A missing dimension in measures of vaccination impacts

Immunological protection, acquired from either natural infection or vaccination, varies among hosts, reflecting underlying biological variation and affecting population-level protection. Owing to the nature of resistance mechanisms, distributions of susceptibility and protection entangle with pathogen dose in a way that can be decoupled by adequately representing the dose dimension. Any infectious processes must depend in some fashion on dose, and empirical evidence exists for an effect of exposure dose on the probability of transmission to mumps-vaccinated hosts [1], the case-fatality ratio of measles [2], and the probability of infection and, given infection, of symptoms in cholera [3]. Extreme distributions of vaccine protection have been termed leaky (partially protects all hosts) and all-or-nothing (totally protects a proportion of hosts) [4]. These distributions can be distinguished in vaccine field trials from the time dependence of infections [5]. Frailty mixing models have also been proposed to estimate the distribution of protection from time to event data [6], [7], although the results are not comparable across regions unless there is explicit control for baseline transmission [8]. Distributions of host susceptibility and acquired protection can be estimated from dose-response data generated under controlled experimental conditions [9]–[11] and natural settings [12], [13]. These distributions can guide research on mechanisms of protection, as well as enable model validity across the entire range of transmission intensities. We argue for a shift to a dose-dimension paradigm in infectious disease science and community health

Folic acid-tagged protein nanoemulsions loaded with CORM-2 enhance the survival of mice bearing subcutaneous A20 lymphoma tumors.

UNLABELLED: Folic Acid (FA)-tagged protein nanoemulsions were found to be preferentially internalized on B-cell lymphoma cell line (A20 cell line), which, for the first time, is reported to express folate receptor (FR)-alpha. Carbon monoxide releasing molecule-2 (CORM-2) was incorporated in the oil phase of the initial formulation. FA-functionalized nanoemulsions loaded with CORM-2 exhibited a considerable antitumor effect and an increased survival of BALB/c mice bearing subcutaneous A20 lymphoma tumors. The developed nanoemulsions also demonstrated to be well tolerated by these immunocompetent mice. Thus, the results obtained in this study demonstrate that FA-tagged protein nanoemulsions can be successfully used in cancer therapy, with the important ability to delivery drugs intracellularly. FROM THE CLINICAL EDITOR: In this research, the authors developed folic acid tagged nanoemulsions containing a carbon monoxide releasing protein molecule for targeted cancer cell treatment. In-vitro and in-vivo experiments showed efficacy against B-cell lymphoma cells. The same nanocarrier platform could be applied to other tumor cells expressing folate receptors on the cell surface.This is the author accepted manuscript. The final version is avilable via Elsevier at http://www.sciencedirect.com/science/article/pii/S1549963415000726

Simonsenia aveniformis sp nov (Bacillariophyceae), molecular phylogeny and systematics of the genus, and a new type of canal raphe system

The genus Simonsenia is reviewed and S. aveniformis described as new for science by light and electron microscopy. The new species originated from estuarine environments in southern Iberia (Atlantic coast) and was isolated into culture. In LM, Simonsenia resembles Nitzschia, with bridges (fibulae) beneath the raphe, which is marginal. It is only electron microscope (EM) examination that reveals the true structure of the raphe system, which consists of a raphe canal raised on a keel (wing), supported by rib like braces (fenestral bars) and tube-like portulae; between the portulae the keel is perforated by open windows (fenestrae). Based on the presence of portulae and a fenestrated keel, Simonsenia has been proposed to be intermediate between Bacillariaceae and Surirellaceae. However, an rbcL phylogeny revealed that Simonsenia belongs firmly in the Bacillariaceae, with which it shares a similar chloroplast arrangement, rather than in the Surirellaceae. Lack of homology between the surirelloid and simonsenioid keels is reflected in subtle differences in the morphology and ontogeny of the portulae and fenestrae. The diversity of Simonsenia has probably been underestimated, particularly in the marine environment.Polish National Science Centre in Cracow within the Maestro program [N 2012/04/A/ST10/00544]; Sciences and Technologies Foundation-FCT (Portugal) [SFRH/BD/62405/2009]info:eu-repo/semantics/publishedVersio

Electric Field-Tuned Topological Phase Transition in Ultra-Thin Na3Bi - Towards a Topological Transistor

The electric field induced quantum phase transition from topological to conventional insulator has been proposed as the basis of a topological field effect transistor [1-4]. In this scheme an electric field can switch 'on' the ballistic flow of charge and spin along dissipationless edges of the two-dimensional (2D) quantum spin Hall insulator [5-9], and when 'off' is a conventional insulator with no conductive channels. Such as topological transistor is promising for low-energy logic circuits [4], which would necessitate electric field-switched materials with conventional and topological bandgaps much greater than room temperature, significantly greater than proposed to date [6-8]. Topological Dirac semimetals(TDS) are promising systems in which to look for topological field-effect switching, as they lie at the boundary between conventional and topological phases [3,10-16]. Here we use scanning probe microscopy/spectroscopy (STM/STS) and angle-resolved photoelectron spectroscopy (ARPES) to show that mono- and bilayer films of TDS Na3Bi [3,17] are 2D topological insulators with bulk bandgaps >400 meV in the absence of electric field. Upon application of electric field by doping with potassium or by close approach of the STM tip, the bandgap can be completely closed then re-opened with conventional gap greater than 100 meV. The large bandgaps in both the conventional and quantum spin Hall phases, much greater than the thermal energy kT = 25 meV at room temperature, suggest that ultrathin Na3Bi is suitable for room temperature topological transistor operation

