Lutzomyia adiketis sp. n. (Diptera: Phlebotomidae), a vector of Paleoleishmania neotropicum sp. n. (Kinetoplastida: Trypanosomatidae) in Dominican amber

<p>Abstract</p> <p>Background</p> <p>Amber fossils can be used to trace the history of disease-vector associations because microorganisms are preserved "in situ" inside the alimentary tract and body cavity of blood-sucking insects.</p> <p>Results</p> <p><it>Lutzomyia adiketis </it>sp. n. (Phlebotomidae: Diptera) is described from Dominican amber as a vector of <it>Paleoleishmania neotropicum </it>sp. n. (Kinetoplastida: Trypanosomatidae). The fossil sand fly differs from all previously described extinct and extant members of the genus by the following combination of characters: Sc forked with the branches meeting the costa and radius veins; wing L/W value of 4.1; a δ value of 18; a ratio β/α value of 0.86, and the shape and size of the spatulate rods on the ninth sternite. The trypanosomatid is characterized by the structure of its promastigotes, amastigotes and paramastigotes and its transmission by an extinct species of sand fly.</p> <p>Conclusion</p> <p>Morphological characters show that the fossil sand fly is a new extinct species and that it is host to a digenetic species of trypanosomatid. This study provides the first fossil evidence that Neotropical sand flies were vectors of trypanosomatids in the mid-Tertiary (20–30 mya).</p

How to prevent viremia rebound? Evidence from a PRRSv data-supported model of immune response Natacha Go1,2,3*, Suzanne Touzeau

International audienceBACKGROUNDUnderstanding what determines the between-host variability in infection dynamics is a key issue to better control the infection spread. In particular, pathogen clearance is desirable over rebounds for the health of the infected individual and its contact group. In this context, the Porcine Respiratory and Reproductive Syndrome virus (PRRSv) is of particular interest. Numerous studies have shown that pigs similarly infected with this highly ubiquitous virus elicit diverse response profiles. Whilst some manage to clear the virus within a few weeks, others experience prolonged infection with a rebound. Despite much speculation, the underlying mechanisms responsible for this undesirable rebound phenomenon remain unclear.RESULTSWe aimed at identifying immune mechanisms that can reproduce and explain the rebound patterns observed in PRRSv infection using a mathematical modelling approach of the within-host dynamics. As diverse mechanisms were found to influence PRRSv infection, we established a model that details the major mechanisms and their regulations at the between-cell scale. We developed an ABC-like optimisation method to fit our model to an extensive set of experimental data, consisting of non-rebounder and rebounder viremia profiles. We compared, between both profiles, the estimated parameter values, the resulting immune dynamics and the efficacies of the underlying immune mechanisms. Exploring the influence of these mechanisms, we showed that rebound was promoted by high apoptosis, high cell infection and low cytolysis by Cytotoxic T Lymphocytes, while increasing neutralisation was very efficient to prevent rebounds.CONCLUSIONSOur paper provides an original model of the immune response and an appropriate systematic fitting method, whose interest extends beyond PRRS infection. It gives the first mechanistic explanation for emergence of rebounds during PRRSv infection. Moreover, results suggest that vaccines or genetic selection promoting strong neutralising and cytolytic responses, ideally associated with low apoptotic activity and cell permissiveness, would prevent rebound

2016 Snow Melt in the NGEE-Arctic Teller Research Watershed

In April 2016, daily transects were made across the Teller Road Basin to begin the several year process of characterizing the largest event in the northern hydrologic year: snow melt. This year was an experiment to see how much could be accomplished (a full suite of time intensive measurements) during this interval.The Next-Generation Ecosystem Experiments (NGEE Arctic) project is supported by the Office of Biological and Environmental Research in the DOE Office of Science

Research-based versus clinical serum creatinine measurements and the association of acute kidney injury with subsequent kidney function: findings from the Chronic Renal Insufficiency Cohort study.

