Translocation of GPIb and Fc receptor gamma-chain to cytoskeleton in mucetin-activated platelets

Recent studies have implied that GPIb-IX-V as well as functioning as an adhesion receptor may also induce signaling to mediate binding of platelets to damaged vessel wall to prevent bleeding. Reorganization of the cytoskeleton and redistribution of platelet structural proteins and signaling molecules are thought to be important in this early activation process, though the molecular mechanisms remain to be fully defined. In this study, we have used mucetin, a snake venom lectin protein that activates platelets via GPIb, to study the redistribution of GPIb in platelets. In unstimulated platelets, a minor portion of GPIb localized to Triton-insoluble cytoskeleton fractions (TIC). This portion increased considerably after platelet activation by mucetin. We also find increased contents of the FcRgamma chain in TIC. Anti-GPIb antibodies, mocarhagin or cytochalasin D completely inhibited the cytoskeletal translocation. In addition, BAPTA-AM, a cytoplasmic calcium chelator, strongly inhibited this process. On the other hand, inhibitors of alphaIIbbeta3, PLCgamma, PKC, tyrosine kinases, ADP receptor, PI3-kinase or EDTA are effective in preventing GPIb relocation in convulxin- but not in mucetin-activated platelets. We propose that cytoskeletal translocation of GPIb is upstream of alphaIIbbeta3 activation and cross-linking of GPIb is sufficient to induce this event in mucetin-activated platelets.

Concurrent activation of dopamine D1 and D2 receptors is required to evoke neural and behavioral phenotypes of cocaine sensitization

Repeated exposure to psychomotor stimulants produces a striking behavioral syndrome involving repetitive, stereotypic behaviors that occur if an additional exposure to the stimulant is experienced. The same stimulant exposure produces specific alterations in gene expression patterns in the striatum. To identify the dopamine receptor subtypes required for the parallel expression of these acquired neural and behavioral responses, we treated rats with different D1-class and D2-class dopamine receptor agonists and compared the responses of drug-naive rats with those of rats given previous intermittent treatment with cocaine. In rats exposed to repeated cocaine treatment, the effects of a subsequent challenge treatment with either a D1-class agonist (SKF 81297) or a D2-class agonist (quinpirole) were not significantly different from those observed in drug-naive animals: the drugs administered singly did not induce robust stereotyped motor behaviors nor produce significantly striosome-predominant expression of early genes in the striatum. In contrast, challenge treatment with the D1-class and D2-class agonists in combination led to marked and correlated increases in stereotypy and striosome-predominant gene expression in the striatum. Thus, immediately after repeated psychomotor stimulant exposure, only the concurrent activation of D1 and D2 receptor subclasses evoked expression of the neural and behavioral phenotypes acquired through repeated cocaine exposure. These findings suggest that D1-D2 dopamine receptor synergisms underlie the coordinate expression of both network-level changes in basal ganglia activation patterns and the repetitive and stereotypic motor response patterns characteristic of psychomotor stimulant sensitization.

Recent skin self-examination and doctor visits in relation to melanoma risk and tumour depth

BACKGROUND Little is known about the potential benefit of skin self-examination for melanoma prevention and early detection. Objectives: To determine whether skin self-examination is associated with reduced melanoma risk, self-detection of tumours, and reduced risk of deeper melanomas. METHODS We used data from a population-based case-control study (423 cases, 678 controls) to assess recent skin self-examination in relation to self-detection, melanoma risk and tumour depth ( ≤1 mm; > 1 mm). Logistic regression was used to estimate odds ratios (ORs) and confidence intervals (CIs) for associations of interest. RESULTS Skin self-examination conducted 1-11 times during a recent year was associated with a possible decrease in melanoma risk (OR 0·74; 95% CI 0·54-1·02). Melanoma risk was decreased for those who conducted skin self-examination and saw a doctor (OR 0·52; 95% CI 0·30-0·90). Among cases, those who examined their skin were twice as likely to self-detect the melanoma (OR 2·23; 95% CI 1·47-3·38), but self-detection was not associated with shallower tumours. Tumour depth was reduced for those who conducted skin self-examination 1-11 times during a recent year (OR 0·39; 95% CI 0·18-0·81), but was not influenced by seeing a doctor, or by conducting skin self-examination and seeing a doctor. CONCLUSIONS Risk of a deeper tumour and possibly risk of melanoma were reduced by skin self-examination 1-11 times annually. Melanoma risk was markedly reduced by skin self-examination coupled with a doctor visit. We cannot, however, exclude the possibility that our findings reflect bias or confounding. Additional studies are needed to elucidate the potential benefits of skin self-examination for melanoma prevention and early detection.

