Jun Dimerization Protein 2 Controls Senescence and Differentiation via Regulating Histone Modification

Transcription factor, Jun dimerization protein 2 (JDP2), binds directly to histones and DNAs and then inhibits the p300-mediated acetylation both of core histones and of reconstituted nucleosomes that contain JDP2 recognition DNA sequences. JDP2 plays a key role as a repressor of adipocyte differentiation by regulation of the expression of the gene C/EBPδ via inhibition of histone acetylation. Moreover, JDP2-deficient mouse embryonic fibroblasts (JDP2−/− MEFs) are resistant to replicative senescence. JDP2 inhibits the recruitment of polycomb repressive complexes (PRC1 and PRC2) to the promoter of the gene encoding p16Ink4a, resulting from the inhibition of methylation of lysine 27 of histone H3 (H3K27). Therefore, it seems that chromatin-remodeling factors, including the PRC complex controlled by JDP2, may be important players in the senescence program. The novel mechanisms that underline the action of JDP2 in inducing cellular senescence and suppressing adipocyte differentiation are reviewed

Role of host genetics in fibrosis

Fibrosis can occur in tissues in response to a variety of stimuli. Following tissue injury, cells undergo transformation or activation from a quiescent to an activated state resulting in tissue remodelling. The fibrogenic process creates a tissue environment that allows inflammatory and matrix-producing cells to invade and proliferate. While this process is important for normal wound healing, chronicity can lead to impaired tissue structure and function

Entry of Herpes Simplex Virus Type 1 (HSV-1) into the Distal Axons of Trigeminal Neurons Favors the Onset of Nonproductive, Silent Infection

Following productive, lytic infection in epithelia, herpes simplex virus type 1 (HSV-1) establishes a lifelong latent infection in sensory neurons that is interrupted by episodes of reactivation. In order to better understand what triggers this lytic/latent decision in neurons, we set up an organotypic model based on chicken embryonic trigeminal ganglia explants (TGEs) in a double chamber system. Adding HSV-1 to the ganglion compartment (GC) resulted in a productive infection in the explants. By contrast, selective application of the virus to distal axons led to a largely nonproductive infection that was characterized by the poor expression of lytic genes and the presence of high levels of the 2.0-kb major latency-associated transcript (LAT) RNA. Treatment of the explants with the immediate-early (IE) gene transcriptional inducer hexamethylene bisacetamide, and simultaneous co-infection of the GC with HSV-1, herpes simplex virus type 2 (HSV-2) or pseudorabies virus (PrV) helper virus significantly enhanced the ability of HSV-1 to productively infect sensory neurons upon axonal entry. Helper-virus-induced transactivation of HSV-1 IE gene expression in axonally-infected TGEs in the absence of de novo protein synthesis was dependent on the presence of functional tegument protein VP16 in HSV-1 helper virus particles. After the establishment of a LAT-positive silent infection in TGEs, HSV-1 was refractory to transactivation by superinfection of the GC with HSV-1 but not with HSV-2 and PrV helper virus. In conclusion, the site of entry appears to be a critical determinant in the lytic/latent decision in sensory neurons. HSV-1 entry into distal axons results in an insufficient transactivation of IE gene expression and favors the establishment of a nonproductive, silent infection in trigeminal neurons

Piloting Upfront Xpert MTB/RIF Testing on Various Specimens under Programmatic Conditions for Diagnosis of TB & DR-TB in Paediatric Population

India accounts for one-fifth of the global TB incidence. While the exact burden of childhood TB is not known, TB remains one of the leading causes of childhood mortality in India. Bacteriological confirmation of TB in children is challenging due to difficulty in obtaining quality specimens, in the absence of which diagnosis is largely based on clinical judgement. While testing multiple specimens can potentially contribute to higher proportion of laboratory confirmed paediatric TB cases, lack of high sensitivity tests adds to the diagnostic challenge. We describe here our experiences in piloting upfront Xpert MTB/RIF testing, for diagnosis of TB in paediatric population in respiratory and extra pulmonary specimens, as recently recommended by WHO.Xpert MTB/RIF testing was offered to all paediatric (0-14 years) presumptive TB cases (both pulmonary and extra-pulmonary) seeking care at public and private health facilities in the project areas covering 4 cities of India.Under this pilot project, 8,370 paediatric presumptive TB & presumptive DR-TB cases were tested between April and-November 2014. Overall, 9,149 specimens were tested, of which 4,445 (48.6%) were non-sputum specimens. Xpert MTB/RIF gave 9,083 (99.2%, CI 99.0-99.4) valid results. Of the 8,143 presumptive TB cases enrolled, 517 (6.3%, CI 5.8-6.9) were bacteriologically confirmed. TB detection rates were two fold higher with Xpert MTB/RIF as compared to smear microscopy. Further, a total of 60 rifampicin resistant TB cases were detected, of which 38 were detected among 512 presumptive TB cases while 22 were detected amongst 227 presumptive DR-TB cases tested under the project.Xpert MTB/RIF with advantages of quick turnaround testing-time, high proportion of interpretable results and feasibility of rapid rollout, substantially improved the diagnosis of bacteriologically confirmed TB in children, while simultaneously detecting rifampicin resistance

Influence of Sintering Temperature on Crystallization Behavior of Cordierite synthesized from Non-Stoichiometric Formulation

