Comorbidities in a sample of adults with HIV in Puerto Rico: an exploratory study.

Background: Puerto Rico is among the areas with the highest estimated rates of people living with HIV in the United States. Despite the epidemiologic data available, there is limited real-world information that can help understand the comorbidities of people with HIV. In this study, we describe common comorbidities among adults with HIV attending treatment clinics in Puerto Rico. Methods: An exploratory, retrospective, cross-sectional study was conducted at five HIV clinics in Puerto Rico. A random sample of medical records was reviewed. Descriptive statistics were used to summarize patient demographics, morbidity, and clinical characteristics. Multivariate analyses were conducted to explore comorbidities by age and sex. Results: A total of 250 (179 men; 71 women) medical records were reviewed. Participants\u27 mean age was 47.9 years and on average they had been living with HIV for 9 years. Most (97.6%) had at least one comorbidity. The most common comorbidities were dyslipidemia and hypertension. Men were more likely to have been diagnosed with alcohol misuse while women were more likely to have been diagnosed with obesity, human papillomavirus (HPV), hypothyroidism, and osteoporosis. Participants younger than 50 years of age were more likely to have history of alcohol misuse while older individuals (50 years and old) were more likely to have been diagnosed with dyslipidemia, hypertension, and diabetes. Adjusting by sex and age, women were more likely to have been diagnosed with obesity and depression and those older than 50 years were more likely to have had a diagnosis of dyslipidemia, hypertension, HPV, and diabetes. Conclusions: This is one of the few studies assessing comorbidities among adults with HIV in Puerto Rico, among Latino/Hispanics within the United States, and Latin America. Consistent with other studies, cardiovascular diseases are common among adults with HIV in Puerto Rico. Findings support the need for awareness and real-world evidence about comorbidities among people with HIV when implementing screenings and prescribing drugs

CODA: Accurate Detection of Functional Associations between Proteins in Eukaryotic Genomes Using Domain Fusion

Background: In order to understand how biological systems function it is necessary to determine the interactions and associations between proteins. Gene fusion prediction is one approach to detection of such functional relationships. Its use is however known to be problematic in higher eukaryotic genomes due to the presence of large homologous domain families. Here we introduce CODA (Co-Occurrence of Domains Analysis), a method to predict functional associations based on the gene fusion idiom.Methodology/Principal Findings: We apply a novel scoring scheme which takes account of the genome-specific size of homologous domain families involved in fusion to improve accuracy in predicting functional associations. We show that CODA is able to accurately predict functional similarities in human with comparison to state-of-the-art methods and show that different methods can be complementary. CODA is used to produce evidence that a currently uncharacterised human protein may be involved in pathways related to depression and that another is involved in DNA replication.Conclusions/Significance: The relative performance of different gene fusion methodologies has not previously been explored. We find that they are largely complementary, with different methods being more or less appropriate in different genomes. Our method is the only one currently available for download and can be run on an arbitrary dataset by the user. The CODA software and datasets are freely available from ftp://ftp.biochem.ucl.ac.uk/pub/gene3d_data/v6.1.0/CODA/. Predictions are also available via web services from http://funcnet.eu/

Expression of a Dominant Negative CELF Protein In Vivo Leads to Altered Muscle Organization, Fiber Size, and Subtype

CUG-BP and ETR-3-like factor (CELF) proteins regulate tissue- and developmental stage-specific alternative splicing in striated muscle. We previously demonstrated that heart muscle-specific expression of a nuclear dominant negative CELF protein in transgenic mice (MHC-CELFΔ) effectively disrupts endogenous CELF activity in the heart in vivo, resulting in impaired cardiac function. In this study, transgenic mice that express the dominant negative protein under a skeletal muscle-specific promoter (Myo-CELFΔ) were generated to investigate the role of CELF-mediated alternative splicing programs in normal skeletal muscle.Myo-CELFΔ mice exhibit modest changes in CELF-mediated alternative splicing in skeletal muscle, accompanied by a reduction of endomysial and perimysial spaces, an increase in fiber size variability, and an increase in slow twitch muscle fibers. Weight gain and mean body weight, total number of muscle fibers, and overall muscle strength were not affected.Although these findings demonstrate that CELF activity contributes to the normal alternative splicing of a subset of muscle transcripts in vivo, the mildness of the effects in Myo-CELFΔ muscles compared to those in MHC-CELFΔ hearts suggests CELF activity may be less determinative for alternative splicing in skeletal muscle than in heart muscle. Nonetheless, even these small changes in CELF-mediated splicing regulation were sufficient to alter muscle organization and muscle fiber properties affected in myotonic dystrophy. This lends further evidence to the hypothesis that dysregulation of CELF-mediated alternative splicing programs may be responsible for the disruption of these properties during muscle pathogenesis

