Adaptive phenotypic plasticity for life-history and less fitness-related traits.

Organisms are faced with variable environments and one of the most common solutions to cope with such variability is phenotypic plasticity, a modification of the phenotype to the environment. These modifications are commonly modelled in evolutionary theories as adaptive, influencing ecological and evolutionary processes. If plasticity is adaptive, we would predict that the closer to fitness a trait is, the less plastic it would be. To test this hypothesis, we conducted a meta-analysis of 213 studies and measured the plasticity of each reported trait as a coefficient of variation. Traits were categorized as closer to fitness-life-history traits including reproduction and survival related traits, and farther from fitness-non-life-history traits including traits related to development, metabolism and physiology, morphology and behaviour. Our results showed, unexpectedly, that although traits differed in their amounts of plasticity, trait plasticity was not related to its proximity to fitness. These findings were independent of taxonomic groups or environmental types assessed. We caution against general expectations that plasticity is adaptive, as assumed by many models of its evolution. More studies are needed that test the adaptive nature of plasticity, and additional theoretical explorations on adaptive and non-adaptive plasticity are encouraged.

Exploring the SAR of the ß-Ketoacyl-ACP Synthase Inhibitor GSK3011724A and Optimization around a Genotoxic Metabolite.

In the course of optimizing a novel indazole sulfonamide series that inhibits ß-ketoacyl-ACP synthase (KasA) of Mycobacterium tuberculosis, a mutagenic aniline metabolite was identified. Further lead optimization efforts were therefore dedicated to eliminating this critical liability by removing the embedded aniline moiety or modifying its steric or electronic environment. While the narrow SAR space against the target ultimately rendered this goal unsuccessful, key structural knowledge around the binding site of this underexplored target for TB was generated to inform future discovery efforts.

Investigating a non-destructive alternative for a preliminary evaluation of fungal growth in solid state fermentations.

Solid state fermentation (SSF) is an ancient technique which keeps attracting the attention of the food and biotechnology industries; however, a direct quantification of microbial biomass is still a fundamental challenge in this type of processes. Typically, growth is measured using indirect and destructive methods which do not allow a continuous evaluation of the evolution of microbial biomass within a single system. This article presents a non-destructive, quick and simple technique, based on digital imaging analysis (DIA) for the evaluation of growth in SSF laboratory experiments. DIA uses computational analysis of images from a SSF to measure areas and colour changes on a surface. The method can then be used to monitor microbial growth by assigning quantitative values for the growth of filamentous fungi. Firstly, studies on agar plates are used for the description of the method and to illustrate how it can be used to monitor fungal colony areas and densities. Following that, agro-industrial residues are used to demonstrate the application of the technique. DIA proved to be a practical and inexpensive tool to measure colony areas and densities. Furthermore, it is a non-destructive and non-intrusive method, which means that the evaluation of growth can be achieved within a single system.

Optimal marine mammal welfare under human care: Current efforts and future directions.

Marine mammals include cetaceans, pinnipeds, sirenians, sea otters and polar bears, many of which are charismatic and popular species commonly kept under human care in zoos and aquaria. However, in comparison with their fully terrestrial counterparts their welfare has been less intensively studied, and their partial or full reliance on the aquatic environment leads to unique welfare challenges. In this paper we attempt to collate and review the research undertaken thus far on marine mammal welfare, and identify the most important gaps in knowledge. We use 'best practice case studies' to highlight examples of research promoting optimal welfare, include suggestions for future directions of research efforts, and make recommendations to strive for optimal welfare, where it is currently lacking, above and beyond minimum legislation and guidelines. Our review of the current literature shows that recently there have been positive forward strides in marine mammal welfare assessment, but fundamental research is still required to validate positive and negative indicators of welfare in marine mammals. Across all marine mammals, more research is required on the dimensions and complexity of pools and land areas necessary for optimal welfare, and the impact of staff absence for most of the 24-h day, as standard working hours are usually between 0900 and 1700.

Easy-To-Synthesize Spirocyclic Compounds Possess Remarkable in Vivo Activity against Mycobacterium tuberculosis.

