Facilitated Transport of EGFR Inhibitors Plays an Important Role in Their Cellular Uptake.

Epidermal growth factor receptor (EGFR) is a transmembrane protein commonly targeted by tyrosine kinase inhibitors (TKIs) as a front-line therapy for patients with many cancers including nonsmall cell lung cancer (NSCLC). Effective treatment requires efficient intracellular drug uptake and target binding. However, despite the recent success in the development of new TKI drugs, the mechanisms of uptake for many TKIs are still poorly understood due to the difficulty in imaging and measuring nonfluorescent drug molecules at a subcellular resolution.

Phenotypic responses of chickens to long-term, bidirectional selection for juvenile body weight--historical perspective.

A long-term selection experiment for high (HWS) and low (LWS) BW at 8 wk of age (BW8) was conducted in White Plymouth Rock chickens. Over 54 generations of selection, responses to bidirectional selection were profound. Increase in BW8 in line HWS was linear, and there was a significant quadratic response in line LWS for BW at both 4 and 8 wk of age.

Combining different design strategies for rational affinity maturation of the MICA-NKG2D interface.

We redesigned residues on the surface of MICA, a protein that binds the homodimeric immunoreceptor NKG2D, to increase binding affinity with a series of rational, incremental changes. A fixed-backbone RosettaDesign protocol scored a set of initial mutations, which we tested by surface plasmon resonance for thermodynamics and kinetics of NKG2D binding, both singly and in combination. We combined the best four mutations at the surface with three affinity-enhancing mutations below the binding interface found with a previous design strategy.

Effect of route of inoculation on humoral immune response of White Leghorn chickens selected for high or low antibody response to sheep red blood cells.

Effects of route of SRBC inoculation and antigen dosage on primary and secondary antibody response of White Leghorn lines selected for high (HA) or low (LA) 5-d antibody response to a single i.v. inoculation with 0.

Antibody responses to different dosages of sheep red blood cells in lines of chickens selected for high and low antibody response to sheep red blood cells.

Temporal patterns of SRBC antibody response after primary and secondary inoculations were measured in White Leghorn males from lines selected 24 generations for high (HA) or low (LA) 5-d antibody titers to an i.v. inoculation with 0.

Heterosis following long-term bidirectional selection for mating frequency in male Japanese quail.

Reciprocal crosses (sire line shown first and dam line second) among high (H) and low (L) selected lines and the randombred control line (C), which was the base population for the selected lines, were made after 40 generations of bidirectional selection for mating frequency of male Japanese quail. Significant heterosis for the selected trait was found only in crosses between Lines C and L, being 62 and 92% for LC and CL, respectively. Heterosis for percentage of maters was present in all crosses, ranging from 8% for HC and CH to 46% for HL.

Kinetics of antibody responses in hens from chicken lines divergently selected for response to sheep red blood cells.

Changes in antibody titers to SRBC were monitored for 180 d after inoculation in hens from two lines divergently selected for 24 generations for high (HAS) or low (LAS) antibody response to SRBC. The HAS hens not only had a higher peak of antibody response (12.9 vs 9.

Immunocompetence and resistance to marble spleen disease of broiler- and layer-type pure lines of chickens.

The intent of this study was to evaluate, under concurrent conditions, certain responses that may be important in chicken breeding and growing. Three commercial broiler pure lines (A, B, and C) and two experimental White Leghorn lines selected for high (HAS) and low (LAS) antibody response to sheep red blood cells were evaluated concurrently for humoral and cell-mediated immunocompetence, resistance to marble spleen disease virus (MSDV), relative asymmetry (RA), and comb weight. Chicks were injected with 0.

Heterosis and developmental stability of body and organ weights at hatch for parental line broiler breeders and specific crosses among them.

Body, yolk sac, left and right shanks with toes, empty left and right ceca, left and right lungs, heart, and bursa of Fabricius weights were obtained at hatch for 50 chicks from each of five commercial broiler parental lines (three sire and two dam) and three F1 crosses involving them. Differences among stocks and between sexes were inconsistent among mating combinations. Although correlation coefficients between yolk-free chick weight with organ weights were generally stock specific, they were high (> 0.

Effect of genetic selection and MHC haplotypes on lymphocyte proliferation and interleukin-2 like activity in chicken lines selected for high and low antibody production against sheep red blood cells.

Chickens from third generation matings of lines of chickens selected for high (HA) and low (LA) antibody production to sheep red blood cells (SRBC) and typed for MHC genotypes B13/13, B13/21, and B21/21 were used in this study. Chickens from both lines carried all the three genotypes B13/13, B13/21, and B21/21. To study T- and B-lymphocytes mitogenic activity, 12-week-old female chickens were injected intravenously with 0.

Diet and immunological memory of lines of White Leghorn chickens divergently selected for antibody response to sheep red blood cells.

Antibody responses to a first, second, and third injection with SRBC, and growth were studied in lines of White Leghorn chickens selected for high (HA) or low (LA) 5-d antibody titers to an i.v. inoculation with 0.

Effects of season and diet on tensile strength and mineral content of the equine hoof wall.

Studies evaluating nutritional and seasonal influences on hoof strength and composition in horses, as well as the scientific justification for feeding supplements to improve hoof quality, are lacking. The horseman and veterinarian need controlled studies in this area to make informed decisions. This project quantified, in 2 trials, relative elasticity, tensile strength, % moisture, and mineral composition of hooves of 48 mature Thoroughbred mares maintained on different nutritional/management regimens, sampled quarterly over 12 month periods.

