Skeletal muscle cells lacking the retinoblastoma protein display defects in muscle gene expression and accumulate in S and G2 phases of the cell cycle.

Viral oncoproteins that inactivate the retinoblastoma tumor suppressor protein (pRb) family both block skeletal muscle differentiation and promote cell cycle progression. To clarify the dependence of terminal differentiation on the presence of the different pRb-related proteins, we have studied myogenesis using isogenic primary fibroblasts derived from mouse embryos individually deficient for pRb, p107, or p130. When ectopically expressed in fibroblasts lacking pRb, MyoD induces an aberrant skeletal muscle differentiation program characterized by normal expression of early differentiation markers such as myogenin and p21, but attenuated expression of late differentiation markers such as myosin heavy chain (MHC). Similar defects in MHC expression were not observed in cells lacking either p107 or p130, indicating that the defect is specific to the loss of pRb. In contrast to wild-type, p107-deficient, or p130-deficient differentiated myocytes that are permanently withdrawn from the cell cycle, differentiated myocytes lacking pRb accumulate in S and G2 phases and express extremely high levels of cyclins A and B, cyclin-dependent kinase (Cdk2), and Cdc2, but fail to readily proceed to mitosis. Administration of caffeine, an agent that removes inhibitory phosphorylations on inactive Cdc2/cyclin B complexes, specifically induced mitotic catastrophe in pRb-deficient myocytes, consistent with the observation that the majority of pRb-deficient myocytes arrest in S and G2. Together, these findings indicate that pRb is required for the expression of late skeletal muscle differentiation markers and for the inhibition of DNA synthesis, but that a pRb-independent mechanism restricts entry of differentiated myocytes into mitosis

Enrollment in YFV Vaccine Trial: An Evaluation of Recruitment Outcomes Associated with a Randomized Controlled Double-Blind Trial of a Live Attenuated Yellow Fever Vaccine

This investigation evaluated several factors associated with diverse participant enrollment of a clinical trial assessing safety, immunogenicity, and comparative viremia associated with administration of 17-D live, attenuated yellow fever vaccine given alone or in combination with human immune globulin. We obtained baseline participant information (e.g., sociodemographic, medical) and followed recruitment outcomes from 2005 to 2007. Of 355 potential Yellow Fever vaccine study participants, 231 cases were analyzed. Strong interest in study participation was observed among racial and ethnically diverse persons with 36.34% eligible following initial study screening, resulting in 18.75% enrollment. The percentage of white participants increased from 63.66% (prescreened sample) to 81.25% (enrollment group). The regression model was significant with white race as a predictor of enrollment (OR=2.744, 95% CI=1.415-5.320, p=0.003).In addition, persons were more likely to enroll via direct outreach and referral mechanisms compared to mass advertising (OR=2.433, 95% CI=1.102-5.369). The findings indicate that racially diverse populations can be recruited to vaccine clinical trials, yet actual enrollment may not reflect that diversit

Newborn care seeking practices in Central and Southern Ethiopia and implications for community based programming

Background: In Ethiopia, close to 120,000 newborns die annually and newborn mortality now constitutes 42% of under-five deaths. The use of health care for newborn illnesses is very limited.Objective: To investigate local perspectives and practices related to newborn care-seeking and the factors affecting them.Methods: Key informant interviews with grandmothers and in-depth interviews with mothers, TBAs and fathers were used to collect data in four communities in Sidama Zone, Southern Nations, Nationalities and Peoples Region and East Shewa Zone and West Arsi Zone in Oromia Region. Analysis consisted of manual thematic coding of the data and synthesis for write-up.Results: Locally recognized signs and types of illness only partially conform to medically recognized danger signs. Households apply home therapies, traditional healers or health facilities to get treatment for sick newborns. Lack of resources, transportation and appropriate treatment are barriers to making use of health facilities.Conclusion: Local conceptions of newborn illnesses, inadequate recognition of danger signs, using traditional treatment, and lack of financial resources, transportation and appropriate treatment constrain or delay resorting to health facilities for newborn illnesses

Multipoint, high time resolution galactic cosmic ray observations associated with two interplanetary coronal mass ejections

[1] Galactic cosmic rays (GCRs) play an important role in our understanding of the interplanetary medium (IPM). The causes of their short timescale variations, however, remain largely unexplored. In this paper, we compare high time resolution, multipoint space-based GCR data to explore structures in the IPM that cause these variations. To ensure that features we see in these data actually relate to conditions in the IPM, we look for correlations between the GCR time series from two instruments onboard the Polar and INTEGRAL (International Gamma Ray Astrophysical Laboratory) satellites, respectively inside and outside Earth\u27s magnetosphere. We analyze the period of 18–24 August 2006 during which two interplanetary coronal mass ejections (ICMEs) passed Earth and produced a Forbush decrease (Fd) in the GCR flux. We find two periods, for a total of 10 h, of clear correlation between small-scale variations in the two GCR time series during these 7 days, thus demonstrating that such variations are observable using space-based instruments. The first period of correlation lasted 6 h and began 2 h before the shock of the first ICME passed the two spacecraft. The second period occurred during the initial decrease of the Fd, an event that did not conform to the typical one- or two-step classification of Fds. We propose that two planar magnetic structures preceding the first ICME played a role in both periods: one structure in driving the first correlation and the other in initiating the Fd

Contribution of cod liver oil-related nutrients (vitamins A, D, E and eicosapentaenoic acid and docosahexaenoic acid) to daily nutrient intake and their associations with plasma concentrations in the EPIC-Norfolk cohort

Total nutrient intake (TNI) is intake from food and supplements. This provides an assessment of nutrient adequacy and the prevalence of excessive intake, as well as the response with respect to biomarkers. Cod liver oil (CLO) is the most frequently consumed supplement in the UK, containing nutrients that might have varying influences on health. We calculated TNI for vitamins A, D and E, as well as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), and assessed associations with the respective blood concentrations

Unusual solar energetic proton fluxes at 1 AU within an interplanetary CME

In mid December 2006 several flares on the Sun occurred in rapid succession, spawning several CMEs and bathing the Earth in multiple solar energetic particle (SEP) events. O ne such SEP occurring on December 15th was observed at the Earth just as an interplanetary CME (ICME) from a previous flare on December 13th was transiting the Earth. Although solar wind observations during this time show typical energetic proton fluxes from the prior SEP and IP shock driven ahead of the ICME, as the ICME passes the Earth unusual energetic particle signatures are observed. Measurem ents from ACE, Wind, and STEREO show unusual proton flux variations at energies ranging from ∼3 MeV up to greater than 70 MeV. Within the Earth’s magnetosphere Polar HIST also sees unusual proton flux v ariations at energies greater than 10 MeV while crossing open field lines in the southern polar cap. However, no such variation in the energetic proton flux is observed at the GOES 10 or GOES 11 spacecraft in geosy nchronous orbit. Differential fluxes observed at GOES 12 in the 15-40 MeV energy range show some variation. However, the overall energetic particle signature within the ICME at GEO orbits remains unclear. This event illustrates the need for caution when using GEO data in detailed studies of SEP events and in interplanetary models of energetic particle transport to 1 AU