Fusarium graminearum is one of the main causal agents of the Fusarium Head Blight, a worldwide disease affecting cereal cultures, whose presence can lead to contaminated grains with chemically stable ...and harmful mycotoxins. Resistant cultivars and fungicides are frequently used to control this pathogen, and several observations suggest an adaptation of F. graminearum that raises concerns regarding the future of current plant disease management strategies. To understand the genetic basis as well as the extent of its adaptive potential, we investigated the landscape of genomic diversity among six French isolates of F. graminearum, at single-nucleotide resolution using whole-genome re-sequencing.
A total of 242,756 high-confidence genetic variants were detected when compared to the reference genome, among which 96% are single nucleotides polymorphisms. One third of these variants were observed in all isolates. Seventy-seven percent of the total polymorphism is located in 32% of the total length of the genome, comprising telomeric/subtelomeric regions as well as discrete interstitial sections, delineating clear variant enriched genomic regions- 7.5 times in average. About 80% of all the F. graminearum protein-coding genes were found polymorphic. Biological functions are not equally affected: genes potentially involved in host adaptation are preferentially located within polymorphic islands and show greater diversification rate than genes fulfilling basal functions. We further identified 29 putative effector genes enriched with non-synonymous effect mutation.
Our results highlight a remarkable level of polymorphism in the genome of F. graminearum distributed in a specific pattern. Indeed, the landscape of genomic diversity follows a bi-partite organization of the genome according to polymorphism and biological functions. We measured, for the first time, the level of sequence diversity for the entire gene repertoire of F. graminearum and revealed that the majority are polymorphic. Those assumed to play a role in host-pathogen interaction are discussed, in the light of the subsequent consequences for host adaptation. The annotated genetic variants discovered for this major pathogen are valuable resources for further genetic and genomic studies.
Forebrain precursor cells are dynamic during early brain development, yet the underlying molecular changes remain elusive. We observed major differences in transcriptional signatures of precursor ...cells from mouse forebrain at embryonic days E8.5 vs. E10.5 (before vs. after neural tube closure). Genes encoding protein biosynthetic machinery were strongly downregulated at E10.5. This was matched by decreases in ribosome biogenesis and protein synthesis, together with age-related changes in proteomic content of the adjacent fluids. Notably, c-MYC expression and mTOR pathway signaling were also decreased at E10.5, providing potential drivers for the effects on ribosome biogenesis and protein synthesis. Interference with c-MYC at E8.5 prematurely decreased ribosome biogenesis, while persistent c-MYC expression in cortical progenitors increased transcription of protein biosynthetic machinery and enhanced ribosome biogenesis, as well as enhanced progenitor proliferation leading to subsequent macrocephaly. These findings indicate large, coordinated changes in molecular machinery of forebrain precursors during early brain development.
A measurement campaign was conducted in the Paris region, focusing on the evolution of chemical composition of wet deposition during rainfall events from sequential sampling. A total of eight rain ...events were documented and characterized by varying meteorological conditions, atmospheric dynamics, and aerosol particle concentrations representative of urban conditions and influenced by long-range mineral dust transport. The intra-event evolution of the chemical composition of wet deposition revealed the predominant role of meteorological parameters and local sources in the observed mass concentration variability. From selected case studies, the washout ratios (WRs) and scavenging coefficients were quantified by conducting simultaneous measurements of aerosol particle composition and wet deposition. The results highlighted a variability of the WR and scavenging coefficients depending on the rainfall rate and on the chemical species. Scavenging coefficients estimated from WR ranged from 5.4×10-8 to 1.1×10-5 s−1 for chemical elements, and they are within the range of values reported in the literature for 0.2–2 µm particle diameters. Our results pointed out that the scavenging coefficient increases with rainfall rate according to a power law, as previously shown in the literature, indicating a stronger removal of particles from the atmosphere with greater precipitation intensity. Quantitative analysis of the data allowed us to estimate the relative contributions of in-cloud scavenging (ICS) for selected rain events. The ICS relative contributions ranged on average from 23 % to 62 % depending on the rain events, and they varied according to the chemical species within the same rain event. This highlights the variability and complexity of the wet deposition process and the influence of specific factors on the contribution of ICS, such as aerosol particle size and hygroscopicity. Overall, this study highlights the variability of wet deposition and its chemical composition and the need to consider the specificities of each event to fully understand the underlying mechanisms.
