An olfactory receptor for food-derived odours promotes male courtship in Drosophila.

Many animals attract mating partners through the release of volatile sex pheromones, which can convey information on the species, gender and receptivity of the sender to induce innate courtship and mating behaviours by the receiver. Male Drosophila melanogaster fruitflies display stereotyped reproductive behaviours towards females, and these behaviours are controlled by the neural circuitry expressing male-specific isoforms of the transcription factor Fruitless (FRU(M)). However, the volatile pheromone ligands, receptors and olfactory sensory neurons (OSNs) that promote male courtship have not been identified in this important model organism. Here we describe a novel courtship function of Ionotropic receptor 84a (IR84a), which is a member of the chemosensory ionotropic glutamate receptor family, in a previously uncharacterized population of FRU(M)-positive OSNs. IR84a-expressing neurons are activated not by fly-derived chemicals but by the aromatic odours phenylacetic acid and phenylacetaldehyde, which are widely found in fruit and other plant tissues that serve as food sources and oviposition sites for drosophilid flies. Mutation of Ir84a abolishes both odour-evoked and spontaneous electrophysiological activity in these neurons and markedly reduces male courtship behaviour. Conversely, male courtship is increased--in an IR84a-dependent manner--in the presence of phenylacetic acid but not in the presence of another fruit odour that does not activate IR84a. Interneurons downstream of IR84a-expressing OSNs innervate a pheromone-processing centre in the brain. Whereas IR84a orthologues and phenylacetic-acid-responsive neurons are present in diverse drosophilid species, IR84a is absent from insects that rely on long-range sex pheromones. Our results suggest a model in which IR84a couples food presence to the activation of the fru(M) courtship circuitry in fruitflies. These findings reveal an unusual but effective evolutionary solution to coordinate feeding and oviposition site selection with reproductive behaviours through a specific sensory pathway.

Association between GIS-based exposure to urban air pollution during pregnancy and birth weight in the INMA Sabadell Cohort

Background: There is growing evidence that traffic-related air pollution reduces birth weight. Improving exposure assessment is a key issue to advance in this research area.Objective: We investigated the effect of prenatal exposure to traffic-related air pollution via geographic information system (GIS) models on birth weight in 570 newborns from the INMA (Environment and Childhood) Sabadell cohort.Methods: We estimated pregnancy and trimester-specific exposures to nitrogen dioxide and aromatic hydrocarbons [benzene, toluene, ethylbenzene, m/p-xylene, and o-xylene (BTEX)] by using temporally adjusted land-use regression (LUR) models. We built models for NO2 and BTEX using four and three 1-week measurement campaigns, respectively, at 57 locations. We assessed the relationship between prenatal air pollution exposure and birth weight with linear regression models. We performed sensitivity analyses considering time spent at home and time spent in nonresidential outdoor environments during pregnancy.Results: In the overall cohort, neither NO2 nor BTEX exposure was significantly associated with birth weight in any of the exposure periods. When considering only women who spent < 2 hr/day in nonresidential outdoor environments, the estimated reductions in birth weight associated with an interquartile range increase in BTEX exposure levels were 77 g [95% confidence interval (CI), 7–146 g] and 102 g (95% CI, 28–176 g) for exposures during the whole pregnancy and the second trimester, respectively. The effects of NO2 exposure were less clear in this subset.Conclusions: The association of BTEX with reduced birth weight underscores the negative role of vehicle exhaust pollutants in reproductive health. Time–activity patterns during pregnancy complement GIS-based models in exposure assessment.

