Structural and biochemical characterisation of Co-binding sites on serum albumins and their interplay with fatty acids.

Serum albumin-Co interactions are of clinical importance. They play a role in mediating the physiological effects associated with cobalt toxicity and are central to the albumin cobalt binding (ACB) assay for diagnosis of myocardial ischemia. To further understand these processes, a deeper understanding of albumin-Co interactions is required.

An intuitionistic approach for the predictability of anti-angiogenic inhibitors in cancer diagnosis.

Malignant cancer angiogenesis has historically attracted enormous scientific attention. Although angiogenesis is requisite for a child's development and conducive to tissue homeostasis, it is deleterious when cancer lurks. Today, anti-angiogenic biomolecular receptor tyrosine kinase inhibitors (RTKIs) to target angiogenesis have been prolific in treating various carcinomas.

Optimised plasma sample preparation and LC-MS analysis to support large-scale proteomic analysis of clinical trial specimens: Application to the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) trial.

Purpose: Robust, affordable plasma proteomic biomarker workflows are needed for large-scale clinical studies. We evaluated aspects of sample preparation to allow liquid chromatography-mass spectrometry (LC-MS) analysis of more than 1500 samples from the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) trial of adults with type 2 diabetes.

Methods: Using LC-MS with data-independent acquisition we evaluated four variables: plasma protein depletion, EDTA or citrated anti-coagulant blood collection tubes, plasma lipid depletion strategies and plasma freeze-thaw cycles.

Identification of plasma proteins associated with oesophageal cancer chemotherapeutic treatment outcomes using SWATH-MS.

Oesophageal adenocarcinoma (OAC) is an aggressive cancer with a five-year survival of <15%. Current chemotherapeutic strategies only benefit a minority (20-30%) of patients and there are no methods available to differentiate between responders and non-responders. We performed quantitative proteomics using Sequential Window Acquisition of all THeoretical fragment-ion spectra-Mass Spectrometry (SWATH-MS) on albumin/IgG-depleted and non-depleted plasma samples from 23 patients with locally advanced OAC prior to treatment.

Fatty acids may influence insulin dynamics through modulation of albumin-Zn interactions.

Insulin is stored within the pancreas in an inactive Zn -bound hexameric form prior to release. Similarly, clinical insulins contain Zn and form multimeric complexes. Upon release from the pancreas or upon injection, insulin only becomes active once Zn disengages from the complex.

Prognostic features of the tumour microenvironment in oesophageal adenocarcinoma.

Oesophageal adenocarcinoma (OAC) is a disease with an incredibly poor survival rate and a complex makeup. The growth and spread of OAC tumours are profoundly influenced by their surrounding microenvironment and the properties of the tumour itself. Constant crosstalk between the tumour and its microenvironment is key to the survival of the tumour and ultimately the death of the patient.

Leptin and Obesity: Role and Clinical Implication.

The peptide hormone leptin regulates food intake, body mass, and reproductive function and plays a role in fetal growth, proinflammatory immune responses, angiogenesis and lipolysis. Leptin is a product of the obese () gene and, following synthesis and secretion from fat cells in white adipose tissue, binds to and activates its cognate receptor, the leptin receptor (LEP-R). LEP-R distribution facilitates leptin's pleiotropic effects, playing a crucial role in regulating body mass a negative feedback mechanism between adipose tissue and the hypothalamus.

Pulse Dipolar EPR Reveals Double-Histidine Motif Cu-NTA Spin-Labeling Robustness against Competitor Ions.

Pulse-dipolar EPR is an appealing strategy for structural characterization of complex systems in solution that complements other biophysical techniques. Significantly, the emergence of genetically encoded self-assembling spin labels exploiting exogenously introduced double-histidine motifs in conjunction with Cu-chelates offers high precision distance determination in systems nonpermissive to thiol-directed spin labeling. However, the noncovalency of this interaction exposes potential vulnerabilities to competition from adventitious divalent metal ions, and pH sensitivity.

Achilles Tendon Rupture: Can the Tendon Gap on Ultrasound Scan Predict the Outcome of Functional Rehabilitation Program?

Background and objectives  There is a growing use of functional rehabilitation programs for the treatment of Achilles tendon rupture. Factors such as patient age and level of activity have been used to guide the decision. One of the debated indications is the gap size between the ruptured ends of the tendon.

Quantitative proteomic changes in LPS-activated monocyte-derived dendritic cells: A SWATH-MS study.

Dendritic cells are key immune cells that respond to pathogens and co-ordinate many innate and adaptive immune responses. Quantitative mass spectrometry using Sequential Window Acquisition of all THeoretical fragment-ion spectra-Mass Spectrometry (SWATH-MS) was performed here to determine the global alterations in monocyte-derived dendritic cells (moDCs) in response to stimulation with lipopolysaccharide (LPS). A moDC library of 4,666 proteins was generated and proteins were quantified at 0, 6 and 24 h post-LPS stimulation using SWATH-MS.

Epistaxis as the initial presentation in a case of rheumatic heart disease.

Rheumatic heart disease (RHD) remains prevalent in developing nations and shows varied presentations, causing diagnostic challenge. Here, we report a case of RHD in a 13-year-old boy who presented with recurrent epistaxis as the initial symptom. On detailed work-up, echocardiography revealed the incidental finding of involvement of mitral and aortic valves but the patient never had any symptom as per the diagnostic criteria for RHD.

