Disorder in milk proteins: adipophilin and TIP47, important constituents of the milk fat globule membrane.

Milk fat globules (MFGs), which are secreted by the epithelial cells of the lactating mammary glands, account for the most of the nutritional value of milk. They are enveloped by the milk fat globule membrane (MFGM), a complex structure consisting of three phospholipid membrane monolayers and containing various lipids. Depending on the origin of milk, specific proteins accounts for 5-70% of the MFGM mass.

Correction to: Variability of Some Milk-Associated Genes and Proteins in Several Breeds of Saudi Arabian Camels.

The original version of this article contained mistakes in author names and affiliations. The last names of the authors Salah Korim, Amro Samra, and Hussein A. Amhedar were misspelled.

Variability of Some Milk-Associated Genes and Proteins in Several Breeds of Saudi Arabian Camels.

To gain knowledge on the molecular basis of diversity of several clans of Saudi camel (Camelus dromedarius) characterization of these animals was conducted at both genetic and protein levels. To this end, blood and milk samples were collected from several camel breeds at different Saudi Arabia locations (northern Jeddah, Riyadh, and Alwagh governorates). Genomic DNA was extracted from blood of four Saudi camel breeds (Majahem, Safra, Wadha, and Hamara), and DNA fragments of the casein and α-lactalbumin genes were amplified.

Transcription factors STAT6 and KLF4 implement macrophage polarization via the dual catalytic powers of MCPIP.

Macrophage polarization plays a critical role in tissue homeostasis, disease pathogenesis, and inflammation and its resolution. IL-4-induced macrophage polarization involves induction of STAT6 and Krüppel-like factor 4 (KLF4), which induce each other and promote M2 polarization. However, how these transcription factors implement M2 polarization is not understood.

Antidicer RNAse activity of monocyte chemotactic protein-induced protein-1 is critical for inducing angiogenesis.

Inflammatory angiogenesis involves the induction of a novel gene ZC3H12A encoding monocyte chemoattractant protein-1 (MCP-1)-induced protein-1 (MCPIP1) that has deubiquitinase and antidicer RNAse activities. If and how these enzymatic activities of MCPIP1 mediate the biological functions of MCPIP1 are unknown. Present studies with human umbilical vein endothelial cells suggest that MCPIP-induced angiogenesis is mediated via hypoxia-inducible factor (HIF-1α), vascular endothelial growth factor (VEGF), and silent information regulator (SIRT-1) induction that results in the inhibition of angiogenesis inhibitor thrombospondin-1.

MCP-1-induced protein promotes endothelial-like and angiogenic properties in human bone marrow monocytic cells.

Monocytic cells enhance neovascularization by releasing proangiogenic mediators and/or by transdifferentiating into endothelial-like cells. However, the mechanisms that govern this transdifferentiation process are largely unknown. Recently, monocyte chemotactic protein-1 (MCP-1)-induced protein (MCPIP) has been identified as a novel CCCH-type zinc-finger protein expressed primarily in monocytic cells.

Participation of MCP-induced protein 1 in lipopolysaccharide preconditioning-induced ischemic stroke tolerance by regulating the expression of proinflammatory cytokines.

Background: Lipopolysaccharide (LPS) preconditioning-induced neuroprotection is known to be related to suppression of the inflammatory response in the ischemic area. This study seeks to determine if monocyte chemotactic protein-induced protein 1 (MCPIP1), a recently identified CCCH Zn finger-containing protein, plays a role in focal brain ischemia and to elucidate the mechanisms of LPS-induced ischemic brain tolerance.

Methods: Transcription and expression of MCPIP1 gene was monitored by qRT-PCR and Western blot.

MCP-induced protein 1 deubiquitinates TRAF proteins and negatively regulates JNK and NF-kappaB signaling.

The intensity and duration of macrophage-mediated inflammatory responses are controlled by proteins that modulate inflammatory signaling pathways. MCPIP1 (monocyte chemotactic protein-induced protein 1), a recently identified CCCH Zn finger-containing protein, plays an essential role in controlling macrophage-mediated inflammatory responses. However, its mechanism of action is poorly understood.

Positional identification of variants of Adamts16 linked to inherited hypertension.

A previously reported blood pressure (BP) quantitative trait locus on rat Chromosome 1 was isolated in a short congenic segment spanning 804.6 kb. The 804.

Investigating the effect of genetic background on proteinuria and renal injury using two hypertensive strains.

An earlier linkage analysis conducted on a population derived from the Dahl salt-sensitive hypertensive (S) and the spontaneously hypertensive rat (SHR) identified 10 genomic regions linked to several renal and/or cardiovascular traits. In particular, loci on rat chromosomes (RNO) 8 and 13 were linked to proteinuria, albuminuria, and renal damage. At both loci, the S allele was associated with increased proteinuria and renal damage.

Blood pressure and proteinuria effects of multiple quantitative trait loci on rat chromosome 9 that differentiate the spontaneously hypertensive rat from the Dahl salt-sensitive rat.

A blood pressure (BP) quantitative trait locus (QTL) was previously located within 117 kb on rat chromosome 9 (RNO9) using hypertensive Dahl salt-sensitive and normotensive Dahl salt-resistant rats. An independent study between two hypertensive rat strains, the Dahl salt-sensitive rat and the spontaneously hypertensive rat (SHR), also detected a QTL encompassing this 117 kb region. Dahl salt-sensitive alleles in both of these studies were associated with increased BP.

