Miracle-dz/UniFAR-FTUs huggingface dataset:
Identification and Evaluation of Twin-Arginine Translocase Inhibitors

ABSTRACT The twin-arginine translocase (TAT) in some bacterial pathogens, including Pseudomonas aeruginosa, Burkholderia pseudomallei, and Mycobacterium tuberculosis, contributes to pathogenesis by translocating extracellular virulence determinants across the inner membrane into the periplasm, thereby allowing access to the Xcp (type II) secretory system for further export in Gram-negative organisms, or directly to the outside surface of the cell, as in M. tuberculosis. TAT-mediated secretion appreciably contributes to virulence in both animal and plant models of bacterial infection. Consequently, TAT function is an attractive target for small-molecular-weight compounds that alone or in conjunction with extant antimicrobial agents could become novel therapeutics. The TAT-transported hemolytic phospholipase C (PlcH) of P. aeruginosa and its multiple orthologs produced by the above pathogens can be detected by an accurate and reproducible colorimetric assay using a synthetic substrate that detects phospholipase C activity. Such an assay could be an effective indicator of TAT function. Using carefully constructed recombinant strains to precisely control the expression of PlcH, we developed a high-throughput screening (HTS) assay to evaluate, in duplicate, >80,000 small-molecular-weight compounds as possible TAT inhibitors. Based on additional TAT-related functional assays, purified PlcH protein inhibition experiments, and repeat experiments of the initial screening assay, 39 compounds were selected from the 122 initial hits. Finally, to evaluate candidate inhibitors for TAT specificity, we developed a TAT titration assay that determines whether inhibition of TAT-mediated secretion can be overcome by increasing the levels of TAT expression. The compounds N-phenyl maleimide and Bay 11-7082 appear to directly affect TAT function based on this approach.
Complete Genome Sequence of Streptococcus anginosus J4211, a Clinical Isolate

ABSTRACT Streptococcus anginosus is an opportunistic human pathogen that causes abscesses of the brain, liver, and other organs. Here, we announce the complete genome sequence of a clinically isolated strain of S. anginosus J4211. The genome sequence contains two prophages and multiple mobile genetic elements.
The RIM/NIM Family of Neuronal C2 Domain Proteins

RIM1 is a putative effector protein for Rab3s, synaptic GTP-binding proteins. RIM1 is localized close to the active zone at the synapse, where it interacts in a GTP-dependent manner with Rab3 located on synaptic vesicles. We now describe a second RIM protein, called RIM2, that is highly homologous to RIM1 and also expressed primarily in brain. Like RIM1, RIM2 contains an N-terminal zinc finger domain that binds to Rab3 as a function of GTP, a central PDZ domain, and two C-terminal C2 domains that are separated by long alternatively spliced sequences. Unexpectedly, the 3′-end of the RIM2 gene produces an independent mRNA that encodes a smaller protein referred as NIM2. NIM2 is composed of a unique N-terminal sequence followed by the C-terminal part of RIM2. Data bank searches identified a third RIM/NIM-related gene, which encodes a NIM isoform referred to as NIM3; no RIM transcript from this gene was detected. To test if NIMs, like RIMs, may function in secretion, we investigated the effect of NIM3 on calcium-triggered exocytosis in PC12 cells. NIM3 induced a dramatic increase in calcium-evoked exocytosis (50%), with no significant effect on base-line release, suggesting that NIMs, like RIMs, regulate exocytosis The combination of conserved and variable sequences in RIMs and NIMs indicates that the individual domains of these proteins provide binding sites for interacting molecules during exocytosis, as shown for the zinc finger domain of RIM, which binds to GTP-bound Rab3s. To search for additional interacting proteins for RIMs, we employed yeast two-hybrid screens with the C-terminal half of RIM1. Two members of a new family of homologous brain proteins, referred to as RIM-binding proteins (RIM-BPs), were identified. RIM-BPs bind to RIM in yeast two-hybrid and GST pull-down assays, suggesting a specific interaction. In RIMs, the binding site for RIM-BPs consists of a conserved proline-rich sequence between the two C2domains, N-terminal to the beginning of NIMs. RIM-BPs are composed of multiple domains, including three fibronectin type III-domains and three Src homology 3 domains, of which the second Src homology 3 domain binds to RIMs. With the RIM-BPs, we have identified a partner for RIMs that may bind to RIMs at the synapse in addition to Rab3.
Nutrient Metabolism Trehalose Can Be Used as a Parenteral Saccharide Source in Rabbits 1