Prenatal exposure to traffic-related air pollution and ultrasound measures of fetal growth in the INMA Sabadell cohort

Background: Few studies have used longitudinal ultrasound measurements to assess the effect of traffic-related air pollution on fetal growth.Objective: We examined the relationship between exposure to nitrogen dioxide (NO2) and aromatic hydrocarbons [benzene, toluene, ethylbenzene, m/p-xylene, and o-xylene (BTEX)] on fetal growth assessed by 1,692 ultrasound measurements among 562 pregnant women from the Sabadell cohort of the Spanish INMA (Environment and Childhood) study.Methods: We used temporally adjusted land-use regression models to estimate exposures to NO2 and BTEX. We fitted mixed-effects models to estimate longitudinal growth curves for femur length (FL), head circumference (HC), abdominal circumference (AC), biparietal diameter (BPD), and estimated fetal weight (EFW). Unconditional and conditional SD scores were calculated at 12, 20, and 32 weeks of gestation. Sensitivity analyses were performed considering time–activity patterns during pregnancy.Results: Exposure to BTEX from early pregnancy was negatively associated with growth in BPD during weeks 20–32. None of the other fetal growth parameters were associated with exposure to air pollution during pregnancy. When considering only women who spent 2 hr/day in nonresidential outdoor locations, effect estimates were stronger and statistically significant for the association between NO2 and growth in HC during weeks 12–20 and growth in AC, BPD, and EFW during weeks 20–32.Conclusions: Our results lend some support to an effect of exposure to traffic-related air pollutants from early pregnancy on fetal growth during mid-pregnancy.

The postmortem diagnosis of alcoholic ketoacidosis.

AIMS: The aim of this article is to review the forensic literature covering the postmortem investigations that are associated with alcoholic ketoacidosis fatalities and report the results of our own analyses. METHODS: Eight cases of suspected alcoholic ketoacidosis that had undergone medico-legal investigations in our facility from 2011 to 2013 were retrospectively selected. A series of laboratory parameters were measured in whole femoral blood, postmortem serum from femoral blood, urine and vitreous humor in order to obtain a more general overview on the biochemical and metabolic changes that occur during alcoholic ketoacidosis. Most of the tested parameters were chosen among those that had been described in clinical and forensic literature associated with alcoholic ketoacidosis and its complications. RESULTS: Ketone bodies and carbohydrate-deficient transferrin levels were increased in all cases. Biochemical markers of generalized inflammation, volume depletion and undernourishment showed higher levels. Adaptive endocrine reactions involving insulin, glucagon, cortisol and triiodothyronine were also observed. CONCLUSIONS: Metabolic and biochemical disturbances characterizing alcoholic ketoacidosis can be reliably identified in the postmortem setting. The correlation of medical history, autopsy findings and biochemical results proves therefore decisive in identifying pre-existing disorders, excluding alternative causes of death and diagnosing alcoholic ketoacidosis as the cause of death.

Effect of Pcbs (Aroclor 1254) on spermatogenesis In Testis Of Mouse

Polychlorinated biphenyls (PCBs) are a group of halogenated aromatic hydrocarbons, synthetic chemicals which do not occur naturally in the environment. PCBs are considered potential endocrine disruptors. They are estrogen-like and anti-androgenic chemicals in the environment contain potentially hazardous effects on male reproductive axis resulting in infertility and other hormonal dependent reproductive functions. These toxic substance cause alteration of the endocrine systems, mimic natural hormones and inhibit the action of hormones. The aim of this study is to examine the effect of Polychlorinated biphenyls (PCBs) on testicular development of male reproductive system in mice. The male mice were randomly assigned to five groups with each group comprising twenty-one members. In those mice were administered 0 μg/kg (control group) and 0.5, 5, 50, 500 μg/kg Aroclor 1254 (treated group) by gavages three time per week. Treatment was carried out for 50 days after which the mouse was sacrificed and the body weight, testicular weight; epedidymis weight, sperm mortality, sperm count and sperm abnormality were taken. However, there was no significant difference in testicular/body weight and epididymis/body weight ratio in treated group compared with the control group. According to the analysis of sperm quality, Aroclor 1254 treated group demonstrated significant increased in sperm mortality in 500 μg/kg; decreased the sperm count in 0.5 μg/kg, 5 μg/kg, 50 μg/kg and 500 μg/kg; and significantly elevate the sperm abnormality in 50 μg/kg and 500 μg/kg compared to the control in a dose-dependent manner. The sex hormone levels in the testes were detected by radio-immunoassay (RIA) method. The levels of testosterone and 17β-estradiol did not reveal significant alteration (p< 0.05) in PCBs treated groups compared to the control in a dose-dependent manner. The testis were obtained and subjected to routine histopathology following exposure to PCBs in supplement diet. The diameter of the seminiferous tubule and the number of Sertoli cells in the treated group increased significantly (p< 0.05) in comparison to the control group. For the spermatogenic cell, the number of germ cell in high concentration decreased significantly (p< 0.05). However, spermatogonia cells in PCB treated group showed non-significant difference (p< 0.05) compared to the control. vii Western blot analysis was used to determine the level of protein between the control and treated group. The level of Proliferating cell nuclear antigen (PCNA) was determined and the results have shown no significant alteration between the treated groups and the control. the level of sex hormone receptor (ER α/β); Androgen receptor (AR) were identified in the testes to detect the proliferative effect induced by PCBs. Statistical analyses of AR, ER α and ER β did not reveal significant difference between the control and the treated groups. In the present study, we continue to investigate adverse effect of Aroclor 1254 and their mechanism on spermatogenesis. The result of Sperm quality and histopathology showed that Aroclor 1254 at low concentration induce inhibitory effect on testicular function of male mouse.

