Miracle-dz/UniFAR-FTUs huggingface dataset:
Novel Effector Control through Modulation of a Preexisting Binding Site of the Aromatic-responsive ς54-Dependent Regulator DmpR*

The Pseudomonas derived ς54-dependent DmpR activator regulates transcription of the (methyl)phenol catabolic dmp-operon. DmpR is constitutively expressed, but its transcriptional promoting activity is positively controlled in direct response to the presence of multiple aromatic effectors. Previous work has led to a model in which effector binding by the amino-terminal region of the protein relieves repression of an intrinsic ATPase activity essential for its transcriptional promoting property. Here, we address whether the observed differences in the potencies of the multiple effectors (i) reside at the level of different aromatic binding sites, or (ii) are mediated through differential binding affinities; furthermore, we address whether binding of distinct aromatic effectors has different functional consequences for DmpR activity. These questions were addressed by comparing wild type and an effector specificity mutant of DmpR with respect to effector binding characteristics and the ability of aromatics to elicit ATPase activity and transcription. The results demonstrate that six test aromatics all share a common binding site on DmpR and that binding affinities determine the concentration at which DmpR responds to the presence of the effector, but not the magnitude of the responses. Interestingly, this analysis reveals that the novel abilities of the effector specificity mutant are not primarily due to acquisition of new binding abilities, but rather, they reside in being able to productively couple ATPase activity to transcriptional activation. The mechanistic implications of these findings in terms of aromatic control of DmpR activity are discussed.
Identifying Candida and other yeast-like fungi: utility of an identification algorithm in resource limited setting.

AIM The increasing recovery rates of unusual yeasts with innate drug resistance make accurate identification crucial for successful therapy and infection control measures. The current study was undertaken to study the utility of CHROMagar Candida (CC) and evaluate an identification algorithm, using germ tube test (GT), CC and a commercial identification kit, API ID 32C. SETTINGS AND DESIGN The prospective study was carried out at a private laboratory in Mumbai, India. MATERIALS AND METHODS Identification of 533 yeast and yeast like isolates was carried out using an identification algorithm, comprising of the GT, CC and API tests. RESULTS CC was useful to detect mixed cultures. We were able to identify 393/533, i.e. 73.7 % of isolates using GT and CC Tests only. This was because C. albicans and C. tropicalis, which can be reliably identified using CC, constituted 75.2 % of the isolates. We were unable to identify 140 isolates, i.e. 26.3 %, using GT and CC tests only and performed additional testing using API ID 32C. CC was not found to be reliable in identifying C. krusei. CONCLUSION The diverse identification profile obtained in our study substantiates the need for all diagnostic microbiology laboratories to be better prepared for identifying unusual yeasts. Though GT or CC testing cannot alone suffice for identification of all clinically encountered Candida and yeast-like fungi, use of GT, CC and automated identification systems in a step-wise algorithm can enable the same in a more cost effective manner.
Absence of IL-4, and Not Suppression of the Th2 Response, Prevents Development of Experimental Autoimmune Graves’ Disease 1

In autoimmune Graves’ disease (GD), autoantibodies bind to the thyrotropin receptor (TSHR) and cause hyperthyroidism. We studied the effects of fms-like tyrosine kinase receptor 3 ligand (Flt3-L) or GM-CSF treatment on the development of experimental autoimmune GD (EAGD) in mice, a slowly progressing Ab-mediated organ-specific autoimmune disease of the thyroid induced by immunization with syngeneic cells expressing TSHR. Flt3-L and GM-CSF treatment resulted in up-regulation of CD8a+ and CD8a− dendritic cells, and skewing of cytokine and immune responses to TSHR in favor of Th1 and Th2, respectively. However, this skewing did not persist until the later stages, and thus failed to affect the course or severity of the disease. To determine whether the total absence of either IL-4 or IFN-γ could affect the development of EAGD, we immunized wild-type, IFN-γ−/− and IL-4−/− BALB/c mice with TSHR. Nearly 100% of the wild-type and IFN-γ−/− mice developed EAGD with optimal TSHR-specific immune responses, while IL-4−/− mice completely resisted disease and showed delayed and suboptimal pathogenic Ab response. These data demonstrated that skewing immune responses to TSHR, using either Flt3-L or GM-CSF, in favor of Th1 or Th2, respectively, may not be sufficient to alter the course of the disease, while the complete absence of IL-4, but not IFN-γ, can prevent the development of EAGD.
Low power reversible variable length decoder for MPEG-4 based on fast codeword detection and table partition

