2,476 research outputs found
SPT5 affects the rate of mRNA degradation and physically interacts with CCR4 but does not control mRNA deadenylation
The CCR4-NOT complex has been shown to have multiple roles in mRNA metabolism, including that of transcriptional elongation, mRNA transport, and nuclear exosome function, but the primary function of CCR4 and CAF1 is in the deadenylation and degradation of cytoplasmic mRNA. As previous genetic analysis supported an interaction between SPT5, known to be involved in transcriptional elongation, and that of CCR4, the physical association of SPT5 with CCR4 was examined. A two-hybrid screen utilizing the deadenylase domain of CCR4 as a bait identified SPT5 as a potential interacting protein. SPT5 at its physiological concentration was shown to immunoprecipitate CCR4 and CAF1, and in vitro purified SPT5 specifically could bind to CAF1 and the deadenylase domain of CCR4. We additionally demonstrated that mutations in SPT5 or an spt4 deletion slowed the rate of mRNA degradation, a phenotype associated with defects in the CCR4 mRNA deadenylase complex. Yet, unlike ccr4 and caf1 deletions, spt5 and spt4 defects displayed little effect on the rate of deadenylation. They also did not affect decapping or 5\u27 - 3\u27 degradation of mRNA. These results suggest that the interactions between SPT5/SPT4 and the CCR4-NOT complex are probably the consequences of effects involving nuclear events and do not involve the primary role of CCR4 in mRNA deadenylation and turnover
Reactivity of Damaged Pyrimidines: DNA Cleavage via Hemiaminal Formation at the C4 Positions of the Saturated Thymine of Spore Photoproduct and Dihydrouridine
Described
here are mechanistic details of the chemical reactivities
of two modified/saturated pyrimidine residues that represent naturally
occurring forms of DNA damage: 5-thyminyl-5,6-dihydrothymine, commonly
referred to as the âspore photoproductâ (SP), and 5,6-dihydro-2â˛-deoxyuridine
(dHdU), formed via ionizing radiation damage to cytosine under anoxic
conditions and also serving as a general model of saturated pyrimidine
residues. It is shown that due to the loss of the pyrimidine C5âC6
double bond and consequent loss of ring aromaticity, the C4 position
of both these saturated pyrimidines is prone to the formation of a
hemiaminal intermediate via water addition. Water addition is facilitated
by basic conditions; however, it also occurs at physiological pH at
a slower rate. The hemiaminal species so-formed subsequently converts
to a ring-opened hydrolysis product through cleavage of the pyrimidine
N3âC4 bond. Further decomposition of this ring-opened product
above physiological pH leads to DNA strand break formation. Taken
together, these results suggest that once the aromaticity of a pyrimidine
residue is lost, the C4 position becomes a âhot spotâ
for the formation of a tetrahedral intermediate, the decay of which
triggers a cascade of elimination reactions that can under certain
conditions convert a simple nucleobase modification into a DNA strand
break
Same Sign WW Scattering Process as a Probe of Higgs Boson in pp Collision at = 10 TeV
WW scattering is an important process to study electroweak symmetry breaking
in the Standard Model at the LHC, in which the Higgs mechanism or other new
physics processes must intervene to preserve the unitarity of the process below
1 TeV. This channel is expected to be one of the most sensitive to determine
whether the Higgs boson exists. In this paper, the final state with two same
sign Ws is studied, with a simulated sample corresponding to the integrated
luminosity of 60 fb in pp collision at 10 TeV. Two
observables, the invariant mass of from W decays and the azimuthal
angle difference between the two s, are utilized to distinguish the Higgs
boson existence scenario from the Higgs boson absence scenario. A good signal
significance for the two cases can be achieved. If we define the separation
power of the analysis as the distance, in the log-likelihood plane, of
pseudo-experiments outcomes in the two cases, with the total statistics
expected from the ATLAS and CMS experiments at the nominal centre-of-mass
energy of 14 TeV, the separation power will be at the level of 4 .Comment: 5 pages, 4 figures, 3 table
Physical detection of misbehavior in relay systems with unreliable channel state information
We study the detection 1 of misbehavior in a Gaussian relay system, where the source transmits information to the destination with the assistance of an amplify-and-forward relay node subject to unreliable channel state information (CSI). The relay node may be potentially malicious and corrupt the network by forwarding garbled information. In this situation, misleading feedback may take place, since reliable CSI is unavailable at the source and/or the destination. By classifying the action of the relay as detectable or undetectable, we propose a novel approach that is capable of coping with any malicious attack detected and continuing to work effectively in the presence of unreliable CSI. We demonstrate that the detectable class of attacks can be successfully detected with a high probability. Meanwhile, the undetectable class of attacks does not affect the performance improvements that are achievable by cooperative diversity, even though such an attack may fool the proposed detection approach. We also extend the method to deal with the case in which there is no direct link between the source and the destination. The effectiveness of the proposed approach has been validated by numerical results
