Three-dimensional structure of human serum albumin

The binding locations to human serum albumin (HSA) of several drug molecules were determined at low resolution using crystallographic methods. The principal binding sites are located within subdomains IIA and IIIA. Preliminary studies suggest that an approach to increasing the in vivo efficacy of drugs which are rendered less effective or ineffective by virtue of their interaction with HSA, would be the use of competitive displacement in drug therapies and/or the development of a general inhibitor to the site within subdomain IIIA. These findings also suggest that the facilitated transfer of various ligands across organ/circulatory interfaces such as liver, kidney, and brain may be associated with binding to the IIIA subdomain

Survival probabilities of loggerhead sea turtles (<i>Caretta caretta</i>) estimated from capture-mark-recapture data in the Mediterranean Sea

Las probabilidades de supervivencia de la tortuga boba (Caretta caretta) se han estimado por primera vez en el Mediterráneo analizando datos de 3254 marcajes y 134 recapturas en esta región. La mayoría de las tortugas eran juveniles encontrados en el mar. Las recapturas fueron reavistamientos de individuos vivos y recuperaciones de individuos muertos. Los datos se analizaron mediante el modelo de Baker, versión modificada del de Cormack-Jolly-Seber que puede combinar recaptura, reavistamientos de individuos vivos e individuos recuperados muertos. Se obtuvo una probabilidad de supervivencia anual de 0.73 (IC 95% = 0.67-0.78; n=3254), y debe considerarse como una estima conservativa debido a una desconocida, aunque no insignificante, tasa de perdida de marcados. Este estudio ofrece una estima preliminar de las probabilidades de supervivencia de los estadios de desarrollo "en el mar" para la población mediterránea amenazada de tortuga boba marina, y proporciona las primeras observaciones sobre la magnitud de la sospechada mortalidad inducida por el hombre en la región. El modelo, utilizado aquí por primera vez en tortugas marinas podría ser utilizado para obtener estimas de supervivencia a partir de otros datos con pocas o sin recapturas reales, pero con otros tipos de datos de recaptura frecuentemente producidos por programas de marcado de estos animales de amplia distribución

Mitochondrial DNA reveals regional and interregional importance of the central Mediterranean African shelf for loggerhead sea turtles (<em>Caretta caretta</em>)

The wide north African continental shelf in the central Mediterranean is known to be one of the few important areas in the basin for loggerhead turtles in the neritic stage. In order to assess the origin of these turtles, sequences of the mtDNA control region were obtained from 70 turtles caught by bottom trawlers in the area, and compared with known sequences from turtles from Mediterranean and Atlantic nesting sites. Five haplotypes were identified (Haplotype diversity = 0.262; nucleotide diversity = 5.4×10-3). Specific haplotypes indicate contributions from distant rookeries such as Turkey and the Atlantic, which shows that Atlantic turtles entering the Mediterranean while in the oceanic phase use at least one Mediterranean continental shelf as a neritic foraging ground. A new haplotype and another one previously found only in foraging areas, highlight the genetic information gaps for nesting sites, which undermine powerful mixed stock analyses. Despite these limitations, the results reveal the regional importance of the study area as a neritic foraging ground for turtles that are probably from most of the Mediterranean nesting aggregates. Therefore, reducing turtle mortality resulting from the high fishing effort in the area should be regarded as key for Mediterranean turtle conservation and is also possibly important for Atlantic populations

Linear Growth through 12 Years is Weakly but Consistently Associated with Language and Math Achievement Scores at Age 12 Years in 4 Low- or Middle-Income Countries.

