Pass-back chain extension expands multimodular assembly line biosynthesis.

Modular nonribosomal peptide synthetase (NRPS) and polyketide synthase (PKS) enzymatic assembly lines are large and dynamic protein machines that generally effect a linear sequence of catalytic cycles. Here, we report the heterologous reconstitution and comprehensive characterization of two hybrid NRPS-PKS assembly lines that defy many standard rules of assembly line biosynthesis to generate a large combinatorial library of cyclic lipodepsipeptide protease inhibitors called thalassospiramides. We generate a series of precise domain-inactivating mutations in thalassospiramide assembly lines, and present evidence for an unprecedented biosynthetic model that invokes intermodule substrate activation and tailoring, module skipping and pass-back chain extension, whereby the ability to pass the growing chain back to a preceding module is flexible and substrate driven. Expanding bidirectional intermodule domain interactions could represent a viable mechanism for generating chemical diversity without increasing the size of biosynthetic assembly lines and challenges our understanding of the potential elasticity of multimodular megaenzymes

Substance use disorders and behavioral addictions during the COVID-19 pandemic and COVID-19-related restrictions

COVID-19 was first identified in Wuhan, China in December of 2019 and appeared in the United States 1 month later. Between the onset of the pandemic and January 13, 2021, over 92 million people have tested positive for the virus and over 1.9 million people have died globally. Virtually every country in the world has been impacted by this virus. Beginning in March 2020, many U.S. state governments enforced a quarantine to respond to the growing health crisis. Citizens were required to remain at home; schools, restaurants, and non-essential businesses were forced to close, and large gatherings were prohibited. Americans\u27 lives were transformed in a span of days as daily routines were interrupted and people were shuttered indoors. Mounting fear and unpredictability coupled with widespread unemployment and social isolation escalated anxiety and impacted the mental health of millions across the globe. Most (53%) U.S. adults reported that the coronavirus outbreak has had a negative impact on their mental health, including inducing or exacerbating use of alcohol, drugs, gambling and overeating as coping mechanisms. In this paper, we will examine substance use and addictive behaviors that have been used to manage the stress and uncertainty wrought by the COVID-19 pandemic. We review the changing treatment landscape as therapy pivoted online and telemedicine became the norm

Toward cognitive digital twins using a BIM-GIS asset management system for a diffused university

The integrated use of building information modeling (BIM) and geographic information system (GIS) is promising for the development of asset management systems (AMSs) for operation and maintenance (O & M) in smart university campuses. The combination of BIM-GIS with cognitive digital twins (CDTs) can further facilitate the management of complex systems such as university building stock. CDTs enable buildings to behave as autonomous entities, dynamically reacting to environmental changes. Timely decisions based on the actual conditions of buildings and surroundings can be provided, both in emergency scenarios or when optimized and adaptive performances are required. The research aims to develop a BIM-GIS-based AMS for improving user experience and enabling the optimal use of resources in the O & M phase of an Italian university. Campuses are complex assets, mainly diffused with buildings spread across the territory, managed with still document-based and fragmented databases handled by several subjects. This results in incomplete and asymmetrical information, often leading to ineffective and untimely decisions. The paper presents a methodology for the development of a BIM-GIS web-based platform (i.e., AMS-app) providing the real-time visualization of the asset in an interactive 3D map connected to analytical dashboards for management support. Two buildings of the University of Turin are adopted as demonstrators, illustrating the development of an easily accessible, centralized database by integrating spatial and functional data, useful also to develop future CDTs. As a first attempt to show the AMS app potential, crowd simulations have been conducted to understand the buildings' actual level of safety in case of fire emergency and demonstrate how CDTs could improve it. The identification of data needed, also gathered through the future implementation of suitable sensors and Internet of Things networks, is the core issue together with the definition of effective asset visualization and monitoring methods. Future developments will explore the integration of artificial intelligence and immersive technologies to enable space use optimization and real-time wayfinding during evacuation, exploiting digital tools to alert and drive users or authorities for safety improvement. The ability to easily optimize the paths with respect to the actual occupancy and conditions of both the asset and surroundings will be enabled

