PIM kinases facilitate lentiviral evasion from SAMHD1 restriction via Vpx phosphorylation

Lentiviruses have evolved to acquire an auxiliary protein Vpx to counteract the intrinsic host restriction factor SAMHD1. Although Vpx is phosphorylated, it remains unclear whether such phosphorylation indeed regulates its activity toward SAMHD1. Here we identify the PIM family of serine/threonine protein kinases as the factors responsible for the phosphorylation of Vpx and the promotion of Vpx-mediated SAMHD1 counteraction. Integrated proteomics and subsequent functional analysis reveal that PIM family kinases, PIM1 and PIM3, phosphorylate HIV-2 Vpx at Ser13 and stabilize the interaction of Vpx with SAMHD1 thereby promoting ubiquitin-mediated proteolysis of SAMHD1. Inhibition of the PIM kinases promotes the antiviral activity of SAMHD1, ultimately reducing viral replication. Our results highlight a new mode of virus–host cell interaction in which host PIM kinases facilitate promotion of viral infectivity by counteracting the host antiviral system, and suggest a novel therapeutic strategy involving restoration of SAMHD1-mediated antiviral response

A new protocol for the preparation of superconducting KBi2

A superconducting KBi2 sample was successfully prepared using a liquid ammonia (NH3) technique. The temperature dependence of the magnetic susceptibility (M/H) showed a superconducting transition temperature (Tc) as high as 3.6 K. In addition, the shielding fraction at 2.0 K was evaluated to be 87%, i.e., a bulk superconductor was realized using the above method. The Tc value was the same as that reported for the KBi2 sample prepared using a high-temperature annealing method. An X-ray diffraction pattern measured based on the synchrotron X-ray radiation was analyzed using the Rietveld method, with a lattice constant, a, of 9.5010(1) Å under the space group of Fd[3 with combining macron]m (face-centered cubic, no. 227). The lattice constant and space group found for the KBi2 sample using a liquid NH3 technique were the same as those reported for KBi2 through a high-temperature annealing method. Thus, the superconducting behavior and crystal structure of the KBi2 sample obtained in this study are almost the same as those for the KBi2 sample reported previously. Strictly speaking, the magnetic behavior of the superconductivity was different from that of a KBi2 sample reported previously, i.e., the KBi2 sample prepared using a liquid NH3 technique was a type-II like superconductor, contrary to that prepared using a high-temperature annealing method, the reason for which is fully discussed. These results indicate that the liquid NH3 technique is effective and simple for the preparation of a superconducting KBi2. In addition, the topological nature of the superconductivity for KBi2 was not confirmed

Enhancement of anti-STLV-1/HTLV-1 immune responses through multimodal effects of anti-CCR4 antibody.

Human T-cell leukemia virus type 1 (HTLV-1) causes adult T-cell leukemia and inflammatory diseases. Because anti-HTLV-1 immune responses are critical for suppressing infected cells, enhancing cellular immunity is beneficial for the treatment of HTLV-1-associated diseases. Using simian T-cell leukemia virus type 1 (STLV-1) infected Japanese macaques, we analyzed the immune responses to viral antigens and the dynamics of virus-infected cells. The chemokine receptor CCR4 is expressed on STLV-1 infected cells, and administration of humanized monoclonal antibody to CCR4, mogamulizumab, dramatically decreased the number of STLV-1-infected cells in vivo. Concurrently, mogamulizumab treatment enhanced STLV-1 specific CD4[+] and CD8[+] T cell responses by simultaneously targeting CCR4[+] effector regulatory T (Treg) cells and infected cells. Mogamulizumab promoted the phagocytosis of CCR4[+] infected cells by macrophages, which likely enhanced antigen presentation. Vaccination with recombinant vaccinia virus (rVV) expressing viral antigens suppressed the proviral load and the number of Tax-expressing cells. Enhanced T-cell responses were also observed in some ATL patients who were treated with mogamulizumab. This study shows that mogamulizumab works not only by killing CCR4[+] infected cells directly, but also by enhancing T cell responses by increasing the phagocytosis of infected cells by antigen-presenting cells and suppressing CCR4[+] effector Treg cells

