Interferon-λ rs12979860 genotype and liver fibrosis in viral and non-viral chronic liver disease

Tissue fibrosis is a core pathologic process that contributes to mortality in ∼45% of the population and is likely to be influenced by the host genetic architecture. Here we demonstrate, using liver disease as a model, that a single-nucleotide polymorphism (rs12979860) in the intronic region of interferon-λ4 (IFNL4) is a strong predictor of fibrosis in an aetiology-independent manner. In a cohort of 4,172 patients, including 3,129 with chronic hepatitis C (CHC), 555 with chronic hepatitis B (CHB) and 488 with non-alcoholic fatty liver disease (NAFLD), those with rs12979860CC have greater hepatic inflammation and fibrosis. In CHC, those with rs12979860CC also have greater stage-constant and stage-specific fibrosis progression rates (P<0.0001 for all). The impact of rs12979860 genotypes on fibrosis is maximal in young females, especially those with HCV genotype 3. These findings establish rs12979860 genotype as a strong aetiology-independent predictor of tissue inflammation and fibrosis

Optimization of the industrial production of bacterial alpha amylase in Egypt. IV. Fermentor production and characterization of the enzyme of two strains of Bacillus subtilis and Bacillus amyloliquefaciens

Production of alpha amylase using amplified variants of Bacillus subtilis (strain SCH) and of Bacillus amyloliquefaciens (strain 267CH) was conducted in a bioreactor with multiprotein-mineral media. Thetime course of fermentation in a bioreactor revealed that the highest yield (about 8 x 104 U/ml within 60 h) by strain SCH was obtained by applying: 3.5% initial starch, 2% additional starch after 19 h, 3 vvmaeration and 300 rpm agitation. The highest yield (about 19 x 104 U/ml within 100 h) by strain 267CH was obtained by applying: 2.5% initial starch, 2% additional starch after 24 h, 3 vvm aeration, and 300 rpmagitation with the productivity after 60 h reaching only about 14 x 104 U/ml. Production occurred in both the logarithmic and postlogarithmic phases of growth. Maximum consumption of starch and proteinoccurred during the first day of incubation. The optical density peak coincided with enzyme production peak in case of strain SCH and preceded that of enzyme production in case of strain 267CH. The alphaamylase produced by the two strains was shown to be of the liquefying and not the saccharifying type. Both enzymes liquefied starch to a dextrose equivalent of about 15 - 17 at 95oC hence they areclassified among thermostable alpha amylases. They exhibited broad pH and temperature activity profiles. The optimum pH for activity was 4 - 7 for alpha amylase produced by strain SCH and 4 - 8 foralpha amylase produced by strain 267CH while the optimum temperatures for their activities were in the range 37 -75oC at 0.5% starch and in the range 85 - 95oC at 35% starch

Neighborhood-Level Deprivation Mediates Racial and Ethnic Disparities in HCC Diagnosis in Texas

BACKGROUND: Texas has the highest HCC rates in the United States, and the greatest burden is among Hispanics. Racial and ethnic disparities in HCC incidence have multiple underpinning factors. We conducted a mediation analysis to examine the role of neighborhood disadvantage (Area Deprivation Index) as a potential mediator of the association between neighborhood race and ethnicity distribution and neighborhood HCC case counts in Texas. METHODS: The primary outcome measure was counts of new HCC diagnoses per census tract based on Texas Department of State Health Services Texas Cancer Registry data. The primary exposure of interest was the race and ethnicity-based Index of Concentration at the Extremes (non-Hispanic Black ICE or Hispanic ICE). We assessed Area Deprivation Index as a potential mediator of the association between Black/Hispanic ICE and HCC case counts. We adjusted the analyses for selected census tract characteristics. RESULTS: We analyzed 4934 census tracts containing 13,632 new HCC diagnoses reported to Texas Cancer Registry between 2016 and 2020. Racial minority (Black/Hispanic ICE)-concentrated neighborhoods had a higher socioeconomic disadvantage. The results of the mediation analyses showed that compared to non-Hispanic White-concentrated census tracts, non-Hispanic Black-concentrated census tracts and Hispanic-concentrated census tracts had higher case counts of HCC (total effects: adjusted case count ratio: 1.03 [95% CI, 1.02-1.04] and adjusted case count ratio: 1.09 [95% CI, 1.08-1.10], respectively). Approximately 48% and 15% of the neighborhood-level disparity in HCC case counts were attributable to neighborhood socioeconomic disadvantage in Black and Hispanic minoritized neighborhoods, respectively. CONCLUSIONS: Neighborhood HCC case counts varied by neighborhood race and ethnicity distribution. The variations were partly explained by neighborhood deprivation, with a stronger effect among Black-concentrated census tracts

