Novel Details of Calsequestrin Gel Conformation in Situ

Calsequestrin (CASQ) is the major component of the sarcoplasmic reticulum (SR) lumen in skeletal and cardiac muscles. This calcium-binding protein localizes to the junctional SR (jSR) cisternae, where it is responsible for the storage of large amounts of Ca2+, whereas it is usually absent, at least in its polymerized form, in the free SR. The retention of CASQ inside the jSR is due partly to its association with other jSR proteins, such as junctin and triadin, and partly to its ability to polymerize, in a high Ca2+ environment, into an intricate gel that holds the protein in place. In this work, we shed some light on the still poorly described in situ structure of polymerized CASQ using detailed EM images from thin sections, with and without tilting, and from deep-etched rotary-shadowed replicas. The latter directly illustrate the fundamental network nature of polymerized CASQ, revealing repeated nodal points connecting short segments of the linear polymer. © 2013 by The American Society for Biochemistry and Molecular Biology, Inc. Published in the U.S.A

Cardiac biomarker testing in the clinical laboratory: Where do we stand? General overview of the methodology with special emphasis on natriuretic peptides

Diagnosis of heart failure (HF) is not based on a single test, but on a combination of history, physical examination and appropriate investigations. For these reasons, the accuracy of diagnosis by clinical means alone is often inadequate, especially in the early, asymptomatic stages of the HF. Thus, there is an increasing interest in the development of new cardiovascular biomarkers and, consequently, a great number of laboratory tests have recently been proposed for their assay. The aim of this article is to provide a general overview on the biomarkers, recommended by international guidelines, for the diagnosis, risk stratification, and follow-up of patients with HF. Cardiac natriuretic peptides and in particular the B-type related peptides, which are considered to be the first line biomarker for HF by international guidelines, will be discussed with special emphasis

Highly extensible skeletal muscle in snakes

Many snakes swallow large prey whole, and this process requires large displacements of the unfused tips of the mandibles and passive stretching of the soft tissues connecting them. Under these conditions, the intermandibular muscles are highly stretched but subsequently recover normal function. In the highly stretched condition we observed in snakes, sarcomere length (SL) increased 210% its resting value (SL0), and actin and myosin filaments no longer overlapped. Myofibrils fell out of register and triad alignment was disrupted. Following passive recovery, SLs returned to 82% SL0, creating a region of double-overlapping actin filaments. Recovery required recoil of intracellular titin filaments, elastic cytoskeletal components for realigning myofibrils, and muscle activation. Stretch of whole muscles exceeded that of sarcomeres as a result of extension of folded terminal tendon fibrils, stretching of extracellular elastin and independent slippage of muscle fibers. Snake intermandibular muscles thus provide a unique model of how basic components of vertebrate skeletal muscle can be modified to permit extreme extensibility. © 2014. Published by The Company of Biologists Ltd

Skeletal muscle microalterations in patients carrying Malignant Hyperthermia-related mutations of the e-c coupling machinery

We have compared the ultrastructure of skeletal muscle biopsies from patients that have survived a [Malignant Hyperthermia, MH] episode and siblings that test positive for MH susceptibility with those from siblings that tested negatives. The aim is to establish whether life long exposure to the MH-related mutation effects may result in subtle abnormalities even in the absence of active episodes and/or clinically detectable deficiencies. Although a specific ultrastructural signature for MH mutants cannot be demonstrated, an MH related pattern of minor alterations does exist. These include the tendency for micro damage to the contractile apparatus and a higher than normal level of mitochondrial abnormalities

Chiral bis(benzo[1,2-b:4,3-b’]dithiophene)s: synthesis and stereochemical characterization

Thiophene-containing fused aromatic compounds are an interesting class of \uf070-conjugated systems in functional organic materials (1). Among them, benzo[1,2-b:4,3-b\u2019]dithiophene (BDT) and its derivatives are widely studied, for instance as units in mono and polydisperse oligomers in the field of the materials science (2), and as \uf070-spacers in push-pull organic chromophores for photovoltaic applications (3). Furthermore, BDT is a key intermediate for the synthesis of inherently chiral helical systems such as tetrathia[7]helicenes (4).Thus, BDT can be identified as a key starting molecule, which can allow access to more complex and interesting systems through a judicious functionalization of the \uf061-positions of the thiophene rings. In our ongoing studies on the synthesis and functionalization of BDTs (5,6), we have developed a novel synthesis to prepare bis(benzo[1,2-b:4,3-b\u2019]dithiophene) systems 2, starting from bromides 1 (Figure 1).Compounds 2 belong to an interesting class of chiral atropisomeric heterobiaryl derivatives with C2-symmetry, which can be selectively functionalized into bromides 3. The chiroptical properties of both systems 2 and 3 have been fully elucidated by experimental and theoretical studies. On the other hand, enantiopure bromides 3 represent useful intermediates for the enantioselective synthesis of the corresponding tetrathiahelicene derivatives

CHiral bis-benzo[1,2-b:4,3-b’]dithiophenes : synthesis and stereochemical properties

Thiophene-containing fused aromatic compounds are an interesting class of \u3c0-conjugated systems with applications in functional organic materials.1 Among them, benzo[1,2-b:4,3-b\u2019]dithiophene (BDT) and its derivatives are widely studied in the field of materials science,2 and for photovoltaic applications.3 Moreover, BDT is a key intermediate for the synthesis of inherently chiral helical systems such as tetrathia[7]helicenes.4 In our ongoing studies on the synthesis and functionalization of BDTs,5 we have developed a novel and convenient route to prepare an interesting class of chiral heterobiaryl bis(benzo[1,2-b:4,3-b\u2019]dithiophene) systems 2 and 3 (Figure 1). In this communication we will report the synthesis of compounds 2 and 3 along with the study of their chiroptical properties. Bromides 3 are also expected to have potential applications in asymmetric reactions, including the enantioselective synthesis of tetrathia[7]helicene derivatives

Axially chiral benzo[1,2-b:4,3-b’]dithiophene derivatives as key intermediates for enantiopure tetrathia[7]helicenes

Thiophene-containing fused aromatic compounds are an interesting class of \u3c0-conjugated systems with applications in functional organic materials.1 Among them, benzo[1,2-b:4,3-b\u2019]dithiophene (BDT) and its derivatives are widely studied, for instance as units in mono and polydisperse oligomers in the field of materials science,2 and as \u3c0-spacers in push-pull organic chromophores for photovoltaic applications.3 Furthermore, BDT is a key intermediate for the synthesis of inherently chiral helical systems such as tetrathia[7]helicenes.4 Thus, BDT can be identified as a key starting molecule, which can allow access to more complex and interesting systems through a judicious functionalization of the \u3b1-position of the thiophene rings. In our ongoing studies on the synthesis and functionalization of BDTs,5 we have developed a novel synthesis to prepare systems 2, starting from bromides 1 (Figure 1). Compounds 2 are an interesting class of chiral atropisomeric heterobiaryl derivatives with C2-symmetry, which can be selectively functionalized into bromides 3, starting reagents for an innovative non-photochemical synthesis of tetrathiahelicenes through Pd-catalysed annulation with internal alkynes as key step. Asymmetric versions of this synthesis is under study thanks to the chiroptical properties of 3, which represent useful intermediates for the enantioselective synthesis of the corresponding tetrathiahelicene derivatives