Late Quaternary Paleoceanography and Sedimentary Environments in Hudson Strait

Airgun and high resolution Huntec seismic reflection profiles are interpreted to show up to 130 m of glacial, glaciomarine and postglacial sediments overlying bedrock. In a basin at the eastern entrance to Hudson Strait most of the surficial sediment was deposited during the last déglaciation, but in western Hudson Strait multiple till sequences from previous glaciations are recognized. Five acoustic units were identified, at least three of which were penetrated with piston cores. Foraminifera of the stratigraphically deepest core in the eastern basin indicate a proximal glaciomarine environment and a likely presence of an ice shelf. A 14C date of 8060 ± 70 yBP (TO 750) on molluscan shells gives a minimum age for the top of the acoustically laminated distal glaciomarine sediments. The early postglacial foraminifera suggest a period of increased influence of offshore bottom waters restricted to the deep eastern basin. The surface sediments of all cores contain species indigenous of colder and fresher inshore waters of the present time. The ratio of 18CV16O in the benthic foraminifer Cibicides lobatulus is herein related to bottom salinity. Downcore measurements of 8'8O on C. lobatulus tests indicate bottom paleosalinities lower by about 0.5%o shortly before the dated horizon of 8000 yBP. By this time Hudson Strait was sufficiently clear of glacial ice for establishment of the present tidal regime. The lower bottom salinities indicate that tidal mixing took place between glacial meltwater leaving Hudson Bay and the offshore counterflow. This process is thought to have reduced the sharpness of the salinity difference between the offshore water and the surface plume of Laurentide meltwater as it entered the ocean.L'utilisation d'un fusil à air comprimé et d'un dispositif explosif Huntec en sismique réflexion a permis d'obtenir des profils à haute résolution révélant que des sédiments glaciaires, glaciomarins et postglaciaires d'une épaisseur de 130 m surmontent la roche en place. Un bassin, à l'entrée est du détroit d'Hudson, renferme des sédiments de surface qui, pour la plupart, se sont déposés au cours de la dernière glaciation. On a relevé cinq unités acoustiques dont au moins trois ont été explorées par carottage. Les foraminifères de la carotte extraite, dans le bassin est, à la plus grande profondeur révèlent qu'existaient un milieu glaciomarin proximal et, vraisemblablement, une plate-forme de glace flottante. La datation au 14C fait remonter à 8060 ± 70 BP (TO 750) les coquilles de mollusques et confère ainsi un âge minimal à la portion supérieure des sédiments glaciomarins distaux, laminés par acoustique. Les foraminifères du début de la période postglaciaire laissent croire que les eaux profondes du large ont pendant un certain temps exercé une influence accrue sur les fonds du bassin de l'est. Dans toutes les carottes, les sédiments de surface renferment des espèces indigènes au milieu aquatique actuel, plus froid et moins salé. Le taux 18OZ16O trouvé chez le foraminifère benthique Cibicides lobatulus se rapporte ici à la salinité des fonds aquatiques. Plus bas, dans les carottes, on a relevé sur C. lobatulus un taux de 818O qui révèle une paléosalinité plus faible d'environ 0,5%o, précédant tout juste l'horizon daté à 8000 BP. À cette époque, le détroit d'Hudson était suffisamment libre de glace pour que s'établissent les marées telles qu'on les connaît actuellement. Plus bas encore, la salinité révèle que les eaux de fusion glaciaire provenant de la baie d'Hudson se sont mêlées aux contre-courants venus du large.Mit Hilfe eines Luftgewehrs und einer Huntec Explosionsanlage mit seismischer Reflexion gewonnene Profile mit hoher Auflôsung lassen bis zu 130 m glazialer, glaziomariner und postglazialer Sedimente erkennen, die den FeIs ùberlagern, In einem Bassin am ôstlichen Eingang zur Hudson-Meerenge ist der grôsste Teil der Oberflàchensedimente wâhrend der letzten Vereisung abgelagert worden, aber in der westlichen Hudson-Meerenge lassen sich vielfache Grundmorànen-Sequenzen von frùheren Vereisungen erkennen. Fùnf akustische Einheiten wurden identifiziert, von denen mindestens drei durch Kernbohrung ergrûndet wurden. Die Foraminifera des stratigraphisch tiefsten Kerns im ôstlichen Bassin weisen auf eine proximale glaziomarine Umwelt und die môgliche Existenz einer Eisdecke. Eine 14C Datierung von 8060 ± 70 Jahren v.u.Z. (bis 750) fur Molluskenschalen ergibt ein Minimalalter fur den oberen Teil der distalen glaziomarinen Sedimente, die durch Akustik eine blàttrige Struktur bekommen haben. Die frùhen postglazialen Foraminifera lassen auf eine Période wachsenden Einflusses des kùstenfernen Tiefwassers auf das tiefe ôstliche Bassin schliessen. Die Oberflàchensedimente aller Bohrkerne enthalten Gattungen, die spezifisch fur die kàlteren und frischeren Kùstengewàsser der gegenwârtigen Zeit sind. Der Anteil an 18OZ16O in dem benthischen Foraminifer Cibicides lobatulus ist hierin mit dem Salzgehalt auf dem Grund verbunden. Tiefer im Bohrkern hat man auf C. lobatulus Werte von 818O gefunden, was einen um etwa 0.5% geringeren Grund-Palàosalzgehalt ergibt, kurz vor dem auf 8000 Jahre v.u.Z. datierten Horizont. Zu diesem Zeitpunkt war die Hudson-Meerenge von glazialem Eis ausreichend befreit, so dass sich der gegenwârtige Gezeiten-Wechsel etablieren konnte

