Miracle-dz/UniFAR-FTUs huggingface dataset:
Crystal structure of lactose permease in complex with an affinity inactivator yields unique insight into sugar recognition

Lactose permease of Escherichia coli (LacY) with a single-Cys residue in place of A122 (helix IV) transports galactopyranosides and is specifically inactivated by methanethiosulfonyl-galactopyranosides (MTS-gal), which behave as unique suicide substrates. In order to study the mechanism of inactivation more precisely, we solved the structure of single-Cys122 LacY in complex with covalently bound MTS-gal. This structure exhibits an inward-facing conformation similar to that observed previously with a slight narrowing of the cytoplasmic cavity. MTS-gal is bound covalently, forming a disulfide bond with C122 and positioned between R144 and W151. E269, a residue essential for binding, coordinates the C-4 hydroxyl of the galactopyranoside moiety. The location of the sugar is in accord with many biochemical studies.
Influence of Rifampicin on the Pharmacokinetics of Salvianolic Acid B May Involve Inhibition of Organic Anion Transporting Polypeptide (Oatp) Mediated Influx

This article studied the possible effect of rifampicin (RIF), an inhibitor of organic anion transporting polypeptide (Oatp), on the pharmacokinetics of salvianolic acid B (SAB) in rats. Rifampicin was administered intravenously 15 min prior to SAB (5 mg/kg) in rats at doses of 0, 5.0, 10.0 and 20.0 mg/kg, respectively. The concentrations of SAB in plasma and bile were determined using a Shimadzu HPLC system coupled to a LC‐MS‐2010EV mass spectrometer. Compared with the control group, the AUC0‐t and Cmax values of SAB were increased significantly, while the CLtotal and CLbile were decreased significantly. These results suggested that pretreatment with rifampicin prior to SAB administration could decrease significantly the total and bile elimination of SAB and alter its pharmacokinetic profiles. The influence of rifampicin on the pharmacokinetics of SAB may be attributed to the inhibition of Oatp‐mediated influx. Copyright © 2011 John Wiley & Sons, Ltd.
Identification of Mycobacterium avium pathogenicity island important for macrophage and amoeba infection

The ability to infect macrophages is a common characteristic shared among many mycobacterial species. Mycobacterium avium, Mycobacterium tuberculosis, and Mycobacterium kansasii enter macrophages, using the complement receptors CR1, CR3, CR4, and the mannose receptor. To identify M. avium genes and host cell pathways involved in the bacterial uptake by macrophages, we screened a M. avium transposon mutant library for the inability to enter macrophages. Uptake-impaired clones were selected. Sequence of six M. avium clones identified one gene involved in glycopeptidolipid biosynthesis, one gene encoding the conserved membrane protein homologue to the M. avium subsp. paratuberculosis MAP2446c gene and four others belonging to the same region of the chromosome. Analysis of the chromosome region revealed a pathogenicity island inserted between two tRNA sequences with 58% of G+C content versus 69% in the M. avium genome. The region is unique for M. avium and is not present in M. tuberculosis or M. paratuberculosis. Although the mutants did not differ from the WT bacterium regarding the binding to macrophage cell membrane, analysis of macrophage proteins after 1 h infection revealed a deficiency in the mutant to phosphorylate certain proteins on uptake. To understand M. avium interaction with two evolutionarily distinct hosts, the mutants were evaluated for Acanthamoeba castellanii invasion. The defect in the ability of the mutants to invade both cells was highly similar, suggesting that M. avium might have evolved mechanisms that are used to enter amoebas and human macrophages.
Potential involvement of cannabinoid receptors in 3-nitropropionic acid toxicity in vivo

Several neurotransmitter systems are involved in the pathogenesis of Huntington's disease. Here, we examined the involvement of cannabinoid CB1 receptors in striatal degeneration in the rat model of this disease generated by administration of 3-nitropropionic acid (3NP). Several days before onset of striatal degeneration, G-protein activation by cannabinoid agonists was significantly decreased whereas density and mRNA levels of CB1 receptors remained essentially normal. This change was transient, CB1 receptors recovering full functionality after few days. Later, at onset of striatal degeneration, profound alterations of CB1 receptors were detected, including marked reductions of their density, mRNA levels and coupling to G proteins. In these rats, the administration of the cannabinoid agonist Δ9-tetrahydrocannabinol was neuroprotective, which indicates that the early loss of CB1 receptor signaling could be instrumental in 3NP toxicity. In conclusion, the present study supports the hypothesis that cannabinoid receptors, possibly the CB1 receptor subtype, may be involved in HD pathogenesis and could be an interesting therapeutic target to slow disease progression.
CCR9-positive lymphocytes and thymus-expressed chemokine distinguish small bowel from colonic Crohn's disease.

