European precipitation connections with large-scale mean sea-level pressure (MSLP) fields

To advance understanding of hydroclimatological processes, this paper links spatiotemporal variability in gridded European precipitation and large-scale mean sea-level pressure (MSLP) time series (1957–2002) using monthly concurrent correlation. Strong negative (positive) correlation near Iceland and (the Azores) is apparent for precipitation in northwest Europe, confirming a positive North Atlantic Oscillation (NAO) association. An opposing pattern is found for southwest Europe, and the Mediterranean in winter. In the lee of mountains, MSLP correlation is lower reflecting reduced influence of westerlies on precipitation generation. Importantly, European precipitation is shown to be controlled by physically interpretable climate patterns that change in extent and position from month to month. In spring, MSLP–precipitation correlation patterns move and shrink, reaching a minimum in summer, before expanding in the autumn, and forming an NAO-like dipole in winter. These space–time shifts in correlation regions explain why fixed-point NAO indices have limited ability to resolve precipitation for some European locations and seasons

The mRNA-bound proteome of the human malaria parasite Plasmodium falciparum.

BackgroundGene expression is controlled at multiple levels, including transcription, stability, translation, and degradation. Over the years, it has become apparent that Plasmodium falciparum exerts limited transcriptional control of gene expression, while at least part of Plasmodium's genome is controlled by post-transcriptional mechanisms. To generate insights into the mechanisms that regulate gene expression at the post-transcriptional level, we undertook complementary computational, comparative genomics, and experimental approaches to identify and characterize mRNA-binding proteins (mRBPs) in P. falciparum.ResultsClose to 1000 RNA-binding proteins are identified by hidden Markov model searches, of which mRBPs encompass a relatively large proportion of the parasite proteome as compared to other eukaryotes. Several abundant mRNA-binding domains are enriched in apicomplexan parasites, while strong depletion of mRNA-binding domains involved in RNA degradation is observed. Next, we experimentally capture 199 proteins that interact with mRNA during the blood stages, 64 of which with high confidence. These captured mRBPs show a significant overlap with the in silico identified candidate RBPs (p < 0.0001). Among the experimentally validated mRBPs are many known translational regulators active in other stages of the parasite's life cycle, such as DOZI, CITH, PfCELF2, Musashi, and PfAlba1-4. Finally, we also detect several proteins with an RNA-binding domain abundant in Apicomplexans (RAP domain) that is almost exclusively found in apicomplexan parasites.ConclusionsCollectively, our results provide the most complete comparative genomics and experimental analysis of mRBPs in P. falciparum. A better understanding of these regulatory proteins will not only give insight into the intricate parasite life cycle but may also provide targets for novel therapeutic strategies

Nascent RNA sequencing reveals mechanisms of gene regulation in the human malaria parasite Plasmodium falciparum.

Gene expression in Plasmodium falciparum is tightly regulated to ensure successful propagation of the parasite throughout its complex life cycle. The earliest transcriptomics studies in P. falciparum suggested a cascade of transcriptional activity over the course of the 48-hour intraerythrocytic developmental cycle (IDC); however, the just-in-time transcriptional model has recently been challenged by findings that show the importance of post-transcriptional regulation. To further explore the role of transcriptional regulation, we performed the first genome-wide nascent RNA profiling in P. falciparum. Our findings indicate that the majority of genes are transcribed simultaneously during the trophozoite stage of the IDC and that only a small subset of genes is subject to differential transcriptional timing. RNA polymerase II is engaged with promoter regions prior to this transcriptional burst, suggesting that Pol II pausing plays a dominant role in gene regulation. In addition, we found that the overall transcriptional program during gametocyte differentiation is surprisingly similar to the IDC, with the exception of relatively small subsets of genes. Results from this study suggest that further characterization of the molecular players that regulate stage-specific gene expression and Pol II pausing will contribute to our continuous search for novel antimalarial drug targets

