Characterization and regulation of a bacterial sugar phosphatase of the haloalkanoate dehalogenase superfamily, AraL, from Bacillus subtilis

AraL from Bacillus subtilis is a member of the ubiquitous haloalkanoate dehalogenase superfamily. The araL gene has been cloned, over-expressed in Escherichia coli and its product purified to homogeneity. The enzyme displays phosphatase activity, which is optimal at neutral pH (7.0) and 65 °C. Substrate screening and kinetic analysis showed AraL to have low specificity and catalytic activity towards several sugar phosphates, which are metabolic intermediates of the glycolytic and pentose phosphate pathways. On the basis of substrate specificity and gene context within the arabinose metabolic operon, a putative physiological role of AraL in the detoxification of accidental accumulation of phosphorylated metabolites has been proposed. The ability of AraL to catabolize several related secondary metabolites requires regulation at the genetic level. In the present study, using site-directed mutagenesis, we show that the production of AraL is regulated by a structure in the translation initiation region of the mRNA, which most probably blocks access to the ribosome-binding site, preventing protein synthesis. Members of haloalkanoate dehalogenase subfamily IIA and IIB are characterized by a broad-range and overlapping specificity anticipating the need for regulation at the genetic level. We provide evidence for the existence of a genetic regulatory mechanism controlling the production of AraL.     

Interaction between obesity-related genes, FTO and MC4R, associated to an increase of breast cancer risk

Breast cancer (BC) is a complex disease and obesity is a well-known risk factor for its development, especially after menopause. Several studies have shown Single Nucleotide Polymorphisms (SNPs) linked to overweight and obesity, such as: rs1121980 (T/C) and rs9939609 (A/T) in Fat Mass and Obesity Associated gene (FTO) and rs17782313 (T/C) in Melanocortin 4 Receptor gene (MC4R). Thus, we aimed to investigate the association between these obesity-related SNPs and BC risk. One hundred BC patients and 148 healthy women from Santa Catarina, Brazil entered the study. SNPs were genotyped using Taqman assays. For statistical analyses SNPStats and SPSS softwares were used. Association analyses were performed by logistic regression and were adjusted for age and Body mass index (BMI). Multiple SNPs inheritance models (log-additive, dominant, recessive, codominant) were performed to determine odds ratios (ORs), assuming 95 % confidence interval (CI) and P value = 0.05 as the significance limit. When analyzed alone, FTO rs1121980 and rs9939609 did not show significant associations with BC development, however MC4R rs17782313 showed increased risk for BC even after adjustments (P-value = 0.032). Interestingly, the interaction of FTO and MC4R polymorphisms showed a powerful association with BC. We observed a 4.59-fold increased risk for woman who have the allele combination C/T/C (FTO rs1121980/FTO rs9939609/MC4R rs17782313) (P-value = 0.0011, adjusted for age and BMI). We found important and unpublished associations between these obesity-related genes and BC risk. These associations seem to be independent of their effect on BMI, indicating a direct role of the interaction between FTO and MC4R polymorphisms in BC development.     

Female presence enhances sexual performance of sterile Anastrepha ludens males of the Tapachula-7 GSS strain

The sterile insect technique (SIT), used for the control of many tephritid fly pests, is based on the rearing and release of large numbers of sexually competitive sterile insects into a wild population. In the interest of reducing expenses and increasing SIT effectiveness, genetic sexing strains (GSS) have been developed. These strains allow the production and release of only males. The objective of our study was to assess the effects of pre-release adult exposure to methoprene and to females on the mating propensity and mating competitiveness of GSS sterile males of Anastrepha ludens (Loew) (Diptera: Tephritidae). GSS sterile males were kept on a protein-sugar (protein-fed) or a protein-sugar-methoprene diet and were exposed to different proportions of females for the normal pre-release period of 5 days. Using laboratory and field-cage bioassays, we examined the influence of methoprene and female presence on the mating success of sterile males of 3–9 days old, in competition for wild females with untreated males and with wild males. Methoprene and female exposure had no significant effects on male mating success in the laboratory, whereas age had a positive relationship with the number of copulations observed. However, in field-cage bioassays, males exposed to females obtained a higher number of copulations than unexposed control males. Possible implications of these findings for programs that use GSS and especially for the campaign against Mexican fruit flies are discussed.     

