Intellectual property management at the National Animal Science Research Institute in India: A case study.

Aim: The National Institute of Veterinary Epidemiology and Disease Informatics is an animal science research institute under the aegis of the Indian Council of Agricultural Research. The intellectual property management system (IPMS) of the institute oversees technology creation, protection, and transfer/commercialization. This study reviews the effectiveness of the IPMS using traditional strengths, weaknesses, opportunities, and threats (SWOT) evaluation.

Hydrogen bonds are a primary driving force for de novo protein folding. Corrigendum.

The paper by Lee et al. [(2017). Acta Cryst.

Unwinding of the Substrate Transmembrane Helix in Intramembrane Proteolysis.

Intramembrane-cleaving proteases (I-CLiPs) activate pools of single-pass helical membrane protein signaling precursors that are key in the physiology of prokaryotic and eukaryotic cells. Proteases typically cleave peptide bonds within extended or flexible regions of their substrates, and thus the mechanism underlying the ability of I-CLiPs to hydrolyze the presumably α-helical transmembrane domain (TMD) of these membrane proteins is unclear. Using deep-ultraviolet resonance Raman spectroscopy in combination with isotopic labeling, we show that although predominantly in canonical α-helical conformation, the TMD of the established I-CLiP substrate Gurken displays 3-helical geometry.

Hydrogen bonds are a primary driving force for de novo protein folding.

The protein-folding mechanism remains a major puzzle in life science. Purified soluble activation-induced cytidine deaminase (AID) is one of the most difficult proteins to obtain. Starting from inclusion bodies containing a C-terminally truncated version of AID (residues 1-153; AID), an optimized in vitro folding procedure was derived to obtain large amounts of AID, which led to crystals with good quality and to final structural determination.

A New Method to Determine the Transmembrane Conformation of Substrates in Intramembrane Proteolysis by Deep-UV Resonance Raman Spectroscopy.

We present a new method based on deep-UV resonance Raman spectroscopy to determine the backbone conformation of intramembrane protease substrates. The classical amide vibrational modes reporting on the conformation of just the transmembrane region of the substrate can be resolved from solvent exchangeable regions outside the detergent micelle by partial deuteration of the solvent. In the presence of isotopically triple-labeled intramembrane protease, these amide modes can be accurately measured to monitor the transmembrane conformation of the substrate during intramembrane proteolysis.

Insights into the aggregation mechanism of Aβ(25-40).

The hydrophobic fragment of the Alzheimer's related β-amyloid (Aβ) peptide, Aβ(25-40), aggregates and forms insoluble amyloid fibrils at a rate similar to the full-length peptide. In order to gain insight into the fibrillization of Aβ(25-40) and the ability of the flavonoid myricetin to inhibit its aggregation, the isoleucine at position 32 (I32A) and the glycine at position 37 (G37A) in the full-length peptide were replaced with alanine. Thioflavin T assays indicate that substitution of isoleucine for alanine significantly reduces the rate and extent of fibrillization compared to the Aβ(25-40) and G37A peptides.

"Parallel factor analysis of multi-excitation ultraviolet resonance Raman spectra for protein secondary structure determination".

Protein secondary structural analysis is important for understanding the relationship between protein structure and function, or more importantly how changes in structure relate to loss of function. The structurally sensitive protein vibrational modes (amide I, II, III and S) in deep-ultraviolet resonance Raman (DUVRR) spectra resulting from the backbone C-O and N-H vibrations make DUVRR a potentially powerful tool for studying secondary structure changes. Experimental studies reveal that the position and intensity of the four amide modes in DUVRR spectra of proteins are largely correlated with the varying fractions of α-helix, β-sheet and disordered structural content of proteins.

Arterial spin labeling perfusion cardiovascular magnetic resonance of the calf in peripheral arterial disease: cuff occlusion hyperemia vs exercise.

Background: Assessment of calf muscle perfusion requires a physiological challenge. Exercise and cuff-occlusion hyperemia are commonly used methods, but it has been unclear if one is superior to the other. We hypothesized that post-occlusion calf muscle perfusion (Cuff) with pulsed arterial spin labeling (PASL) cardiovascular magnetic resonance (CMR) at 3 Tesla (T) would yield greater perfusion and improved reproducibility compared to exercise hyperemia in studies of peripheral arterial disease (PAD).

