Evaluation of changes in sleep breathing patterns after primary palatoplasty in cleft children

Introduction: There is a need to more clearly understand the characteristics of breathing patterns in children with cleft palate in the first year of life, as there is little data available to guide current practice. Pierre Robin patients are known to have a higher incidence, however we hypothesised sleep breathing disturbance is not confined to this sub-group of cleft patient. Methods: We conducted a prospective observational study of sleep disordered breathing patterns in a cohort of infants with oro-nasal clefts (cleft palate with or without cleft lip) to describe the spectrum of sleep breathing patterns both pre and post palate repair. Sleep breathing studies were performed pre- and post-operatively in sequential infants referred to a regional cleft lip and palate unit. Results of sleep breathing studies were analysed according to American Academy of Sleep Medicine scoring guidelines and correlated with clinical history and details of peri-operative respiratory compromise. The degree of sleep disordered breathing was characterised using desaturation indices (number of desaturations from baseline SpO2 of >=4%, per hour). Results: Thirty-nine infants were included in this study, twenty-five female and fourteen male. Twelve had isolated Cleft Palate as part of an associated syndrome. Patients were categorised into Isolated Cleft Palate, Isolated Cleft Palate in the context of Pierre Robin Sequence, and those with Cleft Lip and Palate. All groups demonstrated some degree of sleep breathing abnormality. Not unsurprisingly the eight infants with Pierre Robin Sequence had a significantly higher desaturation index before surgical intervention (p=0.043), and were more likely to require a pre-operative airway intervention (p=0.009). Palate repair in this group did not alter the relative distribution of patients in each severity category of sleep disorder breathing. Surgical repair of the secondary palate in the remaining children was associated with some improvement but by no means complete resolution of their sleep disordered breathing patterns. Conclusions: We conclude that sleep breathing disturbance is not confined to Pierre Robin patients alone and all cleft palate patients should undergo pre-operative and post-operative sleep breathing analysis

Molecular association of glucose-6- phosphate isomerase and pyruvate kinase M2 with glyceraldehyde-3-phosphate dehydrogenase in cancer cells

Background: For a long time cancer cells are known for increased uptake of glucose and its metabolization through glycolysis. Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is a key regulatory enzyme of this pathway and can produce ATP through oxidative level of phosphorylation. Previously, we reported that GAPDH purified from a variety of malignant tissues, but not from normal tissues, was strongly inactivated by a normal metabolite, methylglyoxal (MG).Molecular mechanism behind MG mediated GAPDH inhibition in cancer cells is not well understood. Methods: GAPDH was purified from Ehrlich ascites carcinoma (EAC) cells based on its enzymatic activity. GAPDH associated proteins in EAC cells and 3-methylcholanthrene (3MC) induced mouse tumor tissue were detected by mass spectrometry analysis and immunoprecipitation (IP) experiment, respectively. Interacting domains of GAPDH and its associated proteins were assessed by in silico molecular docking analysis. Mechanism of MG mediated GAPDH inactivation in cancer cells was evaluated by measuring enzyme activity, Circular dichroism (CD) spectroscopy, IP and mass spectrometry analyses. Result: Here, we report that GAPDH is associated with glucose-6-phosphate isomerase (GPI) and pyruvate kinase M2 (PKM2) in Ehrlich ascites carcinoma (EAC) cells and also in 3-methylcholanthrene (3MC) induced mouse tumor tissue. Molecular docking analyses suggest C-terminal domain preference for the interaction between GAPDH and GPI. However, both C and N termini of PKM2 might be interacting with the C terminal domain of GAPDH. Expression of both PKM2 and GPI is increased in 3MC induced tumor compared with the normal tissue. In presence of 1 mM MG,association of GAPDH with PKM2 or GPI is not perturbed, but the enzymatic activity of GAPDH is reduced to 26.8 ± 5 % in 3MC induced tumor and 57.8 ± 2.3 % in EAC cells. Treatment of MG to purified GAPDH complex leads to glycation at R399 residue of PKM2 only, and changes the secondary structure of the protein complex. Conclusion: PKM2 may regulate the enzymatic activity of GAPDH. Increased enzymatic activity of GAPDH in tumor cells may be attributed to its association with PKM2 and GPI. Association of GAPDH with PKM2 and GPI could be a signature for cancer cells. Glycation at R399 of PKM2 and changes in the secondary structure of GAPDH complex could be one of the mechanisms by which GAPDH activity is inhibited in tumor cells by MG

A Weak Neutralizing Antibody Response to Hepatitis C Virus Envelope Glycoprotein Enhances Virus Infection

