Severity of Mitral Valve Degeneration Is Associated with Chromosome 15 Loci in Whippet Dogs

Mitral valve degeneration (MVD) is the most common form of heart disease in dogs, frequently leading to left-sided congestive heart failure and cardiac mortality. Although breed-specific disease characteristics and overrepresentation point towards a genetic origin for MVD, a causative mutation and complete molecular pathogenesis are unknown. Whippet dogs are overrepresented in incidence of MVD, suggesting an inherited component in this breed. Expressivity of this condition is variable with some dogs showing evidence of more severe disease at earlier ages than other dogs. This phenomenon makes a traditional case versus control genetic study prone to phenotyping error. This study sought to avoid these common pitfalls by identifying genetic loci associated with severity of MVD in Whippets through a genome-wide association study (GWAS). 138 Whippet dogs were characterized for MVD by echocardiographic examination and a novel disease severity score was developed and adjusted for age in each subject. Single nucleotide polymorphism (SNP) genotype data (170k Illumina CanineHD SnpChip) was obtained for DNA isolated from blood of each study subject. Continuous variable genome wide association was performed after correction for population stratification by efficient mixed model association expedited (EMMAX) in 130 dogs. A genome wide significant association was identified on chromosome 15 (peak locus 57,770,326; P_adj = 0.049) and secondary loci of suggestive association were identified on chromosome 2 (peak locus 37,628,875; P_adj = 0.079). Positional candidate genes were identified within the primary and secondary loci including follistatin-related protein 5 precursor (FSTL5) and Rho GTPase-activating protein 26 (ARHGAP26). These results support the hypothesis that severity of MVD in whippets has a genetic basis and warrants further study by either candidate gene sequencing or next-generation techniques.     

Determining the Presence of Superantigens in Coagulase Negative Staphylococci from Humans

Superantigens (SAgs) are important virulence factors in S. aureus. Recent studies identified their presence in animal coagulase-negative staphylococci (CNS). The emergence of human-associated SAg⁺ CNS would mark a prodigious shift in virulence capabilities. We examined CNS isolates from healthy human nares and diseased individuals, and determined that no known SAgs were present.     

Can Inconsistent Association between Hypertension and Cognition in Elders be Explained by Levels of Organochlorine Pesticides?

The relation between hypertension and cognition in elders remains unclear, and studies on the effect of antihypertensive drugs on cognition have demonstrated conflicting results. This study was performed to evaluate if the association between hypertension and cognition in elders differed depending on serum concentrations of organochlorine (OC) pesticides, common neurotoxic chemicals. Participants were 644 elders aged 60–85 years who participated in the National Health and Nutrition Examination Survey 1999–2002 and were able to complete a cognitive test. We selected 6 OC pesticides that were commonly detected in the elderly. Cognition was assessed by the Digit Symbol Substitution Test (DSST), a relevant tool for evaluating hypertension-related cognitive function, and low cognition was defined by the DSST score < 25^th percentile. When OC pesticides were not considered in the analyses, elders with hypertension had about 1.7 times higher risk of low cognition than those without hypertension. However, in analyses stratified by serum concentrations of OC pesticides, the associations between hypertension and low cognition were stronger the higher the serum concentrations of p,p’-DDT, p,p’-DDE, β-hexachlorocyclohexane, and trans-nonachlor increased. Among elders in the 3^rd tertile of these pesticides, adjusted odds ratios were from 2.5 to 3.5. In contrast, hypertension was not clearly associated with the risk of low cognition in elders in the 1^st tertile of these pesticides. Similar patterns were observed for the continuous DSST score dependent variable. The difference in the association between hypertension and DSST scores according to the levels of OC pesticides suggest a key role of OC pesticides in the development of hypertension-related cognitive impairment and may help to identify hypertensive elders who are at a high risk of cognitive impairment.     

Nature’s Palette: Characterization of Shared Pigments in Colorful Avian and Mollusk Shells

Pigment-based coloration is a common trait found in a variety of organisms across the tree of life. For example, calcareous avian eggs are natural structures that vary greatly in color, yet just a handful of tetrapyrrole pigment compounds are responsible for generating this myriad of colors. To fully understand the diversity and constraints shaping nature’s palette, it is imperative to characterize the similarities and differences in the types of compounds involved in color production across diverse lineages. Pigment composition was investigated in eggshells of eleven paleognath bird taxa, covering several extinct and extant lineages, and shells of four extant species of mollusks. Birds and mollusks are two distantly related, calcareous shell-building groups, thus characterization of pigments in their calcareous structures would provide insights to whether similar compounds are found in different phyla (Chordata and Mollusca). An ethylenediaminetetraacetic acid (EDTA) extraction protocol was used to analyze the presence and concentration of biliverdin and protoporphyrin, two known and ubiquitous tetrapyrrole avian eggshell pigments, in all avian and molluscan samples. Biliverdin was solely detected in birds, including the colorful eggshells of four tinamou species. In contrast, protoporphyrin was detected in both the eggshells of several avian species and in the shells of all mollusks. These findings support previous hypotheses about the ubiquitous deposition of tetrapyrroles in the eggshells of various bird lineages and provide evidence for its presence also across distantly related animal taxa.     

