Selective interception of gelsolin amyloidogenic stretch results in conformationally distinct aggregates with reduced toxicity.

The pathogenesis of protein misfolding diseases is attributed to the cytotoxicity caused by amyloidogenic prefibrillar aggregates, rather than mature fibrils. The presence of one or more amyloidogenic stretches in different proteins has been proven critical for initiating fibril formation. In the present study, we show that two natural compounds, curcumin and emetine, bind tightly (Kd < 1.

Synthesis and characterization of Cu/Ag nanoparticle loaded mullite nanocomposite system: A potential candidate for antimicrobial and therapeutic applications.

Background: Microbial resistance to antibiotics has triggered the development of nanoscale materials as an alternative strategy. To stabilize these particles an inert support is needed.

Method: Porous nanomullite developed by sol-gel route is loaded with copper and silver nanoparticle by simple adsorption method.

Prestimulation phase predicts the TMS-evoked response.

Prestimulation oscillatory phase and power in particular frequency bands predict perception of at-threshold visual stimuli and of transcranial magnetic stimulation (TMS)-induced phosphenes. These effects may be due to changes in cortical excitability, such that certain ranges of power and/or phase values result in a state in which a particular brain area is more receptive to input, thereby biasing behavior. However, the effects of trial-by-trial fluctuations in phase and power of ongoing oscillations on the brain's electrical response to TMS itself have thus far not been addressed.

Isolation and processing of silk proteins for biomedical applications.

Silk proteins of silkworms are chiefly composed of core fibroin protein and glycoprotein sericin that glues fibroin. Unique mechanical properties, cyto-compatibility and controllable biodegradability facilitate the use of fibroin in biomedical applications. Sericin serves as additive in cosmetic and food industries, as mitotic factor in cell culture media, anti-cancerous drug, anticoagulant and as biocompatible coating.

Thromboelastometric and platelet responses to silk biomaterials.

Silkworm's silk is natural biopolymer with unique properties including mechanical robustness, all aqueous base processing and ease in fabrication into different multifunctional templates. Additionally, the nonmulberry silks have cell adhesion promoting tri-peptide (RGD) sequences, which make it an immensely potential platform for regenerative medicine. The compatibility of nonmulberry silk with human blood is still elusive; thereby, restricts its further application as implants.

Optimization of a Model Corrected Blood Input Function from Dynamic FDG-PET Images of Small Animal Heart .

Quantitative evaluation of dynamic Positron Emission Tomography (PET) of mouse heart in vivo is challenging due to the small size of the heart and limited intrinsic spatial resolution of the PET scanner. Here, we optimized a compartment model which can simultaneously correct for spill over and partial volume effects for both blood pool and the myocardium, compute kinetic rate parameters and generate model corrected blood input function (MCBIF) from ordered subset expectation maximization - maximum a posteriori (OSEM-MAP) cardiac and respiratory gated F-FDG PET images of mouse heart with attenuation correction in vivo, without any invasive blood sampling. Arterial blood samples were collected from a single mouse to indicate the feasibility of the proposed method.

Diversity-oriented synthesis of ketoindoloquinoxalines and indolotriazoloquinoxalines from 1-(2-nitroaryl)-2-alkynylindoles.

A one-pot protocol for the diversity-oriented synthesis of two indole-based annulated polyheterocycles, ketoindoloquinoxalines and indolotriazoloquinoxalines, has been described. The salient features of the methodology involves either a metal/O2-catalyzed aminooxygenation or a [3 + 2] cycloaddition pathway.

Trait-like differences in underlying oscillatory state predict individual differences in the TMS-evoked response.

Background: Combined transcranial magnetic stimulation (TMS) and electroencephalography (EEG) can provide insights into how differing cognitive contexts produce different brain states, through TMS-based measures of effective connectivity. For instance, in a recent study, the amplitude of the TMS-evoked response (TMS-ER) derived during the delay-period of a spatial short-term memory (STM) task had a larger amplitude, and greater spread to distal cortical areas, than the TMS-ER from a fixation condition (Johnson et al. J Neurophysiol, 2012).

Osteochondral tissue engineering in vivo: a comparative study using layered silk fibroin scaffolds from mulberry and nonmulberry silkworms.

The ability to treat osteochondral defects is a major clinical need. Existing polymer systems cannot address the simultaneous requirements of regenerating bone and cartilage tissues together. The challenge still lies on how to improve the integration of newly formed tissue with the surrounding tissues and the cartilage-bone interface.

Synthesis of triazolo isoquinolines and isochromenes from 2-alkynylbenzaldehyde via domino reactions under transition-metal-free conditions.

