Mitochondrial DNA and microsatellite loci data supporting a management plan for a critically endangered lizard from Brazil

Endemic and endangered species are highly vulnerable to habitat perturbations and may be subject to variations in their population size. Management plan for these species is crucial to avoid population decline, loss of genetic variability, inbreeding and ultimately extinction. The sand lizard, Liolaemus lutzae, is endemic to a habitat of sandy coastal plain (restinga). Its geographical distribution extends for only 200 km stretch of the coast of Rio de Janeiro state, Brazil, one of South America’s most densely populated regions. Extensive development and degradation of the beaches where the species inhabits, have led to the species becoming critically endangered. We used mitochondrial DNA sequences and microsatellite loci to resolve patterns of population connectivity and genetic variation within the species in order to provide a platform for a species management plan. Our results indicate the existence of three main populations, separated from each other by the Guanabara Bay and by the Arraial do Cabo Peninsula. The low microsatellite genetic variation and heterozygosity witnessed in each of the three populations, together with high levels of inbreeding and low effective population sizes suggest that the species is in urgent need of intensive management. Based on the results of this study we propose strong measures to protect existing restinga fragments and the implementation of programmes of captive breeding and reintroduction of individuals from the heavily threatened regions to protected refugia. Such measures may be the only way of ensuring the continuity of the species.     

Genetic Recombination Is Targeted towards Gene Promoter Regions in Dogs

The identification of the H3K4 trimethylase, PRDM9, as the gene responsible for recombination hotspot localization has provided considerable insight into the mechanisms by which recombination is initiated in mammals. However, uniquely amongst mammals, canids appear to lack a functional version of PRDM9 and may therefore provide a model for understanding recombination that occurs in the absence of PRDM9, and thus how PRDM9 functions to shape the recombination landscape. We have constructed a fine-scale genetic map from patterns of linkage disequilibrium assessed using high-throughput sequence data from 51 free-ranging dogs, Canis lupus familiaris. While broad-scale properties of recombination appear similar to other mammalian species, our fine-scale estimates indicate that canine highly elevated recombination rates are observed in the vicinity of CpG rich regions including gene promoter regions, but show little association with H3K4 trimethylation marks identified in spermatocytes. By comparison to genomic data from the Andean fox, Lycalopex culpaeus, we show that biased gene conversion is a plausible mechanism by which the high CpG content of the dog genome could have occurred.     

Reconstructing the Population Genetic History of the Caribbean

The Caribbean basin is home to some of the most complex interactions in recent history among previously diverged human populations. Here, we investigate the population genetic history of this region by characterizing patterns of genome-wide variation among 330 individuals from three of the Greater Antilles (Cuba, Puerto Rico, Hispaniola), two mainland (Honduras, Colombia), and three Native South American (Yukpa, Bari, and Warao) populations. We combine these data with a unique database of genomic variation in over 3,000 individuals from diverse European, African, and Native American populations. We use local ancestry inference and tract length distributions to test different demographic scenarios for the pre- and post-colonial history of the region. We develop a novel ancestry-specific PCA (ASPCA) method to reconstruct the sub-continental origin of Native American, European, and African haplotypes from admixed genomes. We find that the most likely source of the indigenous ancestry in Caribbean islanders is a Native South American component shared among inland Amazonian tribes, Central America, and the Yucatan peninsula, suggesting extensive gene flow across the Caribbean in pre-Columbian times. We find evidence of two pulses of African migration. The first pulse—which today is reflected by shorter, older ancestry tracts—consists of a genetic component more similar to coastal West African regions involved in early stages of the trans-Atlantic slave trade. The second pulse—reflected by longer, younger tracts—is more similar to present-day West-Central African populations, supporting historical records of later transatlantic deportation. Surprisingly, we also identify a Latino-specific European component that has significantly diverged from its parental Iberian source populations, presumably as a result of small European founder population size. We demonstrate that the ancestral components in admixed genomes can be traced back to distinct sub-continental source populations with far greater resolution than previously thought, even when limited pre-Columbian Caribbean haplotypes have survived.     

Antioxidant therapy: Still in search of the ‘magic bullet’

The therapeutic potential of natural phenolic antioxidants in human diseases associated with oxidative damage has received great attention to date. Appraisal of literature evidences that, in general, antioxidant therapy has enjoyed relative successes in preclinical studies but little benefits in human intervention studies or clinical trials. In fact, despite the huge, largely untapped potential therapeutic benefit of natural phenolic antioxidants, such as vitamins, non-flavonoid and flavonoid compounds, they appear not to be suitable drug candidates. The problem may be related, among others, to their non-drug-likeness properties. Though controversial the results obtained so far confirm the importance of exploring phenolic natural systems as safe templates for the design of new antioxidants. To support the assumption an outlook of the lead structural optimization process to improve ADME properties was given by means of natural hydroxycinnamic acids as a case study. The optimization of drug physicochemical properties and the development of appropriate delivery antioxidant systems can provide in the next future a way out to attain effective therapeutic antioxidant agents.     

