What dictates the accumulation of desmosterol in the developing brain?

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A robust spectral method for solving Heston’s model

In this paper, we consider the Heston’s volatility model (Heston in Rev. Financ. Stud. 6: 327–343, 1993]. We simulate this model using a combination of the spectral collocation method and the Laplace transforms method. To approximate the two dimensional PDE, we construct a grid which is the tensor product of the two grids, each of which is based on the Chebyshev points in the two spacial directions. The resulting semi-discrete problem is then solved by applying the Laplace transform method based on Talbot’s idea of deformation of the contour integral (Talbot in IMA J. Appl. Math. 23(1): 97–120, 1979)

Ingraft chimerism in lung transplantation - a study in a porcine model of obliterative bronchiolitis

<p>Abstract</p> <p>Background</p> <p>Bronchial epithelium is a target of the alloimmune response in lung transplantation, and intact epithelium may protect allografts from rejection and obliterative bronchiolitis (OB). Herein we study the influence of chimerism on bronchial epithelium and OB development in pigs.</p> <p>Methods</p> <p>A total of 54 immunosuppressed and unimmunosuppressed bronchial allografts were serially obtained 2-90 days after transplantation. Histology (H&E) was assessed and the fluorescence in situ hybridization (FISH) method for Y chromosomes using pig-specific DNA-label was used to detect recipient derived cells in graft epithelium and bronchial wall, and donor cell migration to recipient organs. Ingraft chimerism was studied by using male recipients with female donors, whereas donor cell migration to recipient organs was studied using female recipients with male donors.</p> <p>Results</p> <p>Early appearance of recipient-derived cells in the airway epithelium appeared predictive of epithelial destruction (<it>R </it>= 0.610 - 0.671 and <it>p </it>< 0.05) and of obliteration of the bronchial lumen (<it>R </it>= 0.698 and <it>p </it>< 0.01). All allografts with preserved epithelium showed epithelial chimerism throughout the follow-up. Antirejection medication did not prevent, but delayed the appearance of Y chromosome positive cells in the epithelium (<it>p </it>< 0.05), or bronchial wall (<it>p </it>< 0.05).</p> <p>Conclusions</p> <p>In this study we demonstrate that early appearance of Y chromosomes in the airway epithelium predicts features characteristic of OB. Chimerism occurred in all allografts, including those without features of OB. Therefore we suggest that ingraft chimerism may be a mechanism involved in the repair of alloimmune-mediated tissue injury after transplantation.</p

Cholesterol-Dependent Anaplasma phagocytophilum Exploits the Low-Density Lipoprotein Uptake Pathway

In eukaryotes, intracellular cholesterol homeostasis and trafficking are tightly regulated. Certain bacteria, such as Anaplasma phagocytophilum, also require cholesterol; it is unknown, however, how this cholesterol-dependent obligatory intracellular bacterium of granulocytes interacts with the host cell cholesterol regulatory pathway to acquire cholesterol. Here, we report that total host cell cholesterol increased >2-fold during A. phagocytophilum infection in a human promyelocytic leukemia cell line. Cellular free cholesterol was enriched in A. phagocytophilum inclusions as detected by filipin staining. We determined that A. phagocytophilum requires cholesterol derived from low-density lipoprotein (LDL), because its replication was significantly inhibited by depleting the growth medium of cholesterol-containing lipoproteins, by blocking LDL uptake with a monoclonal antibody against LDL receptor (LDLR), or by treating the host cells with inhibitors that block LDL-derived cholesterol egress from late endosomes or lysosomes. However, de novo cholesterol biosynthesis is not required, since inhibition of the biosynthesis pathway did not inhibit A. phagocytophilum infection. The uptake of fluorescence-labeled LDL was enhanced in infected cells, and LDLR expression was up-regulated at both the mRNA and protein levels. A. phagocytophilum infection stabilized LDLR mRNA through the 3′ UTR region, but not through activation of the sterol regulatory element binding proteins. Extracellular signal–regulated kinase (ERK) was up-regulated by A. phagocytophilum infection, and inhibition of its upstream kinase, MEK, by a specific inhibitor or siRNA knockdown, reduced A. phagocytophilum infection. Up-regulation of LDLR mRNA by A. phagocytophilum was also inhibited by the MEK inhibitor; however, it was unclear whether ERK activation is required for LDLR mRNA up-regulation by A. phagocytophilum. These data reveal that A. phagocytophilum exploits the host LDL uptake pathway and LDLR mRNA regulatory system to accumulate cholesterol in inclusions to facilitate its replication

How Work Impairments and Reduced Work Ability are Associated with Health Care Use in Workers with Musculoskeletal Disorders, Cardiovascular Disorders or Mental Disorders