Variable length coding (VLC) is a widely used technique in digital video compression systems. It is known for its efficient compression, but is susceptible to noisy environments. Due to the increased demand for multimedia systems to be portable, power consumption and power saving become important issues. Current ITU H.263+ and ISO MPEG-4 standards have used reversible variable length coding (RVLC) which provides greater error robustness than non-reversible counterparts (VLC) due to the growing need for wireless exchange of compressed image and video signals over noisy channels. In this paper, a new method for RVLC decoding is described. Since the special structure of RVLC codewords, the decoding techniques that are common for regular VLC are less efficient when used with RVLC. The new method uses simple logical operations to determine the length of codewords quickly, and then codewords are decoded. It is easily implemented with hardware. We propose a VLSI architecture based on this new method. The architecture also uses the technique of table partitioning. The experimental result shows that our architecture can achieve lower power consumption without sacrificing the quality of the performance. The proposed architecture has been implemented using standard cell methodology for TSMC 0.18um 1P6M technology. The chip implementation results show that proposed architecture can work at 100MHz and its power consumption is only 46.69 uW/MHz.
Large-Scale Analysis of Putative Soybean Regulatory Gene Expression Identifies a Myb Gene Involved in Soybean Nodule Development1[W][OA]

Nodulation is the result of a symbiosis between legumes and rhizobial bacteria in soil. This symbiosis is mutually beneficial, with the bacteria providing a source of nitrogen to the host while the plant supplies carbon to the symbiont. Nodule development is a complex process that is tightly regulated in the host plant cell through networks of gene expression. In order to examine this regulation in detail, a library of quantitative reverse transcription-polymerase chain reaction primer sets was developed for a large number of soybean (Glycine max) putative regulatory genes available in the current expressed sequence tag collection. This library contained primers specific to soybean transcription factor genes as well as genes involved in chromatin modification and translational regulation. Using this library, we analyzed the expression of this gene set during nodule development. A large number of genes were found to be differentially expressed, especially at the later stages of nodule development when active nitrogen fixation was occurring. Expression of these putative regulatory genes was also analyzed in response to the addition of nitrate as a nitrogen source. This comparative analysis identified genes that may be specifically involved in nitrogen assimilation, metabolism, and the maintenance of active nodules. To address this possibility, the expression of one such candidate was studied in more detail by expressing in soybean roots promoter β-glucuronidase and green fluorescent protein fusions. This gene, named Control of Nodule Development (CND), encoded a Myb transcription factor gene. When the CND gene was silenced, nodulation was reduced. These results, associated with a strong expression of the CND gene in the vascular tissues, suggest a role for CND in controlling soybean nodulation.
The neuroprotective effect of Activin A and B: implication for neurodegenerative diseases

Activin is a member of the transforming growth factor‐β superfamily which comprises a growing list of multifunctional proteins that function as modulators of cell proliferation, differentiation, hormone secretion and neuronal survival. This study examined the neuroprotective effect of both Activin A and B in serum withdrawal and oxidative stress apoptotic cellular models and investigated the expression of pro‐ and anti‐apoptotic proteins, which may account for the mechanism of Activin‐induced neuroprotection. Here, we report that recombinant Activin A and B are neuroprotective against serum deprivation‐ and toxin‐ [either the parkinsonism‐inducing neurotoxin, 6‐hydroxydopamine (6‐OHDA) or the peroxynitrite donor, 3‐(4‐morpholinyl) sydnonimine hydrochloride (SIN‐1)] induced neuronal death in human SH‐SY5Y neuroblastoma cells. Furthermore, we demonstrate for the first time that transient transfection with Activin βA or βB significantly protect SH‐SY5Y and rat pheochromocytoma PC12 cells against serum withdrawal‐induced apoptosis. This survival effect is mediated by the Bcl‐2 family members and involves inhibition of caspase‐3 activation; reduction of cleaved poly‐ADP ribose polymerase and phosphorylated H2A.X protein levels and elevation of tyrosine hydroxylase expression. These results indicate that both Activin‐A and ‐B share the potential to induce neuroprotective activity and thus may have positive impact on aging and neurodegenerative diseases to retard the accelerated rate of neuronal degeneration.
Prevalence of Chlamydia trachomatis Genital Infection Among Persons Aged 14–39 Years — United States, 2007–2012

