Miracle-dz/UniFAR-FTUs huggingface dataset:
P2X7 Receptor Regulates Internalization of Antimicrobial Peptide LL-37 by Human Macrophages That Promotes Intracellular Pathogen Clearance

Bioactive peptide LL-37/hCAP18, the only human member of the cathelicidin family, plays important roles in killing various pathogens, as well as in immune modulation. We demonstrate that LL-37 is internalized by human macrophages in a time-, dose-, temperature-, and peptide sequence–dependent endocytotic process. Both clathrin- and caveolae/lipid raft–mediated endocytosis pathways are involved in LL-37 internalization. We find that the P2X7 receptor (P2X7R) plays an important role in LL-37 internalization by human macrophages because significantly less internalized LL-37 was detected in macrophages pretreated with P2X7R antagonists or, more specifically, in differentiated THP-1 cells in which the P2X7R gene had been silenced. Furthermore, this P2X7R-mediated LL-37 internalization is primarily connected to the clathrin-mediated endocytosis pathway. In addition, our results demonstrate that internalized LL-37 traffics to endosomes and lysosomes and contributes to intracellular clearance of bacteria by human macrophages, coinciding with increased reactive oxygen species and lysosome formation. Finally, we show that human macrophages have the potential to import LL-37 released from activated human neutrophils. In conclusion, our study unveils a novel mechanism by which human macrophages internalize antimicrobial peptides to improve their intracellular pathogen clearance.
Contribution of Astroglial Cx43 Hemichannels to the Modulation of Glutamatergic Currents by D-Serine in the Mouse Prefrontal Cortex

Astrocytes interact dynamically with neurons by modifying synaptic activity and plasticity. This interplay occurs through a process named gliotransmission, meaning that neuroactive molecules are released by astrocytes. Acting as a gliotransmitter, D-serine, a co-agonist of the NMDA receptor at the glycine-binding site, can be released by astrocytes in a calcium [Ca2+]i-dependent manner. A typical feature of astrocytes is their high expression level of connexin43 (Cx43), a protein forming gap junction channels and hemichannels associated with dynamic neuroglial interactions. Pharmacological and genetic inhibition of Cx43 hemichannel activity reduced the amplitude of NMDA EPSCs in mouse layer 5 prefrontal cortex pyramidal neurons without affecting AMPA EPSC currents. This reduction of NMDA EPSCs was rescued by addition of D-serine in the extracellular medium. LTP of NMDA and AMPA EPSCs after high-frequency stimulation was reduced by prior inhibition of Cx43 hemichannel activity. Inactivation of D-serine synthesis within the astroglial network resulted in the reduction of NMDA EPSCs, which was rescued by adding extracellular D-serine. We showed that the activity of Cx43 hemichannels recorded in cultured astrocytes was [Ca2+]I dependent. Accordingly, in acute cortical slices, clamping [Ca2+]i at a low level in astroglial network resulted in an inhibition of NMDA EPSC potentiation that was rescued by adding extracellular D-serine. This work demonstrates that astroglial Cx43 hemichannel activity is associated with D-serine release. This process, occurring by direct permeation of D-serine through hemichannels or indirectly by Ca2+ entry and activation of other [Ca2+]i-dependent mechanisms results in the modulation of synaptic activity and plasticity. SIGNIFICANCE STATEMENT We recorded neuronal glutamatergic (NMDA and AMPA) responses in prefrontal cortex (PFC) neurons and used pharmacological and genetic interventions to block connexin-mediated hemichannel activity specifically in a glial cell population. For the first time in astrocytes, we demonstrated that hemichannel activity depends on the intracellular calcium concentration and is associated with D-serine release. Blocking hemichannel activity reduced the LTP of these excitatory synaptic currents triggered by high-frequency stimulation. These observations may be particularly relevant in the PFC, where D-serine and its converting enzyme are highly expressed.
Pre-training perceived wellness impacts training output in Australian football players

