Consequences of Selection for Environmental Impact Traits in Dairy Cows

peer reviewedGenetic selection programs aiming to mitigate methane (CH4) emissions require the estimation of genetic correlations with other production and economical traits and predicted selection response. CH4 intensity was predicted from Mid-infrared spectra of milk samples from Holstein cows. Genetic correlations between CH4 intensity and milk yield (MY) was -0.68, fat yield (FY) -0.13, protein yield (PY) -0.47, somatic cell score (SCS) 0.07, longevity 0.05, fertility 0.31, body condition score (BCS) 0.17. Adding 25% relative weight on CH4 intensity to the current Walloon selection index, the response to selection would reduce CH4 intensity by 24%, increase MY by 30%, FY by 17%, PY by 29%, SCS by -14%, longevity by 24% but also reduce fertility by 11% and BCS by 13%. In conclusion, environmental traits can be added without jeopardizing production traits, but energy balance related traits have to be protected.GreenHouseMilk, MethaMil

Consequences of Selection for Environmental Impact Trait in Dairy Cows

Environmental sustainability is gaining importance in dairy industry due to enteric methane (CH4) emission from dairy cows. We predicted CH4 indicator trait (CH4 intensity: CH4 g/kg of milk) from Mid-infrared spectra of milk samples and recorded milk yield. Genetic correlations between CH4 intensity and milk production traits were estimated on Holstein cows from correlations of estimated breeding values. Genetic correlations between CH4 intensity and milk yield (MY) was -0.67, fat yield (FY) -0.13, protein yield (PY) -0.46, somatic cell score (SCS) 0.02, longevity -0.07, fertility 0.31, body condition score (BCS) 0.27 and average of confirmation traits -0.23. Currently, there is no CH4 emission trait in genetic evaluation selection index. Putting an hypothetical 25% weight on CH4 intensity on current Walloon genetic evaluation selection index and proportional reduction on other selection traits, the response to selection will be reduction of CH4 emission intensity by 24%, increase in MY by 30%, FY by 17%, PY by 29%, SCS by -15%, longevity by 24%, fertility by -11%, BCS by -13% and conformation traits by 24%. In conclusion, introduction of environmental traits in current selection index will affect selection responses. As there is no economic value of these traits presently alternative methods like putting correlated traits with clear economic value (e.g. feed efficiency) in the selection objective could generate appropriate index weights.GreenHouseMil

Consequences of Selection for Environmental Impact Trait in Dairy Cows

Environmental sustainability is gaining importance in dairy industry due to enteric methane (CH4) emission from dairy cows. We predicted CH4 indicator trait (CH4 intensity: CH4 g/kg of milk) from Mid-infrared spectra of milk samples and recorded milk yield. Genetic correlations between CH4 intensity and milk production traits were estimated on Holstein cows from correlations of estimated breeding values. Genetic correlations between CH4 intensity and milk yield (MY) was -0.67, fat yield (FY) -0.13, protein yield (PY) -0.46, somatic cell score (SCS) 0.02, longevity -0.07, fertility 0.31, body condition score (BCS) 0.27 and average of confirmation traits -0.23. Currently, there is no CH4 emission trait in genetic evaluation selection index. Putting an hypothetical 25% weight on CH4 intensity on current Walloon genetic evaluation selection index and proportional reduction on other selection traits, the response to selection will be reduction of CH4 emission intensity by 24%, increase in MY by 30%, FY by 17%, PY by 29%, SCS by -15%, longevity by 24%, fertility by -11%, BCS by -13% and conformation traits by 24%. In conclusion, introduction of environmental traits in current selection index will affect selection responses. As there is no economic value of these traits presently alternative methods like putting correlated traits with clear economic value (e.g. feed efficiency) in the selection objective could generate appropriate index weights.GreenHouseMil

Consideration of Nevirapine Analogs To Reduce Metabolically Linked Hepatotoxicity: A Cautionary Tale of the Deuteration Approach