Diet and humoral responsiveness of lines of chickens divergently selected for antibody response to sheep red blood cells.

Growth and humoral immune response were studied in lines of white leghorn chickens selected for high (HA) or low (LA) 5-day antibody titers to an i.v. inoculation with 0.

Hematocrit values in weight-selected and relaxed lines of White Rock chickens.

Hematocrits (PCV) were measured at 29 and 106 d of age (PCV1 and PCV2, respectively) in male and female White Plymouth Rocks. Four lines were used, two of which had undergone 40 generations of divergent selection for 8-wk BW (HWS, LWS), and two respective sublines (HWR, LWR), in which selection had been relaxed for five generations. At both ages, males and females did not differ for PCV in lines HWR, LWR, and LWS.

Forty generations of bidirectional selection for mating frequency in male Japanese quail.

A bidirectional replicated selection experiment for high (H1 and H2) or low (L1 and L2) cumulative number of complete matings (CNCM) in male Japanese quail was conducted for 40 generations. In the S32 generation, a subline was taken from each selected line and selection was relaxed. In the randombred control line (C), CNCM and unselected traits changed significantly over generations.

Mode of inheritance of unselected traits in lines of chickens selected for high or low antibody response to sheep red blood cells. 2. Heterophils, lymphocytes, and hematocrits.

The nuclear lines for this experiment were White Leghorns that had undergone long-term selection for high (HH) or low (LL) antibody response to sheep red blood cell antigen(s). Sixteen progeny types consisting of parental lines, reciprocal F1 and F2 crosses, and backcrosses were produced in a single hatch from age-contemporary parents. At 30 d of age, blood was obtained from a random sample of 10 males per progeny type (n = 160) and slides prepared for subsequent determination of number of heterophils and lymphocytes.

Mode of inheritance of unselected traits in lines of chickens selected for high or low antibody response to sheep red blood cells. 1. Resistance to marble spleen disease virus and juvenile body weight.

Two lines of White Leghorns that had undergone long-term selection for high (HH) or low (LL) antibody response to sheep red blood cell antigen(s) formed the nuclear lines for this experiment. Matings were made in a full diallel cross to produce in a single hatch from age-contemporary breeders the parental lines, reciprocal F1 and F2 crosses, and backcrosses for 16 progeny types. For males and females, there were parental line differences in BW to 42 d of age, after which there was decline between lines for males.

Developmental stability in different genetic stocks of white rock chickens.

Asymmetries were determined for several bilateral traits in females from a line of chickens selected for 39 generations for low 56 day body weight (LWS) and in a subline of LWS where selection had been relaxed for four generations (LWR). Because of reduced food intake under ad libitum feeding, some LWS females do not commence egg production, a condition that can be overcome by relaxing selection for a generation or two. Bilateral traits, measured at 240 days of age in LWS non-layers, LWS layers, and LWR layers, were shank length and diameter, distance between the auditory canal and the posterior junction of the upper and lower mandible, and weight and length of the first primary wing feather.

Comparison of sex-linked dwarf genes in chickens from two sources when introgressed into unrelated genetic backgrounds.

1. Sex-linked dwarfing genes from 2 broiler stock origins (EU and US) were each introgressed into 2 White Leghorn populations that had been divergently selected for antibody response to sheep erythrocytes. 2.

Antibody transmitting ability of hens from lines of chickens differing in response to SRBC antigen.

1. Hens from White Leghorn lines selected for high (HA) or low (LA) antibody response to sheep red blood cells (SRBC) were inoculated with 0.1 ml of either 0.

Developmental stability in stocks of White Leghorn chickens.

The degree of asymmetry in bilateral morphological characters may reflect genetic and environmental stressors. Shank length and diameter, weight and length of the first primary wing feather, and distance between the junction of upper and lower mandibles and auditory canal (face length) were used to classify bilateral types and measure relative asymmetry (RA) in six genetic stocks. The stocks were the S23 generation of White Leghorn lines selected for high or low antibody response to SRBC, sublines in which selection had been relaxed for eight generations, and reciprocal crosses of the selected lines.

Responses of meat-type chickens to choice feeding of diets differing in protein and energy from hatch to market weight.

Chickens from three genetic stocks known to differ in growth potential consumed ad libitum either a single (control) diet or a choice of two diets that differed in protein and energy. Formulation of the choice diets was such that when mixed in specific proportions they provided single diets that decreased in protein and increased in energy over the experimental period. When comparisons of feeding regimens were made at a common age, body weights and feed efficiencies for all stocks were enhanced in chicks fed a single diet.

Genetic selection strategies--population genetics.

This paper provides an overview of the association between population genetics and selection strategies in poultry. Relationships between artificial and natural selection and among causes contributing to limits to artificial selection are discussed. Homeostasis and resource allocations at the individual and at the population level are reviewed.

Effect of tumor necrosis factor-alpha on progesterone production by granulosa cells in laying hens of different genetic lines.

In vitro progesterone production by granulosa cells in the presence or absence of human recombinant tumor necrosis factor-alpha (hrTNF-alpha) was measured at 10, 20, and 30 wk of egg production in White Leghorn hens selected for high (HA)- or low-antibody (LA) response to sheep red blood cell challenge. Isolated granulosa cells from the three largest preovulatory follicles (F1-F3) were incubated with 5 or 250 ng/ml hrTNF-alpha, and progesterone production was determined by the use of a validated radioimmunoassay. F1, F2 and F3 granulosa cells from HA hens produced more (P < or = 0.