BACKGROUND & AIMS Thymus-expressed chemokine (TECK) or CCL25) is selectively expressed in the small bowel (SB), where lamina propria lymphocytes (LPL) and intraepithelial leukocyte expressing the cognate chemokine receptor CCR9 predominate. We characterize the role of TECK and CCR9-expresing lymphocytes in small intestinal Crohn's disease. METHODS CCR9 expression on lymphocytes from lamina propria, mesenteric lymph node, and peripheral blood was analyzed by flow cytometry and by Northern blotting for LPL. TECK expression was analyzed in inflamed SB and colon by reverse-transcription polymerase chain reaction and immunohistochemistry. RESULTS The fraction of CCR9(+) T cells in inflamed SB was significantly lower than in uninvolved SB mucosa. In contrast, in peripheral blood lymphocytes, CCR9(+) lymphocytes were markedly elevated in patients with small bowel Crohn's or celiac disease, but not in patients with purely colonic Crohn's. Also, TECK expression is altered in inflamed small bowel, being intensely expressed in a patchy distribution in crypt epithelial cells in proximity to lymphocytic infiltrates. TECK is not expressed in either normal or inflamed colon. CONCLUSIONS In SB immune-mediated diseases, there is repartitioning of CCR9(+) lymphocytes between SB and blood and an altered pattern of TECK expression in SB Crohn's. The TECK/CCR9 ligand/receptor pair may play an important role in the pathogenesis of SB Crohn's disease.
Colorectal cancer screening: a global overview of existing programmes

Colorectal cancer (CRC) ranks third among the most commonly diagnosed cancers worldwide, with wide geographical variation in incidence and mortality across the world. Despite proof that screening can decrease CRC incidence and mortality, CRC screening is only offered to a small proportion of the target population worldwide. Throughout the world there are widespread differences in CRC screening implementation status and strategy. Differences can be attributed to geographical variation in CRC incidence, economic resources, healthcare structure and infrastructure to support screening such as the ability to identify the target population at risk and cancer registry availability. This review highlights issues to consider when implementing a CRC screening programme and gives a worldwide overview of CRC burden and the current status of screening programmes, with focus on international differences.
Comparison of two drug combinations in total intravenous anesthesia: Propofol–ketamine and propofol–fentanyl

Background and Aims: Keeping in consideration the merits of total intravenous anesthesia (TIVA), a genuine attempt was made to find the ideal drug combinations which can be used in general anesthesia. This study was conducted to evaluate and compare two drug combinations of TIVA using propofol–ketamine and propofol–fentanyl and to study the induction, maintenance and recovery characteristics following anesthesia with these techniques. Settings and Design: A case control study was conducted, which included 100 patients, in the department of Anaesthesiology and Intensive care, Government Medical College and Hospital, Patiala. Patients and Methods: A hundred patients between the ages of 20 and 50 years of either gender were divided into two groups of 50 each, and they underwent elective surgery of approximately 1 h duration. Group I received propofol–ketamine while group II received propofol–fentanyl for induction and maintenance of anesthesia. All the results were tabulated and analyzed statistically with student's unpaired t-test and chi-square test. Results: Propofol–fentanyl combination produced a significantly greater fall in pulse rate (PR; 9.28% versus 0.23%) and in both systolic (7.94% versus 0.12%) and diastolic blood pressures (BP; 8.10% versus 0.35%) as compared to propofol–ketamine during induction of anesthesia. Propofol–ketamine combination produced stable hemodynamics during maintenance phase while on the other hand propofol–fentanyl was associated with a slight increase in both PR and BP. During recovery, ventilation score was better in group I while movement and wakefulness score was better in group II. Mean time to protrusion of tongue and lifting of head was shorter in group I. Conclusions: Both propofol–ketamine and propofol–fentanyl combinations produce rapid, pleasant and safe anesthesia with only a few untoward side effects and only minor hemodynamic effects.
Sensitivity of cognitive tests in four cognitive domains in discriminating MDD patients from healthy controls: a meta-analysis

