Internet Predictions

More than a dozen leading experts give their opinions on where the Internet is headed and where it will be in the next decade in terms of technology, policy, and applications. They cover topics ranging from the Internet of Things to climate change to the digital storage of the future. A summary of the articles is available in the Web extras section

Glycemic index and glycemic load are associated with some cardiovascular risk factors among the PREMIER study participants

Background: The clinical significance of glycemic index (GI) and glycemic load (GL) is inconclusive. Objective : This study was conducted to examine the association of GI and GL with clinical cardiovascular disease (CVD) risk factors including body weight, blood pressure (BP), serum lipids, fasting glucose, insulin and homocysteine over time among the PREMIER participants. Design: PREMIER was an 18-month randomized lifestyle intervention trial, conducted from 2000 to 2002, designed to help participants reduce BP by following the Dietary Approaches to Stop Hypertension (DASH) dietary pattern, losing weight, reducing sodium and increasing physical activity. GI and GL were estimated from 24 h diet recall data at baseline, 6 and 18 months after intervention. PROC MIXED model was used to examine the association of changes in GI or GL with changes in CVD risk factors. Results: A total of 756 randomized participants, 62% females and 34% African Americans and who averaged 50.0±0.3 years old and 95.3±0.7 kg, were included in this report. Neither GI nor GL changes was associated with changes in any risk factors at 6 months. At 18 months, however, the GI change was significantly and positively associated with total cholesterol (TC) change only (p<0.05, β = 23.80±12.11 mg/dL or 0.62±0.31 mmol/L) with a significant age interaction. The GL change was significantly associated with TC (p=0.02, β = 0.28±0.15 mg/dL or 0.01±0.00 mmol/L) positively and with low density lipoprotein cholesterol (LDL-C) changes negatively (p=0.03, β = − 0.01±0.00 mg/dL or −0.00±0.00 mmol/L), and significant age interactions were observed for both. Conclusion: GI and GL was associated with TC and LDL-C after controlling for energy, fat and fiber intake and other potential confounders and the associations were modified by age. Further investigation into this relationship is important because of its potential clinical impact

From Molecular Cores to Planet-forming Disks: An SIRTF Legacy Program

Crucial steps in the formation of stars and planets can be studied only at mid‐ to far‐infrared wavelengths, where the Space Infrared Telescope (SIRTF) provides an unprecedented improvement in sensitivity. We will use all three SIRTF instruments (Infrared Array Camera [IRAC], Multiband Imaging Photometer for SIRTF [MIPS], and Infrared Spectrograph [IRS]) to observe sources that span the evolutionary sequence from molecular cores to protoplanetary disks, encompassing a wide range of cloud masses, stellar masses, and star‐forming environments. In addition to targeting about 150 known compact cores, we will survey with IRAC and MIPS (3.6–70 μm) the entire areas of five of the nearest large molecular clouds for new candidate protostars and substellar objects as faint as 0.001 solar luminosities. We will also observe with IRAC and MIPS about 190 systems likely to be in the early stages of planetary system formation (ages up to about 10 Myr), probing the evolution of the circumstellar dust, the raw material for planetary cores. Candidate planet‐forming disks as small as 0.1 lunar masses will be detectable. Spectroscopy with IRS of new objects found in the surveys and of a select group of known objects will add vital information on the changing chemical and physical conditions in the disks and envelopes. The resulting data products will include catalogs of thousands of previously unknown sources, multiwavelength maps of about 20 deg^2 of molecular clouds, photometry of about 190 known young stars, spectra of at least 170 sources, ancillary data from ground‐based telescopes, and new tools for analysis and modeling. These products will constitute the foundations for many follow‐up studies with ground‐based telescopes, as well as with SIRTF itself and other space missions such as SIM, JWST, Herschel, and TPF/Darwin

Dermal and muscle fibroblasts and skeletal myofibers survive chikungunya virus infection and harbor persistent RNA

Chikungunya virus (CHIKV) is an arthritogenic alphavirus that acutely causes fever as well as severe joint and muscle pain. Chronic musculoskeletal pain persists in a substantial fraction of patients for months to years after the initial infection, yet we still have a poor understanding of what promotes chronic disease. While replicating virus has not been detected in joint-associated tissues of patients with persistent arthritis nor in various animal models at convalescent time points, viral RNA is detected months after acute infection. To identify the cells that might contribute to pathogenesis during this chronic phase, we developed a recombinant CHIKV that expresses Cre recombinase (CHIKV-3'-Cre). CHIKV-3'-Cre replicated in myoblasts and fibroblasts, and it induced arthritis during the acute phase in mice. Importantly, it also induced chronic disease, including persistent viral RNA and chronic myositis and synovitis similar to wild-type virus. CHIKV-3'-Cre infection of tdTomato reporter mice resulted in a population of tdTomato+ cells that persisted for at least 112 days. Immunofluorescence and flow cytometric profiling revealed that these tdTomato+ cells predominantly were myofibers and dermal and muscle fibroblasts. Treatment with an antibody against Mxra8, a recently defined host receptor for CHIKV, reduced the number of tdTomato+ cells in the chronic phase and diminished the levels of chronic viral RNA, implicating these tdTomato+ cells as the reservoir of chronic viral RNA. Finally, isolation and flow cytometry-based sorting of the tdTomato+ fibroblasts from the skin and ankle and analysis for viral RNA revealed that the tdTomato+ cells harbor most of the persistent CHIKV RNA at chronic time points. Therefore, this CHIKV-3'-Cre and tdTomato reporter mouse system identifies the cells that survive CHIKV infection in vivo and are enriched for persistent CHIKV RNA. This model represents a useful tool for studying CHIKV pathogenesis in the acute and chronic stages of disease

