373 research outputs found
DBR1 siRNA inhibition of HIV-1 replication
BACKGROUND: HIV-1 and all retroviruses are related to retroelements of simpler organisms such as the yeast Ty elements. Recent work has suggested that the yeast retroelement Ty1 replicates via an unexpected RNA lariat intermediate in cDNA synthesis. The putative genomic RNA lariat intermediate is formed by a 2'-5' phosphodiester bond, like that found in pre-mRNA intron lariats and it facilitates the minus-strand template switch during cDNA synthesis. We hypothesized that HIV-1 might also form a genomic RNA lariat and therefore that siRNA-mediated inhibition of expression of the human RNA lariat de-branching enzyme (DBR1) expression would specifically inhibit HIV-1 replication. RESULTS: We designed three short interfering RNA (siRNA) molecules targeting DBR1, which were capable of reducing DBR1 mRNA expression by 80% and did not significantly affect cell viability. We assessed HIV-1 replication in the presence of DBR1 siRNA and found that DBR1 knockdown led to decreases in viral cDNA and protein production. These effects could be reversed by cotransfection of a DBR1 cDNA indicating that the inhibition of HIV-1 replication was a specific effect of DBR1 underexpression. CONCLUSION: These data suggest that DBR1 function may be needed to debranch a putative HIV-1 genomic RNA lariat prior to completion of reverse transcription
Programa para Modificar Alteraciones de la Imagen Corporal en Estudiantes de Bachillerato
Eating disorders are associated with several health problems, so it is important to prevent its occurrence. This study evaluated the impact of a selective prevention program designed to modify body image disturbances. Sample included 15 women from 15 to 18 years old, recruited through advertisements placed in a public high school situated in north zone of Mexico City. Participants were randomly assigned to one of two conditions: cognitive-behavioral (n = 8) and wait list control group (n = 7) and completed three measures (Body Shape Questionnaire, Contour Drawing Rating Scale, and Body Image Avoidance Questionnaire) before and after the intervention, which included 7 sessions (two per week) for 2 hours each. The repeated measures ANOVA indicated a reduction in body dissatisfaction and avoidance of social activities. The results provide evidence for the use of cognitive behavioral prevention programs
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Speech and language markers of neurodegeneration: a call for global equity
In the field of neurodegeneration, speech and language assessments are useful for diagnosing aphasic syndromes and for characterizing other disorders. As a complement to classic tests, scalable and low-cost digital tools can capture relevant anomalies automatically, potentially supporting the quest for globally equitable markers of brain health. However, this promise remains unfulfilled due to limited linguistic diversity in scientific works and clinical instruments. Here we argue for cross-linguistic research as a core strategy to counter this problem. First, we survey the contributions of linguistic assessments in the study of primary progressive aphasia and the three most prevalent neurodegenerative disorders worldwide-Alzheimer's disease, Parkinson's disease, and behavioural variant frontotemporal dementia. Second, we address two forms of linguistic unfairness in the literature: the neglect of most of the world's 7000 languages and the preponderance of English-speaking cohorts. Third, we review studies showing that linguistic dysfunctions in a given disorder may vary depending on the patient's language and that English speakers offer a suboptimal benchmark for other language groups. Finally, we highlight different approaches, tools and initiatives for cross-linguistic research, identifying core challenges for their deployment. Overall, we seek to inspire timely actions to counter a looming source of inequity in behavioural neurology
A SAS-6-like protein suggests that the Toxoplasma conoid complex evolved from flagellar components
SAS-6 is required for centriole biogenesis in diverse eukaryotes. Here, we describe a novel family of SAS-6-like (SAS6L) proteins that share an N-terminal domain with SAS-6 but lack coiled-coil tails. SAS6L proteins are found in a subset of eukaryotes that contain SAS-6, including diverse protozoa and green algae. In the apicomplexan parasite Toxoplasma gondii, SAS-6 localizes to the centriole but SAS6L is found above the conoid, an enigmatic tubulin-containing structure found at the apex of a subset of alveolate organisms. Loss of SAS6L causes reduced fitness in Toxoplasma. The Trypanosoma brucei homolog of SAS6L localizes to the basal-plate region, the site in the axoneme where the central-pair microtubules are nucleated. When endogenous SAS6L is overexpressed in Toxoplasma tachyzoites or Trypanosoma trypomastigotes, it forms prominent filaments that extend through the cell cytoplasm, indicating that it retains a capacity to form higher-order structures despite lacking a coiled-coil domain. We conclude that although SAS6L proteins share a conserved domain with SAS-6, they are a functionally distinct family that predates the last common ancestor of eukaryotes. Moreover, the distinct localization of the SAS6L protein in Trypanosoma and Toxoplasma adds weight to the hypothesis that the conoid complex evolved from flagellar components
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Examining the relation between bilingualism and age of symptom onset in frontotemporal dementia.
Bilingualism is thought to confer advantages in executive functioning, thereby contributing to cognitive reserve and a later age of dementia symptom onset. While the relation between bilingualism and age of onset has been explored in Alzheimer's dementia, there are few studies examining bilingualism as a contributor to cognitive reserve in frontotemporal dementia (FTD). In line with previous findings, we hypothesized that bilinguals with behavioral variant FTD would be older at symptom onset compared to monolinguals, but that no such effect would be found in patients with nonfluent/agrammatic variant primary progressive aphasia (PPA) or semantic variant PPA. Contrary to our hypothesis, we found no significant difference in age at symptom onset between monolingual and bilingual speakers within any of the FTD variants, and there were no notable differences on neuropsychological measures. Overall, our results do not support a protective effect of bilingualism in patients with FTD-spectrum disease in a U.S. based cohort
Business Consulting para la empresa Recursos Marítimos Recumar S.A.S
El sector marítimo portuario está pasando por diversos cambios como consecuencia
de la problemática mundial sanitaria, en ese escenario muchas empresas buscan la
oportunidad de crecimiento. Para ello resulta necesario plantearse estrategias alcanzables y
tomar acción a partir de un análisis del entorno.
