Structure Prediction and Functional Characterization of ERG Proteins Involved in Ergosterol Biosynthetic Pathway of Candida albicans

The ERG proteins and enzymes of the ergosterol biosynthetic pathway has been the subject of intensive investigation as a target for several classes of antifungal agents used to treat C. albicans infection. Over the past few decades, a number of drugs and inhibitors with wide spectrum of activity, low toxicity and defined targets have been introduced. Several lines of evidence suggest that allylamines targets squalene epoxidase (ERG1), morpholines affects sterol C8-C7 isomerase (ERG2) and sterol reductase (ERG24), azoles inhibits a cytochrome P450 (ERG11) responsible for the 14 α-demethylation of lanosterol and C-5 sterol desaturase (ERG3) and polyenes binds to ergosterol that leads to the damage of cell plasma membrane, ensuing in leakage of intracellular ions. However, little information about the experimental structure (X-ray and NMR) of proteins from ergosterol biosynthetic pathway is available in RCSB Protein Databank (PDB). Since ERG proteins play a key role in metabolic pathway of ergosterol, their 3D structures are essential to determine most of their functions. Homology modeling approach was employed for comparative modeling. Modeller 9v7 and I-Tasser programs were utilized to serve our purpose. The modeled proteins were further validated by Procheck, Verify-3D, ERRAT and PROVE servers. Expasy’s Prot-param server and Cys_rec tool was used for physico-chemical and functional characterization of these proteins. Studies of secondary structure of these proteins were carried out using computational program, Profunc. Swiss-pdb viewer was used to visualize and analyze homology derived structures. The modeled structures of 12 ERG proteins have been submitted and are available in Protein Model Database (PMDB) so that they become accessible to other users for further studies

A Case of Trichotillomania With Comorbid Depression And Anxiety

BACKGROUND: Trichotillomania also called hair-pulling or compulsive hair-pulling disorder is a psychiatric condition that involves recurrent, irresistible urges to pull out hair from their scalps, eyebrows, or other areas of the body.[1] It is an uncontrollable urge that is present after an anxiety-provoking situation and which causes severe distress it can interfere with one’s social, occupational functioning.[6] The term trichotillomania was coined by the French dermatologist Francois Henri Hallopeou in the year 1889.[2] The lifetime prevalence of trichotillomania is estimated to be between 0.6% and 4.0% of the overall population with a 1% prevalence in gender-wise.[5] The mean age at diagnosis is between 9 and 13 years, the symptoms can be pulling out hair repeatedly breaking off pieces of hair, eating or keeping hair, feeling relieved after pulling hair.[2]. Associated symptoms included sadness, lack of attention and concentration, lack of interest in doing daily activities, which affect the socio- functional aspects of the person. The comorbid conditions or the distress is mainly leading the person for consultation in ICD-10 and DSM IV, trichotillomania is classified under impulse control disorder in DSM V it is under obsessive-compulsive and related disorders. [1] CASE DESCRIPTION: A 20-year-old adult female was referred from the Department of Dermatology presented with a history of hair pulling, hair loss and anxiety, sadness related to her hair-pulling behavior. She had these symptoms for the past 4 years. The reason for referral was that the comorbid anxiety, and their history taking suggestive of hair pulling associated with anxiety. After collecting the detailed history and psychological assessment, it was confirmed as a case of Trichotillomania, the comorbid condition are depression and anxiety. CONCLUSIONS: This case report presents trichotillomania the assessment indicated as a moderate level of anxiety and depression, so it is very essential for a detailed investigation, and also both pharmacotherapy and psychotherapy are very essential for the complete recovery of the patient

Biochemical Effects of Exercise on a Fasciocutaneous Flap in a Rat Model.

