A SCC MO Calculation on the Tetracyanoethylene-benzene Complex

Dr. Shannon Lieb\u27s contribution to Volume 94 of the Proceedings of the Indiana Academy of Science

Abnormal compartmentalization of cartilage matrix components in mice lacking collagen X: Implications for function

There are conflicting views on whether collagen X is a purely structural molecule, or regulates bone mineralization during endochondral ossification. Mutations is the human collagen α1(X) gene (COL10A1) in Schmid metaphyseal chondrodysplasia (SMCD) suggest a supportive role. But mouse collagen α1(X) gene (Col10A1) null mutants were previously reported to show no obvious phenotypic change. We have generated collagen X deficient mice, which shows that deficiency does have phenotypic consequences which partly resemble SMCD, such as abnormal trabecular bone architecture. In particular, the mutant mice develop coxa vara, a phenotypic change common in human SMCD. Other consequences of the mutation are reduction in thickness of growth plate resting zone and articular cartilage, altered bone content, and atypical distribution of matrix components within growth plate cartilage. We propose that collagen X plays a role in the normal distribution of matrix vesicles and proteoglycans within the growth plate matrix. Collagen X deficiency impacts on the supporting properties of the growth plate and the mineralization process, resulting in abnormal trabecular bone. This hypothesis would accommodate the previously conflicting views of the function of collagen X and of the molecular pathogenesis of SMCD.published_or_final_versio

TREX1 DNA exonuclease deficiency, accumulation of single stranded DNA and complex human genetic disorders

Aicardi-Goutieres syndrome (AGS) is an unusual condition that clinically mimics a congenital viral infection. Several genes have recently been implicated in the aetiology of this disorder. One of these genes encodes the DNA exonuclease TREX1. Recent work from Yang, Lindahl and Barnes has provided insight into the cellular consequence of TREX1-deficiency. They found that TREX1-deficiency resulted in the intracellular accumulation of single stranded DNA resulting in chronic activation of the DNA damage response network, even in cells from Trex1-mutated AGS patients. Here, I summarise their findings and discuss them in context with the other AGS causative genes which encode subunits of the RNase H2 complex. I describe mechanisms by which the inappropriate intracellular accumulation of nucleic acid species might deleteriously impact upon normal cell cycle progression. Finally, using the example of Systemic Lupus Erythematosus (SLE), I also summarise the evidence suggesting that the failure to process intermediates of nucleic acid metabolism can result in the activation of uncontrolled autoimmunity

Making data a first class scientific output : data citation and publication by NERC's Environmental Data Centres

The NERC Science Information Strategy Data Citation and Publication project aims to develop and formalise a method for formally citing and publishing the datasets stored in its environmental data centres. It is believed that this will act as an incentive for scientists, who often invest a great deal of effort in creating datasets, to submit their data to a suitable data repository where it can properly be archived and curated. Data citation and publication will also provide a mechanism for data producers to receive credit for their work, thereby encouraging them to share their data more freely

Bostonia

Founded in 1900, Bostonia magazine is Boston University's main alumni publication, which covers alumni and student life, as well as university activities, events, and programs

Epigenetic memory in response to environmental stressors

Exposure to environmental stressors, toxicants, and nutrient deficiencies can affect DNA in several ways. Some exposures cause damage and alter the structure of DNA, but there is increasing evidence that the same or other environmental exposures, including those that occur during fetal development in utero, can cause epigenetic effects that modulate DNA function and gene expression. Some epigenetic changes to DNA that affect gene transcription are at least partially reversible (i.e., they can be enzymatically reversed after cessation of exposure to environmental agents), but some epigenetic modifications seem to persist, even for decades. To explain the effects of early life experiences (such as famine and exposures to other stressors) on the long-term persistence of specific patterns of epigenetic modifications, such as DNA methylation, we propose an analogy with immune memory. We propose that an epigenetic memory can be established and maintained in self-renewing stem cell compartments. We suggest that the observations on early life effects on adult diseases and the persistence of methylation changes in smokers support our hypothesis, for which a mechanistic basis, however, needs to be further clarified. We outline a new model based on methylation changes. Although these changes seem to be mainly adaptive, they are also implicated in the pathogenesis and onset of diseases, depending on individual genotypic background and types of subsequent exposures. Elucidating the relationships between the adaptive and maladaptive consequences of the epigenetic modifications that result from complex environmental exposures is a major challenge for current and future research in epigenetics.-Vineis, P., Chatziioannou, A., Cunliffe, V. T., Flanagan, J. M., Hanson, M., Kirsch-Volders, M., Kyrtopoulos, S. Epigenetic memory in response to environmental stressors

