Synthetic Studies on the Preparation of Alanyl Epoxysulfones as Cathepsin Cysteine Protease Electrophilic Traps.

A Darzens reaction between tert-butoxycarbonyl alaninal and chloromethyl phenyl sulfone afforded chlorohydrins, which were converted into epoxysulfones by reaction with sodium tert-butoxide. Epoxysulfone 10 and chloroketone 14 derived from chlorohydrins by oxidation proved to be inhibitors of cathepsins H, S, and C as determined by competitive activity-based protein profiling.

Radical mechanism in the elimination of 2-arylsulfinyl esters.

The mechanism of the dehydrosulfenylation of 2-arylsulfinyl esters was investigated. The reaction was found to follow a homolytic cleavage mechanism as verified by electrospray ionization tandem mass spectrometry and experimental work. Rearranged sulfoxides are obtained as byproduct during the elimination reaction.

Three-Step Telescoped Synthesis of Monosubstituted Vicinal Diamines from Aldehydes.

Aldehydes are easily transformed into vicinal diamines and piperazines through a one-pot procedure including a Darzens reaction and treatment with an amine or diamine and then with a reducing agent. Additionally, quinoxalines can be accessed by reaction with 1,2-benzenediamine under oxidative conditions. These transformations are simple methods for the preparation of synthetically interesting monosubstituted diamines, piperazines, and quinoxalines.

InTool Explorer: An Interactive Exploratory Analysis Tool for Versatile Visualizations of Neuroscientific Data.

The bottleneck for progress in many research areas within neuroscience has shifted from the data acquisition to the data analysis stages. In the present article, we propose a method named InTool Explorer that we have developed to perform interactive exploratory data analysis, focusing on neuroanatomy as an example of its utility. This tool is freely-available software that has been designed to facilitate the study of complex neuroscience data. InTool Explorer requires no more than an internet connection and a web browser. The main contribution of this tool is to provide a user-designed canvas for data visualization and interaction, to perform specific exploratory tasks according to the user needs. Moreover, InTool Explorer permits visualization of the datasets in a very dynamic and versatile way using a linked-card approach. For this purpose, the tool allows the user to select among different predefined card types. Each card type offers an abstract data representation, a filtering tool or a set of statistical analysis methods. Additionally, InTool Explorer makes it possible linking raw images to the data. These images can be used by InTool Explorer to define new customized filtering cards. Another significant contribution of this tool is that it allows fast visualization of the data, error finding, and re-evaluation to establish new hypotheses or new lines of research. Thus, regarding its practical application in the laboratory, InTool Explorer provides a new opportunity to study and analyze neuroscience data prior to any statistical analysis being carried out.

Dipeptidyl Nitroalkenes as Potent Reversible Inhibitors of Cysteine Proteases Rhodesain and Cruzain.

Dipeptidyl nitroalkenes are potent reversible inhibitors of cysteine proteases. Inhibitor 11 resulted to be the most potent one with Ki values of 0.49 and 0.44 nM against rhodesain and cruzain, respectively. According to enzymatic dilution and dialysis experiments, as well as computational and NMR studies, dipeptidyl nitroalkenes are tightly binding covalent reversible inhibitors.

3D segmentations of neuronal nuclei from confocal microscope image stacks.

In this paper, we present an algorithm to create 3D segmentations of neuronal cells from stacks of previously segmented 2D images. The idea behind this proposal is to provide a general method to reconstruct 3D structures from 2D stacks, regardless of how these 2D stacks have been obtained. The algorithm not only reuses the information obtained in the 2D segmentation, but also attempts to correct some typical mistakes made by the 2D segmentation algorithms (for example, under segmentation of tightly-coupled clusters of cells). We have tested our algorithm in a real scenario-the segmentation of the neuronal nuclei in different layers of the rat cerebral cortex. Several representative images from different layers of the cerebral cortex have been considered and several 2D segmentation algorithms have been compared. Furthermore, the algorithm has also been compared with the traditional 3D Watershed algorithm and the results obtained here show better performance in terms of correctly identified neuronal nuclei.

SINGLE FLOWER TRUSS regulates the transition and maintenance of flowering in tomato.

