Background

Selecting and propagating cattle genetics that are more efficient at converting feed into carcass gain is an important element of a profitable and sustainable livestock industry[1].As a moderately heritable trait,independent of growth and body size,RFI is now a favoured measure of feed efficiency for livestock[2].Independence of RFI from production also affords the opportunity to unravel the inherent variation in biological processes underpinning differences in inter-animal efficiency.Various biologicalprocesses　have　been　identified　as　possible contributors to variation in feed efficiency[2-5],but no one process predominates.

Susceptibility to stress and biological differences in an animal’s stress response is proposed[6,7]as probable drivers of variation in feed efficiency that warrant further investigation.Indeed,an association between stress susceptibility and energetic inefficiency is conceivable,given that one of the noted biological responses to a stressful stimuli is to increase metabolic rate,energy consumption and decrease immunity,through alterations in the functioning of neuro-endocrine-immune pathways[8,9].

Stress response of animals is generally determined by measuring glucocorticoids and HPA axis activity[10].The activity of the HPA axis can be stimulated by way of a physiological stress challenge(following exogenous　administration　of　ACTH　and/or corticotrophin-releasing　hormone;CRH)and　the stress response of the HPA can be assessed at the pituitary and adrenal levels.Knott et al.[6]reported that RFI and cortisol response were positively associated,in rams selected based on their response to an ACTH physiological stress challenge.In laying hens originating from a multi-generational divergent RFI selection line,Luiting et al.[11]reported that the inefficient hen lines had a greater cortisol response following an adrenal ACTH challenge compared to their efficient contemporaries.However,from a cattle perspective there is a dearth of published information on this topic.Therefore,the objective of this study　wasto　determine　whetherendocrine　and hematologic　responses　following　an　exogenous ACTH challenge differ between beef heifers divergent for phenotypic RFI.

Methods

All procedures involving animals in this study were conducted under an experimental licence from the Irish Department of Health and Children in accordance with the cruelty to Animals Act 1876 and the European Communities(Amendment of Cruelty to Animals Act 1876)Regulation 2002 and 2005(http://www.dohc.ie/other_-health_issues/uaeosp).

Animal management and determination of RFI

[17][18] P. W. J Nababan, “Language in Education:The case of Indonesia”, International Review of Education, Vol. 37, No. 1 (1991), p. 121, pp. 122-123.

Performance and RFI data were collected on 34 Simmental weaning beef heifers which were the progeny of a well characterized and divergently bred RFI suckler beef herd established in Teagasc Grange,as described by[12-14].During the post-weaning stage individual daily feed　intakewas recorded　on heifers(mean　initial BW=299±4 kg,mean initial age=258±27 d)over a 91-day period,following which RFI co-efficients were calculated for each animal.Heifers were housed in a slatted floor building with a Calan gate feeding system(American Calan Inc.,Northwood,NH)and were given an adaptation period of 14 d to acclimatise to their diet and environment before recording individual intake began(RFI measurement period).Heifers were individually offered grass silage and 2 kg of concentrate once per day(at 0800 h).The concentrate offered contained 430 kg rolled barley,430 kg beet pulp,80 kg soya bean meal,45 kg molasses and 15 kg minerals and vitamins per tonne.Grass silage allocation was based on approximately 1.1 times the previous day’s intake.The chemical composition and in vitro dry matter digestibility of the grass silage and concentrate offered is outlined in Table 1.

Heifers were weighed(prior to feeding)on two consecutive days at the beginning and end of the period of RFI measurement and every 21 d during the experimental period.Average daily gain was computed as the coefficient of the linear regression of weight(kg)on time using the REG procedure of the Statistical Analysis Systems(SAS Institute Inc.,Cary,NC).Mid-test metabolic body weight(MBW)was estimated from the intercept and slope of the regression line after fitting a linear regression through all metabolic body weight(BW0.75)observations.Feed conversion ratio(F:G)of each animal was computed as the ratio of daily DMI to ADG.Residual feed intake was calculated for each animal as the difference between actual DMI and expected DMI.Expected DMI was computed for each animal using a multiple regression model,regressing DMI on MBW and ADG.The model used was

Where Yjis the average DMI of the jth animal,β0is the partial regression intercept,β1is the partial regression coefficient on MBW0.75,β2is the partial regression coefficient on ADG,and ejis the uncontrolled error of the jth animal.The coefficient of determination(R2)from this model was equal to 0.66(P＜0.001)and the model was subsequently used to predict DMI for each animal.

1.稳定期（1994-2006）：这个阶段为民居植物文化研究的起始阶段。这一时期共有19篇论文发表，其中期刊文章为9篇，占稳定期发表文章总数的49%，博硕论文10篇。1999年由廖晋雄[1]针对客家清代民居客厅天窗装饰的天门阿公、天门公婆进行研究，包括天窗墙壁上的植物、园林等在内的植物装饰，开启了对民居植物文化研究的序幕。

Heifers were turned out to pasture after the RFI experimental period ended.For the duration of the grazing season(7 mo),heifers were rotationally grazed as onegroup under a moderate stocking rate on predominately perennial ryegrass(Lolium perenne L.)pasture until housing at the end of October,when the grazing season ended[mean ADG of 0.80 kg/d(SEM=0.03)].For the physiological stress challenge experiment the 12 highest[mean(0.48±0.08)kg/d];High RFI and 12 lowest[mean-(0.50±0.08)kg/d];Low RFI ranking animals on post weaning RFI were selected.