The Personal Background and Preparation Survey Early Identifies Nursing Students at Risk for Attrition

Introduction Nursing student attrition continues to negatively impact the supply of nurses and nursing workforce diversity. Little research has addressed student attributes affecting nursing student attrition today. Research with college undergraduates has indicated that noncognitive attributes influence academic achievement and retention as much as academic attributes. Early identification of such attributes can help students to timely access appropriate services, providing improved opportunities for success. However, convenient, valid, quantitative, reliable assessment instruments appropriate for nursing students have been lacking. The Personal Background and Preparation Survey (PBPS) addresses the need for such a tool. [See PDF for complete abstract]

Vertical mobility in the Swiss Alps. The alpine pass Schnidejoch and indications of early pastoralism.

Since 2003 a melting ice field on the Schnidejoch pass (2756 a.s.l) delivered several hundred objects from the Neolithic, the Bronze and Iron Age as well as from Roman and Early Medieval times. The oldest finds date to the beginning 5th millennium BC, the youngest ones date around 1000 AD. Most of the objects stem from the Neolithic and the Bronze Age and are of organic origin. A series of more than 70 radiocarbon dates confirms that the Schnidejoch pass, linking the Bernese Highlands with the River Rhone valley, was in use at least from 4800–4500 BC on. The accessibility of the pass was easy when the glaciers descending from the nearby Wildhorn mountain range (peak on 3248 a.s.l) were in a retreating phase. In contrary glacier advances closed the way to the pass. In 2010 a palaeoecological study of sediment cores researched nearby Lake Iffig (2065 m a.s.l.). The results show clear indications of early human impact in this alpine area. Linking archaeological finds from Schnidejoch pass and River Rhone valley with the palaeoecological data can be interpreted as early indications of alpine pastoralism and transhumance. The combined archaeological and paleoecolical research allows to explain vertical mobility in the Swiss Alps.

Dimethylsulfide (DMS) and Dimethylsulfoniopropionate (DMSP) in Relation to Phytoplankton in the Gulf of Maine

Dimethylsulfide (DMS) and its precursor dimethylsulfoniopropionate (DMSP), in both particulate and dissolved forms, were surveyed during the early spring (March and April) and summer (July) of 1991 in coastal and offshore waters of the Gulf of Maine, USA, along with the hydrography, inorganic nutrients, phytoplankton chlorophyll, and phytoplankton taxonomic composition and abundance. Concentrations as high as 15 nM DMS (in April and July), 208 nM particulate DMSP (in April), and 101 nM dissolved DMSP (in July) were recorded. Total DMSP (dissolved plus particulate) reached 293 nM in a patch of the dinoflagellate Katodinium sp. in April. This is the first report of high DMSP concentrations in temperate waters in early spring associated with any organism other than the prymnesiophyte Phaeocystis pouchetii. There were no correlations between phytoplankton biomass, as measured by chlorophyll a, and DMS, and there were only slight correlations between chlorophyll a and DMSP in either dissolved or particulate form. As previously demonstrated by others, concentrations of intracellular (particulate) DMSP were related more to the presence of specific phytoplankton species rather than to overall phytoplankton biomass. The occurrence of high DMSP and DMS levels in early spring, comparable with or higher than those seen in summer maxima, at a time when bacterial activity is minimal and wind speeds are typically high may result in enhanced air-sea-fluxes of DMS.

GMZ27 is a new organic arsenic derivative with anti-leukemic activity, via the induction of reactive oxygen species through NADPH oxidase and mitochondrial pathway that lead to leukemia cell apoptosis

