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ABSTRACT HIV-1 group M was transmitted to humans nearly one century ago. The virus has since evolved to form distinct clades, which spread to different regions of the world. The envelope glycoproteins (Envs) of HIV-1 have rapidly diversified in all infected populations. We examined whether key antigenic sites of Env and signatures of vaccine efficacy are evolving toward similar or distinct structural forms in different populations worldwide. Patterns of amino acid variants that emerged at each position of Env were compared between diverse HIV-1 clades and isolates from different geographic regions. Interestingly, at each Env position, the amino acid in the clade ancestral or regional-founder virus was replaced by a unique frequency distribution (FD) of amino acids. FDs are highly conserved in populations from different regions worldwide and in paraphyletic and monophyletic subclade groups. Remarkably, founder effects of Env mutations at the clade and regional levels have gradually decreased during the pandemic by evolution of each site toward the unique combination of variants. Therefore, HIV-1 Env is evolving at a population level toward well-defined “target” states; these states are not specific amino acids but rather specific distributions of amino acid frequencies. Our findings reveal the powerful nature of the forces that guide evolution of Env and their conservation across different populations. Such forces have caused a gradual decrease in the interpopulation diversity of Env despite an increasing intrapopulation diversity. IMPORTANCE The Env protein of HIV-1 is the primary target in AIDS vaccine design. Frequent mutations in the virus increase the number of Env forms in each population, limiting the efficacy of AIDS vaccines. Comparison of newly emerging forms in different populations showed that each position of Env is evolving toward a specific combination of amino acids. Similar changes are occurring in different HIV-1 subtypes and geographic regions toward the same position-specific combinations of amino acids, often from distinct ancestral sequences. The predictable nature of HIV-1 Env evolution, as shown here, provides a new framework for designing vaccines that are tailored to the unique combination of variants expected to emerge in each virus subtype and geographic region.

ABSTRACT. The present study is a literature review focused on investigating student academic motivation in relationship with academic performance. Much research has been dedicated to exploring student motivation, the types of motivations and the impact of motivation on student behavior and classroom performance. A specific line of research has explored specifically how teachers understand the use of rewards in classroom, what is the student outcome as of result of using various motivational strategies, and which are the most effective ways to motivate students. Practice shows that a vast majority of teachers use predominantly rewards to enhance student academic motivation, but recent research shows that extensive use of rewards in classrooms can have a negative impact on student intrinsic motivation, and in the long run, a negative impact on student academic achievement as well.

Esta es un exposición que en el marco del ciclo “Derecho y Actualidad” organizado por nuestra Facultad de Derecho, se presenta para todos sus egresados, tanto abogados como escribanos.Puede llamar la atención la inclusión de éstos últimos, en virtud de que la ley concursal regula preferentemente una materia contenciosa.Sin embargo, las razones son importantes y hacen legítima su inclusión en estas actividades de actualización.En primer lugar, todos los operadores de Derecho debemos conocer la Ley y el Escribano es un Operador de Derecho.En segundo lugal, la Función notarial no es solamente formativa y autenticante. El Uruguay tiene función notarial completa, la cual comprende también el área de asesoramiento.Esta área de la función notarial suele ser relegada por la mayoría de los Escribanos, dejándola circunscripta a aquellos involucrados en la actividad académica. Creemos que esa actitud es equivocada.Parte 1: Principios de la Ley ConcursalExpositora: María del Carmen AcuñaParte 2: La actuación notarial en el Proceso ConcursalExpositora: Daniela CianciaruloParte 3: La venta en bloque de la empresa en funcionamientoExpositora: Adriana AmadoParte 4: Legitimación del deudor para disponer y obligara la masa del Concurso en la Ley 18.374Expositora: María Wonsiak

Recent pre-clinical studies have shown that complement activation contributes to glomerular and tubular injury in experimental FSGS. Although complement proteins are detected in the glomeruli of some patients with FSGS, it is not known whether this is due to complement activation or whether the proteins are simply trapped in sclerotic glomeruli. We measured complement activation fragments in the plasma and urine of patients with primary FSGS to determine whether complement activation is part of the disease process.Plasma and urine samples from patients with biopsy-proven FSGS who participated in the FSGS Clinical Trial were analyzed.We identified 19 patients for whom samples were available from weeks 0, 26, 52 and 78. The results for these FSGS patients were compared to results in samples from 10 healthy controls, 10 patients with chronic kidney disease (CKD), 20 patients with vasculitis, and 23 patients with lupus nephritis.Longitudinal control of proteinuria and estimated glomerular filtration rate (eGFR).Levels of the complement fragments Ba, Bb, C4a, and sC5b-9 in plasma and urine.Plasma and urine Ba, C4a, sC5b-9 were significantly higher in FSGS patients at the time of diagnosis than in the control groups. Plasma Ba levels inversely correlated with the eGFR at the time of diagnosis and at the end of the study. Plasma and urine Ba levels at the end of the study positively correlated with the level of proteinuria, the primary outcome of the study.Limited number of patients with samples from all time-points.The complement system is activated in patients with primary FSGS, and elevated levels of plasma Ba correlate with more severe disease. Measurement of complement fragments may identify a subset of patients in whom the complement system is activated. Further investigations are needed to confirm our findings and to determine the prognostic significance of complement activation in patients with FSGS.