Table 1　Chemical composition of the dietary ingredients offered during the residual feed intake experimental period

aCorrected for loss of volatiles during oven drying bND not determined cDigestible OM in the total DM,measured in vitro dOM digestibility,measured in vitro eEstimated based on in vitro digestible OM in total DM(AFRC,1993)fExpressed as g/kg volatile corrected DM

RFI experimental period Variable　Silage　Concentrate Dry matter,g/kga　315±33.9　822±0.7 Composition of DM,g/kg DM unless otherwise stated pH　3.9±0.15　NDb In vitro DMD　693±47.3　726±44.0 In vitro DOMDc　625±37.1　676±44.6 OMDd　677±47.5　726±46.9 Ash　75±11.7　73±1.6 Crude protein　121±10.3　115±11.6 NDF　532±54.7　244±31.4 Starch　ND　230±56.3 ME,MJ/kg DMe　10.41±0.45　11.56±0.36 Fermentation characteristicsf,g/kg Lactic acid　102±49.8　ND Acetic acid　33±7.7　ND Propionic acid　2.9±0.66　ND Butyric acid　4.5±2.39　ND Ethanol　13.4±2.82　ND Ammonia N,g/kg total N　76±10.9　ND

The adrenal cortex was successfully stimulated by ACTH administration in this study and the cortisol response and maximum peak time(60 min)was consistent with previous ACTH challenge experiments[9,15,27].For the ACTH response no difference in plasma concentrations were detected between the divergent RFI phenotypes throughout the physiological challenge,concurring with the results that Adago[28]reported in Braham Cattle.Cortisol is the principal stress biomarker and thebiological endpoint for the investigation of HPA function.Knott et al.[29]found that rams selected for greater cortisol concentration following an ACTH challenge also had a higher RFI than their lower cortisol response counterparts.Those authors also attributed up to 35%of the variation in RFI to the changes in cortisol concentrations,indicative of a stress response.Similarly,in a multi-generational selection experiment for RFI in chickens,Luiting and Verstegen[11]reported that inefficient hens had a greater cortisol response following an adrenal ACTH challenge.In cattle,Richardson et al.[30]observed a trend for a positive relationship between blood cortisol concentration of steers and their sire’s estimated breeding value for RFI.Although,admittedly when phenotypic RFI and plasma cortisol concentrations were compared in the Richardson study a negative or inverse relationship was detected between the traits.However,it could also be argued that the ability to truly quantify stress responsiveness or HPA sensitivity in that study may have been somewhat limited,as a physiologicalstressor/challengewasnotimposed　on　the divergent RFI animals.Results from the current experiment agree with the findings in sheep[6,29]and chicken[11]indicating that energetic inefficiency is associated with greater susceptibility to stress and is a likely underlying driver along with other biological processes[2]of variation in the trait.Indeed,our work clearly shows a greater cortisol stress response in High RFI heifers following activation of the HPA axis with exogenous ACTH(adrenal stimulation).In contrast to these findings Kelly et al.[18],failed to show an association between feed efficiency and stress biomarkers when focusing on neuroendocrine responses to a physiological CRH stress challenge.In that study HPA axis stimulation was via exogenous CRH and a more diminished adrenal cortex response was observed relative to that measured in the present study,which may explain the disagreement in results between our study and that of Kelly et al.[18].Indeed,in all other published feed efficiency studies that investigated physiological stressors[6,11],ACTH which was the sectretagogue used to examine adrenal stimulation of HPA and subsequent

During the ACTH stress challenge the 24 heifers(mean age 605±13 d;mean BW 516±31.4 kg)were housed in a slatted-floor facility and were offered grass silage ad libitum.Start weight(P=0.52)and age(P=0.88)were not different between the high and low RFI groups.As part of standard husbandry and research management practices animals were accustomed to stockpersons and routine handling,approximately 14-day prior to the ACTH challenge.To facilitate intensive blood collection and minimize handling stress during blood sampling,heifers were fitted aseptically with indwelling jugular catheters on d-1.The procedure was using 12-gauge Anes spinal needles(Popper and Sons,Inc.,New Hyde Park,NY)and polyvinyl tubing(approximately 1.47 mm i.d.;Ico Rally Corp.,Palo Alto,CA;catalog No.SVL 105-18 CLR)attached to an 18-gauge needle at the blood collection end.After catheterization,catheter patency was maintained by flushing with 3.5%sodium citrate after each blood collection.

HPA axis and feed efficiency

Understanding the biological mechanisms that control feed efficiency is fundamental to the future of profitable livestock production systems[1,20].Susceptibility to stress and the cross regulatory responses between the neuro-endocrine and immune systems have long been postulated as potential processes that contributes to inter-animal variation in feed efficiency in cattle[18].However,despite the credible link between these traits there is a dearth of published work in this area,which is surprising given the importance of feed efficiency and susceptibility to stress(the implications on health and behaviour)to overall animal production efficiency[2].Therefore,this study aimed to further enhance our knowledge of the biological control of feed efficiency in cattle by investigating the sensitivity of the HPA axis(a putative regulator of energetic efficiency)to a physiological ACTH stress challenge.

