Petersmilne1999
s in this study are functioning, EGF-dependent, and erlotinib-resistant. Erlotinib induces differential degree of apoptosis and autophagy among cells harboring different EGFRs. The degree of inhibition of EGFR phosphorylation by erlotinib is the determining factor for the degree of apoptosis and autophagy amongst cells harboring EGFR mutants. This study paves the way for further investigation into the sensitivity of these HCC-derived mutants to the 3rd-generation irreversible EGFR-TKI, osimertinib. © The Author(s) 2020.Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an ongoing global health emergency. Here we highlight nine most important research questions concerning virus transmission, asymptomatic and presymptomatic virus shedding, diagnosis, treatment, vaccine development, origin of virus and viral pathogenesis. © The Author(s) 2020.Fanconi anemia (FA) is a recessive genetic disorder caused by biallelic mutations in at least one of 22 FA genes. Beyond its pathological presentation of bone marrow failure and congenital abnormalities, FA is associated with chromosomal abnormality and genomic instability, and thus represents a genetic vulnerability for cancer predisposition. The cancer relevance of the FA pathway is further established with the pervasive occurrence of FA gene alterations in somatic cancers and observations of FA pathway activation-associated chemotherapy resistance. In this article we describe the role of the FA pathway in canonical interstrand crosslink (ICL) repair and possible contributions of FA gene alterations to cancer development. We also discuss the perspectives and potential of targeting the FA pathway for cancer intervention. © The Author(s) 2020.Background Combined hepatocellular-cholangiocarcinoma (CHC) is a primary hepatic malignancy with heterogeneously combined histological features of putative hepatic progenitor cells (HPC) origin. We describe a mouse model that exhibits the heterogenous histological and phenotypic finding similar to human CHC. Methods We injected hepatoblasts isolated from p53-/- C57BL/6 mice into syngeneic wild-type pre-conditioned C57BL/6 mice. We confirmed that p53-/- murine hepatoblasts act as tumor-initiating cells (TICs) that generate CHC both in situ and within metastases. For comparative pathological study, 8 human cases of CHC with stem cell features were recruited by immunohistochemistry and multicolor fluorescence immunostaining. Results We identified corresponding areas in murine tumors matching each WHO criteria-described subtype of human CHC. In both murine and human tumors, HPC-like cells in tumor nests and associated stem cell features/traits are suggested histologically to be the progenitor origin of the cancer. Conclusions The pathological characteristics of murine tumors recapitulate human CHC with stem cell features. These data provide additional comparative pathological evidence that CHC with stem cell features originate from HPCs and validate a model to study this cancer type in vivo. © The Author(s) 2020.Nucleosome assembly during DNA replication is tightly coupled to ongoing DNA synthesis. This process, termed DNA replication-coupled (RC) nucleosome assembly, is essential for chromatin replication and has a great impact on both genome stability maintenance and epigenetic inheritance. This review discusses a set of recent findings regarding the role of replisome components contributing to RC nucleosome assembly. Starting with a brief introduction to the factors involved in nucleosome assembly and some aspects of the architecture of the eukaryotic replisome, we discuss studies from yeast to mammalian cells and the interactions of replisome components with histones and histone chaperones. We describe the proposed functions of replisome components during RC nucleosome assembly and discuss their impacts on histone segregation and implications for epigenetic inheritance. © The Author(s) 2020.Background Kawasaki disease (KD) is one of the major causes of heart disease and vasculitis in children under 5 years old in the world. Clinical evidence has shown that coronary artery calcification may develop in KD patients, however the mechanism has not been elucidated. Previous studies have found that interferon-γ-inducible protein (IP)-10 and interleukin (IL)-17 can be elevated and may play a role in KD development and coronary artery lesion formation. The purpose of this in vitro study was to investigate the possible role of plasma circulating IP-10 and IL-17 of KD patients in vascular calcification development and its underlying mechanism. Result Human coronary artery smooth muscle cells (HCASMCs) were used in this study. We found that HCASMCs treated with IP-10/IL-17-containing KD serum and co-treated with IP-10/IL-17 recombinant proteins could induce a phenotype that may promote vascular calcification by the bone morphogenetic protein (BMP) 6 autocrine effect. Moreover, the BMP6 autocrine stimulation in IP-10/IL-17 co-treated HCASMCs could upregulate the smad1/5-runx2 signaling activation, thus increasing the expression of bone matrix-related proteins, i.e., osteopontin, osteocalcin, and alkaline phosphatase. Conclusions The presented in vitro results provided new insights into the comprehension of the pathogenesis of vascular calcification in SMCs in KD progression. Although additional in vivo experimental models should be completed to confirm the in vivo relevance of these in vitro findings, the results related to the autocrine role of BMP6 may provide a new direction for theranostic drug development to treat KD. © The Author(s) 2020.Aim To describe exercise preferences and to investigate