220 research outputs found
Hall Effect and Resistivity in High-Tc Superconductors: The Conserving Approximation
The Hall coefficient (R_H) of high-Tc cuprates in the normal state shows the
striking non-Fermi liquid behavior: R_H follows a Curie-Weiss type temperature
dependence, and |R_H|>>1/|ne| at low temperatures in the under-doped compounds.
Moreover, R_H is positive for hole-doped compounds and is negative for
electron-doped ones, although each of them has a similar hole-like Fermi
surface. In this paper, we give the explanation of this long-standing problem
from the standpoint of the nearly antiferromagnetic (AF) Fermi liquid. We
consider seriously the vertex corrections for the current which are
indispensable to satisfy the conservation laws, which are violated within the
conventional Boltzmann transport approximation. The obtained total current J_k
takes an enhanced value and is no more perpendicular to the Fermi surface due
to the strong AF fluctuations. By virtue of this mechanism, the anomalous
behavior of R_H in high-Tc cuprates is neutrally explained. We find that both
the temperature and the (electron, or hole) doping dependences of R_H in
high-T_c cuprates are reproduced well by numerical calculations based on the
fluctuation-exchange (FLEX) approximation, applied to the single-band Hubbard
model. We also discuss the temperature dependence of R_H in other nearly AF
metals, e.g., V_2O_3, kappa-BEDT-TTF organic superconductors, and heavy fermion
systems close to the AF phase boundary.Comment: 19 pages, to appear in Phys. Rev. B, No.59, Vol.22, 199
Prognostic value of cardiovascular magnetic resonance derived right ventricular function in patients with interstitial lung disease
Deficient of a Clock Gene, Brain and Muscle Arnt-Like Protein-1 (BMAL1), Induces Dyslipidemia and Ectopic Fat Formation
A link between circadian rhythm and metabolism has long been discussed. Circadian rhythm is controlled by positive and negative transcriptional and translational feedback loops composed of several clock genes. Among clock genes, the brain and muscle Arnt-like protein-1 (BMAL1) and circadian locomotor output cycles kaput (CLOCK) play important roles in the regulation of the positive rhythmic transcription. In addition to control of circadian rhythm, we have previously shown that BMAL1 regulates adipogenesis. In metabolic syndrome patients, the function of BMAL1 is dysregulated in visceral adipose tissue. In addition, analysis of SNPs has revealed that BMAL1 is associated with susceptibility to hypertension and type II diabetes. Furthermore, the significant roles of BMAL1 in pancreatic ÎČ cells proliferation and maturation were recently reported. These results suggest that BMAL1 regulates energy homeostasis. Therefore, in this study, we examined whether loss of BMAL1 function is capable of inducing metabolic syndrome. Deficient of the Bmal1 gene in mice resulted in elevation of the respiratory quotient value, indicating that BMAL1 is involved in the utilization of fat as an energy source. Indeed, lack of Bmal1 reduced the capacity of fat storage in adipose tissue, resulting in an increase in the levels of circulating fatty acids, including triglycerides, free fatty acids, and cholesterol. Elevation of the circulating fatty acids level induced the formation of ectopic fat in the liver and skeletal muscle in Bmal1 -/- mice. Interestingly, ectopic fat formation was not observed in tissue-specific (liver or skeletal muscle) Bmal1 -/- mice even under high fat diet feeding condition. Therefore, we were led to conclude that BMAL1 is a crucial factor in the regulation of energy homeostasis, and disorders of the functions of BMAL1 lead to the development of metabolic syndrome
The Human Polyoma JC Virus Agnoprotein Acts as a Viroporin