Arsenic trioxide (ATO) is an inorganic arsenic derivative that is very effective against relapsed acute promyelocytic leukemia. It is being investigated as therapy for other cancers, but the risk/benefit ratio is questionable due to significant side effects. In contrast, organic arsenic derivatives (OAD) are known to be much less toxic than ATO. Based on high activity, we selected GMZ27 (dipropil-s-glycerol arsenic) for further study and have confirmed its potent activity against human acute leukemia cell lines. This anti-leukemic activity is significantly higher than that of ATO. Both in vivo and in vitro tests have shown that GMZ27 is significantly less toxic to normal bone marrow mononuclear cells and normal mice. Therefore, further study of the biological activity of GMZ27 was undertaken. ^ GMZ27, in contrast to ATO, can only marginally induce maturation of leukemic cells. GMZ27 has no effect on cell cycle. The anti-leukemic activity of GMZ27 against acute myeolocytic leukemia cells is not dependent upon degradation of PML-RARα fusion protein. GMZ27 causes dissipation of mitochondrial transmembrane potential, cleavage of caspase 9, caspase 3 activation. Further studies indicated that GMZ27 induces intracellular reactive oxygen species (ROS) production, and modification of intracellular ROS levels had profound effect on its potential to inhibit proliferation of leukemic cells. Therefore ROS production plays a major role in the anti-leukemic activity of GMZ27. ^ To identify how GMZ27 induces ROS, our studies focused on mitochondria and NADPH oxidase. The results indicated that the source of ROS generation induced by GMZ27 is dose dependent. At the low dose (0.3 uM) GMZ27 induces NADPH oxidase activity that leads to late ROS production, while at the high dose (2.0 uM) mitochondria function is disrupted and early ROS production is induced leading to dramatic cell apoptosis. Therefore, late, ROS production can be detected in mitochondria are depleted Rho-0 cells. Our work not only delineates a major biologic pathway for the anti-leukemic activity of GMZ27, but also discusses possible ways of enhancing the effect by the co-application of NADPH oxidase activator. Further study of this interaction may lead to achieving better therapeutic index.^

(Table S1) Diatom species richness from the Early Pleistocene to present

The extent to which the spatial distribution of marine planktonic microbes is controlled by local environmental selection or dispersal is poorly understood. Our ability to separate the effects of these two biogeographic controls is limited by the enormous environmental variability both in space and through time. To circumvent this limitation, we analyzed fossil diatom assemblages over the past ~1.5 million years from the world oceans and show that these eukaryotic microbes are not limited by dispersal. The lack of dispersal limitation in marine diatoms suggests that the biodiversity at the microbial level fundamentally differs from that of macroscopic animals and plants for which geographic isolation is a common component of speciation.

Magnetic susceptibility dataset from the early Givetian to early Frasnian in the La Thure section

Recent advances in radiometric dating result in significant improvements in the geological timescale and provide better insight into the timing of various processes and evolutions within the Earth's system. However, no radiometric ages are contained within the Givetian. Consequently, the absolute ages of the Givetian Stage boundaries, as well as the stage's duration, remain poorly constrained. As an alternative, the analysis of sedimentary cycles allows for the estimation of the duration of this stage. We examined the high-resolution magnetic susceptibility signals of four Givetian outcrops in the Givet area for a possible astronomical imprint, to fully understand the rates of evolutionary and environmental change. All four sections are firmly correlated and wavelet analyses of the magnetic susceptibility signals reveal the imprint of astronomical eccentricity forcing. The highly stable 405 kyr cycles constrain the duration of the Givetian Stage at 4.35±0.45 Myr, which is in good agreement with the International Chronostratigraphic Chart (5.0 Myr). The studied sections also exhibit an imprint of obliquity, suggesting a climatic teleconnection between low and high latitudes. The corresponding microfacies curves demonstrate similar astronomical imprint, and thereby indicate that the observed 10**5 year-scale cyclicity is the result of climatic and environmental change.

Silicoflagellates of early Paleocene to early Miocene sediments of the subantarctic South Atlantic

Nearly complete Paleogene sedimentary sequences were recovered by Leg 114 to the subantarctic South Atlantic. Silicoflagellate assemblages from the Paleogene and immediately overlying lower Neogene from Sites 698 (Northeast Georgia Rise), 700 (East Georgia Basin), 702 (Islas Orcadas Rise), and 703 (Meteor Rise) were examined. The described assemblage from Hole 700B represents the most complete yet described from the Paleocene, encompassing planktonic foraminifer Zones Plb (upper part) through P4 and Subchrons C25N to C23N. All lower Eocene sediments are barren as a result of diagenesis, except for a single sample from Hole 698A. Middle Eocene silicoflagellates described from Hole 702B range in age from early middle Eocene (P10) to late Eocene (PI5), with correlations to Subchrons C21N to C18N. Hole 703A contains late Eocene through early Miocene assemblages, with paleomagnetic control from Subchrons C16R to C6AAN. Leg 114 biosiliceous sequences contain exceptionally diverse assemblages of silicoflagellates. Approximately 155 species and separate morphotypes are described from the Paleogene and earliest Neogene. New taxa described from Leg 114 sediments include Bachmannocena vetula n. sp., Corbisema animoparallela n. sp., Corbisema camara n. sp., Corbisema constricta spinosa n. subsp., Corbisema delicata n. sp., Corbisema hastata aha n. subsp., Corbisema praedelicata n. sp., Corbisema scapana n. sp., Corbisema triacantha lepidospinosa n. subsp., Dictyocha deflandreifurtivia n. subsp., Naviculopsis biapiculata nodulifera n. subsp., Naviculopsis cruciata n. sp., Naviculopsis pandalata n. sp., Naviculopsis primativa n. sp., and Naviculopsis trispinosa eminula n. subsp. Taxonomic revisions were made to the following taxa: Corbisema constricta constricta emended, Corbisema disymmetrica crenulata n. comb., Corbisema jerseyensis emended, and Distephanus antarcticus n. comb. Silicoflagellate assemblages from the Paleogene and earliest Neogene of Holes 698A, 699A, 700B, 702B, and 703A are the basis of a silicoflagellate zonation spanning the interval from 63.2 to 22.25 Ma. Silicoflagellate zones recognized in this interval include the Corbisema hastata hastata Zone, Corbisema hastata aha Zone, Dictyocha precarentis Zone, Naviculopsis constricta Zone, Naviculopsis foliacea Zone, Bachmannocena vetula Zone, Dictyocha grandis Zone, Naviculopsis pandalata Zone, Naviculopsis constricta-Bachmannocena paulschulzii Zone, Bachmannocena paulschulzii Zone, Naviculopsis trispinosa Zone with subzones a and b, Corbisema archangelskiana Zone, Naviculopsis biapiculata Zone, Distephanus raupii Zone, Distephanus raupii-Corbisema triacantha Zone, and Corbisema triacantha mediana Zone.

