Rad51 paralogues Rad55-Rad57 balance the antirecombinase Srs2 in Rad51 filament formation

Homologous recombination is a high-fidelity DNA repair pathway. Besides a critical role in accurate chromosome segregation during meiosis, recombination functions in DNA repair and in the recovery of stalled or broken replication forks to ensure genomic stability. In contrast, inappropriate recombination contributes to genomic instability, leading to loss of heterozygosity, chromosome rearrangements and cell death. The RecA/UvsX/RadA/Rad51 family of proteins catalyses the signature reactions of recombination, homology search and DNA strand invasion. Eukaryotes also possess Rad51 paralogues, whose exact role in recombination remains to be defined. Here we show that the Saccharomyces cerevisiae Rad51 paralogues, the Rad55-Rad57 heterodimer, counteract the antirecombination activity of the Srs2 helicase. The Rad55-Rad57 heterodimer associates with the Rad51-single-stranded DNA filament, rendering it more stable than a nucleoprotein filament containing Rad51 alone. The Rad51-Rad55-Rad57 co-filament resists disruption by the Srs2 antirecombinase by blocking Srs2 translocation, involving a direct protein interaction between Rad55-Rad57 and Srs2. Our results demonstrate an unexpected role of the Rad51 paralogues in stabilizing the Rad51 filament against a biologically important antagonist, the Srs2 antirecombination helicase. The biological significance of this mechanism is indicated by a complete suppression of the ionizing radiation sensitivity of rad55 or rad57 mutants by concomitant deletion of SRS2, as expected for biological antagonists. We propose that the Rad51 presynaptic filament is a meta-stable reversible intermediate, whose assembly and disassembly is governed by the balance between Rad55-Rad57 and Srs2, providing a key regulatory mechanism controlling the initiation of homologous recombination. These data provide a paradigm for the potential function of the human RAD51 paralogues, which are known to be involved in cancer predisposition and human disease.     

Universal physical responses to stretch in the living cell

With every beat of the heart, inflation of the lung or peristalsis of the gut, cell types of diverse function are subjected to substantial stretch. Stretch is a potent stimulus for growth, differentiation, migration, remodelling and gene expression. Here, we report that in response to transient stretch the cytoskeleton fluidizes in such a way as to define a universal response class. This finding implicates mechanisms mediated not only by specific signalling intermediates, as is usually assumed, but also by non-specific actions of a slowly evolving network of physical forces. These results support the idea that the cell interior is at once a crowded chemical space and a fragile soft material in which the effects of biochemistry, molecular crowding and physical forces are complex and inseparable, yet conspire nonetheless to yield remarkably simple phenomenological laws. These laws seem to be both universal and primitive, and thus comprise a striking intersection between the worlds of cell biology and soft matter physics.     

Coherent Streamline Generation for 2-D Vector Fields

Visualizing 2-D vector fields using streamlines is one popular ?ow visualization technique.Standard streamline generation algorithms compute the density of streamlines across the domain,detect features,and employ customized rules to emphasize features.In this process,feature characterization and visual clarity are heavily considered.Simultaneously preserving the temporal coherence for time-varying vector fields,however,remains a challenge.In this paper,we present a coherent and feature-aware streamline generation algorithm by employing a feature-guided streamline seeding technique and a coherent streamline placing scheme.For each frame,a feature map is first computed with critical points or the Finite-Time Lyapunov Exponent(FTLE) approach,and is used to initialize a set of seeds by leveraging the Poisson Disk distribution.These seeds are further optimized by using a deformation-driven moving mesh method.To preserve the temporal coherence,the streamlines generated from the seeds are individually checked subject to their correspondences to the ones in the previous frame.Subsequently,additional streamlines are sequentially inserted in low-density regions.We demonstrate our algorithm on both Computation Fluid Dynamics(CFD) and non-CFD datasets,and compare it with the recent literature.     

MicroRNA degeneracy and pluripotentiality within a Lavallière-tie architecture confers robustness to gene expression networks

Modularity, feedback control, functional redundancy and bowtie architecture have been proposed as key factors that confer robustness to complex biological systems. MicroRNAs (miRNAs) are highly conserved but functionally dispensable. These antinomic properties suggest that miRNAs fine-tune gene expression rather than act as genetic switches. We synthesize published and unpublished data and hypothesize that miRNA pluripotentiality acts to buffer gene expression, while miRNA degeneracy tunes the expression of targets, thus providing robustness to gene expression networks. Furthermore, we propose a Lavallière-tie architecture by integrating signal transduction, miRNAs and protein expression data to model complex gene expression networks.     

RNA interference screen for human genes associated with West Nile virus infection

West Nile virus (WNV), and related flaviviruses such as tick-borne encephalitis, Japanese encephalitis, yellow fever and dengue viruses, constitute a significant global human health problem. However, our understanding of the molecular interaction of such flaviviruses with mammalian host cells is limited. WNV encodes only 10 proteins, implying that it may use many cellular proteins for infection. WNV enters the cytoplasm through pH-dependent endocytosis, undergoes cycles of translation and replication, assembles progeny virions in association with endoplasmic reticulum, and exits along the secretory pathway. RNA interference (RNAi) presents a powerful forward genetics approach to dissect virus-host cell interactions. Here we report the identification of 305 host proteins that affect WNV infection, using a human-genome-wide RNAi screen. Functional clustering of the genes revealed a complex dependence of this virus on host cell physiology, requiring a wide variety of molecules and cellular pathways for successful infection. We further demonstrate a requirement for the ubiquitin ligase CBLL1 in WNV internalization, a post-entry role for the endoplasmic-reticulum-associated degradation pathway in viral infection, and the monocarboxylic acid transporter MCT4 as a viral replication resistance factor. By extending this study to dengue virus, we show that flaviviruses have both overlapping and unique interaction strategies with host cells. This study provides a comprehensive molecular portrait of WNV-human cell interactions that forms a model for understanding single plus-stranded RNA virus infection, and reveals potential antiviral targets.     

Interference with AI-2-mediated bacterial cell-cell communication

Bacteria communicate by means of chemical signal molecules called autoinducers. This process, called quorum sensing, allows bacteria to count the members in the community and to alter gene expression synchronously across the population. Quorum-sensing-controlled processes are often crucial for successful bacterial--host relationships--both symbiotic and pathogenic. Most quorum-sensing autoinducers promote intraspecies communication, but one autoinducer, called AI-2, is produced and detected by a wide variety of bacteria and is proposed to allow interspecies communication. Here we show that some species of bacteria can manipulate AI-2 signalling and interfere with other species' ability to assess and respond correctly to changes in cell population density. AI-2 signalling, and the interference with it, could have important ramifications for eukaryotes in the maintenance of normal microflora and in protection from pathogenic bacteria.     

Fruit bats as reservoirs of Ebola virus

The first recorded human outbreak of Ebola virus was in 1976, but the wild reservoir of this virus is still unknown. Here we test for Ebola in more than a thousand small vertebrates that were collected during Ebola outbreaks in humans and great apes between 2001 and 2003 in Gabon and the Republic of the Congo. We find evidence of asymptomatic infection by Ebola virus in three species of fruit bat, indicating that these animals may be acting as a reservoir for this deadly virus.