Thermogenic flux induced by lignoceric acid in peroxisomes isolated from HepG2 cells and from X- adrenoleukodystrophy and control fibroblasts

This work analyzes the thermogenic flux induced by the very long-chain fatty acid (VLCFA) lignoceric acid (C24:0) in isolated peroxisomes. Specific metabolic alterations of peroxisomes are related to a variety of disorders, the most frequent one being the neurodegenerative inherited disease X-linked adrenoleukodystrophy (X-ALD). A peroxisomal transport protein is mutated in this disorder. Due to reduced catabolism and enhanced fatty acid elongation, VLCFA accumulate in plasma and in all tissues, contributing to the clinical manifestations of this disorder. During peroxisomal metabolism, heat is produced but it is considered lost. Instead, it is a form of energy that could play a role in molecular mechanisms of this pathology and other neurodegenerative disorders. The thermogenic flux induced by lignoceric acid (C24:0) was estimated by isothermal titration calorimetry in peroxisomes isolated from HepG2 cells and from fibroblasts obtained from X-linked adrenoleukodystrophy patients and healthy subjects. Heat flux induced by lignoceric acid in HepG2 peroxisomes was exothermic, indicating normal peroxisomal metabolism. In X-ALD peroxisomes the heat flux was endothermic, indicating the requirement of heat/energy, possibly for cellular metabolism. In fibroblasts from healthy subjects the effect was less pronounced than in HepG2, a kind of cell known to have greater FA metabolism than fibroblasts. Our hypothesis is that heat is not lost but it could act a s an activator, for example on the heat-sensitive pathway related to TRVP2 receptors. To investigate this hypothesis we focused on peroxisomal metabolism, considering that impaired heat generation could contribute to the development of peroxisomal neurodegenerative disorders

Unsaturated fatty acids esterified with androgens as active and safer compounds for androgen-required therapy

Unsaturated fatty acids esterified with androgens as active and safer compounds for androgen-required therapy A. Petroni1, F. Aiello2, A. Garofalo2, S. Banni3, M. Blasevich1 and A.M. Aloisi4 [email protected], [email protected], Dipartimento di Scienze Farmacologiche e Biomolecolari, Universita\u300 di Milano, 20133 Milano, Italy; [email protected], [email protected], Dipartimento di Farmacia e Scienze della Salute e della Nutrizione Universita\u300 della Calabria, 87036 Rende (Cs), Italy; [email protected], Dipartimento Scienze Biomediche, Universita' degli Studi Cagliari, Cittadella Universitaria, 09042 Monserrato (CA), Italy; [email protected], Dipartimento di Medicina, Chirurgia e Neuroscienze, via Aldo Moro 2, 53100 Siena, Italy Testosterone and its powerful metabolite dihydrotestosterone can be used in a variety of disorders to improve the symptoms or restore androgen plasma levels. To increase their duration and effects, androgens are administered in different pharmaceutical forms, in particular as esters of carboxylic acids. The goal of our research was to use specific unsaturated fatty acids esterified with androgens to improve the pharmaceutical characteristics of the esters as well as their biological effects and safety. Oleic acid, linoleic acid and the n-3 fatty acids, alpha-linolenic acid, eicosapentaenoic acid and docosahexaenoic acid, were esterified with androgens. Their cytotoxicity was evaluated in mouse NIH3T3 and human astrocyte cell lines. The esters showed good tolerability and no in vitro cytotoxic effects in both cell cultures. Due to the influence of androgens in pain processes and the common opioid- induced hypogonadism, in vivo studies were carried out to investigate their long-term administration in a pain model of persistent pain. Androgen therapy can also be required in neurodegenerative disorders, for instance in X-linked adrenoleukodystrophy, an inherited pathology. Lipid alterations are the major cause of the disorder and hypogonadism can be a secondary event. In this specific disorder and in chronic pathologies with unbalanced lipid and steroid hormone metabolism, the use of the described esters, which are more \u201cphysiological\u201d than the ones currently available, should be carefully considered

Multi-method approach shows stock structure in Loligo forbesii squid

Knowledge of stock structure is a priority for effective assessment of commercially-fished cephalopods. Loligo forbesii squid are thought to migrate inshore for breeding and offshore for feeding and long-range movements are implied from past studies showing genetic homogeneity in the entire neritic population. Only offshore populations (Faroe and Rockall Bank) were considered distinct. The present study applied mitchondrial and microsatellite markers (nine loci) to samples from Rockall Bank, north Scotland, North Sea, various shelf locations in Ireland, English Channel, northern Bay of Biscay, north Spain, and Bay of Cadiz. No statistically significant genetic sub-structure was found, although some non-significant trends involving Rockall were seen using microsatellite markers. Differences in L. forbesii statolith shape were apparent at a subset of locations, with most locations showing pairwise differences and statoliths from north Ireland being highly distinct. This suggests that (i) statolith shape is highly sensitive to local conditions and (ii) L. forbesii forms distinguishable groups (based on shape statistics), maintaining these groups over sufficiently long periods for local conditions to affect the shape of the statolith. Overall evidence suggests that L. forbesii forms separable (ecological) groups over short timescales with a semi-isolated breeding group at Rockall whose distinctiveness varies over time.Postprin

