ALBERT

Description: Sexual differentiation of malaria parasites into gametocytes in the vertebrate host and subsequent gamete fertilization in mosquitoes is essential for the spreading of the disease. The molecular processes orchestrating these transitions are far from fully understood. Here, we report the first transcriptome analysis of male and female Plasmodium falciparum gametocytes coupled with a comprehensive proteome analysis. In male gametocytes there is an enrichment of proteins involved in the formation of flagellated gametes; proteins involved in DNA replication, chromatin organization and axoneme formation. On the other hand, female gametocytes are enriched in proteins required for zygote formation and functions after fertilization; protein-, lipid- and energy-metabolism. Integration of transcriptome and proteome data revealed 512 highly expressed maternal transcripts without corresponding protein expression indicating large scale translational repression in P. falciparum female gametocytes for the first time. Despite a high degree of conservation between Plasmodium species, 260 of these ‘repressed transcripts’ have not been previously described. Moreover, for some of these genes, protein expression is only reported in oocysts and sporozoites indicating that repressed transcripts can be partitioned into short- and long-term storage. Finally, these data sets provide an essential resource for identification of vaccine/drug targets and for further mechanistic studies.

Description: The Borborema province in NE Brazil is characterized by seismic sequences with small earthquakes that can last 10 yr or more. The seismicity in this region is concentrated in three main seismic zones. In this work, we investigate the stress field in one of these zones, the Acaraú Seismic Zone, which is located in the NW part of the Borborema province. This seismic zone exhibits earthquake sequences that contain repeated earthquakes with similar waveforms and a shallow depth. Using a local network, we investigated a seismic sequence close to the town of Santana do Acaraú from December 2009 to December 2010, and we present detailed results (velocity model, hypocentres and focal mechanism) from this network. In addition, we inverted seven focal mechanisms, including six that were used in previous studies, and determined the directions of the three main axes of the regional stress field. Selecting a very precise set of 12 earthquakes, we found an active seismic zone with a depth between 3.5 and 4.8 km and with a horizontal dimension of approximately 2.5 km in the NW–SE direction (azimuth of 118°) and a strike-slip focal mechanism. The new seismic fault and some of the previous seismic faults determined in previous studies occur near the continental-scale Transbrasiliano lineament, but they exhibit no direct relationship with that ancient structure. The stress field is characterized by NW–SE trending compression and NE–SW trending extension. This result suggests that the rheological contrast between the continental–oceanic crusts created flexural stresses with maximum horizontal compression parallel to the continental margin. This stress pattern occurs along the Potiguar basin and continues west as far as the Amazon fan along the Equatorial margin of Brazil. This stress field and related seismicity may be a characteristic of this type of passive margin that is generated during the transform shearing between the South America and Africa plates and that exhibits an abrupt oceanic–continent transition, steep continental slopes and high bathymetric gradients.

Description: Genomic structural variation (SV), a common hallmark of cancer, has important predictive and therapeutic implications. However, accurately detecting SV using high-throughput sequencing data remains challenging, especially for ‘targeted’ resequencing efforts. This is critically important in the clinical setting where targeted resequencing is frequently being applied to rapidly assess clinically actionable mutations in tumor biopsies in a cost-effective manner. We present BreaKmer, a novel approach that uses a ‘kmer’ strategy to assemble misaligned sequence reads for predicting insertions, deletions, inversions, tandem duplications and translocations at base-pair resolution in targeted resequencing data. Variants are predicted by realigning an assembled consensus sequence created from sequence reads that were abnormally aligned to the reference genome. Using targeted resequencing data from tumor specimens with orthogonally validated SV, non-tumor samples and whole-genome sequencing data, BreaKmer had a 97.4% overall sensitivity for known events and predicted 17 positively validated, novel variants. Relative to four publically available algorithms, BreaKmer detected SV with increased sensitivity and limited calls in non-tumor samples, key features for variant analysis of tumor specimens in both the clinical and research settings.

