A model of methane concentration profiles in the open ocean

Methane-bearing particulate matter formed in the upper ocean layer is allowed to settle and degrade, releasing methane into the water column as a source in one-dimensional advection-diffusion equations. Predicted carbon and methane particulate fluxes are in good agreement with sediment trap data, using parameters of expected magnitude and particulate methane production well within the mixed layer. This suggests a rapid pathway to the atmosphere and reduced effects on methane concentrations below. Vertical advection rates yielding a good fit between methane concentration calculations and data are larger than expected unless methane oxidation is included. This confirms the significance of methane oxidation in shaping open-ocean methane concentration profiles in spite of turnover times of decades. Predictions of the isotopic composition of dissolved methane δ13 C with the one-dimensional model are more difficult, although trends in measured vertical profiles can be reproduced. While this work does not shed light on the purported mechanism of methane generation in the upper ocean, it shows that methane of particulate origin is sufficient to explain observed open-ocean methane concentrations

Notes on the modeling of methane in aging hydrothermal plumes

Marine hydrothermal vent fields represent a unique environment for the study of aerobic microbial methane oxidation because of high methane concentrations and limited spatial and temporal scales. Earlier data collected in lateral plumes at the Endeavour Segment of the Juan de Fuca Ridge, including methane concentration, methane oxidation rate and stable carbon isotopic composition (δ13C), are carefully interpreted with a suite of simple analytical models. Methane oxidation is defined with a rate constant k as a first order process with respect to both substrate and methanotroph concentration. This elementary formalism coupled with simplified representations of advection and diffusion through the lateral plume is sufficient to reproduce salient features of the data: maximum methane turnover times of about a week 2 km from the vent field location and stable carbon isotopic enrichment from -47‰ to values exceeding -5‰ over a distance of 15 km. Results suggest that k is of order 10-8 (nM-s)-1 at local conditions and that methane oxidizing bacteria hold about 12 fg of carbon per cell

A Study of Degenerate Four-quark states in SU(2) Lattice Monte Carlo

The energies of four-quark states are calculated for geometries in which the quarks are situated on the corners of a series of tetrahedra and also for geometries that correspond to gradually distorting these tetrahedra into a plane. The interest in tetrahedra arises because they are composed of {\bf three } degenerate partitions of the four quarks into two two-quark colour singlets. This is an extension of earlier work showing that geometries with {\bf two} degenerate partitions (e.g.\ squares) experience a large binding energy. It is now found that even larger binding energies do not result, but that for the tetrahedra the ground and first excited states become degenerate in energy. The calculation is carried out using SU(2) for static quarks in the quenched approximation with $\beta=2.4$ on a $16^3\times 32$ lattice. The results are analysed using the correlation matrix between different euclidean times and the implications of these results are discussed for a model based on two-quark potentials.Comment: Original Raw PS file replace by a tarred, compressed and uuencoded PS fil

Simultaneous disruption of two DNA polymerases, Polη and Polζ, in Avian DT40 cells unmasks the role of Polη in cellular response to various DNA lesions

Replicative DNA polymerases are frequently stalled by DNA lesions. The resulting replication blockage is released by homologous recombination (HR) and translesion DNA synthesis (TLS). TLS employs specialized TLS polymerases to bypass DNA lesions. We provide striking in vivo evidence of the cooperation between DNA polymerase η, which is mutated in the variant form of the cancer predisposition disorder xeroderma pigmentosum (XP-V), and DNA polymerase ζ by generating POLη−/−/POLζ−/− cells from the chicken DT40 cell line. POLζ−/− cells are hypersensitive to a very wide range of DNA damaging agents, whereas XP-V cells exhibit moderate sensitivity to ultraviolet light (UV) only in the presence of caffeine treatment and exhibit no significant sensitivity to any other damaging agents. It is therefore widely believed that Polη plays a very specific role in cellular tolerance to UV-induced DNA damage. The evidence we present challenges this assumption. The phenotypic analysis of POLη−/−/POLζ−/− cells shows that, unexpectedly, the loss of Polη significantly rescued all mutant phenotypes of POLζ−/− cells and results in the restoration of the DNA damage tolerance by a backup pathway including HR. Taken together, Polη contributes to a much wide range of TLS events than had been predicted by the phenotype of XP-V cells

Structure and mechanism of human DNA polymerase η

The variant form of the human syndrome xeroderma pigmentosum (XPV) is caused by a deficiency in DNA polymerase eta (Pol eta), a DNA polymerase that enables replication through ultraviolet-induced pyrimidine dimers. Here we report high-resolution crystal structures of human Pol eta at four consecutive steps during DNA synthesis through cis-syn cyclobutane thymine dimers. Pol eta acts like a 'molecular splint' to stabilize damaged DNA in a normal B-form conformation. An enlarged active site accommodates the thymine dimer with excellent stereochemistry for two-metal ion catalysis. Two residues conserved among Pol eta orthologues form specific hydrogen bonds with the lesion and the incoming nucleotide to assist translesion synthesis. On the basis of the structures, eight Pol eta missense mutations causing XPV can be rationalized as undermining the molecular splint or perturbing the active-site alignment. The structures also provide an insight into the role of Pol eta in replicating through D loop and DNA fragile sites

