Context. It has recently been proposed that the surface composition of icy main-belt asteroids (B-, C-, Cb-, Cg-, P-, and D-types) may be consistent with that of chondritic porous interplanetary dust ...particles (CP IDPs). Aims. In the light of this new association, we re-examine the surface composition of a sample of asteroids belonging to the Themis family in order to place new constraints on the formation and evolution of its parent body. Methods. We acquired near-infrared spectral data for 15 members of the Themis family and complemented this dataset with existing spectra in the visible and mid-infrared ranges to perform a thorough analysis of the composition of the family. Assuming end-member minerals and particle sizes (<2 μm) similar to those found in CP IDPs, we used a radiative transfer code adapted for light scattering by small particles to model the spectral properties of these asteroids. Results. Our best-matching models indicate that most objects in our sample (12/15) possess a surface composition that is consistent with the composition of CP IDPs. We find ultra-fine grained (<2 μm) Fe-bearing olivine glasses to be among the dominant constituents. We further detect the presence of minor fractions of Mg-rich crystalline silicates (enstatite and forsterite). The few unsuccessfully matched asteroids may indicate the presence of interlopers in the family or objects sampling a distinct compositional layer of the parent body. Conclusions. The composition inferred for the Themis family members suggests that the parent body accreted from a mixture of ice and anhydrous silicates (mainly amorphous) and subsequently underwent limited heating. By comparison with existing thermal models that assume a 400-km diameter progenitor, the accretion process of the Themis parent body must have occurred relatively late (>4 Myr after CAIs) so that only moderate internal heating occurred in its interior, preventing aqueous alteration of the outer shell.
DLC1 (deleted in liver cancer 1), a tumor suppressor gene that encodes a RhoGTPase-activating protein, is recurrently downregulated or silenced in various solid tumors and hematological malignancies ...because of epigenetic modifications or genomic deletion. Here, we identified DLC1 promoter hypermethylation in 43 out of 44 multiple myeloma (MM) cell lines, which resulted in downregulation or silencing of DLC1 in 41 samples. High frequency of tumor-specific methylation and attenuation or silencing of DLC1 expression could serve as an independent diagnostic marker for MM. Combined treatment with demethylating and acetylating agents significantly elevated the expression of DLC1 and suppressed MM cell proliferation. Two cell lines exhibiting complete promoter methylation and the absence of DLC1 expression were transduced by an adenoviral vector containing DLC1 cDNA. In both cell lines, the reexpression of DLC1 inhibited myeloma cell invasion and migration, reduced RhoA activity and resulted in the reorganization of actin cytoskeleton. These results provide the first evidence for the antiproliferative effect of DLC1 in a hematological cancer and implicate RhoA pathway in suppression of MM migration and invasion. Given the myeloma cells sensitivity to the reactivation of DLC1 function, the potential for molecular targeted therapy of DLC1-mediated pathways as well as epigenetic therapies hold prospects.
Remyelination and neurodegeneration prevention mitigate disability in Multiple Sclerosis (MS). We have shown acute intermittent hypoxia (AIH) is a novel, non‐invasive and effective therapy for ...peripheral nerve repair, including remyelination. Thus, we posited AIH would improve repair following CNS demyelination and address the paucity of MS repair treatments. AIH's capacity to enhance intrinsic repair, functional recovery and alter disease course in the experimental autoimmune encephalomyelitis (EAE) model of MS was assessed. EAE was induced by MOG35‐55 immunization in C57BL/6 female mice. EAE mice received either AIH (10 cycles—5 min 11% oxygen alternating with 5 min 21% oxygen) or Normoxia (control; 21% oxygen for same duration) once daily for 7d beginning at near peak EAE disease score of 2.5. Mice were followed post‐treatment for an additional 7d before assessing histopathology or 14d to examine maintenance of AIH effects. Alterations in histopathological correlates of multiple repair indices were analyzed quantitatively in focally demyelinated ventral lumbar spinal cord areas to assess AIH impacts. AIH begun at near peak disease significantly improved daily clinical scores/functional recovery and associated histopathology relative to Normoxia controls and the former were maintained for at least 14d post‐treatment. AIH enhanced correlates of myelination, axon protection and oligodendrocyte precursor cell recruitment to demyelinated areas. AIH also effected a dramatic reduction in inflammation, while polarizing remaining macrophages/microglia toward a pro‐repair state. Collectively, this supports a role for AIH as a novel non‐invasive therapy to enhance CNS repair and alter disease course following demyelination and holds promise as a neuroregenerative MS strategy.
