bluuebunny/crossref_metadata_2025_split huggingface dataset:
Enhanced insights from human and animal host-associated molecular marker genes in a freshwater lake receiving wet weather overflows
Authors: Ahmed Warish , Payyappat Sudhi , Cassidy Michele , Besley Colin 
Published: August 2019

AbstractThis study investigated the magnitude of wet weather overflow (WWO)-driven sewage pollution in an urban lake (Lake Parramatta) located in Sydney, New South Wales, Australia. Water samples were collected during a dry weather period and after two storm events, and tested for a range of novel and established sewage- [Bacteroides HF183, crAssphage CPQ_056 and pepper mild mottle virus (PMMoV)] and animal feces-associated (Bacteroides BacCan-UCD, cowM2 and Helicobacter spp. associated GFD) microbial source tracking marker genes along with the enumeration of culturable fecal indicator bacteria (FIB), namely Escherichia coli (E. coli) and Enterococcus spp. The magnitude of general and source-specific fecal pollution was low in water samples collected during dry weather compared to storm events. The levels of HF183, crAssphage and PMMoV in water samples collected during storm events were as high as 6.39, 6.33 and 5.27 log10 GC/L of water, respectively. Moderate to strong positive correlations were observed among the quantitative occurrence of sewage-associated marker genes. The concentrations of HF183 and PMMoV in most storm water samples exceeded the risk benchmark threshold values established in the literature for primary contact recreators. None of the samples tested was positive for the cowM2 (cow) marker gene, while BacCan-UCD (dog) and GFD (avian) animal-associated markers were sporadically detected in water samples collected from both dry weather and storm events. Based on the results, the ongoing advice that swimming should be avoided for several days after storm events appears appropriate. Further research to determine the decay rates of sewage-associated marker genes in relation to each other and enteric viruses would help refine current advice. Microbial source tracking approaches employed in this study provided insights into sources of contamination over currently used FIB.
Photosystem II of Ligustrum lucidum in response to different levels of manganese exposure
Authors: Liang Hui-Zi , Zhu Fan , Wang Ren-Jie , Huang Xin-Hao , Chu Jing-Jing 
Published: August 2019

AbstractThe toxic effect of excessive manganese (Mn) on photosystem II (PSII) of woody species remains largely unexplored. In this study, five Mn concentrations (0, 12, 24, 36, and 48 mM) were used, and the toxicity of Mn on PSII behavior in leaves of Ligustrum lucidum was investigated using in vivo chlorophyll fluorescence transients. Results showed that excessive Mn levels induced positive L- and K- bands. Variable fluorescence at 2 ms (VJ) and 30 ms (VI), absorption flux (ABS/RC), trapped energy flux (TRo/RC), and dissipated energy flux (DIo/RC) increased in Mn-treated leaves, whereas the performance index (PIABS), electron transport flux (ETo/RC), maximum quantum yield (φPo), quantum yield of electron transport (φEo), and probability that an electron moves further than QA− (ψo) decreased. Also, excessive Mn significantly decreased the net photosynthesis rate and increased intercellular CO2 concentration. The results indicated that Mn blocked the electron transfer from the donor side to the acceptor side in PSII, which might be associated with the accumulation of QA−, hence limiting the net photosynthetic rate.
Abundant neuroprotective chaperone Lipocalin-type prostaglandin D synthase (L-PGDS) disassembles the Amyloid-β fibrils
Authors: Kannaian Bhuvaneswari , Sharma Bhargy , Phillips Margaret , Chowdhury Anup , Manimekalai Malathy S. S. , Adav Sunil S. , Ng Justin T. Y. , Kumar Ambrish , Lim Sierin , Mu Yuguang , Sze Siu K. , Grüber Gerhard , Pervushin Konstantin 
Published: August 2019

