Miracle-dz/UniFAR-FTUs huggingface dataset:
Gallic acid causes inactivating phosphorylation of cdc25A/cdc25C-cdc2 via ATM-Chk2 activation, leading to cell cycle arrest, and induces apoptosis in human prostate carcinoma DU145 cells

We recently reported that gallic acid is a major active agent responsible for grape seed extract activity in DU145 human prostate carcinoma cells. The present study was conducted to examine its efficacy and associated mechanism. Gallic acid treatment of DU145 cells resulted in a strong cell growth inhibition, cell cycle arrest, and apoptotic death in a dose- and time-dependent manner, together with a decrease in cyclin-dependent kinases and cyclins but strong induction in Cip1/p21. Additional mechanistic studies showed that gallic acid induces an early Tyr15 phosphorylation of cell division cycle 2 (cdc2). Further upstream, gallic acid also induced phosphorylation of both cdc25A and cdc25C via ataxia telangiectasia mutated (ATM)-checkpoint kinase 2 (Chk2) activation as a DNA damage response evidenced by increased phospho-histone 2AX (H2A.X) that is phosphorylated by ATM in response to DNA damage. Time kinetics of ATM phosphorylation, together with those of H2A.X and Chk2, was in accordance with an inactivating phosphorylation of cdc25A and cdc25C phosphatases and cdc2 kinase, suggesting that gallic acid increases cdc25A/C-cdc2 phosphorylation and thereby inactivation via ATM-Chk2 pathway following DNA damage that induces cell cycle arrest. Caffeine, an ATM/ataxia telangiectasia-rad3-related inhibitor, reversed gallic acid–caused ATM and H2A.X phosphorylation and cell cycle arrest, supporting the role of ATM pathway in gallic acid–induced cell cycle arrest. Additionally, gallic acid caused caspase-9, caspase-3, and poly(ADP)ribose polymerase cleavage, but pan-caspase inhibitor did not reverse apoptosis, suggesting an additional caspase-independent apoptotic mechanism. Together, this is the first report identifying gallic acid efficacy and associated mechanisms in an advanced and androgen-independent human prostate carcinoma DU145 cells, suggesting future in vivo efficacy studies with this agent in preclinical prostate cancer models. [Mol Cancer Ther 2006;5(12):3294–302]
Analysis of Transcriptionally Active Gene Clusters of Major Outer Membrane Protein Multigene Family in Ehrlichia canis and E. chaffeensis

ABSTRACT Ehrlichia canis and E. chaffeensis are tick-borne obligatory intramonocytic ehrlichiae that cause febrile systemic illness in humans and dogs, respectively. The current study analyzed the pleomorphic multigene family encoding approximately 30-kDa major outer membrane proteins (OMPs) of E. canis andE. chaffeensis. Upstream from secA and downstream of hypothetical transcriptional regulator, 22 paralogs of the omp gene family were found to be tandemly arranged except for one or two genes with opposite orientations in a 28- and a 27-kb locus in the E. canis and E. chaffeensisgenomes, respectively. Each locus consisted of three highly repetitive regions with four nonrepetitive intervening regions. E. canis, in addition, had a 6.9-kb locus which contained a repeat of three tandem paralogs in the 28-kb locus. These total 47 paralogous and orthologous genes encoded OMPs of approximately 30 to 35 kDa consisting of several hypervariable regions alternating with conserved regions. In the 5′-end half of the 27-kb locus or the 28-kb locus of each Ehrlichia species, 14 paralogs were linked by short intergenic spaces ranging from −8 bp (overlapped) to 27 bp, and 8 remaining paralogs in the 3′-end half were connected by longer intergenic spaces ranging from 213 to 632 bp. All 22 paralogs, five unknown genes, and secA in the omp cluster inE. canis were transcriptionally active in the monocyte culture, and the paralogs with short intergenic spaces were cotranscribed with their adjacent genes, including the respective intergenic spaces at both the 5′ and the 3′ sides. Althoughomp genes are diverse, our results suggest that the gene organization of the clusters and the gene locus are conserved between two species of Ehrlichia to maintain a unique transcriptional mechanism for adaptation to environmental changes common to them.
A One-to-One Code and Its Anti-Redundancy