ABSTRACT The impact of perceived wellness on a range of external load parameters, rating of perceived exertion (RPE) and external load:RPE ratios, was explored during skill-based training in Australian footballers. Fifteen training sessions involving 36 participants were analysed. Each morning before any physical training, players completed a customised perceived wellness questionnaire (sleep quality, fatigue, stress, mood and muscle soreness). Microtechnology devices provided external load (average speed, high-speed running distance, player load and player load slow). Players provided RPE using the modified Borg category-ratio 10 RPE scale. Mixed-effect linear models revealed significant effects of wellness Z-score on player load and player load slow. Effects are reported with 95% confidence limits. A wellness Z-score of −1 corresponded to a −4.9 ± 3.1 and −8.6 ± 3.9% reduction in player load and player load slow, respectively, compared to those without reduced wellness. Small significant effects were also seen in the average speed:RPE and player load slow:RPE models. A wellness Z-score of −1 corresponded to a 0.43 ± 0.38 m·min−1 and −0.02 ± 0.01 au·min−1 change in the average speed:RPE and player load slow:RPE ratios, respectively. Magnitude-based analysis revealed that the practical size of the effect of a pre-training perceived wellness Z-score of −1 would have on player load slow was likely negative. The results of this study suggests that monitoring pre-training perceived wellness may provide coaches with information about the intensity of output that can be expected from individual players during a training session.
Culture of murine brain microvascular endothelial cells that maintain expression and cytoskeletal association of tight junction-associated proteins

SummaryA readily obtainable in vitro paradigm of the blood-brain barrier (BBB) would offer considerable benefits. Toward this end, in this study, we describe a novel method for purifying murine brain microvascular endothelial cells (BMEC) for culture. The method uses limited collagenase-dispase digestion of enriched brain microvessels, followed by immunoisolation of digested, microvascular fragments by magnetic beads coated with antibody to platelet-endothelial cell adhesion molecule-1. When plated onto collagen IV-coated surfaces, these fragments elaborated confluent monolayers of BMEC that expressed, as judged by immunocytochemistry, the adherens junction-associated proteins, VE-cadherin and β-catenin, as well as the tight junction (TJ)-associated proteins, claudin-5, occludin, and zonula occludin-1 (ZO-1), in concentrated fashion along intercellular borders. In contrast, cultures of an immortalized and transformed line of murine brain capillary-derived endothelial cells, bEND.3, displayed diffuse cytoplasmic localization of occludin and ZO-1. This difference in occludin and ZO-1 staining between the two endothelial cell types was also reflected in the extent of association of these proteins with the detergent-resistant cytoskeletal framework (CSK). Although both occludin and ZO-1 largely partitioned with the CSK fraction in BMEC, they were found predominantly in the soluble fraction of bEND.3 cells, and claudin-5 was found associated equally with both fractions in BMEC and bEND.3 cells. Moreover, detergent-extracted cultures of the BMEC retained pronounced immunostaining of occludin and ZO-1, but not claudin-5, along intercellular borders. Because both occludin and ZO-1 are thought to be functionally coupled to the detergent-resistant CSK and high expression of TJs is considered a seminal characteristic of the BBB, these results impart that this method of purifying murine BMEC provides a suitable platform to investigate BBB properties in vitro.
Neuropilin-1 is a glial cell line-derived neurotrophic factor receptor in glioblastoma

The aim of this study was to identify the receptor for glial cell line-derived neurotrophic factor (GDNF) in glioblastoma multiforme (GBM). After GST pull-down assays, membrane proteins purified from C6 rat glioma cells were subjected to liquid chromatography-tandem mass spectrometry (LC-MS/MS). The differentially expressed proteins were annotated using Gene Ontology, and neuropilin-1 (NRP1) was identified as the putative GDNF receptor in glioma. NRP1 was more highly expressed in human GBM brains and C6 rat glioma cells than in normal human brains or primary rat astrocytes. Immunofluorescence staining showed that NRP1 was recruited to the membrane by GDNF, and NRP1 co-immunoprecipitated with GDNF. Using the NRP1 and GDNF protein structures to assess molecular docking in the ZDOCK server and visualization with the PyMOL Molecular Graphics System revealed 8 H-bonds and stable positive and negative electrostatic interactions between NRP1 and GDNF. RNAi knockdown of NRP1 reduced proliferation of C6 glioma cells when stimulated with GDNF. NRP1 was an independent risk factor for both survival and recurrence in GBM patients. High NRP1 mRNA expression correlated with shorter OS and DFS (OS: χ2=4.6720, P=0.0307; DFS: χ2=11.013, P=0.0009). NRP1 is thus a GDNF receptor in glioma cells and a potential therapeutic target.
Decadal Changes of Radiocarbon in the Surface Bay of Bengal: Three Decades After Geosecs and One Decade After WOCE

