here we perform the chemical ubiquitylation of NEMO using a ligation auxiliary, which only requires a two-step synthesis, and is easily installed onto the lysine side-chain. Chemical ligation occurs directly on the lysine ε amine and remains efficient below pH 7. We show that ubiquitylated NEMO has similar affinity to linear di-ubiquitin chains as unmodified NEMO. The proximal ubiquitin of chemically synthesised NEMOCoZi-Ub is accepted as a substrate for linear extension by the (RING-Between-RING) RBR domain of HOIL-1-interacting protein (HOIP) alone. Our results indicate that NEMO linear ubiquitylation consists of two-steps, an initial priming event and a separate extension step requiring different LUBAC components.
Influence of the Yarkovsky force on Jupiter Trojan asteroids
Authors: Hellmich S. , Mottola S. , Hahn G. , Kührt E. , de Niem D. 
Published: September 2019

Aims.We investigate the influence of the Yarkovsky force on the long-term orbital evolution of Jupiter Trojan asteroids.Methods.Clones of the observed population with different sizes and different thermal properties were numerically integrated for 1 Gyr with and without the Yarkovsky effect. The escape rate of these objects from the Trojan region as well as changes in the libration amplitude, eccentricity, and inclination were used as a metric of the strength of the Yarkovsky effect on the Trojan orbits.Results.Objects with radiiR≤ 1 km are significantly influenced by the Yarkovsky force. The effect causes a depletion of these objects over timescales of a few hundred million years. As a consequence, we expect the size-frequency distribution of small Trojans to show a shallower slope than that of the currently observable population (R≳ 1 km), with a turning point betweenR= 100 m andR= 1 km. The effect of the Yarkovsky acceleration on the orbits of Trojans depends on the sense of rotation in a complex way. The libration amplitude of prograde rotators decreases with time while the eccentricity increases. Retrograde rotators experience the opposite effect, which results in retrograde rotators being ejected faster from the 1:1 resonance region. Furthermore, for objects affected by the Yarkovsky force, we find indications that the effect tends to smooth out the differences in the orbital distribution between the two clouds.