On the origin of proteins in human drusen: The meet, greet and stick hypothesis.

Retinal drusen formation is not only a clinical hallmark for the development of age-related macular degeneration (AMD) but also for other disorders, such as Alzheimer's disease and renal diseases. The initiation and growth of drusen is poorly understood. Attention has focused on lipids and minerals, but relatively little is known about the origin of drusen-associated proteins and how they are retained in the space between the basal lamina of the retinal pigment epithelium and the inner collagenous layer space (sub-RPE-BL space).

Crosstalk between zinc and free fatty acids in plasma.

In mammalian blood plasma, serum albumin acts as a transport protein for free fatty acids, other lipids and hydrophobic molecules including neurodegenerative peptides, and essential metal ions such as zinc to allow their systemic distribution. Importantly, binding of these chemically extremely diverse entities is not independent, but linked allosterically. One particularly intriguing allosteric link exists between free fatty acid and zinc binding.

Ischemia-modified albumin: Crosstalk between fatty acid and cobalt binding.

Myocardial ischemia is difficult to diagnose effectively with still few well-defined biochemical markers for identification in advance, or in the absence of myocardial necrosis. "Ischemia-modified albumin" (IMA), a form of albumin displaying reduced cobalt-binding affinity, is significantly elevated in ischemic patients, and the albumin cobalt-binding (ACB) assay can measure its level indirectly. Elucidating the molecular mechanism underlying the identity of IMA and the ACB assay hinges on understanding metal-binding properties of albumin.

Quantitative analysis of hydroxyapatite-binding plasma proteins in genotyped individuals with late-stage age-related macular degeneration.

Age-related macular degeneration (AMD) is associated with the formation of sub-retinal pigment epithelial (RPE) deposits that block circulatory exchange with the retina. The factors that contribute to deposit formation are not well understood. Recently, we identified the presence of spherular hydroxyapatite (HAP) structures within sub-RPE deposits to which several AMD-associated proteins were bound.

Arrhythmias and sudden death among older children and young adults following tetralogy of Fallot repair in the current era: are previously reported risk factors still applicable?

Background: Young adult patients (pts) with repaired tetralogy of Fallot (TOF) remain at risk for arrhythmias (Ar) and sudden cardiac death (SCD). Based on past studies with earlier pt subsets, Ar/SCD events were associated with right ventricular (RV) systolic pressures >60 mm Hg, outflow tract gradients >20 mm Hg, and QRS duration >180 ms. However, there are limited recent studies to evaluate these risk factors in the current patient generation.

Truncated hemoglobin, HbN, is post-translationally modified in Mycobacterium tuberculosis and modulates host-pathogen interactions during intracellular infection.

Mycobacterium tuberculosis (Mtb) is a phenomenally successful human pathogen having evolved mechanisms that allow it to survive within the hazardous environment of macrophages and establish long term, persistent infection in the host against the control of cell-mediated immunity. One such mechanism is mediated by the truncated hemoglobin, HbN, of Mtb that displays a potent O2-dependent nitric oxide dioxygenase activity and protects its host from the toxicity of macrophage-generated nitric oxide (NO). Here we demonstrate for the first time that HbN is post-translationally modified by glycosylation in Mtb and remains localized on the cell membrane and the cell wall.

Primary endocardial fibroelastosis presenting in a young child as incessant ventricular tachycardia and dilated cardiomyopathy.

Endocardial fibroelastosis is a cardiomyopathy not commonly seen in the present age. We describe the case of a 4-year-old girl who presented with sustained incessant ventricular tachycardia, a severely dilated left ventricle, and cardiac dysfunction refractory to all medical management and even to ablation; she eventually underwent cardiac transplantation. The diagnosis was made only after histopathologic examination of the explanted heart showed clear evidence of endocardial fibroelastosis.

Successful Ablation of Antero-septal Accessory Pathway in the Non-Coronary Cusp in a Child.

A 15-year-old boy with Wolff-Parkinson-White syndrome underwent an electrophysiology study for symptoms of palpitations and persistence of pre-excitation during peak exercise. He was detected to have right antero-septal accessory pathway with relatively long effective refractory period and no inducible tachycardia. He had only transient normalization with cryoablation.

Central venous catheter-associated pericardial tamponade in a 6-day old: a case report.

Introduction. Pericardial effusion (PCE) and tamponade can cause significant morbidity and mortality in neonates. Such cases have been reported in the literature in various contexts.

Role of Pre-A motif in nitric oxide scavenging by truncated hemoglobin, HbN, of Mycobacterium tuberculosis.

Mycobacterium tuberculosis truncated hemoglobin, HbN, is endowed with a potent nitric-oxide dioxygenase activity and has been found to relieve nitrosative stress and enhance in vivo survival of a heterologous host, Salmonella enterica Typhimurium, within the macrophages. These findings implicate involvement of HbN in the defense of M. tuberculosis against nitrosative stress.

Genetic relatedness of six North-Indian butterfly species (Lepidoptera :Pieridae) based on 16S rRNA sequence analysis.

The present work involves the assessment of level of genetic relatedness or divergence amongst the six North-Indian species of Lepidoptera belonging to family Pieridae and sub family Pierinae on the basis of sequence variation of 16S ribosomal RNA. The PCR amplified products of these species were directly sequenced using ABI Prism BigDye Terminator Sequencing Kits (Applied Biosystems). The multiple nucleotide sequence alignment analysis has revealed several differences across these species.