Miracle-dz/UniFAR-FTUs huggingface dataset:
afsR is a pleiotropic but conditionally required regulatory gene for antibiotic production in Streptomyces coelicolor A3(2)

The N‐terminal region of AfsR, a putative pleiotropic regulatory protein for antibiotic production in Strepto‐myces coelicolor A3(2), is homologous to RedD and ActII‐ORF4, pathway‐specific regulatory proteins required for the production of the antibiotics undecylprodigiosin (Red) and actinorhodin (Act), respectively. The recent identification of afsS, which lies immediately 3′ of afsR and which stimulates antibiotic production when cloned at high copy number, questioned whether afsR was a pleiotropic regulatory gene. In this study we demonstrate that multiple copies of afsR can stimulate both Act and Red production and that, despite its homology, it cannot substitute for the pathway‐specific regulatory genes. Moreover, an in‐frame deletion that removed most of the afsR coding sequence resulted in loss of Act and Red production, and a marked reduction in the synthesis of the calcium‐dependent antibiotic (CDA), but only under some (non‐permissive) nutritional conditions. Although additional copies of afsR resulted in elevated levels of the actII‐ORF4 and redD transcripts, transcription of the pathway‐specific regulatory genes under non‐permissive conditions was unaffected by deletion of afsR. While afsR may operate independently of the pathway‐specific regulatory proteins to influence antibiotic production, the activity of ActII‐ORF4 and of RedD under non‐permissive conditions could depend on interaction with, or modification by, AfsR.
Purification of Proteins Susceptible to Oxidation at Cysteine Residues: Identification of Malate Dehydrogenase as a Target for S‐Glutathiolation

Abstract: The cysteine residues of proteins are susceptible to a range of oxidative modifications, including S‐glutathiolation. Here we present a study in which we used glutathione‐agarose to purify cardiac proteins that undergo S‐glutathiolation during oxidative stress. We then identified one of the oxidized proteins as malate dehydrogenase.
Distribution and Relationships of Antimicrobial Resistance Determinants among Extended-Spectrum-Cephalosporin-Resistant or Carbapenem-Resistant Escherichia coli Isolates from Rivers and Sewage Treatment Plants in India

ABSTRACT To determine the distribution and relationship of antimicrobial resistance determinants among extended-spectrum-cephalosporin (ESC)-resistant or carbapenem-resistant Escherichia coli isolates from the aquatic environment in India, water samples were collected from rivers or sewage treatment plants in five Indian states. A total of 446 E. coli isolates were randomly obtained. Resistance to ESC and/or carbapenem was observed in 169 (37.9%) E. coli isolates, which were further analyzed. These isolates showed resistance to numerous antimicrobials; more than half of the isolates exhibited resistance to eight or more antimicrobials. The blaNDM gene was detected in 14/21 carbapenem-resistant E. coli isolates: blaNDM-1 in 2 isolates, blaNDM-5 in 7 isolates, and blaNDM-7 in 5 isolates. The blaCTX-M gene was detected in 112 isolates (66.3%): blaCTX-M-15 in 108 isolates and blaCTX-M-55 in 4 isolates. We extracted 49 plasmids from selected isolates, and their whole-genome sequences were determined. Fifty resistance genes were detected, and 11 different combinations of replicon types were observed among the 49 plasmids. The network analysis results suggested that the plasmids sharing replicon types tended to form a community, which is based on the predicted gene similarity among the plasmids. Four communities each containing from 4 to 17 plasmids were observed. Three of the four communities contained plasmids detected in different Indian states, suggesting that the interstate dissemination of ancestor plasmids has already occurred. Comparison of the DNA sequences of the blaNDM-positive plasmids detected in this study with known sequences of related plasmids suggested that various mutation events facilitated the evolution of the plasmids and that plasmids with similar genetic backgrounds have widely disseminated in India.
Immunoglobulin G (IgG) Anti-Tissue Transglutaminase Antibodies Used as Markers for IgA-Deficient Celiac Disease Patients

