A method to characterize the passive elasticity in contracting muscle bundles

There is concern among researchers whether the passive muscle properties, characterized by purely passive material testing procedures, are an appropriate representation of the actual passive component of the muscle. This aspect is of particular importance in the biomechanical analysis of heart muscle response where it is generally agreed that the so-called parallel elasticity cannot be ignored as is done justifiably in the analysis of skeletal muscle response. In the present article, a method of quantifying the passive elasticity in contracting muscle bundles is presented. The method consists of imposing isometric transients (such as the quick-stretch or quick release) on a muscle bundle during the contraction phase and observing the differences in decayed force levels between a normal twitch and that of a perturbed twitch. The proposed method provides a means of obtaining useful passive properties from contracting muscle bundles and circumvents the difficulty of having to characterize muscle properties from separate experiments on quiescent muscle bundles.     

Metabolomic Profile of the Genus Inula

Plants have a long history as therapeutics in the treatment of human diseases and have been used as source of medicines for ages. Searching for new biologically active natural products, many plants and herbs are screened for natural products with pharmacological activities. In this field, the genus Inula, which comprises more than 100 species, several of them being used in traditional medicine, is very important, especially due to the finding that several of the isolated pure secondary metabolites proved to possess important biological activities. Inula species have been reported as rich sources of sesquiterpene lactones, including eudesmanes, germacranes, guaianes, and dimeric structures, and since 2006 ca. 400 secondary metabolites, including more than 100 new natural products, some of them with relevant pharmacological activities, have been identified. Herein, we critically compile and update the information regarding the types of secondary metabolites found in the genus Inula and the progress in their isolation.     

Adaptive Potential of Hybridization among Malaria Vectors: Introgression at the Immune Locus TEP1 between Anopheles coluzzii and A. gambiae in ‘Far-West’ Africa

“Far-West” Africa is known to be a secondary contact zone between the two major malaria vectors Anopheles coluzzii and A. gambiae. We investigated gene-flow and potentially adaptive introgression between these species along a west-to-east transect in Guinea Bissau, the putative core of this hybrid zone. To evaluate the extent and direction of gene flow, we genotyped site 702 in Intron-1 of the para Voltage-Gated Sodium Channel gene, a species-diagnostic nucleotide position throughout most of A. coluzzii and A. gambiae sympatric range. We also analyzed polymorphism in the thioester-binding domain (TED) of the innate immunity-linked thioester-containing protein 1 (TEP1) to investigate whether elevated hybridization might facilitate the exchange of variants linked to adaptive immunity and Plasmodium refractoriness. Our results confirm asymmetric introgression of genetic material from A. coluzzii to A. gambiae and disruption of linkage between the centromeric "genomic islands" of inter-specific divergence. We report that A. gambiae from the Guinean hybrid zone possesses an introgressed TEP1 resistant allelic class, found exclusively in A. coluzzii elsewhere and apparently swept to fixation in West Africa (i.e. Mali and Burkina Faso). However, no detectable fixation of this allele was found in Guinea Bissau, which may suggest that ecological pressures driving segregation between the two species in larval habitats in this region may be different from those experienced in northern and more arid parts of the species’ range. Finally, our results also suggest a genetic subdivision between coastal and inland A. gambiae Guinean populations and provide clues on the importance of ecological factors in intra-specific differentiation processes.     

Risk Factors for Death from Influenza A(H1N1)pdm09, State of S?o Paulo,Brazil, 2009

