Quantitative Genetics of Response to Novelty and Other Stimuli by Infant Rhesus Macaques (Macaca mulatta) Across Three Behavioral Assessments

Primate behavior is influenced by both heritable factors and environmental experience during development. Previous studies of rhesus macaques (Macaca mulatta) examined the effects of genetic variation on expressed behavior and related neurobiological traits (heritability and/or genetic association) using a variety of study designs. Most of these prior studies examined genetic effects on the behavior of adults or adolescent rhesus macaques, not in young macaques early in development. To assess environmental and additive genetic variation in behavioral reactivity and response to novelty among infants, we investigated a range of behavioral traits in a large number (N?=?428) of pedigreed infants born and housed in large outdoor corrals at the Oregon National Primate Research Center (ONPRC). We recorded the behavior of each subject during a series of brief tests, involving exposure of each infant to a novel environment, to a social threat without the mother present, and to a novel environment with its mother present but sedated. We found significant heritability (h ² ) for willingness to move away from the mother and explore a novel environment (h ² ?=?0.25?±?0.13; P?=?0.003). The infants also exhibited a range of heritable behavioral reactions to separation stress or to threat when the mother was not present (h ² ?=?0.23?±?0.13–0.24?±?0.15, P?<?0.01). We observed no evidence of maternal environmental effects on these traits. Our results extend knowledge of genetic influences on temperament and reactivity in nonhuman primates by demonstrating that several measures of behavioral reactivity among infant rhesus macaques are heritable.     

Neonatal temperament and neuromotor differences are predictive of adolescent alcohol intake in rhesus monkeys (Macaca mulatta)

Identifying predictors of teenage alcohol use disorder (AUDs) is a major health initiative, with studies suggesting that there are distinct personality-related traits that underlie patterns of alcohol intake. As temperament is biologically based, identifiable early in life, and stable across time, it is considered the foundation of personality. As such, we hypothesized that neonatal temperament traits would predict anxiety-mediated adolescent alcohol consumption. To test this, N = 145 rhesus macaque (Macaca mulatta) infants (14 days of age), reared in a neonatal nursery (n = 82) or in a control condition with their mothers (n = 63) were assessed with a widely used standardized nonhuman primate testing battery, the Infant Behavioral Assessment Scale (IBAS), modeled after the Brazelton Neonatal Assessment Scale, evaluating visual orienting, temperament, motor maturity and, more recently, sensory sensitivity. As adolescents (3–4 years of age), these same subjects were allowed unfettered access to a sweetened-alcohol solution for 1 hr/day, 4 days/week, over 5–7 weeks. Subjects were allowed to self-administer alcohol while housed alone (n = 70) or socially in their home cage (n = 55). Linear regressions showed that alcohol intake was predicted by neonatal orienting ability (β = −.35; p = .01), state control (β = −.19; p = .04), and motor maturity (β = −.24; p = .01). Poor neonatal orienting, state control (ease of consolability), and motor maturity were associated with higher adolescent alcohol intake in rhesus monkeys. These findings suggest that neonatal temperament is predictive of patterns of adolescent alcohol intake. To the extent that these results generalize to humans, they provide evidence that early-life temperament and neurodevelopment may be important risk factors for adolescent AUDs and that the IBAS may be used as an assessment tool for identifying such risk.     

Quantification of angiogenesis in estrogen receptor-positive and negative breast carcinoma

Background

The objective of this study was to evaluate angiogenesis according to CD34 antigen expression in estrogen receptor (ER)-positive and negative breast carcinomas.

Methods

This study comprised 64 cases of infiltrating ductal carcinoma in postmenopausal women divided into two groups: Group A: ER-positive, n = 35; and Group B: ER-negative, n = 29. The anti-CD34 monoclonal antibody was used as a marker for endothelial cells. Microvessel count was carried out in 10 fields per slide using a 40× objective lens (magnification 400×). Statistical analysis of the data was performed using Student's t-test (p < 0.05).

Results

The mean number of vessels stained with the anti-CD34 antibody in the estrogen receptor-positive and negative tumors was 23.51 ± 1.15 and 40.24 ± 0.42, respectively. The number of microvessels was significantly greater in the estrogen receptor-negative tumors (p < 0.001).

Conclusion

ER-negative tumors have significantly greater CD34 antigen expression compared to ER-positive tumors.