Metabolic compartmentalization in the human cortex and hippocampus: evidence for a cell- and region-specific localization of lactate dehydrogenase 5 and pyruvate dehydrogenase.

BACKGROUND: For a long time now, glucose has been thought to be the main, if not the sole substrate for brain energy metabolism. Recent data nevertheless suggest that other molecules, such as monocarboxylates (lactate and pyruvate mainly) could be suitable substrates. Although monocarboxylates poorly cross the blood brain barrier (BBB), such substrates could replace glucose if produced locally.The two key enzymatiques systems required for the production of these monocarboxylates are lactate dehydrogenase (LDH; EC1.1.1.27) that catalyses the interconversion of lactate and pyruvate and the pyruvate dehydrogenase complex that irreversibly funnels pyruvate towards the mitochondrial TCA and oxydative phosphorylation. RESULTS: In this article, we show, with monoclonal antibodies applied to post-mortem human brain tissues, that the typically glycolytic isoenzyme of lactate dehydrogenase (LDH-5; also called LDHA or LDHM) is selectively present in astrocytes, and not in neurons, whereas pyruvate dehydrogenase (PDH) is mainly detected in neurons and barely in astrocytes. At the regional level, the distribution of the LDH-5 immunoreactive astrocytes is laminar and corresponds to regions of maximal 2-deoxyglucose uptake in the occipital cortex and hippocampus. In hippocampus, we observed that the distribution of the oxidative enzyme PDH was enriched in the neurons of the stratum pyramidale and stratum granulosum of CA1 through CA4, whereas the glycolytic enzyme LDH-5 was enriched in astrocytes of the stratum moleculare, the alveus and the white matter, revealing not only cellular, but also regional, selective distributions. The fact that LDH-5 immunoreactivity was high in astrocytes and occurred in regions where the highest uptake of 2-deoxyglucose was observed suggests that glucose uptake followed by lactate production may principally occur in these regions. CONCLUSION: These observations reveal a metabolic segregation, not only at the cellular but also at the regional level, that support the notion of metabolic compartmentalization between astrocytes and neurons, whereby lactate produced by astrocytes could be oxidized by neurons.

Composition of the electrocautery smoke: integrative literature review

Abstract OBJECTIVE To identify the composition of the smoke produced by electrocautery use during surgery. METHOD Integrative review with search for primary studies conducted in the databases of the US National Library of Medicine National Institutes of Health, Cumulative Index to Nursing and Allied Health Literature, and Latin American and Caribbean Health Sciences, covering the studies published between 2004 and 2014. RESULTS The final sample consisted of 14 studies grouped into three categories, namely; polycyclic aromatic hydrocarbons, volatile compounds and volatile organic compounds. CONCLUSION There is scientific evidence that electrocautery smoke has volatile toxic, carcinogenic and mutagenic compounds, and its inhalation constitutes a potential chemical risk to the health of workers involved in surgeries.