AbstractMisfolding of Amyloid β (Aβ) peptides leads to the formation of extracellular amyloid plaques. Molecular chaperones can facilitate the refolding or degradation of such misfolded proteins. Here, for the first time, we report the unique ability of Lipocalin-type Prostaglandin D synthase (L-PGDS) protein to act as a disaggregase on the pre-formed fibrils of Aβ(1–40), abbreviated as Aβ40, and Aβ(25–35) peptides, in addition to inhibiting the aggregation of Aβ monomers. Furthermore, our proteomics results indicate that L-PGDS can facilitate extraction of several other proteins from the insoluble aggregates extracted from the brain of an Alzheimer’s disease patient. In this study, we have established the mode of binding of L-PGDS with monomeric and fibrillar Aβ using Nuclear Magnetic Resonance (NMR) Spectroscopy, Small Angle X-ray Scattering (SAXS), and Transmission Electron Microscopy (TEM). Our results confirm a direct interaction between L-PGDS and monomeric Aβ40 and Aβ(25–35), thereby inhibiting their spontaneous aggregation. The monomeric unstructured Aβ40 binds to L-PGDS via its C-terminus, while the N-terminus remains free which is observed as a new domain in the L-PGDS-Aβ40 complex model.
Biosynthesis of Hyaluronic acid polymer: Dissecting the role of sub structural elements of hyaluronan synthase
Authors: Agarwal Garima , K. V. Krishnan , Prasad Shashi Bala , Bhaduri Anirban , Jayaraman Guhan 
Published: August 2019

AbstractHyaluronic acid (HA) based biomaterials have several biomedical applications. HA biosynthesis is catalysed by hyaluronan synthase (HAS). The unavailability of 3-D structure of HAS and gaps in molecular understanding of HA biosynthesis process pose challenges in rational engineering of HAS to control HA molecular weight and titer. Using in-silico approaches integrated with mutation studies, we define a dictionary of sub-structural elements (SSE) of the Class I Streptococcal HAS (SeHAS) to guide rational engineering. Our study identifies 9 SSE in HAS and elucidates their role in substrate and polymer binding and polymer biosynthesis. Molecular modelling and docking assessment indicate a single binding site for two UDP-substrates implying conformationally-driven alternating substrate specificities for this class of enzymes. This is the first report hypothesizing the involvement of sites from SSE5 in polymer binding. Mutation at these sites influence HA production, indicating a tight coupling of polymer binding and synthase functions. Mutation studies show dispensable role of Lys-139 in substrate binding and a key role of Gln-248 and Thr-283 in HA biosynthesis. Based on the functional architecture in SeHAS, we propose a plausible three-step polymer extension model from its reducing end. Together, these results open new avenues for rational engineering of Class I HAS to study and regulate its functional properties and enhanced understanding of glycosyltransferases and processive enzymes.
ADAM15 mediates upregulation of Claudin-1 expression in breast cancer cells
Authors: Mattern Jens , Roghi Christian S. , Hurtz Melanie , Knäuper Vera , Edwards Dylan R. , Poghosyan Zaruhi 
Published: August 2019

AbstractA Disintegrin and Metalloproteinase-15 (ADAM15) is a transmembrane protein involved in protein ectodomain shedding, cell adhesion and signalling. We previously cloned and characterised alternatively spliced variants of ADAM15 that differ in their intracellular domains and demonstrated correlation of the expression of specific variants with breast cancer prognosis. In this study we have created isogenic cell panels (MDA-MB-231 and MCF-7) expressing five ADAM15 variants including wild-type and catalytically inactive forms. The expression of ADAM15 isoforms in MDA-MB-231 cells led to cell clustering to varying degree, without changes in EMT markers vimentin, slug and E-cadherin. Analysis of tight junction molecules revealed ADAM15 isoform specific, catalytic function dependent upregulation of Claudin-1. The expression of ADAM15A, and to a lesser degree of C and E isoforms led to an increase in Claudin-1 expression in MDA-MB-231 cells, while ADAM15B had no effect. In MCF-7 cells, ADAM15E was the principal variant inducing Claudin-1 expression. Sh-RNA mediated down-regulation of ADAM15 in ADAM15 over-expressing cells reduced Claudin-1 levels. Additionally, downregulation of endogenous ADAM15 expression in T47D cells by shRNA reduced endogenous Claudin-1 expression confirming a role for ADAM15 in regulating Claudin-1 expression. The PI3K/Akt/mTOR pathway was involved in regulating Claudin-1 expression downstream of ADAM15. Immunofluorescence analysis of MDA-MB-231 ADAM15A expressing cells showed Claudin-1 at cell-cell junctions, in the cytoplasm and nuclei. ADAM15 co-localised with Claudin-1 and ZO1 at cell-cell junctions. Immunoprecipitation analysis demonstrated complex formation between ADAM15 and ZO1/ZO2. These findings highlight the importance of ADAM15 Intra Cellular Domain-mediated interactions in regulating substrate selection and breast cancer cell phenotype.
Label-free stimulated Raman scattering microscopy visualizes changes in intracellular morphology during human epidermal keratinocyte differentiation
Authors: Egawa Mariko , Iwanaga Shinya , Hosoi Junichi , Goto Makiko , Yamanishi Haruyo , Miyai Masashi , Katagiri Chika , Tokunaga Kyoya , Asai Takuya , Ozeki Yasuyuki 
Published: August 2019

