The novel GATA1-interacting protein HES6 is an essential transcriptional cofactor for human erythropoiesis.

Normal erythropoiesis requires the precise regulation of gene expression patterns, and transcription cofactors play a vital role in this process. Deregulation of cofactors has emerged as a key mechanism contributing to erythroid disorders. Through gene expression profiling, we found HES6 as an abundant cofactor expressed at gene level during human erythropoiesis.

Comprehensive proteomic analysis reveals dynamic phospho-profiling in human early erythropoiesis.

Normal early erythropoiesis depends on the precise regulation of protein expression and phosphorylation modification. Dysregulation of protein levels or modification contributes to erythroid disorders. To date, the dynamics of protein phosphorylation profiling across human erythroid development is not fully understood.

Small-Angle X-ray Scattering Signatures of Conformational Heterogeneity and Homogeneity of Disordered Protein Ensembles.

An accurate account of disordered protein conformations is of central importance to deciphering the physicochemical basis of biological functions of intrinsically disordered proteins and the folding-unfolding energetics of globular proteins. Physically, disordered ensembles of nonhomopolymeric polypeptides are expected to be heterogeneous, i.e.

The regulation of NONO by USP11 via deubiquitination is linked to the proliferation of melanoma cells.

Ubiquitin-specific protease 11 (USP11) has been implicated in the regulation of DNA repair, apoptosis, signal transduction and cell cycle. It belongs to a USP subfamily of deubiquitinases. Although previous research has shown that USP11 overexpression is frequently found in melanoma and is correlated with a poor prognosis, the potential molecular mechanism of USP11 in melanoma remains indefinitive.

Antitumor Drug Combretastatin-A4 Phosphate Aggravates the Symptoms of Dextran Sulfate Sodium-Induced Ulcerative Colitis in Mice.

Ulcerative colitis (UC) is an idiopathic inflammatory bowel disease (IBD) that causes long-lasting inflammation and ulcers in the innermost lining of the colon and rectum. Previous studies demonstrated that resveratrol suppresses colitis and colon cancer associated with colitis by improving glucose metabolism, but resveratrol use is limited by its low oral bioavailability. Combretastatin-A4 phosphate (CA4P) is a vascular-disrupting agent with antitumor activity.

Responses of Periphyton Microbial Growth, Activity, and Pollutant Removal Efficiency to Cu Exposure.

Periphyton is an effective matrix for the removal of pollutants in wastewater and has been considered a promising method of bioremediation. However, it still needs to be verified whether periphyton can maintain microbial activity and pollutant removal efficiency when dealing with the influence with complex components, and the underlying mechanisms of periphyton need to be revealed further. Herein, this study investigated the microbial growth, activity and functional responses of periphyton after removal of Cu from wastewater.

Targeting c-met receptor tyrosine kinase by the DNA aptamer SL1 as a potential novel therapeutic option for myeloma.

Hepatocyte growth factor (HGF)/c-met pathway activation has been implicated in the pathogenesis of multiple myeloma (MM), and blocking this pathway has been considered a rational therapeutic strategy for treating MM. Aptamers are single-stranded nucleic acid molecules that fold into complex 3D structures and bind to a variety of targets. Recently, it was reported that DNA aptamer SL1 exhibited high specificity and affinity for c-met and inhibited HGF/c-met signaling in SNU-5 cells.

Interfacial Synthesis of Conjugated Two-Dimensional N-Graphdiyne.

We explored the interfacial synthesis of 2D N-graphdiyne films at the gas/liquid and liquid/liquid interfaces. Triazine- or pyrazine-based monomers containing ethynyl group were polymerized through the Glaser coupling reactions at interfaces. Several layered, highly ordered and conjugated 2D N-graphdiyne were obtained.

Conformational Heterogeneity and FRET Data Interpretation for Dimensions of Unfolded Proteins.

A mathematico-physically valid formulation is required to infer properties of disordered protein conformations from single-molecule Förster resonance energy transfer (smFRET). Conformational dimensions inferred by conventional approaches that presume a homogeneous conformational ensemble can be unphysical. When all possible-heterogeneous as well as homogeneous-conformational distributions are taken into account without prejudgment, a single value of average transfer efficiency 〈E〉 between dyes at two chain ends is generally consistent with highly diverse, multiple values of the average radius of gyration 〈R〉.

