Three-dimensional jamming and flows of soft glassy materials

Various disordered dense systems such as foams, gels, emulsions and colloidal suspensions, exhibit a jamming transition from a liquid state (they flow) to a solid state below a yield stress. Their structure, thoroughly studied with powerful means of 3D characterization, exhibits some analogy with that of glasses which led to call them soft glassy materials. However, despite its importance for geophysical and industrial applications, their rheological behavior, and its microscopic origin, is still poorly known, in particular because of its nonlinear nature. Here we show from two original experiments that a simple 3D continuum description of the behaviour of soft glassy materials can be built. We first show that when a flow is imposed in some direction there is no yield resistance to a secondary flow: these systems are always unjammed simultaneously in all directions of space. The 3D jamming criterion appears to be the plasticity criterion encountered in most solids. We also find that they behave as simple liquids in the direction orthogonal to that of the main flow; their viscosity is inversely proportional to the main flow shear rate, as a signature of shear-induced structural relaxation, in close similarity with the structural relaxations driven by temperature and density in other glassy systems.Comment: http://www.nature.com/nmat/journal/v9/n2/abs/nmat2615.htm

From Plant Based Therapy to Plant-Derived Vesicle-Like Nanoparticles for Cancer Treatment: Past, Present and Future

Ye An,* Jian-Xuan Sun,* Si-Yang Ma,* Meng-Yao Xu, Jin-Zhou Xu, Chen-Qian Liu, Shao-Gang Wang, Qi-Dong Xia Department and Institute of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China*These authors contributed equally to this workCorrespondence: Shao-Gang Wang; Qi-Dong Xia, Department and Institute of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China, Tel +86 027 83663460, Email [email protected]; [email protected]: Cancer stands as a formidable malady profoundly impacting human health. Throughout history, plant-based therapies have remained pivotal in the arsenal against cancer, evolving alongside the epochs. Presently, challenges such as the arduous extraction of active components and potential safety concerns impede the progression of plant-based anticancer therapies. The isolation of plant-derived vesicle-like nanoparticles (PDVLNs), a kind of lipid bilayer capsules isolated from plants, has brought plant-based anticancer therapy into a novel realm and has led to decades of research on PDVLNs. Accumulating evidence indicates that PDVLNs can deliver plant-derived active substances to human cells and regulate cellular functions. Regulating immunity, inducing cell cycle arrest, and promoting apoptosis in cancer cells are the most commonly reported mechanisms of PDVLNs in tumor suppression. Low immunogenicity and lack of tumorigenicity make PDVLNs a good platform for drug delivery. The molecules within the PDVLNs are all from source plants, so the selection of source plants is crucial. In recent years, there has been a clear trend that the source plants have changed from vegetables or fruits to medicinal plants. This review highlights the mechanisms of medicinal plant-based cancer therapies to identify candidate source plants. More importantly, the current research on PDVLN-based cancer therapy and the applications of PDVLNs for drug delivery are systematically discussed. Keywords: plant-derived vesicle-like nanoparticles, plant-based anticancer therapy, drug delivery system, anticance

Differential Deployment of REST and CoREST Promotes Glial Subtype Specification and Oligodendrocyte Lineage Maturation

The repressor element-1 (RE1) silencing transcription factor/neuron-restrictive silencer factor (REST/NRSF) is a master transcriptional regulator that binds to numerous genomic RE1 sites where it acts as a molecular scaffold for dynamic recruitment of modulatory and epigenetic cofactors, including corepressor for element-1-silencing transcription factor (CoREST). CoREST also acts as a hub for various cofactors that play important roles in epigenetic remodeling and transcriptional regulation. While REST can recruit CoREST to its macromolecular complex, CoREST complexes also function at genomic sites independently of REST. REST and CoREST perform a broad array of context-specific functions, which include repression of neuronal differentiation genes in neural stem cells (NSCs) and other non-neuronal cells as well as promotion of neurogenesis. Despite their involvement in multiple aspects of neuronal development, REST and CoREST are not believed to have any direct modulatory roles in glial cell maturation.We challenged this view by performing the first study of REST and CoREST in NSC-mediated glial lineage specification and differentiation. Utilizing ChIP on chip (ChIP-chip) assays, we identified distinct but overlapping developmental stage-specific profiles for REST and CoREST target genes during astrocyte (AS) and oligodendrocyte (OL) lineage specification and OL lineage maturation and myelination, including many genes not previously implicated in glial cell biology or linked to REST and CoREST regulation. Amongst these factors are those implicated in macroglial (AS and OL) cell identity, maturation, and maintenance, such as members of key developmental signaling pathways and combinatorial transcription factor codes.Our results imply that REST and CoREST modulate not only neuronal but also glial lineage elaboration. These factors may therefore mediate critical developmental processes including the coupling of neurogenesis and gliogenesis and neuronal-glial interactions that underlie synaptic and neural network plasticity and homeostasis in health and in specific neurological disease states

