The fitness trade-off between growth and stress resistance determines the phenotypic landscape.

BACKGROUND: A central challenge in biology is to discover a principle that determines individual phenotypic differences within a species. The growth rate is particularly important for a unicellular organism, and the growth rate under a certain condition is negatively associated with that of another condition, termed fitness trade-off. Therefore, there should exist a common molecular mechanism that regulates multiple growth rates under various conditions, but most studies so far have focused on discovering those genes associated with growth rates under a specific condition. RESULTS: In this study, we found that there exists a recurrent gene expression signature whose expression levels are related to the fitness trade-off between growth preference and stress resistance across various yeast strains and multiple conditions. We further found that the genomic variation of stress-response, ribosomal, and cell cycle regulators are potential causal genes that determine the sensitivity between growth and survival. Intriguingly, we further observed that the same principle holds for human cells using anticancer drug sensitivities across multiple cancer cell lines. CONCLUSIONS: Together, we suggest that the fitness trade-off is an evolutionary trait that determines individual growth phenotype within a species. By using this trait, we can possibly overcome anticancer drug resistance in cancer cells.

Global stabilizing control of large-scale biomolecular regulatory networks.

MOTIVATION: Cellular behavior is determined by complex non-linear interactions between numerous intracellular molecules that are often represented by Boolean network models. To achieve a desired cellular behavior with minimal intervention, we need to identify optimal control targets that can drive heterogeneous cellular states to the desired phenotypic cellular state with minimal node intervention. Previous attempts to realize such global stabilization were based solely on either network structure information or simple linear dynamics. Other attempts based on non-linear dynamics are not scalable. RESULTS: Here, we investigate the underlying relationship between structurally identified control targets and optimal global stabilizing control targets based on non-linear dynamics. We discovered that optimal global stabilizing control targets can be identified by analyzing the dynamics between structurally identified control targets. Utilizing these findings, we developed a scalable global stabilizing control framework using both structural and dynamic information. Our framework narrows down the search space based on strongly connected components and feedback vertex sets then identifies global stabilizing control targets based on the canalization of Boolean network dynamics. We find that the proposed global stabilizing control is superior with respect to the number of control target nodes, scalability, and computational complexity. AVAILABILITY AND IMPLEMENTATION: We provide a GitHub repository that contains the DCGS framework written in Python as well as biological random Boolean network datasets (https://github.com/sugyun/DCGS). SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Inhibition of 3-phosphoinositide-dependent protein kinase 1 (PDK1) can revert cellular senescence in human dermal fibroblasts.

Cellular senescence is defined as a stable, persistent arrest of cell proliferation. Here, we examine whether senescent cells can lose senescence hallmarks and reenter a reversible state of cell-cycle arrest (quiescence). We constructed a molecular regulatory network of cellular senescence based on previous experimental evidence. To infer the regulatory logic of the network, we performed phosphoprotein array experiments with normal human dermal fibroblasts and used the data to optimize the regulatory relationships between molecules with an evolutionary algorithm. From ensemble analysis of network models, we identified 3-phosphoinositide-dependent protein kinase 1 (PDK1) as a promising target for inhibitors to convert the senescent state to the quiescent state. We showed that inhibition of PDK1 in senescent human dermal fibroblasts eradicates senescence hallmarks and restores entry into the cell cycle by suppressing both nuclear factor κB and mTOR signaling, resulting in restored skin regeneration capacity. Our findings provide insight into a potential therapeutic strategy to treat age-related diseases associated with the accumulation of senescent cells.

Cotargeting BET proteins overcomes resistance arising from PI3K/mTOR blockade-induced protumorigenic senescence in colorectal cancer.