In this paper, we address a driver–vehicle scheduling problem in a limousine rental company. Given a set of trips to be covered, the goal consists in finding a driver–vehicle schedule that serves the ...maximum workload and optimizes several economic objectives while satisfying a set of imperative constraints. In this context, we propose a simultaneous scheduling of drivers and vehicles. The problem is modeled using the notion of partial consistent assignment. The solution approach is composed of two phases: the first one is based on constraint programming techniques and leads to the construction of an initial solution, improved in a second phase by a Simulated Annealing algorithm. Significant gains on the resulting solutions are systematically obtained in terms of quality, operational costs and elaboration time, compared to the current practice in the company.
Growth Factor Independent‐1B (Gfi‐1B) is a transcriptional repressor that plays critical roles in the control of erythropoiesis and megakaryopoiesis. Gfi‐1B expression was described to be repressed ...by an autoregulatory feedback control loop. Here, we show that Gfi‐1 transcription is positively regulated early after induction of erythroid differentiation and remains highly active to late erythroblasts. Using chromatin immunoprecipitation assays in CD34+ cells from human cord blood, we found that Gfi‐1 and GATA‐2 in immature progenitors and then Gfi‐1B and GATA‐1 in erythroblasts are bound to the Gfi‐1B promoter as well as to the promoter of c‐myc, a known Gfi‐1B target gene. Surprisingly, this Gfi‐1/GATA‐2–Gfi‐1B/GATA‐1 switch observed at erythroblast stages is associated to an increase in the Gfi‐1B transcription whereas it triggers repression of c‐myc transcription. Accordingly, analysis of chromatin modification patterns shows that HDAC, CoREST, and LSD1 are recruited to the c‐myc promoter leading to appearance of repressive chromatin marks. In contrast, the Gfi‐1B promoter remains associated with a transcriptionally active chromatin configuration as highlighted by an increase in histone H3 acetylation and concomitant release of the LSD1 and CoREST corepressors. The repressive function of Gfi‐1B therefore depends on the nature of the proteins recruited to the target gene promoters and on chromatin modifications. We conclude that Gfi‐1B behaves as a lineage‐affiliated gene with an open chromatin configuration in multipotent progenitors and sustained activation as cells progress throughout erythroid differentiation. STEM CELLS 2009;27:2153–2162
In order to measure the mass flux of atmospheric insoluble deposition and to constrain regional models of dust simulation, a network of automatic deposition collectors (CARAGA) has been installed ...throughout the western Mediterranean Basin. Weekly samples of the insoluble fraction of total atmospheric deposition were collected concurrently on filters at five sites including four on western Mediterranean islands (Frioul and Corsica, France; Mallorca, Spain; and Lampedusa, Italy) and one in the southern French Alps (Le Casset), and a weighing and ignition protocol was applied in order to quantify their mineral fraction. Atmospheric deposition is both a strong source of nutrients and metals for marine ecosystems in this area. However, there are few data on trace-metal deposition in the literature, since their deposition measurement is difficult to perform. In order to obtain more information from CARAGA atmospheric deposition samples, this study aimed to test their relevance in estimating elemental fluxes in addition to total mass fluxes. The elemental chemical analysis of ashed CARAGA filter samples was based on an acid digestion and an elemental analysis by inductively coupled plasma atomic emission spectroscopy (ICP-AES) and mass spectrometry (MS) in a clean room. The sampling and analytical protocols were tested to determine the elemental composition for mineral dust tracers (Al, Ca, K, Mg and Ti), nutrients (P and Fe) and trace metals (Cd, Co, Cr, Cu, Mn, Ni, V and Zn) from simulated wet deposition of dust analogues and traffic soot. The relative mass loss by dissolution in wet deposition was lower than 1 % for Al and Fe, and reached 13 % for P due to its larger solubility in water. For trace metals, this loss represented less than 3 % of the total mass concentration, except for Zn, Cu and Mn for which it could reach 10 %, especially in traffic soot. The chemical contamination during analysis was negligible for all the elements except for Cd, which has a very low concentration in dust. Tests allowed us to conclude that the CARAGA samples could be used to estimate the contents of nutrients and trace metals in the limits of loss by dissolution. Chemical characterization of CARAGA deposition samples corresponding to the most intense dust deposition events recorded between 2011 and 2013 has been performed and showed elemental mass ratios consistent with the ones found in the literature for Saharan dust. However, the chemical analysis of CARAGA samples revealed the presence of some anthropogenic signatures, for instance high Zn concentrations in some samples in Lampedusa, and also pointed out that mineral dust can be mixed with anthropogenic compounds in the deposition samples collected on Frioul. Results showed that the chemical analysis of CARAGA ashed samples can be used to trace the origins of elemental deposition. The elemental atmospheric fluxes estimated from these chemical analyses of samples from the CARAGA network of weekly deposition monitoring constitute the first assessment of mass deposition fluxes of trace metals and P during intense dust deposition events at the scale of the western Mediterranean Basin. The mass fluxes strongly depend on the distance from dust sources and the most intense events, while proximity from anthropogenic sources strongly impacted the masse fluxes of Zn and Cu at Lampedusa and Frioul.