A Group-1 Grass Pollen Allergen Influences the Outcome of Pollen Competition in Maize
Worldwide, 400 million people suffer from hay fever and seasonal asthma. The major causative agents of these allergies are pollen specific proteins called the group-1 grass pollen allergens. Although details of their antigenicity have been studied for 40 years with an eye towards immunotherapy, their function in the plant has drawn scant attention. Zea m 1 constitutes a class of abundant grass pollen allergens coded for by several genes that loosen the walls of grass cells, including the maize stigma and style. We have examined the impact of a transposon insertion into one of these genes (EXPB1, the most abundant isoform of Zea m 1) on the production of Zea m 1 protein, pollen viability, and pollen tube growth, both in vitro and in vivo. We also examined the effect of the insertional mutation on the competitive ability of the pollen by experimentally varying the sizes of the pollen load deposited onto stigmas using pollen from heterozygous plants and then screening the progeny for the presence of the transposon using PCR. We found that the insertional mutation reduced the levels of Zea m 1 in maize pollen, but had no effect on pollen viability, in vitro pollen tube growth or the proportion of progeny sired when small pollen loads are deposited onto stigmas. However, when large pollen loads are deposited onto the stigmas, the transposon mutation is vastly underrepresented in the progeny, indicating that this major pollen allergen has a large effect on pollen tube growth rates in vivo, and plays an important role in determining the outcome of the pollen-pollen competition for access to the ovules. We propose that the extraordinary abundance (4% of the extractable protein in maize pollen) of this major pollen allergen is the result of selection for a trait that functions primarily in providing differential access to ovules
Visualising and semi-quantitatively measuring brain fluid pathways, including meningeal lymphatics, in humans using widely available MRI techniques
l-Dopa induced dyskinesias in Parkinsonian mice: Disease severity or l-Dopa history
AbstractIn Parkinsonâs disease, the efficacy of l-Dopa treatment changes over time, as dyskinesias emerge with previously beneficial doses. Using MitoPark mice, that models mitochondrial failure in dopamine (DA) neurons and mimics the progressive loss of dopamine observed in Parkinsonâs disease, we found that the severity of DA denervation and associated adaptations in striatal neurotransmission at the time of initiation of l-Dopa treatment determines development of l-Dopa induced dyskinesias. We treated 20-week, and 28-week old MitoPark mice with l-Dopa (10mg/kg i.p. twice a day) and found locomotor responses to be significantly different. While all MitoPark mice developed sensitization to l-Dopa treatment over time, 28-week old MitoPark mice with extensive striatal DA denervation developed abnormal involuntary movements rapidly and severely after starting l-Dopa treatment, as compared to a more gradual escalation of movements in 20-week old animals that started treatment at earlier stages of degeneration. Our data support that it is the extent of loss of DA innervation that determines how soon motor complications develop with l-Dopa treatment. Gene array studies of striatal neurotransmitter receptors revealed changes in mRNA expression levels for DA, serotonin, glutamate and GABA receptors in striatum of 28-week old MitoPark mice. Our results support that delaying l-Dopa treatment until Parkinsonâs disease symptoms become more severe does not delay the development of l-Dopa-induced dyskinesias. MitoPark mice model genetic alterations known to impair mitochondrial function in a subgroup of Parkinson patients and provide a platform in which to study treatments to minimize the development of dyskinesia
From charge- to orbital-ordered metal-insulator transition in alkaline-earth ferrites
While CaFeO3 exhibits upon cooling a metal-insulator transition linked to charge ordering, SrFeO3 and BaFeO3 keep metallic behaviors down to very low temperatures. Moreover, alkaline-earth ferrites do not seem prone to orbital ordering in spite of the d4 formal occupancy of Fe4+. Here, from first-principles simulations, we show that the metal-insulator transition of CaFeO3 is structurally triggered by oxygen rotation motions as in rare-earth nickelates. This not only further clarifies why SrFeO3 and BaFeO3 remain metallic but allows us to predict that an insulating charge-ordered phase can be induced in SrFeO3 from an appropriate engineering of oxygen rotation motions. Going further, we unveil the possibility to switch from the usual charge-ordered to an orbital-ordered insulating ground state under moderate tensile strain in CaFeO3 thin films. We rationalize the competition between charge and orbital orderings, highlighting alternative possible strategies to produce such a change of ground state, also relevant to manganite and nickelate compounds. Š 2018 American Physical Society
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