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Abstract Hyperhomocysteinemia is a common metabolic disorder that imposes major adverse health consequences. Reducing homocysteine levels, however, is not always effective against hyperhomocysteinemia‐associated pathologies. Herein, we report the potential roles of methionyl‐tRNA synthetase (MARS)‐generated homocysteine signals in neural tube defects (NTDs) and congenital heart defects (CHDs). Increased copy numbers of MARS and/or MARS2 were detected in NTD and CHD patients. MARSs sense homocysteine and transmit its signal by inducing protein lysine (N)‐homocysteinylation. Here, we identified hundreds of novel N‐homocysteinylated proteins. N‐homocysteinylation of superoxide dismutases (SOD1/2) provided new mechanistic insights for homocysteine‐induced oxidative stress, apoptosis and Wnt signalling deregulation. Elevated MARS expression in developing and proliferating cells sensitizes them to the effects of homocysteine. Targeting MARSs using the homocysteine analogue acetyl homocysteine thioether (AHT) reversed MARS efficacy. AHT lowered NTD and CHD onsets in retinoic acid‐induced and hyperhomocysteinemia‐induced animal models without affecting homocysteine levels. We provide genetic and biochemical evidence to show that MARSs are previously overlooked genetic determinants and key pathological factors of hyperhomocysteinemia, and suggest that MARS inhibition represents an important medicinal approach for controlling hyperhomocysteinemia‐associated diseases.

The switch between quiescence and proliferation is central for neurogenesis and its alteration is linked to neurodevelopmental disorders such as microcephaly. However, intrinsic mechanisms that reactivate Drosophila larval neural stem cells (NSCs) to exit from quiescence are not well established. Here we show that the spindle matrix complex containing Chromator (Chro) functions as a key intrinsic regulator of NSC reactivation downstream of extrinsic insulin/insulin-like growth factor signalling. Chro also prevents NSCs from re-entering quiescence at later stages. NSC-specific in vivo profiling has identified many downstream targets of Chro, including a temporal transcription factor Grainy head (Grh) and a neural stem cell quiescence-inducing factor Prospero (Pros). We show that spindle matrix proteins promote the expression of Grh and repress that of Pros in NSCs to govern their reactivation. Our data demonstrate that nuclear Chro critically regulates gene expression in NSCs at the transition from quiescence to proliferation. [ABSTRACT FROM AUTHOR]

This paper is concerned with the existence results for mild solutions of semilinear fractional evolution equations on an unbounded interval. The methods used in the paper are based on the concept of measure of noncompactness in Fréchet space and classical Tichonov fixed-point theorem. An example is also given to illustrate our main results. [ABSTRACT FROM AUTHOR]

C-kit positive (c-kit+) cells are usual tissue-specific stem cells. However, in postnatal testis, undifferentiated spermatogonial stem cells (SSCs) are c-kit negative (c-kit+) and activation of c-kit represents the start of SSC differentiation, leaving an intriguing question whether other c-kit- cells exist and participate in the postnatal development of testis. To this end, a feasible system for testicular reconstitution, in which a specific type of cells can be manipulated, is needed. Here, we first establish de novo morphogenesis of testis by subcutaneous injection of testicular cells from neonatal testes into the backs of nude mice. We observe testicular tissue formation and spermatogenesis from all injected sites. Importantly, functional spermatids can be isolated from these testicular tissues. Using this system, we systemically analyze the roles of c-kit- cells in testicular reconstitution and identify a small population of cells (c-kit-:CD140a+:F4/80+), which express typical markers of macrophages, are critical for de novo morphogenesis of testis. Interestingly, we demonstrate that these cells are gradually replaced by peripheral blood cells of recipient mice during the morphogenesis of testis. Thus, we develop a system, which may mimic the complete developmental process of postnatal testis, for investigating the testicular development and spermatogenesis. [ABSTRACT FROM AUTHOR]