Therapeutics targeting the phosphatidylinositol 3-kinase/mammalian target of rapamycin (PI3K/mTOR) pathway initially produce potent antitumor effects, but resistance frequently occurs. Using a phosphoproteome analysis, we found that colorectal cancer (CRC) cells exhibit resistance against PI3K/mTOR inhibition through feedback activation of multiple receptor tyrosine kinases, and their downstream focal adhesion kinase, Src and extracellular signal-regulated kinases signaling. Unexpectedly, PI3K/mTOR blockade causes senescence, mediated by the activation of the stress kinase p38. The senescent cancer cells induce the secretion of various cytokines and this senescence-associated secretome increases migration and invasion capabilities of CRC cells. We found that cotargeting PI3K/mTOR and bromodomain and extra-terminal domain can suppress activation of many oncogenic kinases involved in resistance to the PI3K/mTOR inhibition, induce cell death in vitro and tumor regression in vivo, and further prolong the survival of xenograft models. Our findings provide a rationale for a novel therapeutic strategy to overcome resistance to the PI3K/mTOR inhibitors in CRC.

Cooperative activation of PI3K by Ras and Rho family small GTPases.

Phosphoinositide 3-kinases (PI3Ks) and Ras and Rho family small GTPases are key regulators of cell polarization, motility, and chemotaxis. They influence each other's activities by direct and indirect feedback processes that are only partially understood. Here, we show that 21 small GTPase homologs activate PI3K. Using a microscopy-based binding assay, we show that K-Ras, H-Ras, and five homologous Ras family small GTPases function upstream of PI3K by directly binding the PI3K catalytic subunit, p110. In contrast, several Rho family small GTPases activated PI3K by an indirect cooperative positive feedback that required a combination of Rac, CDC42, and RhoG small GTPase activities. Thus, a distributed network of Ras and Rho family small GTPases induces and reinforces PI3K activity, explaining past challenges to elucidate the specific relevance of different small GTPases in regulating PI3K and controlling cell polarization and chemotaxis.

Layer-specific serotonergic induction of long-term depression in the prefrontal cortex of rats.

Layer 2/3 pyramidal neurons (L2/3 PyNs) of the cortex extend their basal dendrites near the soma and as apical dendritic tufts in layer 1, which mainly receive feedforward and feedback inputs, respectively. It is suggested that neuromodulators such as serotonin and acetylcholine may regulate the information flow between brain structures depending on the brain state. However, little is known about the dendritic compartment-specific induction of synaptic transmission in single PyNs. Here, we studied layer-specific serotonergic and cholinergic induction of long-term synaptic plasticity in L2/3 PyNs of the agranular insular cortex, a lateral component of the orbitofrontal cortex. Using FM1-43 dye unloading, we verified that local electrical stimulation to layers 1 (L1) and 3 (L3) activated axon terminals mostly located in L1 and perisomatic area (L2/3). Independent and AMPA receptor-mediated excitatory postsynaptic potential was evoked by local electrical stimulation of either L1 or L3. Application of serotonin (5-HT, 10 µM) induced activity-dependent longterm depression (LTD) in L2/3 but not in L1 inputs. LTD induced by 5-HT was blocked by the 5-HT2 receptor antagonist ketanserin, an NMDA receptor antagonist and by intracellular Ca2+ chelation. The 5-HT2 receptor agonist α-me-5-HT mimicked the LTD induced by 5-HT. However, the application of carbachol induced muscarinic receptor- dependent LTD in both inputs. The differential layer-specific induction of LTD by neuromodulators might play an important role in information processing mechanism of the prefrontal cortex.

Open channel block of Kv1.4 potassium channels by aripiprazole.