Distinct roles of interferon alpha and beta in controlling chikungunya virus replication and modulating neutrophil-mediated inflammation

Type I interferons (IFNs) are key mediators of the innate immune response. Although members of this family of cytokines signal through a single shared receptor, biochemical and functional variation exists in response to different IFN subtypes. While previous work has demonstrated that type I IFNs are essential to control infection by chikungunya virus (CHIKV), a globally emerging alphavirus, the contributions of individual IFN subtypes remain undefined. To address this question, we evaluated CHIKV pathogenesis in mice lacking IFN-β (IFN-β knockout [IFN-β-KO] mice or mice treated with an IFN-β-blocking antibody) or IFN-α (IFN regulatory factor 7 knockout [IRF7-KO] mice or mice treated with a pan-IFN-α-blocking antibody). Mice lacking either IFN-α or IFN-β developed severe clinical disease following infection with CHIKV, with a marked increase in foot swelling compared to wild-type mice. Virological analysis revealed that mice lacking IFN-α sustained elevated infection in the infected ankle and in distant tissues. In contrast, IFN-β-KO mice displayed minimal differences in viral burdens within the ankle or at distal sites and instead had an altered cellular immune response. Mice lacking IFN-β had increased neutrophil infiltration into musculoskeletal tissues, and depletion of neutrophils in IFN-β-KO but not IRF7-KO mice mitigated musculoskeletal disease caused by CHIKV. Our findings suggest disparate roles for the IFN subtypes during CHIKV infection, with IFN-α limiting early viral replication and dissemination and IFN-β modulating neutrophil-mediated inflammation

Objectively Measured Physical Activity in Sixth-Grade Girls

Objectives - To describe the objectively-measured physical activity (PA) characteristics of a diverse sample of 6th grade girls to examine influences on PA, and to report compliance with PA guidelines. Design - Cross-sectional study. Setting - Six locations across the United States. Participants - 1578 6th grade girls. Actigraph accelerometers were worn for 7 days, and data for 6 days were included in the analyses. Main exposure - Race/ethnicity, free-or-reduced price lunch (FRPL), and geographic region. Main outcome measure - Six operational definitions of adequate activity (60 min or 30 min of daily MVPA at or above 4.6, 3.8 or 3.0 METS (metabolic equivalents)) were applied to examine whether girls met physical activity guidelines. Results - Average time spent in sedentary, light, moderate, and vigorous activities was 460, 342, 18, and 6 min/day, respectively. White girls were more active than girls in other race/ethnic groups, and girls who did not receive FRPL were more active than girls who did. Girls in western states were most active. Percentages of girls in compliance with the 6 thresholds for adequate activity varied widely, and ranged from 0.6% to 99.8%. Conclusions - When physical activity is measured objectively and a 4.6 MET cupoint for MVPA is applied, most 6th grade girls fall below guidelines for adequate physical activity. One notable finding was the impact of different accelerometer scoring protocols on estimates of compliance. Conceptual and empirical work is needed to define appropriate physical activity for youth using objective physical activity measures

Interleukin 21 Is a T Helper (Th) Cell 2 Cytokine that Specifically Inhibits the Differentiation of Naive Th Cells into Interferon γ–producing Th1 Cells

The cytokine potential of developing T helper (Th) cells is directly shaped both positively and negatively by the cytokines expressed by the effector Th cell subsets. Here we find that the recently identified cytokine, interleukin (IL)-21, is preferentially expressed by Th2 cells when compared with Th1 cells generated in vitro and in vivo. Exposure of naive Th precursors to IL-21 inhibits interferon (IFN)-γ production from developing Th1 cells. The repression of IFN-γ production is specific in that the expression of other Th1 and Th2 cytokines is unaffected. IL-21 decreases the IL-12 responsiveness of developing Th cells by specifically reducing both signal transducer and activator of transcription 4 protein and mRNA expression. These results suggest that Th2 cell-derived IL-21 regulates the development of IFN-γ–producing Th1 cells which could serve to amplify a Th2 response