One-to-one codes are ldquoone-shotrdquo codes that assign a distinct codeword to source symbols and are not necessarily prefix codes (more generally, uniquely decodable). Interestingly, as Wyner proved in 1972, for such codes the average code length can be <i>smaller</i> than the source entropy. By how much? We call this difference the <i>anti-redundancy</i>. Various authors over the years have shown that the anti-redundancy can be as big as minus the logarithm of the source entropy. However, to the best of our knowledge precise estimates do not exist. In this note, we consider a block code of length <i>n</i> generated for a binary memoryless source, and prove that the average anti-redundancy is -1/2 log<sub>2</sub> <i>n</i> +<i>C</i> +<i>F</i> (<i>n</i>)+<i>o</i> (1) where <i>C</i> is a constant and either <i>F</i> (<i>n</i>) = 0 if log<sub>2</sub>(1-<i>p</i>)/<i>p</i> is irrational (where <i>p</i> is the probability of generating a ldquo0rdquo) or <i>F</i>(<i>n</i>) is a fluctuating function as the code length increases. This relatively simple finding requires a combination of analytic tools such as precise evaluation of Bernoulli sums, the saddle point method, and theory of distribution of sequences modulo 1.
The Value of Routine pH Monitoring in the Diagnosis and Treatment of Laryngopharyngeal Reflux

Objective. To assess the need for pH testing in diagnosing laryngopharyngeal reflux (LPR). Study Design. Case series with planned data collection. Setting. Tertiary care center. Subjects and Methods. On the basis of symptoms and/or abnormal endoscopic findings, more than 500 patients underwent 24-hour pharyngeal pH testing at a single center (using the Dx-pH probe) between January 2009 and June 2011. A total of 163 patients not on proton-pump inhibitors at the time of study and with complete data available for analysis (pH results, body mass index, smoking status, pretest reflux symptom index) were divided into 2 groups by positive (n = 70) and negative (n = 93) Ryan Score. The Reflux Symptom Index (RSI) was compared between groups and assessed overall against Ryan Score parameters at different pH thresholds. The diagnostic utility of an RSI ≥ 13 for prediction of Ryan Score was assessed. Results. No significant difference in RSI was seen between Ryan-positive (17.50 ± 11.47) and Ryan-negative (14.95 ± 11.43) patients (P = .161). Overall, RSI correlated poorly with percentage time spent below pH thresholds 6.5, 6.0, 5.5, and 5.0 and upright and supine Ryan parameters at these thresholds (as determined by linear regression analysis). The sensitivity, specificity, positive predictive value, and negative predictive value of RSI ≥ 13 for Ryan positivity were 55.7%, 47.3%, 44.3%, and 58.7%, respectively. Conclusion. Our findings show that in our population of otolaryngology patients, the diagnosis of LPR cannot be reliably made on the basis of symptoms alone. Diagnosis, and in particular treatment decisions, should ideally be made on the basis of a combination of symptoms, signs, and confirmatory testing.
Pre-Absorbed Immunoproteomics: A Novel Method for the Detection of Streptococcus suis Surface Proteins

Streptococcus suis serotype 2 (SS2) is a zoonotic pathogen that can cause infections in pigs and humans. Bacterial surface proteins are often investigated as potential vaccine candidates and biomarkers of virulence. In this study, a novel method for identifying bacterial surface proteins is presented, which combines immunoproteomic and immunoserologic techniques. Critical to the success of this new method is an improved procedure for generating two-dimensional electrophoresis gel profiles of S. suis proteins. The S. suis surface proteins identified in this study include muramidase-released protein precursor (MRP) and an ABC transporter protein, while MRP is thought to be one of the main virulence factors in SS2 located on the bacterial surface. Herein, we demonstrate that the ABC transporter protein can bind to HEp-2 cells, which strongly suggests that this protein is located on the bacterial cell surface and may be involved in pathogenesis. An immunofluorescence assay confirmed that the ABC transporter is localized to the bacterial outer surface. This new method may prove to be a useful tool for identifying surface proteins, and aid in the development of new vaccine subunits and disease diagnostics.
Antimicrobial Activities of Bacteria Associated with the Brown Alga Padina pavonica

