Characterizing Vocal Tract Dimensions in the Vocal Modes Using Magnetic Resonance Imaging.

Objective: The aim was to study vocal tract dimensions in four vocal modes - Neutral, Curbing, Overdrive and Edge - from Complete Vocal Technique (CVT) by means of magnetic resonance imaging (MRI). Furthermore, the purpose was to test the feasibility of MRI to assess CVT vocal modes.

Methods: Four nonclassical singers (two females, two males) trained in CVT were imaged with an MRI scanner while singing sustained vowels at same pitch (Bb4 for females, F4 for males) in all vocal modes.

The scavenger receptor SCARA5 is an endocytic receptor for von Willebrand factor expressed by littoral cells in the human spleen.

Background: Scavenger receptors play a significant role in clearing aged proteins from the plasma, including the large glycoprotein coagulation factors von Willebrand factor (VWF) and factor VIII (FVIII). A large genome-wide association study meta-analysis has identified genetic variants in the gene SCARA5, which encodes the class A scavenger receptor SCARA5, as being associated with plasma levels of VWF and FVIII.

Objectives: The ability of SCARA5 to regulate the clearance of VWF-FVIII was characterized.

Culturing functional pancreatic islets on α5-laminins and curative transplantation to diabetic mice.

The efficacy of islet transplantation for diabetes treatment suffers from lack of cadaver-derived islets, islet necrosis and long transfer times prior to transplantation. Here, we developed a method for culturing mouse and human islets in vitro on α5-laminins, which are natural components of islet basement membranes. Adhering islets spread to form layers of 1-3 cells in thickness and remained normoxic and functional for at least 7 days in culture.

Preventing tissue fibrosis by local biomaterials interfacing of specific cryptic extracellular matrix information.

Matrix metalloproteinases (MMPs) contribute to the breakdown of tissue structures such as the basement membrane, promoting tissue fibrosis. Here we developed an electrospun membrane biofunctionalized with a fragment of the laminin β1-chain to modulate the expression of MMP2 in this context. We demonstrate that interfacing of the β1-fragment with the mesothelium of the peritoneal membrane via a biomaterial abrogates the release of active MMP2 in response to transforming growth factor β1 and rescues tissue integrity ex vivo and in vivo in a mouse model of peritoneal fibrosis.

Ab initio solution of macromolecular crystal structures without direct methods.

The majority of macromolecular crystal structures are determined using the method of molecular replacement, in which known related structures are rotated and translated to provide an initial atomic model for the new structure. A theoretical understanding of the signal-to-noise ratio in likelihood-based molecular replacement searches has been developed to account for the influence of model quality and completeness, as well as the resolution of the diffraction data. Here we show that, contrary to current belief, molecular replacement need not be restricted to the use of models comprising a substantial fraction of the unknown structure.

Genetic and biological effects of sodium-chloride cotransporter (SLC12A3) in diabetic nephropathy.

Background/aims: Solute carrier family 12 member 3 (SLC12A3) encodes a sodium/chloride transporter in kidneys. Previous reports suggest that Arg913Gln polymorphism in this gene is associated with diabetic nephropathy (DN), but the data appear to be inconsistent. Up to now, there is no biological evidence concerning the effects of SLC12A3 in DN.

Lmx1b and FoxC combinatorially regulate podocin expression in podocytes.

Podocin is a key protein of the kidney podocyte slit diaphragm protein complex, an important part of the glomerular filtration barrier. Mutations in the human podocin gene NPHS2 cause familial or sporadic forms of renal disease owing to the disruption of filtration barrier integrity. The exclusive expression of NPHS2 in podocytes reflects its unique function and raises interesting questions about its transcriptional regulation.

Myo1e impairment results in actin reorganization, podocyte dysfunction, and proteinuria in zebrafish and cultured podocytes.

Background: Podocytes serve as an important constituent of the glomerular filtration barrier. Recently, we and others identified Myo1e as a key molecular component of the podocyte cytoskeleton.

Results: Myo1e mRNA and protein was expressed in human and mouse kidney sections as determined by Northern blot and reverse transcriptase PCR, and its expression was more evident in podocytes by immunofluorescence.

Progressive reactive lymphoid connective tissue disease and development of autoantibodies in scavenger receptor A5-deficient mice.

Scavenger receptor A5 (SCARA5) is a member of the class A scavenger receptors, with most similarity to SCARA1 (SR-A) and SCARA2 (MARCO), which are primarily expressed by macrophages and dendritic cells, in which they participate in clearance of various polyanionic macromolecules, pollution particles, and pathogens. The biological role of SCARA5 has been unknown. Herein, we show that SCARA5 is an endocytotic receptor whose ligand repertoire includes the typical scavenger receptor ligands, whole bacteria, and purified Gram-negative bacterial lipopolysaccharide.

A remote cis-acting variant at 3q links glomerular NCK1 to diabetic nephropathy.

We have previously reported genetic association of a single nucleotide polymorphism (SNP), rs1866813, at 3q locus with increased risk of diabetic nephropathy (DN). The SNP is located approximately 70 kb downstream of a cluster of four genes. This raises a question how the remote noncoding polymorphism affects the risk of DN.

A novel scavenger receptor 5-based antibiotic-independent selection method for generation of stable recombinant protein-producing mammalian cell lines especially suitable for proteins affecting cell adhesion.

The establishment of stable recombinant protein-producing mammalian cell lines is an expensive, time-consuming, tedious procedure. In some cases, expressed recombinant proteins have adverse effects on host cell function, including cell adhesion. Based on the adhesive properties of SCARA5, a scavenger receptor (SR) of the class A SR family, we developed a method for selection of stable recombinant protein-producing cell clones that relies on an internal ribosome entry site (IRES) vector where the protein of interest is expressed in the same messenger RNA as SCARA5, resulting in improved adhesion and increased cell viability of recombinant protein-producing cells in serum-free media.

Crystal structure of the cysteine-rich domain of scavenger receptor MARCO reveals the presence of a basic and an acidic cluster that both contribute to ligand recognition.

MARCO is a trimeric class A scavenger receptor of macrophages and dendritic cells that recognizes polyanionic particles and pathogens. The distal, scavenger receptor cysteine-rich (SRCR) domain of the extracellular part of this receptor has been implicated in ligand binding. To provide a structural basis for understanding the ligand-binding mechanisms of MARCO, we have determined the crystal structure of the mouse MARCO SRCR domain.

A phage display screen and binding studies with acetylated low density lipoprotein provide evidence for the importance of the scavenger receptor cysteine-rich (SRCR) domain in the ligand-binding function of MARCO.

MARCO is a class A scavenger receptor capable of binding both gram-negative and -positive bacteria. Using the surface plasmon resonance technique, we show here that a recombinant, soluble form of MARCO, sMARCO, binds the major gram-negative and -positive bacterial surface components, lipopolysaccharide and lipoteichoic acid. Yet, the interaction of these two polyanions with sMARCO is of much lower affinity than that of polyinosinic acid, a polyanionic inhibitor of bacterial binding to MARCO.

The catalytic cycle of biosynthetic thiolase: a conformational journey of an acetyl group through four binding modes and two oxyanion holes.

Biosynthetic thiolase catalyzes the formation of acetoacetyl-CoA from two molecules of acetyl-CoA. This is a key step in the synthesis of many biological compounds, including steroid hormones and ketone bodies. The thiolase reaction involves two chemically distinct steps; during acyl transfer, an acetyl group is transferred from acetyl-CoA to Cys89, and in the Claisen condensation step, this acetyl group is further transferred to a second molecule of acetyl-CoA, generating acetoacetyl-CoA.