Iron content of ferritin modulates its uptake by intestinal epithelium: implications for co-transport of prions

The spread of Chronic Wasting Disease (CWD) in the deer and elk population has caused serious public health concerns due to its potential to infect farm animals and humans. Like other prion disorders such a sporadic Creutzfeldt-Jakob-disease of humans and Mad Cow Disease of cattle, CWD is caused by PrP-scrapie (PrPSc), a β-sheet rich isoform of a normal cell surface glycoprotein, the prion protein (PrPC). Since PrPSc is sufficient to cause infection and neurotoxicity if ingested by a susceptible host, it is important to understand the mechanism by which it crosses the stringent epithelial cell barrier of the small intestine. Possible mechanisms include co-transport with ferritin in ingested food and uptake by dendritic cells. Since ferritin is ubiquitously expressed and shares considerable homology among species, co-transport of PrPSc with ferritin can result in cross-species spread with deleterious consequences. We have used a combination of in vitro and in vivo models of intestinal epithelial cell barrier to understand the role of ferritin in mediating PrPSc uptake and transport. In this report, we demonstrate that PrPSc and ferritin from CWD affected deer and elk brains and scrapie from sheep resist degradation by digestive enzymes, and are transcytosed across a tight monolayer of human epithelial cells with significant efficiency. Likewise, ferritin from hamster brains is taken up by mouse intestinal epithelial cells in vivo, indicating that uptake of ferritin is not limited by species differences as described for prions. More importantly, the iron content of ferritin determines its efficiency of uptake and transport by Caco-2 cells and mouse models, providing insight into the mechanism(s) of ferritin and PrPSc uptake by intestinal epithelial cells

Local anesthetics induce autophagy in young permanent tooth pulp cells

Pulp cells are essential for tooth development, and dentin repair and regeneration. In addition these cells have been identified as an important stem cell source. Local anesthetics are widely used in dental clinics, as well as the other clinical disciplines and have been suggested to interfere with human permanent tooth development and induce tooth agenesis through unknown mechanisms. Using pig model and human young permanent tooth pulp cells, our research has identified that the local anesthetics commonly used in clinics can affect cell proliferation. Molecular pathway profiling suggested that LC3II is one of the earliest molecules induced by the agents and p62 is the only common downstream target identified for all the drugs tested. The effect of the drugs could be partially recovered by V-ATPase inhibitor only if early intervention is performed. Our results provide novel evidence that local anesthetics could affect tooth cell growth that potentially can have impacts on tooth development

Metamodel-assisted design optimization of piezoelectric flex transducer for maximal bio-kinetic energy conversion

Energy Harvesting Devices (EHD) have been widely used to generate electrical power from the bio-kinetic energy of human body movement. A novel Piezoelectric Flex Transducer (PFT) based on the Cymbal device has been proposed by Daniels et al. (2013) for the purpose of energy harvesting. To further improve the efficiency of the device, optimal design of the PFT for maximum output power subject to stress and displacement constraints is carried out in this paper. Sequential Quadratic Programming (SQP) on metamodels generated with Genetic Programming from a 140-point optimal Latin hypercube design of experiments is used in the optimization. Finally, the optimal design is validated by finite element simulations. The simulations show that the magnitude of the electrical power generated from this optimal PFT harvesting device can be up to 6.5 mw when a safety design factor of 2.0 is applied

Prevalence of Oral Pain and Barriers to use of Emergency Oral Care Facilities Among Adult Tanzanians.

Oral pain has been the major cause of the attendances in the dental clinics in Tanzania. Some patients postpone seeing the dentist for as long as two to five days. This study determines the prevalence of oral pain and barriers to use of emergency oral care in Tanzania. Questionnaire data were collected from 1,759 adult respondents aged 18 years and above. The study area covered six urban and eight rural study clusters, which had been selected using the WHO Pathfinder methodology. Chi-square tests and logistic regression analyses were performed to identify associations.\ud Forty two percent of the respondents had utilized the oral health care facilities sometimes in their lifetime. About 59% of the respondents revealed that they had suffered from oral pain and/or discomfort within the twelve months that preceded the study, but only 26.5% of these had sought treatment from oral health care facilities. The reasons for not seeking emergency care were: lack of money to pay for treatment (27.9%); self medication (17.6%); respondents thinking that pain would disappear with time (15.7%); and lack of money to pay for transport to the dental clinic (15.0%). Older adults were more likely to report that they had experienced oral pain during the last 12 months than the younger adults (OR = 1.57, CI 1.07-1.57, P < 0.001). Respondents from rural areas were more likely report dental clinics far from home (OR = 5.31, CI = 2.09-13.54, P < 0.001); self medication at home (OR = 3.65, CI = 2.25-5.94, P < 0.001); and being treated by traditional healer (OR = 5.31, CI = 2.25-12.49, P < 0.001) as reasons for not seeking emergency care from the oral health care facilities than their counterparts from urban areas. Oral pain and discomfort were prevalent among adult Tanzanians. Only a quarter of those who experienced oral pain or discomfort sought emergency oral care from oral health care facilities. Self medication was used as an alternative to using oral care facilities mainly by rural residents. Establishing oral care facilities in rural areas is recommended

