Refuting misconceptions in medical physiology.

BACKGROUND: In medical physiology, educators and students face a serious challenge termed misconceptions. Misconceptions are incorrect ideas that do not match current scientific views. Accordingly, they have shown to hamper teaching and learning of physiological concepts. Conceptual Change Theory forms the basis of new teaching and learning practices that may alleviate misconceptions and facilitate critical thinking skills that are essential in becoming knowledgeable, self-regulated health professionals. In this study, we examined if such an intervention named refutation texts, could enhance medical students' cognition and metacognition. METHODS: First-year medical students (N = 161) performed a pre-test and post-test on cardiovascular physiology concepts, including a self-perceived confidence rating. In between, students read either a standard text with an explanation of the correct answer, or a refutation text which additionally refuted related misconceptions. RESULTS: In both groups, average performance scores (refutation: + 22.5%, standard: + 22.8%) and overall confidence ratings (refutation: Δ0.42 out of 5, standard: Δ0.35 out of 5) increased significantly (all p < .001), but a significant effect of the specific refutation element was not found. Initially incorrect answers were corrected less frequently in cases of high confidence (35.8%) than low confidence (61.4%). CONCLUSIONS: Our results showed that refutation texts significantly increased students' knowledge, however, the refutation element did not have a significant additional effect. Furthermore, high confidence in incorrect answers negatively affected the likelihood of correction. These findings provide implications for teaching practices on concept learning, by showing that educators should take into account the key role of metacognition, and the nature of misconceptions.

Juno-UVS approach observations of Jupiter's auroras.

Juno ultraviolet spectrograph (UVS) observations of Jupiter's aurora obtained during approach are presented. Prior to the bow shock crossing on 24 June 2016, the Juno approach provided a rare opportunity to correlate local solar wind conditions with Jovian auroral emissions. Some of Jupiter's auroral emissions are expected to be controlled or modified by local solar wind conditions. Here we compare synoptic Juno-UVS observations of Jupiter's auroral emissions, acquired during 3-29 June 2016, with in situ solar wind observations, and related Jupiter observations from Earth. Four large auroral brightening events are evident in the synoptic data, in which the total emitted auroral power increases by a factor of 3-4 for a few hours. Only one of these brightening events correlates well with large transient increases in solar wind ram pressure. The brightening events which are not associated with the solar wind generally have a risetime of ~2 h and a decay time of ~5 h.

MLL2 mutation detection in 86 patients with Kabuki syndrome: a genotype-phenotype study.

Recently, pathogenic variants in the MLL2 gene were identified as the most common cause of Kabuki (Niikawa-Kuroki) syndrome (MIM#147920). To further elucidate the genotype-phenotype correlation, we studied a large cohort of 86 clinically defined patients with Kabuki syndrome (KS) for mutations in MLL2. All patients were assessed using a standardized phenotype list and all were scored using a newly developed clinical score list for KS (MLL2-Kabuki score 0-10). Sequencing of the full coding region and intron-exon boundaries of MLL2 identified a total of 45 likely pathogenic mutations (52%): 31 nonsense, 10 missense and four splice-site mutations, 34 of which were novel. In five additional patients, novel, i.e. non-dbSNP132 variants of clinically unknown relevance, were identified. Patients with likely pathogenic nonsense or missense MLL2 mutations were usually more severely affected (median 'MLL2-Kabuki score' of 6) as compared to the patients without MLL2 mutations (median 'MLL2-Kabuki score' of 5), a significant difference (p < 0.0014). Several typical facial features such as large dysplastic ears, arched eyebrows with sparse lateral third, blue sclerae, a flat nasal tip with a broad nasal root, and a thin upper and a full lower lip were observed more often in mutation positive patients.

A natural history study of late onset spinal muscular atrophy types 3b and 4.