Aripiprazole is a quinolinone derivative approved as an atypical antipsychotic drug for the treatment of schizophrenia and bipolar disorder. It acts as with partial agonist activities at the dopamine D2 receptors. Although it is known to be relatively safe for patients with cardiac ailments, less is known about the effect of aripiprazole on voltage-gated ion channels such as transient A-type K+ channels, which are important for the repolarization of cardiac and neuronal action potentials. Here, we investigated the effects of aripiprazole on Kv1.4 currents expressed in HEK293 cells using a whole-cell patch-clamp technique. Aripiprazole blocked Kv1.4 channels in a concentration-dependent manner with an IC50 value of 4.4 µM and a Hill coefficient of 2.5. Aripiprazole also accelerated the activation (time-to-peak) and inactivation kinetics. Aripiprazole induced a voltage-dependent (δ = 0.17) inhibition, which was use-dependent with successive pulses on Kv1.4 currents without altering the time course of recovery from inactivation. Dehydroaripiprazole, an active metabolite of aripiprazole, inhibited Kv1.4 with an IC50 value of 6.3 µM (p < 0.05 compared with aripiprazole) with a Hill coefficient of 2.0. Furthermore, aripiprazole inhibited Kv4.3 currents to a similar extent in a concentration-dependent manner with an IC50 value of 4.9 µM and a Hill coefficient of 2.3. Thus, our results indicate that aripiprazole blocked Kv1.4 by preferentially binding to the open state of the channels.

Estimation of the genetic milk yield parameters of Holstein cattle under heat stress in South Korea.

OBJECTIVE: The objective of this study was to investigate the genetic components of daily milk yield and to re-rank bulls in South Korea by estimated breeding value (EBV) under heat stress using the temperature-humidity index (THI). METHODS: This study was conducted using 125,312 monthly test-day records, collected from January 2000 to February 2017 for 19,889 Holstein cows from 647 farms in South Korea. Milk production data were collected from two agencies, the Dairy Cattle Genetic Improvement Center and the Korea Animal Improvement Association, and meteorological data were obtained from 41 regional weather stations using the Automated Surface Observing System (ASOS) installed throughout South Korea. A random regression model using the THI was applied to estimate genetic parameters of heat tolerance based on the test-day records. The model included herd-year-season, calving age, and days-in-milk as fixed effects, as well as heat tolerance as an additive genetic effect, permanent environmental effect, and direct additive and permanent environmental effect. RESULTS: Below the THI threshold (≤72; no heat stress), the variance in heat tolerance was zero. However, the heat tolerance variance began to increase as THI exceeded the threshold. The covariance between the genetic additive effect and the heat tolerance effect was -0.33. Heritability estimates of milk yield ranged from 0.111 to 0.176 (average: 0.128). Heritability decreased slightly as THI increased, and began to increase at a THI of 79. The predicted bull EBV ranking varied with THI. CONCLUSION: We conclude that genetic evaluation using the THI function could be useful for selecting bulls for heat tolerance in South Korea.

Comparison of genome-wide association and genomic prediction methods for milk production traits in Korean Holstein cattle.

OBJECTIVE: The objectives of this study were to compare identified informative regions through two genome-wide association study (GWAS) approaches and determine the accuracy and bias of the direct genomic value (DGV) for milk production traits in Korean Holstein cattle, using two genomic prediction approaches: single-step genomic best linear unbiased prediction (ss-GBLUP) and Bayesian Bayes-B. METHODS: Records on production traits such as adjusted 305-day milk (MY305), fat (FY305), and protein (PY305) yields were collected from 265,271 first parity cows. After quality control, 50,765 single-nucleotide polymorphic genotypes were available for analysis. In GWAS for ss-GBLUP (ssGWAS) and Bayes-B (BayesGWAS), the proportion of genetic variance for each 1-Mb genomic window was calculated and used to identify informative genomic regions. Accuracy of the DGV was estimated by a five-fold cross-validation with random clustering. As a measure of accuracy for DGV, we also assessed the correlation between DGV and deregressed-estimated breeding value (DEBV). The bias of DGV for each method was obtained by determining regression coefficients. RESULTS: A total of nine and five significant windows (1 Mb) were identified for MY305 using ssGWAS and BayesGWAS, respectively. Using ssGWAS and BayesGWAS, we also detected multiple significant regions for FY305 (12 and 7) and PY305 (14 and 2), respectively. Both single-step DGV and Bayes DGV also showed somewhat moderate accuracy ranges for MY305 (0.32 to 0.34), FY305 (0.37 to 0.39), and PY305 (0.35 to 0.36) traits, respectively. The mean biases of DGVs determined using the single-step and Bayesian methods were 1.50±0.21 and 1.18±0.26 for MY305, 1.75±0.33 and 1.14±0.20 for FY305, and 1.59±0.20 and 1.14±0.15 for PY305, respectively. CONCLUSION: From the bias perspective, we believe that genomic selection based on the application of Bayesian approaches would be more suitable than application of ss-GBLUP in Korean Holstein populations.

