The RAD51 and DMC1 homoeologous genes of bread wheat: cloning, molecular characterization and expression analysis

<p>Abstract</p> <p>Background</p> <p>Meiotic recombination in eukaryotes requires two homologues of the <it>E. coli </it>RecA proteins: Rad51 and Dmc1. Both proteins play important roles in the binding of single stranded DNA, homology search, strand invasion and strand exchange. Meiotic recombination has been well studied in Arabidopsis, rice, maize and the orthologues of <it>RAD51 </it>and <it>DMC1 </it>have been characterized. However genetic analysis of the <it>RAD51 </it>and <it>DMC1 </it>genes in bread wheat has been hampered due to the absence of complete sequence information and because of the existence of multiple copies of each gene in the hexaploid wheat genome.</p> <p>Findings</p> <p>In this study we have identified that <it>TaRAD51 </it>and <it>TaDMC1 </it>homoeologues are located on group 7 and group 5 chromosomes of hexaploid wheat, respectively. Comparative sequence analysis of cDNA derived from the <it>TaRAD51 </it>and <it>TaDMC1 </it>homoeologues revealed limited sequence divergence at both the nucleotide and the amino acid level. Indeed, comparisons between the predicted amino acid sequences of <it>TaRAD51 </it>and <it>TaDMC1 </it>and those of other eukaryotes reveal a high degree of evolutionary conservation. Despite the high degree of sequence conservation at the nucleotide level, genome-specific primers for cDNAs of <it>TaRAD51 </it>and <it>TaDMC1 </it>were developed to evaluate expression patterns of individual homoeologues during meiosis. QRT-PCR analysis showed that expression of the <it>TaRAD51 </it>and <it>TaDMC1 </it>cDNA homoeologues was largely restricted to meiotic tissue, with elevated levels observed during the stages of prophase I when meiotic recombination occurs. All three homoeologues of both strand-exchange proteins (<it>TaRAD51 </it>and <it>TaDMC1</it>) are expressed in wheat.</p> <p>Conclusions</p> <p>Bread wheat contains three expressed copies of each of the <it>TaRAD51 </it>and <it>TaDMC1 </it>homoeologues. While differences were detected between the three cDNA homoeologues of <it>TaRAD51 </it>as well as the three homoeologues of <it>TaDMC1</it>, it is unlikely that the predicted amino acid substitutions would have an effect on the protein structure, based on our three-dimensional structure prediction analyses. There are differences in the levels of expression of the three homoeologues of <it>TaRAD51 </it>and <it>TaDMC1 </it>as determined by QRT-PCR and if these differences are reflected at the protein level, bread wheat may be more dependent upon a particular homoeologue to achieve full fertility than all three equally.</p

Boosting Long-term Memory via Wakeful Rest: Intentional Rehearsal is not Necessary, Automatic Consolidation is Sufficient.

<div><p>People perform better on tests of delayed free recall if learning is followed immediately by a short wakeful rest than by a short period of sensory stimulation. Animal and human work suggests that wakeful resting provides optimal conditions for the consolidation of recently acquired memories. However, an alternative account cannot be ruled out, namely that wakeful resting provides optimal conditions for intentional rehearsal of recently acquired memories, thus driving superior memory. Here we utilised non-recallable words to examine whether wakeful rest boosts long-term memory, even when new memories could not be rehearsed intentionally during the wakeful rest delay. The probing of non-recallable words requires a recognition paradigm. Therefore, we first established, via Experiment 1, that the rest-induced boost in memory observed via free recall can be replicated in a recognition paradigm, using concrete nouns. In Experiment 2, participants heard 30 non-recallable non-words, presented as ‘foreign names in a bridge club abroad’ and then either rested wakefully or played a visual spot-the-difference game for 10 minutes. Retention was probed via recognition at two time points, 15 minutes and 7 days after presentation. As in Experiment 1, wakeful rest boosted recognition significantly, and this boost was maintained for at least 7 days. Our results indicate that the enhancement of memory via wakeful rest is <i>not</i> dependent upon intentional rehearsal of learned material during the rest period. We thus conclude that consolidation is <i>sufficient</i> for this rest-induced memory boost to emerge. We propose that wakeful resting allows for superior memory consolidation, resulting in stronger and/or more veridical representations of experienced events which can be detected via tests of free recall and recognition.</p></div

QTL detection by multi-parent linkage mapping in oil palm (Elaeis guineensis Jacq.)

