Maternal Expression Relaxes Constraint on Innovation of the Anterior Determinant, bicoid

The origin of evolutionary novelty is believed to involve both positive selection and relaxed developmental constraint. In flies, the redesign of anterior patterning during embryogenesis is a major developmental innovation and the rapidly evolving Hox gene, bicoid (bcd), plays a critical role. We report evidence for relaxation of selective constraint acting on bicoid as a result of its maternal pattern of gene expression. Evolutionary theory predicts 2-fold greater sequence diversity for maternal effect genes than for zygotically expressed genes, because natural selection is only half as effective acting on autosomal genes expressed in one sex as it is on genes expressed in both sexes. We sample an individual from ten populations of Drosophila melanogaster and nine populations of D. simulans for polymorphism in the tandem gene duplicates bcd, which is maternally expressed, and zerknüllt (zen), which is zygotically expressed. In both species, we find the ratio of bcd to zen nucleotide diversity to be two or more in the coding regions but one in the noncoding regions, providing the first quantitative support for the theoretical prediction of relaxed selective constraint on maternal-effect genes resulting from sex-limited expression. Our results suggest that the accelerated rate of evolution observed for bcd is owing, at least partly, to variation generated by relaxed selective constraint

A PI3K-mediated negative feedback regulates Drosophila motor neuron excitability

Negative feedback can act as a homeostatic mechanism to maintain neuronal activity at a particular specified value. At the Drosophila neuromuscular junction, a mutation in the type II metabotropic glutamate receptor gene (mGluRA) increased motor neuron excitability by disrupting an autocrine, glutamate-mediated negative feedback. We show that mGluRA mutations increase neuronal excitability by preventing PI3 kinase (PI3K) activation and consequently hyperactivating the transcription factor Foxo. Furthermore, glutamate application increases levels of phospho-Akt, a product of PI3K signaling, within motor nerve terminals in an mGluRA-dependent manner. In humans, PI3K and type II mGluRs are implicated in epilepsy, neurofibromatosis, autism, schizophrenia and other neurological disorders; however, neither the link between type II mGluRs and PI3K, nor the role of Foxo in the control of neuronal excitability, had been previously reported. Our work suggests that some of the deficits in these neurological disorders might result from disruption of glutamate-mediated homeostasis of neuronal excitability

Rural Community Participation, Social Networks, and Broadband Use: Examples from Localized and National Survey Data

Although attention has been given to how broadband access is related to economic development in rural areas, scant consideration has been given to how it may be associated with voluntary participation. This issue is important in that numerous studies have shown how much more vital community participation is in rural areas as compared to suburban and urban places. Drawing on three diverse data sets, we examine the influence of broadband access on community participation. In addition, we explore whether broadband access exerts its influence through, in conjunction with, or independent of social networks. The results suggest that broadband access and social network size have independent effects on volunteering in rural places.rural sociology, social networks, broadband, digital inequality, volunteerism, Community/Rural/Urban Development, Research and Development/Tech Change/Emerging Technologies,

Surfactant protein D contributes to ocular defense against Pseudomonas aeruginosa in a murine model of dry eye disease.

Dry eye disease can cause ocular surface inflammation that disrupts the corneal epithelial barrier. While dry eye patients are known to have an increased risk of corneal infection, it is not known whether there is a direct causal relationship between these two conditions. Here, we tested the hypothesis that experimentally-induced dry eye (EDE) increases susceptibility to corneal infection using a mouse model. In doing so, we also examined the role of surfactant protein D (SP-D), which we have previously shown is involved in corneal defense against infection. Scopolamine injections and fan-driven air were used to cause EDE in C57BL/6 or Black Swiss mice (wild-type and SP-D gene-knockout). Controls received PBS injections and were housed normally. After 5 or 10 days, otherwise uninjured corneas were inoculated with 10(9) cfu of Pseudomonas aeruginosa strain PAO1. Anesthesia was maintained for 3 h post-inoculation. Viable bacteria were quantified in ocular surface washes and corneal homogenates 6 h post-inoculation. SP-D was measured by Western immunoblot, and corneal pathology assessed from 6 h to 4 days. EDE mice showed reduced tear volumes after 5 and 10 days (each by ∼75%, p<0.001) and showed fluorescein staining (i.e. epithelial disruption). Surprisingly, there was no significant difference in corneal pathology between EDE mice and controls (∼10-14% incidence). Before bacterial inoculation, EDE mice showed elevated SP-D in ocular washes. After inoculation, fewer bacteria were recovered from ocular washes of EDE mice (<2% of controls, p = 0.0004). Furthermore, SP-D knockout mice showed a significant increase in P. aeruginosa corneal colonization under EDE conditions. Taken together, these data suggest that SP-D contributes to corneal defense against P. aeruginosa colonization and infection in EDE despite the loss of barrier function to fluorescein

Extended M-matrices and subtangentiality

AbstractThe concept of a singular M-matrix A with respect to a proper cone K is extended, by replacing the usual regularity condition A = αI − B for a K-nonnegative matrix B with the weaker condition, exponential nonnegativity of - A. As in earlier work which dealt with the nonsingular case, in the present characterizations the lack of regularity is overcome by employing subtangentiality

Migration and the Social Order in Erie County, New York: 1855

Mass transiency remains the most striking and consistent finding to emerge from quantitative studies of Victorian North America. In almost every place where historians have looked at least half, often two thirds, of the adults present at one end of a decade had left ten years later, and rates based on shorter periods reveal a stream of people constantly flowing through nineteenth-century cities. Although 363,000 people lived in Boston in 1880 and 448,000 in 1890, during the decade about one and one-half million people actually had dwelled within the city. When Victorians sought a symbol of progress, they often chose the steam engine; had they wanted a metaphor for their cities, they could have found none more apt than the railroad station. In this paper we confront the question of transiency. Using the New York State Census of 1855 for the entire city of Buffalo and a 10 percent sample of household heads in rural Erie County, we attempt a method of estimating persistence (the proportion of the population remaining in a given place) that is different from that used by most historians. Given the richness of the census, we are able to inquire with great detail into the factors that determined length of residence in a nineteenth-century city and its surrounding countryside

Chiron: Evidence for historic cometary activity

The non-asteroidal brightening of (2060) Chiron, first noted by Tholen in 1988 is now ascribed to cometary activity. Photometry since 1988 has revealed a broad surge in brightness that peaked in 1989 about 1.0 mag above the brightness in the mid-1980s. The surge is evidently due to sporatic formation of dust coma, which is itself driven by the presence of extremely volatile ices at or near the surface. CN emission was recently reported. Since Chiron is now nearing perihelion, there is interest in determining whether it has exhibited anomalous brightening in the past, particularly at greater heliocentric distances. Photographic plates dating back to 1895 are known to contain images of Chiron. Using some of these archival material, the initial results are presented for a project to determine Chiron's brightness history over orbital timescales. A particularly homogeneous and high-quality set of plates taken prior to and around the time of Chiron's discovery in Oct. 1977 at the 1.2 m Oschin Schmidt telescope at Mt. Palomar Observatory were examined. Images of Chiron were identified and digitized using a PDS microdensitometer, and images of field stars around Chiron were both similarly digitized and photometrically calibrated using recently acquired B and V band CCD frames. As a result of the present work, eleven new data, including estimated errors, were added between 1969 and 1977. The implications that Chiron can be active at any heliocentric distance in its present orbit suggest that the active volatile is either N2, CH4, or CO, and that a substantial degree of mantling may have developed. Further historical data is presented, the error bars discussed, and possible mechanisms suggested for the observed activity