Showing papers by "University of Naples Federico II published in 2007"

How to infer gene networks from expression profiles

Abstract: Inferring, or ‘reverse-engineering', gene networks can be defined as the process of identifying gene interactions from experimental data through computational analysis. Gene expression data from microarrays are typically used for this purpose. Here we compared different reverse-engineering algorithms for which ready-to-use software was available and that had been tested on experimental data sets. We show that reverse-engineering algorithms are indeed able to correctly infer regulatory interactions among genes, at least when one performs perturbation experiments complying with the algorithm requirements. These algorithms are superior to classic clustering algorithms for the purpose of finding regulatory interactions among genes, and, although further improvements are needed, have reached a discreet performance for being practically useful.

The metric properties of a novel non-motor symptoms scale for Parkinson's disease: Results from an international pilot study.

Abstract: Non-motor symptoms (NMS) in Parkinson's disease (PD) are common, significantly reduce quality of life and at present there is no validated clinical tool to assess the progress or potential response to treatment of NMS. A new 30-item scale for the assessment of NMS in PD (NMSS) was developed. NMSS contains nine dimensions: cardiovascular, sleep/fatigue, mood/cognition, perceptual problems, attention/memory, gastrointestinal, urinary, sexual function, and miscellany. The metric attributes of this instrument were analyzed. Data from 242 patients mean age 67.2 +/- 11 years, duration of disease 6.4 +/- 6 years, and 57.3% male across all stages of PD were collected from the centers in Europe, USA, and Japan. The mean NMSS score was 56.5 +/- 40.7, (range: 0-243) and only one declared no NMS. The scale provided 99.2% complete data for the analysis with the total score being free of floor and ceiling effect. Satisfactory scaling assumptions (multitrait scaling success rate >95% for all domains except miscellany) and internal consistency were reported for most of the domains (mean alpha, 0.61). Factor analysis supported the a prori nine domain structure (63% of the variance) while a small test-retest study showed satisfactory reproducibility (ICC > 0.80) for all domains except cardiovascular (ICC = 0.45). In terms of validity, the scale showed modest association with indicators of motor symptom severity and disease progression but a high correlation with other measures of NMS (NMSQuest) and health-related quality of life measure (PDQ-8) (both, rS = 0.70). In conclusion, NMSS can be used to assess the frequency and severity of NMS in PD patients across all stages in conjunction with the recently validated non-motor questionnaire.

Correlation of the highest-energy cosmic rays with nearby extragalactic objects.

Abstract: Using data collected at the Pierre Auger Observatory during the past 3.7 years, we demonstrate that there is a correlation between the arrival directions of cosmic rays with energy above {approx} 6 x 10{sup 19} eV and the positions of active galactic nuclei (AGN) lying within {approx} 75 Mpc. We reject the hypothesis of an isotropic distribution of these cosmic rays at over 99% confidence level from a prescribed a priori test. The correlation we observe is compatible with the hypothesis that the highest energy particles originate from nearby extragalactic sources whose flux has not been significantly reduced by interaction with the cosmic background radiation. AGN or objects having a similar spatial distribution are possible sources.