Long-Term Safety of Repeated Blood-Brain Barrier Opening via Focused Ultrasound with Microbubbles in Non-Human Primates Performing a Cognitive Task

Focused Ultrasound (FUS) coupled with intravenous administration of microbubbles (MB) is a non-invasive technique that has been shown to reliably open (increase the permeability of) the blood-brain barrier (BBB) in multiple in vivo models including non-human primates (NHP). This procedure has shown promise for clinical and basic science applications, yet the safety and potential neurological effects of long term application in NHP requires further investigation under parameters shown to be efficacious in that species (500kHz, 200–400 kPa, 4–5μm MB, 2 minute sonication). In this study, we repeatedly opened the BBB in the caudate and putamen regions of the basal ganglia of 4 NHP using FUS with systemically-administered MB over 4–20 months. We assessed the safety of the FUS with MB procedure using MRI to detect edema or hemorrhaging in the brain. Contrast enhanced T1-weighted MRI sequences showed a 98% success rate for openings in the targeted regions. T2-weighted and SWI sequences indicated a lack edema in the majority of the cases. We investigated potential neurological effects of the FUS with MB procedure through quantitative cognitive testing of’ visual, cognitive, motivational, and motor function using a random dot motion task with reward magnitude bias presented on a touchpanel display. Reaction times during the task significantly increased on the day of the FUS with MB procedure. This increase returned to baseline within 4–5 days after the procedure. Visual motion discrimination thresholds were unaffected. Our results indicate FUS with MB can be a safe method for repeated opening of the BBB at the basal ganglia in NHP for up to 20 months without any long-term negative physiological or neurological effects with the parameters used.     

Evolutionary contingency and SETI revisited

The well-known argument against the Search for ExtraTerrestrial Intelligence (SETI) due to George Gaylord Simpson is re-analyzed almost half a century later, in the light of our improved understanding of preconditions for the emergence of life and intelligence brought about by the ongoing “astrobiological revolution”. Simpson’s argument has been enormously influential, in particular in biological circles, and it arguably fueled the most serious opposition to SETI programmes and their funding. I argue that both proponents and opponents of Simpson’s argument have occasionally mispresented its core content. Proponents often oversimplify it as just another consequence of biological contingency, thus leaving their position open to general arguments limiting the scope of contingency in evolution (such as the recent argument of Geerat Vermeij based on selection effects in the fossil record). They also tend to neglect that the argument has been presented as essentially atemporal, while referring to entities and processes that are likely to change over time; this has become even less justifiable as our astrobiological knowledge increased in recent years. Opponents have failed to see that the weaknesses in Simpson’s position could be removed by restructuring of the argument; I suggest one way of such restructuring, envisioned long ago in the fictional context by Stanislaw Lem. While no firm consensus has emerged on the validity of Simpson’s argument so far, I suggest that, contrary to the original motivation, today it is less an anti-SETI argument, and more an astrobiological research programme. In this research programme, SETI could be generalized into a platform for testing some of the deepest assumptions about evolutionary continuity and the relative role of contingency versus convergence on unprecedented spatial and temporal scales.     

Occurrence of Acremonium endophytes in wild populations of Lolium spp. in European countries and a relationship between level of infection and climate in France

Infection with endophytic fungi (Acremonium spp.) was detected in wild populations of Lolium spp. from 15 of 20 European countries. Of 523 populations examined, 38% contained no infection, 48% contained 1–50% infection and 14% contained 51–100% infection. Level of infection was slightly but significantly associated with abundance of Lolium in the sward. For data from France, significant correlations were obtained between level of infection and five climate variables; the highest correlations were with evapotranspiration (0.66, P < 0.001) and water supply deficit (-0.66, P < 0.001). A model established using multiple regression analysis and incorporating five climatic variables, accounted for 56% of total variation; water supply deficit alone accounted for 43%. These climatic variables were shown by geostatistical analysis to account for a spatial structure in infection level. Groups of Lolium populations with a high level of infection were located mostly in Mediterranean regions, where stress from summer drought is common.     

Proteolytic inactivation of an extracellular (1 → 3)-β-glucanase from the fungus Acremonium persicinum is associated with growth at neutral or alkaline medium pH

Abstract The filamentous fungus Acremonium persicinum released high levels of proteolytic enzyme activity into the culture fluid during growth at pH 7 or above. Almost total inhibition of this crude activity by phenylmethylsulfonyl fluoride suggested that it was mainly due to the presence of a serine protease. This protease inactivated one of three extracellular (1 → 3)- β -glucanases produced by this fungus, although the activities of the remaining two (1 → 3)- β -glucanases did not appear to be affected. Growth of A. persicinum in acidic conditions resulted in the presence of much lower extracellular proteolytic activity and no apparent (1 → 3)- β -glucanase inactivation.