Uncovering the Molecular Machinery of the Human Spindle—An Integration of Wet and Dry Systems Biology

The mitotic spindle is an essential molecular machine involved in cell division, whose composition has been studied extensively by detailed cellular biology, high-throughput proteomics, and RNA interference experiments. However, because of its dynamic organization and complex regulation it is difficult to obtain a complete description of its molecular composition. We have implemented an integrated computational approach to characterize novel human spindle components and have analysed in detail the individual candidates predicted to be spindle proteins, as well as the network of predicted relations connecting known and putative spindle proteins. The subsequent experimental validation of a number of predicted novel proteins confirmed not only their association with the spindle apparatus but also their role in mitosis. We found that 75% of our tested proteins are localizing to the spindle apparatus compared to a success rate of 35% when expert knowledge alone was used. We compare our results to the previously published MitoCheck study and see that our approach does validate some findings by this consortium. Further, we predict so-called “hidden spindle hub”, proteins whose network of interactions is still poorly characterised by experimental means and which are thought to influence the functionality of the mitotic spindle on a large scale. Our analyses suggest that we are still far from knowing the complete repertoire of functionally important components of the human spindle network. Combining integrated bio-computational approaches and single gene experimental follow-ups could be key to exploring the still hidden regions of the human spindle system

Dystropathology increases energy expenditure and protein turnover in the mdx mouse model of Duchenne muscular dystrophy

The skeletal muscles in Duchenne muscular dystrophy and the mdx mouse model lack functional dystrophin and undergo repeated bouts of necrosis, regeneration, and growth. These processes have a high metabolic cost. However, the consequences for whole body energy and protein metabolism, and on the dietary requirements for these macronutrients at different stages of the disease, are not well-understood. This study used juvenile (4- to 5- wk-old) and adult (12- to 14-wk-old) male dystrophic C57BL/10ScSn-mdx/J and age-matched C57BL/10ScSn/J control male mice to measure total and resting energy expenditure, food intake, spontaneous activity, body composition, whole body protein turnover, and muscle protein synthesis rates. In juvenile mdx mice that have extensive muscle damage, energy expenditure, muscle protein synthesis, and whole body protein turnover rates were higher than in age-matched controls. Adaptations in food intake and decreased activity were insufficient to meet the increased energy and protein needs of juvenile mdx mice and resulted in stunted growth. In (non-growing) adult mdx mice with less severe dystropathology, energy expenditure, muscle protein synthesis, and whole body protein turnover rates were also higher than in age-matched controls. Food intake was sufficient to meet their protein and energy needs, but insufficient to result in fat deposition. These data show that dystropathology impacts the protein and energy needs of mdx mice and that tailored dietary interventions are necessary to redress this imbalance. If not met, the resultant imbalance blunts growth, and may limit the benefits of therapies designed to protect and repair dystrophic muscles

An expanded evaluation of protein function prediction methods shows an improvement in accuracy

Background: A major bottleneck in our understanding of the molecular underpinnings of life is the assignment of function to proteins. While molecular experiments provide the most reliable annotation of proteins, their relatively low throughput and restricted purview have led to an increasing role for computational function prediction. However, assessing methods for protein function prediction and tracking progress in the field remain challenging. Results: We conducted the second critical assessment of functional annotation (CAFA), a timed challenge to assess computational methods that automatically assign protein function. We evaluated 126 methods from 56 research groups for their ability to predict biological functions using Gene Ontology and gene-disease associations using Human Phenotype Ontology on a set of 3681 proteins from 18 species. CAFA2 featured expanded analysis compared with CAFA1, with regards to data set size, variety, and assessment metrics. To review progress in the field, the analysis compared the best methods from CAFA1 to those of CAFA2. Conclusions: The top-performing methods in CAFA2 outperformed those from CAFA1. This increased accuracy can be attributed to a combination of the growing number of experimental annotations and improved methods for function prediction. The assessment also revealed that the definition of top-performing algorithms is ontology specific, that different performance metrics can be used to probe the nature of accurate predictions, and the relative diversity of predictions in the biological process and human phenotype ontologies. While there was methodological improvement between CAFA1 and CAFA2, the interpretation of results and usefulness of individual methods remain context-dependent. Keywords: Protein function prediction, Disease gene prioritizationpublishedVersio