Historia poblacional y análisis antropogenético de la ciudad de Salta

In the present study, the genetic composition of Salta capital city was estimated in a population sample. A total of 223 non-related​ blood-donors from the Centro Privado de Hemoterapia were included, who provided written informed consent and genealogical information. Twelve autosomal markers, GM allotypes, mtDNA and Y-chromosome continental origin were analysed; genetic admixture was estimated employing the ADMIX program. Autosomal markers show the presence of 50,02% for the Amerindian component, 46,29% for the European and 3,51% for the African component. Amerindians mitochondrial haplogroups represented a 93,75%, while the Europeans haplogroups represented a 3,85% and the Africans a 2,40%; 17,1% of males analysed exhibited the aboriginal variant Q*M3. The data were compared to those obtained previously in other cities, and the genetic admixture of Salta showed the highest values of Amerindian and African component. The intraregional immigration is much more remarkable than interregional or foreign immigration. These studies reinforce the idea that the Argentine population should not be considered as a homogeneus totality but variability must be taken into account

Genetic admixture patterns in argentinian patagonia

As in other Latin American populations, Argentinians are the result of the admixture amongst different continental groups, mainly from America and Europe, and to a lesser extent from Sub-Saharan Africa. However, it is known that the admixture processes did not occur homogeneously throughout the country. Therefore, considering the importance for anthropological, medical and forensic researches, this study aimed to investigate the population genetic structure of the Argentinian Patagonia, through the analysis of 46 ancestry informative markers, in 433 individuals from five different localities. Overall, in the Patagonian sample, the average individual ancestry was estimated as 35.8% Native American (95% CI: 32.2–39.4%), 62.1% European (58.5–65.7%) and 2.1% African (1.7–2.4%). Comparing the five localities studied, statistically significant differences were observed for the Native American and European contributions, but not for the African ancestry. The admixture results combined with the genealogical information revealed intra-regional variations that are consistent with the different geographic origin of the participants and their ancestors. As expected, a high European ancestry was observed for donors with four grandparents born in Europe (96.8%) or in the Central region of Argentina (85%). In contrast, the Native American ancestry increased when the four grandparents were born in the North (71%) or in the South (61.9%) regions of the country, or even in Chile (60.5%). In summary, our results showed that differences on continental ancestry contribution have different origins in each region in Patagonia, and even in each locality, highlighting the importance of knowing the origin of the participants and their ancestors for the correct interpretation and contextualization of the genetic information.Finantial support was granted by Agencia Nacional de Promoción Científica y Tecnológica, Argentina (ANPCyT; https://www.argentina.gob.ar/ ciencia/agencia; grants ref. MPL PICT 2013-2414, JLL PICT 2014-1558), and Conselho Nacional de Desenvolvimento Científico e Tecnológico, Brazil (CNPq; http://www.cnpq.br; grant ref. LG 305330/2016-0)

Analysis of biological diversity and miscegenation in the city of Puerto Madryn (Prov.of Chubut, Argentina)