Infection with the bacterium, Chlamydia trachomatis (often termed "chlamydia") is the most frequently reported sexually transmitted infection in the United States. The urethra is the most common site of infection in males, and the urethra and cervix are most commonly infected in females. Ascending infection in females can cause pelvic inflammatory disease, which can lead to infertility and ectopic pregnancy. Genital chlamydial infections are usually asymptomatic, and screening is necessary to identify most infections. Currently, chlamydia screening for sexually active women aged <25 years is recommended by the U.S. Preventive Services Task Force (grade B recommendation). Chlamydia is nationally notifiable; however, if females do not access care or clinicians do not screen, many infections go undiagnosed, unreported, and untreated. CDC monitors population prevalence of genital chlamydial infection through the National Health and Nutrition Examination Survey (NHANES), which tests a sample of the U.S. population aged 14-39 years for genital C. trachomatis and found that the overall chlamydia burden in the United States decreased during 1999-2008. Using data from the most recent cycles of NHANES (2007-2012), CDC estimated chlamydia prevalence among persons aged 14-39 years overall and by demographic characteristics and sexual behaviors. The prevalence of chlamydia among persons aged 14-39 years was 1.7% (95% confidence interval [CI] = 1.4%-2.0%). Chlamydia prevalence varied by age and race/ethnicity, with prevalence highest among non-Hispanic blacks (5.2%). Among sexually active females aged 14-24 years, the population targeted for routine screening, chlamydia prevalence was 4.7% overall and 13.5% among non-Hispanic black females. As chlamydia is common and infections are usually asymptomatic, health care providers should routinely screen sexually active young women aged <25 years for chlamydial infection, provide prompt treatment for infected persons, and ensure that infected patients' sex partners receive timely treatment to prevent reinfection.
Crystal structure of ethyl 5-acetyl-2-{[(dimethylamino)methylidene]amino}-4-methylthiophene-3-carboxylate

In the title thiophene derivative, C13H18N2O3S, the dihedral angles between the thiophene ring and the [(dimethylamino)methylidene]amino side chain (r.m.s. deviation = 0.009 Å) and the –CO2 ester group are 3.01 (16) and 59.9 (3)°, respectively. In the crystal, inversion dimers linked by pairs of C—H⋯O hydrogen bonds generate R 2 2(16) loops. The dimers are linked by another weak C—H⋯O interaction, forming chains along [001]. In addition, weak C—H⋯π interactions are observed, which link the chains into (001) layers.
Biosynthesis of the Cyanogenic Glucosides Linamarin and Lotaustralin in Cassava: Isolation, Biochemical Characterization, and Expression Pattern of CYP71E7, the Oxime-Metabolizing Cytochrome P450 Enzyme1[OA]

