Class of correlated random networks with hidden variables

We study a class of models of correlated random networks in which vertices are characterized by hidden variables controlling the establishment of edges between pairs of vertices. We find analytical expressions for the main topological properties of these models as a function of the distribution of hidden variables and the probability of connecting vertices. The expressions obtained are checked by means of numerical simulations in a particular example. The general model is extended to describe a practical algorithm to generate random networks with an a priori specified correlation structure. We also present an extension of the class, to map nonequilibrium growing networks to networks with hidden variables that represent the time at which each vertex was introduced in the system.

Correlations in weighted networks

We develop a statistical theory to characterize correlations in weighted networks. We define the appropriate metrics quantifying correlations and show that strictly uncorrelated weighted networks do not exist due to the presence of structural constraints. We also introduce an algorithm for generating maximally random weighted networks with arbitrary P(k,s) to be used as null models. The application of our measures to real networks reveals the importance of weights in a correct understanding and modeling of these heterogeneous systems.

Metabolic role of aquaglyceroporin 9 in astrocytes

Aim: Aquaglyceroporin-9 (AQP9) is a member of the Aquaporin channel family involved in water flux through plasma membranes and exhibits the distinctive feature of also being permeable to glycerol and monocarboxylates. AQP9 is detected in astrocytes and catecholaminergic neurons.1 However, the presence of AQP9 in the brain is now debated after a recent publication claiming that AQP9 is not expressed in the brain.2 Based on our results,3 we have evidence of the presence of AQP9 in the brain and we further hypothesize that AQP9 plays a functional role in brain energy metabolism. Methods: The presence of AQP9 in brain of OF1 mice was studied by RT-PCR and immunohistochemistry. To address the role of AQP9 in brain, we used commercial siRNA against AQP9 to knockdown its expression in 2 cultures of astrocytes from two distinct sources (from differentiated stem cells4 and primary astrocyte cultures). After assessment of the decrease of AQP9, glycerol uptake was measured using [H3]-glycerol. Then, modifications of the astrocytic energy metabolism was evaluated by measurement of glucose consumption, lactate release5 and evaluation of the mitochondrial activity by MTT staining. Results: AQP9 is expressed in astrocytes of OF1 mouse brain (mRNA and protein levels). We also showed that AQP9 mRNA and protein are present in cultured astrocytes. Four days after AQP9 siRNA application, the level of expression is significantly decreased by 76% compared to control. Astrocytes with AQP9 knockdown exhibit a 23% decrease of glycerol uptake, showing that AQP9 is a glycerol channel in cultured astrocytes. In parallel, astrocytes with AQP9 knockdown have a 155% increase of their glucose consumption without modifications of lactate release. Moreover, considering the observed glucose consumption increase and the absence of proliferation induction, the significant MTT activity increase (113%) suggests an increase of oxidative metabolism in astrocytes with AQP9 knockdown. Discussion: The involvement of AQP9 in astrocyte energy metabolism adds a new function for this channel in the brain. The determination of the role of AQP9 in astrocytes provides a new perspective on the controversial expression of AQP9 in brain. We also suggest that AQP9 may have a complementary role to monocarboxylate transporters in the regulation of brain energy metabolism.

Effects of dexamethasone on the metabolic responses to mental stress in humans.

The haemodynamic effects of the sympathetic nervous system (SNS) activations elicited by hypoglycaemia, acute alcohol administration, or insulin can be prevented by a pretreatment with dexamethasone in humans. This suggests a possible role of central corticotropin releasing hormone (GRIT) release. Mental stress activates the SNS, and decreases systemic vascular resistances though a beta-adrenergic-mediated vasodilation thought to involve vascular nitric oxide release. It also increases insulin-mediated glucose disposal, an effect presumably related to vasodilation. In order to evaluate whether activation of SNS by mental stress is glucocorticoid-sensitive, we monitored the haemodynamic and metabolic effects of mental stress during hyperinsulinaemia in healthy humans with and without a 2-day treatment with 8 mg day(-1) dexamethasone. Mental stress decreased systemic vascular resistances by 21.9% and increased insulin-mediated glucose disposal by 2 8.4% without dexamethasone pretreatment. After 2 days of dexamethasone treatment, whole body insulin-mediated glucose disposal was decreased by 40.8%. The haemodynainic effects of mental stress were however, not affected. Mental stress acutely increased insulin-mediated glucose disposal by 28.0%. This indicates that mental stress elicits a stimulation of SNS through dexamethasone-insensitive pathway, distinct of those activated by insulin, alcohol, or hyperglycaemia.

Human metabolic individuality in biomedical and pharmaceutical research.

