Random/nonrandom X-chromosome inactivation in Nesokia indica: possible influence of heterochromatin

Five types of X chromosomes with different amounts of heterochromatin have been observed in Nesokia indica, the Indian mole rat. They have been found in both mosaic and nonmosaic individuals. The influence, if any, of heterochromatin on the kinetics of X-chromosome DNA replication was evaluated in bone marrow cells and peripheral blood lymphocytes of Nesokia females with variant X chromosomes. In bone marrow cells of nonmosaic females a random X-chromosome inactivation (XCI) pattern was observed, except when there was a total loss of heterochromatin from the variant X chromosome, resulting in predominantly early replication. A nonrandom pattern was observed, however, in blood and bone marrow cells of all individuals with mosaic genotypes. In these females the X chromosome with the lesser amount of heterochromatin was predominantly the active one. The amount of heterochromatin per se or, more likely, specific sequences contained in the heterochromatic region seem to influence the XCI pattern in a cis-acting manner. The observations also seem to support a process of cell selection in individuals with variant X chromosomes.     

Distribution of the Val108/158Met polymorphism of the COMT gene in healthy Mexican population

Catechol-O-methyltransferase (COMT) inactivates the catecholamines adrenaline, noradrenaline and dopamine. On the other hand, some studies have reported that the enzymatic activity of COMT is partly genetically determined. With regard to the COMT gene, the most studied polymorphism is the functional variant Val108/158Met (rs4680), which results in substantial three- to four-fold variations in enzyme activity. To date, the rs4680 polymorphism of COMT has been associated with a number of disorders. In addition, this polymorphism has been found to have important differences in frequency according to the studied population. Therefore, the aim of the present study was to evaluate the frequency of a common single nucleotide polymorphism (SNP) Val108/158Met of the COMT gene in the Mexican population. Accordingly, we recruited 431 healthy volunteers. Our sample consisted of 111 healthy individuals from Mexico City and 320 individuals from the state of Tabasco, Mexico. We observed that Met was the most common allele, ranging from 57% (Tabasco) to 85% (Mexico City). In addition, we analyzed the frequency of Val108/158Met polymorphism of Caucasian (54% Met allele), Asian (29% Met allele) and African (34% Met allele) populations separately and also in comparison with Mexican (63% Met allele) population. In conclusion, the distribution of the Val108/158Met polymorphism distinguishes the Mexican population studied from other populations, but it is necessary to increase the size of the sample to get more conclusive results.     

The Age-related Gliosis and Accompanying Deficit in Spatial Learning are Unaffected by Dimebon

A non-selective antihistamine, dimebon, has recently emerged as a potential treatment for Alzheimer’s disease and Huntington’s disease. Dimebon exerts several effects in addition to its anti-histaminergic effect, and of particular interest is its ability to enhance cognitive function in several models. The mechanism underlying this is unknown though it has been suggested that it may be associated with its anti-cholinergic action. Dimebon has also been reported to be neuroprotective, perhaps as a result of its ability to stabilize mitochondria. We considered that these effects might impact on the well-described age-related impairment in spatial learning and therefore examined the effect of repeated administration of dimebon on performance of young and aged animals in the Morris water maze. Whereas a clear age-related deficit was observed, dimebon failed to exert any effect on performance. Similarly, dimebon exerted no effect on the age-related increase in hippocampal expression of several markers of microglial and astroglial activation. We conclude that, despite its cognitive enhancing effects in some models, dimebon failed to modulate the deficit in spatial learning in aged rats and the evidence suggests that the drug does not possess anti-inflammatory properties.     

Effect of nitrate on lipid production by T. suecica, M. contortum, and C. minutissima

Microalgae are an alternative and sustainable source of lipids that can be used as a feedstock for biodiesel production. Nitrate is a good nitrogen source for many microalgae and affects biomass and lipid yields of microalgae. In this study, the effect of nitrate on cell growth and lipid production and composition in Monoraphidium contortum, Tetraselmis suecica, and Chlorella minutissima was investigated. Nitrate affected the production of biomass and the production and composition of lipids of the three microalgae tested. Increasing the nitrate concentration in the culture medium resulted in increased biomass production and higher biomass productivity. Furthermore, increasing the nitrate concentration resulted in a reduction in lipid content and productivity in M. contortum; however, the opposite effect was observed in T. suecica and C. minutissima cultures. C. minutissima and M. contortum lipids contain high levels of oleic acid, with values ranging from 26 to 45.7% and 36.4 to 40.1%, respectively. The data suggest that because of its high lipid productivity (13.79 mg L^?1 d^?1) and high oleic acid productivity (3.78 mg L^?1 d^?1), Chlorella minutissima is a potential candidate for the production of high quality biodiesel.     

Aulacoseira calypsi sp. nov. (Coscinodiscophyceae) from an Amazonian lake,northern Brazil

This paper describes a new diatom species, Aulacoseira calypsi Tremarin, Torgan & Ludwig, from specimens in plankton samples from Água Preta lake. This Amazonian lake is a shallow mesotrophic environment situated in northern Brazil. The species is characterized by long filaments united by spatulate linking spines, obovate to conic separation spines, a valve surface variably ornamented, straight striae on the mantle, a narrow ringleist, and one row of sessile rimoportulae near the ringleist. Aulacoseira calypsi's morphometric features are compared with the following similar species: Aulacoseira nygaardii (Camburn) Camburn & Charles, Aulacoseira lacustris (Grunow) Krammer, Aulacoseira coroniformis Pearce & Cremer, Aulacoseira occulta Siver & Hamilton, Aulacoseira lancea Siver & Hamilton, Aulacoseira gessneri (Hustedt) Simonsen, and Aulacoseira islandica (Müller) Simonsen. The species shares similarities as to frustule size, striation pattern, and narrowness of ringleist; but differs in the morphology of separation and linking spines, and the number and position of the rimoportulae.     

