Colonization of the Southern Hemisphere by fur seals and sea lions (Carnivora: Otariidae) revealed by combined evidence phylogenetic and Bayesian biogeographical analysis

Fur seals and sea lions (Carnivora: Otariidae) evolved in the North Pacific and later dispersed throughout the Southern Hemisphere. However, the timing and number of dispersals into the Southern Hemisphere still remain poorly understood. To determine the biogeographical patterns of dispersal within fur seals and sea lions, we conducted cladistic analyses using combined evidence incorporating morphological and molecular data. The phylogeny produced in this study was then incorporated into Bayesian biogeographical analyses to reconstruct ancestral points of origin and dispersal patterns for otariid clades. Combined evidence analyses supported Callorhinus as the earliest diverging extant otariid, and a strongly supported northern sea lion clade (Zalophus, Eumetopias, and Proterozetes) as the sister group to a southern clade comprising the remainder of Otariidae. Fossil data constrained the timing and location of this dispersal as occurring between 6 and 7 Mya during a period of unusually cool sea surface temperatures and high productivity in the eastern equatorial Pacific, far older than suggested by prior studies. Our study indicates that the distribution of fur seals and sea lions is tightly linked to sea surface temperature and productivity, and suggests that otariids may be vulnerable to future anthropogenic climate change. © 2014 The Linnean Society of London     

Glucose-6-phosphate dehydrogenase from Leuconostoc mesenteroides is a reliable internal standard for radiation-inactivation studies of membranes in the frozen state

The target size of four soluble enzymes (beta-galactosidase, pyruvate kinase, alcohol dehydrogenase, and glucose-6-phosphate dehydrogenase) in the presence or absence of subcellular membrane fractions has been determined by the radiation-inactivation method using samples in the frozen state. For each of the four enzymes, full activity was recovered after freezing and thawing in the absence of radiation. We found minimal (less than 20%) binding of the enzymes to either submitochondrial vesicles or sarcoplasmic reticulum vesicles. Under the conditions tested, beta-galactosidase, pyruvate kinase, and alcohol dehydrogenase exhibited target sizes which varied according to the experimental conditions, i.e., the buffer selected and also the presence or absence of membrane preparations. For these tetrameric enzymes, the target sizes were generally comparable to either a monomer or a dimer. By contrast, the target size of glucose-6-phosphate dehydrogenase from Leuconostoc mesenteroides was found to be essentially invariant when frozen in a variety of buffers and in the presence or absence of either cryoprotectant (sucrose or glycerol) or different membrane preparations. The target size from 19 separate determinations gave an average value of 104 +/- 16 kDa, which is comparable to the molecular weight of the enzyme (104 kDa). We conclude that glucose-6-phosphate dehydrogenase from L. mesenteroides is a reliable internal standard for radiation-inactivation studies of membrane preparations in the frozen state.     

Autoradiographic localization of γ-aminobutyric acidA receptors within the ventral tegmental area

Destruction of intrinsic neurons in the ventral tegmental area (VTA) with the excitotoxin, quinolinic acid produced a significant decrease (80%) in [³H]muscimol binding to GABA_A receptors within the parabrachial pigmented and paranigral nuclei of the VTA. Selective destruction of the dopaminergic neurons with 6-hydroxydopamine (6-OHDA) did not reduce [³H]muscimol binding within the VTA. However, the destruction of dopaminergic neurons did produce an increase (20%) in [³H]muscimol binding contralateral to the lesion, suggesting a reduction in the GABAergic innervation to this region. Additionally, destruction of the VTA afferents with quinolinic acid injections in the medial accumbens failed to produce alterations in [³H]muscimol binding within the VTA. These results are consistent with the predominant localization of GABA_A receptors to non-dopaminergic neurons intrinsic to the VTA.Special issue dedicated to Dr. Frederick E. Samson     

BRONCHOGENIC CARCINOMA IN SAN DIEGO COUNTY—Relation of Mortality Rates to Findings in Mass Chest X-Ray Survey

Nearly half the population of San Diego County was examined by chest x-ray for bronchogenic carcinoma. The disease was correctly diagnosed in 20 persons, of whom 17 died. Twenty-four others in whom it was not detected in survey films died of the disease in the following two years.Of the 20 cases found, 16 were in men, all more than 54 years of age, and of the 24 who died after “negative” classification, 20 were men over 40.The death rate for men over 40 years of age from bronchogenic carcinoma is about one in a thousand. Because of the frequently rapid progress of the disease after onset, and the poor prognosis after the appearance of symptoms, x-ray examination every six months for men over 40 should be considered.     

Neandertal radial tuberosity orientation

Examination of adult and immature Neandertal radii demonstrates that the medial versus anterior orientations of their radial tuberosities fall within recent human ranges of variation, but on the average their radial tuberosities are significantly more medially, as opposed to anteromedially, oriented. This more posterior positioning of their radial tuberosities implies a maintenance of an effective moment arm for M. biceps brachii through the full range of supination, an interpretation which fits with the hypertrophy of and increased moment arms for their forearm pronator muscles. It is an additional indication of the muscular hypertrophy evident elsewhere in Neandertal upper limbs.     

Effect of intrarenal arterial infusion of magnesium on renin release in dogs.

Magnesium chloride was infused into the renal artery of anesthetized dogs in order to determine its effect on renal function. Natriuresis and diuresis were observed during MgCl2 infusion, but there appeared to be no effect on glomerular filtration rate (GFR), or plasma sodium or potassium concentrations. Although mean arterial blood pressure and renal plasma flow (RPF) decreased throughout the experiment, the fall was not significant until after stopping MgCl2 infusion. A significant stimulation of renin secretion occurred during magnesium administration.     

Exome-Based Mapping and Variant Prioritization for Inherited Mendelian Disorders

Exome sequencing in families affected by rare genetic disorders has the potential to rapidly identify new disease genes (genes in which mutations cause disease), but the identification of a single causal mutation among thousands of variants remains a significant challenge. We developed a scoring algorithm to prioritize potential causal variants within a family according to segregation with the phenotype, population frequency, predicted effect, and gene expression in the tissue(s) of interest. To narrow the search space in families with multiple affected individuals, we also developed two complementary approaches to exome-based mapping of autosomal-dominant disorders. One approach identifies segments of maximum identity by descent among affected individuals; the other nominates regions on the basis of shared rare variants and the absence of homozygous differences between affected individuals. We showcase our methods by using exome sequence data from families affected by autosomal-dominant retinitis pigmentosa (adRP), a rare disorder characterized by night blindness and progressive vision loss. We performed exome capture and sequencing on 91 samples representing 24 families affected by probable adRP but lacking common disease-causing mutations. Eight of 24 families (33%) were revealed to harbor high-scoring, most likely pathogenic (by clinical assessment) mutations affecting known RP genes. Analysis of the remaining 17 families identified candidate variants in a number of interesting genes, some of which have withstood further segregation testing in extended pedigrees. To empower the search for Mendelian-disease genes in family-based sequencing studies, we implemented them in a cross-platform-compatible software package, MendelScan, which is freely available to the research community.