265 research outputs found
Theory of dynamic crack branching in brittle materials
The problem of dynamic symmetric branching of an initial single brittle crack
propagating at a given speed under plane loading conditions is studied within a
continuum mechanics approach. Griffith's energy criterion and the principle of
local symmetry are used to determine the cracks paths. The bifurcation is
predicted at a given critical speed and at a specific branching angle: both
correlated very well with experiments. The curvature of the subsequent branches
is also studied: the sign of , with being the non singular stress at the
initial crack tip, separates branches paths that diverge from or converge to
the initial path, a feature that may be tested in future experiments. The model
rests on a scenario of crack branching with some reasonable assumptions based
on general considerations and in exact dynamic results for anti-plane
branching. It is argued that it is possible to use a static analysis of the
crack bifurcation for plane loading as a good approximation to the dynamical
case. The results are interesting since they explain within a continuum
mechanics approach the main features of the branching instabilities of fast
cracks in brittle materials, i.e. critical speeds, branching angle and the
geometry of subsequent branches paths.Comment: 41 pages, 15 figures. Accepted to International Journal of Fractur
Radio Emission from Ultra-Cool Dwarfs
The 2001 discovery of radio emission from ultra-cool dwarfs (UCDs), the very
low-mass stars and brown dwarfs with spectral types of ~M7 and later, revealed
that these objects can generate and dissipate powerful magnetic fields. Radio
observations provide unparalleled insight into UCD magnetism: detections extend
to brown dwarfs with temperatures <1000 K, where no other observational probes
are effective. The data reveal that UCDs can generate strong (kG) fields,
sometimes with a stable dipolar structure; that they can produce and retain
nonthermal plasmas with electron acceleration extending to MeV energies; and
that they can drive auroral current systems resulting in significant
atmospheric energy deposition and powerful, coherent radio bursts. Still to be
understood are the underlying dynamo processes, the precise means by which
particles are accelerated around these objects, the observed diversity of
magnetic phenomenologies, and how all of these factors change as the mass of
the central object approaches that of Jupiter. The answers to these questions
are doubly important because UCDs are both potential exoplanet hosts, as in the
TRAPPIST-1 system, and analogues of extrasolar giant planets themselves.Comment: 19 pages; submitted chapter to the Handbook of Exoplanets, eds. Hans
J. Deeg and Juan Antonio Belmonte (Springer-Verlag
Meiosis-Specific Loading of the Centromere-Specific Histone CENH3 in Arabidopsis thaliana
Centromere behavior is specialized in meiosis I, so that sister chromatids of homologous chromosomes are pulled toward the same side of the spindle (through kinetochore mono-orientation) and chromosome number is reduced. Factors required for mono-orientation have been identified in yeast. However, comparatively little is known about how meiotic centromere behavior is specialized in animals and plants that typically have large tandem repeat centromeres. Kinetochores are nucleated by the centromere-specific histone CENH3. Unlike conventional histone H3s, CENH3 is rapidly evolving, particularly in its N-terminal tail domain. Here we describe chimeric variants of CENH3 with alterations in the N-terminal tail that are specifically defective in meiosis. Arabidopsis thaliana cenh3 mutants expressing a GFP-tagged chimeric protein containing the H3 N-terminal tail and the CENH3 C-terminus (termed GFP-tailswap) are sterile because of random meiotic chromosome segregation. These defects result from the specific depletion of GFP-tailswap protein from meiotic kinetochores, which contrasts with its normal localization in mitotic cells. Loss of the GFP-tailswap CENH3 variant in meiosis affects recruitment of the essential kinetochore protein MIS12. Our findings suggest that CENH3 loading dynamics might be regulated differently in mitosis and meiosis. As further support for our hypothesis, we show that GFP-tailswap protein is recruited back to centromeres in a subset of pollen grains in GFP-tailswap once they resume haploid mitosis. Meiotic recruitment of the GFP-tailswap CENH3 variant is not restored by removal of the meiosis-specific cohesin subunit REC8. Our results reveal the existence of a specialized loading pathway for CENH3 during meiosis that is likely to involve the hypervariable N-terminal tail. Meiosis-specific CENH3 dynamics may play a role in modulating meiotic centromere behavior