The Effect of a Physical Activity Program on the Total Number of Primary Care Visits in Inactive Patients: A 15-Month Randomized Controlled Trial

Background

Effective promotion of exercise could result in substantial savings in healthcare cost expenses in terms of direct medical costs, such as the number of medical appointments. However, this is hampered by our limited knowledge of how to achieve sustained increases in physical activity.

Objectives

To assess the effectiveness of a Primary Health Care (PHC) based physical activity program in reducing the total number of visits to the healthcare center among inactive patients, over a 15-month period.

Research Design

Randomized controlled trial.

Subjects

Three hundred and sixty-two (n = 362) inactive patients suffering from at least one chronic condition were included. One hundred and eighty-three patients (n = 183; mean (SD); 68.3 (8.8) years; 118 women) were randomly allocated to the physical activity program (IG). One hundred and seventy-nine patients (n = 179; 67.2 (9.1) years; 106 women) were allocated to the control group (CG). The IG went through a three-month standardized physical activity program led by physical activity specialists and linked to community resources.

Measures

The total number of medical appointments to the PHC, during twelve months before and after the program, was registered. Self-reported health status (SF-12 version 2) was assessed at baseline (month 0), at the end of the intervention (month 3), and at 12 months follow-up after the end of the intervention (month 15).

Results

The IG had a significantly reduced number of visits during the 12 months after the intervention: 14.8 (8.5). The CG remained about the same: 18.2 (11.1) (P = .002).

Conclusions

Our findings indicate that a 3-month physical activity program linked to community resources is a short-duration, effective and sustainable intervention in inactive patients to decrease rates of PHC visits.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00714831","term_id":"NCT00714831"}}NCT00714831     

Sox2 Level Is a Determinant of Cellular Reprogramming Potential

Epiblast stem cells (EpiSCs) and embryonic stem cells (ESCs) differ in their in vivo differentiation potential. While ESCs form teratomas and efficiently contribute to the development of chimeras, EpiSCs form teratomas but very rarely chimeras. In contrast to their differentiation potential, the reprogramming potential of EpiSCs has not yet been investigated. Here we demonstrate that the epiblast-derived pluripotent stem cells EpiSCs and P19 embryonal carcinoma cells (ECCs) exhibit a lower reprogramming potential than ESCs and F9 ECCs. In addition, we show that the low reprogramming ability is due to the lower levels of Sox2 in epiblast-derived stem cells. Consistent with this observation, overexpression of Sox2 enhances reprogramming efficiency. In summary, these findings suggest that a low reprogramming potential is a general feature of epiblast-derived stem cells and that the Sox2 level is a determinant of the cellular reprogramming potential.     

Structural and Phylogenetic Studies with MjTX-I Reveal a Multi-Oligomeric Toxin – a Novel Feature in Lys49-PLA2s Protein Class

The mortality caused by snakebites is more damaging than many tropical diseases, such as dengue haemorrhagic fever, cholera, leishmaniasis, schistosomiasis and Chagas disease. For this reason, snakebite envenoming adversely affects health services of tropical and subtropical countries and is recognized as a neglected disease by the World Health Organization. One of the main components of snake venoms is the Lys49-phospholipases A₂, which is catalytically inactive but possesses other toxic and pharmacological activities. Preliminary studies with MjTX-I from Bothrops moojeni snake venom revealed intriguing new structural and functional characteristics compared to other bothropic Lys49-PLA₂s. We present in this article a comprehensive study with MjTX-I using several techniques, including crystallography, small angle X-ray scattering, analytical size-exclusion chromatography, dynamic light scattering, myographic studies, bioinformatics and molecular phylogenetic analyses.Based in all these experiments we demonstrated that MjTX-I is probably a unique Lys49-PLA₂, which may adopt different oligomeric forms depending on the physical-chemical environment. Furthermore, we showed that its myotoxic activity is dramatically low compared to other Lys49-PLA₂s, probably due to the novel oligomeric conformations and important mutations in the C-terminal region of the protein. The phylogenetic analysis also showed that this toxin is clearly distinct from other bothropic Lys49-PLA₂s, in conformity with the peculiar oligomeric characteristics of MjTX-I and possible emergence of new functionalities inresponse to environmental changes and adaptation to new preys.