ABSTRACT The role of immunoglobulin A (IgA) anti-tissue transglutaminase antibodies (IgA-tTG) as predictors of untreated celiac disease (CoD) is well documented, and the presence and levels of these antibodies are most accurately monitored with native or recombinant human antigens. However, IgA-deficient CoD patients are not identified by IgA serology, and conflicting results concerning the diagnostic validity of IgG antibodies against gliadin (IgG-AGA), endomysium (IgG-EmA), and tTG (IgG-tTG) have been reported. The aim of the present study was to evaluate the utility of IgG-tTG for the detection of CoD in IgA-deficient patients. Samples from 115 IgA-deficient and 200 IgA-sufficient subjects were collected and tested for the presence of IgA and IgG antibodies against tTG, EmA, and AGA. Antibodies against tTG were measured by an enzyme-linked immunosorbent assay based on recombinant human tTG, and antibodies against EmA were determined by immunofluorescence. The values for IgG-tTG showed a higher correlation (correlation coefficient [r] = 0.91) with those for IgG-EmA for the IgA-deficient subjects than for the IgA-sufficient subjects (r = 0.88). The overall concordance of the positive and negative results between IgG-tTG and IgG-EmA was 97%, and the IgG-tTG assay discriminated between IgG-EmA-positive and -negative subjects with IgA deficiency at a rate of 100%. Elevated levels of IgG-tTG and IgG-EmA were measured in 70% of the IgA-sufficient subjects. IgG-tTG detection with recombinant human tTG is a good alternative to IgG-EmA detection, and the addition of IgG-tTG assessment to present screening methods may improve the ability to identify IgA-deficient subjects with CoD.
Scalable Node-Centric Route Mutation for Defense of Large-Scale Software-Defined Networks

Exploiting software-defined networking techniques, randomly and instantly mutating routes can disguise strategically important infrastructure and protect the integrity of data networks. Route mutation has been to date formulated as NP-complete constraint satisfaction problem where feasible sets of routes need to be generated with exponential computational complexities, limiting algorithmic scalability to large-scale networks. In this paper, we propose a novel node-centric route mutation method which interprets route mutation as a signature matching problem. We formulate the route mutation problem as a three-dimensional earth mover’s distance (EMD) model and solve it by using a binary branch and bound method. Considering the scalability, we further propose that a heuristic method yields significantly lower computational complexities with marginal loss of robustness against eavesdropping. Simulation results show that our proposed methods can effectively disguise key infrastructure by reducing the difference of historically accumulative traffic among different switches. With significantly reduced complexities, our algorithms are of particular interest to safeguard large-scale networks.
Cell lines used in prostate cancer research: a compendium of old and new lines--part 1.

PURPOSE This is part 1 of a 2-part review. Research into the molecular mechanisms underlying the various aspects of prostate cancer (PCa) requires the use of in vivo and in vitro model systems. In the last few years many new cell lines have been established by investigators from primary tissue sources and clonal derivatives of previously established lines. Therefore, the purpose of this 2-part review is to catalogue the current human cell lines developed for PCa research, as reported in the literature. Part 1 includes tissue culture cell lines derived from metastases, primary tumors and nonadenocarcinomas that were established without the use of transgenes. It also includes a section describing lines that have been contaminated with other lines, shown not to be of prostatic origin or whose identity is being challenged. MATERIALS AND METHODS Prostate cell lines included in this review were identified by extensive searching of the literature using several strategies, including PubMed searches and book chapter reviews. RESULTS In total we describe the derivation, phenotype, genotype and characterization of molecular markers expressed by approximately 200 lines and sublines used in PCa research, including those derived from primary tumors, metastases and normal prostate tissue. We paid particular attention to the expression of prostate specific antigen, androgen receptor, cytokeratins and other molecular markers used to indicate the status of PCa and the prostatic lineage of a given line. In an attempt to provide PCa researchers with a resource of information regarding new and established cell lines we have also created an online database of these PCa cell lines freely accessible via the World Wide Web at http://www.CaPCellLines. com. The web based interface allows researchers to peruse and print information regarding cell lines, add new cell lines and update or add new information regarding established cell lines. CONCLUSIONS This compendium of cell lines currently used in PCa research combined with access to our on-line database provides researchers with a continually updated and valuable resource for investigating the molecular mechanisms of PCa.
Computer-aided acute leukemia blast cells segmentation in peripheral blood images

