Miracle-dz/UniFAR-FTUs huggingface dataset:
Susceptibilities of healthcare- and community-associated methicillin-resistant staphylococci to the novel des-F(6)-quinolone DX-619.

OBJECTIVES The aim of the study was to test in vitro activities of the novel des-F(6)-quinolone DX-619 against methicillin-resistant staphylococci (MRS) isolated in hospitals and communities and to compare its activity with other quinolones, sitafloxacin and levofloxacin, and antibiotics used for the treatment of methicillin-resistant Staphylococcus aureus infection, including vancomycin, teicoplanin, arbekacin, linezolid and quinupristin/dalfopristin. METHODS MICs were determined by the agar dilution method using healthcare-associated MRS (S. aureus including strains with reduced susceptibility to vancomycin, 103; coagulase-negative staphylococci, 87) and community-associated MRS (S. aureus including non-multiresistant oxacillin-resistant strains, 37; coagulase-negative staphylococci, 92). The quinolone resistance-determining regions of gyrA, gyrB, grlA and grlB genes from six strains with reduced susceptibility to DX-619 were sequenced. RESULTS DX-619 showed the lowest MIC(90) values for all categories of strains tested, irrespective of the degree of glycopeptide resistance. The six strains with MIC values of >128 mg/L of levofloxacin commonly carried two mutations in gyrA and two mutations in grlA. DX-619 showed potent activity against strains with MIC values of 2 mg/L. CONCLUSIONS DX-619 was potent against all MRS tested, suggesting that it would be a promising candidate for the treatment of methicillin-resistant S. aureus infection if sufficient in vivo concentrations were safely attained.
Network patterns and social architecture in Massively Multiplayer Online Games: Mapping the social world of EverQuest II

This paper presents a critical examination of the social interactions among Massively Multiplayer Online Game (MMOG) participants. Drawing on the conceptual framework of “third places” and prior empirical studies, this study aims to map the social world of a popular MMOG, EverQuest II, primarily relying on unobtrusively collected behavioral server logs. Analysis of network patterns revealed that the social architecture of the world was quite effective in shaping the structure of interaction, as the involvement in various social networks was influenced by class choice and character level. However, sociability among players was quite diffuse, with a sizable number of players opting to play solo despite the built-in mechanisms that encourage collaborative play.
RNA sequence variants in live poliovirus vaccine and their relation to neurovirulence

Mutant analysis by polymerase chain reaction and restriction enzyme cleavage (MAPREC) was used to study sequence heterogeneity and stability in attenuated poliovirus type 3 at positions in which the vaccine virus differs from its wild-type progenitor. Of seven genomic positions tested, only two (positions 472 and 2493) show nucleotide heterogeneity. Propagation of the vaccine virus in cell cultures leads to rapid selection of virus with reversions at these two positions of the genome. The relative abundance of reversions at position 472 correlates with the results of monkey neurovirulence tests, while the mutation at position 2493 is not directly associated with neurovirulence of the virus in monkeys. Instead, the abundance of mutations at the latter position correlates with the source of the seed virus and its passage level. These results further indicate that MAPREC at position 472 can be used to assess the quality of poliovirus type 3 vaccine.
Extraction, Identification, and Functional Characterization of a Bioactive Substance From Automated Compound-Handling Plastic Tips

Disposable plastic labware is ubiquitous in contemporary pharmaceutical research laboratories. Plastic labware is routinely used for chemical compound storage and during automated liquid-handling processes that support assay development, high-throughput screening, structure-activity determinations, and liability profiling. However, there is little information available in the literature on the contaminants released from plastic labware upon DMSO exposure and their resultant effects on specific biological assays. The authors report here the extraction, by simple DMSO washing, of a biologically active substance from one particular size of disposable plastic tips used in automated compound handling. The active contaminant was identified as erucamide ((Z)-docos-13-enamide), a long-chain mono-unsaturated fatty acid amide commonly used in plastics manufacturing, by gas chromatography/mass spectroscopy analysis of the DMSO-extracted material. Tip extracts prepared in DMSO, as well as a commercially obtained sample of erucamide, were active in a functional bioassay of a known G-protein-coupled fatty acid receptor. A sample of a different disposable tip product from the same vendor did not release detectable erucamide following solvent extraction, and DMSO extracts prepared from this product were inactive in the receptor functional assay. These results demonstrate that solvent-extractable contaminants from some plastic labware used in the contemporary pharmaceutical research and development (R&D) environment can be introduced into physical and biological assays during routine compound management liquid-handling processes. These contaminants may further possess biological activity and are therefore a potential source of assay-specific confounding artifacts.
Pathways for recent Cerrado soybean expansion: extending the soy moratorium and implementing integrated crop livestock systems with soybeans