ABSTRACT Background: We performed a meta-analysis in order to determine which neuropsychological domains and tasks would be most sensitive for discriminating between patients with major depressive disorder (MDD) and healthy controls. Methods: Relevant articles were identified through a literature search of the PubMed and Cochrane Library databases for the period between January 1997 and May 2011. A meta-analysis was conducted using the standardized means of individual cognitive tests in each domain. The heterogeneity was assessed, and subgroup analyses according to age and medication status were performed to explore the sources of heterogeneity. Results: A total of 22 trials involving 955 MDD patients and 7,664 healthy participants were selected for our meta-analysis. MDD patients showed significantly impaired results compared with healthy participants on the Digit Span and Continuous Performance Test in the attention domain; the Trail Making Test A (TMT-A) and the Digit Symbol Test in the processing speed domain; the Stroop Test, the Wisconsin Card Sorting Test, and Verbal Fluency in the executive function domain; and immediate verbal memory in the memory domain. The Finger Tapping Task, TMT-B, delayed verbal memory, and immediate and delayed visual memory failed to separate MDD patients from healthy controls. The results of subgroup analysis showed that performance of Verbal Fluency was significantly impaired in younger depressed patients (<60 years), and immediate visual memory was significantly reduced in depressed patients using antidepressants. Conclusions: Our findings have inevitable limitations arising from methodological issues inherent in the meta-analysis and we could not explain high heterogeneity between studies. Despite such limitations, current study has the strength of being the first meta-analysis which tried to specify cognitive function of depressed patients compared with healthy participants. And our findings may provide clinicians with further evidences that some cognitive tests in specific cognitive domains have sensitivity to discriminate MDD patients from healthy controls.
Variation in Motivational Appeals to Survey Completion: Lessons from a Randomized Experiment with Teachers

Abstract Sample attrition increases the risk of statistical bias and hinders the ability to plausibly estimate causal effects when patterns of nonresponse are correlated with key variables of interest. Drawing on leverage-salience theory and other work in the behavioral psychology field, we empirically capture the impact of distinct motivational appeals on the survey response rates of elementary education teachers in a large urban school district in the northeastern United States. During spring 2017, teachers were randomized to receive one of six motivational appeals and were rerandomized to receive a different appeal each subsequent week, conditional on not having completed the survey. We observe the results on four different margins that range in their time intensity (open email and click, start, and complete survey). We find that extrinsic rewards improved teacher response across all four margins, and the social norm of reciprocity substantially improved teacher response along margins of lower time intensity. As researchers continue to conduct multitreatment arm studies and large-scale evaluations that can suffer from serious issues of sample attrition, this work highlights the contribution of message framing in survey response.
Fate of Salmonella montevideo on and in raw tomatoes as affected by temperature and treatment with chlorine

A study was undertaken to determine the survival patterns of Salmonella montevideo G4639 on and in tomatoes during storage and the efficacy of chlorine treatment on inactivation of the pathogen. The population of S. montevideo on the surfaces of inoculated tomatoes stored at 10 degrees C did not change significantly (P < 0.05) throughout an 18-day storage period. Significant increases in population occurred within 7 days and within 1 day when tomatoes were stored at 20 and 30 degrees C, respectively. A significantly higher number of cells was taken up by the core tissue of tomatoes tempered at 25 degrees C when the tomatoes were dipped in a suspension at 10 degrees C compared with the number taken up when the tomatoes were dipped in cell suspensions tempered at 25 or 37 degrees C. Populations remained constant throughout subsequent storage for 8 days at 10 degrees C, regardless of the temperature differential between tomatoes and the dip suspension. Storage of tomatoes at 20 degrees C, however, resulted in significant increases in populations of S. montevideo. Populations of the pathogen on the surfaces and in the core tissues of tomatoes were significantly reduced by dipping for 2 min in a solution containing 60 or 110 ppm (60 or 110 micrograms/ml) chlorine, respectively; however, treatment in solution containing 320 ppm chlorine did not result in complete inactivation. Populations of S. montevideo remained unchanged in chopped tomatoes stored at 5 degrees C for 216 h (9 days) but increased significantly after storage for 96 or 22 h at 20 or 30 degrees C, respectively. (ABSTRACT TRUNCATED AT 250 WORDS)
Capecitabine and timing of radiotherapy during preoperative chemoradiation for rectal cancer.