Description: The Borborema province in NE Brazil is characterized by seismic sequences with small earthquakes that can last 10 yr or more. The seismicity in this region is concentrated in three main seismic zones. In this work, we investigate the stress field in one of these zones, the Acaraú Seismic Zone, which is located in the NW part of the Borborema province. This seismic zone exhibits earthquake sequences that contain repeated earthquakes with similar waveforms and a shallow depth. Using a local network, we investigated a seismic sequence close to the town of Santana do Acaraú from December 2009 to December 2010, and we present detailed results (velocity model, hypocentres and focal mechanism) from this network. In addition, we inverted seven focal mechanisms, including six that were used in previous studies, and determined the directions of the three main axes of the regional stress field. Selecting a very precise set of 12 earthquakes, we found an active seismic zone with a depth between 3.5 and 4.8 km and with a horizontal dimension of approximately 2.5 km in the NW–SE direction (azimuth of 118°) and a strike-slip focal mechanism. The new seismic fault and some of the previous seismic faults determined in previous studies occur near the continental-scale Transbrasiliano lineament, but they exhibit no direct relationship with that ancient structure. The stress field is characterized by NW–SE trending compression and NE–SW trending extension. This result suggests that the rheological contrast between the continental–oceanic crusts created flexural stresses with maximum horizontal compression parallel to the continental margin. This stress pattern occurs along the Potiguar basin and continues west as far as the Amazon fan along the Equatorial margin of Brazil. This stress field and related seismicity may be a characteristic of this type of passive margin that is generated during the transform shearing between the South America and Africa plates and that exhibits an abrupt oceanic–continent transition, steep continental slopes and high bathymetric gradients.

Description: The 2014 April 1, M w 8.1 Iquique (Chile) earthquake struck in the Northern Chile seismic gap. With a rupture length of less than 200 km, it left unbroken large segments of the former gap. Early studies were able to model the main rupture features but results are ambiguous with respect to the role of aseismic slip and left open questions on the remaining hazard at the Northern Chile gap. A striking observation of the 2014 earthquake has been its extensive preparation phase, with more than 1300 events with magnitude above M L 3, occurring during the 15 months preceding the main shock. Increasing seismicity rates and observed peak magnitudes accompanied the last three weeks before the main shock. Thanks to the large data sets of regional recordings, we assess the precursor activity, compare foreshocks and aftershocks and model rupture preparation and rupture effects. To tackle inversion challenges for moderate events with an asymmetric network geometry, we use full waveforms techniques to locate events, map the seismicity rate and derive source parameters, obtaining moment tensors for more than 300 events (magnitudes M w 4.0–8.1) in the period 2013 January 1–2014 April 30. This unique data set of fore- and aftershocks is investigated to distinguish rupture process models and models of strain and stress rotation during an earthquake. Results indicate that the spatial distributions of foreshocks delineated the shallower part of the rupture areas of the main shock and its largest aftershock, well matching the spatial extension of the aftershocks cloud. Most moment tensors correspond to almost pure double couple thrust mechanisms, consistent with the slab orientation. Whereas no significant differences are observed among thrust mechanisms in different areas, nor among thrust foreshocks and aftershocks, the early aftershock sequence is characterized by the presence of normal fault mechanisms, striking parallel to the trench but dipping westward. These events likely occurred in the shallow wedge structure close to the slab interface and are consequence of the increased extensional stress in this region after the largest events. The overall stress inversion result suggests a minor stress rotation after the main shock, but a significant release of the deviatoric stress. The temporal change in the distribution of focal mechanisms can also be explained in terms of the spatial heterogeneity of the stress field: under such interpretation, the potential of a large megathrust earthquake breaking a larger segment offshore Northern Chile remains high.

Description: Detecting allelic biases from high-throughput sequencing data requires an approach that maximises sensitivity while minimizing false positives. Here, we present Allelome.PRO, an automated user-friendly bioinformatics pipeline, which uses high-throughput sequencing data from reciprocal crosses of two genetically distinct mouse strains to detect allele-specific expression and chromatin modifications. Allelome.PRO extends approaches used in previous studies that exclusively analyzed imprinted expression to give a complete picture of the ‘allelome’ by automatically categorising the allelic expression of all genes in a given cell type into imprinted, strain-biased, biallelic or non-informative. Allelome.PRO offers increased sensitivity to analyze lowly expressed transcripts, together with a robust false discovery rate empirically calculated from variation in the sequencing data. We used RNA-seq data from mouse embryonic fibroblasts from F1 reciprocal crosses to determine a biologically relevant allelic ratio cutoff, and define for the first time an entire allelome. Furthermore, we show that Allelome.PRO detects differential enrichment of H3K4me3 over promoters from ChIP-seq data validating the RNA-seq results. This approach can be easily extended to analyze histone marks of active enhancers, or transcription factor binding sites and therefore provides a powerful tool to identify candidate cis regulatory elements genome wide.