BackgroundWhether linear growth through age 12 y is associated with language and math achievement at age 12 y remains unclear.ObjectiveOur objective was to investigate associations of linear growth through age 12 y with reading skill, receptive vocabulary, and mathematics performance at age 12 y in 4 low- or middle-income countries (LMICs).MethodsWe analyzed data from the Young Lives Younger Cohort study in Ethiopia (n&nbsp;=&nbsp;1275), India (n&nbsp;=&nbsp;1350), Peru (n&nbsp;=&nbsp;1402), and Vietnam (n&nbsp;=&nbsp;1594). Age 1, 5, 8, and 12 y height-for-age z scores (HAZ) were calculated. Language and math achievement at age 12 y was assessed with the use of country-specific adaptations of the Peabody Picture Vocabulary Test, the Early Grades Reading Assessment, and a mathematics test; all test scores were standardized by age within country. We used path analysis to examine associations of HAZ with achievement scores. Twelve models were examined at each age (3 tests across 4 countries).ResultsMean HAZ in each country was &lt;-1.00 at all ages. Overall, linear growth through age 12 y was associated with 0.4-3.4% of the variance in achievement scores. HAZ at 1 y was positively and significantly associated with the test score in 11 of the 12 models. This association was significantly mediated through HAZ at 5, 8, and 12 y in 9 of the models. HAZ at 5, 8, and 12 y was positively and significantly associated with test scores in 8, 8, and 6 models, respectively. These associations were mediated through HAZ at older ages in 6 of the HAZ at 5-y models and in 6 of the HAZ at 8-y models.ConclusionChild relative linear growth between ages 1 and 12 y was weakly but consistently associated with language and math achievement at age 12 y in 4 LMICs

Genomic prediction of the recombination rate variation in barley - A route to highly recombinogenic genotypes

Meiotic recombination is not only fundamental to the adaptation of sexually reproducing eukaryotes in nature but increased recombination rates facilitate the combination of favourable alleles into a single haplotype in breeding programmes. The main objectives of this study were to (i) assess the extent and distribution of the recombination rate variation in cultivated barley (Hordeum vulgare L.), (ii) quantify the importance of the general and specific recombination effects, and (iii) evaluate a genomic selection approach’s ability to predict the recombination rate variation. Genetic maps were created for the 45 segregating populations that were derived from crosses among 23 spring barley inbreds with origins across the world. The genome‐wide recombination rate among populations ranged from 0.31 to 0.73 cM/Mbp. The crossing design used in this study allowed to separate the general recombination effects (GRE) of individual parental inbreds from the specific recombination effects (SRE) caused by the combinations of parental inbreds. The variance of the genome‐wide GRE was found to be about eight times the variance of the SRE. This finding indicated that parental inbreds differ in the efficiency of their recombination machinery. The ability to predict the chromosome or genome‐wide recombination rate of an inbred ranged from 0.80 to 0.85. These results suggest that a reliable screening of large genetic materials for their potential to cause a high extent of genetic recombination in their progeny is possible, allowing to systematically manipulate the recombination rate using natural variation

Growth rates and age at adult size of loggerhead sea turtles (<em>Caretta caretta</em>) in the Mediterranean Sea, estimated through capture-mark-recapture records

A partir de registros de capturamarcaje- recaptura, se estimaron por primera vez en el Mediterráneo las tasas de crecimiento de las fases juveniles de la tortuga boba (Caretta caretta). Se liberaron treinta y ocho tortugas a partir de la costa italiana y se reencontraron después de 1.0-10.9 años en el periodo 1986-2007. El promedio de LCC (longitud curvada del caparazón) varió de 32.5 a 82.0 cm y se observaron tasas de crecimiento variables, de 0 a 5.97 cm/año (promedio: 2.5). La asociación entre la tasa de crecimiento anual y tres covariables (año promedio, talla promedio e intervalo de tiempo) se investigó a través de un modelo no-paramétrico. Solamente la talla media mostró un claro efecto en la tasa de crecimiento, descrito por una curva monotónica descendente. La variabilidad observada indica que factores no incluidos en el modelo, probablemente relacionados con el individuo, tienen un importante efecto en las tasas de crecimiento. En base a la función de crecimiento monotónicamente decreciente que indica que no hay esfuerzo en el crecimiento, se uso una función de crecimiento de von Bertalanffy para estimar el tiempo requerido por las tortugas para crecer dentro del rango de tallas observado. Los resultados indican que las tortugas necesitarán de 16-28 años para alcanzar 66.5-84.7 cm LCC, la talla promedio de anidación observada en las más importantes áreas de anidación del Mediterráneo, lo que puede ser considerado como una aproximación a la talla de madurez