On d 0,serial heparinised blood samples were collected at-40,-20,0,20,40,60,80,100,120,150,180,210,240,270,300,330,and 390 min relative to the time of ACTH administration to each heifer.Plasma samples were separated by centrifugation at 1600×g at 8 °C for 15 min and subsequently stored at-20°C until assayed.

Cortisol concentration was determined for all heifers at all blood sampling time points,whereas ACTH concentration was determined only at blood sampling time points-40,-20,20,80,120,180,and 390 min relative to ACTH administration.Plasma cortisol concentrations were determined using the Correlate-EIA kits from Assay Designs(Ann Arbor,MI,USA).The inter-and intra-assay coefficients of variation(CV)were 6.25%and 4.89%,respectively.Plasma ACTH concentrations were measured using a double antibody human ACTH radioimmunoassay(RIA;DiaSorin Inc.,Stillwater,MN,USA)previously validated for bovine ACTH[15].The inter-assay and intra-assay CVs were 8.85%and 7.67%,respectively.

Hematology

国家已经颁布了新的法律法规，对内部控制工作进行明确的规定，对于改进工作误区有着很大的指导作用，但是提升内部控制工作的科学系与合理性，需要将文件与自己单位工作的实际情况结合起来，让文件更加具有实践性与可操作性，不然工作就会出现茫然无措的现象，没有切入点，在具体的工作中，将文件与本单位的实际情况结合起来，对内部控制工作做出新的指引。在工作中，通过详细的文件，对行政事业单位内部控制的相关问题进行分析，规定内部控制的目标、原则、内容、评价等。

An additional blood sample was collected into a 6-mL evacuated tube containing K3EDTA at-40,-20,0,20,80,150,270,330,and 390 min relative to CRH administration for determination of blood hematology variables;white blood cell(WBC)number,red blood cell(RBC)number,hemoglobin(HGB)concentration,hematocrit percentage(HCT%),platelet count(PLT)and total circulating neutrophil,lymphocyte,monocyte,eosinophil,and basophil numbers were determined within 1 h of collection according to the procedures described by Lynch et al.[19].

Activation of the HPA axis is the main defining feature of the stress response[21]and one of the main biological outcomes in response to a stressor is a rise in metabolic rate[8,22].Elevated metabolic rate can influence appetite and energy partitioning and utilisation mainly through altering catabolic process such as increasing the rate of lipolysis and protein degradation[8,23].These biological pathways have all been postulated as inherent regulators of an animal’s energetic efficiency[2-5].

溃决洪水（泥石流）的流动特性包括洪峰流量、溃决泥石流量、行进距离和淹没面积等特性。其中，洪峰流量是最重要的一个量值；溃决泥石流体积将影响行进距离和淹没面积，也较重要。冰碛湖溃决洪水（泥石流）的模拟主要从湖水量计算、溃决洪峰估算、泥石流体积估算、溃决洪水（泥石流）最远距离估算、淹没面积估算等方面进行。

Data were checked for normality and homogeneity of variance by histograms,QQ-plots,and formal statistical tests as part of the UNIVARIATE procedure of SAS(version 9.1.3;SAS Institute,2006).Data that were not normally　distributed　weretransformed　byraising　the variable to the power of lambda.The appropriate lambda value was obtained by conducting a Box-Cox transformation analysis using the TRANSREG procedure of SAS.The transformed data were used to calculate P-values.The corresponding least squares means and SE of the non-transformed data are presented in the results for clarity.To evaluate the response over time for plasma concentrations of cortisol,ACTH and haematological variables,these were analysed using repeated measures ANOVA(MIXED procedure),with terms for RFI group,bleed time,pen and their interactions included in the model.Heifer baseline plasma concentrations(mean of-40,-20 and 0 min prior to ACTH administration for cortisol and haematology variables and-40 and-20 for plasma ACTH concentration)were included as covariates.The type of variance-covariance structure used was chosen depending on the magnitude of the Akaike information criterion(AIC)for models run under compound symmetry,unstructured,autoregressive,heterogeneous 1st order autoregressive,or Toeplitz variance-covariance structures.The model with the least AIC value was selected.The differences between mean values for the two RFI groups were determined by F-tests using Type III sums of squares.The PDIFF option and the Tukey test were applied as appropriate to evaluate pairwise comparisons between RFI group means.A probability of P＜0.05 was selected as the level of significance and statistically tendencies were reported when P＜0.10.Spearman　correlation　coefficients　between　traits　were determined using PROC CORR of SAS.

Results

Feed efficiency

Based upon the results of the post-weaning determination of RFI,the low RFI heifers selected for the ACTH challenge had a 19%reduced DMI compared to the high selected RFI animals for the same level of performance.Residual feed intake averaged 0.00 kg DM/d(SD=0.43)and ranged from-0.87 to 1.02 kg DM/d,equating to a difference of 1.89 kg DM/d between the most and least efficient ranking heifers used in the ACTH challenge.Least squares means for RFI(P＜0.001)and F:G(P=0.03;Table 2)were greater for high RFI than for low RFI animals.Heifers in the high RFI and low RFI groups did not differ in final BW(P=0.21)and ADG(P=0.92).Within the group of weanling heifers RFI was positively correlated with DMI(r=0.59;P＜0.001).Dry matter intake was positively correlated(P＜0.001)with ADG(r=0.55)and negatively correlated(P＜0.05)with F:G(r=-0.27).Feed conversion ratio was negatively correlated(P＜0.001)with ADG during the RFI measurement period(r=-0.85).