Radiocarbon was measured in the surface seawater dissolved inorganic carbon (DIC) of the Bay of Bengal during November 2006. A meridional transect of the Δ14C in DIC was obtained from measurements in closely spaced samples collected roughly along 88°E. The Δ14C of these samples ranged from 44‰ to 57.7‰ (mean 51.8 ± 1.1‰, n = 12), and 38‰ at one station in the northern Bay of Bengal. The overall pattern of 14C distribution in DIC of surface Bay of Bengal during 2006 was roughly similar to that during the WOCE expedition of 1995. These results indicate a Δ14C decline rate of ∼4‰ per decade since WOCE in the surface Bay of Bengal, which is much smaller compared to a decline rate of ∼25‰ per decade observed in the 2 decades between the GEOSECS and WOCE expeditions, due to the smaller atmosphere-ocean Δ14C gradient.
Pathogenicity and Immunogenicity of aListeria monocytogenes Strain That Requiresd-Alanine for Growth

ABSTRACT Listeria monocytogenes is an intracellular bacterial pathogen that elicits a strong cellular immune response following infection and therefore has potential use as a vaccine vector. However, while infections by L. monocytogenes are fairly rare and can readily be controlled by a number of antibiotics, the organism can nevertheless cause meningitis and death, particularly in immunocompromised or pregnant patients. We therefore have endeavored to isolate a highly attenuated strain of this organism for use as a vaccine vector. d-Alanine is required for the synthesis of the mucopeptide component of the cell walls of virtually all bacteria and is found almost exclusively in the microbial world. We have found in L. monocytogenes two genes that control the synthesis of this compound, an alanine racemase gene (dal) and ad-amino acid aminotransferase gene (dat). By inactivating both genes, we produced an organism that could be grown in the laboratory when supplemented with d-alanine but was unable to grow outside the laboratory, particularly in the cytoplasm of eukaryotic host cells, the natural habitat of this organism during infection. In mice, the double-mutant strain was completely attenuated. Nevertheless, it showed the ability, particularly under conditions of transient suppression of the mutant phenotype, to induce cytotoxic T-lymphocyte responses and to generate protective immunity against lethal challenge by wild-type L. monocytogenes equivalent to that induced by the wild-type organism.
Essential and toxic elements in three Pakistan's medicinal fruits (Punica granatumZiziphus jujuba and Piper cubeba) analysed by INAA

Three important medicinal fruits generally used by the people of Pakistan for the treatment of different diseases have been studied for their mineral contents. Twenty-two major and minor trace elements (essential, toxic and non-essential) were identified in Punica granatum (pomegranate), Ziziphus jujuba (jujube) and Piper cubeba L. (cubeb) by employing instrumental neutron activation analysis technique. The studied medicinal herbs are a good source of the essential elements while toxic elements are found in trace amounts. K is detected as a major element in pomegranate, jujube and cubeb with respective values of 1.20%, 1.18% and 2.01%. Pomegranate has significant concentrations of Na, Zn, Cr and Se; jujube has high Cl, Zn, Mn and Co contents while cubeb is a good source of K and Fe. The baseline data presented in this work can be used in understanding the role of mineral elements in nutritive, preventive and therapeutic properties of medicinal herbs.
Molecular identification of bacteria associated with bacterial vaginosis.

