Modelled rainfall response to strong El Nino sea surface temperature anomalies in the tropical Pacific

© 2015 American Meteorological Society.El Niño-Southern Oscillation strongly influences the interannual variability of rainfall over the Pacific, shifting the position and orientation of the South Pacific convergence zone (SPCZ) and intertropical convergence zone (ITCZ). In 1982/83 and 1997/98, very strong El Niño events occurred, during which time the SPCZ and ITCZ merged into a single zonal convergence zone (szCZ) extending across the Pacific at approximately 58S. The sea surface temperature anomalies (SSTAs) reached very large values and peaked farther east compared to other El Niño events. Previous work shows that tropical Pacific precipitation responds nonlinearly to changing the amplitude of the El Niño SSTA even if the structure of the SSTA remains unchanged, but large canonical El Niño SSTAs cannot reproduce the szCZ precipitation pattern. This study conducts idealized, SST-forced experiments, starting with a large-amplitude canonical El Niño SSTA and gradually adding a residual pattern until the full (1982/83) and (1997/98) mean SST is reproduced. Differences between the canonical and strong El Niño SSTA patterns are crucial in generating an szCZ event. Three elements influence the precipitation pattern: (i) the local meridional SST maxima influences the ITCZ position and western Pacific precipitation, (ii) the total zonal SST maximum influences the SPCZ position, and (iii) the equatorial Pacific SST influences the total amount of precipitation. In these experiments, the meridional SST gradient increases as the SSTAs approach szCZ conditions. Additionally, the precipitation changes evident in szCZ years are primarily driven by changes in the atmospheric circulation, rather than thermodynamic changes. The addition of a global warming SST pattern increases the precipitation along the equator and shifts the ITCZ farther equatorward

The non-linear impact of El Nino, La Nina and the Southern Oscillation on seasonal and regional Australian precipitation

The relationship between El Niño-Southern Oscillation (ENSO) indices and precipitation (P) in some parts of Australia has previously been shown to be non-linear on annual and seasonal time scales. Here we examine the relationship between P and the Southern Oscillation Index (SOI) at all Australian locations and in all seasons. We show that in many Australian regions, there is more-than-expected P during strong La Niña years (SOI>13), but less-than-expected drying during strong El Niño years (SOI<-13). Statistically significant non-linearities are found over northern NT, QLD and parts of WA during SON, and parts of QLD, NSW, and VIC during DJF, when regressing P against June-December SOI. During the MAM immediately preceding a June-December ENSO year, and during JJA, the rainfall-SOI relationship is linear over most of the country. Systematic eastward shifts in P patterns can explain non-linearities over northern Australia, but do not explain non-linearities southward of approximately 20°S. The seasonal P distribution is decomposed into FP, the fraction of days on which P falls, and PD, the amount of rain per day on days when P is non-zero. Both FP and PD display a non-linear relationship with SOI similar to the P-SOI relationship, although the relative influence of each term on P is spatially and seasonally dependent

The role of the South Pacific in modulating Tropical Pacific variability

Tropical Pacific variability (TPV) heavily influences global climate, but much is still unknown about its drivers. We examine the impact of South Pacific variability on the modes of TPV: the El Niño-Southern Oscillation (ENSO) and the Interdecadal Pacific Oscillation (IPO). We conduct idealised coupled experiments in which we suppress temperature and salinity variability at all oceanic levels in the South Pacific. This reduces decadal variability in the equatorial Pacific by ~30% and distorts the spatial pattern of the IPO. There is little change to overall interannual variability, however there is a decrease in the magnitude of the largest 5% of both El Niño and La Niña sea-surface temperature (SST) anomalies. Possible reasons for this include: (i) reduced decadal variability means that interannual SST variability is superposed onto a ‘flatter’ background signal, (ii) suppressing South Pacific variability leads to the alteration of coupled processes linking the South and equatorial Pacific. A small but significant mean state change arising from the imposed suppression may also contribute to the weakened extreme ENSO SST anomalies. The magnitude of both extreme El Niño and La Niña SST anomalies are reduced, and the associated spatial patterns of change of upper ocean heat content and wind stress anomalies are markedly different for both types of events

Humans have already increased the risk of major disruptions to Pacific rainfall

© The Author(s) 2017.Intermittent disruptions to rainfall patterns and intensity over the Pacific Ocean lasting up to ∼ 1 year have major impacts on severe weather, agricultural production, ecosystems, and disease within the Pacific, and in many countries beyond. The frequency with which major disruptions to Pacific rainfall occur has been projected to increase over the 21st century, in response to global warming caused by large 21st century greenhouse gas emissions. Here we use the latest generation of climate models to show that humans may have contributed to the major disruption that occurred in the real world during the late 20th century. We demonstrate that although marked and sustained reductions in 21st century anthropogenic greenhouse gas emissions can greatly moderate the likelihood of major disruption, elevated risk of occurrence appears locked in now, and for at least the remainder of the 21st century

