557 research outputs found
From Aspiration to Arrogance and Back: The Once and Future Role of Equal Employment Opportunity Under Title VII
Adaptive Significance of Natural Variations in Maternal Care in Rats: A Translational Perspective
A wealth of data from the last fifty years documents the potency of early life experiences including maternal care on developing offspring. A majority of this research has focused on the developing stress axis and stress-sensitive behaviors in hopes of identifying factors impacting resilience and risk-sensitivity. The power of early life experience to shape later development is profound and has the potential to increase fitness of individuals for their environments. Current findings in a rat maternal care paradigm highlight the complex and dynamic relation between early experiences and a variety of outcomes. In this review we propose adaptive hypotheses for alternate maternal strategies and resulting offspring phenotypes, and ways to distinguish between these hypotheses. We also provide evidence underscoring the critical role of context in interpreting the adaptive significance of early experiences. If our goal is to identify risk-factors relevant to humans, we must better explore the role of the social and physical environment in our basic animal models
Combined antiproliferative activity of imatinib mesylate (STI-571) with radiation or cisplatin in vitro
Little is known about the interaction of novel anticancer drugs with other treatment modalities. The aim of this study was to examine the effect of combining imatinib mesylate (STI-571) with radiation or cisplatin on the survival of two human solid tumor cell lines β SKNMC cells derived from Ewing sarcoma and breast cancer MCF-7 cells. Methods: Cell proliferation was determined using the sulphorodamine B cytotoxicity assay. Cell cycle analysis was performed with flow cytometry. Apoptosis was determined using a commercial cell death ELISA plus kit. Phosphorylated AKT, which has been suggested to be involved in radiation resistance, was detected by Western blot analysis. Results: Exposure of SKNMC cells to STI-571 resulted in a dose-dependent antiproliferative effect and a decrease in phosphorylated AKT expression. There was no evidence of apoptosis. The combination of STI-571 with radiation or cisplatin had an additive antiproliferative effect in SKNMC cells (60% reduction in cell number). A similar effect was observed in human MCF-7 breast cancer cells. Conclusion: STI-571 improves the outcome of cisplatin or irradiation treatment in vitro. AKT pathway may play a role in the additive effect of STI-571 and irradiation.Π¦Π΅Π»Ρ: ΠΎΡΠ΅Π½ΠΈΡΡ Π°Π½ΡΠΈΠΏΡΠΎΠ»ΠΈΡΠ΅ΡΠ°ΡΠΈΠ²Π½ΡΠΉ ΡΡΡΠ΅ΠΊΡ ΠΈΠΌΠ°ΡΠΈΠ½ΠΈΠ±Π° (STI-571) Π² ΠΊΠΎΠΌΠ±ΠΈΠ½Π°ΡΠΈΠΈ Ρ ΠΎΠ±Π»ΡΡΠ΅Π½ΠΈΠ΅ΠΌ ΠΈΠ»ΠΈ ΡΠΈΡΠΏΠ»Π°ΡΠΈΠ½ΠΎΠΉ ΠΏΠΎ ΠΎΡΠ½ΠΎΡΠ΅Π½ΠΈΡ
