Miracle-dz/UniFAR-FTUs huggingface dataset:
Structure of a eukaryotic thiaminase I

Significance Thiaminases, enzymes that cleave vitamin B1 into its pyrimidine and thiazole ring moieties, are sporadically distributed among prokaryotes and eukaryotes. Thiaminase I enzymes accomplish this reaction through substitution of the thiazole ring with a nitrogenous base or sulfhydryl compound. A thiaminase I of the single-celled amoeboflagellate Naegleria gruberi is the first eukaryotic thiaminase I to have been examined structurally. The crystal structures in both apo form and bound to 3-deazathiamin, a noncleavable thiamin analog and inhibitor of the enzyme, define the mode of thiamin binding to this class of thiaminases and indicate the residues important for catalysis. Comparison with thiaminase II argues for convergent evolution between these two enzymes. Thiaminases, enzymes that cleave vitamin B1, are sporadically distributed among prokaryotes and eukaryotes. Thiaminase I enzymes catalyze the elimination of the thiazole ring moiety from thiamin through substitution of the methylene group with a nitrogenous base or sulfhydryl compound. In eukaryotic organisms, these enzymes are reported to have much higher molecular weights than their bacterial counterparts. A thiaminase I of the single-celled amoeboflagellate Naegleria gruberi is the only eukaryotic thiaminase I to have been cloned, sequenced, and expressed. Here, we present the crystal structure of N. gruberi thiaminase I to a resolution of 2.8 Å, solved by isomorphous replacement and pseudo–two-wavelength multiwavelength anomalous diffraction and refined to an R factor of 0.231 (Rfree, 0.265). This structure was used to solve the structure of the enzyme in complex with 3-deazathiamin, a noncleavable thiamin analog and enzyme inhibitor (2.7 Å; R, 0.233; Rfree, 0.267). These structures define the mode of thiamin binding to this class of thiaminases and indicate the involvement of Asp272 as the catalytic base. This enzyme is able to use thiamin as a substrate and is active with amines such as aniline and veratrylamine as well as sulfhydryl compounds such as l-cysteine and β-mercaptoethanol as cosubstrates. Despite significant differences in polypeptide sequence and length, we have shown that the N. gruberi thiaminase I is homologous in structure and activity to a previously characterized bacterial thiaminase I.
Motorized RhoGAP myosin IXb (Myo9b) controls cell shape and motility

Directional motility is a fundamental function of immune cells, which are recruited to sites of pathogen invasion or tissue damage by chemoattractant signals. To move, cells need to generate lamellipodial membrane protrusions at the front and retract the trailing end. These elementary events are initiated by Rho-family GTPases, which cycle between active GTP-bound and inactive GDP-bound states. How the activity of these “molecular switches” is spatially coordinated is only beginning to be understood. Here, we show that myosin IXb (Myo9b), a Rho GTPase-activating protein (RhoGAP) expressed in immune cells, is essential for coordinating the activity of Rho. We generated Myo9b-deficient mice and show that Myo9b−/− macrophages have strikingly defective spreading and polarization. Furthermore, Myo9b−/− macrophages fail to generate lamellipodia in response to a chemoattractant, and migration in a chemotactic gradient is severely impaired. Inhibition of Rho rescues the Myo9b−/− phenotype, but impairs tail retraction. We also found that Myo9b is important in vivo. Chemoattractant-induced monocyte recruitment to the peritoneal cavity is substantially reduced in Myo9b−/− mice. Thus, we identify the “motorized Rho inhibitor” Myo9b as a key molecular component required for spatially coordinated cell shape changes and motility.
SEASONAL HEMATOLOGY AND PLASMA BIOCHEMISTRY REFERENCE RANGE VALUES OF THE YELLOW-MARGINATED BOX TURTLE (CUORA FLAVOMARGINATA)