Effects of fluidity on the ensemble structure of a membrane embedded α-helical peptide.

Melittin, the main hemolytic component of honeybee venom, is unfolded in an aqueous environment and folds into an α-helical conformation in a lipid environment. Membrane fluidity is known to affect the activity and structure of melittin. By combining two structurally sensitive optical methods, circular dichroism (CD) and deep-ultraviolet resonance Raman spectroscopy (dUVRR), we have identified distinct structural fluctuations in melittin correlated with increased and decreased 1,2-dimyristoyl-sn-glycero-3-phosphocholine bilayer fluidities.

Role of bilayer characteristics on the structural fate of aβ(1-40) and aβ(25-40).

The β-amyloid (Aβ) peptide is derived from the transmembrane (TM) helix of the amyloid precursor protein (APP) and has been shown to interact with membrane surfaces. To understand better the role of peptide-membrane interactions in cell death and ultimately in Alzheimer's disease, a better understanding of how membrane characteristics affect the binding, solvation, and secondary structure of Aβ is needed. Employing a combination of circular dichroism and deep-UV resonance Raman spectroscopies, Aβ(25-40) was found to fold spontaneously upon association with anionic lipid bilayers.

Bilayer surface association of the pHLIP peptide promotes extensive backbone desolvation and helically-constrained structures.

Despite their presence in many aspects of biology, the study of membrane proteins lags behind that of their soluble counterparts. Improving structural analysis of membrane proteins is essential. Deep-UV resonance Raman (DUVRR) spectroscopy is an emerging technique in this area and has demonstrated sensitivity to subtle structural transitions and changes in protein environment.

Observation of persistent α-helical content and discrete types of backbone disorder during a molten globule to ordered peptide transition via deep-UV resonance Raman spectroscopy.

The molten globule state can aide in the folding of a protein to a functional structure and is loosely defined as an increase in structural disorder with conservation of the ensemble secondary structure content. Simultaneous observation of persistent secondary structure content with increased disorder has remained experimentally problematic. As a consequence, modeling how the molten globule state remains stable and how it facilitates proper folding remains difficult due to a lack of amenable spectroscopic techniques to characterize this class of partially unfolded proteins.

Reproducibility of rest and exercise stress contrast-enhanced calf perfusion magnetic resonance imaging in peripheral arterial disease.

Background: The purpose was to determine the reproducibility and utility of rest, exercise, and perfusion reserve (PR) measures by contrast-enhanced (CE) calf perfusion magnetic resonance imaging (MRI) of the calf in normal subjects (NL) and patients with peripheral arterial disease (PAD).

Methods: Eleven PAD patients with claudication (ankle-brachial index 0.67 ±0.

Arterial spin labeling MR imaging reproducibly measures peak-exercise calf muscle perfusion: a study in patients with peripheral arterial disease and healthy volunteers.

Objectives: This study hypothesized that arterial spin labeling (ASL) magnetic resonance (MR) imaging at 3-T would be a reliable noncontrast technique for measuring peak exercise calf muscle blood flow in both healthy volunteers and patients with peripheral arterial disease (PAD) and will discriminate between these groups.

Background: Prior work demonstrated the utility of first-pass gadolinium-enhanced calf muscle perfusion MR imaging in patients with PAD. However, patients with PAD often have advanced renal disease and cannot receive gadolinium.

Comparison of methods for determining the partition coefficient of gadolinium in the myocardium using T1 mapping.

Purpose: To develop and validate modified Look-Locker (MOLLI) protocols to generate myocardial T1 maps within clinically acceptable breath-hold durations and to compare partition coefficients (λ) of gadolinium (Gd)-DTPA determined from either bolus injection (BI) or continuous infusion (CI) techniques.

Materials And Methods: T1 mapping was performed in phantoms and in 10 volunteers on a 1.5T scanner using the standard (3-3-5) MOLLI technique and two MOLLI schemes with shorter breath-hold durations.

Influence of the lipid environment on valinomycin structure and cation complex formation.