Table 2　Effect of residual feed intake(RFI)ranking on feed intake,efficiency and animal performance in beef heifers

High RFI　Low RFI　SEM　P-value Number of Animals　12　12　-　-Residual feed intake,kg/d 0.34　-0.48　0.037　0.001 Feed conversion ratio,kg DM/kg gain 8.13　6.19　0.834　0.03 DMI,kg/d　5.92　4.98　0.127　0.001 Mid-test metabolic BW,kg0.75　75　77　1.6　0.27 ADG,kg/d　0.71　0.76　0.028　0.92 Final BW,kg　340　355　9.8　0.21

Exogenous ACTH challenge

Plasma ACTH and cortisol responses to administration of exogenous ACTH for both RFI groupings are presented Figs.1 and 2,respectively.Heifers differing in RFI did not differ(P=0.59)in ACTH concentration.Concentration of ACTH peaked(P＜0.001)in both RFI groups at 20 min post-ACTH administration,following which concentration declined to baseline levels by 150 min.Similarly,cortisol systemic profile peaked at 60 min and concentrations remained continuously elevated for 150 min.A RFI×time interaction was detected for cortisol concentrations(P=0.06).High RFI heifers had a greater cortisol response than Low RFI from 40 min to 150 min relative to ACTH administration(Fig.3),whereas there was no difference between RFI grouping subsequently.Cortisol response,from ACTH adrenal stimulation was positively associated with RFI status(r=0.32;P＜0.01).

Haematology

如图4 所示，实线是（s，p，o）的所有有效时间，虚线是要删除数据的有效时间。情况1：[start，end]包含[t1，t2]，或者相等，直接删除（s，p，o）[t1，t2]记录；2：（s，p，o）在[t1，start-1]的时间内有效，修改记录（s，p，o）有效时间为[t1，start-1]；3：（s，p，o）在[start，end]的时间内无效，删除操作不用执行；4：（s，p，o）在[t3，start-1]和[end+1，t4]时间内是有效的，修改记录（s，p，o）有效时间为[t3，start-1]，再插入一条记录（s，p，o）[end+1，t4]。

No effect of RFI grouping or a RFI×time interaction(P＞0.10;Table 3)was evident for neutrophil,lymphocytes,monocyte,eosinophils and basophil count.Mean plasma RBC number(P=0.02)and HCT percentage(P=0.02)were greater for low RFI than high RFI animals(RBC=6.07 vs.6.23;HCT=23.2 vs.24.5 for high,and low　RFIgroups,respectively).An　effectoftime(P＜0.0001;Table 3)was found neutrophil,monocyte,eosinophils and basophil count and for PLT number and HGB with values generally increasing for leucocytes and monocytes,and decreasing for PLT and HGB as time progressed.

Fig.1　Effect of exogenous adrenocorticotropic(ACTH)administration(1.98 IU/kg metabolic BW0.75)on plasma ACTH concentration(pg/dL)in beef heifers differing in phenotypic RFI.The values are expressed as Lsmeans with SEM.RFI,P=0.59;Time,P＜0.001;RFI×Time interaction,P=0.13.SEM:High RFI=4.98;Low RFI=6.55

Discussion

The response of the adrenal cortex to a standardised dose of ACTH(1.98 IU/kg metabolic BW0.75)was examined.The dose chosen of exogenous ACTH and was previously established by our group[15]to be effective in adequately stimulating HPA responses,with resultant elevations in cortisol not sufficient to cause negative effects on animal health.Dexamethasone(20 μg/kg BW;Faulding Pharmaceuticals Plc,UK)was administered intramuscularly(i.m.)on d-1,12.40 h prior to heifers undergoingACTH　challenge(SynacthenAmpoules,Novartis Pharmaceutical Ltd.,UK)on the following morning(d 0).In cattle,DEX is rapidly absorbed and the elimination half-life of DEX has been reported by Toutain et al.to ranges from 291 to 335 min[16,17].Dexamethasone was administered to equalize systemic concentrations of cortisol[9]in animals across the RFI groups,in an effort to facilitate a more equitable examination of ACTH on cortisol release[18,19].