BACKGROUND: Spinal muscular atrophy (SMA) is caused by a homozygous deletion of the survival motor neuron (SMN)1 gene. The nearly identical SMN2 gene plays a disease modifying role. SMA is classified into four different subtypes based on age of onset and clinical course (SMA types 1-4). The natural history of early onset SMA types 1-3a has been studied extensively. Late onset SMA is rare and disease course has not been studied in detail. OBJECTIVE: To perform a prospective study on the clinical course and the correlation with SMN2 copy numbers of late onset SMA. METHODS: Patients fulfilling the diagnostic criteria for late onset SMA (types 3b and 4) were included in the study. At inclusion and follow-up, muscle strength, respiratory function, functional status and quality of life were assessed. SMN2 copy number was determined in all patients. RESULTS: Twelve patients were identified and included. Six patients were siblings from one family, two patients were brothers from a second family and four patients were sporadic cases. All patients carried four copies of the SMN2 gene. Median age of disease onset was 22.2 years (10-37). Age of disease onset in patients from family one was lower as compared to the other patients. None of the outcome measures changed after a follow-up of 2.5 years. Five patients reported an increase in fatigue and muscle weakness. None of the patients showed symptoms of respiratory insufficiency. CONCLUSIONS: This study indicates that late onset SMA is not characterized by disease progression and that alternative or surrogate disease markers are required for the design of future trials. This study confirms the finding that SMN2 copy number is a SMA disease course modifier.

Io's atmospheric response to eclipse: UV aurorae observations.

The New Horizons (NH) spacecraft observed Io's aurora in eclipse on four occasions during spring 2007. NH Alice ultraviolet spectroscopy and concurrent Hubble Space Telescope ultraviolet imaging in eclipse investigate the relative contribution of volcanoes to Io's atmosphere and its interaction with Jupiter's magnetosphere. Auroral brightness and morphology variations after eclipse ingress and egress reveal changes in the relative contribution of sublimation and volcanic sources to the atmosphere. Brightnesses viewed at different geometries are best explained by a dramatic difference between the dayside and nightside atmospheric density. Far-ultraviolet aurora morphology reveals the influence of plumes on Io's electrodynamic interaction with Jupiter's magnetosphere. Comparisons to detailed simulations of Io's aurora indicate that volcanoes supply 1 to 3% of the dayside atmosphere.

Screening for subtelomeric rearrangements in 210 patients with unexplained mental retardation using multiplex ligation dependent probe amplification (MLPA).

BACKGROUND: Subtelomeric rearrangements contribute to idiopathic mental retardation and human malformations, sometimes as distinct mental retardation syndromes. However, for most subtelomeric defects a characteristic clinical phenotype remains to be elucidated. OBJECTIVE: To screen for submicroscopic subtelomeric aberrations using multiplex ligation dependent probe amplification (MLPA). METHODS: 210 individuals with unexplained mental retardation were studied. A new set of subtelomeric probes, the SALSA P036 human telomere test kit, was used. RESULTS: A subtelomeric aberration was identified in 14 patients (6.7%) (10 deletions and four duplications). Five deletions were de novo; four were inherited from phenotypically normal parents, suggesting that these were polymorphisms. For one deletion, DNA samples of the parents were not available. Two de novo submicroscopic duplications were detected (dup 5qter, dup 12pter), while the other duplications (dup 18qter and dup 22qter) were inherited from phenotypically similarly affected parents. All clinically relevant aberrations (de novo or inherited from similarly affected parents) occurred in patients with a clinical score of >or=3 using an established checklist for subtelomeric rearrangements. Testing of patients with a clinical score of >or=3 increased the diagnostic yield twofold to 12.4%. Abnormalities with clinical relevance occurred in 6.3%, 5.1%, and 1.7% of mildly, moderately, and severely retarded patients, respectively, indicating that testing for subtelomeric aberrations among mildly retarded individuals is necessary. CONCLUSIONS: The value of MLPA is confirmed. Subtelomeric screening can be offered to all mentally retarded patients, although clinical preselection increases the percentage of chromosomal aberrations detected. Duplications may be a more common cause of mental retardation than has been appreciated.

Dogfish alpha-crystallin sequences. Comparison with small heat shock proteins and Schistosoma egg antigen.

The amino acid sequences of the alpha-crystallin A and B chains of the dogfish, Squalus acanthias, have been determined. Comparison with alpha-crystallins from other species reveals that charged amino acid replacements have been strongly avoided in the evolution of this lens protein. The homology of alpha-crystallins with the small heat shock proteins is pronounced throughout the major part of the proteins, starting from the position of the first intron in the alpha-crystallin genes, but is also detectable in the amino-terminal sequences of human, Xenopus, and Drosophila small heat shock proteins. In addition, a remarkable short sequence similarity is present only in the amino termini of dogfish alpha B and Drosophila HSP22. The Schistosoma egg antigen p40 turns out to have a tandemly repeated region of homology with the common sequence domain of alpha-crystallins and small heat shock proteins. Comparison of hydropathy profiles indicates the conservation of conformation of the common domains in these three families of proteins. Construction of phylogenetic trees suggests that the alpha A and alpha B genes apparently originated from a single ancestral small heat shock protein gene and indicates that introns have been lost during the evolution of the heat shock protein genes.

alpha-Crystallin A sequences of Alligator mississippiensis and the lizard Tupinambis teguixin: molecular evolution and reptilian phylogeny.

