Ectopic lingual thyroid with subclinical hypothyroidism in children.

OBJECTIVES: Lingual thyroid is a rare condition that affects approximately 1 in 100,000 individuals. Although it is usually detected in the pediatric population through newborn screening tests or evaluation of congenital hypothyroidism, there are cases in which it remains undetected until adulthood or until symptoms arise because of glandular enlargement. The possible symptoms of lingual thyroid include foreign body sensation in the throat, dysphagia, dyspnea, and hemorrhage. Several cases of lingual thyroid are asymptomatic and accompanied by subclinical hypothyroidism. Herein, we present three cases of lingual thyroid treated with thyroid hormone suppressive therapy. CASE PRESENTATION: The three patients sought medical attention because of a sore throat or foreign body sensation in the throat. Their newborn screening tests and developmental histories were normal. These patients exhibited subclinical hypothyroidism and were treated with hormone suppression therapy. CONCLUSIONS: Patients with lingual thyroid frequently exhibit subclinical hypothyroidism. Hormone treatment may help to reduce the size of the ectopic thyroid and improve symptoms. If an increase in size is noted during follow-up or symptoms do not improve, surgical treatments may be considered.

PhyloSophos: a high-throughput scientific name mapping algorithm augmented with explicit consideration of taxonomic science, and its application on natural product (NP) occurrence database processing.

BACKGROUND: The standardization of biological data using unique identifiers is vital for seamless data integration, comprehensive interpretation, and reproducibility of research findings, contributing to advancements in bioinformatics and systems biology. Despite being widely accepted as a universal identifier, scientific names for biological species have inherent limitations, including lack of stability, uniqueness, and convertibility, hindering their effective use as identifiers in databases, particularly in natural product (NP) occurrence databases, posing a substantial obstacle to utilizing this valuable data for large-scale research applications. RESULT: To address these challenges and facilitate high-throughput analysis of biological data involving scientific names, we developed PhyloSophos, a Python package that considers the properties of scientific names and taxonomic systems to accurately map name inputs to entries within a chosen reference database. We illustrate the importance of assessing multiple taxonomic databases and considering taxonomic syntax-based pre-processing using NP occurrence databases as an example, with the ultimate goal of integrating heterogeneous information into a single, unified dataset. CONCLUSIONS: We anticipate PhyloSophos to significantly aid in the systematic processing of poorly digitized and curated biological data, such as biodiversity information and ethnopharmacological resources, enabling full-scale bioinformatics analysis using these valuable data resources.

Hidden dynamic signatures drive substrate selectivity in the disordered phosphoproteome.

Phosphorylation sites are hyperabundant in the eukaryotic disordered proteome, suggesting that conformational fluctuations play a major role in determining to what extent a kinase interacts with a particular substrate. In biophysical terms, substrate selectivity may be determined not just by the structural-chemical complementarity between the kinase and its protein substrates but also by the free energy difference between the conformational ensembles that are, or are not, recognized by the kinase. To test this hypothesis, we developed a statistical-thermodynamics-based informatics framework, which allows us to probe for the contribution of equilibrium fluctuations to phosphorylation, as evaluated by the ability to predict Ser/Thr/Tyr phosphorylation sites in the disordered proteome. Essential to this framework is a decomposition of substrate sequence information into two types: vertical information encoding conserved kinase specificity motifs and horizontal information encoding substrate conformational equilibrium that is embedded, but often not apparent, within position-specific conservation patterns. We find not only that conformational fluctuations play a major role but also that they are the dominant contribution to substrate selectivity. In fact, the main substrate classifier distinguishing selectivity is the magnitude of change in local compaction of the disordered chain upon phosphorylation of these mostly singly phosphorylated sites. In addition to providing fundamental insights into the consequences of phosphorylation across the proteome, our approach provides a statistical-thermodynamic strategy for partitioning any sequence-based search into contributions from structural-chemical complementarity and those from changes in conformational equilibrium.

DOT1L cooperates with the c-Myc-p300 complex to epigenetically derepress CDH1 transcription factors in breast cancer progression.

DOT1L has emerged as an anticancer target for MLL-associated leukaemias; however, its functional role in solid tumours is largely unknown. Here we identify that DOT1L cooperates with c-Myc and p300 acetyltransferase to epigenetically activate epithelial-mesenchymal transition (EMT) regulators in breast cancer progression. DOT1L recognizes SNAIL, ZEB1 and ZEB2 promoters via interacting with the c-Myc-p300 complex and facilitates lysine-79 methylation and acetylation towards histone H3, leading to the dissociation of HDAC1 and DNMT1 in the regions. The upregulation of these EMT regulators by the DOT1L-c-Myc-p300 complex enhances EMT-induced breast cancer stem cell (CSC)-like properties. Furthermore, in vivo orthotopic xenograft models show that DOT1L is required for malignant transformation of breast epithelial cells and breast tumour initiation and metastasis. Clinically, DOT1L expression is associated with poorer survival and aggressiveness of breast cancers. Collectively, we suggest that cooperative effect of DOT1L and c-Myc-p300 is critical for acquisition of aggressive phenotype of breast cancer by promoting EMT/CSC.

