Wolf Trap continuation study Final report

Critical evaluation of light and X ray scatter, conductivity, and fluorescence as part of Wolf Trap extraterrestrial life detector developmen

Non-Book Materials in Libraries: A Practical Guide (Book Review)

published or submitted for publicatio

SIRT6 stabilizes DNA-dependent Protein Kinase at chromatin for DNA double-strand break repair

The Sir2 chromatin regulatory factor links maintenance of genomic stability to life span extension in yeast. The mammalian Sir2 family member SIRT6 has been proposed to have analogous functions, because SIRT6-deficiency leads to shortened life span and an aging-like degenerative phenotype in mice, and SIRT6 knockout cells exhibit genomic instability and DNA damage hypersensitivity. However, the molecular mechanisms underlying these defects are not fully understood. Here, we show that SIRT6 forms a macromolecular complex with the DNA double-strand break (DSB) repair factor DNA-PK (DNA-dependent protein kinase) and promotes DNA DSB repair. In response to DSBs, SIRT6 associates dynamically with chromatin and is necessary for an acute decrease in global cellular acetylation levels on histone H3 Lysine 9. Moreover, SIRT6 is required for mobilization of the DNA-PK catalytic subunit (DNA-PKcs) to chromatin in response to DNA damage and stabilizes DNA-PKcs at chromatin adjacent to an induced site-specific DSB. Abrogation of these SIRT6 activities leads to impaired resolution of DSBs. Together, these findings elucidate a mechanism whereby regulation of dynamic interaction of a DNA repair factor with chromatin impacts on the efficiency of repair, and establish a link between chromatin regulation, DNA repair, and a mammalian Sir2 factor

Primary antiphospholipid syndrome evolving into systemic lupus erythematosus: may antinucleosome antibodies be predictive?

Objective: It was reported by several groups that patients diagnosed as primary antiphospholipid syndrome (PAPS) had developed a full-blown systemic lupus erythematosus (SLE) even after many years of follow-up. Little is known about clinical and/or serological factors that may help predict such evolution. Antinucleosome antibodies (anti-NCS) were described to appear in early stages of SLE, in particular before anti-dsDNA antibodies. The aim of the study is to evaluate the prevalence of anti-NCS in a large cohort of PAPS patients. Methods: IgG and IgM anti-NCS antibodies were detected using a home made assay with H1-stripped chromatin as antigen. Sera from 106 PAPS patients were tested; 52 of them were also tested during the follow-up, at least 2 years apart form the basal sample. Results: Medium-high titre anti-NCS were found in nearly half of the patients (49/106, 46%), more frequently in those presenting features of "lupus like disease". Most of patients displayed an unchanged pattern of anti-NCS over time. We describe three cases of PAPS patients that developed SLE after many years of follow-up; high titre and low titre anti-NCS were present in two and one of them respectively several years before evolving into SLE. Conclusions: A significant proportion of PAPS patients displayed medium-high titre anti-NCS, suggesting that the autoimmune response against chromatin may be a relevant event not only in patients with SLE. Further studies are warranted to explore the predictive value of anti-NCS with respect to the evolution from PAPS to SLE

Cell-cell adhesion regulates Merlin/NF2 interaction with the PAF complex

The PAF complex (PAFC) coordinates transcription elongation and mRNA processing and its CDC73/parafibromin subunit functions as a tumour suppressor. The NF2/Merlin tumour suppressor functions both at the cell cortex and nucleus and is a key mediator of contact inhibition but the molecular mechanisms remain unclear. In this study we have used affinity proteomics to identify novel Merlin interacting proteins and show that Merlin forms a complex with multiple proteins involved in RNA processing including the PAFC and the CHD1 chromatin remodeller. Tumour-derived inactivating mutations in both Merlin and the CDC73 PAFC subunit mutually disrupt their interaction and growth suppression by Merlin requires CDC73. Merlin interacts with the PAFC in a cell density-dependent manner and we identify a role for FAT cadherins in regulating the Merlin-PAFC interaction. Our results suggest that in addition to its function within the Hippo pathway, Merlin is part of a tumour suppressor network regulated by cell-cell adhesion which coordinates post-initiation steps of the transcription cycle of genes mediating contact inhibition

Lunar Outgassing, Transient Phenomena and The Return to The Moon, I: Existing Data

Herein the transient lunar phenomena (TLP) report database is subjected to a discriminating statistical filter robust against sites of spurious reports, and produces a restricted sample that may be largely reliable. This subset is highly correlated geographically with the catalog of outgassing events seen by the Apollo 15, 16 and Lunar Prospector alpha-particle spectrometers for episodic Rn-222 gas release. Both this robust TLP sample and even the larger, unfiltered sample are highly correlated with the boundary between mare and highlands, as are both deep and shallow moonquakes, as well as Po-210, a long-lived product of Rn-222 decay and a further tracer of outgassing. This offers another significant correlation relating TLPs and outgassing, and may tie some of this activity to sagging mare basalt plains (perhaps mascons). Additionally, low-level but likely significant TLP activity is connected to recent, major impact craters (while moonquakes are not), which may indicate the effects of cracks caused by the impacts, or perhaps avalanches, allowing release of gas. The majority of TLP (and Rn-222) activity, however, is confined to one site that produced much of the basalt in the Procellarum Terrane, and it seems plausible that this TLP activity may be tied to residual outgassing from the formerly largest volcanic ffusion sites from the deep lunar interior. With the coming in the next few years of robotic spacecraft followed by human exploration, the study of TLPs and outgassing is both promising and imperiled. We will have an unprecedented pportunity to study lunar outgassing, but will also deal with a greater burden of anthropogenic lunar gas than ever produced. There is a pressing need to study lunar atmosphere and its sources while still pristine. [Abstract abridged.]Comment: 35 pages, 3 figures, submitted to Icarus. Other papers in series found at http://www.astro.columbia.edu/~arlin/TLP

Nonlinear Dynamics and Interpersonal Correlates of Verbal Turn-Taking Patterns in a Group Therapy Session

Interpersonal processes and dynamics are ubiquitous topics in psychotherapy, yet they are difficult to study and are theoretically fragmented across therapeutic subdisciplines. The current study tests an integrative model of interpersonal dynamics in small groups using nonlinear dynamical systems theory. The conversation of one group therapy session (with six adolescent sex offenders) is analyzed using orbital decomposition, which allows for the identification of patterns in categorical time series data. The results show evidence of selforganizing social patterns, based on formal measures of turbulence (Lyapunov dimension), information novelty (Shannon\u27s entropy), and complexity (fractal dimension). The degree of patterning in turn taking is significantly correlated with measurements of control, closeness, and conflict among group members. Clinical implications and directions for future research are discussed