Expansion and functional diversification of a leucyl aminopeptidase family that encodes the major protein constituents of Drosophila sperm
<p>Abstract</p> <p>Background</p> <p>The evolutionary diversification of gene families through gene creation (and loss) is a dynamic process believed to be critical to the evolution of functional novelty. Previous identification of a closely related family of eight annotated metalloprotease genes of the M17 Merops family in the <it>Drosophila </it>sperm proteome (termed, Sperm-LeucylAminoPeptidases, S-LAPs 1-8) led us to hypothesize that this gene family may have experienced such a diversification during insect evolution.</p> <p>Results</p> <p>To assess putative functional activities of S-LAPs, we (i) demonstrated that all S-LAPs are specifically expressed in the testis, (ii) confirmed their presence in sperm by two-dimensional gel electrophoresis and mass spectrometry, (iii) determined that they represent a major portion of the total protein in sperm and (iv) identified aminopeptidase enzymatic activity in sperm extracts using LAP-specific substrates. Functionally significant divergence at the canonical M17 active site indicates that the largest phylogenetic group of S-LAPs lost catalytic activity and likely acquired novel, as yet undetermined, functions in sperm prior to the expansion of the gene family.</p> <p>Conclusions</p> <p>Comparative genomic and phylogenetic analyses revealed the dramatic expansion of the S-LAP gene family during <it>Drosophila </it>evolution and copy number heterogeneity in the genomes of related insects. This finding, in conjunction with the loss of catalytic activity and potential neofunctionalization amongst some family members, extends empirical support for pervasive "revolving door" turnover in the evolution of reproductive gene family composition and function.</p
Monitoring the Long-Term Molecular Epidemiology of the Pneumococcus and Detection of Potential βVaccine Escapeβ Strains
While the pneumococcal protein conjugate vaccines reduce the incidence in invasive pneumococcal disease (IPD), serotype replacement remains a major concern. Thus, serotype-independent protection with vaccines targeting virulence genes, such as PspA, have been pursued. PspA is comprised of diverse clades that arose through recombination. Therefore, multi-locus sequence typing (MLST)-defined clones could conceivably include strains from multiple PspA clades. As a result, a method is needed which can both monitor the long-term epidemiology of the pneumococcus among a large number of isolates, and analyze vaccine-candidate genes, such as pspA, for mutations and recombination events that could result in 'vaccine escape' strains.We developed a resequencing array consisting of five conserved and six variable genes to characterize 72 pneumococcal strains. The phylogenetic analysis of the 11 concatenated genes was performed with the MrBayes program, the single nucleotide polymorphism (SNP) analysis with the DNA Sequence Polymorphism program (DnaSP), and the recombination event analysis with the recombination detection package (RDP).The phylogenetic analysis correlated with MLST, and identified clonal strains with unique PspA clades. The DnaSP analysis correlated with the serotype-specific diversity detected using MLST. Serotypes associated with more than one ST complex had a larger degree of sequence polymorphism than a serotype associated with one ST complex. The RDP analysis confirmed the high frequency of recombination events in the pspA gene.The phylogenetic tree correlated with MLST, and detected multiple PspA clades among clonal strains. The genetic diversity of the strains and the frequency of recombination events in the mosaic gene, pspA were accurately assessed using the DnaSP and RDP programs, respectively. These data provide proof-of-concept that resequencing arrays could play an important role within research and clinical laboratories in both monitoring the molecular epidemiology of the pneumococcus and detecting 'vaccine escape' strains among vaccine-candidate genes
Inhibition of Casein kinase-2 induces p53-dependent cell cycle arrest and sensitizes glioblastoma cells to tumor necrosis factor (TNFΞ±)-induced apoptosis through SIRT1 inhibition