How to supercharge the Amazon T2: observations and suggestions

Cloud service providers adopt a credit system to allow users to obtain periods of performance bursts without additional cost. For example, the Amazon EC2 T2 instance offers low baseline performance and the capability to achie ve short periods of high performance using CPU credits. Once a T2 instance is created and assigned some initial credits, wh ile its CPU utilization is above the baseline threshold, there i s a transient period where performance is boosted and the assig ned CPU credits are used. After all credits are used, the maximum achievable performance drops to baseline. Credits accrue p e- riodically, when the instance utilization is below the base line threshold. This paper proposes a methodology to increase th e performance benefits of T2 by seamlessly extending the dura tion of the transient period while maintaining high performance . This extension of the high performance transient period is combi ned with proactive migration to further take advantage of the in itially assigned credits. We conduct experiments to demonstrate th e benefits of this methodology for both single-tier and multi -tier applications

Evolution of International Psychiatry

International psychiatry is currently facing serious challenges triggered by the global economic crisis and the COVID-19 pandemic. These global events lead to the need to broaden our nosographic and therapeutic horizons, and to make use of the newest psychological approaches and the latest neuroscience acquisitions. The focus should be on the psychological consequences of the pandemic, not only on people suffering from mental disorders, but also on the general population, for which the risk of developing psychic symptoms appears to be increased. A population that needs special attention is that of health workers involved in the management of the pandemic. In facing these problems, psychiatry today can use numerous new clinical applications and technologies in the fields of precision medicine. These include genomics, neuroimaging, and microbiomics, which can also be integrated with each other through machine learning systems. They can provide new contributions both in treatment personalization and in the evolution of nosographic systems. Besides this, the contribution of psychotherapies and dynamic and clinical psychology appears to be indispensable for a complete understanding of the clinical and personological aspects of patients. This journal aims to include innovative studies deriving from original, clinical, and basic research in the fields of mental health, precision psychiatry, genomics, neuroimaging, neuropsychopharmacology, and dynamic and clinical psychology

Mitochondrial myopathy and comorbid major depressive disorder. effectiveness of dTMS on gait and mood symptoms

Background: Mitochondrial myopathies (MMs) often present with leukoencephalopathy and psychiatric symptoms, which do not respond to or worsen with psychiatric drugs. Case report: A 67-year-old woman with a 10-year history of probable chronic progressive external ophthalmoplegia, an MM, had drug-resistant, anxious-depressive symptoms. Since she had never had seizures, we proposed 20 sessions of deep transcranial magnetic stimulation (dTMS) for her depression. Surprisingly, besides the expected improvement of depression, we observed marked improvement of movement disorder that lasted as long as the patient was undergoing dTMS. She also improved her performance on neuropsychological tests of executive function and cognitive speed. Depressive symptom improvement was persistent, while anxiety symptoms recurred after the end of the sessions. Conclusions: dTMSmay be an alternative antidepressant strategy in patients withMMs, provided that they are free from seizures. The mechanism of improvement of motor disturbance may relate to dorsolateral prefrontal cortex stimulation and improved executive function and needs further investigation

Improvements of safety conditions of unstable rock slopes through the use of explosives

The paper discusses operations aimed at creating a safer natural or man made rock slope by artificially inducing the displacement of unstable elements by blasting. A detailed analysis of the problems with the use of explosives present when conducting these activities is carried out focusing on the advantages and disadvantages of this technology. The results of two examples of demolition of instable rock elements are presented and discussed thus providing suggestions for future blasting designs