Background: Cotton workers are highly exposed to organic dust. Inhalation of cotton based particulate has been associated with various respiratory symptoms and impaired lung function. This study investigates the respiratory health profile of textile mill workers in Nepal in relation to dust and endotoxin exposure. Methods: This study was conducted in four sectors (garment, carpet, weaving and recycling) of the textile industry in Kathmandu, Nepal. A total of 938 individuals completed a health questionnaire and performed spirometry. A subset of 384 workers performed cross-shift spirometry. Personal exposure to inhalable dust and airborne endotoxin was measured during a full-shift for a 114 workers. Results: Geometric mean concentrations of personal exposure to cotton dust and endotoxin were 0.81 mg/m3 and 2160 EU/m3 respectively. Overall prevalence of persistent cough, persistent phlegm, wheeze, breathlessness and chest tightness were 8.5%, 12.5%, 3.2%, 6.5%and 3.6% respectively. Symptoms were most common among the recyclers and less in the garment sector. Exposure to inhalable dust significantly predicted the symptoms of persistent cough and chest tightness. Significant cross-shift reduction in FEV1, FVC, and FEF25_75 were measured in the textile workers (p<0.001 for all); reductions being greater in the recyclers (-143 ml) and smallest in the garment workers (-38 ml) (p=0.012). Cross-shift reduction in FEV1 was significantly predicated by exposure to inhalable dust. Exposure to endotoxin did not correlate with any of the respiratory symptoms nor to lung function. Conclusion: The measured association between exposure to inhalable dust and reporting of respiratory symptoms and lung function suggests that despite high levels of endotoxin exposures, inhalable dust is the driver for these effects and attention should turn to what might be the toxic component in this dust other than endotoxin.

Poster / Soc 397a / 2017 Poverty in Tucson Field Workshop

Poster / Soc 397a / 2017 Poverty in Tucson Field Workshop

Poster / Soc 397a / 2017 Poverty in Tucson Field Workshop

Poster / Soc 397a / 2017 Poverty in Tucson Field Workshop

Poster / Soc 397a / 2017 Poverty in Tucson Field Workshop

Poster / Soc 397a / 2017 Poverty in Tucson Field Workshop

The determination of a symbiotic association as beneficial requires good assessment of the costs and benefits involved in the maintenance and transmission of these microbes across generations. In social insects, symbiotic associations are complex as they may involve a network of interactions between individual and colony that result in stable associations over evolutionary time. My goal was to investigate the roles of behavior and morphology as integrators that have enabled the benefits of harboring gut microbes to reach both adult and growing brood in a colony. To achieve this goal, I used turtle ants (Cephalotes), a group that has co-evolved with their gut microbes since the Eocene (Sanders et al. 2014) and that shows a variety of morphological and behavioral specializations likely connected to this symbiotic association. In my dissertation I present evidence that the specialized behavior and morphology of Cephalotes are indeed strongly associated with mechanisms that ensure stability of ant-gut microbe interactions over evolutionary time. In Appendix A, I show that a valve between the crop and midgut (proventriculus) of C. rohweri works as a filtration organ, capable of excluding possible pathogens from the mostly liquid diet consumed by turtle ants. In addition, the proventricular filter is also associated with the structuring of the gut microbiota, dividing it in at least two great groups: one upstream and another downstream of the proventriculus. Through behavioral observation and microscopy, we also suggest that the formation of the proventricular filter is only complete after young and sterile workers (callows) are inoculated with the core group of symbiotic bacteria. In Appendix B, I present results confirming that the compartmentalization of gut microbiota is also present in the congener C. varians. I compare these results with previously published data, defining the meta-communities of the gut microbiota, and demonstrate that the previously recognized core microbiota is composed of compartment-specific microbial communities and lineages. This compartmentalization of the gut microbiota is similar to the one found in highly specialized herbivores, both vertebrates and invertebrates. In addition, I also sampled the infrabuccal pocket, a characteristic oral cavity found in ants and that has largely been ignored in studies of gut symbiosis. Based on my results, I provide compelling evidence that hindgut microbes are inoculated into food particles trapped in the infrabuccal pocket, aiding in digestion of this substrate. Moreover, I suggest that trophallaxis olays a central role in inoculation of food and individuals, and might be responsible for the transmission of nutrients that are predicted to result from the gut bacteria metabolism. Finally, in Appendix C I characterize abdominal trophallaxis in C. rohweri to gain insight on its role in the context of symbiotic associations with gut microbes. I show that the hindgut contents, including bacteria, can be transmitted via abdominal trophallaxis. This interaction is found to occur between all combinations of major and minor workers, in addition to callows. The rate of solicitation of abdominal trophallaxis is higher when individuals are protein starved, indicating that hindgut content may also be nutritive. Using shotgun metagenomic data, we show that the microbiota present in the infrabuccal pocket (mostly hindgut bacteria) are indeed capable of re-utilizing nitrogen and synthesizing essential amino acids, in addition to breaking down plant material. We also report that oral trophallaxis is a possible route for transmission of crop-specific bacteria for callows, as this group has performed oral trophallaxis at a relatively higher rate than older workers. Put together, these results highlight the importance of nestmate interactions and gut morphology in the establishment and maintenance of symbiotic microbes in a social insect, introducing a new model for explaining the evolution and functioning of ant-gut microbe symbiosis.