We describe two simple straightforward syntheses of triazolo isoquinolines (3) and isochromenes (7) from 2-alkynylbenzaldehydes (1) as a common synthon. The synthetic strategy for 3 involves formation of the (E)-1-(2-nitrovinyl)-2-(alkynyl)benzene species 2 via condensation of synthon 1 with nitromethane followed by a [3 + 2] cycloaddition/extrusion of the nitro group/regioselective 6-endo cyclization domino sequence. In yet another strategy, the synthon 1 was condensed with nitromethane followed by electrophilic iodo cyclization of the resulting 2-nitro-1-(2-(alkynyl)phenyl)ethanol (6) to furnish iodo isochromene derivatives.

A study on drug utilization and prescription habits of physicians in a government homeopathic hospital in West Bengal, India.

Objective: Improper prescribing habits and inappropriate drug use lead to serious health and economic consequences. This study was undertaken to evaluate drug utilization services and prescription patterns of homeopathic doctors in a government homeopathic teaching hospital in India.

Methods: No standardized homeopathic drug use indicators are available.

A silk fibroin based hepatocarcinoma model and the assessment of the drug response in hyaluronan-binding protein 1 overexpressed HepG2 cells.

Microenvironment around tumor cells plays an important role in its malignancy or invasiveness. Hyaluronan (HA), a major component of extracellular matrix is found to be elevated in most of cancerous niche/microenvironment and performs regulatory role in the progression of tumors and metastasis. Overexpression of the hyaladherin, hyaluronan-binding protein 1 (HABP1) in the hepatocarcinoma cells (HepG2) termed as HepR21 leads to enhanced cell proliferation with increased HA 'pool' associated with HA 'cables' indicating elevated tumorous potential under 2D culture conditions.

Bio-inspired fabrication of fibroin cryogels from the muga silkworm Antheraea assamensis for liver tissue engineering.

Conventional scaffold fabrication techniques result in narrow pore architectures causing a limited interconnectivity and use of porogens, which affects the bio- or cyto-compatibility. To ameliorate this, cryogels are immensely explored due to their macro-porous nature, ease in fabrication, using ice crystals as porogens, the shape property, easy reproducibility and cost-effective fabrication technique. Cryogels in the present study are prepared from nonmulberry Indian muga silk gland protein fibroin of Antheraea assamensis using two different fabrication temperatures (-20 and -80 °C).

Systematic approach to treat chronic osteomyelitis through localized drug delivery system: bench to bed side.

Chronic osteomyelitis is a challenging setback to the orthopedic surgeons in deciding an optimal therapeutic strategy. Conversely, patients feel frustrated of the therapeutic outcomes and development of adverse drug effects, if any. Present investigation deals with extensive approach incorporating in vivo animal experimentation and human application to treat chronic osteomyelitis, using antibiotic loaded porous hydroxyapatite scaffolds.

Counter ion effect in Au/Ag-catalyzed chemoselective 6-endo-dig N- and O-cyclizations of enyne-urea system: diversity-oriented synthesis of annulated indoles.

A two-step protocol for the diversity-oriented synthesis of annulated indoles following MCR-post MCR modification concept is described. The reaction initially proceeds through the annulation of 2-(2,2-dibromovinyl)aniline, an isocyanate, and a terminal alkyne in a three-component tandem format via Cu/Pd-catalyzed cross coupling to afford N-1 and C-2 functionalized indole. In the subsequent step, the enyne-urea derivative undergoes chemo- and regioselective 6-endo cyclization to afford O-cyclized product in the presence of Au(I)/AgNO3 and N-cyclized product in the presence of Au(I)/AgOTf under a post-MCR modification step.

Thermodynamic stabilization of the folded domain of prion protein inhibits prion infection in vivo.

Prion diseases, or transmissible spongiform encephalopathies (TSEs), are associated with the conformational conversion of the cellular prion protein, PrP(C), into a protease-resistant form, PrP(Sc). Here, we show that mutation-induced thermodynamic stabilization of the folded, α-helical domain of PrP(C) has a dramatic inhibitory effect on the conformational conversion of prion protein in vitro, as well as on the propagation of TSE disease in vivo. Transgenic mice expressing a human prion protein variant with increased thermodynamic stability were found to be much more resistant to infection with the TSE agent than those expressing wild-type human prion protein, in both the primary passage and three subsequent subpassages.

Protein growth factors loaded highly porous chitosan scaffold: a comparison of bone healing properties.

Present study aimed to investigate and compare effectiveness of porous chitosan alone and in combination with insulin like growth factor-1 (IGF-1) and bone morphogenetic protein-2 (BMP-2) in bone healing. Highly porous (85±2%) with wide distribution of macroporous (70-900 μm) chitosan scaffolds were fabricated as bone substitutes by employing a simple liquid hardening method using 2% (w/v) chitosan suspension. IGF-1 and BMP-2 were infiltrated using vacuum infiltration with freeze drying method.

