An Improved Animal Model of Multiple Myeloma Bone Disease

Multiple myeloma (MM) is a plasma cell malignancy that causes an accumulation of terminally differentiated monoclonal plasma cells in the bone marrow, accompanied by multiple myeloma bone disease (MMBD). MM animal models have been developed and enable to interrogate the mechanism of MM tumorigenesis. However, these models demonstrate little or no evidence of MMBD. We try to establish the MMBD model with severe bone lesions and easily accessible MM progression. 1 x 10(6) luciferase-expressing 5TGM1 cells were injected into 8-12 week-old NOD SCID gamma mouse (NSG) and C57BL/KaLwRij mouse via the tail vein. Myeloma progression was assessed weekly via in vivo bioluminescence (BL) imaging using IVIS-200. The spine and femur/tibia were extracted and scanned by the micro-computer tomography for bone histo-morphometric analyses at the postmortem. The median survivals were 56 days in NSG while 44.5 days in C57BL/KaLwRij agreed with the BL imaging results. Histomorphic and DEXA analyses demonstrated that NSG mice have severe bone resorption that occurred at the lumbar spine but no significance at the femur compared to C57BL/KaLwRij mice. Based on these, we conclude that the systemic 5TGM1 injected NSG mouse slowly progresses myeloma and develops more severe MMBD than the C57BL/KaLwRij model

Marine cage culture and the environment: twenty-first century science informing a sustainable industry

Technological innovation has made it possible to grow marine finfish in the coastal and open ocean. Along with this opportunity comes environmental risk. As a federal agency charged with stewardship of the nation’s marine resources, the National Oceanic and Atmospheric Administration (NOAA) requires tools to evaluate the benefits and risks that aquaculture poses in the marine environment, to implement policies and regulations which safeguard our marine and coastal ecosystems, and to inform production designs and operational procedures compatible with marine stewardship. There is an opportunity to apply the best available science and globally proven best management practices to regulate and guide a sustainable United States (U.S.) marine finfish farming aquaculture industry. There are strong economic incentives to develop this industry, and doing so in an environmentally responsible way is possible if stakeholders, the public and regulatory agencies have a clear understanding of the relative risks to the environment and the feasible solutions to minimize, manage or eliminate those risks. This report spans many of the environmental challenges that marine finfish aquaculture faces. We believe that it will serve as a useful tool to those interested in and responsible for the industry and safeguarding the health, productivity and resilience of our marine ecosystems. This report aims to provide a comprehensive review of some predominant environmental risks that marine fish cage culture aquaculture, as it is currently conducted, poses in the marine environment and designs and practices now in use to address these environmental risks in the U.S. and elsewhere. Today’s finfish aquaculture industry has learned, adapted and improved to lessen or eliminate impacts to the marine habitats in which it operates. What progress has been made? What has been learned? How have practices changed and what are the results in terms of water quality, benthic, and other environmental effects? To answer these questions we conducted a critical review of the large body of scientific work published since 2000 on the environmental impacts of marine finfish aquaculture around the world. Our report includes results, findings and recommendations from over 420 papers, primarily from peer-reviewed professional journals. This report provides a broad overview of the twenty-first century marine finfish aquaculture industry, with a targeted focus on potential impacts to water quality, sediment chemistry, benthic communities, marine life and sensitive habitats. Other environmental issues including fish health, genetic issues, and feed formulation were beyond the scope of this report and are being addressed in other initiatives and reports. Also absent is detailed information about complex computer simulations that are used to model discharge, assimilation and accumulation of nutrient waste from farms. These tools are instrumental for siting and managing farms, and a comparative analysis of these models is underway by NOAA

Treatment of brain tumors in children is associated with abnormal MRS ratios in brain tissue remote from the tumor site.

