Targeting of the hepatitis B virus precore protein to the endoplasmic reticulum membrane: after signal peptide cleavage translocation can be aborted and the product released into the cytoplasm.

The major hepatitis B virus (HBV) core protein is a viral structural protein involved in nucleic acid binding. Its coding sequence contains an extension of 29 codons (the "precore" region) at the amino terminus of the protein which is present in a fraction of the viral transcripts. This region is evolutionarily conserved among mammalian and avian HBVs, suggesting it has functional importance, although at least for duck HBV it has been shown to be nonessential for replication of infectious virions. Using in vitro assays for protein translocation across the endoplasmic reticulum membrane, we found that the precore region of the HBV genome encodes a signal sequence. This signal sequence was recognized by signal recognition particle, which targeted the nascent precore protein to the endoplasmic reticulum membrane with efficiencies comparable to those of other mammalian secretory proteins. A 19-amino acid signal peptide was removed by signal peptidase on the lumenal side of the microsomal membrane, generating a protein similar to the HBV major core protein, but containing 10 additional amino acids from the precore region at its amino terminus. Surprisingly, we found that 70-80% of this signal peptidase-cleaved product was localized on the cytoplasmic side of the microsomal vesicles and was not associated with the membranes. We conclude that translocation was aborted by an unknown mechanism, then the protein disengaged from the translocation machinery and was released back into the cytoplasm. Thus, a cytoplasmically disposed protein was created whose amino terminus resulted from signal peptidase cleavage. The remaining 20-30% appeared to be completely translocated into the lumen of the microsomes. A deletion mutant lacking the carboxy-terminal nucleic acid binding domain of the precore protein was similarly partitioned between the lumen of the microsomes and the cytoplasmic compartment, indicating that this highly charged domain is not responsible for the aborted translocation. We discuss the implications of our findings for the protein translocation process and suggest a possible role in the virus life cycle

Deep analysis of perception through dynamic structures that emerge in cortical activity from self-regulated noise

The statistical properties of the spontaneous background electrocorticogram (ECoG) were modeled, starting with random numbers, constraining the distributions, and identifying characteristic deviations from randomness in ECoG from subjects at rest and during intentional behaviors. The ECoG had been recorded through 8 × 8 arrays of 64 electrodes, from the surfaces of auditory, visual, or somatic cortices of 9 rabbits, and from the inferotemporal cortex of a human subject. Power spectral densities (PSD) in coordinates of log10 power versus log10 frequency of ECoG from subjects at rest usually conformed to noise in power-law distributions in a continuum. PSD of ECoG from active subjects usually deviated from noise in having peaks in log10 power above the power-law line in various frequency bands. The analytic signals from the Hilbert transform after band pass filtering in the beta and gamma ranges revealed beats from interference among distributed frequencies in band pass filtered noise called Rayleigh noise. The beats were displayed as repetitive down spikes in log10 analytic power. Repetition rates were proportional to filter bandwidths for all center frequencies. Resting ECoG often gave histograms of the magnitudes and intervals of down spikes that conformed to noise. Histograms from active ECoG often deviated from noise in Rayleigh distributions of down spike intervals by giving what are called Rice (Mathematical analysis of random noise—and appendixes—technical publications monograph B-1589. Bell Telephone Labs Inc., New York, 1950) distributions. Adding power to noise as signals at single frequencies simulated those deviations. The beats in dynamic theory are deemed essential for perception, by gating beta and gamma bursts at theta rates through enhancement of the cortical signal-to-noise ratio in exceptionally deep down spikes called null spikes

Survival of the fittest: Retrospective cohort study of the longevity of Olympic medallists in the modern era

Objective: To determine whether Olympic medallists live longer than the general population. Design: Retrospective cohort study, with passive follow-up and conditional survival analysis to account for unidentified loss to follow-up. Setting and participants: 15 174 Olympic athletes from nine country groups (United States, Germany, Nordic countries, Russia, United Kingdom, France, Italy, Canada, and Australia and New Zealand) who won medals in the Olympic Games held in 1896-2010. Medallists were compared with matched cohorts in the general population (by country, age, sex, and year of birth). Main outcome measures Relative conditional survival. Results: More medallists than matched controls in the general population were alive 30 years after winning (relative conditional survival 1.08, 95% confidence interval 1.07 to 1.10). Medallists lived an average of 2.8 years longer than controls. Medallists in eight of the nine country groups had a significant survival advantage compared with controls. Gold, silver, and bronze medallists each enjoyed similar sized survival advantages. Medallists in endurance sports and mixed sports had a larger survival advantage over controls at 30 years (1.13, 1.09 to 1.17; 1.11, 1.09 to 1.13) than that of medallists in power sports (1.05, 1.01 to 1.08). Conclusions: Olympic medallists live longer than the general population, irrespective of country, medal, or sport. This study was not designed to explain this effect, but possible explanations include genetic factors, physical activity, healthy lifestyle, and the wealth and status that come with international sporting glory. © BMJ Publishing Group Ltd 2012

