Sparse balance: Excitatory-inhibitory networks with small bias currents and broadly distributed synaptic weights

Cortical circuits generate excitatory currents that must be cancelled by strong inhibition to assure stability. The resulting excitatory-inhibitory (E-I) balance can generate spontaneous irregular activity but, in standard balanced E-I models, this requires that an extremely strong feedforward bias current be included along with the recurrent excitation and inhibition. The absence of experimental evidence for such large bias currents inspired us to examine an alternative regime that exhibits asynchronous activity without requiring unrealistically large feedforward input. In these networks, irregular spontaneous activity is supported by a continually changing sparse set of neurons. To support this activity, synaptic strengths must be drawn from high-variance distributions. Unlike standard balanced networks, these sparse balance networks exhibit robust nonlinear responses to uniform inputs and non-Gaussian input statistics. Interestingly, the speed, not the size, of synaptic fluctuations dictates the degree of sparsity in the model. In addition to simulations, we provide a mean-field analysis to illustrate the properties of these networks.     

Studies on the interaction between Cd(2+) ions and DNA

Cadmium is a potent carcinogen in rodents and has recently been accepted by the International Agency for Research on Cancer as a category 1 (human) carcinogen, but the molecular mechanism of its action remains largely unclear. It has however been suggested that cadmium-induced carcinogenesis may involve either direct or indirect interaction of Cd²⁺ with DNA. Cd²⁺ is believed to bind covalently with N7 centres of adenine and guanine. At low concentrations (≤50 mM), Cd²⁺ is found to react with plasmid DNA to produce a mixture of Form I and Form II bands whereas at higher concentrations (≥100 mM), Cd²⁺ causes extensive damage to DNA at a pH 5.8 solution of cadmium nitrate. Within the range 0–100 mM (when pH is adjusted to 7.4 by adding NaOH) an increase in concentration of Cd²⁺ is found to cause a decrease in the gel mobility rate of plasmid and an increase in the intensity of the Form II band. When plasmid DNA is digested with BamH1, only the Form III band is observed both in the presence and absence of Cd²⁺. However, the mobility of the band is found to decrease with the increase in the concentration of Cd²⁺. When the enzyme Ssp1 which cuts plasmid DNA at the AT sites is used instead of BamH1, two bands are observed in the presence of cadmium as against one band in the absence of cadmium. These results suggest that Cd²⁺ binds covalently with DNA (possibly at G, A and T centres) and can form intrastrand bifunctional AT adducts but not the GG adducts. It may also be that neither GG nor AT adducts are formed and yet Ssp1 digestion is prevented because of a structural modification introduced in adenine by its interaction with Cd²⁺. In the presence of antioxidants such as cysteine, glutathione and ascorbate (especially cysteine and ascorbate), DNA damage is found to be greater than expected for the combined effects of the antioxidant and Cd²⁺. The increased DNA damage is believed to be due to the formation of reactive oxygen species (ROS).     

Evaluation of adverse effects in tamoxifen exposed healthy female dogs

Background

Hypertension and proteinuria are medical complications associated with the multisystemic effects of long-term hypercortisolism in dogs with hyperadrenocorticism (HAC).

Methods

This study investigated the relationships among adrenocorticotropic hormone (ACTH)-stimulation test results, systemic blood pressure, and microalbuminuria in clinically-healthy dogs (n = 100), in dogs affected with naturally occurring pituitary-dependent (PDH; n = 40), or adrenal-dependent hyperadrenocorticism (ADH; n = 30).

Results

Mean systemic blood pressure was similar between clinically healthy dogs and dogs with HAC (p = 0.803). However the incidence of hypertension was highest in dogs with ADH (p = 0.017), followed by dogs with PDH, with the lowest levels in clinically healthy dogs (p = 0.019). Presence of microalbuminuria and albuminuria in clinically healthy dogs and dogs affected with HAC was significantly different (p < 0.001); incidences of albuminuria followed the same pattern of hypertension; highest incidence in dogs with ADH, and lowest level in clinically healthy dogs; but microalbuminuria showed a different pattern: clinically healthy dogs had highest incidences and dogs with ADH had lowest incidence. The presence of albuminuria was not associated with blood pressure values, regardless of whether dogs were clinically healthy or affected with ADH or PDH (p = 0.306).

Conclusions

Higher incidence of hypertension and albuminuria, not microalbuminuria was seen in dogs affected with HAC compared to clinically healthy dogs; incidence of hypertension and albuminuria was significantly higher in dogs affected with ADH compared to PDH. However, presence of albuminuria was not correlated with systemic blood pressure.     

