Slow and soft passage through tipping point of the Atlantic Meridional Overturning Circulation in a changing climate

Paleo-proxy records suggest that the Atlantic Meridional Overturning Circulation (AMOC) exhibits a threshold for an abrupt change, a so-called tipping point. A classical bifurcation theory, a basis of the tipping dynamics of AMOC implicitly assumes that the tipping point is fixed. However, when a system is subjected to time-varying forcing (e.g., AMOC exposed to ice meltwater) an actual tipping point can be overshot due to delayed tipping, referred to as the slow passage effect. Here, using an Earth system model of intermediate complexity and a low-order model with freshwater forcing, we show that the tipping point of AMOC is largely delayed by the slow passage effect. It causes a large tipping lag of up to 1300 years, and strongly relaxes the abruptness of tipping as well. We further demonstrate that the tipping modulation can actively occur in past, present, and future climates by quantifying the effect during Dansgaard-Oeschger events, meltwater pulse 1A (MWP-1A), and current Greenland ice sheet melting. The suggested slow passage effect may explain the observed lagged AMOC collapse to MWP-1A of about 1000 years and provides implications tipping risk in the future

Involvement of mTOR signaling in sphingosylphosphorylcholine-induced hypopigmentation effects

<p>Abstract</p> <p>Background</p> <p>Sphingosylphosphorylcholine (SPC) acts as a potent lipid mediator and signaling molecule in various cell types. In the present study, we investigated the effects of SPC on melanogenesis and SPC-modulated signaling pathways related to melanin synthesis.</p> <p>Methods</p> <p>Melanin production was measured in Mel-Ab cells. A luciferase assay was used to detect transcriptional activity of the MITF promoter. Western blot analysis was performed to examine SPC-induced signaling pathways.</p> <p>Results</p> <p>SPC produced significant hypopigmentation effects in a dose-dependent manner. It was found that SPC induced not only activation of Akt but also stimulation of mTOR, a downstream mediator of the Akt signaling pathway. Moreover, SPC decreased the levels of LC3 II, which is known to be regulated by mTOR. Treatment with the mTOR inhibitor rapamycin eliminated decreases in melanin and LC3 II levels by SPC. Furthermore, we found that the Akt inhibitor LY294002 restored SPC-mediated downregulation of LC3 II and inhibited the activation of mTOR by SPC.</p> <p>Conclusions</p> <p>Our data suggest that the mTOR signaling pathway is involved in SPC-modulated melanin synthesis.</p

Utility of targeted deep sequencing for detecting circulating tumor DNA in pancreatic cancer patients.

Targeted deep sequencing across broad genomic regions has been used to detect circulating tumor DNA (ctDNA) in pancreatic ductal adenocarcinoma (PDAC) patients. However, since most PDACs harbor a mutation in KRAS, sequencing of broad regions needs to be systemically compared to analyzing only KRAS mutations for PDAC. Using capture-based targeted deep sequencing, we detected somatic tumor mutations in 17 fine needle aspiration biopsy and 69 longitudinal cell-free DNA (cfDNA) samples from 17 PDAC patients. KRAS mutations were detected in 10 out of 17 pretreatment patient plasma samples. Next, interrogation of genetic alterations in matched primary tumor samples detected ctDNA in 12 of 17 pretreatment plasma samples and cfDNA sequencing across the 83 target genes identified ctDNA in 15 of 17 cases (88.2% sensitivity). This improved sensitivity of ctDNA detection resulted in enhanced tumor burden monitoring when we analyzed longitudinal plasma samples. We found that cfDNA sequencing detected the lowest mutant allelic fractions and number of variants when complete response or partial response to chemotherapy was achieved. We demonstrated that ctDNA levels measured by targeted deep sequencing sensitively indicate the presence of cancer and correlate well with clinical responses to therapy and disease progression in PDAC patients

Primary Calcified T-Cell Lymphoma of the Urinary Bladder: A Case Report

Primary malignant lymphoma of the urinary bladder is extremely rare, and to our knowledge, no case described in the radiologic literature has been accompanied by calcification. We report a case in which the condition was associated with calcification, and describe the pelvic CT and MR imaging findings

Trib2 regulates the pluripotency of embryonic stem cells and enhances reprogramming efficiency