Alternative splicing (AS) of RNA molecules is a key contributor to transcriptome diversity. In humans, 90%–95% of multi-exon genes produce alternatively spliced RNA transcripts. Therefore, every ...single gene has the opportunity of producing multiple splice variants, including long non-coding RNA (lncRNA) genes that undergo RNA maturation steps such as conventional and alternative splicing. Emerging evidence suggests significant roles for these lncRNA splice variants in many aspects of cell biology. Differential changes in expression of specific lncRNA splice variants have also been associated with many diseases including cancer. This review covers the current knowledge on this emerging topic of investigation. We provide exclusive insights on the AS landscape of lncRNAs and also describe at the molecular level the functional relevance of lncRNA splice variants, i.e., RNA-based differential functions, production of micropeptides, and generation of circular RNAs. Finally, we discuss exciting perspectives for this emerging field and outline the work required to further develop research endeavors in this field.
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Laurent B. and colleagues provide in this review insights on the splicing landscape of long non-coding RNAs (lncRNAs) and describe the functional relevance of lncRNA splice variants in health and diseases. They also discuss therapeutic perspectives for this emerging field of investigation.
Detection of a gravitational-wave signal of non-astrophysical origin would be a landmark discovery, potentially providing a significant clue to some of our most basic, big-picture scientific ...questions about the Universe. In this white paper, we survey the leading early-Universe mechanisms that may produce a detectable signal—including inflation, phase transitions, topological defects, as well as primordial black holes—and highlight the connections to fundamental physics. We review the complementarity with collider searches for new physics, and multimessenger probes of the large-scale structure of the Universe.
RUNX1-RUNX1T1 (formerly AML1-ETO), a transcription factor generated by the t(8;21) translocation in acute myeloid leukemia (AML), dictates a leukemic program by increasing self-renewal and inhibiting ...differentiation. Here we demonstrate that the histone demethylase JMJD1C functions as a coactivator for RUNX1-RUNX1T1 and is required for its transcriptional program. JMJD1C is directly recruited by RUNX1-RUNX1T1 to its target genes and regulates their expression by maintaining low H3K9 dimethyl (H3K9me2) levels. Analyses in JMJD1C knockout mice also establish a JMJD1C requirement for RUNX1-RUNX1T1's ability to increase proliferation. We also show a critical role for JMJD1C in the survival of multiple human AML cell lines, suggesting that it is required for leukemic programs in different AML cell types through its association with key transcription factors.
Summary
Recombination is a major evolutionary force, increasing genetic diversity and permitting efficient coevolution of fungal pathogen(s) with their host(s). The ascomycete Fusarium graminearum is ...a devastating pathogen of cereal crops, and can contaminate food and feed with harmful mycotoxins. Previous studies have suggested a high adaptive potential of this pathogen, illustrated by an increase in pathogenicity and resistance to fungicides. In this study, we provide the first detailed picture of the crossover events occurring during meiosis and discuss the role of recombination in pathogen evolution. An experimental recombinant population (n = 88) was created and genotyped using 1306 polymorphic markers obtained from restriction site‐associated DNA sequencing (RAD‐seq) and aligned to the reference genome. The construction of a high‐density linkage map, anchoring 99% of the total length of the reference genome, allowed the identification of 1451 putative crossovers, positioned at a median resolution of 24 kb. The majority of crossovers (87.2%) occurred in a relatively small portion of the genome (30%). All chromosomes demonstrated recombination‐active sections, which had a near 15‐fold higher crossover rate than non‐active recombinant sections. The recombination rate showed a strong positive correlation with nucleotide diversity, and recombination‐active regions were enriched for genes with a putative role in host–pathogen interaction, as well as putative diversifying genes. Our results confirm the preliminary analysis observed in other F. graminearum strains and suggest a conserved ‘two‐speed’ recombination landscape. The consequences with regard to the evolutionary potential of this major fungal pathogen are also discussed.
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