Brain microvasculature defects and Glut1 deficiency syndrome averted by early repletion of the glucose transporter-1 protein

Haploinsufficiency of the SLC2A1 gene and paucity of its translated product, the glucose transporter-1 (Glut1) protein, disrupt brain function and cause the neurodevelopmental disorder, Glut1 deficiency syndrome (Glut1 DS). There is little to suggest how reduced Glut1 causes cognitive dysfunction and no optimal treatment for Glut1 DS. We used model mice to demonstrate that low Glut1 protein arrests cerebral angiogenesis, resulting in a profound diminution of the brain microvasculature without compromising the blood–brain barrier. Studies to define the temporal requirements for Glut1 reveal that pre-symptomatic, AAV9-mediated repletion of the protein averts brain microvasculature defects and prevents disease, whereas augmenting the protein late, during adulthood, is devoid of benefit. Still, treatment following symptom onset can be effective; Glut1 repletion in early-symptomatic mutants that have experienced sustained periods of low brain glucose nevertheless restores the cerebral microvasculature and ameliorates disease. Timely Glut1 repletion may thus constitute an effective treatment for Glut1 DS

Peer navigation improves diagnostic follow-up after breast cancer screening among Korean American women: results of a randomized trial

To test an intervention to increase adherence to diagnostic follow-up tests among Asian American women. Korean American women who were referred for a diagnostic follow-up test (mainly diagnostic mammograms) and who had missed their follow-up appointment were eligible to participate in the study. Women from two clinics (n = 176) were randomly allocated to a usual care control arm or a peer navigator intervention arm. A 20-min telephone survey was administered to women in both study arms six months after they were identified to assess demographic and socio-economic characteristics and the primary outcome, self-reported completion of the recommended follow-up exam. Among women who completed the survey at six-month follow-up, self-reported completion of follow-up procedures was 97% in the intervention arm and 67% in the control arm (p < 0.001). Based on an intent-to-treat analysis of all women who were randomized and an assumption of no completion of follow-up exam for women with missing outcome data, self-reported completion of follow-up was 61% in the intervention arm and 46% in the usual care control arm (p < 0.069). Our results suggest that a peer navigator intervention to assist Korean American women to obtain follow-up diagnostic tests after an abnormal breast cancer screening test is efficacious

Ectopic Expression of Vaccinia Virus E3 and K3 Cannot Rescue Ectromelia Virus Replication in Rabbit RK13 Cells

Citation: Hand, E. S., Haller, S. L., Peng, C., Rothenburg, S., & Hersperger, A. R. (2015). Ectopic Expression of Vaccinia Virus E3 and K3 Cannot Rescue Ectromelia Virus Replication in Rabbit RK13 Cells. Plos One, 10(3), 15. doi:10.1371/journal.pone.0119189As a group, poxviruses have been shown to infect a wide variety of animal species. However, there is individual variability in the range of species able to be productively infected. In this study, we observed that ectromelia virus (ECTV) does not replicate efficiently in cultured rabbit RK13 cells. Conversely, vaccinia virus (VACV) replicates well in these cells. Upon infection of RK13 cells, the replication cycle of ECTV is abortive in nature, resulting in a greatly reduced ability to spread among cells in culture. We observed ample levels of early gene expression but reduced detection of virus factories and severely blunted production of enveloped virus at the cell surface. This work focused on two important host range genes, named E3L and K3L, in VACV. Both VACV and ECTV express a functional protein product from the E3L gene, but only VACV contains an intact K3L gene. To better understand the discrepancy in replication capacity of these viruses, we examined the ability of ECTV to replicate in wild-type RK13 cells compared to cells that constitutively express E3 and K3 from VACV. The role these proteins play in the ability of VACV to replicate in RK13 cells was also analyzed to determine their individual contribution to viral replication and PKR activation. Since E3L and K3L are two relevant host range genes, we hypothesized that expression of one or both of them may have a positive impact on the ability of ECTV to replicate in RK13 cells. Using various methods to assess virus growth, we did not detect any significant differences with respect to the replication of ECTV between wild-type RK13 compared to versions of this cell line that stably expressed VACV E3 alone or in combination with K3. Therefore, there remain unanswered questions related to the factors that limit the host range of ECTV

Introduction to “Binary Binds”: Deconstructing Sex and Gender Dichotomies in Archaeological Practice

YesGender archaeology has made significant strides toward deconstructing the hegemony of binary categorizations. Challenging dichotomies such as man/woman, sex/gender, and biology/culture, approaches informed by poststructuralist, feminist, and queer theories have moved beyond essentialist and universalist identity constructs to more nuanced configurations. Despite the theoretical emphasis on context, multiplicity, and fluidity, binary starting points continue to streamline the spectrum of variability that is recognized, often reproducing normative assumptions in the evidence. The contributors to this special issue confront how sex, gender, and sexuality categories condition analytical visibility, aiming to develop approaches that respond to the complexity of theory in archaeological practice. The papers push the ontological and epistemological boundaries of bodies, personhood, and archaeological possibility, challenging a priori assumptions that contain how sex, gender, and sexuality categories are constituted and related to each other. Foregrounding intersectional approaches that engage with ambiguity, variability, and difference, this special issue seeks to “de-contain” categories, assumptions, and practices from “binding” our analytical gaze toward only certain kinds of persons and knowledges, in interpretations of the past and practices in the present

Control of urea hydrolysis and nitrification in soil by chemicals - Prospects and problems

A review is made of the recent work to assess the prospects of regulating urea hydrolysis and nitrification processes in soils by employing chemicals that can retard urea hydrolysis and nitrification. The possible benefits from control of nitrogen transformations in terms of conserving and enhancing fertilizer nitrogen efficiency for crop production and the problems associated with their use with regard to N metabolism of plants have also been discussed with examples. Prospects of using cheap and effective indigenous materials and chemicals for control of urea hydrolysis and nitrification under specific soil situations appear eminent in improving the fertilizer nitrogen efficiency. Urease inhibitors may be helpful in reducing problems associated with ammonia volatilization if this is not offset by leaching of urea. On the other hand retardation of nitrification appears useful in reducing losses that accompany nitrification due to leaching and denitrification, and with the plants that metabolize equally well with relatively higher amounts of NH4–N may be more effective in improving the utilization of fertilizer N under these situation

Strengthening the citizens' role in international organizations

Today’s international organizations are characterized by a fundamental deficit in democracy. We therefore propose institutional measures to increase the direct participation possibilities of the citizens in international organizations. In order to reduce the number of citizens involved in decision-making to a manageable size, a representative sample of trustees is selected using a random mechanism. The trustees are given the right to launch initiatives and to vote in referendums on issues related to an international organization’s constitution. They can also recall executives when they are dissatisfied with their behavior. No specific changes to the organization of these entities, especially their executive function, are proposed. Rather, the executives of international organizations must obey the constitutional changes adopted by the trustees. The proposal gives international organizations democratic legitimacy. Moreover, the executives are subjected to the control of the citizens of the member states, which induces better responsiveness to the preferences of the people, as well as higher organizational efficiency