Abstract: The yellow-marginated box turtle (Cuora flavomarginata) is critically endangered and very few studies have been performed to aid the conservation effort. This study reports the first complete analysis of blood parameters for this species and will provide a reference for future conservation studies. Hematology and biochemistry reference range values were established from 52 (18 males and 35 females) clinically healthy yellow-marginated box turtles (C. flavomarginata). In order to investigate the gender and seasonal differences in these ranges, blood samples were collected from the jugular veins of the turtles in January, April, July, and October to represent the four seasons. To detect significant variation (P < 0.05), data were analyzed using repeated measurements of analysis of variance. Significant gender differences were observed in red blood cell mass parameters, absolute eosinophils, absolute monocytes, alkaline phosphatase, aspartate aminotransferase, blood urea nitrogen, calcium, uric acid, cholesterol, creatine kinase, glucose, phosphorus (P), total protein, and triglycerides. Marked seasonal variations were noted in red blood cell mass parameters, absolute monocytes, albumin, alkaline phosphatase, aspartate aminotransferase, blood urea nitrogen, uric acid, creatine kinase, creatinine, glucose, P, and triglycerides. Primary reasons for the differences between gender and season were associated with reproduction and temperature change. Cuora flavomarginata has lower alanine aminotransferase values compared with other chelonians.
Polyphenols compounds from red grapes acutely improve endothelial function in patients with coronary heart disease

Background It has been shown that acute intake of red wine improves endothelial-dependent vasodilatation. It is not clear, however, which constituents of red wine are responsible for this effect. We examined whether acute intake of a red grape polyphenol extract has a positive effect on brachial artery flow-mediated dilatation. Methods We recruited 30 male patients with coronary heart disease. They were randomly assigned either to a red grape polyphenol extract (600 mg) dissolved in 20 ml of water (n = 15) or 20 ml of water (placebo) (n = 15). The extract of grapes contained 4.32 mg epicatechin, 2.72 mg catechin, 2.07 mg gallic acid, 0.9 mg trans-resveratrol, 0.47 mg rutin, 0.42 mg ε-viniferin, 0.28 mg, p-coumaric acid, 0.14 mg ferulic acid and 0.04 mg quercetin per gram. Flow-mediated dilatation of the brachial artery was evaluated after reactive hyperemia induced by cuff obstruction of the forearm, using high-resolution ultasonography. Particularly, flow-mediated dilatation was measured after fasting and 30, 60 and 120 min after the intake of the grape extract or placebo. Results Intake of the red grape polyphenol extract caused an increase in flow-mediated dilatation, peaking at 60 min, which was significantly higher than the baseline values (4.52 ± 1.34 versus 2.6 ± 1.5%; P < 0.001) and the corresponding values at 60 min after the intake of placebo (4.52 ± 1.34 versus 2.64 ± 1.8%, P < 0.001). There was no change in FMD values after the intake of placebo throughout the whole duration of the study. Conclusion Polyphenolic compounds from red grapes acutely improve endothelial function in patients with coronary heart disease. These results could probably, at least partly, explain the favorable effects of red wine on the cardiovascular system.
Distinct signatures of B‐cell homeostatic and activation‐dependent chemokine receptors in the development and progression of extragastric MALT lymphomas

Chemokine receptors mediate migration and activation of lymphocytes through binding of their ligands. Recent studies have revealed important contributions of chemokine receptors to the development, progression, and dissemination of haematopoietic neoplasms. Because the chemokine receptor expression profile in extragastric MALT lymphoma is unknown, we performed a comprehensive study on tissue samples of parotid glands, parotid glands affected by Sjögren syndrome, extragastric MALT lymphoma, and extranodal diffuse large B‐cell lymphoma (eDLBCL) originating from MALT lymphoma (transformed MALT lymphoma). By investigating the expression of 19 chemokine receptors by real‐time PCR using a semi‐quantitative approach and of four chemokine receptors (CCR1, CCR5, CXCR6, and XCR1) by immunohistochemistry, we show that the chemokine receptor expression profiles of extragastric MALT lymphomas differ substantially from those of extranodal DBLCL, with lower expression of CCR1, CCR8, and CXCR3, and the absence of expression of CX3CR1 and XCR1 in eDLBCL. Expression of CCR6, CCR7, CXCR3, CXCR4, and CXCR5, responsible for B‐cell homing to secondary lymphoid tissue, was detected in both B‐cell malignancies. Expression of CCR4 was just detected in trisomy 3‐positive MALT lymphoma cases. Comparing gastric with extragastric MALT lymphomas, up‐regulation of CXCR1 and CXCR2 accompanied by down‐regulation of CCR8 and CX3CR1 and loss of XCR1 expression in extragastric MALT lymphomas appear to be key determinants for the site of origin of MALT lymphomagenesis. Our results support a model of stepwise progression of extragastric MALT lymphoma from a non‐neoplastic event to Sjögren syndrome, to MALT lymphoma, and finally to overt eDLBCL, guided by differentially expressed B‐cell homeostatic and activation‐dependent chemokine receptors and their ligands. Copyright © 2008 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Multifactor Expected-Returns Models and the Performance of Superstock Portfolios in the UK Equity Market

