1,115 research outputs found
Activation of mating type genes by transposition in Saccharomyces cerevisiae
Yeast Saccharomyces cerevisiae may express an a or alpha mating type. These cells types may be interconverted as a consequence of heritable genetic alteractions at the mating type locus (MAT). According to the more general controlling element model [Oshima, U. & Takano, I. (1971) Genetics 67, 327--335] and the specific cassette model [Hicks, J., Strathern, J. & Herskowitz, I. (1977) in DNA Insertion Elements, Plasmids and Episomes, eds. Bukhari, A. I., Shapiro, J.A. & Adhya, S. L.(Cold Spring Harbor Laboratory, Cold Spring Harbor, NY), pp. 457--462], the regulatory information required for switching the MAT locus exists at two other loosely linked loci, HMa and HMalpha. Specifically, the HMa and HMalpha loci are proposed to carry silent alpha and silent a genes, respectively. According to these models, switching occurs when a replica of a silent gene replaces the resident information at the mating type locus and is thereby expressed. These models predict that mutations at the silent ("storage") loci would generate defective MAT loci subsequent to the switching process. Therefore, the behavior of HMalpha mutants during the mating type interconversion was investigated. The results demonstrate that defective MATa alleles are generated by switching the MATalpha locus in HMalpha mutants. Thus, the genetic information from HMalpha is transposed to the mating type locus. These results provide genetic evidence in support of these models
Photoluminescence and photoluminescence excitation studies of lateral size effects in Zn_{1-x}Mn_xSe/ZnSe quantum disc samples of different radii
Quantum disc structures (with diameters of 200 nm and 100 nm) were prepared
from a Zn_{0.72}Mn_{0.28}Se/ZnSe single quantum well structure by electron beam
lithography followed by an etching procedure which combined dry and wet etching
techniques. The quantum disc structures and the parent structure were studied
by photoluminescence and photoluminescence excitation spectroscopy. For the
light-hole excitons in the quantum well region, shifts of the energy positions
are observed following fabrication of the discs, confirming that strain
relaxation occurs in the pillars. The light-hole exciton lines also sharpen
following disc fabrication: this is due to an interplay between strain effects
(related to dislocations) and the lateral size of the discs. A further
consequence of the small lateral sizes of the discs is that the intensity of
the donor-bound exciton emission from the disc is found to decrease with the
disc radius. These size-related effects occur before the disc radius is reduced
to dimensions necessary for lateral quantum confinement to occur but will
remain important when the discs are made small enough to be considered as
quantum dots.Comment: LaTeX2e, 13 pages, 6 figures (epsfig
Molecular mode of action and role of TP53 in the sensitivity to the novel epothilone sagopilone (ZK-EPO) in A549 non-small cell lung cancer cells
Sagopilone, an optimized fully synthetic epothilone, is a microtubule-stabilizing compound that has shown high in vitro and in vivo activity against a broad range of human tumor models. We analyzed the differential mechanism of action of sagopilone in non-small cell lung cancer cell lines in vitro. Sagopilone inhibited proliferation of non-small cell lung cancer cell lines at lower nanomolar concentration. The treatment with sagopilone caused strong disturbances of cellular cytoskeletal organization. Two concentration-dependent phenotypes were observed. At 2.5 nM sagopilone or 4 nM paclitaxel an aneuploid phenotype occur whereas a mitotic arrest phenotype was induced by 40 nM sagopilone or paclitaxel. Interestingly, treatment with 2.5 nM of sagopilone effectively inhibited cell proliferation, but - compared to high concentrations (40 nM) - only marginally induced apoptosis. Treatment with a high versus a low concentration of sagopilone or paclitaxel regulates a non-overlapping set of genes, indicating that both phenotypes substantially differ from each other. Genes involved in G2/M phase transition and the spindle assembly checkpoint, like Cyclin B1 and BUBR1 were upregulated by treatment with 40 nM sagopilone. Unexpectedly, also genes involved in DNA damage response were upregulated under that treatment. In contrast, treatment of A549 cells with a low concentration of sagopilone revealed an upregulation of direct transcriptional target genes of TP53, like CDKN1A, MDM2, GADD45A, FAS. Knockdown of TP53, which inhibited the transcriptional induction of TP53 target genes, led to a significant increase in apoptosis induction in A549 cells when treated with a low concentration of sagopilone. The results indicate that activation of TP53 and its downstream effectors like CDKN1A by low concentrations of sagopilone is responsible for the relative apoptosis resistance of A549 cells and might represent a mechanism of resistance to sagopilone
Comparison of Zn_{1-x}Mn_xTe/ZnTe multiple-quantum wells and quantum dots by below-bandgap photomodulated reflectivity
Large-area high density patterns of quantum dots with a diameter of 200 nm
have been prepared from a series of four Zn_{0.93}Mn_{0.07}Te/ZnTe multiple
quantum well structures of different well width (4 nm, 6 nm, 8 nm and 10 nm) by
electron beam lithography followed by Ar+ ion beam etching. Below-bandgap
photomodulated reflectivity spectra of the quantum dot samples and the parent
heterostructures were then recorded at 10 K and the spectra were fitted to
