Miracle-dz/UniFAR-FTUs huggingface dataset:
Leukemia Inhibitory Factor Is Linked to Regulatory Transplantation Tolerance

Background. The specific regulation of allo-tolerance in vivo occurs within a complex microenvironment and involves co-operation between a small proportion of different cell types within the spleen or draining lymph node. By analyzing unmanipulated whole spleen cell populations we have aimed to mimic this in vivo situation to identify critical signaling molecules in regulatory allo-tolerance. Methods. We compared the kinetics of cytokine release and induction of signaling proteins in BALB/c-tolerantCBA, versus BALB/c-rejectedCBA, spleen cells after challenge with BALB/c antigen. Results. The distinguishing features of allo-tolerance were Foxp3 protein expression, LIF release, and increased levels of STAT3. Comparison of isogenic clones of Tr1, Th1, and Th2 cells revealed that only the regulatory Tr1 cells are characterized by both LIF and IL10 release. Conclusions. Overall, our findings demonstrate that allo-antigen driven signaling events can be detected within a whole spleen cell population and identify a role for LIF in the regulation of transplantation tolerance in vivo.
Constitutive expression in gal7 mutants of Kluyveromyces lactis is due to internal production of galactose as an inducer of the Gal/Lac regulon

The induction process of the galactose regulon has been intensively studied, but until now the nature of the inducer has remained unknown. We have analyzed a delta gal7 mutant of the yeast Kluyveromyces lactis, which lacks the galactotransferase activity and is able to express the genes of the Gal/Lac regulon also in the absence of galactose. We found that this expression is semiconstitutive and undergoes a strong induction during the stationary phase. The gal1-209 mutant, which has a reduced kinase activity but retains its positive regulatory function, also shows a constitutive expression of beta-galactosidase, suggesting that galactose is the inducer. A gal10 deletion in delta gal7 or gal1-209 mutants reduces the expression to under wild-type levels. The presence of the inducer could be demonstrated in both delta gal7 crude extracts and culture medium by means of a bioassay using the induction in gal1-209 cells. A mutation in the transporter gene LAC12 decreases the level of induction in gal7 cells, indicating that galactose is partly released into the medium and then retransported into the cells. Nuclear magnetic resonance analysis of crude extracts from delta gal7 cells revealed the presence of 50 microM galactose. We conclude that galactose is the inducer of the Gal/Lac regulon and is produced via UDP-galactose through a yet-unknown pathway.
De novo Synthesis of Sphingolipids Is Defective in Experimental Models of Huntington's Disease

Alterations of lipid metabolism have been frequently associated with Huntington's disease (HD) over the past years. HD is the most common neurodegenerative disorder, with a complex pathogenic profile, typically characterized by progressive striatal and cortical degeneration and associated motor, cognitive and behavioral disturbances. Previous findings from our group support the idea that disturbed sphingolipid metabolism could represent an additional hallmark of the disease. Although such a defect represents a common biological denominator among multiple disease models ranging from cells to humans through mouse models, more efforts are needed to clearly define its clinical significance and the role it may play in the progression of the disease. In this study, we provided the first evidence of a defective de novo biosynthetic pathway of sphingolipids in multiple HD pre-clinical models. qPCR analysis revealed perturbed gene expression of sphingolipid-metabolizing enzymes in both early and late stage of the disease. In particular, reduction in the levels of sptlc1 and cerS1 mRNA in the brain tissues from manifest HD mice resulted in a significant decrease in the content of dihydroSphingosine, dihydroSphingosine-1-phospahte and dihydroCeramide [C18:0] as assessed by mass spectrometry. Moreover, in vitro studies highlighted the relevant role that aberrant sphingolipid metabolism may have in the HD cellular homeostasis. With this study, we consolidate the evidence of disturbed sphingolipid metabolism in HD and demonstrate for the first time that the de novo biosynthesis pathway is also significantly affected in the disease. This finding further supports the hypothesis that perturbed sphingolipid metabolism may represent a crucial factor accounting for the high susceptibility to disease in HD.
in vivo Cell Lineage Analysis During Chemical Hepatocarcinogenesis in Rats Using Retroviral-Mediated Gene Transfer: Evidence for Dedifferentiation of Mature Hepatocytes