Decitabine (DAC) is used for treatment of patients with myelodysplastic syndromes and acute myeloid leukemia (AML). Following cellular uptake, DAC is activated to DAC-triphosphate (TP) and incorporated into DNA. Once incorporated into the DNA, DAC-TP binds and inactivates DNA methyltransferases (DNMTs), thereby leading to hypomethylation and re-expression of epigenetically silenced tumor suppressor genes and ultimately antileukemia activity. However, direct evidence of in vivo DAC-TP occurrence in DAC-treated patients has been difficult to demonstrate due to a lack of suitable validated analytical methodology. Thus, we developed and validated a nonradioactive sensitive and specific LC-MS/MS assay for quantification of DAC-TP. The assay is linear from 50 to 1,000 nM and from 1 to 10 µM and has a lower limit of quantitation of 50 nM and a coefficient of variation for both withinand between-day precision <20%. Following DAC treatment, we detected DAC-TP in parental and DAC-resistant AML cells (in vitro) and bone marrow (BM) and spleen of normal and leukemic mice (in vivo). Downregulation of DNMTs and correlation of DAC-TP concentration with proteins involved in mechanisms of DAC resistance were also demonstrated. The clinical applicability of this method was proven by measuring DAC-TP level in BM and blood mononuclear cells from DAC-treated AML patients. Higher levels are seemingly associated with clinical response. Monitoring the DAC-TP intracellular level may serve as a novel pharmacological endpoint for designing more effective DACbased regimens. [ABSTRACT FROM AUTHOR]

sensitive amperometric sensor has been constructed for the determination of hydrogen peroxide (HP). It is based on a glassy carbon electrode modified with a composite made from thionin, EDTA, multiwalled carbon nanotubes, and chitosan. Thionin was covalently immobilized on the surface of the electrode. The sensor exhibits a powerful electrocatalytic activity for the reduction of HP. The amperometric signal is proportional to the concentration of HP in the range from 0.2 μM to 85.0 μM, with a detection limit of 0.065 μM. The sensor displays excellent selectivity, good reproducibility and long-term stability. [ABSTRACT FROM AUTHOR]

In order to quantify and predict the water resistance of membrane, a multi-scales association model was built up based on the Fick’s second law. Two water resistance indexes, balance time and seepage velocity, were put forward and calculated by the model for measuring the property of membrane water resistance. The association model linked macro-scale factors and micro-scale parameters together. The influence of macro-scale factors, environmental temperature and membrane thickness, and micro-scale parameters, water molecules diffusivity, membrane saturated water absorption rate and water escape concentration, were discussed. The properties of water resistances for two groups including 10 waterborne acrylate membranes samples were measured for validating the indexes calculated by the model. The well consistency between the results of calculations and experiments proved that the method of multi-scales association modeling for quantifying and predicting the membrane water resistance was feasible. [ABSTRACT FROM AUTHOR]

Soluble guanylate cyclase (sGC), as a nitric oxide (NO) sensor, is a critical heme-containing enzyme in NO-signaling pathway of eukaryotes. Human sGC is a heterodimeric hemoprotein, composed of a α-subunit (690 AA) and a heme-binding β-subunit (619 AA). Upon NO binding, sGC catalyzes the conversion of guanosine 5′-triphosphate (GTP) to 3′,5′-cyclic guanosine monophosphate (cGMP). cGMP is a second messenger and initiates the nitric oxide signaling, triggering vasodilatation, smooth muscle relaxation, platelet aggregation, and neuronal transmission etc. The breakthrough of the bottle neck problem for sGC-mediated NO singling was made in this study. The recombinant human sGC β1 subunit (HsGCβ619) and its truncated N-terminal fragments (HsGCβ195 and HsGCβ384) were efficiently expressed in Escherichia coli and purified successfully in quantities. The three proteins in different forms (ferric, ferrous, NO-bound, CO-bound) were characterized by UV–vis and EPR spectroscopy. The homology structure model of the human sGC heme domain was constructed, and the mechanism for NO binding to sGC was proposed. The EPR spectra showed a characteristic of five-coordinated heme-nitrosyl species with triplet hyperfine splitting of NO. The interaction between NO and sGC was investigated and the schematic mechanism was proposed. This study provides new insights into the structure and NO-binding of human sGC. Furthermore, the efficient expression system of E. coli will be beneficial to the further studies on structure and activation mechanism of human sGC. [ABSTRACT FROM AUTHOR]

Integrin binding to ligand plays essential roles in the differentiation and function of mammalian cells. β2 integrins in leukocytes are needed for migration to sites of inflammation and in lymph nodes as well as for cellular events such as phagocytosis and the formation of the conjugates between T cells and antigen-presenting cells. In T cells, integrin adhesion is activated primarily by the antigen-receptor (TCR complex) and chemokines in a process known as ‘inside-out’ signalling. Great progress has been made in identifying mutations that are responsible for leukocyte adhesion deficiency (LAD) syndromes, a disorder that presents with an impaired ability to clear pathogens and recurrent life-threatening infections. LAD mutations have been identified with defects in integrins, fucosylation and in the new intracellular mediator kindlin-3. Here, we review the key players in the ‘inside-out’ and ‘outside-in’ signalling pathways that will serve as new potential targets in the design of novel therapeutics to treat various immunodeficiencies. [ABSTRACT FROM AUTHOR]

