On the origins of Mendelian disease genes in man: the impact of gene duplication

Over 3,000 human diseases are known to be linked to heritable genetic variation, mapping to over 1,700 unique genes. Dating of the evolutionary age of these disease-associated genes has suggested that they have a tendency to be ancient, specifically coming into existence with early metazoa. The approach taken by past studies, however, assumes that the age of a disease is the same as the age of its common ancestor, ignoring the fundamental contribution of duplication events in the evolution of new genes and function. Here, we date both the common ancestor and the duplication history of known human disease-associated genes. We find that the majority of disease genes (80%) are genes that have been duplicated in their evolutionary history. Periods for which there are more disease-associated genes, for example, at the origins of bony vertebrates, are explained by the emergence of more genes at that time, and the majority of these are duplicates inferred to have arisen by whole-genome duplication. These relationships are similar for different disease types and the disease-associated gene's cellular function. This indicates that the emergence of duplication-associated diseases has been ongoing and approximately constant (relative to the retention of duplicate genes) throughout the evolution of life. This continued until approximately 390 Ma from which time relatively fewer novel genes came into existence on the human lineage, let alone disease genes. For single-copy genes associated with disease, we find that the numbers of disease genes decreases with recency. For the majority of duplicates, the disease-associated mutation is associated with just one of the duplicate copies. A universal explanation for heritable disease is, thus, that it is merely a by-product of the evolutionary process; the evolution of new genes (de novo or by duplication) results in the potential for new diseases to emerge

Process for bonding elastomers to metals

A process for bonding elastomeric material to a metal part includes coating a heat curable adhesive on the surfaces of the metal part to be bonded. The metal part is placed in a mold, a bottom plate and an upper transfer pot of a transfer molding machine is preheated to a predetermined cure temperature. A predetermined quantity of uncured elastomeric material is loaded into the transfer pot. The mold containing the adhesive coated metal part is clamped to the bottom plate, and almost contemporaneously, the uncured elastomeric material is pressed into the mold while maintaining heat and pressure in the mold for a time sufficient to vulcanize and thereby cure the elastomeric material simultaneously with the adhesive, whereby contacting surfaces of the metal part are strongly bonded to the vulcanized elastomeric material

Performance of Booroola Merino and Finnsheep crossbred lambs and ewes

Booroola Merino (B, n= 18) and Finnsheep (F, n =31) rams were mated to F ewes and C3 ewes (1/2 Columbia, 1/4 Suffolk, 1/4 Hampshire). Progeny of these matings were evaluated for performance traits including ewe reproduction through 3 years of age. Averaged over dam breeds, there was no significant difference between B and F sires for conception rate (CR), litter size (LS) at birth or weaning or for lamb mortality to weaning. The difference among sire breeds was not large or significant for birth weight but F sired lambs were significantly heavier than B sired lambs at 63 and 147 days of age. Relative to F sired lambs, B sired lambs had a higher dressing percentage and less fat at the 12th rib but equal estimated percentage kidney fat. A significantly smaller percentage of B-C3 than F, F-C3 or B-F ewe lambs reached puberty by the end of their first breeding season. Ovulation rate at first mating was higher but embryo survival rate tended to be lower for B sired ewes than for F sired ewes. At 2 years of age, B sired ewes produced about 1 kg more wool than F sired ewes. With the exception of the very poor CR of B-C3 ewes at first parity, the differences between the four ewe genotypes were not large or significant for CR at first, second and third parity. The difference between B and F sired ewes in LS at birth was not significant at first parity but B sired ewes were more prolific at second and third parities. However, differences in lamb mortality reduced, and in some cases removed, the differences in LS by weaning time. Relative use of these breeds in commercial U.S. production schemes is discussed

The life-history and early stages of Corythucha parshleyi Gibson.

v. 50 (1918

The biological context of HIV-1 host interactions reveals subtle insights into a system hijack

<p>Abstract</p> <p>Background</p> <p>In order to replicate, HIV, like all viruses, needs to invade a host cell and hijack it for its own use, a process that involves multiple protein interactions between virus and host. The HIV-1, Human Protein Interaction Database available at NCBI's website captures this information from the primary literature, containing over 2,500 unique interactions. We investigate the general properties and biological context of these interactions and, thus, explore the molecular specificity of the HIV-host perturbation. In particular, we investigate (i) whether HIV preferentially interacts with highly connected and 'central' proteins, (ii) known phenotypic properties of host proteins inferred from essentiality and disease-association data, and (iii) biological context (molecular function, processes and location) of the host proteins to identify attributes most strongly associated with specific HIV interactions.</p> <p>Results</p> <p>After correcting for ascertainment bias in the literature, we demonstrate a significantly greater propensity for HIV to interact with highly connected and central host proteins. Unexpectedly, we find there are no associations between HIV interaction and inferred essentiality. Similarly, we find a tendency for HIV not to interact with proteins encoded by genes associated with disease. Crucially, we find that functional categories over-represented in HIV-host interactions are innately enriched for highly connected and central proteins in the host system.</p> <p>Conclusions</p> <p>Our results imply that HIV's propensity to interact with highly connected and central proteins is a consequence of interactions with particular cellular functions, rather than being a direct effect of network topological properties. The lack of a propensity for interactions with phenotypically essential proteins suggests a selective pressure to minimise virulence in retroviral evolution. Thus, the specificity of HIV-host interactions is complex, and only superficially explained by network properties.</p

