Recent advances in malaria genomics and epigenomics

Malaria continues to impose a significant disease burden on low- and middle-income countries in the tropics. However, revolutionary progress over the last 3 years in nucleic acid sequencing, reverse genetics, and post-genome analyses has generated step changes in our understanding of malaria parasite (Plasmodium spp.) biology and its interactions with its host and vector. Driven by the availability of vast amounts of genome sequence data from Plasmodium species strains, relevant human populations of different ethnicities, and mosquito vectors, researchers can consider any biological component of the malarial process in isolation or in the interactive setting that is infection. In particular, considerable progress has been made in the area of population genomics, with Plasmodium falciparum serving as a highly relevant model. Such studies have demonstrated that genome evolution under strong selective pressure can be detected. These data, combined with reverse genetics, have enabled the identification of the region of the P. falciparum genome that is under selective pressure and the confirmation of the functionality of the mutations in the kelch13 gene that accompany resistance to the major frontline antimalarial, artemisinin. Furthermore, the central role of epigenetic regulation of gene expression and antigenic variation and developmental fate in P. falciparum is becoming ever clearer. This review summarizes recent exciting discoveries that genome technologies have enabled in malaria research and highlights some of their applications to healthcare. The knowledge gained will help to develop surveillance approaches for the emergence or spread of drug resistance and to identify new targets for the development of antimalarial drugs and perhaps vaccines

Eighty years of food-web response to interannual variation in discharge recorded in river diatom frustules from an ocean sediment core.

Little is known about the importance of food-web processes as controls of river primary production due to the paucity of both long-term studies and of depositional environments which would allow retrospective fossil analysis. To investigate how freshwater algal production in the Eel River, northern California, varied over eight decades, we quantified siliceous shells (frustules) of freshwater diatoms from a well-dated undisturbed sediment core in a nearshore marine environment. Abundances of freshwater diatom frustules exported to Eel Canyon sediment from 1988 to 2001 were positively correlated with annual biomass of Cladophora surveyed over these years in upper portions of the Eel basin. Over 28 years of contemporary field research, peak algal biomass was generally higher in summers following bankfull, bed-scouring winter floods. Field surveys and experiments suggested that bed-mobilizing floods scour away overwintering grazers, releasing algae from spring and early summer grazing. During wet years, growth conditions for algae could also be enhanced by increased nutrient loading from the watershed, or by sustained summer base flows. Total annual rainfall and frustule densities in laminae over a longer 83-year record were weakly and negatively correlated, however, suggesting that positive effects of floods on annual algal production were primarily mediated by "top-down" (consumer release) rather than "bottom-up" (growth promoting) controls

Dynamic RKKY interaction in graphene

The growing interest in carbon-based spintronics has stimulated a number of recent theoretical studies on the RKKY interaction in graphene, based on which the energetically favourable alignment between magnetic moments embedded in this material can be calculated. The general consensus is that the strength of the RKKY interaction in graphene decays as 1/D3 or faster, where D is the separation between magnetic moments. Such an unusually fast decay for a 2-dimensional system suggests that the RKKY interaction may be too short ranged to be experimentally observed in graphene. Here we show in a mathematically transparent form that a far more long ranged interaction arises when the magnetic moments are taken out of their equilibrium positions and set in motion. We not only show that this dynamic version of the RKKY interaction in graphene decays far more slowly but also propose how it can be observed with currently available experimental methods.Comment: 7 pages, 2 figures, submitte

Extended Timed Up and Go assessment as a clinical indicator of cognitive state in Parkinson\u27s disease