The boron-oxygen core of borinate esters is responsible for the store-operated calcium entry potentiation ability

International audienceBACKGROUND: Store-Operated Calcium Entry (SOCE) is the major Ca2+ ion entry pathway in lymphocytes and is responsible of a severe combined immunodeficiency (SCID) when deficient. It has recently been observed or highlighted in other cell types such as myoblasts and neurons, suggesting a wider physiological role of this pathway. Whereas Orai1 protein is considered to be the channel allowing the SOCE in T cells, it is hypothesized that other proteins like TRPC could associate with Orai1 to form SOCE with different pharmacology and kinetics in other cell types. Unraveling SOCE cell functions requires specific effectors to be identified, just as dihydropyridines were crucial for the study of Ca2+ voltage-gated channels, or spider/snake toxins for other ion channel classes. To identify novel SOCE effectors, we analyzed the effects of 2-aminoethyl diphenylborinate (2-APB) and its analogues. 2-APB is a molecule known to both potentiate and inhibit T cell SOCE, but it is also an effector of TRP channels and endoplasmic reticulum Ca2+-ATPase. RESULTS: A structure-function analysis allowed to discover that the boron-oxygen core present in 2-APB and in the borinate ester analogues is absolutely required for the dual effects on SOCE. Indeed, a 2-APB analogue where the boron-oxygen core is replaced by a carbon-phosphorus core is devoid of potentiating capacity (while retaining inhibition capacity), highlighting the key role of the boron-oxygen core present in borinate esters for the potentiation function. However, dimesityl borinate ester, a 2-APB analogue with a terminal B-OH group showed an efficient inhibitory ability, without any potentiating capacity. The removal or addition of phenyl groups respectively decrease or increase the efficiency of the borinate esters to potentiate and inhibit the SOCE. mRNA expression revealed that Jurkat T cells mainly expressed Orai1, and were the more sensitive to 2-APB modulation of SOCE. CONCLUSIONS: This study allows the discovery of new boron-oxygen core containing compounds with the same ability as 2-APB to both potentiate and inhibit the SOCE of different leukocyte cell lines. These compounds could represent new tools to characterize the different types of SOCE and the first step in the development of new immunomodulators

Nestin depletion induces melanoma matrix metalloproteinases and invasion

Matrix metalloproteinases (MMPs) are key biological mediators of processes as diverse as wound healing, embryogenesis, and cancer progression. Although MMPs may be induced through multiple signaling pathways, the precise mechanisms for their regulation in cancer are incompletely understood. Because cytoskeletal changes are known to accompany MMP expression, we sought to examine the potential role of the poorly understood cytoskeletal protein, nestin, in modulating melanoma MMPs. Nestin knockdown (KD) upregulated expression of specific MMPs and MMP-dependent invasion both through extracellular matrix barriers in vitro and in peritumoral connective tissue of xenografts in vivo. Development of 3-dimensionsal melanospheres that in vitro partially recapitulate non-invasive tumorigenic melanoma growth was inhibited by nestin KD, although ECM invasion by aberrant melanospheres that did form was enhanced. Mechanistically, nestin KD-dependent melanoma invasion was associated with intracellular redistribution of phosphorylated focal adhesion kinase (pFAK) and increased melanoma cell responsiveness to transforming growth factor-beta (TGF-β), both implicated in pathways of melanoma invasion. The results suggest that the heretofore poorly understood intermediate filament, nestin, may serve as a novel mediator of MMPs critical to melanoma virulence

Sporadic renal cell carcinoma in young and elderly patients: are there different clinicopathological features and disease specific survival rates?

BACKGROUND: Sporadic renal cell carcinoma (RCC) is rare in young adults. In the present retrospective study we reviewed clinicopathological features and disease specific survival rates in young patients (≤45 years) with RCC and compared them to old patients (≥75 years) with RCC. METHODS: Between 1992 and 2005 a total of 1042 patients were treated for RCC at our institution. We found 70 patients 45 years or younger (YP) and 150 patients 75 years or older (OP) at time of diagnosis. There were no differences in therapeutical approaches between both groups. Clinical and biologic parameters at diagnosis were compared and subjected to uni- and multivariate analysis to study cancer specific survival and progression rate. Mean postoperative follow-up in both groups was 50.1 months. RESULTS: Mean age was 39 years in YP and 80 years in OP, respectively. YP demonstrated significantly lower stage (pT1-pT2 N0 M0, p = 0.03), lower tumor grade (p = 0.01) and higher male-to-female ratio (p < 0.001). The rate of lymph node metastases or distant metastatic disease at presentation did not differ significantly between both groups. In multivariate analysis young age was independently associated with a higher 5-year cancer specific survival (95.2% vs. 72.3%, p = 0.009) and a lower 5-year progression rate (11.3% vs. 42.5%, p = 0.002). CONCLUSION: Sporadic RCC in young patients have lower tumor stages and grades and a better outcome compared to elderly. Age≤45 years was an independent prognostic factor for survival and progression