Two empirically testable behavioural finance hypotheses are that (1) 'superstock' portfolios derived from multifactor expected-returns models will have higher than average returns and lower than average risk in terms of statistical and economic significance; and, (2) the expected-returns factor models will demonstrate greater predictive and explanatory power than the risk- and expected-returns-risk factor models of modern finance. Using a dataset comprised of the entire universe of fully-listed stocks in the UK market for the period 1987 to 2002 a multifactor expected-returns model is constructed to estimate security payoffs to factors related to various characteristics such as risk, price level, liquidity, growth potential and previous performance. These payoffs are then used to estimate out-of-sample expected returns and to construct a 'superstock' portfolio. Our analysis suggests that compared to the existing risk-factor models, an 'expected-returns' factor model exhibits increased predictive power of expected returns and has consistently higher than average realised returns with lower than average risk. These results are significant in both statistical and economic terms and corroborate the above behavioural finance hypotheses.
Antibiotic resistance in Saudi Arabia and some Middle Eastern countries: Current status

Antibiotic resistance has become a major threat to human health worldwide, especially for serious infections, leaving limited choices for antimicrobials to be used. The World Health Organization (WHO) launched several strategies to control the spread of this resistance. However, in the Middle East the problem can become worse if these strategies are not applied due to the geographical location between developed and developing worlds, and the heavy misuse of antibiotics in the region. The current picture of antibiotic resistance in Saudi Arabia and some of the Middle Eastern countries represents high resistance rates among other regions to penicillin, erythromycin, fluoroquinolone, carbapenem and anti-tuberculosis drugs. Misuse of antibiotics is one of the major factors that contribute to the increase in antimicrobial resistance (AMR). This includes self-medication, incomplete dosage of the medication, missing doses, and re-use of excess antibiotics from previous prescription. Moreover, lack of adherence to infection control practice by healthcare professionals can contribute in spreading antibiotic resistance. An action plan has already been set by the WHO to limit antibiotic resistance. Application of this plan requires efforts of stakeholders from all regional countries to successfully stop the spread of AMR in the Middle East. Actions should include spreading public awareness of antibiotic resistance, as well as educational programs for healthcare professionals on infection prevention and control. National surveillances of antibiotic resistant bacteria that cause nosocomial infections are essential to identify outbreaks. Strict regulations regarding dispensing antibiotics should be imposed. Each country should take action to limit the spread of antibiotic resistance. If resistance is left uncontrolled, the region may face a time in which treatments of minor infections may become impossible. Key words: Antimicrobial resistance, Saudi Arabia, Middle East, antibiotic misuse, penicillin, erythromycin, fluoroquinolone, carbapenem.
Vancomycin-resistant enterococcus: risk factors, surveillance, infections, and treatment.

BACKGROUND The use of vancomycin has continued to expand because of the increasing number of patients infected or colonized with methicillin-resistant Staphylococcus aureus, causing an increase in the prevalence of vancomycin-resistant Enterococcus (VRE). METHODS Review of the pertinent English language literature. RESULTS Vancomycin-resistant Enterococcus spp. are being identified more often in nosocomial infections of surgical patients. The biology of resistance, modes of transmission, patient risk factors, and current treatment strategies are discussed. CONCLUSIONS The reservoir of resistance in enterococci looms as a major threat for genetic transfer and the emergence of increasing numbers of vancomycin-resistant S. aureus.
The influence of muscle load on tibiofemoral knee kinematics

