Acquired dysfibrinogenemia: monoclonal λ-type IgA binding to fibrinogen caused lower functional plasma fibrinogen level and abnormal clot formation

ArticleInternational journal of hematology. 112(1): 96-104. (2020)journal articl

Low Surface Potential with Glycoconjugates Determines Insect Cell Adhesion at Room Temperature

Cell-coupled field-effect transistor (FET) biosensors have attracted considerable attention because of their high sensitivity to biomolecules. The use of insect cells (Sf21) as a core sensor element is advantageous due to their stable adhesion to sensors at room temperature. Although visualization of the insect cell-substrate interface leads to logical amplification of signals, the spatiotemporal processes at the interfaces have not yet been elucidated. We quantitatively monitored the adhesion dynamics of Sf21 using interference reflection microscopy (IRM). Specific adhesion signatures with ring-like patches along the cellular periphery were detected. A combination of zeta potential measurements and lectin staining identified specific glycoconjugates with low electrostatic potentials. The ring-like structures were disrupted after cholesterol depletion, suggesting a raft domain along the cell periphery. Our results indicate dynamic and asymmetric cell adhesion is due to low electrostatic repulsion with fluidic sugar rafts. We envision the logical design of cell-sensor interfaces with an electrical model that accounts for actual adhesion interfaces.Matsuzaki T., Terutsuki D., Sato S., et al. Low Surface Potential with Glycoconjugates Determines Insect Cell Adhesion at Room Temperature. Journal of Physical Chemistry Letters 2022 13(40), 9494-9500. DOI: 10.1021/acs.jpclett.2c01673. Copyright © 2022 American Chemical Society

Slc3a2 Mediates Branched-Chain Amino-Acid-Dependent Maintenance of Regulatory T Cells

Foxp3+ regulatory T (Treg) cells, which suppress immune responses, are highly proliferative in vivo. However, it remains unclear how the active replication of Treg cells is maintained in vivo. Here, we show that branched-chain amino acids (BCAAs), including isoleucine, are required for maintenance of the proliferative state of Treg cells via the amino acid transporter Slc3a2-dependent metabolic reprogramming. Mice fed BCAA-reduced diets showed decreased numbers of Foxp3+ Treg cells with defective in vivo proliferative capacity. Mice lacking Slc3a2 specifically in Foxp3+ Treg cells showed impaired in vivo replication and decreased numbers of Treg cells. Slc3a2-deficient Treg cells showed impaired isoleucine-induced activation of the mTORC1 pathway and an altered metabolic state. Slc3a2 mutant mice did not show an isoleucine-induced increase of Treg cells in vivo and exhibited multi-organ inflammation. Taken together, these findings demonstrate that BCAA controls Treg cell maintenance via Slc3a2-dependent metabolic regulation

Probiotic Bifidobacterium breve Induces IL-10-Producing Tr1 Cells in the Colon

Specific intestinal microbiota has been shown to induce Foxp3+ regulatory T cell development. However, it remains unclear how development of another regulatory T cell subset, Tr1 cells, is regulated in the intestine. Here, we analyzed the role of two probiotic strains of intestinal bacteria, Lactobacillus casei and Bifidobacterium breve in T cell development in the intestine. B. breve, but not L. casei, induced development of IL-10-producing Tr1 cells that express cMaf, IL-21, and Ahr in the large intestine. Intestinal CD103+ dendritic cells (DCs) mediated B. breve-induced development of IL-10-producing T cells. CD103+ DCs from Il10−/−, Tlr2−/−, and Myd88−/− mice showed defective B. breve-induced Tr1 cell development. B. breve-treated CD103+ DCs failed to induce IL-10 production from co-cultured Il27ra−/− T cells. B. breve treatment of Tlr2−/− mice did not increase IL-10-producing T cells in the colonic lamina propria. Thus, B. breve activates intestinal CD103+ DCs to produce IL-10 and IL-27 via the TLR2/MyD88 pathway thereby inducing IL-10-producing Tr1 cells in the large intestine. Oral B. breve administration ameliorated colitis in immunocompromised mice given naïve CD4+ T cells from wild-type mice, but not Il10−/− mice. These findings demonstrate that B. breve prevents intestinal inflammation through the induction of intestinal IL-10-producing Tr1 cells

