Chiral resolution of (±)-flurbiprofen using molecularly imprinted hydrazidine-modified cellulose microparticles.

Flurbiprofen (FP) is one of the non-steroidal anti-inflammatory drugs (NSAIDs) commonly used to treat arthritic conditions. FP has two enantiomers: S-FP and R-FP. S-FP has potent anti-inflammatory effects, while R-FP has nearly no such effects. Herein, molecularly imprinted microparticles produced from hydrazidine-cellulose (CHD) biopolymer for the preferential uptake of S-FP and chiral resolution of (±)-FP were developed. First, cyanoethylcellulose (CECN) was synthesized, and the -CN units were transformed into hydrazidine groups. The developed CHD was subsequently shaped into microparticles and ionically interacted with the S-FP enantiomer. The particles were then imprinted after being cross-linked with glutaraldehyde, and then the S-FP was removed to provide the S-FP enantio-selective sorbent (S-FPCHD). After characterization, the optimal removal settings for the S- and R-FP enantiomers were determined. The results indicated a capacity of 125 mg/g under the optimum pH range of 5-7. Also, S-FPCHD displayed a noticeable affinity toward S-FP with a 12-fold increase compared to the R-FP enantiomer. The chiral resolution of the (±)-FP was successfully attempted using separation columns, and the outlet sample of the loading solution displayed an enantiomeric excess (ee) of 93 % related to the R-FP, while the eluent solution displayed an ee value of 95 % related to the S-FP.

Rapid adsorption of acid dyes using Cu(II) thiourea modified cellulose complex.

In the present work, the acid dyes namely, eriochrome cyanine R (ECR) and 2-(4-Sulfo phenyl azo)-1,8 dihydroxy-3,6 naphthalene disulfonic acid, trisodium salt (SPADNS) were effectively adsorbed by Cu(II)-thiourea modified cotton fibers (Cu(II)/Tu-MC) complex. FTIR, SEM, XPS analysis, thermogravimetric analysis, and potentiometric titration were utilized for characterization. The impact of the fundamental adsorption parameters was systematically investigated. The results reveal that the adsorption of ECR and SPADNS acid dyes occurs via a metal-coordination mechanism. Furthermore, the adsorption process follows the 2nd order kinetic model and Langmuir model adsorption isotherm. The Cu(II)/Tu-MC shows high adsorption capacities of 0.27 and 0.22 mmol/g for ECR and SPADNS, respectively. These findings indicate that the cationization of cellulose fibers with metal ions is a promising and efficient strategy toward enhancing the adsorption of acid dyes.

Biosynthesis and Characterization of Silver Nanoparticles Produced by Phormidium ambiguum and Desertifilum tharense Cyanobacteria.

The world faces a challenge with the pervasion of multidrug-resistant bacteria that encourages scientists to develop and discover alternative, ecofriendly, and easy-to-produce new antibacterial agents. Our work is part of the greater effort of scientists around the world to achieve this goal by the biological synthesis of silver nanoparticles using cyanobacterial extracellular and intracellular components as nonchemical reducing agents. Two Egyptian cyanobacteria were isolated and identified according to 16S rRNA gene sequencing as Phormidium ambiguum and a novel species Desertifilum tharense. The sequences were deposited with accession numbers MW762709 and MW762710 for Desertifilum tharense and Phormidium ambiguum, respectively, in the GenBank. The results of UV-Vis analysis showed promising extracellular Ag-NPs synthesis by Desertifilum tharense and Phormidium ambiguum under light conditions. Therefore, these Ag-NPs were characterized and evaluated for antibacterial and antioxidant activity. TEM and SEM analyses revealed the spherical crystals with face-centered cubic structures and size range of 6.24-11.4 nm and 6.46-12.2 nm for Ag-NPs of Desertifilum tharense and Phormidium ambiguum, respectively. XRD and EDX results confirmed the successful synthesis of Ag-NPs in their oxide form or chloride form. The FTIR spectrum data confirmed the presence of hydroxyl and amide groups. Desertifilum tharense Ag-NPs displayed the largest inhibition zone that ranged from 9 mm against Micrococcus luteus ATCC 10240 to 25 mm against methicillin-resistant Staphylococcus aureus (MRSA) ATCC 43300. For Phormidium ambiguum Ag-NPs, the inhibition zone diameter was in the range of 9 mm to 18 mm. The biosynthesized Ag-NPs significantly inhibited the growth of medically important resistance-pathogenic Gram-positive and Gram-negative bacteria. The Ag-NPs of Phormidium ambiguum exhibited the highest scavenging activity of 48.7% when compared with that of Desertifilum tharense, which displayed 43.753%.

