Adaptor protein complex-1 (AP-1) is recruited by the HEATR5 protein Laa1 and its co-factor Laa2 in yeast.

Cellular membrane trafficking mediated by the clathrin adaptor protein complex-1 (AP-1) is important for the proper composition and function of organelles of the endolysosomal system. Normal AP-1 function requires proteins of the HEAT repeat-containing 5 (HEATR5) family. Although HEATR5 proteins were first identified based on their ability to interact with AP-1, the functional significance of this interaction was unknown. We used bioinformatics-based phenotypic profiling and information from genome-wide fluorescence microscopy studies in the budding yeast Saccharomyces cerevisiae to identify a protein, Laa2, that mediates the interaction between AP-1 and the yeast HEATR5 protein Laa1. Further characterization of Laa2 revealed that it binds to both Laa1 and AP-1. Laa2 contains a motif similar to the characterized γ-ear-binding sites found in other AP-1-binding proteins. This motif in Laa2 is essential for the Laa1-AP-1 interaction. Moreover, mutation of this motif disrupted AP-1 localization and function and caused effects similar to mutations that remove the γ-ear of AP-1. These results indicate that Laa2 mediates the interaction between Laa1 and AP-1 and reveal that this interaction promotes the stable association of AP-1 with membranes in yeast.

Structural and functional characterization of the PNKP-XRCC4-LigIV DNA repair complex.

Non-homologous end joining (NHEJ) repairs DNA double strand breaks in non-cycling eukaryotic cells. NHEJ relies on polynucleotide kinase/phosphatase (PNKP), which generates 5΄-phosphate/3΄-hydroxyl DNA termini that are critical for ligation by the NHEJ DNA ligase, LigIV. PNKP and LigIV require the NHEJ scaffolding protein, XRCC4. The PNKP FHA domain binds to the CK2-phosphorylated XRCC4 C-terminal tail, while LigIV uses its tandem BRCT repeats to bind the XRCC4 coiled-coil. Yet, the assembled PNKP-XRCC4-LigIV complex remains uncharacterized. Here, we report purification and characterization of a recombinant PNKP-XRCC4-LigIV complex. We show that the stable binding of PNKP in this complex requires XRCC4 phosphorylation and that only one PNKP protomer binds per XRCC4 dimer. Small angle X-ray scattering (SAXS) reveals a flexible multi-state complex that suggests that both the PNKP FHA and catalytic domains contact the XRCC4 coiled-coil and LigIV BRCT repeats. Hydrogen-deuterium exchange indicates protection of a surface on the PNKP phosphatase domain that may contact XRCC4-LigIV. A mutation on this surface (E326K) causes the hereditary neuro-developmental disorder, MCSZ. This mutation impairs PNKP recruitment to damaged DNA in human cells and provides a possible disease mechanism. Together, this work unveils multipoint contacts between PNKP and XRCC4-LigIV that regulate PNKP recruitment and activity within NHEJ.

HPLC Analysis and In Vivo Renoprotective Evaluation of Hydroalcoholic Extract of Cucumis melo Seeds in Gentamicin-Induced Renal Damage.

BACKGROUND AND OBJECTIVES: Cucumis melo, of family Cucurbitaceae, has traditionally been used to treat variety of kidney disorders. However to best of our knowledge there is no scientific study available that validates its renaoprotective uses. Therefore, this study aimed to evaluate nephroprotective effects of hydroalcoholic extract of Cucumis melo seeds (CMHE) and to identify its phytoconstituents. MATERIALS AND METHODS: HPLC was performed to identify key phytochemicals of CMHE. Gentamicin (100 mg/kg/day, i.p) was administered to induce nephrotoxicity in Swiss albino mice for 8 days. Gentamicin (100 mg/kg/day, i.p) and oral CMHE were co-administered to mice at doses of 250 and 500 mg/kg to evaluate protective effects of CMHE. Normal control group mice were administered normal saline. Changes in body weights, biochemical and histopathological studies were conducted to establish nephroprotective effects of CMHE. Results: HPLC analysis indicated presence of quercetin, m-coumaric acid, gallic acid, chlorogenic acid, and trans-4-hydroxy-3-methoxy cinnamic acid in CMHE. Mice treated with CMHE showed significant increase in body weight and decrease in kidney weight as compared with toxic control group. Dose-dependent significant decrease in total blood urea nitrogen, serum creatinine, serum urea, and uric acid levels were observed in CMHE-treated groups as compared with toxic control group. Histopathological analysis of CMHE-treated groups showed improvement in kidney structures as compared with toxic control group. Conclusions: Biochemical, histopathological, and phytochemical screening of hydroalcoholic extract of Cucumis melo seeds suggest that it has nephroprotective potential. Furthermore, standardization of extract against identified phytochemicals, as well as long-term toxicological studies are suggested before commencement of clinical trials.

