1. |
- Andrén, Anders, et al.
(author)
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The occurrence of noncoagulating milk and the association of bovine milk coagulation properties with genetic variants of the caseins in 3 Scandinavian dairy breeds
- 2013
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In: Journal of Dairy Science. - : American Dairy Science Association. - 1525-3198 .- 0022-0302. ; 96:8, s. 4830-4842
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Journal article (peer-reviewed)abstract
- Substantial variation in milk coagulation properties has been observed among dairy cows. Consequently, raw milk from individual cows and breeds exhibits distinct coagulation capacities that potentially affect the technological properties and milk processing into cheese. This variation is largely influenced by protein composition, which is in turn affected by underlying genetic polymorphisms in the major milk proteins. In this study, we conducted a large screening on 3 major Scandinavian breeds to resolve the variation in milk coagulation traits and the frequency of milk with impaired coagulation properties (noncoagulation). In total, individual coagulation properties were measured on morning milk collected from 1,299 Danish Holstein (DH), Danish Jersey (DJ), and Swedish Red (SR) cows. The 3 breeds demonstrated notable interbreed differences in coagulation properties, with DJ cows exhibiting superior coagulation compared with the other 2 breeds. In addition, milk samples from 2% of DH and 16% of SR cows were classified as noncoagulating. Furthermore, the cows were genotyped for major genetic variants in the alpha(S1)- (CSN1S1), beta- (CSN2), and kappa-casein (CSN3) genes, revealing distinct differences in variant frequencies among breeds. Allele I of CSN2, which had not formerly been screened in such a high number of cows in these Scandinavian breeds, showed a frequency around 7% in DH and DJ, but was not detected in SR. Genetic polymorphisms were significantly associated with curd firming rate and rennet coagulation time. Thus, CSN1S1 C, CSN2 B, and CSN3 B positively affected milk coagulation, whereas CSN2 A(2), in particular, had a negative effect. In addition to the influence of individual casein genes, the effects of CSN1S1-CSN2-CSN3 composite genotypes were also examined, and revealed strong associations in all breeds, which more or less reflected the single gene results. Overall, milk coagulation is under the influence of additive genetic variation. Optimal milk for future cheese production can be ensured by monitoring the frequency of unfavorable variants and thus preventing an increase in the number of cows producing milk with impaired coagulation. Selective breeding for variants associated with superior milk coagulation can potentially increase raw milk quality and cheese yield in all 3 Scandinavian breeds.
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2. |
- Barlind, Jonas G, et al.
(author)
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Design and optimization of pyrazinecarboxamide-based inhibitors of diacylglycerol acyltransferase 1 (DGAT1) leading to a clinical candidate dimethylpyrazinecarboxamide phenylcyclohexylacetic acid (AZD7687)
- 2012
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In: Journal of Medicinal Chemistry. - : American Chemical Society (ACS). - 0022-2623 .- 1520-4804. ; 55:23, s. 10610-10629
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Journal article (peer-reviewed)abstract
- A new series of pyrazinecarboxamide DGAT1 inhibitors was designed to address the need for a candidate drug with good potency, selectivity, and physical and DMPK properties combined with a low predicted dose in man. Rational design and optimization of this series led to the discovery of compound 30 (AZD7687), which met the project objectives for potency, selectivity, in particular over ACAT1, solubility, and preclinical PK profiles. This compound showed the anticipated excellent pharmacokinetic properties in human volunteers.
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3. |
- Gustavsson, Frida, et al.
(author)
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Effects of breed and casein genetic variants on protein profile in milk from Swedish Red, Danish Holstein, and Danish Jersey cows.
- 2014
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In: Journal of Dairy Science. - : American Dairy Science Association. - 1525-3198 .- 0022-0302. ; 97:6, s. 3866-3877
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Journal article (peer-reviewed)abstract
- In selecting cows for higher milk yields and milk quality, it is important to understand how these traits are affected by the bovine genome. The major milk proteins exhibit genetic polymorphism and these genetic variants can serve as markers for milk composition, milk production traits, and technological properties of milk. The aim of this study was to investigate the relationships between casein (CN) genetic variants and detailed protein composition in Swedish and Danish dairy milk. Milk and DNA samples were collected from approximately 400 individual cows each of 3 Scandinavian dairy breeds: Swedish Red (SR), Danish Holstein (DH), and Danish Jersey (DJ). The protein profile with relative concentrations of α-lactalbumin, β-lactoglobulin, and αS1-, αS2-, κ-, and β-CN was determined for each milk sample using capillary zone electrophoresis. The genetic variants of the αS1- (CSN1S1), β- (CSN2), and κ-CN (CSN3) genes for each cow were determined using TaqMan SNP genotyping assays (Applied Biosystems, Foster City, CA). Univariate statistical models were used to evaluate the effects of composite genetic variants, αS1-β-κ-CN, on the protein profile. The 3 studied Scandinavian breeds differed from each other regarding CN genotypes, with DH and SR having similar genotype frequencies, whereas the genotype frequencies in DJ differed from the other 2 breeds. The similarities in genotype frequencies of SR and DH and differences compared with DJ were also seen in milk production traits, gross milk composition, and protein profile. Frequencies of the most common composite αS1-β-κ-CN genotype BB/A(2)A(2)/AA were 30% in DH and 15% in SR, and cows that had this genotype gave milk with lower relative concentrations of κ- and β-CN and higher relative concentrations of αS-CN, than the majority of the other composite genotypes in SR and DH. The effect of composite genotypes on relative concentrations of the milk proteins was not as pronounced in DJ. The present work suggests that a higher frequency of BB/A(1)A(2)/AB, together with a decrease in BB/A(2)A(2)/AA, could have positive effects on DH and SR milk regarding, for example, the processing of cheese.