Fig.2　Effect of exogenous adrenocorticotropic(ACTH)administration(1.98 IU/kg metabolic BW0.75)on plasma cortisol concentration(ng/mL)in beef heifers differing in phenotypic residual feed intake(RFI).The values are expressed as Lsmeans with SEM.RFI,P=0.45;Time,P＜0.001;RFI×Time interaction,P=0.06.SEM:High RFI=0.712;Low RFI=0.688

Fig.3　Mean plasma cortisol stress response from 40 min to 150 min relative to exogenous adrenocorticotropic(ACTH)administration(1.98 IU/kg metabolic BW0.75)in beef heifers differing in phenotypic residual feed intake(RFI).The values are expressed as Lsmeans with SEM.RFI,P=0.006.SEM:High RFI=0.57;Low RFI=0.52

ACTH challenge

Statistical analysis

十二、来稿刊登后本刊编辑部按国家版权局有关规定从优一次性支付稿酬，稿酬中含光盘版和网络版的稿酬。杂志出版后向论文第一作者赠送当期杂志2册（短篇1册）。

To monitor animal’s stress response measuring glucocorticoid hormones and HPA axis activity is the standard approach.Through dynamic testing methodologies the HPA axis can be pharmacologically stimulated with the use of exogenous CRH or ACTH,and response at both the pituitary and adrenal levels can be evaluated.Indeed,HPA axis challenges by way of exogenous CRH or ACTH stimulation have been shown by our group previously[15,24]and others[25,26]to be appropriate for investigation of the bovine stress response.

Jugular vein catheterisation

式中：ρ为水的密度，kg/m3;T为温度，℃；u为速度，m/s；P为压力，Pa；λ1,λ2为导热系数，W/(m2·℃)；cp1,cp2为比热容，J/(kg·℃)，μ为湍流粘性扩散系数；T∞为参考温度，℃.

同时，对于上市问题，宗庆后此前一直坚持娃哈哈不差钱、不上市。而今年3月，也有媒体报道称，娃哈哈开始为上市而瘦身——清退员工股份。宗庆后也改口表示，未来如果有大的产业要投资，娃哈哈也要上市募集资金。

①检查预制构件的堆放和场地转弯平面的布置（场地面积，承载能力和道路回转半径应满足项目建设的需要）。②检查起重机械的选择和布局（机器的起重能力和回转半径应满足起重和安装部件的要求）。③检查预制构件的整体安装过程（根据组装顺序和工艺流程）。④对工程的质量进行严格监控，对其严格把关。⑤审查子项目的施工方法（按照规定的要求和数据编制的相关要求）。⑥检查组件产品（运输，堆叠，存储）的保护措施。⑦审查技术措施，确保施工安全和质量。⑧审查绿色施工和文明施工的措施。

stress response.Foote et al.[31]also showed in cattle that efficient or low RFI heifers have lower concentrations of fecal corticosterone than the high RFI heifers and fecal corticosterone was identified as a useful physiological indicator for feed efficiency in finishing beef cattle.This finding complements our results,in that corticosterone is an informative representative of adrenal activity and is a glucocorticoid produced in a pattern similar to cortisol in response to ACTH release.

Table 3　Effect of exogenous adrenocorticotropic(ACTH)administrationaon haematology variables in beef heifers differing in phenotypic residual feed intake(RFI)

aExogenous ACTH(1.98 IU/kg metabolic BW075) bWBCP White blood cell number,RBC red blood cell number,HGB hemoglobin concentration,HCTH hematocrit percentage,MCHC mean corpuscular hemoglobin concentration,PLT platelet number

Time(min)relative to ACTH administration Cell typeb　RFI Group　0　20　80　150　270　330　390　SEM　RFI　Time　RFI×Time Neutrophils,× 103cells/μL　High　9.1　11.7　10.9　11.4　11.9　11.9　12.2　0.36　0.90　0.001　0.92 Low　8.5　11.3　10.8　12.2　12.9　11.9　11.7　0.41 Lymphocytes,× 103cells/μL　High　3.36　3.51　3.3　2.92　3.21　3.41　4.02　0.159　0.99　0.71　0.78 Low　3.88　3.38　3.16　3.07　3.55　3.32　3.27　0.175 Monocytes,× 103cells/μL　High　0.69　0.39　0.53　0.39　0.45　0.47　0.58　0.04　0.99　0.01　0.95 Low　0.7　0.5　0.68　0.39　0.49　0.38　0.42　0.045 Eosinophils,× 103cells/μL　High　0.18　0.08　0.21　0.12　0.12　0.12　0.36　0.027　0.85　0.001　0.06 Low　0.19　0.21　0.06　0.13　0.19　0.31　0.24　0.031 Basophils,× 103cells/μL　High　0.05　0.06　0.05　0.06　0.06　0.06　0.07　0.003　0.61　0.001　0.3 Low　0.05　0.05　0.05　0.06　0.07　0.06　0.06　0.003 WBC,× 103cells/μL　High　16.6　14.7　15.3　14　14.8　14.7　16.3　0.3　0.35　0.53　0.7 Low　15.4　16.2　16.1　15.3　16.6　15.4　15.3　0.34 RBC,× 106cells/μL　High　6.19　6.33　6.04　5.66　6.08　6.03　6.17　0.093　0.02　0.1　0.81 Low　5.89　6.66　6.42　6.41　6.53　6.43　6.57　0.107 HGB,g/dL　High　9.46　9.6　9.14　8.63　9.25　9.25　9.54　0.124　0.08　0.04　0.8 Low　8.77　9.94　9.6　9.51　9.78　9.62　9.81　0.142 HCT,%　High　23.6　24.3　23.1　21.8　23.3　22.9　23.6　0.36　0.02　0.06　0.87 Low　22.4　24.5　24.5　24.4　24.8　24.5　25.1　0.42 MCHC,g/dL　High　40.3　39.5　40　44.8　40.2　40.7　40.9　0.63　0.23　0.71　0.92 Low　44.3　38.7　38.7　38.8　39.2　39.1　38.8　0.74 PLT,× 103cells/μL　High　366.6　312.7　458.9　327　420.5　300.7　346.4　22.82　0.69　0.001　0.76 Low　309.3　329.4　405.2　269.1　436.3　274.4　310.4　26.11

