On-Body Channel Measurement Using Wireless Sensors

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Folding Pathways of Prion and Doppel

The relevance of various residue positions for the stability and the folding characteristics of the prion protein are investigated by using molecular dynamics simulations of models exploiting the topology of the native state. Highly significant correlations are found between the most relevant sites in our analysis and the single point mutations known to be associated with the arousal of the genetic forms of prion disease (caused by the conformational change from the cellular to the scrapie isoform). Considerable insight into the conformational change is provided by comparing the folding process of prion and doppel (a newly discovered protein) sharing very similar native state topology: the folding pathways of the former can be grouped in two main classes according to which tertiary structure contacts are formed first enroute to the native state. For the latter a single class of pathways leads to the native state. Our results are consistent and supportive of the recent experimental findings that doppel lacks the scrapie isoform and that such remarkably different behavior results from differences in the region containing the two $\beta-$strands and the intervening helix.Comment: 16 pages, 2 tables, 5 figure

Cerebrospinal Fluid Cortisol Mediates Brain-Derived Neurotrophic Factor Relationships to Mortality after Severe TBI: A Prospective Cohort Study

Distinct regulatory signaling mechanisms exist between cortisol and brain derived neurotrophic factor (BDNF) that may influence secondary injury cascades associated with traumatic brain injury (TBI) and predict outcome. We investigated concurrent CSF BDNF and cortisol relationships in 117 patients sampled days 0–6 after severe TBI while accounting for BDNF genetics and age. We also determined associations between CSF BDNF and cortisol with 6-month mortality. BDNF variants, rs6265 and rs7124442, were used to create a gene risk score (GRS) in reference to previously published hypothesized risk for mortality in “younger patients” (<48 years) and hypothesized BDNF production/secretion capacity with these variants. Group based trajectory analysis (TRAJ) was used to create two cortisol groups (high and low trajectories). A Bayesian estimation approach informed the mediation models. Results show CSF BDNF predicted patient cortisol TRAJ group (P = 0.001). Also, GRS moderated BDNF associations with cortisol TRAJ group. Additionally, cortisol TRAJ predicted 6-month mortality (P = 0.001). In a mediation analysis, BDNF predicted mortality, with cortisol acting as the mediator (P = 0.011), yielding a mediation percentage of 29.92%. Mediation effects increased to 45.45% among younger patients. A BDNF*GRS interaction predicted mortality in younger patients (P = 0.004). Thus, we conclude 6-month mortality after severe TBI can be predicted through a mediation model with CSF cortisol and BDNF, suggesting a regulatory role for cortisol with BDNF's contribution to TBI pathophysiology and mortality, particularly among younger individuals with severe TBI. Based on the literature, cortisol modulated BDNF effects on mortality after TBI may be related to known hormone and neurotrophin relationships to neurological injury severity and autonomic nervous system imbalance

The hierarchical build-up of the Tully-Fisher relation

We use the semi-analytic model GalICS to predict the Tully-Fisher relation in the B, I and for the first time, in the K band, and its evolution with redshift, up to z~1. We refined the determination of the disk galaxies rotation velocity, with a dynamical recipe for the rotation curve, rather than a simple conversion from the total mass to maximum velocity. The new recipe takes into account the disk shape factor, and the angular momentum transfer occurring during secular evolution leading to the formation of bulges. This produces model rotation velocities that are lower by ~20-25% for the majority of the spirals. We implemented stellar population models with a complete treatment of the TP-AGB, which leads to a revision of the mass-to-light ratio in the near-IR. I/K band luminosities increase by ~0.3/0.5 mags at redshift z=0 and by ~0.5/1 mags at z=3. With these two new recipes in place, the comparison between the predicted Tully-Fisher relation with a series of datasets in the optical and near-IR, at redshifts between 0 and 1, is used as a diagnostics of the assembly and evolution of spiral galaxies in the model. At 0.4<z<1.2 the match between the new model and data is remarkably good, especially for later-type spirals (Sb/Sc). At z=0 the new model shows a net improvement in comparison with its original version of 2003, and in accord with recent observations in the K band, the model Tully-Fisher also shows a morphological differentiation. However, in all bands the z=0 model Tully-Fisher is too bright. We argue that this behaviour is caused by inadequate star formation histories in the model galaxies at low redshifts. The star-formation rate declines too slowly, due to continuous gas infall that is not efficiently suppressed. An analysis of the model disk scale lengths, at odds with observations, hints to some missing physics in the modeling of disk formation inside dark matter halos.Comment: Accepted for publication on MNRAS. 2 new plots, 1 new section, and extended discussion. 21 pages, 11 figures in tota