     

Differential responsiveness to immunoablative therapy in refractory rheumatoid arthritis is associated with level and avidity of anti-cyclic citrullinated protein autoantibodies: a case study

In order to identify pathogenic correlates of refractory rheumatoid arthritis (RA), antibodies against anti-cyclic citrullinated protein (ACPAs) were investigated in RA patients in whom the dysregulated immune system had been ablated by high-dose chemotherapy (HDC) and autologous haematopoietic stem cell transplantation (HSCT). Six patients with refractory RA were extensively characterized in terms of levels of total immunoglobulins, RA-specific autoantibodies (ACPAs and rheumatoid factor) and antibodies against rubella, tetanus toxoid (TT) and phosphorylcholine before and after HDC plus HSCT. Additionally, the avidity of ACPAs was measured before and after treatment and compared with the avidity of TT antibodies following repeated immunizations. Synovial biopsies were obtained by arthroscopy before HDC plus HSCT, and analyzed by immunohistochemistry. In the three patients with clinically long-lasting responses to HDC plus HSCT (median 423 days), significant reductions in ACPA-IgG levels after therapy were observed (median level dropped from 215 to 34 arbitrary units/ml; P = 0.05). In contrast, stable ACPA-IgG levels were observed in three patients who relapsed shortly after HDC plus HSCT (median of 67 days). Clinical responders had ACPA-IgG of lower avidity (r = 0.75; P = 0.08) and higher degree of inflammation histologically (r = 0.73; P = 0.09). Relapse (after 38 to 530 days) in all patients was preceded by rising levels of low avidity ACPA-IgG (after 30 to 388 days), in contrast to the stable titres of high avidity TT antibodies. In conclusion, humoral autoimmune responses were differentially modulated by immunoablative therapy in patients with synovial inflammation and low avidity ACPA-IgG autoantibodies as compared with patients with high levels of high avidity ACPA-IgG. The distinct clinical disease course after immunoablative therapy based on levels and avidity of ACPA-IgG indicates that refractory RA is not a single disease entity.     

Physiological responses of resistant and susceptible barley, Hordeum vulgare to the Russian wheat aphid, Diurpahis noxia (Mordvilko)

Knowledge of the physiological responses of barley, Hordeum vulgare L., to the Russian wheat aphid, Diuraphis noxia (Mordvilko) (Hemiptera: Aphididae) is critical to understanding the defense response of barley to aphid injury and identifying resistance mechanisms. This study documented the impact of D. noxia feeding on resistant (‘Sidney’) and susceptible (‘Otis’) barley through chlorophyll fluorescence measurements, chlorophyll content, and carbon assimilation (A–C_i) curves recorded at 1, 3, 6, 10, and 13 days after aphid introduction. All chlorophyll fluorescence parameters evaluated were similar between aphid-infested and control plants for both cultivars. A–C_i curves showed that D. noxia feeding negatively impacts the photosynthetic capacity in both cultivars, but this effect was greater in the susceptible plants. From the A–C_i curves, it is apparent that compensation occurs in resistant barley by day 10, but by the conclusion of the experiment, aphid populations reached levels that overwhelmed the resistant barley seedlings. Differences observed in carbon assimilation curves between control and infested plants show that D. noxia feeding impacts the dark reaction, specifically rubisco activity and RuBP regeneration. It is likely that declines in the photochemical efficiency and chlorophyll content of the plants may be a secondary effect and not the primary trigger of declines in host plant function.     

Functional genomics of the yeast DNA-damage response

High-throughput approaches are beginning to have an impact on many areas of yeast biology. Two recent studies, using different experimental platforms, provide insight into new pathways involved in the response of yeast to DNA damage.     

The tomato Cf-9 disease resistance gene functions in tobacco and potato to confer responsiveness to the fungal avirulence gene product avr 9

The Cf-9 gene encodes an extracytoplasmic leucine-rich repeat protein that confers resistance in tomato to races of the fungus Cladosporium fulvum that express the corresponding avirulence gene Avr 9. We investigated whether the genomic Cf-9 gene functions in potato and tobacco. Transgenic tobacco and potato plants carrying Cf-9 exhibit a rapid hypersensitive cell death response (HR) to Avr 9 peptide injection. Cf 9 tobacco plants were reciprocally crossed to Avr 9-producing tobacco. A developmentally regulated seedling lethal phenotype occurred in F1 progeny when Cf9 was used as the male parent and Avr 9 as the female parent. However, when Cf9 was inherited in the maternal tissue and a heterozygous Avr 9 plant was used as the pollen donor, a much earlier reaction was caused, leading to no germination of any F1 seed. Detailed analysis of the Avr 9-induced responses in Cf 9 tobacco leaves revealed that (1) most mesophyll cells died within 3 hr (compared with 12 to 16 hr in tomato); (2) the macroscopic HR was visible at an Avr 9 titer five times lower than that which caused visible symptoms in tomato; (3) the HR invariably extended into noninjected panels of the tobacco leaf; (4) no HR occurred in leaves of young tobacco plants; (5) in older plants, the HR was dramatically enhanced by sequential Avr 9 challenges; and (6) coexpression of a salicylate hydroxylase transgene (nahG) from Pseudomonas putida reduced the severity of the macroscopic leaf HR and also restored germination to Cf 9 x 35S:Avr 9 F1 seedlings. Simultaneous introduction of Cf-9 homologs (Hcr 9-9 genes A and B or D) along with the native Cf-9 gene did not alter the responses that were specifically induced by Avr 9. Various ways to use the Cf-9-Avr 9 gene combination to engineer broad-spectrum disease resistance in several solanaceous species are discussed.