Layer-specific cholinergic modulation of synaptic transmission in layer 2/3 pyramidal neurons of rat visual cortex.

It is known that top-down associative inputs terminate on distal apical dendrites in layer 1 while bottom-up sensory inputs terminate on perisomatic dendrites of layer 2/3 pyramidal neurons (L2/3 PyNs) in primary sensory cortex. Since studies on synaptic transmission in layer 1 are sparse, we investigated the basic properties and cholinergic modulation of synaptic transmission in layer 1 and compared them to those in perisomatic dendrites of L2/3 PyNs of rat primary visual cortex. Using extracellular stimulations of layer 1 and layer 4, we evoked excitatory postsynaptic current/potential in synapses in distal apical dendrites (L1-EPSC/L1-EPSP) and those in perisomatic dendrites (L4-EPSC/L4-EPSP), respectively. Kinetics of L1-EPSC was slower than that of L4-EPSC. L1-EPSC showed presynaptic depression while L4-EPSC was facilitating. In contrast, inhibitory postsynaptic currents showed similar paired-pulse ratio between layer 1 and layer 4 stimulations with depression only at 100 Hz. Cholinergic stimulation induced presynaptic depression by activating muscarinic receptors in excitatory and inhibitory synapses to similar extents in both inputs. However, nicotinic stimulation enhanced excitatory synaptic transmission by ~20% in L4-EPSC. Rectification index of AMPA receptors and AMPA/NMDA ratio were similar between synapses in distal apical and perisomatic dendrites. These results provide basic properties and cholinergic modulation of synaptic transmission between distal apical and perisomatic dendrites in L2/3 PyNs of the visual cortex, which might be important for controlling information processing balance depending on attentional state.

Systems biological approaches to the cardiac signaling network.

Recent systems biological studies of cardiac systems have greatly advanced our understanding of cardiac physiology with a particular focus on the excitation-contraction coupling. With these advancements, there is a growing interest in systems analysis of the cardiac signaling network because its dynamical property is closely associated with cardiac diseases. In this article, we review recent attempts at computational modeling of the cardiac signaling network and provide a system-level perspective on the analysis of the large-scale cardiac signaling network. We discuss why the systems biological approach is useful and what novel insights it can provide for the development of personalized therapeutic strategies for cardiac diseases in the post-genomic era.

Protein disulfide isomerase inhibition synergistically enhances the efficacy of sorafenib for hepatocellular carcinoma.

Sorafenib is the only approved targeted drug for hepatocellular carcinoma (HCC), but its effect on patients' survival gain is limited and varies over a wide range depending on pathogenetic conditions. Thus, enhancing the efficacy of sorafenib and finding a reliable predictive biomarker are crucial to achieve efficient control of HCCs. In this study, we utilized a systems approach by combining transcriptome analysis of the mRNA changes in HCC cell lines in response to sorafenib with network analysis to investigate the action and resistance mechanism of sorafenib. Gene list functional enrichment analysis and gene set enrichment analysis revealed that proteotoxic stress and apoptosis modules are activated in the presence of sorafenib. Further analysis of the endoplasmic reticulum stress network model, combined with in vitro experiments, showed that introducing an additional stress by treating the orally active protein disulfide isomerase (PDI) inhibitor (PACMA 31) can synergistically increase the efficacy of sorafenib in vitro and in vivo, which was confirmed using a mouse xenograft model. We also found that HCC patients with high PDI expression show resistance to sorafenib and poor clinical outcomes, compared to the low-PDI-expression group. CONCLUSION: These results suggest that PDI is a promising therapeutic target for enhancing the efficacy of sorafenib and can also be a biomarker for predicting sorafenib responsiveness. (Hepatology 2017;66:855-868).