ΠΊ Π΄Π²ΡΠΌ ΠΊΠ»Π΅ΡΠΎΡΠ½ΡΠΌ Π»ΠΈΠ½ΠΈΡΠΌ β ΠΊΠ»Π΅ΡΠΊΠ°ΠΌ Π»ΠΈΠ½ΠΈΠΈ SKNMC, ΠΏΠΎΠ»ΡΡΠ΅Π½Π½ΡΠΌ ΠΈΠ· ΡΠ°ΡΠΊΠΎΠΌΡ ΠΠ²ΠΈΠ½Π³Π°, ΠΈ ΠΊΠ»Π΅ΡΠΊΠ°ΠΌ ΡΠ°ΠΊΠ° ΠΌΠΎΠ»ΠΎΡΠ½ΠΎΠΉ ΠΆΠ΅Π»Π΅Π·Ρ
ΡΠ΅Π»ΠΎΠ²Π΅ΠΊΠ° Π»ΠΈΠ½ΠΈΠΈ MCF-7. ΠΠ΅ΡΠΎΠ΄Ρ: Π΄Π»Ρ ΠΎΡΠ΅Π½ΠΊΠΈ ΠΏΡΠΎΠ»ΠΈΡΠ΅ΡΠ°ΡΠΈΠΈ ΠΊΠ»Π΅ΡΠΎΠΊ ΠΏΡΠΈΠΌΠ΅Π½ΡΠ»ΠΈ ΠΌΠ΅ΡΠΎΠ΄ Π°Π½Π°Π»ΠΈΠ·Π° ΡΠΈΡΠΎΡΠΎΠΊΡΠΈΡΠ½ΠΎΡΡΠΈ Ρ ΠΈΡΠΏΠΎΠ»ΡΠ·ΠΎΠ²Π°Π½ΠΈΠ΅ΠΌ
ΡΡΠ»ΡΡΠΎΡΠΎΠ΄Π°ΠΌΠΈΠ½Π° B. ΠΠ»Ρ Π°Π½Π°Π»ΠΈΠ·Π° ΡΠ°ΡΠΏΡΠ΅Π΄Π΅Π»Π΅Π½ΠΈΡ ΠΊΠ»Π΅ΡΠΎΠΊ ΠΏΠΎ ΡΠ°Π·Π°ΠΌ ΠΊΠ»Π΅ΡΠΎΡΠ½ΠΎΠ³ΠΎ ΡΠΈΠΊΠ»Π° ΠΏΡΠΈΠΌΠ΅Π½ΡΠ»ΠΈ ΠΌΠ΅ΡΠΎΠ΄ ΠΏΡΠΎΡΠΎΡΠ½ΠΎΠΉ ΡΠΈΡΠΎΠΌΠ΅ΡΡΠΈΠΈ,
Π°ΠΏΠΎΠΏΡΠΎΠ·Π° β Ρ ΠΏΡΠΈΠΌΠ΅Π½Π΅Π½ΠΈΠ΅ΠΌ ΠΊΠΎΠΌΠΌΠ΅ΡΡΠ΅ΡΠΊΠΎΠ³ΠΎ Π½Π°Π±ΠΎΡΠ° Π΄Π»Ρ ΠΏΡΠΎΠ²Π΅Π΄Π΅Π½ΠΈΡ ΠΠ€Π. Π£ΡΠΎΠ²Π΅Π½Ρ ΡΠΎΡΡΠΎΡΠΈΠ»ΠΈΡΠΎΠ²Π°Π½Π½ΠΎΠΉ ΠΊΠΈΠ½Π°Π·Ρ ΠΠΠ’,
ΠΏΡΠ΅Π΄ΠΏΠΎΠ»ΠΎΠΆΠΈΡΠ΅Π»ΡΠ½ΠΎ ΡΠ²ΡΠ·Π°Π½Π½ΠΎΠΉ Ρ ΡΠ°Π΄ΠΈΠΎΡΠ΅Π·ΠΈΡΡΠ΅Π½ΡΠ½ΠΎΡΡΡΡ, ΠΎΠΏΡΠ΅Π΄Π΅Π»ΡΠ»ΠΈ ΠΌΠ΅ΡΠΎΠ΄ΠΎΠΌ ΠΠ΅ΡΡΠ΅ΡΠ½-Π±Π»ΠΎΡ Π°Π½Π°Π»ΠΈΠ·Π°. Π Π΅Π·ΡΠ»ΡΡΠ°ΡΡ: ΠΈΠ½ΠΊΡΠ±Π°ΡΠΈΡ
ΠΊΠ»Π΅ΡΠΎΠΊ SKNMC STI-571 ΠΏΡΠΈΠ²ΠΎΠ΄ΠΈΠ»Π° ΠΊ Π΄ΠΎΠ·ΠΎΠ·Π°Π²ΠΈΡΠΈΠΌΠΎΠΌΡ Π°Π½ΡΠΈΠΏΡΠΎΠ»ΠΈΡΠ΅ΡΠ°ΡΠΈΠ²Π½ΠΎΠΌΡ ΡΡΡΠ΅ΠΊΡΡ ΠΈ ΡΠ½ΠΈΠΆΠ΅Π½ΠΈΡ ΡΠΎΡΡΠΎΡΠΈΠ»ΠΈΡΠΎΠ²Π°Π½ΠΈΡ
AKT, Π½ΠΎ Π½Π΅ Π°ΠΏΠΎΠΏΡΠΎΠ·Ρ ΠΊΠ»Π΅ΡΠΎΠΊ. ΠΠΎΠΌΠ±ΠΈΠ½ΠΈΡΠΎΠ²Π°Π½Π½ΠΎΠ΅ ΠΏΡΠΈΠΌΠ΅Π½Π΅Π½ΠΈΠ΅ STI-571 ΠΈ ΠΎΠ±Π»Π΅Π½ΠΈΡ ΠΈΠ»ΠΈ ΡΠΈΡΠΏΠ»Π°ΡΠΈΠ½Ρ ΠΎΠΊΠ°Π·ΡΠ²Π°Π»ΠΎ Π΄ΠΎΠΏΠΎΠ»Π½ΠΈΡΠ΅Π»ΡΠ½ΠΎΠ΅
Π°Π½ΡΠΈΠΏΡΠΎΠ»ΠΈΡΠ΅ΡΠ°ΡΠΈΠ²Π½ΠΎΠ΅ Π²ΠΎΠ·Π΄Π΅ΠΉΡΡΠ²ΠΈΠ΅ Π½Π° ΠΊΠ»Π΅ΡΠΊΠΈ Π»ΠΈΠ½ΠΈΠΈ SKNMC (60% ΡΠΌΠ΅Π½ΡΡΠ΅Π½ΠΈΡ ΠΊΠΎΠ»ΠΈΡΠ΅ΡΡΠ²Π° ΠΊΠ»Π΅ΡΠΎΠΊ). ΠΠ½Π°Π»ΠΎΠ³ΠΈΡΠ½ΡΠ΅ ΡΡΡΠ΅ΠΊΡΡ
ΠΎΡΠΌΠ΅ΡΠ°Π»ΠΈ Π½Π° ΠΊΠ»Π΅ΡΠΊΠ°Ρ
Π»ΠΈΠ½ΠΈΠΈ MCF-7. ΠΡΠ²ΠΎΠ΄Ρ: ΠΎΠ±ΡΠ°Π±ΠΎΡΠΊΠ° ΠΎΠΏΡΡ
ΠΎΠ»Π΅Π²ΡΡ
ΠΊΠ»Π΅ΡΠΎΠΊ STI-571 ΡΡΠΈΠ»ΠΈΠ²Π°Π΅Ρ ΡΡΡΠ΅ΠΊΡ ΠΎΠ±Π»Π΅Π½ΠΈΡ ΠΈ ΡΠΈΡΠΏΠ»Π°ΡΠΈΠ½Ρ
in, ΠΏΡΠΈΡΠ΅ΠΌ ΡΠ°ΠΊΠΎΠ²ΠΎΠΉ ΠΌΠΎΠΆΠ΅Ρ Π±ΡΡΡ ΠΎΠΏΠΎΡΡΠ΅Π΄ΠΎΠ²Π°Π½ ΡΠΈΠ³Π½Π°Π»ΡΠ½ΡΠΌ ΠΊΠ°ΡΠΊΠ°Π΄ΠΎΠΌ AK
Natural Variation in Maternal Care and Cross-Tissue Patterns of Oxytocin Receptor Gene Methylation in Rats
Since the first report of maternal care effects on DNA methylation in rats, epigenetic modifications of the genome in response to life experience have become the subject of intense focus across many disciplines. Oxytocin receptor expression varies in response to early experience, and both oxytocin signaling and methylation status of the oxytocin receptor gene (Oxtr) in blood have been related to disordered social behavior. It is unknown whether Oxtr methylation varies in response to early life experience, and whether currently employed peripheral measures of Oxtr methylation reflect variation in the brain. We examined the effects of early life rearing experience via natural variation in maternal licking and grooming during the first week of life on behavior, physiology, gene expression, and epigenetic regulation of Oxtr across blood and brain tissues (mononucleocytes, hippocampus, striatum, and hypothalamus). Rats reared by βhighβ licking-grooming (HL) and βlowβ licking-grooming (LL) rat dams exhibited differences across study outcomes: LL offspring were more