Comment to "Diabetic peripheral neuropathy: the potential role of vitamin D deficiency" by Oraby et al.

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NLRP3 inflammasome pathways in atherosclerosis.

Atherosclerosis is the major cause of death and disability. Atherosclerotic plaques are characterized by a chronic sterile inflammation in the large blood vessels, where lipid-derived and damage-associated molecular patterns play important roles in inciting immune responses. Following the initial demonstration that NLR family Pyrin domain containing 3 (NLRP3) was important for atherogenesis, a substantial number of studies have emerged addressing the basic mechanisms of inflammasome activation and their relevance to atherosclerosis. In this review, we introduce the basic cellular and molecular mechanisms of NLRP3 inflammasome activation, and discuss the current findings and therapeutic strategies that target NLRP3 inflammasome activation during the development and progression of atherosclerosis

Supramolecular Hierarchy among Halogen-Bond Donors

Through a combination of structural chemistry, vibrational spectroscopy, and theory, we have systematically examined the relative structure-directing importance of a series of ditopic halogen-bond (XB) donors. The molecular electrostatic potential surfaces of six XB donors were evaluated, which allowed for a charge-based ranking. Each molecule was then co-crystallized with 21 XB acceptors and the results have made it possible to map out the supramolecular landscape describing the competition between I/Br-ethynyl donors, perfluorinated I/Br donors, and I/Br-phenyl based donors. The results offer practical guidelines for synthetic crystal engineering driven by robust and directional halogen bonds. Copyright 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim

Halogen and hydrogen bonding in multicomponent crystals of tetrabromo-1H-benzotriazole

4,5,6,7-Tetrabromo-1H-benzotriazole (TBBT) is still considered a reference inhibitor of casein kinase II (CK2), a valuable target for anticancer therapy, even though the poor solubility in water of this active pharmaceutical ingredient (API) has prevented its implementation in therapy. We decided to explore the interactions preferentially formed by TBBT in crystalline solids in order to obtain information helpful for the development of new TBBT cocrystals possibly endowed with improved bioavailability. In this paper, we describe the synthesis and the structural characterization of the TBBT methanol solvate and of the TBBT salt with N,N,Nâ\u80²,Nâ\u80²-tetramethylethylenediamine. It is shown that TBBT can give rise to several competing interactions. This API is clearly a good halogen bond (XB) donor, with bromine atoms adjacent to the triazole ring possibly better donors than the two others. TBBT is also a good hydrogen bond (HB) donor, with the triazole hydrogen forming an HB with the acceptor or being transferred to it. Interestingly, one of the triazole nitrogens was proven to be able to work as a hydrogen bond acceptor

Microsurgery in pediatric upper limb reconstructions: An overview

Pediatric microsurgery; Brachial plexus palsy; Upper limbMicrocirugía pediátrica; Parálisis del plexo braquial; Extremidad superiorMicrocirurgia pediàtrica; Paràlisi del plexe braquial; Extremitat superiorThe use of microsurgery has spread during the last decades, making resolvable many complex defects considered hitherto inapproachable. Although the small vessel diameter in children was initially considered a technical limitation, the increase in microsurgical expertise over the past three decades allowed us to manage many pediatric conditions by means of free tissue transfers. Pediatric microsurgery has been shown to be feasible, gaining a prominent place in the treatment of children affected by limb malformations, tumors, nerve injuries, and post-traumatic defects. The aim of this current concepts review is to describe the more frequent pediatric upper limb conditions in which the use of microsurgical reconstructions should be considered in the range of treatment options

Desde microorganismos a la macrofauna: un estudio comparativo de las comunidades bentónicas profundas y su respuesta a las variables ambientales a lo largo del talud de Malta (mar Jónico)

A comparative study for abundance, biomass and diversity was carried out for the prokaryote, meiofauna and macrofauna communities at three depth stations (1200, 1800 and 2100 m) along the Malta Escarpment (Mediterranean Sea). Our investigation showed a two-fold increase with depth in prokaryote abundance; the contribution of prokaryote biomass to the total benthic biomass was predominant at all depths. Bacteria were the dominant prokaryote component and Archaea formed a considerable fraction (20%-30%) of the prokaryote assemblages. The meio- and macrofauna abundances and meiofauna biomass did not decrease significantly with depth but macrofauna biomass did. The α diversity did not follow a clear bathymetric trend for both nematode and macrofauna species. Probably because of the large number of eurybathic nematode genera, nor did the turnover diversity in nematode composition change down the depth gradient. Conversely, for the macrofauna there was a perceptible change in community composition between the shallowest station and the two deeper stations. Food availability affected only the macrobenthic component. The increase in the prokaryote organisms with depth and the dominance of nematodes and macrofauna deposit feeders suggest active grazing by the two benthic components on microbes. This would transfer energy to the higher trophic levels through the microbial compartment.Se llevó a cabo un estudio comparativo de las comunidades de procariotas, meiofauna y macrofauna sobre la abundancia, biomasa y diversidad. Fue realizado en tres estaciones en varias profundidades (1200, 1800 y 2100 m) a lo largo del talud de Malta (mar Mediterráneo). Nuestra investigación muestra que, aumentando la profundidad, la abundancia de procariotas se duplica. La contribución de la biomasa procariota al total de la biomasa bentónica predominó en todas las profundidades. Las bacterias eran la fracción procariota dominante y junto con los Archaea representaban al 20-30% del total de procariotas. Por otra parte la abundancia de la meiofauna y macrofauna y la biomasa de la meiofauna no disminuían significativamente con la profundidad, mientras que la biomasa de la macrofauna sí lo hacía. La diversidad α no siguió una tendencia batimétrica muy clara para las especies de los nematodos y macrofauna. Probablemente debido a la gran abundancia de géneros de nematodos eurybatiales, la tasa derenovación de la diversidad en la composición de nematodos tampoco cambió por el gradiente de profundidad. En cambio, para la macrofauna hubo un cambio apreciable en la composición de la comunidad entre la estación más superficial y las dos estaciones más profundas. La disponibilidad de alimentos afectó sólo al componente macrobentónico. El aumento con la profundidad de los organismos procariotas, el dominio de los nematodos y la macrofauna que se alimenta de los materiales depositados sugieren un medio activo para los dos componentes bentónicos microbianos. Esto daría lugar a una transferencia de energía a niveles tróficos superiores a través del compartimento microbiano

Alpha-synuclein aggresomes inhibit ciliogenesis and multiple functions of the centrosome.

Protein aggregates are the pathogenic hallmarks of many different neurodegenerative diseases and include the accumulation of α-synuclein, the main component of Lewy bodies found in Parkinson's disease. Aggresomes are closely-related, cellular accumulations of misfolded proteins. They develop in a juxtanuclear position, adjacent to the centrosome, the microtubule organizing centre of the cell, and share some protein components. Despite the long-standing observation that aggresomes/Lewy bodies and the centrosome sit side-by-side in the cell, no studies have been done to see whether these protein accumulations impede organelle function. We investigated whether the formation of aggresomes affected key centrosome functions: its ability to organise the microtubule network and to promote cilia formation. We find that when aggresomes are present, neuronal cells are unable to organise their microtubule network. New microtubules are not nucleated and extended, and the cells fail to respond to polarity cues. Since neurons are polarised, ensuring correct localisation of organelles and the effective intracellular transport of neurotransmitter vesicles, loss of centrosome activity could contribute to functional deficits and neuronal cell death in Parkinson's disease. In addition, we provide evidence that many cell types, including dopaminergic neurons, cannot form cilia when aggresomes are present, which would affect their ability to receive extracellular signals