What might cause pain in the thyroid gland? Report of a patient with subacute thyroiditis of atypical presentation

Subacute granulomatous thyroiditis (SAT), also known as de Quervain's thyroiditis or painful subacute thyroiditis, is the commonest thyroid condition responsible for neck tenderness. Other causes of pain in the thyroid gland should be taken into consideration during differential diagnosis, especially when a patient presents with misleading or equivocal signs and symptoms. We report the case of a 39 year-old woman diagnosed as having SAT whose clinical, biochemical and radiological presentation varied significantly from the common SAT manifestation. A tentative diagnosis of SAT was made based on the presented symptoms, ultrasonography and fine-needle biopsy results. However, biochemical analysis suggested neither inflammatory process nor the presence of thyrotoxicosis. Moreover, technetium scan of the thyroid revealed normal uptake of the isotope and there was neither clinical nor ultasonographic response for corticosteroids. The patient's symptoms, despite being prescribed typical treatment, gradually deteriorated and the pain became increasingly debilitating. Eventually, the patient underwent total thyroidectomy. As a result, she has become free of symptoms, but the macroscopic picture of thyroid gland, noted during the operation, gave a suspicion of neoplastic process. Nevertheless, histological study of flow samples confirmed the tentative diagnosis of de Quervain's thyroiditis, despite all previous findings that were not suggestive of it. This report confirms the likelihood that SAT can present atypically. Additionally, it indicates that surgical treatment may be considered in patients with severe, debilitating, persistent thyroid gland pain connected with SAT clinical course.     

Sprouty2-mediated inhibition of fibroblast growth factor signaling is modulated by the protein kinase DYRK1A

Raf-MEK-extracellular signal-regulated kinase (Erk) signaling initiated by growth factor-engaged receptor tyrosine kinases (RTKs) is modulated by an intricate network of positive and negative feedback loops which determine the specificity and spatiotemporal characteristics of the intracellular signal. Well-known antagonists of RTK signaling are the Sprouty proteins. The activity of Sprouty proteins is modulated by phosphorylation. However, little is known about the kinases responsible for these posttranslational modifications. We identify DYRK1A as one of the protein kinases of Sprouty2. We show that DYRK1A interacts with and regulates the phosphorylation status of Sprouty2. Moreover, we identify Thr75 on Sprouty2 as a DYRK1A phosphorylation site in vitro and in vivo. This site is functional, since its mutation enhanced the repressive function of Sprouty2 on fibroblast growth factor (FGF)-induced Erk signaling. Further supporting the idea of a functional interaction, DYRK1A and Sprouty2 are present in protein complexes in mouse brain, where their expression overlaps in several structures. Moreover, both proteins copurify with the synaptic plasma membrane fraction of a crude synaptosomal preparation and colocalize in growth cones, pointing to a role in nerve terminals. Our results suggest, therefore, that DYRK1A positively regulates FGF-mitogen-activated protein kinase signaling by phosphorylation-dependent impairment of the inhibitory activity of Sprouty2.     

Autophagy regulation depends on ER homeostasis controlled by lipid droplets

Macroautophagy (hereafter autophagy) is a highly conserved homeostasis and quality control process critically linked to neurodegeneration, metabolic diseases, cancer, and aging. A key feature of autophagy is the de novo formation of autophagosomes, double-membrane vesicular structures encapsulating cytoplasmic cargo for vacuolar turnover and recycling. The membrane rearrangements underlying nucleation, expansion, closure, and vacuolar fusion of autophagosomes are driven by multicomponent core autophagy machinery in cooperation with numerous factors involved in a variety of cellular processes. Our current understanding of the origin and contribution of diverse membrane sources to autophagosome biogenesis and of cellular functions enabling stress-appropriate autophagy responses critical for cell health and survival remains limited. Here, we summarize and discuss our recent findings analyzing the role of lipid droplets (LDs), conserved intracellular storage compartments for neutral lipids, for autophagy regulation. Our data indicate that LDs are dispensable as membrane sources, but fulfill critical functions for maintaining endoplasmic reticulum (ER) homeostasis, including buffering of newly synthesized fatty acids and maintenance of phospholipid composition, required for intact autophagy regulation and cell survival during nutrient stress.     