An atlas of mouse CD4(+) T cell transcriptomes.

BACKGROUND: CD4(+) T cells are key regulators of the adaptive immune system and can be divided into T helper (Th) cells and regulatory T (Treg) cells. During an immune response Th cells mature from a naive state into one of several effector subtypes that exhibit distinct functions. The transcriptional mechanisms that underlie the specific functional identity of CD4(+) T cells are not fully understood. RESULTS: To assist investigations into the transcriptional identity and regulatory processes of these cells we performed mRNA-sequencing on three murine T helper subtypes (Th1, Th2 and Th17) as well as on splenic Treg cells and induced Treg (iTreg) cells. Our integrated analysis of this dataset revealed the gene expression changes associated with these related but distinct cellular identities. Each cell subtype differentially expresses a wealth of 'subtype upregulated' genes, some of which are well known whilst others promise new insights into signalling processes and transcriptional regulation. We show that hundreds of genes are regulated purely by alternative splicing to extend our knowledge of the role of post-transcriptional regulation in cell differentiation. CONCLUSIONS: This CD4(+) transcriptome atlas provides a valuable resource for the study of CD4(+) T cell populations. To facilitate its use by others, we have made the data available in an easily accessible online resource at www.th-express.org

Computed tomographic pulmonary angiography and pulmonary embolism: predictive value of a d-dimer assay

<p>Abstract</p> <p>Background</p> <p>Computed tomographic pulmonary angiography (CTPA) is increasingly being used as first investigation for suspected pulmonary embolism (PE). The investigation has high predictive value, but is resource and time intensive and exposes patients to considerable radiation. Our aim was to assess the potential value of a negative d-dimer assay to exclude pulmonary emboli and reduce the number of performed CTPAs.</p> <p>Methods</p> <p>All CTPAs performed in a Scottish secondary care hospital for a fourteen month period were retrospectively reviewed. Collected data included the presence or absence of PE, d-dimer results and patient demographics. PE positive CTPAs were reviewed by a specialist panel.</p> <p>Results</p> <p>Pulmonary embolisms were reported for 66/405 (16.3%) CTPAs and d-dimer tests were performed for 216 (53%). 186/216 (86%) patients had a positive and 30 (14%) a negative d-dimer result. The panel agreed 5/66 (7.6%) false positive examinations. The d-dimer assay's negative predictive value was 93.3% (95% CI = 76.5%-98.8%) based on the original number of positive CTPAs and 100% (95% CI = 85.9%-100%) based on expert review. Significant non-PE intrapulmonary pathology was reported for 312/405 (77.0) CTPAs, including 13 new diagnoses of carcinoma.</p> <p>Conclusions</p> <p>We found that a low d-dimer score excluded all pulmonary embolisms, after a further specialist panel review identified initial false positive reports. However, current evidence-based guidelines still recommend that clinicians combine a d-dimer result with a validated clinical risk score when selecting suitable patients for CTPA. This may result in better use of limited resources, prevent patients being exposed to unnecessary irradiation and prevent potential complications as a result of iodinated contrast.</p

Characterization of the Proteostasis Roles of Glycerol Accumulation, Protein Degradation and Protein Synthesis during Osmotic Stress in C. elegans

Exposure of C. elegans to hypertonic stress-induced water loss causes rapid and widespread cellular protein damage. Survival in hypertonic environments depends critically on the ability of worm cells to detect and degrade misfolded and aggregated proteins. Acclimation of C. elegans to mild hypertonic stress suppresses protein damage and increases survival under more extreme hypertonic conditions. Suppression of protein damage in acclimated worms could be due to 1) accumulation of the chemical chaperone glycerol, 2) upregulation of protein degradation activity, and/or 3) increases in molecular chaperoning capacity of the cell. Glycerol and other chemical chaperones are widely thought to protect proteins from hypertonicity-induced damage. However, protein damage is unaffected by gene mutations that inhibit glycerol accumulation or that cause dramatic constitutive elevation of glycerol levels. Pharmacological or RNAi inhibition of proteasome and lyosome function and measurements of cellular protein degradation activity demonstrated that upregulation of protein degradation mechanisms plays no role in acclimation. Thus, changes in molecular chaperone capacity must be responsible for suppressing protein damage in acclimated worms. Transcriptional changes in chaperone expression have not been detected in C. elegans exposed to hypertonic stress. However, acclimation to mild hypertonicity inhibits protein synthesis 50–70%, which is expected to increase chaperone availability for coping with damage to existing proteins. Consistent with this idea, we found that RNAi silencing of essential translational components or acute exposure to cycloheximide results in a 50–80% suppression of hypertonicity-induced aggregation of polyglutamine-YFP (Q35::YFP). Dietary changes that increase protein production also increase Q35::YFP aggregation 70–180%. Our results demonstrate directly for the first time that inhibition of protein translation protects extant proteins from damage brought about by an environmental stressor, demonstrate important differences in aging- versus stress-induced protein damage, and challenge the widely held view that chemical chaperones are accumulated during hypertonic stress to protect protein structure/function