Description: Our study compares the seismic properties between the flat and normal subduction regions in central Chile, to better understand the links between the slab geometry, surface deformation and the deeper structures. In comparison with previous studies, we show the most complete 3-D regional seismic tomography images for this region, in which we use (1) a larger seismic data set compiled from several short-term seismic catalogues, (2) a denser seismic array allowing a better resolution of the subduction zone from the trench to the backarc and into the upper ~30 km of the slab and (3) a starting 1-D background velocity model specifically calculated for this region and refined over the years. We assess and discuss our tomography results using regional seismic attenuation models and estimating rock types on the basis of pressure and temperature conditions computed from thermomechanical models. Our results show significant seismic differences between the flat and normal subduction zones. As expected, the faster seismic velocities and increased seismicity within the flat slab and overriding lithosphere are generally consistent with a cooler thermal state. Our results are also consistent with dehydration of the mantle above the subducted Juan Fernandez Ridge at the eastern tip of the flat slab segment, indicating that the latter retains some fluids during subduction. However, fluids in the upper portion of the flat slab segment are not seismically detected, since we report instead fast slab seismic velocities which contradict the argument of its buoyancy being the cause of horizontal subduction. The forearc region, above the flat slab, exhibits high Vs and very low Vp / Vs ratios, uncorrelated with typical rock compositions, increased density or reduced temperature; this feature is possibly linked with the aftershock effects of the M w7.1 1997 Punitaqui earthquake, the flat slab geometry and/or seismic anisotropy. At the surface, the seismic variations correlate with the geological terranes. The Andean crust is strongly reduced in seismic velocities along the La Ramada–Aconcagua deformation belt, suggesting structural damage. Slow seismic velocities along the Andean Moho match non-eclogitized hydrated rocks, consistent with a previous delamination event or a felsic composition, which in turn supports the extent of the Chilenia terrane at these depths. We confirm previous studies that suggest that the Cuyania terrane in the backarc region is mafic and contains an eclogitized lower crust below 50-km depth. We also hypothesize major Andean basement detachment faults (or shear zones) to extend towards the plate interface and canalize slab-derived fluids into the continental crust.

Description: We present a methodology to model the spatio-temporal variations of microbarom detections at a global scale. Our model combines the source term resulting from the non-linear ocean-wave interaction and a simplified description of the long-range infrasound propagation through the stratospheric waveguide. We compare model predictions with observations at infrasound stations of the International Monitoring System between 2008 and 2009. Our results show a first-order consistency between the observed and modelled trends of microbarom backazimuth detections for most stations. Taking into account stratospheric wind effect on the infrasound propagation systematically improves the fit between the observations the model predictions. However, correctly predicting patterns of weekly variation of detections turns out to be more challenging and would require further improving the source and the propagation models. Short-term and regional quantitative comparisons could then be carried out based on the metrics developed in this study.

Description: The M  7.8 2015 April 25 Gorkha earthquake devastated the mountainous southern rim of the High Himalayan range in central Nepal. The main shock was followed by 553 earthquakes of local magnitude greater than 4.0 within the first 45 days. In this study, we present and qualify the bulletin of the permanent National Seismological Centre network to determine the spatio-temporal distribution of the aftershocks. The Gorkha sequence defines a ~140-km-long ESE trending structure, parallel to the mountain range, abutting on the presumed extension of the rupture plane of the 1934 M  8.4 earthquake. In addition, we observe a second seismicity belt located southward, under the Kathmandu basin and in the northern part of the Mahabarat range. Many aftershocks of the Gorkha earthquake sequence have been felt by the 3 millions inhabitants of the Kathmandu valley.

Description: Classically or alternatively activated macrophages (M1 and M2, respectively) play distinct and important roles for microbiocidal activity, regulation of inflammation and tissue homeostasis. Despite this, their transcriptional regulatory dynamics are poorly understood. Using promoter-level expression profiling by non-biased deepCAGE we have studied the transcriptional dynamics of classically and alternatively activated macrophages. Transcription factor (TF) binding motif activity analysis revealed four motifs, NFKB1_REL_RELA, IRF1,2, IRF7 and TBP that are commonly activated but have distinct activity dynamics in M1 and M2 activation. We observe matching changes in the expression profiles of the corresponding TFs and show that only a restricted set of TFs change expression. There is an overall drastic and transient up-regulation in M1 and a weaker and more sustainable up-regulation in M2. Novel TFs, such as Thap6, Maff , (M1) and Hivep1, Nfil3, Prdm1 , (M2) among others, were suggested to be involved in the activation processes. Additionally, 52 (M1) and 67 (M2) novel differentially expressed genes and, for the first time, several differentially expressed long non-coding RNA (lncRNA) transcriptome markers were identified. In conclusion, the finding of novel motifs, TFs and protein-coding and lncRNA genes is an important step forward to fully understand the transcriptional machinery of macrophage activation.