An ultrasensitive platform is presented for the determination of hydrazine by combining the high specific surface area and higher electrical conductivity of poly(sodium styrenesulfonate) (PSS) graphene nanocomposite film with amperometric detection. The PSS-graphene were synthesized by the Hummers method and used to modify a glassy carbon electrode. The material was characterized by scanning electron microscopy and is found to be suitable for sensing hydrazine. The overpotential of hydrazine on the modified electrode is 0.31 V which is lower than in many electrochemical sensors. The calibration curve for hydrazine is linear in the range from 3.0 to 300 µmol L−1, and the detection limit is as low as 1 µmol L−1. This is the first report in which such a high sensitivity and low limit of detection has been achieved. It is concluded that PSS graphene represents an efficient electron mediator for sensing hydrazine. [ABSTRACT FROM AUTHOR]

Pruning that selectively eliminates neuronal processes is crucial for the refinement of neural circuits during development. In Drosophila, the class IV dendritic arborization neuron (ddaC) undergoes pruning to remove its larval dendrites during metamorphosis. We identified Sox14 as a transcription factor that was necessary and sufficient to mediate dendrite severing during pruning in response to ecdysone signaling. We found that Sox14 mediated dendrite pruning by directly regulating the expression of the target gene mical. mical encodes a large cytosolic protein with multiple domains that are known to associate with cytoskeletal components. mical mutants had marked severing defects during dendrite pruning that were similar to those of sox14 mutants. Overexpression of Mical could significantly rescue pruning defects in sox14 mutants, suggesting that Mical is a major downstream target of Sox14 during pruning. Thus, our findings indicate that a previously unknown pathway composed of Sox14 and its cytoskeletal target Mical governs dendrite severing. [ABSTRACT FROM AUTHOR]

Multi-objective simultaneous prediction of waterborne coating properties was studied by the neural network combined with programming. The conditions of network with one input layer, three hidden layers and one output layer were confirmed. The monomers mass of BA, MMA, St and pigments mass of TiO2 and CaCO3 were used as input data. Four properties, which were hardness, adhesion, impact resistance and reflectivity, were used as network output. After discussing the hidden layer neurons, learn rate and the number of hidden layers, the best net parameters were confirmed. The results of experiment show that multi-hidden layers was advantageous to improve the accuracy of multi-objective simultaneous prediction. 36 kinds of coating formulations were used as the training subset and 9 acrylate waterborne coatings were used as testing subset in order to predict the performance. The forecast error of hardness was 8.02% and reflectivity was 0.16%. Both forecast accuracy of adhesion and impact resistance were 100%. [ABSTRACT FROM AUTHOR]

Poly(vinyl alcohol) (PVA)/CuS composite nanofibres were successfully prepared by electrospinning technique and gas-solid reaction. Scanning electron microscopic (SEM) images showed that the average diameter of PVA/CuS fibres was about 150-200 nm. Transmission electron microscopy (TEM) proved that a majority of CuS nanoparticles with an average diameter of about 15-25 nm are incorporated in the PVA fibres. Xray diffraction (XRD) analyses and electron diffraction pattern also revealed the forming of CuS crystal structure in the PVA fibres. [ABSTRACT FROM AUTHOR]

Abstract  The formulation of food-grade microemulsions with glycerol monolaurate (GML) for antimicrobial applications has been studied. The compositions included water, GML, short-chain alcohols (such as ethanol), polyols (propylene glycol and glycerol), salts (organic, such as sodium benzoate, sodium lactate and sodium propionate, and inorganic, such as NaCl) and several nonionic surfactants [such as ethoxylated sorbitan esters, sucrose esters (SEs)]. The phase behavior of these systems is discussed with respect to the influence of composition on the degree of oil solubilization in the aqueous phase. The oil solubilization was dramatically improved in the presence of the short-chain alcohols and polyols, organic salts contributed to the improvement of oil solubilization as hydrotropes. Tween 20 being the most hydrophilic surfactant in Tweens solubilized the maximum oil, but in the presence of SEs it is hard to form oil-in-water microemulsions. Viscosity measurements along selected dilution lines indicate that at a certain composition the system inverts from a water-in-oil to an oil-in-water microemulsion. [ABSTRACT FROM AUTHOR]