Macroalgae belonging to the genus Padina are known to produce antibacterial compounds that may inhibit growth of human- and animal pathogens. Hitherto, it was unclear whether this antibacterial activity is produced by the macroalga itself or by secondary metabolite producing epiphytic bacteria. Here we report antibacterial activities of epiphytic bacteria isolated from Padina pavonica (Peacocks tail) located on northern coast of Tunisia. Eighteen isolates were obtained in pure culture and tested for antimicrobial activities. Based on the 16S rRNA gene sequences the isolates were closely related to Proteobacteria (12 isolates; 2 Alpha- and 10 Gammaproteobacteria), Firmicutes (4 isolates) and Actinobacteria (2 isolates). The antimicrobial activity was assessed as inhibition of growth of 12 species of pathogenic bacteria (Aeromonas salmonicida, A. hydrophila, Enterobacter xiangfangensis, Enterococcus faecium, Escherichia coli, Micrococcus sp., Salmonella typhimurium, Staphylococcus aureus, Streptococcus sp., Vibrio alginoliticus, V. proteolyticus, V. vulnificus) and one pathogenic yeast (Candida albicans). Among the Firmicutes, isolate P8, which is closely related to Bacillus pumilus, displayed the largest spectrum of growth inhibition of the pathogenic bacteria tested. The results emphasize the potential use of P. pavonica associated antagonistic bacteria as producers of novel antibacterial compounds.
Purification and in vitro antioxidant activities of tellurium-containing phycobiliproteins from tellurium-enriched Spirulina platensis

Tellurium-containing phycocyanin (Te-PC) and allophycocyanin (Te-APC), two organic tellurium (Te) species, were purified from tellurium-enriched Spirulina platensis by a fast protein liquid chromatographic method. It was found that the incorporation of Te into the peptides enhanced the antioxidant activities of both phycobiliproteins. With fractionation by ammonium sulfate precipitation and hydroxylapatite chromatography, Te-PC and Te-APC could be effectively separated with high purity, and Te concentrations were 611.1 and 625.3 μg g−1 protein in Te-PC and Te-APC, respectively. The subunits in the proteins were identified by using MALDI-TOF-TOF mass spectrometry. Te incorporation enhanced the antioxidant activities of both phycobiliproteins, as examined by 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid assay. Moreover, Te-PC and Te-APC showed dose-dependent protection on erythrocytes against the water-soluble free radical initiator 2,2′-azo(2-asmidinopropane)dihydrochloride-induced hemolysis. In the hepatoprotective model, apoptotic cell death and nuclear condensation induced by tert-butyl hydroperoxide in HepG2 cells was significantly attenuated by Te-PC and Te-APC. Taken together, these results suggest that Te-PC and Te-APC are promising Te-containing proteins with application potential for treatment of diseases related to oxidative stress.
Does awareness affect the restorative function and perception of street trees?

Urban streetscapes are outdoor areas in which the general public can appreciate green landscapes and engage in outdoor activities along the street. This study tested the extent to which the degree of awareness of urban street trees impacts attention restoration and perceived restorativeness. We manipulated the degree of awareness of street trees. Participants were placed into four groups and shown different images: (a) streetscapes with absolutely no trees; (b) streetscapes with flashes of trees in which participants had minimal awareness of the content; (c) streetscapes with trees; and (d) streetscapes with trees to which participants were told to pay attention. We compared the performance of 138 individuals on measures of attention and their evaluations of perceived restorativeness. Two main findings emerged. First, streetscapes with trees improved the performance of participants on attentional tests even without their awareness of the trees. Second, participants who had raised awareness of street trees performed best on the attentional test and rated the streetscapes as being more restorative. These findings enhance our knowledge about the role of an individual's awareness of restorative elements and have implications for designers and individuals who are at risk of attentional fatigue.
The Laccase Engineering Database: a classification and analysis system for laccases and related multicopper oxidases

Laccases and their homologues form the protein superfamily of multicopper oxidases (MCO). They catalyze the oxidation of many, particularly phenolic substances, and, besides playing an important role in many cellular activities, are of interest in biotechnological applications. The Laccase Engineering Database (LccED, http://www.lcced.uni-stuttgart.de) was designed to serve as a tool for a systematic sequence-based classification and analysis of the diverse multicopper oxidase protein family. More than 2200 proteins were classified into 11 superfamilies and 56 homologous families. For each family, the LccED provides multiple sequence alignments, phylogenetic trees and family-specific HMM profiles. The integration of structures for 14 different proteins allows a comprehensive comparison of sequences and structures to derive biochemical properties. Among the families, the distribution of the proteins regarding different kingdoms was investigated. The database was applied to perform a comprehensive analysis by MCO- and laccase-specific patterns. The LccED combines information of sequences and structures of MCOs. It serves as a classification tool to assign new proteins to a homologous family and can be applied to investigate sequence–structure–function relationship and to guide protein engineering. Database URL: http://www.lcced. uni-stuttgart.de
Cryptoraptor: High throughput reconfigurable cryptographic processor