Robust fast direct integral equation solver for quasi-periodic scattering problems with a large number of layers.

We present a new boundary integral formulation for time-harmonic wave diffraction from two-dimensional structures with many layers of arbitrary periodic shape, such as multilayer dielectric gratings in TM polarization. Our scheme is robust at all scattering parameters, unlike the conventional quasi-periodic Green's function method which fails whenever any of the layers approaches a Wood anomaly. We achieve this by a decomposition into near- and far-field contributions. The former uses the free-space Green's function in a second-kind integral equation on one period of the material interfaces and their immediate left and right neighbors; the latter uses proxy point sources and small least-squares solves (Schur complements) to represent the remaining contribution from distant copies. By using high-order discretization on interfaces (including those with corners), the number of unknowns per layer is kept small. We achieve overall linear complexity in the number of layers, by direct solution of the resulting block tridiagonal system. For device characterization we present an efficient method to sweep over multiple incident angles, and show a 25× speedup over solving each angle independently. We solve the scattering from a 1000-layer structure with 3 × 105 unknowns to 9-digit accuracy in 2.5 minutes on a desktop workstation.

Interaction between nucleophosmin and HBV core protein increases HBV capsid assembly.

Host factors are involved in Hepatitis B virus (HBV) genome replication and capsid formation during the viral life cycle. A host factor, nucleophosmin (B23), was found to bind to HBV core protein dimers, but its functional role has not been studied. This interaction promoted HBV capsid assembly and decreased the degree of capsid dissociation when subjected to denaturant treatments in vitro. In addition, inhibition of B23 reduced intracellular capsid formation resulting in a decrease of HBV production in HepG2.2.15 cells. These results provide important evidence that B23 acts on core capsid assembly via its interaction with HBV core dimers.

Structure-based design and biochemical evaluation of sulfanilamide derivatives as hepatitis B virus capsid assembly inhibitors.

Virus capsid structure is essential in virion maturation and durability, so disrupting capsid assembly could be an effective way to reduce virion count and cure viral diseases. However, currently there is no known antiviral which affects capsid inhibition, and only a small number of assembly inhibitors were experimentally successful. In this present study, we aimed to find hepatitis B virus (HBV) capsid assembly inhibitor which binds to the HBV core protein and changes protein conformation. Several candidate molecules were found to bind to certain structure in core protein with high specificity. Furthermore, these molecules significantly changed the protein conformation and reduced assembly affinity of core protein, leading to decrease of the number of assembled capsid or virion, both in vitro and in vivo. In addition, prediction also suggests that improvements in inhibition efficiency could be possible by changing functional groups and ring structures.

Myoplasmic [ca], crossbridge phosphorylation and latch in rabbit bladder smooth muscle.

TONIC SMOOTH MUSCLE EXHIBIT THE LATCH PHENOMENON: high force at low myosin regulatory light chains (MRLC) phosphorylation, shortening velocity (Vo), and energy consumption. However, the kinetics of MRLC phosphorylation and cellular activation in phasic smooth muscle are unknown. The present study was to determine whether Ca(2+)-stimulated MRLC phosphorylation could suffice to explain the agonist- or high K(+)-induced contraction in a fast, phasic smooth muscle. We measured myoplasmic [Ca(2+)], MRLC phosphorylation, half-time after step-shortening (a measure of Vo) and contractile stress in rabbit urinary bladder strips. High K(+)-induced contractions were phasic at both 22℃ and 37℃: myoplasmic [Ca(2+)], MRLC phosphorylation, 1/half-time, and contractile stress increased transiently and then all decreased to intermediate values. Carbachol (CCh)-induced contractions exhibited latch at 37℃: stress was maintained at high levels despite decreasing myoplasmic [Ca(2+)], MRLC phosphorylation, and 1/half-time. At 22℃ CCh induced sustained elevations in all parameters. 1/half-time depended on both myoplasmic [Ca(2+)] and MRLC phosphorylation. The steady-state dependence of stress on MRLC phosphorylation was very steep at 37℃ in the CCh- or K(+)-depolarized tissue and reduced temperature flattend the dependence of stress on MRLC phosphorylation compared to 37℃. These data suggest that phasic smooth muscle also exhibits latch behavior and latch is less prominent at lower temperature.

Rigorous approach on diffracted magneto-optical effects from polar and longitudinal gyrotropic gratings.

The rigorous coupled-wave analysis with Airy-like internal-reflection series and Fourier-factorization for the calculation of the diffracted magneto-optical (MO) effects from polar and longitudinally magnetized gyrotropic gratings are fully described. For both gratings the numerical and experimental results are in good agreement, and the enhancement of Kerr rotation in higher orders compared to that of the 0th order diffraction is calculated as a function of grating depth. At last, this numerical method can be applied to many other applications such as extraordinary optical transmission from metallic gratings either through surface plasmon or cavity mode, and MO hysteresis loops.