Odorant binding proteins : a biotechnological tool for odour control

The application of an odorant binding protein for odour control and fragrance delayed release from a textile surface was first explored in this work. Pig OBP-1 gene was cloned and expressed in Escherichia coli , and the purified protein was biochemically characterized. The IC50 values(concentrations of competitor that caused a decay of fluorescence to half-maximal intensity) were determined for four distinct fragrances, namely, citronellol, benzyl benzoate,citronellyl valerate and ethyl valerate. The results showed a strong binding of citronellyl valerate,citronellol and benzyl benzoate to the recombinant protein, while ethyl valerate displayed weaker binding. Cationized cotton substrates were coated with porcine odorant binding protein and tested for their capacity to retain citronellol and to mask the smell of cigarette smoke. The immobilized protein delayed the release of citronellol when compared to the untreated cotton. According to a blind evaluation of 30 assessors, the smell of cigarette smoke, trapped onto the fabrics’ surface, was successfully attenuated by porcine odorant binding protein (more than 60 % identified the weakest smell intensity after protein exposure compared to β-cyclodextrin-treated and untreated cotton fabrics). This work demonstrated that porcine odorant binding protein can be an efficient solution to prevent and/orremove unpleasant odours trapped on the large surface of textiles. Its intrinsic properties make odorant binding proteins excellent candidates for controlled release systems which constitute a new application for this class of proteins.This work was co-funded by the European Social Fund through the management authority POPH and FCT. The authors Carla Silva and Teresa Matama would like to acknowledge their post-doctoral fellowships: SFRH/BPD/46515/2008 and SFRH/BPD/47555/2008, respectively

Neighborhood-Level Factors Contribute to Disparities in Hepatocellular Carcinoma Incidence in Texas

BACKGROUND AND AIMS: Texas has the highest hepatocellular carcinoma (HCC) incidence rates in the continental United States, but these rates vary by race-ethnicity. We examined racial-ethnic disparities through a geospatial analysis of the social determinants of health. METHODS: Using data from the Texas Cancer Registry, we assembled 11,547 HCC cases diagnosed between 2011 and 2015 into Texas\u27s census tracts geographic units. Twenty-nine neighborhood measures representing demographics and socioeconomic, and employment domains were retrieved from the U.S. Census Bureau. We performed a series of aspatial and spatially weighted regression models to identify neighborhood-level characteristics associated with HCC risk. RESULTS: We found positive associations between HCC and proportion of population in census tracts that are Black or African American, Hispanic, over 60 years of age, in the construction industry, and in the service occupation but an inverse association with the proportion of population employed in the agricultural industry. The magnitude of these associations varied across Texas census tracts. CONCLUSIONS: We found evidence that neighborhood-level factors are differentially associated with variations in HCC incidence across Texas. Our findings reinforce existing knowledge about HCC risk factors and expose others, including neighborhood-level employment status

Defence response of host plants for cyst nematode: A review on parasitism and defence

The Cyst nematodes (CN), such as Heterodera spp. and Globodera spp. are key biotrophic pathogens inflicting high levels of damage to agricultural and horticultural crops. This review sheds light on the parasitism of the CN and molecular defence responses of infected plants. We highlight the role of effector proteins secreted from the oesophageal gland cells of the CN, hormone-signalling pathway, and miRNA regulation of gene expression that modulate the differentiation of the feeding site. In addition, we speak of the role of pattern-triggered immunity (PTI), effector-triggered immunity (ETI), resistance genes (R genes), and pathogenesis-related proteins in the immune defence responses of the CN. We conclude this review by discussing recent progress in genomic studies and molecular mechanisms involved in the recognition process of the infesting CN that provides scope for future investigations and the discovery of novel strategies to manage these biotrophic pathogens

Mediating Effects of Neighborhood-Level Socioeconomic Deprivation on the Association Between Race/Ethnicity and Advanced Hepatocellular Carcinoma

