Weak Ca Research Articles

Antidiarrheal and antispasmodic activities of <i>Polygonum bistorta</i> rhizomes are mediated predominantly through K+ channels activation

<p class="Abstract"><em>Polygonum bistorta</em> is a popular medicinal herb used to treat diarrhea. This study provides pharmacological basis to its folk use in diarrhea using <em>in vivo</em> and <em>in vitro</em> assays. Administration of<em> P. bistorta</em> rhizomes extract to mice offered protection against castor oil-induced diarrhea at 300-1,000 mg/kg and was found safe up to the dose of 5 g/kg. In isolated rabbit jejunum, the extract caused a dose-dependent relaxation of spontaneous and low K<sup>+</sup> (25 mM)-induced contractions with weak effect against high K<sup>+ </sup>(80 mM). In tissues pretreated with glibenclamide or tetraethylammonium chloride (TEA), the relaxant effect of the extract was markedly inhibited by TEA only. While verapamil showed complete relaxation of spontaneous, low K<sup>+</sup>, low K<sup>+</sup> with TEA and high K<sup>+</sup>-induced contractions. In guinea-pig ileum, mild atropine-sensitive effect was observed. This study indicates that <em>P. bistorta</em> possesses anti-diarrheal and antispasmodic activities mediated predominantly through K<sup>+</sup>-channels activation along with weak Ca<sup>++</sup> antagonist effect.</p><p> </p>

Antidiarrhoeal, antisecretory and antispasmodic activities of Matricaria chamomilla are mediated predominantly through K+-channels activation

BackgroundMatricaria chamomilla commonly known as “Chamomile” (Asteraceae) is a popular medicinal herb widely used in indigenous system of medicine for a variety of ailments. However, there is no detailed study available showing its effectiveness in hyperactive gut disorders like, abdominal colic and diarrhoea. This study was designed to determine the pharmacological basis for the folkloric use of Matricaria chamomilla in diarrhoea.MethodsThe crude aqueous-methanolic extract of Matricaria chamomilla (Mc.Cr) was studied for its protective effect in mice against castor oil-induced diarrhoea and intestinal fluid accumulation. The isolated rabbit jejunum was selected for the in-vitro experiments using tissue bath assembly coupled with PowerLab data acquisition system.ResultsOral administration of Mc.Cr to mice at 150 and 300 mg/kg showed marked antidiarrhoeal and antisecretory effects against castor oil-induced diarrhoea and intestinal fluid accumulation, simultaneously, similar to the effects of cromakalim and loperamide. These effects of plant extract were attenuated in animals pretreated with K+ channel antagonist, glibenclamide (GB) or 4-aminopyridine (4-AP). When tested in isolated rabbit jejunum, Mc.Cr caused a dose-dependent (0.3-3 mg/ml) relaxation of spontaneous and low K+ (25 mM)-induced contractions, while it exhibited weak inhibitory effect on high K+ (80 mM). The inhibitory effect of Mc.Cr on low K+-induced contractions was partially inhibited in the presence of GB, while completely blocked by 4-AP. Cromakalim, an ATP-sensitive K+ channel opener, caused complete relaxation of low K+-induced contractions with little effect on high K+. Pretreatment of tissues with GB blocked the inhibitory effects of cromakalim on low K+, while the presence of 4-AP did not alter the original effect. Verapamil, a Ca++ channel antagonist, caused complete relaxation of both low and high K+-induced contractions with similar potency. The inhibitory effect of verapamil was insensitive to GB or 4-AP. When assessed for Ca++ antagonist like activity, Mc.Cr at high concentrations caused rightward shift in the Ca++ concentration-response curves with suppression of the maximum response, similar to the effect of verapamil, while cromakalim did not show similar effect.ConclusionsThis study indicates that Matricaria chamomilla possesses antidiarrhoeal, antisecretory and antispasmodic activities mediated predominantly through K+-channels activation along with weak Ca++ antagonist effect.

