218 research outputs found
Gamma oscillations in V1 are correlated with GABA(A) receptor density: A multi-modal MEG and Flumazenil-PET study.
High-frequency oscillations in the gamma-band reflect rhythmic synchronization of spike timing in active neural networks. The modulation of gamma oscillations is a widely established mechanism in a variety of neurobiological processes, yet its neurochemical basis is not fully understood. Modeling, in-vitro and in-vivo animal studies suggest that gamma oscillation properties depend on GABAergic inhibition. In humans, search for evidence linking total GABA concentration to gamma oscillations has led to promising -but also to partly diverging- observations. Here, we provide the first evidence of a direct relationship between the density of GABA(A) receptors and gamma oscillatory gamma responses in human primary visual cortex (V1). By combining Flumazenil-PET (to measure resting-levels of GABA(A) receptor density) and MEG (to measure visually-induced gamma oscillations), we found that GABA(A) receptor densities correlated positively with the frequency and negatively with amplitude of visually-induced gamma oscillations in V1. Our findings demonstrate that gamma-band response profiles of primary visual cortex across healthy individuals are shaped by GABA(A)-receptor-mediated inhibitory neurotransmission. These results bridge the gap with in-vitro and animal studies and may have future clinical implications given that altered GABAergic function, including dysregulation of GABA(A) receptors, has been related to psychiatric disorders including schizophrenia and depression
The loss of NKX3.1 expression in testicular – and prostate – cancers is not caused by promoter hypermethylation
BACKGROUND: Recent studies have demonstrated that the NKX3.1 protein is commonly down-regulated in testicular germ cell tumors (TGCTs) and prostate carcinomas. The homeobox gene NKX3.1 maps to chromosome band 8p21, which is a region frequently lost in prostate cancer, but not in TGCT. Mutations have not been reported in the NKX3.1 sequence, and the gene is hypothesized to be epigenetically inactivated. In the present study we examined the methylation status of the NKX3.1 promoter in relevant primary tumors and cell lines: primary TGCTs (n = 55), intratubular germ cell neoplasias (n = 7), germ cell tumor cell lines (n = 3), primary prostate adenocarcinomas (n = 20), and prostate cancer cell lines (n = 3) by methylation-specific PCR and bisulphite sequencing. RESULTS AND CONCLUSIONS: Down-regulation of NKX3.1 expression was generally not caused by promoter hypermethylation, which was only found in one TGCT. However, other epigenetic mechanisms, such as modulation of chromatin structure or modifications of histones, may explain the lack of NKX3.1 expression, which is seen in most TGCTs and prostate cancer specimens
Recent African derivation of Chrysomya putoria from C. chloropyga and mitochondrial DNA paraphyly of cytochrome oxidase subunit one in blowflies of forensic importance
Chrysomya chloropyga (Wiedemann) and C. putoria (Wiedemann) (Diptera: Calliphoridae) are closely related Afrotropical blowflies that breed in carrion and latrines, reaching high density in association with humans and spreading to other continents. In some cases of human death, Chyrsomya specimens provide forensic clues. Because the immature stages of such flies are often difficult to identify taxonomically, it is useful to develop DNA-based tests for specimen identification. Therefore we attempted to distinguish between C. chloropyga and C. putoria using mitochondrial DNA (mtDNA) sequence data from a 593-bp region of the gene for cytochrome oxidase subunit one (COI). Twelve specimens from each species yielded a total of five haplotypes, none being unique to C. putoria. Therefore it was not possible to distinguish between the two species using this locus. Maximum parsimony analysis indicated paraphyletic C. chloropyga mtDNA with C. putoria nested therein. Based on these and previously published data, we infer that C. putoria diverged very recently from C. chloropyga
Diffusion controlled initial recombination
This work addresses nucleation rates in systems with strong initial
recombination. Initial (or `geminate') recombination is a process where a
dissociated structure (anion, vortex, kink etc.) recombines with its twin
brother (cation, anti-vortex, anti-kink) generated in the same nucleation
event. Initial recombination is important if there is an asymptotically
vanishing interaction force instead of a generic saddle-type activation
barrier. At low temperatures, initial recombination strongly dominates
homogeneous recombination. In a first part, we discuss the effect in one-,
two-, and three-dimensional diffusion controlled systems with spherical
symmetry. Since there is no well-defined saddle, we introduce a threshold which
is to some extent arbitrary but which is restricted by physically reasonable
conditions. We show that the dependence of the nucleation rate on the specific
choice of this threshold is strongest for one-dimensional systems and decreases
in higher dimensions. We discuss also the influence of a weak driving force and
show that the transport current is directly determined by the imbalance of the
activation rate in the direction of the field and the rate against this
direction. In a second part, we apply the results to the overdamped sine-Gordon
system at equilibrium. It turns out that diffusive initial recombination is the
essential mechanism which governs the equilibrium kink nucleation rate. We
emphasize analogies between the single particle problem with initial
recombination and the multi-dimensional kink-antikink nucleation problem.Comment: LaTeX, 11 pages, 1 ps-figures Extended versio
Modulation of the nucleation rate pre-exponential in a low-temperature Ising system
A metastable lattice gas with nearest-neighbor interactions and
continuous-time dynamics is studied using a generalized Becker-Doring approach
in the multidimensional space of cluster configurations. The pre-exponential of
the metastable state lifetime (inverse of nucleation rate) is found to exhibit
distinct peaks at integer values of the inverse supersaturation. Peaks are
unobservable (infinitely narrow) in the strict limit T->0, but become
detectable and eventually dominate at higher temperatures.Comment: 4 pages, 2 Postscript figures, LaTeX, submitted to Phys. Rev. Lett.