Society urgently needs new, effective medicines for the treatment of tuberculosis. To kick-start the required hit-to-lead campaigns, the libraries of pharmaceutical companies have recently been evaluated for starting points. The GlaxoSmithKline (GSK) library yielded many high-quality hits, and the associated data were placed in the public domain to stimulate engagement by the wider community. One such series, the spiro compounds, are described here. The compounds were explored by a combination of traditional in-house research and open source methods. The series benefits from a particularly simple structure and a short associated synthetic chemistry route. Many members of the series displayed striking potency and low toxicity, and highly promising in vivo activity in a mouse model was confirmed with one of the analogues. Ultimately the series was discontinued due to concerns over safety, but the associated data remain public domain, empowering others to resume the series if the perceived deficiencies can be overcome.

Resultados visuales en la cirugía de catarata en pacientes con uveítis / Visual outcomes in Cataract Surgery in patients with uveitis

RESUMEN Introducción: los resultados visuales de la cirugía de catarata en pacientes con uveítis son menos predecibles. Objetivo: analizar los resultados visuales de pacientes con uveítis operados de catarata en la provincia de Pinar del Río entre enero de 2018 y agosto de 2020. Métodos: se realizó un estudio observacional, analítico de cohorte en el Hospital General Docente "Abel Santamaría Cuadrado" de la provincia de Pinar del Río. El universo estuvo constituido por pacientes con uveítis que asistieron a la consulta de infecciones e inflamaciones oculares y recibieron cirugía de catarata; la muestra quedó conformada por 42 ojos de 42 pacientes. Para el análisis estadístico se empleó Chi cuadrado de independencia, probabilidad exacta de Fisher y riesgo relativo con su intervalo de confianza; se utilizó una significación estadística del 95 %. Resultados: el 83,3 % de los ojos logró una agudeza visual final superior a 0,3. El resultado visual no mostró diferencias según grupos de edades (p=0,679), sexo (p=0,690), color de la piel (p=1,000), zona de residencia (p=1,000) y agudeza visual preoperatoria (p=0,569). Hubo diferencias significativas según clasificación anatómica (p<0,001), técnica quirúrgica (p=0,011) y complicaciones intraoperatorias (p=0,002). El resultado visual y las complicaciones posoperatorias no mostraron asociación. Conclusión: la cirugía de catarata en pacientes con uveítis logra una evidente mejoría en la agudeza visual final; los resultados son favorables en casos de uveítis anterior, tratados con facoemulsificación y ausencia de complicaciones intraoperatorias.

ABSTRACT Introduction: the visual results of cataract surgery in patients with uveitis are less predictable. Objective: to analyze the visual outcomes of patients with uveitis operated on cataract in Pinar del Rio province between January 2018 and August 2020. Methods: an observational, analytical cohort study was conducted at Abel Santamaria Cuadrado General Teaching Hospital in Pinar del Rio province. The target group comprised the patients with uveitis who attended the ocular infections and inflammations consultation and who underwent cataract surgery; the sample included 42 eyes of 42 patients. For the statistical analysis we used Chi-square of independence, Fisher's exact probability and relative risk with its confidence interval; a statistical significance of 95 % was used. Results: the eyes achieved a final visual acuity higher than 0.3 (83,3 %). Visual outcome showed no differences according to age group (p=0,679), sex (p=0,690), skin color (p=1,000), area of residence (p=1,000) and preoperative visual acuity (p=0,569). There were significant differences according to anatomical classification (p<0,001), surgical technique (p=0,011) and intraoperative complications (p=0,002). Visual outcome and postoperative complications showed no association. Conclusion: cataract surgery in patients with uveitis achieves an evident improvement in final visual acuity; results are favorable in cases of anterior uveitis, treated with phacoemulsification and absence of intraoperative complications.

Robust succinic acid production from crude glycerol using engineered Yarrowia lipolytica.