Total phytoplankton abundance and biomass in the surface and fluorescence maximum layers and contributions of dominant species to their values in the Werstern Arctic in July-August 2003

Phytoplankton community was studied in the Bering Strait and over the shelf, continental slope, and deep-water zones of the Chukchi and Beaufort Seas in the middle of the vegetative season (July-August 2003). Its structure was analyzed in relation to ice conditions and seasonal patterns of water warming, stratification, and nutrient concentrations. Overall variations in phytoplankton abundance from 200 to 6000000 cells/l and biomass from 0.1 to 444.1 µg C/l.were estimated. The bulk of phytoplankton cells concentrated in the seasonal picnocline at depths 10-25 m. The highest values of cell abundance and biomass were recorded in regions influenced by inflow of Bering Sea waters or characterized by intense hydrodynamics, such as the Bering Strait, Barrow Canyon, and the outer shelf and slope of the Chukchi Sea. In the middle of the vegetative season, phytoplankton in the study region of the Western Arctic proved to comprise three successional (seasonal) assemblages: early spring, late spring, and summer assemblages. Their spatial distribution was dependent mainly on local features of hydrological and nutrient regimes rather than on general latitudinal trends of seasonal succession characteristic of arctic ecosystems.

Response of three krill species to hypoxia and warming: An experimental approach to oxygen minimum zones expansion in coastal ecosystems

To understand the adaptation of euphausiid (krill) species to oxygen minimum zones (OMZ), respiratory response and stress experiments combining hypoxia/reoxygenation exposure with warming were conducted. Experimental krill species were obtained from the Antarctic (South Georgia area), the Humboldt Current system (HCS, Chilean coast), and the Northern California Current system (NCCS, Oregon). Euphausia mucronata from the HCS shows oxyconforming or oxygen partial pressure (pO2)-dependent respiration below 80% air saturation (18 kPa). Normoxic subsurface oxygenation in winter posed a "high oxygen stress" for this species. The NCCS krill, Euphausia pacifica, and the Antarctic krill, Euphausia superba maintain respiration rates constant down to low critical pO2 values of 6 kPa (30% air saturation) and 11 kPa (55% air saturation), respectively. Antarctic krill had the lowest antioxidant enzyme activities, but the highest concentrations of the molecular antioxidant glutathione (GSH) and was not affected by 6 h exposure to moderate hypoxia. Temperate krill species had higher SOD (superoxide dismutase) values in winter than in summer, which relate to higher winter metabolic rate (E. pacifica). In all species, antioxidant enzyme activities remained constant during hypoxic exposure at habitat temperature. Warming by 7°C above habitat temperature in summer increased SOD activities and GSH levels in E. mucronata (HCS), but no oxidative damage occurred. In winter, when the NCCS is well mixed and the OMZ is deeper, +4°C of warming combined with hypoxia represents a lethal condition for E. pacifica. In summer, when the OMZ expands upwards (100 m subsurface), antioxidant defences counteracted hypoxia and reoxygenation effects in E. pacifica, but only at mildly elevated temperature (+2°C). In this season, experimental warming by +4°C reduced antioxidant activities and the hypoxia combination again caused mortality of exposed specimens. We conclude that a climate change scenario combining warming and hypoxia represents a serious threat to E. pacifica and, as a consequence, NCCS food webs.