Background:Observational studies relying on clinically obtained data have shown that acute kidney injury (AKI) is linked to accelerated chronic kidney disease (CKD) progression. However, prior reports lacked uniform collection of important confounders such as proteinuria and pre-AKI kidney function trajectory, and may be susceptible to ascertainment bias, as patients may be more likely to undergo kidney function testing after AKI. Methods:We studied 444 adults with CKD who participated in the prospective Chronic Renal Insufficiency Cohort (CRIC) Study and were concurrent members of a large integrated healthcare delivery system. We estimated glomerular filtration rate (eGFR) trajectories using serum creatinine measurements from (i) the CRIC research protocol (yearly) and (ii) routine clinical care. We used linear mixed effects models to evaluate the associations of AKI with acute absolute change in eGFR and post-AKI eGFR slope, and explored whether these varied by source of creatinine results. Models were adjusted for demographic characteristics, diabetes status and albuminuria. Results:During median follow-up of 8.5 years, mean rate of eGFR loss was -0.31 mL/min/1.73&nbsp;m2/year overall, and 73 individuals experienced AKI (55% Stage 1). A significant interaction existed between AKI and source of serum creatinine for acute absolute change in eGFR level after discharge; in contrast, AKI was independently associated with a faster rate of eGFR decline (mean additional loss of -0.67 mL/min/1.73&nbsp;m2/year), which was not impacted by source of serum creatinine. Conclusions:AKI is independently associated with subsequent steeper eGFR decline regardless of the serum creatinine source used, but the strength of association is smaller than observed in prior studies after taking into account key confounders such as pre-AKI eGFR slope and albuminuria

Spanish Influenza in Japanese Armed Forces, 1918–1920

Medical records of Japanese army hospitals show high death rates during the first influenza pandemic

Human-GDPR Interaction: Practical Experiences of Accessing Personal Data

In our data-centric world, most services rely on collecting and using personal data. The EU's General Data Protection Regulation (GDPR) aims to enhance individuals’ control over their data, but its practical impact is not well understood. We present a 10-participant study, where each participant filed 4-5 data access requests. Through interviews accompanying these requests and discussions scrutinising returned data, it appears that GDPR falls short of its goals due to non-compliance and low-quality responses. Participants found their hopes to understand providers’ data practices or harness their own data unmet. This causes increased distrust without any subjective improvement in power, although more transparent providers do earn greater trust. We propose designing more effective, data-inclusive and open policies and data access systems to improve both customer relations and individual agency, and also that wider public use of GDPR rights could help with delivering accountability and motivating providers to improve data practices

Influences on the Design and Purification of Soluble, Recombinant Native-Like HIV-1 Envelope Glycoprotein Trimers

We have investigated factors that influence the production of native-like soluble, recombinant trimers based on the env genes of two isolates of human immunodeficiency virus type 1 (HIV-1), specifically 92UG037.8 (clade A) and CZA97.012 (clade C). When the recombinant trimers based on the env genes of isolates 92UG037.8 and CZA97.012 were made according to the SOSIP.664 design and purified by affinity chromatography using broadly neutralizing antibodies (bNAbs) against quaternary epitopes (PGT145 and PGT151, respectively), the resulting trimers are highly stable and they are fully native-like when visualized by negative-stain electron microscopy. They also have a native-like (i.e., abundant) oligomannose glycan composition and display multiple bNAb epitopes while occluding those for nonneutralizing antibodies. In contrast, uncleaved, histidine-tagged Foldon (Fd) domain-containing gp140 proteins (gp140UNC-Fd-His), based on the same env genes, very rarely form native-like trimers, a finding that is consistent with their antigenic and biophysical properties and glycan composition. The addition of a 20-residue flexible linker (FL20) between the gp120 and gp41 ectodomain (gp41ECTO) subunits to make the uncleaved 92UG037.8 gp140-FL20 construct is not sufficient to create a native-like trimer, but a small percentage of native-like trimers were produced when an I559P substitution in gp41ECTO was also present. The further addition of a disulfide bond (SOS) to link the gp120 and gp41 subunits in the uncleaved gp140-FL20-SOSIP protein increases native-like trimer formation to ∼20 to 30%. Analysis of the disulfide bond content shows that misfolded gp120 subunits are abundant in uncleaved CZA97.012 gp140UNC-Fd-His proteins but very rare in native-like trimer populations. The design and stabilization method and the purification strategy are, therefore, all important influences on the quality of trimeric Env proteins and hence their suitability as vaccine components

The usefulness of a free self-test for screening albuminuria in the general population: a cross-sectional survey