This paper describes a high performance, low power, and highly flexible cryptographic processor, Cryptoraptor, which is designed to support both today's and tomorrow's symmetric-key cryptography algorithms and standards. To the best of our knowledge, the proposed cryptographic processor supports the widest range of cryptographic algorithms compared to other solutions in the literature and is the only crypto-specific processor targeting future standards as well. Our 1GHz design achieves a peak throughput of 128Gbps for AES-128 which is competitive with ASIC designs and has 25X and 160X higher throughputs per area than CPU and GPU solutions, respectively.
Salt-dependent renal effects of an angiotensin II antagonist in healthy subjects.

This study was designed to evaluate in healthy volunteers the renal hemodynamic and tubular effects of the orally active angiotensin II receptor antagonist losartan (DuP 753 or MK 954). Losartan or a placebo was administered to 23 subjects maintained on a high-sodium (200 mmol/d) or a low-sodium (50 mmol/d) diet in a randomized, double-blind, crossover study. The two 6-day diet periods were separated by a 5-day washout period. On day 6, the subjects were water loaded, and blood pressure, renal hemodynamics, and urinary electrolyte excretion were measured for 6 hours after a single 100-mg oral dose of losartan (n = 16) or placebo (n = 7). Losartan induced no significant changes in blood pressure, glomerular filtration rate, or renal blood flow in these water-loaded subjects, whatever the sodium diet. In subjects on a low-salt diet, losartan markedly increased urinary sodium excretion from 115 +/- 9 to 207 +/- 21 mumol/min (P < .05). The fractional excretion of endogenous lithium was unchanged, suggesting no effect of losartan on the early proximal tubule in our experimental conditions. Losartan also increased urine flow rate (from 10.5 +/- 0.4 to 13.1 +/- 0.6 mL/min, P < .05); urinary potassium excretion (from 117 +/- 6.9 to 155 +/- 11 mumol/min); and the excretion of chloride, magnesium, calcium, and phosphate. In subjects on a high-salt diet, similar effects of losartan were observed, but the changes induced by the angiotensin II antagonist did not reach statistical significance. In addition, losartan demonstrated significant uricosuric properties with both sodium diets. (ABSTRACT TRUNCATED AT 250 WORDS)
Fungal Enolase, β-Tubulin, and Chitin Are Detected in Brain Tissue from Alzheimer’s Disease Patients

Recent findings provide evidence that fungal structures can be detected in brain tissue from Alzheimer’s disease (AD) patients using rabbit polyclonal antibodies raised against whole fungal cells. In the present work, we have developed and tested specific antibodies that recognize the fungal proteins, enolase and β-tubulin, and an antibody that recognizes the fungal polysaccharide chitin. Consistent with our previous studies, a number of rounded yeast-like and hyphal structures were detected using these antibodies in brain sections from AD patients. Some of these structures were intracellular and, strikingly, some were found to be located inside nuclei from neurons, whereas other fungal structures were detected extracellularly. Corporya amylacea from AD patients also contained enolase and β-tubulin as revealed by these selective antibodies, but were devoid of fungal chitin. Importantly, brain sections from control subjects were usually negative for staining with the three antibodies. However, a few fungal structures can be observed in some control individuals. Collectively, these findings indicate the presence of two fungal proteins, enolase and β-tubulin, and the polysaccharide chitin, in CNS tissue from AD patients. These findings are consistent with our hypothesis that AD is caused by disseminated fungal infection.
In vitro/in vivo performance of different complexes of itraconazole used in the treatment of vaginal candidiasis

