Implication of RNA-Binding Protein La in Proliferation, Migration and Invasion of Lymph Node-Metastasized Hypopharyngeal SCC Cells

The 5-year survival rate for oral cavity cancer is poorer than for breast, colon or prostate cancer, and has improved only slightly in the last three decades. Hence, new therapeutic strategies are urgently needed. Here we demonstrate by tissue micro array analysis for the first time that RNA-binding protein La is significantly overexpressed in oral squamous cell carcinoma (SCC). Within this study we therefore addressed the question whether siRNA-mediated depletion of the La protein may interfere with known tumor-promoting characteristics of head and neck SCC cells. Our studies demonstrate that the La protein promotes cell proliferation, migration and invasion of lymph node-metastasized hypopharyngeal SCC cells. We also reveal that La is required for the expression of beta-catenin as well as matrix metalloproteinase type 2 (MMP-2) within these cells. Taken together these data suggest a so far unknown function of the RNA-binding protein La in promoting tumor progression of head and neck SCC.

International recommendations for training future toxicologic pathologists participating in regulatory-type, nonclinical toxicity studies

The International Federation of Societies of Toxicologic Pathologists (IFSTP) proposes a common global framework for training future toxicologic pathologists who will support regulatory-type - nonclinical toxicology studies. Trainees optimally should undertake a scientific curriculum of at least 5 years at an accredited institution leading to a clinical degree (veterinary medicine or medicine). Trainees should then obtain 4 or more years of intensive pathology practice during a residency and/or on-the-job "apprenticeship," at least 2 years of which must be focused on regulatory-type toxicologic pathology topics. Possession of a recognized pathology qualification (i.e., certification) is highly recommended. A nonclinical pathway (e.g., a graduate degree in medical biology or pathology) may be possible if medically trained pathologists are scarce, but this option is not optimal. Regular, lifelong continuing education (peer review of nonclinical studies, professional meetings, reading, short courses) will be necessary to maintain and enhance one's understanding of current toxicologic pathology knowledge, skills, and tools. This framework should provide a rigorous yet flexible way to reliably train future toxicologic pathologists to generate, interpret, integrate, and communicate data in regulatory-type, nonclinical toxicology studies. (C) 2010 Reprinted by Permission of SAGE Publications Inc. Published by Elsevier GmbH. All rights reserved.

Nonmodal energetics of resistive drift waves

The modal and nonmodal linear properties of the Hasegawa-Wakatani system are examined. This linear model for plasma drift waves is nonnormal in the sense of not having a complete set of orthogonal eigenvectors. A consequence of nonnormality is that finite-time nonmodal growth rates can be larger than modal growth rates. In this system, the nonmodal time-dependent behavior depends strongly on the adiabatic parameter and the time scale of interest. For small values of the adiabatic parameter and short time scales, the nonmodal growth rates, wave number, and phase shifts (between the density and potential fluctuations) are time dependent and differ from those obtained by normal mode analysis. On a given time scale, when the adiabatic parameter is less than a critical value, the drift waves are dominated by nonmodal effects while for values of the adiabatic parameter greater than the critical value, the behavior is that given by normal mode analysis. The critical adiabatic parameter decreases with time and modal behavior eventually dominates. The nonmodal linear properties of the Hasegawa-Wakatani system may help to explain features of the full system previously attributed to nonlinearity.

Nonmodal energetics of electromagnetic drift waves

The linear properties of an electromagnetic drift-wave model are examined. The linear system is non-normal in that its eigenvectors are not orthogonal with respect to the energy inner product. The non-normality of the linear evolution operator can lead to enhanced finite-time growth rates compared to modal growth rates. Previous work with an electrostatic drift-wave model found that nonmodal behavior is important in the hydrodynamic limit. Here, similar behavior is seen in the hydrodynamic regime even with the addition of magnetic fluctuations. However, unlike the results for the electrostatic drift-wave model, nonmodal behavior is also important in the adiabatic regime with moderate to strong magnetic fluctuations. © 2000 American Institute of Physics.