BACKGROUND Capecitabine is effective in treating colorectal cancer and is increasingly being investigated for use in preoperative chemoradiation of rectal cancer. Since capecitabine and its metabolites have a plasma half-life of 0.5-1 hour, the relative timing of capecitabine and radiotherapy may affect clinical outcomes. We retrospectively investigated whether the timing of radiotherapy affects rates of acute toxicity, pathologic response, and relapse in rectal cancer patients receiving capecitabine. METHODS Between June 2001 and July 2004, 111 rectal cancer patients were treated with preoperative radiotherapy and concurrent capecitabine given twice daily, in the early morning and at night. Of these, 44 received at least 70% of their radiation treatments before 12 PM (AM group), and 47 received at least 70% of their radiation treatments after 12 PM (PM group). RESULTS There were no significant differences between the AM vs. PM groups in rates of grade >/= 2 acute gastrointestinal toxicity (61% vs. 47%) or skin toxicity (23% vs. 26%) or grades >/= 1 hand-foot syndrome (27% vs. 15%). Although the PM group had numerically higher rates of pathologic complete response (28% vs. 16%) and tumor downstaging (57% vs. 39%), differences in these outcomes and in sphincter preservation were not significant. Rates of 2-year local control, distant control, and disease-free survival were nearly identical in the two groups. CONCLUSIONS No significant differences were seen in the rates of acute toxicity, pathologic response, and relapse between patients in the AM and PM groups. The timing of radiotherapy does not appear to be critical in patients with rectal cancer receiving concurrent capecitabine.
Survey Article: A tour of the weak and strong Lefschetz properties

An artinian graded algebra, A, is said to have the weak Lefschetz property (WLP) if multiplication by a general linear form has maximal rank in every degree. A vast quantity of work has been done studying and applying this property, touching on numerous and diverse areas of algebraic geometry, commutative algebra and combinatorics. Amazingly, though, much of this work has a “common ancestor” in a theorem originally due to Stanley, although subsequently reproved by others. In this paper we describe the different directions in which research has moved starting with this theorem, and we discuss some of the open questions that continue to motivate current research.
Analysis of envelope sequence variants suggests multiple mechanisms of mother-to-child transmission of human immunodeficiency virus type 1

In order to elucidate the molecular mechanisms involved in human immunodeficiency virus type 1 (HIV-1) mother-to-child transmission, we have analyzed the genetic variation within the V3 hypervariable domain and flanking regions of the HIV-1 envelope gene in four mother-child transmission pairs. Phylogenetic analysis and amino acid sequence comparison were performed on cell-associated viral sequences derived from maternal samples collected at different time points during pregnancy, after delivery, and from child samples collected from the time of birth until the child was approximately 1 year of age. Heterogeneous sequence populations were observed to be present in all maternal samples collected during pregnancy and postdelivery. In three newborns, viral sequence populations obtained within 2 weeks after birth revealed a high level of V3 sequence variability. In contrast, V3 sequences obtained from the fourth child (diagnosed at the age of 1 month) displayed a more restricted heterogeneity. The phylogenetic analysis performed for each mother-child sequence set suggested that several mechanisms may potentially be involved in HIV-1 vertical transmission. For one pair, child sequences were homogeneous and clustered in a single branch within the phylogenetic tree, consistent with selective transmission of a single maternal variant. For the other three pairs, the child sequences were more heterogeneous and clustered in several separate branches within the tree. In these cases, it appeared likely that more than one maternal variant was responsible for infection of the child. In conclusion, no single mechanism can account for mother-to-child HIV-1 transmission; both the selective transmission of a single maternal variant and multiple transmission events may occur.
Partnerships for Success in Washington State : Supporting Evidence-Based Programming for Children ’ s Mental Health