Assignment strategies for large proteins by magic-angle spinning NMR: the 21-kDa disulfide-bond-forming enzyme DsbA.

We present strategies for chemical shift assignments of large proteins by magic-angle spinning solid-state NMR, using the 21-kDa disulfide-bond-forming enzyme DsbA as prototype. Previous studies have demonstrated that complete de novo assignments are possible for proteins up to approximately 17 kDa, and partial assignments have been performed for several larger proteins. Here we show that combinations of isotopic labeling strategies, high field correlation spectroscopy, and three-dimensional (3D) and four-dimensional (4D) backbone correlation experiments yield highly confident assignments for more than 90% of backbone resonances in DsbA. Samples were prepared as nanocrystalline precipitates by a dialysis procedure, resulting in heterogeneous linewidths below 0.2 ppm. Thus, high magnetic fields, selective decoupling pulse sequences, and sparse isotopic labeling all improved spectral resolution. Assignments by amino acid type were facilitated by particular combinations of pulse sequences and isotopic labeling; for example, transferred echo double resonance experiments enhanced sensitivity for Pro and Gly residues; [2-(13)C]glycerol labeling clarified Val, Ile, and Leu assignments; in-phase anti-phase correlation spectra enabled interpretation of otherwise crowded Glx/Asx side-chain regions; and 3D NCACX experiments on [2-(13)C]glycerol samples provided unique sets of aromatic (Phe, Tyr, and Trp) correlations. Together with high-sensitivity CANCOCA 4D experiments and CANCOCX 3D experiments, unambiguous backbone walks could be performed throughout the majority of the sequence. At 189 residues, DsbA represents the largest monomeric unit for which essentially complete solid-state NMR assignments have so far been achieved. These results will facilitate studies of nanocrystalline DsbA structure and dynamics and will enable analysis of its 41-kDa covalent complex with the membrane protein DsbB, for which we demonstrate a high-resolution two-dimensional (13)C-(13)C spectrum.

Differential Recognition of Old World and New World Arenavirus Envelope Glycoproteins by Subtilisin Kexin Isozyme 1 (SKI-1)/Site 1 Protease (S1P).

The arenaviruses are an important family of emerging viruses that includes several causative agents of severe hemorrhagic fevers in humans that represent serious public health problems. A crucial step of the arenavirus life cycle is maturation of the envelope glycoprotein precursor (GPC) by the cellular subtilisin kexin isozyme 1 (SKI-1)/site 1 protease (S1P). Comparison of the currently known sequences of arenavirus GPCs revealed the presence of a highly conserved aromatic residue at position P7 relative to the SKI-1/S1P cleavage side in Old World and clade C New World arenaviruses but not in New World viruses of clades A and B or cellular substrates of SKI-1/S1P. Using a combination of molecular modeling and structure-function analysis, we found that residueY285 of SKI-1/S1P, distal from the catalytic triad, is implicated in the molecular recognition of the aromatic "signature residue" at P7 in the GPC of Old World Lassa virus. Using a quantitative biochemical approach, we show that Y285 of SKI-1/S1P is crucial for the efficient processing of peptides derived from Old World and clade C New World arenavirus GPCs but not of those from clade A and B New World arenavirus GPCs. The data suggest that during coevolution with their mammalian hosts, GPCs of Old World and clade C New World viruses expanded the molecular contacts with SKI-1/S1P beyond the classical four-amino-acid recognition sequences and currently occupy an extended binding pocket.