Main Points
Acute intermittent hypoxia is a promising, novel, non‐invasive therapy for demyelinating disease. It greatly improves clinical scores, myelin repair, axon protection and resolution of inflammation in the mouse EAE Multiple Sclerosis model.
Abstract
We present a detailed analysis of the specific star formation rate–stellar mass (sSFR–M*) of z ≤ 0.13 disc central galaxies using a morphologically selected mass-complete sample (M* ≥ 109.5 ...M⊙). Considering samples of grouped and ungrouped galaxies, we find the sSFR–M* relations of disc-dominated central galaxies to have no detectable dependence on host dark-matter halo (DMH) mass, even where weak-lensing measurements indicate a difference in halo mass of a factor ≳ 5. We further detect a gradual evolution of the sSFR–M* relation of non-grouped (field) central disc galaxies with redshift, even over a Δz ≈ 0.04 (≈5 × 108 yr) interval, while the scatter remains constant. This evolution is consistent with extrapolation of the ‘main sequence of star-forming-galaxies’ from previous literature that uses larger redshift baselines and coarser sampling. Taken together, our results present new constraints on the paradigm under which the SFR of galaxies is determined by a self-regulated balance between gas inflows and outflows, and consumption of gas by star formation in discs, with the inflow being determined by the product of the cosmological accretion rate and a fuelling efficiency – $\dot{M}_{\mathrm{b,halo}}\zeta$. In particular, maintaining the paradigm requires $\dot{M}_{\mathrm{b,halo}}\zeta$ to be independent of the mass Mhalo of the host DMH. Furthermore, it requires the fuelling efficiency ζ to have a strong redshift dependence (∝(1 + z)2.7 for M* = 1010.3 M⊙ over z = 0–0.13), even though no morphological transformation to spheroids can be invoked to explain this in our disc-dominated sample. The physical mechanisms capable of giving rise to such dependencies of ζ on Mhalo and z for discs are unclear.
Human Mitochondrial Topoisomerase I Zhang, Hongliang; Barceló, Juana M.; Lee, Benson ...
Proceedings of the National Academy of Sciences - PNAS,
09/2001, Letnik:
98, Številka:
19
Journal Article
Recenzirano
Odprti dostop
Tension generated in the circular mitochondrial genome during replication and transcription points to the need for mtDNA topoisomerase activity. Here we report a 601-aa polypeptide highly homologous ...to nuclear topoisomerase I. The N-terminal domain of this novel topoisomerase contains a mitochondrial localization sequence and lacks a nuclear localization signal. Therefore, we refer to this polypeptide as top1mt. The pattern of top1mt expression matches the requirement for high mitochondrial activity in specific tissues. top1mt is a type IB topoisomerase that requires divalent metal (Ca2+or Mg2+) and alkaline pH for optimum activity. The TOP1mt gene is highly homologous to the nuclear TOP1 gene and consists of 14 exons. It is localized on human chromosome 8q24.3.
Ribonuclease A (RNase A) enzyme was immobilized on solid holders by matrix-assisted pulsed laser evaporation (MAPLE) technique. The experiments were performed inside a stainless steel irradiation ...chamber. A UV KrF* (λ = 248 nm, τ
FWHM
≅ 25 ns, ν = 10 Hz) excimer laser source was used for irradiations. Surface morphology, molecular structure, and enzymatic activity of laser transferred RNase A samples were investigated as a function of RNase A concentration in the frozen composite MAPLE targets. Surface morphology and thickness of the immobilized enzyme were investigated by atomic force microscopy, scanning electron microscopy, and surface profilometry. The molecular structure of the laser transferred RNase A was determined by Fourier transform infrared spectroscopy. The enzymatic activity of RNase A after immobilization was tested through ribonucleic acid removal from deoxyribonucleic acid (DNA) extract solutions isolated from plant and animal tissues. A molecular method based on polymerase chain reaction was used to investigate the functional properties of DNA extracts treated with laser immobilized RNase A.