Association Between Uric Acid Levels and Obstructive Sleep Apnea Syndrome in a Large Epidemiological Sample

Introduction

Recurrent hypoxia, which is associated with obstructive sleep apnea syndrome (OSAS), leads to an increase in the degradation of adenosine triphosphatase into xanthine, which in turn increases uric acid concentrations.

Objective

The current study aimed to determine whether an association exists between OSAS and uric acid levels in the peripheral blood from a representative population of Sao Paulo (Brazil).

Methods

A population-based survey adopting a probabilistic 3-stage cluster sample of Sao Paulo was used to represent the population according to gender, age, and socioeconomic class. A total of 1,042 volunteers underwent polysomnography recordings for OSAS diagnosis, blood pressure assessment, and biochemical blood analysis, and answered questionnaires.

Results

Uric acid levels were correlated with most important risk factors for OSAS, such as AHI, desaturation time and index, minimum oxyhemoglobin saturation (SpO₂), blood pressure, cholesterol, BMI, triglycerides and arousal, and with OSAS itself. Also, uric acid was increased in OSAS volunteers even after controlling for all confounders. Hyperuricemic volunteers presented lower mean and minimum SpO₂ and increased desaturation index. Importantly, minimum SpO₂ was a significant predictor of uric acid levels, which in turn was considered an independent predictor for OSAS in the binary logistic model. However, a ROC curve analysis for establishing cut-off points for uric acid levels as a biomarker of OSAS revealed moderate sensitivity and specificity.

Conclusion

A strong association was found between uric acid levels and OSAS in a representative sample of the population of Sao Paulo. Although they do not qualify for a biomarker alone, uric acid levels may be involved in OSAS severity and should be considered in sleep apnea management in the future.     

Au nanospheres and nanorods for enzyme-free electrochemical biosensor applications

Au nanocrystals with different morphologies were prepared and used for enzyme-free electrochemical biosensor applications. To investigate the electrocatalytic properties of Au nanocrystals as a function on their morphologies, Au nanocrystals, Au nanospheres (NSs) on silica, Au NSs, and Au nanorods (NRs) with aspect ratios of 1:3 and 1:5, were coated on the screen printed electrodes and further measure the amperometric responses to hydrogen peroxide via three-electrode system. The electrodes modified with Au nanocrystals showed biosensing properties without any enzyme being attached or immobilized at their surface. The hydrogen peroxide detection limits of the biosensors with Au NSs, Au NRs (1:3), and Au NRs (1:5) were 6.48, 8.65, and 9.38 μM (S/N = 3), respectively. The biosensors with Au NSs, Au NRs (1:3), and Au NRs (1:5) showed the sensitivities of 11.13, 54.53, and 58.51 μA/mM, respectively. These results indicate that morphologies of Au nanocrystals significantly influence the sensitivity of the biosensors. In addition, the enzyme-free biosensors with Au nanocrystals were stable for 2 months. Au nanocrystal-based enzyme-free system, which is proposed in this study, can be used as a platform for various electrochemical biosensors.     

Effect of local weather on butterfly flight behaviour,movement, and colonization: significance for dispersal under climate change

Recent climate change is recognized as a main cause of shifts in geographical distributions of species. The impacts of climate change may be aggravated by habitat fragmentation, causing regional or large scale extinctions. However, we propose that climate change also may diminish the effects of fragmentation by enhancing flight behaviour and dispersal of ectothermic species like butterflies. We show that under weather conditions associated with anticipated climate change, behavioural components of dispersal of butterflies are enhanced, and colonization frequencies increase. In a field study, we recorded flight behaviour and mobility of four butterfly species: two habitat generalists (Coenonympha pamphilus; Maniola jurtina) and two specialists (Melitaea athalia; Plebejus argus), under different weather conditions. Flying bout duration generally increased with temperature and decreased with cloudiness. Proportion of time spent flying decreased with cloudiness. Net displacement generally increased with temperature. When butterflies fly longer, start flying more readily and fly over longer distances, we expect dispersal propensity to increase. Monitoring data showed that colonization frequencies moreover increased with temperature and radiation and decreased with cloudiness. Increased dispersal propensity at local scale might therefore lower the impact of habitat fragmentation on the distribution at a regional scale. Synergetic effects of climate change and habitat fragmentation on population dynamics and species distributions might therefore appear to be more complex than previously assumed.     