Objective: To evaluate a modified extended Timed Up and Go (extended-TUG) assessment against a panel of validated clinical assessments, as an indicator of Parkinson’s disease (PD) severity and cognitive impairment. Methods: Eighty-seven participants with idiopathic PD were sequentially recruited from a Movement Disorders Clinic. An extended-TUG assessment was employed which required participants to stand from a seated position, walk in a straight line for 7 metres, turn 180 degrees and then return to the start, in a seated position. The extended-TUG assessment duration was correlated to a panel of clinical assessments, including the Unified Parkinson’s Disease Rating Scale (MDS-UPDRS), Quality of Life (PDQ-39), Scales for Outcomes in Parkinson’s disease (SCOPA-Cog), revised Addenbrooke’s Cognitive Index (ACE-R) and Barratt’s Impulsivity Scale 11 (BIS-11). Results: Extended-TUG time was significantly correlated to MDS-UPDRS III score and to SCOPA-Cog, ACE-R (p\u3c0.001) and PDQ-39 scores (p\u3c0.01). Generalized linear models determined the extended-TUG to be a sole variable in predicting ACE-R or SCOPA-Cog scores. Patients in the fastest extended-TUG tertile were predicted to perform 8.3 and 13.4 points better in the SCOPA-Cog and ACE-R assessments, respectively, than the slowest group. Patients who exceeded the dementia cut-off scores with these instruments exhibited significantly longer extended-TUG times. Conclusions: Extended-TUG performance appears to be a useful indicator of cognition as well as motor function and quality of life in PD, and warrants further evaluation as a first line assessment tool to monitor disease severity and response to treatment. Poor extended-TUG performance may identify patients without overt cognitive impairment form whom cognitive assessment is needed

Thermal imprinting modifies adult stress and innate immune responsiveness in the teleost sea bream

The impact of thermal imprinting on the plasticity of the hypothalamic-pituitary-interrenal (HPI) axis and stress response in an adult ectotherm, the gilthead sea bream (Sparus aurata, L.), during its development was assessed. Fish were reared under 4 thermal regimes, and the resulting adults exposed to acute confinement stress and plasma cortisol levels and genes of the HPI axis were monitored. Changes in immune function, a common result of stress, were also evaluated using histomorphometric measurements of melanomacrophages centers (MMCs) in the head kidney and by monitoring macrophage-related transcripts. Thermal history significantly modified the HPI responsiveness in adult sea bream when eggs and larvae were reared at a higher than optimal temperature (HT, 22 degrees C), and they had a reduced amplitude in their cortisol response and significantly upregulated pituitary pomc and head kidney star transcripts. Additionally, after an acute stress challenge, immune function was modified and the head kidney of adult fish reared during development at high temperatures (HT and LHT, 18-22 degrees C) had a decreased number of MMCs and a significant downregulation of dopachrome tautomerase. Thermal imprinting during development influenced adult sea bream physiology and increased plasma levels of glucose and sodium even in the absence of an acute stress in fish reared under a high-low thermal regime (HLT, 22-18 degrees C). Overall, the results demonstrate that temperature during early development influences the adult HPI axis and immune function in a teleost fish.project Lifecycle EU-FP7 [222719]FCT- Foundation for Science and Technology [CCMAR/Multi/04326/2013]info:eu-repo/semantics/publishedVersio

The spatial distribution of neutral hydrogen as traced by low HI mass galaxies

The formation and evolution of galaxies with low neutral atomic hydrogen (HI) masses, M$_{\rm HI}$$<$10$^{8}h^{-2}$M$_{\odot}$, are affected by host dark matter halo mass and photoionisation feedback from the UV background after the end of reionization. We study how the physical processes governing the formation of galaxies with low HI mass are imprinted on the distribution of neutral hydrogen in the Universe using the hierarchical galaxy formation model, GALFORM. We calculate the effect on the correlation function of changing the HI mass detection threshold at redshifts $0 \le z \le 0.5$. We parameterize the clustering as $\xi(r)=(r/r_{0})^{-\gamma}$ and we find that including galaxies with M$_{\rm HI}$$<$10$^{8}h^{-2}$M$_{\odot}$ increases the clustering amplitude $r_{0}$ and slope $\gamma$ compared to samples of higher HI masses. This is due to these galaxies with low HI masses typically being hosted by haloes with masses greater than 10$^{12}{h}^{-1}$M$_{\odot}$, and is in contrast to optically selected surveys for which the inclusion of faint, blue galaxies lowers the clustering amplitude. We show the HI mass function for different host dark matter halo masses and galaxy types (central or satellite) to interpret the values of $r_{0}$ and $\gamma$ of the clustering of HI-selected galaxies. We also predict the contribution of low HI mass galaxies to the 21cm intensity mapping signal. We calculate that a dark matter halo mass resolution better than $\sim$10$^{10}{h}^{-1}$M$_{\odot}$ at redshifts higher than 0.5 is required in order to predict converged 21cm brightness temperature fluctuations.Comment: 14 pages, 10 figures, accepted for pubication in MNRA