Carrier-type molecular ionophores, such as the cyclic dodecadepsipeptide valinomycin, often must undergo structural changes during the binding and transport of a cation across the lipid membrane. Observing the structural fluctuations that occur during this process experimentally has proven extremely difficult due to the complexities of spectroscopic analysis of protein structure/dynamics in native lipid bilayer environments. Currently, our understanding of how valinomycin selectively transports ions across membranes is derived from atomic structures solved of the cyclic macromolecule solvated in various organic solvents and complimentary in silico dynamics experiments.

Non-invasive imaging and monitoring cardiotoxicity of cancer therapeutic drugs.

Cardiotoxicity due to administration of cancer therapeutic agents such as anthracyclines and herceptin are well described. Established guidelines to screen for chemotherapy-related cardiotoxicity (CRC) are primarily based on serial assessment of left ventricular (LV) ejection fraction (EF). However, other parameters such as LV volume, diastolic function, and strain may also be useful in screening for cardiotoxicity.

Evolution of quantitative methods in protein secondary structure determination via deep-ultraviolet resonance Raman spectroscopy.

Deep-ultraviolet resonance Raman (DUVRR) spectra is sensitive to secondary structural motifs but, similar to circular dichroism (CD) and infrared spectroscopy, requires the application of multivariate and advanced statistical analysis methods to resolve the pure secondary structure Raman spectra (PSSRS) for determination of secondary structure composition. Secondary structure motifs are selectively enhanced by different excitation wavelengths, a characteristic that inspired the first methods for quantifying secondary structures by DUVRR. This review traces the evolution of multivariate methods and their application to secondary structure composition analyses of proteins by DUVRR spectroscopy from the first experiments using two-wavelengths, and culminating with recent studies utilizing time-resolved DUVRR measurements.

The effect of obesity on regadenoson-induced myocardial hyperemia: a quantitative magnetic resonance imaging study.

The A2(A) receptor agonist, regadenoson, is increasingly used as a vasodilator during nuclear myocardial perfusion imaging. Regadenoson is administered as a single, fixed dose. Given the frequency of obesity in patients with symptoms of heart disease, it is important to know whether the fixed dose of regadenoson produces maximal coronary hyperemia in subjects of widely varying body size.

Cardiovascular magnetic resonance: applications in daily practice.

Over the last 10 years, the development of newer pulse sequences and applications in new clinical areas has enabled cardiovascular magnetic resonance to emerge as a powerful tool for the physicians to both diagnose and guide treatments of various cardiac pathologies. The greatest strengths of cardiovascular magnetic resonance include the assessment of ischemia and viability, evaluation of nonischemic cardiomyopathies, including myocarditis, pericardial disease, congenital heart disease, and tissue characterization of cardiac masses.

Deep-UV resonance Raman analysis of the Rhodobacter capsulatus cytochrome bc₁complex reveals a potential marker for the transmembrane peptide backbone.

Classical strategies for structure analysis of proteins interacting with a lipid phase typically correlate ensemble secondary structure content measurements with changes in the spectroscopic responses of localized aromatic residues or reporter molecules to map regional solvent environments. Deep-UV resonance Raman (DUVRR) spectroscopy probes the vibrational modes of the peptide backbone itself, is very sensitive to the ensemble secondary structures of a protein, and has been shown to be sensitive to the extent of solvent interaction with the peptide backbone [ Wang , Y. , Purrello , R.

Spectroscopic detection of β -sheet structure in nascent Aβ oligomers.

Deep-UV resonance Raman (UVRR) spectroscopy and circular dichroism (CD) were employed to study the secondary structure of Aβ(1-42) in fresh samples with increasing fractions of oligomeric peptide. A feature with a minimum at ~217 nm appeared in CD spectra of samples containing oligomeric Aβ(1-42). UVRR spectra more closely resembled those of disordered proteins.

Resolution of localized small molecule-Aβ interactions by deep-ultraviolet resonance Raman spectroscopy.

The mechanism by which flavonoids prevent formation of amyloid-β (Aβ) fibrils, as well as how they associate with non-fibrillar Aβ is still unclear. Fresh, un-oxidized myricetin exhibited excitation and emission fluorescence maxima at 481 and 531 nm, respectively. Introduction of either Aβ(1-42) or Aβ(25-40) resulted in a fluorescence decrease, when measured at 481 nm, suggesting formation of a myricetin-Aβ complex.