Embryonic stem (ES) cells are pluripotent cells characterized by self-renewability and differentiation potential. Induced pluripotent stem (iPS) cells are ES cell-equivalent cells derived from somatic cells by the introduction of core reprogramming factors. ES and iPS cells are important sources for understanding basic biology and for generating therapeutic cells for clinical applications. Tribbles homolog 2 (Trib2) functions as a scaffold in signaling pathways. However, the relevance of Trib2 to the pluripotency of ES and iPS cells is unknown. In the present study, we elucidated the importance of Trib2 in maintaining pluripotency in mouse ES cells and in generating iPS cells from somatic cells through the reprogramming process. Trib2 expression decreased as ES cells differentiated, and Trib2 knockdown in ES cells changed their colony morphology while reducing the activity of alkaline phosphatase and the expression of the pluripotency marker genes Oct4, Sox2, Nanog and Klf4. Trib2 directly interacted with Oct4 and elevated Oct4 promoter activity. During the generation of iPS cells, Trib2 knockdown decreased the reprogramming efficiency of mouse embryonic fibroblasts, whereas Trib2 overexpression significantly increased their reprogramming efficiency. In summary, our results suggest that Trib2 is important for maintaining self-renewal in ES cells and for pluripotency induction during the reprogramming process

Invasive Micropapillary Carcinoma of the Breast: MR Imaging Findings

ObjectiveTo analyze the magnetic resonance (MR) imaging findings of invasive micropapillary carcinoma of the breast.Materials and MethodsMR images were retrospectively evaluated in 14 patients (age range: 37-67, mean age: 49 years) with pathologically confirmed invasive micropapillary carcinoma of the breast. The enhancement type (mass/non-mass), shape, margin, contrast enhancement, and time-intensity curve pattern on the dynamic study were correlated with the histopathologic features. Associated findings, such as edema, nipple change, skin change and enlarged axillary lymph nodes were also studied.ResultsThe most common features of the masses were irregular shape (12 of 14 patients, 85.8%) and irregular or spiculated margin (11 of 14 patients, 78.7%). The contrast enhancement was heterogeneous in 11 patients (78.7%), rim enhancement in 2 cases (14.2%), and homogeneous in one patient (7.1%). The predominant kinetic pattern was rapid increase (14 of 14, 100%) in the initial phase and washout (11 of 14, 78.7%) in the delayed phase. Associated non-mass like enhancement was shown in 4 patients, representing ductal carcinoma in situ. MR imaging helped detect additional sites of cancer other than the index lesion in 3 patients (21.4%). Enlarged axillary lymphadenopathy was identified in 7 of the 14 patients (50%).ConclusionInvasive micropapillary carcinoma appears as a mass with an irregular shape, irregular or spiculated margin and heterogeneous enhancement on MR imaging. Though these findings are not specific and are also observed with other breast malignancies, invasive micropapillary carcinoma frequently showed multiple lesions, accompanying non-mass enhancement and axillary lymph node enlargement

Self-esteem as a Moderator of the Effects of Happiness, Depression, and Hostility on Suicidality Among Early Adolescents in Korea

Objectives The purpose of this study was to investigate the role of self-esteem as a moderator of the factors influencing suicidality among middle-schoolers. Methods Moderated multiple regression analysis was applied to assess the influence of happiness, depression, and hostility on suicidality and to determine the degree to which self-esteem served as a moderator of those relationships. Data were collected from 268 students at a middle school in Busan, Korea, using a self-administered structured questionnaire. Results Happiness, depression, and hostility had significant direct effects on suicidality. Self-esteem showed no direct effect, but had a significant moderating effect on the relationship between hostility and suicidal behavior. Conclusions These results suggest that various interventions, such as counseling programs, should be designed to alleviate hostility and depression and to enhance happiness and self-esteem among early adolescents

Type 2 Myocardial Infarction Following Generalized Tonic-Clonic Seizure

Myocardial infarction is diagnosed when blood levels of biomarkers are increased in the clinical setting of acute myocardial ischemia. Among the biomarkers, troponin I is the preferred biomarker indicative of myocardial necrosis. It is tissue specific for the heart. Myocardial infarction is rarely reported following seizure. We report a case of elevated troponin I in a patient after an episode of generalized tonic-clonic seizure. The diagnosis was type 2 myocardial infarction