Tsetse fly (Glossina pallidipes) midgut responses to Trypanosoma brucei challenge

Abstract Background Tsetse flies (Glossina spp.) are the prominent vector of African trypanosome parasites (Trypanosoma spp.) in sub-Saharan Africa, and Glossina pallidipes is the most widely distributed species in Kenya. This species displays strong resistance to infection by parasites, which are typically eliminated in the midgut shortly after acquisition from the mammalian host. Although extensive molecular information on immunity for the related species Glossina morsitans morsitans exists, similar information is scarce for G. pallidipes. Methods To determine temporal transcriptional responses of G. pallidipes to Trypanosoma brucei brucei challenge, we conducted Illumina based RNA-seq on midgut organ and carcass from teneral females G. pallidipes at 24 and 48 h post-challenge (hpc) with T. b. brucei relative to their respective controls that received normal blood meals (without the parasite). We used a suite of bioinformatics tools to determine differentially expressed and enriched transcripts between and among tissues, and to identify expanded transcripts in G. pallidipes relative to their orthologs G. m. morsitans. Results Midgut transcripts induced at 24 hpc encoded proteins were associated with lipid remodelling, proteolysis, collagen metabolism, apoptosis, and cell growth. Midgut transcripts induced at 48 hpc encoded proteins linked to embryonic growth and development, serine endopeptidases and proteosomal degradation of the target protein, mRNA translation and neuronal development. Temporal expression of immune responsive transcripts at 48 relative to 24 hpc was pronounced, indicative of a gradual induction of host immune responses the following challenge. We also searched for G. m. morsitans orthologous groups that may have experienced expansions in the G. pallidipes genome. We identified ten expanded groups in G. pallidipes with putative immunity-related functions, which may play a role in the higher refractoriness exhibited by this species. Conclusions There appears to be a lack of strong immune responses elicited by gut epithelia of teneral adults. This in combination with a compromised peritrophic matrix at this stage during the initial phase of T. b. brucei challenge may facilitate the increased parasite infection establishment noted in teneral flies relative to older adults. Although teneral flies are more susceptible than older adults, the majority of tenerals are still able to eliminate parasite infections. Hence, robust responses elicited at a later time point, such as 72 hpc, may clear parasite infections from the majority of flies. The expanded G. m. morsitans orthologous groups in G. pallidipes may also be functionally associated with the enhanced refractoriness to trypanosome infections reported in G. pallidipes relative to G. m. morsitans

Why do people not attend for treatment for trachomatous trichiasis in Ethiopia? A study of barriers to surgery.

BACKGROUND: Trachomatous trichiasis (TT) surgery is provided free or subsidised in most trachoma endemic settings. However, only 18-66% of TT patients attend for surgery. This study analyses barriers to attendance among TT patients in Ethiopia, the country with the highest prevalence of TT in the world. METHODOLOGY/PRINCIPAL FINDINGS: Participants with previously un-operated TT were recruited at 17 surgical outreach campaigns in Amhara Region, Ethiopia. An interview was conducted to ascertain why they had not attended for surgery previously. A trachoma eye examination was performed by an ophthalmologist. 2591 consecutive individuals were interviewed. The most frequently cited barriers to previous attendance for surgery were lack of time (45.3%), financial constraints (42.9%) and lack of an escort (35.5% in females, 19.6% in males). Women were more likely to report a fear of surgery (7.7% vs 3.2%, p<0.001) or be unaware of how to access services (4.5% vs 1.0% p<0.001); men were more frequently asymptomatic (19.6% vs 10.1%, p<0.001). Women were also less likely to have been previously offered TT surgery than men (OR = 0.70, 95%CI 0.53-0.94). CONCLUSIONS/SIGNIFICANCE: The major barriers to accessing surgery from the patients' perspective are the direct and indirect costs of surgery. These can to a large extent be reduced or overcome through the provision of free or low cost surgery at the community level. TRIAL REGISTRATION: ClinicalTrials.gov NCT00522860 and NCT00522912

Cross-genetic determination of maternal and neonatal immune mediators during pregnancy.

