Laboratory of Molecular Genetics

Città della Pieve, Italy

Laboratory of Molecular Genetics

Città della Pieve, Italy
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Montuschi A.,University of Turin | Iazzolino B.,University of Turin | Calvo A.,University of Turin | Calvo A.,Neuroscience Institute of Turin NIT | And 9 more authors.
Journal of Neurology, Neurosurgery and Psychiatry | Year: 2015

Background: There is less data available regarding the characteristics of cognitive impairment in patients with amyotrophic lateral sclerosis (ALS) in a population-based series. Methodology: Patients with ALS incident in Piemonte, Italy, between 2009 and 2011 underwent an extensive neuropsychological battery. Cognitive status was classified as follows: normal cognition, frontotemporal dementia (ALS-FTD), executive cognitive impairment (ALS-ECI), non-executive cognitive impairment (ALS-NECI), behavioural impairment (ALS-Bi), nonclassifiable cognitive impairment. We also assessed 127 age-matched and gender-matched controls identified through patients' general practitioners. Results: Out of the 281 incident patients, 207 (71.9%) underwent the neuropsychological testing; of these, 19 were excluded from the analysis due previous conditions affecting cognition. Ninety-one (49.7%) patients were cognitively normal, 23 (12.6%) had ALS-FTD, 36 (19.7%) ALS-ECI, 10 (5.5%) ALS-NECI, 11 (6.0%) ALS-Bi and 11 (6.0%) non-classifiable cognitive impairment, 1 had comorbid Alzheimer 's disease. Patients with ALS-FTD were older, had a lower education level, and had a shorter survival than any other cognitive group. Of the nine cases with C9ORF72 mutation, six had ALS-FTD, two ALS-ECI and one was cognitively normal; one of the five patients with SOD1 mutations and one of the five patients with TARBDP mutations had ALS-Bi. Conclusions: About 50% of Italian patients with ALS had some degree of cognitive impairment, in keeping with a previous Irish study, despite the largely different genetic background of the two populations. The lower educational attainment in patients with ALS-FTD indicated a possible role of cognitive reserve in ALS-related cognitive impairment. ALS-ECI and ALS-NECI may represent discrete cognitive syndromes in the continuum of ALS and FTD. © 2015, BMJ Publishing Group. All rights reserved.

Faria N.A.,Laboratory of Molecular Genetics | Faria N.A.,Institute Tecnologia Quymica e Biolo Gica | Miragaia M.,Institute Tecnologia Quymica e Biolo Gica | De Lencastre H.,Laboratory of Molecular Genetics | De Lencastre H.,Rockefeller University
Microbial Drug Resistance | Year: 2013

Portugal is the European country with the highest prevalence of methicillin resistant Staphylococcus aureus (MRSA), in which EMRSA-15 (ST22-IVh) has been the dominant clone since soon after its introduction in Portuguese hospitals in 2001. In this study, we intend to not only, assess the evolution of the invasive MRSA in Portuguese hospitals, but also to evaluate the invasive methicillin susceptible S. aureus (MSSA) population and the relationship between both populations. In the current study, two major MRSA clones were identified: EMRSA-15 that has been dominant for more than 10 years and accounts for 75% of the MRSA isolates, and ST105-II, a clone related with the New York/Japan clone (ST5-II). In contrast, among MSSA, several clonal backgrounds were identified. Despite of the massive predominance of EMRSA-15 in the last decade, an increase in spa diversity has been observed in the last few years, which suggests a recent and local diversification of this clone. Interestingly, MRSA and MSSA populations with related clonal backgrounds appear to have increased as a result of the dissemination of MRSA to the community environment. © Mary Ann Liebert, Inc.