Negative Transpulmonary Pressure Disrupts Airway Morphogenesis by Suppressing Fgf10.

Mechanical forces are increasingly recognized as important determinants of cell and tissue phenotype and also appear to play a critical role in organ development. During the fetal stages of lung morphogenesis, the pressure of the fluid within the lumen of the airways is higher than that within the chest cavity, resulting in a positive transpulmonary pressure. Several congenital defects decrease or reverse transpulmonary pressure across the developing airways and are associated with a reduced number of branches and a correspondingly underdeveloped lung that is insufficient for gas exchange after birth. The small size of the early pseudoglandular stage lung and its relative inaccessibility in utero have precluded experimental investigation of the effects of transpulmonary pressure on early branching morphogenesis. Here, we present a simple culture model to explore the effects of negative transpulmonary pressure on development of the embryonic airways. We found that negative transpulmonary pressure decreases branching, and that it does so in part by altering the expression of fibroblast growth factor 10 (Fgf10). The morphogenesis of lungs maintained under negative transpulmonary pressure can be rescued by supplementing the culture medium with exogenous FGF10. These data suggest that Fgf10 expression is regulated by mechanical stress in the developing airways. Understanding the mechanical signaling pathways that connect transpulmonary pressure to FGF10 can lead to the establishment of novel non-surgical approaches for ameliorating congenital lung defects.

Designing and investigation of photo-active gellan gum for the efficient immobilization of catalase by entrapment.

A photo-active gellan gum (Gel) derivative was developed by amide bond combination with trans-4-[p-(amino)styryl]pyridine (SP). The SP-Gel was cross-linked by UV curing via the intermolecular 2π + 2π cycloaddition of the inserted SP-CH=CH- moieties. The chemical structure of the obtained photo-crosslinkable biopolymer was investigated before and after the UV curing and the progress of the performed 2π + 2π cycloaddition-based cross-linking was detected via UV-visible light spectra. SP-Gel was evaluated as a polymeric matrix for the immobilization of catalase via entrapment technique. The synthesized biopolymer was mixed with the catalase and molded in the form of membranes that were UV cured to encapsulate the enzyme. The membranes were able to entrap 0.75 mg/cm2 with retained activity reached above 95%. The immobilized catalase displayed higher thermal stability and higher resistance toward the environmental pH disturbances compared to the free enzyme. Also, despite the observed lower catalase-H2O2 affinity upon the entrapment that was indicated from the performed kinetic studies, the reusability and storage stability experiments revealed the economic value of the entire process by preserving around 95% and 83% of the initial catalase activity after the fifth and tenth operation cycles, respectively.

Surface molecularly imprinted amino-functionalized alginate microspheres for enantio-selective extraction of l-ascorbic acid.

A surface molecular imprinting technique was utilized in the fabrication of an enantio-selective adsorbent based on amino-functionalized alginate microspheres for chiral resolution of ascorbic acid. Alginate microspheres were first strengthened via epichlorohydrin (ECH) covalent cross-linking then functionalized with amino groups through graft copolymerization of polyacrylamide (PAm) followed by Hofmann degradation. Surface molecular imprinting was then performed under mild conditions by ionic interaction between the surface incorporated amine groups and the template l-ascorbic acid enantiomers followed by cross-linking with glyoxal. l-Ascorbic acid enantio-selective adsorbent (LA-Alg) was finally obtained by removing the template molecules out of the cross-linked network formed on the surface of the modified alginate particles. The synthetic steps were monitored using elemental analysis and FTIR spectra. Also, the surface morphologies of the native unmodified alginate along with both imprinted and non-imprinted adsorbent particles were examined by SEM. Moreover, the crystalline profile and thermal properties of both native and modified samples were investigated using XRD spectra and thermogravimetric analysis (TGA), respectively. The effect of pH on the extraction process was studied and indicated that the maximum adsorption was obtained at pH 4. Also, adsorption isotherms over LA-Alg adsorbent displayed the best fit with Langmuir model with maximum adsorption capacity 116 ±â€¯1 and 67 ±â€¯1 mg/g with respect to both l- and d-ascorbic acid, respectively. Moreover, the chiral resolution experiment using batch technique indicated 72% enantiomeric excess.

