harbors and paralogous genes that encode branched chain aminotransferases and have opposed expression profiles and physiological roles . Accordingly, in primary nitrogen sources such as glutamine, expression is induced, supporting Bat1-dependent valine-isoleucine-leucine (VIL) biosynthesis, while expression is repressed. Conversely, in the presence of VIL as the sole nitrogen source, expression is hindered while that of is activated, resulting in Bat2-dependent VIL catabolism. The presented results confirm that expression is determined by transcriptional activation through the action of the Leu3-α-isopropylmalate (α-IPM) active isoform, and uncovers the existence of a novel α-IPM biosynthetic pathway operating in aΔ mutant grown on VIL, through Bat2-Leu2-Leu1 consecutive action. The classic α-IPM biosynthetic route operates in glutamine through the action of the leucine-sensitive α-IPM synthases. The presented results also show that repression in glutamine can be alleviated in aΔ mutant or through Gcn4-dependent transcriptional activation. Thus, when is grown on glutamine, VIL biosynthesis is predominant and is preferentially achieved through; while on VIL as the sole nitrogen source, catabolism prevails and is mainly afforded by .
Eukaryotic ssDNA viruses encode a rolling-circle replication (RCR) initiation protein, Rep, which binds to iterated DNA elements functioning as essential elements for virus-specific replication. By using the iterons of all known circoviruses, nanoviruses and nanovirus-like satellites as heuristic devices, we have identified certain amino acid residues that presumably determine the DNA-binding specificity of their Rep proteins. These putative "specificity determinants" (SPDs) cluster in two discrete protein regions, which are adjacent to distinct conserved motifs. A comparable distribution of SPDs was uncovered in the Rep protein of geminiviruses. Modeling of the tertiary structure of diverse Rep proteins showed that SPD regions interact to form a small beta-sheet element that has been proposed to be critical for high-affinity DNA-binding of Rep. Our findings indicate that eukaryotic circular ssDNA viruses have a common ancestor and suggest that SPDs present in replication initiators from a huge variety of viral and plasmid RCR systems are associated with the same conserved motifs.
To investigate the ancestral admixture in the Mestizo population in northeastern Mexico, we genotyped 74 ancestral informative markers (AIMs) and 15 Y-single-nucleotide polymorphisms (Y-SNPs) in 100 individuals. The Native American contribution is 56% (range: 27.4-81.2%), the European contribution is 38% (range: 16.7-70.5%) and the West African contribution is 6%. The results show a higher European contribution than was reported in other similar studies in the country, albeit with a predominant Native American ancestry. No remarkable differences in the ancestry proportions were observed using subgroups of 74, 54, 34 and 24 AIMs. The paternal lineage calculated by genotyping of 15 Y-SNPs, shows a major component of European and Eurasian ancestry markers (B78%), compared with Amerindian (B12%) and African markers (10%). This information will set a reference for future determinations of admixture proportions in the Mestizo population from Mexico and for populationbased association studies of complex diseases.
BackgroundAlthough epidemiologic and socioeconomic criteria and biomedical risk factors indicate high-priority for tuberculosis (TB) control in Mexico, molecular epidemiology studies of the disease in the country are scarce.MethodsComplete sociodemographic and clinical data were obtained from 248 of the 432 pulmonary TB (PTB) cases confirmed from 2006 to 2010 on the population under epidemiological surveillance in the state of San Luis Potosí, México. From most PTB cases with complete data Mycobacterium tuberculosis complex (MTC) isolates were recovered and their spoligotypes, lineages and families, geographic distribution and drug resistance determined.ResultsPulmonary tuberculosis incidence ranged from 2.4 to 33.4 (cases per 100,000 inhabitants) in the six state sanitary jurisdictions that were grouped in regions of low (jurisdictions I-II-III), intermediate (jurisdictions IV-V) and high incidence (jurisdiction VI) with 6.2, 17.3 and 33.4 rates, respectively. Most patients were poor, 50-years-median-age males and housewives. Among the 237 MTC spoligotyped isolates, 232 corresponded to M. tuberculosis (104 spoligotypes in 24 clusters) and five to M. bovis. The predominant Euro-American lineage was distributed all over the state, the East-Asian lineage (Beijing family) in the capital city, the Indo-Oceanic (Manila family) in eastern localities, and M. bovis in rural localities.ConclusionsIn San Luis Potosí TB affects mainly poor male adults and is caused by M. tuberculosis and to a minor extent by M. bovis. There is great genotypic diversity among M. tuberculosis strains, the Euro-American lineage being much more prevalent than the Indo-Oceanic and East-Asian lineages. The frequency of resistant strains is relatively low and not associated to any particular lineage.