ホウカゴジドウクラブ ニ オケル オヤツ ト セイカツカツドウ ニ カンスル チヨウサ

We conducted a survey on the present conditions of after-school children clubs (Gakudohoiku), the method of providing snacks to younger schoolchildren during after-school care, the awareness toward feeding snacks among child care workers and guardians of admitted children, the interaction with other members in groups of different ages, and the children\u27s life activities in facilities for After School Care Program in Mieprefecture. The results were summarized as follows: (1) The female childcare workers made up roughly 90%; the childcare workers in their 40\u27s to 60\u27s made up around 80% of the total. (2) The child care mostly began "at two p.m." during weekdays, and "at eight a.m." on weekends, and mostly closed "at six p.m." through the week. (3) The most common expense budget for snack for a child per day at after-school children clubs was "between 50 yen and 100 yen", being the lowest "20yen" and the highest "200 yen and more". (4) "Children\u27s preferences" were the biggest elements taken into considerations, followed by "prices" in providing snacks at the after-school facilities. (5) The top food education programs at after-school children clubs were "Let\u27s Cook Together", "Good Manners at the Table", and "Growing Vegetables and Potatoes" (6) Among after-school care operators, parent\u27s associations accounted for about 30%, and local communities accounted for about 20%. Around 30% of after-school children clubs were operated inside school premises, while 70% were outside school premises. (7) Children in lower grades of primary school (aged 6 through 8) made up around 80% of children admitted in after-school children clubs, which corresponded to a national-level figure. (8) Child care workers encouraged significantly more interactions among multiage groups at medium or large-sized after-school children clubs than at small-sized ones. Comparing the ratio of low graders, children had significantly more opportunities for multi-age interaction at after-school children clubs with low ratio of low graders. (9) Boys and girls were almost equal in numbers at after-school children clubs. Around 90% of children joined the child care facilities in the first grade. As for visiting frequency, "five times a week" was the most common. With regard to reasons for visiting these facilities, "double income family" accounted for 80%. (10) As for frequency of snacks at home, "once" was most common during weekdays and weekends. (11) "Snack food", "chocolate confectionery" and "ice cream" are the most popular snacks given to children at home, which showed that parents were likely to provide snack of their children\u27s preferences. (12) Regarding snack time at home, "five to eight p.m." is most common on weekdays; "three to six p.m." was predominantly common on weekends. (13) As for appropriate budget for snack at home, "50 yen to 100 yen" for a child per day was most common. (14) Concerning life activities of those admitted in after school clubs, physical activities, such as "playground equipment", "soccer", "tag", and "jump rope" were most popular types of child\u27s play during weekdays

シン キユウシヨクジツシユウシツ ヲ シヨウ シタ キユウシヨク ジツシユウ ニ オケル エイセイ カンリ ノ ケントウ : タイリヨウ チヨウリ シセツ エイセイ カンリ マニユアル トノ ヒカク

In order to examine whether sufficient instruction was completed, hygiene supervision and accident prevention were compared with the manual by food service management practice in new food service management room. As a result, it became clear that the consciousness of a work area and the consciousness ofprevention of cross contamination were insufficient. Things important in order to raise the consciousness of zoning are classification by color of a zone or an instrument, and manual preparation. In addition, repair of a door, installation of curtain, cleaning of a ceiling, and extermination of a rat are required for hygiene supervision. Although it is impossible to carry all out as a manual, I think that we would like to strive to be able to study hygiene supervision equivalent to carrying out with the actual possible institution

Quantification system for the viral dynamics of a highly pathogenic simian/human immunodeficiency virus based on an in vitro experiment and a mathematical model

