Gut-Specific Delivery of T-Helper 17 Cells Reduces Obesity and Insulin Resistance in Mice

Hong, C.P.,Park, A.,Yang, B.G.,Yun, C.H.,Kwak, M.J.,Lee, G.W.,Kim, J.H.,Jang, M.S.,Lee, E.J.,Jeun, E.J.,You, G.,Kim, K.S.,Choi, Y.,Park, J.H.,Hwang, D.,Im, S.H.,Kim, J.F.,Kim, Y.K.,Seoh, J.Y.,Surh, C. Elsevier North Holland [etc.] 2017 Gastroenterology Vol.152 No.8

<P>BACKGROUND & AIMS: Obesity and metabolic syndrome have been associated with alterations to the intestinal microbiota. However, few studies examined the effects of obesity on the intestinal immune system. We investigated changes in subsets of intestinal CD4(+) T-helper (T-H) cells with obesity and the effects of gut-tropic T(H)17 cells in mice on a high-fat diet (HFD). METHODS: We isolated immune cells from small intestine and adipose tissue of C57BL/6 mice fed a normal chow diet or a HFD for 10 weeks and analyzed the cells by flow cytometry. Mice fed a vitamin A-deficient HFD were compared with mice fed a vitamin A-sufficient HFD. Obese RAG1-deficient mice were given injections of only regulatory T cells or a combination of regulatory T cells and T(H)17 cells (wild type or deficient in integrin beta 7 subunit or interleukin 17 [IL17]). Mice were examined for weight gain, fat mass, fatty liver, glucose tolerance, and insulin resistance. Fecal samples were collected before and after T cell transfer and analyzed for microbiota composition by metagenomic DNA sequencing and quantitative polymerase chain reaction. RESULTS: Mice placed on a HFD became obese, which affected the distribution of small intestinal CD4(+) T-H cells. Intestinal tissues from obese mice had significant reductions in the proportion of T(H)17 cells but increased proportion of T(H)1 cells, compared with intestinal tissues from nonobese mice. Depletion of vitamin A in obese mice further reduced the proportion of T(H)17 cells in small intestine; this reduction correlated with more weight gain and worsening of glucose intolerance and insulin resistance. Adoptive transfer of in vitro-differentiated gut-tropic T(H)17 cells to obese mice reduced these metabolic defects, which required the integrin beta 7 subunit and IL17. Delivery of T(H)17 cells to intestines of mice led to expansion of commensal microbes associated with leanness. CONCLUSIONS: In mice, intestinal T(H)17 cells contribute to development of a microbiota that maintains metabolic homeostasis, via IL17. Gut-homing T(H)17 cells might be used to reduce metabolic disorders in obese individuals.</P>

GP3 is a structural component of the PRRSV type II (US) virion

de Lima, M.,Ansari, I.H.,Das, P.B.,Ku, B.J.,Martinez-Lobo, F.J.,Pattnaik, A.K.,Osorio, F.A. Academic Press 2009 Virology Vol.390 No.1

Glycoprotein 3 (GP3) is a highly glycosylated PRRSV envelope protein which has been reported as being present in the virions of PRRSV type I, while missing in the type II PRRSV (US) virions. We herein present evidence that GP3 is indeed incorporated in the virus particles of a North American strain of PRRSV (FL12), at a density that is consistent with the minor structural role assigned to GP3 in members of the Arterivirus genus. Two 15aa peptides corresponding to two different immunodominant linear epitopes of GP3 derived from the North American strain of PRRSV (FL12) were used as antigen to generate a rabbit monospecific antiserum to this protein. The specificity of this anti-GP3 antiserum was confirmed by radioimmunoprecipitation (RIP) assay using BHK-21 cells transfected with GP3 expressing plasmid, MARC-145 cells infected with FL12 PRRSV, as well as by confocal microscopy on PRRSV-infected MARC-145 cells. To test if GP3 is a structural component of the virion, <SUP>35</SUP>S-labelled PRRSV virions were pelleted through a 30% sucrose cushion, followed by a second round of purification on a sucrose gradient (20-60%). Virions were detected in specific gradient fractions by radioactive counts and further confirmed by viral infectivity assay in MARC 145 cells. The GP3 was detected in gradient fractions containing purified virions by RIP using anti-GP3 antiserum. Predictably, the GP3 was less abundant in purified virions than other major structural envelope proteins such as GP5 and M. Further evidence of the presence of GP3 at the level of PRRSV FL12 envelope was obtained by immunogold staining of purified virions from the supernatant of infected cells with anti-GP3 antiserum. Taken together, these results indicate that GP3 is a minor structural component of the PRRSV type II (FL12 strain) virion, as had been previously described for PRRSV type I.

