Structural Dynamics of Neutral Amino Acid Transporter SLC6A19 in Simple and Complex Lipid Bilayers.

B0AT1 (SLC6A19) is a major sodium-coupled neutral amino acid transporter that relies on angiotensin converting enzyme 2 (ACE2) or collectrin for membrane trafficking. Despite its significant role in disorders associated with amino acid metabolism, there is a deficit of comprehensive structure-function understanding of B0AT1 in lipid environment. Herein, we have employed molecular dynamics (MD) simulations to explore the architectural characteristics of B0AT1 in two distinct environments: a simplified POPC bilayer and a complex lipid system replicating the native membrane composition.

Type 2 Usher Syndrome - A Cause for Sensorineural Hearing Loss.

Usher syndrome is a genetic condition involving Sensorineural hearing loss and Retinitis pigmentosa (RP). Although considered a rare disease, it is the most frequent cause of deaf- blindness in humans. It is inherited in an autosomal recessive pattern.

Natural product-inspired [3 + 2] cycloaddition-based spirooxindoles as dual anticancer agents: synthesis, characterization, and biological evaluation by and methods.

Breast and colorectal cancers are the most common tumors, with high recurrence and low survival rates. We designed and synthesized a series of spirooxindole pyrrolidinyl derivatives, which were further evaluated for anti-proliferative activity using MDA-MB-468 and HCT 15 cell lines. The best inhibitor of this class, compound 6f, showed a very good inhibition potency, both on the MDA-MB-468 and HCT 15 cells as confirmed by molecular docking and molecular dynamic studies that predicted its binding mode into the active site of the targets.

From sugar binders to diabetes fighters: the lectin saga of antihyperglycemic activity through systematic review and meta-analysis.

Introduction: Lectins are carbohydrate-binding proteins that are extremely selective for sugar groups in the other molecules. As a result, they perform a variety of roles in biological processes involving cell, carbohydrate, and protein recognition at the cellular and molecular levels. Because lectins can bind to carbohydrates, they may play a role in determining the rate of carbohydrate digestion.

Identification of a novel, MSC-induced macrophage subtype via single-cell sequencing: implications for intervertebral disc degeneration therapy.

Intervertebral disc (IVD) degeneration is a common pathological condition associated with low back pain. Recent evidence suggests that mesenchymal signaling cells (MSCs) promote IVD regeneration, but underlying mechanisms remain poorly defined. One postulated mechanism is via modulation of macrophage phenotypes.

Synthesis, molecular docking, analgesic, anti-inflammatory, and ulcerogenic evaluation of thiophene-pyrazole candidates as COX, 5-LOX, and TNF-α inhibitors.

The thiophene bearing pyrazole derivatives (7a-j) were synthesized and examined for their in vitro cyclooxygenase, 5-lipoxygenase, and tumour inducing factor-α inhibitory activities followed by the in vivo analgesic, anti-inflammatory, and ulcerogenic evaluations. The synthesized series (7a-j) were characterized using H NMR, C NMR, FT-IR, and mass spectral analysis. Initially, the compounds (7a-j) were evaluated for their in vitro cyclooxygenase, 5-lipoxygenase, and tumour inducing factor-α inhibitory activities and the compound (7f) with two phenyl substituents in the pyrazole ring and chloro substituent in the thiophene ring and the compound (7g) with two phenyl substituents in the pyrazole ring and bromo substituent in the thiophene ring were observed as potent compounds among the series.

Protocol to identify multiple protein targets and therapeutic compounds using an in silico polypharmacological approach.

Polypharmacology aids in the identification of multiple protein targets involved in disease pathology and selecting appropriate therapeutic compounds interacting with protein targets. Here, we present a protocol to identify the targets involved in obesity-linked diabetes and suitable phytocompounds to bind with the identified target. We describe steps to install and use softwares for identifying several protein targets by linking multiple diseases.

A leaky integrate-and-fire computational model based on the connectome of the entire adult brain reveals insights into sensorimotor processing.

The forthcoming assembly of the adult central brain connectome, containing over 125,000 neurons and 50 million synaptic connections, provides a template for examining sensory processing throughout the brain. Here, we create a leaky integrate-and-fire computational model of the entire brain, based on neural connectivity and neurotransmitter identity, to study circuit properties of feeding and grooming behaviors. We show that activation of sugar-sensing or water-sensing gustatory neurons in the computational model accurately predicts neurons that respond to tastes and are required for feeding initiation.

Definition of Terms Used in Limitation of Treatment and Providing Palliative Care at the End of Life: The Indian Council of Medical Research Commission Report.

Background: Indian hospitals, in general, lack policies on the limitation of inappropriate life-sustaining interventions at the end of life. To facilitate discussion, preparation of guidelines and framing of laws, terminologies relating to the treatment limitation, and providing palliative care at the end-of-life care (EOLC) need to be defined and brought up to date.

Methodology: This consensus document on terminologies and definitions of terminologies was prepared under the aegis of the Indian Council of Medical Research.

Temporal Dilation of Animal Cardiac Recordings Registered to Human Torso Geometries.

Recordings of cardiac surface potentials from animal hearts can be mapped into human torso and used as source potentials for torso simulation. However, geometric registration of the heart can introduce changes in the effective conduction velocity due to change in relative positions of the recording sites. We developed a time dilation technique to ensure that adjusted cardiac potential recordings had physiological timing similar to human recordings after registration and corrected for conduction velocity.