Glioblastoma multiforme (GBM) are resistant to TNFΞ±-induced apoptosis and blockade of TNFΞ±-induced NF-ΞΊB activation sensitizes glioma cells to apoptosis. As Casein kinase-2 (CK2) induces aberrant NF-ΞΊB activation and as we observed elevated CK2 levels in GBM tumors, we investigated the potential of CK2 inhibitors (CK2-Is) - DRB and Apigenin in sensitizing glioma cells to TNFΞ±-induced apoptosis. CK2-Is and CK2 small interfering RNA (siRNA) reduced glioma cell viability, inhibited TNFΞ±-mediated NF-ΞΊB activation, and sensitized cell to TNFΞ±-induced apoptosis. Importantly, CK2-Is activated p53 function in wild-type but not in p53 mutant cells. Activation of p53 function involved its increased transcriptional activation, DNA-binding ability, increased expression of p53 target genes associated with cell cycle progression and apoptosis. Moreover, CK2-Is decreased telomerase activity and increased senescence in a p53-dependent manner. Apoptotic gene profiling indicated that CK2-Is differentially affect p53 and TNFΞ± targets in p53 wild-type and mutant glioma cells. CK2-I decreased MDM2-p53 association and p53 ubiquitination to enhance p53 levels. Interestingly, CK2-Is downregulated SIRT1 activity and over-expression of SIRT1 decreased p53 transcriptional activity and rescued cells from CK2-I-induced apoptosis. This ability of CK2-Is to sensitize glioma to TNFΞ±-induced death via multiple mechanisms involving abrogation of NF-ΞΊB activation, reactivation of wild-type p53 function and SIRT1 inhibition warrants investigation
Female responses to experimental removal of sexual selection components in Drosophila melanogaster
Despite the common assumption that multiple mating should in general be favored in males, but not in females, to date there is no consensus on the general impact of multiple mating on female fitness. Notably, very little is known about the genetic and physiological features underlying the female response to sexual selection pressures. By combining an experimental evolution approach with genomic techniques, we investigated the effects of single and multiple matings on female fecundity and gene expression. We experimentally manipulated the opportunity for mating in replicate populations of Drosophila melanogaster by removing components of sexual selection, with the aim of testing differences in short term post-mating effects of females evolved under different mating strategies
Microarray-Based Analysis of Differential Gene Expression between Infective and Noninfective Larvae of Strongyloides stercoralis
Strongyloides stercoralis is a soil-transmitted helminth that
affects an estimated 30β100 million people worldwide. Chronically infected
persons who are exposed to corticosteroids can develop disseminated disease, which
carries a high mortality (87β100%) if untreated. Despite this, little is
known about the fundamental biology of this parasite, including the features that
enable infection. We developed the first DNA microarray for this parasite and used it
to compare infective third-stage larvae (L3i) with non-infective first stage larvae
(L1). Using this method, we identified 935 differentially expressed genes. Functional
characterization of these genes revealed L3i biased expression of heat shock proteins
and genes with products that have previously been shown to be immunoreactive in
infected humans. Genes putatively involved in transcription were found to have L1
biased expression. Potential chemotherapeutic and vaccine targets such as
far-1, ucr 2.1 and hsp-90 were
identified for further study
A Switching Mechanism in Doxorubicin Bioactivation Can Be Exploited to Control Doxorubicin Toxicity
Although doxorubicin toxicity in cancer cells is multifactorial, the enzymatic bioactivation of the drug can significantly contribute to its cytotoxicity. Previous research has identified most of the components that comprise the doxorubicin bioactivation network; however, adaptation of the network to changes in doxorubicin treatment or to patient-specific changes in network components is much less understood. To investigate the properties of the coupled reduction/oxidation reactions of the doxorubicin bioactivation network, we analyzed metabolic differences between two patient-derived acute lymphoblastic leukemia (ALL) cell lines exhibiting varied doxorubicin sensitivities. We developed computational models that accurately predicted doxorubicin bioactivation in both ALL cell lines at high and low doxorubicin concentrations. Oxygen-dependent redox cycling promoted superoxide accumulation while NADPH-dependent reductive conversion promoted semiquinone doxorubicin. This fundamental switch in control is observed between doxorubicin sensitive and insensitive ALL cells and between high and low doxorubicin concentrations. We demonstrate that pharmacological intervention strategies can be employed to either enhance or impede doxorubicin cytotoxicity in ALL cells due to the switching that occurs between oxygen-dependent superoxide generation and NADPH-dependent doxorubicin semiquinone formation
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