Genetic parameter estimation for milk ß-hydroxybutyrate and acetone in early lactation and its association with fat to protein ratio and energy balance in Korean Holstein cattle.

OBJECTIVE: The objective of this study was to estimate the genetic parameters for milk ß-hydroxybutyrate (BHBA), acetone (Ac), fat protein ratio (FPR), and energy balance (EB) using milk test day records and investigate the effect of early lactation FPR and EB on milk ketone body concentrations. METHODS: Total 262,940 test-day records collected from Korea Animal Improvement Association during the period of 2012 to 2016 were used in this study. BHBA and Ac concentrations in milk were measured by Fourier transform infrared spectroscopy (FTIR). FPR values were obtained using test day records of fat and protein percentage. EB was calculated using previously developed equation based on parity, lactation week, and milk composition data. Genetic parameters were estimated by restricted maximum likelihood procedure based on repeatability model using Wombat program. RESULTS: Elevated milk BHBA and Ac concentrations were observed during the early lactation under the negative energy balance. Milk FPR tends to decrease with the decreasing ketone body concentrations. Heritability estimates for milk BHBA, Ac, EB, and FPR ranged from 0.09 to 0.14, 0.23 to 0.31, 0.19 to 0.52, and 0.16 to 0.42 respectively at parity 1, 2, 3, and 4. The overall heritability for BHBA, Ac, EB and FPR were 0.29, 0.32, 0.58, and 0.38 respectively. A common pattern was observed in heritability of EB and FPR along with parities. CONCLUSION: FPR and EB can be suggested as potential predictors for risk of hyperketonemia. The heritability estimates of milk BHBA, Ac, EB, and FPR indicate that the selective breeding may contribute to maintaining the milk ketone bodies at optimum level during early lactation.

Design and Performance Evaluation of an Electro-Hydraulic Camless Engine Valve Actuator for Future Vehicle Applications.

This paper details the new design and dynamic simulation of an electro-hydraulic camless engine valve actuator (EH-CEVA) and experimental verification with lift position sensors. In general, camless engine technologies have been known for improving fuel efficiency, enhancing power output, and reducing emissions of internal combustion engines. Electro-hydraulic valve actuators are used to eliminate the camshaft of an existing internal combustion engines and used to control the valve timing and valve duration independently. This paper presents novel electro-hydraulic actuator design, dynamic simulations, and analysis based on design specifications required to satisfy the operation performances. An EH-CEVA has initially been designed and modeled by means of a powerful hydraulic simulation software, AMESim, which is useful for the dynamic simulations and analysis of hydraulic systems. Fundamental functions and performances of the EH-CEVA have been validated through comparisons with experimental results obtained in a prototype test bench.

Genetic Parameters of Milk ß-Hydroxybutyric Acid and Acetone and Their Genetic Association with Milk Production Traits of Holstein Cattle.

This study was conducted to estimate the genetic parameters of ß-hydroxybutyrate (BHBA) and acetone concentration in milk by Fourier transform infrared spectroscopy along with test-day milk production traits including fat %, protein % and milk yield based on monthly samples of milk obtained as part of a routine milk recording program in Korea. Additionally, the feasibility of using such data in the official dairy cattle breeding system for selection of cows with low susceptibility of ketosis was evaluated. A total of 57,190 monthly test-day records for parities 1, 2, and 3 of 7,895 cows with pedigree information were collected from April 2012 to August 2014 from herds enrolled in the Korea Animal Improvement Association. Multi-trait random regression models were separately applied to estimate genetic parameters of test-day records for each parity. The model included fixed herd test-day effects, calving age and season effects, and random regressions for additive genetic and permanent environmental effects. Abundance of variation of acetone may provide a more sensitive indication of ketosis than many zero observations in concentration of milk BHBA. Heritabilities of milk BHBA levels ranged from 0.04 to 0.17 with a mean of 0.09 for the interval between 4 and 305 days in milk during three lactations. The average heritabilities for milk acetone concentration were 0.29, 0.29, and 0.22 for parities 1, 2, and 3, respectively. There was no clear genetic association of the concentration of two ketone bodies with three test-day milk production traits, even if some correlations among breeding values of the test-day records in this study were observed. These results suggest that genetic selection for low susceptibility of ketosis in early lactation is possible. Further, it is desirable for the breeding scheme of dairy cattle to include the records of milk acetone rather than the records of milk BHBA.