The Brazilian Soy Moratorium has effectively reduced forest conversion for soybeans in Amazonia. This has come at the expense of the region’s pasturelands, which have increasingly ceded space for compliant soy expansion. The question of extending the policy to the Cerrado, where recent soy expansion has come at the cost of ecologically valuable vegetation, plugs into a wider discussion on how to reconcile competing commodities on finite amounts of cleared area. Innovative management strategies that allow different land uses to coexist are urgently needed. Integrated crop-livestock systems with soybeans (ICLS) rotates beef and soy on the same area, and shows promise as a means to improve production, farmer benefit, and environmental impacts. Here we reconstruct historical land use maps to estimate Cerrado Soy Moratorium outcomes with benchmark years in 2008 and 2014, we then estimate additional production afforded by ICLS implementation between 2008 and 2014. We find that if a 2008 Cerrado Soy Moratorium were in place, 0.7 Mha of 2014 Cerrado soy area would currently be in violation of the policy. Roughly 96% of this acreage is found in Matopiba (82%) and Mato Grosso (14%) states, suggesting that adoption may have slowed recent production in these rapidly transforming soy centers, in contrast to central and southwestern Cerrado where there is more concentrated eligible expansion area. Changing the benchmark to 2014 could have added 0.7 Mha of eligible expansion area, though over 80% of these additions would be in states with the most 2008 eligible area (Distrito Federal, Mato Grosso, Maranhão, Minas Gerais, Mato Grosso do Sul). Meanwhile, ICLS adoption could have added between 4.0 and 32 Mha of new soy land to the study area without additional clearing between 2008 and 2014, though this would depend on rigorous accompanying land zoning policy to guide implementation. The roughly 5 Mha of Cerrado soybean expansion that actually occurred between 2008 and 2014 could have been accommodated on 2008 suitable pasture area given an ICLS rotation frequency of every 6 years or less. Conservation estimates presented here represent the upper limit of what is possible, as our scenario modeling does not account for variables such as leakage, laundering, or rebound effects.
Drosophila RNA Polymerase II Mutants That Affect Transcription Elongation (*)

We have examined the properties of two Drosophila RNA polymerase II mutants, C4 and S1, during elongation, pyrophosphorolysis, and DmS-II-stimulated transcript cleavage. The C4 and S1 mutants contain a single amino acid substitution in the largest and second largest subunits, respectively. Compared with wild type, C4 had a lower elongation rate and was less efficient at reading through intrinsic elongation blocks. S1 had a higher elongation rate than wild type and was more efficient at reading through the same blocks. During elongation, C4 and wild type responded similarly to DmS-II and NH, whereas the S1 mutant was less responsive to both. Differences between the two mutants also appeared during DmS-II-mediated transcript cleavage and pyrophosphorolysis. During extended pyrophosphorolysis, S1 polymerase was fastest and C4 polymerase was slowest at generating the final pattern of shortened transcripts. S1 and wild type were equal in the rate of extended DmS-II-mediated transcript cleavage, and C4 was slower. Our results suggest that the S1 mutation increases the time spent by the polymerase in elongation competent mode and that the C4 mutation may affect the movement of the polymerase.
Expression of microRNA-218 and its clinicopathological and prognostic significance in human glioma cases.

