The DNA sequence of chromosome I of an African trypanosome: gene content,chromosome organisation,recombination and polymorphism

The African trypanosome, Trypanosoma brucei, causes sleeping sickness in humans in sub-Saharan Africa. Here we report the sequence and analysis of the 1.1 Mb chromosome I, which encodes approximately 400 predicted genes organised into directional clusters, of which more than 100 are located in the largest cluster of 250 kb. A 160-kb region consists primarily of three gene families of unknown function, one of which contains a hotspot for retroelement insertion. We also identify five novel gene families. Indeed, almost 20% of predicted genes are members of families. In some cases, tandemly arrayed genes are 99–100% identical, suggesting an active process of amplification and gene conversion. One end of the chromosome consists of a putative bloodstream-form variant surface glycoprotein (VSG) gene expression site that appears truncated and degenerate. The other chromosome end carries VSG and expression site-associated genes and pseudogenes over 50 kb of subtelomeric sequence where, unusually, the telomere-proximal VSG gene is oriented away from the telomere. Our analysis includes the cataloguing of minor genetic variations between the chromosome I homologues and an estimate of crossing-over frequency during genetic exchange. Genetic polymorphisms are exceptionally rare in sequences located within and around the strand-switches between several gene clusters.     

Resistance to extinction of low fitness virus subjected to plaque-to-plaque transfers: diversification by mutation clustering.

Plaque-to-plaque transfers of RNA viruses lead to accumulation of mutations and fitness decrease. To test whether continuing plaque-to-plaque transfers would lead to viral extinction, we have subjected several low fitness foot-and-mouth disease virus (FMDV) clones to up to 130 successive plaque transfers, and have analyzed the evolution of plaque titers and genomic nucleotide sequences. No case of viral extinction could be documented. Some low fitness clones that posses an internal poly(A) tract evaded extinction by modifying the length or base composition of the poly(A) tract. The comparison of entire genomic sequences of FMDV clones at increasing plaque transfer number revealed that mutations accumulated at a uniform rate, and that they were distributed unevenly along the genome. Clusters of mutations were identified at different genomic sites in two plaque transfer lineages. Mutation clustering appears to occur stochastically and could not be related to fixation of compensatory mutations. The results document resistance of viral clones to extinction, and suggest that mutation clustering may be a mechanism of genetic diversification of low fitness virus.     

Tailoring of physical and chemical properties of macro- and microhydrogels based on telechelic PVA

Poly(vinyl alcohol), PVA, is amenable to several structural modifications because of the presence of the hydroxyl moiety in the backbone. The chemical versatility of this polymer can be used for the obtainment of new wall-to-wall pH-responsive PVA chemical hydrogels and for the preparation of air-filled microspheres, for example, microbubbles. Here, we report on the characterization of the physical and chemical properties of these novel networks that can be potentially used in different biomedical applications as controlled drug delivery and as ultrasonic contrast agent.     

Xanthan and glucomannan mixtures: synergistic interactions and gelation

The synergistic interaction between xanthan and glucomannan in solution and in the gel phase has been studied by circular dichroism spectroscopy and differential scanning calorimetry. The study in solution of the polysaccharidic mixture indicates a preferred stoichiometry of the interaction corresponding to a weight fraction of xanthan around 0.55. This finding is in reasonable agreement with the differential scanning calorimetry measurements carried out on the gel phase. Models from conformational analysis based on these results were formulated in terms of 1:1 and 2:1 Konjac glucomannan/xanthan molecular assemblies. The experimental and calculation results clearly indicate the involvement of the side chains of xanthan and suggest that the ordered portions of the macromolecular complex in solution act in the gel phase as junction zones.     

Comparison of the efficacy of 1% flutrimazole cream twice a day with 1% flutrimazole cream once a day for the treatment of superficial dermatophytoses

Different clinical studies have demonstrated flutrimazole's efficacy in the treatment of superficial dermatomycoses when administered either twice daily or once daily for four weeks. The aim of the present study was to compare both dosing schedules for the treatment of superficial dermatomycoses. In this randomized, controlled, double blind study, we included 84 patients suffering superficial dermatophytosis (confirmed by microscopic examination (KOH) and culture) susceptible for topical monotherapy. Forty-one patients received flutrimazole 1% twice daily (TD) and forty-three once daily (OD) for four weeks. The efficacy of treatment was evaluated by clinical and mycological criteria at the end of treatment (D28) and after four weeks without treatment (D58). Clinical and mycological cure rates on D28 were 50% with TD and 65% with OD treatment. Only considering clinical evaluation, clinical cure rates on D28 were 63% (TD) and 70% (OD). Also, clinical and mycological cure rates on D56 were 65% with TD and 72% with OD treatment. Only considering clinical evaluation, clinical cure rates on D56 were of 68% (TD) and 72% (OD). The overall tolerability was similar in both treatment groups. The efficacy assessment at the end of treatment (D28) and four weeks after treatment discontinuation (D56) showed that the OD treatment is not inferior to the TD treatment, with similar clinical and mycological cure rates and clinical cure rates in both cases. The OD administration of flutrimazole cream 1% is the most appropriate dosing schedule as it provides the same efficacy, it improves patient's compliance and the cost per day of treatment.     

Comparative Phenomenology of Ataques de Nervios,Panic Attacks,and Panic Disorder

This article examines a clinicalsample of 66 Dominican and Puerto Ricansubjects who reported ataques de nerviosand also psychiatric disorder, and disentanglesthe phenomenological experiences of ataquede nervios, panic attacks, and panic disorder. In-depth cultural interviews assessed thesymptomatic phenomenology of ataqueepisodes from the local perspective as well asin terms of key panic features, such asrecurrence, rapid peaking of symptoms, and lackof provocation. Independent diagnosticassessments of panic attacks and disorder werealso used to establish the phenomenologicaloverlap between ataque and panic. Ourfindings indicate that 36 percent ofataques de nervios fulfill criteria for panicattacks and between 17 percent and 33 percentfor panic disorder, depending on the overlapmethod used. The main features distinguishingataques that fulfill panic criteria fromataques that do not include whether theepisodes were provoked by an upsetting event inthe person's life and the rapidity of crescendoof the actual attack. A key finding is thatataques often share individualphenomenological features with panic episodes,but that these features usually do not ``runtogether' during the ataque experience.This confirms previous findings thatataque is a more inclusive construct thanpanic disorder. The importance of thesefindings for the clinical diagnosis andtreatment of persons with ataques isdiscussed.     

Effects of MCH/NEI in the striatum and interactions between them and with alpha-MSH on IP3 levels

In this study, we investigated: (a) the effect of melanocyte concentrating hormone (MCH) and neuropeptide glutamine (E)-isoleusine-(I) (NEI) on IP(3) production on an "in vitro" model using slices containing caudate putamen (CP) and accumbens nuclei (ACC); and (b) the interaction between these peptides and with alpha-melanocyte-stimulating-hormone (alpha-MSH) on the production of this second messenger. Only MCH at the highest dose studied (3.6 microM) increased the production of IP(3), whereas at the low concentration (0.6 microM) it did not affect IP(3) levels. NEI and alpha-MSH at both concentrations tested (0.6 and 3.6 microM), did not affect IP(3) production either. However, when NEI or alpha-MSH (at 3.6 microM) were added together with 3.6 microM MCH, the increase in the IP(3) content induced by this last peptide was blocked.