Computer-aided diagnosis system of leukemic cells is vital tool, which can assist domain experts in the diagnosis and evaluation procedure. Accurate blast cells segmentation is the initial stage in building a successful computer-aided diagnosis system. Blast cells segmentation is still an open research topic due to several problems such as variation of blats cells in terms of color, shape and texture, touching and overlapping of cells, inconsistent image quality, etc. Although numerous blast cells segmentation methods have been developed, only few studies attempted to address these problems simultaneously. This paper presents a new image segmentation method to extract acute leukemia blast cells in peripheral blood. The first aim is to segment the leukemic cells by mean of color transformation and mathematical morphology. The method also introduces an approach to split overlapping cells using the marker-controlled watershed algorithm based on a new marker selection scheme. Furthermore, the paper presents a powerful approach to separate the nucleus region and the cytoplasm region based on the seeded region growing algorithm powered by histogram equalization and arithmetic addition to handle the issue of non-homogenous nuclear chromatin pattern. The robustness of the proposed method is tested on two datasets comprise of 1024 peripheral blood images acquired from two different medical centers. The quantitative evaluation reveals that the proposed method obtain a better segmentation performance compared with its counterparts and achieves remarkable segmentation results of approximately 96 % in blast cell extraction and 94 % in nucleus/cytoplasm separation.
Is AIDS chronic or terminal? The perceptions of persons living with AIDS and their informal support partners

Abstract Viewed as a terminal disease just a decade ago, HIV/AIDS is now often characterized as a chronic yet manageable disease. The goal of this study is to assess the perceptions of the course of the disease among persons living with AIDS and their informal support partners and to identify the themes that distinguish the differing perceptions of the epidemic. The findings from this research reveal that 41% of persons living with AIDS and 39% of their informal support partners perceive AIDS as chronic. By contrast, 37% of persons living with AIDS and 39% of the informal support partners perceive AIDS to be terminal rather than chronic. Among persons living with HIV/AIDS, those with lower levels of education and higher levels of perceived race-based discrimination were significantly more likely to view AIDS as a terminal rather than chronic condition. In addition, informal support partners in poor health were significantly more likely than others to view AIDS as terminal rather than chronic. Content analyses of the qualitative data revealed five broad themes related to the specific perceptions of AIDS, including medications, personal experience, cure, time/eventuality and education. The implications of these findings are discussed.
Effect of honey supplementation into Tris Extender on Cryopreservation of Bull Spermatozoa

The aim of this study was to evaluate the effects of using honey as a supplement into Tris extender in comparison with a commercial Bioxcell ® extender on bull semen cryopreservation quality. Semen samples from four fertile bulls, which comprised of two Friesian Sahiwal, one Braford and one Kedah-Kelantan breeds, were collected using an electro-ejaculation method. Collected samples were freshly evaluated physically and microscopically before divided and diluted using four Tris-based extenders containing 0% (control), 2.5%, 5% and 10% honey, and a commercial Bioxcell ® extender. The processed semen was equilibrated at 5°C for 3 h (chilling), packed into straws (0.25 ml), frozen and stored in a liquid nitrogen tank for 24 h before thawing and assessment of quality. Semen quality parameters used for evaluation and comparison after chilling and thawing included general and progressive motility (analyzed using a computer assisted semen analyzer), livability and sperm morphology (done using eosin-nigrosin staining technique). The experiment revealed that among all Tris-based extenders, improved postcryopreservation semen quality was obtained from Tris+2.5% honey; comparable to Bioxcell ® which was superior to all other extenders. Use of honey at concentrations of 5 and 10% however, were not suitable and showed significantly poor semen quality following cryopreservation. Therefore, Tris extender with 2.5% honey could be considered as a cheaper alternative to Bioxcell ® as it could be prepared in the laboratory whenever needed.
Long-term regulation of neuronal calcium currents by prolonged changes of membrane potential

