Structure and function of the external ciliation of larval bivalves with different life history strategies

Cilia are of particular importance to the planktonic veliger larva, fulfilling feeding, locomotory and sensory roles. This study concentrates on the ciliation of the larval mantle and velum. The mantle is an important adult organ yet one scarcely studied in the larval form. The larval velum is the characteristic swimming and feeding organ of the veliger larval form. Knowledge of the ciliary arrangement of larval bivalves, especially in relation to different life history strategies, provides important information for arguments over the phylogeny of such characteristics within the Mollusca. Anatomical work explored the possibility of ciliary sense organs being found on the mantle and further elucidates the pattern of distribution of cilia on the velum. Larval ciliary swimming in varying water temperatures has been investigated via the development of a filming methodology, revealing the thermal tolerance of swimming using velar ciliation and the ability of the larva to detect and respond to temperature stimuli. Cilia were investigated throughout larval development from veliger stage to metamorphosis in two bivalve families, the Ostreidae (Crassostrea gigas and Ostrea edulis) and the Teredinidae (Lyrodus pedicellatus). The three larvae represented three developmental modes with C. gigas planktonic, O. edulis partly brooded and L. pedicellatus long-term brooded. Scanning electron microscopy (SEM) and light microscopy was used for anatomical investigations. Confocal laser scanning microscopy was used to locate catecholamines and serotonin in C. gigas larvae, with reference to the cilia locations identified by SEM. Swimming larvae were filmed in fixed and changing temperatures to identify behavioural or physiological reactions. The mantle of the ostreid larvae had 13 different cilia groups which have been identified and photographed in C. gigas and O. edulis. Two of these groups appear to be sensory. One group is associated with the developing gill bud, and the other is located directly under the posterodorsal shell notch. The location of this group under the shell notch also was the location for several cells containing catecholamines. The ventral inner mantle rim of ostreid larvae has large tracts of cilia, probably primitive larval versions of adult rejection tracts. There were several flask-shaped cells with catecholamines and two long serotonin containing fibres in the mantle where these tracts were found. The mantle of L. pedicellatus had 2 distinct groups of cilia. One of these groups formed discrete clumps on the inner mantle fold and featured sensory structures. The velar ciliation of both the ostreid species larvae was almost identical, and both revealed a previously unreported band of cilia. This band may increase the efficiency of the opposed band particle capture system. The velum of L. pedicellatus was different from the ostreid larvae; its velar ciliature was similar to other long-term brooded larvae recorded in the literature with a large adoral tract and the loss of the post-oral band. Larval swimming velocity increased with increasing water temperature. Acclimated larvae were able to swim in water temperatures where larval activity stopped during sudden temperature changes. Changes in larval swimming during sudden temperature changes are probably due to an interaction of three factors: water viscosity changes affecting cilia efficiency, the physiological effect of temperature and behavioural responses. The additional ciliary band on the ostreid velum probably increases particle capture efficiency, and further investigations are needed to determine if this is a characteristic unique to the ostreids. The velar ciliation of the brooded L. pedicellatus is, by the pediveliger stage, similarly modified to the velum of other brooded larvae from widely separated taxonomic groups. Mantle ciliation is more extensive in ostreids than in teredinids, but both have sensory stereocilia on the mantle. The presence of catecholamines and serotonin suggests that the larva has a measure of control both of mantle and velar ciliary beat, seen in the variation in swimming patterns and particle rejection. The filming and analytical techniques developed offer an accessible method for gathering laboratory data on larval behaviours. Analysis of swimming suggested larvae can sense changes in temperature and effect a behavioural response to it. Such responses may enable larvae to control their vertical position in the water column when encountering environmental discontinuities or heterogeneities such as thermoclines. Variation in larval swimming velocity between larval batches suggests this method could also be used as a quick assay to determine the fitness of different larval batches within a hatchery.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Cumulative effects of heat exposure and storage conditions of Oxytocin-in-Uniject in rural Ghana: implications for scale up.