Inhibition of carbonic anhydrase isoforms I, II, IX and XII with Schiff’s bases incorporating iminoureido moieties

A series of new Schiff’s bases was obtained from the sulfanilamide semicarbazone (4-aminosulfonylphenyl semicarbazide) and aromatic/heterocyclic aldehydes. The new compounds were designed to incorporate moieties known to induce effective inhibitory activity against carbonic anhydrase (CA, EC 4.2.1.1) isoforms involved in crucial physiologic or pathologic processes such as the cytosolic CA I and II or the transmembrane, tumor-associated CA IX and XII: the compounds were medium potency – weak CA I inhibitors, highly effective, low nanomolar CA II inhibitors, but few of them inhibited effectively CA IX and XII. This may probably due to the long spacer between the sulfamoylphenyl and imine fragments of the molecules, which probably induces a highly flexible conformation of the inhibitor bound to the active site of the enzyme, with destabilizing effects for the adduct. The detailed structure activity relationship for this class of inhibitors is discussed.

Ebola in West Africa.

Ebola viral disease (EVD) is a severe and life-threatening disease. The current Ebola outbreak in West Africa entered its second year and is unprecedented because it is the largest one in history, involved urban centers and affected a large number of health care workers. It quickly escalated from medical into a humanitarian, social, economic, and security crisis. The primary pillars to prevent EVD are: early diagnosis, isolation of patients, contact tracing and monitoring, safe burials, infection prevention and control and social mobilization. The implementation of all these components was challenged in the field. Key lessons from this Ebola outbreak are that countries with weak health care systems can’t withstand the major outbreaks; preparedness to treat the first confirmed cases is a national emergency; all control measures must be coordinated together and community engagement is the great factor to combat this disease.

Epithelial DLD-1 Cells with Disrupted E-cadherin Gene Retain the Ability to Form Cell Junctions and Apico-basal Polarity.

Gene editing methods were applied to the study of E-cadherin function in epithelial cells. The E-cadherin gene in epithelial DLD-1 cells was ablated using TALEN. The resultant cells showed round fibroblast-like morphology and had almost no Ca(2+)-dependent cell aggregation activity. E-cadherin re-expression in the knockout cells restored epithelial cell morphology and strong Ca(2+)-dependent cell-cell adhesion activity, indicating that the knockout cells retained the ability to support cadherin function. The knockout cells showed partial localization of desmoplakin and ZO-1 at intercellular contact sites. The transfectants expressing mutant E-cadherin lacking the cytoplasmic domain showed clear localization of desmoplakin and ZO-1 at cell-cell contact sites, although the cells had only weak Ca(2+)-dependent cell adhesion activity. Electron microscopy revealed the formation of intercellular junctions and apico-basal polarity in these cells. A portion of these cells occasionally formed an epithelial-like structure after prolonged culture. When the cells were treated with blebbistatin, the localization was enhanced. However, the localization was incomplete and contained defects. Double-knockout MDCK cells for the E-cadherin and cadherin-6 genes showed similar results, suggesting that the above properties were general. The present results showed that an epithelial-like structure could be formed without E-cadherin, but that the construction of mature epithelia requires E-cadherin.

