Fluorescent probes of the orientation of myosin regulatory light chains in relaxed, rigor, and contracting muscle.

The orientation of the light-chain region of myosin heads in relaxed, rigor, and isometrically contracting fibers from rabbit psoas muscle was studied by fluorescence polarization. Cysteine 108 of chicken gizzard myosin regulatory light chain (cgRLC) was covalently modified with iodoacetamidotetramethylrhodamine (iodo-ATR). Native RLC of single glycerinated muscle fibers was exchanged for labeled cgRLC in a low [Mg2+] rigor solution at 30 degrees C. Troponin and troponin C removed in this procedure were replaced. RLC exchange had little effect on active force production. X-ray diffraction showed normal structure in rigor after RLC exchange, but loss of axial and helical order in relaxation. In isolated myofibrils labeled cgRLC was confined to the regions of the sarcomere containing myosin heads. The ATR dipoles showed a preference for orientations perpendicular to the fiber axis, combined with limited nanosecond rotational motion, in all conditions studied. The perpendicular orientation preference was more marked in rigor than in either relaxation or active contraction. Stretching relaxed fibers to sarcomere length 4 microns to eliminate overlap between actin- and myosin-containing filaments had little effect on the orientation preference. There was no change in orientation preference when fibers were put into rigor at sarcomere length 4.0 microns. Qualitatively similar results were obtained with ATR-labeled rabbit skeletal RLC

The Development of a New Questionnaire to Measure the Burden of Immunoglobulin Treatment in Patients with Primary Immunodeficiencies: The IgBoT-35.

Purpose: To describe the development and psychometric testing of a new questionnaire to measure the burden of immunoglobulin treatment (Ig) from the perspective of patients with primary immunodeficiencies (PID). Patients and Methods: An online, cross-sectional survey was administered to PID patients across 10 countries (nine European and Canada) who were receiving either intravenous (IVIg) or subcutaneous (SCIg) immunoglobulin therapy. The range and distribution of the responses (ie, levels of missing data, floor and ceiling effects), exploratory factor analysis (using factor loadings of 0.4 or greater) and measures of internal consistency reliability (ie, Cronbach's alpha coefficient, inter-item and item-total correlations) were used to identify the domain and item pool. Results: In total, 472 patients completed the questionnaire, of which 395 were included in the analysis (32% underwent IVIg and 67% underwent SCIg). The final instrument contained 34 items across eight domains of treatment burden (time, organisation and planning, leisure and social, interpersonal relationships, employment and education, travel, consequences of treatment and emotional) and an additional Ig treatment burden global question at the end of the measure. All the scales achieved good internal reliability (Cronbach's alpha coefficient ranged from 0.70 to 0.85) and, with the exception of one item exceeded the minimum threshold of 0.35 for item-total correlations. Treatment burden was lower than anticipated across the different treatment routes and countries, although overall was more burdensome for patients undergoing IVIg compared to SCIg treatment. Conclusion: The IgBoT-35 appears to be a reliable, patient-generated questionnaire and may help to identify more individualised and preferred therapies for the PID patient when used in clinical practice. A new survey with a sample of US patients is currently being undertaken to further establish its validity and conceptual model. The overall Ig burden of treatment scores appeared to be low. PID patient preferences are important to guide treatment decisions and ensuring patients receive the right treatment at the right time

Security Analysis of NIST CTR-DRBG

We study the security of CTR-DRBG, one of NIST\u27s recommended Pseudorandom Number Generator (PRNG) designs. Recently, Woodage and Shumow (Eurocrypt\u27 19), and then Cohney et al. (S&P\u27 20) point out some potential vulnerabilities in both NIST specification and common implementations of CTR-DRBG. While these researchers do suggest counter-measures, the security of the patched CTR-DRBG is still questionable. Our work fills this gap, proving that CTR-DRBG satisfies the robustness notion of Dodis et al. (CCS\u2713), the standard security goal for PRNGs

Sheldon-Hall syndrome

Sheldon-Hall syndrome (SHS) is a rare multiple congenital contracture syndrome characterized by contractures of the distal joints of the limbs, triangular face, downslanting palpebral fissures, small mouth, and high arched palate. Epidemiological data for the prevalence of SHS are not available, but less than 100 cases have been reported in the literature. Other common clinical features of SHS include prominent nasolabial folds, high arched palate, attached earlobes, mild cervical webbing, short stature, severe camptodactyly, ulnar deviation, and vertical talus and/or talipes equinovarus. Typically, the contractures are most severe at birth and non-progressive. SHS is inherited in an autosomal dominant pattern but about half the cases are sporadic. Mutations in either MYH3, TNNI2, or TNNT3 have been found in about 50% of cases. These genes encode proteins of the contractile apparatus of fast twitch skeletal muscle fibers. The diagnosis of SHS is based on clinical criteria. Mutation analysis is useful to distinguish SHS from arthrogryposis syndromes with similar features (e.g. distal arthrogryposis 1 and Freeman-Sheldon syndrome). Prenatal diagnosis by ultrasonography is feasible at 18–24 weeks of gestation. If the family history is positive and the mutation is known in the family, prenatal molecular genetic diagnosis is possible. There is no specific therapy for SHS. However, patients benefit from early intervention with occupational and physical therapy, serial casting, and/or surgery. Life expectancy and cognitive abilities are normal

First records of Baetis vernus Curtis (Ephemeroptera: Baetidae) in North America, with morphological notes

The Baetis vernus group (Ephemeroptera: Baetidae) – which includes B. brunneicolor McDunnough, B. bundyae Lehmkuhl, B. hudsonicus Ide, B. jaervii Savolainen, B. liebenauae Keffermüller, B. macani Kimmins, B. subalpinus Bengtsson, B. tracheatus Keffermüller & Machel, and B. vernus Curtis – is both diverse and taxonomically tangled. Some members of the group – B. brunneicolor, B. bundyae, and B. hudsonicus – have been previously found in North America. The remainder of the group is known to be only of Palearctic distribution, including B. vernus, which has a wide trans-Palearctic distribution. We report the collection of specimens from the Northwest Territories and British Columbia that we have identified as B. vernus using DNA barcoding and morphological examination and provide characters to assist separation of the North American members of the group from B. vernus. A genetically cohesive Holarctic clade for B. vernus likely relates to a Beringian dispersal event. This substantial expansion of the known range of B. vernus adds new phylogeographic and ecological complexity, but it may also help to provide further clues to the evolutionary history of this group