IDENTIFICATION CAMPAIGN OF SUPERNOVA REMNANT CANDIDATES IN THE MILKY WAY. I.<i>CHANDRA</i>OBSERVATION OF G308.3-1.4

Hui, C. Y.,Seo, K. A.,Huang, R. H. H.,Trepl, L.,Woo, Y. J.,Lu, T.-N.,Kong, A. K. H.,Walter, F. M. IOP Publishing 2012 The Astrophysical journal Vol.750 No.1

<P>ROSAT all-sky survey data have provided another window in which to search for supernova remnants (SNRs). In re-examining this data archive, a list of unidentified extended X-ray objects have been suggested as promising SNR candidates. However, most of these targets have not yet been fully explored by state-of-the-art X-ray observatories. To select a pilot target for a long-term identification campaign, we observed the brightest candidate, G308.3-1.4, with the Chandra X-ray Observatory. An incomplete shell-like X-ray structure that is well correlated with the radio shell emission at 843 MHz has been revealed. The X-ray spectrum suggests the presence of a shock-heated plasma. All these evidences confirm G308.3-1.4 as an SNR. The brightest X-ray point source detected in this field of view is also the one located closest to the geometrical center of G308.3-1.4, which has a soft spectrum. The intriguing temporal variability and the identification of the optical/infrared counterpart rule out the possibility of an isolated neutron star. On the other hand, the spectral energy distribution from the K-s band to the R band suggests a late-type star. Together with a putative periodicity of similar to 1.4 hr, the interesting excesses in the V and B bands and in H alpha suggest that this source is a promising candidate for a compact binary that survived a supernova explosion.</P>

Isostructural metal-insulator transition in VO₂

Lee, D.,Chung, B.,Shi, Y.,Kim, G.-Y.,Campbell, N.,Xue, F.,Song, K.,Choi, S.-Y.,Podkaminer, J. P.,Kim, T. H.,Ryan, P. J.,Kim, J.-W.,Paudel, T. R.,Kang, J.-H.,Spinuzzi, J. W.,Tenne, D. A.,Tsymbal, E. Y. American Association for the Advancement of Scienc 2018 Science Vol.362 No.6418

<P><B>Separating structure and electrons in VO<SUB>2</SUB></B></P><P>Above 341 kelvin—not far from room temperature—bulk vanadium dioxide (VO<SUB>2</SUB>) is a metal. But as soon as the material is cooled below 341 kelvin, VO<SUB>2</SUB> turns into an insulator and, at the same time, changes its crystal structure from rutile to monoclinic. Lee <I>et al.</I> studied the peculiar behavior of a heterostructure consisting of a layer of VO<SUB>2</SUB> placed underneath a layer of the same material that has a bit less oxygen. In the VO<SUB>2</SUB> layer, the structural transition occurred at a higher temperature than the metal-insulator transition. In between those two temperatures, VO<SUB>2</SUB> was a metal with a monoclinic structure—a combination that does not occur in the absence of the adjoining oxygen-poor layer.</P><P><I>Science</I>, this issue p. 1037</P><P>The metal-insulator transition in correlated materials is usually coupled to a symmetry-lowering structural phase transition. This coupling not only complicates the understanding of the basic mechanism of this phenomenon but also limits the speed and endurance of prospective electronic devices. We demonstrate an isostructural, purely electronically driven metal-insulator transition in epitaxial heterostructures of an archetypal correlated material, vanadium dioxide. A combination of thin-film synthesis, structural and electrical characterizations, and theoretical modeling reveals that an interface interaction suppresses the electronic correlations without changing the crystal structure in this otherwise correlated insulator. This interaction stabilizes a nonequilibrium metallic phase and leads to an isostructural metal-insulator transition. This discovery will provide insights into phase transitions of correlated materials and may aid the design of device functionalities.</P>