BACKGROUND MicroRNAs are a class of noncoding RNAs which regulate multiple cellular processes during tumor development. The purpose of this report is to investigate the clinicopathological and prognostic significance of miR-218 in human gliomas. MATERIALS AND METHODS Quantitative RT-PCR (qRT-PCR) was conducted to detect the expression of miR-218 in primary normal human astrocytes, three glioma cell lines and 98 paired glioma and adjacent normal brain tissues.Associations of miR-218 with clinicopathological variables of glioma patients were statistically analyzed. Finally, a survival analysis was performed using the Kaplan-Meier method and Cox's proportional hazards model. RESULTS The expression level of miR-218 in primary normal human astrocytes was significantly higher than that in glioma cell lines (p<0.01). Also, the expression level of miR-218 in glioma tissues was significantly downregulated in comparison with that in the adjacent normal brain tissues (p<0.001). Statistical analyses demonstrated that low miR-218 expression was closely associated with advanced WHO grade (p=0.002) and low Karnofsky performance score (p=0.010) of glioma patients. Kaplan-Meier analysis with the log-rank test showed that patients with low-miR-218 expression had poorer disease-free survival and overall survival (p=0.0045 and 0.0124, respectively). Multivariate analysis revealed that miR-218 expression was independently associated with the disease-free survival (p=0.009) and overall survival (p=0.004) of glioma patients. CONCLUSIONS Our results indicate that miR-218 is downregulated in gliomas and that its status might be a potential valuable biomarker for glioma patients.
Why are some graduate entrepreneurs more innovative than others? The effect of human capital, psychological factor and entrepreneurial rewards on entrepreneurial innovativeness

Abstract This study investigates the innovation behaviour of graduate start-ups at the individual level. It bridges the graduate enterprise literature and innovative entrepreneurship literature to put forward three arguments that ascertain why highly educated graduate entrepreneurs are not always innovative in starting new businesses. First, anchoring on the individual opportunity costs–entrepreneurial rewards nexus, it argues that graduate entrepreneurs will exploit opportunities innovatively if they expect the levels of entrepreneurial rewards that match their high human capital and high opportunity costs. Second, it is argued that entrepreneurial innovativeness is conditional on psychological factors such as students’ managerial self-efficacy and overconfidence. Third, it is also argued that the nonlinear relationship between entrepreneurial innovativeness and entrepreneurial rewards will drive graduate entrepreneurs to exploit even riskier opportunities in search for high rewards. This study operationalizes the theoretical framework with an empirical model and estimates it using a graduate entrepreneur sample from a questionnaire survey in China. Our results suggest that innovation behaviour of graduate start-ups is influenced by the quantity of human capital, psychological make-up and expectations of entrepreneurial rewards.
Variation Among Cell Types in the Signaling Pathways by which IGF-I Stimulates Specific Cellular Responses*

This review compares the signaling pathways leading to cellular responses (primarily proliferation and differentiation) of cells to the insulin-like growth factors (IGFs). Although some systems (such as myoblasts and adipocytes) clearly employ the Ras-Raf-Mitogen Activated Protein (MAP) kinase pathway in signaling for cell proliferation, others (such as MCF-7 mammary tumors and brain capillary cells) proliferate in response to signals mediated by phosphatidylinositol-3 kinase and p70 S6 kinase. Similarly, most of the systems surveyed use a phosphatidylinositol-3 kinase pathway in differentiating in response to IGFs, but others (such as SH-SY5Y neuroblastoma cells) differentiate in response to the MAP kinase pathway. Thus, it seems that there are no simple generalizations that can be used to forecast the signaling pathway that will be involved in any response to the IGFs.
Association states of the transcription activator protein NtrC from E. coli determined by analytical ultracentrifugation.