Probiotics in the intestinal tract of juvenile whiteleg shrimp Litopenaeus vannamei: modulation of the bacterial community

Molecular analysis of the 16S rDNA of the intestinal microbiota of whiteleg shrimp Litopenaeus vannamei was examined to investigate the effect of a Bacillus mix (Bacillus endophyticus YC3-b, Bacillus endophyticus C2-2, Bacillus tequilensisYC5-2) and the commercial probiotic (Alibio^®) on intestinal bacterial communities and resistance to Vibrio infection. PCR and single strain conformation polymorphism (SSCP) analyses were then performed on DNA extracted directly from guts. Injection of shrimp with V. parahaemolyticus at 2.5 × 10⁵ CFU g^?1 per shrimp followed 168 h after inoculation with Bacillus mix or the Alibio probiotic or the positive control. Diversity analyses showed that the bacterial community resulting from the Bacillus mix had the highest diversity and evenness and the bacterial community of the control had the lowest diversity. The bacterial community treated with probiotics mainly consisted of α- and γ-proteobacteria, fusobacteria, sphingobacteria, and flavobacteria, while the control mainly consisted of α-proteobacteria and flavobacteria. Differences were grouped using principal component analyses of PCR-SSCP of the microbiota, according to the time of inoculation. In Vibrio parahaemolyticus-infected shrimp, the Bacillus mix (~33 %) induced a significant increase in survival compared to Alibio (~21 %) and the control (~9 %). We conclude that administration of the Bacillus mix induced modulation of the intestinal microbiota of L. vannamei and increased its resistance to V. parahaemolyticus.     

Carious lesions and maize consumption among the Prehispanic Maya: an analysis of a coastal community in northern Yucatan

Patterns of carious lesions were analyzed in the Classic period coastal Maya population of Xcambó, a salt production and administration center in northern Yucatan. To this end, the study investigated caries in the permanent dentitions of 163 adult skeletons, 23 from the Early Classic (AD 250-550) and 140 from the Late Classic period (AD 550-750), equally distributed between sexes. The archaeological and bioarchaeological evidence indicates a wealthy and socially homogeneous population dedicated to salt production and administration in the Early Classic that switched to pure administrative functions in the Late Classic. The results indicate an increase in caries from 7.4% and 21.2% (males and females respectively) from the Early Classic to 14.0% in males and 27.4% in females from the Late Classic period. The rate of caries in the Early and in the Late Classic phases of continuous occupation is not consistent with a simple interpretation of a heavier reliance on maize during the latter phase, characterized by a sedentary lifestyle, particularly for the male segment of the society now dedicated completely to the administration of the salt mines. Rather, the increase in caries rates in both sexes is best explained within a broader context of overall food habits, new cariogenic foods for both sexes, and the changes in lifestyle imposed by the increased socioeconomic role of the site. Our conclusions stress the limitations imposed by interpreting carious lesions solely in terms of single dietary components, such as maize consumption, without taking into account broader aspects of cultural and socioeconomic relevance.     

Improvement in oral bioavailability of 2,4-diaminopyrimidine c-Met inhibitors by incorporation of a 3-amidobenzazepin-2-one group

The hepatocyte growth factor (HGF)-c-Met signaling axis is involved in the mediation of many biological activities, including angiogenesis, proliferation, cell survival, cell motility, and morphogenesis. Dysregulation of c-Met signaling (e.g., overexpression or increased activation) is associated with the proliferation and metastasis of a wide range of tumor types, including breast, liver, lung, colorectal, gastric, bladder, and prostate, among others. Inhibiting the HGF-c-Met pathway is predicted to lead to anti-tumor effects in many cancers. Elaboration of the SAR around a series of 2,4-diaminopyrimidines led to a number of c-Met inhibitors in which pharmaceutical properties were modulated by substituents appended on the C2-benzazepinone ring. In particular, certain-3-amidobenzazepin-2-one analogs had improved oral bioavailability and were evaluated in PK/PD and efficacy models. Lead compounds demonstrated tumor stasis with partial regressions when evaluated in a GTL-16 tumor xenograft mouse model.     

Population and genomic lessons from genetic analysis of two Indian populations

Indian demographic history includes special features such as founder effects, interpopulation segregation, complex social structure with a caste system and elevated frequency of consanguineous marriages. It also presents a higher frequency for some rare mendelian disorders and in the last two decades increased prevalence of some complex disorders. Despite the fact that India represents about one-sixth of the human population, deep genetic studies from this terrain have been scarce. In this study, we analyzed high-density genotyping and whole-exome sequencing data of a North and a South Indian population. Indian populations show higher differentiation levels than those reported between populations of other continents. In this work, we have analyzed its consequences, by specifically assessing the transferability of genetic markers from or to Indian populations. We show that there is limited genetic marker portability from available genetic resources such as HapMap or the 1,000 Genomes Project to Indian populations, which also present an excess of private rare variants. Conversely, tagSNPs show a high level of portability between the two Indian populations, in contrast to the common belief that North and South Indian populations are genetically very different. By estimating kinship from mates and consanguinity in our data from trios, we also describe different patterns of assortative mating and inbreeding in the two populations, in agreement with distinct mating preferences and social structures. In addition, this analysis has allowed us to describe genomic regions under recent adaptive selection, indicating differential adaptive histories for North and South Indian populations. Our findings highlight the importance of considering demography for design and analysis of genetic studies, as well as the need for extending human genetic variation catalogs to new populations and particularly to those with particular demographic histories.