Mesothelial cell differentiation into osteoblast- and adipocyte-like cells

Serosal pathologies including malignant mesothelioma (MM) can show features of osseous and/or cartilaginous differentiation although the mechanism for its formation is unknown. Mesothelial cells have the capacity to differentiate into cells with myofibroblast, smooth muscle and endothelial cell characteristics. Whether they can differentiate into other cell types is unclear. This study tests the hypothesis that mesothelial cells can differentiate into cell lineages of the embryonic mesoderm including osteoblasts and adipocytes. To examine this, a functional assay of bone formation and an adipogenic assay were performed in vitro with primary rat and human mesothelial cells maintained in osteogenic or adipogenic medium (AM) for 0–26 days. Mesothelial cells expressed increasing levels of alkaline phosphatase, an early marker of the osteoblast phenotype, and formed mineralized bone-like nodules. Mesothelial cells also accumulated lipid indicative of a mature adipocyte phenotype when cultured in AM. All cells expressed several key osteoblast and adipocyte markers, including osteoblast-specific runt-related transcription factor 2, and demonstrated changes in mRNA expression consistent with epithelial-to-mesenchymal transition. In conclusion, these studies confirm that mesothelial cells have the capacity to differentiate into osteoblast- and adipocyte-like cells, providing definitive evidence of their multipotential nature. These data strongly support mesothelial cell differentiation as the potential source of different tissue types in MM tumours and other serosal pathologies, and add support for the use of mesothelial cells in regenerative therapies

Engineering Rhodosporidium toruloides for production of 3-hydroxypropionic acid from lignocellulosic hydrolysate

Microbial production of valuable bioproducts is a promising route towards green and sustainable manufacturing. The oleaginous yeast, Rhodosporidium toruloides, has emerged as an attractive host for the production of biofuels and bioproducts from lignocellulosic hydrolysates. 3-hydroxypropionic acid (3HP) is an attractive platform molecule that can be used to produce a wide range of commodity chemicals. This study focuses on establishing and optimizing the production of 3HP in R. toruloides. As R. toruloides naturally has a high metabolic flux towards malonyl-CoA, we exploited this pathway to produce 3HP. Upon finding the yeast capable of catabolizing 3HP, we then implemented functional genomics and metabolomic analysis to identify the catabolic pathways. Deletion of a putative malonate semialdehyde dehydrogenase gene encoding an oxidative 3HP pathway was found to significantly reduce 3HP degradation. We further explored monocarboxylate transporters to promote 3HP transport and identified a novel 3HP transporter in Aspergillus pseudoterreus by RNA-seq and proteomics. Combining these engineering efforts with media optimization in a fed-batch fermentation resulted in 45.4&nbsp;g/L 3HP production. This represents one of the highest 3HP titers reported in yeast from lignocellulosic feedstocks. This work establishes R. toruloides as a host for 3HP production from lignocellulosic hydrolysate at high titers, and paves the way for further strain and process optimization towards enabling industrial production of 3HP in the future

TGF-β1 Exerts Opposing Effects on Grass Carp Leukocytes: Implication in Teleost Immunity, Receptor Signaling and Potential Self-Regulatory Mechanisms

In fish immunity, the regulatory role of transforming growth factor-β1 (TGF-β1) has not been fully characterized. Here we examined the immunoregulatory effects of TGF-β1 in grass carp peripheral blood leukocytes (PBL) and head kidney leukocytes (HKL). It is interesting that TGF-β1 consistently stimulated the cell viability and the mRNA levels of pro-inflammatory cytokines (Tnfα and Ifnγ) and T/B cell markers [Cd4-like (Cd4l), Cd8α, Cd8β and Igμ] in PBL, which contrasted with its inhibitory tone in HKL. Further studies showed that grass carp TGF-β1 type I receptor, activin receptor-like kinase 5 (ALK5), was indispensable for the immunoregulatory effects of TGF-β1 in PBL and HKL. Notably, TGF-β1 persistently attenuated ALK5 expression, whereas immunoneutralization of endogenous grass carp TGF-β1 could increase ALK5 mRNA and protein levels. It is consistent with the observation that TGF-β1 decreased the number of ALK5+ leukocytes in PBL and HKL, revealing a negative regulation of TGF-β1 signaling at the receptor level. Moreover, transient treatment with TGF-β1 for 24 h was sufficient to induce similar cellular responses compared with the continuous treatment. This indicated a possible mechanism by which TGF-β1 triggered the down-regulation of ALK5 mRNA and protein, leading to the desensitization of grass carp leukocytes toward TGF-β1. Accordingly, our data revealed a dual role of TGF-β1 in teleost immunity in which it can serve as a positive or negative control device and provided additional mechanistic insights as to how TGF-β1 controls its signaling in vertebrate leukocytes

Deep exclusive π+\pi^+ electroproduction off the proton at CLAS

The exclusive electroproduction of $\pi^+$ above the resonance region was studied using the $\rm{CEBAF}$ Large Acceptance Spectrometer ($\rm{CLAS}$) at Jefferson Laboratory by scattering a 6 GeV continuous electron beam off a hydrogen target. The large acceptance and good resolution of $\rm{CLAS}$, together with the high luminosity, allowed us to measure the cross section for the $\gamma^* p \to n \pi^+$ process in 140 ($Q^2$, $x_B$, $t$) bins: $0.16<x_B<0.58$, 1.6 GeV$^2<$$Q^2$$<4.5$ GeV$^2$ and 0.1 GeV$^2<$$-t$$<5.3$ GeV$^2$. For most bins, the statistical accuracy is on the order of a few percent. Differential cross sections are compared to two theoretical models, based either on hadronic (Regge phenomenology) or on partonic (handbag diagram) degrees of freedom. Both can describe the gross features of the data reasonably well, but differ strongly in their ingredients. If the handbag approach can be validated in this kinematical region, our data contain the interesting potential to experimentally access transversity Generalized Parton Distributions.Comment: 18pages, 21figures,2table