Cos2/Kif7 and Osm-3/Kif17 regulate onset of outer segment development in zebrafish photoreceptors through distinct mechanisms.

Zebrafish morphants of osm-3/kif17, a kinesin-2 family member and intraflagellar transport motor, have photoreceptor outer segments that are dramatically reduced in number and size. However, two genetic mutant lines, osm-3/kif17sa0119 and osm-3/kif17sa18340, reportedly lack any observable morphological outer segment defects. In this work, we use TALENs to generate an independent allele, osm-3/kif17mw405, and show that both osm-3/kif17sa0119 and osm-3/kif17mw405 have an outer segment developmental delay in both size and density that is fully recovered by 6 days post-fertilization. Additionally, we use CRISPRs to generate cos2/kif7mw406, a mutation in the kinesin-4 family member cos2/kif7 that has been implicated in controlling ciliary architecture and Hedgehog signaling to test whether it may be functioning redundantly with osm-3/kif17. We show that cos2/kif7mw406 has an outer segment developmental delay similar to the osm-3/kif17 mutants. Using a three-dimensional mathematical model of outer segments, we show that while cos2/kif7mw406 and osm-3/kif17mw405 outer segments are smaller throughout the first 6 days of development, the volumetric rates of outer segment morphogenesis are not different among wild-type, cos2/kif7mw406, and osm-3/kif17mw405 after 60hpf. Instead, our model suggests that cos2/kif7mw406 and osm-3/kif17mw405 impact outer segment morphogenesis through upstream events that that are different for each motor. In the case of cos2/kif7mw406 mutants, we show that early defects in Hedgehog signaling lead to a general, non-photoreceptor-specific delay of retinal neurogenesis, which in turn causes the secondary phenotype of delayed outer segment morphogenesis. In contrast, the osm-3/kif17mw405 outer segment morphogenesis delays are linked specifically to initial disc morphogenesis of photoreceptors rather than an upstream event. Further, we show that osm-3/kif17 mutant mice also exhibit a similarly delayed outer segment development, suggesting a role for osm-3/kif17 in early outer segment development that is conserved across species. In conclusion, we show that both osm-3/kif17 and cos2/kif7 have comparable outer segment developmental delays, although through independent mechanisms.

Morphogenesis and morphometric scaling of lung airway development follows phylogeny in chicken, quail, and duck embryos.

BACKGROUND: New branches within the embryonic chicken lung form via apical constriction, in which epithelial cells in the primary bronchus become trapezoidal in shape. These branches form at precise locations along the primary bronchus that scale relative to the size of the organ. Here, we examined the extent to which this scaling relationship and branching mechanism are conserved within lungs of three species of birds. FINDINGS: Analyzing the development of embryonic lungs from chicken, quail, and duck, as well as lungs explanted and cultured ex vivo, revealed that the patterns of branching are remarkably conserved. In particular, secondary bronchi form at identical positions in chicken and quail, the patterns of which are indistinguishable, consistent with the close evolutionary relationship of these two species. In contrast, secondary bronchi form at slightly different positions in duck, the lungs of which are significantly larger than those of chicken and quail at the same stage of development. Confocal analysis of fixed specimens revealed that each secondary bronchus forms by apical constriction of the dorsal epithelium of the primary bronchus, a morphogenetic mechanism distinct from that used to create branches in mammalian lungs. CONCLUSIONS: Our findings suggest that monopodial branching off the primary bronchus is driven by apical constriction in lungs of chicken, quail, and duck. The relative positions at which these branches form are also conserved relative to the evolutionary relationship of these species. It will be interesting to determine whether these mechanisms hold in more distant species of birds, and why they differ so significantly in mammals.