We have completed a phase 1 safety and immunogenicity trial with hepatitis C virus (HCV) envelope glycoproteins, E1 and E2, with MF59 adjuvant as a candidate vaccine. Neutralizing activity to HCV genotype 1a was detected in approximately 25% of the vaccinee sera. In this study, we evaluated vaccinee sera from poor responders as a potential source of antibody dependent enhancement (ADE) of HCV infection. Sera with poor neutralizing activity enhanced cell culture grown HCV genotype 1a or 2a, and surrogate VSV/HCV pseudotype infection titer, in a dilution dependent manner. Surrogate pseudotypes generated from individual HCV glycoproteins suggested that antibody to the E2 glycoprotein; but not the E1 glycoprotein, was the principle target for enhancing infection. Antibody specific to FcRII expressed on the hepatic cell surface or to the Fc portion of Ig blocked enhancement of HCV infection by vaccinee sera. Together, the results from in vitro studies suggested that enhancement of viral infectivity may occur in the absence of a strong antibody response to HCV envelope glycoproteins

The eukaryotic initiation factor 2-associated 67-kDa polypeptide (p\u3csup\u3e67\u3c/sup\u3e) plays a critical role in regulation of protein synthesis initiation in animal cells

The eukaryotic initiation factor 2 (eIF-2)- associated 67-kDa polypeptide (p67) isolated from reticulocyte lysate protects the eIF-2 α subunit from eIF-2 kinase-catalyzed phosphorylation and promotes protein synthesis in the presence of active eIF-2 kinases. We have now studied the roles of p67 and eIF-2 kinases in regulation of protein synthesis using several animal cell lysates and an animal cell line (KRC-7) in culture under various growth conditions. The results are as follows. (i) Both p67 and eIF-2 kinase(s) are present in active forms in all animal cells under normal growth conditions and p67 protects the eIF-2 α subunit from eIF-2 kinase-catalyzed phosphorylation, thus promoting protein synthesis in the presence of active eIF-2 kinases. (ii) In heme-deficient reticulocyte lysates and in serum-starved KRC-7 cells in culture, p67 is deglycosylated and subsequently degraded. This leads to eIF-2 kinase-catalyzed eIF-2 α-subunit phosphorylation and thus to protein synthesis inhibition. (iii) Addition of a mitogen (namely, phorbol 12-myristate 13-acetate) to serum-starved KRC-7 cells in culture induces an increase of p67 and thus increases protein synthesis. These results suggest the following conclusions. (i) Protein synthesis inhibition in a heme-deficient reticulocyte lysate is not due to the activation of an eIF-2 kinase (heme-regulated inhibitor), as is generally believed, but is due to degradation of p67. The heme-regulated inhibitor is present in an active form and possibly in equal amounts in both heme-deficient and heme-supplemented reticulocyte lysates but cannot phosphorylate eIF-2 α subunit because of the presence of p67. (ii) p67 is essential for protein synthesis as it protects the eIF-2 α subunit from eIF-2 kinase-catalyzed phosphorylation and promotes protein synthesis in the presence of one or more active eIF-2 kinases present in all animal cells. (iii) p67 is both degradable and inducible. Only the p67 level correlates directly with the protein synthesis activity of the cell, indicating that p67 is a critical factor in protein synthesis regulation in animal cells

On orthogonal permutation arrays, seminets and groups

SIGLECopy held by FIZ Karlsruhe; available from UB/TIB Hannover / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekDEGerman

Not Available

Not AvailableSweet potato (Ipomoea batatas L.) and taro [Colocasia esculenta (L.) Schott] are the important tuber crops used as staple or subsistence food by millions of people in developing nations. Both tubers and leaves of these crops are an alternative source of dietary energy. Visibility of these crops as life support crops species has been enhanced during post super cyclone in Odisha and Tsunami in coastal states of India. Genetic diversity of these crops, and their wide distribution and potential to adapt in harsh environmental condition advocate for their further exploitation to develop stress tolerant crops with valued traits. Gene fl ow through conventional breeding is hindered owing to fl owering behaviours, cytogenetical anomalies in taro and hexaploidy coupled with self incompatibility in sweet potato. To make these crops more resilient, an extensive study was taken up integrating conventional and non conventional methods to tap the vast potential of genetic diversity in isolating the stress tolerant sweet potato and taro genotypes. The varietal gene bank of sweet potato maintained at the Regional Centre farm of the Central Tuber Crops Research Institute (CTCRI) were also tested under in situ to study tolerance to environmental stresses. Under such conditions, percentage of leaf damage and vine weight were recorded to identify the varieties to cope with unfavorable agro-climatic conditions. Results to isolate and develop stress tolerant sweet potato and taro and, their impact on livelihood security under climatic adversities are discussed.Not Availabl

Kinetic and Mechanistic Studies on the Interaction of Glycyl-L-alanine, Glycyl-L-asparagine, and Glycyl-L-tyrosine with Hydroxopentaaquarhodium(III) Ion

