Regional seesaw between the North Atlantic and Nordic Seas during the last glacial abrupt climate events

Dansgaard–Oeschger oscillations constitute one of the most enigmatic features of the last glacial cycle. Their cold atmospheric phases have been commonly associated with cold sea-surface temperatures and expansion of sea ice in the North Atlantic and adjacent seas. Here, based on dinocyst analyses from the 48–30 ka interval of four sediment cores from the northern Northeast Atlantic and southern Norwegian Sea, we provide direct and quantitative evidence of a regional paradoxical seesaw pattern: cold Greenland and North Atlantic phases coincide with warmer sea-surface conditions and shorter seasonal sea-ice cover durations in the Norwegian Sea as compared to warm phases. Combined with additional palaeorecords and multi-model hosing simulations, our results suggest that during cold Greenland phases, reduced Atlantic meridional overturning circulation and cold North Atlantic sea-surface conditions were accompanied by the subsurface propagation of warm Atlantic waters that reemerged in the Nordic Seas and provided moisture towards Greenland summit

Stratification of surface waters during the last glacial millennial climatic events: a key factor in subsurface and deep-water mass dynamics

The last glacial period was punctuated by abrupt climatic events with extrema known as Heinrich and Dansgaard–Oeschger events. These millennial events have been the subject of many paleoreconstructions and model experiments in the past decades, but yet the hydrological processes involved remain elusive. In the present work, high-resolution analyses were conducted on the 12–42 ka BP section of core MD99-2281 retrieved southwest of the Faeroe Islands, and combined with analyses conducted in two previous studies (Zumaque et al., 2012; Caulle et al., 2013). Such a multiproxy approach, coupling micropaleontological, geochemical and sedimentological analyses, allows us to track surface, subsurface, and deep hydrological processes occurring during these rapid climatic changes. Records indicate that the coldest episodes of the studied period (Greenland stadials and Heinrich stadials) were characterized by a strong stratification of surface waters. This surface stratification seems to have played a key role in the dynamics of subsurface and deep-water masses. Indeed, periods of high surface stratification are marked by a coupling of subsurface and deep circulations which sharply weaken at the beginning of stadials, while surface conditions progressively deteriorate throughout these cold episodes; conversely, periods of decreasing surface stratification (Greenland interstadials) are characterized by a coupling of surface and deep hydrological processes, with progressively milder surface conditions and gradual intensification of the deep circulation, while the vigor of the subsurface northward Atlantic flow remains constantly high. Our results also reveal different and atypical hydrological signatures during Heinrich stadials (HSs): while HS1 and HS4 exhibit a "usual" scheme with reduced overturning circulation, a relatively active North Atlantic circulation seems to have prevailed during HS2, and HS3 seems to have experienced a re-intensification of this circulation during the middle of the event. Our findings thus bring valuable information to better understand hydrological processes occurring in a key area during the abrupt climatic shifts of the last glacial period

Downregulation of urokinase plasminogen activator receptor expression inhibits Erk signalling with concomitant suppression of invasiveness due to loss of uPAR–β1 integrin complex in colon cancer cells

Cancer invasion is regulated by cell surface proteinases and adhesion molecules. Interaction between specific cell surface molecules such as urokinase plasminogen activator receptor (uPAR) and integrins is crucial for tumour invasion and metastasis. In this study, we examined whether uPAR and beta1 integrin form a functional complex to mediate signalling required for tumour invasion. We assessed the expression of uPAR/beta1 integrin complex, Erk signalling pathway, adhesion, uPA and matrix metalloproteinase (MMP) expression, migration/invasion and matrix degradation in a colon cancer cell line in which uPAR expression was modified. Antisense inhibition of the cell surface expression of uPAR by 50% in human colon carcinoma HCT116 cells (A/S) suppressed Erk-MAP kinase activity by two-fold. Urokinase plasminogen activator receptor antisense treatment of HCT116 cells was associated with a 1.3-fold inhibition of adhesion, approximately four-fold suppression of HMW-uPA secretion and inhibition of pro-MMP-9 secretion. At a functional level, uPAR antisense resulted in a four-fold decline in migration/invasion and abatement of plasmin-mediated matrix degradation. In empty vector-transfected cells (mock), uPA strongly elevated basal Erk activation. In contrast, in A/S cells, uPA induction of Erk activation was not observed. Urokinase plasminogen activator receptor associated with beta1 integrin in mock-transfected cells. Disruption of uPAR-beta1 integrin complex in mock-transfected cells with a specific peptide (P25) inhibited uPA-mediated Erk-MAP kinase pathway and inhibited migration/invasion and plasmin-dependent matrix degradation through suppression of pro-MMP-9/MMP-2 expression. This novel paradigm of uPAR-integrin signalling may afford opportunities for alternative therapeutic strategies for the treatment of cancer

Elastin Peptides Signaling Relies on Neuraminidase-1-Dependent Lactosylceramide Generation

The sialidase activity of neuraminidase-1 (Neu-1) is responsible for ERK 1/2 pathway activation following binding of elastin peptide on the elastin receptor complex. In this work, we demonstrate that the receptor and lipid rafts colocalize at the plasma membrane. We also show that the disruption of these microdomains as well as their depletion in glycolipids blocks the receptor signaling. Following elastin peptide treatment, the cellular GM3 level decreases while lactosylceramide (LacCer) content increases consistently with a GM3/LacCer conversion. The use of lactose or Neu-1 siRNA blocks this process suggesting that the elastin receptor complex is responsible for this lipid conversion. Flow cytometry analysis confirms this elastin peptide-driven LacCer generation. Further, the use of a monoclonal anti-GM3 blocking antibody shows that GM3 is required for signaling. In conclusion, our data strongly suggest that Neu-1-dependent GM3/LacCer conversion is the key event leading to signaling by the elastin receptor complex. As a consequence, we propose that LacCer is an early messenger for this receptor

