The molecular basis of Human FN3K mediated phosphorylation of glycated substrates.

Glycation, a non-enzymatic post-translational modification occurring on proteins, can be actively reversed via site-specific phosphorylation of the fructose-lysine moiety by FN3K kinase, to impact the cellular function of the target protein. A regulatory axis between FN3K and glycated protein targets has been associated with conditions like diabetes and cancer. However, the molecular basis of this relationship has not been explored so far.

The molecular basis of Human FN3K mediated phosphorylation of glycated substrate.

Glycation, a non-enzymatic post-translational modification occurring on proteins, can be actively reversed via site-specific phosphorylation of the fructose-lysine moiety by FN3K kinase, to impact the cellular function of target protein. A regulatory axis between FN3K and glycated protein targets has been associated with conditions like diabetes and cancer. However the molecular basis of this relationship has not been explored so far.

Mothers' use of touch across infants' development and its implications for word learning: Evidence from Korean dyadic interactions.

Caregivers' touches that occur alongside words and utterances could aid in the detection of word/utterance boundaries and the mapping of word forms to word meanings. We examined changes in caregivers' use of touches with their speech directed to infants using a multimodal cross-sectional corpus of 35 Korean mother-child dyads across three age groups of infants (8, 14, and 27 months). We tested the hypothesis that caregivers' frequency and use of touches with speech change with infants' development.

Visualizing murine breast and melanoma tumor microenvironment using intravital multiphoton microscopy.

Intravital multiphoton imaging of the tumor milieu allows for the dissection of intricate and dynamic biological processes . Herein, we present a step-by-step protocol for setting up an experimental cancer imaging model that has been optimized for solid tumors such as breast cancer and melanoma implanted in the flanks of mice. This protocol can be utilized for dissecting tumor-immune cell dynamics or other tumor-specific biological questions.

Unified deep learning model for El Niño/Southern Oscillation forecasts by incorporating seasonality in climate data.

Although deep learning has achieved a milestone in forecasting the El Niño-Southern Oscillation (ENSO), the current models are insufficient to simulate diverse characteristics of the ENSO, which depends on the calendar season. Consequently, a model was generated for specific seasons which indicates these models did not consider physical constraints between different target seasons and forecast lead times, thereby leading to arbitrary fluctuations in the predicted time series. To overcome this problem and account for ENSO seasonality, we developed an all-season convolutional neural network (A_CNN) model.

Drosophila telomere capping protein HOAP interacts with DSB sensor proteins Mre11 and Nbs.

In eukaryotes, specific DNA-protein structures called telomeres exist at linear chromosome ends. Telomere stability is maintained by a specific capping protein complex. This capping complex is essential for the inhibition of the DNA damage response (DDR) at telomeres and contributes to genome integrity.

Introducing the Ko Corpus of Korean Mother-Child Interaction.

We describe a corpus of speech taking place between 30 Korean mother-child pairs, divided in three groups of Prelexical ( = 0;08), Early-Lexical ( = 1;02), and Advanced-Lexical ( = 2;03). In addition to the child-directed speech (CDS), this corpus includes two different formalities of adult-directed speech (ADS), i.e.

The dynamic nature of the human origin recognition complex revealed through five cryoEM structures.

Genome replication is initiated from specific origin sites established by dynamic events. The Origin Recognition Complex (ORC) is necessary for orchestrating the initiation process by binding to origin DNA, recruiting CDC6, and assembling the MCM replicative helicase on DNA. Here we report five cryoEM structures of the human ORC (HsORC) that illustrate the native flexibility of the complex.

Tumor-Targeting Glycol Chitosan Nanoparticles for Image-Guided Surgery of Rabbit Orthotopic VX2 Lung Cancer.

Theranostic nanoparticles can deliver therapeutic agents as well as diverse imaging agents to tumors. The enhanced permeation and retention (EPR) effect is regarded as a crucial mechanism for the tumor-targeted delivery of nanoparticles. Although a large number of studies of the EPR effect of theranostic nanoparticles have been performed, the effect of the change in the body size of the host on the EPR effect is not fully understood.

Prognostic stratification of patients with nasopharyngeal carcinoma based on tumor immune microenvironment.

Background: Little is known about immune-related prognostic factors in patients with nasopharyngeal carcinoma (NPC).

Methods: We retrospectively reviewed 66 patients with NPC. Epstein-Barr virus (EBV) status, programmed cell death-ligand 1 (PD-L1) expression, and tumor-infiltrating lymphocyte (TIL) densities were analyzed, and a prognostic evaluation of these immune-related parameters was performed.

Treatment outcomes of locally advanced squamous cell carcinoma of the maxillary sinus treated with chemoradioselection using superselective intra-arterial cisplatin and concomitant radiation: Implications for prognostic factors.

Background: This study clarified the clinical results of locally advanced squamous cell carcinoma of the maxillary sinus (SCC-MS) that was treated with chemoradioselection using superselective intra-arterial cisplatin and concomitant radiation (RADPLAT). Prognostic factors were also investigated.

Methods: We retrospectively analyzed 63 locally advanced SCC-MS patients treated with initial RADPLAT followed by sequential RADPLAT (S-RADPLAT) or surgery.

Structure of the active form of human origin recognition complex and its ATPase motor module.

Binding of the Origin Recognition Complex (ORC) to origins of replication marks the first step in the initiation of replication of the genome in all eukaryotic cells. Here, we report the structure of the active form of human ORC determined by X-ray crystallography and cryo-electron microscopy. The complex is composed of an ORC1/4/5 motor module lobe in an organization reminiscent of the DNA polymerase clamp loader complexes.

Transmission electron microscopy as an orthogonal method to characterize protein aggregates.

