Circularization of the HIV-1 RNA genome

Genomic RNA circularization has been proposed for several RNA viruses. In this study, we examined if the 5′ and 3′ ends of the 9-kb HIV-1 RNA genome can interact. In vitro assays demonstrated a specific interaction between transcripts encompassing the 5′ and 3′ terminal 1 kb, suggesting that the HIV-1 RNA genome can circularize. Truncation of the transcripts indicated that the 5′–3′ interaction is formed by 600–700 nt in the gag open reading frame and the terminal 123 nt of the genomic RNA. Detailed RNA structure probing indicates that sequences flanking the 3′ TAR hairpin interact with complementary sequences in the gag gene. Phylogenetic analysis indicates that all HIV-1 subtypes can form the 5′/3′ interaction despite considerable sequence divergence, suggesting an important role of RNA circularization in the HIV-1 replication cycle

Arts Integration into Elementary Science: Force and Motion and Natural Disasters

This study explored the effect of arts integration into science during an instructional unit on force and motion and one addressing natural weather disasters. Seventy-eight elementary students in four classrooms (grade 5, grade 4, and two at grade 3) participated in the study. This study assessed content retention, student-made products (rollercoasters and hurricane shelters), and student attitudes. All students in each classroom experienced the two units of instruction, one unit in the experimental condition of arts integration and one unit in the control condition without arts integration. Both conditions involved students in constructing models of given materials. Each unit consisted of three weeks of instruction with the last week being a final project scored for science content and creativity. This final rollercoaster model or hurricane shelter model supported engineering standard 3-5-ETS1-2. Grade 4 and grade 5 classes showed significant posttest gains and distal posttest gains regarding content scores in favor of the experimental condition with a large effect size. The mean overall product scores favored the experimental condition with a very large effect size. The results indicated that arts integration produced greater creativity, collaboration, and more positive overall perceptions of learning

From international health to global health: how to foster a better dialogue between empirical and normative disciplines.

BACKGROUND: Public health recommendations are usually based on a mixture of empirical evidence and normative arguments: to argue that authorities ought to implement an intervention that has proven effective in improving people's health requires a normative position confirming that the authorities are responsible for improving people's health. While public health (at the national level) is based on a widely accepted normative starting point - namely, that it is the responsibility of the state to improve people's health - there is no widely accepted normative starting point for international health or global health. As global health recommendations may vary depending on the normative starting point one uses, global health research requires a better dialogue between researchers who are trained in empirical disciplines and researchers who are trained in normative disciplines. DISCUSSION: Global health researchers with a background in empirical disciplines seem reluctant to clarify the normative starting point they use, perhaps because normative statements cannot be derived directly from empirical evidence, or because there is a wide gap between present policies and the normative starting point they personally support. Global health researchers with a background in normative disciplines usually do not present their work in ways that help their colleagues with a background in empirical disciplines to distinguish between what is merely personal opinion and professional opinion based on rigorous normative research. If global health researchers with a background in empirical disciplines clarified their normative starting point, their recommendations would become more useful for their colleagues with a background in normative disciplines. If global health researchers who focus on normative issues used adapted qualitative research guidelines to present their results, their findings would be more useful for their colleagues with a background in empirical disciplines. Although a single common paradigm for all scientific disciplines that contribute to global health research may not be possible or desirable, global health researchers with a background in empirical disciplines and global health researchers with a background in normative disciplines could present their 'truths' in ways that would improve dialogue. This paper calls for an exchange of views between global health researchers and editors of medical journals

Portaria n. 478 de 24 de julho de 2008

Interrompe férias de servidor do Superior Tribunal de Justiça

Loss of HR6B ubiquitin-conjugating activity results in damaged synaptonemal complex structure and increased crossing-over frequency during the male meiotic prophase.

