Toll‐like receptor‐mediated IRE1α activation as a therapeutic target for inflammatory arthritis

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/102185/1/embj2013183-sup-0004-SourceData-S4.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/102185/2/embj2013183-sup-0001.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/102185/3/embj2013183-sup-0008-SourceData-S8.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/102185/4/embj2013183-sup-0005-SourceData-S5.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/102185/5/embj2013183-sup-0001-SourceData-S1.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/102185/6/embj2013183-sup-0009-SourceData-S9.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/102185/7/embj2013183-sup-0006-SourceData-S6.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/102185/8/embj2013183-sup-0002-SourceData-S2.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/102185/9/embj2013183-sup-0010-SourceData-S10.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/102185/10/embj2013183-sup-0007-SourceData-S7.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/102185/11/embj2013183-sup-0003-SourceData-S3.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/102185/12/embj2013183.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/102185/13/embj2013183.reviewer_comments.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/102185/14/embj2013183-sup-0011-SourceData-S11.pd

CNS-Native Myeloid Cells Drive Immune Suppression in the Brain Metastatic Niche through Cxcl10

Brain metastasis (br-met) develops in an immunologically unique br-met niche. Central nervous system-native myeloid cells (CNS-myeloids) and bone-marrow-derived myeloid cells (BMDMs) cooperatively regulate brain immunity. The phenotypic heterogeneity and specific roles of these myeloid subsets in shaping the br-met niche to regulate br-met outgrowth have not been fully revealed. Applying multimodal single-cell analyses, we elucidated a heterogeneous but spatially defined CNS-myeloid response during br-met outgrowth. We found Ccr2+ BMDMs minimally influenced br-met while CNS-myeloid promoted br-met outgrowth. Additionally, br-met-associated CNS-myeloid exhibited downregulation of Cx3cr1. Cx3cr1 knockout in CNS-myeloid increased br-met incidence, leading to an enriched interferon response signature and Cxcl10 upregulation. Significantly, neutralization of Cxcl10 reduced br-met, while rCxcl10 increased br-met and recruited VISTAHi PD-L1+ CNS-myeloid to br-met lesions. Inhibiting VISTA- and PD-L1-signaling relieved immune suppression and reduced br-met burden. Our results demonstrate that loss of Cx3cr1 in CNS-myeloid triggers a Cxcl10-mediated vicious cycle, cultivating a br-met-promoting, immune-suppressive niche

Análise dos Fatores Que Influenciam a Intenção de Uso do M-Commerce por Americanos da Geração Millennial

Over the last few years, there has been an increase in m-commerce (mobile commerce) sales by means of smartphones, which has had a significant impact on the electronic commerce of the countries. Thus, there is a need to investigate the factors that influence users’ Intention to Use m-commerce. Through an adaptation of the UTAUT (Unified Theory of Acceptance and Use of Technology) model, this study looked at the factors that affect the Usage Intention of Americans. The results reaffirm the relationship between the Expectation of Performance and the Facilitating Conditions in the Intention to Use. Besides, it confirmed the relationship between the Expectation of Performance and the Expectation of Effort, as well as between the Expectations of Effort in the Facilitating Conditions. Finally, it presents the moderating effect of age between social influence and the Intention to Use mobile m-commerce.Ao longo dos últimos anos, evidenciou-se um crescimento de vendas através do m-commerce (mobile commerce), por meio dos smartphones, que passou a ter impacto significativo no comércio eletrônico dos países. Com isso, surge a necessidade de investigar quais são os fatores que influenciam a Intenção de Uso do m-commerce pelos usuários. Por intermédio de uma adaptação do modelo da UTAUT (Unified Theory of Acceptance and Use of Technology – Teoria Unificada de Aceitação e Uso de Tecnologia), este estudo analisou fatores que afetam a Intenção de Uso de americanos. Os resultados reafirmam a relação entre a Expectativa de Performance e as Condições Facilitadoras e a Intenção de Uso. Além disso, confirmou-se a relação entre a Expectativa de Performance e a Expectativa de Esforço e entre a Expectativa de Esforço e as Condições Facilitadoras. Por fim, apresenta-se o efeito moderador da idade entre a Influência Social e a Intenção de Uso do m-commerce

Fault geometry and fluid-rock reaction: combined controls on mineralization in the Xinli gold deposit, Jiaodong Peninsula, China