Changes: updated references, re-written section around eqs.(5),(6), typos,
minor wording changes in conclusion and other parts of text (mostly in
response to referees' comments). Paper resubmitted to PR
Current clinical criteria for Lynch syndrome are not sensitive enough to identify MSH6 mutation carriers
Background: Reported prevalence, penetrance and expression of deleterious mutations in the mismatch repair (MMR) genes, MLH1, MSH2, MSH6 and PMS2, may reflect differences in the clinical criteria used to select families for DNA testing. The authors have previously reported that clinical criteria are not sensitive enough to identify MMR mutation carriers among incident colorectal cancer cases. Objective: To describe the sensitivity of the criteria when applied to families with a demonstrated MMR mutation. Methods: Families with an aggregation of colorectal cancers were examined for deleterious MMR mutations according to the Mallorca guidelines. All families with a detected MMR mutation as of November 2009 were reclassified according to the Amsterdam and Bethesda criteria. Results: Sixty-nine different DNA variants were identified in a total of 129 families. The original Amsterdam clinical criteria were met by 38%, 12%, 78% and 25% of families with mutations in MSH2, MSH6, MLH1 and PMS2, respectively. Corresponding numbers for the revised Amsterdam criteria were 62%, 48%, 87% and 38%. Similarly, each of the four clinical Bethesda criteria had low sensitivity for identifying MSH6 or PMS2 mutations. Conclusion: Amsterdam criteria and each of the Bethesda criteria were inadequate for identifying MSH6 mutation-carrying kindreds. MSH6 mutations may be more common than currently assumed, and the penetrance/expression of MSH6 mutations, as derived from families meeting current clinical criteria, may be misleading. To increase detection rate of MMR mutation carriers, all cancers in the Lynch syndrome tumour spectrum should be subjected to immunohistochemical analysis and/or analysis for microsatellite instability
Dislocation Kinks in Copper: Widths, Barriers, Effective Masses, and Quantum Tunneling
We calculate the widths, migration barriers, effective masses, and quantum
tunneling rates of kinks and jogs in extended screw dislocations in copper,
using an effective medium theory interatomic potential. The energy barriers and
effective masses for moving a unit jog one lattice constant are close to
typical atomic energies and masses: tunneling will be rare. The energy barriers
and effective masses for the motion of kinks are unexpectedly small due to the
spreading of the kinks over a large number of atoms. The effective masses of
the kinks are so small that quantum fluctuations will be important. We discuss
implications for quantum creep, kink--based tunneling centers, and Kondo
resonances
Heterogeneous condensation in dense media
The theoretical description of the heterogeneous nucleation kinetics is
presented. This description takes into account the perturbation of the vapor
phase initiated by the growing droplets. The form of the density profile around
the growing droplet is analyzed which leads to some special approximations.
Then the process of nucleation in the whole system is described. As the result
all main characteristics of the process are determined analytically.Comment: 50 pages, LATE
Effects of boundary conditions on magnetization switching in kinetic Ising models of nanoscale ferromagnets
Magnetization switching in highly anisotropic single-domain ferromagnets has
been previously shown to be qualitatively described by the droplet theory of
metastable decay and simulations of two-dimensional kinetic Ising systems with
periodic boundary conditions. In this article we consider the effects of
boundary conditions on the switching phenomena. A rich range of behaviors is
predicted by droplet theory: the specific mechanism by which switching occurs
depends on the structure of the boundary, the particle size, the temperature,
and the strength of the applied field. The theory predicts the existence of a
peak in the switching field as a function of system size in both systems with
periodic boundary conditions and in systems with boundaries. The size of the
peak is strongly dependent on the boundary effects. It is generally reduced by
open boundary conditions, and in some cases it disappears if the boundaries are
too favorable towards nucleation. However, we also demonstrate conditions under
which the peak remains discernible. This peak arises as a purely dynamic effect
and is not related to the possible existence of multiple domains. We illustrate
the predictions of droplet theory by Monte Carlo simulations of two-dimensional
Ising systems with various system shapes and boundary conditions.Comment: RevTex, 48 pages, 13 figure
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