Trehalose is a saccharide that possesses no reducing group and so has possible use in parenteral nutrition, especially because it can be stored with amino acids without undergoing the Maillard reaction. To evaluate this possibility, a series of experiments were conducted. The activity of trehalase, an enzyme that metabolizes trehalose to glucose, was measured in rabbit serum and kidney. Conversion of trehalose to glucose and excretion of trehalose in the urine were measured in rabbits administered 10% trehalose intravenously. The effects on nutritional indices as indicators of its use as an energy source were also measured in rabbits infused with 8.23 g z kg z d (4.12 g z kg on d 1) of trehalose for 5 d. Trehalase activity resembled maltase activity, both being high in the renal cortex (2.04 6 0.71 and 2.93 6 0.26 mmol z g z min, respectively), weak in the medulla, and undetectable in the serum. Serum glucose and insulin concentrations were increased significantly by trehalose infusion. Significant elevations were observed in serum glucose but not insulin levels by maltose infusion. On the other hand, urinary excretion of trehalose (1.1 6 2.1% of dose) was significantly lower than that of maltose (10.1 6 4.9% of dose). Similar effects of trehalose and maltose infusions as seen in normal rabbits occurred in rabbits with alloxan diabetes (urinary excretion rate, 3.8 6 3.0% of the infused trehalose dose and 35.6 6 9.7% of the infused maltose dose). Nitrogen balance was positive in the trehaloseand glucose-infused normal rabbits with significant difference from the control group infused with saline, suggesting that trehalose was used as an energy source. These results suggest that trehalose has the potential for use as a saccharide source for parenteral nutrition. J. Nutr. 129: 158–164, 1999.
Epstein‐Barr virus and human immunodeficiency virus serological responses and viral burdens in HIV‐infected patients treated with HAART

Epstein‐Barr virus (EBV) associated non‐Hodgkin lymphoma is recognized as a complication of human immunodeficiency virus (HIV) infection. Little is known regarding the influence of highly active antiretroviral therapy (HAART) on the biology of EBV in this population. To characterize the EBV‐ and HIV‐specific serological responses together with EBV DNA levels in a cohort of HIV‐infected adults treated with HAART, a study was conducted to compare EBV and HIV serologies and EBV DNA copy number (DNAemia) over a 12‐month period after the commencement of HAART. All patients were seropositive for EBV at baseline. Approximately 50% of patients had detectable EBV DNA at baseline, and 27/30 had detectable EBV DNA at some point over the follow‐up period of 1 year. Changes in EBV DNA copy number over time for any individual were unpredictable. Significant increases in the levels of Epstein‐Barr nuclear antigen (EBNA) and Epstein‐Barr early antigen (EA) antibodies were demonstrated in the 17 patients who had a good response to HAART. Of 29 patients with paired samples tested, four‐fold or greater increases in titers were detected for EA in 12/29 (41%), for EBNA in 7/29 (24%), for VCA‐IgG in 4/29 (14%); four‐fold decreases in titers were detected in 2/29 (7%) for EA and 12/29 (41%) for EBNA. A significant decline in the titer of anti‐HIV antibodies was also demonstrated. It was concluded that patients with advanced HIV infection who respond to HAART have an increase in their EBV specific antibodies and a decrease in their HIV‐specific antibodies. For the cohort overall, there was a transient increase in EBV DNA levels that had declined by 12 months. J. Med Virol. 67:320–326, 2002. © 2002 Wiley‐Liss, Inc.
Automated 3-D Intraretinal Layer Segmentation of Macular Spectral-Domain Optical Coherence Tomography Images