Accurate polyp size estimation during colonoscopy has an impact on clinical decision-making. A laser-based virtual scale endoscope (VSE) is available to allow measuring polyp size using a virtual ...adaptive scale. This study evaluates video-based polyp size measurement accuracy among expert endoscopists using either VSE or visual assessment (VA) with either snare as reference size or without any reference size information.
A prospective, video-based study was conducted with 10 expert endoscopists. Video sequences from 90 polyps with known reference size (fresh specimen measured using calipers) were distributed on three different slide sets so that each slide set showed the same polyp only once with either VSE, VA or snare-based information. A slide set was randomly assigned to each endoscopist. Endoscopists were asked to provide size estimation based on video review.
Relative accuracies for VSE, VA, and snare-based estimation were 75.1% (95% CI 71.6-78.5), 65.0% (95% CI 59.5-70.4) and 62.0% (95% CI 54.8-69.0), respectively. VSE yielded significantly higher relative accuracy compared to VA (
= 0.002) and to snare (
= 0.001). A significantly lower percentage of polyps 1-5 mm were misclassified as >5 mm using VSE versus VA and snare (6.52% vs. 19.6% and 17.5%,
= 0.004) and a significantly lower percentage of polyps >5 mm were misclassified as 1-5 mm using VSE versus VA and snare (11.4% vs. 31.9% and 14.9%,
= 0.038).
Endoscopists estimate polyp size with the highest accuracy when virtual adaptive scale information is displayed. Using a snare to assist sizing did not improve measurement accuracy compared to displaying visual information alone.
Significant (moderate or greater) mitral regurgitation (MR) could augment the hemodynamic effects of aortic valvular disease in patients with bicuspid aortic valve (BAV), imposing a greater ...hemodynamic burden on the left ventricle and atrium, possibly culminating in a faster onset of left ventricular dilation and/or symptoms. The aim of this study was to determine the prevalence and prognostic implications of significant MR in patients with BAV.
In this large, multicenter, international registry, a total of 2,932 patients (mean age, 48 ± 18 years; 71% men) with BAV were identified. All patients were evaluated for the presence of significant primary or secondary MR by transthoracic echocardiography and were followed up for the end points of all-cause mortality and event-free survival.
Overall, 147 patients (5.0%) had significant primary (1.5%) or secondary (3.5%) MR. Significant MR was associated with all-cause mortality (hazard ratio HR, 2.80; 95% CI, 1.91-4.11; P < .001) and reduced event-free survival (HR, 1.97; 95% CI, 1.58-2.46; P < .001) on univariable analysis. MR was not associated with all-cause mortality (adjusted HR, 1.33; 95% CI, 0.85-2.07; P = .21) or event-free survival (adjusted HR, 1.10; 95% CI, 0.85-1.42; P = .49) after multivariable adjustment. However, sensitivity analyses demonstrated that significant MR not due to aortic valve disease retained an independent association with mortality (adjusted HR, 1.81; 95% CI, 1.04-3.15; P = .037). Subgroup analyses demonstrated an independent association between significant MR and all-cause mortality for individuals with significant aortic regurgitation (HR, 2.037; 95% CI, 1.025-4.049; P = .042), although this association was not observed for subgroups with significant aortic stenosis or without significant aortic valve dysfunction.
Significant MR is uncommon in patients with BAV. Following adjustment for important confounding variables, significant MR was not associated with adverse prognosis in this large study of patients with BAV, except for the patient subgroup with moderate to severe aortic regurgitation. In addition, significant MR not due to aortic valve disease demonstrated an independent association with all-cause mortality.
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