Putkonen M.,University of Turku | Kairisto V.,Laboratory of Molecular Genetics | Juvonen V.,Laboratory of Molecular Genetics | Pelliniemi T.-T.,Laboratory of Haematology | And 3 more authors.
European Journal of Haematology | Year: 2010

Achievement of complete response (CR) is a new goal of therapy for multiple myeloma (MM). By sensitive methods, the depth of response can be measured even among the patients in CR. We used a sensitive real-time quantitative polymerase chain reaction by allele-specific primers (qASO-PCR) to assess the level of minimal residual disease (MRD) in bone marrow of 37 patients with myeloma who had achieved CR/near-to-CR after autologous or allogeneic stem cell transplantation (SCT). Allele-specific primers could be successfully designed for 86% of patients. Three to six months after autotransplantation, the PCR target was not detectable in 53% of patients (16/30 patients), and the respective figure after allotransplantation was 71% (5/7 patients); the median sensitivity of PCR assay was <0.002%. The proportion of patients without detectable PCR target was 22% of all autotransplanted patients. A threshold level of 0.01% in the qASO-PCR assay 3-6 months after SCT was found to be a useful cut-off limit to divide the patients into two prognostic groups: MRD low/negative vs. MRD high. Low/negative MRD after SCT was a significant predictive factor for the prolongation of progression free (70 vs. 19 months; P = 0.003) and suggestively also for overall survival. We conclude that not only CR but also its depth is important for the long-term outcome in MM. © 2010 John Wiley & Sons A/S.

Gradilone S.A.,Miles College | Masyuk T.V.,Miles College | Huang B.Q.,Miles College | Banales J.M.,Miles College | And 8 more authors.
Gastroenterology | Year: 2010

Background & Aims: In polycystic liver diseases, cyst formation involves cholangiocyte hyperproliferation. In polycystic kidney (PCK) rats, an animal model of autosomal-recessive polycystic kidney disease (ARPKD), decreased intracellular calcium [Ca2+]i in cholangiocytes is associated with hyperproliferation. We recently showed transient receptor potential vanilloid 4 (Trpv4), a calcium-entry channel, is expressed in normal cholangiocytes and its activation leads to [Ca2+]i increase. Thus, we hypothesized that pharmacologic activation of Trpv4 might reverse the hyperproliferative phenotype of PCK cholangiocytes. Methods: Trpv4 expression was examined in liver of normal and PCK rats, normal human beings, and patients with autosomal-dominant polycystic kidney disease or ARPKD. Trpv4 activation effect on cell proliferation and cyst formation was assessed in cholangiocytes derived from normal and PCK rats. The in vivo effects of Trpv4 activation on kidney and liver cysts was analyzed in PCK rats. Results: Trpv4 was overexpressed both at messenger RNA (8-fold) and protein (3-fold) levels in PCK cholangiocytes. Confocal and immunogold electron microscopy supported Trpv4 overexpression in the livers of PCK rats and ARPKD or autosomal-dominant polycystic kidney disease patients. Trpv4 activation in PCK cholangiocytes increased [Ca2+]i by 30%, inhibiting cell proliferation by approximately 25%-50% and cyst growth in 3-dimensional culture (3-fold). Trpv4-small interfering RNA silencing blocked effects of Trpv4 activators by 70%. Trpv4 activation was associated with Akt phosphorylation and β-Raf and Erk1/2 inhibition. In vivo, Trpv4 activation induced a significant decrease in renal cystic area and a nonsignificant decrease in liver cysts. Conclusions: Taken together, our in vitro and in vivo data suggest that increasing intracellular calcium by Trpv4 activation may represent a potential therapeutic approach in PKD. © 2010 AGA Institute.

Chio A.,University of Turin | Calvo A.,University of Turin | Moglia C.,University of Turin | Ossola I.,Laboratory of Molecular Genetics | And 6 more authors.
Neurobiology of Aging | Year: 2011

Mutations in the Cu/Zn superoxide dismutase (SOD1), transactive response (TAR)-DNA binding protein (TARDBP) and fused in sarcoma (FUS) genes account for approximately 1 third of familial amyotrophic lateral sclerosis (ALS) cases. Mutations in these genes have been found in 1% to 2% of apparently sporadic cases. We present the first case of an ALS patient carrying a de novo missense mutation of the FUS gene (c.1561C>T, p.R521C). This report highlights the importance of screening ALS patients, both familial and sporadic, for FUS mutations and also suggests that de novo mutations is a relevant mechanism underlying sporadic neurodegenerative disease. © 2011 Elsevier Inc.