Feeding adult rats with a diet containing 2-acetylaminofluorene (2-AAF) results in suppression of hepatocyte proliferation and stimulation of oval cell proliferation. Although oval cells may be facultative liver stem cells, the actual relationship between oval cells and liver cancer has not been clearly established in vivo. Our goal was to label hepatic cells in vivo using retroviral vectors and follow their fate during the early steps of chemically induced hepatocarcinogenesis. Oval cell proliferation was induced by continuous feeding with a carcinogenic diet containing 2-AAF. We used two different strategies to genetically label hepatic cells: (a) labeling of proliferating cells in rats fed 2-AAF by injecting recombinant retroviral vectors containing the β-galactosidase gene either in a peripheral vein or in the common bile duct at the peak of oval cell proliferation and (b) prelabeling of hepatocytes by intravenously injecting recombinant vectors 1 day after partial hepatectomy and 1 week before subsequent administration of 2-AAF. Using the first strategy, transgene expression occurred in both oval cells and hepatocytes. Using the second strategy, we could selectively label, and hence study the fate of, differentiated hepatocytes. In the latter case, we observed clusters of β-galactosidase–positive hepatocytes, some of them also expressing preneoplastic markers such as gamma-glutamyl transpeptidase as well as the placental form of glutathione-S-transferase. These results demonstrate that preneoplastic foci can originate from mature hepatocytes and are consistent with the hypothesis that dedifferentiation of mature hepatocytes may occur during the course of carcinogenic regimen.
Impact of late incomplete stent apposition after sirolimus-eluting stent implantation on 4-year clinical events: intravascular ultrasound analysis from the multicentre, randomised, RAVEL, E-SIRIUS and SIRIUS trials

Background: The impact of incomplete stent apposition (ISA) after drug-eluting stent implantation determined by intravascular ultrasound (IVUS) on late clinical events is not well defined. Objective: To evaluate the clinical impact of ISA after sirolimus-eluting stent (SES) placement during a follow-up period of 4 years. Design: Pooled analysis from the RAVEL, E-SIRIUS and SIRIUS trials, three randomised, multicentre studies comparing SES and bare-metal stents (BMS). Methods: IVUS at angiographic follow-up was available in 325 patients (SES: n = 180, BMS: n = 145). IVUS images were reviewed for the presence of ISA defined as one or more unapposed stent struts. Clinical follow-up was available for a 4-year period in all patients. Frequency, predictors and clinical sequel of ISA at follow-up after SES and BMS implantation were determined. Results: ISA at follow-up was more common after SES (n = 45 (25%)) than after BMS (n = 12 (8.3%), p<0.001). Canadian Cardiology Society class III or IV angina at stent implantation (odds ratio (OR) = 4.69, 95% CI 2.15 to 10.23, p<0.001) and absence of diabetes (OR = 3.42, 95% CI 1.05 to 11.1, p = 0.041) were predictors of ISA at follow-up after SES placement. Rate of myocardial infarction tended to be slightly higher for ISA than for non-ISA patients. When SES patients only were considered, major adverse cardiac event free survival at 4 years was identical for those with and without ISA at follow-up (11.1% vs 16.3%, p = 0.48). Conclusions: ISA at follow-up is more common after SES implantation than after BMS implantation. Considering the current very sensitive IVUS definition, ISA appears to be an IVUS finding without significant impact on the incidence of major adverse cardiac events even during long-term follow-up.
On the Interannual Variability of the Indonesian Throughflow and Its Linkage with ENSO

Abstract The Indonesian Throughflow (ITF) variability is assessed using a retrospective analysis of the global ocean based on the Simple Ocean Data Assimilation (SODA) experiment spanning the period 1950–99. A comparison between the 1983–95 observed ITF, and the simulated ITF suggests a reasonably accurate reconstruction of ocean circulation in the vicinity of the ITF during the available measurement record. A wavelet analysis shows that once the seasonal cycle is removed, the dominant variation of the ITF anomaly is an interannual oscillation with a period of about 4–7 yr. This interannual variability is significantly correlated with the El Nino–Southern Oscillation (ENSO) pattern, with the ITF lagging the ENSO cycle by 8–9 months. This suggests that large-scale tropical ocean–atmosphere interaction plays an important role in the interannual variability of the ITF. Regional upper-ocean heat content variability might also play a role in controlling interannual fluctuations of the ITF transport via geostro.
Impaired Quality of the Hepatitis B Virus (HBV)-Specific T-Cell Response in Human Immunodeficiency Virus Type 1-HBV Coinfection