Effects of different resistance training frequencies on flexibility in older women

Objective: The main purpose of the investigation reported here was to analyze the effect of resistance training (RT) performed at different weekly frequencies on flexibility in older women.Participants and methods: Fifty-three older women (>= 60 years old) were randomly assigned to perform RT either two (n= 28; group "G2x"), or three (n= 25; group "G3x") times per week. The RT program comprised eight exercises in which the participants performed one set of 10-15 repetitions maximum for a period of 12 weeks. Anthropometric, body-composition, and flexibility measurements were made at baseline and post-study. The flexibility measurements were obtained by a fleximeter.Results: A significant group-by-time interaction (P<0.01) was observed for frontal hip flexion, in which G3x showed a higher increase than G2x (+12.8% and +3.0%, respectively). Both groups increased flexibility in cervical extension (G2x=+19.1%, G3x=+20.0%), right hip flexion (G2x=+14.6%, G3x=+15.9%), and left hip flexion (G2x=+25.7%, G3x=+19.2%), with no statistical difference between groups. No statistically significant differences were noted for the increase in skeletal muscle mass between training three versus two times a week (+7.4% vs +4.4%, respectively).Conclusion: Twelve weeks of RT improves the flexibility of different joint movements in older women, and the higher frequency induces greater increases for frontal hip flexion.

Draft U.S. Pacific Marine Mammal Stock Assessments: 2009

Under the 1994 amendments to the Marine Mammal Protection Act (MMPA), the National Marine Fisheries Service (NMFS) and the U.S. Fish and Wildlife Service (USFWS) are required to publish Stock Assessment Reports for all stocks of marine mammals within U.S. waters, to review new information every year for strategic stocks and every three years for non-strategic stocks, and to update the stock assessment reports when significant new information becomes available. This report presents stock assessments for 13 Pacific marine mammal stocks under NMFS jurisdiction, including 8 “strategic” stocks and 5 “non-strategic” stocks (see summary table). A new stock assessment for humpback whales in American Samoa waters is included in the Pacific reports for the first time. New or revised abundance estimates are available for 9 stocks, including Eastern North Pacific blue whales, American Samoa humpback whales, five U.S. west coast harbor porpoise stocks, the Hawaiian monk seal, and southern resident killer whales. A change in the abundance estimate of Eastern North Pacific blue whales reflects a recommendation from the Pacific Scientific Review Group to utilize mark-recapture estimates for this population, which provide a better estimate of total population size than the average of recent line-transect and mark-recapture estimates. The ‘Northern Oregon/Washington Coast Stock’ harbor porpoise stock assessment includes a name change (‘Oregon’ is appended to ‘Northern Oregon’) to reflect recent stock boundary changes. Changes in abundance estimates for the two stocks of harbor porpoise that occur in Oregon waters are the result of these boundary changes, and do not reflect biological changes in the populations. Updated information on the three stocks of false killer whales in Hawaiian waters is also included in these reports. Information on the remaining 50 Pacific region stocks will be reprinted without revision in the final 2009 reports and currently appears in the 2008 reports (Carretta et al. 2009). Stock Assessments for Alaskan marine mammals are published by the National Marine Mammal Laboratory (NMML) in a separate report. Pacific region stock assessments include those studied by the Southwest Fisheries Science Center (SWFSC, La Jolla, California), the Pacific Islands Fisheries Science Center (PIFSC, Honolulu, Hawaii), the National Marine Mammal Laboratory (NMML, Seattle, Washington), and the Northwest Fisheries Science Center (NWFSC, Seattle, WA). Northwest Fisheries Science Center staff prepared the report on the Eastern North Pacific Southern Resident killer whale. National Marine Mammal Laboratory staff prepared the Northern Oregon/Washington coast harbor porpoise stock assessment. Pacific Islands Fisheries Science Center staff prepared the report on the Hawaiian monk seal. Southwest Fisheries Science Center staff prepared stock assessments for 9 stocks. The stock assessment for the American Samoa humpback whale was prepared by staff from the Center for Coastal Studies, Hawaiian Islands Humpback National Marine Sanctuary, the Smithsonian Institution, and the Southwest Fisheries Science Center. Draft versions of the stock assessment reports were reviewed by the Pacific Scientific Review Group at the November 2008, Maui meeting. The authors also wish to thank those who provided unpublished data, especially Robin Baird and Joseph Mobley, who provided valuable information on Hawaiian cetaceans. Any omissions or errors are the sole responsibility of the authors. This is a working document and individual stock assessment reports will be updated as new information on marine mammal stocks and fisheries becomes available. Background information and guidelines for preparing stock assessment reports are reviewed in Wade and Angliss (1997). The authors solicit any new information or comments which would improve future stock assessment reports. These Stock Assessment Reports summarize information from a wide range of sources and an extensive bibliography of all sources is given in each report. We strongly urge users of this document to refer to and cite original literature sources rather than citing this report or previous Stock Assessment Reports. If the original sources are not accessible, the citation should follow the format: [Original source], as cited in [this Stock Assessment Report citation].