The γ-aminobutyric acid (GABA) shunt constitutes a conserved metabolic route generating nicotinamide adenine dinucleotide phosphate (NADPH) and regulating stress response in most organisms. Here we show that in the presence of GABA, Saccharomyces cerevisiae produces glutamate and alanine through the irreversible action of Uga1 transaminase. Alanine induces expression of alanine transaminase (ALT1) gene. In an alt1Δ mutant grown on GABA, alanine accumulation leads to repression of the GAD1, UGA1, and UGA2 genes, involved in the GABA shunt, which could result in growth impairment. Induced ALT1 expression and negative modulation of the GABA shunt by alanine constitute a novel regulatory circuit controlling both alanine biosynthesis and catabolism. Consistent with this, the GABA shunt and the production of NADPH are repressed in a wild-type strain grown in alanine, as compared to those detected in the wild-type strain grown on GABA. We also show that heat shock induces alanine biosynthesis and ALT1, UGA1, UGA2, and GAD1 gene expression, whereas an uga1Δ mutant shows heat sensitivity and reduced NADPH pools, as compared with those observed in the wild-type strain. Additionally, an alt1Δ mutant shows an unexpected alanine-independent phenotype, displaying null expression of mitochondrial COX2, COX3, and ATP6 genes and a notable decrease in mitochondrial/nuclear DNA ratio, as compared to a wild-type strain, which results in a petite phenotype. Our results uncover a new negative role of alanine in stress defense, repressing the transcription of the GABA shunt genes, and support a novel Alt1 moonlighting function related to the maintenance of mitochondrial DNA integrity and mitochondrial gene expression.
BackgroundStudies of avian haemosporidians allow understanding how these parasites affect wild bird populations, and if their presence is related to factors such as habitat loss, degradation and fragmentation, and climate change. Considering the importance of the highland Plateau of Mexico as part of the North American bird migratory route and as a region containing important habitat for numerous bird species, the purpose of this study was to document haemosporidian species richness and how habitat degradation, bird body condition, and distance from water sources correlate with bird parasitemia.MethodsWe assessed the presence of avian haemosporidians in three resident bird species through microscopy and PCR amplification of a fragment of the haemosporidian cytochrome b gene. Average parasitemia was estimated in each species, and its relationship with habitat degradation through grazing, bird body condition and distance from water bodies was assessed.ResultsHigh levels of parasitemia were recorded in two of the three bird species included in this study. Four lineages of haemosporidians were identified in the study area with nearly 50 % prevalence. Areas with highly degraded shrublands and villages showed higher parasitemia relative to areas with moderately degraded shrublands. No strong relationship between parasitemia and distance from water bodies was observed. There were no significant differences in prevalence and parasitemia between the two bird species infected with the parasites. Two of the sequences obtained from the fragments of the parasite’s cytochrome b gene represent a lineage that had not been previously reported.ConclusionsHaemosporidian diversity in arid zones of the Mexican highland plateau is high. Shrubland habitat degradation associated to the establishment of small villages, as well as tree extraction and overgrazing in the surroundings of these villages, significantly enhances parasitemia of birds by haemosporidians.Electronic supplementary materialThe online version of this article (doi:10.1186/s13071-016-1569-3) contains supplementary material, which is available to authorized users.
In the yeast Saccharomyces cerevisiae, the ScGDH1 and ScGDH3 encoded glutamate dehydrogenases (NADP‐GDHs) catalyze the synthesis of glutamate from ammonium and α‐ketoglutarate (α‐KG). Previous kinetic characterization showed that these enzymes displayed different allosteric properties and respectively high or low rate of α‐KG utilization. Accordingly, the coordinated action of ScGdh1 and ScGdh3, regulated balanced α‐KG utilization for glutamate biosynthesis under either fermentative or respiratory conditions, safeguarding energy provision. Here, we have addressed the question of whether there is a correlation between the regulation and kinetic properties of the NADP‐GDH isozymes present in S. cerevisiae (ScGdh1 and ScGdh3), Kluyveromyces lactis (KlGdh1), and Lachancea kluyveri (LkGdh1) and their evolutionary history. Our results show that the kinetic properties of K. lactis and L. kluyveri single NADP‐GDHs are respectively similar to either ScGDH3 or ScGDH1, which arose from the whole genome duplication event of the S. cerevisiae lineage, although, KlGDH1 and LkGDH1 originated from a GDH clade, through an ancient interspecies hybridization event that preceded the divergence between the Saccharomyces clade and the one containing the genera Kluyveromyces, Lachancea, and Eremothecium. Thus, the kinetic properties which determine the NADP‐GDHs capacity to utilize α‐KG and synthesize glutamate do not correlate with their evolutionary origin.
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