1,720,984 research outputs found
Melanocortin-4 receptor mutations in obesity
No full textThe current alarming spread of obesity in many parts of the world is caused by a sudden environmental shift characterized by replacement of a frugal diet with low cost, energy dense food, and little requests for physical activity during work and leisure time. Yet, not all people exposed to an obesogenic environment become obese, and individual differences in the propensity to gain weight as well as the occurrence of different obese phenotypes within the same environment indicate that the genetic heritage in this regard is significant and heterogeneous. The central melanocortin circuit has received much attention during the past decade, since mutations of genes expressing some key molecules in neurons of this system were discovered, which may cause monogenic forms of obesity in animals and humans. Within the arcuate nucleus of the hypothalamus the prohormone proopiomelanocortin is posttranslationally cleaved to produce the alpha-melanocyte stimulating hormone, a peptide with anorexigenic effects upon activation of the melanocortin-4 receptor (MC4R) expressed on the surface of target neurons. Studies regarding the frequency of MC4R mutations associated with human obesity have provided variable results (up to 6% of obese subjects). Various findings suggest an oligogenic and codominant mode of inheritance for MC4R deficiency, with modulation of expressivity and penetrance of the phenotype. The yield of MC4R testing in clinical diagnosis and treatment of obesity is at present undefined since the relatively low prevalence of MC4R pathogenic variants in the general population, along with the high number of sequence variants, has so far compromised the devising of systematic controlled intervention studies. Hopefully, in the future, MC4R testing will have practical implications for the development of new mechanism-based therapy of obesity as well as for the design of specific and more effective protocols, based on lifestyle intervention and current pharmacological or surgical approaches, for management of obesity in MC4R-mutated individuals
Obesity-related gut hormones and cancer: novel insight into the pathophysiology
No full textThe number of cancers attributed to obesity is increasing over time. The mechanisms classically implicated in cancer pathogenesis and progression in patients with obesity involve adiposity-related alteration of insulin, sex hormones, and adipokine pathways. However, they do not fully capture the complexity of the association between obesity-related nutritional imbalance and cancer. Gut hormones are secreted by enteroendocrine cells along the gastrointestinal tract in response to nutritional cues, and act as nutrient sensors, regulating eating behavior and energy homeostasis and playing a role in immune-modulation. The dysregulation of gastrointestinal hormone physiology has been implicated in obesity pathogenesis. For their peculiar function, at the cross-road between nutrients intake, energy homeostasis and inflammation, gut hormones might represent an important but still underestimated mechanism underling the obesity-related high incidence of cancer. In addition, cancer research has revealed the widespread expression of gut hormone receptors in neoplastic tissues, underscoring their implication in cell proliferation, migration, and invasion processes that characterize tumor growth and aggressiveness. In this review, we hypothesize that obesity-related alterations in gut hormones might be implicated in cancer pathogenesis, and provide evidence of the pathways potentially involved
Identification of a novel mutation in the polymerase delta 1 (POLD1) gene in a lipodystrophic patient affected by mandibular hypoplasia, deafness, progeroid features (MDPL) syndrome
No full textObjective. Progressive lipodystrophy is one of the major features of the rare MDPL
syndrome. Until now, 9 patients affected by this syndrome have been described and a recent
study identified in 4 of them an in-frame deletion (Ser605del) of a single codon in the POLD1
gene. Sequence alterations of the POLD1 gene at different sites have been previously
reported in human colorectal and endometrial carcinomas.
Materials/methods. A 48-year-old woman was admitted to our department for the
assessment of a previously diagnosed lipodystrophy. She did not report a family history
of diabetes or other metabolic disorders. Hypertriglyceridemia was diagnosed incidentally
when she was 25 years old. At that time she was also diagnosed with sensorineural bilateral
hearing loss. At physical examination she presented lipoatrophy affecting nearly the entire
body, mandibular hypoplasia, bird-like face, beaked nose, progeroid facial features, with
crowded teeth, small mouth and uvula. Abdominal ultrasound showed hepatomegaly and
hepatosteatosis. Fat mass index measured with DXA was 4.59 kg/m2, indicating a fat deficit;
the oral glucose tolerance test showed an impaired glucose tolerance.
