The effects of two days of partial sleep deprivation on basketball skill performance

This study examined the effect of two nights of partial sleep deprivation (PSD) on basketball skill performance. [This is an excerpt from the abstract. For the complete abstract, please see the document.

Identification of genetic variants in CFAP221 as a cause of primary ciliary dyskinesia

Primary ciliary dyskinesia (PCD) is a rare disorder that affects the biogenesis or function of motile cilia resulting in chronic airway disease. PCD is genetically and phenotypically heterogeneous, with causative mutations identified in over 40 genes; however, the genetic basis of many cases is unknown. Using whole-exome sequencing, we identified three affected siblings with clinical symptoms of PCD but normal ciliary structure, carrying compound heterozygous loss-of-function variants in CFAP221. Computational analysis suggests that these variants are the most damaging alleles shared by all three siblings. Nasal epithelial cells from one of the subjects demonstrated slightly reduced beat frequency (16.5 Hz vs 17.7 Hz, p = 0.16); however, waveform analysis revealed that the CFAP221 defective cilia beat in an aberrant circular pattern. These results show that genetic variants in CFAP221 cause PCD and that CFAP221 should be considered a candidate gene in cases where PCD is suspected but cilia structure and beat frequency appear normal

Mutation of CFAP57, a protein required for the asymmetric targeting of a subset of inner dynein arms in Chlamydomonas, causes primary ciliary dyskinesia

Primary ciliary dyskinesia (PCD) is characterized by chronic airway disease, reduced fertility, and randomization of the left/right body axis. It is caused by defects of motile cilia and sperm flagella. We screened a cohort of affected individuals that lack an obvious axonemal defect for pathogenic variants using whole exome capture, next generation sequencing, and bioinformatic analysis assuming an autosomal recessive trait. We identified one subject with an apparently homozygous nonsense variant [(c.1762C\u3eT), p.(Arg588*)] in the uncharacterized CFAP57 gene. Interestingly, the variant results in the skipping of exon 11 (58 amino acids), which may be due to disruption of an exonic splicing enhancer. In normal human nasal epithelial cells, CFAP57 localizes throughout the ciliary axoneme. Nasal cells from the PCD patient express a shorter, mutant version of CFAP57 and the protein is not incorporated into the axoneme. The missing 58 amino acids include portions of WD repeats that may be important for loading onto the intraflagellar transport (IFT) complexes for transport or docking onto the axoneme. A reduced beat frequency and an alteration in ciliary waveform was observed. Knockdown of CFAP57 in human tracheobronchial epithelial cells (hTECs) recapitulates these findings. Phylogenetic analysis showed that CFAP57 is highly conserved in organisms that assemble motile cilia. CFAP57 is allelic with the BOP2/IDA8/FAP57 gene identified previously in Chlamydomonas reinhardtii. Two independent, insertional fap57 Chlamydomonas mutant strains show reduced swimming velocity and altered waveforms. Tandem mass tag (TMT) mass spectroscopy shows that FAP57 is missing, and the g inner dyneins (DHC7 and DHC3) and the d inner dynein (DHC2) are reduced, but the FAP57 paralog FBB7 is increased. Together, our data identify a homozygous variant in CFAP57 that causes PCD that is likely due to a defect in the inner dynein arm assembly process

Racism, gun ownership and gun control: Biased attitudes in US whites may influence policy decisions

Objective: Racism is related to policies preferences and behaviors that adversely affect blacks and appear related to a fear of blacks (e.g., increased policing, death penalty). This study examined whether racism is also related to gun ownership and opposition to gun controls in US whites. Method: The most recent data from the American National Election Study, a large representative US sample, was used to test relationships between racism, gun ownership, and opposition to gun control in US whites. Explanatory variables known to be related to gun ownership and gun control opposition (i.e., age, gender, education, income, conservatism, anti-government sentiment, southern vs. other states, political identification) were entered in logistic regression models, along with measures of racism, and the stereotype of blacks as violent. Outcome variables included; having a gun in the home, opposition to bans on handguns in the home, support for permits to carry concealed handguns. Results: After accounting for all explanatory variables, logistic regressions found that for each 1 point increase in symbolic racism there was a 50% increase in the odds of having a gun at home. After also accounting for having a gun in the home, there was still a 28% increase in support for permits to carry concealed handguns, for each one point increase in symbolic racism. The relationship between symbolic racism and opposition to banning handguns in the home (OR1.27 CI 1.03,1.58) was reduced to non-significant after accounting for having a gun in the home (OR1.17 CI.94,1.46), which likely represents self-interest in retaining property (guns). Conclusions: Symbolic racism was related to having a gun in the home and opposition to gun control policies in US whites. The findings help explain US whites' paradoxical attitudes towards gun ownership and gun control. Such attitudes may adversely influence US gun control policy debates and decisions