active in behavioral arenas, exhibited lower body mass in adulthood, and showed reduced corticosterone responsivity to a stressor. Oxtr methylation was significantly lower at multiple CpGs in the blood of LL versus HL rats, but no differences were found in the brain. Across groups, Oxtr transcript levels in the hypothalamus were associated with reduced corticosterone secretion in response to stress, congruent with the role of oxytocin signaling in this region. Methylation of specific CpGs at a high or low level was consistent across tissues, especially within the brain. However, individual variation in methylation relative to these global patterns was not consistent across tissues. These results suggest that blood Oxtr methylation may reflect early experience of maternal care, and that Oxtr methylation across tissues is highly concordant for specific CpGs, but that inferences across tissues are not supported for individual variation in Oxtr methylation
Septal Oxytocin Administration Impairs Peer Affiliation via V1a Receptors in Female Meadow Voles
The peptide hormone oxytocin (OT) plays an important role in social behaviors, including social bond formation. In different contexts, however, OT is also associated with aggression, social selectivity, and reduced affiliation. Female meadow voles form social preferences for familiar same-sex peers under short, winter-like day lengths in the laboratory, and provide a means of studying affiliation outside the context of reproductive pair bonds. Multiple lines of evidence suggest that the actions of OT in the lateral septum (LS) may decrease affiliative behavior, including greater density of OT receptors in the LS of meadow voles that huddle less. We infused OT into the LS of female meadow voles immediately prior to cohabitation with a social partner to determine its effects on partner preference formation. OT prevented the formation of preferences for the partner female. Co-administration of OT with a specific OT receptor antagonist did not reverse the effect, but co-administration of OT with a specific vasopressin 1a receptor (V1aR) antagonist did, indicating that OT in the LS likely acted through V1aRs to decrease partner preference. Receptor autoradiography revealed dense V1aR binding in the LS of female meadow voles. These results suggest that the LS is a brain region that may be responsible for inhibitory effects of OT administration on affiliation, which will be important to consider in therapeutic administrations of OT
Chronic Stress Elevates Telomerase Activity in Rats