Health Risk of PCBs and DDTs in Seafood from Southern Iran

Levels of polychlorinated biphenyls (PCBs) congeners and dichlorodiphenyltrichloroethane and its metabolites (DDTs) were measured in 18 species of fish, crab, shrimp, and bivalve samples collected from the northern region of the Persian Gulf in Iran. The levels of ∑PCBs varied from 259.92 ± 31.04 ng/g to 1648.88 ± 176.96 ng/g in lipid weight. CB118 showed the highest concentration. ∑DDT variations ranged from ND to 570.45 ± 806.74 ng/g in lipid weight. Health risk was assessed by estimating both dietary intakes and screening values (SVs). Daily intake levels were much lower than the Food and Agriculture Organization (FAO)/World Health Organization (WHO) standards for PCBs and DDTs. Based on an average bodyweight of 73 kg and consumption rates of 0.055 kg/person. day, the SVs for the carcinogen and non-carcinogen effects of PCB and DDT were calculated. Average concentrations of PCBs and DDTs showed that the levels of PCBs exceeded the established SV for carcinogens. This finding suggests the need to enhance risk management regarding seafood consumption through public advisory.     

Weight loss is not mandatory for exercise-induced effects on health indices in females with metabolic syndrome

The aim of this study was to investigate the impact of moderate aerobic training on functional, anthropometric, biochemical, and health-related quality of life (HRQOL) parameters on women with metabolic syndrome (MS). Fifteen untrained women with MS performed moderate aerobic training for 15 weeks, without modifications of dietary behaviours. Functional, anthropometric, biochemical, control diet record and HRQOL parameters were assessed before and after the training. Despite body weight maintenance, the patients presented decreases in waist circumference (P = 0.001), number of MS components (P = 0.014), total cholesterol (P = 0.049), HDL cholesterol (P = 0.004), LDL cholesterol (P = 0.027), myeloperoxidase activity (P = 0.002) and thiobarbituric acid-reactive substances levels (P = 0.006). There were no differences in total energy, carbohydrate, protein and lipid intake pre- and post-training. Furthermore, improvements in the HRQOL subscales of physical functioning (P = 0.03), role-physical (P = 0.039), bodily pain (P = 0.048), general health (P = 0.046) and social functioning scoring (P = 0.011) were reported. Despite the absence of weight loss, aerobic training induced beneficial effects on functional, anthropometric, biochemical and HRQOL parameters in women with MS.     

Origin and history of the IVS-I-110 and codon 39 beta-thalassemia mutations in the Lebanese population

Using restriction fragment length polymorphisms (RFLPs) and sequence haplotype analysis, we studied the chromosomal background of the beta-globin gene in 31 unrelated Lebanese IVS-I-110 or codon 39 (Cd39) subjects, and five normal betaAbeta/A individuals. Our results are compared with those from similar studies in other parts of the Mediterranean in an attempt to provide insights into historical patterns of selection and disease. The great majority of the Lebanese chromosomes with the IVS-I-110 mutation are associated with the RFLP haplotype I and sequence haplotype HT1, which is probably the ancestral structure on which the mutation first emerged. The remainder of the IVS-I-110 alleles are linked to the 5'-subhaplotype 12 RFLP haplotype and/or HTR sequence haplotype. In contrast, in Turkey, IVS-I-110 is associated with six distinct sequence haplotypes and four distinct RFLP haplotypes, suggesting that the mutation probably emerged there. The diversity of sequence haplotypes described in Turkey was probably generated through recombination or gene conversion events with the most frequent betaA autochthonous structures. Our data on Lebanese betaA chromosomes and Algerian betaA chromosomes, along with previously described Turkish betaA chromosomes, strengthen this hypothesis. Following its emergence in Turkey, the IVS-1-110 mutation was probably introduced to Lebanon later, by migration or settlements. Cd39 demonstrates a remarkable level of sequence and RFLP haplotype heterogeneity in Algeria, in contrast to its relative homogeneity in Turkish samples. However, its rarity in the Near East, and more specifically in Lebanon, does not allow us to draw any conclusions concerning its origin and gene flow.     

A statistical experiment design approach for optimizing biodegradation of weathered crude oil in coastal sediments

This work studied the bioremediation of weathered crude oil (WCO) in coastal sediment samples using central composite face centered design (CCFD) under response surface methodology (RSM). Initial oil concentration, biomass, nitrogen and phosphorus concentrations were used as independent variables (factors) and oil removal as dependent variable (response) in a 60 days trial. A statistically significant model for WCO removal was obtained. The coefficient of determination (R² = 0.9732) and probability value (P < 0.0001) demonstrated significance for the regression model. Numerical optimization based on desirability function were carried out for initial oil concentration of 2, 16 and 30 g per kg sediment and 83.13, 78.06 and 69.92 per cent removal were observed respectively, compare to 77.13, 74.17 and 69.87 per cent removal for un-optimized results.