Cell death modalities: classification and pathophysiological implications

Abstract: Cell death can be classified according to the morphological appearance of the lethal process (that may be apoptotic, necrotic, autophagic or associated with mitosis), enzymological criteria (with and without the involvement of nucleases or distinct classes of proteases, like caspases or cathepsins), functional aspects (programmed or accidental, physiological or pathological) or immunological characteristics (immunogenic or non-immunogenic). Thanks to the advancing comprehension of cellular demise, it has become clear that the textbook equation ‘programmed cell death1⁄4 apoptosis1⁄4 caspase activation1⁄4 non-immunogenic cell death’, although applicable to some instances of cell death, constitutes an incorrect generalization, at several levels. Thus, necrosis can be programmed both in its course and its occurrence. Apoptosis can be lethal without caspase activation, and caspase activation does not necessarily cause cell death. Finally, cell death with an apoptotic appearance can be immunogenic, in which case the immunogenicity is caspasedependent. These examples illustrate the urgent need to strive towards a more detailed comprehension of cell death subroutines, with far-reaching implications for the pharmacological management of pathological cell loss and growth. In conditions of homeostasis, in the adult organism, each event of cell duplication must be compensated by the elimination of another cell. Although in the human body cell deaths occur at the dazzling frequency of several millions per second, the subtle regulation of cell death – coupled to a perfect waste management – allows us to enjoy a peaceful existence for several years, until we are affected by disease. Pathological conditions are often, if not always, tied to deregulated (excessive or deficient) cell death (Figure 1). The loss of post-mitotic cells such as neurons and cardiomyocytes occurs acutely in stroke and infarction or progressively in degenerative diseases. Moreover, AIDS is caused by the loss of proliferating immune cells at a pace that cannot be compensated for by proliferation. Conversely, oncogenesis is characterized by the (at least) partial suppression of cell death programs, which in turn causes chemoand radio-therapy resistance, thus ultimately sealing the patient’s fate. The physiological importance and pathological impact of cell death has spurred great interest, leading to the accumulation of more than 150 000 research papers over the last 20 years. Nonetheless, apparently simple questions on the very definition of cell death (Table 1) and on the classification of cell death modalities in stereotyped patterns have not yet been solved. In this review, we will synthetically and critically enumerate the current classifications of cell death, laying special emphasis on the link between the morphological, biochemical and pathophysiological characteristics of different cell death modalities.

Implantable cardioverter-defibrillators and prevention of sudden cardiac death in hypertrophic cardiomyopathy

Abstract: ContextRecently, the implantable cardioverter-defibrillator (ICD) has been promoted for prevention of sudden death in hypertrophic cardiomyopathy (HCM). However, the effectiveness and appropriate selection of patients for this therapy is incompletely resolved.ObjectiveTo study the relationship between clinical risk profile and incidence and efficacy of ICD intervention in HCM.Design, Setting, and PatientsMulticenter registry study of ICDs implanted between 1986 and 2003 in 506 unrelated patients with HCM. Patients were judged to be at high risk for sudden death; had received ICDs; underwent evaluation at 42 referral and nonreferral institutions in the United States, Europe, and Australia; and had a mean follow-up of 3.7 (SD, 2.8) years. Measured risk factors for sudden death included family history of sudden death, massive left ventricular hypertrophy, nonsustained ventricular tachycardia on Holter monitoring, and unexplained prior syncope.Main Outcome MeasureAppropriate ICD intervention terminating ventricular tachycardia or fibrillation.ResultsThe 506 patients were predominately young (mean age, 42 [SD, 17] years) at implantation, and most (439 [87%]) had no or only mildly limiting symptoms. ICD interventions appropriately terminated ventricular tachycardia/fibrillation in 103 patients (20%). Intervention rates were 10.6% per year for secondary prevention after cardiac arrest (5-year cumulative probability, 39% [SD, 5%]), and 3.6% per year for primary prevention (5-year probability, 17% [SD, 2%]). Time to first appropriate discharge was up to 10 years, with a 27% (SD, 7%) probability 5 years or more after implantation. For primary prevention, 18 of the 51 patients with appropriate ICD interventions (35%) had undergone implantation for only a single risk factor; likelihood of appropriate discharge was similar in patients with 1, 2, or 3 or more risk markers (3.83, 2.65, and 4.82 per 100 person-years, respectively; P = .77). The single sudden death due to an arrhythmia (in the absence of advanced heart failure) resulted from ICD malfunction. ICD complications included inappropriate shocks in 136 patients (27%).ConclusionsIn a high-risk HCM cohort, ICD interventions for life-threatening ventricular tachyarrhythmias were frequent and highly effective in restoring normal rhythm. An important proportion of ICD discharges occurred in primary prevention patients who had undergone implantation for a single risk factor. Therefore, a single marker of high risk for sudden death may be sufficient to justify consideration for prophylactic defibrillator implantation in selected patients with HCM.