PURPOSE: Children who have brain tumors are at risk for a variety of treatment-related sequelae, including neuropsychological and cognitive impairment, neurologic deficits, and neuroendocrinologic disturbances. We sought to determine the value of proton MR spectroscopy in assessing brain tissue remote from the tumor site to ascertain the effects of chemotherapy and radiation treatment in these patients. METHODS: Single-voxel proton MR spectra from 70 patients (111 spectra) and 11 healthy volunteers (11 spectra) were analyzed. NAA/Cr, NAA/Cho, and Cho/Cr ratios based on peak areas were obtained from nonneoplastic regions of the frontal lobe. The relationship between MR spectroscopic ratios and treatment was determined. RESULTS: NAA-containing ratios were decreased in patients as compared with control subjects. The presence of gadolinium-based contrast material did not cause significant changes in the ratios as compared with precontrast data. When chemotherapy was a component of a child’s treatment protocol, we found a significant decline in NAA/Cr ratios. Patients who underwent both chemotherapy and radiation therapy showed a trend toward lower NAAcontaining ratios if the chemotherapy was administered before the radiation therapy. Patients receiving whole-brain radiation had a trend toward lower NAA-containing ratios than did those who had only focal tumor treatment. CONCLUSION: In children with brain tumors, MR spectroscopy of brain tissue remote from the tumor reveals treatment-related biochemical changes

Repeated dietary exposure to low levels of domoic acid and problems with everyday memory: Research to public health outreach

Domoic Acid (DA) is a marine-based neurotoxin. Dietary exposure to high levels of DA via shellfish consumption has been associated with Amnesic Shellfish Poisoning, with milder memory decrements found in Native Americans (NAs) with repetitive, lower level exposures. Despite its importance for protective action, the clinical relevance of these milder memory problems remains unknown. The purpose of this study was to determine whether repeated, lower-level exposures to DA impact everyday memory (EM), i.e., the frequency of memory failures in everyday life. A cross-sectional sample of 60 NA men and women from the Pacific NW was studied with measures of dietary exposure to DA via razor clam (RC) consumption and EM. Findings indicated an association between problems with EM and elevated consumption of RCs with low levels of DA throughout the previous week and past year after controlling for age, sex, and education. NAs who eat a lot of RCs with presumably safe levels of DA are at risk for clinically significant memory problems. Public health outreach to minimize repetitive exposures are now in place and were facilitated by the use of community-based participatory research methods, with active involvement of state regulatory agencies, tribe leaders, and local physicians

Bags, junctions, and networks of BPS and non-BPS defects

We investigate several models of coupled scalar fields that present discrete Z_2, Z_2 x Z_2, Z_3 and other symmetries. These models support topological domain wall solutions of the BPS and non-BPS type. The BPS solutions are stable, but the stability of the non-BPS solutions may depend on the parameters that specify the models. The BPS and non-BPS states give rise to bags, and also to three-junctions that may allow the presence of networks of topological defects. In particular, we show that the non-BPS defects of a specific model that engenders the Z_3 symmetry give rise to a stable regular hexagonal network of domain walls.Comment: Revtex, 16 pages, 6 ps figures; Shorter version to be published in Phys. Rev.

A combined phase I and II open label study on the effects of a seaweed extract nutrient complex on osteoarthritis