This case-control study aimed to assess the risk factors for death from influenza A(H1N1)pdm09 in patients with laboratory confirmation, who had severe acute respiratory illness-SARI and were hospitalized between June 28^th and August 29^th 2009, in the metropolitan regions of São Paulo and Campinas, Brazil. Medical charts of all the 193 patients who died (cases) and the 386 randomly selected patients who recovered (controls) were investigated in 177 hospitals. Household interviews were conducted with those who had survived and the closest relative of those who had died. 73.6% of cases and 38.1% of controls were at risk of developing influenza-related complications. The 18-to-59-year age group (OR = 2.31, 95%CI: 1.31–4.10 (reference up to 18 years of age)), presence of risk conditions for severity of influenza (OR = 1.99, 95%CI: 1.11–3.57, if one or OR = 6.05, 95%CI: 2.76–13.28, if more than one), obesity (OR = 2.73, 95%CI: 1.28–5.83), immunosuppression (OR = 3.43, 95%CI: 1.28–9.19), and search for previous care associated with the hospitalization (OR = 3.35, 95%CI: 1.75–6.40) were risk factors for death. Antiviral treatment performed within 72 hours of the onset of symptoms (OR = 0.17, 95%CI: 0.08–0.37, if within 48hours, and OR = 0.30, 95%CI: 0.11–0.81, if between 48 and 72 hours) was protective against death. The identification of high-risk patients and early treatment are important factors for reducing morbi-mortality from influenza.     

Ten-Year Follow-up of Patients with Epidemic Post Infectious Glomerulonephritis

BackgroundScarce information on outcomes of epidemic post infectious glomerulonephritis is available. This is a 10-year follow-up of the patients that developed acute glomerulonephritis in an epidemic outbreak caused by group C Streptococcus zooepidemicus in Brazil in 1998, that were also previously evaluated 2 and 5 years after the acute episode.MethodsIn this prospective study 60 cases (out of 134 in 1998) were reevaluated after 10 years, as well as community controls matched by gender and age. They underwent clinical and renal function evaluation, including serum creatinine and cystatin C, estimated glomerular filtration rate (eGFR), albuminuria and hematuria.ResultsComparisons of clinical and renal function aspects of 60 patients and 48 community controls have not shown significant differences (eGFR <60 ml/min/1.73m² and/or albuminuria >30mg/g creatinine: 13.8% vs. 12.2%, respectively, p = 0.817) except for a higher frequency of hypertension in the cases (45.0% vs. 20.8%, p = 0.009). Comparing the same patients affected in the acute episode, 2, 5 and 10 years later, it was observed an improvement of median eGFR levels at 2 years and a trend toward subsequent stabilization in these levels, associated with decrease in albuminuria and increased hypertension rates in the last survey. At 10 years it was not observed additional reduction of renal function using serum creatinine, eGFR and cystatin C.ConclusionsDuring the acute episode of epidemic GN a considerable proportion of patients presented hypertension and reduced renal function; after 2 years and particularly at this 10-year follow-up survey there was no worsening of renal function parameters, except for persistent higher frequency of hypertension. Nevertheless, a longer follow up is necessary to confirm that progressive loss of renal function will not occur.     

Do Brain Networks Evolve by Maximizing Their Information Flow Capacity?

We propose a working hypothesis supported by numerical simulations that brain networks evolve based on the principle of the maximization of their internal information flow capacity. We find that synchronous behavior and capacity of information flow of the evolved networks reproduce well the same behaviors observed in the brain dynamical networks of Caenorhabditis elegans and humans, networks of Hindmarsh-Rose neurons with graphs given by these brain networks. We make a strong case to verify our hypothesis by showing that the neural networks with the closest graph distance to the brain networks of Caenorhabditis elegans and humans are the Hindmarsh-Rose neural networks evolved with coupling strengths that maximize information flow capacity. Surprisingly, we find that global neural synchronization levels decrease during brain evolution, reflecting on an underlying global no Hebbian-like evolution process, which is driven by no Hebbian-like learning behaviors for some of the clusters during evolution, and Hebbian-like learning rules for clusters where neurons increase their synchronization.     

