Maladaptation and the paradox of robustness in evolution

Background. Organisms use a variety of mechanisms to protect themselves against perturbations. For example, repair mechanisms fix damage, feedback loops keep homeostatic systems at their setpoints, and biochemical filters distinguish signal from noise. Such buffering mechanisms are often discussed in terms of robustness, which may be measured by reduced sensitivity of performance to perturbations. Methodology/Principal Findings. I use a mathematical model to analyze the evolutionary dynamics of robustness in order to understand aspects of organismal design by natural selection. I focus on two characters: one character performs an adaptive task; the other character buffers the performance of the first character against perturbations. Increased perturbations favor enhanced buffering and robustness, which in turn decreases sensitivity and reduces the intensity of natural selection on the adaptive character. Reduced selective pressure on the adaptive character often leads to a less costly, lower performance trait. Conclusions/Significance. The paradox of robustness arises from evolutionary dynamics: enhanced robustness causes an evolutionary reduction in the adaptive performance of the target character, leading to a degree of maladaptation compared to what could be achieved by natural selection in the absence of robustness mechanisms. Over evolutionary time, buffering traits may become layered on top of each other, while the underlying adaptive traits become replaced by cheaper, lower performance components. The paradox of robustness has widespread implications for understanding organismal design

Divergent mathematical treatments in utility theory

In this paper I study how divergent mathematical treatments affect mathematical modelling, with a special focus on utility theory. In particular I examine recent work on the ranking of information states and the discounting of future utilities, in order to show how, by replacing the standard analytical treatment of the models involved with one based on the framework of Nonstandard Analysis, diametrically opposite results are obtained. In both cases, the choice between the standard and nonstandard treatment amounts to a selection of set-theoretical parameters that cannot be made on purely empirical grounds. The analysis of this phenomenon gives rise to a simple logical account of the relativity of impossibility theorems in economic theory, which concludes the paper

A 4% Geometric Distance to the Galaxy NGC4258 from Orbital Motions in a Nuclear Gas Disk

The water maser in the mildly active nucleus in the nearby galaxy NGC4258 traces a thin, nearly edge-on, subparsec-scale Keplerian disk. Using the technique of very long baseline interferometry, we have detected the proper motions of these masers as they sweep in front of the central black hole at an orbital velocity of about 1100 km/s. The average maser proper motion of 31.5 microarcseconds per year is used in conjunction with the observed acceleration of the masers to derive a purely geometric distance to the galaxy of 7.2 +- 0.3 Mpc. This is the most precise extragalactic distance measured to date, and, being independent of all other distance indicators, is likely to play an important role in calibrating the extragalactic distance scale.Comment: 11 pages, 3 figures. Accepted for publication in Natur

Transcription profiling reveals potential mechanisms of dysbiosis in the oral microbiome of rhesus macaques with chronic untreated SIV infection.

A majority of individuals infected with human immunodeficiency virus (HIV) have inadequate access to antiretroviral therapy and ultimately develop debilitating oral infections that often correlate with disease progression. Due to the impracticalities of conducting host-microbe systems-based studies in HIV infected patients, we have evaluated the potential of simian immunodeficiency virus (SIV) infected rhesus macaques to serve as a non-human primate model for oral manifestations of HIV disease. We present the first description of the rhesus macaque oral microbiota and show that a mixture of human commensal bacteria and "macaque versions" of human commensals colonize the tongue dorsum and dental plaque. Our findings indicate that SIV infection results in chronic activation of antiviral and inflammatory responses in the tongue mucosa that may collectively lead to repression of epithelial development and impact the microbiome. In addition, we show that dysbiosis of the lingual microbiome in SIV infection is characterized by outgrowth of Gemella morbillorum that may result from impaired macrophage function. Finally, we provide evidence that the increased capacity of opportunistic pathogens (e.g. E. coli) to colonize the microbiome is associated with reduced production of antimicrobial peptides

Coexisting conical bipolar and equatorial outflows from a high-mass protostar

The BN/KL region in the Orion molecular cloud is an archetype in the study of the formation of stars much more massive than the Sun. This region contains luminous young stars and protostars, but it is difficult to study because of overlying dust and gas. Our basic expectations are shaped to some extent by the present theoretical picture of star formation, the cornerstone of which is that protostars acrete gas from rotating equatorial disks, and shed angular momentum by ejecting gas in bipolar outflows. The main source of the outflow in the BN/KL region may be an object known as radio source I, which is commonly believed to be surrounded by a rotating disk of molecular material. Here we report high-resolution observations of silicon monoxide (SiO) and water maser emission from the gas surrounding source I; we show that within 60 AU (about the size of the Solar System), the region is dominated by a conical bipolar outflow, rather than the expected disk. A slower outflow, close to the equatorial plane of the protostellar system, extends to radii of 1,000 AU.Comment: 10 pages, 2 figures. Accepted by Nature. To appear December 199