Using variograms to detect and attribute hydrological change

There have been many published studies aiming to identify temporal changes in river flow time series, most of which use monotonic trend tests such as the Mann–Kendall test. Although robust to both the distribution of the data and incomplete records, these tests have important limitations and provide no information as to whether a change in variability mirrors a change in magnitude. This study develops a new method for detecting periods of change in a river flow time series, using temporally shifting variograms (TSVs) based on applying variograms to moving windows in a time series and comparing these to the long-term average variogram, which characterises the temporal dependence structure in the river flow time series. Variogram properties in each moving window can also be related to potential meteorological drivers. The method is applied to 91 UK catchments which were chosen to have minimal anthropogenic influences and good quality data between 1980 and 2012 inclusive. Each of the four variogram parameters (range, sill and two measures of semi-variance) characterise different aspects of the river flow regime, and have a different relationship with the precipitation characteristics. Three variogram parameters (the sill and the two measures of semi-variance) are related to variability (either day-to-day or over the time series) and have the largest correlations with indicators describing the magnitude and variability of precipitation. The fourth (the range) is dependent on the relationship between the river flow on successive days and is most correlated with the length of wet and dry periods. Two prominent periods of change were identified: 1995–2001 and 2004–2012. The first period of change is attributed to an increase in the magnitude of rainfall whilst the second period is attributed to an increase in variability of the rainfall. The study demonstrates that variograms have considerable potential for application in the detection and attribution of temporal variability and change in hydrological systems

DNA-encoded nucleosome occupancy is associated with transcription levels in the human malaria parasite Plasmodium falciparum.

BackgroundIn eukaryotic organisms, packaging of DNA into nucleosomes controls gene expression by regulating access of the promoter to transcription factors. The human malaria parasite Plasmodium falciparum encodes relatively few transcription factors, while extensive nucleosome remodeling occurs during its replicative cycle in red blood cells. These observations point towards an important role of the nucleosome landscape in regulating gene expression. However, the relation between nucleosome positioning and transcriptional activity has thus far not been explored in detail in the parasite.ResultsHere, we analyzed nucleosome positioning in the asexual and sexual stages of the parasite's erythrocytic cycle using chromatin immunoprecipitation of MNase-digested chromatin, followed by next-generation sequencing. We observed a relatively open chromatin structure at the trophozoite and gametocyte stages, consistent with high levels of transcriptional activity in these stages. Nucleosome occupancy of genes and promoter regions were subsequently compared to steady-state mRNA expression levels. Transcript abundance showed a strong inverse correlation with nucleosome occupancy levels in promoter regions. In addition, AT-repeat sequences were strongly unfavorable for nucleosome binding in P. falciparum, and were overrepresented in promoters of highly expressed genes.ConclusionsThe connection between chromatin structure and gene expression in P. falciparum shares similarities with other eukaryotes. However, the remarkable nucleosome dynamics during the erythrocytic stages and the absence of a large variety of transcription factors may indicate that nucleosome binding and remodeling are critical regulators of transcript levels. Moreover, the strong dependency between chromatin structure and DNA sequence suggests that the P. falciparum genome may have been shaped by nucleosome binding preferences. Nucleosome remodeling mechanisms in this deadly parasite could thus provide potent novel anti-malarial targets

The multifunctional autophagy pathway in the human malaria parasite, Plasmodium falciparum.