Lithocholic acid attenuates cAMP-dependent Cl- secretion in human colonic epithelial T84 cells.

Bile acids (BAs) play a complex role in colonic fluid secretion. We showed that dihydroxy BAs, but not the monohydroxy BA lithocholic acid (LCA), stimulate Cl(-) secretion in human colonic T84 cells (Ao M, Sarathy J, Domingue J, Alrefai WA, Rao MC. Am J Physiol Cell Physiol 305: C447-C456, 2013). In this study, we explored the effect of LCA on the action of other secretagogues in T84 cells. While LCA (50 µM, 15 min) drastically (>90%) inhibited FSK-stimulated short-circuit current (Isc), it did not alter carbachol-stimulated Isc LCA did not alter basal Isc, transepithelial resistance, cell viability, or cytotoxicity. LCA's inhibitory effect was dose dependent, acted faster from the apical membrane, rapid, and not immediately reversible. LCA also prevented the Isc stimulated by the cAMP-dependent secretagogues 8-bromo-cAMP, lubiprostone, or chenodeoxycholic acid (CDCA). The LCA inhibitory effect was BA specific, since CDCA, cholic acid, or taurodeoxycholic acid did not alter FSK or carbachol action. While LCA alone had no effect on intracellular cAMP concentration ([cAMP]i), it decreased FSK-stimulated [cAMP]i by 90%. Although LCA caused a small increase in intracellular Ca(2+) concentration ([Ca(2+)]i), chelation by BAPTA-AM did not reverse LCA's effect on Isc LCA action does not appear to involve known BA receptors, farnesoid X receptor, vitamin D receptor, muscarinic acetylcholine receptor M3, or bile acid-specific transmembrane G protein-coupled receptor 5. LCA significantly increased ERK1/2 phosphorylation, which was completely abolished by the MEK inhibitor PD-98059. Surprisingly PD-98059 did not reverse LCA's effect on Isc Finally, although LCA had no effect on basal Isc, nystatin permeabilization studies showed that LCA both stimulates an apical cystic fibrosis transmembrane conductance regulator Cl(-) current and inhibits a basolateral K(+) current. In summary, 50 µM LCA greatly inhibits cAMP-stimulated Cl(-) secretion, making low doses of LCA of potential therapeutic interest for diarrheal diseases.

Exploring psychosocial experiences of behavior therapists dealing with children having autism spectrum disorder.

Behavior therapists play an important role in the life of children with an autism spectrum disorder (ASD). Literature reported that child's improvement depends on the quality of therapy they receive. Therefore, the current study aims to explore the psychosocial experiences of behavior therapist working with children having ASD, and suggest the coping strategies which they use to deal with those stressors. The study utilizes a qualitative research design with a phenomenological research approach to explore the psychosocial experiences. For this purpose, the researchers conduct semi-structured interviews of 6 behavior therapists, ages ranging from 25 to 35 years. They note the verbatim of the therapists and convert into codes to create themes and categories. Furthermore, the study utilizes Interpretative Phenomenological Analysis for the interpretation of the results. The results of this phenomenological research indicate six superordinate themes emerged from the transcripts. The results demonstrate professional and psychological experiences of behavior therapists along with the social and the health issues faced by the children with ASD, and the coping strategies used by the therapists that is emotion focused coping, problem focused coping and maladaptive copings. Gaining insight into therapists' psychosocial experiences can pave the way for developing approaches aimed at enhancing their overall welfare. These approaches may encompass initiatives to alleviate stress, mitigate burnout, and boost job satisfaction.

