289 research outputs found
Spread Supersymmetry
In the multiverse the scale of SUSY breaking, \tilde{m} = F_X/M_*, may scan
and environmental constraints on the dark matter density may exclude a large
range of \tilde{m} from the reheating temperature after inflation down to
values that yield a LSP mass of order a TeV. After selection effects, the
distribution for \tilde{m} may prefer larger values. A single environmental
constraint from dark matter can then lead to multi-component dark matter,
including both axions and the LSP, giving a TeV-scale LSP lighter than the
corresponding value for single-component LSP dark matter.
If SUSY breaking is mediated to the SM sector at order X^* X, only squarks,
sleptons and one Higgs doublet acquire masses of order \tilde{m}. The gravitino
mass is lighter by a factor of M_*/M_Pl and the gaugino masses are suppressed
by a further loop factor. This Spread SUSY spectrum has two versions; the
Higgsino masses are generated in one from supergravity giving a wino LSP and in
the other radiatively giving a Higgsino LSP. The environmental restriction on
dark matter fixes the LSP mass to the TeV domain, so that the squark and
slepton masses are order 10^3 TeV and 10^6 TeV in these two schemes. We study
the spectrum, dark matter and collider signals of these two versions of Spread
SUSY. The Higgs is SM-like and lighter than 145 GeV; monochromatic photons in
cosmic rays arise from dark matter annihilations in the halo; exotic short
charged tracks occur at the LHC, at least for the wino LSP; and there are the
eventual possibilities of direct detection of dark matter and detailed
exploration of the TeV-scale states at a future linear collider. Gauge coupling
unification is as in minimal SUSY theories.
If SUSY breaking is mediated at order X, a much less hierarchical spectrum
results---similar to that of the MSSM, but with the superpartner masses 1--2
orders of magnitude larger than in natural theories.Comment: 20 pages, 5 figure
Ochratoxin A and citrinin loads in stored wheat grains: Impact of grain dust and possible prediction using ergosterol measurement
Horizontal Transfer of a Nitrate Assimilation Gene Cluster and Ecological Transitions in Fungi: A Phylogenetic Study
High affinity nitrate assimilation genes in fungi occur in a cluster (fHANT-AC) that can be coordinately regulated. The clustered genes include nrt2, which codes for a high affinity nitrate transporter; euknr, which codes for nitrate reductase; and NAD(P)H-nir, which codes for nitrite reductase. Homologs of genes in the fHANT-AC occur in other eukaryotes and prokaryotes, but they have only been found clustered in the oomycete Phytophthora (heterokonts). We performed independent and concatenated phylogenetic analyses of homologs of all three genes in the fHANT-AC. Phylogenetic analyses limited to fungal sequences suggest that the fHANT-AC has been transferred horizontally from a basidiomycete (mushrooms and smuts) to an ancestor of the ascomycetous mold Trichoderma reesei. Phylogenetic analyses of sequences from diverse eukaryotes and eubacteria, and cluster structure, are consistent with a hypothesis that the fHANT-AC was assembled in a lineage leading to the oomycetes and was subsequently transferred to the Dikarya (Ascomycota+Basidiomycota), which is a derived fungal clade that includes the vast majority of terrestrial fungi. We propose that the acquisition of high affinity nitrate assimilation contributed to the success of Dikarya on land by allowing exploitation of nitrate in aerobic soils, and the subsequent transfer of a complete assimilation cluster improved the fitness of T. reesei in a new niche. Horizontal transmission of this cluster of functionally integrated genes supports the βselfish operonβ hypothesis for maintenance of gene clusters
Anticancer activity of a sub-fraction of dichloromethane extract of Strobilanthes crispus on human breast and prostate cancer cells in vitro
<p>Abstract</p> <p>Background</p> <p>The leaves of <it>Strobilanthes crispus </it>(<it>S. crispus</it>) which is native to the regions of Madagascar to the Malay Archipelago, are used in folk medicine for their antidiabetic, diuretic, anticancer and blood pressure lowering properties. Crude extracts of this plant have been found to be cytotoxic to human cancer cell lines and protective against chemically-induced hepatocarcinogenesis in rats. In this study, the cytotoxicity of various sub-fractions of dichloromethane extract isolated from the leaves of <it>S. crispus </it>was determined and the anticancer activity of one of the bioactive sub-fractions, SC/D-F9, was further analysed in breast and prostate cancer cell lines.</p> <p>Methods</p> <p>The dichloromethane extract of <it>S. crispus </it>was chromatographed on silica gel by flash column chromatography. The ability of the various sub-fractions obtained to induce cell death of MCF-7, MDA-MB-231, PC-3 and DU-145 cell lines was determined using the LDH assay. The dose-response effect and the EC<sub>50 </sub>values of the active sub-fraction, SC/D-F9, were determined. Apoptosis was detected using Annexin V antibody and propidium iodide staining and analysed by fluorescence microscopy and flow cytometry, while caspase 3/7 activity was detected using FLICA caspase inhibitor and analysed by fluorescence microscopy.