Although rapid-onset, short-term regulation of neuronal Ca currents by neurotransmitters and second messengers is well documented, little is known about conditions that can cause longer-lasting changes in Ca channel function. We report here that persistent depolarization is accompanied by slowly developing long-term reduction of neuronal Ca currents. Rat myenteric neurons grown in cell culture for 1–7 d were studied with the tight-seal whole-cell recording technique. Macroscopic Ca-channel currents had decaying and sustained components at all days studied. When the neurons were grown in medium containing 25 mM KCl, which depolarized them to -40 mV and caused significant elevation of intracellular Ca, the densities of both components of Ca-channel current decreased by 40–80%. Several results suggest that different mechanisms underlie the downregulation of the two components. (1) The density of the decaying component decreased approximately four times faster than did that of the sustained component. (2) When neurons were returned to control medium, which contained 5 mM KCl, the density of the sustained component returned to control levels within 24 hr, while that of the decaying component did not recover significantly. (3) Inhibitors of RNA and protein synthesis reduced or prevented downregulation of the sustained but not of the decaying component. (4) The dihydropyridine antagonist nitrendipine, which prevented the sustained elevation of intracellular Ca in neurons grown in 25 mM KCl, prevented downregulation of the sustained component but had no effect on downregulation of the decaying component. We suggest that these forms of regulation of Ca current density could help neurons adapt to altered levels of electrical activity and may contribute to changes in synaptic strength that occur during periods of increased or decreased electrical activity.
Reply: Glucagon-like peptide-1 mediates cardioprotection by remote ischaemic conditioning.

We read with interest the Letter by Drs Giblett and Hoole in response to our research article ‘Glucagon-Like Peptide-1 (GLP-1) Mediates Cardioprotection by Remote Ischaemic Conditioning’. 1 We thank Drs Giblett and Hoole for their interest in our work and provide our responses to the critical comments raised. First, we believe that it is not entirely appropriate to compare the effects of exogenous application of native GLP-1 or GLP-1 receptor (GLP-1R) agonists with the effects induced by remote ischaemic conditioning (RIc). The efficacy of RIc in protecting against left ventricular dysfunction and myocardial stunning may be compromised by the study design and/or inability of a significant proportion of patients to recruit vagal activity, which appears to be critically important for RIc cardioprotection.2,3 We reported that in rats vagotomy blocks RIc cardioprotection, …
Characteristics of hydrocarbon uptake in cultures with two liquid phases

In hydrocarbon fermentation, the efficiency of hydrocarbon uptake by cells ins one of the keys to the economical production of single‐cell protein. This work is concerned with characterization of cultures with two liquid phases for understanding the hydrocarbon uptake process by cells. Batch cultivation of Candida lipolytica was carried out in shaking flasks and in a tower fermentor with motionless mixers. Micorscopic observation and cell and hydrocarbon concentration distribution in batch cultivation showed that some cells are attached to the large oil drops ad others are free from them. Interfacial tension between oil and water and Sauter mean drop size decreased as cultivation proceeded. On the basis of the experimental results, the process of hydrocarbon uptake by cells is discussed.
A haemophagocytic lymphohistiocytosis (HLH)-like picture following breastmilk transmitted cytomegalovirus infection in a preterm infant

Due to septic illness, neutro- and thrombocytopenia, blocked myelopoiesis, CMV-positive breast milk and CMV-pp65 antigen in bone marrow mononuclear cells, CMV-related HLH was presumed in a breast fed neonate (gestational age 24 weeks). Treatment was successful with foscarnet and methylprednisolone. HLH may be a complication of post-natal CMV-infection acquired from breast milk.
Stem cell transcription factor NANOG in cancers – is eternal youth a curse?

ABSTRACT Introduction: Targeting cancer stem cells can be a more effective approach to treat cancer. NANOG is one of the key factors for maintaining the self-renewal ability and pluripotency of stem cells, including cancer stem cells. Overexpression of NANOG has been observed in various human malignancies. Several reports have suggested that NANOG contributes to carcinogenesis by initiating and preserving cancer stem cells. It is obvious that NANOG is also involved in establishing other hallmarks of cancer such as uncontrolled cell growth, chemoresistance, metastasis, and immune evasion. Areas covered: This review will discuss the molecular properties and oncogenic roles of NANOG. The idea of using agents that inhibit the transcription factor to treat cancer is presented. Interfering with NANOG-mediated transcriptions using small interfering RNA, transcription factor decoy, genome editing, and small-molecule inhibitors may provide novel strategies to target cancer stem cells. Expert opinion: As a pivotal controller in cancer stem cell maintenance and a positive regulator of various oncogenic pathways, NANOG may be an important target for cancer therapy. However, as a transcription factor, it is inherently difficult to target by pharmacological means. Novel approaches need to be explored before the inhibition of NANOG can be applied in a clinical setting.
Sources of nitrate yields in the Mississippi River Basin.