The characterisation of the single flower truss ( sft) mutant phenotype of tomato ( Lycopersicon esculentum Mill.), as well as its genetic interactions with other mutations affecting FALSIFLORA ( FA) and SELF PRUNING ( SP) genes, has revealed that SFT is a key gene in the control of floral transition and floral meristem identity. The single sft mutation produces a late-flowering phenotype in both long-day and short-day conditions. In combination with fa, a mutation affecting the tomato gene orthologous to LFY, sft completely blocks the transition to flowering in this species. Thus, the phenotype of the sft fa double mutants indicates that SFT and FA participate in two parallel pathways that regulate the switch from vegetative to reproductive phase in tomato, and that both genes are indispensable for flowering. On the other hand, the replacement of flowers by vegetative shoots observed in the sft inflorescence suggests that SFT regulates flower meristem identity during inflorescence development of tomato. In addition to these two main functions, SFT is involved in the development of both flowers and sympodial shoots of tomato. First, the mutation produces a partial conversion of sepals into leaves in the first floral whorl, and a reduction in the number of floral organs, particularly carpels. Secondly, the sympodial development in the mutant plants is altered, which can be related to the interaction between SFT and SP, a gene controlling the number of nodes in sympodial shoots. In fact, we have found that the sft phenotype is epistatic to that of sp, and that the level of SP mRNA in the apical buds of sft around flowering is reduced. SFT can therefore co-ordinate the regulation of two simultaneous developmental processes in the tomato apical shoot, the promotion of flowering in one sympodial segment and the vegetative development of the next segment.

Diagnostico prenatal de holoprosencefalia alobar / Prenatal diagnosis of alobar holoprosencephaly

El artículo describe el caso de una mujer de 36 años de edad, quien acudió a su primer control ecográfico prenatal a las 27,4 semanas de gestación por amenorrea. Dicha gestación evolucionaba satisfactoriamente y no existían antecedentes de importancia; sin embargo, en la ecografía obstétrica se evidenció ventrículo único central, tálamos fusionados, ausencia de fisura interhemisférica, hipotelorismo ocular y labio leporino, hallazgos éstos que se confirmaron en el espécimen patológico, y que corroboran el diagnóstico prenatal de holoprosencefalia alobar

Uso de la calcitonina en el tratamiento multifactorial de la osteoporosis / Use of calcitonin in the multifactorial treatment of osteoporosis

Estudiamos 12 pacientes con osteoporosis, con edades promedio de 75,42 + ou - 6,79 años. Les evaluamos capacidad funcional en escala de 0 a 3 y dolor osteoarticular en escala de 0 a 5 repitiéndolos semanalmente durante el período experimental de 13 semanas. Al inicio y final de éste se les practicó laboratorio de rutina y radiografías con misma técnica para calcáneo, fémur proximal y manos, para evaluar patrón travecular (compresión y tensión) y la cortical como índices de osteoporosis y calcificación. El estado radiográfico del hueso se clasificó en escala de 0 a 3. Previa información y consentimiento, a 10 pacientes se les sometió a tratamiento con 100 unidades internacionales (UI) subcutáneas de calcitonina (CT) 4 veces por semana por 90 días, 1800 mgr. diarios de carbonato de calcio y 2 sesiones diarias de sol y ejercícios estandarizados. Otras 2 pacientes recibieron igual tratamiento sin incluir CT. Cinco pacientes de 6 con limitaciones funcionales y 7 de 8 con dolores osteoarticulares mejoraron con tratamiento de CT. La respuesta radiográfica al tratamiento con calcitonina se mostró favorable en el 70% de las pacientes al evaluar calcáneo, 78% en fémur proximal y 50% en manos. La evaluación ósea antes y después de tratamiento mostró radiográficamente marcada mejoría en 6 de las 10 pacientes, ligera en 3 y sin respuesta en una. Hubo una diferencia estadística en los patrones pre y post-CT de P<0,0005. Una de las 2 pacientes sin CT tuvo una mejoría en algunos de los parámetros radiológicos que nosotros atribuimos a su mayor actividad física cotidiana. Los resultados obtenidos nos sugieren que el tratamiento de la osteoporosis con Ct asociado con medidas generales de higiene, ejercicio, aporte adecuado de sol y calcio puede ser beneficioso para el manejo de la osteoporosis senil. Por otra parte la evaluación radiográfica de fémur proximal y calcáneo constituyen una ayuda diagnóstica en el seguimiento de la osteoporosis en nuestro medio