Cordierite body with formulation of non-stoichiometric composition (2.5 MgO. 1.8 Al2O3. 5 SiO2) was synthesized using conventional techniques with standard raw materials. The sintering and crystallization behavior of the compositions was observed by Differential Thermal Analysis and Thermogravimetric Analysis (DTA/TG). The sequence of reaction and phase transformation was analyzed using X-ray Diffraction (XRD) technique and Rietveld structural refinement after sintering the samples at different temperature regarding the information from the DTA. The Scanning electron microscopy (SEM) was employed for morphology analysis. The DTA curve shows the crystallization temperature, Tc occur at 1259°C.Rietveld quantitative phase analysis results reveal that α phase Cordierite constitutes up to 96.4 wt% when the samples was sintered for 2 hours at the optimal temperature of 1375°C. The SEM micrograph revealed that the sample was heat treated at 1375°C obtained densified body with well alignment of crystal structure

Influence of Sintering Temperature on Crystallization Behavior of Cordierite synthesized from Non-Stoichiometric Formulation

Cordierite body with formulation of non-stoichiometric composition (2.5 MgO. 1.8 Al2O3. 5 SiO2) was synthesized using conventional techniques with standard raw materials. The sintering and crystallization behavior of the compositions was observed by Differential Thermal Analysis and Thermogravimetric Analysis (DTA/TG). The sequence of reaction and phase transformation was analyzed using X-ray Diffraction (XRD) technique and Rietveld structural refinement after sintering the samples at different temperature regarding the information from the DTA. The Scanning electron microscopy (SEM) was employed for morphology analysis. The DTA curve shows the crystallization temperature, Tc occur at 1259°C.Rietveld quantitative phase analysis results reveal that α phase Cordierite constitutes up to 96.4 wt% when the samples was sintered for 2 hours at the optimal temperature of 1375°C. The SEM micrograph revealed that the sample was heat treated at 1375°C obtained densified body with well alignment of crystal structure

Dynamic Trk and G Protein Signalings Regulate Dopaminergic Neurodifferentiation in Human Trophoblast Stem Cells.

Understanding the mechanisms in the generation of neural stem cells from pluripotent stem cells is a fundamental step towards successful management of neurodegenerative diseases in translational medicine. Albeit all-trans retinoic acid (RA) has been associated with axon outgrowth and nerve regeneration, the maintenance of differentiated neurons, the association with degenerative disease like Parkinson's disease, and its regulatory molecular mechanism from pluripotent stem cells to neural stem cells remain fragmented. We have previously reported that RA is capable of differentiation of human trophoblast stem cells to dopamine (DA) committed progenitor cells. Intracranial implantation of such neural progenitor cells into the 6-OHDA-lesioned substantia nigra pars compacta successfully regenerates dopaminergic neurons and integrity of the nigrostriatal pathway, ameliorating the behavioral deficits in the Parkinson's disease rat model. Here, we demonstrated a dynamic molecular network in systematic analysis by addressing spatiotemporal molecular expression, intracellular protein-protein interaction and inhibition, imaging study, and genetic expression to explore the regulatory mechanisms of RA induction in the differentiation of human trophoblast stem cells to DA committed progenitor cells. We focused on the tyrosine receptor kinase (Trk), G proteins, canonical Wnt2B/β-catenin, genomic and non-genomic RA signaling transductions with Tyrosine hydroxylase (TH) gene expression as the differentiation endpoint. We found that at the early stage, integration of TrkA and G protein signalings aims for axonogenesis and morphogenesis, involving the novel RXRα/Gαq/11 and RARβ/Gβ signaling pathways. While at the later stage, five distinct signaling pathways together with epigenetic histone modifications emerged to regulate expression of TH, a precursor of dopamine. RA induction generated DA committed progenitor cells in one day. Our results provided substantial mechanistic evidence that human trophoblast stem cell-derived neural stem cells can potentially be used for neurobiological study, drug discovery, and as an alternative source of cell-based therapy in neurodegenerative diseases like Parkinson's disease

Responses of plant cells and tissues to pulsed electric field treatments

Cell membrane electroporation/permeabilization may be achieved without affecting cell viability through strict control of the electric pulse parameters. This process is referred to as reversible permeabilization. Even if the cells survive the electric field treatment, they are subjected to stress due to the opening of pores and the struggle of the cells to recover their normal functionality. Very little is known about what actually occurs in the cell and its membranes at the molecular level upon reversible electroporation, and the physiological responses to pulsed electric field (PEF)-induced stress are still largely unknown. This chapter explores the current state of the art on the influence of the complexity of plant tissues on electroporation. Focusing on reversible electroporation, metabolic responses of plant cells and tissues induced by PEF application are also reviewed. One of the first challenges when electroporating plant tissue is their heterogeneous structures where cells vary in shape, size, and cell wall structure. This heterogeneity influences the effect of different electric fields protocols aiming at permeabilizing all cells in the tissue. Once cells are reversibly permeabilized, physiological responses to PEF-induced stress include the production of reactive oxygen species, mobilization of stored energy, activation of stress-related genes, and the production of secondary metabolites. The application of reversible PEF has also been shown to barley seed germination as well as to increase the strength of the cell wall in potatoes and, in consequence, their textural properties. This chapter finishes by revising the effect of reversible PEF on protoplasts (plant cells where the cell walls have been removed) and, in consequence, on the regeneration of new plants. Overall, reports on reversible permeabilization of plant cells and tissues are not common in the literature; however, they have laid the foundation for a fascinating area of research and technological innovation