ABSTRACT Hepatits B virus (HBV)-specific T cells play a key role both in the control of HBV replication and in the pathogenesis of liver disease. Human immunodeficiency virus type 1 (HIV-1) coinfection and the presence or absence of HBV e (precore) antigen (HBeAg) significantly alter the natural history of chronic HBV infection. We examined the HBV-specific T-cell responses in treatment-naïve HBeAg-positive and HBeAg-negative HIV-1-HBV-coinfected (n = 24) and HBV-monoinfected (n = 39) Asian patients. Peripheral blood was stimulated with an overlapping peptide library for the whole HBV genome, and tumor necrosis factor alpha and gamma interferon cytokine expression in CD8+ T cells was measured by intracellular cytokine staining and flow cytometry. There was no difference in the overall magnitude of the HBV-specific T-cell responses, but the quality of the response was significantly impaired in HIV-1-HBV-coinfected patients compared with monoinfected patients. In coinfected patients, HBV-specific T cells rarely produced more than one cytokine and responded to fewer HBV proteins than in monoinfected patients. Overall, the frequency and quality of the HBV-specific T-cell responses increased with a higher CD4+ T-cell count (P = 0.018 and 0.032, respectively). There was no relationship between circulating HBV-specific T cells and liver damage as measured by activity and fibrosis scores, and the HBV-specific T-cell responses were not significantly different in patients with either HBeAg-positive or HBeAg-negative disease. The quality of the HBV-specific T-cell response is impaired in the setting of HIV-1-HBV coinfection and is related to the CD4+ T-cell count.
Vancouver dietitians' perspectives on their roles in long-term care.

PURPOSE In this study, we sought insight into the clinical practice experiences of dietitians working independently (i.e., as the only dietitian in a facility) in long-term care (LTC). We hoped to learn about their work roles and identify specific factors that facilitate their success. METHODS Grounded theory methods were used. Data were collected through 11 semi-structured interviews. Verbatim transcripts were analyzed using a constant comparative method, which included coding, memo writing, and ongoing discussion between the two researchers. RESULTS When speaking about their roles, participants identified both specific tasks they had to complete and broader roles they fulfilled. Many of these roles focused on relationships with co-workers and building effective multidisciplinary teams. Effective teamwork was linked with dietitians' personal feelings of success in providing resident-focused nutritional care in the LTC setting. CONCLUSIONS The LTC dietitians' various roles were generally self-appointed, and they focused more on the purpose of their work than on tasks. A primary focus of these roles was the multidisciplinary team and the promotion of effective teamwork, especially, but not exclusively, as it applies to the provision of nutritional care. Successful teamwork was linked to dietitians' reports of personal success in their work.
Pleuropulmonary blastoma in an adult

Pleuropulmonary blastoma (PPB) is a unique dysontogenetic neoplasm of childhood. Its primitive, sarcomatous features are analogous to those of other dysembryonic or dysontogenetic tumors, such as Wilms tumor, hepatoblastoma, neuroblastoma, and embryonal rhabdomyosarcoma. PPB typically presents in young children, most younger than 5 years, as a pulmonary and/or pleural‐based tumor with cystic, solid, or combined cystic and solid features. These neoplasms are characterized histologically by primitive mesenchymal or a mixture of primitive and sarcomatous components and generally have an unfavorable clinical outcome: death occurs within 1–2 years after diagnosis.
Conformational Epitope-Specific Broadly Neutralizing Plasma Antibodies Obtained from an HIV-1 Clade C-Infected Elite Neutralizer Mediate Autologous Virus Escape through Mutations in the V1 Loop