Diversity of bacteria nesting the plant cover of north Sinai deserts, Egypt.

North Sinai deserts were surveyed for the predominant plant cover and for the culturable bacteria nesting their roots and shoots. Among 43 plant species reported, 13 are perennial (e.g. Fagonia spp., Pancratium spp.) and 30 annuals (e.g. Bromus spp., Erodium spp.). Eleven species possessed rhizo-sheath, e.g. Cyperus capitatus, Panicum turgidum and Trisetaria koelerioides. Microbiological analyses demonstrated: the great diversity and richness of associated culturable bacteria, in particular nitrogen-fixing bacteria (diazotrophs); the majority of bacterial residents were of true and/or putative diazotrophic nature; the bacterial populations followed an increasing density gradient towards the root surfaces; sizeable populations were able to reside inside the root (endorhizosphere) and shoot (endophyllosphere) tissues. Three hundred bacterial isolates were secured from studied spheres. The majority of nitrogen-fixing bacilli isolates belonged to Bacillus megaterium, Bacillus pumilus, Bacillus polymexa, Bacillus macerans, Bacillus circulans and Bacillus licheniformis. The family Enterobacteriaceae represented by Enterobacter agglomerans, Enterobacter sackazakii, Enterobacter cloacae, Serratia adorifera, Serratia liquefaciens and Klebsiella oxytoca. The non-Enterobacteriaceae population was rich in Pantoae spp., Agrobacterium rdiobacter, Pseudomonas vesicularis, Pseudomonas putida, Stenotrophomonas maltophilia, Ochrobactrum anthropi, Sphingomonas paucimobilis and Chrysemonas luteola. Gluconacetobacter diazotrophicus were reported inside root and shoot tissues of a number of tested plants. The dense bacterial populations reported speak well to the very possible significant role played by the endophytic bacterial populations in the survival, in respect of nutrition and health, of existing plants. Such groups of diazotrophs are good candidates, as bio-preparates, to support the growth of future field crops grown in deserts of north Sinai and irrigated by the water of El-Salam canal.

Inhibitory morphogens and monopodial branching of the embryonic chicken lung.

BACKGROUND: Branching morphogenesis generates a diverse array of epithelial patterns, including dichotomous and monopodial geometries. Dichotomous branching can be instructed by concentration gradients of epithelial-derived inhibitory morphogens, including transforming growth factor-ß (TGFß), which is responsible for ramification of the pubertal mammary gland. Here, we investigated the role of autocrine inhibitory morphogens in monopodial branching morphogenesis of the embryonic chicken lung. RESULTS: Computational modeling and experiments using cultured organ explants each separately revealed that monopodial branching patterns cannot be specified by a single epithelial-derived autocrine morphogen gradient. Instead, signaling by means of TGFß1 and bone morphogenetic protein-4 (BMP4) differentially affect the rates of branching and growth of the airways. Allometric analysis revealed that development of the epithelial tree obeys power-law dynamics; TGFß1 and BMP4 have distinct but reversible effects on the scaling coefficient of the power law. CONCLUSIONS: These data suggest that although autocrine inhibition cannot specify monopodial branching, inhibitory morphogens define the dynamics of lung morphogenesis.

Mammary branch initiation and extension are inhibited by separate pathways downstream of TGFß in culture.

During the branching morphogenesis process that builds epithelial trees, signaling from stimulatory and inhibitory growth factors is integrated to control branch initiation and extension into the surrounding stroma. Here, we examined the relative roles played by these stimulatory and inhibitory signals in the patterning of branch initiation and extension of model mammary epithelial tubules in culture. We found that although several growth factors could stimulate branching, they did not determine the sites at which new branches formed or the lengths to which branches extended. Instead, branch initiation and extension were defined by two separate signals downstream of the inhibitory morphogen, transforming growth factor (TGF)-ß. Branch initiation was controlled by signaling through p38 mitogen-activated protein kinase, whereas branch extension was controlled by Smad-mediated induction of a second diffusible inhibitor, Wnt5a. These data suggest that mammary epithelial branching is patterned predominately by repulsive signaling, and that TGFß activates multiple inhibitory pathways to refine the architecture of the tree.