BACKGROUND: Integrating waste management with fuels and chemical production is considered to address the food waste problem and oil crisis. Approximately, 600 million tonnes crude glycerol is produced from the biodiesel industry annually, which is a top renewable feedstock for succinic acid production. To meet the increasing demand for succinic acid production, the development of more efficient and cost-effective production methods is urgently needed. Herein, we have proposed a new strategy for integration of both biodiesel and SA production in a biorefinery unit by construction of an aerobic yeast Yarrowia lipolytica with a deletion in the gene coding succinate dehydrogenase subunit 5. RESULTS: Robust succinic acid production by an engineered yeast Y. lipolytica from crude glycerol without pre-treatment was demonstrated. Diversion of metabolic flow from tricarboxylic acid cycle led to the success in generating a succinic acid producer Y. lipolytica PGC01003. The fermentation media and conditions were optimized, which resulted in 43 g L(-1) succinic acid production from crude glycerol. Using the fed-batch strategy in 2.5 L fermenter, up to 160 g L(-1) SA was yielded, indicating the great industrial potential. CONCLUSIONS: Inactivation of SDH5 in Y. lipolytica Po1f led to succinic acid accumulation and secretion significantly. To our best knowledge, this is the highest titer obtained in fermentation on succinic acid production. In addition, the performance of batch and fed-batch fermentation showed high tolerance and yield on biodiesel by-product crude glycerol. All these results indicated that PGC01003 is a promising microbial factorial cell for the highly efficient strategy solving the environmental problem in connection with the production of value-added product.

The acute response of the amygdalar TRH system to psychogenic stressors varies dependent on the paradigm and circadian condition.

Central administration of thyrotropin releasing hormone (TRH) reduces anxiety; amygdalar TRH expression is inversely proportional to the anxious behavior displayed in the elevated plus maze performed during the dark phase (EPM-D). To better understand the role of TRH in amygdala function, we evaluated the expression of TRH and the elements involved in its transmission in various stressful paradigms and how they associated with behavior. Wistar male rats were exposed to restraint (RES), EPM, or the open field test (OFT) and sacrificed 0-60 min afterwards; OFT, RES and EPM were performed during the light (L), and OFT during the dark phase. Restraint increased amygdalar levels of proCRH mRNA, without change in proTRH. All paradigms augmented corticosterone release, highest after OFT-L that also enhanced proCRH mRNA levels and decreased those of proTRH. OFT-D activated the TRH system. Levels of anxiety or locomotion were similar in animals tested in light or dark phases but their association with biochemical parameters differed. ProTRH expression and TRH release correlated positively with decreased anxiety in EPM-L and in OFT-D. No association with anxiety was detected in OFT-L where proCRH and proTRH expression correlated with locomotion supporting their involvement in arousal. The responses of TRH amygdalar systems appeared modulated by the extent of the stress response and by the circadian conditions. Increased proTRH expression of animals exposed to OFT-D was specifically observed in the cortical nucleus of the amygdala, area involved in processing fear stimuli; these TRH neurons may thus be part of a circuit with anxiolytic properties.

Comportamiento clínico- epidemiológico de las ametropías / Clinical-epidemiological behavior of ametropia

Fundamento: en Cuba, las ametropías constituyen una causa frecuente de asistencia a las consultas oftalmológicas. La existencia de estos defectos se ha convertido en un problema que afecta a la sociedad, tanto por los daños orgánicos y físicos que puede provocar en el sistema visual, como por los trastornos psicológicos que se presentan en quienes los padecen, ya sea por cuestiones estéticas o de incapacidad de realizar determinadas actividades cotidianas. Objetivos: determinar el comportamiento clínico-epidemiológico de las ametropías en el policlínico Previsora del municipio Camagüey, en el mes de octubre de 2008. Método: se realizó un estudio observacional descriptivo de los pacientes que acudieron a la consulta de refracción, el universo y la muestra estuvo conformado por los doscientos pacientes diagnosticados como amétropes. Resultados: el grupo de edades más afectado es el de cuarenta a cuarenta y nueve años y el sexo femenino fue el que más incidió, el astigmatismo fue la ametropía más frecuente, y según el valor dióptrico predominó el grado leve. La mayoría de los casos presentó buena agudeza visual con corrección y sólo una cuarta parte aproximadamente fue regular o mala. Conclusiones: el glaucoma, la retinopatía miópica y la catarata fueron las enfermedades oftalmológicas que más se asociaron a pacientes miopes, mientras que la retinopatía diabética se encontró con más frecuencia en hipermétropes.