Membrane Regulation and Signal Transduction by Annexin A5

Annexins are an abundant family of proteins well known for their Ca2+-dependent membrane binding ability. Though they've been implicated in numerous membrane processes their method of action and signal integration is largely unknown. Here we propose a mechanism for annexin to integrate information regarding Ca2+ concentration and resting distribution of lipid and cholesterol in one leaflet, and transduce that information across the bilayer. In a system poised near random distribution, such as lipids of the inner leaflet of the plasma membrane, order can be imposed through even weak interactions. We've previously shown annexin's weak Ca2+-independent membrane binding acts to create a cooperative Ca2+ binding response. In this work we demonstrate not only annexin's ability to respond to and integrate information of membrane composition; but also its ability change and regulate that distribution. Protein interactions with membranes can induce membrane order and domain formation if the protein has specificity for individual lipids distributed non-ideally, or even randomly throughout the membrane. A protein that preferentially binds a free component of the membrane alters the amount of that component within other membrane domains. Annexin perturbs membrane distribution through its preferential binding and sequestration of phosphatidylserine headgroups (PS). Cholesterol perturbs phospholipid physical properties and preferentially forms complexes with PS. Then the local sequestering of PC-cholesterol complexes, and annexin-induced membrane domain formation upon Ca2+ influx, can act as the driving force for cholesterol redistribution across the bilayer. Using ITC as well as fluorescent probes such as DHE (cholesterol analogue) and carboxyfluorescein encapsulating LUVs. We show annexin's binding of cholesterol-PS complexes induces differential Ca2+ binding sites, and redistributes cholesterol throughout the bilayer without disrupting membrane permeability. Together this suggests that annexin has the capacity to redistribute cholesterol across the bilayer in a calcium-ion and membrane composition dependent manner.

Disability for Function: Loss of Ca2+-Binding Is Obligatory for Fitness of Mammalian βγ-Crystallins

Vertebrate βγ-crystallins belonging to the βγ-crystallin superfamily lack functional Ca(2+)-binding sites, while their microbial homologues do not; for example, three out of four sites in lens γ-crystallins are disabled. Such loss of Ca(2+)-binding function in non-lens βγ-crystallins from mammals (e.g., AIM1 and Crybg3) raises the possibility of a trade-off in the evolutionary extinction of Ca(2+)-binding. We test this hypothesis by reconstructing ancestral Ca(2+)-binding motifs (transforming disabled motifs into the canonical ones) in the lens γB-crystallin by introducing minimal sets of mutations. Upon incorporation of serine at the fifth position in the N/D-N/D-X-X-S/T(5)-S motif, which endowed a domain with microbial characteristics, a decreased domain stability was observed. Ca(2+) further destabilized the N-terminal domain (NTD) and its serine mutants profoundly, while the incorporation of a C-terminal domain (CTD) nullified this destabilization. On the other hand, Ca(2+)-induced destabilization of the CTD was not rescued by the introduction of an NTD. Of note, only one out of four sites is functional in the NTD of γB-crystallins responsible for weak Ca(2+) binding, but the deleterious effects of Ca(2+) are overcome by introduction of a CTD. The rationale for the onset of cataracts by certain mutations, such as R77S, which have not been clarified by structural means, could be explained by this work. The findings presented here shed light on the evolutionary innovations in terms of the functional loss of Ca(2+)-binding and acquisition of a bilobed domain, besides imparting additional advantages (e.g., protection from light) required for specialized functions.

Structural study of the location of the phenyl tail of benzene sulfonamides and the effect on human carbonic anhydrase inhibition

The crystal structure of 4-phenylacetamidomethyl-benzenesulfonamide (4ITP) bound to human carbonic anhydrase (hCA, EC 4.2.1.1) II is reported. 4ITP is a medium potency hCA I and II inhibitor (KIs of 54–75nM), a strong mitochondrial CA VA/VB inhibitor (KIs of 8.3–8.6nM) and a weak transmembrane CA inhibitor (KIs of 136–212nM against hCA IX and XII). This elongated compound binds in an extended conformation to hCA II, with its tail lying towards the hydrophobic half of the active site whereas the sulfonamide moiety coordinates the zinc ion. The present structure was compared to that of structurally related aromatic sulfonamides, such as 4-phenylacetamido-benzene-sulfonamide (3OYS), 4-(2-mercaptophenylacetamido)-benzene-sulfonamide (2HD6) and 4-(3-nitrophenyl)-ureido-benzenesulfonamide (3N2P). Homology models of the hCA I, VA, VB, IX and XII structures were build which afforded an understanding of the amino acids involved in the binding of these compounds to these isoforms. The main conclusion of the study is that the orientation of the tail moiety and the presence of flexible linkers as well polar groups in it, strongly influence the potency and the selectivity of the sulfonamides for the inhibition of cytosolic, mitochondrial or transmembrane CA isoforms.