Aggregation of protein-based therapeutics is a challenging problem in the biopharmaceutical industry. Of particular concern are implications for product efficacy and clinical safety because of potentially increased immunogenicity of the aggregates. We used transmission electron microscopy (TEM) to characterize biophysical and morphological features of antibody aggregates formed upon controlled environmental stresses.

Prereplicative complexes assembled in vitro support origin-dependent and independent DNA replication.

Eukaryotic DNA replication initiates from multiple replication origins. To ensure each origin fires just once per cell cycle, initiation is divided into two biochemically discrete steps: the Mcm2-7 helicase is first loaded into prereplicative complexes (pre-RCs) as an inactive double hexamer by the origin recognition complex (ORC), Cdt1 and Cdc6; the helicase is then activated by a set of "firing factors." Here, we show that plasmids containing pre-RCs assembled with purified proteins support complete and semi-conservative replication in extracts from budding yeast cells overexpressing firing factors.

Regulating DNA replication in eukarya.

DNA replication is tightly controlled in eukaryotic cells to ensure that an exact copy of the genetic material is inherited by both daughter cells. Oscillating waves of cyclin-dependent kinase (CDK) and anaphase-promoting complex/cyclosome (APC/C) activities provide a binary switch that permits the replication of each chromosome exactly once per cell cycle. Work from several organisms has revealed a conserved strategy whereby inactive replication complexes are assembled onto DNA during periods of low CDK and high APC activity but are competent to execute genome duplication only when these activities are reversed.

Comparison of fatty acid analysis methods for assessing biorefinery applicability of wastewater cultivated microalgae.

In this study, we compared the performances of four different gas chromatography (GC) based microalgal fatty acid analysis methods that are typically applied to biorefinery research using wastewater-adapted microalgae. Compared with the HP-5-type non-polar column, WAX-type polar columns exhibited excellent abilities to quantitatively separate C(16)-C(18) polyunsaturated fatty acids (PUFAs) from selected wastewater-adapted microalgae (Chlorella vulgaris, Ankistrodesmus gracilis and Scenedesmus quadricauda) isolates. GC-mass spectroscopy (MS) using the WAX-type polar column provided the strongest detection sensitivity among the tested methods by lowest detection limit, and GC-flame ionized detector (FID) with the same polar column exhibited nearly consistent results to GC-MS analysis.

Depletion of p31comet protein promotes sensitivity to antimitotic drugs.

Antimitotic spindle poisons are among the most important chemotherapeutic agents available. However, precocious mitotic exit by mitotic slippage limits the cytotoxicity of spindle poisons. The MAD2-binding protein p31(comet) is implicated in silencing the spindle assembly checkpoint after all kinetochores are attached to spindles.

Localized surface plasmon resonances of anisotropic semiconductor nanocrystals.

We demonstrate that anisotropic semiconductor nanocrystals display localized surface plasmon resonances that are dependent on the nanocrystal shape and cover a broad spectral region in the near-IR wavelengths. In-plane and out-of-plane dipolar resonances were observed for colloidal dispersions of Cu(2-x)S nanodisks, and the wavelengths of these resonances are in good agreement with calculations carried out in the electrostatic limit. The wavelength, line shape, and relative intensities of these plasmon bands can be tuned during the synthetic process by controlling the geometric aspect ratio of the disk or using a postsynthetic thermal-processing step to increase the free carrier densities.

Polyelectrolyte-templated synthesis of bimetallic nanoparticles.

Bimetallic nanoparticles (NPs) are known to exhibit enhanced optical and catalytic properties that can be optimized by tailoring NP composition, size, and morphology. Galvanic deposition of a second metal onto a primary metal NP template is a versatile method for fabricating bimetallic NPs using a scalable, solution-based synthesis. We demonstrate that the galvanic displacement reaction pathway can be controlled through appropriate surface modification of the NP template.

Determinants of mitotic catastrophe on abrogation of the G2 DNA damage checkpoint by UCN-01.

Genotoxic stress such as ionizing radiation halts entry into mitosis by activation of the G(2) DNA damage checkpoint. The CHK1 inhibitor 7-hydroxystaurosporine (UCN-01) can bypass the checkpoint and induce unscheduled mitosis in irradiated cells. Precisely, how cells behave following checkpoint abrogation remains to be defined.

CDK1 inhibitors antagonize the immediate apoptosis triggered by spindle disruption but promote apoptosis following the subsequent rereplication and abnormal mitosis.

Spindle-disrupting agents and CDK inhibitors are important cancer therapeutic agents. Spindle toxins activate the spindle-assembly checkpoint and lead to sustained activation of CDK1. Different published results indicate that CDK1 activity is either important or dispensable for the cytotoxicity associated with spindle disruption.

The kinetics of p53 activation versus cyclin E accumulation underlies the relationship between the spindle-assembly checkpoint and the postmitotic checkpoint.

Although cells can exit mitotic block aberrantly by mitotic slippage, they are prevented from becoming tetraploids by a p53-dependent postmitotic checkpoint. Intriguingly, disruption of the spindle-assembly checkpoint also compromises the postmitotic checkpoint. The precise mechanism of the interplay between these two pivotal checkpoints is not known.

Integral value of JT interval in magnetocardiography is sensitive to coronary stenosis and improves soon after coronary revascularization.

Background: Magnetocardiography (MCG) is sensitive to minute cardiac electric abnormalities, but its clinical utility in diagnosing ischemic heart disease (IHD) has not been established. The present study examined the usefulness of an integral MCG value of ventricular repolarization in patients with IHD.

Methods And Results: MCG was performed at rest in 14 patients with coronary stenosis >75% confirmed by coronary angiography (IHD group) using a 64-channel system, and then the sum of the 64-channel integral values of the QRS or JT intervals (QRSi and JTi, respectively) was calculated.