The Prediction of the Expected Current Selection Coefficient of Single Nucleotide Polymorphism Associated with Holstein Milk Yield, Fat and Protein Contents.

Milk-related traits (milk yield, fat and protein) have been crucial to selection of Holstein. It is essential to find the current selection trends of Holstein. Despite this, uncovering the current trends of selection have been ignored in previous studies. We suggest a new formula to detect the current selection trends based on single nucleotide polymorphisms (SNP). This suggestion is based on the best linear unbiased prediction (BLUP) and the Fisher's fundamental theorem of natural selection both of which are trait-dependent. Fisher's theorem links the additive genetic variance to the selection coefficient. For Holstein milk production traits, we estimated the additive genetic variance using SNP effect from BLUP and selection coefficients based on genetic variance to search highly selective SNPs. Through these processes, we identified significantly selective SNPs. The number of genes containing highly selective SNPs with p-value <0.01 (nearly top 1% SNPs) in all traits and p-value <0.001 (nearly top 0.1%) in any traits was 14. They are phosphodiesterase 4B (PDE4B), serine/threonine kinase 40 (STK40), collagen, type XI, alpha 1 (COL11A1), ephrin-A1 (EFNA1), netrin 4 (NTN4), neuron specific gene family member 1 (NSG1), estrogen receptor 1 (ESR1), neurexin 3 (NRXN3), spectrin, beta, non-erythrocytic 1 (SPTBN1), ADP-ribosylation factor interacting protein 1 (ARFIP1), mutL homolog 1 (MLH1), transmembrane channel-like 7 (TMC7), carboxypeptidase X, member 2 (CPXM2) and ADAM metallopeptidase domain 12 (ADAM12). These genes may be important for future artificial selection trends. Also, we found that the SNP effect predicted from BLUP was the key factor to determine the expected current selection coefficient of SNP. Under Hardy-Weinberg equilibrium of SNP markers in current generation, the selection coefficient is equivalent to 2*SNP effect.

Minimal systems analysis of mitochondria-dependent apoptosis induced by cisplatin.

Recently, it was reported that the role of mitochondria-reactive oxygen species (ROS) generating pathway in cisplatin-induced apoptosis is remarkable. Since a variety of molecules are involved in the pathway, a comprehensive approach to delineate the biological interactions of the molecules is required. However, quantitative modeling of the mitochondria-ROS generating pathway based on experiment and systemic analysis using the model have not been attempted so far. Thus, we conducted experiments to measure the concentration changes of critical molecules associated with mitochondrial apoptosis in both human mesothelioma H2052 and their ρ(0) cells lacking mitochondrial DNA (mtDNA). Based on the experiments, a novel mathematical model that can represent the essential dynamics of the mitochondrial apoptotic pathway induced by cisplatin was developed. The kinetic parameter values of the mathematical model were estimated from the experimental data. Then, we have investigated the dynamical properties of this model and predicted the apoptosis levels for various concentrations of cisplatin beyond the range of experiments. From parametric perturbation analysis, we further found that apoptosis will reach its saturation level beyond a certain critical cisplatin concentration.

Robustness and evolvability of the human signaling network.

