Mixed partial anomalous pulmonary venous drainage coexistent with an aortic valve abnormality – analysis of ultrasound diagnostics in a 10-year-old girl with Turner syndrome

The authors present a case of echocardiographic diagnosis of a rare congenital cardiovascular anomaly in the form of mixed partial anomalous pulmonary veins connection in a 10-year-old girl with Turner syndrome and congenital mild stenosis of insufficient bicuspid aortic valve, made while diagnosing the causes of intestinal tract bleeding. The article presents various diagnostic difficulties leading to the delayed determination of a correct diagnosis, resulting from the absence of symptoms of circulatory failure in the early stage of the disease and the occurrence of severe and dominant auscultatory phenomena typical for congenital aortic valve defect which effectively masked the syndromes of increased pulmonary flow. The authors discuss the role of the impact of phenotypic characteristics of the Turner syndrome, in particular a short webbed neck restricting the suprasternal echocardiographic access and the presence of psychological factors associated with a long-term illness. The importance of indirect echocardiographic symptoms suggesting partial anomalous pulmonary veins connection in the presence of bicuspid aortic valve, e.g. enlargement of the right atrium and right ventricle, and paradoxical interventricular septum motion were emphasized in patients lacking ASD, pulmonary hypertension or tricupid and pulmonary valve abnormalities. The methodology of echocardiographic examination enabling direct visualization of the abnormal vascular structures was presented. Special attention was paid to the significance of highly sensitive echocardiographic projections: high right and left parasternal views in sagittal and transverse planes with patient lying on the side, with the use of two-dimensional imaging and color Doppler. Finally, the limitations of echocardiography resulting from the visualization and tracking of abnormal vascular structures hidden behind ultrasound non-conductive tissues were indicated, as was the role of other diagnostic modalities, such as angio-CT and/or nuclear magnetic resonance

Involvement of unconventional myosin VI in myoblast function and myotube formation

10.1007/s00418-015-1322-6Histochemistry and Cell Biology144121-3

Myosin VI Localization and Expression in Striated Muscle Pathology

We study the solutions of the matrix equation $S\exp(S) = A$. Our motivation comes from the study of systems of delay differential equations $y'(t) = A y(t-1)$, which occur in some models of practical interest, especially in mathematical biology. This paper concentrates on the distinction between \emph{evaluating a matrix function} and \emph{solving a matrix equation}. In particular, it shows that the matrix Lambert $W$ function evaluated at the matrix $A$ does not represent all possible solutions of $S\exp(S) = A$. These results can easily be extended to more general matrix equations

Two Desmin Gene Mutations Associated with Myofibrillar Myopathies in Polish Families

<div><p>Desmin is a muscle-specific intermediate filament protein which forms a network connecting the sarcomere, T tubules, sarcolemma, nuclear membrane, mitochondria and other organelles. Mutations in the gene coding for desmin (<i>DES</i>) cause skeletal myopathies often combined with cardiomyopathy, or isolated cardiomyopathies. The molecular pathomechanisms of the disease remain ambiguous. Here, we describe and comprehensively characterize two <i>DES</i> mutations found in Polish patients with a clinical diagnosis of desminopathy. The study group comprised 16 individuals representing three families. Two mutations were identified: a novel missense mutation (Q348P) and a small deletion of nine nucleotides (A357_E359del), previously described by us in the Polish population. A common ancestry of all the families bearing the A357_E359del mutation was confirmed. Both mutations were predicted to be pathogenic using a bioinformatics approach, including molecular dynamics simulations which helped to rationalize abnormal behavior at molecular level. To test the impact of the mutations on <i>DES</i> expression and the intracellular distribution of desmin muscle biopsies were investigated. Elevated desmin levels as well as its atypical localization in muscle fibers were observed. Additional staining for M-cadherin, α-actinin, and myosin heavy chains confirmed severe disruption of myofibrill organization. The abnormalities were more prominent in the Q348P muscle, where both small atrophic fibers as well large fibers with centrally localized nuclei were observed. We propose that the mutations affect desmin structure and cause its aberrant folding and subsequent aggregation, triggering disruption of myofibrils organization.</p></div

Pedigree diagram of family ZP.

<p>Open diamond (IV:17). indicates sex unknown. Open triangle (V:4) indicates miscarriage. The other symbols indications as above. Family ZP consisted of 52 members, five of which participated in the study. Genetic analyses were performed for individuals III:7, IV:2, IV:4, IV:5, and IV:14.</p

Alignment of WT (blue), point-mutated (yellow) and deletion (purple) structures of desmin dimer after a 30ns MD simulation.

<p>Residue 348 is colored green in both helices.</p

Quantification of desmin content in muscle by immunoblotting.

<p>Equal volumes of homogenates (A) and supernatants (B) from control (C1-C4), patient IV:2, ZP family (P1, A357_E359del mutation), and patient III:3, DP family (P2, Q348P mutation) muscle were subjected to SDS polyacrylamide gel electrophoresis, blotted on nitrocellulose membrane and probed with anti-desmin and anti-GAPDH antibodies, as described in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0115470#s3" target="_blank">Materials and Methods</a>. Lower panels in A and B, densitometric analyses of desmin content in the examined muscles. For controls, the data are presented as mean ± SEM for n = 4.</p