Autophagy is a catabolic pathway typically induced by nutrient starvation to recycle amino acids, but can also function in removing damaged organelles. In addition, this pathway plays a key role in eukaryotic development. To date, not much is known about the role of autophagy in apicomplexan parasites and more specifically in the human malaria parasite Plasmodium falciparum. Comparative genomic analysis has uncovered some, but not all, orthologs of autophagy-related (ATG) genes in the malaria parasite genome. Here, using a genome-wide in silico analysis, we confirmed that ATG genes whose products are required for vesicle expansion and completion are present, while genes involved in induction of autophagy and cargo packaging are mostly absent. We subsequently focused on the molecular and cellular function of P. falciparum ATG8 (PfATG8), an autophagosome membrane marker and key component of the autophagy pathway, throughout the parasite asexual and sexual erythrocytic stages. In this context, we showed that PfATG8 has a distinct and atypical role in parasite development. PfATG8 localized in the apicoplast and in vesicles throughout the cytosol during parasite development. Immunofluorescence assays of PfATG8 in apicoplast-minus parasites suggest that PfATG8 is involved in apicoplast biogenesis. Furthermore, treatment of parasite cultures with bafilomycin A 1 and chloroquine, both lysosomotropic agents that inhibit autophagosome and lysosome fusion, resulted in dramatic morphological changes of the apicoplast, and parasite death. Furthermore, deep proteomic analysis of components associated with PfATG8 indicated that it may possibly be involved in ribophagy and piecemeal microautophagy of the nucleus. Collectively, our data revealed the importance and specificity of the autophagy pathway in the malaria parasite and offer potential novel therapeutic strategies

Evaluation of changing surface water abstraction reliability for supplemental irrigation under climate change

In many temperate parts of the world, supplemental irrigation is crucial to assure both crop yield and quality. Climate change could increase the risks of irrigation being restricted by increasing crop water requirements and/or decreasing water availability. In England, water abstraction for irrigation is limited by maximum annual volumetric limits, as specified in the abstraction licences, and surface water abstraction restrictions imposed by the regulator during drought. This paper assesses how climate change might impact future irrigation abstraction reliability from surface water in England. Firstly, the probability of annual abstraction being close to the maximum licence limit was estimated for the baseline (1961–1990) and future (2071–2098) periods in each catchment based on observed relationships between annual weather and irrigation abstraction in three licence usage groups. Secondly, the current river discharge triggers for mandatory drought restrictions were used to assess the annual probability of surface water abstraction restrictions being imposed by the regulator in each period. Results indicate significant future increases in irrigated abstraction licence use due to an increase in aridity, particularly in the most productive agricultural areas located in eastern and southern England, assuming no adaptation. The annual probability of having less than 20% licence headroom in the highest usage group is projected to exceed 0.7 in 45% of the management units, mostly in the south and east. In contrast, irrigators in central and western England face an increased risk of drought restrictions due to the lower buffering capacity of groundwater on river flows, with the annual probability of mandatory drought restrictions reaching up to 0.3 in the future. Our results highlight the increasing abstraction reliability risks for irrigators due to climate change, and the need for the farming community and the regulator to adapt and collaborate to mitigate the associated impacts

Evaluation of global impact models' ability to reproduce runoff characteristics over the central United States

The central United States experiences a wide array of hydrological extremes, with the 1993, 2008, 2013, and 2014 flooding events and the 1988 and 2012 droughts representing some of the most recent extremes, and is an area where water availability is critical for agricultural production. This study aims to evaluate the ability of a set of global impact models (GIMs) from the Water Model Intercomparison Project to reproduce the regional hydrology of the central United States for the period 1963–2001. Hydrological indices describing annual daily maximum, medium and minimum flow, and their timing are extracted from both modeled daily runoff data by nine GIMs and from observed daily streamflow measured at 252 river gauges. We compare trend patterns for these indices, and their ability to capture runoff volume differences for the 1988 drought and 1993 flood. In addition, we use a subset of 128 gauges and corresponding grid cells to perform a detailed evaluation of the models on a gauge-to-grid cell basis. Results indicate that these GIMs capture the overall trends in high, medium, and low flows well. However, the models differ from observations with respect to the timing of high and medium flows. More specifically, GIMs that only include water balance tend to be closer to the observations than GIMs that also include the energy balance. In general, as it would be expected, the performance of the GIMs is the best when describing medium flows, as opposed to the two ends of the runoff spectrum. With regards to low flows, some of the GIMs have considerably large pools of zeros or low values in their time series, undermining their ability in capturing low flow characteristics and weakening the ensemble's output. Overall, this study provides a valuable examination of the capability of GIMs to reproduce observed regional hydrology over a range of quantities for the central United States