An allosteric conduit facilitates dynamic multisite substrate recognition by the SCF ubiquitin ligase.

The ubiquitin ligase SCF mediates phosphorylation-dependent elimination of numerous substrates by binding one or more Cdc4 phosphodegrons (CPDs). Methyl-based NMR analysis of the Cdc4 WD40 domain demonstrates that Cyclin E, Sic1 and Ash1 degrons have variable effects on the primary Cdc4 binding pocket. Unexpectedly, a Sic1-derived multi-CPD substrate (pSic1) perturbs methyls around a previously documented allosteric binding site for the chemical inhibitor SCF-I2.

Unexpected role for p19INK4d in posttranscriptional regulation of GATA1 and modulation of human terminal erythropoiesis.

Terminal erythroid differentiation is tightly coordinated with cell-cycle exit, which is regulated by cyclins, cyclin-dependent kinases, and cyclin-dependent kinase inhibitors (CDKI), yet their roles in erythropoiesis remain to be fully defined. We show here that p19, a member of CDKI family, is abundantly expressed in erythroblasts and that p19 knockdown delayed erythroid differentiation, inhibited cell growth, and led to increased apoptosis and generation of abnormally nucleated late-stage erythroblasts. Unexpectedly, p19 knockdown did not affect cell cycle.

Tough and Cell-Compatible Chitosan Physical Hydrogels for Mouse Bone Mesenchymal Stem Cells in Vitro.

Most hydrogels involve synthetic polymers and organic cross-linkers that cannot simultaneously fulfill the mechanical and cell-compatibility requirements of biomedical applications. We prepared a new type of chitosan physical hydrogel with various degrees of deacetylation (DDs) via the heterogeneous deacetylation of nanoporous chitin hydrogels under mild conditions. The DD of the chitosan physical hydrogels ranged from 56 to 99%, and the hydrogels were transparent and mechanically strong because of the extra intra- and intermolecular hydrogen bonding interactions between the amino and hydroxyl groups on the nearby chitosan nanofibrils.

The linear structure of β-glucan from baker's yeast and its activation of macrophage-like RAW264.7 cells.

Yeast β-glucan has many formulations with different chemical structures, water solubility and purity. In particular, the purity of β-glucan in these formulations is variable and relatively low, contributing to different data on its biological activity. In this study, the major polysaccharide component in the crude Baker's yeast polysaccharides coded as BBG with high purity of 99% was obtained, and its chemical structure was determined to be a linear β-(1,3)-glucan.

Conformations of a Metastable SH3 Domain Characterized by smFRET and an Excluded-Volume Polymer Model.

Conformational states of the metastable drkN SH3 domain were characterized using single-molecule fluorescence techniques. Under nondenaturing conditions, two Förster resonance energy transfer (FRET) populations were observed that corresponded to a folded and an unfolded state. FRET-estimated radii of gyration and hydrodynamic radii estimated by fluorescence correlation spectroscopy of the two coexisting conformations are in agreement with previous ensemble x-ray scattering and NMR measurements.

A Dual-Function Transcription Factor, AtYY1, Is a Novel Negative Regulator of the Arabidopsis ABA Response Network.

Abscisic acid (ABA) plays crucial roles in plant growth and development, as well as in response to various environmental stresses. To date, many regulatory genes involved in the ABA response network have been identified; however, their roles have remained to be fully elucidated. In this study, we identified AtYY1, an Arabidopsis homolog of the mammalian C2H2 zinc-finger transcription factor Yin Yang 1 (YY1), as a novel negative regulator of the ABA response.

An Adequate Account of Excluded Volume Is Necessary To Infer Compactness and Asphericity of Disordered Proteins by Förster Resonance Energy Transfer.

Single-molecule Förster resonance energy transfer (smFRET) is an important tool for studying disordered proteins. It is commonly utilized to infer structural properties of conformational ensembles by matching experimental average energy transfer ⟨E⟩exp with simulated ⟨E⟩sim computed from the distribution of end-to-end distances in polymer models. Toward delineating the physical basis of such interpretative approaches, we conduct extensive sampling of coarse-grained protein chains with excluded volume to determine the distribution of end-to-end distances conditioned upon given values of radius of gyration Rg and asphericity A.

miR-150 inhibits terminal erythroid proliferation and differentiation.