Immune response and feed efficiency

垃圾分类、废品回收及处理、再循环再利用整个链条有待全面打通。政策的利好，以及互联网和物联网技术的介入，“物联网+智能回收” 技术如星星之火开始燎原。在智能垃圾分类回收领域，小黄狗环保科技有限公司崭露头角，实现了对生活垃圾前端分类回收、中端统一运输、末端集中处理。此外，笨哥哥科技、虎哥、绿猫、闲豆、千鸟回收、章鱼等一批环保回收行业的优秀企业，也正在切入回收领域的上游与后端环节，通过互联网提升回收效率。

The central nervous system regulation of the immune system acts principally via the HPA[32,33].Neutrophils,as well as many other immune cells,are well known targets of stress hormones,possessing receptors for catecholamines and glucocorticoids secreted during an acute stress response.A profound leukocytosis,with marked neutrophilia,has often been observed in association with elevated circulating glucocorticoids[8,23]indicating a disruption of neutrophilhomeostasis in response to stress in cattle.This cross regulation between neuro-endocrine-immune systems is critical for homeostasis and has profound effects on the health,behaviour and performance of animals[33].In general,the data from the current trial failed to show a relationship between feed efficiency,and the principal indicators of immune-competence in response to a physiological stressor.When Kelly et al.[18]investigated neuroendocrine responses to an exogenous physiological CRH physiological challenge in animals of differing RFI status,they did not find an association between haematological subpopulations and RFI.Additionally,Lawrence et al.[13]reported that high and low RFI heifers did not differ in any of the haematology variables measured,except at parturition when lymphocyte and monocyte counts were positively associated with RFI.Theis et al.[34]did not detect any relationship between phenotypic RFI with a similar set of haematological variables as was reported on in this study.However,recent work from our group[35]has shown that feed efficient pigs had lower gene expression profiles for intestinal innate immune response genes following a lipopolysaccharide(LPS)challenge compared to their inefficient contemporaries,suggesting that feed efficient animals have an altered immune response to infection.Indeed,mounting effective innate immune responses is metabolically costly to the animal which demands a nutrient tradeoff at the expense of other biological demanding processes and as such could be an underlying contributor to variation in energetic efficiency[36].Richardson et al.[37]reported a genetic association between sire estimated breeding value(EBV)for RFI with white blood cell count,lymphocyte count and haemoglobin level,in crossbred beef steers.Gomes et al.[38]also reported that white blood cell count was lower and haemoglobin concentration was higher in high RFI heifers than low RFI heifers.In our study,we did detect that red blood cell count and hematocrit percentage was greater in Low RFI compared to High RFI animals,potentially indicating some deviations in oxygen requirement or carbon dioxide transport within their haem structure due to stress sensitivity[39].

Conclusions

The data presented provide evidence that animals differing in feed efficiency have an altered HPA axis function in response to a physiological stressor(ACTH adrenal stimuli)and susceptibility to stress and responsiveness of the HPA axis is likely to contribute to appreciable variation in the efficiency feed utilisation of cattle.As such,these findings add greater clarity and focus to the body of published work examining the biological control of feed efficiency in cattle.

Abbreviations

ACTH:Adrenocorticotropic hormone;ADG:Average daily gain;BW:Bodyweight;CRH:Corticotrophin-releasing hormone;CV:Co-efficient of variation;DMI:Dry matter intake;EBV:Estimated breeding value;F:G:Feed conversion ratio;HCT%:Hematocrit percentage;HGB:Hemoglobin;HPA:Hypothalamic-pituitary-adrenal;LPS:Lipopolysaccharide;MBW:Metabolic body weight;RBC:Red blood cell;RFI:Residual feed intake;WBC:white blood cell

Acknowledgements

(5)“有效氯含量”可用来衡量含氯消毒剂的消毒能力,其定义是:每克含氯消毒剂的氧化能力相当于多少克Cl2的氧化能力。NaClO2的有效氯含量为____。(计算结果保留两位小数)

The authors of this study gratefully acknowledge skilled technical assistance from Mr.Eddie Mulligan(Teagasc Animal Bioscience Research Centre,Grange)and the farm manager and his staff at Teagasc,Grange.

Availability of data and materials

幼儿教育是一生学习的启蒙阶段，对以后的学习有着重要的影响，而语言学习更是学习的基础，只有语言学习的更好，才能更好地开始其它学科的学习。因此这对教师语言教学能力有着严格的要求，教师语言教学能力的高低直接影响了幼儿的语言学习能力。教师的语言教学能力不仅体现了教师的个人素养，也对幼儿养成正确的言语有着重要的影响。因此，教师可以针对语言教学能力进行相关的训练，例如对教师组织培训活动、教师之间观察交流活动。教师在日常上课时，也可有意识地进行相关的训练。经过长时间的积累，教师就会掌握系统的语言教学方法，提高语言教学能力。

The datasets during and/or analyzed during the current study available from the corresponding authors on reasonable request.

