The immunoglobulin A isotype of the Arabian camel () preserves the dualistic structure of unconventional single-domain and canonical heavy chains.

Introduction: The evolution of adaptive immunity in resulted in the concurrent expression of classic heterotetrameric and unconventional homodimeric heavy chain-only IgG antibodies. Heavy chain-only IgG bears a single variable domain and lacks the constant heavy (C) γ1 domain required for pairing with the light chain. It has not been reported whether this distinctive feature of IgG is also observed in the IgA isotype.

Partners in diabetes epidemic: A global perspective.

There is a recent increase in the worldwide prevalence of both obesity and diabetes. In this review we assessed insulin signaling, genetics, environment, lipid metabolism dysfunction and mitochondria as the major determinants in diabetes and to identify the potential mechanism of gut microbiota in diabetes diseases. We searched relevant articles, which have key information from laboratory experiments, epidemiological evidence, clinical trials, experimental models, meta-analysis and review articles, in PubMed, MEDLINE, EMBASE, Google scholars and Cochrane Controlled Trial Database.

Transcriptomal Insights of Heart Failure from Normality to Recovery.

Current management of heart failure (HF) is centred on modulating the progression of symptoms and severity of left ventricular dysfunction. However, specific understandings of genetic and molecular targets are needed for more precise treatments. To attain a clearer picture of this, we studied transcriptome changes in a chronic progressive HF model.

Toward allogenizing a xenograft: Xenogeneic cardiac scaffolds recellularized with human-induced pluripotent stem cells do not activate human naïve neutrophils.

The limited availability of human donor organs suitable for transplantation has resulted in ever-increasing patient waiting lists globally. Xenotransplantation is considered a potential option, but is yet to reach clinical practice. Although remarkable progress has been made in overcoming immunological rejection, issues with functionality are still to be resolved.

Review of Palliative Radiation Therapy Patterns of Practice for Adrenal Metastases in British Columbia.

Purpose: The adrenal gland is a common site of metastasis in patients with advanced cancer, but it is rarely symptomatic. A subset of patients develop a complex pain syndrome with anorexia, nausea, and poorly localized visceral pain in the back, flank, or epigastric region. These symptoms can affect quality of life and are occasionally challenging to palliate.

AGO2 Mediates mRNA Stability in Hepatocellular Carcinoma.

Deregulated RNA-binding proteins (RBP), such as Argonaute 2 (AGO2), mediate tumor-promoting transcriptomic changes during carcinogenesis, including hepatocellular carcinoma (HCC). While AGO2 is well characterized as a member of the RNA-induced silencing complex (RISC), which represses gene expression through miRNAs, its role as a bona fide RBP remains unclear. In this study, we investigated AGO2's role as an RBP that regulates the transcript to promote HCC.

Data on hypoxia-induced VEGF, leptin and NF-kB p65 expression.

The data set presented here is associated with the article "Intracellular calcium and NF-B regulate hypoxia-induced leptin, VEGF, IL-6 and adiponectin secretion in human adipocytes" (Al-Anazi et al., 2018). Data illustrate hypoxia-induced VEGF and leptin expression in human adipocytes treated with the calcium chelator BAPTA-AM (1 µM).

Intracellular calcium and NF-B regulate hypoxia-induced leptin, VEGF, IL-6 and adiponectin secretion in human adipocytes.

Aims: Hypoxia-induced adipokine release has been attributed mainly to HIF-1α. Here we investigate the role of intracellular calcium and NF-kB in the hypoxia-dependent release of leptin, VEGF, IL-6 and the hypoxia-induced inhibition of adiponectin release in human adipocytes.

Main Methods: We used intracellular calcium imaging to compare calcium status in preadipocytes and in adipocytes.

Defective lipid metabolism associated with mutation in and : important roles of essential dietary salts in fat storage.

Background: Dietary salts are important factors in metabolic disorders. They are vital components of enzymes, vitamins, hormones, and signal transduction that act synergistically to regulate lipid metabolism. Our previous studies have identified that Krüppel-like factor -3 (KLF-3) is an essential regulator of lipid metabolism.

Attenuation Limits Progression of -Induced Papillary Thyroid Cancer Cells and Sensitizes Them to BRAF Inhibitor PLX4720.

CYP24A1, the primary inactivating enzyme for vitamin D, is often overexpressed in human cancers, potentially neutralizing the antitumor effects of calcitriol, the active form of vitamin D. However, it is unclear whether CYP24A1 expression serves as a functional contributor versus only a biomarker for tumor progression. In this study, we investigated the role of CYP24A1 on malignant progression of a murine model of -induced papillary thyroid cancer (PTC).

IL-12 immunotherapy of Braf(V600E)-induced papillary thyroid cancer in a mouse model.

Papillary thyroid carcinoma (PTC) accounts for >80% thyroid malignancies, and BRAF(V600E) mutation is frequently found in >40% PTC. Interleukin-12 (IL-12) is a proinflammatory heterodimeric cytokine with strong antitumor activity. It is not known whether IL-12 immunotherapy is effective against Braf(V600E)-induced PTC.

TSH overcomes Braf(V600E)-induced senescence to promote tumor progression via downregulation of p53 expression in papillary thyroid cancer.

The BRAF(V600E) mutation is found in approximately 40% of papillary thyroid cancers (PTC). Mice with thyroid-specific expression of Braf(V600E) (TPO-Braf(V600E)) develop PTC rapidly with high levels of serum thyroid-stimulating hormone (TSH). It is unclear to what extent the elevated TSH contributes to tumor progression.

KRAS(G12D)-mediated oncogenic transformation of thyroid follicular cells requires long-term TSH stimulation and is regulated by SPRY1.