PAA-PAMPS Copolymers as an Efficient Tool to Control CaCO3 Scale Formation

Scale formation, the deposition of certain minerals such as CaCO3, MgCO3, and CaSO4·2H2O in industrial facilities and household devices, leads to reduced efficiency or severe damage. Therefore, incrustation is a major problem in everyday life. In recent years, double hydrophilic block copolymers (DHBCs) have been the focus of interest in academia with regard to their antiscaling potential. In this work, we synthesized well-defined blocklike PAA-PAMPS copolymers consisting of acrylic acid (AA) and 2-acrylamido-2-methyl-propane sulfonate (AMPS) units in a one-step reaction by RAFT polymerization. The derived copolymers had dispersities of 1.3 and below. The copolymers have then been investigated in detail regarding their impact on the different stages of the crystallization process of CaCO3. Ca(2+) complexation, the first step of a precipitation process, and polyelectrolyte stability in aqueous solution have been investigated by potentiometric measurements, isothermal titration calorimetry (ITC), and dynamic light scattering (DLS). A weak Ca(2+) induced copolymer aggregation without concomitant precipitation was observed. Nucleation, early particle growth, and colloidal stability have been monitored in situ with DLS. The copolymers retard or even completely suppress nucleation, most probably by complexation of solution aggregates. In addition, they stabilize existing CaCO3 particles in the nanometer regime. In situ AFM was used as a tool to verify the coordination of the copolymer to the calcite (104) crystal surface and to estimate its potential as a growth inhibitor in a supersaturated CaCO3 environment. All investigated copolymers instantly stopped further crystal growth. The carboxylate richest copolymer as the most promising antiscaling candidate proved its enormous potential in scale inhibition as well in an industrial-filming test (Fresenius standard method).

Calcium, mitochondria, and the pathogenesis of ALS: the good, the bad, and the ugly

Calcium, mitochondria, and the pathogenesis of ALS: the good, the bad, and the ugly

Calorimetric Evidence in Support of the Nanopore Inner Sphere Enhancement Theory on Cation Adsorption

The nanopore inner sphere enhancement (NISE) theory provides a new theoretical model of cation adsorption within confining nanopore channels. Inside nanopore channels, hydrated ions can dehydrate and more easily adsorb via an inner sphere mechanism. Adsorption data showed that in certain nanopores, weakly hydrated monovalent cations adsorbed more strongly than divalent cations, which tend to be strongly hydrated. Flow adsorption calorimetry is a valuable tool for directly measuring the heats of the ion exchange process and was used to measure the heats of Na and Ca exchange on three zeolite minerals: zeolite Y, mordenite, and ZSM‐5. The data collected showed equal and reversible exchange reactions on mordenite but a strong endothermic Na adsorption and weak exothermic Ca adsorption on ZSM‐5. On zeolite Y, the calorimetric signal was below the instrument detection limit of 5 to 7.5 mV. These differences coincide with the adsorption mechanisms and relative competitiveness predicted by the NISE theory for these two ions on the three zeolites studied. These data elucidate an exchange reaction where Ca is outcompeted by Na, which is often considered to be a weak background electrolyte.

