Antigen Complexed with a TLR9 Agonist Bolsters c-Myc and mTORC1 Activity in Germinal Center B Lymphocytes.

The germinal center (GC) is the anatomical site where humoral immunity evolves. B cells undergo cycles of proliferation and selection to produce high-affinity Abs against Ag. Direct linkage of a TLR9 agonist (CpG) to a T-dependent Ag increases the number of GC B cells. We used a T-dependent Ag complexed with CpG and a genetic model for ablating the TLR9 signaling adaptor molecule MyD88 specifically in B cells (B-MyD88- mice) together with transcriptomics to determine how this innate pathway positively regulates the GC. GC B cells from complex Ag-immunized B-MyD88- mice were defective in inducing gene expression signatures downstream of c-Myc and mTORC1. In agreement with the latter gene signature, ribosomal protein S6 phosphorylation was increased in GC B cells from wild-type mice compared with B-MyD88- mice. However, GC B cell expression of a c-Myc protein reporter was enhanced by CpG attached to Ag in both wild-type and B-MyD88- mice, indicating a B cell-extrinsic effect on c-Myc protein expression combined with a B cell-intrinsic enhancement of gene expression downstream of c-Myc. Both mTORC1 activity and c-Myc are directly induced by T cell help, indicating that TLR9 signaling in GC B cells either enhances their access to T cell help or directly influences these pathways to further enhance the effect of T cell help. Taken together, these findings indicate that TLR9 signaling in the GC could provide a surrogate prosurvival stimulus, "TLR help," thus lowering the threshold for selection and increasing the magnitude of the GC response

An Examination of the Factors and Characteristics that Contribute to the Success of Putnam Fellows

The William Lowell Putnam Mathematical Competition is an intercollegiate mathematics competition for students in the United States and Canada and is regarded as the most prestigious and challenging mathematics competition in North America (Alexanderson, 2004; AMS, 2020; Grossman, 2002; Reznick, 1994; Schoenfeld, 1985). Students who earn the five highest scores on the examination are named Putnam Fellows. Since its inception in 1938, only 306 individuals have won the competition and a select few have won multiple times. Clearly, being named a Putnam Fellow is a remarkable achievement and therefore, understanding the factors and characteristics that contribute to their success is important for students interested in mathematics and STEM-related fields. Twenty-five males who were named Putnam Fellows either four, three, or two times were recruited for the study. A 17-item questionnaire was created from various research sources (Campbell, 1996a, 1996b; Campbell & Wu, 1996; DeFranco, 1996), and used to collect information around four broad areas—personal experiences, formal educational experiences, the affective domain and the cognitive domain. Qualitative research techniques were used to analyze the data. The results indicated that four subcategories of personal experiences, five subcategories of formal educational experiences, seven subcategories involving the affective domain, and three subcategories of the cognitive domain all played an important role in the development of Putnam Fellows. Future research recommendations should examine the factors and characteristics of female Putnam winners and ways to promote and support them as well as the role that Pólya-like heuristics play in the development of Putnam winners

A Critical Role for Syk in Signal Transduction and Phagocytosis Mediated by Fcγ Receptors on Macrophages

Receptors on macrophages for the Fc region of IgG (FcγR) mediate a number of responses important for host immunity. Signaling events necessary for these responses are likely initiated by the activation of Src-family and Syk-family tyrosine kinases after FcγR cross-linking. Macrophages derived from Syk-deficient (Syk−) mice were defective in phagocytosis of particles bound by FcγRs, as well as in many FcγR-induced signaling events, including tyrosine phosphorylation of a number of cellular substrates and activation of MAP kinases. In contrast, Syk− macrophages exhibited normal responses to another potent macrophage stimulus, lipopolysaccharide. Phagocytosis of latex beads and Escherichia coli bacteria was also not affected. Syk− macrophages exhibited formation of polymerized actin structures opposing particles bound to the cells by FcγRs (actin cups), but failed to proceed to internalization. Interestingly, inhibitors of phosphatidylinositol 3-kinase also blocked FcγR-mediated phagocytosis at this stage. Thus, PI 3-kinase may participate in a Syk-dependent signaling pathway critical for FcγR-mediated phagocytosis. Macrophages derived from mice deficient for the three members of the Src-family of kinases expressed in these cells, Hck, Fgr, and Lyn, exhibited poor Syk activation upon FcγR engagement, accompanied by a delay in FcγR-mediated phagocytosis. These observations demonstrate that Syk is critical for FcγR-mediated phagocytosis, as well as for signal transduction in macrophages. Additionally, our findings provide evidence to support a model of sequential tyrosine kinase activation by FcγR's analogous to models of signaling by the B and T cell antigen receptors

All-plastic electrochemical transistor for glucose sensing using a ferrocene mediator.

We demonstrate a glucose sensor based on an organic electrochemical transistor (OECT) in which the channel, source, drain, and gate electrodes are made from the conducting polymer poly(3,4-ethylenedioxythiophene) doped with poly(styrene sulfonate) (PEDOT:PSS). The OECT employs a ferrocene mediator to shuttle electrons between the enzyme glucose oxidase and a PEDOT:PSS gate electrode. The device can be fabricated using a one-layer patterning process and offers glucose detection down to the micromolar range, consistent with levels present in human saliva

Area-level poverty and preterm birth risk: A population-based multilevel analysis

<p>Abstract</p> <p>Background</p> <p>Preterm birth is a complex disease with etiologic influences from a variety of social, environmental, hormonal, genetic, and other factors. The purpose of this study was to utilize a large population-based birth registry to estimate the independent effect of county-level poverty on preterm birth risk. To accomplish this, we used a multilevel logistic regression approach to account for multiple co-existent individual-level variables and county-level poverty rate.</p> <p>Methods</p> <p>Population-based study utilizing Missouri's birth certificate database (1989–1997). We conducted a multilevel logistic regression analysis to estimate the effect of county-level poverty on PTB risk. Of 634,994 births nested within 115 counties in Missouri, two levels were considered. Individual-level variables included demographics factors, prenatal care, health-related behavioral risk factors, and medical risk factors. The area-level variable included the percentage of the population within each county living below the poverty line (US census data, 1990). Counties were divided into quartiles of poverty; the first quartile (lowest rate of poverty) was the reference group.</p> <p>Results</p> <p>PTB < 35 weeks occurred in 24,490 pregnancies (3.9%). The rate of PTB < 35 weeks was 2.8% in counties within the lowest quartile of poverty and increased through the 4^thquartile (4.9%), p < 0.0001. High county-level poverty was significantly associated with PTB risk. PTB risk (< 35 weeks) was increased for women who resided in counties within the highest quartile of poverty, adjusted odds ratio (_adjOR) 1.18 (95% CI 1.03, 1.35), with a similar effect at earlier gestational ages (< 32 weeks), _adjOR 1.27 (95% CI 1.06, 1.52).</p> <p>Conclusion</p> <p>Women residing in socioeconomically deprived areas are at increased risk of preterm birth, above other underlying risk factors. Although the risk increase is modest, it affects a large number of pregnancies.</p