BACKGROUND Bacterial vaginosis affects millions of women and is associated with several serious health conditions. The cause of bacterial vaginosis remains poorly understood despite numerous studies based on cultures. Bacteria in microbial communities can be identified without cultivation by characterizing their ribosomal DNA (rDNA) sequences. METHODS We identified bacteria in samples of vaginal fluid with a combination of broad-range polymerase-chain-reaction (PCR) amplification of 16S rDNA with clone analysis, bacterium-specific PCR assay of 16S rDNA, and fluorescence in situ hybridization (FISH) performed directly on vaginal fluid from 27 subjects with bacterial vaginosis and 46 without the condition. Twenty-one subjects were studied with the use of broad-range PCR of 16S rDNA, and 73 subjects were studied with the use of bacterium-specific PCR. RESULTS Women without bacterial vaginosis had 1 to 6 vaginal bacterial species (phylotypes) in each sample (mean, 3.3), as detected by broad-range PCR of 16S rDNA, and lactobacillus species were the predominant bacteria noted (83 to 100 percent of clones). Women with bacterial vaginosis had greater bacterial diversity (P<0.001), with 9 to 17 phylotypes (mean, 12.6) detected per sample and newly recognized species present in 32 to 89 percent of clones per sample library (mean, 58 percent). Thirty-five unique bacterial species were detected in the women with bacterial vaginosis, including several species with no close cultivated relatives. Bacterium-specific PCR assays showed that several bacteria that had not been previously described were highly prevalent in subjects with bacterial vaginosis but rare in healthy controls. FISH confirmed that newly recognized bacteria detected by PCR corresponded to specific bacterial morphotypes visible in vaginal fluid. CONCLUSIONS Women with bacterial vaginosis have complex vaginal infections with many newly recognized species, including three bacteria in the Clostridiales order that were highly specific for bacterial vaginosis.
Identification of novel causative genes determining the complex trait of high ethanol tolerance in yeast using pooled-segregant whole-genome sequence analysis

High ethanol tolerance is an exquisite characteristic of the yeast Saccharomyces cerevisiae, which enables this microorganism to dominate in natural and industrial fermentations. Up to now, ethanol tolerance has only been analyzed in laboratory yeast strains with moderate ethanol tolerance. The genetic basis of the much higher ethanol tolerance in natural and industrial yeast strains is unknown. We have applied pooled-segregant whole-genome sequence analysis to map all quantitative trait loci (QTL) determining high ethanol tolerance. We crossed a highly ethanol-tolerant segregant of a Brazilian bioethanol production strain with a laboratory strain with moderate ethanol tolerance. Out of 5974 segregants, we pooled 136 segregants tolerant to at least 16% ethanol and 31 segregants tolerant to at least 17%. Scoring of SNPs using whole-genome sequence analysis of DNA from the two pools and parents revealed three major loci and additional minor loci. The latter were more pronounced or only present in the 17% pool compared to the 16% pool. In the locus with the strongest linkage, we identified three closely located genes affecting ethanol tolerance: MKT1, SWS2, and APJ1, with SWS2 being a negative allele located in between two positive alleles. SWS2 and APJ1 probably contained significant polymorphisms only outside the ORF, and lower expression of APJ1 may be linked to higher ethanol tolerance. This work has identified the first causative genes involved in high ethanol tolerance of yeast. It also reveals the strong potential of pooled-segregant sequence analysis using relatively small numbers of selected segregants for identifying QTL on a genome-wide scale.
Internal pH crisis, lysine decarboxylase and the acid tolerance response of Salmonella typhimurium

Salmonella typhimurium possesses an adaptive response to acid that increases survival during exposure to extremely low pH values. The acid tolerance response (ATR) includes both log‐phase and stationary‐phase systems. The log‐phase ATR appears to require two components for maximum acid tolerance, namely an inducible pH homeostasis system, and a series of acid‐shock proteins. We have discovered one of what appears to be a series of inducible exigency pH homeostasis systems that contribute to acid tolerance in extreme acid environments. The low pH‐inducible lysine decarboxylase was shown to contribute significantly to pH homeostasis in environments as low as pH 3.0. Under the conditions tested, both lysine decarboxylase and σs‐dependent acid‐shock proteins were required for acid tolerance but only lysine decarboxylase contributed to pH homeostasis. The cadBA operon encoding lysine decarboxylase and a lysine/cadaverine antiporter were cloned from S. typhimurium and were found to be 79% homologous to the cadBA operon from Escherichia coli. The results suggest that S. typhimurium has a variety of means of fulfilling the pH homeostasis requirement of the ATR in the form of inducible amino acid decarboxylases.
Effect on the inter-nodes cooperative innovation performance of supply chain from knowledge transfer stickiness (KTS)