With the introduction of spectral-domain optical coherence tomography (OCT), much larger image datasets are routinely acquired compared to what was possible using the previous generation of time-domain OCT. Thus, the need for 3-D segmentation methods for processing such data is becoming increasingly important. We report a graph-theoretic segmentation method for the simultaneous segmentation of multiple 3-D surfaces that is guaranteed to be optimal with respect to the cost function and that is directly applicable to the segmentation of 3-D spectral OCT image data. We present two extensions to the general layered graph segmentation method: the ability to incorporate varying feasibility constraints and the ability to incorporate true regional information. Appropriate feasibility constraints and cost functions were learned from a training set of 13 spectral-domain OCT images from 13 subjects. After training, our approach was tested on a test set of 28 images from 14 subjects. An overall mean unsigned border positioning error of 5.69 plusmn 2.41 mum was achieved when segmenting seven surfaces (six layers) and using the average of the manual tracings of two ophthalmologists as the reference standard. This result is very comparable to the measured interobserver variability of 5.71 plusmn 1.98 mum.
The Human T-Lymphotropic Virus Type 1 Tax Protein Inhibits Nonsense-Mediated mRNA Decay by Interacting with INT6/EIF3E and UPF1

ABSTRACT In this report, we analyzed whether the degradation of mRNAs by the nonsense-mediated mRNA decay (NMD) pathway was affected in human T-lymphotropic virus type 1 (HTLV-1)-infected cells. This pathway was indeed strongly inhibited in C91PL, HUT102, and MT2 cells, and such an effect was also observed by the sole expression of the Tax protein in Jurkat and HeLa cells. In line with this activity, Tax binds INT6/EIF3E (here called INT6), which is a subunit of the translation initiation factor eukaryotic initiation factor 3 (eIF3) required for efficient NMD, as well as the NMD core factor upstream frameshift protein 1 (UPF1). It was also observed that Tax expression alters the morphology of processing bodies (P-bodies), the cytoplasmic structures which concentrate RNA degradation factors. The presence of UPF1 in these subcellular compartments was increased by Tax, whereas that of INT6 was decreased. In line with these effects, the level of the phosphorylated form of UPF1 was increased in the presence of Tax. Analysis of several mutants of the viral protein showed that the interaction with INT6 is necessary for NMD inhibition. The alteration of mRNA stability was observed to affect viral transcripts, such as that coding for the HTLV-1 basic leucine zipper factor (HBZ), and also several cellular mRNAs sensitive to the NMD pathway. Our data indicate that the effect of Tax on viral and cellular gene expression is not restricted to transcriptional control but can also involve posttranscriptional regulation.
The Impact of Having A Young Child with Disabilities on Maternal Labor Supply by Race and Marital Status

Data from the National Maternal and Infant Health Survey (NMIHS) with the three-year follow-up survey data were used to assess the impact of having a young child with disabilities on maternal labor supply. The oversampling of low birth-weight and African-American births in NMIHS provides a larger proportion of disabled children and a bigger sample of black mothers than available in data used in prior studies. The empirical analyses examined the impact of child disability on maternal employment participation and conditional intensity by race and marital status using alternative measures of disability based on occurrence of specific health conditions as well as activity performance and general development. Exogeneity of activity-based disability measures was tested using health conditions as instruments and instrumental variable models were used to estimate their impacts on maternal labor supply. The results indicated that activity-based measures are endogenous for black single and white married mothers. Model results suggested large reductions in likelihood of employment participation of black single as well as white single and married mothers. Work intensity of employed black single mothers was also substantially reduced by child disability. Overall, no consistent effects of child disability were observed for black married mothers.
Hybrid intelligent algorithms for color image segmentation

The single arithmetic of color image segmentation inevitably has some deficiencies and defects, and we can combine different algorithms according to the actual situation or have a hierarchical division of image segmentation. This paper suggests a hybrid intelligent color image segmentation method. Region growing is used to finish initial segmentation, the final segmentation images is realized by MST method which looks every region produced by region growing as a node, and an particle swarm optimization is used to get the best thresholding of MST. Region growing focuses on local variations of an image with fast speed while MST can extract the global property of an image, and particle swarm optimization can improve the algorithm speed. The method presented in this paper combines their advantages. Experiment results show that the new method has good effectiveness and efficiency.
Gain of 1q25–32, 12q23–24.3, and 17q12–22 facilitates tumorigenesis and progression of human squamous cell lung cancer