Advances in guided bone regeneration membranes: a comprehensive review of materials and techniques.

Guided tissue/bone regeneration (GTR/GBR) is a widely used technique in dentistry to facilitate the regeneration of damaged bone and tissue, which involves guiding materials that eventually degrade, allowing newly created tissue to take its place. This comprehensive review the evolution of biomaterials for guided bone regeneration that showcases a progressive shift from non-resorbable to highly biocompatible and bioactive materials, allowing for more effective and predictable bone regeneration. The evolution of biomaterials for guided bone regeneration GTR/GBR has marked a significant progression in regenerative dentistry and maxillofacial surgery. Biomaterials used in GBR have evolved over time to enhance biocompatibility, bioactivity, and efficacy in promoting bone growth and integration. This review also probes into several promising fabrication techniques like electrospinning and latest 3D printing fabrication techniques, which have shown potential in enhancing tissue and bone regeneration processes. Further, the challenges and future direction of GTR/GBR are explored and discussed.

Design and Characterization of Chitosan-Based Smart Injectable Hydrogel for Improved Sustained Release of Antinarcotics.

The treatment adherence of narcotics-addicted individuals with reduced incidences of relapse can be enhanced by a sustained drug release formulation of antinarcotics. So far, different drug formulations have been reported with sustained drug release periods of 28 and 35 days. To further enhance this duration, different formulations of injectable hydrogels (IHs) have been developed by combining low molecular weight (LMW) and high molecular weight (HMW) chitosan (CS) with guar gum (GG) and crosslinking them by sodium bi phosphate dibasic. The structural, morphological, and physicochemical properties of LMW-CS IH, and HMW-CS IH were evaluated using Fourier transform infrared spectroscopy (FT-IR), thermo-gravimetric analysis (TGA), scanning electron microscopy (SEM), and rheological, swelling, and biodegradation analysis. The HMW-CS IH showed high crosslinking, increased thermal stability, high mechanical strength, elevated swelling, and low biodegradation. The antinarcotic drugs naltrexone (NTX) and disulfiram (DSF) were loaded separately into the HMW-CS IH and LMW-CS IH. The release of NTX and DSF was investigated in phosphate buffer saline (PBS) and ethanol (0.3%, 0.4%, and 0.5%) over a 56-day period using an UV spectrophotometer. The drug release data were tested in zero-order, first-order, and Korsemeyer-Peppas mathematical models. In PBS, all prepared formulations followed non-Fickian drug release, while in ethanol, only NTX HMW-CS IH followed non-Fickian release in all three different concentrations of ethanol.

Fast-evolving cofactors regulate the role of HEATR5 complexes in intra-Golgi trafficking.

The highly conserved HEATR5 proteins are best known for their roles in membrane traffic mediated by the adaptor protein complex-1 (AP1). HEATR5 proteins rely on fast-evolving cofactors to bind to AP1. However, how HEATR5 proteins interact with these cofactors is unknown. Here, we report that the budding yeast HEATR5 protein, Laa1, functions in two biochemically distinct complexes. These complexes are defined by a pair of mutually exclusive Laa1-binding proteins, Laa2 and the previously uncharacterized Lft1/Yml037c. Despite limited sequence similarity, biochemical analysis and structure predictions indicate that Lft1 and Laa2 bind Laa1 via structurally similar mechanisms. Both Laa1 complexes function in intra-Golgi recycling. However, only the Laa2-Laa1 complex binds to AP1 and contributes to its localization. Finally, structure predictions indicate that human HEATR5 proteins bind to a pair of fast-evolving interacting partners via a mechanism similar to that observed in yeast. These results reveal mechanistic insight into how HEATR5 proteins bind their cofactors and indicate that Laa1 performs functions besides recruiting AP1.

(O-Methyl di-thio-carbonato-κS)tri-phenyl-tin(IV).

