Predictive Values of Factors Affecting Reading Comprehension Assessment

The complex nature of reading comprehension makes it challenging to assess. Comprehension assessment results frequently do not directly indicate which skills should be addressed to remediate comprehension difficulties. The current study investigated which underlying skills are most related to a common reading comprehension test. The reading skills that were measured in this study include single-word reading accuracy, single-word reading fluency, textual reading fluency and accuracy, oral reading comprehension abilities, and silent reading comprehension abilities. The findings indicate that reading rate is associated with oral reading comprehension abilities and that word reading accuracy is important for oral reading comprehension abilities

Caffeine: friend or foe?

The debate on the safety of and regulatory approaches for caffeine continues among various stakeholders and regulatory authorities. This decision-making process comes with significant challenges, particularly when considering the complexities of the available scientific data, making the formulation of clear science-based regulatory guidance more difficult. To allow for discussions of a number of key issues, the North American Branch of the International Life Sciences Institute (ILSI) convened a panel of subject matter experts for a caffeine-focused session entitled “Caffeine: Friend or Foe?,” which was held during the 2015 ILSI Annual Meeting. The panelists’ expertise covered topics ranging from the natural occurrence of caffeine in plants and interindividual metabolism of caffeine in humans to specific behavioral, reproductive, and cardiovascular effects related to caffeine consumption. Each presentation highlighted the potential risks, benefits, and challenges that inform whether caffeine exposure warrants concern. This paper aims to summarize the key topics discussed during the session

Herpes Simplex Virus Virion Host Shutoff Protein Is Stimulated by Translation Initiation Factors eIF4B and eIF4H

The virion host shutoff protein (vhs) of herpes simplex virus triggers accelerated degradation of cellular and viral mRNAs while sparing other cytoplasmic RNA species. Previous work has shown that vhs forms a complex with translation initiation factor eIF4H, which displays detectable RNase activity in the absence of other viral or host proteins. However, the contributions of eIF4H and other host factors to the activity and mRNA targeting properties of vhs have not yet been directly examined. An earlier report from our laboratory demonstrated that rabbit reticulocyte lysate (RRL) contains one or more factors that strongly stimulate the RNase activity of vhs produced in Saccharomyces cerevisiae. We report here that such yeast extracts display significant vhs-dependent RNase activity in the absence of mammalian factors. This activity differs from that displayed by vhs generated in RRL in that it is not targeted to the encephalomyocarditis virus (EMCV) internal ribosome entry site (IRES). Activity was strongly enhanced by the addition of RRL, eIF4H, or the related translation factor eIF4B. RRL also reconstituted strong targeting to the EMCV IRES, resulting in a major change in the RNA cleavage pattern. In contrast, eIF4H and eIF4B did not reconstitute IRES-directed targeting. These data indicate that eIF4B and 4H stimulate the nuclease activity of vhs, and they provide evidence that additional mammalian factors are required for targeting to the EMCV IRES

Cell-Type-Specific Tyrosine Phosphorylation of the Herpes Simplex Virus Tegument Protein VP11/12 Encoded by Gene UL46▿

Cytotoxic T lymphocytes (CTL) and natural killer (NK) cells play key roles in limiting herpesvirus infections; consequently, many herpesviruses, including herpes simplex virus (HSV), have evolved diverse strategies to evade and/or disarm these killer lymphocytes. Previous studies have shown that CTL and NK cells are functionally inactivated following contact with HSV-infected fibroblasts. During studies of the mechanisms involved, we discovered that HSV-inactivated NK-92 NK cells and Jurkat T cells contain a strikingly prominent, novel, ca. 90-kDa tyrosine-phosphorylated protein that we identified as the HSV tegument protein VP11/12. Inasmuch as VP11/12 produced in fibroblasts and epithelial cells is not obviously tyrosine phosphorylated, these data suggested that VP11/12 serves as the substrate of a cell-type-specific protein tyrosine kinase. Consistent with this hypothesis, VP11/12 was also tyrosine phosphorylated in B lymphocytes, and this modification was severely reduced in Jurkat T cells lacking the lymphocyte-specific Src family kinase Lck. These findings demonstrate that HSV tegument proteins can be differentially modified depending on the cell type infected. Our data also raise the possibility that VP11/12 may modulate one or more lymphocyte-specific signaling pathways or serve another lymphocyte-specific function. However, HSV type 1 mutants lacking the UL46 gene retained the ability to block signaling through the T-cell receptor in Jurkat cells and remained competent to functionally inactivate the NK-92 NK cell line, indicating that VP11/12 is not essential for lymphocyte inactivation. Further studies are therefore required to determine the biological function of tyrosine-phosphorylated VP11/12