Cell specific patterns of methylation in the human placenta

Epigenetic processes, such as DNA methylation, are known to regulate tissue specific gene expression. We explored this concept in the placenta to define whether DNA methylation is cell-type specific. Cytotrophoblasts and fibroblasts were isolated from normal midtrimester placentas. Using immunocytochemistry, we demonstrated 95% purity for cytotrophoblasts and 60–70% for fibroblasts. We compared DNA methylation profiles from cytotrophoblasts, fibroblasts and whole placental villi using bisulfite modified genomic DNA hybridized to the Illumina Methylation27 array. Euclidean cluster analysis of the DNA methylation profiles showed two main clusters, one containing cytotrophoblasts and placenta, the other fibroblasts. Differential methylation analysis identified 442 autosomal CpG sites that differed between cytotrophoblasts and fibroblasts, 315 between placenta and fibroblasts and 61 between placenta and cytotrophoblasts. Three candidate methylation differences were validated by targeted pyrosequencing assays. Pyrosequencing assays were developed for CpG sites less methylated in cytotrophoblasts than fibroblasts mapping to the promoter region of the beta subunit of human chorionic gonadotropin 5 (CGB5), as well as two CpG sites mapping to each of two tumor suppressor genes. Our data suggest that epigenetic regulation of gene expression is likely to be a key factor in the functional specificity of cytotrophoblasts. These data are proof of principle for cell-type specific epigenetic regulation in placenta and demonstrate that the methylation profile of placenta is mainly driven by cytotrophoblasts.Key words: cytotrophoblast purification, placental fibroblast purification, DNA methylation, epigenetics, placenta, cell type-specific methylation     

Reproductive isolation between diploid and tetraploid cytotypes of Libidibia ferrea (= Caesalpinia ferrea) (Leguminosae): ecological and taxonomic implications

Polyploidy is the most common chromosomal mechanism involved in the evolution of plants. However, the emergence of polyploid individuals does not guarantee the establishment of a new lineage, and the relationship between polyploidy and reproductive biology is therefore relevant. Libidibia ferrea is a legume tree that has diploid and tetraploid populations. In this work we analyse the reproductive biology of the species to verify the degree of reproductive isolation between the two cytotypes. Observations on phenology, floral morphology, biology, and visitors, breeding system, reproductive success and reproductive isolation were made for both cytotypes in two municipalities of northeastern Brazil. Cytotypes differed for all morphometric parameters analysed, with tetraploids exhibiting higher mean values than diploids. Both cytotypes had the same effective pollinators (native bees from the genera Centris and Xylocopa, and the introduced Apis mellifera). However, since stamens of diploids and tetraploids were of different size, it is possible that spatial separation occurs when pollen of each cytotype is deposited on a bee’s body. Diploids were self-incompatible (ISI?=?0) and exhibited high fruit-set after intraploidy crossing (20?%), whereas tetraploids were self-compatible (ISI?=?0.47) and set only 3.9?% of fruits after intraploidy crossing. Both cytotypes showed low fruit- and seed-set under natural conditions, and there was no fruit-set after crosses between them. Data are discussed in relation to the establishment of polyploids, to the pattern of distribution of the species and to the taxonomic implications. The cytotypes of L. ferrea should be considered as distinct species, since they are reproductively isolated from each other.     

Reduced Introgression of Sex Chromosome Markers in the Mexican Howler Monkey (Alouatta palliata × A. pigra) Hybrid Zone

International Journal of Primatology - Interspecific hybridization allows the introgression or movement of alleles from one genome to another. While some genomic regions freely exchange alleles...