OBJECTIVE: Postpartum hemorrhage can be reduced substantially in home deliveries attended by community-based workers by using Oxytocin-in-Uniject (OIU) devices affixed with temperature-time indicators. We characterized the distribution of time to discard of these devices when stored under normal field conditions in Ghana. METHODS: Two drug storage simulation studies were conducted in rural Ghana in 2011 and 2012. Devices were transported under refrigeration from manufacture (Argentina) to storage at the study site. Twenty-three field workers each stored at home (unrefrigerated) 25 OIU devices and monitored them daily to record: (1) time to transition from usable to unusable, and (2) continuous digital ambient temperature to determine heat exposure over the simulation period. Time to discard was estimated and compared with mean kinetic temperature exposure of the devices during the shipment and storage phases and with characteristics of the storage locations using Weibull regression models. We used the time to discard distributions in a Monte Carlo simulation to estimate wastage rates in a hypothetical program setting. RESULTS: Time for shipment and transfer to long-term refrigerated storage and mean kinetic temperature during the shipment phase was 8.6 days/10.3°C and 13.4 days/12.1°C, for the first and second simulation studies, respectively. Median (range) time to discard when stored under field conditions (unrefrigerated) was 43 (6 to 59) days and 33 (14 to 50) days, respectively. Mean time to discard was 10.0 days shorter in the second simulation, during which mean kinetic temperature exposure was 3.9°C higher. Simulating a monthly distribution system and assuming typical usage, predicted wastage of product was less than 10%. CONCLUSION: The time to discard of devices was highly sensitive to small changes in temperature exposure. Under field conditions typical in rural Ghana, OIU packages will have a half-life of approximately 30 to 40 days based on the temperature monitor used during the study. Program managers will need to carefully consider variations in both ambient temperature and rate of use to allocate the appropriate supply level that will maximize coverage and minimize stock loss

Design, analysis, and feedback control of a nonlinear micro-piezoelectric–electrostatic energy harvester

A nonlinear micro-piezoelectric–electrostatic energy harvester is designed and studied using mathematical and computational methods. The system consists of a cantilever beam substrate, a bimorph piezoelectric transducer, a pair of tuning parallel-plate capacitors, and a tip–mass. The governing nonlinear mathematical model of the electro-mechanical system including nonlinear material and quadratic air-damping is derived for the series connection of the piezoelectric layers. The static and modal frequency curves are computed to optimize the operating point, and a parametric study is performed using numerical methods. A bias DC voltage is used to adapt the system to resonate with respect to the frequency of external vibration. Furthermore, to improve the bandwidth and performance of the harvester (and achieve a high level of harvested power without sacrificing the bandwidth), a nonlinear feedback loop is integrated into the design

Adjuvant Effect of Orally Applied Preparations Containing Non-Digestible Polysaccharides on Influenza Vaccination in Healthy Seniors: A Double-Blind, Randomised, Controlled Pilot Trial.

Senior individuals can suffer from immunosenescence and novel strategies to bolster the immune response could contribute to healthy ageing. In this double-blind, randomised, controlled pilot trial, we investigated the ability of non-digestible polysaccharide (NPS) preparations to enhance the immune response in a human vaccination model. In total, 239 subjects (aged 50-79 years) were randomised to consume one of five different NPS (yeast β-glucan (YBG), shiitake β-glucan (SBG), oat β-glucan (OBG), arabinoxylan (AX), bacterial exopolysaccharide (EPS)) or control (CTRL) product daily for five weeks. After two weeks of intervention, subjects were vaccinated with seasonal influenza vaccine. The post-vaccination increases in haemagglutination inhibition antibody titres and seroprotection rate against the influenza strains were non-significantly enhanced in the NPS intervention groups compared to CTRL. Specifically, a trend towards a higher mean log2 fold increase was observed in the AX group (uncorrected p = 0.074) combined with a trend for an increased seroprotection rate, AX group (48.7%) compared to CTRL (25.6%) (uncorrected p = 0.057), for the influenza A H1N1 strain. Subjects consuming AX also had a reduced incidence of common colds compared to CTRL (1 vs. 8; p = 0.029 in Fisher exact test). No adverse effects of NPS consumption were reported. The findings of this pilot study warrant further research to study AX as an oral adjuvant to support vaccine efficacy

Excess Pressure Integral Predicts Cardiovascular Events Independent of Other Risk Factors in the Conduit Artery Functional Evaluation Substudy of Anglo-Scandinavian Cardiac Outcomes Trial