Self-renewal and differentiation are cardinal features of stem cells. Asymmetric cell division provides one fundamental mechanism by which stem cell self-renewal and differentiation are balanced. A failure of this balance could lead to diseases such as cancer. During asymmetric division of stem cells, factors controlling their self-renewal and differentiation are unequally segregated between daughter cells. Numb is one such factor that is segregated to the differentiating daughter cell during the stem-cell-like neuroblast divisions in Drosophila melanogaster, where it inhibits self-renewal. The localization and function of Numb is cell-cycle-dependent. Here we show that Polo (ref. 13), a key cell cycle regulator, the mammalian counterparts of which have been implicated as oncogenes as well as tumour suppressors, acts as a tumour suppressor in the larval brain. Supernumerary neuroblasts are produced at the expense of neurons in polo mutants. Polo directly phosphorylates Partner of Numb (Pon, ref. 16), an adaptor protein for Numb, and this phosphorylation event is important for Pon to localize Numb. In polo mutants, the asymmetric localization of Pon, Numb and atypical protein kinase C are disrupted, whereas other polarity markers are largely unaffected. Overexpression of Numb suppresses neuroblast overproliferation caused by polo mutations, suggesting that Numb has a major role in mediating this effect of Polo. Our results reveal a biochemical link between the cell cycle and the asymmetric protein localization machinery, and indicate that Polo can inhibit progenitor self-renewal by regulating the localization and function of Numb. [ABSTRACT FROM AUTHOR]

Abstract  Polytetrafluoroethylene (PTFE)/polyacrylate core-shell nanoparticles were produced via the emulsifier-free seeded emulsion polymerization of acrylate monomers with PTFE latex as seed. The monomer conversions under different synthesis parameters were monitored by a gravimetric method. The polymerization conditions for preparing PTFE/polyacrylate core-shell nanoparticles were surveyed and optimized. The chemical component of the PTFE/polyacrylate particles was confirmed by comparing the Fourier-transform infrared spectra of PTFE and PTFE/polyacrylate particles. The core-shell structure of the resulting PTFE/polyacrylate nanocomposite particles was investigated by transmission electron microscopy. The water contact angles of the films prepared from PTFE/polyacrylate nanocomposite particles showed that the films were hydrophilic, which confirmed that polyacrylate covered the surface of the PTFE particles. This kind of PTFE/polyacrylate core-shell nanoparticles might advance the compatibility of PTFE with other materials due to the covering of the polyacrylate shell on the surface of PTFE, which would make them promising in various fields. [ABSTRACT FROM AUTHOR]

Asymmetric division of Drosophila neuroblasts (NBs) and the Caenorhabditis elegans zygote uses polarity cues provided by the Par proteins, as well as heterotrimeric G-protein-signalling that is activated by a receptor-independent mechanism mediated by GoLoco/GPR motif proteins. Another key component of this non-canonical G-protein activation mechanism is a non-receptor guanine nucleotide-exchange factor (GEF) for Gα, RIC-8, which has recently been characterized in C. elegans and in mammals. We show here that the Drosophila Ric-8 homologue is required for asymmetric division of both NBs and pI cells. Ric-8 is necessary for membrane targeting of Gαi, Pins and Gβ13F, presumably by regulating multiple Gα subunit(s). Ric-8 forms an in vivo complex with Gαi and interacts preferentially with GDP–Gαi, which is consistent with Ric-8 acting as a GEF for Gαi. Comparisons of the phenotypes of Gαi, Ric-8, Gβ13F single and Ric-8;Gβ13F double loss-of-function mutants indicate that, in NBs, Ric-8 positively regulates Gαi activity. In addition, Gβγ acts to restrict Gαi (and GoLoco proteins) to the apical cortex, where Gαi (and Pins) can mediate asymmetric spindle geometry. [ABSTRACT FROM AUTHOR]

One method of preparation of polytetrafluoroethylene(PFTE)-modified polyacrylate emulsion has been studied. Through pre-emulsion technology, PTFE powder could be dispersed by high speed shearing with high-speed dispersor. PFTE-modified polyacrylate has been prepared by in situ copolymerization of n-butyl acrylate, n-methyl methacrylate, n-styrene, and α-methacrylic acid in the presence of seed particles of dispersed PTFE by semi-starved addition method. The properties of the emulsion under various polymerization conditions were investigated. The morphology of the latex particles with about 180 nm were observed by scanning electron microscopy (SEM). It was shown that the particles with linear PTFE/core–polyacrylate/shell could eventually be dispersed homogeneously. TG showed that the heat-stability was improved obviously. [ABSTRACT FROM AUTHOR]