Background: In Cuba, ametropia constitutes a frequent cause of attendance in ophthalmologic consultations. The existence of these defects has become a problem that affects society, so much for organic and physical damages that it may cause in the visual system, as for psychological dysfunctions that are presented who suffer them, either for aesthetic matters or for inability of carrying out certain daily activities. Objective: to determine the clinical-epidemic behavior of ametropia at the Previsora polyclinic of Camagüey municipality, in October 2008. Method: a descriptive observational study of patients that assisted to the refraction consultation was carried out, the universe and the sample was comply with two hundred patients diagnosed with ametropia. Results: the most affected age group is the one from forty to forty-nine years and the female sex with the most occurrence, astigmatism was the most frequent ametropia, and according to the dioptric value, light grade prevailed. Most of the cases presented good visual acuity with correction and only a fourth part approximately was regular or bad. Conclusions: glaucoma, myopic retinopathy and cataract were ophthalmologic diseases most associate to myopic patients, while diabetic retinopathy was most frequent in hypermetrope patients.

Apuntes sobre la situación social existente en Camagüey durante la Tregua Fecunda / Social Situation in Camagüey during the Tregua Fecunda (The Inter-War Period)

En la investigación sobre el proceso revolucionario cubano durante el siglo XIX en Camagüey, el aspecto social ha sido el menos estudiado en comparación con las argumentaciones de carácter económico y político. Ello refleja un vacío cognoscitivo del que no escapan los estudios que abordan la Tregua Fecunda. En el presente trabajo-fruto de una investigación más amplia- intento solucionar lo antes expuesto. Sostenido por una sólida base documental, en el estudio se aportan informaciones e interpretaciones novedosas que permiten reflexionar sobre las peculiaridades demográficas de la región y la incapacidad del Gobierno Colonial para resolver los problemas que más afectaban a la sociedad principeña en los años que precedieron al reinicio de la lucha independentista.

In investigations on the Cuban revolutionary process during the XIX century in Camagüey, the social aspect has been the less studied, in comparison with the arguments of economic and political nature.This shows a knowledge gap that also involves the period known as the Tregua Fecunda (Inter-War Period). This work-fruit of a wider investigation - tries to solve the before exposed problem. Sustained by a solid documental base, in this study information and novel interpretations are provided, which allow meditating about the demographic peculiarities of the region and the Colonial Government's inability to solve the problems that affected the Camagueyan society the most in the years that preceded the restart of the fight for independence.

El humanismo del Che / Che's Humanism

Los autores, estudiosos de la raigal influencia del pensamiento y la obra del Comandante Dr. Ernesto Guevara de la Serna (Che) en Cuba y América, proyectan la estampa humanista de este revolucionario médico, con el empleo de las más trascendentes pinceladas históricas de un amplia hoja de vida en distintas latitudes del mundo. El Che, joven estudiante, médico graduado con prometedoras dotes que sabe ubicar al ser humano y sus valores por encima de un promisorio futuro como científico y profesional de la medicina. El artículo dedica atención especial a sus conceptos sobre el hombre, su vida e historia y a su proverbial apego a una ética revolucionaria de elevado calibre. El artículo contribuye al enriquecimiento de los conocimientos sobre el desarrollo histórico del humanismo médico cubano, al proyectarlo en la figura de uno de sus más míticos modelos.

The authors, studious of the extraordinary influence of Commandant and Dr. Ernesto Guevara de la Serna 's thought in Cuba and America, unveil the humanist perspective of this revolutionary doctor, through the most transcendental historical events in this man's life in different latitudes of the world. Che, young student, medicine doctor with promising gifts that knew how to place the human being and his values above his promissory future as scientific and medicine professional. The article dedicates special attention to his concepts about men, as well as his life and history and to his proverbial attachment to valuable revolutionary ethics. The article contributes to the enrichment of knowledge on the historical development of Cuban medical humanism, by reflecting this in the figure of one of its most mythical models.