Roles of HMGA proteins in cancer.

Abstract: High mobility group A (HMGA) proteins alter chromatin structure and therefore affect the transcription of large sets of genes. This can contribute to both benign and malignant disease in several ways. The high mobility group A (HMGA) non-histone chromatin proteins alter chromatin structure and thereby regulate the transcription of several genes by either enhancing or suppressing transcription factors. This protein family is implicated, through different mechanisms, in both benign and malignant neoplasias. Rearrangements of HMGA genes are a feature of most benign human mesenchymal tumours. Conversely, unrearranged HMGA overexpression is a feature of malignant tumours and is also causally related to neoplastic cell transformation. Here, we focus on the role of the HMGA proteins in human neoplastic diseases, the mechanisms by which they contribute to carcinogenesis, and therapeutic strategies based on targeting HMGA proteins.

Clinical and molecular genetic spectrum of congenital deficiency of the leptin receptor.

Abstract: Of the 300 subjects, 8 (3%) had nonsense or missense LEPR mutations — 7 were homozygotes, and 1 was a compound heterozygote. All missense mutations resulted in impaired receptor signaling. Affected subjects were characterized by hyperphagia, severe obesity, alterations in immune function, and delayed puberty due to hypogonadotropic hypogonadism. Serum leptin levels were within the range predicted by the elevated fat mass in these subjects. Their clinical features were less severe than those of subjects with congenital leptin deficiency. CONCLUSIONS The prevalence of pathogenic LEPR mutations in a cohort of subjects with severe, earlyonset obesity was 3%. Circulating levels of leptin were not disproportionately elevated, suggesting that serum leptin cannot be used as a marker for leptin-receptor deficiency. Congenital leptin-receptor deficiency should be considered in the differential diagnosis in any child with hyperphagia and severe obesity in the absence of developmental delay or dysmorphism.

Adjuvant mitotane treatment for adrenocortical carcinoma.

Abstract: Background Adrenocortical carcinoma is a rare neoplasm characterized by a high risk of recurrence after radical resection. Whether the use of mitotane is beneficial as an adjuvant treatment has been controversial. Our aim was to evaluate the efficacy of adjuvant mitotane in prolonging recurrence-free survival. Methods We performed a retrospective analysis involving 177 patients with adrenocortical cancer who had undergone radical surgery at 8 centers in Italy and 47 centers in Germany between 1985 and 2005. Adjuvant mitotane was administered to 47 Italian patients after radical surgery (mitotane group), whereas 55 Italian patients and 75 German patients (control groups 1 and 2, respectively) did not receive adjuvant treatment after surgery. Results Baseline features in the mitotane group and the control group from Italy were similar; the German patients were significantly older (P=0.03) and had more stage I or II adrenocortical carcinomas (P=0.02) than did patients in the mitotane group. Recurrence-free s...

Physical illness and schizophrenia: a review of the literature

Abstract: Objective: The lifespan of people with schizophrenia is shortened compared to the general population. We reviewed the literature on comorbid physical diseases in schizophrenia to provide a basis for initiatives to fight this unacceptable situation. Method: We searched MEDLINE (1966 – May 2006) combining the MeSH term of schizophrenia with the 23 MeSH terms of general physical disease categories to identify relevant epidemiological studies. Results: A total of 44 202 abstracts were screened. People with schizophrenia have higher prevalences of HIV infection and hepatitis, osteoporosis, altered pain sensitivity, sexual dysfunction, obstetric complications, cardiovascular diseases, overweight, diabetes, dental problems, and polydipsia than the general population. Rheumatoid arthritis and cancer may occur less frequently than in the general population. Eighty-six per cent of the studies came from industrialized countries limiting the generalizability of the findings. Conclusion: The increased frequency of physical diseases in schizophrenia might be on account of factors related to schizophrenia and its treatment, but undoubtedly also results from the unsatisfactory organization of health services, from the attitudes of medical doctors, and the social stigma ascribed to the schizophrenic patients.

