Barriers encountered during enrollment in an internet-mediated randomized controlled trial

Background

Research evidence from observational studies suggests that cognitive activity reduces the risk of cognitive impairment in later life as well as the rate of cognitive decline of people with dementia. The Promoting Healthy Ageing with Cognitive Exercise (PACE) study has been designed to determine whether a cognitive activity intervention decreases the rate of cognitive decline amongst older adults with mild cognitive impairment (MCI).

Methods/Design

The study will recruit 160 community-dwelling men and women aged 65 years of age or over with mild cognitive impairment (MCI). Participants will be randomly allocated to two treatment groups: non-specific education and cognitive activity. The intervention will consist of ten 90-minute sessions delivered twice per week over a period of five weeks. The primary outcome measure of the study is the change from baseline in the total score on the Cambridge Cognitive Score (CAMCOG). Secondary outcomes of interest include changes in memory, attention, executive functions, mood and quality of life. Primary endpoints will be collected 12, 52 and 104 weeks after the baseline assessment.

Discussion

The proposed project will produce the best available evidence on the merits of increased cognitive activity as a strategy to prevent cognitive decline among older adults with MCI. We anticipate that the results of this study will have implications for the development of evidence-based preventive strategies to reduce the rate of cognitive decline amongst older people at risk of dementia.

Trial registration

ACTRN12608000556347     

Development and characterization of microsatellite markers for Arenaria grandiflora L. (Caryophyllaceae)

Genomic libraries of Arenaria grandiflora enriched for di- and trinucleotide repeats were used for the development of novel microsatellite markers. The subset of 13 polymorphic markers was characterized on 40 individuals of A. grandiflora originating from lowland locations in France. The loci amplified 3 to 10 alleles per locus and expected heterozygosities ranged from 0.46 to 0.83. The newly developed markers will be used for population genetic studies and for assessing genetic composition of a restoration experiment of lowland A. grandiflora populations that are protected in France.     

Mus81 and Yen1 promote reciprocal exchange during mitotic recombination to maintain genome integrity in budding yeast

Holliday junction (HJ) resolution is required for segregation of chromosomes and for formation of crossovers during homologous recombination. The identity of the resolvase(s) that functions in?vivo has yet to be established, although several proteins able to cut HJs in?vitro have been identified as candidates in yeasts and mammals. Using an assay to detect unselected products of mitotic recombination, we found a significant decrease in crossovers in the Saccharomyces cerevisiae mus81Δ mutant. Yen1 serves a backup function responsible for resolving intermediates in mus81Δ mutants, or when conversion tracts are short. In the absence of both Mus81 and Yen1, intermediates are not channeled exclusively to noncrossover recombinants, but instead are processed by Pol32-dependent break-induced replication (BIR). The channeling of recombination from reciprocal exchange to BIR results in greatly increased spontaneous loss of heterozygosity (LOH) and chromosome mis-segregation in the mus81Δ yen1Δ mutant, typical of the genomic instability found in tumor cells.     

Functional significance of AtHMA4 C-terminal domain in planta

Background

Enhancing the upward translocation of heavy metals such as Zn from root to shoot through genetic engineering has potential for biofortification and phytoremediation. This study examined the contribution of the heavy metal-transporting ATPase, AtHMA4, to the shoot ionomic profile of soil-grown plants, and investigated the importance of the C-terminal domain in the functioning of this transporter.

Principal Findings

The Arabidopsis hma2 hma4 mutant has a stunted phenotype and a distinctive ionomic profile, with low shoot levels of Zn, Cd, Co, K and Rb, and high shoot Cu. Expression of AtHMA4 (AtHMA4-FL) under the CaMV-35S promoter partially rescued the stunted phenotype of hma2 hma4; rosette diameter returned to wild-type levels in the majority of lines and bolts were also produced, although the average bolt height was not restored completely. AtHMA4-FL expression rescued Co, K, Rb and Cu to wild-type levels, and partially returned Cd and Zn levels (83% and 28% of wild type respectively). In contrast, expression of AtHMA4-trunc (without the C-terminal region) in hma2 hma4 only partially restored the rosette diameter in two of five lines and bolt production was not rescued. There was no significant effect on the shoot ionomic profile, apart from Cd, which was increased to 41% of wild-type levels. When the AtHMA4 C-terminal domain (AtHMA4-C-term) was expressed in hma2 hma4 it had no marked effect. When expressed in yeast, AtHMA4-C-term and AtHMA4-trunc conferred greater Cd and Zn tolerance than AtHMA4-FL.

Conclusion

The ionome of the hma2 hma4 mutant differs markedly from wt plants. The functional relevance of domains of AtHMA4 in planta can be explored by complementing this mutant. AtHMA4-FL is more effective in restoring shoot metal accumulation in this mutant than a C-terminally truncated version of the pump, indicating that the C-terminal domain is important in the functioning of AtHMA4 in planta.     

GTPase signaling: bridging the GAP between ARF and Rho

Membrane traffic and actin cytoskeleton dynamics are intimately linked, and GTPases of the Rho and ARF families may work together to regulate both. Recent studies have identified a family of GTPase activating proteins (GAPs) that contain both ARF-GAP and Rho-GAP domains, providing the first direct link between these two signaling pathways.     

A multilateral effort to develop DNA vaccines against falciparum malaria

Scientists from several organizations worldwide are working together to develop a multistage, multigene DNA-based vaccine against Plasmodium falciparum malaria. This collaborative vaccine development effort is named Multi-Stage DNA-based Malaria Vaccine Operation. An advisory board of international experts in vaccinology, malariology and field trials provides the scientific oversight to support the operation. This article discusses the rationale for the approach, underlying concepts and the pre-clinical development process, and provides a brief outline of the plans for the clinical testing of a multistage, multiantigen malaria vaccine based on DNA plasmid immunization technology.     

1,3,4-Trisubstituted pyrrolidine CCR5 receptor antagonists. Part 3: polar functionality and its effect on anti-HIV-1 activity

Incorporation of acidic functional groups into a lead CCR5 antagonist identified from a targeted combinatorial library resulted in compounds with enhanced anti-HIV-1 activity and attenuated L-type calcium channel affinity.     

Epigenetic reprogramming: how now, cloned cow?

DNA methylation patterns are dynamic in cleavage-stage embryos of a number of mammalian species. A failure to properly recapitulate preimplantation DNA methylation patterns in embryos derived by nuclear transfer may contribute to the low efficiency of nuclear transfer in producing live offspring.     

Overproduction of wild-type and bioengineered derivatives of the lantibiotic lacticin 3147

Lacticin 3147 is a broad-spectrum two-peptide lantibiotic whose genetic determinants are located on two divergent operons on the lactococcal plasmid pMRC01. Here we introduce each of 14 subclones, containing different combinations of lacticin 3147 genes, into MG1363 (pMRC01) and determine that a number of them can facilitate overproduction of the lantibiotic. Based on these studies it is apparent that while the provision of additional copies of genes encoding the biosynthetic/production machinery and the regulator LtnR is a requirement for high-level overproduction, the presence of additional copies of the structural genes (i.e., ltnA1A2) is not.