extract the linewidths and the energy positions of the excitonic transitions in
each sample. The fitted results are compared to calculations of the transition
energies in which the different strain states in the samples are taken into
account. We show that the main effect of the nanofabrication process is a
change in the strain state of the quantum dot samples compared to the parent
heterostructures. The quantum dot pillars turn out to be freestanding, whereas
the heterostructures are in a good approximation strained to the ZnTe lattice
constant. The lateral size of the dots is such that extra confinement effects
are not expected or observed.Comment: 23 pages, LaTeX2e (amsmath, epsfig), 7 EPS figure
Threshold Laws for the Break-up of Atomic Particles into Several Charged Fragments
The processes with three or more charged particles in the final state exhibit
particular threshold behavior, as inferred by the famous Wannier law for (2e +
ion) system. We formulate a general solution which determines the threshold
behavior of the cross section for multiple fragmentation. Applications to
several systems of particular importance with three, four and five leptons
(electrons and positrons) in the field of charged core; and two pairs of
identical particles with opposite charges are presented. New threshold
exponents for these systems are predicted, while some previously suggested
threshold laws are revised.Comment: 40 pages, Revtex, scheduled for the July issue of Phys.Rev.A (1998
Inclusion of additional studies yields different conclusions: Comment on Sedikides, Gaertner, & Vevea (2005), Journal of Personality and Social Psychology
Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/75100/1/j.1467-839X.2007.00211.x.pd
Identification of a novel type of spacer element required for imprinting in fission yeast
Asymmetrical segregation of differentiated sister chromatids is thought to be important for cellular differentiation in higher
eukaryotes. Similarly, in fission yeast, cellular differentiation involves the asymmetrical segregation of a chromosomal
imprint. This imprint has been shown to consist of two ribonucleotides that are incorporated into the DNA during laggingstrand
synthesis in response to a replication pause, but the underlying mechanism remains unknown. Here we present key
novel discoveries important for unravelling this process. Our data show that cis-acting sequences within the mat1 cassette
mediate pausing of replication forks at the proximity of the imprinting site, and the results suggest that this pause dictates
specific priming at the position of imprinting in a sequence-independent manner. Also, we identify a novel type of cis-acting
spacer region important for the imprinting process that affects where subsequent primers are put down after the
replication fork is released from the pause. Thus, our data suggest that the imprint is formed by ligation of a not-fullyprocessed
Okazaki fragment to the subsequent fragment. The presented work addresses how differentiated sister
chromatids are established during DNA replication through the involvement of replication barriers
Key Features Relevant to Select Antigens and TCR From the MHC-Mismatched Repertoire to Treat Cancer
Adoptive transfer of T cells transgenic for tumor-reactive T-cell receptors (TCR) is an attractive immunotherapeutic approach. However, clinical translation is so far limited due to challenges in the identification of suitable target antigens as well as TCRs that are concurrent safe and efficient. Definition of key characteristics relevant for effective and specific tumor rejection is essential to improve current TCR-based adoptive T-cell immunotherapies. We here characterized in-depth two TCRs derived from the human leukocyte antigen (HLA)-mismatched allogeneic repertoire targeting two different myeloperoxidase (MPO)-derived peptides presented by the same HLA-restriction element side by side comprising state of the art biochemical and cellular in vitro, in vivo, and in silico experiments. In vitro experiments reveal comparable functional avidities, off-rates, and cytotoxic activities for both TCRs. However, we observed differences especially with respect to cytokine secretion and cross-reactivity as well as in vivo activity. Biochemical and in silico analyses demonstrate different binding qualities of MPO-peptides to the HLA-complex determining TCR qualities. We conclude from our biochemical and in silico analyses of peptide-HLA-binding that rigid and high-affinity binding of peptides is one of the most important factors for isolation of TCRs with high specificity and tumor rejection capacity from the MHC-mismatched repertoire. Based on our results, we developed a workflow for selection of such TCRs with high potency and safety profile suitable for clinical translation
Oscillatory Size-Dependence of the Surface Plasmon Linewidth in Metallic Nanoparticles
We study the linewidth of the surface plasmon resonance in the optical
absorption spectrum of metallic nanoparticles, when the decay into
electron-hole pairs is the dominant channel. Within a semiclassical approach,
we find that the electron-hole density-density correlation oscillates as a
function of the size of the particles, leading to oscillations of the
linewidth. This result is confirmed numerically for alkali and noble metal
particles. While the linewidth can increase strongly, the oscillations persist
when the particles are embedded in a matrix.Comment: RevTeX4, 5 pages, 2 figures, final versio
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