An integrated biostratigraphy and seismic stratigraphy for the late Neogene continental margin succession in northern Taranaki Basin, New Zealand

Our aim has been to develop an integrated biostratigraphy and seismic stratigraphy for the Pliocene and Pleistocene formations (Ariki, Mangaa, Giant Foresets) in northern Taranaki Basin to better understand the evolution of the modern continental margin offshore central-western North Island, New Zealand. Detailed mapping of seismic reflectors in part of the basin, when compared with correlations of late Neogene stage boundaries between 11 well sections, has highlighted crossover between the datasets. To help resolve this issue, the biostratigraphy of the Pliocene-Pleistocene parts of each of four well sections (Arawa-1, Ariki-1, Kora-1, and Wainui-1) has been re-examined using a dense suite of samples. In addition, the biostratigraphy of seven other well sections (Awatea-1, Kahawai-1, Mangaa-1, Taimana-1, Tangaroa-1, Te Kumi-1, and Turi-1) has been re-evaluated. The crossover is partly attributed to a combination of sampling resolution inherent in exploration well sections, the mixed nature of cuttings samples, and the general scarcity of age-diagnostic planktic foraminifera in the late Neogene formations. The achievement of seismic closure suggests that error in the mapping of the seismic reflectors is not a significant source of the uncertainty (crossover). We have developed a workable time-stratigraphic framework by qualitatively weighting the biostratigraphic data in each of the well sections, thereby identifying the parts of particular well sections with the highest resolution microfossil data and the optimal stratigraphic position of stage boundaries with respect to the mapped seismic horizons/seismic units. Hence, it is possible to assign the known numerical ages for these stage boundaries to reflection horizons/seismic units mapped within the basin. We have applied this information to produce a series of isopach maps for successive stage boundaries that help show the sedimentary evolution of the continental margin succession west of central North Island

An effective all-atom potential for proteins

We describe and test an implicit solvent all-atom potential for simulations of protein folding and aggregation. The potential is developed through studies of structural and thermodynamic properties of 17 peptides with diverse secondary structure. Results obtained using the final form of the potential are presented for all these peptides. The same model, with unchanged parameters, is furthermore applied to a heterodimeric coiled-coil system, a mixed alpha/beta protein and a three-helix-bundle protein, with very good results. The computational efficiency of the potential makes it possible to investigate the free-energy landscape of these 49--67-residue systems with high statistical accuracy, using only modest computational resources by today's standards

Histone deacetylase regulates high mobility group A2-targeting microRNAs in human cord blood-derived multipotent stem cell aging

Cellular senescence involves a reduction in adult stem cell self-renewal, and epigenetic regulation of gene expression is one of the main underlying mechanisms. Here, we observed that the cellular senescence of human umbilical cord blood-derived multipotent stem cells (hUCB-MSCs) caused by inhibition of histone deacetylase (HDAC) activity leads to down-regulation of high mobility group A2 (HMGA2) and, on the contrary, to up-regulation of p16INK4A, p21CIP1/WAF1 and p27KIP1. We found that let-7a1, let-7d, let-7f1, miR-23a, miR-26a and miR-30a were increased during replicative and HDAC inhibitor-mediated senescence of hUCB-MSCs by microRNA microarray and real-time quantitative PCR. Furthermore, the configurations of chromatins beading on these miRNAs were prone to transcriptional activation during HDAC inhibitor-mediated senescence. We confirmed that miR-23a, miR-26a and miR-30a inhibit HMGA2 to accelerate the progress of senescence. These findings suggest that HDACs may play important roles in cellular senescence by regulating the expression of miRNAs that target HMGA2 through histone modification

CDK2 and PKA Mediated-Sequential Phosphorylation Is Critical for p19INK4d Function in the DNA Damage Response

DNA damage triggers a phosphorylation-based signaling cascade known as the DNA damage response. p19INK4d, a member of the INK4 family of CDK4/6 inhibitors, has been reported to participate in the DNA damage response promoting DNA repair and cell survival. Here, we provide mechanistic insight into the activation mechanism of p19INK4d linked to the response to DNA damage. Results showed that p19INK4d becomes phosphorylated following UV radiation, β-amyloid peptide and cisplatin treatments. ATM-Chk2/ATR-Chk1 signaling pathways were found to be differentially involved in p19INK4d phosphorylation depending on the type of DNA damage. Two sequential phosphorylation events at serine 76 and threonine 141 were identified using p19INK4d single-point mutants in metabolic labeling assays with 32P-orthophosphate. CDK2 and PKA were found to participate in p19INK4d phosphorylation process and that they would mediate serine 76 and threonine 141 modifications respectively. Nuclear translocation of p19INK4d induced by DNA damage was shown to be dependent on serine 76 phosphorylation. Most importantly, both phosphorylation sites were found to be crucial for p19INK4d function in DNA repair and cell survival. In contrast, serine 76 and threonine 141 were dispensable for CDK4/6 inhibition highlighting the independence of p19INK4d functions, in agreement with our previous findings. These results constitute the first description of the activation mechanism of p19INK4d in response to genotoxic stress and demonstrate the functional relevance of this activation following DNA damage

Trends in template/fragment-free protein structure prediction

Predicting the structure of a protein from its amino acid sequence is a long-standing unsolved problem in computational biology. Its solution would be of both fundamental and practical importance as the gap between the number of known sequences and the number of experimentally solved structures widens rapidly. Currently, the most successful approaches are based on fragment/template reassembly. Lacking progress in template-free structure prediction calls for novel ideas and approaches. This article reviews trends in the development of physical and specific knowledge-based energy functions as well as sampling techniques for fragment-free structure prediction. Recent physical- and knowledge-based studies demonstrated that it is possible to sample and predict highly accurate protein structures without borrowing native fragments from known protein structures. These emerging approaches with fully flexible sampling have the potential to move the field forward