Search results for " Biochemistry"

Chaperonin of Group I: Oligomeric spectrum and biochemical and biological implications

2018

Chaperonins play various physiological roles and can also be pathogenic. Elucidation of their structure, e.g., oligomeric status and post-translational modifications (PTM), is necessary to understand their functions and mechanisms of action in health and disease. Group I chaperonins form tetradecamers with two stacked heptameric rings. The tetradecamer is considered the typical functional complex for folding of client polypeptides. However, other forms such as the monomer and oligomers with smaller number of subunits than the classical tetradecamer, also occur in cells. The properties and functions of the monomer and oligomers, and their roles in chaperonin-associated diseases are still inc…

International descriptive and interventional survey for oxycholesterol determination by gas- and liquid-chromatographic methods

2018

International audience; Increasing numbers of laboratories develop new methods based on gas-liquid and high-performance liquid chromatography to determine serum concentrations of oxygenated cholesterol metabolites such as 7alpha-, 24(S)-, and 27-hydroxycholesterol. We initiated a first international descriptive oxycholesterol (OCS) survey in 2013 and a second interventional survey 2014 in order to compare levels of OCS reported by different laboratories and to define possible sources of analytical errors. In 2013 a set of two lyophilized serum pools (A and B) was sent to nine laboratories in different countries for OCS measurement utilizing their own standard stock solutions. In 2014 eleven…

2019

Abstract Background Comprehensive transcriptomic analyses have shown that colorectal cancer (CRC) is heterogeneous and have led to the definition of molecular subtypes among which the stem-cell, mesenchymal-like group is associated with poor prognosis. The molecular pathways orchestrating the emergence of this subtype are incompletely understood. In line with the contribution of the cellular prion protein PrPC to stemness, we hypothesize that deregulation of this protein could lead to a stem-cell, mesenchymal-like phenotype in CRC. Methods We assessed the distribution of the PrPC-encoding PRNP mRNA in two large CRC cohorts according to molecular classification and its association with patie…

Fast Regulation of GABAAR Diffusion Dynamics by Nogo-A Signaling.

2019

Summary: Precisely controlling the excitatory and inhibitory balance is crucial for the stability and information-processing ability of neuronal networks. However, the molecular mechanisms maintaining this balance during ongoing sensory experiences are largely unclear. We show that Nogo-A signaling reciprocally regulates excitatory and inhibitory transmission. Loss of function for Nogo-A signaling through S1PR2 rapidly increases GABAAR diffusion, thereby decreasing their number at synaptic sites and the amplitude of GABAergic mIPSCs at CA3 hippocampal neurons. This increase in GABAAR diffusion rate is correlated with an increase in Ca2+ influx and requires the calcineurin-mediated dephospho…

Clinical and hormonal characteristics in heterozygote carriers of congenital adrenal hyperplasia

2020

Abstract Non-classical congenital adrenal hyperplasia (NC-CAH) includes a group of genetic disorders due to a broad class of CYP21A2 variants identifying a disease-causing ‘C’ genotype. The heterozygous carriers of CYP21 mutations are at increased risk of developing clinically evident hyperandrogenism, even though clinical and laboratory characteristics are still underestimated. With the aim of obtaining a more accurate delineation of the phenotype of heterozygous carrier of CAH, we analyzed clinical, biochemical and molecular characteristics in a cohort of Sicilian subjects. Fifty-seven females with biallelic and monoallelic CYP21A2 variants classifying NC-CAH (24) and heterozygous carrier…

Complete chromogen separation and analysis in double immunohistochemical stains using Photoshop-based image analysis.

1998

Simultaneous detection of two different antigens on paraffin-embedded and frozen tissues can be accomplished by double immunohistochemistry. However, many double chromogen systems suffer from signal overlap, precluding definite signal quantification. To separate and quantitatively analyze the different chromogens, we imported images into a Macintosh computer using a CCD camera attached to a diagnostic microscope and used Photoshop software for the recognition, selection, and separation of colors. We show here that Photoshop-based image analysis allows complete separation of chromogens not only on the basis of their RGB spectral characteristics, but also on the basis of information concernin…

Let-7d miRNA Shows Both Antioncogenic and Oncogenic Functions in Osteosarcoma-Derived 3AB-OS Cancer Stem Cells

2016

Osteosarcoma (OS), an aggressive highly invasive and metastatic bone-malignancy, shows therapy resistance and recurrence, two features that likely depend on cancer stem cells (CSCs), which hold both self-renewing and malignant potential. So, effective anticancer therapies against OS should specifically target and destroy CSCs. We previously found that the let-7d microRNA was downregulated in the 3AB-OS-CSCs, derived from the human OS-MG63 cells. Here, we aimed to assess whether let-7d modulation affected tumorigenic and stemness properties of these OS-CSCs. We found that let-7d-overexpression reduced cell proliferation by decreasing CCND2 and E2F2 cell-cycle-activators and increasing p21 an…

Modulating endothelial adhesion and migration impacts stem cell therapies efficacy

2020

Abstract Background Limited knowledge of stem cell therapies` mechanisms of action hampers their sustainable implementation into the clinic. Specifically, the interactions of transplanted stem cells with the host vasculature and its implications for their therapeutic efficacy are not elucidated. We tested whether adhesion receptors and chemokine receptors on stem cells can be functionally modulated, and consequently if such modulation may substantially affect therapeutically relevant stem cell interactions with the host endothelium. Methods We investigated the effects of cationic molecule polyethylenimine (PEI) treatment with or without nanoparticles on the functions of adhesion receptors a…

Autophagy interferes with human cytomegalovirus genome replication, morphogenesis, and progeny release.

2020

Viral infections are often accompanied by the induction of autophagy as an intrinsic cellular defense mechanism. Herpesviruses have developed strategies to evade autophagic degradation and to manipulate autophagy of the host cells to their benefit. Here we addressed the role of macroautophagy/autophagy in human cytomegalovirus replication and for particle morphogenesis. We found that proteins of the autophagy machinery localize to cytoplasmic viral assembly compartments and enveloped virions in the cytoplasm. Surprisingly, the autophagy receptor SQSTM1/p62 was also found to colocalize with HCMV capsids in the nucleus of infected cells. This finding indicates that the autophagy machinery int…

TLR3-independent activation of mast cells by cytomegalovirus contributes to control of pulmonary infection.

2017

Interstitial pneumonia is a life-threatening clinical manifestation of human cytomegalovirus (hCMV) infection. In particular, it can be deadly in patients with hematopoietic malignancies who undergo hematopoietic cell transplantation (HCT) in whom a ‘window of risk’, which is defined by transient immunodeficiency, occurs between hematoablative therapeutic treatment and immunological reconstitution. As few clinical studies have addressed the underlying mechanisms for this phenomenon, a mouse model of HCT and murine cytomegalovirus (mCMV) infection has been established and has revealed a key role for antiviral CD8+ T cells in controlling pulmonary infections. Using this mouse model, recent st…