The transcription activator protein NtrC (nitrogen regulatory protein C) can catalyze the transition of E. coli RNA polymerase complexed with the sigma54 factor (RNAP.sigma54) from the closed complex (RNAP.sigma54 bound at the promoter) to the open complex (melting of the promoter DNA). This process involves phosphorylation of NtrC, assembly of a multimeric NtrC complex at the enhancer DNA sequence, interaction of this complex with promoter bound RNAP. sigma54 via DNA looping, and hydrolysis of ATP. We have used analytical ultracentrifugation to study the different NtrC association states and to derive hydrodynamic models for the conformation of the various NtrC species. The following results were obtained. (i) The unphosphorylated wild-type protein formed a dimer with a measured molecular weight of 102(+/-3) kDa, which compares to a calculated molecular weight of 54 kDa for a monomer (concentration range studied 2 to 8 microM NtrC monomer). (ii) In the unphosphorylated state one NtrC dimer was bound to one binding site as determined with DNA oligonucleotide duplexes containing one or two binding sites (concentration range studied 50 to 1000 nM NtrC dimer). (iii) The data obtained at protein concentrations that were below the concentration of binding sites indicate that binding to the DNA duplex with two binding sites occurred with essentially no cooperativity. The experiments were conducted in the absence of ATP. (iv) The phosphorylated protein formed a specific complex at the DNA duplex with the enhancer sequence (two NtrC binding sites) that consisted of four dimers (concentration range studied 100 to 1000 nM NtrC dimer). (v) The formation of this octameric complex was highly cooperative, and the data suggest that two DNA strands could bind simultaneously to this complex. (vi) From the sedimentation data a model was derived in which the NtrC dimer adopts a V shaped structure with the DNA binding domains being located at the bottom and the two receiver domains at the top of the V. In this conformation higher order NtrC complexes can be stabilized by interaction between the phosphorylated receiver domain and the central activation domain of different NtrC dimers.
Navigating around the DRCs statistical potholes: new estimates on welfare and poverty trends (2005-2012) following a spatially disaggregated approach

Relying on two rounds of household budget data (2005 and 2012), this paper presents a proposal for an integrated analysis of the most recent changes in welfare and poverty in the Democratic Republic of the Congo (DRC). Confronted with various methodological challenges, it proposes four ways to improve comparability of welfare and poverty across time and space. Its most salient feature is the high degree of spatial precision, which aims to capture better the variation in living conditions and economic opportunities in the DRC. Compared with the official statistics, this approach yields a completely different poverty outlook, both in terms of levels and trends. The new estimates are also triangulated with changes in undernutrition. Using the consumption indicator generated by this approach, growth at the micro level on average has been slightly positive and pro-poor for urban households, while negative and pro-rich for their rural counterparts. The combined effect of these opposing welfare trends is a minor reduction of poverty in Congolese cities and an increase in the countryside. Marked regional differences however exist, which we classify in four welfare trends. Given the differences between our analysis and the official statistics, further work is needed to check on the proposed methodology, on the robustness of the results and on the resulting poverty profile.
Detection of Pathogenic Leptospira Bacteria in Pinniped Populations via PCR and Identification of a Source of Transmission for Zoonotic Leptospirosis in the Marine Environment

ABSTRACT Leptospirosis, caused by the spirochete Leptospira, is a geographically widespread disease that affects a broad range of mammals, including marine mammals. Among pinniped populations, periodic epizootics of leptospirosis are responsible for significant die-offs. Along the west coast of North America, the most recent leptospirosis epizootic occurred in 2004, during which samples were collected from cases ranging from California to British Columbia. The primary objective of this study was to use this well-defined sample set to determine the feasibility of using PCR techniques to diagnose Leptospira infection among pinniped populations in comparison with diagnostic methodologies commonly used for marine mammals. Successful amplification was achieved from a variety of samples, including freshly collected urine, urine stored at −80°C for less than 6 months, and kidney (freshly collected, frozen, and decomposed), as well as feces- and urine-contaminated sand collected in the vicinity of a live-stranded animal. Pathological examination of tissue collected from Leptospira-infected animals revealed the presence of leptospiral antigen in the kidneys. The use of species-specific primer pairs revealed a pattern of host specificity for Leptospira interrogans in sea lions and Leptospira kirschneri in elephant seals. These studies indicate PCR is a sensitive and specific diagnostic tool for the detection of Leptospira infection in pinnipeds and reveal a potential source for epizootic, enzootic, and zoonotic spread of leptospirosis in a marine environment.
Atrial Electromechanical Delay Is Impaired in Patients with Psoriasis

