The role of microRNAs in thyroid carcinomas

Thyroid cancers (TCs) are the most common malignancies of endocrine organs. They originate from cells of different origin within the thyroid gland, which is located at the base of the neck. Several forms of TCs have been classified and great variability is observed in molecular, cellular and clinical features. The most common forms have favorable prognosis but a number of very aggressive TCs, which are characterized by a less differentiated cellular phenotype, have no effective treatment at the moment. While TC causes are not completely understood, many genetic factors involved in their onset have been discovered. In particular, activating mutations of BRAF, RET or RAS genes are known to be specifically associated with TC initiation, progression and outcome. The involvement of microRNAs in thyroid neoplasms has recently changed the paradigm for biomarker discovery in TC, suggesting that these small non-coding RNAs could be used to develop, refine or strengthen strategies for diagnosis and management of TCs. In this review, the importance of microRNA profiling in TC is explored suggesting that these molecules can be included in procedures that can perform better than any known clinical index in the identification of adverse outcomes

AIRE illuminates the feature of medullary thymic epithelial cells in thymic carcinoma

Despite the clear distinction between cortical (cTECs) and medullary thymic epithelial cells (mTECs) in physiology, the cell of origin of thymic carcinomas (TCs) and other thymic epithelial tumors remained enigmatic. We addressed this issue by focusing on AIRE, an mTEC-specific transcriptional regulator that is required for immunological self-tolerance. We found that a large proportion of TCs expressed AIRE with typical nuclear dot morphology by immunohistochemistry. AIRE expression in TCs was supported by the RNA-seq data in the TCGA-THYM database. Furthermore, our bioinformatics approach to the recent single-cell RNA-seq data on human thymi has revealed that TCs hold molecular characteristics of multiple mTEC subpopulations. In contrast, TCs lacked the gene signatures for cTECs. We propose that TCs are tumors derived from mTECs

Spatial and temporal variation of north-west pacific tropical cyclone under the background of upper ocean warming

879-885Under the background of global warming, the activities of north-west pacific (NWP) tropical cyclones (TCs) are undergoing significant changes. The TC frequencies have been characterized by an initial slow increase followed by a rapid increase and then a decrease, the past 33 years. During the 21st century, the TC frequency of the NWP has clearly decreased. However, the three TC origin types in the NWP have experienced different types of changes. The TC frequencies of origin 1 (10°~22°N,110°~120°E) and origin 2 (8°~20°N,125°~145°E) are both increasing, but the TC frequency of origin 3 (5°~20°N,145°~155°E) is decreasing. Under the background of upper ocean warming, the average TC duration has shown a decreasing trend (-0.27d/10a), while the TC mean and maximum intensity has increased (0.93 m/s/10a and 1.57 m/s/10a, respectively). Therefore, the potential threats of TC activities to NWP coastal countries are likely to intensify. The changes in the thermal state of the upper ocean have many effects on TC activities. Sea surface temperature is not the main factor affecting the frequency of TCs. However, the response of TCs to the upper ocean heat content is obvious

An interview with Thomas C. Schelling: Interpretation of game theory and the checkerboard model

This note is mainly based on a short interview with Thomas C. Schelling (TCS), who shared the Nobel Prize with Robert J. Aumann in 2005. The interview took place on 06.03.2001 at University of Maryland, College Park, USA. It consists of two parts. The first part is about his interpretation of game theory, particularly about the use of game-theoretic models in explaining the origin and maintenance of conventions, and norms. The second part is on the origin of Schelling's influential checkerboard model of residential segregation, particularly about his approach to modeling social phenomena exemplified by this model. The note ends with some concluding remarks.checkerboard model

How Well Do Global Climate Models Simulate the Variability of Atlantic Tropical Cyclones Associated with ENSO?

The variability of Atlantic tropical cyclones (TCs) associated with El Nino-Southern Oscillation (ENSO) in model simulations is assessed and compared with observations. The model experiments are 28-yr simulations forced with the observed sea surface temperature from 1982 to 2009. The simulations were coordinated by the U.S. CLIVAR Hurricane Working Group and conducted with five global climate models (GCMs) with a total of 16 ensemble members. The model performance is evaluated based on both individual model ensemble means and multi-model ensemble mean. The latter has the highest anomaly correlation (0.86) for the interannual variability of TCs. Previous observational studies show a strong association between ENSO and Atlantic TC activity, as well as distinctions in the TC activities during eastern Pacific (EP) and central Pacific (CP) El Nino events. The analysis of track density and TC origin indicates that each model has different mean biases. Overall, the GCMs simulate the variability of Atlantic TCs well with weaker activity during EP El Nino and stronger activity during La Nina. For CP El Nino, there is a slight increase in the number of TCs as compared with EP El Nino. However, the spatial distribution of track density and TC origin is less consistent among the models. Particularly, there is no indication of increasing TC activity over the U.S. southeast coastal region as in observations. The difference between the models and observations is likely due to the bias of vertical wind shear in response to the shift of tropical heating associated with CP El Nino, as well as the model bias in the mean circulation

An interview with Thomas C. Schelling: Interpretation of game theory and the checkerboard model