Genome-wide association studies (GWAS) have identified many risk loci for complex diseases, but effect sizes are typically small and information on the underlying biological processes is often lacking. Associations with metabolic traits as functional intermediates can overcome these problems and potentially inform individualized therapy. Here we report a comprehensive analysis of genotype-dependent metabolic phenotypes using a GWAS with non-targeted metabolomics. We identified 37 genetic loci associated with blood metabolite concentrations, of which 25 show effect sizes that are unusually high for GWAS and account for 10-60% differences in metabolite levels per allele copy. Our associations provide new functional insights for many disease-related associations that have been reported in previous studies, including those for cardiovascular and kidney disorders, type 2 diabetes, cancer, gout, venous thromboembolism and Crohn's disease. The study advances our knowledge of the genetic basis of metabolic individuality in humans and generates many new hypotheses for biomedical and pharmaceutical research.

Networks of people in specialty production: family firms in the iron and steel Wire industries in Spain (1870-2000)

Capital intensive industries in specialized niches of production have constituted solid ground for family firms in Spain , as evidenced by the experience of the iron and steel wire industries between 1870 and 2000. The embeddedness of these firms in their local and regional environments have allowed the creation of networks that, together with favourable institutional conditions, significantly explain the dominance of family entrepreneurship in iron and steel wire manufacturing in Spain, until the end of the 20 th century. Dominance of family firms at the regional level has not been not an obstacle for innovation in wire manufacturing in Spain, which has taken place even when institutional conditions blocked innovation and traditional networking. Therefore, economic theories about the difficulties dynastic family firms may have to perform appropriately in science-based industries must be questioned

Analysis of linear networks with inconsistent initial conditions

This paper presents a new method to analyze timeinvariant linear networks allowing the existence of inconsistent initial conditions. This method is based on the use of distributions and state equations. Any time-invariant linear network can be analyzed. The network can involve any kind of pure or controlled sources. Also, the transferences of energy that occur at t=O are determined, and the concept of connection energy is introduced. The algorithms are easily implemented in a computer program.

Metabolic syndrome according to different definitions in a rapidly developing country of the African region

AIMS: We examined, in a country of the African region, i) the prevalence of the metabolic syndrome (MetS) according to three definitions (ATP, WHO and IDF); ii) the distribution of the MetS criteria; iii) the level of agreement between these three definitions and iv) we also examined these issues upon exclusion of people with diabetes. METHODS: We conducted an examination survey on a sample representative of the general population aged 25-64 years in the Seychelles (Indian Ocean, African region), attended by 1255 participants (participation rate of 80.3%). RESULTS: The prevalence of MetS increased markedly with age. According to the ATP, WHO and IDF definitions, the prevalence of MetS was, respectively, 24.0%, 25.0%, 25.1% in men and 32.2%, 24.6%, 35.4% in women. Approximately 80% of participants with diabetes also had MetS and the prevalence of MetS was approximately 7% lower upon exclusion of diabetic individuals. High blood pressure and adiposity were the criteria found most frequently among MetS holders irrespective of the MetS definitions. Among people with MetS based on any of the three definitions, 78% met both ATP and IDF criteria, 67% both WHO and IDF criteria, 54% both WHO and ATP criteria and only 37% met all three definitions. CONCLUSION: We identified a high prevalence of MetS in this population in epidemiological transition. The prevalence of MetS decreased by approximately 32% upon exclusion of persons with diabetes. Because of limited agreement between the MetS definitions, the fairly similar proportions of MetS based on any of the three MetS definitions classified, to a substantial extent, different subjects as having MetS.

Splenium of corpus callosum: patterns of interhemispheric interaction in children and adults.

The splenium of the corpus callosum connects the posterior cortices with fibers varying in size from thin late-myelinating axons in the anterior part, predominantly connecting parietal and temporal areas, to thick early-myelinating fibers in the posterior part, linking primary and secondary visual areas. In the adult human brain, the function of the splenium in a given area is defined by the specialization of the area and implemented via excitation and/or suppression of the contralateral homotopic and heterotopic areas at the same or different level of visual hierarchy. These mechanisms are facilitated by interhemispheric synchronization of oscillatory activity, also supported by the splenium. In postnatal ontogenesis, structural MRI reveals a protracted formation of the splenium during the first two decades of human life. In doing so, the slow myelination of the splenium correlates with the formation of interhemispheric excitatory influences in the extrastriate areas and the EEG synchronization, while the gradual increase of inhibitory effects in the striate cortex is linked to the local inhibitory circuitry. Reshaping interactions between interhemispherically distributed networks under various perceptual contexts allows sparsification of responses to superfluous information from the visual environment, leading to a reduction of metabolic and structural redundancy in a child's brain.