In the title compound, [Sn(C6H5)3(C2H3OS2)], the Sn(IV) atom adopts a distorted SnC3S tetra-hedral coordination geometry. A short Sn⋯O contact [2.988 (4) Å] is also present. The phenyl rings are each disordered over two sets of sites with an occupancy ratio of 0.550 (8):0.450 (8). The crystal studied was found to be a racemic twin with a twin component ratio of 0.57 (18):0.43 (18).

Zinc Ortho Methyl Carbonodithioate Improved Pre and Post-Synapse Memory Impairment via SIRT1/p-JNK Pathway against Scopolamine in Adult Mice.

Alzheimer's disease (AD) is globally recognized as a prominent cause of dementia for which efficient treatment is still lacking. New candidate compounds that are biologically potent are regularly tested. We, therefore, hypothesized to study the neuroprotective potential of Zinc Ortho Methyl Carbonodithioate (thereafter called ZOMEC) against Scopolamine (SCOP) induced Alzheimer's disease (AD) model using adult albino mice. We post-administered ZOMEC (30 mg/Kg) into two group of mice for three weeks on daily basis that received either 0.9% saline or SCOP (1 mg/Kg) for initial two weeks. The other two groups of mice received 0.9% saline and SCOP (1 mg/Kg) respectively. After memory related behavioral analysis the brain homogenates were evaluated for the antioxidant potential of ZOMEC and multiple protein markers were examined through western blotting. Our results provide enough evidences that ZOMEC decrease oxidative stress by increasing catalase (CAT) and glutathione S transferase (GST) and decreasing the lipid peroxidation (LPO). The SIRT1 and pre and post synaptic marker proteins, synaptophysin (SYP) as well as post synaptic density protein (PSD-95) expression were also enhanced upon ZOMEC treatment. Furthermore, memory impairment was rescued and ZOMEC appreciably abrogated the Aß accumulation, BACE1 expression C and the p-JNK pathway. The inflammatory protein markers, NF-kß and IL-1ß in ZOMEC treated mice were also comparable with control group. The predicted interaction of ZOMEC with SIRT1 was further confirmed by molecular docking. These findings thus provide initial reports on efficacy of ZOMEC in SCOP induced AD model.

Clarithromycin and Pantoprazole Gastro-Retentive Floating Bilayer Tablet for the Treatment of Helicobacter Pylori: Formulation and Characterization.

Bilayer/multilayer tablets have been introduced to formulate incompatible components for compound preparations, but they are now more commonly used to tailor drug release. This research aimed to formulate a novel gastro-retentive tablet to deliver a combination of a fixed dose of two drugs to eliminate Helicobacter pylori (H. pylori) in the gastrointestinal tract. The bilayer tablets were prepared by means of the direct compression technique. The controlled-release bilayer tablets were prepared using various hydrophilic swellable polymers (sodium alginate, chitosan, and HPMC-K15M) alone and in combination to investigate the percent of swelling behavior and average drug release. The weight of the controlled-release floating layer was 500 mg, whereas the weight of the floating tablets of pantoprazole was 100 mg. To develop the most-effective formulation, the effects of the experimental components on the floating lag time, the total floating time, T 50%, and the amount of drug release were investigated. The drugs' and excipients' compatibilities were evaluated using ATR-FTIR and DSC. Pre-compression and post-compression testing were carried out for the prepared tablets, and they were subjected to in vitro characterization studies. The pantoprazole layer of the prepared tablet demonstrated drug release (95%) in 2 h, whereas clarithromycin demonstrated sustained drug release (83%) for up to 24 h (F7). The present study concluded that the combination of sodium alginate, chitosan, and HPMC polymers (1:1:1) resulted in a gastro-retentive and controlled-release drug delivery system of the drug combination. Thus, the formulation of the floating bilayer tablets successfully resulted in a biphasic drug release. Moreover, the formulation (F7) offered the combination of two drugs in a single-tablet formulation containing various polymers (sodium alginate, chitosan, and HPMC polymers) as the best treatment option for local infections such as gastric ulcers.