Hasnaoui N.,Higher Agronomic Institute | Hasnaoui N.,Laboratory of Molecular Genetics | Mars M.,Higher Agronomic Institute | Ghaffari S.,Institute of Arid regions | And 3 more authors.
Industrial Crops and Products | Year: 2011

Tunisian pomegranate genetic resources consist of sweet and sour cultivars, showing large morphometric variability. In the present work we characterized seeds and juice contents of sugars and organic acids of 5 sour and 7 sweet pomegranate cultivars. Results showed that citric acid was predominant in sour pomegranates, while malic acid was the most prevalent in sweet ones. Paradoxically, sour cultivars have higher sugar content than the sweet ones. A strong correlation was found between sourness and citric acid content, which is assumed to be the major factor that determines sour taste in pomegranate fruits. Besides, some of the seed parameters showed a significant positive correlation with acidity. Sweet cultivars were appropriate for fresh consumption and juice production due to several attributes in addition to their sweetness. Equally, sour pomegranate showed several characteristics that could be of great interest for food and nutraceutical industries. © 2010 Elsevier B.V.

Hasnaoui N.,Higher Agronomic Institute | Hasnaoui N.,Laboratory of Molecular Genetics | Buonamici A.,CNR Institute of Plant Genetics | Sebastiani F.,University of Florence | And 3 more authors.
Gene | Year: 2012

Pomegranate (Punica granatum L.) is one of the oldest known edible fruits and more and more it arouse interest of scientific community given its numerous biological activities. However, information about its genetic resources and characterization using reliable molecular markers are still scarce. In the present study, we report the development of 4 new polymorphic SSR markers. They have been used in addition to 11 SSRs previously published to investigate molecular diversity of 33 P. granatum ecotypes. Based on the multi-locus profiles, twenty-two distinctive genotypes were identified. Globally, quite low genetic diversity has been revealed, as measured by allele richness (2.83 per locus) and heterozygosity (He = 0.245; Ho = 0.243), reflecting the narrow genetic background of the plant material. Four synonymous groups could be detected involving 15 accessions. Results of ordination and cluster analysis suggested that almost all the Tunisian cultivars share similar genetic background, and are likely derived from a small number of introductions in ancient times. Results issued from this study provide essential information to project a pomegranate core-collection without plant material duplication and for sustainable management of pomegranate landraces at national and international level. Furthermore, these SSR markers are powerful tool for marker assisted selection (MAS) program and for QTL studies. © 2011 Elsevier B.V.