Pharmacological basis for the medicinal use of <i>Morus alba</i> in gut and airways disorders

Crude extract of Morus alba at 100 mg/kg exhibited protective effect against castor oil-induced diarrhea in mice. In isolated rabbit jejunum, M. alba (0.3-10 mg/mL) inhibited the spontaneous contractions and caused glibenclamide-sensitive inhibition of low K + (20 mM)-induced contractions, with mild effect on high K + (80 mM). Similarly, cromakalim caused inhibition of low K + , but not of high K + , while verapamil did not differentiate in its inhibitory effect on two concentrations of K + . M. alba (3.0-30 mg/kg) caused suppression of carbachol (100 µg/kg)-induced increase in inspiratory pressure of anaesthetized rats. In guinea-pig trachea, M. alba completely inhibited low K + contractions, with partial effect on high K + . M. alba (0.3-1.0 mg/mL) caused leftward shift of isoprenaline-induced inhibitory concentration response curves, like papaverine. These results indicate that M. alba possesses a combination of K ATP channel opening, weak Ca ++ -antagonist and phosphodiesterase inhibitory mechanisms, which explain its medicinal use in hyperactive gut and airways disorders.

Self‐assembly of model graft copolymers of agarose and weak polyelectrolyte‐based amphiphilic diblock copolymers: Controlled drug release and degradation

Polysaccharide-based copolymers are promising biomaterials due to their biocompatibility and biodegradability. For potential biomedical applications the copolymer as a whole and all the degraded species must be biocompatible and easily removable from the system. In this regards, new model pH-responsive seaweed agarose (Agr) grafted with weak polyelectrolyte-based well-defined amphiphilic block copolymers ca. poly[(methyl methacrylate)-b-(2-dimethylamino)ethyl methacrylate)] (PMMA-b-PDMA) were designed and synthesized to study the self-assembly, degradation, and in vitro hydrophobic/hydrophilic drug release behavior. The graft copolymer solutions display extremely low critical micelle concentration (CMC) and form pH responsive stable micelles. The degradation study of the graft copolymer reveals that the entire degraded components are well soluble/dispersible in water due to formation of mixed micelles. The micelles are also strongly adsorbed on the mica surface owing to electrostatic interaction. One application of the graft copolymer micelles is that it can entrap both hydrophilic and poorly water soluble hydrophobic drugs effectively and exhibit slow release kinetics. The release kinetics of both the hydrophilic and poorly water soluble hydrophobic drugs change with pH as well as with the composition of the graft copolymer.

An Improved Space Debris ISAR Imaging Algorithm

According to the Characteristics of space debris, single-range matching filtering (SRMF) can be used for space debris inverse synthetic aperture radar (ISAR) imaging. Combined SRMF and Coherent CLEAN algorithm can effectively solve high sidelobes problem brought by Fourier transform. However, when the SNR is low, the position error of scattering centers extracted by SRMF-CLEAN is big, and even some weak scatterings can’t be extracted. This paper uses Sequence CLEAN instead of Coherent CLEAN to availably solve the above problems. The experiment results confirm the validness of the proposed algorithm.

WASP-44b, WASP-45b and WASP-46b: three short-period, transiting extrasolar planets

We report the discovery of three extrasolar planets that transit their moderately bright (Vmag = 12-13) host stars. WASP-44b is a 0.89-MJup planet in a 2.42-day orbit around a G8V star. WASP-45b is a 1.03-MJup planet which passes in front of the limb of its K2V host star every 3.13 days. Weak Ca II H+K emission seen in the spectra of WASP-45 suggests the star is chromospherically active. WASP-46b is a 2.10-MJup planet in a 1.43-day orbit around a G6V star. Rotational modulation of the light curves of WASP-46 and weak Ca II H+K emission in its spectra show the star to be photospherically and chromospherically active. We imposed circular orbits in our analyses as the radial velocity data are consistent with (near-)circular orbits, as could be expected from both empirical and tidal-theory perspectives for such short-period, Jupiter-mass planets. We discuss the impact of fitting for eccentric orbits for such planets when not supported by the data. The derived planetary and stellar radii depend on the fitted eccentricity and these parameters inform intense theoretical efforts concerning tidal circularisation and heating, bulk planetary composition and the observed systematic errors in planetary and stellar radii. As such, we recommend exercising caution in fitting the orbits of short period, Jupiter-mass planets with an eccentric model when there is no evidence of non-circularity.