Impact of host age on viral and bacterial communities in a waterbird population

Wildlife harbour pathogens that can harm human or livestock health and are the source of most emerging infectious diseases. It is rarely considered how changes in wildlife population age-structures or how age-stratified behaviours might alter the level of pathogen detection within a species, or risk of spillover to other species. Micro-organisms that occur in healthy animals can be an important model for understanding and predicting the dynamics of pathogens of greater health concern, which are hard to study in wild populations due to their relative rarity. We therefore used a metagenomic approach to jointly characterise viral and prokaryotic carriage in faeces collected from a healthy wild bird population (Cygnus olor; mute swan) that has been subject to long-term study. Using 223 samples from known individuals allowed us to compare differences in prokaryotic and eukaryotic viral carriage between adults and juveniles at an unprecedented level of detail. We discovered and characterised 77 novel virus species, of which 21% belong putatively to bird-infecting families, and described the core prokaryotic microbiome of C. olor. Whilst no difference in microbiota diversity was observed between juveniles and adult individuals, 50% (4/8) of bird-infecting virus families (picornaviruses, astroviruses, adenoviruses and bornaviruses) and 3.4% (9/267) of prokaryotic families (including Helicobacteraceae, Spirochaetaceae and Flavobacteriaceae families) were differentially abundant and/or prevalent between juveniles and adults. This indicates that perturbations that affect population age-structures of wildlife could alter circulation dynamics and spillover risk of microbes, potentially including pathogens.Subject terms: Metagenomics, Molecular biology, Microbial ecology, Next-generation sequencing, Infectious diseases     

Heteroclinic orbits indicate overexploitation in predator-prey systems with a strong Allee effect

Species establishment in a model system in a homogeneous environment can be dependent not only on the parameter setting, but also on the initial conditions of the system. For instance, predator invasion into an established prey population can fail and lead to system collapse, an event referred to as overexploitation. This phenomenon occurs in models with bistability properties, such as strong Allee effects. The Allee effect then prevents easy re-establishment of the prey species. In this paper, we deal with the bifurcation analyses of two previously published predator-prey models with strong Allee effects. We expand the analyses to include not only local, but also global bifurcations. We show the existence of a point-to-point heteroclinic cycle in these models, and discuss numerical techniques for continuation in parameter space. The continuation of such a cycle in two-parameter space forms the boundary of a region in parameter space where the system collapses after predator invasion, i.e. where overexploitation occurs. We argue that the detection and continuation of global bifurcations in these models are of vital importance for the understanding of the model dynamics.     

Synaptic Synthesis,Dephosphorylation, and Degradation: A NOVEL PARADIGM FOR AN ACTIVITY-DEPENDENT NEURONAL CONTROL OF CDKL5*

Mutations in the X-linked CDKL5 (cyclin-dependent kinase-like 5) gene have been associated with several forms of neurodevelopmental disorders, including atypical Rett syndrome, autism spectrum disorders, and early infantile epileptic encephalopathy. Accordingly, loss of CDKL5 in mice results in autistic-like features and impaired neuronal communication. Although the biological functions of CDKL5 remain largely unknown, recent pieces of evidence suggest that CDKL5 is involved in neuronal plasticity. Herein, we show that, at all stages of development, neuronal depolarization induces a rapid increase in CDKL5 levels, mostly mediated by extrasomatic synthesis. In young neurons, this induction is prolonged, whereas in more mature neurons, NMDA receptor stimulation induces a protein phosphatase 1-dependent dephosphorylation of CDKL5 that is mandatory for its proteasome-dependent degradation. As a corollary, neuronal activity leads to a prolonged induction of CDKL5 levels in immature neurons but to a short lasting increase of the kinase in mature neurons. Recent results demonstrate that many genes associated with autism spectrum disorders are crucial components of the activity-dependent signaling networks regulating the composition, shape, and strength of the synapse. Thus, we speculate that CDKL5 deficiency disrupts activity-dependent signaling and the consequent synapse development, maturation, and refinement.