Whole-Genome Sequencing of a Haarlem Extensively Drug-Resistant Mycobacterium tuberculosis Clinical Isolate from Medellín, Colombia.

Colombia is one of the 105 countries that has reported at least one case of extensively drug-resistant tuberculosis (XDR-TB). The Mycobacterium tuberculosis Haarlem genotype is ubiquitous worldwide. Here, we report the high-quality draft genome sequence of a Colombian Haarlem XDR-TB clinical isolate composed of 4,329,127 bp with 4,386 genes.

Draft Genome Sequence of a Mycobacterium africanum Clinical Isolate from Antioquia, Colombia.

Mycobacterium africanum is a member of the Mycobacterium tuberculosis complex. Most commonly found in West African countries, it has scarcely been described in South America. Here, we report the first genome sequence of a Colombian M. africanum clinical isolate. It is composed of 4,493,502 bp, with 4,069 genes.

Whole-Genome Sequencing of Two Latin American-Mediterranean Extensively Drug-Resistant Mycobacterium tuberculosis Clinical Isolates from Medellín, Colombia.

Colombia, with a tuberculosis incidence of 33 cases per 100,000 population, is one of the countries that have reported extensively drug-resistant Mycobacterium tuberculosis (XDR-TB). We report the high-quality draft genome sequences of two Latin American-Mediterranean XDR-TB clinical isolates (TBR-152 and TBR-175), comprising 4,303,775 bp and 4,330,115 bp, respectively.

Whole-Genome Sequence of a Beijing Extensively Drug-Resistant Mycobacterium tuberculosis Clinical Isolate from Buenaventura, Colombia.

Extensively drug-resistant Mycobacterium tuberculosis (XDR-TB) has been reported to the WHO by 100 countries, including Colombia. An estimated 9.0% of people with multidrug-resistant TB have XDR-TB. We report the genome sequence of a Beijing XDR-TB clinical isolate from Buenaventura, Colombia. The genome sequence is composed of 4,298,162 bp with 4,359 genes.

The structural modeling of the interaction between levofloxacin and the Mycobacterium tuberculosis gyrase catalytic site sheds light on the mechanisms of fluoroquinolones resistant tuberculosis in Colombian clinical isolates.

We compared the prevalence of levofloxacin (LVX) resistance with that of ofloxacin (OFX) and moxifloxacin (MFX) among multidrug resistant (MDR) MTB clinical isolates collected in Medellin, Colombia, between 2004 and 2009 and aimed at unraveling the underlying molecular mechanisms that explain the correlation between QRDR-A mutations and LVX resistance phenotype. We tested 104 MDR isolates for their susceptibility to OFX, MFX, and LVX. Resistance to OFX was encountered in 10 (9.6%) of the isolates among which 8 (7.7%) were also resistant to LVX and 6 (5.7%) to MFX. Four isolates resistant to the 3 FQ were harboring the Asp94Gly substitution, whilst 2 other isolates resistant to OFX and LVX presented the Ala90Val mutation. No mutations were found in the QRDR-B region. The molecular modeling of the interaction between LVX and the DNA-DNA gyrase complex indicates that the loss of an acetyl group in the Asp94Gly mutation removes the acid base interaction with LVX necessary for the quinolone activity. The Ala90Val mutation that substitutes a methyl for an isopropyl group induces a steric modification that blocks the LVX access to the gyrase catalytic site.

Carbon nanotube reinforced polylactide-caprolactone copolymer: mechanical strengthening and interaction with human osteoblasts in vitro.

This study proposes the use of carbon nanotubes (CNTs) as reinforcement to enhance the mechanical properties of a polylactide-caprolactone copolymer (PLC) matrix. Biological interaction of PLC-CNT composites with human osteoblast cells is also investigated. Addition of 2 wt % CNT shows very uniform dispersion in the copolymer matrix, whereas 5 wt % CNT shows severe agglomeration and high porosity. PLC-2 wt % CNT composite shows an improvement in the mechanical properties with an increase in the elastic modulus by 100% and tensile strength by 160%, without any adverse effect on the ductility up to 240% elongation. An in vitro biocompatibility study on the composites shows an increase in the viability of human osteoblast cells compared to the PLC matrix, which is attributed to the combined effect of CNT content and surface roughness of the composite films.

Analysis of the transcriptional regulation of melanocytic genes by alphaMSH using the cDNA microarray technique.

Studies of mammalian pigmentation have identified many genes involved in the development, migration, and function of melanocytes. Molecular and biochemical mechanisms that switch melanocytes between the production of eumelanin or pheomelanin involve the opposing action of two signaling molecules, alpha-Melanocyte Stimulating Hormone (alphaMSH) and Agouti Signal Protein (ASP). AlphaMSH affects various aspects of melanocyte behavior, stimulating melanocyte dendricity, attachment to extracellular matrix proteins, but also up-regulating the expression of eumelanogenic genes. In response to ASP, melanocytes switch from producing eumelanin to pheomelanin concomitant with the down-regulation of melanogenic genes transcription. Since activation of signaling pathways leads to mRNA expression, microarray technology can provide a quantitative assessment of the consequences of this activation. Significant up/down regulation of all known melanogenic genes by alphaMSH/ASP in cultured melanocytes has been previously reported. We have now used the cDNA microarray technique to screen alphaMSH-treated melanocytes to identify genes that are transcriptionally enhanced by this factor. We report the melanocytic expression and alphaMSH up-regulation of 11 genes spanning 7 functional categories such as apoptosis, body weight control, intracellular transport, signal transduction, oncogenic transformation, transcription factors and genes coding for keratin associated proteins.

A first genotyping assay of French cattle breeds based on a new allele of the extension gene encoding the melanocortin-1 receptor (Mc1r).

The seven transmembrane domain melanocortin-1 receptor (Mc1r) encoded by the coat color extension gene (E) plays a key role in the signaling pathway of melanin synthesis. Upon the binding of agonist (melanocortin hormone, alpha-MSH) or antagonist (Agouti protein) ligands, the melanosomal synthesis of eumelanin and/or phaeomelanin pigments is stimulated or inhibited, respectively. Different alleles of the extension gene were cloned from unrelated animals belonging to French cattle breeds and sequenced. The wild type E allele was mainly present in Normande cattle, the dominant E(D) allele in animals with black color (i.e. Holstein), whereas the recessive e allele was identified in homozygous animals exhibiting a more or less strong red coat color (Blonde d'Aquitaine, Charolaise, Limousine and Salers). A new allele, named E1, was found in either homozygous (E1/E1) or heterozygous (E1/E) individuals in Aubrac and Gasconne breeds. This allele displayed a 4 amino acid duplication (12 nucleotides) located within the third cytoplasmic loop of the receptor, a region known to interact with G proteins. A first genotyping assay of the main French cattle breeds is described based on these four extension alleles.