Comparison of Single-Photon Emission Computed Tomography–Computed Tomography (SPECT/CT) and Conventional Planar Lymphoscintigraphy for Sentinel Node Localization in Patients with Cutaneous Malignancies

BackgroundAccurate preoperative lymphoscintigraphy is vital to performing sentinel lymph node biopsy (SLNB) for cutaneous malignancies. Potential advantages of single-photon emission computed tomography with integrated computed tomography (SPECT/CT) include the ability to readily identify aberrant drainage patterns as well as provide the surgeon with three-dimensional anatomic landmarks not seen on conventional planar lymphoscintigraphy (PLS).MethodsPatients with cutaneous malignancies who underwent SLNB with preoperative imaging using both SPECT/CT and PLS from 2011 to 2014 were identified.ResultsBoth SPECT/CT and PLS were obtained in 351 patients (median age, 69 years; range, 5-94 years) with cutaneous malignancies (melanoma = 300, Merkel cell carcinoma = 33, squamous cell carcinoma = 8, other = 10) after intradermal injection of 99mtechnetium sulfur colloid (median dose 300 µCi). A mean of 4.3 hot spots were identified on SPECT/CT compared to 3.0 on PLS (p < 0.001). One hundred fifty-three patients (43.6 %) had identical findings between SPECT/CT and PLS, while 172 (49 %) had additional hot spots identified on SPECT/CT compared to only 24 (6.8 %) additional on PLS. SPECT/CT demonstrated additional nodal basins in 103 patients (29.4 %), compared to only 11 patients (3.1 %) with additional basins on PLS.ConclusionsSPECT/CT is a useful adjunct that can help with sentinel node localization in challenging cases. It identified additional hot spots not seen on PLS in almost 50 % of patients. Because PLS identified hot spots not seen on SPECT/CT in 6.8 % of patients, we recommend using both modalities jointly. Long-term follow-up will be required to validate the clinical significance of the additional hot spots identified by SPECT/CT

Negative regulation of eosinophil recruitment to the lung by the chemokine monokine induced by IFN-γ (Mig, CXCL9)

Experimental analysis of allergic airway inflammation (AAI) in animals and humans is associated with coordinate gene induction. Using DNA microarray analysis, we have identified a large panel of AAI signature genes. Unexpectedly, the allergen-challenged lung (a T helper 2 microenvironment) was found to be associated with the expression of T helper 1-associated CXCR3 ligands, monokine induced by IFN-γ (Mig), and IFN-γ-inducible protein of 10 kDa (IP-10). Here we report that Mig functions as a negative regulator of murine eosinophils. Whereas Mig was not able to induce chemotaxis of eosinophils, pretreatment with Mig induced a dose-dependent inhibition of chemoattractant-induced eosinophil transmigration in vitro. Moreover, i.v. administration of low doses of Mig (≈10–30 μg/kg) induced strong and specific dose-dependent inhibition of chemokine-, IL-13-, and allergen-induced eosinophil recruitment and, conversely, neutralization of Mig before allergen challenge increased airway eosinophilia. Importantly, Mig also inhibited a CCR3-mediated functional response in eosinophils. These results indicate that the ultimate distribution and function of inflammatory cells within the allergic lung is dictated by a balance between positively and negatively regulatory chemokines. The identification of a naturally occurring eosinophil inhibitory chemokine pathway in vivo provides a strategic basis for future therapeutic consideration