ABSTRACT Broadly neutralizing antibodies isolated from infected patients who are elite neutralizers have identified targets on HIV-1 envelope (Env) glycoprotein that are vulnerable to antibody neutralization; however, it is not known whether infection established by the majority of the circulating clade C strains in Indian patients elicit neutralizing antibody responses against any of the known targets. In the present study, we examined the specificity of a broad and potent cross-neutralizing plasma obtained from an Indian elite neutralizer infected with HIV-1 clade C. This plasma neutralized 53/57 (93%) HIV pseudoviruses prepared with Env from distinct HIV clades of different geographical origins. Mapping studies using gp120 core protein, single-residue knockout mutants, and chimeric viruses revealed that G37080 broadly cross-neutralizing (BCN) plasma lacks specificities to the CD4 binding site, gp41 membrane-proximal external region, N160 and N332 glycans, and R166 and K169 in the V1-V3 region and are known predominant targets for BCN antibodies. Depletion of G37080 plasma with soluble trimeric BG505-SOSIP.664 Env (but with neither monomeric gp120 nor clade C membrane-proximal external region peptides) resulted in significant reduction of virus neutralization, suggesting that G37080 BCN antibodies mainly target epitopes on cleaved trimeric Env. Further examination of autologous circulating Envs revealed the association of mutation of residues in the V1 loop that contributed to neutralization resistance. In summary, we report the identification of plasma antibodies from a clade C-infected elite neutralizer that mediate neutralization breadth via epitopes on trimeric gp120 not yet reported and confer autologous neutralization escape via mutation of residues in the V1 loop. IMPORTANCE A preventive vaccine to protect against HIV-1 is urgently needed. HIV-1 envelope glycoproteins are targets of neutralizing antibodies and represent a key component for immunogen design. The mapping of epitopes on viral envelopes vulnerable to immune evasion will aid in defining targets of vaccine immunogens. We identified novel conformational epitopes on the viral envelope targeted by broadly cross-neutralizing antibodies elicited in natural infection in an elite neutralizer infected with HIV-1 clade C. Our data extend our knowledge on neutralizing epitopes associated with virus escape and potentially contribute to immunogen design and antibody-based prophylactic therapy.
The President as Legislative Leader: The Use of Veto Power in Environmental Policy Making

Abstract Presidents use legislative powers in many ways to influence environmental policy. The relationship between partisanship and the use of these powers is an open question. Previous research has shown that legislative powers such as the passage of legislation and budgetary decisions display bipartisan effects. This study argues that this does not hold true for veto power. Presidents of different parties approach environmental legislation differently and use vetoes in dissimilar ways. Understanding these differences allows for a better comprehension of how environmental policy decisions are made and the role of presidents in this process.
Clinical Significance of Serum Uric Acid Levels in Mexican Young Adults.

BACKGROUND High serum uric acid concentration (SUA >6 for women [W] or 7 mg/dL for men [M]) in adults is an independent risk factor for causing cardiovascular disease and chronic kidney disease (CKD); the risk of high SUA in young population is still being debated. SUMMARY We conducted an epidemiological study to determine the association between SUA quartiles with cardiometabolic risk factors (CRF) and renal impairment in apparently healthy young adults. CRF (dyslipidemia, overweight [Ow], obesity [Ob], blood pressure [BP], hyperglycemia, insulin resistance [IR]) and renal impairment were defined as glomerular filtration rate (GFR) by CKD-Epidemiology Collaboration formula >130/120, <90 mL/min/1.73 m2, and proteinuria were measured in 18- to 25-year-old students (total n = 5,531). Adjusted ORs by sex were calculated using logistic regression. RESULTS The mean SUA was 4.5 ± 1.04 and 6.2 ± 1.2 mg/dL in W and M respectively. High SUA was found in 13.9% (n = 767); prevalence of Ow/Ob 69% (528 of 767), high BP 9% (67), hyperglycemia 15% (112), IR 47% (214), hypertriglyceridemia 35% (269), high LDL-c 16% (120), low HDL-c 52% (399), and metabolic syndrome 33% (249). Prevalence of high GFR was 13% (103), low GFR 8% (62) and proteinuria 5% (37). All risk factors showed a positive relationship with the SUA quartiles with high LDL-c with lowest risk (OR 1.7) and Ow/Ob with highest risk (OR 4.1), independent of sex. Key Messages: High SUA concentrations (M ≥6.2/W ≥4.5 mg/dL) are associated with CRF and renal impairment in young adults. It is necessary to reevaluate the cutoff points for UA in young adults.
Urine flavonoids and plasma carotenoids in the validation of fruit, vegetable and tea intake during pregnancy in the Norwegian Mother and Child Cohort Study (MoBa)

