'Solvency rule' and capital centralization in a monetary union

Brancaccio and Fontana (2013) have suggested that the central bank influences the solvency conditions of firms and households in the economic system. This ‘solvency rule’ is examined here within a stylised model of a monetary union characterised by different rates of accumulation and inflation across its two member countries. The rule highlights the existence of a relationship between the interest rate set by the central monetary authority and the allocation of ownership of existing physical capital among the member countries of the monetary union, i.e. the ‘rates of capital centralisation’. The paper also shows the nexus between solvency and government debt sustainability, and examines the implications of deflationary or currency devaluation policies for the solvency conditions

Analysis of α-dystroglycan/LG domain binding modes:investigating protein motifs that regulate the affinity of isolated LG domains

Dystroglycan (DG) is an adhesion complex that links the cytoskeleton to the surrounding extracellular matrix in skeletal muscle and a wide variety of other tissues. It is composed of a highly glycosylated extracellular α-DG associated noncovalently with a transmembrane β-DG whose cytodomain interacts with dystrophin and its isoforms. Alpha-dystroglycan (α-DG) binds tightly and in a calcium-dependent fashion to multiple extracellular proteins and proteoglycans, each of which harbors at least one, or, more frequently, tandem arrays of laminin-globular (LG) domains. Considerable biochemical and structural work has accumulated on the α-DG-binding LG domains, highlighting a significant heterogeneity in ligand-binding properties of domains from different proteins as well as between single and multiple LG domains within the same protein. Here we review biochemical, structural, and functional information on the LG domains reported to bind α-dystroglycan. In addition, we have incorporated bioinformatics and modeling to explore whether specific motifs responsible for α-dystroglycan recognition can be identified within isolated LG domains. In particular, we analyzed the LG domains of slits and agrin as well as those of paradigmatic α-DG non-binders such as laminin-α3. While some stretches of basic residues may be important, no universally conserved motifs could be identified. However, the data confirm that the coordinated calcium atom within the LG domain is needed to establish an interaction with the sugars of α-DG, although it appears that this alone is insufficient to mediate significant α-DG binding. We develop a scenario involving different binding modes of a single LG domain unit, or tandemly repeated units, with α-DG. A variability of binding modes might be important to generate a range of affinities to allow physiological regulation of this interaction, reflecting its crucial biological importance

Melusin gene (ITGB1BP2) nucleotide variations study in hypertensive and cardiopathic patients

<p>Abstract</p> <p>Background</p> <p>Melusin is a muscle specific signaling protein, required for compensatory hypertrophy response in pressure-overloaded heart. The role of Melusin in heart function has been established both by loss and gain of function experiments in murine models. With the aim of verifying the hypothesis of a potential role of the Melusin encoding gene, <it>ITGB1BP2</it>, in the modification of the clinical phenotype of human cardiomyopathies, we screened the <it>ITGB1BP2 </it>gene looking for genetic variations possibly associated to the pathological phenotype in three selected groups of patients affected by hypertension and dilated or hypertrophic cardiomyopathy</p> <p>Methods</p> <p>We analyzed <it>ITGB1BP2 </it>by direct sequencing of the 11 coding exons and intron flanking sequences in 928 subjects, including 656 hypertensive or cardiopathic patients and 272 healthy individuals.</p> <p>Results</p> <p>Only three nucleotide variations were found in patients of three distinct families: a C>T missense substitution at position 37 of exon 1 causing an amino acid change from His-13 to Tyr in the protein primary sequence, a duplication (IVS6+12_18dupTTTTGAG) near the 5'donor splice site of intron 6, and a silent 843C>T substitution in exon 11.</p> <p>Conclusions</p> <p>The three variations of the <it>ITGB1BP2 </it>gene have been detected in families of patients affected either by hypertension or primary hypertrophic cardiomyopathy; however, a clear genotype/phenotype correlation was not evident. Preliminary functional results and bioinformatic analysis seem to exclude a role for IVS6+12_18dupTTTTGAG and 843C>T in affecting splicing mechanism.</p> <p>Our analysis revealed an extremely low number of variations in the <it>ITGB1BP2 </it>gene in nearly 1000 hypertensive/cardiopathic and healthy individuals, thus suggesting a high degree of conservation of the melusin gene within the populations analyzed.</p

Intraring allostery controls the function and assembly of a hetero‐oligomeric class II chaperonin

Class II chaperonins are essential multisubunit complexes that aid the folding of nonnative proteins in the cytosol of archaea and eukarya. They use energy derived from ATP to drive a series of structural rearrangements that enable polypeptides to fold within their central cavity. These events are regulated by an elaborate allosteric mechanism in need of elucidation. We employed mutagenesis and experimental analysis in concert with in silico molecular dynamics simulations and interface-binding energy calculations to investigate the class II chaperonin from Thermoplasma acidophilum. Here we describe the effects on the asymmetric allosteric mechanism and on hetero-oligomeric complex formation in a panel of mutants in the ATP-binding pocket of the α and β subunits. Our observations reveal a potential model for a nonconcerted folding mechanism optimized for protecting and refolding a range of nonnative substrates under different environmental conditions, starting to unravel the role of subunit heterogeneity in this folding machine and establishing important links with the behavior of the most complex eukaryotic chaperonins.—Shoemark, D. K., Sessions, R. B., Brancaccio, A., Bigotti, M. G. Intraring allostery controls the function and assembly of a hetero-oligomeric class II chaperonin

A preliminary study for quantitative assessment with HFUS (High-frequency ultrasound) of nodular skin melanoma breslow thickness in adults before surgery: Interdisciplinary team experience

Background: Cutaneous melanoma is one of the most severe skin diseases. Nodular melanoma is the second melanoma subtype in order of frequency. The prognosis of skin melanoma depends on the vertical growth of the tumor (Breslow index). For this measurement, excisional biopsy is strongly recommended. This is, however, an invasive procedure and may cause damage to the lymphatic drainage system. The HFUS system,, can be extremely useful for determining tumor thickness in the preoperative phase, given its high resolution capacity. The aim of this preliminary study is to define the role of HFUS for the nodular skin melanoma Breslow thickness in adults before surgery by making a comparison with histological features. Methods: In this study, 14 melanocytic lesions (8 male and 6 female) were evaluated with derma-toscopic clinical features strongly indicative of nodular melanoma. Out of these, excisional biopsy of 7 lesions was requested. The ultrasounds were performed preoperatively. The images were acquired through the first ultrasound scanner with ultra-high frequency probes (range from 50MHz to 70 MHz) available on the market under the EEC mark (Vevo "MD, FUJIFILM Visual Sonics, Amsterdam, the Netherlands) equipped with a linear probe of 50-70 MHz. Results: From the ultrasonographic analysis of 14 nodular melanoma thickness was determined for the presence of two hyperechogenic laminae, separated by a hypo / anechoic space. The twelve lesions were in situ while the other two lesions showed ultrasonography for example; the satellite lesions (less than two centimeters from the primary lesion) and in transit (localizable to more than two centimeters from the primary lesion). Four of these lesions were ulcerated. A comparsion was made the 7 lesions on between the thickness calculated with this method, and that obtained on the bioptic piece. The presence of a positive concordance has been evident in all of the cases. Conclusion: If further studies are needed to support its widespread clinical use, its is believed that, in expert hands and with an interdisciplinary team, HFUS is already capable to reliably calculate a Breslow index in a large majority of patients with cutaneous melanoma