Biological systems are known to be both robust and evolvable to internal and external perturbations, but what causes these apparently contradictory properties? We used Boolean network modeling and attractor landscape analysis to investigate the evolvability and robustness of the human signaling network. Our results show that the human signaling network can be divided into an evolvable core where perturbations change the attractor landscape in state space, and a robust neighbor where perturbations have no effect on the attractor landscape. Using chemical inhibition and overexpression of nodes, we validated that perturbations affect the evolvable core more strongly than the robust neighbor. We also found that the evolvable core has a distinct network structure, which is enriched in feedback loops, and features a higher degree of scale-freeness and longer path lengths connecting the nodes. In addition, the genes with high evolvability scores are associated with evolvability-related properties such as rapid evolvability, low species broadness, and immunity whereas the genes with high robustness scores are associated with robustness-related properties such as slow evolvability, high species broadness, and oncogenes. Intriguingly, US Food and Drug Administration-approved drug targets have high evolvability scores whereas experimental drug targets have high robustness scores.

Biphasic RLR-IFN-ß response controls the balance between antiviral immunity and cell damage.

In RNA virus-infected cells, retinoic acid-inducible gene-I-like receptors (RLRs) sense foreign RNAs and activate signaling cascades to produce IFN-α/ß. However, not every infected cell produces IFN-α/ß that exhibits cellular heterogeneity in antiviral immune responses. Using the IFN-ß-GFP reporter system, we observed bimodal IFN-ß production in the uniformly stimulated cell population with intracellular dsRNA. Mathematical simulation proposed the strength of autocrine loop via RLR as one of the contributing factor for biphasic IFN-ß expression. Bimodal IFN-ß production with intracellular dsRNA was disturbed by blockage of IFN-α/ß secretion or by silencing of the IFN-α/ß receptor. Amplification of RLRs was critical in the generation of bimodality of IFN-ß production, because IFN-ß(high) population expressed more RLRs than IFN-ß(low) population. In addition, bimodality in IFN-ß production results in biphasic cellular response against infection, because IFN-ß(high) population was more prone to apoptosis than IFN-ß(low) population. These results suggest that RLR-mediated biphasic cellular response may act to restrict the number of cells expressing IFN-ß and undergoing apoptosis in the infected population.

Genetic Parameters of Reproductive and Meat Quality Traits in Korean Berkshire Pigs.

Genetic parameters of Berkshire pigs for reproduction, carcass and meat quality traits were estimated using the records from a breeding farm in Korea. For reproduction traits, 2,457 records of the total number of piglets born (TNB) and the number of piglets born alive (NBA) from 781 sows and 53 sires were used. For two carcass traits which are carcass weight (CW) and backfat thickness (BF) and for 10 meat quality traits which are pH value after 45 minutes (pH45m), pH value after 24 hours (pH24h), lightness in meat color (LMC), redness in meat color (RMC), yellowness in meat color (YMC), moisture holding capacity (MHC), drip loss (DL), cooking loss (CL), fat content (FC), and shear force value (SH), 1,942 pig records were used to estimate genetic parameters. The genetic parameters for each trait were estimated using VCE program with animal model. Heritability estimates for reproduction traits TNB and NBA were 0.07 and 0.06, respectively, for carcass traits CW and BF were 0.37 and 0.57, respectively and for meat traits pH45m, pH24h, LMC, RMC, YMC, MHC, DL, CL, FC, and SH were 0.48, 0.15, 0.19, 0.36, 0.28, 0.21, 0.33, 0.45, 0.43, and 0.39, respectively. The estimate for genetic correlation coefficient between CW and BF was 0.27. The Genetic correlation between pH24h and meat color traits were in the range of -0.51 to -0.33 and between pH24h and DL and SH were -0.41 and -0.32, respectively. The estimates for genetic correlation coefficients between reproductive and meat quality traits were very low or zero. However, the estimates for genetic correlation coefficients between reproductive traits and drip and cooking loss were in the range of 0.12 to 0.17 and -0.14 to -0.12, respectively. As the estimated heritability of meat quality traits showed medium to high heritability, these traits may be applicable for the genetic improvement by continuous measurement. However, since some of the meat quality traits showed negative genetic correlations with carcass traits, an appropriate breeding scheme is required that carefully considers the complexity of genetic parameters and applicability of data.