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4. |
- Gustavsson, Frida, et al.
(author)
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Impact of genetic variants of milk proteins on chymosin-induced gelation properties of milk from individual cows of Swedish Red dairy cattle
- 2014
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In: International Dairy Journal. - : Elsevier BV. - 0958-6946 .- 1879-0143. ; 39:1, s. 102-107
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Journal article (peer-reviewed)abstract
- Chymosin-induced gelation properties of the milk of around 400 Swedish Red dairy cows was investigated with the aim of identifying genetic protein variants that influence chymosin-induced gelation for optimisation of cheese milk through breeding practices. The variation in chymosin-induced gelation properties was shown to be large in the milk of Swedish Red and there was a high frequency of cows producing non-coagulating milk, 18%. The present study showed that the common composite beta-kappa-casein genotypes A(1)A(2)/AE and A(2)A(2)/AA were associated with both poor gelation properties and non-coagulation in the milk of Swedish Red. The present study suggests that if the frequencies of composite genotypes A(1)A(2)/AE and A(2)A(2)/AA were decreased in the Swedish Red population in favour for A(1)A(1)/AA and A(1)A(1)/AE, this could have a positive effect on the rennetability of the milk. (C) 2014 Elsevier Ltd. All rights reserved.
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5. |
- Bielig, H, et al.
(author)
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NOD-like receptor activation by outer-membrane vesicles (OMVs) from non-O1 non-O139 Vibrio cholerae is modulated by the quorum sensing regulator HapR
- 2011
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In: Infection and Immunity. - : American Society for Microbiology. - 0019-9567 .- 1098-5522. ; 79:4, s. 1418-1427
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Journal article (peer-reviewed)abstract
- Vibrio cholerae is an inhabitant of aquatic systems and one of the causative agents of severe dehydrating diarrhea in humans. It has also emerged as an important cause of different kinds of inflammatory responses and in particular, V. cholerae strains of the non-O1 non-O139 serogroups (NOVC) have been associated with such infections in human. We analyzed the potential of outer membrane vesicles (OMVs) derived from the NOVC strain V:5/04 to induce inflammatory responses in human host cells. V:5/04 OMVs were taken up by human epithelial cells and induced inflammatory responses. siRNA-mediated gene knock-down revealed that the inflammatory potential of NOVC OMVs was partially mediated by the nucleotide-binding domain, leucine rich repeat containing family member NOD1. Physiochemical analysis of the content of these OMVs, in conjunction with NOD1 and NOD2 reporter assays in HEK293T cells, confirmed the presence of both NOD1 and NOD2 active peptidoglycan in the OMVs. Furthermore, we show that deletion of the quorum sensing regulator HapR which mimics an infective life style, specifically reduced the inflammatory potential of the V:5/04 OMVs and their ability to activate NOD1 and NOD2. In conclusion, our study shows that NOVC OMVs elicit immune responses mediated by NOD1 and NOD2 in mammalian host cells. Moreover, we provide evidence that the quorum sensing machinery plays an important regulatory role in this process by attenuating the inflammatory potential of OMVs in infective conditions. This work thus identified a new facet of how Vibrio affects host immune responses and defines a role for the quorum sensing machinery in this process.
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6. |
- Gustavsson, Frida, et al.
(author)
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Factors influencing chymosin-induced gelation of milk from individual dairy cows: Major effects of casein micelle size and calcium
- 2014
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In: International Dairy Journal. - : Elsevier BV. - 0958-6946 .- 1879-0143. ; 39:1, s. 201-208
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Journal article (peer-reviewed)abstract
- Optimisation of cheese yield is crucial for cheese production; a previous study showed large variations in chymosin-induced coagulation in milk from the second most common Swedish dairy breed, Swedish Red. In the present study, the effect of gross composition, protein composition, total and ionic calcium content, phosphorous content and casein micelle size on chymosin-induced gelation was determined in milk from 98 Swedish Red cows. The study showed that protein content and total calcium content, ionic calcium concentration and casein micelle size were the most important factors explaining the variation of gelation properties in this sample set. Non-coagulating milk was suggested to have lower ionic and total calcium content as well as lower relative concentrations of beta-lactoglobulin than coagulating milk. The lower total calcium content in non-coagulating milk poses a problem as the difference was, theoretically, four times larger than the amount of calcium that is normally added in cheese processing. (C) 2014 Elsevier Ltd. All rights reserved.
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7. |
- Gustavsson, Frida, et al.
(author)
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Genetic parameters for rennet- and acid-induced coagulation properties in milk from Swedish Red dairy cows.