Adipocyte Secreted Factors Enhance Aggressiveness of Prostate Carcinoma Cells

Obesity has been associated with increased incidence and risk of mortality of prostate cancer. One of the proposed mechanisms underlying this risk association is the change in adipokines expression that could promote the development and progression of the prostate tumor cells. The main goal of this study was to evaluate the effect of preadipocyte and adipocyte secretome in the proliferation, migration and invasion of androgen independent prostate carcinoma cells (RM1) and to assess cell proliferation in the presence of the adiposity signals leptin and insulin. RM1 cells were co-cultured in with preadipocytes, adipocytes or cultured in their respective conditioned medium. Cell proliferation was assessed by flow cytometry and XTT viability test. Cell migration was evaluated using a wound healing injury assay of RM1 cells cultured with conditioned media. Cellular invasion of RM1 cells co-cultured with adipocytes and preadipocytes was assessed using matrigel membranes. Preadipocyte conditioned medium was associated with a small increase in RM1 proliferation, while adipocytes conditioned media significantly increased RM1 cell proliferation (p<0.01). Adipocytes also significantly increased the RM1 cells proliferation in co-culture (p <0.01). Cell migration was higher in RM1 cells cultured with preadipocyte and adipocyte conditioned medium. RM1 cell invasion was significantly increased after co-culture with preadipocytes and adipocytes (p <0.05). Insulin also increased significantly the cell proliferation in contrast to leptin, which showed no effect. In conclusion, prostate carcinoma cells seem to be influenced by factors secreted by adipocytes that are able to increase their ability to proliferate, migrate and invade.     

Probabilistic Models to Describe the Dynamics of Migrating Microbial Communities

In all but the most sterile environments bacteria will reside in fluid being transported through conduits and some of these will attach and grow as biofilms on the conduit walls. The concentration and diversity of bacteria in the fluid at the point of delivery will be a mix of those when it entered the conduit and those that have become entrained into the flow due to seeding from biofilms. Examples include fluids through conduits such as drinking water pipe networks, endotracheal tubes, catheters and ventilation systems. Here we present two probabilistic models to describe changes in the composition of bulk fluid microbial communities as they are transported through a conduit whilst exposed to biofilm communities. The first (discrete) model simulates absolute numbers of individual cells, whereas the other (continuous) model simulates the relative abundance of taxa in the bulk fluid. The discrete model is founded on a birth-death process whereby the community changes one individual at a time and the numbers of cells in the system can vary. The continuous model is a stochastic differential equation derived from the discrete model and can also accommodate changes in the carrying capacity of the bulk fluid. These models provide a novel Lagrangian framework to investigate and predict the dynamics of migrating microbial communities. In this paper we compare the two models, discuss their merits, possible applications and present simulation results in the context of drinking water distribution systems. Our results provide novel insight into the effects of stochastic dynamics on the composition of non-stationary microbial communities that are exposed to biofilms and provides a new avenue for modelling microbial dynamics in systems where fluids are being transported.     

Childhood Maltreatment and BMI Trajectories to Mid-Adult Life: Follow-Up to Age 50y in a British Birth Cohort

Background

Childhood maltreatment including abuse and neglect has been associated with adult obesity, but evidence on life-course development of obesity or BMI gain is unclear. We aim to establish whether childhood maltreatments are related to obesity or BMI at different life-stages 7y-50y and to identify possible explanations for associations.

Methods

Childhood physical, psychological and sexual abuse, neglect and BMI at seven ages were recorded in the 1958 birth cohort (n~15,000). Associations of child maltreatments with BMI at separate ages were tested using linear regression or logistic regression for obesity, and with rate of child-to-adult BMI gain using multilevel models. We adjusted for potential covariates.

Results

Abuse was reported in ~12% of the population. Abuse was not associated with elevated childhood BMI, but adult associations were observed: i.e. the abused had faster child-adult BMI gain than the non-abused; associations were independent of adult covariates. For physical abuse in both genders there was a positive linear association of ~0.006/y zBMI gain with age after adjustment for all covariates. Similarly, there was a linear association of physical abuse with obesity risk: e.g. among females from a low OR_adjusted of 0.34 (0.16,0.71) at 7y to 1.67 (1.25,2.24) at 50y. In females faster zBMI gains with age of ~0.0034/y were observed for sexual abuse and increases in obesity risk were faster: from a low OR_adjusted of 0.23 (0.06,0.84) at 7y to 1.34 (0.86,2.10) at 50y. Psychological abuse and neglect associations were less consistent.

Conclusions

Childhood maltreatment associations with BMI or obesity varied across life: physical and, in females, sexual abuse were associated with faster lifetime BMI gains, which may have detrimental long-term health consequences.