1,069 research outputs found
The novel MAPT mutation K298E:mechanisms of mutant tau toxicity, brain pathology and tau expression in induced fibroblast-derived neurons
Frontotemporal lobar degeneration (FTLD) consists of a group of neurodegenerative diseases characterized by behavioural and executive impairment, language disorders and motor dysfunction. About 20-30 % of cases are inherited in a dominant manner. Mutations in the microtubule-associated protein tau gene (MAPT) cause frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17T). Here we report a novel MAPT mutation (K298E) in exon 10 in a patient with FTDP-17T. Neuropathological studies of post-mortem brain showed widespread neuronal loss and gliosis and abundant deposition of hyperphosphorylated tau in neurons and glia. Molecular studies demonstrated that the K298E mutation affects both protein function and alternative mRNA splicing. Fibroblasts from a skin biopsy of the proband taken at post-mortem were directly induced into neurons (iNs) and expressed both 3-repeat and 4-repeat tau isoforms. As well as contributing new knowledge on MAPT mutations in FTDP-17T, this is the first example of the successful generation of iNs from skin cells retrieved post-mortem
Polymorphisms of the Flavin containing monooxygenase 3 (FMO3) gene do not predispose to essential hypertension in Caucasians.
BACKGROUND: The recessive disorder trimethylaminuria is caused by defects in the FMO3 gene, and may be associated with hypertension. We investigated whether common polymorphisms of the FMO3 gene confer an increased risk for elevated blood pressure and/or essential hypertension.
METHODS: FMO3 genotypes (E158K, V257M, E308G) were determined in 387 healthy subjects with ambulatory systolic and diastolic blood pressure measurements, and in a cardiovascular disease population of 1649 individuals, 691(41.9%) of whom had a history of hypertension requiring drug treatment. Haplotypes were determined and their distribution noted.
RESULTS: There was no statistically significant association found between any of the 4 common haplotypes and daytime systolic blood pressure in the healthy population (p = 0.65). Neither was a statistically significant association found between the 4 common haplotypes and hypertension status among the cardiovascular disease patients (p = 0.80).
CONCLUSION: These results suggest that the variants in the FMO3 gene do not predispose to essential hypertension in this population
On the modulation instability development in optical fiber systems
Extensive numerical simulations were performed to investigate all stages of
modulation instability development from the initial pulse of pico-second
duration in photonic crystal fiber: quasi-solitons and dispersive waves
formation, their interaction stage and the further propagation. Comparison
between 4 different NLS-like systems was made: the classical NLS equation, NLS
system plus higher dispersion terms, NLS plus higher dispersion and
self-steepening and also fully generalized NLS equation with Raman scattering
taken into account. For the latter case a mechanism of energy transfer from
smaller quasi-solitons to the bigger ones is proposed to explain the dramatical
increase of rogue waves appearance frequency in comparison to the systems when
the Raman scattering is not taken into account.Comment: 9 pages, 54 figure
Quantum Dynamics in Non-equilibrium Strongly Correlated Environments
We consider a quantum point contact between two Luttinger liquids coupled to
a mechanical system (oscillator). For non-vanishing bias, we find an effective
oscillator temperature that depends on the Luttinger parameter. A generalized
fluctuation-dissipation relation connects the decoherence and dissipation of
the oscillator to the current-voltage characteristics of the device. Via a
spectral representation, this result is generalized to arbitrary leads in a
weak tunneling regime.Comment: 4 pages, 1 figur
Quantum theory of electromechanical noise and momentum transfer statistics
A quantum mechanical theory is developed for the statistics of momentum
transferred to the lattice by conduction electrons. Results for the
electromechanical noise power in the semiclassical diffusive transport regime
agree with a recent theory based on the Boltzmann-Langevin equation. All
moments of the transferred momentum are calculated for a single-channel
conductor with a localized scatterer, and compared with the known statistics of
transmitted charge.Comment: 10 pages, 2 figure
Spectral compression of single photons
Photons are critical to quantum technologies since they can be used for
virtually all quantum information tasks: in quantum metrology, as the
information carrier in photonic quantum computation, as a mediator in hybrid
systems, and to establish long distance networks. The physical characteristics
of photons in these applications differ drastically; spectral bandwidths span
12 orders of magnitude from 50 THz for quantum-optical coherence tomography to
50 Hz for certain quantum memories. Combining these technologies requires
coherent interfaces that reversibly map centre frequencies and bandwidths of
photons to avoid excessive loss. Here we demonstrate bandwidth compression of
single photons by a factor 40 and tunability over a range 70 times that
bandwidth via sum-frequency generation with chirped laser pulses. This
constitutes a time-to-frequency interface for light capable of converting
time-bin to colour entanglement and enables ultrafast timing measurements. It
is a step toward arbitrary waveform generation for single and entangled
photons.Comment: 6 pages (4 figures) + 6 pages (3 figures
Does race impact functional outcomes in patients undergoing robotic partial nephrectomy?