An Expanded Evaluation of Protein Function Prediction Methods Shows an Improvement In Accuracy

Background: A major bottleneck in our understanding of the molecular underpinnings of life is the assignment of function to proteins. While molecular experiments provide the most reliable annotation of proteins, their relatively low throughput and restricted purview have led to an increasing role for computational function prediction. However, assessing methods for protein function prediction and tracking progress in the field remain challenging. Results: We conducted the second critical assessment of functional annotation (CAFA), a timed challenge to assess computational methods that automatically assign protein function. We evaluated 126 methods from 56 research groups for their ability to predict biological functions using Gene Ontology and gene-disease associations using Human Phenotype Ontology on a set of 3681 proteins from 18 species. CAFA2 featured expanded analysis compared with CAFA1, with regards to data set size, variety, and assessment metrics. To review progress in the field, the analysis compared the best methods from CAFA1 to those of CAFA2. Conclusions: The top-performing methods in CAFA2 outperformed those from CAFA1. This increased accuracy can be attributed to a combination of the growing number of experimental annotations and improved methods for function prediction. The assessment also revealed that the definition of top-performing algorithms is ontology specific, that different performance metrics can be used to probe the nature of accurate predictions, and the relative diversity of predictions in the biological process and human phenotype ontologies. While there was methodological improvement between CAFA1 and CAFA2, the interpretation of results and usefulness of individual methods remain context-dependent

Causes, consequences and biomarkers of stress in swine: an update

BACKGROUND: In recent decades there has been a growing concern about animal stress on intensive pig farms due to the undesirable consequences that stress produces in the normal physiology of pigs and its effects on their welfare and general productive performance. This review analyses the most important types of stress (social, environmental, metabolic, immunological and due to human handling), and their biological consequences for pigs. The physio-pathological changes associated with stress are described, as well as the negative effects of stress on pig production. In addition an update of the different biomarkers used for the evaluation of stress is provided. These biomarkers can be classified into four groups according to the physiological system or axis evaluated: sympathetic nervous system, hypothalamic-pituitary-adrenal axis, hypothalamic-pituitary-gonadal axis and immune system. CONCLUSIONS: Stress it is a process with multifactorial causes and produces an organic response that generates negative effects on animal health and production. Ideally, a panel of various biomarkers should be used to assess and evaluate the stress resulting from diverse causes and the different physiological systems involved in the stress response. We hope that this review will increase the understanding of the stress process, contribute to a better control and reduction of potential stressful stimuli in pigs and, finally, encourage future studies and developments to better monitor, detect and manage stress on pig farms

Calibración de un modelo basado en agentes que describe la evolución de la resistencia del Acinetobacter baumannii a la colistina en la ciudad de Valencia