Spatial Relationships Among Young Cercocarpus ledifolius (Curlleaf Mountain Ylahogany)

This study analyzed spatial location patterns of Cercocarpus ledifolius Nutt. (curlleaf mountain mahogany) plants, classified as current-year seedling, established seedling, juvenile, and immature individuals, at a central Nevada study site. Most current-year seedlings were located in mahogany stands in which large, mature individuals had the greatest abundance. These stands had greater litter cover and a thicker layer of litter than areas with few current- year seedlings. Most established young Cercocarpus were located in adjacent Artemisia tridentata ssp. vaseyana (mountain big sagebrush) communities, or in infrequent canopy gaps between relatively few large, mature Cercocarpus. We discuss potential roles of plant litter, root growth characteristics, nurse plants, and herbivory in the establishment and renewal of Cercocarpus communities.

Human Endogenous Retrovirus K(HML-2) Gag and Env specific T-cell responses are not detected in HTLV-I-infected subjects using standard peptide screening methods

Abstract Background An estimated 10–20 million individuals are infected with the retrovirus human T-cell leukemia virus type 1 (HTLV-1). While the majority of these individuals remain asymptomatic, 0.3-4% develop a neurodegenerative inflammatory disease, termed HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). HAM/TSP results in the progressive demyelination of the central nervous system and is a differential diagnosis of multiple sclerosis (MS). The etiology of HAM/TSP is unclear, but evidence points to a role for CNS-inflitrating T-cells in pathogenesis. Recently, the HTLV-1-Tax protein has been shown to induce transcription of the human endogenous retrovirus (HERV) families W, H and K. Intriguingly, numerous studies have implicated these same HERV families in MS, though this association remains controversial. Results Here, we explore the hypothesis that HTLV-1-infection results in the induction of HERV antigen expression and the elicitation of HERV-specific T-cells responses which, in turn, may be reactive against neurons and other tissues. PBMC from 15 HTLV-1-infected subjects, 5 of whom presented with HAM/TSP, were comprehensively screened for T-cell responses to overlapping peptides spanning HERV-K(HML-2) Gag and Env. In addition, we screened for responses to peptides derived from diverse HERV families, selected based on predicted binding to predicted optimal epitopes. We observed a lack of responses to each of these peptide sets. Conclusions Thus, although the limited scope of our screening prevents us from conclusively disproving our hypothesis, the current study does not provide data supporting a role for HERV-specific T-cell responses in HTLV-1 associated immunopathology.

Large Sample Theory for Semiparametric Regression Models with Two-Phase, Outcome Dependent Sampling

Outcome-dependent, two-phase sampling designs can dramatically reduce the costs of observational studies by judicious selection of the most informative subjects for purposes of detailed covariate measurement. Here we derive asymptotic information bounds and the form of the efficient score and influence functions for the semiparametric regression models studied by Lawless, Kalbfleisch, and Wild (1999) under two-phase sampling designs. We show that the maximum likelihood estimators for both the parametric and nonparametric parts of the model are asymptotically normal and efficient. The efficient influence function for the parametric part aggress with the more general information bound calculations of Robins, Hsieh, and Newey (1995). By verifying the conditions of Murphy and Van der Vaart (2000) for a least favorable parametric submodel, we provide asymptotic justification for statistical inference based on profile likelihood.

Experimental ovine model of primary venous valve incompetence: a pilot study

PURPOSE: To compare two techniques used to create a larger animal model of venous valve incompetence. MATERIALS AND METHODS: To achieve vein dilatation as the primary cause of valve incompetence, common carotid jugular vein (JV) fistulas were created and optional filters were placed into the JV of sheep. Altogether, nine inferior vena cava filters were placed in three sheep in two stages. Six filters were placed caudal to the most caudal JV valve in three sheep and removed 6 weeks later. Then, three filters were placed across the most caudal valve in two sheep with competent valves and removed 3 weeks later. A common carotid artery-JV fistula was created in three sheep and followed-up for 1-3 weeks. Ascending and descending venograms were obtained to determine the JV sizes and function of their valves. The JVs removed at necropsy were studied with venoscopy. RESULTS: Only one of the six JVs with filters caudal to the most caudal valve had incompetent valves after filter removal at 6 weeks. In addition, only one of three JVs with the filter across the valve had incompetent valves after filter removal at 3 weeks. At 1-3-week follow-up of the group with common carotid artery-JV fistula, all three JVs had incompetent valves in the cephalad vein portion, but only one JV had an incompetent valve in its caudal portion. At venoscopy, the incompetent valves showed various degrees of damage ranging from shortening to the destruction of valve leaflets. CONCLUSION: Dilation of the valve annulus with a removable vena cava filter failed to produce valve incompetence. The promising results with the common carotid artery-JV fistula justify further detailed research.