KRAS(G12D) can cause lung cancer rapidly, but is not sufficient to induce thyroid cancer. It is not clear whether long-term serum thyroid stimulating hormone (TSH) stimulation can promote KRAS(G12D)-mediated thyroid follicular cell transformation. In the present study, we investigated the effect of long-term TSH stimulation in KRAS(G12D) knock-in mice and the role of Sprouty1 (SPRY1) in KRAS(G12D)-mediated signaling.

Progression of matrixin and cardiokine expression patterns in an ovine model of heart failure and recovery.

Background: The molecular mechanisms underlying the geometrical changes of the left ventricle during the progression to heart failure and recovery are not well defined.

Objective: Here we investigate the involvement of matrixins and cardiokines in an ovine model of pressure-induced left ventricular failure (LVF).

Methods: Fifteen sheep underwent supracoronary aortic banding with an inflatable cuff.

Human cancer: is it linked to dysfunctional lipid metabolism?

Background: Lipid metabolism dysfunction leading to excess fat deposits (obesity) may cause tumor (cancer) development. Both obesity and cancer are the epicenter of important medical issues. Lipid metabolism and cell death/proliferation are controlled by biochemical and molecular pathways involving many proteins, and organelles; alteration in these pathways leads to fat accumulation or tumor growth.

Identification of the tetraspanin CD82 as a new barrier to xenotransplantation.

Significant immunological obstacles are to be negotiated before xenotransplantation becomes a clinical reality. An initial rejection of transplanted vascularized xenograft is attributed to Galα1,3Galβ1,4GlcNAc-R (Galα1,3-Gal)-dependent and -independent mechanisms. Hitherto, no receptor molecule has been identified that could account for Galα1,3-Gal-independent rejection.

Regulation of lipoprotein assembly, secretion and fatty acid β-oxidation by Krüppel-like transcription factor, klf-3.

Lipid metabolism is coordinately regulated through signaling networks that integrate biochemical pathways of fat assimilation, mobilization and utilization. Excessive diversion of fat for storage is a key risk factor for many fat-related human diseases. Dietary lipids are absorbed from the intestines and transported to various organs and tissues to provide energy and maintain lipid homeostasis.

A C. elegans model to study human metabolic regulation.

Lipid metabolic disorder is a critical risk factor for metabolic syndrome, triggering debilitating diseases like obesity and diabetes. Both obesity and diabetes are the epicenter of important medical issues, representing a major international public health threat. Accumulation of fat in adipose tissue, muscles and liver and/or the defects in their ability to metabolize fatty acids, results in insulin resistance.

Partner in fat metabolism: role of KLFs in fat burning and reproductive behavior.

The abnormalities caused by excess fat accumulation can result in pathological conditions which are linked to several interrelated diseases, such as cardiovascular disease and obesity. This set of conditions, known as metabolic syndrome, is a global pandemic of enormous medical, economic, and social concern affecting a significant portion of the world's population. Although genetics, physiology and environmental components play a major role in the onset of disease caused by excessive fat accumulation, little is known about how or to what extent each of these factors contributes to it.

Molecular characterization of a novel p.R118C mutation in the insulin receptor gene from patients with severe insulin resistance.

Context: Mutations of the insulin receptor gene (INSR) can cause genetic syndromes associated with severe insulin resistance.

Objectives: We aimed to analyse INSR mutations in Saudi patients with severe insulin resistance.

Design: Ten patients with Type A insulin resistance syndrome from five unrelated Saudi families were investigated.

Phylogenetically clustered extinction risks do not substantially prune the Tree of Life.

Anthropogenic activities have increased the rate of biological extinction many-fold. Recent empirical studies suggest that projected extinction may lead to extensive loss to the Tree of Life, much more than if extinction were random. One suggested cause is that extinction risk is heritable (phylogenetically patterned), such that entire higher groups will be lost.

Regulation of fat storage and reproduction by Krüppel-like transcription factor KLF3 and fat-associated genes in Caenorhabditis elegans.

Coordinated regulation of fat storage and utilization is essential for energy homeostasis, and its disruption is associated with metabolic syndrome and atherosclerosis in humans. Across species, Krüppel-like transcription factors (KLFs) have been identified as key components of adipogenesis. In humans, KLF14 acts as a master transregulator of adipose gene expression in type 2 diabetes and cis-acting expression quantitative trait locus associated with high-density lipoprotein cholesterol.

Mutation prediction by PolyPhen or functional assay, a detailed comparison of CYP27B1 missense mutations.

Vitamin D-dependent rickets type 1 (VDDR-I) is caused by mutation in CYP27B1. The glycine residue at codon 102 is not conserved between human (G(102)) and rodent (S(102)). G102E mutation results in 80% reduction in its enzymatic activity but PolyPhen predicts benign change.

Preliminary evaluation of two radioiodinated maleimide derivatives targeting peripheral and membrane sulfhydryl groups for in vitro cell labeling.

A factor impeding the advancement of cell mediated therapy is the inability to track these cells in vivo by noninvasive techniques. It has been shown that cells express high levels of sulfhydryl groups. We sought to explore these groups to covalently label cells with radiolabeled maleimide derivatives.

Biallelic p.R2223H mutation in the thyroglobulin gene causes thyroglobulin retention and severe hypothyroidism with subsequent development of thyroid carcinoma.

Context: Dyshormonogenesis due to genetic defect in thyroglobulin (Tg) synthesis and secretion can lead to congenital hypothyroidism.

Objectives: The aim of the study was to analyze the TG gene for the presence of mutations and to study the underlying mechanisms leading to dyshormonogenesis.

Cases: Two siblings aged 25 and 31 yr presented with recurrent goitrous hypothyroidism with undetectable serum Tg.