Objective: In this study, we aimed to investigate atrial electromechanical delay (EMD) in patients with psoriasis. Subjects and Methods: A total of 43 patients with psoriasis (26 mild-moderate, 17 severe) and 17 healthy control subjects were enrolled. Patients with psoriasis were divided into two groups: the mild-moderate group and the severe group according to their psoriasis area severity index (PASI) scores. Atrial EMD was measured from the lateral mitral annulus and called ‘PA lateral', from the septal mitral annulus, called ‘PA septal', and from the right ventricle tricuspid annulus, called ‘PA tricuspid'. Atrial EMD was defined as the time interval from the onset of atrial electrical activity (P wave on surface ECG) to the beginning of mechanical atrial contraction (late diastolic A wave). All three groups were compared with each other, and correlation analysis was performed to investigate the relationship between the PASI score and interatrial EMD. Results: PA lateral was significantly higher in both the mild-moderate psoriasis group and the severe psoriasis group compared to controls (69 ± 12 and 78 ± 13 vs. 60 ± 6 ms; p = 0.001). Also, PA septal (63 ± 11 vs. 53 ± 6 ms; p = 0.005, post hoc analysis) and PA tricuspid (49 ± 7 vs. 41 ± 5 ms; p = 0.009, post hoc analysis) were significantly higher in the severe psoriasis group than in the control group. Correlation analysis revealed that the PASI score was well correlated with PA lateral (r = 0.520, p < 0.001), PA septum (r = 0.460, p = 0.002), interatrial EMD (r = 0.371, p = 0.014) and intra-atrial EMD (r = 0.393, p = 0.009). Conclusion: Atrial EMD was prolonged in patients with psoriasis. The measurement of atrial EMD might be used to determine the risk of development of AF in patients with psoriasis.
Role of antimicrobial applications to the umbilical cord in neonates to prevent bacterial colonization and infection: a review of the evidence

Indeveloping countries umbilical cord infections constitute a major cause of neonatal morbidity and pose significant risk for mortality, whereas outbreaks of cord infections continue to occur in developed country nurseries. Cord infections in developing countries can be prevented through increasing access to tetanus toxoid immunization during pregnancy, promoting clean cord care and reducing harmful cord applications and behaviors. Interventions introduced in both developed and developing countries to reduce exposure of the cord to infectious pathogens include clean cord cutting, hand-washing before and after handling the baby, bathing of the infant with antimicrobial agents and application of antimicrobials to the cord. Despite the importance of umbilical cord care, both traditionally and medically, there have been few randomized trials investigating the impact of different cord care regimens on rates of local or systemic infections, particularly in developing countries. This review examines available data on umbilical cord care, with a particular focus on those comparing rates of bacterial colonization and/or rates of cord infection among neonates receiving different umbilical cord care regimens. Although most investigators agree that topical antimicrobials reduce bacterial colonization of the cord, a firm relationship between colonization and infection has not been established. Further research in developed countries, including follow-up beyond hospital discharge, is required before advising on “best cord care practices. ” The paucity of published reports from developing countries indicates the need to investigate the impact of antimicrobial applications on cord and systemic infections in a community-based, prospective manner.
Polymethoxylated Flavones from Orange Peels Inhibit Cell Proliferation in a 3D Cell Model of Human Colorectal Cancer

ABSTRACT Polymethoxylated flavones (PMFs) have been recognized to inhibit colorectal cancer proliferation through various mechanisms, however most of these studies have been performed on cells grown as monolayers that present limitations in mimicking the 3D tumor architecture and microenvironment. The main aim of this study was to investigate the anticancer potential of an orange peel extract (OPE) enriched in PMFs in a 3D cell model of colorectal cancer. The OPE was developed by supercritical fluid extraction and the anticancer effect was evaluated in HT29 spheroids cultures in a stirred-tank based system. Results showed that OPE inhibited cell proliferation, induced cell cycle arrest (G2/M phase), promoted apoptosis, and reduced ALDH+ population on HT29 spheroids. The antiproliferative activity was significantly lower than that obtained for 2D model (EC50 value of 0.43 ± 0.02 mg/mL) and this effect was dependent on diameter and cell composition/phenotype of spheroids derived from different culture days (day 3 – 0.53 ± 0.05 mg/mL; day 5 – 0.55 ± 0.03 mg/mL; day 7 – 1.24 ± 0.15 mg/mL). HT29 spheroids collected at day 7 presented typical characteristics of in vivo solid tumors including a necrotic/apoptotic core, hypoxia regions, presence of cancer stem cells, and a less differentiated invasive front. Nobiletin, sinesentin, and tangeretin were identified as the main compounds responsible for the anticancer activity.