Resistance to diet-induced obesity and associated metabolic perturbations in haploinsufficient monocarboxylate transporter 1 mice

The monocarboxylate transporter 1 (MCT1 or SLC16A1) is a carrier of short-chain fatty acids, ketone bodies, and lactate in several tissues. Genetically modified C57BL/6J mice were produced by targeted disruption of the mct1 gene in order to understand the role of this transporter in energy homeostasis. Null mutation was embryonically lethal, but MCT1 (+/-) mice developed normally. However, when fed high fat diet (HFD), MCT1 (+/-) mice displayed resistance to development of diet-induced obesity (24.8% lower body weight after 16 weeks of HFD), as well as less insulin resistance and no hepatic steatosis as compared to littermate MCT1 (+/+) mice used as controls. Body composition analysis revealed that reduced weight gain in MCT1 (+/-) mice was due to decreased fat accumulation (50.0% less after 9 months of HFD) notably in liver and white adipose tissue. This phenotype was associated with reduced food intake under HFD (12.3% less over 10 weeks) and decreased intestinal energy absorption (9.6% higher stool energy content). Indirect calorimetry measurements showed ∼ 15% increase in O2 consumption and CO2 production during the resting phase, without any changes in physical activity. Determination of plasma concentrations for various metabolites and hormones did not reveal significant changes in lactate and ketone bodies levels between the two genotypes, but both insulin and leptin levels, which were elevated in MCT1 (+/+) mice when fed HFD, were reduced in MCT1 (+/-) mice under HFD. Interestingly, the enhancement in expression of several genes involved in lipid metabolism in the liver of MCT1 (+/+) mice under high fat diet was prevented in the liver of MCT1 (+/-) mice under the same diet, thus likely contributing to the observed phenotype. These findings uncover the critical role of MCT1 in the regulation of energy balance when animals are exposed to an obesogenic diet.

Euglossine bee communities in small forest fragments of the Atlantic Forest, Rio de Janeiro state, southeastern Brazil (Hymenoptera, Apidae)

Euglossine bee communities in small forest fragments of the Atlantic Forest, Rio de Janeiro state, southeastern Brazil (Hymenoptera, Apidae). Euglossine bees are important pollinators in forests and agricultural areas. Although the structure of their communities is critically affected by anthropogenic disturbances, little is known about these bees in small forest fragments. The objectives of this study were to analyze the composition, abundance, and diversity of euglossine bee species in nine small fragments of different phytophysiognomies of the Atlantic Forest in southeastern Brazil, and to identify the environmental variables that may be related to the species composition of these communities. Males were sampled quarterly from May 2007 to May 2009 with aromatic traps containing methyl cinnamate, vanillin, eucalyptol, benzyl acetate, and methyl salicylate. A total of 1558 males, belonging to 10 species and three genera of Euglossina were collected. The richness ranged from five to seven species per fragment. Euglossa cordata, E. securigera, Eulaema nigrita e E. cingulata were common to all fragments studied. The diversity differed significantly among areas, ranging from H' = 1.04 to H' = 1.65. The precipitation, phytophysiognomy, and altitude had the highest relative importance over the species composition variation. The results presented in this study demonstrate that small forest fragments are able to support populations of euglossine bee species, most of which are widely distributed and reportedly tolerant to open and/or disturbed areas and suggest that the conservation of such areas is important, particularly in areas that are regenerating and in regions with agricultural matrices where these bees can act as important pollinators

Homologous DNA pairing domain peptides of RecA protein: intrinsic propensity to form beta-structures and filaments.

The 20 amino acid residue peptides derived from RecA loop L2 have been shown to be the pairing domain of RecA. The peptides bind to ss- and dsDNA, unstack ssDNA, and pair the ssDNA to its homologous target in a duplex DNA. As shown by circular dichroism, upon binding to DNA the disordered peptides adopt a beta-structure conformation. Here we show that the conformational change of the peptide from random coil to beta-structure is important in binding ss- and dsDNA. The beta-structure in the DNA pairing peptides can be induced by many environmental conditions such as high pH, high concentration, and non-micellar sodium dodecyl sulfate (6 mM). This behavior indicates an intrinsic property of these peptides to form a beta-structure. A beta-structure model for the loop L2 of RecA protein when bound to DNA is thus proposed. The fact that aromatic residues at the central position 203 strongly modulate the peptide binding to DNA and subsequent biochemical activities can be accounted for by the direct effect of the aromatic amino acids on the peptide conformational change. The DNA-pairing domain of RecA visualized by electron microscopy self-assembles into a filamentous structure like RecA. The relevance of such a peptide filamentous structure to the structure of RecA when bound to DNA is discussed.