Cassava (Manihot esculenta) is a eudicotyledonous plant that produces the valine- and isoleucine-derived cyanogenic glucosides linamarin and lotaustralin with the corresponding oximes and cyanohydrins as key intermediates. CYP79 enzymes catalyzing amino acid-to-oxime conversion in cyanogenic glucoside biosynthesis are known from several plants including cassava. The enzyme system converting oxime into cyanohydrin has previously only been identified in the monocotyledonous plant great millet (Sorghum bicolor). Using this great millet CYP71E1 sequence as a query in a Basic Local Alignment Search Tool-p search, a putative functional homolog that exhibited an approximately 50% amino acid sequence identity was found in cassava. The corresponding full-length cDNA clone was obtained from a plasmid library prepared from cassava shoot tips and was assigned CYP71E7. Heterologous expression of CYP71E7 in yeast afforded microsomes converting 2-methylpropanal oxime (valine-derived oxime) and 2-methylbutanal oxime (isoleucine-derived oxime) to the corresponding cyanohydrins, which dissociate into acetone and 2-butanone, respectively, and hydrogen cyanide. The volatile ketones were detected as 2.4-dinitrophenylhydrazone derivatives by liquid chromatography-mass spectrometry. A KS of approximately 0.9 μm was determined for 2-methylbutanal oxime based on substrate-binding spectra. CYP71E7 exhibits low specificity for the side chain of the substrate and catalyzes the conversion of aliphatic and aromatic oximes with turnovers of approximately 21, 17, 8, and 1 min−1 for the oximes derived from valine, isoleucine, tyrosine, and phenylalanine, respectively. A second paralog of CYP71E7 was identified by database searches and showed approximately 90% amino acid sequence identity. In tube in situ polymerase chain reaction showed that in nearly unfolded leaves, the CYP71E7 paralogs are preferentially expressed in specific cells in the endodermis and in most cells in the first cortex cell layer. In fully unfolded leaves, the expression is pronounced in the cortex cell layer just beside the epidermis and in specific cells in the vascular tissue cortex cells. Thus, the transcripts of the CYP71E7 paralogs colocalize with CYP79D1 and CYP79D2. We conclude that CYP71E7 is the oxime-metabolizing enzyme in cyanogenic glucoside biosynthesis in cassava.
Cellular Quality Control Screening to Identify Amino Acid Pairs for Substituting the Disulfide Bonds in Immunoglobulin Fold Domains*

We are interested in determining which amino acid pairs can be substituted for the disulfide (S–S) bonds in proteins without disrupting their native structures under physiological conditions. In this study, we focused on the intradomain S–S bonds in Ig fold domains and aimed to determine a simple rule for replacement of their S–S bonds. The cysteines of four different Ig fold domains were mutated randomly, and the amino acid pairs substituted for the S–S bonds were screened by the method utilizing a cellular quality control system. Among the 36 selected mutants, 31 were natively folded without S–S bonds, as judged from the cooperativity of thermal unfolding. In addition, the selected mutant llama heavy chain antibodies retained antigen-binding affinity. At least two of the pairs Ala:Ala, Ala:Val, Val: Ala, and Val:Val were found in the selected mutants for all four different Ig fold domains, and they were stably folded at 30 °C. This suggests that examination of these four pairs could be enough to obtain natively folded Ig fold domains without S–S bonds.
Randomness-Enhanced Chaotic Source With Dual-Path Injection From a Single Master Laser

The randomness and bandwidth enhancement of chaotic signals in optically injected semiconductor lasers (SLs) with dual-path injection from a single master laser are investigated experimentally and numerically. It is shown that both the randomness and bandwidth of chaotic signals generated in a slave SL (SSL) can be enhanced significantly, especially for positive frequency detuning, by simply adding an additional injection path in the conventional master-slave configuration. The region of injection parameter space leading to wideband randomness-enhanced chaos in SSL can be greatly broadened compared to the SSL with single-path injection. This low-cost and simple configuration for wideband randomness-enhanced chaotic source is highly desirable for high-speed random number generators based on chaotic SLs.
Predictive value of cellular immune response in cervical cancer.

UNLABELLED Despite recent advances in the immune mechanisms of cervical cancer (CC), the relapse still remains an actual issue and recognition of new predictive biomarkers is essential. AIM The purpose of this retrospective study was to investigate possible differences in the primary, in situ, cellular immune response between cervical carcinoma with and without relapse. MATERIAL AND METHODS Paraffin-embedded tissue samples from 61 consecutive women with CC (34 with and 27 without relapse) were immunostained for CD3, CD20 and CD45 cells. Immune cell profile densities were further assessed, assigning scores between 0 and 3: "0" meaning the absence of inflammatory infiltrate, "1+" low, "2+" intense and "3+" intense infiltrate with lymphoid follicles. Statistical analysis was performed in SPSS-13 software, p<0.05. RESULTS Statistically significant intra- and peri-tumoral low numbers of several immune cell subtypes are strongly associated with relapse of disease within three and five years in patients with CC (p<0.05); moreover, statistical significant correlations between immune cells and both free survival (CD3: r=0.382; CD20: r=0.404; CD45: r=0.376) and relapse (CD3: r=-0.408; CD20: r=-0.355; CD45: r=-0.354) have been demonstrated. Only CD3 was reported as predictive biomarker of relapse in CC (ANOVA, t-Student, p<0.05). CONCLUSIONS Major differences in the cellular immune response among patients with cervical cancer with and without relapse within three and five years have been demonstrated. CD3 may be used as potential prognostic biomarkers, whereas the results are promising for adjuvant immunotherapy.
Longitudinal study on the role of body size in premenopausal breast cancer.