Idiosyncratic drug reactions (IDRs) in their most deleterious form can lead to serious medical complications and potentially fatal events. Nevirapine (NVP), still widely used in developing countries for combinatorial antiretroviral and prophylactic therapies against HIV infection, represents a prototypical example of IDRs causing severe skin rashes and hepatotoxicity. Complex metabolic pathways accompanied by production of multiple reactive metabolites often complicate our understanding of IDR’s origin. While assessment of NVP analogs has helped characterize the pathways involved in IDRs for NVP, which are largely driven by metabolism at the 12-methyl position, it has yet to be investigated if some of these analogs could be valuable replacement drugs with reduced reactive metabolite properties and drug–drug interaction (DDI) risks. Here, we evaluated a set of eight NVP analogs, including the deuterated 12-d3-NVP and two NVP metabolites, for their efficacy and inhibitory potencies against HIV reverse transcriptase (HIV-RT). A subset of three analogs, demonstrating >85% inhibition for HIV-RT, was further assessed for their hepatic CYP induction-driven DDI risks. This led to a closer investigation of the inactivation properties of 12-d3-NVP for hepatic CYP3A4 and a comparison of its propensity in generating reactive metabolite species. The metabolic shift triggered with 12-d3-NVP, increasing formation of the 2-hydroxy and glutathione metabolites, emphasized the importance of the dynamic balance between induction and metabolism-dependent inactivation of CYP3A4 and its impact on clearance of NVP during treatment. Unfortunately, the strategy of incorporating deuterium to reduce NVP metabolism and production of the electrophile species elicited opposite results, illustrating the great challenges involved in tackling IDRs through deuteration

5-Hydroxytryptamine4 Receptor Activation of the Extracellular Signal-regulated Kinase Pathway Depends on Src Activation but Not on G Protein or β-Arrestin Signaling

The 5-hydroxytryptamine4 (5-HT4) receptors have recently emerged as key modulators of learning, memory, and cognitive processes. In neurons, 5-hydroxytryptamine4 receptors (5-HT4Rs) activate cAMP production and protein kinase A (PKA); however, nothing is known about their ability to activate another key signaling pathway involved in learning and memory: the extracellular signal-regulated kinase (ERK) pathway. Here, we show that 5-HT4R stimulation, in primary neurons, produced a potent but transient activation of the ERK pathway. Surprisingly, this activation was mostly PKA independent. Similarly, using pharmacological, genetic, and molecular tools, we observed that 5-HT4Rs in human embryonic kidney 293 cells, activated the ERK pathway in a Gs/cAMP/PKA-independent manner. We also demonstrated that other classical G proteins (Gq/Gi/Go) and associated downstream messengers were not implicated in the 5-HT4R–activated ERK pathway. The 5-HT4R–mediated ERK activation seemed to be dependent on Src tyrosine kinase and yet totally independent of β-arrestin. Immunocytofluorescence revealed that ERK activation by 5-HT4R was restrained to the plasma membrane, whereas p-Src colocalized with the receptor and carried on even after endocytosis. This phenomenon may result from a tight interaction between 5-HT4R and p-Src detected by coimmunoprecipitation. Finally, we confirmed that the main route by which 5-HT4Rs activate ERKs in neurons was Src dependent. Thus, in addition to classical cAMP/PKA signaling pathways, 5-HT4Rs may use ERK pathways to control memory process

Peer selection and socialization in adolescent depression: The role of school transitions

Item does not contain fulltextPrevious studies have indicated homophily in depressive symptoms among adolescent friends, resulting from both peer selection and socialization processes. However, developmental differences and the role of school transitions in these processes have not been elucidated. A sample of 367 (51% female) adolescents was followed from 6th to 11th grade to investigate prospective relationships between adolescents' and their friends' depressive symptoms in middle school and in high school. Results revealed that students selected friends with similar levels of depressive symptoms after each school transition. Additionally, friends appeared to socialize adolescents to become more similar in depressive affect in late middle school years. These findings suggest normative selection effects after school transitions, followed by socialization effects in middle school, but not high school

The Association between Early Childhood and Later Childhood Sugar-Containing Beverage Intake: A Prospective Cohort Study

Sugar-containing beverages (SCBs) are a major source of sugar intake in children. Early life intake of SCBs may be a strong predictor of SCB intake later in life. The primary objective of this study was to evaluate if SCB intake (defined as 100% fruit juice, soda, and sweetened drinks) in early childhood (≤2.5 years of age) was associated with SCB intake in later childhood (5-9 years of age). A prospective cohort study was conducted using data from the TARGet Kids! primary care practice network (n = 999). Typical daily SCB intake was measured by parent-completed questionnaires. Odds ratios (OR) and 95% confidence intervals (CI) were estimated using logistic regression. A total of 43% of children consumed ≥0.5 cups/day of SCBs at ≤2.5 years and this increased to 64% by 5-9 years. Daily SCB intake, compared to no daily intake, at ≤2.5 years was significantly associated with SCB intake at 5-9 years (adjusted OR: 4.03; 95% CI: 2.92-5.55) and this association was much stronger for soda/sweetened drinks (adjusted OR: 12.83; 95% CI: 4.98, 33.0) than 100% fruit juice (OR: 3.61; 95% CI: 2.63-4.95). Other early life risk factors for SCB intake at 5-9 years were presence of older siblings, low household income, and shorter breastfeeding duration. Daily intake of SCBs in early childhood was strongly associated with greater SCB intake in later childhood. Early life may be an important period to target for population prevention strategies. </p