167 research outputs found
Crustal architecture in Northern Mozambique : results from a regional bedrock mapping project [abstract]
Hypoxia Sensitive Metal Ξ²-Ketoiminate Complexes Showing Induced Single Strand DNA Breaks and Cancer Cell Death by Apoptosis
A series of ruthenium and iridium complexes have been synthesised and characterised with 20 novel crystal structures discussed. The library of Ξ²-ketoiminate complexes has been shown to be active against MCF-7 (human breast carcino-ma), HT-29 (human colon carcinoma), A2780 (human ovarian carcinoma) and A2780cis (cisplatin resistant human ovarian carcinoma) cell lines, with selected complexes being more than three times as active as cisplatin against the A2780cis cell line. Complexes have also been shown to be highly active under hypoxic conditions, with the activities of some complexes increasing with a decrease in O2 concentration. The enzyme thioredoxin reductase is over-expressed in cancer cells and complexes reported herein have the advantage of inhibiting this enzyme, with IC50 values measured in the nanomolar range. The anti-cancer activity of these complexes was further investigated to determine whether activity is due to effects on cellular growth or cell survival. The complexes were found to induce significant cancer cell death by apoptosis with levels induced correlating closely with activity in chemosensitivity studies. As a possible cause of cell death, the ability of the complexes to induce damage to cellular DNA was also assessed. The complexes failed to induce double strand DNA break or DNA crosslinking but induced significant levels of single DNA strand breaks indi-cating a different mechanism of action to cisplatin
Fossil woods (Coniferales) from the BaquerΓ³ Group (Aptian), Santa Cruz Province, Argentina
The sex locus is tightly linked to factors conferring sex-specific lethal effects in the mosquito Aedes aegypti
In many taxa, sex chromosomes are heteromorphic and largely non-recombining. Evolutionary models predict that spread of recombination suppression on the Y chromosome is fueled by the accumulation of sexually antagonistic alleles in close linkage to the sex determination region. However, empirical evidence for the existence of sexually antagonistic alleles is scarce. In the mosquito Aedes aegypti, the sex-determining chromosomes are homomorphic. The region of suppressed recombination, which surrounds the male-specific sex-determining gene, remains very small, despite ancient origin of the sex chromosomes in the Aedes lineage. We conducted a genetic analysis of the A. aegypti chromosome region tightly linked to the sex locus. We used a strain with an enhanced green fluorescent protein (EGFP)-tagged transgene inserted near the male-determining gene to monitor crossing-over events close to the boundary of the sex-determining region (SDR), and to trace the inheritance pattern of the transgene in relation to sex. In a series of crossing experiments involving individuals with a recombinant sex chromosome we found developmental abnormalities leading to 1:2 sex biases, caused by lethality of half of the male or female progeny. Our results suggest that various factors causing sex-specific lethal effects are clustered within the neighborhood of the SDR, which in the affected sex are likely lost or gained through recombination, leading to death. These may include genes that are recessive lethal, vital for development and/or sexually antagonistic. The sex chromosome fragment in question represents a fascinating test case for the analysis of processes that shape stable boundaries of a non-recombining region
Search for solar bosonic dark matter annual modulation with COSINE-100
We present results from a search for solar bosonic dark matter using the
annual modulation method with the COSINE-100 experiment. The results were
interpreted considering three dark sector bosons models: solar dark photon;
DFSZ and KSVZ solar axion; and Kaluza-Klein solar axion. No modulation signal
that is compatible with the expected from the models was found from a data-set
of 2.82 yr, using 61.3 kg of NaI(Tl) crystals. Therefore, we set a 90
confidence level upper limits for each of the three models studied. For the
solar dark photon model, the most stringent mixing parameter upper limit is
for dark photons with a mass of 215 eV. For the DFSZ and
KSVZ solar axion, and the Kaluza-Klein axion models, the upper limits exclude
axion-electron couplings, , above for axion mass
below 0.2 keV; and axion-photon couplings, , above GeV for an axion number density of cm. This is the first experimental search for solar dark
photons and DFSZ and KSVZ solar axions using the annual modulation method. The
lower background, higher light yield and reduced threshold of NaI(Tl) crystals
of the future COSINE-200 experiment are expected to enhance the sensitivity of
the analysis shown in this paper. We show the sensitivities for the three
models studied, considering the same search method with COSINE-200.Comment: 13 pages, 16 figure
Search for Boosted Dark Matter in COSINE-100
We search for energetic electron recoil signals induced by boosted dark
matter (BDM) from the galactic center using the COSINE-100 array of NaI(Tl)
crystal detectors at the Yangyang Underground Laboratory. The signal would be
an excess of events with energies above 4MeV over the well-understood
background. Because no excess of events are observed in a 97.7 kgyears
exposure, we set limits on BDM interactions under a variety of hypotheses.