En el marco del estudio de la composición genética de las poblaciones cosmopolitas de Argentina, se analizó una muestra poblacional de la localidad de Puerto Madryn (PM) con la finalidad de evaluar su diversidad biológica mediante la utilización de marcadores biparentales y uniparentales y comparar los resultados con los obtenidos previamente por nuestro equipo de investigación en seis poblaciones cosmopolitas de distintas regiones de la Argentina, aunque poniendo el énfasis a las correspondientes a la Región Patagónica. Las muestras biológicas fueron tomadas con consentimiento informado a 82 dadores de sangre no emparentados que concurrieron al Banco de Sangre y al Hospital Subzonal de dicha localidad, a quienes también se les realizó una encuesta genealógica. A partir de los datos proporcionados por los marcadores autosómicos se registró una contribución europea de 67.2%, amerindia de 29.4% y africana de 3.4%. A un origen amerindio fueron adscriptos el 59.9% y 8.7% de los linajes maternos y paternos, respectivamente, revelando un desigual aporte autóctono por género. El aporte europeo se vio representado principalmente por el Hg H (19.5%) y se detectaron sólo dos linajes subsaharianos. En PM las migraciones desde el centro del país han generado un fuerte impacto, reflejado en la mayor contribución de marcadores europeos respecto de dos muestras estudiadas previamente en Chubut (Comodoro Rivadavia y Esquel). Estas diferencias al interior de una misma provincia nos advierten que no puede abordarse el análisis de la constitución genética de las poblaciones sin dar cuenta de las particularidades regionales.In the frame of the study of the genetic composition of Argentinean cosmopolitan populations, a population sample of the city of Puerto Madryn (PM) was analyzed in order to evaluate its biological diversity using biparental and uniparental markers and compare the results with those previously obtained by our research team in six cosmopolitan populations from different regions of Argentina. The emphasis was laid on the populations of the Patagonia region. Biological samples were taken with informed consent from 82 unrelated blood donors, who attended the Regional Blood Bank and Hospital of the town and also underwent a genealogical survey. From the data obtained by analyzing autosomal markers, a European contribution of 67.2%, an Amerindian one of 29.4%, and an African one of 3.4% were estimated. The 59.9% and 8.7% of the maternal and paternal lineages, respectively, were ascribed to Native American origins, revealing an unequal gender indigenous contribution. The European contribution was mainly represented by H Hg (19.5%), and only two sub-Saharan lineages were detected. In PM, migrations from the center of the country have had a strong impact, as reflected in the greater contribution of European markers, with respect to the two samples previously studied in the province of Chubut (Comodoro Rivadavia and Esquel). These differences warn us of the necessity of accounting for the regional particularities when analyzing the genetic constitution of populations.Fil: Parolin, María Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Nacional Patagónico; ArgentinaFil: Avena, Sergio Alejandro. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Maimónides. Area de Investigaciones Biomédicas y Biotecnológicas. Centro de Estudios Biomédicos, Biotecnológicos, Ambientales y de Diagnóstico; Argentina. Universidad de Buenos Aires. Facultad de Filosofía y Letras. Instituto de Ciencias Antropologicas; ArgentinaFil: Fleischer, Silvina. Puerto Madryn. Hospital Subzonal Andrés Isola; ArgentinaFil: Pretell, Mariana. Puerto Madryn. Hospital Subzonal Andrés Isola; ArgentinaFil: Di Fabio Rocca, Francisco. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Filosofía y Letras. Instituto de Ciencias Antropologicas; Argentina. Universidad Maimónides. Area de Investigaciones Biomédicas y Biotecnológicas. Centro de Estudios Biomédicos, Biotecnológicos, Ambientales y de Diagnóstico; ArgentinaFil: Rodriguez, Debora A.. Universidad Maimonides. Area de Invest.biomedicas y Biotecnologicas; Argentina. Universidad Maimónides. Area de Investigaciones Biomédicas y Biotecnológicas. Centro de Estudios Biomédicos, Biotecnológicos, Ambientales y de Diagnóstico; ArgentinaFil: Dejean, Cristina B.. Universidad Maimónides. Area de Investigaciones Biomédicas y Biotecnológicas. Centro de Estudios Biomédicos, Biotecnológicos, Ambientales y de Diagnóstico; Argentina. Universidad de Buenos Aires. Facultad de Filosofía y Letras. Instituto de Ciencias Antropologicas; ArgentinaFil: Postillone, María Bárbara. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Filosofía y Letras. Instituto de Ciencias Antropologicas; Argentina. Universidad Maimónides. Area de Investigaciones Biomédicas y Biotecnológicas. Centro de Estudios Biomédicos, Biotecnológicos, Ambientales y de Diagnóstico; ArgentinaFil: Vaccaro, Maria S.. Universidad Maimónides. Area de Investigaciones Biomédicas y Biotecnológicas. Centro de Estudios Biomédicos, Biotecnológicos, Ambientales y de Diagnóstico; Argentina. Universidad de Buenos Aires. Facultad de Filosofía y Letras. Instituto de Ciencias Antropologicas; ArgentinaFil: Dahinten, Silvia Lucrecia V.. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Nacional Patagónico; ArgentinaFil: Manera, Guillermo. Puerto Madryn. Hospital Subzonal Andrés Isola; ArgentinaFil: Carnese, Francisco Raul. Universidad de Buenos Aires. Facultad de Filosofía y Letras. Instituto de Ciencias Antropologicas; Argentina. Universidad Maimónides. Area de Investigaciones Biomédicas y Biotecnológicas. Centro de Estudios Biomédicos, Biotecnológicos, Ambientales y de Diagnóstico; Argentin