Caveolae are integral part of the smooth muscle membrane and caveolins, the defining proteins of caveolae, act as scaffolding proteins for several G protein-coupled receptor signaling molecules and regulate cellular signaling through direct and indirect interactions with signaling proteins. Caveolin-1 is the predominant isoform in the smooth muscle and drives the formation of caveolae. However, little is known about the role of caveolin-1 in the regulation of excitation-contraction and excitation-transcription coupling in gastrointestinal smooth muscle. In the present study we have characterized muscarinic m2 and m3 receptor signaling in gastric smooth muscle and tested the hypothesis that caveolin-1 positively regulates muscarinic receptor signaling and contractile protein expression in smooth muscle. The role of caveolae/caveolin-1 in the regulation of muscarinic signaling was examined using complementary approaches: a) methyl b-cyclodextrin (MbCD) to deplete cholesterol in dispersed muscle cells, b) caveolin-1 siRNA to suppress caveolin-1 expression in cultured muscle cells, and c) caveolin-1 knockout (KO) mice. RT-PCR, western blot and radioligand binding studies demonstrated the selective expression of m2 and m3 receptor in gastric smooth muscle cells. Carbachol (CCh), acting via m3 receptors caused stimulation of phosphoinositide (PI) hydrolysis, Rho kinase and ZIP kinase activity, and induced phosphorylation of MYPT1 (at Thr696) and MLC20 (at Ser19), and muscle contraction, and acting via m2 receptors caused inhibition of forskolin stimulated cAMP formation. Stimulation of PI hydrolysis, Rho kinase and ZIP kinase activities, phosphorylation of MYPT1 and MLC20 phosphorylation and muscle contraction in response to CCh was attenuated in dispersed cells treated with MbCD or in cultured cells transfected with caveolin-1 siRNA. Similar inhibition of all responses was obtained in gastric muscle cells from caveolin-1 KO mice compared to gastric muscle cells to WT mice. Although, caveolin-1 had no effect on m2 receptor signaling, agonist-induced internalization of m2, but not m3 receptors was blocked in dispersed cells treated with MbCD or in cultured cells transfected with caveolin-1 siRNA. These results suggest that caveolin-1 selectively and positively regulates Gq/13-coupled m3 receptor signaling, Gi-coupled m2 receptor internalization. The expression of contractile proteins, g-actin and caldesmone and the transcription factors SRF and myocardin that regulate the expression of contractile proteins are down regulated, whereas EGF-stimulated EGF receptor phosphorylation and ERK1/2 activity are up-regulated in cells transfected with caveolin-1 siRNA. These results suggest using pharmacological, molecular and genetic approaches provide conclusive evidence that caveolae and caveolin-1 play an important role in orchestrating G protein coupled receptor signaling to have dual pro- excitation-contraction and excitation-transcription coupling, and anti-proliferative role in gastric smooth muscle.

The purpose of this study was to further develop a multi-tier model of the vocal tract area function in which the modulations of shape to produce speech are generated by the product of a vowel substrate and a consonant superposition function. The new approach consists of specifying input parameters for a target consonant as a set of directional changes in the resonance frequencies of the vowel substrate. Using calculations of acoustic sensitivity functions, these "resonance deflection patterns" are transformed into time-varying deformations of the vocal tract shape without any direct specification of location or extent of the consonant constriction along the vocal tract. The configuration of the constrictions and expansions that are generated by this process were shown to be physiologically-realistic and produce speech sounds that are easily identifiable as the target consonants. This model is a useful enhancement for area function-based synthesis and can serve as a tool for understanding how the vocal tract is shaped by a talker during speech production. (C) 2016 Elsevier B.V. All rights reserved.