Inhibition of Hedgehog Delays Liver Regeneration through Disrupting the Cell Cycle

Liver regeneration is a complicated biological process orchestrated by various liver resident cells. Hepatic cell proliferation and reconstruction of the hepatic architecture involve multiple signaling pathways. It has been reported that the Hh signal is involved in liver regeneration. However, the signal transduction pathways and cell types involved are ill studied. This study aimed to investigate hedgehog signal response cell types and the specific molecular mechanism involved in the process of liver regeneration. Partial hepatectomy (PH) of 70% was performed on ICR (Institute of Cancer Research) mice to study the process of liver regeneration. We found that the hedgehog signal was activated significantly after PH, including hedgehog ligands, receptors and intracellular signaling molecules. Ligand signals were mainly expressed in bile duct cells and non-parenchymal hepatic cells, while receptors were expressed in hepatocytes and some non-parenchymal cells. Inhibition of the hedgehog signal treated with vismodegib reduced the liver regeneration rate after partial hepatectomy, including inhibition of hepatic cell proliferation by decreasing Cyclin D expression and disturbing the cell cycle through the accumulation of Cyclin B. The current study reveals the important role of the hedgehog signal and its participation in the regulation of hepatic cell proliferation and the cell cycle during liver regeneration. It provides new insight into the recovery of the liver after liver resection.     

Prevalence of Mental Distress and Associated Factors among Undergraduate Students of University of Gondar,Northwest Ethiopia: A Cross-Sectional Institutional Based Study

Background

Mental health problems affect society as a whole and no group is immune to mental disorders; however, students have significantly high level of mental distress than their community peers.

Objectives

The purpose of this study was to assess the prevalence and associated factors of mental distress among undergraduate students of University of Gondar, Northwest Ethiopia.

Methods

Institution based cross sectional study was conducted among 836 students from April 9–11/2014. Stratified multistage sampling technique was used to select the study participants. Data were collected using pretested and structured self-administered questionnaire. Bivariate and multivariate logistic regression model was fitted to identify factors associated with mental distress among students. An adjusted odds ratio with 95% confidence interval was computed to determine the level of significance.

Results

Prevalence of mental distress among students was found to be 40.9%. Female sex (AOR = 1.65; 95% CI 1.17–2.30), lack of interest towards their field of study (AOR = 2.28; 95% CI 1.49–3.50), not having close friends (AOR = 1.48; 95% CI 1.03–2.14), never attend religious programs (AOR = 1.58; 95% CI 1.02–2.46), conflict with friends (AOR = 1.93; 95% CI 1.41–2.65), having financial distress (AOR1.49 = 95% CI 1.05, 2.10), family history of mental illness (AOR = 2.12; 95% CI 1.31–3.45), Ever use of Khat (AOR = 1.71; 95% CI 1.12–2.59), lower grade than anticipated(AOR = 2.07; 95% CI 1.51–2.83), lack of vacation or break (AOR = 1.46; 95% CI 1.06–2.02), and low social support(AOR = 2.58; 95% CI 1.58–4.22) were significantly associated with mental distress.

Conclusion

The overall prevalence of mental distress among students was found to be high. Therefore, it is recommended that mental distress needs due attention and remedial action from policy makers, college officials, non-governmental organizations, parents, students and other concerned bodies.     

Current Efavirenz (EFV) or Ritonavir-Boosted Lopinavir (LPV/r) Use Correlates with Elevate Markers of Atherosclerosis in HIV-Infected Subjects in Addis Ababa,Ethiopia

Background

HIV patients on antiretroviral therapy have shown elevated incidence of dyslipidemia, lipodystrophy, and cardiovascular disease (CVD). Most studies, however, focus on cohorts from developed countries, with less data available for these co-morbidities in Ethiopia and sub-Saharan Africa.