Intra- and inter-individual genetic differences in gene expression

Genetic variation is known to influence the amount of mRNA produced by a gene. Given that the molecular machines control mRNA levels of multiple genes, we expect genetic variation in the components of these machines would influence multiple genes in a similar fashion. In this study we show that this assumption is correct by using correlation of mRNA levels measured independently in the brain, kidney or liver of multiple, genetically typed, mice strains to detect shared genetic influences. These correlating groups of genes (CGG) have collective properties that account for 40-90% of the variability of their constituent genes and in some cases, but not all, contain genes encoding functionally related proteins. Critically, we show that the genetic influences are essentially tissue specific and consequently the same genetic variations in the one animal may up-regulate a CGG in one tissue but down-regulate the same CGG in a second tissue. We further show similarly paradoxical behaviour of CGGs within the same tissues of different individuals. The implication of this study is that this class of genetic variation can result in complex inter- and intra-individual and tissue differences and that this will create substantial challenges to the investigation of phenotypic outcomes, particularly in humans where multiple tissues are not readily available.&#xd;&#xa;&#xd;&#xa

Ultrahard carbon film from epitaxial two-layer graphene

Atomically thin graphene exhibits fascinating mechanical properties, although its hardness and transverse stiffness are inferior to those of diamond. To date, there hasn't been any practical demonstration of the transformation of multi-layer graphene into diamond-like ultra-hard structures. Here we show that at room temperature and after nano-indentation, two-layer graphene on SiC(0001) exhibits a transverse stiffness and hardness comparable to diamond, resisting to perforation with a diamond indenter, and showing a reversible drop in electrical conductivity upon indentation. Density functional theory calculations suggest that upon compression, the two-layer graphene film transforms into a diamond-like film, producing both elastic deformations and sp2-to-sp3 chemical changes. Experiments and calculations show that this reversible phase change is not observed for a single buffer layer on SiC or graphene films thicker than 3 to 5 layers. Indeed, calculations show that whereas in two-layer graphene layer-stacking configuration controls the conformation of the diamond-like film, in a multilayer film it hinders the phase transformation.Comment: Published online on Nature Nanotechnology on December 18, 201

Ecosystem Carbon Stock Influenced by Plantation Practice: Implications for Planting Forests as a Measure of Climate Change Mitigation

Uncertainties remain in the potential of forest plantations to sequestrate carbon (C). We synthesized 86 experimental studies with paired-site design, using a meta-analysis approach, to quantify the differences in ecosystem C pools between plantations and their corresponding adjacent primary and secondary forests (natural forests). Totaled ecosystem C stock in plant and soil pools was 284 Mg C ha−1 in natural forests and decreased by 28% in plantations. In comparison with natural forests, plantations decreased aboveground net primary production, litterfall, and rate of soil respiration by 11, 34, and 32%, respectively. Fine root biomass, soil C concentration, and soil microbial C concentration decreased respectively by 66, 32, and 29% in plantations relative to natural forests. Soil available N, P and K concentrations were lower by 22, 20 and 26%, respectively, in plantations than in natural forests. The general pattern of decreased ecosystem C pools did not change between two different groups in relation to various factors: stand age (<25 years vs. ≥25 years), stand types (broadleaved vs. coniferous and deciduous vs. evergreen), tree species origin (native vs. exotic) of plantations, land-use history (afforestation vs. reforestation) and site preparation for plantations (unburnt vs. burnt), and study regions (tropic vs. temperate). The pattern also held true across geographic regions. Our findings argued against the replacement of natural forests by the plantations as a measure of climate change mitigation

Attention-dependent modulation of cortical taste circuits revealed by granger causality with signal-dependent noise

We show, for the first time, that in cortical areas, for example the insular, orbitofrontal, and lateral prefrontal cortex, there is signal-dependent noise in the fMRI blood-oxygen level dependent (BOLD) time series, with the variance of the noise increasing approximately linearly with the square of the signal. Classical Granger causal models are based on autoregressive models with time invariant covariance structure, and thus do not take this signal-dependent noise into account. To address this limitation, here we describe a Granger causal model with signal-dependent noise, and a novel, likelihood ratio test for causal inferences. We apply this approach to the data from an fMRI study to investigate the source of the top-down attentional control of taste intensity and taste pleasantness processing. The Granger causality with signal-dependent noise analysis reveals effects not identified by classical Granger causal analysis. In particular, there is a top-down effect from the posterior lateral prefrontal cortex to the insular taste cortex during attention to intensity but not to pleasantness, and there is a top-down effect from the anterior and posterior lateral prefrontal cortex to the orbitofrontal cortex during attention to pleasantness but not to intensity. In addition, there is stronger forward effective connectivity from the insular taste cortex to the orbitofrontal cortex during attention to pleasantness than during attention to intensity. These findings indicate the importance of explicitly modeling signal-dependent noise in functional neuroimaging, and reveal some of the processes involved in a biased activation theory of selective attention