NK2 homeobox gene cluster: Functions and roles in human diseases

NK2 genes (NKX2 gene cluster in humans) encode for homeodomain-containing transcription factors that are conserved along the phylogeny. According to the most detailed classifications, vertebrate NKX2 genes are classified into two distinct families, NK2.1 and NK2.2. The former is constituted by NKX2-1 and NKX2-4 genes, which are homologous to the Drosophila scro gene; the latter includes NKX2-2 and NKX2-8 genes, which are homologous to the Drosophila vnd gene. Conservation of these genes is not only related to molecular structure and expression, but also to biological functions. In Drosophila and vertebrates, NK2 genes share roles in the development of ventral regions of the central nervous system. In vertebrates, NKX2 genes have a relevant role in the development of several other organs such as the thyroid, lung, and pancreas. Loss-of-function mutations in NKX2-1 and NKX2-2 are the monogenic cause of the brain-lung-thyroid syndrome and neonatal diabetes, respectively. Alterations in NKX2-4 and NKX2-8 genes may play a role in multifactorial diseases, autism spectrum disorder, and neural tube defects, respectively. NKX2-1, NKX2-2, and NKX2-8 are expressed in various cancer types as either oncogenes or tumor suppressor genes. Several data indicate that evaluation of their expression in tumors has diagnostic and/or prognostic value

Role of m6A RNA Methylation in Thyroid Cancer Cell Lines

N6-methyladenosine (m6A) is the most abundant internal modification of RNA in eukaryotic cells, and, in recent years, it has gained increasing attention. A good amount of data support the involvement of m6A modification in tumorigenesis, tumor progression, and metastatic dissemination. However, the role of this RNA modification in thyroid cancer still remains poorly investigated. In this study, m6A-related RNA methylation profiles are compared between a normal thyroid cell line and different thyroid cancer cell lines. With this approach, it was possible to identify the different patterns of m6A modification in different thyroid cancer models. Furthermore, by silencing METTL3, which is the main player in the RNA methylation machinery, it was possible to evaluate the impact of m6A modification on gene expression in an anaplastic thyroid cancer model. This experimental approach allowed us to identify DDI2 as a gene specifically controlled by the m6A modification in anaplastic thyroid cancer cell lines. Altogether, these data are a proof of concept that RNA methylation widely occurs in thyroid cancer cell models and open a way forward in the search for new molecular patterns for diagnostic discrimination between benign and malignant lesions

Custos em pomares de pessegueiros conduzidos nos sistemas integrado e convencional, nos municípios de Araucária e Lapa, Paraná.

Este trabalho teve como objetivo o cálculo e a análise de custos nos sistemas de produção integrada (PI) e convencional (PC) de pêssego, em dois estabelecimentos agrícolas localizados nos municípios de Araucária e Lapa, Paraná. Foram apropriados os custos de produção baseados nas atividades. Os coeficientes técnicos e os indicadores foram empregados por hectare e por ano, sendo relativos à utilização de insumos ao longo de três anos, contemplando: quantidade dos direcionadores de custo, custo unitário da atividade, percentual de participação dos coeficientes na atividade e os gastos de cada componente dos custos, divididos esses em grandes grupos como: serviços, insumos, outros insumos e administrativos. Os custos totais por hectare nos pomares da PI, nos três anos, foram 5,86 e 5,05% inferiores ao custo da PC, respectivamente para Araucária e Lapa, PR. Os itens mais representativos na composição dos custos foram os gastos com mão-de-obra e agrotóxicos

High-sensitivity optical measurement of mechanical Brownian motion

We describe an experiment in which a laser beam is sent into a high-finesse optical cavity with a mirror coated on a mechanical resonator. We show that the reflected light is very sensitive to small mirror displacements. We have observed the Brownian motion of the resonator with a very high sensitivity.Comment: 4 pages, 4 figures, RevTe

Adaptive experimental design for one-qubit state estimation with finite data based on a statistical update criterion

We consider 1-qubit mixed quantum state estimation by adaptively updating measurements according to previously obtained outcomes and measurement settings. Updates are determined by the average-variance-optimality (A-optimality) criterion, known in the classical theory of experimental design and applied here to quantum state estimation. In general, A-optimization is a nonlinear minimization problem; however, we find an analytic solution for 1-qubit state estimation using projective measurements, reducing computational effort. We compare numerically two adaptive and two nonadaptive schemes for finite data sets and show that the A-optimality criterion gives more precise estimates than standard quantum tomography.Comment: 15 pages, 7 figure

RNA Profile of Cell Bodies and Exosomes Released by Tumorigenic and Non-Tumorigenic Thyroid Cells

