Pth4, an ancient parathyroid hormone lost in eutherian mammals, reveals a new brain-to-bone signaling pathway

Regulation of bone development, growth, and remodeling traditionally has been thought to depend on endocrine and autocrine/paracrine modulators. Recently, however, brain-derived signals have emerged as key regulators of bone metabolism, although their mechanisms of action have been poorly understood. We reveal the existence of an ancient parathyroid hormone (Pth)4 in zebrafish that was secondarily lost in the eutherian mammals' lineage, including humans, and that is specifically expressed in neurons of the hypothalamus and appears to be a central neural regulator of bone development and mineral homeostasis. Transgenic fish lines enabled mapping of axonal projections leading from the hypothalamus to the brainstem and spinal cord. Targeted laser ablation demonstrated an essential role for of pth4-expressing neurons in larval bone mineralization. Moreover, we show that Runx2 is a direct regulator of pth4 expression and that Pth4 can activate cAMP signaling mediated by Pth receptors. Finally, gain-of-function experiments show that Pth4 can alter calcium/phosphorus levels and affect expression of genes involved in phosphate homeostasis. Based on our discovery and characterization of Pth4, we propose a model for evolution of bone homeostasis in the context of the vertebrate transition from an aquatic to a terrestrial lifestyle.Spanish Economy and Competitiveness Ministry Project [ALG2011-23581, AGL2014-52473R]; Portuguese Foundation for Science and Technology [PTDC/BIA-ANM/4225/2012-phos-fate]; U. S. National Institutes of Health/Office of the Director Grant [R01OD011116, R01 RR020833]; Generalitat de Catalunya [SGR2014-290]; Spanish Economy and Competitiveness Ministry [BFU2010-14875]; Science and Innovation Ministry [AGL2010-22247-C03-01]; Campus do Mar Ph.D. grant; Xunta de Galicia (Santiago, Spain) [AGL2014-52473R]info:eu-repo/semantics/publishedVersio

Bioinformatics challenges and potentialities in studying extreme environments

Cold environments are populated by organisms able to contravene deleterious effects of low temperature by diverse adaptive strategies, including the production of ice binding proteins (IBPs) that inhibit the growth of ice crystals inside and outside cells. We describe the properties of such a protein (EfcIBP) identified in the metagenome of an Antarctic biological consortium composed of the ciliate Euplotes focardii and psychrophilic non-cultured bacteria. Recombinant EfcIBP can resist freezing without any conformational damage and is moderately heat stable, with a midpoint temperature of 66.4 degrees C. Tested for its effects on ice, EfcIBP shows an unusual combination of properties not reported in other bacterial IBPs. First, it is one of the best-performing IBPs described to date in the inhibition of ice recrystallization, with effective concentrations in the nanomolar range. Moreover, EfcIBP has thermal hysteresis activity (0.53 degrees C at 50 mu M) and it can stop a crystal from growing when held at a constant temperature within the thermal hysteresis gap. EfcIBP protects purified proteins and bacterial cells from freezing damage when exposed to challenging temperatures. EfcIBP also possesses a potential N-terminal signal sequence for protein transport and a DUF3494 domain that is common to secreted IBPs. These features lead us to hypothesize that the protein is either anchored at the outer cell surface or concentrated around cells to provide survival advantage to the whole cell consortium

Biology and biotechnology of Trichoderma

Fungi of the genus Trichoderma are soilborne, green-spored ascomycetes that can be found all over the world. They have been studied with respect to various characteristics and applications and are known as successful colonizers of their habitats, efficiently fighting their competitors. Once established, they launch their potent degradative machinery for decomposition of the often heterogeneous substrate at hand. Therefore, distribution and phylogeny, defense mechanisms, beneficial as well as deleterious interaction with hosts, enzyme production and secretion, sexual development, and response to environmental conditions such as nutrients and light have been studied in great detail with many species of this genus, thus rendering Trichoderma one of the best studied fungi with the genome of three species currently available. Efficient biocontrol strains of the genus are being developed as promising biological fungicides, and their weaponry for this function also includes secondary metabolites with potential applications as novel antibiotics. The cellulases produced by Trichoderma reesei, the biotechnological workhorse of the genus, are important industrial products, especially with respect to production of second generation biofuels from cellulosic waste. Genetic engineering not only led to significant improvements in industrial processes but also to intriguing insights into the biology of these fungi and is now complemented by the availability of a sexual cycle in T. reesei/Hypocrea jecorina, which significantly facilitates both industrial and basic research. This review aims to give a broad overview on the qualities and versatility of the best studied Trichoderma species and to highlight intriguing findings as well as promising applications