Background: The role of race on functional outcomes after robotic partial nephrectomy (RPN) is still a matter of debate. We aimed to evaluate the clinical and pathologic characteristics of African American (AA) and Caucasian patients who underwent RPN and analyzed the association between race and functional outcomes.
Methods: Data was obtained from a multi-institutional database of patients who underwent RPN in 6 institutions in the USA. We identified 999 patients with complete clinical data. Sixty-three patients (6.3%) were AA, and each patient was matched (1:3) to Caucasian patients by age at surgery, gender, Charlson Comorbidity Index (CCI) and renal score. Bivariate and multivariate logistic regression analyses were used to evaluate predictors of acute kidney injury (AKI). Kaplan-Meier method and multivariable semiparametric Cox regression analyses were performed to assess prevalence and predictors of significant eGFR reduction during follow-up.
Results: Overall, 252 patients were included. AA were more likely to have hypertension (58.7%
Conclusions: Although African American patients were more likely to have hypertension, renal function outcomes of robotic partial nephrectomies were not significantly different when stratified by race. However, future studies with larger cohorts are necessary to validate these findings
Theory of extraordinary optical transmission through subwavelength hole arrays
We present a fully three-dimensional theoretical study of the extraordinary
transmission of light through subwavelength hole arrays in optically thick
metal films. Good agreement is obtained with experimental data. An analytical
minimal model is also developed, which conclusively shows that the enhancement
of transmission is due to tunneling through surface plasmons formed on each
metal-dielectric interfaces. Different regimes of tunneling (resonant through a
''surface plasmon molecule", or sequential through two isolated surface
plasmons) are found depending on the geometrical parameters defining the
system.Comment: 4 pages, 4 figure
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Phenotypic heterogeneity and genetic modification of P102L inherited prion disease in an international series
The largest kindred with inherited prion disease P102L, historically Gerstmann-Sträussler-Scheinker syndrome, originates from central England, with émigrés now resident in various parts of the English-speaking world. We have collected data from 84 patients in the large UK kindred and numerous small unrelated pedigrees to investigate phenotypic heterogeneity and modifying factors. This collection represents by far the largest series of P102L patients so far reported. Microsatellite and genealogical analyses of eight separate European kindreds support multiple distinct mutational events at a cytosine-phosphate diester-guanidine dinucleotide mutation hot spot. All of the smaller P102L kindreds were linked to polymorphic human prion protein gene codon 129M and were not connected by genealogy or microsatellite haplotype background to the large kindred or each other. While many present with classical Gerstmann-Sträussler-Scheinker syndrome, a slowly progressive cerebellar ataxia with later onset cognitive impairment, there is remarkable heterogeneity. A subset of patients present with prominent cognitive and psychiatric features and some have met diagnostic criteria for sporadic Creutzfeldt-Jakob disease. We show that polymorphic human prion protein gene codon 129 modifies age at onset: the earliest eight clinical onsets were all MM homozygotes and overall age at onset was 7 years earlier for MM compared with MV heterozygotes (P = 0.02). Unexpectedly, apolipoprotein E4 carriers have a delayed age of onset by 10 years (P = 0.02). We found a preponderance of female patients compared with males (54 females versus 30 males, P = 0.01), which probably relates to ascertainment bias. However, these modifiers had no impact on a semi-quantitative pathological phenotype in 10 autopsied patients. These data allow an appreciation of the range of clinical phenotype, modern imaging and molecular investigation and should inform genetic counselling of at-risk individuals, with the identification of two genetic modifiers
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