Membrane Toxicity of Antimicrobial Compounds from Essential Oils

Abstract: Natural antimicrobial compounds perform their action mainly against cell membranes. The aim of this work was to evaluate the interaction, meant as a mechanism of action, of essential oil antimicrobial compounds with the microbial cell envelope. The lipid profiles of Escherichia coli O157:H7, Staphylococcus aureus, Salmonella enterica serovar Typhimurium, Pseudomonas fluorescens, and Brochothrix thermosphacta cells treated with thymol, carvacrol, limonene, eugenol, and cinnamaldehyde have been analyzed by gas chromatography. In line with the fatty acids analysis, the treated cells were also observed by scanning electron microscopy (SEM) to evaluate structural alterations. The overall results showed a strong decrease of the unsaturated fatty acids (UFAs) for the treated cells; in particular, the C18:2trans and C18:3cis underwent a notable reduction contributing to the total UFA decreases, while the saturated fatty acid C17:0 raised the highest concentration in cinnamaldehyde-treated cells. SEM images showed that the used antimicrobial compounds quickly exerted their antimicrobial activities, determining structural alterations of the cell envelope.

Aerosol-type-dependent lidar ratios observed with Raman lidar

Abstract: [1] We summarize our Raman lidar observations which were carried out in Europe, Asia, and Africa during the past 10 years, with focus on particle extinction-to-backscatter ratios (lidar ratios) and Angstrom exponents. For the first time, we present statistics on lidar ratios for almost all climatically relevant aerosol types solely based on Raman lidar measurements. Sources of continental particles were in North America and Europe, the Sahara, and south and Southeast and east Asia. The North Atlantic Ocean, and the tropical and South Indian Ocean were the sources of marine particles. The statistics are complemented with lidar ratios describing aged forest fire smoke and pollution from polar regions (Arctic haze) after long-range transport. In addition, we present particle Angstrom exponents for the wavelength range from 355 to 532 nm and from 532 to 1064 nm. We compare our data set of lidar ratios to the recently published AERONET (Aerosol Robotic Network) lidar ratio climatology. That climatology is based on aerosol scattering modeling in which AERONET Sun photometer observations serve as input. Raman lidar measurements of extinction-to-backscatter ratios of Saharan dust and urban aerosols differ significantly from the numbers obtained with AERONET Sun photometers. There are also differences for some of the Angstrom exponents. Further comparison studies are needed to reveal the reason for the observed differences.

Prevalence of nonmotor symptoms in Parkinson's disease in an international setting; Study using nonmotor symptoms questionnaire in 545 patients

Abstract: 2006, there was, no single instrument (questionnaire or scale) for attempting a comprehensive assessment of the wide range of nonmotor symptoms (NMS) of Parkinson's disease (PD). The PD nonmotor group, a multidisciplinary group of experts including patient group representatives developed and validated the NMS screening questionnaire (NMSQuest) comprising 30 items. The NMSQuest is a self completed screening tool designed to draw attention to the presence of NMS. In this paper, we present the results gathered from 545 patients using the definitive version of the NMSQuest highlighting the prevalence of the wide range of NMS flagged in the NMSQuest from consecutive PD patients in an international setting.