Autophagy in major human diseases

Autophagy is a core molecular pathway for the preservation of cellular and organismal homeostasis. Pharmacological and genetic interventions impairing autophagy responses promote or aggravate disease in a plethora of experimental models. Consistently, mutations in autophagy-related processes cause severe human pathologies. Here, we review and discuss preclinical data linking autophagy dysfunction to the pathogenesis of major human disorders including cancer as well as cardiovascular, neurodegenerative, metabolic, pulmonary, renal, infectious, musculoskeletal, and ocular disorders

The Marine Microbial Eukaryote Transcriptome Sequencing Project (MMETSP): Illuminating the Functional Diversity of Eukaryotic Life in the Oceans through Transcriptome Sequencing

Microbial ecology is plagued by problems of an abstract nature. Cell sizes are so small and population sizes so large that both are virtually incomprehensible. Niches are so far from our everyday experience as to make their very definition elusive. Organisms that may be abundant and critical to our survival are little understood, seldom described and/or cultured, and sometimes yet to be even seen. One way to confront these problems is to use data of an even more abstract nature: molecular sequence data. Massive environmental nucleic acid sequencing, such as metagenomics or metatranscriptomics, promises functional analysis of microbial communities as a whole, without prior knowledge of which organisms are in the environment or exactly how they are interacting. But sequence-based ecological studies nearly always use a comparative approach, and that requires relevant reference sequences, which are an extremely limited resource when it comes to microbial eukaryotes

La rete dell’università

Questa ricerca ha esaminato il sistema universitario italiano dal punto di vista della sua capacità di svolgere le funzioni di alta formazione e di promozione dell’innovazione nei diversi campi del sapere, con particolare riferimento ai settori strategici per lo sviluppo del paese. Sono stati presi in considerazione i seguenti profili: – l’adeguatezza dell’attuale articolazione del sistema universitario italiano sotto il profilo delle dimensioni degli atenei e della loro specializzazione nell’assicurare una formazione di alto livello; – il collegamento fra università e territorio, soprattutto dal punto di vista delle relazioni con i settori produttivi e della ricerca e innovazione; – l’attuale assetto della governance dell’università e le valutazioni possibili sull’autonomia dei singoli atenei. Nell’ambito della ricerca sono state svolte le audizioni di alcuni rettori di atenei italiani: Luigi Frati (rettore dell’Università La Sapienza di Roma), Domenico Laforgia (rettore dell’Università del Salento), Fulvio Esposito (rettore dell’Università di Camerino)

From nutritional bioactive compounds to the development of therapies for neurodegenerative disorders

Common metabolic alterations are associated with the progression of a growing number of neurodegenerative disorders, characterized by different ethiopatogenesis. In the case of adrenoleukodystrophy (X-ALD), an inherited demyelinating disorder, the mutated protein (ALDP) impair lipid catabolism. During the progression of this pathology, ALDP-related proteins can be overexpressed and partially compensate the lipid metabolic impairment. Other secondary alterations develop during the progression of the disorder such as oxidative stress, inflammatory cascade, peroxisomal impairment amplify neurodegenerative conditions. The therapeutic control of these secondary events are fundamental. A crucial factor for the treatment of X-ALD and neurodegenerative conditions is the passage of drugs through the blood-brain barrier. The aim of our research was to develop a therapeutic strategy utilizing nutritional bioactive compounds. We have demonstrated that specific compounds, utilized in the dietary therapy for X-ALD, can pass through blood-brain-barrier and they are detected in the liquor of treated patients (Cappa et al., J Inherit Metab Dis, 35:899-907, 2012). We investigated the molecular mechanisms of specific bioactive compounds to develop a dietary strategy aimed to modulate the progression of neurodegenerative disorders

Impact of testosterone on body fat composition

An excessive food supply has resulted in an increasing prevalence of overweight and obesity, conditions accompanied by serious health problems. Several studies have confirmed the significant inverse correlation between testosterone and obesity. Indeed after decades of intense controversy, a consensus has emerged that androgens are important regulators of fat mass and distribution in mammals and that androgen status affects cellularity in vivo. The high correlation of testosterone levels with body composition and its contribution to the balance of lipid metabolism are also suggested by the fact that testosterone lowering is associated with important clinical disorders such as dyslipidemia, atherosclerosis, cardiovascular diseases, metabolic syndrome and diabetes. In contrast, testosterone supplementation therapy in hypogonadic men has been shown to improve the lipid profile by lowering cholesterol, blood sugar and insulin resistance. Leptin, ghrelin and adiponectin are some of the substances related to feeding as well as androgen regulation. Thus, complex and delicate mechanisms appear to link androgens with various tissues (liver, adipose tissue, muscles, coronary arteries and heart) and the subtle alteration of some of these interactions might be the cause of correlated diseases. This review underlines some aspects regarding the high correlations between testosterone physiology and body fat composition