A novel organ-slice culturing system to simulate meniscal repair: Proof of concept using a synovium-based pool of meniscoprogenitor cells.

Meniscal injuries can occur secondary to trauma or be instigated by the changes in knee-joint function that are associated with aging, osteo- and rheumatoid arthritis, disturbances in gait and obesity. Sixty per cent of persons over 50 years of age manifest signs of meniscal pathology. The surgical and arthroscopic measures that are currently implemented to treat meniscal deficiencies bring only transient relief from pain and effect but a temporary improvement in joint function. Although tissue-engineering-based approaches to meniscal repair are now being pursued, an appropriate in-vitro model has not been conceived. The aim of this study was to develop an organ-slice culturing system to simulate the repair of human meniscal lesions in vitro. The model consists of a ring of bovine meniscus enclosing a chamber that represents the defect and reproduces its sequestered physiological microenvironment. The defect, which is closed with a porous membrane, is filled with fragments of synovial tissue, as a source of meniscoprogenitor cells, and a fibrin-embedded, calcium-phosphate-entrapped depot of the meniscogenic agents BMP-2 and TGF-ß1. After culturing for 2 to 6 weeks, the constructs were evaluated histochemically and histomorphometrically, as well as immunohistochemically for the apoptotic marker caspase 3 and collagen types I and II. Under the defined conditions, the fragments of synovium underwent differentiation into meniscal tissue, which bonded with the parent meniscal wall. Both the parent and the neoformed meniscal tissue survived the duration of the culturing period without significant cell losses. The concept on which the in-vitro system is based was thus validated. This article is protected by copyright. All rights reserved.

The Dental School Applicant Pool and the Oral Healthcare Workforce

One of the major challenges faced by the dental profession today is the recruitment of the most qualified dental school applicants who are capable of serving the nation’s future oral healthcare needs. The Association of Schools of Public Health (ASPH) also recognizes this challenge, describing one of the three core functions of public health as “assuring that all populations have access to appropriate and cost effective care, including health promotion and disease prevention services.” To achieve this core function, the ASPH cites “a competent public health and personal healthcare workforce” as one of the ten essential public health services. Unfortunately, the goals of both quality and equality in terms of the dental workforce and access to oral healthcare have yet to be realized. When considering access to oral health services on a national or state level, a thoughtful and thorough consideration of the dental school applicant pool is essential. According to a recent study published in the Journal of the American Dental Association, the annual number of retiring dentists will exceed the number of newly licensed dental practitioners in 2009, a trend which is projected to continue throughout the next decade. The approximately 4,400 dentists produced each year from the nation’s 57 accredited dental education programs are charged with the responsibility of meeting the oral healthcare needs of the population at large.

Le chemin de fer du Congo de Matadi au Stanley-Pool : résultats des études ; rédaction de l'avant-projet ; conclusion avec 24 annexes

Compagnie du Congo pour le Commerce et l'Industrie ...

Effects of thymus size and involution on the contribution of recent thymic emigrants to the peripheral T cell pool

The contribution of recent thymic emigrants (RTEs) to the peripheral naïve T cell population is necessary to maintain diversity of the T cell receptor (TCR) repertoire and produce immune responses against newly encountered antigens. The thymus involutes with age, after irradiation or chemotherapy, and due to severe viral infections. Thymus involution results in decreased thymopoiesis and RTE output leading to a reduced diversity of peripheral T cells. This increases susceptibility to disease and impairs immune responsiveness to vaccines. Therefore, studies aimed at maintaining or regenerating thymic function are integral for maintaining and restoring peripheral TCR diversity. Mice that express a K5.CyclinD1 transgene expression have a severely hyperplastic thymus that fails to undergo involution. Both thymocyte and TEC development appear normal in these mice. We have used the K5.CyclinD1 transgenic model to test the hypothesis that preventing thymus involution will sustain RTE output and incorporation into the peripheral T cell pool to prevent naïve T cell depletion with age. The K5.CyclinD1 transgene was crossed to the RAG2p-GFP transgenic model so that RTEs could be tracked by the intensity of the GFP signal. The frequency and number of RTEs in naïve CD4 splenic T cells was analyzed at monthly intervals to 5 months of age. Using this double transgenic approach, we determined that preventing thymus involution does maintain or enhance the number of RTEs in the peripheral T cell pool before and after thymus involution.

Genome instability quantified in constitutive tissues as well as putatively stable tumor tissue in hereditary non -polyposis colon cancer patients by small pool PCR

