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

Monorail/Foxa2 regulates floorplate differentiation and specification of oligodendrocytes, serotonergic raphe neurones and cranial motoneurones

In this study, we elucidate the roles of the winged-helix transcription factor Foxa2 in ventral CNS development in zebrafish. Through cloning of monorail (mol), which we find encodes the transcription factor Foxa2, and phenotypic analysis of mol(-/-) embryos, we show that floorplate is induced in the absence of Foxa2 function but fails to further differentiate. In mol(-/-) mutants, expression of Foxa and Hh family genes is not maintained in floorplate cells and lateral expansion of the floorplate fails to occur. Our results suggest that this is due to defects both in the regulation of Hh activity in medial floorplate cells as well as cell-autonomous requirements for Foxa2 in the prospective laterally positioned floorplate cells themselves. Foxa2 is also required for induction and/or patterning of several distinct cell types in the ventral CNS. Serotonergic neurones of the raphe nucleus and the trochlear motor nucleus are absent in mol(-/-) embryos, and oculomotor and facial motoneurones ectopically occupy ventral CNS midline positions in the midbrain and hindbrain. There is also a severe reduction of prospective oligodendrocytes in the midbrain and hindbrain. Finally, in the absence of Foxa2, at least two likely Hh pathway target genes are ectopically expressed in more dorsal regions of the midbrain and hindbrain ventricular neuroepithelium, raising the possibility that Foxa2 activity may normally be required to limit the range of action of secreted Hh proteins

A magnetically collimated jet from an evolved star

Planetary nebulae often have asymmetric shapes, which could arise due to collimated jets from evolved stars before evolution to the planetary nebula phase. The source of jet collimation in these stars is unknown. Magnetic fields are thought to collimate outflows that are observed in many other astrophysical sources, such as active galactic nuclei and proto-stars, although hitherto there are no direct observations of both the magnetic field direction and strength in any collimated jet. Theoretical models have shown that magnetic fields could also be the dominant source of collimation of jet in evolved stars. Here we report measurements of the polarization of water vapour masers that trace the precessing jet emanating from the asymptotic giant branch star W43A at 2.6 kpc from the Sun, which is undergoing rapid evolution into a planetary nebula. The masers occur in two clusters at opposing tips of the jets, ~1,000 AU from the star. We find direct evidence that the magnetic field is collimating the jet.Comment: Published in Nature 440 (March 2nd 2006). High-res figures can be found at http://www.jb.man.ac.uk/~wouter/papers/w43a/w43a.htm

Comparison of Hospital Costs and Length of Stay for Community Internists, Hospitalists, and Academicians

BACKGROUND: The model of inpatient medical management has evolved toward Hospitalists because of greater cost efficiency compared to traditional practice. The optimal model of inpatient care is not known. OBJECTIVE: To compare three models of inpatient Internal Medicine (traditional private practice Internists, private Hospitalist Internists, and Academic Internists with resident teams) for cost efficiency and quality at a community teaching hospital. DESIGN: Single-institution retrospective cohort study. MEASUREMENTS AND MAIN RESULTS: Measurements were hospital cost, length of stay (LOS), mortality, and 30-day readmission rate adjusted for severity, demographics, and case mix. Academic Internist teams had 30% lower cost and 40% lower LOS compared to traditional private Internists and 24% lower cost and 30% lower LOS compared to private Hospitalists. Hospital mortality was equivalent for all groups. Academic teams had 2.3–2.6% more 30-day readmissions than the other groups. CONCLUSIONS: Academic teams compare favorably to private Hospitalists and traditional Internists for hospital cost efficiency and quality

Sexual attraction, sexual identity, and psychosocial well-being in a national sample of young women during emerging adulthood.

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/106627/1/Sexual attraction, sexual identity, and psychosocial well-being in a national sample of young women during emerging adulthood.pd

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

Multi-parallel qPCR provides increased sensitivity and diagnostic breadth for gastrointestinal parasites of humans: field-based inferences on the impact of mass deworming