Background: Isolated fucoidans from brown marine algae have been shown to have a range of anti-inflammatory effects. Purpose: This present study tested a Maritech® extract formulation, containing a blend of extracts from three different species of brown algae, plus nutrients in an open label combined phase I and II pilot scale study to determine both acute safety and efficacy in osteoarthritis of the knee. Patients and methods: Participants (n = 12, five females [mean age, 62 ± 11.06 years] and seven males [mean age, 57.14 ± 9.20 years]) with a confirmed diagnosis of osteoarthritis of the knee were randomized to either 100 mg (n = 5) or 1000 mg (n = 7) of a Maritech® extract formulation per day. The formulation contained Maritech® seaweed extract containing Fucus vesiculosis (85% w/w), Macrocystis pyrifera (10% w/w) and Laminaria japonica (5% w/w) plus vitamin B6, zinc and manganese. Primary outcome was the average comprehensive arthritis test (COAT) score which is comprised of four sub-scales: pain, stiffness, difficulty with physical activity and overall symptom severity measured weekly. Safety measures included full blood count, serum lipids, liver function tests, urea, creatinine and electrolytes determined at baseline and week 12. All adverse events were recorded. Results: Eleven participants completed 12 weeks and one completed 10 weeks of the study. Using a multilevel linear model, the average COAT score was reduced by 18% for the 100 mg treatment and 52% for the 1000 mg dose at the end of the study. There was a clear dose response effect seen between the two treatments (P≤0.0005) on the average COAT score and each of the four COAT subscales (pain, stiffness, difficulty with physical activity and overall symptom severity) (P≤0.05). The preparation was well tolerated and the few adverse events were unlikely to be related to the study medication. There were no changes in blood parameters measured over the course of the study with the exception of an increase in serum albumin which was not clinically significant. Conclusion: The seaweed extract nutrient complex when taken orally over twelve weeks decreased the symptoms of osteoarthritis in a dose-dependent manner. It was demonstrated to be safe to use over the study period at the doses tested. The efficacy of the preparation now needs to be demonstrated in a phase III randomized controlled trial (RCT). Australian and New Zealand Clinical Trials Register: ACTRN12607000229471

A combined Phase I and II open-label study on the immunomodulatory effects of seaweed extract nutrient complex

Background: Isolated fucoidans from brown marine algae have been shown to have a range of immune-modulating effects. This exploratory study aimed to determine whether a seaweed nutrient complex containing a blend of extracts from three different species of brown algae plus nutrients is safe to administer and has biological potential as an immune modulator. The study was undertaken as an open-label combined Phase I and II study. Methods: Participants (n = 10) were randomized to receive the study medication at either a 100 mg (n = 5) or 1000 mg (n = 5) dose over 4 weeks. The primary outcome measurement was in vivo changes in lymphocyte subsets. The secondary outcome measures were ex vivo changes in T-lymphocyte (CD4 and CD8) activation, phagocytosis of granulocytes and monocytes, T helper 1/T helper 2 cytokines, and serum oxygen radical absorbance capacity. Results: The preparation was found to be safe over the 4 weeks at both doses tested. There were no clinically relevant changes to blood measurements of hemopoietic, hepatic, or renal function. Immunomodulatory measurements showed no dose response between the two doses. The combined results from the two doses demonstrated a significant increase in cytotoxic T cell numbers and phagocytic capacity in monocytes, and a significant decrease in levels of the inflammatory cytokine interleukin 6. A separate analysis of the 100 mg dose (n = 5) alone showed a significant linear component over time (P \u3c 0.05) for phagocytosis by both granulocytes and monocytes. Conclusion: The seaweed nutrient complex was safe to use when taken orally over 4 weeks. The preparation was demonstrated to have potential as an immune modulator, and this bioactivity deserves further exploration

High-resolution temporal profiling of transcripts during Arabidopsis leaf senescence reveals a distinct chronology of processes and regulation

Leaf senescence is an essential developmental process that impacts dramatically on crop yields and involves altered regulation of thousands of genes and many metabolic and signaling pathways, resulting in major changes in the leaf. The regulation of senescence is complex, and although senescence regulatory genes have been characterized, there is little information on how these function in the global control of the process. We used microarray analysis to obtain a highresolution time-course profile of gene expression during development of a single leaf over a 3-week period to senescence. A complex experimental design approach and a combination of methods were used to extract high-quality replicated data and to identify differentially expressed genes. The multiple time points enable the use of highly informative clustering to reveal distinct time points at which signaling and metabolic pathways change. Analysis of motif enrichment, as well as comparison of transcription factor (TF) families showing altered expression over the time course, identify clear groups of TFs active at different stages of leaf development and senescence. These data enable connection of metabolic processes, signaling pathways, and specific TF activity, which will underpin the development of network models to elucidate the process of senescence

Linguistics

Contains report on one research project and abstracts for seven theses