Properties of the redshift

Central to any analysis of dynamical systems, or large scale motion, is the interpretation of redshifts of galaxies as classical Doppler velocity shifts. This is a testable assumption and for many years evidence has accumulated that is inconsistent with the assumption. Here, the authors review recent evidence suggesting systematic radial dependence and temporal variation of redshifts

Novel pathogenic COX20 variants causing dysarthria, ataxia, and sensory neuropathy.

COX20/FAM36A encodes a mitochondrial complex IV assembly factor important for COX2 activation. Only one homozygous COX20 missense mutation has been previously described in two separate consanguineous families. We report four subjects with features that include childhood hypotonia, areflexia, ataxia, dysarthria, dystonia, and sensory neuropathy. Exome sequencing in all four subjects identified the same novel COX20 variants. One variant affected the splice donor site of intron-one (c.41A>G), while the other variant (c.157+3G>C) affected the splice donor site of intron-two. cDNA and protein analysis indicated that no full-length cDNA or protein was generated. These subjects expand the phenotype associated with COX20 deficiency

Whole-Exome Sequencing Identifies Homozygous AFG3L2 Mutations in a Spastic Ataxia-Neuropathy Syndrome Linked to Mitochondrial m-AAA Proteases

We report an early onset spastic ataxia-neuropathy syndrome in two brothers of a consanguineous family characterized clinically by lower extremity spasticity, peripheral neuropathy, ptosis, oculomotor apraxia, dystonia, cerebellar atrophy, and progressive myoclonic epilepsy. Whole-exome sequencing identified a homozygous missense mutation (c.1847G>A; p.Y616C) in AFG3L2, encoding a subunit of an m-AAA protease. m-AAA proteases reside in the mitochondrial inner membrane and are responsible for removal of damaged or misfolded proteins and proteolytic activation of essential mitochondrial proteins. AFG3L2 forms either a homo-oligomeric isoenzyme or a hetero-oligomeric complex with paraplegin, a homologous protein mutated in hereditary spastic paraplegia type 7 (SPG7). Heterozygous loss-of-function mutations in AFG3L2 cause autosomal-dominant spinocerebellar ataxia type 28 (SCA28), a disorder whose phenotype is strikingly different from that of our patients. As defined in yeast complementation assays, the AFG3L2Y616C gene product is a hypomorphic variant that exhibited oligomerization defects in yeast as well as in patient fibroblasts. Specifically, the formation of AFG3L2Y616C complexes was impaired, both with itself and to a greater extent with paraplegin. This produced an early-onset clinical syndrome that combines the severe phenotypes of SPG7 and SCA28, in additional to other “mitochondrial” features such as oculomotor apraxia, extrapyramidal dysfunction, and myoclonic epilepsy. These findings expand the phenotype associated with AFG3L2 mutations and suggest that AFG3L2-related disease should be considered in the differential diagnosis of spastic ataxias

Mechanism of KMT5B haploinsufficiency in neurodevelopment in humans and mice.

Pathogenic variants in KMT5B, a lysine methyltransferase, are associated with global developmental delay, macrocephaly, autism, and congenital anomalies (OMIM# 617788). Given the relatively recent discovery of this disorder, it has not been fully characterized. Deep phenotyping of the largest (n = 43) patient cohort to date identified that hypotonia and congenital heart defects are prominent features that were previously not associated with this syndrome. Both missense variants and putative loss-of-function variants resulted in slow growth in patient-derived cell lines. KMT5B homozygous knockout mice were smaller in size than their wild-type littermates but did not have significantly smaller brains, suggesting relative macrocephaly, also noted as a prominent clinical feature. RNA sequencing of patient lymphoblasts and Kmt5b haploinsufficient mouse brains identified differentially expressed pathways associated with nervous system development and function including axon guidance signaling. Overall, we identified additional pathogenic variants and clinical features in KMT5B-related neurodevelopmental disorder and provide insights into the molecular mechanisms of the disorder using multiple model systems