Internal Transcribed Spacer 2 (nu ITS2 rRNA) Sequence-Structure Phylogenetics: Towards an Automated Reconstruction of the Green Algal Tree of Life

L). Some have advocated the use of the nuclear-encoded, internal transcribed spacer two (ITS2) as an alternative to the traditional chloroplast markers. However, the ITS2 is broadly perceived to be insufficiently conserved or to be confounded by introgression or biparental inheritance patterns, precluding its broad use in phylogenetic reconstruction or as a DNA barcode. A growing body of evidence has shown that simultaneous analysis of nucleotide data with secondary structure information can overcome at least some of the limitations of ITS2. The goal of this investigation was to assess the feasibility of an automated, sequence-structure approach for analysis of IT2 data from a large sampling of phylum Chlorophyta.Sequences and secondary structures from 591 chlorophycean, 741 trebouxiophycean and 938 ulvophycean algae, all obtained from the ITS2 Database, were aligned using a sequence structure-specific scoring matrix. Phylogenetic relationships were reconstructed by Profile Neighbor-Joining coupled with a sequence structure-specific, general time reversible substitution model. Results from analyses of the ITS2 data were robust at multiple nodes and showed considerable congruence with results from published phylogenetic analyses.Our observations on the power of automated, sequence-structure analyses of ITS2 to reconstruct phylum-level phylogenies of the green algae validate this approach to assessing diversity for large sets of chlorophytan taxa. Moreover, our results indicate that objections to the use of ITS2 for DNA barcoding should be weighed against the utility of an automated, data analysis approach with demonstrated power to reconstruct evolutionary patterns for highly divergent lineages

Risk of cancer-specific, cardiovascular, and all-cause mortality among Asian and Pacific Islander breast cancer survivors in the United States, 1991–2011

Asian and Pacific Islander (API) women in the United States (U.S.) are a heterogeneous group reported to have better prognosis after breast cancer (BC) compared to their Non-Hispanic White (NHW) counterparts. Few studies have examined differences in BC survival between individual API ethnic groups. We conducted a retrospective cohort study of 462,005 NHW and 44,531 API women diagnosed with incident, stage I–III BC between 1991 and 2011 in the Surveillance, Epidemiology and End Results (SEER) 18 registries. SEER-reported API ethnicity was grouped as Chinese, Japanese, Filipino, Hawaiian, Korean, Vietnamese, Asian Indian and Pakistani, and Pacific Islander. Multivariable Cox proportional hazards models were used to estimate hazard ratios (HR) and 95 % confidence intervals (CI) for risk of BC-specific, cardiovascular and all-cause mortality comparing API to NHW women. We also estimated mortality risk comparing U.S.-born to non-U.S.-born women. Compared to NHW women, API women overall had lower BC-specific, cardiovascular and all-cause mortality. BC-specific mortality risk was lowest among Japanese women (HR 0.69, 95 % CI 0.63–0.77). Other women had similar (Filipino, HR 0.93, 0.86–1.00; Hawaiian, HR 1.01, 0.89–1.17) or greater (Pacific Islander, HR 1.44, 1.17–1.78) risk of BC-specific death. Compared to non-U.S. born API women, findings were suggestive of increased cardiovascular (HR 1.12, 1.03–1.20) and all-cause mortality (HR 1.29, 1.08–1.54) among U.S.-born API women. Mortality risk varies greatly between BC survivors from different API backgrounds. Further research is warranted to understand these disparities in BC survivorship and the social and cultural factors that possibly contribute to greater mortality among later-generation API women born in the United States

Pan-cancer analysis of whole genomes

Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale(1-3). Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4-5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter(4); identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation(5,6); analyses timings and patterns of tumour evolution(7); describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity(8,9); and evaluates a range of more-specialized features of cancer genomes(8,10-18).Peer reviewe