<p>Abstract</p> <p>Background</p> <p>Developing a quantitative understanding of viral kinetics is useful for determining the pathogenesis and transmissibility of the virus, predicting the course of disease, and evaluating the effects of antiviral therapy. The availability of data in clinical, animal, and cell culture studies, however, has been quite limited. Many studies of virus infection kinetics have been based solely on measures of total or infectious virus count. Here, we introduce a new mathematical model which tracks both infectious and total viral load, as well as the fraction of infected and uninfected cells within a cell culture, and apply it to analyze time-course data of an SHIV infection <it>in vitro</it>.</p> <p>Results</p> <p>We infected HSC-F cells with SHIV-KS661 and measured the concentration of Nef<it>-</it>negative (target) and Nef<it>-</it>positive (infected) HSC-F cells, the total viral load, and the infectious viral load daily for nine days. The experiments were repeated at four different MOIs, and the model was fitted to the full dataset simultaneously. Our analysis allowed us to extract an infected cell half-life of 14.1 h, a half-life of SHIV-KS661 infectiousness of 17.9 h, a virus burst size of 22.1 thousand RNA copies or 0.19 TCID₅₀, and a basic reproductive number of 62.8. Furthermore, we calculated that SHIV-KS661 virus-infected cells produce at least 1 infectious virion for every 350 virions produced.</p> <p>Conclusions</p> <p>Our method, combining <it>in vitro </it>experiments and a mathematical model, provides detailed quantitative insights into the kinetics of the SHIV infection which could be used to significantly improve the understanding of SHIV and HIV-1 pathogenesis. The method could also be applied to other viral infections and used to improve the <it>in vitro </it>determination of the effect and efficacy of antiviral compounds.</p

Mechanisms of HIV-associated lymphocyte apoptosis: 2010

The inevitable decline of CD4T cells in untreated infection with the Human immunodeficiency virus (HIV) is due in large part to apoptosis, one type of programmed cell death. There is accumulating evidence that the accelerated apoptosis of CD4T cells in HIV infection is multifactorial, with direct viral cytotoxicity, signaling events triggered by viral proteins and aberrant immune activation adding to normal immune defense mechanisms to contribute to this phenomenon. Current antiviral treatment strategies generally lead to reduced apoptosis, but this approach may come at the cost of preserving latent viral reservoirs. It is the purpose of this review to provide an update on the current understanding of the role and mechanisms of accelerated apoptosis of T cells in the immunopathogenesis of HIV infection, and to highlight potential ways in which this seemingly deleterious process could be harnessed to not just control, but treat HIV infection

Gene-expression patterns during regeneration of the multi-organ complex after evisceration in the sea cucumber Eupentacta quinquesemita

Many species of sea cucumbers (Echinodermata, Holothuroidea) perform evisceration, i.e., ejection of internal organs including digestive tracts when responding to environmental stresses. After evisceration, they also show a high regenerative capacity, in which all the eviscerated organs regenerate. Especially in anterior evisceration species, the oral complex structure consisting of multiple organs, including the digestive tract and central nervous system, are reconstructed. The detailed developmental mechanisms underlying the process remains unclear, and therefore, in this study, focusing on Eupentacta quinquesemita, gene expression analyses in the regenerating tissues were carried out. For the formation of the gut tube, genes involved in mesenchymal-epithelial transition were upregulated consistently with the histological changes. Upregulation of Hox and Parahox genes along the anterior-posterior axis was observed, implying the involvement of these genes in the spatial differentiation of the digestive tract. In addition, the expression of otx, six and pax, i.e., transcription factors patterning anterior nervous tissues, was upregulated during the regeneration of the central nervous system. Taken together, these results suggest that conserved genes are co-opted to the internal organ regeneration after evisceration in sea cucumbers

Comparison of Antioxidant Properties of Different Crude Extracts from <i>Citrus natsudaidai</i> Peel

International audienceCitrus natsudaidai is a popular citrus in Japan, but the peel is of limited use and its composition is not well documented. The purposes of this study were to obtain health-beneficial compounds from C. natsudaidai peel for food use by simple methods and to investigate the antioxidant capacities of extracts of different polarities without overestimating the effects. C. natsudaidai peel was extracted with water-ethanol and hexane-ethanol solutions to obtain five different soluble fractions. The highest total phenolic content (TPC) was obtained from the water-soluble fraction (WSF), and the lowest content was observed in the hexane soluble fraction (HSF). The WSF also showed the highest antioxidant activities, and the lowest activities were found in HSF. A positive correlation was detected between TPC and antioxidant activities. The polar extract of C. natsudaidai peel has potential as a natural additive or ingredient in foods, cosmetics and pharmaceutical products with antioxidant activity