Microsatellite instability (MSI) is a hallmark of the mutator phenotype associated with Hereditary Non-Polyposis Colon Cancer (HNPCC). The MSI-High (MSI-H) HNPCC population has been well characterized, but the microsatellite low and stable (MSI-L/MSS) HNPCC population is much less understood. We hypothesize there are significant levels of MSI in HNPCC DNA classified as MSI-L/MSS, but no single variant allele makes up a sufficient population in the tumor DNA to be detected by standard analysis. Finding variants would suggest there is a mutator phenotype for the MSI-L/MSS HNPCC population that is distinct from the MSI-H HNPCC populations. This study quantified and compared MSI in HNPCC patients previously shown to be MSI-H, MSI-L/MSS and an MSI-H older, sporadic colorectal cancer patient. Small-pool Polymerase Chain Reactions (SP-PCRs) were conducted where the DNAs from each sample and controls are diluted into multiple pools, each containing approximately single genome equivalents. At least 100 alleles/sample were studied at six microsatellite loci. Mutant fragments were identified, quantified, and compared using Poisson statistics. Most of the variants were small deletions or insertions, with more mutants being deletions, as has been previously described in yeast and transgenic mice. SP-PCR, where most of the pools contained only 3 or less fragments, enabled identification of variants too infrequent to be detected by large pool PCR. Mutant fragments in positive control MSI-H tumor samples ranged from 0.26 to 0.68 in at least 4 of the 6 loci tested and were consistent with their MSI-H status. In the so called MSS tumors and constitutive tissues (normal colon tissue, and PBLs) of all the HNPCC patients, low, but significant levels of MSI were seen in at least two of the loci studied. This phenomenon was not seen in the sporadic MSI constitutive tissues nor the normal controls and suggests haploinsufficiency, gain-of-function, or a dominant/negative basis of the instability in HNPCC patients carrying germline mutations for tumor suppressor genes. A different frequency and spectrum of mutant fragments suggests a different genetic basis (other than a major mutation in MLH1 or MSH2) for disease in MSI-L and MSS HNPCC patients. ^

Late Miocene development of the western Pacific warm pool: Planktonic foraminifer and oxygen isotopic evidence

The disappearance at ~10 Ma of the deep dwelling planktonic foraminifer Globoquadrina dehiscens from the western Pacific including the South China Sea was about 3 Myr earlier than its final extinction elsewhere. Accompanying this event at ~10 Ma was a series of faunal turnover characterized by increase in mixed layer, warm-water species and decrease to a minimum in deepwater species. Paleobiological and isotopic evidence indicates sea surface warming and a deepened local thermocline that we interpret as related to the development of an early western Pacific warm pool. The stepwise decline of G. dehiscens and other deep dwelling species from the NW and SW Pacific suggests more intensive warm water pileup than equatorial localities where surface bypass flow through the narrowing Indonesia seaway appears to remain efficient during the late Miocene. Planktonic delta18O values from the South China Sea consistently lighter than the tropical western Pacific during the Miocene also suggest, similar to today, more variable hydrologic conditions along the periphery than in the core of the warm pool. Stronger hydrologic variability affected mainly by monsoons and increased thermal gradient along the western margin of the late Miocene warm pool may have contributed to the decline of deep dwelling planktonic species including the early extinction of G. dehiscens from the South China Sea region. The late Miocene warm pool became influential and paleobiologically detectable from ~10 Ma, but the modern warm pool did not appear until about 4 Ma, in the middle Pliocene.

Chronology and stable carbon isotopic ratios of sediments from the Western Pacific Warm Pool region

Instrumental data suggest that major shifts in tropical Pacific atmospheric dynamics and hydrology have occurred within the past century, potentially in response to anthropogenic warming. To better understand these trends, we use the hydrogen isotopic ratios of terrestrial higher plant leaf waxes (DDwax) in marine sediments from southwest Sulawesi, Indonesia, to compile a detailed reconstruction of central Indo-Pacific Warm Pool (IPWP) hydrologic variability spanning most of the last two millennia. Our paleodata are highly correlated with a monsoon reconstruction from Southeast Asia, indicating that intervals of strong East Asian summer monsoon (EASM) activity are associated with a weaker Indonesian monsoon (IM). Furthermore, the centennial-scale oscillations in our data follow known changes in Northern Hemisphere climate (e.g., the Little Ice Age and Medieval Warm Period) implying a dynamic link between Northern Hemisphere temperatures and IPWP hydrology. The inverse relationship between the EASM and IM suggests that migrations of the Intertropical Convergence Zone and associated changes in monsoon strength caused synoptic hydrologic shifts in the IPWP throughout most of the past two millennia.

Detection of a variable intracellular acid-labile carbon pool in Thalassiosira weissflogii (Heterokontophyta) and Emiliania huxleyi (Haptophyta) in response to changes in the seawater carbon system

Accumulation of an intracellular pool of carbon (C(i) pool) is one strategy by which marine algae overcome the low abundance of dissolved CO2 (CO2 (aq) ) in modern seawater. To identify the environmental conditions under which algae accumulate an acid-labile C(i) pool, we applied a (14) C pulse-chase method, used originally in dinoflagellates, to two new classes of algae, coccolithophorids and diatoms. This method measures the carbon accumulation inside the cells without altering the medium carbon chemistry or culture cell density. We found that the diatom Thalassiosira weissflogii [(Grunow) G. Fryxell & Hasle] and a calcifying strain of the coccolithophorid Emiliania huxleyi [(Lohmann) W. W. Hay & H. P. Mohler] develop significant acid-labile C(i) pools. C(i) pools are measureable in cells cultured in media with 2-30 µmol/l CO2 (aq), corresponding to a medium pH of 8.6-7.9. The absolute C(i) pool was greater for the larger celled diatoms. For both algal classes, the C(i) pool became a negligible contributor to photosynthesis once CO2 (aq) exceeded 30 µmol/l. Combining the (14) C pulse-chase method and (14) C disequilibrium method enabled us to assess whether E. huxleyi and T. weissflogii exhibited thresholds for foregoing accumulation of DIC or reduced the reliance on bicarbonate uptake with increasing CO2 (aq) . We showed that the C(i) pool decreases with higher CO2 :HCO3 (-) uptake rates.