As we write the editorial for this issue of EBDY , both Houses of Congress as well as the President are in the midst of intensive deliberations on how we can reform our health care system. The outcome of this debate is uncertain. What is clear is that the status quo is unacceptable as it relates to both the health and behavioral health needs of families and their children. The increasing costs of maintaining our current system of health care delivery negatively affect not only families’ ability to purchase health insurance but also states’ capacity to support Medicaid programs. Moreover, business as usual will continue to impair the capacity of our country to move out of the current recession. How does the health reform debate specifically relate to children’s mental health? It will come as no surprise to the readers of EBDY —as well as to primary care providers—that the most prevalent overall health problems of children are those associated with emotional and behavioral health (Kessler, 2009). There are ample data indicating that adverse and untreated childhood problems lead to a host of bad social and emotional outcomes in adulthood. Even more striking is the f inding that ineffectively
Akceptacja choroby i strategie radzenia sobie z bólem jako istotne komponenty oceny jakości życia zależnej od stanu zdrowia u chorych z migreną. Doniesienie wstępne

Wstep. Migrena jest schorzeniem, w ktorym dominuje napadowy bol glowy z objawami towarzyszącymi, jak: nudności, wymioty, zawroty glowy, nadwrazliwośc na dźwieki, światlo, zapach. W czasie napadu pacjenci nie są w stanie funkcjonowac aktywnie w zyciu codziennym. Cel pracy. Ocena poziomu akceptacji choroby i określenie wystepujących trudności mających istotny wplyw na funkcjonowanie spoleczne u pacjentow z rozpoznaną migreną. Określenie najcześciej stosowanych przez pacjentow strategii radzenia sobie z bolem. Material i metody. Narzedziem badawczym byl autorski kwestionariusz ankiety, ktory zawieral Skale Akceptacji Choroby (AIS) i kwestionariusz Strategii Radzenia Sobie z Bolem (CSQ). W badaniu wziela udzial grupa 60 osob aktywnych zawodowo z rozpoznaną migreną. U 39 badanych (65%) stwierdzono migrene przebiegającą z aurą, natomiast u 21 osob (35%) wystepowala migrena bez aury. W badanej grupie wystepowaly napady o roznym stopniu nasilenia objawow zasadniczych i dodatkowych. Wyniki. Najliczniejszą grupe stanowili pacjenci, u ktorych wystepowala migrena z aurą - 65% badanych w wieku od 25 do 45 lat. W przypadku 87% osob, u ktorych wystepowaly napady o przebiegu średnio ciezkim, ciezkim lub bardzo ciezkim, stosowano w terapii tryptany. Liczbe punktow w skali AIS w przedziale 30-40 uzyskalo 26 pacjentow (44%), co wskazuje na wysoką akceptacje migreny. Wartości średnie uzyskaly 23 osoby (38%) uczestniczące w badaniu. Wiekszośc badanych chorych stosuje strategie, ktore zmierzają do aktywnego zaangazowania tworczego w zyciu: radzenia sobie z bolem i przewartościowanie jego doznan. Wnioski: 1.Sytuacja zdrowotna zdecydowanie utrudnia lub uniemozliwia okresowo codzienne funkcjonowanie w przypadku chorych, u ktorych wystepują napady o natezeniu średnim, ciezkim i bardzo ciezkim objawow klinicznych. 2. Wiekszośc chorych przejawia wysoką akceptacje choroby. 3.Badani stosują wybrane strategie: deklarowanie radzenia sobie i przewartościowanie doznan bolu w trakcie napadow.
Perception of Macao Teachers and Students Regarding Gaming Operators' Social Responsibility

The study brings to the forefront a discussion of corporate social responsibility of gaming operators. It assessed Macao high school students' and teachers' perceptions of the extent of social responsibility being exercised by the six local gaming operators, as well as their support for the operators, and desire for further gaming investment and work opportunities in the gaming sector. The majority of the respondents were not aware of gaming operators exercising socially responsible activities. Among those who were, the majority perceived that only one company was involved and none has participated in protecting the environment, beautifying the city, creating a harmonious environment, treating local staff fairly, and promoting responsible gambling. Five social responsibility factors were identified. Poisson regression analysis indicated that perception of gaming operators' being considerate of Macao's interests was influenced significantly by their contribution to three socially responsible activities.