The amino acid sequences of the eye lens protein alpha-crystallin A from many mammalian and avian species, two frog species, and a dogfish have provided detailed information about the molecular evolution of this protein and allowed some useful inferences about phylogenetic relationships among these species. We now have isolated and sequenced the alpha-crystallins of the American alligator and the common tegu lizard. The reptilian alpha A chains appear to have evolved as slowly as those of other vertebrates, i.e., at two to three amino acid replacements per 100 residues in 100 Myr. The lack of charged replacements and the general types and distribution of replacements also are similar to those in other vertebrate alpha A chains. Maximum-parsimony analyses of the total data set of 67 vertebrate alpha A sequences support the monophyletic origin of alligator, tegu, and birds and favor the grouping of crocodilians and birds as surviving sister groups in the subclass Archosauria.

Ratites as oldest offshoot of avian stem--evidence from alpha-crystallin A sequences.

One of the most disputed issues in avian phylogeny is the origin of the ratites, the large flightless birds of the Southern Hemisphere (reviewed in refs 1-3). It is still not generally agreed whether the ostriches, rheas, emus and cassowaries, and probably kiwis, form a natural, monophyletic group, although much recent evidence supports this view. Also, their phylogenetic relationship with the other avian orders remains unresolved, comparative protein sequence studies might shed new light on this problem. Therefore, we determined the amino acid sequence of the eye lens protein alpha-crystallin A in ostrich, rhea and emu, and in representatives of 13 other avian orders. Comparison of these sequences with known alpha A sequences of mammals, reptiles, frog and dogfish provides strong evidence that the ratites, as a monophyletic assemblage, represent the first offshoot of the avain line.

Primary structures of the alpha-crystallin A chains of twenty-eight mammalian species, chicken and frog.

The amino acid sequences of the alpha-crystallin A chains of 28 mammalian species, representing 14 different orders, have been analyzed, mainly on the basis of amino acid compositions of the composing peptides. The alpha A sequences of chicken and a frog have been completely determined by Edman degradation. A method is described to transport eye lenses, to be used for protein sequence studies, at ambient temperature in a solution of guanidine . HCl. The number of cysteine residues in different alpha A chains could be determined by alkaline urea gel electrophoresis after aminoethylation . In some cases the alpha A chains have been isolated from total lens extracts in a single ion-exchange chromatographic step. The average rate of substitutions in the evolution of the alpha A chains is moderately slow, approximately 3 amino acid substitutions per 100 residues in 100 million years, but varies considerably in different lineages. Substitutions involving changes in charge are strongly underrepresented; the alpha A chains tend to keep their net charge constant throughout evolution. Analysis of the types of substitutions suggests a directional trend leading to an increase in functional density of alpha A in the course of evolution.

Large-scale preparation of gamma-crystallin and fractionation by chromatofocusing.

Large quantities of calf gamma-crystallin can be prepared by a single and rapid salting-out procedure. The final product is indistinguishable from the gamma-crystallin fraction obtained after gel filtration of a 15000 g lens protein supernatant over Sephadex G 200. Further fractionation is achieved by the mild procedure of chromatofocusing yielding six to eight subfractions. The latter have been characterized by polyacrylamide gel electrophoresis (PAGE) in 6 M-urea, SDS-gel electrophoresis, partial digestion with Staphylococcus aureus protease and amino acid analysis.

Primary structures of alpha-crystallin A chains of elephant, whale, hyrax and rhinoceros.

As part of a study of the evolutionary development of the eye lens protein alpha-crystallin the 173-residue A chain of this protein has been studied in elephant, whale, hyrax and rhinoceros. The primary structures were inferred mainly from amino acid compositions of peptides obtained by enzymic digestions and CNBr cleavage. The positions of substitutions, as compared to the known bovine A chain, were confirmed by Edman degradation. In accordance with the previously observed slow rate of evolution of the A chain only a small number of substitutions was found among these species. Elephant and hyrax share a number of unique substitutions, strongly indicating a common ancestry of these two species within the mammalian class.