Methods

Adult HIV-negative (n = 36), treatment naïve (n = 51), efavirenz (EFV)-treated (n = 91), nevirapine (NVP)-treated (n = 95), or ritonavir-boosted lopinavir (LPV/r)-treated (n=44) subjects were recruited from Black Lion Hospital in Addis Ababa, Ethiopia. Aortic pressure, augmentation pressure, and pulse wave velocity (PWV) were measured via applanation tonometry and carotid intima-media thickness (cIMT) and carotid arterial stiffness, and brachial artery flow-mediated dilation (FMD) were measured via non-invasive ultrasound. Body mass index, waist-to-hip circumference ratio (WHR), skinfold thickness, and self-reported fat redistribution were used to quantify lipodystrophy. CD4+ cell count, plasma HIV RNA levels, fasting glucose, total-, HDL-, and LDL-cholesterol, triglycerides, hsCRP, sVCAM-1, sICAM-1, leptin and complete blood count were measured.

Results

PWV and normalized cIMT were elevate and FMD impaired in EFV- and LPV/r-treated subjects compared to NVP-treated subjects; normalized cIMT was also elevated and FMD impaired in the EFV- and LPV/r-treated subjects compared to treatment-naïve subjects. cIMT was not statistically different across groups. Treated subjects exhibited elevated markers of dyslipidemia, inflammation, and lipodystrophy. PWV was associated with age, current EFV and LPV/r used, heart rate, blood pressure, triglycerides, LDL, and hsCRP, FMD with age, HIV duration, WHR, and glucose, and cIMT with age, current EFV use, skinfold thickness, and blood pressure.

Conclusions

Current EFV- or LPV/r-treatment, but not NVP-treatment, correlated with elevated markers of atherosclerosis, which may involve mechanisms distinct from traditional risk factors.     

Impact of combining planting date and chemical control to reduce larval densities of stem-infesting pests of sunflower in the central plains

The guild of stem-infesting insect pests of sunflower, Helianthus annuus L., within the central Plains is a concern to producers chiefly due to losses caused by plant lodging from the sunflower stem weevil, Cylindrocopturus adspersus (LeConte) (Coleoptera: Curculionidae), and Dectes texanus texanus LeConte (Coleoptera: Cerambycidae). The incidence of a root boring moth, Pelochrista womonana (Kearfott) (Lepidoptera: Tortricidae), also has increased. Experiments were conducted in three locations in Colorado and Kansas during 2001-2003 to investigate the potential of combining planting date and foliar and seed treatment insecticide applications to lower insect stalk densities of these three pests. The impact of these strategies on weevil larval parasitoids also was studied. Eight sunflower stem weevil larval parasitoid species were identified. All were Hymenoptera and included the following (relative composition in parentheses): Nealiolus curculionis (Fitch) (42.6%), Nealiolus collaris (Brues) (3.2%) (Braconidae), Quadrastichus ainsliei Gahan (4.2%) (Eulophidae), Eurytoma tylodermatis Ashmead (13.1%) (Eurytomidae), Neocatolaccus tylodermae (Ashmead) (33.7%), Chlorocytus sp. (1.6%), Pteromalus sp. (0.5%) (Pteromalidae), and Eupelmus sp. (1.0%) (Eupelmidae). The results from this 3-yr study revealed that chemical control was often reliable in protecting the sunflower crop from stem pests and was relatively insensitive to application timing. Although results in some cases were mixed, overall, delayed planting can be a reliable and effective management tool for growers in the central Plains to use in reducing stem-infesting pest densities in sunflower stalks. Chemical control and planting date were compatible with natural mortality contributed by C. adspersus larval parasitoids.     

Natural and within-farmland biodiversity enhances crop productivity

Ongoing expansion of large-scale agriculture critically threatens natural habitats and the pollination services they offer. Creating patches with high plant diversity within farmland is commonly suggested as a measure to benefit pollinators. However, farmers rarely adopt such practice, instead removing naturally occurring plants (weeds). By combining pollinator exclusion experiments with analysis of honeybee behaviour and flower-visitation webs, we found that the presence of weeds allowed pollinators to persist within sunflower fields, maximizing the benefits of the remaining patches of natural habitat to productivity of this large-scale crop. Weed diversity increased flower visitor diversity, hence ameliorating the measured negative effects of isolation from natural habitat. Although honeybees were the most abundant visitors, diversity of flower visitors enhanced honeybee movement, being the main factor influencing productivity. Conservation of natural patches combined with promoting flowering plants within crops can maximize productivity and, therefore, reduce the need for cropland expansion, contributing towards sustainable agriculture.     