AbstractEpidermal keratinocyte (KC) differentiation, which involves the process from proliferation to cell death for shedding the outermost layer of skin, is crucial for the barrier function of skin. Therefore, in dermatology, it is important to elucidate the epidermal KC differentiation process to evaluate the symptom level of diseases and skin conditions. Previous dermatological studies used staining or labelling techniques for this purpose, but they have technological limitations for revealing the entire process of epidermal KC differentiation, especially when applied to humans. Here, we demonstrate label-free visualization of three-dimensional (3D) intracellular morphological changes ofex vivohuman epidermis during epidermal KC differentiation using stimulated Raman scattering (SRS) microscopy. Specifically, we observed changes in nuclei during the initial enucleation process in which the nucleus is digested prior to flattening. Furthermore, we found holes left behind by improperly digested nuclei in the stratum corneum, suggesting abnormal differentiation. Our findings indicate the great potential of SRS microscopy for discrimination of the degree of epidermal KC differentiation.
DNA methylation silencing of microRNA gene methylator in the precancerous background mucosa with and without gastric cancer: Analysis of the effects of H. pylori eradication and long-term aspirin use
Authors: Watari Jiro , Ito Chiyomi , Shimoda Tadakazu , Tomita Toshihiko , Oshima Tadayuki , Fukui Hirokazu , Das Kiron M. , Miwa Hiroto 
Published: August 2019

AbstractThe risk of gastric cancer (GC) declines after Helicobacter pylori (H. pylori) eradication and long-term aspirin use. We evaluated the effects of H. pylori eradication (Cohort 1) and aspirin use (Cohort 2) on the methylation of microRNAs (miRNAs), such as miR-34c, miR-124a-3, miR-129-2, and miR-137, in the gastric mucosa with and without GC, i.e., in atrophic mucosal glands without intestinal metaplasia (non-IM) and intestinal metaplastic glands (IM). DNA was isolated from non-IM and IM separately using laser caption microdissection. In Cohort 1, H. pylori eradication was associated with a significant reduction of miR-124a-3 methylation only in non-IM, but not in IM. miR-129-2 methylation in non-IM may be a surrogate marker of GC in H. pylori-infected patients. In Cohort 2, aspirin did not reverse miRNA methylation in either non-IM or IM, irrespective of H. pylori infection. miR-129-2 methylation in non-IM was an independent predictive marker of GC in H. pylori-infected but not -eradicated patients. These results indicate that H. pylori eradication and aspirin use were less effective for improving methylation in IM than in non-IM; thus, these interventions are recommended at an early stage prior to the development of IM to prevent GC development. In addition, the effects of the interventions were not uniform for each miRNA gene.
Seasonal payoff variations and the evolution of cooperation in social dilemmas
Authors: Szolnoki Attila , Perc Matjaž 
Published: August 2019