Riverine nitrate N in the Mississippi River leads to hypoxia in the Gulf of Mexico. Several recent modeling studies estimated major N inputs and suggested source areas that could be targeted for conservation programs. We conducted a similar analysis with more recent and extensive data that demonstrates the importance of hydrology in controlling the percentage of net N inputs (NNI) exported by rivers. The average fraction of annual riverine nitrate N export/NNI ranged from 0.05 for the lower Mississippi subbasin to 0.3 for the upper Mississippi River basin and as high as 1.4 (4.2 in a wet year) for the Embarras River watershed, a mostly tile-drained basin. Intensive corn (Zea mays L.) and soybean [Glycine max (L.) Merr. ] watersheds on Mollisols had low NNI values and when combined with riverine N losses suggest a net depletion of soil organic N. We used county-level data to develop a nonlinear model ofN inputs and landscape factors that were related to winter-spring riverine nitrate yields for 153 watersheds within the basin. We found that river runoff times fertilizer N input was the major predictive term, explaining 76% of the variation in the model. Fertilizer inputs were highly correlated with fraction of land area in row crops. Tile drainage explained 17% of the spatial variation in winter-spring nitrate yield, whereas human consumption of N (i.e., sewage effluent) accounted for 7%. Net N inputs were not a good predictor of riverine nitrate N yields, nor were other N balances. We used this model to predict the expected nitrate N yield from each county in the Mississippi River basin; the greatest nitrate N yields corresponded to the highly productive, tile-drained cornbelt from southwest Minnesota across Iowa, Illinois, Indiana, and Ohio. This analysis can be used to guide decisions about where efforts to reduce nitrate N losses can be most effectively targeted to improve local water quality and reduce export to the Gulf of Mexico.
Syncytium-inducing (SI) phenotype suppression at seroconversion after intramuscular inoculation of a non-syncytium-inducing/SI phenotypically mixed human immunodeficiency virus population

Two distinct biological phenotypes of human immunodeficiency virus (HIV) have been described: the non-syncytium-inducing (NSI) phenotype, best characterized by the inability to infect MT-2 cells, and the syncytium-inducing (SI) phenotype, with the ability to infect MT-2 cells. The earliest virus population observed following HIV transmission is generally of the NSI phenotype, even after exposure to inocula of mixed NSI/SI phenotype. In this study, the issue of intrapatient selection of virus phenotype following transmission was addressed by studying two cases of accidental transmission. A comparison of the sequences of the V1-V2 and the V3 coding regions of the envelope gene and the p17 region of the gag gene showed that the donor-recipient pairs were tightly clustered in all gene segments, but away from local and published transmission controls. The intrasample variation of the p17 sequence was greater in the recipients and smaller in the donors than that of the V3 region sequence, indicating selection of V3 at transmission. In these transmission cases, the effects of an intravenous inoculation of a small quantity of blood containing predominantly SI V3 sequences (6 of 8 clonal sequences) were compared with those of an intramuscular inoculation of a large quantity of blood containing predominantly NSI viruses (14 of 16 clonal sequences). Both SI and NSI V3 regions were demonstrated to be phenotypic expressions of genetically related viral strains. The inoculation of the predominantly SI virus population resulted in the persistence of an SI virus population in the recipient and a rapid CD4+ T-cell decline. The inoculation of the predominantly NSI population resulted in a selective amplification of SI viruses before seroconversion, followed by a suppression of SI viruses at seroconversion and a rapid decline of CD4+ T-cell numbers. These data suggest that the suppression of SI viruses can be accomplished following the development of HIV-specific immunity and that the ability to suppress SI viruses does not prevent the development of immunodeficiency.