Purpose. To explore the interactions between child and parents psychosocial factors and team integration variables that may explain improvements in physical dimensions of the PEDS QL quality of life of children with complex needs after 2 years. Methods. In this 2-year study, parents were identified by the Children's Treatment Network. Families were eligible if the child was aged 0–19 years, had physical limitations, resided in either Simcoe County or the Region of York, Ontario, and there were multiple other family needs. Regression analysis used to explore associations and interactions; n=110. Results. A child's physical quality of life was affected by interacting factors including child's behavior, parenting, and integrated care. Statistically significant interactions between team integration, processes of care, and child/parent variables highlight the complexity of the rehabilitation approach in real-life situations. Conclusions. Rehabilitation providers working with children with complex needs and their families should also address child and parent problematic behaviors. When this was the case in high integrated teams, the child's physical quality of life improved after two years.

Purpose. To determine the quality of life, associations, and costs of a multidiagnosis group of special needs children. Methods. In this cross-sectional survey families were identified from the Children's Treatment Network, a Canadian multisector program for children with special needs. Families were eligible if the child was aged 2–19 years, resided in Simcoe/York, and if there were multiple child/family needs. Quality of life was measured using the PedsQL (n=429). Results. Quality of life scores were lower in this group compared to published healthy and single disorder groups of children. Quality of life scores decreased with advancing age. Child psychosocial well-being was more strongly associated with child/family variables compared to physical well-being. Health Utilization costs were higher in children with greater physical challenges. Conclusions. Further research is needed in other complex needs child samples to confirm the decrease in quality of life found in these children into adolescence. Investigations into the interactions of child and family variables are needed.

Promoter hypermethylation coupled with loss of heterozygosity at the same locus results in loss of gene function in many tumor cells. The "rules" governing which genes are methylated during the pathogenesis of individual cancers, how specific methylation profiles are initially established, or what determines tumor type-specific methylation are unknown. However, DNA methylation markers that are highly specific and sensitive for common tumors would be useful for the early detection of cancer, and those required for the malignant phenotype would identify pathways important as therapeutic targets.In an effort to identify new cancer-specific methylation markers, we employed a high-throughput global expression profiling approach in lung cancer cells. We identified 132 genes that have 5' CpG islands, are induced from undetectable levels by 5-aza-2'-deoxycytidine in multiple non-small cell lung cancer cell lines, and are expressed in immortalized human bronchial epithelial cells. As expected, these genes were also expressed in normal lung, but often not in companion primary lung cancers. Methylation analysis of a subset (45/132) of these promoter regions in primary lung cancer (n = 20) and adjacent nonmalignant tissue (n = 20) showed that 31 genes had acquired methylation in the tumors, but did not show methylation in normal lung or peripheral blood cells. We studied the eight most frequently and specifically methylated genes from our lung cancer dataset in breast cancer (n = 37), colon cancer (n = 24), and prostate cancer (n = 24) along with counterpart nonmalignant tissues. We found that seven loci were frequently methylated in both breast and lung cancers, with four showing extensive methylation in all four epithelial tumors.By using a systematic biological screen we identified multiple genes that are methylated with high penetrance in primary lung, breast, colon, and prostate cancers. The cross-tumor methylation pattern we observed for these novel markers suggests that we have identified a partial promoter hypermethylation signature for these common malignancies. These data suggest that while tumors in different tissues vary substantially with respect to gene expression, there may be commonalities in their promoter methylation profiles that represent targets for early detection screening or therapeutic intervention.

Cellular localization of severe acute respiratory syndrome coronavirus (SARS-CoV) in the lungs of patients with SARS is important in confirming the etiological association of the virus with disease as well as in understanding the pathogenesis of the disease. To our knowledge, there have been no comprehensive studies investigating viral infection at the cellular level in humans.We collected the largest series of fatal cases of SARS with autopsy material to date by merging the pathological material from two regions involved in the 2003 worldwide SARS outbreak in Hong Kong, China, and Toronto, Canada. We developed a monoclonal antibody against the SARS-CoV nucleoprotein and used it together with in situ hybridization (ISH) to analyze the autopsy lung tissues of 32 patients with SARS from Hong Kong and Toronto. We compared the results of these assays with the pulmonary pathologies and the clinical course of illness for each patient. SARS-CoV nucleoprotein and RNA were detected by immunohistochemistry and ISH, respectively, primarily in alveolar pneumocytes and, less frequently, in macrophages. Such localization was detected in four of the seven patients who died within two weeks of illness onset, and in none of the 25 patients who died later than two weeks after symptom onset.The pulmonary alveolar epithelium is the chief target of SARS-CoV, with macrophages infected subsequently. Viral replication appears to be limited to the first two weeks after symptom onset, with little evidence of continued widespread replication after this period. If antiviral therapy is considered for future treatment, it should be focused on this two-week period of acute clinical disease.