Notably, we explored the dark photon parameter space, leading to competitive
limits compared to direct dark photon search experiments, particularly for dark
photon masses below 4MeV and considering the invisible decay mode. Furthermore,
by comparing our results with a previous BDM search conducted by the Super-
Kamionkande experiment, we found that the COSINE-100 detector has advantages in
searching for low-mass dark matter. This analysis demonstrates the potential of
the COSINE-100 detector to search for MeV electron recoil signals produced by
the dark sector particle interactions.Comment: 7 pages, 4 figure
sodC-Based Real-Time PCR for Detection of Neisseria meningitidis
Real-time PCR (rt-PCR) is a widely used molecular method for detection of
Neisseria meningitidis (Nm). Several rt-PCR assays for Nm
target the capsule transport gene, ctrA. However, over
16% of meningococcal carriage isolates lack ctrA,
rendering this target gene ineffective at identification of this sub-population
of meningococcal isolates. The Cu-Zn superoxide dismutase gene,
sodC, is found in Nm but not in other
Neisseria species. To better identify Nm, regardless of
capsule genotype or expression status, a sodC-based TaqMan
rt-PCR assay was developed and validated. Standard curves revealed an average
lower limit of detection of 73 genomes per reaction at cycle threshold
(Ct) value of 35, with 100% average reaction efficiency
and an average R2 of 0.9925. 99.7% (624/626) of Nm isolates
tested were sodC-positive, with a range of average
Ct values from 13.0 to 29.5. The mean sodC
Ct value of these Nm isolates was 17.6Β±2.2 (Β±SD).
Of the 626 Nm tested, 178 were nongroupable (NG) ctrA-negative
Nm isolates, and 98.9% (176/178) of these were detected by
sodC rt-PCR. The assay was 100% specific, with all
244 non-Nm isolates testing negative. Of 157 clinical specimens tested,
sodC detected 25/157 Nm or 4 additional specimens compared
to ctrA and 24 more than culture. Among 582 carriage specimens,
sodC detected Nm in 1 more than ctrA and
in 4 more than culture. This sodC rt-PCR assay is a highly
sensitive and specific method for detection of Nm, especially in carriage
studies where many meningococcal isolates lack capsule genes
Direct susceptibility testing by disk diffusion on clinical samples: a rapid and accurate tool for antibiotic stewardship
Identification of novel conserved peptide uORF homology groups in Arabidopsis and rice reveals ancient eukaryotic origin of select groups and preferential association with transcription factor-encoding genes
Abstract Background Upstream open reading frames (uORFs) can mediate translational control over the largest, or major ORF (mORF) in response to starvation, polyamine concentrations, and sucrose concentrations. One plant uORF with conserved peptide sequences has been shown to exert this control in an amino acid sequence-dependent manner but generally it is not clear what kinds of genes are regulated, or how extensively this mechanism is invoked in a given genome. Results By comparing full-length cDNA sequences from Arabidopsis and rice we identified 26 distinct homology groups of conserved peptide uORFs, only three of which have been reported previously. Pairwise Ka/Ks analysis showed that purifying selection had acted on nearly all conserved peptide uORFs and their associated mORFs. Functions of predicted mORF proteins could be inferred for 16 homology groups and many of these proteins appear to have a regulatory function, including 6 transcription factors, 5 signal transduction factors, 3 developmental signal molecules, a homolog of translation initiation factor eIF5, and a RING finger protein. Transcription factors are clearly overrepresented in this data set when compared to the frequency calculated for the entire genome (p = 1.2 Γ 10-7). Duplicate gene pairs arising from a whole genome duplication (ohnologs) with a conserved uORF are much more likely to have been retained in Arabidopsis (Arabidopsis thaliana) than are ohnologs of other genes (39% vs 14% of ancestral genes, p = 5 Γ 10-3). Two uORF groups were found in animals, indicating an ancient origin of these putative regulatory elements. Conclusion Conservation of uORF amino acid sequence, association with homologous mORFs over long evolutionary time periods, preferential retention after whole genome duplications, and preferential association with mORFs coding for transcription factors suggest that the conserved peptide uORFs identified in this study are strong candidates for translational controllers of regulatory genes.</p
Parvovirus Minute Virus of Mice Induces a DNA Damage Response That Facilitates Viral Replication
Infection by DNA viruses can elicit DNA damage responses (DDRs) in host cells. In some cases the DDR presents a block to viral replication that must be overcome, and in other cases the infecting agent exploits the DDR to facilitate replication. We find that low multiplicity infection with the autonomous parvovirus minute virus of mice (MVM) results in the activation of a DDR, characterized by the phosphorylation of H2AX, Nbs1, RPA32, Chk2 and p53. These proteins are recruited to MVM replication centers, where they co-localize with the main viral replication protein, NS1. The response is seen in both human and murine cell lines following infection with either the MVMp or MVMi strains. Replication of the virus is required for DNA damage signaling. Damage response proteins, including the ATM kinase, accumulate in viral-induced replication centers. Using mutant cell lines and specific kinase inhibitors, we show that ATM is the main transducer of the signaling events in the normal murine host. ATM inhibitors restrict MVM replication and ameliorate virus-induced cell cycle arrest, suggesting that DNA damage signaling facilitates virus replication, perhaps in part by promoting cell cycle arrest. Thus it appears that MVM exploits the cellular DNA damage response machinery early in infection to enhance its replication in host cells
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