- 2014
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In: Journal of Dairy Science. - : American Dairy Science Association. - 1525-3198 .- 0022-0302. ; 97:8, s. 5219-5229
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Journal article (peer-reviewed)abstract
- Milk coagulation is an important processing trait, being the basis for production of both cheese and fermented products. There is interest in including technological properties of these products in the breeding goal for dairy cattle. The aim of the present study was therefore to estimate genetic parameters for milk coagulation properties, including both rennet- and acid-induced coagulation, in Swedish Red dairy cattle using genomic relationships. Morning milk samples and blood samples were collected from 395 Swedish Red cows that were selected to be as genetically unrelated as possible. Using a rheometer, milk samples were analyzed for rennet- and acid-induced coagulation properties, including gel strength (G'), coagulation time, and yield stress (YS). In addition to the technological traits, milk composition was analyzed. A binary trait was created to reflect that milk samples that had not coagulated 40 min after rennet addition were considered noncoagulating milk. The cows were genotyped by using the Illumina BovineHD BeadChip (Illumina Inc., San Diego, CA). Almost 600,000 markers remained after quality control and were used to construct a matrix of genomic relationships among the cows. Multivariate models including fixed effects of herd, lactation stage, and parity were fitted using the ASReml software to obtain estimates of heritabilities and genetic and phenotypic correlations. Heritability estimates (h(2)) for G' and YS in rennet and acid gels were found to be high (h(2) = 0.38-0.62) and the genetic correlations between rennet-induced and acid-induced coagulation properties were weak but favorable, with the exception of YSrennet with G'acid and YSacid, both of which were strong. The high heritability (h(2) = 0.45) for milk coagulating ability expressed as a binary trait suggests that noncoagulation could be eliminated through breeding. Additionally, the results indicated that the current breeding objective could increase the frequency of noncoagulating milk and lead to deterioration of acid-induced coagulation through unfavorable genetic associations with protein content (0.38) and milk yield (-0.61 to -0.71), respectively. The outcome of this study suggests that by including more detailed compositional traits genetically associated with milk coagulation or by including milk coagulation properties directly within the breeding goal, it appears possible to breed cows that produce milk better suited for production of cheese and fermented products.
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8. |
- Larsson, I. A. Sofia, et al.
(author)
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Visualization of merging flow by usage of PIV and CFD with application to grate-kiln induration machines
- 2012
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In: Journal of Applied Fluid Mechanics. - 1735-3572 .- 1735-3645. ; 5:4, s. 81-89
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Journal article (peer-reviewed)abstract
- One way to upgrade iron ore is to process it into pellets. Such a process includes several stages involving complex fluid dynamics. In this work, focus is on the grate-kiln pelletizing process and especially on the rotary kiln, with the objective to get a deeper understanding of the aerodynamics in order to improve the combustion. A down-scaled, simplified model of the real kiln is created and both numerical and experimental analyses of the flow field are performed. Conclusions are that steady state simulations can be used to get an overview over the main features of the flow field. Precautions should though be taken when analyzing the recirculation zone since steady state simulations do not capture the transient, oscillating behavior of the flow seen in the physical experiment. These oscillations will under certain conditions considerably affect the size of the recirculation zone.
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11. |
- Wiklund, Fredrik E, et al.
(author)
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Macrophage inhibitory cytokine-1 (MIC-1/GDF15) : a new marker of all-cause mortality
- 2010
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In: Aging Cell. - : Wiley. - 1474-9718 .- 1474-9726. ; 9:6, s. 1057-1064
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Journal article (peer-reviewed)abstract
- Macrophage inhibitory cytokine-1 (MIC-1/GDF15) is a member of the TGF-b superfamily, previously studied in cancer and inflammation. In addition to regulating body weight, MIC-1/GDF15 may be used to predict mortality and/or disease course in cancer, cardiovascular disease (CVD), chronic renal and heart failure, as well as pulmonary embolism. These data suggested that MIC-1/GDF15 may be a marker of all-cause mortality. To determine whether serum MIC-1/GDF15 estimation is a predictor of all-cause mortality, we examined a cohort of 876 male subjects aged 35-80 years, selected from the Swedish Population Registry, and followed them for overall mortality. Serum MIC-1/GDF15 levels were determined for all subjects from samples taken at study entry. A second (independent) cohort of 324 same-sex twins (69% female) from the Swedish Twin Registry was similarly examined. All the twins had telomere length measured and 183 had serum levels of interleukin 6 (IL-6) and C-reactive protein (CRP) available. Patients were followed for up to 14 years and had cause-specific and all-cause mortality determined. Serum MIC-1/GDF15 levels predicted mortality in the all-male cohort with an adjusted odds ratio (OR) of death of 3.38 (95%CI 1.38-8.26). This finding was validated in the twin cohort. Serum MIC-1/GDF15 remained an independent predictor of mortality when further adjusted for telomere length, IL-6 and CRP. Additionally, serum MIC-1/GDF15 levels were directly correlated with survival time independently of genetic background. Serum MIC-1/GDF15 is a novel predictor of all-cause mortality.
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