BACKGROUND A high body mass index (BMI) has been related to a reduced risk of breast cancer in premenopausal women. The mechanisms underlying this association have not been elucidated. METHODS We explored whether factors affecting ovulation may explain the inverse association between BMI (calculated as weight in kilograms divided by the square of height in meters) and breast cancer in 113,130 premenopausal participants in the Nurses' Health Study II. During 1,225,520 person-years of prospective follow-up between 1989 and 2003, 1398 incident cases of invasive breast cancer were diagnosed. Weight, height, ovulatory infertility, menstrual cycle patterns, and a multitude of covariates were assessed throughout follow-up. Cox proportional hazards regression was used to compute hazard ratios and 95% confidence intervals (CIs). RESULTS We observed a significant linear inverse trend between current BMI and breast cancer incidence (P<.001) that was not explained by menstrual cycle characteristics or infertility due to an ovulatory disorder (covariate-adjusted hazard ratio for breast cancer in women with a BMI > or =30 vs 20.0-22.4, 0.81; 95% CI, 0.68-0.96). We found BMI at age 18 years to be the strongest predictor of breast cancer incidence (covariate-adjusted hazard ratio for breast cancer in women with a BMI at age 18 years > or =27.5 vs 20.0-22.4, 0.57; 95% CI, 0.41-0.81). CONCLUSIONS Body size during the early phases of adult life seems to be particularly important in the development of premenopausal breast cancer. Factors other than anovulation are likely to mediate the protection conferred by a high BMI.
The Cochrane Collaboration: Preparing, Maintaining, and Disseminating Systematic Reviews of the Effects of Health Care

In an influential book published more than twenty years ago, Archie Cochrane drew attention to our great collective ignorance about the effects of health care, and explained how evidence from randomized controlled trials (RCTs) could help us to use resources more rationally. He recognized that people who want to take more informed decisions about health care do not have ready access to reliable reviews of the available evidence. In 1979, he wrote: "It is surely a great criticism of our profession that we have not organised a critical summary, by specialty or subspecialty, adapted periodically, of all relevant randomised controlled trials. " The Cochrane Collaboration has evolved in response to this challenge and will eventually cover all areas of health care. Contributors in many countries and specialties are preparing and maintaining systematic reviews of RCTs, and reviews of other evidence when appropriate. These reviews will be disseminated using electronic media through the Cochrane Database of Systematic Reviews.
Association between occupational exposure and control measures for antineoplastic drugs in a pharmacy of a hospital.

OBJECTIVES To investigate the association between occupational contamination and exposure levels to antineoplastic drugs and the application of control measures in a hospital work environment. METHODS Wipe samples of equipments were collected at a hospital in Osaka Prefecture, Japan, from 2007 to 2011. These samples were subjected to measurements of cyclophosphamide (CP), gemcitabine (GEM), platinum-containing drugs (Pt), and fluorouracil (5FU). Additionally, 24-h urine samples were collected from pharmacists who handled antineoplastic drugs, which were analyzed for CP and alpha-fluoro-beta-alanine (AFBA). The application of control measures was scored according to a checklist, which consisted of the following five items: safety equipment and maintenance, training and documentation, devices for safe handling, personal protective equipment, and emergency care. The aim was to obtain a score of 80%. RESULTS The median CP, GEM, and 5FU concentrations of all wipe samples were significantly lower during the period when the mean score was >80% (attainment period) versus when the mean score was ≤80% (nonattainment period; all P < 0.001, Mann-Whitney's U-test). Additionally, the median urinary CP and AFBA concentrations of pharmacists during the attainment period tended to be lower than that of those during the nonattainment period (P = 0.061 and 0.061, respectively, using Mann-Whitney's U-test). CONCLUSIONS Contamination and levels of exposure to antineoplastic drugs decreased with a score higher than 80%. The scores of the items on the checklist appeared to adequately reflect the condition of the control measures, as increases in all five items were associated with reductions in the contamination by and levels of exposure to all drugs.