Obesity and addiction: can a complication of surgery help us understand the connection?

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/137403/1/obr12542_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/137403/2/obr12542.pd

Linajes mitocondriales amerindios en una muestra poblacional de la Región Metropolitana de Buenos Aires

En trabajos previos se evaluó el aporte aborígen, utilizando marcadores genéticos proteicos, en la Región Metropolitana de Buenos Aires. En este estudio nos proponemos estimar el grado de contribución de los linajes maternos amerindios mediante el análisis del ADNmt (haplogrupos A, B, C y D) en individuos que residen en esa región. Las muestras provienen de dadores del Hospital Italiano de Buenos Aires. El ADN extraído se amplificó mediante la técnica de PCR y luego se realizó la digestión enzimática para caracterizar los distintos haplogrupos: HaeIII para ganancia de un sitio en 663 (A), Hinc II, pérdida de un sitio en posición 13259 (C) y pérdida de un sitio Alu I en 5176 (D), y la deleción de 9pb típica del haplogrupo B de la región V. El 50% (25/50) de las muestras estudiadas fueron de origen amerindio, detectándose un 28% de A, 16% de B, 44% de C y 12% de D. Los resultados obtenidos indican alta participación de linajes maternos amerindios en la muestra estudiada que se corresponden con los datos genealógicos relevados.Asociación de Antropología Biológica de la República Argentin

Valoración antropométrica y nutricional de estudiantes de Nutrición de la Universidad Maza

Siendo la obesidad la pandemia del siglo XXI, es necesario analizar cuál es la incidencia de la misma en personas especializadas en la temá- tica, de ahí la importancia de evaluar su prevalencia en estudiantes de Nutrición. Su objetivo es determinar la composición y peso corporal de alumnas de la carrera de Nutrición de la UMaza

Mezcla génica en la población de la región metropolitana de Buenos Aires

El presente trabajo tiene como objetivo estimar la contribución del componente africano en la Región Metropolitana de Buenos Aires, constituida por la Capital Federal (CF), primera corona (1C) y segunda corona (2C) del conurbano, utilizando los sistemas Gm y Km. Se estudió una muestra hospitalaria de la ciudad, constituida por 455 individuos (CF=216, 1C=129 y 2C=110). Las frecuencias haplotípicas se determinaron mediante un método de máxima verosimilitud y la mezcla génica se calculó aplicando el programa Admix (trihíbrido). El componente africano se detectó en las tres regiones (CF=3,5%, 1C=3,5%, y 2C=4,6%). Este aporte fue mayor en la submuestra de nacidos en el norte del país (4,9%) y en países sudamericanos (6,4%). Estos datos difieren respecto de los obtenidos con los sistemas ABO y Rh, donde no se registró la presencia de aporte subsahariano. Estos resultados ratificarían la utilidad de los sistemas Gm y Km para los estudios de mestizaje y son concordantes con la información sociodemográfica e histórica obtenida.Asociación de Antropología Biológica de la República Argentin