The enzyme telomerase lengthens telomeresβprotective structures containing repetitive DNA sequences at chromosome ends. Telomere shortening is associated with diseases of ageing in mammals. Chronic stress has been related to shorter immune-cell telomeres, but telomerase activity under stress may be low, permitting telomere loss, or high, partially attenuating it. We developed an experimental model to examine the impacts of extended unpredictable stress on telomerase activity in male rats. Telomerase activity was 54 per cent higher in stressed rats than in controls, and associated with stress-related physiological and behavioural outcomes. This significant increase suggests a potential mechanism for resilience to stress-related replicative senescence
Administration of Lactobacillus johnsonii FI9785 to chickens affects colonisation by Campylobacter jejuni and the intestinal microbiota
Emergent Intra-Pair Sex Differences and Organized Behavior in Pair Bonded Prairie Voles (Microtus ochrogaster)
In pair bonding animals, coordinated behavior between partners is required for the pair to accomplish shared goals such as raising young. Despite this, experimental designs rarely assess the behavior of both partners within a bonded pair. Thus, we lack an understanding of the interdependent behavioral dynamics between partners that likely facilitate relationship success. To identify intra-pair behavioral correlates of pair bonding, we used socially monogamous prairie voles (Microtus ochrogaster) and tested both partners using social choice and non-choice tests at short- and long-term pairing timepoints. Females developed a preference for their partner more rapidly than males, with preference driven by different behaviors in each sex. Further, as bonds matured, intra-pair behavioral sex differences and organized behavior emergedβfemales consistently huddled more with their partner than males did regardless of overall intra-pair affiliation levels. When animals were allowed to freely interact with a partner or a novel vole in sequential free interaction tests, pairs spent more time interacting together than either animal did with a novel vole, consistent with partner preference in the more commonly employed choice test. Total pair interaction in freely moving voles was correlated with female, but not male, behavior. Via a social operant paradigm, we found that pair-bonded females, but not males, are more motivated to access and huddle with their partner than a novel vole. Together, our data indicate that as pair bonds mature, sex differences and organized behavior emerge within pairs, and that these intra-pair behavioral changes are likely organized and driven by the female animal
Determinants of response to a parent questionnaire about development and behaviour in 3 year olds: European multicentre study of congenital toxoplasmosis.
Background:
We aimed to determine how response to a parent-completed postal questionnaire measuring development, behaviour, impairment, and parental concerns and anxiety, varies in different European centres.
Methods:
Prospective cohort study of 3 year old children, with and without congenital toxoplasmosis, who were identified by prenatal or neonatal screening for toxoplasmosis in 11 centres in 7 countries. Parents were mailed a questionnaire that comprised all or part of existing validated tools. We determined the effect of characteristics of the centre and child on response, age at questionnaire completion, and response to child drawing tasks.
Results:
The questionnaire took 21 minutes to complete on average. 67% (714/1058) of parents responded. Few parents (60/1058) refused to participate. The strongest determinants of response were the score for organisational attributes of the study centre (such as direct involvement in follow up and access to an address register), and infection with congenital toxoplasmosis. Age at completion was associated with study centre, presence of neurological abnormalities in early infancy, and duration of prenatal treatment. Completion rates for individual questions exceeded 92% except for child completed drawings of a man (70%), which were completed more by girls, older children, and in certain centres.
Conclusion:
Differences in response across European centres were predominantly related to the organisation of follow up and access to correct addresses. The questionnaire was acceptable in all six countries and offers a low cost tool for assessing development, behaviour, and parental concerns and anxiety, in multinational studies
The reliability of two visual motor integration tests used with children
Occupational therapists often assess the visual motor integration (VMI) skills of children and young people. It is important that therapists use tools with strong psychometric properties. This study aims to examine the reliability of 2 VMI tests. Ninety-two children between the ages of 5 and 17 years (response rate of 31%) completed 2 VMI tests: the Developmental Test of Visual Motor Integration (DTVMI) and the Full Range Test of Visual Motor Integration (FRTVMI). Cronbach\u27s alpha coefficient was used to examine the internal consistency of the 2 VMI tests whereas Spearman\u27s rho correlation was used to evaluate the test–retest reliability, intrarater reliability, and interrater reliability of the 2 VMI tests. The Cronbach\u27s alpha coefficient for the DTVMI was .82 and .72 for the FRTVMI. The test–retest reliability coefficient was .73 (p = .000) for the DTVMI and .49 (p = .05) for the FRTVMI. The interrater correlation was significant for both the DTVMI at .94 (p = .000) and FRTVMI at .68 (p = .001). The DTVMI intrarater reliability correlation result was .90 (p = .000) and the FRTVMI at .85 (p = .000). Overall, the DTVMI exhibited a higher level of reliability than the FRTVMI. Both VMI tests appear to exhibit reasonable levels of reliability and are recommended for use with children and young people.<br /
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