A quantitative trait locus (QTL) analysis designed for a multi-parent population was carried out and tested in oil palm (Elaeis guineensis Jacq.), which is a diploid cross-fertilising perennial species. A new extension of the MCQTL package was especially designed for crosses between heterozygous parents. The algorithm, which is now available for any allogamous species, was used to perform and compare two types of QTL search for small size families, within-family analysis and across-family analysis, using data from a 2 × 2 complete factorial mating experiment involving four parents from three selected gene pools. A consensus genetic map of the factorial design was produced using 251 microsatellite loci, the locus of the Sh major gene controlling fruit shell presence, and an AFLP marker of that gene. A set of 76 QTLs involved in 24 quantitative phenotypic traits was identified. A comparison of the QTL detection results showed that the across-family analysis proved to be efficient due to the interconnected families, but the family size issue is just partially solved. The identification of QTL markers for small progeny numbers and for marker-assisted selection strategies is discussed

Plasmodium vivax: paroxysm-associated lipids mediate leukocyte aggregation

<p>Abstract</p> <p>Background</p> <p>Paroxysms are recurrent febrile episodes, characteristic of <it>Plasmodium vivax </it>infections, which coincide with the rupture of schizont-infected erythrocytes in the patients' circulation. The present study describes the formation of prominent aggregates of leukocytes <it>in vitro </it>in the presence of parasite and host factors released during paroxysms.</p> <p>Methods</p> <p>Whole blood cells from uninfected malaria-naïve donors were incubated with plasma taken during a paroxysm or normal human plasma as a control and cell smears were observed under the microscope for the presence of leukocyte aggregates. Plasma factors involved in mediating the leukocyte aggregation were identified using immune depletion and reconstitution experiments. Furthermore, biochemical characterization was carried out to determine the chemical nature of the active moieties in plasma present during paroxysms.</p> <p>Results</p> <p>Leukocyte aggregates were seen exclusively when cells were incubated in plasma collected during a paroxysm. Immune depletion and reconstitution experiments revealed that the host cytokines TNF-alpha, GM-CSF, IL-6 and IL-10 and two lipid fractions of paroxysm plasma comprise the necessary and sufficient mediators of this phenomenon. The two lipid components of the paroxysm plasmas speculated to be of putative parasite origin, were a phospholipid-containing fraction and another containing cholesterol and triglycerides. The phospholipid fraction was dependent upon the presence of cytokines for its activity unlike the cholesterol/triglyceride-containing fraction which in the absence of added cytokines was much more active than the phospholipids fraction. The biological activity of the paroxysm plasmas from non-immune patients who presented with acute <it>P. vivax </it>infections was neutralized by immune sera raised against schizont extracts of either <it>P. vivax </it>or <it>Plasmodium falciparum</it>. However, immune sera against <it>P. vivax </it>were more effective than that against <it>P. falciparum </it>indicating that the parasite activity involved may be antigenically at least partially parasite species-specific.</p> <p>Conclusion</p> <p>Leukocyte aggregation was identified as associated with paroxysms in <it>P. vivax </it>infections. This phenomenon is mediated by plasma factors including host-derived cytokines and lipids of putative parasite origin. The characteristics of the phospholipid fraction in paroxysm plasma are congruent with those of the parasite-derived, TNF-inducing GPI moieties described by others. The more active cholesterol/triglyceride(s), however, represent a novel malarial toxin, which is a new class of biologically active lipid associated with the paroxysm of <it>P. vivax </it>malaria.</p