To explore the genetic changes involved in the stepwise development of lung cancer, we have determined the genetic events associated with the histological progression from normal bronchial epithelium to squamous cell carcinoma. Comparative genomic hybridization was used to identify chromosomal imbalances in 54 microdissected samples, including squamous metaplasia, dysplasia, carcinoma in situ, and invasive tumour derived from 23 patients with squamous cell carcinoma of the lung. Histopathological progression was accompanied by an increased number of chromosomal abnormalities. Gains of 1q25–32, 12q23–24.3, and 17q12–22, in particular, were detected at high frequencies in both carcinoma in situ and invasive tumours and were found more often in the cases with lymph node metastases than in those without. Our previous expression profiling of squamous cell carcinomas had identified overexpression of laminin5 γ2, a gene located at 1q25–31. Therefore, this was investigated at the protein level by immunohistochemical analysis in 336 samples of squamous cell carcinoma of the lung. Consistent with the genomic data for this region, the expression level of laminin5 γ2 was higher in the primary tumours with lymph node metastases than in tumours without metastases (p = 0.012). These data suggest that gains of genes from 1q25–32, 12q23–24.3, and 17q12–22 facilitate tumorigenesis and progression of squamous cell carcinoma of the lung, and may serve as potential predictors for this disease. Copyright © 2006 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Candida auris–Associated Candidemia, South Africa

To the Editor: We noted the report by Chowdhary et al. (1) and report Candida auris as a causative agent of candidemia in South Africa, with an estimated prevalence of 0.3% (N.P. Govender et al., unpub. data). First isolated in 2009, C. auris is an emerging species associated with clinical disease (2–6). We analyzed 4 isolates submitted to the National Institute for Communicable Diseases (Johannesburg, South Africa) from 4 patients with candidemia who had been admitted to different public- and private-sector hospitals from October 2012 through October 2013. Identification of the isolates was undertaken by using ChromAgar Candida medium (Mast Diagnostics, Merseyside, UK), Vitek-2 YST (bioMerieux, Marcy ľEtoile, France), API 20C AUX (bioMerieux), and sequencing of internal transcribed spacer (ITS) and D1/D2 domains of the ribosomal RNA gene (7), followed by microbroth dilution susceptibility testing (8). All isolates were misidentified as C. haemulonii and Rhodotorula glutinis by Vitek-2 YST and API 20C AUX assays, respectively (Table). Table Identification and antifungal susceptibility results of 4 Candida auris isolates from 4 male patients with candidemia, South Africa, October 2012–October 2013* Similar to the findings of Chowdhary et al., all isolates assimilated N-acetyl-glucosamine (1). With the use of the CBS-KNAW database, pairwise sequence alignment of ITS region showed 99% sequence homology to Kuwait isolates, and alignment of D1/D2 domain showed 98% homology to the Kuwait/India isolates (9). In a neighbor-joining phylogenetic tree based on ITS sequences, South Africa isolates formed a cluster with India and Kuwait isolates (Technical Appendix Figure). Fluconazole MICs were high for all isolates (Table). Isolates 209 and 224 showed reduced voriconazole susceptibility with MICs of 1 μg/mL and 2 μg/mL, respectively, which is above the epidemiologic cutoff value for 11 Candida species (10). Isolates were susceptible to amphotericin B and echinocandins at low MICs Clinical data were available for 1 patient (Technical Appendix Table). Two C. haemulonii isolates were identified during laboratory-based sentinel surveillance for candidemia in South Africa; the ITS region of one isolate was sequenced and the isolate identified as C. auris (N.P. Govender, pers. comm.). In this study, C. auris was misidentified by routinely used tests and was accurately identified by sequencing, in keeping with previous findings (1,3,4,6). Technical Appendix: Phylogenetic relatedness of internal transcribed spacer region of the ribosomal RNA gene of Candida auris with closely related Candida species and clinical characteristics of a patient with candidemia caused by C. auris, South Africa. Click here to view. (69K, pdf)
Tractor Wheel Tracks Detection, Delineation, and Characterization in Very High Spatial Resolution SAR Imagery

