1,820 research outputs found

    Distinct Gene Expression and Epigenetic Signatures in Hepatocyte-like Cells Produced by Different Strategies from the Same Donor

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    Summary: Hepatocyte-like cells (HLCs) can be generated through directed differentiation or transdifferentiation. Employing two strategies, we generated induced pluripotent stem cell (iPSC)-HLCs and hiHeps from the same donor cell line. Both types of HLCs clustered distinctly from each other during gene expression profiling. In particular, differences existed in gene expression for phase II drug metabolism and lipid accumulation, underpinned by H3K27 acetylation status in iPSC-HLCs and hiHeps. While distinct phenotypes were achieved in vitro, both types of HLCs demonstrated similar phenotypes following transplantation into Fah-deficient mice. In conclusion, functional HLCs can be obtained from the same donor using two strategies. Global gene expression defined the differences between those populations in vitro. Importantly, both HLCs displayed partial but markedly improved hepatic function following transplantation in vivo, demonstrating plasticity and the potential for cell-based modeling in the dish and cell-based therapy in the future. : In this article, Hui and colleagues show that hiHeps and iPSC-HLCs generated from the same donor display different gene expression patterns that correlate with their hepatic functions. Distinct H3K27ac modifications partially explain the functional differences between the two types of HLCs. Importantly, both HLCs show improved hepatic gene expression after repopulation in murine livers. Keywords: transdifferentiation, directed differentiation, hepatocyte-like cells, gene expression patter

    Model of leadership characteristics in addressing construction challenges

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    Failure of construction projects could be attributed from several challenges that emerged along the construction processes. These challenges are categorised as resources allocation, time, cost, quality, safety, project complexity, changes, uncertainties, and communication. It requires several approaches to handle these challenges and one of it is to have good quality of leadership that not rely on their authority. A study has shown that poor leadership contributed 67% to the project’s failure. Hence, this study was intended to develop relationship between leadership characteristics with construction challenges in avoiding project failure. This study was carried out based on quantitative approach that involved questionnaire survey using face-to-face technique with selected respondents at managerial level of G7 Contractor Company. The survey has resulted with 117 valid responses. Results from the survey analysis were applied to develop PLS-SEM relationship model which consisted of 43 leadership characteristics which are categorised into 4 groups and 9 construction challenges which is categorised into single group. The model was statistically validated with Goodness-of-Fit (GoF) value of 0.349 which is categorised as medium validating power. Based on the developed model, the most influential leadership characteristic group in handling the construction challenges is smart decision. While the most challenging construction challenges is safety management. To ensure that the model is applicable to the Malaysia construction industry, expert verification by selected construction experts was conducted and found that majority of the experts agreed on the model outcomes thus indicate that the model is suitable to the industry. Hence, it can be concluded that the study has uncovered the importance of leadership characteristics and its relationship with the construction challenges which fills the gap of study on Malaysia construction industry

    Implementation of a standardized protocol to manage elderly patients with low energy pelvic fractures: can service improvement be expected?

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    Purpose: The incidence of low energy pelvic fractures (FPFs) in the elderly is increasing. Comorbidities, decreased bone-quality, problematic fracture fixation and poor compliance represent some of their specific difficulties. In the absence of uniform management, a standard operating procedure (SOP) was introduced to our unit, aiming to improve the quality of services provided to these patients. Methods: A cohort study was contacted to test the impact of (1) using a specific clinical algorithm and (2) using different antiosteoporotic drugs. Multivariate regression analysis was used to determine prognostic factors. Study endpoints were the time-to-healing, length-of-stay, return to pre-injury mobility, union status, mortality and complications. Results: A total of 132 elderly patients (≥65 years) admitted during the period 2012–2014 with FPFs were enrolled. High-energy fractures, acetabular fractures, associated trauma affecting mobility, pathological pelvic lesions and operated FPFs were used as exclusion criteria. The majority of included patients were females (108/132; 81.8%), and the mean age was 85.8 years (range 67–108). Use of antiosteoporotics was associated with a shorter time of healing (p = 0.036). Patients treated according to the algorithm showed a significant protection against malunion (p < 0.001). Also, adherence to the algorithm allowed more patients to return to their pre-injury mobility status (p = 0.039). Conclusions: The use of antiosteoporotic medication in elderly patients with fragility pelvic fractures was associated with faster healing, whilst the adherence to a structured clinical pathway led to less malunions and non-unions and return to pre-injury mobility state

    Effect of Argania spinosa oil extract on proliferation and Notch1 and ERK1/2 signaling of T-cell acute lymphoblastic leukemia cell lines

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    The Argan tree, called Argania spinosa (L.) Skeels, is a tropical plant, which belongs to the Sapotaceae family, it is exploited essentially for its fruits. The endosperm seed of the fruit constitutes a good potential source of edible oil for human consumption and is endowed with important medicinal properties such as antioxidant, antimalarial and anti-proliferative. The aim of the present work is to evaluate the anti-proliferative effect of the oil extracted from seeds of A. spinosa in T-cell acute lymphoblastic leukemia human (T-ALL) context. The activity was assessed through an in vitro test on three T-ALL cell lines: JURKAT, MOLT3 and DND41. The cytotoxicity effects of A. spinosa oil extract were checked by MTT assay and the change in the activity levels of two T-ALL proliferation-related proteins (Notch1 and ERK) was investigated by Western blot, the results demonstrate that treatment with A. spinosa oil extract at the dose of 100 μg/mL inhibited the growth of JURKAT, MOLT3 and DND41 cells, and reduced the expression levels and the activity of proliferation-related proteins such as ERK1/2 and Notch1 intracellular domain. A. spinosa oil extract could be a potential preventive and therapeutic approach recommended as anti-proliferative against leukemia

    Senior Programmers: Characteristics of Elderly Users from Stack Overflow

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    In this paper we presents results of research about elderly users of Stack Overflow (Question and Answer portal for programmers). They have different roles, different main activities and different habits. They are an important part of the community, as they tend to have higher reputation and they like to share their knowledge. This is a great example of possible way of keeping elderly people active and helpful for society

    What on Earth have we been burning? Deciphering sedimentary records of pyrogenic carbon

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    Humans have interacted with fire for thousands of years, yet the utilization of fossil fuels marked the beginning of a new era. Ubiquitous in the environment, pyrogenic carbon (PyC) arises from incomplete combustion of biomass and fossil fuels, forming a continuum of condensed aromatic structures. Here we develop and evaluate 14C records for two complementary PyC molecular markers, benzene-polycarboxylic-acids (BPCAs) and polycyclic-aromatic-hydrocarbons (PAHs) preserved in aquatic sediments from a sub-urban and a remote catchment in the United States (U.S.) from mid-1700s to 1998. Results show that the majority of PyC stems from local sources and is transferred to aquatic sedimentary archives on sub-decadal to millennial time scales. Whereas a small portion stems from near-contemporaneous production and sedimentation, the majority of PyC (&lt;90%) experiences delayed transmission due to ‘pre-aging’ on millennial timescales in catchment soils prior to its ultimate deposition. BPCAs (soot) and PAHs (precursors of soot) trace fossil fuel-derived PyC. Both markers parallel historical records of the consumption of fossil fuels in U.S., yet never account for more than 19% total PyC. This study demonstrates that isotopic characterization of multiple tracers is necessary to constrain histories and inventories of PyC, and that sequestration of PyC can markedly lag its production
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