[ES] Uno de los retos mas complejos en el mundo de la sanidad es la resistencia a los tratamientos con antibióticos (AMR). El uso a nivel mundial de los fármacos antibióticos ha sido un factor clave en la lucha contra las enfermedades infecciosas, pero a su vez ha provocado que cada vez mas microorganismos desarrollen, mediante adaptaciones genéticas, resistencia o incluso inmunidad frente a los fármacos. Ante esta amenaza de salud publica, los modelos matemáticos van a resultar fundamentales en la predicción de la evolución de la AMR y en la toma de decisiones objetivas en materia de salud publica. Por ello, en este trabajo proponemos un modelo basado en agentes que describe la evolución de la bacteria Acinetobacter baumannii resistente al antibiótico colistina en una población sintética con las características demográficas de la ciudad de Valencia. Para hallar los parámetros del modelo y simular un escenario realista, se ha llevado a cabo un proceso de calibrado, utilizado para ello datos epidemiológicos de la ciudad de Valencia y de España. Para la exploración del espacio de parámetros, se ha empleado el algoritmo de optimización Particle Swarm Optimization (PSO) y una función de fitness que mide el error entre los resultados del modelo y los datos epidemiológicos reales.Esta investigacion ha sido financiada por el Ministerio de Economia, Industria y Competitividad (MINECO), la Agencia Estatal de Investigacion (AEI) y Fondo Europeo de Desarrollo Regional (FEDER UE) MTM2017-89664-PI, y el Instituto Universitario de Matematica Multidisciplinar de la Universitat Politècnica de València.Aledo, JA.; Andreu-Vilarroig, C.; Cortés, J.; Orengo, JC.; Villanueva Micó, RJ. (2021). Calibración de un modelo basado en agentes que describe la evolución de la resistencia del Acinetobacter baumannii a la colistina en la ciudad de Valencia. Asociacion Española para la Inteligencia Artificial. 566-571. http://hdl.handle.net/10251/181073S56657

Current knowledge of the regulatory hormones in food intake in swine

Este trabajo es una revisión de los estudios realizados en la especie porcina sobre el comportamiento de la insulina, leptina y grelina, y su implicación en la regulación de la ingestión de alimentos. Desde el punto de vista productivo es de gran interés por constituir una fuente de información importante para conocer el estado metabólico y energético del animal. Los animales, durante su crecimiento y a lo largo de su vida productiva, pasan por diferentes etapas con necesidades específicas que deben ser cubiertas mediante el aporte de nutrientes a través de la alimentación. La salud de los animales dependen de la habilidad del cuerpo para regular de forma adecuada el equilibrio entre las necesidades y los aportes, y este equilibrio está regulado por del sistema nervioso central mediante señales neuronales o la liberación de hormonas. Las hormonas implicadas en la ingestión de alimentos, es decir, aquellas que ejercen un papel regulador sobre el apetito o la saciedad, pueden clasificarse en orexigénica o anorexigénicas según su capacidad de estimular o inhibir, respectivamente, el consumo de alimentos. La grelina, también llamada hormona del hambre, es la principal hormona orexigénica, es producida principalmente en el estómago en respuesta al hambre y la inanición. Durante el ayuno, o en estados energéticos insuficientes eleva sus niveles en sangre y tras la alimentación recupera los niveles basales. Entre las hormonas anorexigénicas destaca la leptina secretada principalmente por las células del tejido adiposo, cuya función primordial es la regulación de la ingestión de alimentos y del gasto energético, a largo plazo, para mantener las reservas corporales, de manera que, cuando un individuo está en balance energético positivo los niveles de leptina aumentan presentando un estado de saciedad que provoca la disminución en el consumo alimentos y/o apetito. Además, tras la ingestión de alimento, se secreta insulina, que es la principal hormona encargada de regular la glucemia y esta implicada en la regulación del apetito por interactuar con otras hormonas. Aunque estas hormonas han sido ampliamente estudiadas en la especie humana y roedores, es de esperar que en las próximas décadas su estudio se extienda a todos las especies domésticas.ABSTRACT This paper is a review about research of insulin, leptin and ghrelin in pigs and their implications in regulation of appetite. Their study could be very important in animal production as they are a source of important information to know metabolic and energetic states of animals. The animals during their growth have different states with their own needs which should be covered with the nutrients intake. The balance between needs and feed nutrient inputs are regulated by central neuronal system through hormones. The hormones involved in feed intake are orexigenic or anorexigenic according their capacity to activate or inhibit feed intake. The most important orexigenic hormone is the ghrelin, which is a «hunger hormone» is high in the fasting state and decreases in serum after feed intake. Leptin, anorexigenic hormone, is thought to be a satiety factor that regulates body weight through modulation of feeding behaviour and energy expenditure and it is directly related to the animals’ adiposity degree. Insulin, besides regulating blood glucose levels, is involved in food intake by interacting with other hormones. However, these actions are affected by many factors as the feeding pattern, the diet composition or the productive stage of swine