This note is mainly based on a short interview with Thomas C. Schelling (TCS), who shared the Nobel Prize with Robert J. Aumann in 2005. The interview took place on 06.03.2001 at University of Maryland, College Park, USA. It consists of two parts. The first part is about his interpretation of game theory, particularly about the use of game- theoretic models in explaining the origin and maintenance of conventions, and norms. The second part is on the origin of Schelling’s influential checkerboard model of residential segregation, particularly about his approach to modeling social phenomena exemplified by this model. The note ends with some concluding remarks. Citation: Aydinonat, N. Emrah, (2005) 'An interview with Thomas C. Schelling: Interpretation of game theory and the checkerboard model,' Economics Bulletin, Vol. 2 no. 2 pp. 1-7.Thomas Schelling, game theory, checkerboard model

High Prevalence of Sequences Included in Transmission Clusters Within Newly Diagnosed HIV-1 Patients in Southern Spain (2004-2015)

The presence of transmission clusters (TCs) and their epidemiological characteristics in a treatment-naive cohort of HIV-1 patients in southern Spain over a decade (2004-2015) were evaluated. Protease and reverse transcriptase sequences provided by each genotype test were used in the phylogenetic study, performed first by the neighbor-joining method and then confirmed by Bayesian analysis. We collected clinical, immunovirological, and demographic data for all patients included. Our cohort comprised 757 patients, 428 (56.5%) belonging to a TC. Overall, we found 123 TCs, 21 of them comprising five or more individuals and three with ≥10 sequences. Forty-three TCs (35.0%) remained active. The clustered patients were mainly men (92.8%) who had sex with men (MSM) (81.5%), Spanish (80.6%), and young adults (median age at diagnosis of 32.6 years). They had lower percentages of late diagnosis and AIDS cases (42.1% and 13.6%, respectively), whereas the presence of recent seroconverters (31.1%), HIV-1 B subtypes (79.4%), and transmission drug resistance (20.3%) increased within TCs, with regard to not-clustered individuals. Among the TCs of non-B variants, circulating recombinant forms (CRF) were predominant (87.5%), with the highest frequencies for CRF19_cpx (17.0% of non-B subtype sequences in TCs); CRF02_AG (15.9%); and CRF01_AE (9.1%). In conclusion, over half of our cohort was included within a TC. More than a third of TCs found could be considered active transmission events. Belonging to a TC was related to MSM, Spanish origin, recent seroconversion, high prevalence of resistance mutations, and B HIV subtype. Among the non-B genetic forms in TCs, we found a high prevalence of CRF19_cpx, CRF02_AG, and CRF01_AE variants.This work was mainly supported by the National R+D+I Plan (RD16/0025/0032 project); the Institute of Health Carlos III (ISCIII); and the European Regional Development Fund

Recapitulating thyroid cancer histotypes through engineering embryonic stem cells

Thyroid carcinoma (TC) is the most common malignancy of endocrine organs. The cell subpopulation in the lineage hierarchy that serves as cell of origin for the different TC histotypes is unknown. Human embryonic stem cells (hESCs) with appropriate in vitro stimulation undergo sequential differentiation into thyroid progenitor cells (TPCs-day 22), which maturate into thyrocytes (day 30). Here, we create follicular cell-derived TCs of all the different histotypes based on specific genomic alterations delivered by CRISPR-Cas9 in hESC-derived TPCs. Specifically, TPCs harboring BRAFV600E or NRASQ61R mutations generate papillary or follicular TC, respectively, whereas addition of TP53R248Q generate undifferentiated TCs. Of note, TCs arise by engineering TPCs, whereas mature thyrocytes have a very limited tumorigenic capacity. The same mutations result in teratocarcinomas when delivered in early differentiating hESCs. Tissue Inhibitor of Metalloproteinase 1 (TIMP1)/Matrix metallopeptidase 9 (MMP9)/Cluster of differentiation 44 (CD44) ternary complex, in cooperation with Kisspeptin receptor (KISS1R), is involved in TC initiation and progression. Increasing radioiodine uptake, KISS1R and TIMP1 targeting may represent a therapeutic adjuvant option for undifferentiated TCs

Evaluating changes in the moisture sources for tropical cyclones precipitation in the North Atlantic that underwent extratropical transition

In this study, we investigated the changes in the origin of moisture for the precipitation associated with tropical cyclones (TCs) after extratropical transition (ET) over the North Atlantic Ocean basin from 1980 to 2018. We analyzed the 24 hr before and after the occurrence of ET events. By applying a TC-centric methodology we found that the moisture uptake (MU) occurred predominantly in the south and southwest sectors within ∼2,000 km of TC center before ET and from the southwest and west sectors after ET. In addition, the development of the cold front and the warm conveyor belt after ET induces changes in the moisture transport pattern. Overall, the secondary circulation of TCs favored the moisture flux inward for TCs precipitation, while the large-scale baroclinic environment controlled the MU after ET.Xunta de Galicia | Ref. ED481A‐2020/193Xunta de Galicia | Ref. ED431C 2021/44Agencia Estatal de Investigación | Ref. PID2021‐122314OB‐I0