PTPN22.6, a Dominant Negative Isoform of PTPN22 and Potential Biomarker of Rheumatoid Arthritis

PTPN22 is a tyrosine phosphatase and functions as a damper of TCR signals. A C-to-T single nucleotide polymorphism (SNP) located at position 1858 of human PTPN22 cDNA and converting an arginine (R620) to tryptophan (W620) confers the highest risk of rheumatoid arthritis among non-HLA genetic variations that are known to be associated with this disease. The effect of the R-to-W conversion on the phosphatase activity of PTPN22 protein and the impact of the minor T allele of the C1858T SNP on the activation of T cells has remained controversial. In addition, how the overall activity of PTPN22 is regulated and how the R-to-W conversion contributes to rheumatoid arthritis is still poorly understood. Here we report the identification of an alternative splice form of human PTPN22, namely PTPN22.6. It lacks the nearly entire phosphatase domain and can function as a dominant negative isoform of the full length PTPN22. Although conversion of R620 to W620 in the context of PTPN22.1 attenuated T cell activation, expression of the tryptophan variant of PTPN22.6 reciprocally led to hyperactivation of human T cells. More importantly, the level of PTPN22.6 in peripheral blood correlates with disease activity of rheumatoid arthritis. Our data depict a model that can reconcile the conflicting observations on the functional impact of the C1858T SNP and also suggest that PTPN22.6 is a novel biomarker of rheumatoid arthritis

Expression and prognostic value of circulating angiogenic cytokines in pancreatic cancer

<p>Abstract</p> <p>Background</p> <p>The utility of circulating angiogenic cytokines (CAC) as biomarkers in pancreatic cancer has not been clarified yet. We investigated the expression and prognostic associations of seven CAC in patients with pancreatic cancer.</p> <p>Methods</p> <p>Serum samples were collected preoperatively in patients undergoing surgery for localized pancreatic cancer (n = 74), metastatic pancreatic cancer (n = 24) or chronic pancreatitis (n = 20) and in healthy controls (n = 48). Quantitative enzyme-linked immunosorbent assays and multiplex protein arrays were used to determine circulating levels of VEGF, VEGFR-1, PlGF, PDGF-AA, PDGF-BB, Ang-1 and EGF. Multivariate analyses on cancer-specific survival were performed with a Cox proportional hazards model.</p> <p>Results</p> <p>VEGF (p < 0.0001), PDGF-AA (p < 0.0001), Ang-1 (p = 0.002) and EGF (p < 0.0001) were differentially expressed in patients with pancreatic cancer compared to healthy controls. The presence of lymph node metastases was associated with increased levels of all CAC except for PlGF, whereas there were only minor associations of CAC with other clinicopathologic variables. The multivariate model including the entire angiogenic panel revealed high levels of circulating PDGF-AA (hazard ratio 4.58; 95% confidence interval 1.43 - 14.69) as predictor of poor cancer-specific survival, whereas high levels of PDGF-BB (0.15; 0.15 - 0.88), Ang-1 (0.30; 0.10 - 0.93) and VEGF (0.24; 0.09 - 0.57) were associated with a favorable prognosis.</p> <p>Conclusion</p> <p>Circulating levels of certain angiogenic cytokines correlate with patients' prognosis after resection for pancreatic cancer, if a panel of several CAC is considered simultaneously. These data should be considered in future studies evaluating angiogenic factors as prognostic biomarkers and therapeutic targets in patients with pancreatic cancer.</p

DNA Methylation Analysis of Bone Marrow Cells at Diagnosis of Acute Lymphoblastic Leukemia and at Remission

To detect genes with CpG sites that display methylation patterns that are characteristic of acute lymphoblastic leukemia (ALL) cells, we compared the methylation patterns of cells taken at diagnosis from 20 patients with pediatric ALL to the methylation patterns in mononuclear cells from bone marrow of the same patients during remission and in non-leukemic control cells from bone marrow or blood. Using a custom-designed assay, we measured the methylation levels of 1,320 CpG sites in regulatory regions of 413 genes that were analyzed because they display allele-specific gene expression (ASE) in ALL cells. The rationale for our selection of CpG sites was that ASE could be the result of allele-specific methylation in the promoter regions of the genes. We found that the ALL cells had methylation profiles that allowed distinction between ALL cells and control cells. Using stringent criteria for calling differential methylation, we identified 28 CpG sites in 24 genes with recurrent differences in their methylation levels between ALL cells and control cells. Twenty of the differentially methylated genes were hypermethylated in the ALL cells, and as many as nine of them (AMICA1, CPNE7, CR1, DBC1, EYA4, LGALS8, RYR3, UQCRFS1, WDR35) have functions in cell signaling and/or apoptosis. The methylation levels of a subset of the genes were consistent with an inverse relationship with the mRNA expression levels in a large number of ALL cells from published data sets, supporting a potential biological effect of the methylation signatures and their application for diagnostic purposes