Adipose stroma induces branching morphogenesis of engineered epithelial tubules.

The mammary gland and other treelike organs develop their characteristic fractal geometries through branching morphogenesis, a process in which the epithelium bifurcates and invades into the surrounding stroma. Controlling the pattern of branching is critical for engineering these organs. In vivo, the branching process is instructed by stromal-epithelial interactions and adipocytes form the largest component of the fatty stroma that surrounds the mammary epithelium. Here, we used microlithographic approaches to engineer a three-dimensional culture model that enables analysis of the effect of adipocytes on the pattern of branching morphogenesis of mammary epithelial cells. We found that adipocyte-rich stroma induces branching through paracrine signals, including hepatocyte growth factor, but does not affect the branching pattern per se. This tissue engineering approach can be expanded to other organs, and should enable piecemeal analysis of the cellular populations that control patterning during normal development.

Branched chain amino acids decrease tardive dyskinesia symptoms.

RATIONALE: Prior studies had suggested (a) that a lessened ability to clear ingested forms of the large neutral amino acid (LNAA), phenylalanine (Phe), was associated with having tardive dyskinesia (TD), and (b) that greater availability of a group of LNAA, the branched chain amino acids (BCAA), concomitant with the lower availability of Phe to the brain are associated with a decrease in TD symptoms. The present study was then conducted to test whether increasing the daily intake of the BCAA would decrease the symptoms of TD. METHODS: A 2-week trial of a BCAA medical food administered three times a day was conducted in nine men with long neuroleptic treatment histories. Frequency counts of TD movements were collected by videotape throughout the trial and these tapes were analyzed in blind random sequence for both patient and time for TD symptom level changes subsequent to completion of the trial. Plasma levels of the LNAA were also collected throughout the trial. RESULTS: A statistically significant decrease in the level of TD symptoms was observed for the sample. The symptom changes were also clinically significant in that six of the nine subjects had symptom decreases of at least 58%, with all subjects having a decrease of at least 38%. BCAA administration increased plasma BCAA concentrations and BCAA/LNAA ratios and decreased plasma Phe concentrations and the Phe/LNAA ratio. Analyses indicated a strong significant correlation between the percent increase in the plasma BCAA values at the first administration and the percent improvement in TD over the trial in eight of the nine subjects. CONCLUSIONS: The BCAA show promise as a treatment for TD. The decrease in TD symptoms seen in the trial may have been modulated by the BCAA treatment-induced increased availability of the BCAA and decreased availability of Phe to the brain.

Predictors of response and nonresponse to light treatment for winter depression.

OBJECTIVE: The authors' goal was to determine whether the pattern and severity of depressive symptoms predict response to light treatment for seasonal affective disorder. METHOD: Subjects with winter depression (N = 103) were given bright light treatment. Seventy-one were classified as responders, 15 as nonresponders, and 17 as partial responders. Using depression rating scale data and correlational and multivariate analysis, the authors sought predictors of response in baseline symptom and scale scores. RESULTS: Responders were characterized by atypical symptoms, especially hypersomnia, afternoon or evening slump, reverse diurnal variation (evenings worse), and carbohydrate craving. By contrast, nonresponders were characterized mainly by melancholic symptoms, retardation, suicidality, depersonalization, typical diurnal variation (mornings worse), anxiety, early and late insomnia, appetite loss, and guilt. The ratio of atypical to classical symptoms of depression, rather than severity per se, best predicted treatment outcome for the group as a whole. Pretreatment expectations were positively correlated with improvement on the Hamilton Depression Rating Scale but not on a supplementary scale of atypical symptoms. CONCLUSIONS: Light-responsive seasonal affective disorder is distinguished by a dominant atypical symptom profile closely associated with depressed mood. Nonresponders from a clinically distinct group with melancholic features. The patient's symptom profile, therefore, should be considered when diagnosing seasonal affective disorder and selecting treatment.