Molecular Gas in Three z ∼ 7 Quasar Host Galaxies

We present ALMA band 3 observations of the CO(6-5), CO(7-6), and [C i] 369 μm emission lines in three of the highest-redshift quasar host galaxies at . These measurements constitute the highest-redshift CO detections to date. The target quasars have previously been detected in [C ii] 158 μm emission and the underlying FIR dust continuum. We detect (spatially unresolved, at a resolution of > 2″, or ≈14 kpc) CO emission in all three quasar hosts. In two sources, we detect the continuum emission around 400 μm (rest-frame), and in one source we detect [C i] at low significance. We derive molecular gas reservoirs of (1-3) T10 10 in the quasar hosts, i.e., approximately only 10 times the mass of their central supermassive black holes. The extrapolated [C ii]-to-CO(1-0) luminosity ratio is 2500-4200, consistent with measurement s in galaxies at lower redshift. The detection of the [C i] line in one quasar host galaxy and the limit on the [C i] emission in the other two hosts enables a first characterization of the physical properties of the interstellar medium in z ∼ 7 quasar hosts. In the sources, the derived global CO/[C ii] /[C i] line ratios are consistent with expectations from photodissociation regions, but not X-ray-dominated regions. This suggest that quantities derived from the molecular gas and dust emission are related to ongoing star-formation activity in the quasar hosts, providing further evidence that the quasar hosts studied here harbor intense starbursts in addition to their active nucleus

Behavioral states may be associated with distinct spatial patterns in electrocorticogram

To determine if behavioral states are associated with unique spatial electrocorticographic (ECoG) patterns, we obtained recordings with a microgrid electrode array applied to the cortical surface of a human subject. The array was constructed with the intent of extracting maximal spatial information by optimizing interelectrode distances. A 34-year-old patient with intractable epilepsy underwent intracranial ECoG monitoring after standard methods failed to reveal localization of seizures. During the 8-day period of invasive recording, in addition to standard clinical electrodes a square 1 × 1 cm microgrid array with 64 electrodes (1.25 mm separation) was placed on the right inferior temporal gyrus. Careful review of video recordings identified four extended naturalistic behaviors: reading, conversing on the telephone, looking at photographs, and face-to-face interactions. ECoG activity recorded with the microgrid that corresponded to these behaviors was collected and ECoG spatial patterns were analyzed. During periods of ECoG selected for analysis, no electrographic seizures or epileptiform patterns were present. Moments of maximal spatial variance are shown to cluster by behavior. Comparisons between conditions using a permutation test reveal significantly different spatial patterns for each behavior. We conclude that ECoG recordings obtained on the cortical surface with optimal high spatial frequency resolution reveal distinct local spatial patterns that reflect different behavioral states, and we predict that similar patterns will be found in many if not most cortical areas on which a microgrid is placed

Transmutations and spectral parameter power series in eigenvalue problems

We give an overview of recent developments in Sturm-Liouville theory concerning operators of transmutation (transformation) and spectral parameter power series (SPPS). The possibility to write down the dispersion (characteristic) equations corresponding to a variety of spectral problems related to Sturm-Liouville equations in an analytic form is an attractive feature of the SPPS method. It is based on a computation of certain systems of recursive integrals. Considered as families of functions these systems are complete in the $L_{2}$-space and result to be the images of the nonnegative integer powers of the independent variable under the action of a corresponding transmutation operator. This recently revealed property of the Delsarte transmutations opens the way to apply the transmutation operator even when its integral kernel is unknown and gives the possibility to obtain further interesting properties concerning the Darboux transformed Schr\"{o}dinger operators. We introduce the systems of recursive integrals and the SPPS approach, explain some of its applications to spectral problems with numerical illustrations, give the definition and basic properties of transmutation operators, introduce a parametrized family of transmutation operators, study their mapping properties and construct the transmutation operators for Darboux transformed Schr\"{o}dinger operators.Comment: 30 pages, 4 figures. arXiv admin note: text overlap with arXiv:1111.444