Expression of a Truncated Form of ODAD1 Associated with an Unusually Mild Primary Ciliary Dyskinesia Phenotype

Primary ciliary dyskinesia (PCD) is a rare lung disease caused by mutations that impair the function of motile cilia, resulting in chronic upper and lower respiratory disease, reduced fertility, and a high prevalence of situs abnormalities. The disease is genetically and phenotypically heterogeneous, with causative mutations in > 50 genes identified, and clinical phenotypes ranging from mild to severe. Absence of ODAD1 (CCDC114), a component of the outer dynein arm docking complex, results in a failure to assemble outer dynein arms (ODAs), mostly immotile cilia, and a typical PCD phenotype. We identified a female (now 34 years old) with an unusually mild clinical phenotype who has a homozygous non-canonical splice mutation (c.1502+5G>A) in ODAD1. To investigate the mechanism for the unusual phenotype, we performed molecular and functional studies of cultured nasal epithelial cells. We demonstrate that this splice mutation results in the expression of a truncated protein that is attached to the axoneme, indicating that the mutant protein retains partial function. This allows for the assembly of some ODAs and a significant level of ciliary activity that may result in the atypically mild clinical phenotype. The results also suggest that partial restoration of ciliary function by therapeutic agents could lead to significant improvement of disease symptoms

Fall, Recovery and Characterization of the Novato L6 Chondrite Breccia

The Novato L6 chondrite fragmental breccia fell in California on 17 October 2012, and was recovered after the Cameras for Allsky Meteor Surveillance (CAMS) project determined the meteor's trajectory between 95 and 45 km altitude. The final fragmentation at 33 1 km altitude was exceptionally well documented by digital photographs. The first sample was recovered before rain hit the area. First results from a consortium study of the meteorite's characterization, cosmogenic and radiogenic nuclides, origin and conditions of the fall are presented. Some meteorites did not retain fusion crust and show evidence of spallation. Before entry, the meteoroid was 35+/-5 cm in diameter (mass 80+/-35 kg) with a cosmic ray exposure age of 9+/-1 Ma, if it had a one-stage exposure history. However, based on the cosmogenic nuclide inventory, a two-stage exposure history is more likely, with lower shielding in the last few Ma. Thermoluminescence data suggest a collision event within the last approx. 0.1 Ma. Novato likely belonged to the class of shocked L chondrites that have a common shock age of 470 Ma, based on the U,Th-He age of 460+/-220 Ma. The measured orbits of Novato, Jesenice and Innisfree are consistent with a proposed origin of these shocked L chondrites in the Gefion asteroid family, but leave open the possibility that they came to us directly from the 5:2 mean motion resonance with Jupiter. Novato experienced a stronger compaction than did other L6 chondrites of shock-stage S4. Despite this, a freshly broken surface shows a wide range of organic compounds

Mutations in RSPH1 cause primary ciliary dyskinesia with a unique clinical and ciliary phenotype