Environmental and Lifestyle Factors Associated with Perceived Facial Age in Chinese Women

Perceived facial age has been proposed as a biomarker of ageing with ‘looking young for one’s age' linked to physical and cognitive functioning and to increased survival for Caucasians. We have investigated the environmental and lifestyle factors associated with perceived facial ageing in Chinese women. Facial photographs were collected from 250 Chinese women, aged 25–70 years in Shanghai, China. Perceived facial age was determined and related to chronological age for each participant. Lifestyle and health information was collected by questionnaire. Bivariate analyses (controlling for chronological age) identified and quantified lifestyle variables associated with perceived facial age. Independent predictors of perceived age were identified by multivariate modelling. Factors which significantly associated with looking younger for one's chronological age included greater years of education (p<0.001), fewer household members (p = 0.027), menopausal status (p = 0.020), frequency of visiting one's doctor (p = 0.013), working indoors (p<0.001), spending less time in the sun (p = 0.015), moderate levels of physical activity (p = 0.004), higher frequency of teeth cleaning (p<0.001) and more frequent use of facial care products: cleanser (p<0.001); moisturiser (p = 0.016) or night cream (p = 0.016). Overall, 36.5% of the variation in the difference between perceived and chronological age could be explained by a combination of chronological age and 6 independent lifestyle variables. We have thus identified and quantified a number of factors associated with younger appearance in Chinese women. Presentation of these factors in the context of facial appearance could provide significant motivation for the adoption of a range of healthy behaviours at the level of both individuals and populations

Evaluation of a manualised speech and language therapy programme for children with social communication disorder: the SCIP feasibility study

Background: Children with Social (Pragmatic) Communication Disorder (SPCD) have long-3 term needs in using and processing social language and have a high risk of later mental health difficulties. A manualised speech and language therapy programme, the Social Communication Intervention Programme (SCIP) provides therapy content for SPCD. A feasibility study is required to derive more precise estimates of key parameters for a future trial of SCIP. Aims: To assess the feasibility of conducting a substantive randomized controlled trial of SCIP for children with SPCD. Methods: A questionnaire was distributed to paediatric speech and language therapists in England. Survey questions addressed number of eligible children, routine intervention provision and trial recruitment factors. In the second phase, a single-arm intervention feasibility study was completed. 15 speech and language practitioners identified 24 children aged 5-11 years with SPCD. Practitioners received training/supervision to deliver 20 SCIP therapy sessions to each child. At Time 1 parents of participating children provided three communication goals; expected steps in each goal were defined. After intervention, parents and practitioners independently rated each goal compared to baseline ability. Two research practitioners compared parent post-intervention commentaries with outcome scores to derive guidance about clinical significance. All practitioners recorded audio commentaries on therapy experiences. Post-intervention interviews were conducted with 6 practitioners and 6 parents. An expert panel completed a Delphi consultation on trial design. Results: Routine practice for SPCD varies widely. Children tend to be embedded in autism provision. Participation in a future trial was well-supported, provided resources are available to services. Outcomes analysis indicated all children except one made some progress on parent ratings; all children made progress on practitioner ratings. A power analysis for a future trial was carried out using current outcome measure as putative primary endpoint. Practitioners’ audio-diaries provided suggestions for training and adaption in a future trial. Outcomes and therapy methods were acceptable to practitioners and parents. Conclusions: The feasibility study evaluated a novel outcome measure of social communication skills in SPCD. A power calculation indicated a feasible framework for a trial within a realistic period of time. Recommendations for recruitment methods, adaptation of manual and training were 6 supported by practitioners and an expert panel

Breast density and polymorphisms in genes coding for CYP1A2 and COMT: the Multiethnic Cohort