Long-Term Follow-Up and Outcome of a Large Cohort of Patients with Common Variable Immunodeficiency

Abstract: Common Variable Immunodeficiency belongs to the group of rare diseases encompassing antibody deficiency syndromes of highly variable clinical presentation and outcome. The multicenter prospective study on a cohort of 224 patients with Common Variable Immunodeficiency provides an updated view of the spectrum of illnesses which occurred at the clinical onset and over a long period of follow-up (mean time: 11 years) and information on the effects of long-term immunoglobulin treatment. The mean age at the time of diagnosis was 26.6 years. Seventy-five patients were younger than 14 years of age. The mean age at the onset of symptoms was 16.9 years. This implicates with a mean diagnostic delay of 8.9 years. Respiratory tract infections were the most prominent clinical problem observed at diagnosis and during the follow-up. Intravenous immunoglobulin administration induced a significant reduction in the incidence of acute infections, mainly acute pneumonia and acute otitis. However, a progressive increase in the prevalence of patients with chronic diseases, mainly sinusitis and lung disease, was observed in all age groups, including the pediatric population. The morbidity of Common Variable Immunodeficiency due to all associated clinical conditions increased over time despite an adequate replacement with intravenous immunoglobulins. Our data stressed the need to develop international guidelines for the prevention and therapy of chronic lung disease, chronic sinusitis, chronic diarrhoea, and chronic granulomatosis in patients with humoral immunodeficiencies.

MicroRNAs (miR)-221 and miR-222, both overexpressed in human thyroid papillary carcinomas, regulate p27Kip1 protein levels and cell cycle.

Abstract: We have recently reported that MicroRNAs (miR)-221 and miR-222 were up-regulated in human thyroid papillary carcinomas in comparison with the normal thyroid tissue. Bioinformatic analysis proposed the p27(Kip1) protein, a key regulator of cell cycle, as a candidate target for the miR-221/222 cluster. Here, we report that the enforced expression of miR-221 and miR-222 was able to reduce p27(Kip1) protein levels in thyroid carcinoma and HeLa cells in the absence of significant changes in specific p27(Kip1) mRNA levels. This effect is direct as miR-221 and miR-222 negatively regulate the expression of the 3'-untranslated region-based reporter construct from the p27(Kip1) gene, and is dependent on two target sites in this region. Consistent with these results, an enforced expression of the miR-221 and miR-222 induced the thyroid papillary carcinoma cell line (TPC-1) to progress to the S phase of the cell cycle. It is likely that the negative regulation of p27(Kip1) by miR-221 and miR-222 might also have a role in vivo since we report an inverse correlation between miR-221 and miR-222 up-regulation and down-regulation of the p27(Kip1) protein levels in human thyroid papillary carcinomas. Therefore, the data reported here demonstrate that miR-221 and miR-222 are endogenous regulators of p27(Kip1) protein expression, and thereby, the cell cycle.

Controllability of complex networks via pinning.

Abstract: We study the problem of controlling a general complex network toward an assigned synchronous evolution by means of a pinning control strategy We define the pinning controllability of the network in terms of the spectral properties of an extended network topology The roles of the control and coupling gains, as well as of the number of pinned nodes, are also discussed

Recognition of unmethylated histone H3 lysine 4 links BHC80 to LSD1-mediated gene repression

Abstract: Histone methylation is crucial for regulating chromatin structure, gene transcription and the epigenetic state of the cell. LSD1 is a lysine-specific histone demethylase that represses transcription by demethylating histone H3 on lysine 4 (ref. 1). The LSD1 complex contains a number of proteins, all of which have been assigned roles in events upstream of LSD1-mediated demethylation apart from BHC80 (also known as PHF21A), a plant homeodomain (PHD) finger-containing protein. Here we report that, in contrast to the PHD fingers of the bromodomain PHD finger transcription factor (BPTF) and inhibitor of growth family 2 (ING2), which bind methylated H3K4 (H3K4me3), the PHD finger of BHC80 binds unmethylated H3K4 (H3K4me0), and this interaction is specifically abrogated by methylation of H3K4. The crystal structure of the PHD finger of BHC80 bound to an unmodified H3 peptide has revealed the structural basis of the recognition of H3K4me0. Knockdown of BHC80 by RNA inhibition results in the de-repression of LSD1 target genes, and this repression is restored by the reintroduction of wild-type BHC80 but not by a PHD-finger mutant that cannot bind H3. Chromatin immunoprecipitation showed that BHC80 and LSD1 depend reciprocally on one another to associate with chromatin. These findings couple the function of BHC80 to that of LSD1, and indicate that unmodified H3K4 is part of the 'histone code'. They further raise the possibility that the generation and recognition of the unmodified state on histone tails in general might be just as crucial as post-translational modifications of histone for chromatin and transcriptional regulation.