Gold-catalyzed sequential alkyne activation: one-pot synthesis of NH-carbazoles via cascade hydroarylation of alkyne/6-endo-dig carbocyclization reactions.

A simple and efficient one-pot protocol for the synthesis of NH-carbazoles has been described. The strategy comprises a one-pot reaction involving the treatment of 2-alkynyl indoles with arylacetylenes in the presence of an Au-Ag combination catalyst. The salient feature of the strategy involves sequential activation of terminal and internal alkynes leading to the cascade hydroarylation of terminal alkynes and 6-endo-dig carbocyclization reactions.

Glucose regulation of load-induced mTOR signaling and ER stress in mammalian heart.

Background: Changes in energy substrate metabolism are first responders to hemodynamic stress in the heart. We have previously shown that hexose-6-phosphate levels regulate mammalian target of rapamycin (mTOR) activation in response to insulin. We now tested the hypothesis that inotropic stimulation and increased afterload also regulate mTOR activation via glucose 6-phosphate (G6P) accumulation.

Strengthened effective connectivity underlies transfer of working memory training to tests of short-term memory and attention.

Although long considered a natively endowed and fixed trait, working memory (WM) ability has recently been shown to improve with intensive training. What remains controversial and poorly understood, however, are the neural bases of these training effects and the extent to which WM training gains transfer to other cognitive tasks. Here we present evidence from human electrophysiology (EEG) and simultaneous transcranial magnetic stimulation and EEG that the transfer of WM training to other cognitive tasks is supported by changes in task-related effective connectivity in frontoparietal and parieto-occipital networks that are engaged by both the trained and transfer tasks.

Diagnosing the SAPHO syndrome: a report of three cases and review of literature.

SAPHO, an acronym for synovitis, acne, pustulosis, hyperostosis and osteitis, is a heterogeneous entity with myriad presentations and features overlapping with other entities. It is a differential in patients presenting with skin and bone symptoms, either singly or in combination. Often misdiagnosed radiologically as a malignancy or infection, the diagnosis is seldom thought of.

N-terminal domain of Pyrococcus furiosus l-asparaginase functions as a non-specific, stable, molecular chaperone.

The enzyme l-asparaginase of Pyrococcus furiosus (PfA) functions as a dimer with each monomer consisting of distinct N- and C-terminal domains (NPfA and CPfA, respectively), connected by a linker. Here we present data to show that NPfA functions as a non-specific molecular chaperone. Independently expressed NPfA refolded spontaneously whereas CPfA formed insoluble aggregates.

The role of secondary motor and language cortices in morbidity and mortality: a retrospective functional MRI study of surgical planning for patients with intracranial tumors.

Object: Functional MRI (fMRI) is commonly used by neurosurgeons preoperatively to identify brain regions associated with essential behaviors, such as language and motor abilities. In this study the authors investigated the relationship between patient morbidity and mortality and the distance from the tumor border area to functional activations in secondary motor and language cortices.

Methods: Patients with primary or metastatic brain tumors who underwent preoperative fMRI motor and language mapping were selected from a large database of patients with tumors.

Association of functional magnetic resonance imaging indices with postoperative language outcomes in patients with primary brain tumors.

Object: Functional MRI (fMRI) has the potential to be a useful presurgical planning tool to treat patients with primary brain tumor. In this study the authors retrospectively explored relationships between language-related postoperative outcomes in such patients and multiple factors, including measures estimated from task fMRI maps (proximity of lesion to functional activation area, or lesion-to-activation distance [LAD], and activation-based language lateralization, or lateralization index [LI]) used in the clinical setting for presurgical planning, as well as other factors such as patient age, patient sex, tumor grade, and tumor volume.

Methods: Patient information was drawn from a database of patients with brain tumors who had undergone preoperative fMRI-based language mapping of the Broca and Wernicke areas.

Microwave-assisted three-component domino reaction: Synthesis of indolodiazepinotriazoles.

A microwave-assisted three-component protocol involving N-1 alkylation of 2-alkynylindoles with epichlorohydrin, ring opening of the epoxide with sodium azide, and an intramolecular Huisgen azide-internal alkyne 1,3-dipolar cycloaddition domino sequence has been described. The efficacy of the methodology has been demonstrated by treating various 2-alkynylindoles (aromatic/aliphatic) with epichlorohydrin and sodium azide furnishing annulated tetracyclic indolodiazepinotriazoles in satisfactory yields.