__Abstract__ Purpose the aim of this study was to explore how work impairments and work ability are associated with health care use by workers with musculoskeletal disorders (MSD), cardiovascular disorders (CVD), or mental disorders (MD). Methods in this cross-sectional study, subjects with MSD (n = 2,074), CVD (n = 714), and MD (n = 443) were selected among health care workers in 12 Dutch organizations. Using an online questionnaire, data were collected on in

The International Soil Moisture Network:Serving Earth system science for over a decade

In 2009, the International Soil Moisture Network (ISMN) was initiated as a community effort, funded by the European Space Agency, to serve as a centralised data hosting facility for globally available in situ soil moisture measurements (Dorigo et al., 2011b, a). The ISMN brings together in situ soil moisture measurements collected and freely shared by a multitude of organisations, harmonises them in terms of units and sampling rates, applies advanced quality control, and stores them in a database. Users can freely retrieve the data from this database through an online web portal (https://ismn.earth/en/, last access: 28 October 2021). Meanwhile, the ISMN has evolved into the primary in situ soil moisture reference database worldwide, as evidenced by more than 3000 active users and over 1000 scientific publications referencing the data sets provided by the network. As of July 2021, the ISMN now contains the data of 71 networks and 2842 stations located all over the globe, with a time period spanning from 1952 to the present. The number of networks and stations covered by the ISMN is still growing, and approximately 70 % of the data sets contained in the database continue to be updated on a regular or irregular basis. The main scope of this paper is to inform readers about the evolution of the ISMN over the past decade, including a description of network and data set updates and quality control procedures. A comprehensive review of the existing literature making use of ISMN data is also provided in order to identify current limitations in functionality and data usage and to shape priorities for the next decade of operations of this unique community-based data repository

Infection with 2009 H1N1 influenza virus primes for immunological memory in human nose-associated lymphoid tissue, offering cross-reactive immunity to H1N1 and avian H5N1 viruses

Influenza is a highly contagious mucosal infection in the respiratory tract. 2009 pandemic H1N1 (pH1N1) virus infection resulted in substantial morbidity and mortality in humans. Little is known on whether immunological memory develops following pH1N1 infection and whether it provides protection against other virus subtypes. Enzyme-linked immunosorbent spot assay was used to analyze hemagglutinin (HA)-specific memory B cell responses after virus antigen stimulation in nasal-associated lymphoid tissues (NALT) from children and adults. Individuals with serological evidence of previous exposure to pH1N1 showed significant cross-reactive HA-specific memory B responses to pH1N1, seasonal H1N1(sH1N1) and avian H5N1(aH5N1) viruses upon pH1N1 virus stimulation. pH1N1 virus antigen elicited stronger cross-reactive memory B cell responses than sH1N1 virus. Intriguingly, aH5N1 virus also activated cross-reactive memory responses to sH1N1 and pH1N1 HAs in those who had previous pH1N1 exposure, and that correlated well with the memory response stimulated by pH1N1 virus antigen. These memory B cell responses resulted in cross-reactive neutralizing antibodies against sH1N1, 1918 H1N1 and aH5N1viruses. 2009 pH1N1 infection appeared to have primed human host with B cell memory in NALT that offers cross-protective mucosal immunity against not only H1N1 but also aH5N1 viruses. These findings may have important implications to future vaccination strategies against influenza. It will be important to induce and/or enhance such cross-protective mucosal memory B cells

Trypanosoma cruzi Epimastigotes Are Able to Store and Mobilize High Amounts of Cholesterol in Reservosome Lipid Inclusions

Reservosomes are lysosome-related organelles found in Trypanosoma cruzi epimastigotes. They represent the last step in epimastigote endocytic route, accumulating a set of proteins and enzymes related to protein digestion and lipid metabolism. The reservosome matrix contains planar membranes, vesicles and lipid inclusions. Some of the latter may assume rectangular or sword-shaped crystalloid forms surrounded by a phospholipid monolayer, resembling the cholesterol crystals in foam cells.Using Nile Red fluorimetry and fluorescence microscopy, as well as electron microscopy, we have established a direct correlation between serum concentration in culture medium and the presence of crystalloid lipid inclusions. Starting from a reservosome purified fraction, we have developed a fractionation protocol to isolate lipid inclusions. Gas-chromatography mass-spectrometry (GC-MS) analysis revealed that lipid inclusions are composed mainly by cholesterol and cholesterol esters. Moreover, when the parasites with crystalloid lipid-loaded reservosomes were maintained in serum free medium for 48 hours the inclusions disappeared almost completely, including the sword shaped ones.Taken together, our results suggest that epimastigote forms of T. cruzi store high amounts of neutral lipids from extracellular medium, mostly cholesterol or cholesterol esters inside reservosomes. Interestingly, the parasites are able to disassemble the reservosome cholesterol crystalloid inclusions when submitted to serum starvation