<p>Abstract</p> <p>Background</p> <p>In this study we evaluated the usefulness of a free self-test for screening albuminuria in the general population.</p> <p>Methods</p> <p>Dutch adults were invited by the Dutch Kidney Foundation to order a free albuminuria self-test, consisting of three semi quantitative dipstick tests, via the Internet. Results were classified in negative, low-positive and high-positive. In case of a positive test result, the tester was recommended to visit a GP for supplementary examination and/or treatment. Participants of the programme were sent a questionnaire for evaluation by e-mail eight weeks after receiving the self-test.</p> <p>Results</p> <p>During the first 30 days of the self-test programme, 996,927 self-tests were ordered. In total, 71,714 participants completed the questionnaire: 79% had a negative test result and 21% had a positive test result (20% low-positive and 1% high-positive). Of the positive testers, 25% visited a GP after testing for albuminuria. Among the 3,983 participants who visited a GP, 193 new diseases were detected: 25 chronic renal failure, 152 hypertension and 31 diabetes mellitus.</p> <p>Conclusion</p> <p>Using a free self-test for screening albuminuria in the general population resulted in a large response and a number of newly detected diseases. However, we found a very high percentage of positive testers of which probably a large part is false positive. Furthermore, only a small part of the positive testers visited a GP for additional examination and/or treatment. The efficiency of such a campaign could be increased by embedding the testing in health care to reduce the number of false-positive results and to ensure follow-up and treatment in case of a positive test result.</p

Commutative association schemes

Association schemes were originally introduced by Bose and his co-workers in the design of statistical experiments. Since that point of inception, the concept has proved useful in the study of group actions, in algebraic graph theory, in algebraic coding theory, and in areas as far afield as knot theory and numerical integration. This branch of the theory, viewed in this collection of surveys as the "commutative case," has seen significant activity in the last few decades. The goal of the present survey is to discuss the most important new developments in several directions, including Gelfand pairs, cometric association schemes, Delsarte Theory, spin models and the semidefinite programming technique. The narrative follows a thread through this list of topics, this being the contrast between combinatorial symmetry and group-theoretic symmetry, culminating in Schrijver's SDP bound for binary codes (based on group actions) and its connection to the Terwilliger algebra (based on combinatorial symmetry). We propose this new role of the Terwilliger algebra in Delsarte Theory as a central topic for future work.Comment: 36 page

Cyclic Density Functional Theory : A route to the first principles simulation of bending in nanostructures

We formulate and implement Cyclic Density Functional Theory (Cyclic DFT) -- a self-consistent first principles simulation method for nanostructures with cyclic symmetries. Using arguments based on Group Representation Theory, we rigorously demonstrate that the Kohn-Sham eigenvalue problem for such systems can be reduced to a fundamental domain (or cyclic unit cell) augmented with cyclic-Bloch boundary conditions. Analogously, the equations of electrostatics appearing in Kohn-Sham theory can be reduced to the fundamental domain augmented with cyclic boundary conditions. By making use of this symmetry cell reduction, we show that the electronic ground-state energy and the Hellmann-Feynman forces on the atoms can be calculated using quantities defined over the fundamental domain. We develop a symmetry-adapted finite-difference discretization scheme to obtain a fully functional numerical realization of the proposed approach. We verify that our formulation and implementation of Cyclic DFT is both accurate and efficient through selected examples. The connection of cyclic symmetries with uniform bending deformations provides an elegant route to the ab-initio study of bending in nanostructures using Cyclic DFT. As a demonstration of this capability, we simulate the uniform bending of a silicene nanoribbon and obtain its energy-curvature relationship from first principles. A self-consistent ab-initio simulation of this nature is unprecedented and well outside the scope of any other systematic first principles method in existence. Our simulations reveal that the bending stiffness of the silicene nanoribbon is intermediate between that of graphene and molybdenum disulphide. We describe several future avenues and applications of Cyclic DFT, including its extension to the study of non-uniform bending deformations and its possible use in the study of the nanoscale flexoelectric effect.Comment: Version 3 of the manuscript, Accepted for publication in Journal of the Mechanics and Physics of Solids, http://www.sciencedirect.com/science/article/pii/S002250961630368