BACKGROUND: Although chronic morbidity in humans from soil transmitted helminth (STH) infections can be reduced by anthelmintic treatment, inconsistent diagnostic tools make it difficult to reliably measure the impact of deworming programs and often miss light helminth infections. METHODS: Cryopreserved stool samples from 796 people (aged 2-81 years) in four villages in Bungoma County, western Kenya, were assessed using multi-parallel qPCR for 8 parasites and compared to point-of-contact assessments of the same stools by the 2-stool 2-slide Kato-Katz (KK) method. All subjects were treated with albendazole and all Ascaris lumbricoides expelled post-treatment were collected. Three months later, samples from 633 of these people were re-assessed by both qPCR and KK, re-treated with albendazole and the expelled worms collected. RESULTS: Baseline prevalence by qPCR (n = 796) was 17 % for A. lumbricoides, 18 % for Necator americanus, 41 % for Giardia lamblia and 15% for Entamoeba histolytica. The prevalence was <1% for Trichuris trichiura, Ancylostoma duodenale, Strongyloides stercoralis and Cryptosporidium parvum. The sensitivity of qPCR was 98% for A. lumbricoides and N. americanus, whereas KK sensitivity was 70% and 32%, respectively. Furthermore, qPCR detected infections with T. trichiura and S. stercoralis that were missed by KK, and infections with G. lamblia and E. histolytica that cannot be detected by KK. Infection intensities measured by qPCR and by KK were correlated for A. lumbricoides (r = 0.83, p < 0.0001) and N. americanus (r = 0.55, p < 0.0001). The number of A. lumbricoides worms expelled was correlated (p < 0.0001) with both the KK (r = 0.63) and qPCR intensity measurements (r = 0.60). CONCLUSIONS: KK may be an inadequate tool for stool-based surveillance in areas where hookworm or Strongyloides are common or where intensity of helminth infection is low after repeated rounds of chemotherapy. Because deworming programs need to distinguish between populations where parasitic infection is controlled and those where further treatment is required, multi-parallel qPCR (or similar high throughput molecular diagnostics) may provide new and important diagnostic information

An Anti-Human ICAM-1 Antibody Inhibits Rhinovirus-Induced Exacerbations of Lung Inflammation

Human rhinoviruses (HRV) cause the majority of common colds and acute exacerbations of asthma and chronic obstructive pulmonary disease (COPD). Effective therapies are urgently needed, but no licensed treatments or vaccines currently exist. Of the 100 identified serotypes, ∼90% bind domain 1 of human intercellular adhesion molecule-1 (ICAM-1) as their cellular receptor, making this an attractive target for development of therapies; however, ICAM-1 domain 1 is also required for host defence and regulation of cell trafficking, principally via its major ligand LFA-1. Using a mouse anti-human ICAM-1 antibody (14C11) that specifically binds domain 1 of human ICAM-1, we show that 14C11 administered topically or systemically prevented entry of two major groups of rhinoviruses, HRV16 and HRV14, and reduced cellular inflammation, pro-inflammatory cytokine induction and virus load in vivo. 14C11 also reduced cellular inflammation and Th2 cytokine/chemokine production in a model of major group HRV-induced asthma exacerbation. Interestingly, 14C11 did not prevent cell adhesion via human ICAM-1/LFA-1 interactions in vitro, suggesting the epitope targeted by 14C11 was specific for viral entry. Thus a human ICAM-1 domain-1-specific antibody can prevent major group HRV entry and induction of airway inflammation in vivo

Population genomics of domestic and wild yeasts

The natural genetics of an organism is determined by the distribution of sequences of its genome. Here we present one- to four-fold, with some deeper, coverage of the genome sequences of over seventy isolates of the domesticated baker&#x27;s yeast, _Saccharomyces cerevisiae_, and its closest relative, the wild _S. paradoxus_, which has never been associated with human activity. These were collected from numerous geographic locations and sources (including wild, clinical, baking, wine, laboratory and food spoilage). These sequences provide an unprecedented view of the population structure, natural (and artificial) selection and genome evolution in these species. Variation in gene content, SNPs, indels, copy numbers and transposable elements provide insights into the evolution of different lineages. Phenotypic variation broadly correlates with global genome-wide phylogenetic relationships however there is no correlation with source. _S. paradoxus_ populations are well delineated along geographic boundaries while the variation among worldwide _S. cerevisiae_ isolates show less differentiation and is comparable to a single _S. paradoxus_ population. Rather than one or two domestication events leading to the extant baker&#x27;s yeasts, the population structure of _S. cerevisiae_ shows a few well defined geographically isolated lineages and many different mosaics of these lineages, supporting the notion that human influence provided the opportunity for outbreeding and production of new combinations of pre-existing variation

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