El presente documento tiene como finalidad mostrar el desarrollo de la consultoría de
negocios realizada a la empresa colombiana denominada RECUMAR SAS, dedicada a
brindar servicios, asesoría y venta de suministros en el sector marítimo portuario de
Colombia, Panamá, Ecuador, Perú y Chile. Basados en la información brindada por la
compañía, se identificó diversos problemas internos y externos que fueron originados por la
ausencia de una ruta estratégica, que permita a la empresa lograr el futuro deseado en este
contexto de incertidumbre y complejidad.
El desarrollo de la consultoría consistirá en el diseño de una ruta estratégica teniendo
como marco de referencia una adaptación del modelo secuencial del proceso estratégico
desarrollado por el profesor Fernando D’Alessio, así como los seis pilares de la gestión
estratégica y los aspectos estratégicos del entorno VUCA. Logrando de esta manera,
proporcionar a la compañía un análisis de la situación actual, la identificación de los
principales problemas, visión, misión, objetivos de largo plazo, estrategias y objetivos de
corto plazo que permitan que la empresa logre una situación futura deseada.The maritime port sector is going through various changes as a result of the global
sanitary problem, in this scenario many companies seek the opportunity for growth. For this,
it is necessary to consider achievable strategies and take actions based on analysis of the
environment.
The purpose of this document is to show the development of the business consulting
carried out to the Colombian company called RECUMAR SAS, dedicated to providing
services, consulting and supplies in the maritime/port sector of Colombia, Panama, Ecuador,
Peru and Chile. Based on the information provided by the company, various internal and
external problems were identified, caused by the absence of a strategic plan, which will allow
the company to achieve the desired future in this context of uncertainty and complexity.
The development of the consultancy will consist of the design of a strategic route
taking as a frame of reference an adaptation of the sequential model of the strategic process
developed by Professor Fernando D'Alessio, as well as the six pillars of strategic
management and the strategic aspects of the environment VUCA. Achieving in this way,
provide the company with an analysis of the current situation, the identification of the main
problems, vision, mission, long-term objectives, strategies and short-term objectives that
allow the company to achieve a desired future situation
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Network anatomy in logopenic variant of primary progressive aphasia
The logopenic variant of primary progressive aphasia (lvPPA) is a neurodegenerative syndrome characterized linguistically by gradual loss of repetition and naming skills resulting from left posterior temporal and inferior parietal atrophy. Here, we sought to identify which specific cortical loci are initially targeted by the disease (epicenters) and investigate whether atrophy spreads through predetermined networks. First, we used cross-sectional structural MRI data from individuals with lvPPA to define putative disease epicenters using a surface-based approach paired with an anatomically fine-grained parcellation of the cortical surface (i.e., HCP-MMP1.0 atlas). Second, we combined cross-sectional functional MRI data from healthy controls and longitudinal structural MRI data from individuals with lvPPA to derive the epicenter-seeded resting-state networks most relevant to lvPPA symptomatology and ascertain whether functional connectivity in these networks predicts longitudinal atrophy spread in lvPPA. Our results show that two partially distinct brain networks anchored to the left anterior angular and posterior superior temporal gyri epicenters were preferentially associated with sentence repetition and naming skills in lvPPA. Critically, the strength of connectivity within these two networks in the neurologically-intact brain significantly predicted longitudinal atrophy progression in lvPPA. Taken together, our findings indicate that atrophy progression in lvPPA, starting from inferior parietal and temporoparietal junction regions, predominantly follows at least two partially nonoverlapping pathways, which may influence the heterogeneity in clinical presentation and prognosis
Blinded, multi-centre evaluation of drug-induced changes in contractility using human induced pluripotent stem cell-derived cardiomyocytes
Animal models are 78% accurate in determining whether drugs will alter contractility of the human heart. To evaluate the suitability of human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) for predictive safety pharmacology, we quantified changes in contractility, voltage, and/or Ca2+ handling in 2D monolayers or 3D engineered heart tissues (EHTs). Protocols were unified via a drug training set, allowing subsequent blinded multicenter evaluation of drugs with known positive, negative, or neutral inotropic effects. Accuracy ranged from 44% to 85% across the platform-cell configurations, indicating the need to refine test conditions. This was achieved by adopting approaches to reduce signal-to-noise ratio, reduce spontaneous beat rate to ≤ 1 Hz or enable chronic testing, improving accuracy to 85% for monolayers and 93% for EHTs. Contraction amplitude was a good predictor of negative inotropes across all the platform-cell configurations and of positive inotropes in the 3D EHTs. Although contraction- and relaxation-time provided confirmatory readouts forpositive inotropes in 3D EHTs, these parameters typically served as the primary source of predictivity in 2D. The reliance of these “secondary” parameters to inotropy in the 2D systems was not automatically intuitive and may be a quirk of hiPSC-CMs, hence require adaptations in interpreting the data from this model system. Of the platform-cell configurations, responses in EHTs aligned most closely to the free therapeutic plasma concentration. This study adds to the notion that hiPSC-CMs could add value to drug safety evaluation
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