Abstract Objective To validate a new food-frequency questionnaire (FFQ) for measuring the intake of fruit, vegetables and tea reported by women participating in the Norwegian Mother and Child Cohort Study (MoBa). Design Intake of fruits, vegetables and tea estimated by the FFQ was compared with urinary flavonoid excretion, plasma carotenoid concentration and intake measured by a 4-day weighed food diary (FD). The triangular method was applied to calculate FFQ validity coefficients using two independent biomarkers. Setting and subjects One hundred and nineteen women participating in MoBa. Results The FFQ estimate of fruit intake was significantly correlated with urine phloretin (r = 0.33), citrus fruit/juice with urine hesperetin (r = 0.44), cooked vegetables with plasma α-carotene (r = 0.37), and tea with urine kaempferol (r = 0.41) (P < 0.01 for all). On average, 60% of the participants fell into the same or adjacent quintiles when classified by FFQ and biomarkers. Significant correlations between the FFQ and FD were found for fruit (r = 0.39), vegetables (r = 0.34), juices (r = 0.50) and tea (r = 0.53). The FFQ validity coefficient was 0.65 for citrus fruit/juice and 0.59 for cooked vegetables as calculated by the triangular method. Conclusions The validation study shows that the MoBa FFQ can be used to estimate fruit, juice, vegetable and tea intake in pregnant Norwegian women, and to rank individuals within the distribution.
Evaluation of selective direct plating media for their suitability to recover uninjured, heat-injured, and freeze-injured Listeria monocytogenes from foods

Six direct plating media were evaluated for their suitability to recover uninjured, heat-injured, and freeze-injured cells of four strains of Listeria monocytogenes from four foods. Cells were inoculated into foods to achieve ca. 10(2) to 10(3), 10(4) to 10(5), or 10(5) to 10(6) viable cells per ml or g (low, medium, and high populations, respectively). No appreciable differences in recovery of the four test strains within a treatment were observed. Generally, recovery on all test media was similar and not markedly affected by freeze treatment. Modified Despierres agar and modified McBride Listeria agar yielded poorer recovery of heat-injured cells than did McBride Listeria agar and gum base-nalidixic acid-tryptone soya agar. Overall, gum base-nalidixic acid-tryptone soya agar was best for recovering L. monocytogenes from pasteurized milk and chocolate ice cream mix. Enumeration was complicated by the growth of background microflora present in Brie cheese and cabbage, especially at the low inoculum. Dominguez Rodriguez isolation agar was superior for recovering L. monocytogenes from Brie cheese, whereas modified Despierres agar was best for recovering the organism from cabbage. Direct plating procedures can successfully be utilized for recovering healthy and injured L. monocytogenes from foods containing low populations of background microflora.
Information System Success in Tanzania Customs Operations: Taxpayers’ Optimism Bias and Perceived Ease of Use

This study aimed at investigating the information systems (IS) success from activities rendered by different actors in customs clearance operations in Tanzania. Specifically, the study intended to assess users’ optimism bias perception and perceived ease of use due to challenges encountered in clearance of cargo. To attain the study objectives, primary data was collected from 223 tax practitioners and taxpayers from Customs and Excise Department of the Tanzania Revenue Authority. Descriptive analysis was used to summarize the data. Besides, principal component analysis assisted in determining the constructs of the study. Subsequently, confirmatory factor analysis was run for data validity; whereas, structural equation modeling tested the developed hypotheses. The study found that optimism bias and perceived ease of use were both positively and significantly associated with IS success in customs clearance operations. The study recommends provision of user friendly systems and reliable website applications for taxpayers continual usage of the developed systems for IS success. Furthermore, the study provides useful inputs relevant to different stakeholders such as researchers useful for future research as well as practitioners, especially tax administrators. Keywords : IS success, optimism bias, perceived ease of use DOI : 10.7176/IKM/9-3-02 Publication date :March 31 st 2019