The ubiquitin-conjugating enzymes HR6A and HR6B are the two mammalian homologs of Saccharomyces cerevisiae RAD6. In yeast, RAD6 plays an important role in postreplication DNA repair and in sporulation. HR6B knockout mice are viable, but spermatogenesis is markedly affected during postmeiotic steps, leading to male infertility. In the present study, increased apoptosis of HR6B knockout primary spermatocytes was detected during the first wave of spermatogenesis, indicating that HR6B performs a primary role during the meiotic prophase. Detailed analysis of HR6B knockout pachytene nuclei showed major changes in the synaptonemal complexes. These complexes were found to be longer. In addition, we often found depletion of synaptonemal complex proteins from near telomeric regions in the HR6B knockout pachytene nuclei. Finally, we detected an increased number of foci containing the mismatc

Association of the ATN Research Framework With Clinical Profile, Ccognitive Decline, and Mortality in Patients With Dementia With Lewy Bodies

Background and Objectives: The ATN framework has been developed to categorize biological processes within the Alzheimer’s disease (AD) continuum. Since AD pathology often coincides with dementia with Lewy Bodies (DLB), we aimed to investigate the distribution of ATN profiles in DLB and associate ATN-profiles in DLB to prognosis. / Methods: We included 202 DLB patients from the Amsterdam Dementia Cohort (68±7yrs, 19%F, MMSE: 24±3, DAT-SPECT abnormal: 105/119). Patients were classified into eight profiles according to the ATN framework, using CSF Aβ42 (A), CSF p-tau (T) and medial temporal atrophy scores (N). We compared presence of clinical symptoms in ATN profiles and used linear mixed models to analyze decline on cognitive tests (follow-up 3±2yrs for n=139). Mortality risk was assessed using Cox proportional hazards analysis. Analyses were performed on both the eight profiles, as well as three clustered categories (normal AD biomarkers, non-AD pathologic change, AD continuum). / Results: Fifty (25%) DLB patients had normal AD biomarkers (A-T-N-), 37 (18%) had non-AD pathologic change (A-T+N-: 10%/A-T-N+: 6%/A-T+N+: 3%) and 115 (57%) were classified within the AD continuum (A+T-N-: 20%/A+T+N-: 16%/A+T-N+: 10%/A+T+N+: 9%). A+T+N+ patients were older and least often had RBD symptoms. Parkinsonism was more often present in A+T-, compared to A-T+ (independent of N). Compared to patients with normal AD biomarkers, patients in A+ categories showed steeper decline on memory tests and higher mortality risk. Cognitive decline and mortality did not differ between non-AD pathologic change and normal AD biomarkers. / Discussion: In our DLB cohort, we found clinically relevant associations between ATN categories and disease manifestation. Patients within the AD continuum had steeper cognitive decline and shorter survival. Implementing the ATN framework within DLB patients aids in subtyping patients based on underlying biological processes and could provide targets for future treatment strategies, e.g. AD modifying treatment. Expanding the framework by incorporating markers for alpha-synucleinopathy would improve the use of the framework to characterize dementia patients with mixed pathology, which could enhance proper stratification of patients for therapeutic trials

Task shifting and integration of HIV care into primary care in South Africa: The development and content of the streamlining tasks and roles to expand treatment and care for HIV (STRETCH) intervention

Background: Task shifting and the integration of human immunodeficiency virus (HIV) care into primary care services have been identified as possible strategies for improving access to antiretroviral treatment (ART). This paper describes the development and content of an intervention involving these two strategies, as part of the Streamlining Tasks and Roles to Expand Treatment and Care for HIV (STRETCH) pragmatic randomised controlled trial. Methods: Developing the intervention: The intervention was developed following discussions with senior management, clinicians, and clinic staff. These discussions revealed that the establishment of separate antiretroviral treatment services for HIV had resulted in problems in accessing care due to the large number of patients at ART clinics. The intervention developed therefore combined the shifting from doctors to nurses of prescriptions of antiretrovirals (ARVs) for uncomplicated patients and the stepwise integration of HIV care into primary care services. Results: Components of the intervention: The intervention consisted of regulatory changes, training, and guidelines to support nurse ART prescription, local management teams, an implementation toolkit, and a flexible, phased introduction. Nurse supervisors were equipped to train intervention clinic nurses in ART prescription using outreach education and an integrated primary care guideline. Management teams were set up and a STRETCH coordinator was appointed to oversee the implementation process. Discussion: Three important processes were used in developing and implementing this intervention: active participation of clinic staff and local and provincial management, educational outreach to train nurses in intervention sites, and an external facilitator to support all stages of the intervention rollout