Search results for "MUTATION"

The cytoplasmic PASC domain of the sensor kinase DcuS of Escherichia coli : role in signal transduction, dimer formation, and DctA interaction

2013

The cytoplasmic PAS(C) domain of the fumarate responsive sensor kinase DcuS of Escherichia coli links the transmembrane to the kinase domain. PAS(C) is also required for interaction with the transporter DctA serving as a cosensor of DcuS. Earlier studies suggested that PAS(C) functions as a hinge and transmits the signal to the kinase. Reorganizing the PAS(C) dimer interaction and, independently, removal of DctA, converts DcuS to the constitutive ON state (active without fumarate stimulation). ON mutants were categorized with respect to these two biophysical interactions and the functional state of DcuS: type I-ON mutations grossly reorganize the homodimer, and decrease interaction with Dct…

The PCSK9 gene: a new gene controlling cholesterolemia

2007

The distribution of cholesterol plasma is regulated by complex interactions between genes and environmental factors. Mutations of PCSK9 gene seem to modulate the levels of LDLC. Mutations of PCSK9 gene with gain of function are associated to hypercholesterolemia and mutations with loss of function determine hypocholesterolemia.

Pancreatic undifferentiated carcinoma with osteoclast-like giant cells is genetically similar to, but clinically distinct from, conventional ductal a…

2017

Undifferentiated carcinoma of the pancreas with osteoclast-like giant cells (UCOGC) is currently considered a morphologically and clinically distinct variant of pancreatic ductal adenocarcinoma (PDAC). In this study, we report clinical and pathological features of a series of 22 UCOGCs, including the whole exome sequencing of eight UCOGCs. We observed that 60% of the UCOGCs contained a well-defined epithelial component and that patients with pure UCOGC had a significantly better prognosis than did those with an UCOGC with an associated epithelial neoplasm. The genetic alterations in UCOGC are strikingly similar to those known to drive conventional PDAC, including activating mutations in the…

Gists eredo familiari e pediatrici: aspetti biomolecolari e clinici.

2008

Combined Therapy of Interferon Plus Ribavirin Promotes Multiple Adaptive Solutions in Hepatitis C Virus

2009

Hepatitis C virus (HCV) presents several regions involved potentially in evading antiviral treatment and host immune system. Two regions, known as PKR-BD and V3 domains, have been proposed to be involved in resistance to interferon. Additionally, hypervariable regions in the envelope E2 glycoprotein are also good candidates to participate in evasion from the immune system. In this study, we have used a cohort of 22 non-responder patients to combined therapy (interferon alpha-2a plus ribavirin) for which samples obtained just before initiation of therapy and after 6 or/and 12 months of treatment were available. A range of 25-100 clones per patient, genome region and time sample were obtained…

An siRNA-based functional genomics screen for the identification of regulators of ciliogenesis and ciliopathy genes

2015

Item does not contain fulltext Defects in primary cilium biogenesis underlie the ciliopathies, a growing group of genetic disorders. We describe a whole-genome siRNA-based reverse genetics screen for defects in biogenesis and/or maintenance of the primary cilium, obtaining a global resource. We identify 112 candidate ciliogenesis and ciliopathy genes, including 44 components of the ubiquitin-proteasome system, 12 G-protein-coupled receptors, and 3 pre-mRNA processing factors (PRPF6, PRPF8 and PRPF31) mutated in autosomal dominant retinitis pigmentosa. The PRPFs localize to the connecting cilium, and PRPF8- and PRPF31-mutated cells have ciliary defects. Combining the screen with exome sequen…

The dark side of the moon: The PI3K/PTEN/AKT pathway in colorectal carcinoma

2009

Wild-type KRAS status is required but not sufficient to confer sensitivity to anti-epidermal growth factor receptor (EGFR) monoclonal antibodies (mAbs) in colorectal cancer patients. As a consequence, one of the major challenges is to identify, in non-mutant KRAS patients, other markers that can predict lack of response to this therapy. Small series have investigated the clinical effect of PIK3CA mutations on resistance to anti-EGFR mAbs and discrepant results have been observed. Furthermore, PTEN loss in metastases may be predictive of resistance to anti-EGFR mAbs, even if PTEN determination is far from an immediate clinical application. The introduction of modulators of the PI3K/AKT/mTOR …

Targeting the Cancer Initiating Cell: The Ultimate Target for Cancer Therapy

2012

An area of therapeutic interest in cancer biology and treatment is targeting the cancer stem cell, more appropriately referred to as the cancer initiating cell (CIC). CICs comprise a subset of hierarchically organized, rare cancer cells with the ability to initiate cancer in xenografts in genetically modified murine models. CICs are thought to be responsible for tumor onset, self-renewal/maintenance, mutation accumulation and metastasis. CICs may lay dormant after various cancer therapies which eliminate the more rapidly proliferating bulk cancer (BC) mass. However, CICs may remerge after therapy is discontinued as they may represent cells which were either intrinsically resistant to the or…

Paraphyly of the Blue Tit (Parus caeruleus) suggested from cytochrome b sequences

2002

The phylogenetic relationships of the Blue Tit-Azure Tit assemblage (genus Parus; Aves: Passeriformes) were studied using mitochondrial DNA sequences of 24 specimens representing seven subspecies from Eurasia and North Africa. Previous work based on comparative morphological and acoustic data suggested a division of the Blue Tit (Parus caeruleus) into two species. Our analyses clearly indicate that the Blue Tit represents a paraphyletic assemblage, including a European/Middle Asian clade that is the sister group to the Azure Tit (Parus cyanus) and a North African clade. The North African clade (teneriffae subspecies group) is a sister group to the European Blue Tit/Azure Tit clade. We sugge…

Effects of pharmacological agents on the lifespan phenotype of Drosophila DJ-1beta mutants.

2010

Mutations in the DJ-1 gene cause autosomal recessive, early-onset Parkinsonism. The DJ-1 protein exerts a protective role against oxidative stress damage, working as a cellular oxidative stress sensor, and it seems to regulate gene expression at different levels. In Drosophila, two DJ-1 orthologs have been identified: DJ-1β and DJ-1β. Several studies have shown that loss of DJ-1β function causes Parkinson's disease (PD)-like phenotypes in flies such as age-dependent locomotor defects, reduced lifespan, and enhanced sensitivity to toxins that induce oxidative stress, like the herbicide paraquat. However, no dopaminergic neurodegeneration is observed. These results suggested that both locomot…