Energy Requirements in Early Life Are Similar for Male and Female Goat Kids

Bompadre, T.F.V.,Neto, O. Boaventura,Mendonca, A.N.,Souza, S.F.,Oliveira, D.,Fernandes, M.H.M.R.,Harter, C.J.,Almeida, A.K.,Resende, K.T.,Teixeira, I.A.M.A. Asian Australasian Association of Animal Productio 2014 Animal Bioscience Vol.27 No.12

Little is known about the gender differences in energetic requirements of goats in early life. In this study, we determined the energy requirements for maintenance and gain in intact male, castrated male and female Saanen goat kids using the comparative slaughter technique and provide new data on their body composition and energy efficiency. To determine the energy requirements for maintenance, we studied 21 intact males, 15 castrated males and 18 females ($5.0{\pm}0.1kg$ initial body weight (BW) and $23{\pm}5d$ of age) using a split-plot design with the following main factors: three genders (intact males, castrated males, and females) and three dry matter intake levels (ad libitum, 75% and 50% of ad libitum intake). A slaughter group included three kids, one for each nutritional plane, of each gender, and all three animals within a group were slaughtered when the ad libitum kid reached 15 kg in BW. Net energy requirements for gain were obtained for 17 intact males, eight castrated males and 15 females ($5.1{\pm}0.4kg$ BW and $23{\pm}13d$ of age). Animals were fed ad libitum and slaughtered when they reached 5, 10, and 15 kg in BW. A digestion trial was performed with nine kids of each gender to determine digestible energy, metabolizable energy and energy metabolizability of the diet. Our results show no effect of gender on the energy requirements for maintenance and gain, and overall net energy for maintenance was $205.6kJ/kg^{0.75}$ empty body weight gain (EBW) ($170.3kJ/kg^{0.75}$ BW) from 5 to 15 kg BW. Metabolizable energy for maintenance was calculated by iteration, assuming heat production equal to metabolizable energy intake at maintenance, and the result was $294.34kJ/kg^{0.75}$ EBW and $k_m$ of 0.70. As BW increased from 5 to 15 kg for all genders, the net energy required for gain increased from 9.5 to 12.0 kJ/g EBW gain (EWG), and assuming $k_g=0.47$, metabolizable energy for gain ranged from 20.2 to 25.5 kJ/g EWG. Our results indicate that it is not necessary to formulate diets with different energetic content for intact male, castrated male and female Saanen goat kids weighing from 5 to 15 kg.

Mutations in SEC24D, Encoding a Component of the COPII Machinery, Cause a Syndromic Form of Osteogenesis Imperfecta

Garbes, L.,Kim, K.,Riesz, A.,Hoyer-Kuhn, H.,Beleggia, F.,Bevot, A.,Kim, M.,Huh, Y.,Kweon, H.S.,Savarirayan, R.,Amor, D.,Kakadia, Purvi M.,Lindig, T.,Kagan, K.,Becker, J.,Boyadjiev, Simeon A.,Wollnik, University of Chicago Press [etc.] 2015 American journal of human genetics Vol.96 No.3