Characterization of the 1st and 2nd EF-hands of NADPH oxidase 5 by fluorescence, isothermal titration calorimetry, and circular dichroism

BackgroundSuperoxide generated by non-phagocytic NADPH oxidases (NOXs) is of growing importance for physiology and pathobiology. The calcium binding domain (CaBD) of NOX5 contains four EF-hands, each binding one calcium ion. To better understand the metal binding properties of the 1st and 2nd EF-hands, we characterized the N-terminal half of CaBD (NCaBD) and its calcium-binding knockout mutants.ResultsThe isothermal titration calorimetry measurement for NCaBD reveals that the calcium binding of two EF-hands are loosely associated with each other and can be treated as independent binding events. However, the Ca2+ binding studies on NCaBD(E31Q) and NCaBD(E63Q) showed their binding constants to be 6.5 × 105 and 5.0 × 102 M-1 with ΔHs of -14 and -4 kJ/mol, respectively, suggesting that intrinsic calcium binding for the 1st non-canonical EF-hand is largely enhanced by the binding of Ca2+ to the 2nd canonical EF-hand. The fluorescence quenching and CD spectra support a conformational change upon Ca2+ binding, which changes Trp residues toward a more non-polar and exposed environment and also increases its α-helix secondary structure content. All measurements exclude Mg2+-binding in NCaBD.ConclusionsWe demonstrated that the 1st non-canonical EF-hand of NOX5 has very weak Ca2+ binding affinity compared with the 2nd canonical EF-hand. Both EF-hands interact with each other in a cooperative manner to enhance their Ca2+ binding affinity. Our characterization reveals that the two EF-hands in the N-terminal NOX5 are Ca2+ specific.Graphical abstract

Characterization of the Metal Binding in NADPH Oxidase 5 by Fluorescence, Isothermal Titration Calorimetry, and Circular Dichroism

Superoxide generated by non‐phagocytic NADPH oxidases (NOXs) plays roles in disease development and cancer. The activity of NOX5 appears to be regulated by its self‐contained calcium binding domain (CaBD). To study its calcium binding properties, we isolated the N‐ and C‐terminal halves of CaBD (N‐ / C‐CaBD), and separately studied their metal binding. Isothermal titration calorimetry reveals a positive cooperation for both halves, with differences in enthalpy values ranging from −30 to −40 kJ/mol. Using mutants whose Glu residue (−z) in each EF‐hand was replaced with Gln, we determined the semi‐microscopic binding constants of Ca2+ for the 1st and 2nd EF‐hands; the result indicates a weak Ca2+ binding to the 1st EF‐hand is enhanced by the binding of Ca2+ to its 2nd EF‐hand. No Mg2+ binding was seen in N‐CaBD. The binding of Ca2+ and Mg2+ to C‐CaBD are exothermic, and Ca2+ binding is only 2–3 fold tighter than Mg2+. Our findings suggest that in the resting cells, the 3rd and 4th EF‐hands are Mg2+‐bound; increasing Ca2+ levels affects the EF‐hands of N‐terminal half. Our results imply that Ca2+ binding to the 1st and 2nd EF‐hands is more critical in controlling NOX5 activity. To investigate structural dependency between half domains that affects metal binding, we created CaBD mutants, such as CaBD(E31Q/E64Q) and CaBD(E99Q/E143Q), and determined their metal binding affinities. This work is supported in part by NSF‐CCLI grant.