Hydrophobic ammonium based ionic liquids for efficient extraction of textile dyes from aqueous media: Extraction study and antibacterial evaluation.

Alizarin red S (ARS) extraction from aqueous medium was carried out using hydrophobic ionic liquids (ILs) containing trioctylammonium cation paired with 4-tert-butylbenzoate ([TOA][Butbenz] (IL1), 4-phenylbutanoate ([TOA][PheBut] (IL2), 3-4-dimethylbenzoate ([TOA][DMbenz] (IL3), naphthoate, ([TOA][Naph]) (IL4), salicylate ([TOA][Sali]) (IL5) and nonanedioate ([TOA]2[Nona]) (IL6). The findings demonstrated that all of the tested ILs were efficient for extracting ARS, however, [TOA]2[Nona] was more effective than others. For the extraction of ARS from the aqueous phase, the effects of various parameters including the initial pH of the dye solution, contact time, ILs to dye volume ratio (VIL:VW), dye concentration, temperature, and salt effect were investigated. The spontaneity of the liquid-liquid extraction of ARS from the aqueous phase to the IL phase was confirmed by thermodynamic parameters. More than 90% of the ARS was extracted from the aqueous phase to the IL phase throughout all experiments. Interaction of selected IL with dyes were confirmed using FTIR analysis. The standard bacterial strains of Escherichia coli (E. coli) ATCC BAA-2471 (gram negative) and Methicillin-resistant Staphylococcus (MRSA) ATCC 43300 (gram positive) were used for evaluating antibacterial activity. The lower dose (250 ppm), the ILs1, 2, 3, 4, 5, and 6 inhibited 0.40, 1.50, 6.50, 1.50, 2.50, and 0.50 mm growth of E. coli, and 4.0, 2.0, 16.50, 0.40, 5.0, and 3.50 mm growth of MRSA, respectively. The experimental findings confirmed that the present ILs can be utilized as an effective solvent for ARS and other dyes extraction from aqueous media.

Classification, processing, and applications of bioink and 3D bioprinting: A detailed review.

With the advancement in 3D bioprinting technology, cell culture methods can design 3D environments which are both, complex and physiologically relevant. The main component in 3D bioprinting, bioink, can be split into various categories depending on the criterion of categorization. Although the choice of bioink and bioprinting process will vary greatly depending on the application, general features such as material properties, biological interaction, gelation, and viscosity are always important to consider. The foundation of 3D bioprinting is the exact layer-by-layer implantation of biological elements, biochemicals, and living cells with the spatial control of the implantation of functional elements onto the biofabricated 3D structure. Three basic strategies underlie the 3D bioprinting process: autonomous self-assembly, micro tissue building blocks, and biomimicry or biomimetics. Tissue engineering can benefit from 3D bioprinting in many ways, but there are still numerous obstacles to overcome before functional tissues can be produced and used in clinical settings. A better comprehension of the physiological characteristics of bioink materials and a higher level of ability to reproduce the intricate biologically mimicked and physiologically relevant 3D structures would be a significant improvement for 3D bioprinting to overcome the limitations.

Development of highly-reproducible hydrogel based bioink for regeneration of skin-tissues via 3-D bioprinting technology.

3-D Bioprinting is employed as a novel approach in biofabrication to promote skin regeneration following chronic-wounds and injury. A novel bioink composed of carbohydrazide crosslinked {polyethylene oxide-co- Chitosan-co- poly(methylmethacrylic-acid)} (PEO-CS-PMMA) laden with Nicotinamide and human dermal fibroblast was successfully synthesized via Free radical-copolymerization at 73 °C. The developed bioink was characterized in term of swelling, structural-confirmation by solid state 13C-Nuclear Magnetic Resonance (NMR), morphology, thermal, 3-D Bioprinting via extrusion, rheological and interaction with DNA respectively. The predominant rate of gelation was attributed to the electrostatic interactions between cationic CS and anionic PMMA pendant groups. The morphology of developed bioink presented a porous architecture satisfying the cell and growth-factor viability across the barrier. The thermal analysis revealed two-step degradation with 85 % weight loss in term of decomposition and molecular changes in the bioink moieties By applying low pressure in the range of 25-50 kPa, the optimum reproducibility and printability were determined at 37 °C in the viscosity range of 500-550 Pa. s. A higher survival rate of 92 % was observed for (PEO-CS-PMMA) in comparison to 67 % for pure chitosan built bioink. A binding constant of K ≈ 1.8 × 106 M-1 recognized a thermodynamically stable interaction of (PEO-CS-PMMA) with the Salmon-DNA. Further, the addition of PEO (5.0 %) was addressed with better self-healing and printability to produce skin-tissue constructs to replace the infected skin in human.