Multicolor photoelectric photometry of bright extragalactic systems

57 galaxies and 52 stars have been observed in four colors using a blue sensitive phototube. The response bands of the photometric system have effective reciprocal wave lengths of (micron units) 2.66, 2.39, 2.07, and 1.68. In addition to the blue measurements 8 galaxies and 19 stars have been observed in four colors using a red sensitive photocell. The effective reciprocal wave lengths of the red response bands are 1.55, 1.26, 1.14, and 1.00. From one to five different aperture sizes have been used in the photometry of each galaxy, with an average of three per galaxy. The entire eight color photometric system has been calibrated to place color index measurements on an absolute energy basis. Correlations between nuclear color index and inclination, spectral class, and nebular type indicate that most of the observed galaxies fall into fairly distinct groups. Radial color variations are also found to correlate with group membership. The dominant characteristics of the groups are as follows: Spectral type A, spectral type F, spectral type FG, nebular type SA, nebular type E, nebular type SO, nebular type SB. The correlation between nuclear color and inclination (axis ratio) is found to show a distinct separation of SA, SB, and elliptical galaxies, probably due in part to differences in internal absorption. The correlation of nuclear color and spectral type shows that FG galaxies, while later in spectral class than F galaxies, have nuclei bluer than those in F galaxies. A possible explanation is offered which interprets the inversion in terms of the relative numbers of normal and low metal abundance stars in each type of galaxy. Radial color investigation reveal the existence of blue nuclei in three galaxies. Synthetic models are given for five distinct types of extragalactic nuclei. K nuclei can be represented with a mixture of old population I and II stars. F, FG, and probably AF nuclei can be produced by adding various numbers of young blue stars to K galaxies. A type galaxies appear to be completely dominated by young stars

THE CORRELATION OF OPTICAL ABNORMALITIES AND SMALL RADIO SOURCES IN GALAXY NUCLEI

Radio emission from small sources in galaxy nuclei is shown to be correlated with the optical photometric properties. Within the limitations of the small sample available, the following observations are made: (1) no galaxy with a photometrically normal nuclear region contains a small radio source, although it may contain a large source; (2) when a small radio source is present the galaxy nuclei are abnormally red or blue. The opposite is not true, however, since (3) not all photometrically blue or red nuclei contain small radio sources. Finally, (4+) the sources in red nuclei are apparently smaller than in blue nuclei and are the ones showing abnormal radio spectra. A close similarity between the abnormal nuclei and QSS phenomena is noted and it is proposed that the phenomena is either (1) a small scale QSS phenomena or (2) pre and /or post QSS stages.This title from the Steward Observatory Preprints collection is made available by the Steward Observatory Parker Library and the University Libraries, The University of Arizona. If you have questions about titles in this collection, please contact Parker Library librarian Betty Fridena, [email protected]

Novel pathogenic COX20 variants causing dysarthria, ataxia, and sensory neuropathy.

COX20/FAM36A encodes a mitochondrial complex IV assembly factor important for COX2 activation. Only one homozygous COX20 missense mutation has been previously described in two separate consanguineous families. We report four subjects with features that include childhood hypotonia, areflexia, ataxia, dysarthria, dystonia, and sensory neuropathy. Exome sequencing in all four subjects identified the same novel COX20 variants. One variant affected the splice donor site of intron-one (c.41A>G), while the other variant (c.157+3G>C) affected the splice donor site of intron-two. cDNA and protein analysis indicated that no full-length cDNA or protein was generated. These subjects expand the phenotype associated with COX20 deficiency

yippee like 3 (ypel3) is a novel gene required for myelinating and perineurial glia development.

Hypomyelination, a neurological condition characterized by decreased production of myelin sheets by glial cells, often has no known etiology. Elucidating the genetic causes of hypomyelination provides a better understanding of myelination, as well as means to diagnose, council, and treat patients. Here, we present evidence that YIPPEE LIKE 3 (YPEL3), a gene whose developmental role was previously unknown, is required for central and peripheral glial cell development. We identified a child with a constellation of clinical features including cerebral hypomyelination, abnormal peripheral nerve conduction, hypotonia, areflexia, and hypertrophic peripheral nerves. Exome and genome sequencing revealed a de novo mutation that creates a frameshift in the open reading frame of YPEL3, leading to an early stop codon. We used zebrafish as a model system to validate that YPEL3 mutations are causative of neuropathy. We found that ypel3 is expressed in the zebrafish central and peripheral nervous system. Using CRISPR/Cas9 technology, we created zebrafish mutants carrying a genomic lesion similar to that of the patient. Our analysis revealed that Ypel3 is required for development of oligodendrocyte precursor cells, timely exit of the perineurial glial precursors from the central nervous system (CNS), formation of the perineurium, and Schwann cell maturation. Consistent with these observations, zebrafish ypel3 mutants have metabolomic signatures characteristic of oligodendrocyte and Schwann cell differentiation defects, show decreased levels of Myelin basic protein in the central and peripheral nervous system, and develop defasciculated peripheral nerves. Locomotion defects were observed in adult zebrafish ypel3 mutants. These studies demonstrate that Ypel3 is a novel gene required for perineurial cell development and glial myelination

Correction: yippee like 3 (ypel3) is a novel gene required for myelinating and perineurial glia development.

[This corrects the article DOI: 10.1371/journal.pgen.1008841.]