Opposing action of conantokin-G on synaptically and extrasynaptically-activated NMDA receptors

Synaptic and extrasynaptic activation of the N-methyl-d-aspartate receptor (NMDAR) has distinct consequences on cell signaling and neuronal survival. Since conantokin (con)-G antagonism is NR2B-selective, which is the key subunit involved in extrasynaptic activation of the receptor, its ability to specifically elicit distinct signaling outcomes in neurons with synaptically or extrasynaptically-activated NMDARs was evaluated. Inhibition of Ca2+ influx through extrasynaptic NMDAR ion channels was neuroprotective, as it effectively enhanced levels of activated extracellular signal-regulated kinase 1/2 (ERK1/2), activated cAMP response element binding protein (CREB), enhanced mitochondrial viability, and attenuated the actin disorganization observed by extrasynaptic activation of NMDARs. Conversely, the pro-signaling pathways stimulated by synaptically-induced Ca2+ influx were abolished by con-G. Furthermore, subunit non-selective con-T was unable to successfully redress the impairments in neurons caused by extrasynaptically-activated NMDARs, thus indicating that NR2B-specific antagonists are beneficial for neuron survival. Neurons ablated for the NR2B subunit showed weak synaptic Ca2+ influx, reduced sensitivity to MK-801 blockage, and diminished extrasynaptic current compared to WT and NR2A−/− neurons. This indicates that the NR2B subunit is an integral component of both synaptic and extrasynaptic NMDAR channels. Altogether, these data suggest that con-G specifically targets the NR2B subunit in the synaptic and extrasynaptic locations, resulting in the opposing action of con-G on differentially activated pools of NMDARs.

Calcium-sensitive Activity and Conformation of Caenorhabditis elegans Gelsolin-like Protein 1 Are Altered by Mutations in the First Gelsolin-like Domain

The gelsolin family of actin regulatory proteins is activated by Ca(2+) to sever and cap actin filaments. Gelsolin has six homologous gelsolin-like domains (G1-G6), and Ca(2+)-dependent conformational changes regulate its accessibility to actin. Caenorhabditis elegans gelsolin-like protein-1 (GSNL-1) has only four gelsolin-like domains (G1-G4) and still exhibits Ca(2+)-dependent actin filament-severing and -capping activities. We found that acidic residues (Asp-83 and Asp-84) in G1 of GSNL-1 are important for its Ca(2+) activation. These residues are conserved in GSNL-1 and gelsolin and previously implicated in actin-severing activity of the gelsolin family. We found that alanine mutations at Asp-83 and Asp-84 (D83A/D84A mutation) did not disrupt actin-severing or -capping activity. Instead, the mutants exhibited altered Ca(2+) sensitivity when compared with wild-type GSNL-1. The D83A/D84A mutation enhanced Ca(2+) sensitivity for actin severing and capping and its susceptibility to proteolytic digestion, suggesting a conformational change. Single mutations caused minimal changes in its activity, whereas Asp-83 and Asp-84 were required to stabilize Ca(2+)-free and Ca(2+)-bound conformations, respectively. On the other hand, the D83A/D84A mutation suppressed sensitivity of GSNL-1 to phosphatidylinositol 4,5-bisphosphate inhibition. The structure of an inactive form of gelsolin shows that the equivalent acidic residues are in close contact with G3, which may maintain an inactive conformation of the gelsolin family.

Effect of adhesive on the morphology and mechanical properties of electrospun fibrous mat of cellulose acetate

Ultrafine fibers of cellulose acetate/poly(butyl acrylate) (CA/PBA) composite in which PBA acted as an adhesive and CA acted as a matrix, were successfully prepared as fibrous mat via electrospinning. The morphology observation from the electrospun CA/PBA composite fibers, after treatment with heat hardener, revealed that the fibers were cylindrical and had point-bonded structures. SEM, FT-IR spectra, Raman spectra, TGA analysis, and mechanical properties measurement were used to study the different properties of hybrid mats. The tensile strength of blend fibrous electrospun mats was found to be effectively increased. This resultant enhancement of the mechanical properties of polymer fibrous mats, caused by generating the point-bonded structures (due to adhesive), could increase the number of potential applications of mechanically weak electrospun CA fibers.