Two functionally distinct HEATR5 protein complexes are defined by fast-evolving co-factors in yeast.

The highly conserved HEATR5 proteins are best known for their roles in membrane traffic mediated by the adaptor protein complex-1 (AP1). HEATR5 proteins rely on fast-evolving co-factors to bind to AP1. However, how HEATR5 proteins interact with these co-factors is unknown. Here, we report that the budding yeast HEATR5 protein, Laa1, functions in two biochemically distinct complexes. These complexes are defined by a pair of mutually exclusive Laa1-binding proteins, Laa2 and the previously uncharacterized Lft1/Yml037c. Despite limited sequence similarity, biochemical analysis and structure predictions indicate that Lft1 and Laa2 bind Laa1 via structurally similar mechanisms. Both Laa1 complexes function in intra-Golgi recycling. However, only the Laa2-Laa1 complex binds to AP1 and contributes to its localization. Finally, structure predictions indicate that human HEATR5 proteins bind to a pair of fast-evolving interacting partners via a mechanism similar to that observed in yeast. These results reveal mechanistic insight into how HEATR5 proteins bind their co-factors and indicate that Laa1 performs functions besides recruiting AP1.

Herpes zoster vaccine awareness among people ≥ 50 years of age and its implications on immunization.

Herpes zoster (HZ) vaccine was recently approved for adults ≥ 50 years of age and has been shown to reduce the incidence of zoster, postherpetic neuralgia (PHN), and associated healthcare costs. However, currently HZ immunization is sub-optimal. We examined awareness of HZ and of the HZ vaccine. Information was gathered via a one-page survey given to patients ≥ 50 years of age presenting at the dermatology clinic. From the surveyed population of 1000 individuals, the HZ vaccination rate was 11.9 percent. Vaccination coverage was highest for the ≥ 70 age group (18.3%), followed by age groups 60-69 (8.9%) and 50-59 (1.4%). Individuals with female gender, older age (≥ 70 years), higher level of education (college and beyond), retired employment status, memory of chickenpox, knowledge of shingles, and history of shingles and influenza vaccination in the past year all were more likely to have heard of and have received the HZ vaccine (except female gender, education level, and awareness of shingles). Our study suggests lack of awareness to be a significant factor in non-immunization with zoster vaccine. Targeting adults in younger age groups and minorities would be beneficial towards increasing zoster vaccine awareness and thus preventing herpes zoster and its many complications.

Optimize PLA/EVA Polymers Blend Compositional Coating for Next Generation Biodegradable Drug-Eluting Stents.

In this research work, polymer blends of poly-lactic acid (PLA)/ethylene vinyl acetate (EVA) were prepared as the drug carrier materials for a bi-layer drug-loaded coating film for coronary stents. Different optimum compositions of blends were prepared by using an intense mixer. Then, the blends were hot-pressed and later cold-pressed to prepare for films of different thickness. The changes in weight, surface analysis and biodegradability with increasing time were studied using Scanning electron microscopy (SEM), weight loss and biodegradability tests. The mechanical and thermal properties of drug-loaded films were studied through universal testing machine (UTM) and thermo-gravimetric analysis (TGA). The effects of PLA, EVA and drug contents on in-vitro drug contents were investigated through the Ultraviolet-Visible Spectroscopy (UV-VIS) chemical analysis technique. The results obtained clearly showed that the addition of PLA promoted the unleashing of the drug whereas the addition of EVA nearly did not have the same affect. The mechanical properties of these various films can be tuned by adjusting the contents of blend parts. The factors affecting the unleashing of the drug became a serious matter of concern in evaluating the performance of bio-resorbable drug eluting stents. As a result, today's chemical blends may be useful drug carrier materials for drug-loaded tube coatings capable delivering purgative drug in an incredibly tunable and regulated manner.

