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Advances in drug-induced cholestasis: Clinical perspectives, potential mechanisms and in vitro systems
2018
Despite growing research, drug-induced liver injury (DILI) remains a serious issue of increasing importance to the medical community that challenges health systems, pharmaceutical industries and drug regulatory agencies. Drug-induced cholestasis (DIC) represents a frequent manifestation of DILI in humans, which is characterised by an impaired canalicular bile flow resulting in a detrimental accumulation of bile constituents in blood and tissues. From a clinical point of view, cholestatic DILI generates a wide spectrum of presentations and can be a diagnostic challenge. The drug classes mostly associated with DIC are anti-infectious, anti-diabetic, anti-inflammatory, psychotropic and cardiov…
Translating nanoparticulate-personalized cancer vaccines into clinical applications: case study with RNA-lipoplexes for the treatment of melanoma
2016
The development of nucleic acid based vaccines against cancer has gained considerable momentum through the advancement of modern sequencing technologies and on novel RNA-based synthetic drug formats, which can be readily adapted following identification of every patient's tumor-specific mutations. Furthermore, affordable and individual ‘on demand’ production of molecularly optimized vaccines should allow their application in large groups of patients. This has resulted in the therapeutic concept of an active personalized cancer vaccine, which has been brought into clinical testing. Successful trials have been performed by intranodal administration of sterile isotonic solutions of synthetic …
Early ERK1/2 activation promotes DRP1-dependent mitochondrial fission necessary for cell reprogramming.
2016
During the process of reprogramming to induced pluripotent stem (iPS) cells, somatic cells switch from oxidative to glycolytic metabolism, a transition associated with profound mitochondrial reorganization. Neither the importance of mitochondrial remodelling for cell reprogramming, nor the molecular mechanisms controlling this process are well understood. Here, we show that an early wave of mitochondrial fragmentation occurs upon expression of reprogramming factors. Reprogramming-induced mitochondrial fission is associated with a minor decrease in mitochondrial mass but not with mitophagy. The pro-fission factor Drp1 is phosphorylated early in reprogramming, and its knockdown and inhibition…
Biological and Ecological Features, Trophic Structure and Energy Flow in Meromictic Lakes
2017
Case studies and typical examples for meromictic lakes are used to provide a review of the biology and ecology of these ecosystems. Water column in meromictic lakes is not entirely mixed. These lakes are chemically and/or thermally stratified for several years and have several specific ecological features. The chemocline —the habitat created between the mixolimnion on top and monimolimnion below—is characterised by the existence of complex bacterial communities, autotrophic and heterotrophic protists and metazooplankton, commonly dominated by rotifers , high rates of oxygenic and anoxygenic photosynthesis and some biogeochemical processes . In these lakes, the sulphur, carbon and nitrogen c…
Mixed topological semimetals driven by orbital complexity in two-dimensional ferromagnets
2018
The concepts of Weyl fermions and topological semimetals emerging in three-dimensional momentum space are extensively explored owing to the vast variety of exotic properties that they give rise to. On the other hand, very little is known about semimetallic states emerging in two-dimensional magnetic materials, which present the foundation for both present and future information technology. Here, we demonstrate that including the magnetization direction into the topological analysis allows for a natural classification of topological semimetallic states that manifest in two-dimensional ferromagnets as a result of the interplay between spin-orbit and exchange interactions. We explore the emerg…
Autophagy is required for sea urchin oogenesis and early development.
2016
SummaryAutophagy is a major intracellular pathway for the degradation and recycling of cytosolic components. Emerging evidence has demonstrated its crucial role during the embryo development of invertebrates and vertebrates. We recently demonstrated a massive activation of autophagy in Paracentrotus lividus embryos under cadmium stress conditions, and the existence of a temporal relationship between induced autophagy and apoptosis. Although there have been numerous studies on the role of autophagy in the development of different organisms, information on the autophagic process during oogenesis or at the start of development in marine invertebrates is very limited. Here we report our recent …
Rabphilin involvement in filtration and molecular uptake in Drosophila nephrocytes suggests a similar role in human podocytes
2020
ABSTRACT Drosophila nephrocytes share functional, structural and molecular similarities with human podocytes. It is known that podocytes express the rabphilin 3A (RPH3A)-RAB3A complex, and its expression is altered in mouse and human proteinuric disease. Furthermore, we previously identified a polymorphism that suggested a role for RPH3A protein in the development of urinary albumin excretion. As endocytosis and vesicle trafficking are fundamental pathways for nephrocytes, the objective of this study was to assess the role of the RPH3A orthologue in Drosophila, Rabphilin (Rph), in the structure and function of nephrocytes. We confirmed that Rph is required for the correct function of the en…
Regulation of long-term repopulating hematopoietic stem cells by EPCR/PAR1 signaling
2016
The common developmental origin of endothelial and hematopoietic cells is manifested by coexpression of several cell surface receptors. Adult murine bone marrow (BM) long-term repopulating hematopoietic stem cells (LT-HSCs), endowed with the highest repopulation and self-renewal potential, express endothelial protein C receptor (EPCR), which is used as a marker to isolate them. EPCR/protease-activated receptor-1 (PAR1) signaling in endothelial cells has anticoagulant and anti-inflammatory roles, while thrombin/PAR1 signaling induces coagulation and inflammation. Recent studies define two new PAR1-mediated signaling cascades that regulate EPCR(+) LT-HSC BM retention and egress. EPCR/PAR1 sig…
Application of modern computer algebra systems in food formulations and development: A case study
2017
Abstract Background Nutritional security determines the level of public health within a population while inadequate nutrition is one of the major factors in development of various health problems. This can be alleviated with sufficient and affordable access to currently available or newly designed nutritious foods. Scope and approach Formulation of new foods can be very costly, so methods able to lower design expanses are of utmost importance to the industry. Hence, the purpose of this work was to rationalize utilization of modern computerized algebraic systems (CAS) in solving traditional problems for formulating food mixtures by food combinatoric principles (FCP). Key findings and conclus…
Childhood supratentorial ependymomas with YAP1-MAMLD1 fusion: an entity with characteristic clinical, radiological, cytogenetic and histopathological…
2018
Ependymoma with YAP1-MAMLD1 fusion is a rare, recently described supratentorial neoplasm of childhood, with few cases published so far. We report on 15 pediatric patients with ependymomas carrying YAP1-MAMLD1 fusions, with their characteristic histopathology, immunophenotype and molecular/cytogenetic, radiological and clinical features. The YAP1-MAMLD1 fusion was documented by RT-PCR/Sanger sequencing, and tumor genomes were studied by molecular inversion probe (MIP) analysis. Significant copy number alterations were identified by GISTIC (Genomic Identification of Significant Targets in Cancer) analysis. All cases showed similar histopathological features including areas of high cellularity…