The structures and fluid-rock reaction in the Xinli gold deposit, Jiaodong Peninsula, were investigated to further understand their combined controls on the development of permeability associated with ore-forming fluid migration. Orebodies in this deposit are hosted by the moderately SE-to S-dipping Sanshandao-Cangshang fault (SCF). Variations in both dip direction and dip angle along the SCF plane produced fault bends, which controlled the fluid accumulation and ore-shoot formation. Gold mineralizations occurred in early gold-quartz-pyrite and late gold-quartz-polymetallic sulphide stages following pervasive sericitization and silicification alterations. Theoretical calculation indicates that sericitization caused 8-57% volume decrease resulting in the development/enlargement of voids, further increase of grain-scale permeability, and resultant precipitation of the early gold-quartz-pyrite pods, which destroyed permeability. The rock softening produced by alterations promoted activities of SCF secondary faults and formation of new fractures, which rebuilt the permeability and controlled the late gold-quartz-polymetallic sulfide veins. Quantitative studies on permeability distributions show that the southwestern and northeastern bend areas with similar alteration and mineralization have persistent and anti-persistent permeability networks, respectively. These were likely caused by different processes of rebuilding permeability due to different stress states resulting from changes in fault geometry

Identification and mapping of geochemical patterns and their significance for regional metallogeny in the southern Sanjiang, China

The southern Sanjiang region, southwestern China, comprises various continental blocks, tectonic sutures and arcs. This complex structural area is a proper place for the recognition of geochemical patterns and understanding of regional metallogenesis. Considering each individual tectonic unit (i.e., western South China block, Ailaoshan suture, Simao block, Changning-Menglian suture, Baoshan block and Tengchong block) as a statistical unit, this study identifies the distribution patterns of geochemical elements, distinguishes elemental associations for different geological backgrounds (controlled by the regional lithology) and diverse mineralizations, and thereby delineates the mineralized anomalies. To achieve the goals, the kriging interpolation, staged factor analysis and local singularity technology were utilized after the centered logratio (clr) transformation of stream sediment geochemical data. The spatial distributions of metallogenic elements (Au, Ag, Cu, Pb, Zn and Sn) show that not all the areas with high concentrations of elements contain ore deposits. It means that the formation of ore deposits is an independent anomalous geological event, not necessarily related to the original regional abundance of geochemical elements. The different element associations obtained by staged factor analysis of 28 elements are able to reveal the geological backgrounds and metallogenic signatures for different tectonic units. For example, the element associations for the first, second and third factors (Fs) in the western South China block are groups of Ti-Co-V, Sb-Ag-As and Th-U-Be (see text for the detailed element associations), which represent the Emeishan flood basalts, Ag-Pb mineralization and felsic rocks, respectively. Similarly, the element associations Co-V-Cu, Be-U-Th and Sb-Ag-Au for F1, F2 and F3 in the Ailaoshan suture respectively represent the ophiolite complex and mafic rocks, felsic rocks and Au mineralization. The associations from F1 to F4 in the Simao block are ThU-Sn, V-Co-Cr, Cd-Ag-Pb and Au-Sb, which represent the Linchang batholith, mafic rocks, Ag-Pb-Zn mineralization and Au mineralization, respectively. The distribution patterns of their factor scores can roughly distinguish the anomalies caused by regional backgrounds and mineralizations. The local singularity of factor scores for mineralization can further identify mineralized areas in most of the tectonic units. Nevertheless, an exception occurs in the western South China block where the background element association, Ti-Co-V-Cu-Ni-Cr-P-MnNb-Zn (F1), obscures the Au signature. Therefore, we substituted the single element Au for mineralized element association (F1) to perform singularity mapping, and obtained better result. It was concluded that the combination of staged factor analysis, local singularity and tectonic setting is effective in regional metallogenic potential analysis

Chiral Surfactant-Type Catalyst: Enantioselective Reduction of Long-Chain Aliphatic Ketoesters in Water

A series of amphiphilic ligands were designed and synthesized. The rhodium complexes with the ligands were applied to the asymmetric transfer hydrogenation of broad range of long-chained aliphatic ketoesters in neat water. Quantitative conversion and excellent enantioselectivity (up to 99% ee) was observed for α-, β-, γ-, δ- and ε-ketoesters as well as for α- and β-acyloxyketone using chiral surfactant-type catalyst <b>2</b>. The CH/π interaction and the strong hydrophobic interaction of long aliphatic chains between the catalyst and the substrate in the metallomicelle core played a key role in the catalytic transition state. Synergistic effects between the metal-catalyzed site and the hydrophobic microenvironment of the core in the micelle contributed to high stereoselectivity