Depletion of stromal cells expressing fibroblast activation protein-α from skeletal muscle and bone marrow results in cachexia and anemia.

Fibroblast activation protein-α (FAP) identifies stromal cells of mesenchymal origin in human cancers and chronic inflammatory lesions. In mouse models of cancer, they have been shown to be immune suppressive, but studies of their occurrence and function in normal tissues have been limited. With a transgenic mouse line permitting the bioluminescent imaging of FAP(+) cells, we find that they reside in most tissues of the adult mouse. FAP(+) cells from three sites, skeletal muscle, adipose tissue, and pancreas, have highly similar transcriptomes, suggesting a shared lineage. FAP(+) cells of skeletal muscle are the major local source of follistatin, and in bone marrow they express Cxcl12 and KitL. Experimental ablation of these cells causes loss of muscle mass and a reduction of B-lymphopoiesis and erythropoiesis, revealing their essential functions in maintaining normal muscle mass and hematopoiesis, respectively. Remarkably, these cells are altered at these sites in transplantable and spontaneous mouse models of cancer-induced cachexia and anemia. Thus, the FAP(+) stromal cell may have roles in two adverse consequences of cancer: their acquisition by tumors may cause failure of immunosurveillance, and their alteration in normal tissues contributes to the paraneoplastic syndromes of cachexia and anemia

Potency analysis of cellular therapies: the emerging role of molecular assays

Potency testing is an important part of the evaluation of cellular therapy products. Potency assays are quantitative measures of a product-specific biological activity that is linked to a relevant biological property and, ideally, a product's in vivo mechanism of action. Both in vivo and in vitro assays can be used for potency testing. Since there is often a limited period of time between the completion of production and the release from the laboratory for administration to the patient, in vitro assays such are flow cytometry, ELISA, and cytotoxicity are typically used. Better potency assays are needed to assess the complex and multiple functions of cellular therapy products, some of which are not well understood. Gene expression profiling using microarray technology has been widely and effectively used to assess changes of cells in response to stimuli and to classify cancers. Preliminary studies have shown that the expression of noncoding microRNA which play an important role in cellular development, differentiation, metabolism and signal transduction can distinguish different types of stem cells and leukocytes. Both gene and microRNA expression profiling have the potential to be important tools for testing the potency of cellular therapies. Potency testing, the complexities associated with potency testing of cellular therapies, and the potential role of gene and microRNA expression microarrays in potency testing of cellular therapies is discussed

Realization and Properties of Biochemical-Computing Biocatalytic XOR Gate Based on Enzyme Inhibition by a Substrate

We consider a realization of the XOR logic gate in a process biocatalyzed by an enzyme (here horseradish peroxidase: HRP), the function of which can be inhibited by a substrate (hydrogen peroxide for HRP), when the latter is inputted at large enough concentrations. A model is developed for describing such systems in an approach suitable for evaluation of the analog noise amplification properties of the gate. The obtained data are fitted for gate quality evaluation within the developed model, and we discuss aspects of devising XOR gates for functioning in "biocomputing" systems utilizing biomolecules for information processing

A systematic approach to biomarker discovery; Preamble to "the iSBTc-FDA taskforce on immunotherapy biomarkers"

The International Society for the Biological Therapy of Cancer (iSBTc) has initiated in collaboration with the United States Food and Drug Administration (FDA) a programmatic look at innovative avenues for the identification of relevant parameters to assist clinical and basic scientists who study the natural course of host/tumor interactions or their response to immune manipulation. The task force has two primary goals: 1) identify best practices of standardized and validated immune monitoring procedures and assays to promote inter-trial comparisons and 2) develop strategies for the identification of novel biomarkers that may enhance our understating of principles governing human cancer immune biology and, consequently, implement their clinical application. Two working groups were created that will report the developed best practices at an NCI/FDA/iSBTc sponsored workshop tied to the annual meeting of the iSBTc to be held in Washington DC in the Fall of 2009. This foreword provides an overview of the task force and invites feedback from readers that might be incorporated in the discussions and in the final document