Rationale: Primary ciliary dyskinesia (PCD) is a genetically heterogeneous recessive disorder of motile cilia, but the genetic cause is not defined for all patients with PCD. Objectives: To identify disease-causingmutations in novel genes, we performed exome sequencing, follow-up characterization, mutation scanning, and genotype-phenotype studies in patients with PCD. Methods: Whole-exome sequencing was performed using NimbleGen capture and Illumina HiSeq sequencing. Sanger-based sequencing was used for mutation scanning, validation, and segregation analysis. Measurements and Main Results: We performed exome sequencing on an affected sib-pair with normal ultrastructure in more than 85% of cilia. A homozygous splice-site mutation was detected in RSPH1 in both siblings; parents were carriers. Screening RSPH1 in 413 unrelated probands, including 325 with PCD and 88 with idiopathic bronchiectasis, revealed biallelic loss-of-function mutations in nine additional probands. Five affected siblings of probands in RSPH1 families harbored the familial mutations. The 16 individuals with RSPH1 mutations had some features of PCD; however, nasal nitric oxide levels were higher than in patients with PCD with other gene mutations (98.3 vs. 20.7 nl/min; P , 0.0003). Additionally, individuals with RSPH1 mutations had a lower prevalence (8 of 16) of neonatal respiratory distress, and later onset of daily wet cough than typical for PCD, and better lung function (FEV1), compared with 75 age- and sex-matched PCD cases (73.0 vs. 61.8, FEV1 % predicted; P = 0.043). Cilia from individuals with RSPH1 mutations had normal beat frequency (6.16Hz at 258C), but an abnormal, circular beat pattern. Conclusions: The milder clinical disease and higher nasal nitric oxide in individuals with biallelic mutations in RSPH1 provides evidence of a unique genotype-phenotype relationship in PCD, and suggests that mutations in RSPH1 may be associated with residual ciliary function

A human ciliopathy reveals essential functions for NEK10 in airway mucociliary clearance

© 2020, The Author(s), under exclusive licence to Springer Nature America, Inc. Mucociliary clearance, the physiological process by which mammalian conducting airways expel pathogens and unwanted surface materials from the respiratory tract, depends on the coordinated function of multiple specialized cell types, including basal stem cells, mucus-secreting goblet cells, motile ciliated cells, cystic fibrosis transmembrane conductance regulator (CFTR)-rich ionocytes, and immune cells1,2. Bronchiectasis, a syndrome of pathological airway dilation associated with impaired mucociliary clearance, may occur sporadically or as a consequence of Mendelian inheritance, for example in cystic fibrosis, primary ciliary dyskinesia (PCD), and select immunodeficiencies3. Previous studies have identified mutations that affect ciliary structure and nucleation in PCD4, but the regulation of mucociliary transport remains incompletely understood, and therapeutic targets for its modulation are lacking. Here we identify a bronchiectasis syndrome caused by mutations that inactivate NIMA-related kinase 10 (NEK10), a protein kinase with previously unknown in vivo functions in mammals. Genetically modified primary human airway cultures establish NEK10 as a ciliated-cell-specific kinase whose activity regulates the motile ciliary proteome to promote ciliary length and mucociliary transport but which is dispensable for normal ciliary number, radial structure, and beat frequency. Together, these data identify a novel and likely targetable signaling axis that controls motile ciliary function in humans and has potential implications for other respiratory disorders that are characterized by impaired mucociliary clearance

Debris Field of the July 19, 2009, Impact in Jupiter and Its Long-term Evolution

A multi-platform suite of imaging and spectroscopic observations of Jupiter\u27s atmosphere tracked the evolution of the debris field of an unknown impactor on 2009 July 19. The initial debris field is similar to those of intermediate Shoemaker-Levy 9 fragments, suggesting a body hundreds of meters in size, if icy, entering from the west and slightly north. The field is detectable in the visible as dark material and in the near-IR by high-altitude particulate reflectivity; it was quickly redistributed by different zonal flows across its latitudinal range. At first, the particulate field was highly correlated with areas of enhanced temperatures and enhanced ammonia and ethane emission, but this was no longer true by mid-August. As of Sept. 2, the debris field was undetectable in the thermal, detectable in the visible with good seeing, and still prominent near 2 microns wavelength. Visibly, the impact scar consists of two dark regions along the same latitude, ostensibly different from the central bright region associated with the near-IR debris pattern. Both morphologies show eastern and western extensions propagating away from the original impact site, which appear to be influenced by flows around vortices previously undetected in Jupiter atmosphere. These observations define the flow field just north of Jupiter\u27s southern polar vortex at higher altitudes than tracked in Jupiter\u27s main cloud deck