Temporal Progression Patterns of Brain Atrophy in Corticobasal Syndrome and Progressive Supranuclear Palsy Revealed by Subtype and Stage Inference (SuStaIn)

Differentiating corticobasal degeneration presenting with corticobasal syndrome (CBD-CBS) from progressive supranuclear palsy with Richardson's syndrome (PSP-RS), particularly in early stages, is often challenging because the neurodegenerative conditions closely overlap in terms of clinical presentation and pathology. Although volumetry using brain magnetic resonance imaging (MRI) has been studied in patients with CBS and PSP-RS, studies assessing the progression of brain atrophy are limited. Therefore, we aimed to reveal the difference in the temporal progression patterns of brain atrophy between patients with CBS and those with PSP-RS purely based on cross-sectional data using Subtype and Stage Inference (SuStaIn)—a novel, unsupervised machine learning technique that integrates clustering and disease progression modeling. We applied SuStaIn to the cross-sectional regional brain volumes of 25 patients with CBS, 39 patients with typical PSP-RS, and 50 healthy controls to estimate the two disease subtypes and trajectories of CBS and PSP-RS, which have distinct atrophy patterns. The progression model and classification accuracy of CBS and PSP-RS were compared with those of previous studies to evaluate the performance of SuStaIn. SuStaIn identified distinct temporal progression patterns of brain atrophy for CBS and PSP-RS, which were largely consistent with previous evidence, with high reproducibility (99.7%) under cross-validation. We classified these diseases with high accuracy (0.875) and sensitivity (0.680 and 1.000, respectively) based on cross-sectional structural brain MRI data; the accuracy was higher than that reported in previous studies. Moreover, SuStaIn stage correctly reflected disease severity without the label of disease stage, such as disease duration. Furthermore, SuStaIn also showed the genialized performance of differentiation and reflection for CBS and PSP-RS. Thus, SuStaIn has potential for improving our understanding of disease mechanisms, accurately stratifying patients, and providing prognoses for patients with CBS and PSP-RS

Branching ratio change in K- absorption at rest and the nature of the Lambda(1405)

We investigate in-medium corrections to the branching ratio in K- absorption at rest and their effect on the (positively and negatively) charged pion spectrum. The in-medium corrections are due to Pauli blocking, which arises if the Lambda(1405) is assumed to be a $\bar{K}$-nucleon bound state and leads to a density and momentum dependent mass shift of the Lambda(1405). Requiring that the optical potential as well as the branching ratio are derived from the same elementary T-matrix, we find that the in-medium corrected, density dependent T-matrix gives a better description of the K- absorption reaction than the free, density-independent one. This result suggests that the dominant component of the Lambda(1405) wave function is the $\bar{K}N$ bound state.Comment: 8 Pages, Revtex with epsf, and embedded 8 ps figure

Evidence for a Rad18-Independent Frameshift Mutagenesis Pathway in Human Cell-Free Extracts

Bypass of replication blocks by specialized DNA polymerases is crucial for cell survival but may promote mutagenesis and genome instability. To gain insight into mutagenic sub-pathways that coexist in mammalian cells, we examined N-2-acetylaminofluorene (AAF)-induced frameshift mutagenesis by means of SV40-based shuttle vectors containing a single adduct. We found that in mammalian cells, as previously observed in E. coli, modification of the third guanine of two target sequences, 5'-GGG-3' (3G) and 5'-GGCGCC-3' (NarI site), induces –1 and –2 frameshift mutations, respectively. Using an in vitro assay for translesion synthesis, we investigated the biochemical control of these events. We showed that Pol eta, but neither Pol iota nor Pol zeta, plays a major role in the frameshift bypass of the AAF adduct located in the 3G sequence. By complementing PCNA-depleted extracts with either a wild-type or a non-ubiquitinatable form of PCNA, we found that this Pol eta-mediated pathway requires Rad18 and ubiquitination of PCNA. In contrast, when the AAF adduct is located within the NarI site, TLS is only partially dependent upon Pol eta and Rad18, unravelling the existence of alternative pathways that concurrently bypass this lesion

Collybistin and gephyrin are novel components of the eukaryotic translation initiation factor 3 complex

<p>Abstract</p> <p>Background</p> <p>Collybistin (CB), a neuron-specific guanine nucleotide exchange factor, has been implicated in targeting gephyrin-GABA_Areceptors clusters to inhibitory postsynaptic sites. However, little is known about additional CB partners and functions.</p> <p>Findings</p> <p>Here, we identified the p40 subunit of the eukaryotic translation initiation factor 3 (eIF3H) as a novel binding partner of CB, documenting the interaction in yeast, non-neuronal cell lines, and the brain. In addition, we demonstrated that gephyrin also interacts with eIF3H in non-neuronal cells and forms a complex with eIF3 in the brain.</p> <p>Conclusions</p> <p>Together, our results suggest, for the first time, that CB and gephyrin associate with the translation initiation machinery, and lend further support to the previous evidence that gephyrin may act as a regulator of synaptic protein synthesis.</p