As a result of a whole-exome sequencing study, we report three mutant alleles in SEC24D, a gene encoding a component of the COPII complex involved in protein export from the ER: the truncating mutation c.613C>T (p.Gln205<SUP>*</SUP>) and the missense mutations c.3044C>T (p.Ser1015Phe, located in a cargo-binding pocket) and c.2933A>C (p.Gln978Pro, located in the gelsolin-like domain). Three individuals from two families affected by a similar skeletal phenotype were each compound heterozygous for two of these mutant alleles, with c.3044C>T being embedded in a 14 Mb founder haplotype shared by all three. The affected individuals were a 7-year-old boy with a phenotype most closely resembling Cole-Carpenter syndrome and two fetuses initially suspected to have a severe type of osteogenesis imperfecta. All three displayed a severely disturbed ossification of the skull and multiple fractures with prenatal onset. The 7-year-old boy had short stature and craniofacial malformations including macrocephaly, midface hypoplasia, micrognathia, frontal bossing, and down-slanting palpebral fissures. Electron and immunofluorescence microscopy of skin fibroblasts of this individual revealed that ER export of procollagen was inefficient and that ER tubules were dilated, faithfully reproducing the cellular phenotype of individuals with cranio-lentico-sutural dysplasia (CLSD). CLSD is caused by SEC23A mutations and displays a largely overlapping craniofacial phenotype, but it is not characterized by generalized bone fragility and presented with cataracts in the original family described. The cellular and morphological phenotypes we report are in concordance with the phenotypes described for the Sec24d-deficient fish mutants vbi (medaka) and bulldog (zebrafish).

Long-lived K isomer and enhanced γ vibration in the neutron-rich nucleus ¹⁷²Dy: Collectivity beyond double midshell

Watanabe, H.,Zhang, G.X.,Yoshida, K.,Walker, P.M.,Liu, J.J.,Wu, J.,Regan, P.H.,Soderstrom, P.A.,Kanaoka, H.,Korkulu, Z.,Lee, P.S.,Nishimura, S.,Yagi, A.,Ahn, D.S.,Alharbi, T.,Baba, H.,Browne, F.,Bruce North-Holland Pub. Co 2016 Physics letters. Section B Vol.760 No.-

The level structure of <SUP>172</SUP>Dy has been investigated for the first time by means of decay spectroscopy following in-flight fission of a <SUP>238</SUP>U beam. A long-lived isomeric state with T<SUB>½</SUB>=0.71(5) s and K<SUP>π</SUP>=8<SUP>-</SUP> has been identified at 1278 keV, which decays to the ground-state and γ-vibrational bands through hindered electromagnetic transitions, as well as to the daughter nucleus <SUP>172</SUP>Ho via allowed β decays. The robust nature of the K<SUP>π</SUP>=8<SUP>-</SUP> isomer and the ground-state rotational band reveals an axially-symmetric structure for this nucleus. Meanwhile, the γ-vibrational levels have been identified at unusually low excitation energy compared to the neighboring well-deformed nuclei, indicating the significance of the microscopic effect on the non-axial collectivity in this doubly mid-shell region. The underlying mechanism of enhanced γ vibration is discussed in comparison with the deformed Quasiparticle Random-Phase Approximation based on a Skyrme energy-density functional.

Cleaved c-FLIP mediates the antiviral effect of TNF-α against hepatitis B virus by dysregulating hepatocyte nuclear factors

Park, Y.K.,Park, E.S.,Kim, D.H.,Ahn, S.H.,Park, S.H.,Lee, A.R.,Park, S.,Kang, H.S.,Lee, J.H.,Kim, J.M.,Lee, S.K.,Lim, K.H.,Isorce, N.,Tong, S.,Zoulim, F.,Kim, K.H. Elsevier Science Publishers 2016 Journal of hepatology Vol. No.