A comparative kinematics study was conducted on six cadaver limbs, comparing tibiofemoral kinematics in five conditions: unloaded, under a constant 130 N ankle load with a variable quadriceps load, with and without a simultaneous constant 50 N medial and lateral hamstrings load. Kinematics were described as translation of the projected centers of the medial (MFT) and lateral femoral condyles (LFT) in the horizontal plane of the tibia, and tibial axial rotation (TR) as a function of flexion angle. In passive conditions, the tibia rotated internally with increasing flexion to an average of −16° (range: −12/−20°, SD = 3.0°). Between 0 and 40° flexion, the medial condyle translated forwards 4 mm (range: 0.8/5.5 mm, SD = 2.5 mm), followed by a gradual posterior translation, totaling −9 mm (range: −5.8/−18.5 mm, SD = 4.9 mm) between 40–140° flexion. The lateral femoral condyle translated posteriorly with increasing flexion completing −25 mm (range: −22.6 to −28.2 mm, SD = 2.5 mm). Dynamic, loaded measurements simulating a deep knee bend were carried out in a knee rig. Under a fixed ankle load of 130 N and variable quadriceps loading, tibial rotation was inverted, mean TR = 4.7° (range: −3.3°/11.8° SD = 5.4°), MFT = −0.5 mm (range: = −4.3/2.4 mm, SD = 2.4 mm), LFT = 3.3 mm (range: = −3.6/10.6 mm, SD = 5.1 mm). Compared to the passive condition, all these excursions were significantly different (p ≤ 0.015). Adding medial and lateral hamstrings force of 50 N each reduced TR, MFT, and LFT significantly compared to the passive condition. In general, loading the knee with hamstrings and quadriceps reduces rotation and translation compared to the passive condition. Lateral hamstring action is more influential on knee kinematics than medial hamstrings action. © 2009 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 28:419–428, 2010
Strict Volume Control and Longitudinal Changes in Cardiac Biomarker Levels in Hemodialysis Patients

Background: Our aim was to analyze the longitudinal changes in cardiac biomarker levels in hemodialysis patients with high comorbidity treated in our special hospital unit. We hypothesize that strict volume control strategy (salt-restricted diet, extended dialysis sessions and dry weight clinical assessment and reassessment in every session) could prevent progression of left-ventricular damage and, therefore, progressive increment in cardiac biomarker levels over time. Methods: This is a longitudinal cohort study including 46 dialysis patients in which a strategy of strict volume control has been adopted. N-terminal pro-B-type natriuretic peptide (NT-proBNP), troponin T and C-reactive protein (CRP) levels were measured at baseline and prospectively at 4, 8 and 12 months. The possible association between volume control and cardiac biomarker levels was analyzed. Results: Dry weight could be reduced (p < 0.01) over time. A reduction in systolic BP (p < 0.05) and in CRP levels (p < 0.05) was observed, whereas NT-proBNP and troponin T values remained stable. However, patients in the high quartile of NT-proBNP at baseline showed a reduction (p = 0.02) in troponin T over time with no significant trend (p = 0.08) to progressive reduction in NT-proBNP values. Conclusions: Strict volume control in dialysis patients may prevent progressive increment in cardiac biomarker levels over time. The impact seems to be higher among patients with higher levels at baseline in whom strict volume control can even reduce cardiac biomarker levels on follow-up.
Association of Mucinous Tumors of the Ovary and Appendix: A Clinicopathologic Study of 25 Cases

Twenty-five patients with mucinous tumors of the ovary and appendix were studied. The average age of the patients was 52 years, and the ovarian and appendiceal tumors were discovered synchronously in all but two cases. The majority had either a pelvic mass or abdominal or pelvic pain. A high frequency of bilateral ovarian tumors (11/25), and right-sided predominance for the unilateral ovarian tumors (nine right, five left) were found. Four patients had ovarian mucinous carcinomas, 10 had mucinous tumors of low malignant potential, 10 had mucinous cystadenomas, and one had a mucinous cyst. Pseudomyxoma ovarii was present in 22 cases. Twenty-two of 24 appendices were grossly abnormal. There were six appendiceal mucinous adenocarcinomas, 10 mucinous tumors of uncertain malignant potential, seven mucinous cystadenomas, one hyperplastic polyp, and one mucocele. Twelve patients had ovarian and appendiceal tumors of similar malignant potential, nine had appendiceal tumors with more aggressive morphologic features than the corresponding ovarian tumor, and four had ovarian tumors with more aggressive morphologic features than the appendiceal tumor. Eighteen patients had peritoneal involvement by mucinous epithelium admixed with mucus (nine localized, nine diffuse). Immunoperoxidase reactions for four epithelial antigens in 15 cases showed complete concordance between ovarian and appendiceal lesions in only five cases and were not helpful in determining the site of origin of the peritoneal tumor. Our findings suggest an independent origin of the ovarian and appendiceal tumors in most cases and do not favor an origin in a single site. Furthermore, it is proposed that the peritoneal lesions may arise de novo as part of a multifocal neoplastic process.
Career advising as an institutional model of academic advising