the contribution of exercise preferences, walking ability, and current levels of physical activity in predicting exercise adherence in individuals with chronic stroke. Methods For this exploratory study, exercise adherence was measured using the first question of the first section of the Exercise Preference Questionnaire (stroke)-Brazil (EPQ (stroke)-Brazil). Nine independent variables were included as potential predictors of exercise adherence the seven factors of the EPQ (stroke)-Brazil, walking speed, and level of physical activity. Results Participated 93 individuals with stroke, who had a mean age of 62 (SD 12) years and a mean time since the onset of the stroke of 58 (SD 67) months. The most preferable exercise was walking. Logistic regression analysis revealed that self-efficacy to engage in physical exercise and walking ability predicted and explained 80% of the variance in exercise adherence. Conclusion The findings showed that feeling able to perform physical exercise and having higher walking ability predicted higher exercise adherences in individuals with chronic stroke. The knowledge of potential contributors to exercise adherence may help in designing exercise programs for individuals with stroke. Copyright © 2020 Lívia C. G. Caetano et al.The objective of this study was to identify the phylogenetic analysis and antibiotic resistance of Listeria monocytogenes contaminating chicken meat in Surabaya. 60 chicken meat samples were collected from supermarkets, mobile vendors, and traditional markets in Surabaya. A selective medium is used for isolation and identification of Listeria monocytogenes by chopping 25 grams of the chicken meat and to put it into the sterilized Erlenmeyer flasks. Some methods were used for the identification procedures, such as biochemical and morphological tests, antibiotic resistance test, PCR, and sequencing; also a phylogenetic analysis was conducted by a neighbor-joining analysis using Genetix Mac ver 8.0 with hlyA genes of Listeria monocytogenes recorded in GenBank, such as Lineage I (KC808543), Lineage II (AY229462, AY229346, AY229499, and AY229404), Lineage III (KJ504139, HQ686043, KJ504116, and DQ988349), and Lineage IV (EU840690, EF030606). The result shows that the prevalence of L. monocytogenes in Surabaya contaminating the chicken meat samples from the supermarkets was 10% (2/20), from the mobile vendors was 0/20 (0%), and from the traditional markets was 5% (1/20). It was seen from the band at 456 bp fragment. Furthermore, three isolates found in Surabaya were included in the new lineages which were resistant to old-generation antibiotics such as sulfamethonazole-trimetophrim (SXT) and amoxyllin sulbactam (MAS), but they were still sensitive to new-generation antibiotics such as cefotaxime (CTX) and meropenem (MEM). Copyright © 2020 Eduardus Bimo Aksono et al.Ethiopia's livestock resource is one of the largest globally. It is estimated at around 59.5 million cattle, about 30.5 million sheep, and 30.2 million goats. The sector is irreplaceable in the means of livelihood of the population as a source of meat, milk, drought power, and income. Yet, the country is unable to exploit the sector entirely because of highly prevalent infectious diseases and lack of appropriate disease control policy. These constraints are worse in districts of Lalibela, Sekota, and Ziquala, where this specific study was carried out. Despite the availability of scanty animal health services in these areas, information on animal health, especially cattle, was never a significant focus of research. This study was conducted with the objectives of identifying and prioritizing primary cattle disease with the aid of participatory epidemiology tools. Focus group discussions (FGD) and questionnaires were used in prioritizing the top economically important cattle diseases of the selected areas. Accordingly, the result of FGD indicated that ectoparasites, CBPP, FMD, blackleg, bloody diarrhea, and pasteurellosis were the major diseases affecting cattle production in the area. These areas can be representative of most of the countries where a mixed farming system is practiced. Therefore, this result can be used as a basis for broader planning of prevention and control strategies for these kinds of diseases. click here However, a laboratory-supported extensive investigation of these diseases is highly recommended to validate findings of such types of prioritization of diseases. Copyright © 2020 Adane Bahiru and Ayalew Assefa.A cross-sectional calf mortality study was conducted in urban and periurban dairy farms in Addis Ababa, special zones of Oromia and Amhara regions in July and August 2015. The objectives of the study were to estimate the annual mortality and to assess the major causes of calf mortality in the dairy farms. One-year retrospective data on calf mortality were collected from 330 farms by face-to-face interview using the pretested and structured questionnaire format and direct observation of farm practices. A logistic regression analysis was performed in order to identify the predictor variables associated with early calf mortality. Data were analysed using Statistical Package, Stata SE for Windows, version 12.0. The annual mean calf mortality from birth-to-weaning was reported as 18.5% (95% CI 12.6, 24.3%). The prenatal loss due to fetal death and stillbirth was 10.1% (95% CI 6.7, 13.6%). The overall annual loss due to fetal death and calf preweaning mortality was 26.7% (95% CI 21.2, 32.2%). Age-specific mortality declined with increased age, and the highest mortality was recorded during the first month of life extending up to the third month of age.