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Kim-Howard, Xana,Sun, Celi,Molineros, Julio E.,Maiti, Amit K.,Chandru, Hema,Adler, Adam,Wiley, Graham B.,Kaufman, Kenneth M.,Kottyan, Leah,Guthridge, Joel M.,Rasmussen, Astrid,Kelly, Jennifer,Sá Oxford University Press 2014 Human Molecular Genetics Vol.23 No.6
<P>Recent reports have associated <I>NCF2</I>, encoding a core component of the multi-protein NADPH oxidase (NADPHO), with systemic lupus erythematosus (SLE) susceptibility in individuals of European ancestry. To identify ethnicity-specific and -robust variants within <I>NCF2</I>, we assessed 145 SNPs in and around the <I>NCF2</I> gene in 5325 cases and 21 866 controls of European-American (EA), African-American (AA), Hispanic (HS) and Korean (KR) ancestry. Subsequent imputation, conditional, haplotype and bioinformatic analyses identified seven potentially functional SLE-predisposing variants. Association with non-synonymous rs17849502, previously reported in EA, was detected in EA, HS and AA (<I>P</I><SUB>EA</SUB> = 1.01 × 10<SUP>−54</SUP>, <I>P</I><SUB>HS</SUB> = 3.68 × 10<SUP>−10</SUP>, <I>P</I><SUB>AA</SUB> = 0.03); synonymous rs17849501 was similarly significant. These SNPs were monomorphic in KR. Novel associations were detected with coding variants at rs35937854 in AA (<I>P</I><SUB>AA</SUB> = 1.49 × 10<SUP>−9</SUP>), and rs13306575 in HS and KR (<I>P</I><SUB>HS</SUB> = 7.04 × 10<SUP>−7</SUP>, <I>P</I><SUB>KR</SUB> = 3.30 × 10<SUP>−3</SUP>). In KR, a 3-SNP haplotype was significantly associated (<I>P</I> = 4.20 × 10<SUP>−7</SUP>), implying that SLE predisposing variants were tagged. Significant SNP–SNP interaction (<I>P</I> = 0.02) was detected between rs13306575 and rs17849502 in HS, and a dramatically increased risk (OR = 6.55) with a risk allele at each locus. Molecular modeling predicts that these non-synonymous mutations could disrupt NADPHO complex assembly. The risk allele of rs17849501, located in a conserved transcriptional regulatory region, increased reporter gene activity, suggesting <I>in vivo</I> enhancer function. Our results not only establish allelic heterogeneity within <I>NCF2</I> associated with SLE, but also emphasize the utility of multi-ethnic cohorts to identify predisposing variants explaining additional phenotypic variance (‘missing heritability’) of complex diseases like SLE.</P>
L. Molinero,J. Esteban,F. Sanchez,F. Garcia-Ochoa,M. Ladero 한국공업화학회 2022 Journal of Industrial and Engineering Chemistry Vol.109 No.-
As a way to valorise glycerol, the main by-product of biodiesel, this study is focused on the production ofesters of p-methoxycinnamic acid and glycerol. These esters can replace hazardous octylmethoxycinnamatein the cosmetic industry, which is thought to act as an endocrine disruptor and can interfere withthyroid function. Several sulfonated mesoporous catalysts, with and without endcapping, were easilysynthetized using several alcohols as porogens. These catalysts were characterized for structure and surfacearea, chemical composition and acidity, and tested under solventless conditions for the esterificationof glycerol with p-methoxycinnamic acid. Their activity was similar to that of p-toluenesulfonic acid. Thebest catalysts for the reaction under study was the end-capped mesoporous solid prepared in isopropanol. Finally, the selected catalyst was tested in 9 runs conducted at 150–170 C and at molar ratiosglycerol:p-methoxycinnamic acid ranging from 3:1 to 9:1. The kinetic model that better fits to the experimentaldata comprises two esterification reactions in-series and a first-order catalyst deactivation. Theactivation energies were 87.33 ± 5.67 kJ mol1 for the average esterification to the monoglycerides, 69. 17 ± 9.84 kJ mol1 in average for the reactions yielding the diglycerides, and 104.00 ± 15.30 kJ mol1for the catalyst deactivation.
McNerney, M. E.,Lee, K.-M.,Zhou, P.,Molinero, L.,Mashayekhi, M.,Guzior, D.,Sattar, H.,Kuppireddi, S.,Wang, C.-R.,Kumar, V.,Alegre, M.-L. Wiley (Blackwell Publishing) 2006 American journal of transplantation Vol.6 No.3
<P>To achieve donor-specific immune tolerance to allogeneic organ transplants, it is imperative to understand the cell types involved in acute allograft rejection. In wild-type mice, CD4(+) T cells are necessary and sufficient for acute rejection of cardiac allografts. However, when T-cell responses are suboptimal, such as in mice treated with costimulation-targeting agents or in CD28-deficient mice, and perhaps in transplanted patients taking immunosuppressive drugs, the participation of other lymphocytes such as CD8(+) T cells and NK1.1(+) cells becomes apparent. We found that host NK but not NKT cells were required for cardiac rejection. Ly49G2(+) NK cells suppressed rejection, whereas a subset of NK cells lacking inhibitory Ly49 receptors for donor MHC class I molecules was sufficient to promote rejection. Notably, rejection was independent of the activating receptors Ly49D and NKG2D. Finally, our experiments supported a mechanism by which NK cells promote expansion and effector function of alloreactive T cells. Thus, therapies aimed at specific subsets of NK cells may facilitate transplantation tolerance in settings of impaired T-cell function.</P>
Movement of the people: Violence and internal displacement
James Meernik,Diego Esparza,Jessica Lucas,Enrique Martinez,Ignacio Molinero,Victoria Nevarez 한국외국어대학교 국제지역연구센터 2020 International Area Studies Review Vol.23 No.3
Individuals internally displaced by conflict are a prominent feature of wars, political violence and other forms of repression. We suggest that a subnational analysis of internally displaced person (IDP) generation can help us determine the extent to which more specific flight-precipitating factors can account for individuals’ behaviors. In particular, we are interested in how different conflict actors and the interactions of these actors affect the production of internally displaced persons. We suggest that some types of conflict actors are more likely to be responsible for greater numbers of internally displaced persons because of their political strategies. We focus on one of the most complex and yet data-rich environments in which the problem of internal displacement has been profound—Colombia. Using extensive data on internally displaced persons in Colombia among its over 1100 municipalities, we examine our expectations using negative binomial analyses to better understand the dynamics of conflict actors, the violence they perpetrate and internal displacement. We find that the identity of the conflict actor does make a difference in producing more internally displaced persons and that conflict between certain conflict actors is especially likely to produce more displaced persons.