The 5′ Leader of the mRNA Encoding the Mouse Neurotrophin Receptor TrkB Contains Two Internal Ribosomal Entry Sites that Are Differentially Regulated

A single internal ribosomal entry site (IRES) in conjunction with IRES transactivating factors (ITAFs) is sufficient to recruit the translational machinery to a eukaryotic mRNA independent of the cap structure. However, we demonstrate that the mouse TrkB mRNA contains two independent IRESes. The mouse TrkB mRNA consists of one of two 5′ leaders (1428 nt and 448 nt), both of which include the common 3′ exon (Ex2, 344 nt). Dicistronic RNA transfections and in vitro translation of monocistronic RNA demonstrated that both full-length 5′ leaders, as well as Ex2, exhibit IRES activity indicating the IRES is located within Ex2. Additional analysis of the upstream sequences demonstrated that the first 260 nt of exon 1 (Ex1a) also contains an IRES. Dicistronic RNA transfections into SH-SY5Y cells showed the Ex1a IRES is constitutively active. However, the Ex2 IRES is only active in response to retinoic acid induced neural differentiation, a state which correlates with the synthesis of the ITAF polypyrimidine tract binding protein (PTB1). Correspondingly, addition or knock-down of PTB1 altered Ex2, but not Ex1a IRES activity in vitro and ex vivo, respectively. These results demonstrate that the two functionally independent IRESes within the mouse TrkB 5′ leader are differentially regulated, in part by PTB1

Plasmacytoid Dendritic Cells Sequester High Prion Titres at Early Stages of Prion Infection

In most transmissible spongiform encephalopathies prions accumulate in the lymphoreticular system (LRS) long before they are detectable in the central nervous system. While a considerable body of evidence showed that B lymphocytes and follicular dendritic cells play a major role in prion colonization of lymphoid organs, the contribution of various other cell types, including antigen-presenting cells, to the accumulation and the spread of prions in the LRS are not well understood. A comprehensive study to compare prion titers of candidate cell types has not been performed to date, mainly due to limitations in the scope of animal bioassays where prohibitively large numbers of mice would be required to obtain sufficiently accurate data. By taking advantage of quantitative in vitro prion determination and magnetic-activated cell sorting, we studied the kinetics of prion accumulation in various splenic cell types at early stages of prion infection. Robust estimates for infectious titers were obtained by statistical modelling using a generalized linear model. Whilst prions were detectable in B and T lymphocytes and in antigen-presenting cells like dendritic cells and macrophages, highest infectious titers were determined in two cell types that have previously not been associated with prion pathogenesis, plasmacytoid dendritic (pDC) and natural killer (NK) cells. At 30 days after infection, NK cells were more than twice, and pDCs about seven-fold, as infectious as lymphocytes respectively. This result was unexpected since, in accordance to previous reports prion protein, an obligate requirement for prion replication, was undetectable in pDCs. This underscores the importance of prion sequestration and dissemination by antigen-presenting cells which are among the first cells of the immune system to encounter pathogens. We furthermore report the first evidence for a release of prions from lymphocytes and DCs of scrapie-infected mice ex vivo, a process that is associated with a release of exosome-like membrane vesicles

Law, Environment, and the “Nondismal” Social Sciences

Over the past 30 years, the influence of economics over the study of environmental law and policy has expanded considerably, becoming in the process the predominant framework for analyzing regulations that address pollution, natural resource use, and other environmental issues. This review seeks to complement the expansion of economic reasoning and methodology within the field of environmental law and policy by identifying insights to be gleaned from various “nondismal” social sciences. In particular, three areas of inquiry are highlighted as illustrative of interdisciplinary work that might help to complement law and economics and, in some cases, compensate for it: the study of how human individuals perceive, judge, and decide; the observation and interpretation of how knowledge schemes are created, used, and regulated; and the analysis of how states and other actors coordinate through international and global regulatory regimes. The hope is to provide some examples of how environmental law and policy research can be improved by deeper and more diverse engagement with social science

It’s Not Only Rents: Explaining the Persistence and Change of Neopatrimonialism in Indonesia