Authors’contributions

MM and AK conceived the study,conducted the statistical analysis and prepared the manuscript.BE conducted the laboratory analyses and prepared the manuscript.PL managed the animal model and assisted with manuscript preparation.DK assisted with diet formulation,sample recovery,statistical analysis and manuscript preparation.All authors read and approved the final manuscript.

Ethics approval

All procedures involving animals in this study were conducted under an experimental licence from the Irish Department of Health and Children in accordance with the cruelty to Animals Act 1876 and the European Communities(Amendment of Cruelty to Animals Act 1876)Regulation 2002 and 2005(http://www.dohc.ie/other_health_issues/uaeosp).

Consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.

Author details

1School of Agriculture and Food Science,College of Health and Agricultural Sciences,University College Dublin,Belfield,Dublin 4,Ireland.2Animal and Bioscience Research Department,Animal&Grassland Research and Innovation Centre,Teagasc,Dunsany,Co.Meath,Ireland.3Livestock Systems Research Department Teagasc,Animal&Grassland Research and Innovation Centre,Grange,Dunsany,Co.Meath,Ireland.

其一，报告制度。《破产法》第69条规定，管理人在决定履行债务人和对方当事人均未履行完毕的合同时，应当及时报告债权人委员会；未设立债权人委员会的，应当及时报告人民法院。第26条规定，在第一次债权人会议召开前，管理人决定继续或者停止债务人的营业的，应当报经人民法院许可。此处管理人决定继续营业的，通常会涉及到对于一些待履行合同继续履行，《破产法》规定其应当报告人民法院并经许可方能作出决定。在债权人会议成立之前，由人民法院履行审查职责，以制衡和监督管理人依法合理履行职责。

References

1.　Moore S,Mujibi F,Sherman E.Molecular basis for residual feed intake in beef cattle.J Anim Sci.2009;87:E41-7.

2.　Herd R,Arthur P.Physiological basis for residual feed intake.J Anim Sci.2009;87:E64-71.

3.　Kelly AK,Waters SM,McGee M,Fonseca RG,Carberry C,Kenny DA.mRNA expression of genes regulating oxidative phosphorylation in the muscle of beef cattle divergently ranked on residual feed intake.Physiol Genomics.2011;43:12-23.

4.　Kelly A,Waters S,McGee M,Browne J,Magee D,Kenny D.Expression of key genes of the somatotropic axis in longissimus dorsi muscle of beef heifers phenotypically divergent for residual feed intake.J Anim Sci.2013;91:159-67.

5.　Kelly A,McGee M,Crews D,Fahey A,Wylie A,Kenny D.Effect of divergence in residual feed intake on feeding behavior,blood metabolic variables,and body composition traits in growing beef heifers.J Anim Sci.2010;88:109-23.

6.　Knott S,Cummins L,Dunshea F,Leury B.Rams with poor feed efficiency are highly responsive to an exogenous adrenocorticotropin hormone(ACTH)challenge.Domest Anim Endocrinol.2008;34:261-8.

7.　Richardson E,Herd R.Biological basis for variation in residual feed intake in beef cattle.2.Synthesis of results following divergent selection.Anim Prod Sci.2004;44:431-40.

8.　Burton JL,Madsen SA,Chang LC,Weber PS,Buckham KR,van Dorp R,et al.Gene expression signatures in neutrophils exposed to glucocorticoids:A new paradigm to help explain “neutrophil dysfunction”in parturient dairy cows.Vet Immunol Immunopathol.2005;105:197-219.

9.　Gupta S,Earley B,Crowe M.Pituitary,adrenal,immune and performance responses of mature Holstein×Friesian bulls housed on slatted floors at various space allowances.Vet J.2007;173:594-604.

10.Ralph C,Tilbrook A.The hypothalamo-pituitary-adrenal(HPA)axis in sheep is attenuated during lactation in response to psychosocial and predator stress.Domest Anim Endocrinol.2016;55:66-73.

11.Luiting P,Urff E,Verstegen M.Between-animal variation in biological efficiency as related to residual feed consumption.NJAS Wagen J Life Sci.1994;42:59-67.

12.Lawrence P,Kenny D,Earley B,McGee M.Intake of conserved and grazed grass and performance traits in beef suckler cows differing in phenotypic residual feed intake.Livest Sci.2013;152:154-66.

13.Lawrence P,Kenny DA,Earley B,Crews DH,McGee M.Grass silage intake,rumen and blood variables,ultrasonic and body measurements,feeding behavior,and activity in pregnant beef heifers differing in phenotypic residual feed intake1.J Anim Sci.2011;89:3248-261.

14.Fitzsimons C,Kenny D,Deighton M,Fahey A,McGee M.Methane emissions,body composition,and rumen fermentation traits of beef heifers differing in residual feed intake.J Anim Sci.2013;91:5789-800.

15.Gupta S,Earley B,Ting S,Leonard N,Crowe M.Technical Note:Effect of corticotropin-releasing hormone on adrenocorticotropic hormone and cortisol in steers.J Anim Sci.2004;82:1952-6.