Virus infections can result in a range of cellular injuries and commonly this involves both the plasma and intracellular membranes, resulting in enhanced permeability. Viroporins are a group of proteins that interact with plasma membranes modifying permeability and can promote the release of viral particles. While these proteins are not essential for virus replication, their activity certainly promotes virus growth. Progressive multifocal leukoencephalopathy (PML) is a fatal demyelinating disease resulting from lytic infection of oligodendrocytes by the polyomavirus JC virus (JCV). The genome of JCV encodes six major proteins including a small auxiliary protein known as agnoprotein. Studies on other polyomavirus agnoproteins have suggested that the protein may contribute to viral propagation at various stages in the replication cycle, including transcription, translation, processing of late viral proteins, assembly of virions, and viral propagation. Previous studies from our and other laboratories have indicated that JCV agnoprotein plays an important, although as yet incompletely understood role in the propagation of JCV. Here, we demonstrate that agnoprotein possesses properties commonly associated with viroporins. Our findings demonstrate that: (i) A deletion mutant of agnoprotein is defective in virion release and viral propagation; (ii) Agnoprotein localizes to the ER early in infection, but is also found at the plasma membrane late in infection; (iii) Agnoprotein is an integral membrane protein and forms homo-oligomers; (iv) Agnoprotein enhances permeability of cells to the translation inhibitor hygromycin B; (v) Agnoprotein induces the influx of extracellular Ca2+; (vi) The basic residues at amino acid positions 8 and 9 of agnoprotein key are determinants of the viroporin activity. The viroporin-like properties of agnoprotein result in increased membrane permeability and alterations in intracellular Ca2+ homeostasis leading to membrane dysfunction and enhancement of virus release
Arabidopsis HDA6 Regulates Locus-Directed Heterochromatin Silencing in Cooperation with MET1
Heterochromatin silencing is pivotal for genome stability in eukaryotes. In
Arabidopsis, a plant-specific mechanism called
RNAâdirected DNA methylation (RdDM) is involved in heterochromatin
silencing. Histone deacetylase HDA6 has been identified as a component of such
machineries; however, its endogenous targets and the silencing mechanisms have
not been analyzed globally. In this study, we investigated the silencing
mechanism mediated by HDA6. Genome-wide transcript profiling revealed that the
loci silenced by HDA6 carried sequences corresponding to the RDR2-dependent
24-nt siRNAs, however their transcript levels were mostly unaffected in the
rdr2 mutant. Strikingly, we observed significant overlap of
genes silenced by HDA6 to those by the CG DNA methyltransferase MET1.
Furthermore, regardless of dependence on RdDM pathway, HDA6 deficiency resulted
in loss of heterochromatic epigenetic marks and aberrant enrichment for
euchromatic marks at HDA6 direct targets, along with ectopic expression of these
loci. Acetylation levels increased significantly in the hda6
mutant at all of the lysine residues in the H3 and H4 N-tails, except H4K16.
Interestingly, we observed two different CG methylation statuses in the
hda6 mutant. CG methylation was sustained in the
hda6 mutant at some HDA6 target loci that were surrounded
by flanking DNAâmethylated regions. In contrast, complete loss of CG
methylation occurred in the hda6 mutant at the HDA6 target loci
that were isolated from flanking DNA methylation. Regardless of CG methylation
status, CHG and CHH methylation were lost and transcriptional derepression
occurred in the hda6 mutant. Furthermore, we show that HDA6
binds only to its target loci, not the flanking methylated DNA, indicating the
profound target specificity of HDA6. We propose that HDA6 regulates
locus-directed heterochromatin silencing in cooperation with MET1, possibly
recruiting MET1 to specific loci, thus forming the foundation of silent
chromatin structure for subsequent non-CG methylation
Rationale and design of a randomized trial to test the safety and non-inferiority of canagliflozin in patients with diabetes with chronic heart failure: the CANDLE trial
Why Are Outcomes Different for Registry Patients Enrolled Prospectively and Retrospectively? Insights from the Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF).