Nutrition, physical activity, and cardiovascular disease: an update.

Abstract: Many epidemiological studies have indicated a protective role for a diet rich in fruits and vegetables against the development and progression of cardiovascular disease (CVD), one of the leading causes of morbidity and mortality worldwide. Physical inactivity and unhealthy eating contribute to these conditions. This article assesses the scientific rationale of benefits of physical activity and good nutrition on CVD, especially on atherosclerosis-related diseases. Compelling evidence has accumulated on the role of oxidative stress in endothelial dysfunction and in the pathogenesis of CVD. Reduced nitric oxide (NO) bioavailability due to oxidative stress seems to be the common molecular disorder comprising stable atherosclerotic narrowing lesions. Energy expenditure of about 1000 kcal (4200 kJ) per week (equivalent to walking 1 h 5 days a week) is associated with significant health benefits. Such benefits can be achieved through structured or nonstructured physical activity, accumulated throughout the day (even through short 10-min bouts) on most days of the week. Some prospective studies showed a direct inverse association between fruit and vegetable intake and the development of CVD incidents such as acute plaque rupture causing unstable angina or myocardial infarction and stroke. Many nutrients and phytochemicals in fruits and vegetables, including fiber, potassium, and folate, could be independently or jointly responsible for the apparent reduction in CVD risk. Novel findings and critical appraisal regarding antioxidants, dietary fibers, omega-3 polyunsaturated fatty acids (n-3 PUFAs), nutraceuticals, vitamins, and minerals, are presented here in support of the current dietary habits together with physical exercise recommendations for prevention and treatment of CVD.

Specific microRNAs are downregulated in human thyroid anaplastic carcinomas.

Abstract: Thyroid carcinomas comprise a broad spectrum of tumors with different clinical behaviors. On the one side, there are occult papillary carcinomas (PTC), slow growing and clinically silent, and on the other side, rapidly growing anaplastic carcinomas (ATC), which are among the most lethal human neoplasms. We have analysed the microRNA (miR) profile of ATC in comparison to the normal thyroid using a microarray (miRNACHIP microarray). By this approach, we found an aberrant miR expression profile that clearly differentiates ATC from normal thyroid tissues and from PTC analysed in previous studies. In particular, a significant decrease in miR-30d, miR-125b, miR-26a and miR-30a-5p was detected in ATC in comparison to normal thyroid tissue. These results were further confirmed by northern blots, quantitative reverse transcription-PCR analyses and in situ hybridization. The overexpression of these four miRs in two human ATC-derived cell lines suggests a critical role of miR-125b and miR-26a downregulation in thyroid carcinogenesis, since a cell growth inhibition was achieved. Conversely, no effect on cell growth was observed after the overexpression of miR-30d and miR-30a-5p in the same cells. In conclusion, these data indicate a miR signature associated with ATC and suggest the miR deregulation as an important event in thyroid cell transformation.