Evaluation of the influence of kyphosis and scoliosis on intervertebral disc extrusion in French bulldogs

Although thoracic vertebral malformations with kyphosis and scoliosis are often considered incidental findings on diagnostic imaging studies of screw-tailed brachycephalic breeds, they have been suggested to interfere with spinal biomechanics and intervertebral disc degeneration. It is however unknown if an abnormal spinal curvature also predisposes dogs to develop clinically relevant intervertebral disc herniations. The aim of this study was to evaluate if the occurrence of thoracic vertebral malformations, kyphosis or scoliosis would be associated with a higher prevalence of cervical or thoracolumbar intervertebral disc extrusion in French bulldogs

Autoinflammatory periodic fever, immunodeficiency, and thrombocytopenia (PFIT) caused by mutation in actinregulatory gene WDR1

The importance of actin dynamics in the activation of the inflammasome is becoming increasingly apparent. IL-1β, which is activated by the inflammasome, is known to be central to the pathogenesis of many monogenic autoinflammatory diseases. However, evidence from an autoinflammatory murine model indicates that IL-18, the other cytokine triggered by inflammasome activity, is important in its own right. In this model, autoinflammation was caused by mutation in the actin regulatory gene WDR1 We report a homozygous missense mutation in WDR1 in two siblings causing periodic fevers with immunodeficiency and thrombocytopenia. We found impaired actin dynamics in patient immune cells. Patients had high serum levels of IL-18, without a corresponding increase in IL-18-binding protein or IL-1β, and their cells also secreted more IL-18 but not IL-1β in culture. We found increased caspase-1 cleavage within patient monocytes indicative of increased inflammasome activity. We transfected HEK293T cells with pyrin and wild-type and mutated WDR1 Mutant protein formed aggregates that appeared to accumulate pyrin; this could potentially precipitate inflammasome assembly. We have extended the findings from the mouse model to highlight the importance of WDR1 and actin regulation in the activation of the inflammasome, and in human autoinflammation

Environmental stresses inhibit splicing in the aquatic fungus Blastocladiella emersonii

<p>Abstract</p> <p>Background</p> <p>Exposure of cells to environmental stress conditions can lead to the interruption of several intracellular processes, in particular those performed by macromolecular complexes such as the spliceosome.</p> <p>Results</p> <p>During nucleotide sequencing of cDNA libraries constructed using RNA isolated from <it>B. emersonii </it>cells submitted to heat shock and cadmium stress, a large number of ESTs with retained introns was observed. Among the 6,350 ESTs obtained through sequencing of stress cDNA libraries, 181 ESTs presented putative introns (2.9%), while sequencing of cDNA libraries from unstressed <it>B. emersonii </it>cells revealed only 0.2% of ESTs containing introns. These data indicate an enrichment of ESTs with introns in <it>B. emersonii </it>stress cDNA libraries. Among the 85 genes corresponding to the ESTs that retained introns, 19 showed more than one intron and three showed three introns, with intron length ranging from 55 to 333 nucleotides. Canonical splicing junctions were observed in most of these introns, junction sequences being very similar to those found in introns from genes previously characterized in <it>B. emersonii</it>, suggesting that inhibition of splicing during stress is apparently a random process. Confirming our observations, analyses of <it>gpx3 </it>and <it>hsp70 </it>mRNAs by Northern blot and S1 protection assays revealed a strong inhibition of intron splicing in cells submitted to cadmium stress.</p> <p>Conclusion</p> <p>In conclusion, data indicate that environmental stresses, particularly cadmium treatment, inhibit intron processing in <it>B. emersonii</it>, revealing a new adaptive response to cellular exposure to this heavy metal.</p

Study of Bc+B_c^+ decays to the K+K−π+K^+K^-\pi^+ final state and evidence for the decay Bc+→χc0π+B_c^+\to\chi_{c0}\pi^+

A study of $B_c^+\to K^+K^-\pi^+$ decays is performed for the first time using data corresponding to an integrated luminosity of 3.0 $\mathrm{fb}^{-1}$ collected by the LHCb experiment in $pp$ collisions at centre-of-mass energies of $7$ and $8$ TeV. Evidence for the decay $B_c^+\to\chi_{c0}(\to K^+K^-)\pi^+$ is reported with a significance of 4.0 standard deviations, resulting in the measurement of $\frac{\sigma(B_c^+)}{\sigma(B^+)}\times\mathcal{B}(B_c^+\to\chi_{c0}\pi^+)$ to be $(9.8^{+3.4}_{-3.0}(\mathrm{stat})\pm 0.8(\mathrm{syst}))\times 10^{-6}$. Here $\mathcal{B}$ denotes a branching fraction while $\sigma(B_c^+)$ and $\sigma(B^+)$ are the production cross-sections for $B_c^+$ and $B^+$ mesons. An indication of $\bar b c$ weak annihilation is found for the region $m(K^-\pi^+)<1.834\mathrm{\,Ge\kern -0.1em V\!/}c^2$, with a significance of 2.4 standard deviations.Comment: All figures and tables, along with any supplementary material and additional information, are available at https://lhcbproject.web.cern.ch/lhcbproject/Publications/LHCbProjectPublic/LHCb-PAPER-2016-022.html, link to supplemental material inserted in the reference