Background: Retrospective and prospective observational studies are designed to reflect real-world evidence on clinical practice, but can yield conflicting results. The GARFIELD-AF Registry includes both methods of enrolment and allows analysis of differences in patient characteristics and outcomes that may result. Methods and Results: Patients with atrial fibrillation (AF) and â„1 risk factor for stroke at diagnosis of AF were recruited either retrospectively (nâ=â5069) or prospectively (nâ=â5501) from 19 countries and then followed prospectively. The retrospectively enrolled cohort comprised patients with established AF (for a least 6, and up to 24 months before enrolment), who were identified retrospectively (and baseline and partial follow-up data were collected from the emedical records) and then followed prospectively between 0-18 months (such that the total time of follow-up was 24 months; data collection Dec-2009 and Oct-2010). In the prospectively enrolled cohort, patients with newly diagnosed AF (â€6 weeks after diagnosis) were recruited between Mar-2010 and Oct-2011 and were followed for 24 months after enrolment. Differences between the cohorts were observed in clinical characteristics, including type of AF, stroke prevention strategies, and event rates. More patients in the retrospectively identified cohort received vitamin K antagonists (62.1% vs. 53.2%) and fewer received non-vitamin K oral anticoagulants (1.8% vs . 4.2%). All-cause mortality rates per 100 person-years during the prospective follow-up (starting the first study visit up to 1 year) were significantly lower in the retrospective than prospectively identified cohort (3.04 [95% CI 2.51 to 3.67] vs . 4.05 [95% CI 3.53 to 4.63]; pâ=â0.016). Conclusions: Interpretations of data from registries that aim to evaluate the characteristics and outcomes of patients with AF must take account of differences in registry design and the impact of recall bias and survivorship bias that is incurred with retrospective enrolment. Clinical Trial Registration: - URL: http://www.clinicaltrials.gov . Unique identifier for GARFIELD-AF (NCT01090362)
Risk profiles and one-year outcomes of patients with newly diagnosed atrial fibrillation in India: Insights from the GARFIELD-AF Registry.
BACKGROUND: The Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF) is an ongoing prospective noninterventional registry, which is providing important information on the baseline characteristics, treatment patterns, and 1-year outcomes in patients with newly diagnosed non-valvular atrial fibrillation (NVAF). This report describes data from Indian patients recruited in this registry. METHODS AND RESULTS: A total of 52,014 patients with newly diagnosed AF were enrolled globally; of these, 1388 patients were recruited from 26 sites within India (2012-2016). In India, the mean age was 65.8 years at diagnosis of NVAF. Hypertension was the most prevalent risk factor for AF, present in 68.5% of patients from India and in 76.3% of patients globally (P < 0.001). Diabetes and coronary artery disease (CAD) were prevalent in 36.2% and 28.1% of patients as compared with global prevalence of 22.2% and 21.6%, respectively (P < 0.001 for both). Antiplatelet therapy was the most common antithrombotic treatment in India. With increasing stroke risk, however, patients were more likely to receive oral anticoagulant therapy [mainly vitamin K antagonist (VKA)], but average international normalized ratio (INR) was lower among Indian patients [median INR value 1.6 (interquartile range {IQR}: 1.3-2.3) versus 2.3 (IQR 1.8-2.8) (P < 0.001)]. Compared with other countries, patients from India had markedly higher rates of all-cause mortality [7.68 per 100 person-years (95% confidence interval 6.32-9.35) vs 4.34 (4.16-4.53), P < 0.0001], while rates of stroke/systemic embolism and major bleeding were lower after 1 year of follow-up. CONCLUSION: Compared to previously published registries from India, the GARFIELD-AF registry describes clinical profiles and outcomes in Indian patients with AF of a different etiology. The registry data show that compared to the rest of the world, Indian AF patients are younger in age and have more diabetes and CAD. Patients with a higher stroke risk are more likely to receive anticoagulation therapy with VKA but are underdosed compared with the global average in the GARFIELD-AF. CLINICAL TRIAL REGISTRATION-URL: http://www.clinicaltrials.gov. Unique identifier: NCT01090362
Association between blood glucose variability and coronary plaque instability in patients with acute coronary syndromes
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