Processing of Temporal Unpredictability in Human and Animal Amygdala

Abstract: The amygdala has been studied extensively for its critical role in associative fear conditioning in animals and humans. Noxious stimuli, such as those used for fear conditioning, are most effective in eliciting behavioral responses and amygdala activation when experienced in an unpredictable manner. Here, we show, using a translational approach in mice and humans, that unpredictability per se without interaction with motivational information is sufficient to induce sustained neural activity in the amygdala and to elicit anxiety-like behavior. Exposing mice to mere temporal unpredictability within a time series of neutral sound pulses in an otherwise neutral sensory environment increased expression of the immediate-early gene c-fos and prevented rapid habituation of single neuron activity in the basolateral amygdala. At the behavioral level, unpredictable, but not predictable, auditory stimulation induced avoidance and anxiety-like behavior. In humans, functional magnetic resonance imaging revealed that temporal unpredictably causes sustained neural activity in amygdala and anxiety-like behavior as quantified by enhanced attention toward emotional faces. Our findings show that unpredictability per se is an important feature of the sensory environment influencing habituation of neuronal activity in amygdala and emotional behavior and indicate that regulation of amygdala habituation represents an evolutionary-conserved mechanism for adapting behavior in anticipation of temporally unpredictable events.

Low surface brightness galaxy rotation curves in the low energy limit of Rn gravity: no need for dark matter?

Abstract: We investigate the possibility that the observed flatness of the rotation curves of spiral galaxies is not evidence for the existence of dark matter haloes, but rather a signal of the breakdown of General Relativity. To this aim, we consider power-law fourth-order theories of gravity obtained by replacing the scalar curvature R with f(R) =f 0 R n in the gravity Lagrangian. We show that, in the low energy limit, the gravitational potential generated by a point-like source may be written as Φ(r) ∝ r -1 [1 + (r/r c ) β ] with β a function of the slope n of the gravity Lagrangian and r c a scalelength depending on the gravitating system properties. In order to apply the model to realistic systems, we compute the modified potential and the rotation curve for spherically symmetric and for thin disc mass distributions. It turns out that the potential is still asymptotically decreasing, but the corrected rotation curve, although not flat, is higher than the Newtonian one, thus offering the possibility to fit rotation curves without dark matter. To test the viability of the model, we consider a sample of 15 low surface brightness galaxies with combined H [I and Ha measurements of the rotation curve extending in the putative dark matter dominated region. We find a very good agreement between the theoretical rotation curve and the data using only stellar disc and interstellar gas when the slope n of the gravity Lagrangian is set to the value n = 3.5 (giving β = 0.817) obtained by fitting the Type Ia supernova Hubble diagram with the assumed power-law f(R) model and no dark matter. The excellent agreement between theoretical and observed rotation curves and the values of the stellar mass-to-light ratios in agreement with the predictions of population synthesis models make us confident that R n gravity may represent a good candidate to solve both the dark energy problem on cosmological scales and the dark matter one on galactic scales with the same value of the slope n of the higher-order gravity Lagrangian.

Regulation of autophagy by the inositol trisphosphate receptor

Abstract: The reduction of intracellular 1,4,5-inositol trisphosphate (IP(3)) levels stimulates autophagy, whereas the enhancement of IP(3) levels inhibits autophagy induced by nutrient depletion. Here, we show that knockdown of the IP(3) receptor (IP(3)R) with small interfering RNAs and pharmacological IP(3)R blockade is a strong stimulus for the induction of autophagy. The IP(3)R is known to reside in the membranes of the endoplasmic reticulum (ER) as well as within ER-mitochondrial contact sites, and IP(3)R blockade triggered the autophagy of both ER and mitochondria, as exactly observed in starvation-induced autophagy. ER stressors such as tunicamycin and thapsigargin also induced autophagy of ER and, to less extent, of mitochondria. Autophagy triggered by starvation or IP(3)R blockade was inhibited by Bcl-2 and Bcl-X(L) specifically targeted to ER but not Bcl-2 or Bcl-X(L) proteins targeted to mitochondria. In contrast, ER stress-induced autophagy was not inhibited by Bcl-2 and Bcl-X(L). Autophagy promoted by IP(3)R inhibition could not be attributed to a modulation of steady-state Ca(2+) levels in the ER or in the cytosol, yet involved the obligate contribution of Beclin-1, autophagy-related gene (Atg)5, Atg10, Atg12 and hVps34. Altogether, these results strongly suggest that IP(3)R exerts a major role in the physiological control of autophagy.