News Article | February 2, 2017

For most people who contract it, dengue fever is a relatively mild-mannered disease - at least the first time around. For some, however, a subsequent infection by the virus unleashes a vicious and potentially deadly illness. New research from a team based at The Rockefeller University has begun to reveal why certain people are more vulnerable to these dangerous secondary infections. Their latest findings, described in Science, could lead to better strategies to identify and better treat those most at risk. "Patients with severe secondary disease have high levels of a particular type of antibody that triggers a forceful immune response. This distinctive signature did not show up in patients with more mild illness," says senior author Jeffrey V. Ravetch, Theresa and Eugene M. Lang Professor and head of the Leonard Wagner Laboratory of Molecular Genetics and Immunology. "Our work sheds new light on the way in which the dengue virus co-opts antibodies produced as a result of the previous infection, using them to inflict more damage the second time around," Ravetch adds. Known as "breakbone fever" for the intense aches it causes, dengue is transmitted by mosquitos in the tropics and subtropics. In the more severe form of the disease, which typically occurs among people who have been infected before, patients can develop hemorrhagic fever, which causes them to leak fluid from their blood vessels and bleed abnormally, sometimes from the nose, gums, and under the skin. In extreme cases, people lose so much blood that they develop a critical condition known as shock. Researchers have long thought this happens because, when it infects a second time, the virus somehow takes advantage of antibodies the immune system is still producing as a result of the first infection. But this doesn't explain why less than 15 of percent people who catch dengue for the second time develop full-blown hemorrhagic fever or shock. Previous work in Ravetch's lab suggested differences in antibodies might account for why only some develop severe secondary infections. These Y-shaped proteins help the body defend itself against viruses and other intruders by latching onto infected cells with their arms. Meanwhile, their stems, known as Fc regions, bind to immune cells and tell them how to respond. Ravetch's lab has shown that the structure of the Fc region can influence an immune response by, for example, promoting inflammation versus calming it. For the current study, first author Taia Wang, then a postdoc in the lab, and her collaborators took a close look at the Fc regions of antibodies in blood collected from patients with mild and severe secondary dengue infections at Siriraj Hospital in Bangkok, Thailand. These people's immune systems were still producing antibodies as a result of their first encounter with the virus, but the structure of these antibodies varied between individuals. The researchers found that the dengue patients with more serious disease had high levels of antibodies whose Fc regions lack a particular sugar, a variation known to strongly activate immune cells. In experiments, the researchers showed that activating signals from these antibodies aggravated the disease by leading to the destruction of blood-clotting cells called platelets. When their platelet levels plummet, patients bleed abnormally - a hallmark of hemorrhagic fever. The lower a patient's platelet count, the more of these distinctive antibodies he or she tended to have. "We found that some people's immune systems respond to dengue infection by producing elevated levels of these pathogenic antibodies, which make them more vulnerable to a severe secondary dengue infection," says Wang, who is now an assistant professor at Stanford School of Medicine. "It's not yet clear if they produce more of these highly activating antibodies even before they encounter the virus." The discovery of this antibody signature could help fight the disease in a number of ways. "Because we now know what to look for, it may become possible to identify patients at risk of severe illness, so they can receive intensive, supportive care early on," Ravetch says. "It could also aid in the development of safe dengue vaccines that stimulate the immune system without triggering a secondary, potentially harmful response, and of new drugs designed to help patients recover by blocking the antibody signaling," he adds. Since dengue belongs to the same family as Zika and other dangerous viruses, the implications go beyond this particular disease. "It will be important to consider the possibility that other, related viruses employ a similar strategy, and that infection with one may affect the subsequent response to another," he says. Article: IgG antibodies to dengue enhanced for FcγRIIIA binding determine disease severity, Jeffrey V. Ravetch et al., Science, doi: 10.1126/science.aai8128, published 27 January 2017.

Bu F.,University of Iowa | Borsa N.,Laboratory of Molecular Genetics | Borsa N.,Center for Control | Gianluigi A.,Center for Control | Smith R.J.H.,University of Iowa
Clinical and Developmental Immunology | Year: 2012

Atypical hemolytic uremic syndrome (aHUS) is a rare renal disease (two per one million in the USA) characterized by microangiopathic hemolytic anemia, thrombocytopenia, and acute renal failure. Both sporadic (80 of cases) and familial (20 of cases) forms are recognized. The study of familial aHUS has implicated genetic variation in multiple genes in the complement system in disease pathogenesis, helping to define the mechanism whereby complement dysregulation at the cell surface level leads to both sporadic and familial disease. This understanding has culminated in the use of Eculizumab as first-line therapy in disease treatment, significantly changing the care and prognosis of affected patients. However, even with this bright outlook, major challenges remain to understand the complexity of aHUS at the genetic level. It is possible that a more detailed picture of aHUS can be translated to an improved understanding of disease penetrance, which is highly variable, and response to therapy, both in the short and long terms. © 2012 Fengxiao Bu et al.

MANHASSET, N.Y., Feb. 21, 2017 /PRNewswire-USNewswire/ -- The Feinstein Institute for Medical Research today announced that Jeffrey V. Ravetch, MD, PhD, the Theresa and Eugene M. Lang professor and head of the Leonard Wagner Laboratory of Molecular Genetics and Immunology at The...

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