Importance: An overwhelming amount of data suggest that cardiovascular exercise has a positive effect on the mind and body, although the precise mechanism is not always clear. Objective: To assess the clinical and biochemical effects of voluntary cardiovascular exercise on pedicled flaps in a rodent model. Design, Setting, and Participants: Eighteen adult Sprague-Dawley male rats were randomized into a resting animal group (RAG) (n=9) and an exercise animal group (EAG) (n=9) for 14 days (July 23, 2013, through July 30, 2013). A pedicled transposition flap was performed on the ventral surface of the rat, and biopsy specimens were taken from the proximal, middle, and distal portions on postoperative days 0, 2, 5, and 9. Flap survival was analyzed planimetrically, and biopsy specimens were analyzed by hematoxylin-eosin-stained microscopy and immunoblotting. The housing, exercise, surgery, and analysis of the rats were conducted at a single basic science research laboratory at the tertiary care center campus of Thomas Jefferson University in Philadelphia, Pennsylvania. Exposures: The rats were caged for 14 days or housed in a cage connected to an exercise wheel and pedometer. Main Outcomes and Measures: Study measures were gross and micrographic necrosis and expression of proteins within cell survival and apoptosis pathways. Results: A total of 18 rats were studied, 9 in the RAG and 9 in the EAG. the mean (SEM) amount of necrosis in flaps was 41.3% (3%) in the RAG rats and 10.5% (3.5%) in the EAG rats (P \u3c .001). Immunoblotting revealed increased Caspase-9 activity resulting in poly-(adenosine diphosphate-ribose) polymerase 1 cleavage in the RAG vs the EAG, as well as lower phosphorylated protein kinase B (also known as Akt), signal transducer and activator of transcription 3, and total B-cell leukemia/lymphoma 2 protein levels. Throughout the postoperative period, the cumulative vascular endothelial growth factor A levels of the EAG flaps were significantly higher than those of the RAG flaps (2.30 vs 1.25 fold induction [FI], P = .002), with differences of 2.76 vs 1.54 FI in the proximal segment, 2.40 vs 1.20 FI in the middle segment, and 1.90 vs 0.79 FI in the distal segment. A similar response was noted when comparing phosphorylated Akt, with cumulative mean (SEM) p-Akt expression levels of 0.62 (0.04) for RAG and 1.98 (0.09) for EAG (P = .002 between the 2 groups). Conclusions and Relevance: Voluntary preoperative exercise improves survival in pedicled fasciocutaneous flaps; the EAG rats had less necrosis, decreased apoptotic markers, and increased amounts of vascular endothelial growth factor A and prosurvival proteins. These results have implications to increase flap survival in other mammal populations, such as humans. Level of Evidence: 3

Implementing a Neonatal Hypoglycemia Procedure with Glucose Gel

https://digitalcommons.psjhealth.org/summit_all/1064/thumbnail.jp

PhytoAFP: In Silico Approaches for Designing Plant-Derived Antifungal Peptides

Emerging infectious diseases (EID) are serious problems caused by fungi in humans and plant species. They are a severe threat to food security worldwide. In our current work, we have developed a support vector machine (SVM)-based model that attempts to design and predict therapeutic plant-derived antifungal peptides (PhytoAFP). The residue composition analysis shows the preference of C, G, K, R, and S amino acids. Position preference analysis shows that residues G, K, R, and A dominate the N-terminal. Similarly, residues N, S, C, and G prefer the C-terminal. Motif analysis reveals the presence of motifs like NYVF, NYVFP, YVFP, NYVFPA, and VFPA. We have developed two models using various input functions such as mono-, di-, and tripeptide composition, as well as binary, hybrid, and physiochemical properties, based on methods that are applied to the main data set. The TPC-based monopeptide composition model achieved more accuracy, 94.4%, with a Matthews correlation coefficient (MCC) of 0.89. Correspondingly, the second-best model based on dipeptides achieved an accuracy of 94.28% under the MCC 0.89 of the training dataset

Physicochemical Characterization, Molecular Docking, and In Vitro Dissolution of GlimepirideCaptisol Inclusion Complexes

This present study investigated the effect of Captisol, a chemically modified cyclodextrin, on the in vitro dissolution of glimepiride. We prepared glimepirideCaptisol complexes of different mass ratios (1:1, 1:2, and 1:3 w/w) by a physical mixing or freeze-drying technique, and found that complexation with Captisol enhanced the water solubility of glimepiride. Molecular docking and dynamic simulation predicted complex formation; at the same time, Fourier transform infrared spectroscopy, differential scanning calorimetry, powder X-ray diffractometry, and scanning electron microscope indicated molecular interactions that support complexation. We also found that an inclusion complex was better than a physical mixture in enhancing the complexation of glimepiride with Captisol and enhancing water solubility. Phase solubility study of the glimepirideCaptisol complex showed an AL-type profile, implying the formation of a 1:1 inclusion complex. The study also revealed that pH influenced the stability of the complex because the stability constant of the glimepirideCaptisol complex was higher in distilled water of pH 6.0 than in phosphate buffer of pH 7.2

Electrospinning over Solvent Casting: Tuning of Mechanical Properties of Membranes

We put forth our opinion regarding the enhanced plasticity and modulation of mechanical properties of polymeric films obtained through electrospinning process in this article. In majority of the pharmaceutical, biomedical, and packaging applications, it is desirable that polymer based matrices should be soft, flexible, and have a moderate toughness. In order to convert inflexible and brittle polymers, adjuvants in the form of plasticizers are added to improve the flexibility and smoothness of solvent casted polymer films. However, many of these plasticizers are under scrutiny for their toxic effects and environmental hazards. In addition, plasticizers also increase the cost of end products. This has motivated the scientific community to investigate alternate approaches. The changes imparted in membrane casted by electrospinning were tried to be proved by SEM, Mechanical property study, DSC and XRD studies. We have showed dramatic improvement in flexibility of poly(ε-caprolactone) based nanofiber matrix prepared by electrospinning method whereas solvent casting method without any plasticizer produced very brittle, inflexible film of PCL. Modulation capacity of mechanical properties is also recorded. We tried to support our opinion by citing several similar findings available in the open literature. The electrospinning method helps in plasticization and in tuning mechanical properties