The kinetics of the interaction of three glycine-containing dipeptides, namely, glycyl-L-alanine (L1-L′H), glycyl-L-asparagine (L2-L′H), and glycyl-L-tyrosine (L3-L′H) with has been studied spectrophotometrically in aqueous medium as a function of the molar concentration of , [dipeptide], pH, and temperature at constant ionic strength. Reactions were studied at pH 4.3, where the substrate complex exists predominantly as the hydroxopentaaqua species and dipeptides as the zwitterion. The reaction has been found to proceed via two parallel paths: both processes are ligand dependent. The rate constant for the processes are and . The activation parameters for both the steps were evaluated using Eyring’s equation. The low and large negative value of as well as and indicate an associative mode of activation for both the aqua ligand substitution processes for both the parallel paths. The product of the reaction has been characterized by IR and ESI-mass spectroscopic analyses

Kinetic and Mechanistic Studies on the Interaction of Glycyl-L-alanine, Glycyl-L-asparagine, and Glycyl-L-tyrosine with Hydroxopentaaquarhodium(III) Ion

The kinetics of the interaction of three glycine-containing dipeptides, namely, glycyl-L-alanine ( , pH, and temperature at constant ionic strength. Reactions were studied at pH 4.3, where the substrate complex exists predominantly as the hydroxopentaaqua species and dipeptides as the zwitterion. The reaction has been found to proceed via two parallel paths: both processes are ligand dependent. The rate constant for the processes are 1 ∼ 10 −3 s −1 and 2 ∼ 10 −5 s −1 . The activation parameters for both the steps were evaluated using Eyring's equation 2 indicate an associative mode of activation for both the aqua ligand substitution processes for both the parallel paths. The product of the reaction has been characterized by IR and ESI-mass spectroscopic analyses

Synthesis, Characterization and Catalytic Activity of Quadruple Perovskite CaCu3-xMnxTi4-xMnxO12 (x=0, 0.5 and 1.0)

International audienceWe report the low temperature synthesis of nanosized CaCu3-xMnxTi4-xMnxO12 (x = 0, 0.5 and 1.0) quadruple perovskites and their magnetic, dielectric and catalytic performance towards CO oxidation and methanol steam reforming (MSR). Our investigations reveal the pronounced effects of particle size and chemical substitution on all the physical properties reported here. The manganese doped samples exhibit remarkable change in magnetic properties, where antiferromagnetic pristine phase converted to ferrimagnetic phase for x = 1. The dielectric constant values of the cold-pressed nanosized perovskites are similar to 10(3) and follows Maxwell-Wagner type relaxation. This value is about 100 fold lower than that of the bulk samples that has been ascribed to the effect of particle size and the absence of nano-twinning in the material as revealed from HRTEM studies. The doping of manganese further reduces the magnitude of dielectric value, which is the chemical effect. Mn-doped samples show greater catalytic activity compared to the pristine sample towards CO oxidation due to a synergistic Cu-Mn interaction. The catalytic performance of these oxides for MSR reaction is intriguing. Although the catalyst undergoes decomposition in the MSR atmosphere causing a decrease in methanol conversion during time-on-stream (TOS) tests, the activity can be regenerated by in-situ or ex-situ annealing in air. The notable catalytic activity and reversibility between pristine and decomposed form are very interesting

Characteristics of the Eukaryotic Initiation Factor 2 Associated 67-kDa Polypeptide

A eukaryotic initiation factor 2 (eIF-2) associated 67-kDa polypeptide (p67) protects the eIF-2 alpha-subunit from eIF-2 kinase(s) catalyzed phosphorylation, and this promotes protein synthesis in the presence of active eIF-2 kinase(s), [Datta, B., et al. (1988) Proc. Natl. Acad. Sci. U.S.A. 85, 3324-3328]. This report presents the results of studies related to characteristics of p67 action and the mechanism of p67:eIF-2 interaction: (1) p67 antibodies inhibited protein synthesis in hemin-supplemented rabbit reticulocyte lysates, and such inhibition was reversed by preincubation of the antibodies, specifically with p67. (2) p67 inhibited HRI- and dsI-catalyzed phosphorylations of the eIF-2 alpha-subunit and histones, but it did not inhibit casein kinase catalyzed phosphorylation of the eIF-2 beta-subunit. (3) p67 bound specifically to the eIF-2 gamma-subunit. p67 co-immunoprecipitated with the eIF-2 subunits when a p67/eIF-2 mixture was treated with p67 or eIF-2 subunit antibodies and protein A agarose. However, when eIF-2 was preincubated specifically with the eIF-2 gamma-subunit antibodies, subsequent co-immunoprecipitation of p67 with the eIF-2 subunits was completely inhibited. Similarly, preincubation of p67 and p67 antibodies prevented subsequent p67 binding to eIF-2. Preincubation of eIF-2, with either eIF-2 alpha- or beta-subunit antibodies, had no effect on p67 co-immunoprecipitation with the eIF-2 subunits. (4) p67:eIF-2 interaction is necessary for p67 activity to protect the eIF-2 alpha-subunit from eIF-2 kinase(s) catalyzed phosphorylation