ACE (I/D) polymorphism and response to treatment in coronary artery disease: a comprehensive database and meta-analysis involving study quality evaluation

<p>Abstract</p> <p>Background</p> <p>The role of angiotensin-converting enzyme (<it>ACE</it>) gene insertion/deletion (<it>I/D</it>) polymorphism in modifying the response to treatment modalities in coronary artery disease is controversial.</p> <p>Methods</p> <p>PubMed was searched and a database of 58 studies with detailed information regarding <it>ACE I/D </it>polymorphism and response to treatment in coronary artery disease was created. Eligible studies were synthesized using meta-analysis methods, including cumulative meta-analysis. Heterogeneity and study quality issues were explored.</p> <p>Results</p> <p>Forty studies involved invasive treatments (coronary angioplasty or coronary artery by-pass grafting) and 18 used conservative treatment options (including anti-hypertensive drugs, lipid lowering therapy and cardiac rehabilitation procedures). Clinical outcomes were investigated by 11 studies, while 47 studies focused on surrogate endpoints. The most studied outcome was the restenosis following coronary angioplasty (34 studies). Heterogeneity among studies (p < 0.01) was revealed and the risk of restenosis following balloon angioplasty was significant under an additive model: the random effects odds ratio was 1.42 (95% confidence interval:1.07–1.91). Cumulative meta-analysis showed a trend of association as information accumulates. The results were affected by population origin and study quality criteria. The meta-analyses for the risk of restenosis following stent angioplasty or after angioplasty and treatment with angiotensin-converting enzyme inhibitors produced non-significant results. The allele contrast random effects odds ratios with the 95% confidence intervals were 1.04(0.92–1.16) and 1.10(0.81–1.48), respectively. Regarding the effect of <it>ACE I/D </it>polymorphism on the response to treatment for the rest outcomes (coronary events, endothelial dysfunction, left ventricular remodeling, progression/regression of atherosclerosis), individual studies showed significance; however, results were discrepant and inconsistent.</p> <p>Conclusion</p> <p>In view of available evidence, genetic testing of <it>ACE I/D </it>polymorphism prior to clinical decision making is not currently justified. The relation between <it>ACE </it>genetic variation and response to treatment in CAD remains an unresolved issue. The results of long-term and properly designed prospective studies hold the promise for pharmacogenetically tailored therapy in CAD.</p

2017 HRS/EHRA/ECAS/APHRS/SOLAECE expert consensus statement on catheter and surgical ablation of atrial fibrillation: executive summary.

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Microlensig Binaries with Candidate Brown Dwarf Companions

Brown dwarfs are important objects because they may provide a missing link between stars and planets, two populations that have dramatically different formation history. In this paper, we present the candidate binaries with brown dwarf companions that are found by analyzing binary microlensing events discovered during 2004 - 2011 observation seasons. Based on the low mass ratio criterion of q < 0.2, we found 7 candidate events, including OGLE-2004-BLG-035, OGLE-2004-BLG-039, OGLE-2007-BLG-006, OGLE-2007-BLG-399/MOA-2007-BLG-334, MOA-2011-BLG-104/OGLE-2011-BLG-0172, MOA-2011-BLG-149, and MOA-201-BLG-278/OGLE-2011-BLG-012N. Among them, we are able to confirm that the companions of the lenses of MOA-2011-BLG-104/OGLE-2011-BLG-0172 and MOA-2011-BLG-149 are brown dwarfs by determining the mass of the lens based on the simultaneous measurement of the Einstein radius and the lens parallax. The measured mass of the brown dwarf companions are (0.02 +/- 0.01) M_Sun and (0.019 +/- 0.002) M_Sun for MOA-2011-BLG-104/OGLE-2011-BLG-0172 and MOA-2011-BLG-149, respectively, and both companions are orbiting low mass M dwarf host stars. More microlensing brown dwarfs are expected to be detected as the number of lensing events with well covered light curves increases with new generation searches.Comment: 10 pages, 9 figures, 4 table

Uncovering Ubiquitin and Ubiquitin-like Signaling Networks

Microscopic imaging and technolog

2017 HRS/EHRA/ECAS/APHRS/SOLAECE expert consensus statement on catheter and surgical ablation of atrial fibrillation: executive summary.

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