16.Gaignage P,Lognay G,Bosson D,Vertongen D,Dreze P,Marlier M,et al.Dexamethasone bovine pharmacokinetics.Eur J Drug Metab Pharmacokinet.1991;16:219-21.

17.Toutain P,Brandon R,Alvinerie M,Garcia-Villar R,Ruckebusch Y.Dexamethasone in cattle:pharmacokinetics and action on the adrenal gland.J Vet Pharmacol Ther.1982;5:33-43.

18.Kelly A,Earley B,McGee M,Fahey A,Kenny D.Endocrine and hematological responses of beef heifers divergently ranked for residual feed intake following a bovine corticotropin-releasing hormone challenge.J Anim Sci.2016;94:1703-11.

19.Lynch EM,Earley B,McGee M,Doyle S.Effect of abrupt weaning at housing on leukocyte distribution,functional activity of neutrophils,and acute phase protein response of beef calves.BMC Vet Res.2010;6:39.

20.Kelly A,McGee M,Crews D,Sweeney T,Boland T,Kenny D.Repeatability of feed efficiency,carcass ultrasound,feeding behavior,and blood metabolic variables in finishing heifers divergently selected for residual feed intake.J Anim Sci.2010;88:3214-25.

21.Smagin GN,Heinrichs SC,Dunn AJ.The role of CRH in behavioral responses to stress.Peptides.2001;22:713-24.

22.Buckham Sporer K,Weber P,Burton J,Earley B,Crowe M.Transportation of young beef bulls alters circulating physiological parameters that may be effective biomarkers of stress.J Anim Sci.2008;86:1325-34.

23.Gomes RDC,Sainz RD,Leme PR.Protein metabolism,feed energy partitioning,behavior patterns and plasma cortisol in Nellore steers with high and low residual feed intake.Rev Bras Zootec.2013;42:44-50.

24.Fisher A,Verkerk G,Morrow C,Matthews L.The effects of feed restriction and lying deprivation on pituitary-adrenal axis regulation in lactating cows.Livest Prod Sci.2002;73:255-63.

25.Verkerk G,Macmillan K.Adrenocortical responses to an adrenocorticotropic hormone in bulls and steers.J Anim Sci.1997;75:2520-5.

26.Fisher A,Crowe M,O’Kiely P,Enright W.Growth,behaviour,adrenal and immune responses of finishing beef heifers housed on slatted floors at 1.5,2.0,2.5 or 3.0 m2space allowance.Livest Prod Sci.1997;51:245-54.

27.Gupta S,Earley B,Crowe M.Effect of 12-hour road transportation on physiological,immunological and haematological parameters in bulls housed at different space allowances.Vet J.2007;173:605-16.

28.Agado BJ.Serum concentrations of cortisol induced by exogenous adrenocorticotropic hormone(ACTH)are not predictive of residual feed intake(RFI)in Brahman cattle.PhD Diss.2011.

29.Knott S,Cummins L,Dunshea F,Leury B.Feed efficiency and body composition are related to cortisol response to adrenocorticotropin hormone and insulin-induced hypoglycemia in rams.Domest Anim Endocrinol.2010;39:137-46.

30.Richardson E,Herd R,Archer J,Arthur P.Metabolic differences in Angus steers divergently selected for residual feed intake.Anim Prod Sci.2004;44:441-52.

31.Foote A,Hales K,Tait R,Berry E,Lents C,Wells J,et al.Relationship of glucocorticoids and hematological measures with feed intake,growth,and efficiency of finishing beef cattle.J Anim Sci.2016;94:275-83.

32.Buckingham JC.Glucocorticoids:exemplars of multi-tasking.Br J Pharmacol.2006;147:S258-68.

33.Carroll J,Burdick Sanchez N,Bill E.Kunkle interdisciplinary beef symposium:Overlapping physiological responses and endocrine biomarkers that are indicative of stress responsiveness and immune function in beef cattle.J Anim Sci.2014;92:5311-8.

34.Theis C,Carstens G,Hollenbeck R,Kurz M,Bryan T,Slay LJ,et al.Residual feed intake in beef steers:II.Correlations with hematological parameters and serum cortisol.In:Proceed-American Soc Anim Sci Western Sec;2002.p.483-6.

35.Vigors S,O’Doherty JV,Kelly AK,O’Shea CJ,Sweeney T.The Effect of Divergence in Feed Efficiency on the Intestinal Microbiota and the Intestinal Immune Response in Both Unchallenged and Lipopolysaccharide Challenged Ileal and Colonic Explants.PLoS One.2016;11:e0148145.

36.van der Most PJ,de Jong B,Parmentier HK,Verhulst S.Trade-off between growth and immune function:a meta-analysis of selection experiments.Funct Ecol.2011;25:74-80.

37.Richardson E,Herd R,Colditz I,Archer J,Arthur P.Blood cell profiles of steer progeny from parents selected for and against residual feed intake.Anim Prod Sci.2002;42:901-8.

38.Gomes RDC,Siqueira RFD,Ballou MA,Stella TR,Leme PR.Hematological profile of beef cattle with divergent residual feed intake,following feed deprivation.Pesq Agrop Brasileira.2011;46:1105-11.

39.Jones ML,Allison RW.Evaluation of the ruminant complete blood cell count.Vet Clin North Am Food Anim Pract.2007;23:377-402.