Addressing Urban High-Poverty School Teacher Attrition by Addressing Urban High Poverty School Teacher Retention: Why Effective Teachers Perservere

Recruiting and retaining quality teachers specific for high-poverty schools in urban areas is a national concern, especially in light of the No Child Left Behind federal legislation. The educational realities, detrimental effects of poverty, and human despair that often depress low-income communities can prove to be quite overpowering for many teachers new to the profession and significantly contribute to high levels of teacher absenteeism, attrition rates, and teacher shortages. Examining this issue through a new lens, that being through the eyes of effective urban high-poverty school educators, has the potential to spark spirited conversations and debates among policy makers and educators alike so that significant polices and efforts can be developed and implemented. Therefore, the intent of this study was to develop a profile of high-quality educators who remain in urban high-poverty schools within a large metropolitan school district, and identify the indicators that influence them to remain. The results indicated that teachers who are African American, older, and more experienced define the profile of teachers most likely to remain beyond the first three years in this demanding setting. Additionally, these teachers reported that they remain because they believe they are well suited for teaching in high-poverty schools. Unless more attention is given to teacher retention, and why some educators are successful and persevere in even the most hard-to-staff schools, teacher attrition will continue to be a national concern

SIMULATION OF BREED AND CROSSBREEDING EFFECTS ON COSTS OF PORK PRODUCTION

A bio-economic model of swine production was used to simulate expected performance effects of breeds in alternative breeding systems on total costs/100 kg of live weight (EWW) or/l00 kg lean (ELW) for marketing at 100 kg live weight and on costs/100 kg lean for marketing at mean 185-d weight (ELA). Effects of heterosis and of six U.S. breeds were simulated for integrated industry purebred (P), two-breed specific (2S), backcross (2B) and rotation cross (2R), and three-breed specific (3S) and rotation cross (3R) breeding systems. Traits considered were age at puberty (-PUB), conception rate (CR), litter size born alive (NBA), preweaning viability (VIAB), milk production (MILK), age at 100 kg live weight (-DAYS) and empty body fat percentage (-FAT). Cost reductions from crossbreeding systems were greater for ELA than for ELW or EWW, ranging from -3 to -5% for 2S, -6 to -7% for 2B and 2R, and -7 to -9% for 3S and 3R. Reductions in nonfeed costs were much greater than those in feed costs for EWW and ELW (-4 to -12% vs -2 to -4%), and especially for ELA (-9 to -17% vs -1 to -2%). Order of maternal trait importance in ranking breeds was NBA, VIAB, CR, MILK and -PUB for P, 2R and 3R systems and as maternal breeds in 2S and 3S systems. For cost of lean, -FAT was as important as NBA in all except maternal breed roles. For ELA, -DAYS was important in all breed roles, but not for EWW and ELW, especially in maternal breed roles. In ranking paternal breeds for use in 2S and 3S systems, the important traits were only VIAB for EWW, VIAB and -FAT for ELW, but VIAB,-FAT and -DAYS for ELA. Existing breeds ranked differently as paternal breeds than as maternal or general purpose breeds. Complementary paternal-maternal effects permitted greater cost reductions from best 3S (-7 to -10%) than from best 3R (-6 to -8%) breed combinations. Maternal breeds in crosses benefited from superiority in components of both sow and pig performance

Electric-Field Tuning of Spin-Dependent Exciton-Exciton Interactions in Coupled Quantum Wells

We have shown experimentally that an electric field decreases the energy separation between the two components of a dense spin-polarized exciton gas in a coupled double quantum well, from a maximum splitting of $\sim 4$ meV to zero, at a field of $\sim$35 kV/cm. This decrease, due to the field-induced deformation of the exciton wavefunction, is explained by an existing calculation of the change in the spin-dependent exciton-exciton interaction with the electron-hole separation. However, a new theory that considers the modification of screening with that separation is needed to account for the observed dependence on excitation power of the individual energies of the two exciton components.Comment: 5 pages, 4 eps figures, RevTeX, Physical Review Letters (in press