<P>Background & Aims: Cytokines are key molecules implicated in the defense against virus infection. Tumor necrosis factor-alpha (TNF-alpha) is well known to block the replication of hepatitis B virus (HBV). However, the molecular mechanism and the downstream effector molecules remain largely unknown. Methods: In this study, we investigated the antiviral effect and mechanism of p22-FLIP (FLICE-inhibitory protein) by ectopic expression in vitro and in vivo. In addition, to provide the biological relevance of our study, we examined that the p22-FLIP is involved in TNF-alpha-mediated suppression of HBV in primary human hepatocytes. Results: We found that p22-FLIP, a newly discovered c-FLIP cleavage product, inhibited HBV replication at the transcriptional level in both hepatoma cells and primary human hepatocytes, and that c-FLIP conversion to p22-FLIP was stimulated by the TNF-alpha/NF-kappa B pathway. p22-FLIP inhibited HBV replication through the upregulation of HNF3 beta but downregulation of HNF4 alpha, thus inhibiting both HBV enhancer elements. Finally, p22-FLIP potently inhibited HBV DNA replication in a mouse model of HBV replication. Conclusions: Taken together, these findings suggest that the anti-apoptotic p22-FLIP serves a novel function of inhibiting HBV transcription, and mediates the antiviral effect of TNF-a against HBV replication. (C) 2015 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.</P>

A Pd Doped PVDF Hollow Fibre for the Dissolved Oxygen Removal Process

Batbieri G.,Brunetti A.,Scura F.,Lentini F.,Agostino R G.,Kim, M.J.,Formoso V.,Drioli E.,Lee, K.H. The Membrane Society of Korea 2006 Korean Membrane Journal Vol.8 No.1

In semiconductor industries, dissolved oxygen is one of the most undesirable contaminants of ultrapure water. A method for dissolved oxygen removal (DOR) consists in the use of polymeric hollow fibres, loaded with a catalyst and fed with a reducing agent such as hydrogen. In this work, PVDF hollow fibres loaded with Pd were characterized by means of perporometry, scanning electron microscopy (SEM), energy dispersive X-ray (EDX). The hollow fibre analyzed shows a five-layer structure with remarkable morphological differences. An estimation of pore diameters and their distribution was performed giving a mean pore diameter of 100 nm. The permeance and selectivity of the fibres were measured using $H_2,\;N_2,\;O_2$ as single gases, at different operating conditions. An $H_2$ permeance of $37 mmol/m^2s$ was measured and $H_2/O_2$ and $H_2/N_2$ selectivities of ca. 3 were obtained. $H_2$ permeance was 1/3 when a water stream flows in the shell side. Catalytic fibrebehaviour was simulated using a mathematical model for a loop membrane reactor, considering only $O_2$ and $H_2$ diffusive transport inside the membrane and their catalytic reaction. Dimensionless parameters such as the Thiele modulus are employed to describe the system behaviour. The model agrees well with the experimental reaction data.

INTERPRETATION OF A SHORT-TERM ANOMALY IN THE GRAVITATIONAL MICROLENSING EVENT MOA-2012-BLG-486

Hwang, K.-H.,Choi, J.-Y.,Bond, I. A.,Sumi, T.,Han, C.,Gaudi, B. S.,Gould, A.,Bozza, V.,Beaulieu, J.-P.,Tsapras, Y.,Abe, F.,Bennett, D. P.,Botzler, C. S.,Chote, P.,Freeman, M.,Fukui, A.,Fukunaga, D.,Ha IOP Publishing 2013 The Astrophysical journal Vol.778 No.1

<P>A planetary microlensing signal is generally characterized by a short-term perturbation to the standard single lensing light curve. A subset of binary-source events can produce perturbations that mimic planetary signals, thereby introducing an ambiguity between the planetary and binary-source interpretations. In this paper, we present the analysis of the microlensing event MOA-2012-BLG-486, for which the light curve exhibits a short-lived perturbation. Routine modeling not considering data taken in different passbands yields a best-fit planetary model that is slightly preferred over the best-fit binary-source model. However, when allowed for a change in the color during the perturbation, we find that the binary-source model yields a significantly better fit and thus the degeneracy is clearly resolved. This event not only signifies the importance of considering various interpretations of short-term anomalies, but also demonstrates the importance of multi-band data for checking the possibility of false-positive planetary signals.</P>