The myeloid transcription factor KLF2 regulates the host response to polymicrobial infection and endotoxic shock

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Highlights? KLF2 deficiency confers a proinflammatory phenotype to myeloid cells ? Myeloid KLF2 deficiency renders animals resistant to polymicrobial infection ? Myeloid KLF2 deficiency renders animals susceptible to endotoxic shock ? KLF2 negatively regulates the NF-κB-HIF-1α axis in macrophages     

Arachidonate 5-lipoxygenase establishes adaptive humoral immunity by controlling primary B cells and their cognate T-cell help

In this study, we report the unique role of arachidonate 5-lipoxygenase (Alox5) in the regulation of specific humoral immune responses. We previously reported an L22 monoclonal antibody with which human primary resting B cells in the mantle zones of lymphoid follicles are well-defined. Proteomics analyses enabled identification of an L22 antigen as Alox5, which was highly expressed by naive and memory B cells surrounding germinal centers. Cellular growth of mantle cell lymphoma cells also seemed to depend on Alox5. Alox5(-/-) mice exhibited weak antibody responses specific to foreign antigens at the initial and recall phases. This was probably attributable to the low number of follicular and memory B cells and the functional loss of interleukin-21-mediated responses of follicular B cells. Moreover, Alox5(-/-) mice could not fully foster the development of follicular B helper T (Tfh) cells even after immunization with foreign antigens. Further experiments indicated that Alox5 affected mortality in experimentally induced enterocolitis in germ-prone circumstances, indicating that Alox5 would endow immunologic milieu. Our results illustrate the novel role of Alox5 in adaptive humoral immunity by managing primary B cells and Tfh cells in vivo.     

Acrylamide genotoxicity in young versus adult gpt delta male rats

The recent discovery that the potent carcinogen acrylamide (AA) is present in a variety of fried and baked foods raises health concerns, particularly for children, because AA is relatively high in child-favoured foods such as potato chips and French fries. To compare the susceptibility to AA-induced genotoxicity of young versus adult animals, we treated 3- and 11-week-old male gpt delta transgenic F344 rats with 0, 20, 40 or 80 p.p.m. AA via drinking water for 4 weeks and then examined genotoxicity in the bone marrow, liver and testis. We also analysed the level of N7-(2-carbamoyl-2-hydroxyethyl)-guanine (N7-GA-Gua), the major DNA adduct induced by AA, in the liver, testis and mammary gland. At 40 and 80 p.p.m., both age groups yield similar results in the comet assay in liver; but at 80 p.p.m., the bone marrow micronucleus frequency and the gpt-mutant frequency in testis increased significantly only in the young rats, and N7-GA-Gua adducts in the testis was significantly higher in the young rats. These results imply that young rats are more susceptible than adult rats to AA-induced testicular genotoxicity.     

Molecular evidence for multicentric development of thyroid carcinomas in patients with familial adenomatous polyposis

Familial adenomatous polyposis is characterized by multiple colorectal adenomas and an increased incidence of colorectal carcinomas. Patients also develop various extracolonic tumors, of which, thyroid carcinoma is common in young females. The occurrence of multiple carcinomas in one thyroid is frequently observed, although some carcinomas are solitary. To clarify whether each carcinoma develops independently or metastatically spreads from the first one formed, we analyzed the adenomatous polyposis coli (APC) gene mutation in each carcinoma. We found that each carcinoma had a different somatic mutation of the APC gene. This is molecular confirmation for the multicentric development of thyroid carcinomas in familial adenomatous polyposis through biallelic inactivation of the APC gene.     

Measurement of Individual Red Blood Cell Motions Under High Hematocrit Conditions Using a Confocal Micro-PTV System

Developments in optical experimental techniques have helped in elucidating how blood flows through microvessels. Although initial developments were encouraging, studies on the flow properties of blood in microcirculation have been limited by several technical factors, such as poor spatial resolution and difficulty obtaining quantitative detailed measurements at such small scales. Recent advances in computing, microscopy, and digital image processing techniques have made it possible to combine a particle tracking velocimetry (PTV) system with a confocal microscope. We document the development of a confocal micro-PTV measurement system for capturing the dynamic flow behavior of red blood cells (RBCs) in concentrated suspensions. Measurements were performed at several depths through 100-μm glass capillaries. The confocal micro-PTV system was able to detect both translational and rotational motions of individual RBCs flowing in concentrated suspensions. Our results provide evidence that RBCs in dilute suspensions (3% hematocrit) tended to follow approximately linear trajectories, whereas RBCs in concentrated suspensions (20% hematocrit) exhibited transversal displacements of about 2% from the original path. Direct and quantitative measurements indicated that the plasma layer appeared to enhance the fluctuations in RBC trajectories owing to decreased obstruction in transversal movements caused by other RBCs. Using optical sectioning and subsequent image contrast and resolution enhancement, the system provides previously unobtainable information on the motion of RBCs, including the trajectories of two or more RBCs interacting in the same focal plane and RBC dispersion coefficients in different focal planes. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