BACKGROUND:The immune system plays a fundamental role in development during pregnancy and early life. Alterations in circulating maternal and neonatal immune mediators have been associated with pregnancy complications as well as susceptibility to autoimmune and neurodevelopmental conditions in later life. Evidence suggests that the immune system in adults not only responds to environmental stimulation but is also under strong genetic control. METHODS:This is the first genetic study of &gt; 700 mother-infant pairs to analyse the circulating levels of 22 maternal mid-gestational serum-derived and 42 neonatal bloodspot-derived immune mediators (cytokines/chemokines) in the context of maternal and fetal genotype. We first estimated the maternal and fetal genome-wide SNP-based heritability (h2g) for each immune molecule and then performed genome-wide association studies (GWAS) to identify specific loci contributing to individual immune mediators. Finally, we assessed the relationship between genetic immune determinants and ASD outcome. RESULTS:We show maternal and neonatal cytokines/chemokines displaying genetic regulation using independent methodologies. We demonstrate that novel fetal loci for immune function independently affect the physiological levels of maternal immune mediators and vice versa. The cross-associated loci are in distinct genomic regions compared with individual-specific immune mediator loci. Finally, we observed an interaction between increased IL-8 levels at birth, autism spectrum disorder (ASD) status, and a specific maternal genotype. CONCLUSIONS:Our results suggest that maternal and fetal genetic variation influences the immune system during pregnancy and at birth via distinct mechanisms and that a better understanding of immune factor determinants in early development may shed light on risk factors for developmental disorders

Three-Dimensional Spheroid Cell Model of In Vitro Adipocyte Inflammation

To improve treatment of obesity, a contributing factor to multiple systemic and metabolic diseases, a better understanding of metabolic state and environmental stress at the cellular level is essential. This work presents development of a three-dimensional (3D) in vitro model of adipose tissue displaying induced lipid accumulation as a function of fatty acid supplementation that, subsequently, investigates cellular responses to a pro-inflammatory stimulus, thereby recapitulating key stages of obesity progression. Three-dimensional spheroid organization of adipose cells was induced by culturing 3T3-L1 mouse preadipocytes on an elastin-like polypeptide-polyethyleneimine (ELP-PEI)-coated surface. Results indicate a more differentiated phenotype in 3D spheroid cultures relative to two-dimensional (2D) monolayer analogues based on triglyceride accumulation, CD36 and CD40 protein expression, and peroxisome proliferator-activated receptor-? (PPAR-?) and adiponectin mRNA expression. The 3T3-L1 adipocyte spheroid model was then used to test the effects of a pro-inflammatory microenvironment, namely maturation in the presence of elevated fatty acid levels followed by acute exposure to tumor necrosis factor alpha (TNF-α). Under these conditions, we demonstrate that metabolic function was reduced across all cultures exposed to TNF-α, especially so when pre-exposed to linoleic acid. Further, in response to TNF-α, enhanced lipolysis, monitored as increased extracellular glycerol and fatty acids levels, was observed in adipocytes cultured in the presence of exogenous fatty acids. Taken together, our 3D spheroid model showed enhanced adipogenic differentiation and presents a platform for elucidating the key phenotypic responses that occur in pro-inflammatory microenvironments that characterize obesogenic states.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/140235/1/ten.tea.2014.0531.pd

Relationships among classifications of ayurvedic medicine diagnostics for imbalances and western measures of psychological states: An exploratory study.