Pain in elderly people with severe dementia: A systematic review of behavioural pain assessment tools

BACKGROUND: Pain is a common and major problem among nursing home residents. The prevalence of pain in elderly nursing home people is 40–80%, showing that they are at great risk of experiencing pain. Since assessment of pain is an important step towards the treatment of pain, there is a need for manageable, valid and reliable tools to assess pain in elderly people with dementia. METHODS: This systematic review identifies pain assessment scales for elderly people with severe dementia and evaluates the psychometric properties and clinical utility of these instruments. Relevant publications in English, German, French or Dutch, from 1988 to 2005, were identified by means of an extensive search strategy in Medline, Psychinfo and CINAHL, supplemented by screening citations and references. Quality judgement criteria were formulated and used to evaluate the psychometric aspects of the scales. RESULTS: Twenty-nine publications reporting on behavioural pain assessment instruments were selected for this review. Twelve observational pain assessment scales (DOLOPLUS2; ECPA; ECS; Observational Pain Behavior Tool; CNPI; PACSLAC; PAINAD; PADE; RaPID; Abbey Pain Scale; NOPPAIN; Pain assessment scale for use with cognitively impaired adults) were identified. Findings indicate that most observational scales are under development and show moderate psychometric qualities. CONCLUSION: Based on the psychometric qualities and criteria regarding sensitivity and clinical utility, we conclude that PACSLAC and DOLOPLUS2 are the most appropriate scales currently available. Further research should focus on improving these scales by further testing their validity, reliability and clinical utility

Interplay between cell adhesion and growth factor receptors: from the plasma membrane to the endosomes

The emergence of multicellular animals could only take place once evolution had produced molecular mechanisms for cell adhesion and communication. Today, all metazoans express integrin-type adhesion receptors and receptors for growth factors. Integrins recognize extracellular matrix proteins and respective receptors on other cells and, following ligand binding, can activate the same cellular signaling pathways that are regulated by growth factor receptors. Recent reports have indicated that the two receptor systems also collaborate in many other ways. Here, we review the present information concerning the role of integrins as assisting growth factor receptors and the interplay between the receptors in cell signaling and in the orchestration of receptor recycling

Restoration of caveolin-1 expression suppresses growth and metastasis of head and neck squamous cell carcinoma

Caveolin-1 (Cav-1) plays an important role in modulating cellular signalling, but its role in metastasis is not well defined. A significant reduction in Cav-1 levels was detected in lymph node metastases as compared with primary tumour of head and neck squamous cell carcinoma (HNSCC) specimens (P<0.0001), confirming the downregulation of Cav-1 observed in a highly metastatic M4 cell lines derived from our orthotopic xenograft model. To investigate the function of Cav-1 in metastasis of HNSCC, we compared stable clones of M4 cells carrying human cav-1 cDNA (CavS) with cells expressing an empty vector (EV) in vitro and in the orthotopic xenograft model. Overexpression of Cav-1 suppressed growth of the CavS tumours compared with the EV tumours. The incidence of lung metastases was significantly lower in animals carrying CavS tumours than those with EV tumours (P=0.03). In vitro, CavS cells displayed reduced cell growth, invasion, and increased anoikis compared with EV cells. In CavS cells, Cav-1 formed complex with integrin β1 and Src. Further application of integrin β1 neutralising antibody or Src inhibitor PP2 to EV cells illustrated similar phenotypes as CavS cells, suggesting that Cav-1 may play an inhibitory role in tumorigenesis and lung metastasis through regulating integrin β1- and Src-mediated cell–cell and cell–matrix interactions

Detection of delirium by nurses among long-term care residents with dementia

<p>Abstract</p> <p>Background</p> <p>Delirium is a prevalent problem in long-term care (LTC) facilities where advanced age and cognitive impairment represent two important risk factors for this condition. Delirium is associated with numerous negative outcomes including increased morbidity and mortality. Despite its clinical importance, delirium often goes unrecognized by nurses. Although rates of nurse-detected delirium have been studied among hospitalized older patients, this issue has been largely neglected among demented older residents in LTC settings. The goals of this study were to determine detection rates of delirium and delirium symptoms by nurses among elderly residents with dementia and to identify factors associated with undetected cases of delirium.</p> <p>Methods</p> <p>In this prospective study (N = 156), nurse ratings of delirium were compared to researcher ratings of delirium. This procedure was repeated for 6 delirium symptoms. Sensitivity, specificity, positive and negative predictive values were computed. Logistic regressions were conducted to identify factors associated with delirium that is undetected by nurses.</p> <p>Results</p> <p>Despite a high prevalence of delirium in this cohort (71.5%), nurses were able to detect the delirium in only a minority of cases (13%). Of the 134 residents not identified by nurses as having delirium, only 29.9% of them were correctly classified. Detection rates for the 6 delirium symptoms varied between 39.1% and 58.1%, indicating an overall under-recognition of symptoms of delirium. Only the age of the residents (≥ 85 yrs) was associated with undetected delirium (OR: 4.1; 90% CI: [1.5–11.0]).</p> <p>Conclusion</p> <p>Detection of delirium is a major issue for nurses that clearly needs to be addressed. Strategies to improve recognition of delirium could result in a reduction of adverse outcomes for this very vulnerable population.</p