</p> <p>Results</p> <p>Selected sub-fractions of the dichloromethane extract induced death of MCF-7, MDA-MB-231, PC-3 and DU-145 cells. The sub-fraction SC/D-F9, consistently killed breast and prostate cancer cell lines with low EC<sub>50 </sub>values but is non-cytotoxic to the normal breast epithelial cell line, MCF-10A. SC/D-F9 displayed relatively higher cytotoxicity compared to tamoxifen, paclitaxel, docetaxel and doxorubicin. Cell death induced by SC/D-F9 occurred via apoptosis with the involvement of caspase 3 and/or 7.</p> <p>Conclusions</p> <p>A dichloromethane sub-fraction of <it>S. crispus </it>displayed potent anticancer activities <it>in vitro </it>that can be further exploited for the development of a potential therapeutic anticancer agent.</p
Three endo-Ξ²-mannanase genes expressed in the micropylar endosperm and in the radicle influence germination of Arabidopsis thaliana seeds
Mannans are hemicellulosic polysaccharides in the plant primary cell wall (CW). Mature seeds, specially their endosperm cells, have CWs rich in mannan-based polymers that confer a strong mechanical resistance for the radicle protrusion upon germination. The rupture of the seed coat and endosperm are two sequential events during the germination of Arabidopsis thaliana. Endo-Ξ²-mannanases (MAN; EC. 3.2.1.78) are hydrolytic enzymes that catalyze cleavage of Ξ²1 β 4 bonds in the mannan-polymer. In the genome of Arabidopsis, the endo-Ξ²-mannanase (MAN) family is represented by eight members. The expression of these eight MAN genes has been systematically explored in different organs of this plant and only four of them (AtMAN7, AtMAN6, AtMAN2 and AtMAN5) are expressed in the germinating seeds. Moreover, in situ hybridization analysis shows that their transcript accumulation is restricted to the micropylar endosperm and to the radicle and this expression disappears soon after radicle emergence. T-DNA insertion mutants in these genes (K.O. MAN7, K.O. MAN6, K.O. MAN5), except that corresponding to AtMAN2 (K.O. MAN2), germinate later than the wild type (Wt). K.O. MAN6 is the most affected in the germination time course with a t 50 almost double than that of the Wt. These data suggest that AtMAN7, AtMAN5 and specially AtMAN6 are important for the germination of A. thaliana seeds by facilitating the hydrolysis of the mannan-rich endosperm cell walls
Identification and genome characterization of genotype B and genotype C bovine parainfluenza type 3 viruses isolated in the United States
BACKGROUND: Bovine parainfluenza 3 viruses (BPI3V) are respiratory pathogens of cattle that cause disease singly but are often associated with bovine respiratory disease complex (BRDC) in conjunction with other viral and bacterial agents. Bovine vaccines currently contain BPI3V to provide protection against the virus, but there is no current information regarding the BPI3V strains that are circulating in the U.S. RESULTS: A project was initiated to sequence archival BPI3V isolates to study viral evolution over time. This was done with a deep sequencing protocol that generated sequences of multiple RNA virus genomes simultaneously. Analysis of the BPI3V sequences revealed that, in addition to the genotype A (BPI3Va) viruses previously described in the United States, there were two additional genotypes of BPI3V circulating that had been described only in Australia (BPI3Vb) and Asia (BPI3Vc). The U.S. BPI3Vb and BPI3Vc isolates showed some divergence from the Australian and Asian strains; the BPI3Vb were 93Β % similar to the Australian Q5592 strain and the BPI3Vc viruses were 98Β % similar to the 12Q061 strain that was described in South Korea. Overall, the three genotypes were 82 to 84Β % identical to each other and 80Β % identical to the most similar human PI3V. Cross-neutralization studies using an APHIS/NVSL BPI3V reference serum showed that neutralization titers against the genotype B and C viruses were 4- to β₯16-fold less then the titer against the APHIS BPI3Va reference strain, SF-4. CONCLUSIONS: This study clearly demonstrated that BPI3Vb and BPI3Vc strains, previously thought to be foreign to the U.S., are indeed circulating in domestic livestock herds. Based on virus neutralization using polyclonal antisera, there were antigenic differences between viruses from these genotypes and the BPI3Va viruses that are included in currently marketed bovine vaccines. Further study of these viruses is warranted to determine pathogenic potential and cross-protection afforded by vaccination
Tissue distribution of residual antimony in rats treated with multiple doses of meglumine antimoniate
Cellular uptake, cytotoxicity and DNA-binding studies of the novel imidazoacridinone antineoplastic agent C1311