AbstractVarying environmental conditions affect relations between interacting individuals in social dilemmas, thus affecting also the evolution of cooperation. Oftentimes these environmental variations are seasonal and can therefore be mathematically described as periodic changes. Accordingly, we here study how periodic shifts between different manifestations of social dilemmas affect cooperation. We observe a non-trivial interplay between the inherent spatiotemporal dynamics that characterizes the spreading of cooperation in a particular social dilemma type and the frequency of payoff changes. In particular, we show that periodic changes between two available games with global ordering best be fast, while periodic changes between global and local ordering games best be slow for cooperation to thrive. We also show that the frequency of periodic changes between two local ordering social dilemmas is irrelevant, because then the process is fast and simply the average cooperation level of the two is returned. The structure of the interaction network plays an important role too in that lattices promote local ordering, whilst random graphs hinder the formation of compact cooperative clusters. Conversely, for local ordering the regular structure of the interaction network is only marginally relevant as role-separating checkerboard patterns do not rely on long-range order.
Triboelectrification of Two-Dimensional Chemical Vapor Deposited WS2 at Nanoscale
Authors: Wang He , Huang Chung-Che , Polcar Tomas 
Published: August 2019

AbstractTriboelectric properties of chemical vapor deposited WS2 nanoflakes have been characterized in nano-range by atomic force microscopy (AFM) and Kelvin force microscopy (KFM). The triboelectric process is dependent on the thickness of WS2 nanoflakes, and it is sensitive to the adsorbates like water molecules, as well as transferred Pt from the tip on the sample. The density of tribo-charge can be modified by applying various biases to the conductive Pt-coated tip during the frictional process. Tunneling of the tribo-charge into the gap between WS2 and the underlying substrate results in a long lifetime, which is about 100 times longer than conventional triboelectric charges. Moreover, we observe a positive correlation between the layer number and resistance to charge dissipation. Our finding can become the driving force for a new category of two-dimensional (2D) WS2 triboelectrically controllable nanodevices.
Mobility of pectin methylesterase in pectin/cellulose gels is enhanced by the presence of cellulose and by its catalytic capacity
Authors: Bonnin Estelle , Alvarado Camille , Crépeau Marie-Jeanne , Bouchet Brigitte , Garnier Catherine , Jamme Frédéric , Devaux Marie-Françoise 
Published: August 2019

AbstractThe pectin methylesterase action is usually studied in a homogeneous aqueous medium in the presence of a large excess of soluble substrate and water. However in the cell wall, the water content is much lower, the substrate is cross-linked with itself or with other polymers, and the enzyme has to diffuse through the solid matrix before catalysing the linkage breakdown. As plant primary cell walls can be considered as cellulose-reinforced hydrogels, this study investigated the diffusion of a fungal pectin methylesterase in pectin/cellulose gels used as cell wall-mimicking matrix to understand the impact of this matrix and its (micro) structure on the enzyme’s diffusion within it. The enzyme mobility was followed by synchrotron microscopy thanks to its auto-fluorescence after deep-UV excitation. Time-lapse imaging and quantification of intensity signal by image analysis revealed that the diffusion of the enzyme was impacted by at least two criteria: (i) only the active enzyme was able to diffuse, showing that the mobility was related to the catalytic ability, and (ii) the diffusion was improved by the presence of cellulose in the gel.
ERK1/2 signaling regulates the immune microenvironment and macrophage recruitment in glioblastoma
Authors: Lailler Claire , Louandre Christophe , Morisse Mony Chenda , Lhossein Thomas , Godin Corinne , Lottin Marine , Constans Jean-Marc , Chauffert Bruno , Galmiche Antoine , Saidak Zuzana 
Published: August 2019

Abstract
The tumor microenvironment is an important determinant of glioblastoma (GBM) progression and response to treatment. How oncogenic signaling in GBM cells modulates the composition of the tumor microenvironment and its activation is unclear. We aimed to explore the potential local immunoregulatory function of ERK1/2 signaling in GBM. Using proteomic and transcriptomic data (RNA seq) available for GBM tumors from The Cancer Genome Atlas (TCGA), we show that GBM with high levels of phosphorylated ERK1/2 have increased infiltration of tumor-associated macrophages (TAM) with a non-inflammatory M2 polarization. Using three human GBM cell lines in culture, we confirmed the existence of ERK1/2-dependent regulation of the production of the macrophage chemoattractant CCL2/MCP1. In contrast with this positive regulation of TAM recruitment, we found no evidence of a direct effect of ERK1/2 signaling on two other important aspects of TAM regulation by GBM cells: (1) the expression of the immune checkpoint ligands PD-L1 and PD-L2, expressed at high mRNA levels in GBM compared with other solid tumors; (2) the production of the tumor metabolite lactate recently reported to dampen tumor immunity by interacting with the receptor GPR65 present on the surface of TAM. Taken together, our observations suggest that ERK1/2 signaling regulates the recruitment of TAM in the GBM microenvironment. These findings highlight some potentially important particularities of the immune microenvironment in GBM and could provide an explanation for the recent observation that GBM with activated ERK1/2 signaling may respond better to anti-PD1 therapeutics.
Quantitative reduction in short-chain fatty acids, especially butyrate, contributes to the progression of chronic kidney disease
Authors: Wang Siqi , Lv Dan , Jiang Shuanghong , Jiang Jianpin , Liang Min , Hou Fanfan , Chen Ye 
Published: August 2019