Closely linked non-additive blood pressure quantitative trait loci.

There is enough evidence through linkage and substitution mapping to indicate that rat chromosome 1 harbors multiple blood pressure (BP) quantitative trait loci (QTLs). Of these, BP QTL1b was previously reported from our laboratory using congenic strains derived by introgressing normotensive alleles from the LEW rat onto the genetic background of the hypertensive Dahl salt-sensitive (S) rat. The region spanned by QTL1b is quite large (20.

Arterial thrombosis in mice with factor V Leiden mutation.

The factor V Leiden (FVL) mutation has been demonstrated to be associated with the development of venous thrombosis in humans. Whether such a propensity also exists in the arterial circulation remains controversial. In an effort to minimize the variability that clouds the clinical study of arterial thrombosis, we studied FVL-associated arterial thrombosis in an experimental model of homozygous, heterozygous, and wild-type mice.

Congenic mapping of a blood pressure QTL region on rat chromosome 10 using the Dahl salt-sensitive rat with introgressed alleles from the Milan normotensive strain.

Multiple blood pressure (BP) quantitative trait loci (QTLs) are reported on rat chromosome 10 (RNO10). Of these, QTLs detected by contrasting the genome of the hypertensive Dahl salt-sensitive (S) rat with two different relatively normotensive strains, Lewis (LEW) and the Milan normotensive strain (MNS), are reported. Because the deduced QTL regions of both S vs.

Congenic interval mapping of RNO10 reveals a complex cluster of closely-linked genetic determinants of blood pressure.

Genetic dissection of the rat genome for identifying alleles that cause abnormalities in blood pressure (BP) resulted in the mapping of a significant number of BP quantitative trait loci (QTLs). In this study we mapped at least one such BP QTL on rat chromosome 10 (RNO10) as being within the introgressed segment of a S.LEW congenic strain S.

Fine-mapping and comprehensive transcript analysis reveals nonsynonymous variants within a novel 1.17 Mb blood pressure QTL region on rat chromosome 10.

The presence of blood pressure (BP) quantitative trait loci (QTL) on rat chromosome 10 has been clearly demonstrated by linkage analysis and substitution mapping. Using congenic strains containing the LEW rat chromosomal segments on the Dahl salt-sensitive (S) rat background, further iterations of congenic substrains were constructed and characterized to fine-map a chromosome 10 region (QTL1) linked to blood pressure. Comparison of seven congenic substrains refined QTL1 to a 1.

Angiotensinergic stimulation of vascular endothelium in mice causes hypotension, bradycardia, and attenuated angiotensin response.

It is not clear whether endothelial cell (EC) activation by the hormone angiotensin II (Ang II) modulates contraction of vascular smooth muscle cells (VSMCs) in the vasculature and whether impairment of this regulation in vivo contributes to hypertension. Delineation of the actions of Ang II through the type 1 receptor (AT1R) on ECs in the blood vessels has been a challenging problem because of the predominance of the AT1R functions in VSMCs that lie underneath the endothelium. We have obviated this limitation by generating transgenic (TG) mice engineered to target expression of the constitutively active N111G mutant AT1R only in ECs.

Characterization and functional significance of myotrophin: a gene with multiple transcripts.

The underlying mechanism for the development of cardiac hypertrophy that advances to heart failure is not known. Many factors have been implied to play a role in this process. Among others, we have isolated and identified myotrophin, a factor that stimulates myocytes growth, from spontaneously hypertensive rat (SHR) heart and patients with dilated cardiomyopathy.

Cardiac angiotensin II receptors as predictors of transplant coronary artery disease following heart transplantation.

Aims: We tested the hypothesis that cardiac angiotensin II (Ang II) receptor gene transcription may predict the development of transplant coronary artery disease (TCAD) following heart transplantation.

Methods And Results: We examined the gene transcripts of Ang II type 1 (AT1R) and type 2 receptors (AT2R) in endomyocardial biopsy specimens from 50 heart transplant recipients. The progression of TCAD was measured as change in maximal intimal thickness (CMIT) and change in plaque volume (CPV) by intravascular ultrasound (IVUS) examinations from baseline to one year after transplantation.

"Network leaning" as a mechanism of insurmountable antagonism of the angiotensin II type 1 receptor by non-peptide antagonists.

A mechanistic understanding of the insurmountable antagonism of the angiotensin II type 1 (AT(1)) receptor could be fundamental in the quest for discovery and improvement of drugs. Candesartan and EXP3174 are competitive, reversible insurmountable antagonists of the AT(1) receptor. They contain di-acidic substitutions, whereas the surmountable antagonist, losartan, contains only one acidic group.

Activation of G-protein-coupled receptors: a common molecular mechanism.

G-protein-coupled receptors (GPCRs) are a large family of proteins that contain a seven transmembrane helical structural motif. They mediate responses to several ligands by binding and activating intracellular heterotrimeric G proteins. Since the cloning of the first GPCR, insights gained from structure-function studies, genetics and drug development have contributed to uncovering a common mechanism that explains the activation of diverse GPCRs by their cognate agonists.