Probiotics for treatment of acute diarrhoea in children: randomised clinical trial of five different preparations

Abstract: Objective To compare the efficacy of five probiotic preparations recommended to parents in the treatment of acute diarrhoea in children. Design Randomised controlled clinical trial in collaboration with family paediatricians over 12 months. Setting Primary care. Participants Children aged 3-36 months visiting a family paediatrician for acute diarrhoea. Intervention Children's parents were randomly assigned to receive written instructions to purchase a specific probiotic product: oral rehydration solution (control group); Lactobacillus rhamnosus strain GG; Saccharomyces boulardii; Bacillus clausii; mix of L delbrueckii var bulgaricus, Streptococcus thermophilus, L acidophilus, and Bifidobacterium bifidum; or Enterococcus faecium SF68. Main outcome measures Primary outcomes were duration of diarrhoea and daily number and consistency of stools. Secondary outcomes were duration of vomiting and fever and rate of admission to hospital. Safety and tolerance were also recorded. Results 571 children were allocated to intervention. Median duration of diarrhoea was significantly shorter (P<0.001) in children who received L rhamnosus strain GG (78.5 hours) and the mix of four bacterial strains (70.0 hours) than in children who received oral rehydration solution alone (115.0 hours). One day after the first probiotic administration, the daily number of stools was significantly lower (P<0.001) in children who received L rhamnosus strain GG and in those who received the probiotic mix than in the other groups. The remaining preparations did not affect primary outcomes. Secondary outcomes were similar in all groups. Conclusions Not all commercially available probiotic preparations are effective in children with acute diarrhoea. Paediatricians should choose bacterial preparations based on effectiveness data. Trial registration number Current Controlled Trials ISRCTN56067537.

Abdominal fat quantity and distribution in women with polycystic ovary syndrome and extent of its relation to insulin resistance.

Abstract: Context: Increased abdominal fat has been linked to insulin resistance and increased cardiovascular risk. Because many patients with polycystic ovary syndrome (PCOS) present abdominal obesity, it may be the cause of insulin resistance in this disorder. Setting: Fat quantity and distribution were evaluated by dual x-ray absorptiometry at the Departments of Clinical Medicine at the University of Palermo and the University of Naples, Italy. Patients: A total of 110 patients with PCOS and 112 weight-matched controls were studied. Anthropometric data, blood glucose, serum insulin, and testosterone were evaluated. Total, trunk, and central abdominal fat quantity were measured by total-body dual x-ray absorptiometry. Results: Compared with weight-matched controls, patients with PCOS had similar quantity of total and trunk fat but higher quantity of central abdominal fat. This difference was not observed when comparing obese PCOS and obese controls but depended on differences between overweight and normoweight pa...

An Overview of the Small BAseline Subset Algorithm: a DInSAR Technique for Surface Deformation Analysis

Abstract: We present an overview of the Differential SAR Interferometry algorithm referred to as Small BAseline Subset (SBAS) technique, that allows us to detect surface deformation and to analyze their space-time characteristics. Following the description of the main theoretical aspects of the algorithm, we present several results obtained by applying the SBAS approach in selected case studies relevant to phenomena affecting volcanic areas (Campi Flegrei caldera and Somma-Vesuvio complex, Italy), aquifers (Santa Clara area within the San Francisco bay, California) and landslides (Maratea Valley, Italy). The overall analysis is carried out by using multilook DInSAR interferograms with a spatial resolution of the order of 100 × 100 m, computed from SAR data acquired by the ERS-1 and ERS-2 sensors. In particular, we highlight the peculiarities of the SBAS technique and its surface deformation retrieval capability for what concerns both large-scale deformation phenomena and more localized displacement effects.