Faunal remains from Porc-Epic: paleoecological and zooarchaeological investigations from a Middle Stone Age site in southeastern Ethiopia

The Middle Stone Age (MSA) sediments of Porc-Epic Cave near Dire Dawa, Ethiopia, have produced a large assemblage of archaeofaunal remains dating to the later periods of the Late Pleistocene. As one of the few MSA faunal assemblages from East Africa subject to detailed analysis, it provides rare insight into the foraging behavior of the early modern humans in this region. The MSA fauna include taxa that were not historically present in the area, with the occurrence of reduncines and alcelaphines indicating widespread grasslands and proximity to a perennial source of water. The faunal analysis examined several lines of evidence, including breakage patterns, surface modification, and skeletal-element representation. By incorporating comparisons with multiple actualistic data sets, the analysis of the assemblage demonstrates that, while the influence of carnivores and other biotic agents was evident, the faunal remains were accumulated primarily by hominid activity. The skeletal-element representation at Porc-Epic includes an abundance of high utility bones, in contrast to the predominance of "head-and-foot" elements documented at other MSA and Middle Paleolithic (MP) sites. The MSA occupants of Porc-Epic effectively exploited a wide range of prey with more emphasis on small- and medium-sized mammals.     

Genetic Diversity and Population Structure of Ethiopian Chickpea (Cicer arietinum L.) Germplasm Accessions from Different Geographical Origins as Revealed by Microsatellite Markers

Genetic diversity and population structure were studied in 155 chickpea (Cicer arietinum L.) entries using 33 polymorphic microsatellite (SSR) markers. Molecular analysis of variance showed variations of 73% within and 27% among populations. Introduced genotypes exhibited highest polymorphism (70.27%) than the landraces (36?C57%). Collections from Shewa, Harerge, W. Gojam and S. Gonder regions also showed higher polymorphism (50?C57%) than the rest of the local accessions (36?C45%). Analyses of pairwise population Nei genetic distance and PhiPT coefficients, expected heterozygosity (He) and unbiased expected heterozygosity (UHe), Shannon??s information index (I) and percent polymorphism (% P) showed existence of high genetic variation between geographical regions. Accessions from adjoining geographical regions mostly showed more genetic similarities than those from origins far isolated apart. This could be associated with the ease and likelihood of inter-regional gene flow and seed movement particularly during times of drought. The 155 entries were grouped into five clusters following analysis of population structure. The first cluster (C₁) constituted accessions from Arsi; the second (C₂) from Gojam and Gonder; the third (C₃) from Harerge and E. and N. Shewa; and the fourth (C₄) from W. Shewa, Tigray, and Wello regions. The fifth cluster (C₅) was entirely consisted of improved genotypes. Improved genotypes of both Kabuli and Desi types distinctly fell into cluster five (C₅) regardless of their difference in seed types. The result has firmly established that introduction of genetic materials from exotic sources has broadened the genetic base of the national chickpea breeding program. Further implications of the findings as regards to chickpea germplasm management and its utilization in breeding program are also discussed.     

G protein coupled receptor transactivation: extending the paradigm to include serine/threonine kinase receptors

The current paradigm of G protein coupled receptor signaling involves a classical pathway being the activation of phospholipase C and the generation of 1,4,5-inositol trisphosphate, signaling through β-arrestin scaffold molecules and the transactivation of tyrosine kinase growth factor receptors. Transactivation greatly expands the range of signaling pathways and responses attributable to the receptor. Recently it has been revealed that G protein coupled receptor agonists can also transactivate the serine/threonine kinase cell surface receptor for transforming growth factor-β (Alk5). This leads to the generation of carboxyl terminal phosphorylated Smad2 which is the immediate downstream product of the activated Alk5. Thus, the current paradigm of G protein coupled signaling can be expanded to include the transactivation of the serine kinase receptor Alk5. These insights expand the possibilities for outcomes of therapeutically targeting GPCRs where more substantive and prolonged actions such as the synthesis of extracellular matrix may be affected.