BACKGROUND: Racial/ethnic minorities are more likely than non-Hispanic whites (NHW) to be diagnosed with advanced stage hepatocellular carcinoma (HCC). We examined the role of neighborhood disadvantage as a mediator of the association between race/ethnicity and HCC stage at diagnosis. METHODS: We used data from HCC cases diagnosed in Texas from 2007 to 2015. HCC cases were classified as local versus regional/advanced stage. A mediation model approach was used to estimate the average direct effect, average mediated (indirect) effect, total effect, and proportion mediated by the Area Deprivation Index (ADI), a composite measure of disadvantage. RESULTS: 7,622 had local while 6303 had regional/advanced HCC. 46.1% of cases were NHW, 15.0% non-Hispanic Black (NHB), and 38.9% Hispanic. NHBs were less likely than NHWs to be diagnosed with local stage HCC [total effect RR, 0.921; 95% confidence interval (95% CI), 0.898-0.947]; however, only 2.26% of this effect was mediated through ADI. Conversely, Hispanics were more likely than NHWs to be diagnosed with local stage HCC (total effect RR, 1.019; 95% CI, 1.001-1.037) and ADI mediated 12.56% of the effect of race/ethnicity on HCC stage. ADI was not associated with HCC stage and therefore was not a mediator of the association with HCC stage when we compared Hispanics with NHBs. CONCLUSIONS: Neighborhood socioeconomic disadvantage may explain/mediate some of the association between race/ethnicity and HCC stage; however, the mediating effect was not uniform across populations. IMPACT: For NHBs, other individual and neighborhood level factors, not reflected in the ADI, contribute to their lower likelihood of being diagnosed with local HCC

Doxorubicin-induced chronic dilated cardiomyopathy—the apoptosis hypothesis revisited

The chemotherapeutic agent doxorubicin (DOX) has significantly increased survival rates of pediatric and adult cancer patients. However, 10% of pediatric cancer survivors will 10–20 years later develop severe dilated cardiomyopathy (DCM), whereby the exact molecular mechanisms of disease progression after this long latency time remain puzzling. We here revisit the hypothesis that elevated apoptosis signaling or its increased likelihood after DOX exposure can lead to an impairment of cardiac function and cause a cardiac dilation. Based on recent literature evidence, we first argue why a dilated phenotype can occur when little apoptosis is detected. We then review findings suggesting that mature cardiomyocytes are protected against DOX-induced apoptosis downstream, but not upstream of mitochondrial outer membrane permeabilisation (MOMP). This lack of MOMP induction is proposed to alter the metabolic phenotype, induce hypertrophic remodeling, and lead to functional cardiac impairment even in the absence of cardiomyocyte apoptosis. We discuss findings that DOX exposure can lead to increased sensitivity to further cardiomyocyte apoptosis, which may cause a gradual loss in cardiomyocytes over time and a compensatory hypertrophic remodeling after treatment, potentially explaining the long lag time in disease onset. We finally note similarities between DOX-exposed cardiomyocytes and apoptosis-primed cancer cells and propose computational system biology as a tool to predict patient individual DOX doses. In conclusion, combining recent findings in rodent hearts and cardiomyocytes exposed to DOX with insights from apoptosis signal transduction allowed us to obtain a molecularly deeper insight in this delayed and still enigmatic pathology of DC

Terminal uranium(V/VI) nitride activation of carbon dioxide and carbon disulfide: factors governing diverse and well-defined cleavage and redox reactions

The reactivity of terminal uranium(V/VI) nitrides with CE2 (E=O, S) is presented. Well-defined C=E cleavage followed by zero-, one-, and two-electron redox events is observed. The uranium(V) nitride [U(TrenTIPS)(N)][K(B15C5)2] (1, TrenTIPS=N(CH2CH2NSiiPr3)3; B15C5=benzo-15-crown-5) reacts with CO2 to give [U(TrenTIPS)(O)(NCO)][K(B15C5)2] (3), whereas the uranium(VI) nitride [U(TrenTIPS)(N)] (2) reacts with CO2 to give isolable [U(TrenTIPS)(O)(NCO)] (4); complex 4 rapidly decomposes to known [U(TrenTIPS)(O)] (5) with concomitant formation of N2 and CO proposed, with the latter trapped as a vanadocene adduct. In contrast, 1 reacts with CS2 to give [U(TrenTIPS)(κ2-CS3)][K(B15C5)2] (6), 2, and [K(B15C5)2][NCS] (7), whereas 2 reacts with CS2 to give [U(TrenTIPS)(NCS)] (8) and “S”, with the latter trapped as Ph3PS. Calculated reaction profiles reveal outer-sphere reactivity for uranium(V) but inner-sphere mechanisms for uranium(VI); despite the wide divergence of products the initial activation of CE2 follows mechanistically related pathways, providing insight into the factors of uranium oxidation state, chalcogen, and NCE groups that govern the subsequent divergent redox reactions that include common one-electron reactions and a less-common two-electron redox event. Caution, we suggest, is warranted when utilising CS2 as a reactivity surrogate for CO2