BACKGROUND: Mammographic density is a strong predictor of breast cancer risk and is increased by hormone replacement therapy (HRT). Some associations with genetic polymorphisms in enzymes involved in estrogen metabolism have been described. This cross-sectional analysis examined the relation between mammographic density and the CYP1A2*1F and COMT Val(58 )Met polymorphisms among 332 breast cancer cases and 254 controls in the Hawaii component of the Multiethnic Cohort. METHODS: Mammographic density, before diagnosis in cases, was quantified by using a validated computer-assisted method. Blood samples were genotyped by standard PCR/RFLP methods. Adjusted mean percent density was calculated by genotype using mixed models with the unstructured covariance option. RESULTS: A positive association between the C allele in the CYP1A2*1F gene and percent density, but not the dense area, was suggested (p = 0.11). The relation was limited to controls (p = 0.045), postmenopausal women not using HRT (p = 0.08), and normal weight subjects (p = 0.046). We did not observe any relation between the COMT Val(58 )Met polymorphism and breast density. CONCLUSION: The lack of an association between the CYP1A2 genotype and the size of the dense areas suggests an effect on the non-dense, i.e., fatty breast tissue. The discrepancies among studies may be due to differential susceptibility; changes in enzyme activity as a result of the CYP1A2*1F polymorphism may influence breast tissue differently depending on hormonal status. Larger studies with the ability to look at interactions would be useful to elucidate the influence of genetic variation in CYP1A2 and COMT on the risk of developing breast cancer

Explainable AI reveals changes in skin microbiome composition linked to phenotypic differences

Alterations in the human microbiome have been observed in a variety of conditions such as asthma, gingivitis, dermatitis and cancer, and much remains to be learned about the links between the microbiome and human health. The fusion of artificial intelligence with rich microbiome datasets can offer an improved understanding of the microbiome’s role in human health. To gain actionable insights it is essential to consider both the predictive power and the transparency of the models by providing explanations for the predictions. We combine the collection of leg skin microbiome samples from two healthy cohorts of women with the application of an explainable artificial intelligence (EAI) approach that provides accurate predictions of phenotypes with explanations. The explanations are expressed in terms of variations in the relative abundance of key microbes that drive the predictions. We predict skin hydration, subject's age, pre/post-menopausal status and smoking status from the leg skin microbiome. The changes in microbial composition linked to skin hydration can accelerate the development of personalized treatments for healthy skin, while those associated with age may offer insights into the skin aging process. The leg microbiome signatures associated with smoking and menopausal status are consistent with previous findings from oral/respiratory tract microbiomes and vaginal/gut microbiomes respectively. This suggests that easily accessible microbiome samples could be used to investigate health-related phenotypes, offering potential for non-invasive diagnosis and condition monitoring. Our EAI approach sets the stage for new work focused on understanding the complex relationships between microbial communities and phenotypes. Our approach can be applied to predict any condition from microbiome samples and has the potential to accelerate the development of microbiome-based personalized therapeutics and non-invasive diagnostics

Observation of associated near-side and away-side long-range correlations in √sNN=5.02 TeV proton-lead collisions with the ATLAS detector

Two-particle correlations in relative azimuthal angle (Δϕ) and pseudorapidity (Δη) are measured in √sNN=5.02  TeV p+Pb collisions using the ATLAS detector at the LHC. The measurements are performed using approximately 1  μb-1 of data as a function of transverse momentum (pT) and the transverse energy (ΣETPb) summed over 3.1<η<4.9 in the direction of the Pb beam. The correlation function, constructed from charged particles, exhibits a long-range (2<|Δη|<5) “near-side” (Δϕ∼0) correlation that grows rapidly with increasing ΣETPb. A long-range “away-side” (Δϕ∼π) correlation, obtained by subtracting the expected contributions from recoiling dijets and other sources estimated using events with small ΣETPb, is found to match the near-side correlation in magnitude, shape (in Δη and Δϕ) and ΣETPb dependence. The resultant Δϕ correlation is approximately symmetric about π/2, and is consistent with a dominant cos⁡2Δϕ modulation for all ΣETPb ranges and particle pT