Ferrocene-Based Terpolyamides and Their PDMS-Containing Block Copolymers: Synthesis and Physical Properties.

Aromatic polyamides are well-known as high-performance materials due to their outstanding properties making them useful in a wide range of applications. However, their limited solubility in common organic solvents restricts their processability and becomes a hurdle in their applicability. This study is focused on the synthesis of processable ferrocene-based terpolyamides and their polydimethylsiloxane (PDMS)-containing block copolymers, using low-temperature solution polycondensation methodology. All the synthesized materials were structurally characterized using FTIR and 1H NMR spectroscopic techniques. The ferrocene-based terpolymers and block copolymers were soluble in common organic solvents, while the organic analogs were found only soluble in sulfuric acid. WXRD analysis showed the amorphous nature of the materials, while the SEM analysis exposed the modified surface of the ferrocene-based block copolymers. The structure-property relationship of the materials was further elucidated by their water absorption and thermal behavior. These materials showed low to no water absorption along with their high limiting oxygen index (LOI) values depicting their good flame-retardant behavior. DFT studies also supported the role of various monomers in the polycondensation reaction where the electron pair donation from HOMO of diamine monomer to the LUMO of acyl chloride was predicted, along with the calculation of various other parameters of the representative terpolymers and block copolymers.

Ceramide-rich microdomains facilitate nuclear envelope budding for non-conventional exosome formation.

Neutrophils migrating towards chemoattractant gradients amplify their recruitment range by releasing the secondary chemoattractant leukotriene B4 (LTB4) refs. 1,2. We previously demonstrated that LTB4 and its synthesizing enzymes, 5-lipoxygenase (5-LO), 5-LO activating protein (FLAP) and leukotriene A4 hydrolase, are packaged and released in exosomes3. Here we report that the biogenesis of the LTB4-containing exosomes originates at the nuclear envelope (NE) of activated neutrophils. We show that the neutral sphingomyelinase 1 (nSMase1)-mediated generation of ceramide-enriched lipid-ordered microdomains initiates the clustering of the LTB4-synthesizing enzymes on the NE. We isolated and analysed exosomes from activated neutrophils and established that the FLAP/5-LO-positive exosome population is distinct from that of the CD63-positive exosome population. Furthermore, we observed a strong co-localization between ALIX and FLAP at the periphery of nuclei and within cytosolic vesicles. We propose that the initiation of NE curvature and bud formation is mediated by nSMase1-dependent ceramide generation, which leads to FLAP and ALIX recruitment. Together, these observations elucidate the mechanism for LTB4 secretion and identify a non-conventional pathway for exosome generation.

Trichobezoer: An Unusual Presentation with Congestive Heart Failure.

Description Trichobezoars are impactions of hair that accumulate in the gastrointestinal track and are most often located in the stomach. They are often associated with psychiatric illnesses like trichotillomania and trichophagia, which usually occurs in young and adolescent females. Gastric trichobezoars (GT) are the most common variety of bezoar found in the stomach. The most common complications that arise alongside GT include gastric erosion, ulceration or perforation of the small intestine. Gastric outlet obstruction, obstructive jaundice, pancreatitis and death have been reported, though these complications are rare. We report a 40-year-old female who presented to the hospital with dyspnea on exertion and ankle swellings. She also reported abdominal distension, a 40 pound weight loss, nausea and vomiting. Her examination was remarkable for sinus tachycardia, displaced apex beat and a split second sound. She was suspected of congestive heart failure. Upper endoscopy revealed a large trichobezoar in the antrum and the body of the stomach. She was found to be markedly anemic and in hypothyroid state. She underwent surgical removal of the GT subsequent to stabilization of heart failure. She later admitted to psychiatry a history of hair pulling and swallowing under stressful conditions.