The intersection of COVID-19 and autoimmunity

Acute coronavirus disease 2019 (COVID-19), caused by SARS-CoV-2, is characterized by diverse clinical presentations, ranging from asymptomatic infection to fatal respiratory failure, and often associated with varied longer-term sequelae. Over the past 18 months, it has become apparent that inappropriate immune responses contribute to the pathogenesis of severe COVID-19. Researchers working at the intersection of COVID-19 and autoimmunity recently gathered at an American Autoimmune Related Disease Association (AARDA) Noel R. Rose Colloquium to address the current state of knowledge regarding two important questions: Does established autoimmunity predispose to severe COVID-19? And, at the same time, can SARS-CoV-2 infection trigger de novo autoimmunity? Indeed, work to date has demonstrated that 10 to 15% of patients with critical COVID-19 pneumonia exhibit autoantibodies against type I interferons, suggesting that preexisting autoimmunity underlies severe disease in some patients. Other studies have identified functional autoantibodies following infection with SARS-CoV-2, such as those that promote thrombosis or antagonize cytokine signaling. These autoantibodies may arise from a predominantly extrafollicular B cell response that is more prone to generating autoantibody-secreting B cells. This review highlights the current understanding, evolving concepts, and unanswered questions provided by this unique opportunity to determine mechanisms by which a viral infection can be exacerbated by, and even trigger, autoimmunity. The potential role of autoimmunity in post-acute sequelae of COVID-19 is also discussed

Differentiated transplant derived airway epithelial cell cytokine secretion is not regulated by cyclosporine

<p>Abstract</p> <p>Background</p> <p>While lung transplantation is an increasingly utilized therapy for advanced lung diseases, chronic rejection in the form of Bronchiolitis Obliterans Syndrome (BOS) continues to result in significant allograft dysfunction and patient mortality. Despite correlation of clinical events with eventual development of BOS, the causative pathophysiology remains unknown. Airway epithelial cells within the region of inflammation and fibrosis associated with BOS may have a participatory role.</p> <p>Methods</p> <p>Transplant derived airway epithelial cells differentiated in air liquid interface culture were treated with IL-1β and/or cyclosporine, after which secretion of cytokines and growth factor and gene expression for markers of epithelial to mesenchymal transition were analyzed.</p> <p>Results</p> <p>Secretion of IL-6, IL-8, and TNF-α, but not TGF-β1, was increased by IL-1β stimulation. In contrast to previous studies using epithelial cells grown in submersion culture, treatment of differentiated cells in ALI culture with cyclosporine did not elicit cytokine or growth factor secretion, and did not alter IL-6, IL-8, or TNF-α production in response to IL-1β treatment. Neither IL-1β nor cyclosporine elicited expression of markers of the epithelial to mesenchymal transition E-cadherin, EDN-fibronectin, and α-smooth muscle actin.</p> <p>Conclusion</p> <p>Transplant derived differentiated airway epithelial cell IL-6, IL-8, and TNF-α secretion is not regulated by cyclosporine <it>in vitro</it>; these cells thus may participate in local inflammatory responses in the setting of immunosuppression. Further, treatment with IL-1β did not elicit gene expression of markers of epithelial to mesenchymal transition. These data present a model of differentiated airway epithelial cells that may be useful in understanding epithelial participation in airway inflammation and allograft rejection in lung transplantation.</p

Exoplanet Atmosphere Measurements from Transmission Spectroscopy and other Planet-Star Combined Light Observations

It is possible to learn a great deal about exoplanet atmospheres even when we cannot spatially resolve the planets from their host stars. In this chapter, we overview the basic techniques used to characterize transiting exoplanets - transmission spectroscopy, emission and reflection spectroscopy, and full-orbit phase curve observations. We discuss practical considerations, including current and future observing facilities and best practices for measuring precise spectra. We also highlight major observational results on the chemistry, climate, and cloud properties of exoplanets.Comment: Accepted review chapter; Handbook of Exoplanets, eds. Hans J. Deeg and Juan Antonio Belmonte (Springer-Verlag). 22 pages, 6 figure

Development of a reliable and construct valid measure of nutritional literacy in adults

BACKGROUND: Research into the relation of literacy to health status has not included measures of nutritional literacy. This may be a critical area in the study of chronic conditions such as hypertension and diabetes, which can both relate to obesity and nutrition. This paper details the development and psychometric characteristics of the Nutritional Literacy Scale (NLS), offered as a measure of adults' ability to comprehend nutritional information. METHODS: In order to assess the internal consistency and construct validity of the NLS, demographic data, readability statistics, NLS scores and scores on the Reading Comprehension Section of the Short Test of Functional Health Literacy in Adults (S-TOFHLA) were collected in a cross-sectional study of 341 patients from two primary care practices. RESULTS: The NLS score showed acceptable internal consistency of 0.84 by Cronbach's alpha coefficient. The Pearson correlation between the NLS and the S-TOFHLA was 0.61, supporting evidence for construct validity. CONCLUSION: Given the importance of proper weight and nutrition in the health of the public, as well as the absence of research on literacy skills as related to nutritional concepts, the NLS has the potential to add to the national research agenda in these areas

Vanishing native American dog lineages

<p>Abstract</p> <p>Background</p> <p>Dogs were an important element in many native American cultures at the time Europeans arrived. Although previous ancient DNA studies revealed the existence of unique native American mitochondrial sequences, these have not been found in modern dogs, mainly purebred, studied so far.</p> <p>Results</p> <p>We identified many previously undescribed mitochondrial control region sequences in 400 dogs from rural and isolated areas as well as street dogs from across the Americas. However, sequences of native American origin proved to be exceedingly rare, and we estimate that the native population contributed only a minor fraction of the gene pool that constitutes the modern population.</p> <p>Conclusions</p> <p>The high number of previously unidentified haplotypes in our sample suggests that a lot of unsampled genetic variation exists in non-breed dogs. Our results also suggest that the arrival of European colonists to the Americas may have led to an extensive replacement of the native American dog population by the dogs of the invaders.</p