Compacted tractor wheel tracks have been recognized as key factors controlling runoff and erosion processes in agricultural landscapes. In this context, the availability of an automatic tool for wheel tracks detection and characterization would be very useful. In this letter, an original algorithm based on Radon Transform is proposed for automatic wheel tracks detection on Synthetic aperture radar images with a spatial resolution of 1 m. Compared to on-screen measurements, wheel tracks orientations and widths were accurately estimated for the images acquired with shallow incidence angles whereas poorer results were observed for sharp incidence angles.
Distinct cis-acting elements mediate clock, light, and developmental regulation of the Neurospora crassa eas (ccg-2) gene

The Neurospora crassa eas (ccg-2) gene, which encodes a fungal hydrophobin, is transcriptionally regulated by the circadian clock. In addition, eas (ccg-2) is positively regulated by light and transcripts accumulate during asexual development. To sort out the basis of this complex regulation, deletion analyses of the eas (ccg-2) promoter were carried out to localize the cis-acting elements mediating clock, light, and developmental control. The primary sequence determinants of a positive activating clock element (ACE) were found to reside in a 45-bp region, just upstream from the TATA box. Using a novel unregulated promoter/reporter system developed for this study, we show that a 68-bp sequence encompassing the ACE is sufficient to confer clock regulation on the eas (ccg-2) gene. Electrophoretic mobility shift assays using the ACE reveal factors present in N. crassa protein extracts that recognize and bind specifically to DNA containing this element. Separate regions of the eas (ccg-2) promoter involved in light induction and developmental control are identified and shown not to be required for clock-regulated expression of eas (ccg-2). The distinct nature of the ACE validates its use as a tool for the identification of upstream regulatory factors involved in clock control of gene expression.
Design of an 8192-bit RSA cryptoprocessor based on systolic architecture

This paper presents the design of an 8192-bit RSA cryptoprocessor using a radix 2 Montgomery multiplier based on a systolic architecture. In this case, the Montgomery multiplier simultaneously performs two multiplications, and the cryptoprocessor carries out the modular exponentiation using the binary exponentiation algorithm. The designs are described using generic structural VHDL and synthesized on the EP3SL150F1152C2, using Quartus II 11. The hardware synthesis and performance results show that the designed cryptoprocessor presents a good area-throughput trade-off and it can be used as a suitable core for an RSA cryptosystem embedded into a SoC.
Prevention of Bronchial Hyperplasia by EGFR Pathway Inhibitors in an Organotypic Culture Model

Lung cancer is the leading cause of cancer-related mortality worldwide. Early detection or prevention strategies are urgently needed to increase survival. Hyperplasia is the first morphologic change that occurs in the bronchial epithelium during lung cancer development, followed by squamous metaplasia, dysplasia, carcinoma in situ, and invasive tumor. This study was designed to determine the molecular mechanisms that control bronchial epithelium hyperplasia. Using primary normal human tracheobronchial epithelial (NHTBE) cells cultured by using the 3-dimensional (3D) organotypic method, we found that the epidermal growth factor receptor (EGFR) ligands, EGF, TGF-α, and amphiregulin induced hyperplasia, as determined by cell proliferation and multilayered epithelium formation. We also found that EGF induced increased cyclin D1 expression, which plays a critical role in bronchial hyperplasia; this overexpression was mediated by activating the mitogen-activated protein kinase pathway but not the phosphoinositide 3-kinase/Akt signaling pathway. Erlotinib, an EGFR tyrosine kinase inhibitor, and U0126, a MAP/ERK kinase (MEK) inhibitor, completely inhibited EGF-induced hyperplasia. Furthermore, a promoter analysis revealed that the activator protein-1 transcription factor regulates EGF-induced cyclin D1 overexpression. Activator protein-1 depletion by using siRNA targeting its c-Jun component completely abrogated EGF-induced cyclin D1 expression. In conclusion, we showed that bronchial hyperplasia can be modeled in vitro by using primary NHTBE cells maintained in a 3D organotypic culture. EGFR and MEK inhibitors completely blocked EGF-induced bronchial hyperplasia, suggesting that they have a chemopreventive role. Cancer Prev Res; 4(8); 1306–15. ©2011 AACR.