Tumor cells release exosomes, extracellular vesicle containing various bioactive molecules such as protein, DNA and RNA. The analysis of RNA molecules packaged in exosomes may provide new potential diagnostic or prognostic tumor biomarkers. The treatment of radioiodine-refractory aggressive thyroid cancer is still an unresolved clinical challenge, and the search for biomarkers that are detectable in early phase of the disease has become a fundamental goal for thyroid cancer research. By using transcriptome analysis, this study aimed to analyze the gene expression profiles of exosomes secreted by a non-tumorigenic thyroid cell line (Nthy-ori 3.1-exo) and a papillary thyroid cancer (TPC-1-exo) cell line, comparing them with those of cell bodies (Nthy-ori 3.1-cells and TPC-1-cells). A total of 9107 transcripts were identified as differentially expressed when comparing TPC-1-exo with TPC-1-cells and 5861 when comparing Nthy-ori 3.1-exo with Nthy-ori 3.1-cells. Among them, Sialic acid-binding immunoglobulin-like lectins 10 and 11 (SIGLEC10, SIGLEC11) and Keratin-associated protein 5 (KRTAP5-3) transcripts, genes known to be involved in cancer progression, turned out to be up-regulated only in TPC-1-exo. Gene ontology analysis revealed significantly enriched pathways, and only in TPC-1-exo were the differential expressed genes associated with an up-regulation in epigenetic processes. These findings provide a proof of concept that some mRNA species are specifically packaged in tumor-cell-derived exosomes and may constitute a starting point for the identification of new biomarkers for thyroid tumors

A novel de novo HDAC8 missense mutation causing Cornelia de Lange syndrome

Background: Cornelia de Lange syndrome (CdLS) is a rare and clinically variable syndrome characterized by growth impairment, multi-organ anomalies, and a typical set of facial dysmorphisms. Here we describe a 2-year-old female child harboring a novel de novo missense variant in HDAC8, whose phenotypical score, according to the recent consensus on CdLS clinical diagnostic criteria, allowed the diagnosis of a non-classic CdLS. Methods: Clinical exome sequencing was performed on the trio, identifying a de novo heterozygous variant in HDAC8 (NM_018486; c. 356C>G p.Thr119Arg). Molecular modeling was performed to evaluate putative functional consequence of the HDAC8 protein. Results: The variant HDAC8 c.356C>G is classified as pathogenic following the ACMG (American College of Medical Genetics and Genomics)/AMP (Association for Molecular Pathology) guidelines. By molecular modeling, we confirmed the deleterious effect of this variant, since the amino acid change compromises the conformational flexibility of the HDAC8 loop required for optimal catalytic function. Conclusion: We described a novel Thr119Arg mutation in HDAC8 in a patient displaying the major phenotypic traits of the CdLS. Our results suggest that a modest change outside an active site is capable of triggering global structural changes that propagate through the protein scaffold to the catalytic site, creating de facto haploinsufficiency

Parametric instabilities in magnetized multicomponent plasmas

This paper investigates the excitation of various natural modes in a magnetized bi-ion or dusty plasma. The excitation is provided by parametrically pumping the magnetic field. Here two ion-like species are allowed to be fully mobile. This generalizes our previous work where the second heavy species was taken to be stationary. Their collection of charge from the background neutral plasma modifies the dispersion properties of the pump and excited waves. The introduction of an extra mobile species adds extra modes to both these types of waves. We firstly investigate the pump wave in detail, in the case where the background magnetic field is perpendicular to the direction of propagation of the pump wave. Then we derive the dispersion equation relating the pump to the excited wave for modes propagating parallel to the background magnetic field. It is found that there are a total of twelve resonant interactions allowed, whose various growth rates are calculated and discussed.Comment: Published in May 2004; this is a late submission to the archive. 14 pages, 8 figure

Brain Endothelial Cells Activate Neuroinflammatory Pathways in Response to Early Cerebral Small Vessel Disease (CSVD) Patients’ Plasma

The pathogenesis of cerebral small vessel disease (CSVD) is largely unknown. Endothelial disfunction has been suggested as the turning point in CSVD development. In this study, we tested the effect of plasma from CSVD patients on human cerebral microvascular endothelial cells with the aim of describing the pattern of endothelial activation. Plasma samples from three groups of young subjects have been tested: PTs (subjects affected by early stage CSVD); CTRLs (control subjects without abnormalities at MRI scanning); BDs (blood donors). Human Brain Endothelial Cells 5i (HBEC5i) were treated with plasma and total RNA was extracted. RNAs were pooled to reduce gene expression-based variability and NGS analysis was performed. Differentially expressed genes were highlighted comparing PTs, CTRLs and BDs with HBEC5i untreated cells. No significantly altered pathway was evaluated in BD-related treatment. Regulation of p38 MAPK cascade (GO:1900744) was the only pathway altered in CTRL-related treatment. Indeed, 36 different biological processes turned out to be deregulated after PT treatment of HBEC5i, i.e., the cytokine-mediated signaling pathway (GO:0019221). Endothelial cells activate inflammatory pathways in response to stimuli from CSVD patients' plasma, suggesting the pathogenetic role of neuroinflammation from the early asymptomatic phases of cerebrovascular disease