BackgroundAccording to Ayurveda, the traditional medical system of India, doshas are a combination of characteristics based on a five-element philosophy that drive our mental and physical tendencies. When the doshas, or functional principles, are out of balance in quality or quantity, wellbeing is adversely affected and symptoms manifest.ObjectiveThis study examined relationships among imbalances in the doshas (termed Vikruti) reported via questionnaire and Western measures of psychological states.Materials and methodsStudy participants were 101 women (n = 81) and men (n = 20), mean age 53.9 years (SD = 11.7; range 32-80). Participants completed questionnaires to categorize their Vikruti type and psychological states, which included depressed mood (CESD), anxiety (PROMIS), rumination &amp; reflection (RRQ), mindfulness (MAAS), stress (PSS), and quality of life (Ryff).ResultsMultivariate general linear modeling, controlling for age, gender and body mass index (BMI), showed that Vata imbalance was associated with more anxiety (p ≤ 0.05), more rumination (p ≤ 0.01), less mindfulness (p ≤ 0.05), and lower overall quality of life (p ≤ 0.01). Pitta imbalance was associated with poorer mood (p ≤ 0.01) and less mindfulness (p ≤ 0.05), more anxiety (p ≤ 0.05) and stress (p ≤ 0.05). Kapha imbalance was associated with more stress (p ≤ 0.05), more rumination (p ≤ 0.05) and less reflection (p ≤ 0.05).ConclusionThese findings suggest that symptoms of mind-body imbalances in Ayurveda are differentially associated with western assessments of psychological states. Ayurvedic dosha assessment may be an effective way to assess physical as well as emotional wellbeing in research and clinical settings

Aureobacterium resistens sp. nov., exhibiting vancomycin resistance and teicoplanin susceptibility

Two similar strains of a coryneform bacterium were isolated from human clinical material. Both strains were resistant to vancomycin but susceptible to teicoplanin. Detailed biochemical, chemotaxonomical, and molecular genetic investigations revealed that both isolates were members of a hitherto undescribed species of the genus Aureobacterium. The name Aureobacterium resistens sp. nov. is proposed for the new bacterium and the type strain is CCUG 3831

Student Performance In Upper-Division Business Core Courses: Using Control Variables To Determine The Effect Of Class Size

Although the effect of class size upon student performance has been the focus of numerous studies, the results have been extremely mixed, including positive effects, no effects, and negative effects.&nbsp; The authors of this study believe that this lack of consensus could be due, at least in part, to the shortage of control variables employed in previous studies. &nbsp;The purpose of this study was to determine whether the addition of four control variables (course being taught, length of class period, instructor, and student ability level) to the analysis would be helpful in isolating the effect, if any, of class size upon student performance. &nbsp;To more fully explore the effects of including control variables upon the results, the control variables would be added sequentially, one at a time.&nbsp; The analysis would thus consist of a series of five regression sets.&nbsp; The first set would be a single, simple regression of student performance on class size.&nbsp; The second and subsequent sets would each consist of a group of simple regressions that controlled for one, two, three, and then finally all four of the control variables.&nbsp; The data to be used would be 113,468 course grade records (for the years 1990-2002) for 10 upper-division business core courses. Student performance would be defined as course grade; class size would be defined as either large (75 or more students) or small (60 or fewer students).&nbsp; The results showed that an initial slightly positive effect (.06 grade points) of class size on student performance (found in the Regression Set 1 before the addition of any control variables) changed substantially to 4 positive effects, 57 no effects, and 21 negative effects (after the addition of all four control variables in Regression Set 5).&nbsp; The Adjusted R-Squares also increased (from a rounded value of .000 in Regression Set 1 to a high of .428 in Regression Set 5) as did the grade point differences in performance between small and large classes (from .06 grade points in Regression Set 1 to a range of from .68 to -1.24 grade points in Regression Set 5).&nbsp; Although more research is certainly needed in this area before definitive conclusions can be reached about the effect of class size upon student performance, it appears that the control variable approach used in this study does shed some light on the seemingly inconsistent results of previous studies.&nbsp; Specifically, our results show that: (1) it quite likely (57/82 or 70%) that there will be no significant effect of class size upon student performance, (2) if there is an effect, it will most likely (21/25 or 84%) be a negative one, and (3) the effect, if any, is highly dependent upon the specific combination of course, class length, instructor, and student ability level involved