Excess pressure integral (XSPI), a new index of surplus work performed by the left ventricle, can be calculated from blood pressure waveforms and may indicate circulatory dysfunction. We investigated whether XSPI predicted future cardiovascular events and target organ damage in treated hypertensive individuals. Radial blood pressure waveforms were acquired by tonometry in 2069 individuals (aged, 63±8 years) in the Conduit Artery Functional Evaluation (CAFE) substudy of the Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT). Measurements of left ventricular mass index (n=862) and common carotid artery intima media thickness (n=923) were also performed. XSPI and the integral of reservoir pressure were lower in people treated with amlodipine±perindopril than in those treated with atenolol±bendroflumethiazide, although brachial systolic blood pressure was similar. A total of 134 cardiovascular events accrued during a median 3.4 years of follow-up; XSPI was a significant predictor of cardiovascular events after adjustment for age and sex, and this relationship was unaffected by adjustment for conventional cardiovascular risk factors or Framingham risk score. XSPI, central systolic blood pressure, central augmentation pressure, central pulse pressure, and integral of reservoir pressure were correlated with left ventricular mass index, but only XSPI, augmentation pressure, and central pulse pressure were associated positively with carotid artery intima media thickness. Associations between left ventricular mass index, XSPI, and integral of reservoir pressure and carotid artery intima media thickness and XSPI were unaffected by multivariable adjustment for other covariates. XSPI is a novel indicator of cardiovascular dysfunction and independently predicts cardiovascular events and targets organ damage in a prospective clinical trial

A geospatial analysis of local intermediate snail host distributions provides insight into schistosomiasis risk within under-sampled areas of southern Lake Malawi

Background: Along the southern shoreline of Lake Malawi, the incidence of schistosomiasis is increasing with snails of the genera Bulinus and Biomphalaria transmitting urogenital and intestinal schistosomiasis, respectively. Since the underlying distribution of snails is partially known, often being focal, developing pragmatic spatial models that interpolate snail information across under-sampled regions is required to understand and assess current and future risk of schistosomiasis. Methods: A secondary geospatial analysis of recently collected malacological and environmental survey data was undertaken. Using a Bayesian Poisson latent Gaussian process model, abundance data were fitted for Bulinus and Biomphalaria. Interpolating the abundance of snails along the shoreline (given their relative distance along the shoreline) was achieved by smoothing, using extracted environmental rainfall, land surface temperature (LST), evapotranspiration, normalised difference vegetation index (NDVI) and soil type covariate data for all predicted locations. Our adopted model used a combination of two-dimensional (2D) and one dimensional (1D) mapping. Results: A significant association between normalised difference vegetation index (NDVI) and abundance of Bulinus spp. was detected (log risk ratio − 0.83, 95% CrI − 1.57, − 0.09). A qualitatively similar association was found between NDVI and Biomphalaria sp. but was not statistically significant (log risk ratio − 1.42, 95% CrI − 3.09, 0.10). Analyses of all other environmental data were considered non-significant. Conclusions: The spatial range in which interpolation of snail distributions is possible appears < 10km owing to fine-scale biotic and abiotic heterogeneities. The forthcoming challenge is to refine geospatial sampling frameworks with future opportunities to map schistosomiasis within actual or predicted snail distributions. In so doing, this would better reveal local environmental transmission possibilities

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin

Spatial Organization and Molecular Correlation of Tumor-Infiltrating Lymphocytes Using Deep Learning on Pathology Images

Beyond sample curation and basic pathologic characterization, the digitized H&E-stained images of TCGA samples remain underutilized. To highlight this resource, we present mappings of tumorinfiltrating lymphocytes (TILs) based on H&E images from 13 TCGA tumor types. These TIL maps are derived through computational staining using a convolutional neural network trained to classify patches of images. Affinity propagation revealed local spatial structure in TIL patterns and correlation with overall survival. TIL map structural patterns were grouped using standard histopathological parameters. These patterns are enriched in particular T cell subpopulations derived from molecular measures. TIL densities and spatial structure were differentially enriched among tumor types, immune subtypes, and tumor molecular subtypes, implying that spatial infiltrate state could reflect particular tumor cell aberration states. Obtaining spatial lymphocytic patterns linked to the rich genomic characterization of TCGA samples demonstrates one use for the TCGA image archives with insights into the tumor-immune microenvironment