A large majority of new chemical entities and many existing drug molecules exhibit poor aqueous solubility, which may limit their potential use in developing drug formulations, with optimum bioavailability. One of the approaches to improve the solubility of a poorly water soluble drug and eventually its bioavailability is complexation with agents like humic acid (HA), fulvic acid (FA), β-cyclodextrin (β-CD), 2-hydroxypropyl-β-cyclodextrin (HP-β-CD) and caffeine (Caff). The current work emphasized at employing these agents to prepare different complexes and their in vitro/in vivo assessment. All the complexes evaluated for their complexation efficiency and authenticated by molecular modeling; conformational analysis, differential scanning calorimetry (DSC), X-ray diffraction (XRD), nuclear magnetic resonance (NMR) and mass spectroscopy. Furthermore, the complexes were assessed in an in vivo, rat vaginal model for their efficacy in treatment of vaginal candidiasis. Amongst the five tested complexes, fulvic acid-itraconazole complex yielded better solubility as well as in vivo efficacy and therefore may further be explored for developing a commercial formulation for treating vaginal candidiasis.
Second-Best Road Pricing Through Highway Franchising

This paper considers the welfare impacts of a range of franchising regimes for congestible highways. For a single road in isolation, it is shown that a competitive auction with the level of road use as the decision criterion produces the socially optimal road (in terms of capacity and toll level) as the equilibrium outcome, provided constant returns to scale characterize highway operations. The auction outperforms various alternatives, in which the bidders are asked to minimize the toll level or toll revenues, or to maximize capacity or the bid for the franchise. When second-best network aspects are taken into account, the patronage-maximizing auction is no longer optimal. When unpriced congestion on parallel capacity dominates, the second-best highway would generate losses and the zero-profit condition becomes binding. The auction produces a below-optimal capacity. When unpriced congestion on serial capacity dominates, the auction produces an above-optimal capacity.
The etiology of functional somatic symptoms in adolescents. A new perspective on lumping and splitting

Background: Functional somatic symptoms (FSS), like chronic pain and overtiredness, are often assumed to be stress-related. Altered levels of the stress hormone cortisol could explain the association between stress and somatic complaints. We hypothesized that low cortisol levels after awakening and low cortisol levels during stress are differentially associated with specific FSS. Methods: This study is performed in a subsample of TRAILS (Tracking Adolescents’ Individual Lives Survey) consisting of 715 adolescents (mean age: 16.1 years, SD = 0.6, 51.3% girls). Adolescents’ cortisol levels after awakening and during a social stress task were assessed. The area under the curve with respect to the ground (AUCg) and the area under the curve above the baseline (AUCab) were calculated for these cortisol levels. FSS were measured using the Youth Self-Report (YSR) and pain questions. Based upon a factor analysis, FSS were divided into two clusters, one consisting of headache and gastrointestinal symptoms and the other consisting of overtiredness, dizziness and musculoskeletal pain. Results: Regression analyses revealed that the cluster of headache and gastrointestinal symptoms was associated with a low AUCg of cortisol levels during stress ( β = -.09, p =.03) and the cluster of overtiredness, dizziness and musculoskeletal pain with a low AUCg of cortisol levels after awakening ( β = -.15, p = .008). All these analyses were adjusted for the potential confounders smoking, physical activity level, depression, corticosteroid use, oral contraceptive use, gender, body mass index and, if applicable, awakening time. Conclusion: Two clusters of FSS are differentially associated with the stress hormone cortisol.
Heme oxygenase-1 and acute kidney injury

Purpose of review Heme oxygenase activity, possessed by an inducible heme oxygenase-1 (HO-1) and a constitutive isoform (HO-2), catalyzes the conversion of heme to biliverdin, liberates iron, and generates carbon monoxide. First shown in acute kidney injury (AKI), HO-1 is now recognized as a protectant against diverse insults in assorted tissues. This review summarizes recent contributions to the field of HO-1 and AKI. Recent findings Recent findings elucidate the following: the transcriptional regulation and significance of human HO-1 in AKI; the protective effects of HO-1 in age-dependent and sepsis-related AKI, cardiorenal syndromes, and acute vascular rejection in renal xenografts; the role of heme oxygenase in tubuloglomerular feedback and renal resistance to injury; the basis for cytoprotection by HO-1; the protective properties of ferritin and carbon monoxide; HO-1 and the AKI–chronic kidney disease transition; HO-1 as a biomarker in AKI; the role of HO-1 in mediating the protective effects of specific cytokines, stem cells, and therapeutic agents in AKI; and HO-2 as a protectant in AKI. Summary Recent contributions support, and elucidate the basis for, the induction of HO-1 as a protectant against AKI. Translating such therapeutic potential into a therapeutic reality requires well tolerated and effective modalities for upregulating HO-1 and/or administering its products, which, optimally, should be salutary even when AKI is already established.