Asymmetry of prefrontal cortex activities and catechol-O-methyltransferase Val158Met genotype in patients with panic disorder during a verbal fluency task: Near-infrared spectroscopy study

We examined the relationship between the catechol-O-methyltransferase (COMT) Val158Met genotype and frontal lobe function by using multi-channel near-infrared spectroscopy (NIRS). The present study investigated oxygenated ([oxy-Hb]) and deoxygenated ([deoxy-Hb]) hemoglobin concentration changes during the performance of a verbal fluency task in the frontal region of 71 patients with panic disorder (PD). The activation of [oxy-Hb] on the right lateral prefrontal cortex was observed in the Met/Met genotype of the COMT gene polymorphism of PD patient groups in the analysis of NIRS, which seems to be related to the autonomic dysfunction in the pathogenesis of PD.     

Regulation of osteoclast differentiation and function by receptor activator of NFkB ligand and osteoprotegerin

The differentiation and functions of osteoclasts (OCs) are regulated by osteoblast-derived factors. Receptor activator of NFkB ligand (RANKL) is one of the key regulatory molecules in OC formation. Osteoprotegerin (OPG) is a novel secreted member of the TNF receptor superfamily that negatively regulates osteoclastogenesis and binds to RANKL. We examined the biological actions of macrophage-colony-stimulating factor (M-CSF), RANKL, and OPG on the differentiation of OCs isolated from cocultures of mouse osteoblastic cells and bone marrow cells. Preosteoclasts (pOCs) and OCs were characterized by their ultrastructure and the expression of OC markers such as tartrate-resistant acid phosphatase (TRAP) and vacuolar-type H(+)-ATPase. pOCs formed without any additives expressed TRAP, but showed little resorptive activity on cocultured dentine slices. TRAP-positive pOCs treated with M-CSF began to fuse with each other, but lacked a ruffled border (RB) and showed almost no resorptive activity. pOCs treated with RANKL became TRAP-positive multinucleated cells, which expressed intense vacuolar-type H(+)-ATPase along the RB membranes and exhibited prominent resorptive activity. Such effects of RANKL on pOCs were completely inhibited by the addition of OPG. OPG inhibited RB formation in mature OCs and reduced their resorptive activity, and also induced apoptosis of some OCs. These results suggest that 1) RANKL induces differentiation of functional OCs from pOCs, 2) M-CSF induces macrophage-like multinucleated cells, but not OCs, 3) OPG inhibits RB formation and resorptive activity in mature OCs, 4) OPG also induces apoptosis of OCs, and 5) RANKL and OPG are, therefore, important regulators of not only the terminal differentiation of OCs but also their resorptive function.     

Cellular expression of CD markers in immune thrombocytopenic purpura: implications for prognosis

Immune thrombocytopenic purpura (ITP) is an autoimmune bleeding disorder associated with platelet destruction. Abnormalities in frequency and function of different immune cells can play a crucial role in this disease. The aim of this study was to evaluate the prognostic value of CD markers’ expressions by immune cells in ITP. Peripheral blood samples were collected from 25 ITP patients before and after treatment. The expression of CD markers was evaluated by flow cytometry technique. The expression of CD38 and CD56 was significantly lower before treatment than after it (p = 0.025 and p = 0.036, respectively). Furthermore, a positive correlation was found between CD38 expression with platelet count before (r = 0.496, p = 0.012) and after treatment (r = 0.404, p = 0.045). No significant relationship was found between this marker and platelet count while CD4 expression was higher before treatment than after it (p = 0.002). In conclusion, CD38 may have independent prognostic value in ITP and we suggest that it can be a prognostic marker for this disease.     

Molecular phylogeny of Blastocystis isolates from wild rodents captured in Indonesia and Japan

Parasitology Research - Blastocystis sp. is a common intestinal protist found worldwide in a variety of animals, including humans. Currently, 17 subtypes (STs) of Blastocystis isolates from...