Many college students need assistance as they navigate academic, departmental, and university requirements necessary to complete a degree. Many students also require assistance in connecting academic learning to their vocational interests. Although academic advising and career development are both necessary to student success, academic advising functions and career development processes most often occur independently of one another on college campuses. Career advising is a model that combines academic advising and career counseling processes to emphasize relationships between educational choice and general career field to help students form appropriate academic and career goals based on this information. This dissertation used a qualitative single case study research design to gain an understanding of how one college chose the career advising model of academic advising, including exploring decision making and implementation processes that occurred as a means to move the institution from a more traditional model of advising to career advising. This qualitative approach allowed an opportunity to discover and examine why such decisions were made, how the change process occurred, how such a change affected the structure and function of the advising office, and staff impressions regarding the success of the model, in an effort to provide guidance for institutions that may wish to restructure their own advising program toward career advising. Implications for other institutions considering this model of advising were discussed and future research ideas identified. INDEX WORDS: Career advising, Academic advising, Advising models CAREER ADVISING AS AN INSTITUTIONAL MODEL OF ACADEMIC ADVISING: A CASE STUDY
Optical Coherence Tomography of Retinal Degeneration in Royal College of Surgeons Rats and Its Correlation with Morphology and Electroretinography

Purpose To evaluate the correlation between optical coherence tomography (OCT) and the histological, ultrastructural and electroretinography (ERG) findings of retinal degeneration in Royal College of Surgeons (RCS-/-) rats. Materials and Methods Using OCT, we qualitatively and quantitatively observed the continual retinal degeneration in RCS-/- rats, from postnatal (PN) day 17 until PN day 111. These findings were compared with the corresponding histological, electron microscopic, and ERG findings. We also compared them to OCT findings in wild type RCS+/+ rats, which were used as controls. Results After PN day 17, the hyperreflective band at the apical side of the photoreceptor layer became blurred. The inner segment (IS) ellipsoid zone then became obscured, and the photoreceptor IS and outer segment (OS) layers became diffusely hyperreflective after PN day 21. These changes correlated with histological and electron microscopic findings showing extracellular lamellar material that accumulated in the photoreceptor OS layer. After PN day 26, the outer nuclear layer became significantly thinner (P < 0.01) and hyperreflective compared with that in the controls; conversely, the photoreceptor IS and OS layers, as well as the inner retinal layers, became significantly thicker (P < 0.001 and P = 0.05, respectively). The apical hyperreflective band, as well as the IS ellipsoid zone, gradually disappeared between PN day 20 and PN day 30; concurrently, the ERG a- and b-wave amplitudes deteriorated. In contrast, the thicknesses of the combined retinal pigment epithelium and choroid did not differ significantly between RCS-/- and RCS+/+ rats. Conclusion Our results suggest that OCT demonstrates histologically validated photoreceptor degeneration in RCS rats, and that OCT findings partly correlate with ERG findings. We propose that OCT is a less invasive and useful method for evaluating photoreceptor degeneration in animal models of retinitis pigmentosa.
Strategic Cooperation

How do competing motivations influence the decisions of justices to author concurring opinions? Justices must balance their desire to shape the law and public policy toward their preferred position with the need for strong and stable coalitions. We construct a theoretical model of cooperative behavior that explicitly accounts for the competing individual- and group-level considerations of U.S. Supreme Court justices. Our theory identifies conditions specific to justices, coalitions, and cases that make the authoring of a separate opinion attractive to justices. We test these expectations using data from 40 years of justice votes within some 4,500 cases. The results of our empirical analyses support our theoretical expectations and show that the choice of a justice in the initial majority to write separately is conditional on characteristics of the justices and the coalition. We also highlight the important implications of our findings for the study of judicial decision making and policymaking more generally.