Gestational diabetes mellitus and the risk of metabolic syndrome: a population-based study in Lausanne, Switzerland.

AIMS: To investigate the relationships between gestational diabetes mellitus (GDM) and the metabolic syndrome (MS), as it was suggested that insulin resistance was the hallmark of both conditions. To analyse post-partum screening in order to identify risk factors for the subsequent development of type 2 diabetes mellitus (DM). METHODS: A retrospective analysis of all singleton pregnancies diagnosed with GDM at the Lausanne University Hospital for 3 consecutive years. Pre-pregnancy obesity, hypertension and dyslipidaemia were recorded as constituents of the MS. RESULTS: For 5788 deliveries, 159 women (2.7%) with GDM were identified. Constituents of the MS were present before GDM pregnancy in 26% (n = 37/144): 84% (n = 31/37) were obese, 38% (n = 14/37) had hypertension and 22% (n = 8/37) had dyslipidaemia. Gestational hypertension was associated with obesity (OR = 3.2, P = 0.02) and dyslipidaemia (OR = 5.4, P=0.002). Seventy-four women (47%) returned for post-partum OGTT, which was abnormal in 20 women (27%): 11% (n = 8) had type 2 diabetes and 16% (n = 12) had impaired glucose tolerance. Independent predictors of abnormal glucose tolerance in the post-partum were: having > 2 abnormal values on the diagnostic OGTT during pregnancy and presenting MS constituents (OR = 5.2, CI 1.8-23.2 and OR = 5.3, CI 1.3-22.2). CONCLUSIONS: In one fourth of GDM pregnancies, metabolic abnormalities precede the appearance of glucose intolerance. These women have a high risk of developing the MS and type 2 diabetes in later years. Where GDM screening is not universal, practitioners should be aware of those metabolic risks in every pregnant woman presenting with obesity, hypertension or dyslipidaemia, in order to achieve better diagnosis and especially better post-partum follow-up and treatment.

The rewards of cooperation: The effects of membership in European regulatory networks

Networks famously epitomize the shift from 'government' to 'governance' as governing structures for exercising control and coordination besides hierarchies and markets. Their distinctive features are their horizontality, the interdependence among member actors and an interactive decision-making style. Networks are expected to increase the problem-solving capacity of political systems in a context of growing social complexity, where political authority is increasingly fragmented across territorial and functional levels. However, very little attention has been given so far to another crucial implication of network governance - that is, the effects of networks on their members. To explore this important question, this article examines the effects of membership in European regulatory networks on two crucial attributes of member agencies, which are in charge of regulating finance, energy, telecommunications and competition: organisational growth and their regulatory powers. Panel analysis applied to data on 118 agencies during a ten-year period and semi-structured interviews provide mixed support regarding the expectation of organisational growth while strongly confirming the positive effect of networks on the increase of the regulatory powers attributed to member agencies.

Utilization of dietary glucose in the metabolic syndrome

This review is focused on the fate of dietary glucose under conditions of chronically high energy (largely fat) intake, evolving into the metabolic syndrome. We are adapted to carbohydrate-rich diets similar to those of our ancestors. Glucose is the main energy staple, but fats are our main energy reserves. Starvation drastically reduces glucose availability, forcing the body to shift to fatty acids as main energy substrate, sparing glucose and amino acids. We are not prepared for excess dietary energy, our main defenses being decreased food intake and increased energy expenditure, largely enhanced metabolic activity and thermogenesis. High lipid availability is a powerful factor decreasing glucose and amino acid oxidation. Present-day diets are often hyperenergetic, high on lipids, with abundant protein and limited amounts of starchy carbohydrates. Dietary lipids favor their metabolic processing, saving glucose, which additionally spares amino acids. The glucose excess elicits hyperinsulinemia, which may derive, in the end, into insulin resistance. The available systems of energy disposal could not cope with the excess of substrates, since they are geared for saving not for spendthrift, which results in an unbearable overload of the storage mechanisms. Adipose tissue is the last energy sink, it has to store the energy that cannot be used otherwise. However, adipose tissue growth also has limits, and the excess of energy induces inflammation, helped by the ineffective intervention of the immune system. However, even under this acute situation, the excess of glucose remains, favoring its final conversion to fat. The sum of inflammatory signals and deranged substrate handling induce most of the metabolic syndrome traits: insulin resistance, obesity, diabetes, liver steatosis, hyperlipidemia and their compounded combined effects. Thus, a maintained excess of energy in the diet may result in difficulties in the disposal of glucose, eliciting inflammation and the development of the metabolic syndrome