Knowledge transfer is an important function of inter-nodes cooperative innovation of the supply chain. But there are many difficulties to realize knowledge transfer, which can be named as knowledge transfer stickiness (KTS). The paper divides KTS in cooperative innovation of supply chain as knowledge stickiness, participant stickiness and process stickiness, and divides cooperative innovation performance as knowledge innovation, technology innovation and management innovation performance, and then select knowledge integration as the intermediary variable. The paper examines the effect on cooperative innovation performance from KTS through positive studies based on structural equation model. After data and statistical analysis and a case study of the cooperative innovation between DCT and DFM, the paper indicates that the relationship among KTS, knowledge integration and cooperative innovation performance, and reveals the impact on cooperative innovation performance from KTS. It can be found that knowledge stickiness, participant stickiness both have significant negative impact on knowledge integration, and knowledge integration has significant positive impact on cooperative innovation performance, but the relationship between process stickiness and knowledge integration can not be found, and there is not a positive correlation between knowledge innovation performance and management innovation performance. Meanwhile, it can be found that knowledge integration significantly plays the intermediary role between KTS and cooperative innovation performance. Therefore, nodal enterprises of a supply chain should pay more attentions to decrease KTS systematically and improve the knowledge integration, enhancing the cooperative innovation performance and the competitiveness of supply chain.
The performance of cross-border acquirers from emerging economies

Purpose - – This paper aims to evaluate the value creation of cross-border acquisitions conducted by Chinese firms and determinants that result in the different performance. During the recent decades, the world has witnessed multinational enterprises (MNEs) from emerging economies undertaking aggressive cross-border mergers and acquisitions (M & - As). This phenomenon raises great attention in the international business community, and also challenges the traditional understanding in the extant literature. Design/methodology/approach - – The authors examine 272 cross-border M & - As associated with 48 target countries during the period 1996-2012. Findings - – Evidences show that cross-border expansions on average point to negative performance in the short term. The authors also find that prior cross-border M & - A experiences, ownership structure of the acquirer (state-owned vs private) and acquirer size positively affect the performance of the acquiring firm. Originality/value - – In addition to contributing to cross-border M & - A literature, the findings also provide useful guidance to outward foreign direct investment by firms from emerging economies.
A cleaner bill of health.

The Bioinformatics Links Directory, http://bioinformatics.ca/links_directory, is an actively maintained compilation of servers published in this and previous issues of Nucleic Acids Research issues together with many other useful tools, databases and resources for life sciences research. The 2007 update includes the 130 websites highlighted in the July 2007 Web Server issue of Nucleic Acids Research and brings the total number of servers listed in the Bioinformatics Links Directory to just under 1200 links. In addition to the updated content, the 2007 update of the Bioinformatics Links Directory includes new features for improved navigation, accessibility and open data exchange. A complete listing of all links listed in this Nucleic Acids Research 2007 Web Server issue can be accessed online at, http://bioinformatics.ca/links_directory/narweb2007. The 2007 update of the Bioinformatics Links Directory, which includes the Web Server list and summaries is also available online, at the Nucleic Acids Research web site, http://nar.oupjournals. org.
On the use of stability regions in the numerical analysis of initial value problems

This paper deals with the stability analysis of one-step methods in the numerical solution of initial (-boundary) value problems for linear, ordinary, and partial differential equations. Restrictions on the stepsize are derived which guarantee the rate of error growth in these methods to be of moderate size. These restrictions are related to the stability region of the method and to numerical ranges of matrices stemming from the differential equation under consideration. The errors in the one-step methods are measured in arbitrary norms (not necessarily generated by an inner product). The theory is illustrated in the numerical solution of the heat equation and some other differential equations, where the error growth is measured in the maximum norm.
Actively Managed Mutual Funds Holding Passive Investments: What Do ETF Positions Tell Us About Mutual Fund Ability?

We provide the first in-depth examination of exchange-traded funds (ETFs) within actively managed mutual fund (AMMF) portfolios to better understand why AMMFs make substantial investments in passive ETFs. We examine the association between holding ETF positions and AMMF performance, as well as indirect measures of performance, including market timing, flow management, and cash holdings. We find that over one-third of AMMFs take an ETF position between 2004 and 2015. Our results indicate that AMMFs allocating large portions of their portfolio to ETFs perform worse, by between 0.41% and 1.63% annually using various performance measures. These AMMFs also exhibit worse market timing and hold more cash. In contrast, AMMFs that hold ETFs in small amounts have similar characteristics to non-user AMMFs. Therefore, the act of holding an ETF does not signal inferior ability, however, taking large ETF positions does.