Indonesia has long been associated with neopatrimonialism, corruption, collusion, and nepotism as the main modi operandi of politics, economics and public administration. Despite various measures and initiatives to fight these practises, little evidence for a significant decline can be found over the years. Rather, longitudinal analysis points to changes in the character of neopatrimonialism. Based on more than 60 in-depth interviews, focus-group discussions, and the analysis of both primary and secondary data, the aim of this article is, first, to describe the changes that have taken place, and, second, to investigate what accounts for these changes. Political economy concepts posit the amount and development of economic rents as the explanatory factor for the persistence and change of neopatrimonialism. This study's findings, however, indicate that rents alone cannot explain what has taken place in Indonesia. Democratisation and decentralisation exert a stronger impact

THE ECOLOGY OF CHONDRUS CRISPUS AT PLYMOUTH, MASSACHUSETTS. III. EFFECT OF ELEVATED TEMPERATURE ON GROWTH AND SURVIVAL

Volume: 145Start Page: 580End Page: 58

Factors Associated with the Presence of Strong Social Supports in Bhutanese Refugee Women During Pregnancy

Social support may mitigate stress related to the refugee experience, including during resettlement. For refugee women, social support can play an important role during pregnancy. In-depth interviews were conducted within a sample of 45 Bhutanese refugee women. Perceived social support was measured using the Norbeck Social Support Questionnaire. Averaged social support scores are reported to account for personal network size. Participants were identified as “low support” and “high support” based on their reported score. The mean social support score reported was 18.9. Participants experiencing a secondary resettlement within the U.S. were 4.52 (95% CI 1.19–17.15) times as likely to report a “high support” network compared to participants who resettled directly from Nepal. Personal social networks are an important source of support for resettled refugee women during pregnancy in the U.S.. Refugee women who experience secondary resettlement may perceive stronger support from their personal connections

Exploring supports or incentives to promote undergraduate students’ use of cooperative study groups

Collaborative study groups provide crucial learning opportunities for undergraduate students in STEM learning contexts. In this paper, we use a concurrent, nested mixed method design toward two primary aims: (a) to examine whether an instructional module about study groups could increase undergraduate students’ use of study groups and (b) to identify supports or incentives that could be used in future research to better encourage students’ use of study groups. Participating undergraduate students (n = 220), who were enrolled in an introductory anatomy and physiology course, were randomly assigned to an instructional module, either about the use of collaborative study groups (i.e., treatment condition) or about how to study effectively on their own (i.e., independent studying comparison condition). All students reported the extent to which they studied collaboratively before and after completing the randomly assigned module (i.e., at pretest and posttest). At the end of the study, students responded to an open-ended prompt asking what could encourage them to use study groups. Quantitative analysis of pretest to posttest changes on the extent to which students reported using study groups revealed no statistically significant condition differences between the two instructional modules. Qualitative thematic analysis of students’ open-ended prompt responses revealed a set of seven themes that emerged from the data about the supports or incentives students wanted that could be leveraged to design future innovations to promote students’ use of collaborative study groups. Follow-up analyses were also conducted to delineate patterns across the supports or incentives requested and further guide recommendations for future research

Co-design of zinc titanium nitride semiconductor towards durable photoelectrochemical applications

Photoelectrochemical fuel generation is a promising route to sustainable liquid fuels produced from water and captured carbon dioxide with sunlight as the energy input. Development of such technologies requires photoelectrode materials that are both photocatalytically active and operationally stable in harsh oxidative and/or reductive electrochemical environments. Such photocatalysts can be discovered based on co-design principles, wherein design for stability is based on the propensity for the photocatalyst to self-passivate under operating conditions and design for photoactivity is based on the ability to integrate the photocatalyst with established semiconductor substrates. Here we report on synthesis and characterization of zinc titanium nitride (ZnTiN2) that follows these design rules by having a wurtzite-derived crystal structure and showing self-passivating surface oxides created by electrochemical polarization. The sputtered ZnTiN2 thin films have optical absorption onsets below 2 eV and n-type electrical conduction of 0.1 S/cm. The band gap of this material is reduced from the 3.5 eV theoretical value by cation site disorder, and the impact of cation antisites on the band structure of ZnTiN2 is explored using density functional theory. Under electrochemical polarization, the ZnTiN2 surfaces have TiO2- or ZnO-like character, consistent with Materials Project Pourbaix calculations predicting the formation of stable solid phases under near-neutral pH. These results show that ZnTiN2 is a promising candidate for photoelectrochemical liquid fuel generation and demonstrate a new materials design approach to other photoelectrodes with self-passivating native operational surface chemistry