Atypical carcinoid of larynx: a case study and a brief review.

Atypical Carcinoids, Malignancy arising from neuroendocrine cells are among the non-Epidermoid cancers of larynx.The present study reports an interesting and rare case of atypical carcinoid of larynx. An 85-year-old male patient presented with a history of dysphagia.

Formulary availability and regulatory barriers to accessibility of opioids for cancer pain in India: a report from the Global Opioid Policy Initiative (GOPI).

India is the world's largest democracy with control of opioids divided between the national and state governments. While the global consumption of opioids has increased, the consumption has not increased at the same rate. This is the first comprehensive study of opioid availability and accessibility for cancer patients in India.

Abrasion and fatigue resistance of PDMS containing multiblock polyurethanes after accelerated water exposure at elevated temperature.

Segmented polyurethane multiblock polymers containing polydimethylsiloxane and polyether soft segments form tough and easily processed thermoplastic elastomers (PDMS-urethanes). Two commercially available examples, PurSil 35 (denoted as P35) and Elast-Eon E2A (denoted as E2A), were evaluated for abrasion and fatigue resistance after immersion in 85 °C buffered water for up to 80 weeks. We previously reported that water exposure in these experiments resulted in a molar mass reduction, where the kinetics of the hydrolysis reaction is supported by a straight forward Arrhenius analysis over a range of accelerated temperatures (37-85 °C).

Networking of palliative care at the corporate level.

This article is a story of networking of palliative care at the corporate level. This gives an insight that if you have will and dedication then you can imagine and make it true that networking can start even before the birth of an organization.

Anterior-posterior asymmetry in iris mechanics measured by indentation.

Indentation and histological analysis of the porcine iris were done to assess the relative stiffness of the anterior (stroma) and posterior (dilator and sphincter) layers. The dimensions of the constituent structures were documented histologically by staining with a monoclonal anti-human α-smooth muscle actin antibody to determine the location of the stroma, sphincter, and dilator. Intact porcine irides (4-8 h post-mortem) were bisected into two equal C-shaped halves to indent both surfaces.

Poroviscoelastic cartilage properties in the mouse from indentation.

A method for fitting parameters in a poroviscoelastic (PVE) model of articular cartilage in the mouse is presented. Indentation is performed using two different sized indenters and then these data are fitted using a PVE finite element program and parameter extraction algorithm. Data from a smaller indenter, a 15 mum diameter flat-ended 60 deg cone, is first used to fit the viscoelastic (VE) parameters, on the basis that for this tip size the gel diffusion time (approximate time constant of the poroelastic (PE) response) is of the order of 0.

Effect of dermatan sulfate on the indentation and tensile properties of articular cartilage.

Objective: This paper examines the hypothesis that the dermatan sulfate (DS) chain on decorin is a load carrying element in cartilage and that its damage or removal will alter the material properties.

Methods: To test this hypothesis, indentation and tensile testing of cartilage from bovine patella were performed before and after digestion with chondroitinase B (cB). Removal of significant amounts of DS by cB digestion was verified by Western blot analysis of proteoglycans extracted from whole and sectioned specimens.

Photo-cross-linked hybrid polymer networks consisting of poly(propylene fumarate) and poly(caprolactone fumarate): controlled physical properties and regulated bone and nerve cell responses.

Aiming to achieve suitable polymeric biomaterials with controlled physical properties for hard and soft tissue replacements, we have developed a series of blends consisting of two photo-cross-linkable polymers: polypropylene fumarate (PPF) and polycaprolactone fumarate (PCLF). Physical properties of both un-cross-linked and UV cross-linked PPF/PCLF blends with PPF composition ranging from 0% to 100% have been investigated extensively. It has been found that the physical properties such as thermal, rheological, and mechanical properties could be modulated efficiently by varying the PPF composition in the blends.

Effect of indenter size on elastic modulus of cartilage measured by indentation.

Our preliminary indentation experiments showed that the equilibrium elastic modulus of murine tibial cartilage increased with decreasing indenter size: flat-ended 60 deg conical tips with end diameters of 15 microm and 90 microm gave 1.50+/-0.82 MPa (mean+/-standard deviation) and 0.

Evaluation of fracture toughness of cartilage by micropenetration.

Failure properties of cartilage are important in injury repair and disease, but few methods exist for measuring these properties, especially in small animals. To meet this need, a new indentation/penetration method for measuring fracture toughness of cartilage is proposed. During indentation, a conical tip is displaced into the surface of the cartilage, causing first a non-penetrating indentation, and then a penetration into the tissue.

A composites theory predicts the dependence of stiffness of cartilage culture tissues on collagen volume fraction.

The tensile stiffness of tissue grown from chondrocyte culture was both measured experimentally and predicted using a composites model theory relating tissue microstructure to macroscopic material stiffness. The tissue was altered by several treatment protocols to provide a wide range of collagen fibril volume fraction (0.015-0.

Results of 87 cases of intraocular lens implantation at the front of the whole capsular bag.

To prevent or delay Elschnig pearl formation, we performed an unusual surgical technique on 87 patients: intraocular lens implantation at the front of the whole capsular bag. We tried to obtain tight adhesion between the anterior and posterior capsules so the lens epithelial cells could not proliferate and form Elschnig pearls. In fact, the patients exhibited no Elschnig pearls or Soemmering's ring, but developed large anterior capsular folds and a multilayer cell membrane between both capsules after two (three cases), six (19 cases), and 12 months (14 cases).