MicroRNAs (miRNAs), a class of small non-coding linear RNAs, have been shown to play a crucial role in erythropoiesis. To evaluate the indispensable role of constant suppression of miR-150 during terminal erythropoiesis, we performed miR-150 gain- and loss-of-function experiments on hemin-induced K562 cells and EPO-induced human CD34+ cells. We found that forced expression of miR-150 suppresses commitment of hemoglobinization and CD235a labeling in both cell types.

Theoretical perspectives on nonnative interactions and intrinsic disorder in protein folding and binding.

The diverse biological functions of intrinsically disordered proteins (IDPs) have markedly raised our appreciation of protein conformational versatility, whereas the existence of energetically favorable yet functional detrimental nonnative interactions underscores the physical limitations of evolutionary optimization. Here we survey recent advances in using biophysical modeling to gain insight into experimentally observed nonnative behaviors and IDP properties. Simulations of IDP interactions to date focus mostly on coupled folding-binding, which follows essentially the same organizing principle as the local-nonlocal coupling mechanism in cooperative folding of monomeric globular proteins.

Extraordinary reinforcement effect of three-dimensionally nanoporous cellulose gels in poly(ε-caprolactone) bionanocomposites.

Three-dimensionally nanoporous cellulose gels (NCG) were prepared by dissolution and coagulation of cellulose from aqueous alkali hydroxide-urea solution, and used to fabricate NCG/poly(ε-caprolactone) (PCL) nanocomposites by in situ ring-opening polymerization of ε-CL monomer in the NCG. The NCG content of the NCG/PCL nanocomposite could be controlled between 7 and 38% v/v by changing water content of starting hydrogel by compression dewatering. FT-IR and solid-state (13)C NMR showed that the grafting of PCL onto cellulose are most likely occurred at the C6-OH groups and the grafting percentage of PCL is 25 wt % for the nanocomposite with 7% v/v NCG.

Polycation-π interactions are a driving force for molecular recognition by an intrinsically disordered oncoprotein family.

Molecular recognition by intrinsically disordered proteins (IDPs) commonly involves specific localized contacts and target-induced disorder to order transitions. However, some IDPs remain disordered in the bound state, a phenomenon coined "fuzziness", often characterized by IDP polyvalency, sequence-insensitivity and a dynamic ensemble of disordered bound-state conformations. Besides the above general features, specific biophysical models for fuzzy interactions are mostly lacking.

[Mycoplasma pneumoniae infection and drug resistance in children: an analysis of 1026 cases].

Objective: To investigate the Mycoplasma pneumoniae (MP) infection and drug resistance in children with respiratory tract infection and to provide a rational basis for the clinical diagnosis and treatment of MP infection.

Methods: Throat swabs were collected from 3529 children with respiratory tract infection, who visited the pediatric outpatient department or received treatment in the pediatric ward of our hospital from September 2010 to September 2011. The swabs were cultured to detect MP.

Monte Carlo simulation of self-assembly of symmetric ABC three-arm star copolymers under cylindrical confinement.

Self-assembly of symmetric ABC three-arm star copolymers confined in cylindrical nanopores is investigated by means of a lattice Monte Carlo simulation method. The dependence of morphologies on the degree of confinement and preference of pore surface is studied systematically. For the symmetric ABC three-arm star copolymers which form polygonal cylinder structures with periodic spacing L(0) in bulk, various novel structures are observed inside the nanopores.

[An epidemiologic survey on blood lead levels in preschool children living in towns of Hunan Province].

Objective: To investigate blood lead levels (BLLs) and influencing factors of BLLs among preschool children living in towns of Hunan Province.

Methods: A total of 2 044 preschool children (1,108 boys and 936 girls) from towns of 12 regions in Hunan Province were enrolled by a cluster sampling between September 2008 and June 2009. The average age of the children was 4.

Alternative reaction mechanism for the cross-linking of gelatin with glutaraldehyde.

FT-IR, in combination with residual amino group determination using a fluorescence technique, has been used to investigate the chemical functional groups involved in the cross-linking reaction between glutaraldehyde and gelatin molecules. The results suggest that, at high pH values (i.e.