C1311 is a novel therapeutic agent with potent activity against experimental colorectal cancer that has been selected for entry into clinical trial. The compound has previously been shown to have DNA-binding properties and to inhibit the catalytic activity of topoisomerase II. In this study, cellular uptake and mechanisms by which C1311 interacts with DNA and exerts cytotoxic effects in intact colon carcinoma cells were investigated. The HT29 colon cancer cell line was chosen to follow cellular distribution of C1311 over a time course of 24 h at drug concentrations that just inhibited cell proliferation by 50% or 100%. Nuclear uptake of C1311 and co-localization with lysosomal or mitochondrial dyes was examined by fluorescence microscopy and effects on these cellular compartments were determined by measurement of acid phosphatase levels, rhodamine 123 release or DNA-binding behaviour. The strength and mode of DNA binding was established by thermal melting stabilization, direct titration and viscometric studies of host duplex length. The onset of apoptosis was followed using a TUNEL assay and DNA-fragmentation to determine a causal relationship of cell death. Growth inhibition of HT29 cells by C1311 was concomitant with rapid drug accumulation in nuclei and in this context we showed that the compound binds to duplex DNA by intercalation, with likely A/T sequence-preferential binding. Drug uptake was also seen in lysosomes, leading to lysosomal rupture and a marked increase of acid phosphatase activity 8 h after exposure to C1311 concentrations that effect total growth inhibition. Moreover, at these concentrations lysosomal swelling and breakdown preceded apoptosis, which was not evident up to 24 h after exposure to drug. Thus, the lysosomotropic effect of C1311 appears to be a novel feature of this anticancer agent. As it is unlikely that C1311-induced DNA damage alone would be sufficient for cytotoxic activity, lysosomal rupture may be a critical component for therapeutic efficacy. Β© 1999 Cancer Research Campaig
Mutualism and Adaptive Divergence: Co-Invasion of a Heterogeneous Grassland by an Exotic Legume-Rhizobium Symbiosis
Species interactions play a critical role in biological invasions. For example, exotic plant and microbe mutualists can facilitate each other's spread as they co-invade novel ranges. Environmental context may influence the effect of mutualisms on invasions in heterogeneous environments, however these effects are poorly understood. We examined the mutualism between the legume, Medicago polymorpha, and the rhizobium, Ensifer medicae, which have both invaded California grasslands. Many of these invaded grasslands are composed of a patchwork of harsh serpentine and relatively benign non-serpentine soils. We grew legume genotypes collected from serpentine or non-serpentine soil in both types of soil in combination with rhizobium genotypes from serpentine or non-serpentine soils and in the absence of rhizobia. Legumes invested more strongly in the mutualism in the home soil type and trends in fitness suggested that this ecotypic divergence was adaptive. Serpentine legumes had greater allocation to symbiotic root nodules in serpentine soil than did non-serpentine legumes and non-serpentine legumes had greater allocation to nodules in non-serpentine soil than did serpentine legumes. Therefore, this invasive legume has undergone the rapid evolution of divergence for soil-specific investment in the mutualism. Contrary to theoretical expectations, the mutualism was less beneficial for legumes grown on the stressful serpentine soil than on the non-serpentine soil, possibly due to the inhibitory effects of serpentine on the benefits derived from the interaction. The soil-specific ability to allocate to a robust microbial mutualism may be a critical, and previously overlooked, adaptation for plants adapting to heterogeneous environments during invasion
Extracorporeal Membrane Oxygenation for Acute Pediatric Respiratory Failure
This article is made available for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.The use of extracorporeal membrane oxygenation (ECMO) to support children with acute respiratory failure has steadily increased over the past several decades, with major advancements having been made in the care of these children. There are, however, many controversies regarding indications for initiating ECMO in this setting and the appropriate management strategies thereafter. Broad indications for ECMO include hypoxia, hypercarbia, and severe air leak syndrome, with hypoxia being the most common. There are many disease-specific considerations when evaluating children for ECMO, but there are currently very few, if any, absolute contraindications. Venovenous rather than veno-arterial ECMO cannulation is the preferred configuration for ECMO support of acute respiratory failure due to its superior side-effect profile. The approach to lung management on ECMO is variable and should be individualized to the patient, with the main goal of reducing the risk of VILI. ECMO is a relatively rare intervention, and there are likely a minimum number of cases per year at a given center to maintain competency. Patients who have prolonged ECMO runs (i.e., greater than 21 days) are less likely to survive, though no absolute duration of ECMO that would mandate withdrawal of ECMO support can be currently recommended
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