Precision Test of Holographic Flavourdynamics

We study the Berkooz–Douglas matrix model using holography, lattice simulation and high temperature perturbative expansion. In particular we calculate the mass susceptibility of the theory. Our results show excellent agreement between lattice simulations and holography at low and intermediate temperatures T≤λ1/3. We also report a surprisingly good agreement between holography and perturbative high temperature expansion at T∼λ1/3

Operationalizing Equity in Surgical Prioritization

The allocation of critical care resources and triaging patients garnered a great deal of attention during the COVID-19 pandemic, but there is a paucity of guidance regarding the ethical aspects of resource allocation and patient prioritization in ‘normal’ circumstances for Canadian healthcare systems. One context where allocation and prioritization decisions are required are surgical waitlists, which have been globally exacerbated due to the COVID-19 pandemic. In this paper, we detail the process used to develop an ethics framework to support prioritization for elective surgery at The Hospital for Sick Children, Toronto, a tertiary pediatric hospital. Our goal was to provide guidance for the more value-laden aspects of prioritization, particularly when clinical urgency alone is insufficient to dictate priority. With this goal in mind, we worked to capture familial, relational, and equity considerations. As part of our institution’s concerted efforts to ethically and effectively address our surgical backlog, an ethics working group was formed comprising clinicians from surgery, anesthesiology, intensive care, a hospital bioethicist, a parent advisor, and an academic bioethics researcher. A reflective equilibrium process was used to develop an ethics framework. To this end, the same methodology was used to create a support for patient prioritization that identifies clinically and morally relevant factors for prioritization among medically similar surgical cases, with a substantive goal being to identify and redress health inequities in surgical prioritization, inasmuch as this is possible. While further steps are needed to validate several aspects of the framework, our research suggests that an ethics framework grounded in the practical realities of hospital operations provides consistency, transparency, and needed support for decisions that are often left to individual clinicians, as well as an opportunity to reflect upon the presence of health inequities in all domains of healthcare delivery

Present-day stress orientations and tectonic provinces of the NW Borneo collisional margin

Extent: 15p.Borehole failure observed on image and dipmeter logs from 55 petroleum wells across the NW Borneo collisional margin were used to determine maximum horizontal stress (σH) orientations; combined with seismic and outcrop data, they define seven tectonic provinces. The Baram Delta–Deepwater Fold-Thrust Belt exhibits three tectonic provinces: its inner shelf inverted province (σH is NW-SE, margin-normal), its outer shelf extension province (σH is NE-SW, margin-parallel), and its slope to basin floor compression province (σH is NW-SE, margin-normal). In the inverted province, σH reflects inversion of deltaic normal faults. The σH orientations in the extension and compression provinces reflect deltaic gravitational tectonics. The shale and minibasin provinces have been recognized in offshore Sabah. In the shale province, σH is N010°E, which aligns around the boundary of a massif of mobile shale. Currently, no data are available to determine σH in the minibasin province. In the Balingian province, σH is ESE-WNW, reflecting ESE absolute Sunda plate motions due to the absence of a thick detachment seen elsewhere in NW Borneo. The Central Luconia province demonstrates poorly constrained and variable σH orientations. These seven provinces result from the heterogeneous structural and stratigraphic development of the NW Borneo margin and formed due to complex collisional tectonics and the varied distribution and thicknesses of stratigraphic packages.Rosalind C. King, Mark R. P. Tingay, Richard R. Hillis, Christopher K. Morley, and James Clar