Abstract
Chronic kidney disease (CKD) affects 10–15% of the population worldwide, results in high morbidity and mortality, and requires costly treatment and renal replacement therapy. Glomerulosclerosis, tubulointerstitial fibrosis, and persistent intestinal flora disturbance are common in CKD. Short-chain fatty acids (SCFAs), produced by the intestinal microbiota, have been previously reported to ameliorate kidney injury; however, the specific concentrations and types that are required to improve renal function remain unknown. The present study aims to evaluate the levels of SCFAs in healthy and CKD patients, and to test the hypothesis that SCFAs play a critical role in delaying CKD progression. One hundred and twenty-seven patients with CKD and 63 healthy controls from China were enrolled in the present study. Butyrate, which is considered beneficial to humans, was almost three-times higher in healthy volunteers than that in CKD5 subjects (P=0.001). Moreover, the serum SCFA levels in controls were significantly higher than that in CKD patients (P&lt;0.05), and the butyrate level among CKD5 patients (1.48 ± 0.60 μmol/l) was less than half of that in controls (3.44 ± 2.12 μmol/l, P&lt;0.001). In addition, we observed an inverse correlation between butyrate level and renal function (P&lt;0.05). A CKD rat model transplanted with microbiota obtained from CKD patients exhibited accelerated CKD progression via increased production of trimethylamine N-oxide (TMAO), which was reversed by supplementation with extra butyrate. Our results showed that SCFA levels were reduced in CKD patients and that butyrate supplementation might delay CKD progression.
Predicting Speech Intelligibility Based on Spatial Tongue–Jaw Coupling in Persons With Amyotrophic Lateral Sclerosis: The Impact of Tongue Weakness and Jaw Adaptation
Authors: Rong Panying , Green Jordan R. 
Published: August 2019

PurposeMotor neuron diseases, such as amyotrophic lateral sclerosis (ALS), have a devastating effect on speech muscle function that often results in severe communication deficits. Over the course of bulbar disease, tongue and jaw movements are modified, but their impact on speech is poorly understood. The aim of this study was to determine the effect of disease-related changes in tongue–jaw movement coupling on speech intelligibility in persons at different stages of bulbar ALS.MethodParallel factor analysis was used to quantify the pattern of spatial coupling between 4 semi-independent regions of the tongue and the jaw in various vowels and consonants in 10 individuals with ALS and 10 healthy individuals, respectively, from the X-Ray Microbeam database (Westbury, 1994). The relation of spatial tongue–jaw coupling to speech intelligibility was examined in individuals at the early and late stages of bulbar ALS and healthy individuals.ResultsTongue movement, independent of the jaw, decreased early and progressively, which negatively impacted speech intelligibility. Jaw contribution to tongue movement was increased during the early stages of bulbar ALS compared to that of the healthy subjects, which was followed by a decrease during the late stages of bulbar ALS. The early-stage increase of jaw contribution significantly improved speech intelligibility and is thus most likely to be an adaptive strategy to mitigate the negative impact of tongue movement reductions on speech intelligibility. This adaptive strategy became unavailable during the late stages of bulbar ALS, which might accelerate intelligibility decline.ConclusionsThe loss of functional tongue–jaw coupling may be the critical physiological factor leading to the eventual loss of functional speech in ALS. Monitoring changes in tongue–jaw coupling may improve the prediction about the timing of speech loss and guide clinical management of dysarthria in ALS.