Orchid bee baits attracting bees of the genus Megalopta (Hymenoptera, Halictidae) in Bauru region, São Paulo, Brazil: abundance, seasonality, and the importance of odors for dim-light bees

Nocturnal bees in the genus Megalopta Smith, 1853 are generally collected using artificial light sources. However, between 1993 and 2000, a total of 946 females (no males were captured) were captured using aromatic baits commonly used for orchid bees (Euglossini) in five localities in Bauru region, São Paulo, Brazil. Aromatic compounds used in bait traps were: benzyl acetate, eucalyptol, eugenol, skatole, methyl salicylate, and vanillin. The Megalopta species collected were: M. guimaraesi (71.2% of total number of specimens), M. amoena (28.1%), and M. aegis (0.6%). Using the data from these traps, we showed that there was a positive and significant correlation between the abundance of individuals and meteorological factors, rainfall and temperature. Bees were more commonly collected in the spring (September to December) and summer (December to March) than in the autumn and winter, the latter characterized for being a drier and colder period. Variations in the abundance were also detected among localities and years. The most attractive compounds were eugenol (54%), methyl salicylate (22%), and eucalyptol (16%). The ability to detect smells may have an important role in searching for flowers during dim-light conditions. We suggest the use of aromatic compounds in future studies on the biology of Megalopta in the Neotropical region.

Impact of biological and environmental variabilities on biological monitoring: an approach using toxicokinetic models

Biological monitoring of occupational exposure is characterized by important variability, due both to variability in the environment and to biological differences between workers. A quantitative description and understanding of this variability is important for a dependable application of biological monitoring. This work describes this variability,using a toxicokinetic model, for a large range of chemicals for which reference biological reference values exist. A toxicokinetic compartmental model describing both the parent compound and its metabolites was used. For each chemical, compartments were given physiological meaning. Models were elaborated based on physiological, physicochemical, and biochemical data when available, and on half-lives and central compartment concentrations when not available. Fourteen chemicals were studied (arsenic, cadmium, carbon monoxide, chromium, cobalt, ethylbenzene, ethyleneglycol monomethylether, fluorides, lead, mercury, methyl isobutyl ketone, penthachlorophenol, phenol, and toluene), representing 20 biological indicators. Occupational exposures were simulated using Monte Carlo techniques with realistic distributions of both individual physiological parameters and exposure conditions. Resulting biological indicator levels were then analyzed to identify the contribution of environmental and biological variability to total variability. Comparison of predicted biological indicator levels with biological exposure limits showed a high correlation with the model for 19 out of 20 indicators. Variability associated with changes in exposure levels (GSD of 1.5 and 2.0) is shown to be mainly influenced by the kinetics of the biological indicator. Thus, with regard to variability, we can conclude that, for the 14 chemicals modeled, biological monitoring would be preferable to air monitoring. For short half-lives (less than 7 hr), this is very similar to the environmental variability. However, for longer half-lives, estimated variability decreased. [Supplementary materials are available for this article. Go to the publisher's online edition of Journal of Occupational and Environmental Hygiene for the following free supplemental resource: tables detailing the CBTK models for all 14 chemicals and the symbol nomenclature that was used.] [Authors]

Knock, knock, knocking on muscle doors. Visions on the transport of substrates across the plasma membrane in muscle.

Muscle is a major player in metabolism. It uses large amounts of glucose in the absorptive state and changes in muscle insulin-stimulated glucose uptake alter whole-body glucose disposal. Lipid substrates such as fatty acids or ketone bodies are preferentially used by muscle in certain physiological conditions. Muscle is also the main reservoir of amino acids and protein. The activity of many different plasma membrane transporters such as glucose carriers, carnitine, creatine or amino acid transporters maintain muscle metabolism by taking up or releasing substrates or metabolites across the cell surface. The goal of this review is the molecular characterization of muscle membrane transporter proteins and the analysis of their regulatory roles.