Circular dichroism evidence of the left-handed conformation adopted by cyclopropylpyrroloindole antitumor antibiotics in solution

The purpose of this work was to determine the conformation adopted in solution by adozelesin, carzelesin, and their derivatives obtained under basic or acidic conditions. Circular dichroism in the 270–330 nm wavelengths region was studied. In solution adozelesin can adopt two different conformations: a left-handed one which is thermodynamically favoured at low temperature and is mainly present at room temperature, and a right-handed one which is observed either at high temperature or at room temperature in the presence of DNA. This was ascertained by the presence of circular dichroism signals of the couplet type. The active form of carzelesin, i.e., U-76074, also exhibited a left-handed conformation in solution. Carzelesin and the derivatives obtained under acidic conditions that lack the cyclopropyl ring, and cyclopropylpyrroloindole, obtained under basic conditions, cannot adopt such a conformation. Chirality 8:585–589, 1996. © 1997 Wiley-Liss, Inc.     

Progressive Cognitive Deficit,Motor Impairment and Striatal Pathology in a Transgenic Huntington Disease Monkey Model from Infancy to Adulthood

One of the roadblocks to developing effective therapeutics for Huntington disease (HD) is the lack of animal models that develop progressive clinical traits comparable to those seen in patients. Here we report a longitudinal study that encompasses cognitive and motor assessment, and neuroimaging of a group of transgenic HD and control monkeys from infancy to adulthood. Along with progressive cognitive and motor impairment, neuroimaging revealed a progressive reduction in striatal volume. Magnetic resonance spectroscopy at 48 months of age revealed a decrease of N-acetylaspartate (NAA), further suggesting neuronal damage/loss in the striatum. Postmortem neuropathological analyses revealed significant neuronal loss in the striatum. Our results indicate that HD monkeys share similar disease patterns with HD patients, making them potentially suitable as a preclinical HD animal model.     

Inclusion and human rights in health policies: comparative and benchmarking analysis of 51 policies from Malawi, Sudan, South Africa and Namibia

While many health services strive to be equitable, accessible and inclusive, peoples' right to health often goes unrealized, particularly among vulnerable groups. The extent to which health policies explicitly seek to achieve such goals sets the policy context in which services are delivered and evaluated. An analytical framework was developed--EquiFrame--to evaluate 1) the extent to which 21 Core Concepts of human rights were addressed in policy documents, and 2) coverage of 12 Vulnerable Groups who might benefit from such policies. Using this framework, analysis of 51 policies across Malawi, Namibia, South Africa and Sudan, confirmed the relevance of all Core Concepts and Vulnerable Groups. Further, our analysis highlighted some very strong policies, serious shortcomings in others as well as country-specific patterns. If social inclusion and human rights do not underpin policy formation, it is unlikely they will be inculcated in service delivery. EquiFrame facilitates policy analysis and benchmarking, and provides a means for evaluating policy revision and development.     

Contribution to the study of land-use dynamics in the plains of Macta (Algeria) with the aid of remote sensing and GIS

The plains of Macta, where the Macta marshes are located, form a wetland with particular ecological characteristics in the Maghreb and are subject to distinct land use dynamics. The plant formations are exposed to multiple forms of degradation, primarily due to climate (period of dryness) and to increasing anthropogenic activities in the area. The new methods of breeding and cultivation contribute to ongoing degradation in this natural ecosystem, with a deterioration of the wetland's biological potentialities. With the aim of safeguarding Macta's marshes, a better knowledge of vegetation distribution patterns and dynamics, together with the interpretation of the remote sensing data and GIS, makes it possible to consider programmes of natural environment restoration and sustainable management. The results of land-use dynamics analysis show a decline in agricultural land use from 33,000 ha in 1958 to 21,000 ha in 2005. Halophytic vegetation currently occupies 47,000 ha, while in 1958 it occupied only 27,000 ha. Tamarix, Inula, Joncus and Scirpus species are experiencing a decrease in surface cover, while Salicornia, Suaeda, and Atriplex are extending their area. To cite this article:     

Inhibition and Substrate Specificity of Adenosine Deaminase. Interaction with 2′-, 3′- and/or 5′-Substituted Adenine Nucleoside Derivatives

Abstract

A series of adenine nucleoside derivatives, most of them prepared for the first time, have been evaluated as substrates or inhibitors of adenosine deaminase. The best inhibitory results were obtained with the 3′, 5′-di-O-benzoyl esters of 9-β-D-pentofuranosyladenines.     

General characteristics of optimal feed rate profiles for various fed-batch fermentation processes

General Characteristics of the optimal feed rate profiles have been deduced for various fed-batch fermentation processes by analyzing singular controls and singular arcs. The optimal control sequences depend on the shapes of the specific growth and product formation rates, mu andpi, and the initial conditions. For fed-batch processes described by four mass balance equations, the most general optimal control sequence consists of a period of maximum feed rate, a period of minimum feed rate (a batch period), a period of singular feed rate (variable and intermediate), and a batch period. Degenerate sequences in which one or more periods are missing can result with a particular set of initial conditions. If the fermentation time is not critical, the singular control maximizes the net yield of product and only when the time is also important, it balances a trade off between the yield of product and the specific growth rate which dictates the fermentation time. With the sequence of optimal control known, the optimal feed rate profile determination is reduced to a problem of determining switching times.     

Deletion mutations in Duchenne muscular dystrophy (DMD) in Western Saudi children

Duchenne and Becker muscular dystrophy (DMD and BMD) are caused, in the majority of cases, by deletions in the dystrophin gene (DMD). The disease is an X-linked neuromuscular diseases typically caused by disrupting (DMD) or non-disrupting (BMD) the reading frame in the dystrophin (DMD) gene. In the present study, amplifications of the genomic DNAs of unrelated 15 Saudi DMD males were carried out using multiplex polymerase chain reaction (PCR) for nine-hotspot regions of exons 4, 8, 12, 17, 19, 44, 45, 48 and 51. We detected six Saudi patients having deletions in a frequency of 40%. The frequency of deletions in exon 51 (20%) was the most common deletion frequently associated with our Saudi sample males. Exons 19, 45, and 48 were present in a frequency of 6.7% each. All deletions were recognized as an individual exonic deletions, while no gross deletion where detected. Finally, the molecular deletions in the Saudi males was expected to be characterized by a moderate frequency among different populations due to the geographical KSA region, which it is in the crossroad of intense migrations and admixture of people coming from continental Asia, Africa, and even Europe. In conclusion, attempts to include an extra DNA samples might reflect a valid vision of the deletions within the high frequency deletion regions (HFDR’s) in the DMD gene mutations in KSA.     

Molecular determination of progesterone receptor’s PROGINS allele (Alu insertion) and its association with the predisposition and susceptibility to polycystic ovary syndrome (PCOS)

Mammalian Genome - Polycystic ovary syndrome, previously known as Stein–Leventhal syndrome, is associated with altered reproductive endocrinology, predisposing a young woman towards the risk...