Results. Sequence analysis of the entire coding region of the POLD1 gene, disclosed a
novel heterozygous mutation in exon 13 (R507C)
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Aspetti clinici e molecolari nella lipodistrofia congenita generalizzata: descrizione di una mutazione in una paziente con Sindrome di Berardinelli-Seip.
No full textIl termine “lipodistrofia” identifica un gruppo eterogeneo di sindromi contraddistinte da anomalie del tessuto adiposo, perdita generalizzata o parziale del grasso corporeo, alterazioni del metabolismo glucidico e lipidico, importante resistenza all'insulina endogena ed esogena e disordini immunologici.
La lipodistrofia congenita generalizzata o Sindrome di Berardinelli-Seip, è una malattia rara a trasmissione autosomica recessiva caratterizzata dall’assenza quasi totale di tessuto adiposo fin dalla nascita. La prevalenza stimata è di 1 caso su 10 milioni di nati vivi e attualmente il numero di pazienti descritti in letteratura è di circa 200.
I geni responsabili del 95% dei casi di lipodistrofia congenita generalizzata sono l’1-acil-sn-glicerol-3-fosfato aciltransferasi beta (AGPAT2) e il gene denominato Berardinelli-Seip congenital lipodystrophy 2 (BSCL2), entrambi coinvolti nel processo di differenziamento adipocitario. AGPAT2 è localizzato sul cromosoma 9q34 e codifica per l’enzima 1-acil-sn-glicerol-3 fosfato aciltransferasi, responsabile della conversione dell’acido lisofosfatidico in fosfatidato.
BSCL2, localizzato sul cromosoma 11q13, codifica per la seipina, una proteina che se mutata risulta responsabile delle forme più gravi della malattia.
In questa tesi viene presentato il caso di una paziente italiana di 54 anni giunta al Dipartimento di Endocrinologia nel Luglio 2009 per diabete mellito di tipo 2 scarsamente controllato con terapia insulinica. Nata da genitori consanguinei (cugini di primo grado), la donna presentava sin dall’infanzia fenotipo acromegaloide, lipoatrofia diffusa e pseudoipertrofia muscolare. Venivano inoltre riscontrate ipercolesterolemia, ipertrigliceridemia, ipoleptinemia (0,76 ng/ml) e ipoadiponectinemia (1,10 ng/ml). Tali caratteristiche orientavano verso la sindrome di Berardinelli-Seip (BSCL). Al fine di confermare questa impressione diagnostica venivano analizzate le sequenze dei due geni candidati. Il DNA della paziente veniva estratto dai leucociti di sangue periferico ed amplificato mediante PCR. Dallo screening genetico non risultavano mutazioni nella sequenza del gene BSCL2, mentre veniva riscontrata una variante in forma omozigote nell’esone 3 del gene AGPAT2, che determina la sostituzione dell’aminoacido prolina in posizione 112 con l’aminoacido leucina (P112L). I risultati ottenuti dallo screening genetico hanno permesso di confermare la diagnosi di sindrome di Berardinelli-Seip e di identificare per la prima volta la mutazione P112L in un soggetto di razza caucasica
Oxidative and DNA damage in obese patients undergoing bariatric surgery: A one-year follow-up study
Full text linkThe pathogenesis of obesity and related comorbidities has long been associated with oxidative stress. The excess of adipose tissue contributes to the production of free radicals that sustain both a local and a systemic chronic inflammatory state, whereas its reduction can bring to an improvement in inflammation and oxidative stress. In our work, using the fluorescent lipid probe BODIPY® 581/591 C11 and the γH2AX foci assay, a well-known marker of DNA double strand breaks (DSB), we evaluated the extent of cell membrane oxidation and DNA damage in peripheral blood lymphocytes of normal weight (NW) controls and obese patients sampled before and after bariatric surgery. Compared to NW controls, we observed a marked increase in both the frequencies of oxidized cells or nuclei exhibiting phosphorylation of histone H2AX in preoperatory obese patients. After bariatric surgery, obese patients, resampled over one-year follow-up, improved oxidative damage and reduced the presence of DSB. In conclusion, the present study highlights the importance for obese patients undergoing bariatric surgery to also monitor these molecular markers during their postoperative follow-up
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