Reemplazo valvular aórtico con bioprótesis sin sutura Perceval S: experiencia de un solo centro

Resumen: Introducción y objetivos: La introducción de la prótesis aórtica sin sutura Perceval S ha supuesto una gran alternativa para el tratamiento quirúrgico de la estenosis aórtica severa, especialmente en pacientes añosos.Se trata de un estudio observacional, retrospectivo, de un grupo de pacientes de nuestro centro sometidos a reemplazo valvular aórtico con bioprótesis sin sutura Perceval S (LivaNova, Saluggia, Italia). Métodos: Entre junio de 2015 y octubre de 2018, 105 pacientes fueron sometidos a reemplazo valvular aórtico con bioprótesis Perceval S. Los procedimientos combinados fueron: reemplazo valvular mitral (n = 1), reparación valvular tricúspide (n = 2), revascularización miocárdica (n = 16) y miectomía (n = 1). El seguimiento clínico y ecocardiográfico se realizó al alta, a los 6 meses y anualmente. Resultados: La edad media fue de 80,5 ± 3,8 años; 57 (54,3%) fueron mujeres. La mortalidad a los 30 días fue del 1,9% (2 de 105). La tasa de supervivencia a los 30 días fue del 98% y al año fue del 95%. La media del Euroscore II fue de 3,8 ± 5,5%. Los tiempos de circulación extracorpórea y de isquemia fueron de 58,4 ± 41,8 min y de 44 ± 19,9 min para el reemplazo valvular aórtico aislado, 94,2 ± 44,1 min y 73,9 ± 35,6 min para procedimientos combinados, respectivamente. La media del gradiente de presión medio transvalvular fue de 13,5 ± 4,9 mmHg. La función ventricular izquierda aumentó desde el 56,8 ± 10,8% al 58,6 ± 11,1%. Solo 7 pacientes requirieron implante de marcapasos definitivo, con una incidencia del 6,7%. Solo 2 pacientes presentaron fuga paravalvular moderada al alta, que no requirió ningún tratamiento. Conclusiones: El reemplazo valvular aórtico con la bioprótesis sin sutura Perceval S se asocia a una baja mortalidad y a un excelente comportamiento clínico y hemodinámico, especialmente en pacientes de edad avanzada. Abstract: Introduction and objectives: Sutureless aortic valve replacement has emerged as an alternative for surgical treatment of severe aortic stenosis, especially in older patients.This is an observational, retrospective study of a group of patients from a single centre undergoing aortic valve replacement with Perceval S sutureless bioprosthesis (LivaNova, Saluggia, Italy). Methods: A total of 105 patients had an aortic valve replacement with a Perceval S bioprosthesis between June 2015 and October 2018. The combined procedures were, mitral valve replacement (n = 1), tricuspid valve repair (n = 2), myocardial revascularisation (n = 16), and myectomy (n = 1). The clinical and echocardiographic follow-up was performed at discharge, at 6 months, and yearly, after surgery. Results: The mean age was 80.5 ± 3.8 years, and 57 (54.3%) were women. The mortality rate at 30 days was 1.9% (2 out of 105).The 30-day survival rate was 98%, and at one year it was 95%. The mean Euroscore II was 3.8% ± 5.5%. The cardiopulmonary bypass and ischaemia times were 58.4 ± 41.8 min, and 44 ± 19.9 min for isolated aortic valve replacement, 94.2 ± 44.1 min and 73.9 ± 35.6 min for combined procedures, respectively. The mean trans-prosthetic gradient was 13.5 ± 4.9 mmHg. The left ventricle function increased from 56.8% ± 10.8% to 58.6% ± 11.1%. Only 7 patients have required a definitive pacemaker implant (6.7%). Only 2 patients presented with a moderate para-valvular leak that did not require any treatment. Conclusions: Aortic valve replacement with the Perceval S sutureless bioprosthesis is associated with low mortality and excellent clinical and haemodynamic behaviour, especially in elderly patients. Palabras clave: Reemplazo valvular aórtico, Perceval S, Estenosis valvular aórtica, Prótesis biológica, Revisión, Keywords: Aortic valve replacement, Perceval S, Aortic valve stenosis, Biological prosthesis, Revie