Excessive Cell Growth Causes Cytoplasm Dilution And Contributes to Senescence

Cell size varies greatly between cell types, yet within a specific cell type and growth condition, cell size is narrowly distributed. Why maintenance of a cell-type specific cell size is important remains poorly understood. Here we show that growing budding yeast and primary mammalian cells beyond a certain size impairs gene induction, cell-cycle progression, and cell signaling. These defects are due to the inability of large cells to scale nucleic acid and protein biosynthesis in accordance with cell volume increase, which effectively leads to cytoplasm dilution. We further show that loss of scaling beyond a certain critical size is due to DNA becoming limiting. Based on the observation that senescent cells are large and exhibit many of the phenotypes of large cells, we propose that the range of DNA:cytoplasm ratio that supports optimal cell function is limited and that ratios outside these bounds contribute to aging

Exploring the success factors of hybrid micro-enterprises

This research explores hybrid micro-entrepreneurs’ founding motivations and the transformation of those motivations into visions of success, by applying multiple criteria decision analysis (MCDA). We find that entrepreneurs of hybrid micro-enterprises are driven mostly by noneconomic goals and that those influence their vision of success. The success framework consists of seven indicators (training, professional development, marketing, management, external factors, infrastructures, and organizational aspects). Human capital is perceived as the most important for success – translating the professional motivations for founding. Reversely, external factors, which are usually considered crucial to attain legitimacy, are perceived the least important factors. Given the findings, are hybrid micro-entrepreneurs ready to succeed?info:eu-repo/semantics/publishedVersio

Protease activity measurement in milk as a diagnostic test for clinical mastitis in dairy cows

Due to the increasing use of automated milking systems, automated detection of clinical mastitis is becoming more important. Various in- or on-line diagnostic tests are in use, but generally suffer from false mastitis alerts. In this study, we explored a new diagnostic approach based on measurement of protease activity using fluorogenic protease substrates, which can be performed on site, at high speed, and at low costs. Samples from cows with clinical mastitis submitted for bacteriological culture at the University Farm Animal Practice were collected during several months and kept at -20°C until protease activity measurement. A reference set of milk samples from clinically healthy cows were collected on 9 different farms and were tested for protease activity directly and after freezing at -20°C to allow for comparison with the samples from clinical cases. The protease activity in mastitic milk samples was significantly higher than in samples from healthy animals. Based on 71 clinical mastitis samples and 180 milk samples from clinically healthy quarters, the area under the receiver-operating characteristic curve was estimated to be between 0.88 and 0.90, and at a threshold of 38 fluorescence per minute the test had a specificity of 0.99 at a sensitivity of 0.58. Protease activity measured in fresh milk from clinically healthy cows was significantly associated with somatic cell count and parity, but not with electrical conductivity, whereas protease activity in milk that had been frozen was statistically significantly associated with all 3 parameters. This study indicates that protease activity measurement as a stand-alone test can be used for detecting mastitis samples, using milk samples that have been frozen. Because protease activity acts in part on a different biological mechanism than somatic cell count or electrical conductivity, this test may increase the accuracy of mastitis diagnosis in combination with currently available in- or on-line tests in automated milking systems

Noninvasive quantification of hepatic steatosis inrats using 3.0 T (1)H-magnetic resonance spectroscopy

PURPOSE:: To assess the accuracy of noninvasive 3.0 T (1)H-magnetic resonance spectroscopy ((1)H-MRS) in an experimental steatosis model for the discrimination of clinically relevant macrovesicular steatosis degrees and to evaluate three different (1)H-MR spectrum-based fat quantification methods. MATERIALS AND METHODS:: Steatosis was induced in rats by a methionine/choline-deficient diet for 0-5 weeks. (1)H-MRS measurements of hepatic fat content were compared with histopathological and biochemical steatosis degree. In (1)H-MR spectra, areas under the curve (AUC) of fat (1.3 ppm), water (4.7 ppm), total fat (0.5-5.3 ppm), and total spectrum peaks (0.5-5.3 ppm) were determined and hepatic fat content calculated as follows: [AUC(total fat peaks)/AUC(total peaks)], [AUC(fat)/AUC(fat) + (AUC(water)/0.7)], and [AUC(fat)/AUC(water)]. RESULTS:: A significant correlation was found between (1)H-MRS and macrovesicular steatosis (r = 0.932, P < 0.0001) and between (1)H-MRS and total fatty acids (r = 0.935, P < 0.0001). (1)H-MRS accurately distinguished mild from moderate and moderate from severe steatosis. Calculations using [AUC(fat)/AUC(water)] ratio in severe steatotic livers resulted in higher hepatic fat percentages as compared to the other methods due to a decrease in hepatic water content. CONCLUSION:: (1)H-MRS quantification of hepatic fat content showed high correlations with histological and biochemical steatosis determination in an experimental steatosis rat model and accurately discriminated between clinically relevant steatosis degrees. These results encourage further application of (1)H-MRS in patients for accurate steatosis assessment. J. Magn. Reson. Imaging 2010;32:148-154. (c) 2010 Wiley-Liss, In

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An investigation of the dynamics of intramammary infections acquired during the dry period on European dairy farms

The dry period is acknowledged as playing a key role in mastitis epidemiology and yet surprisingly few studies have explored dry period infection dynamics in detail. The aim of this study was to investigate the dynamics of intramammary infection across a cohort of dairy herds in Europe. Five hundred and twenty-two cows were recruited from 12 farms in 6 European countries. All cows received antibiotic dry cow therapy but teat sealants were not used. All quarters of all cows were sampled for bacteriology at drying off and in the week immediately postcalving. Two ipsilateral quarters were also sampled for bacteriology in each cow 2 and 6wk after drying off. Cows were body condition scored and teats assessed for cleanliness at all sampling time points and for the presence of a keratin plug during the dry period. Other cow-level parameters such as historic somatic cell counts and milk yields before drying off were collated from farm records. Univariable and multivariable analyses were undertaken to investigate the etiology, prevalence, and dynamics of infection during the dry period and associated influential factors. In summary, environmental mastitis pathogens predominated. Although gram-positive major pathogens were typically well controlled and did not increase in prevalence across the dry period, gram-negative pathogens generally increased in prevalence. There was an increase in the number of quarters that yielded no growth across the dry period, although this was driven by minor rather than major mastitis pathogen control. Other than the presence of a gram-positive or gram-negative pathogen 6wk after drying off, the measured parameters were not influential when considering their effect on the presence of pathogens postcalving. Analysis also suggested that the early and mid dry period may be more important with respect to the timing of acquisition of infection than previously thought. We observed substantial variation in the etiology and prevalence of different pathogens on different farms with, in all cases, at least one of the 12 herds experiencing the opposite of the others with respect to increases and decreases in pathogen prevalence. Overall, this study confirms the importance of the dry period in mastitis epidemiology but highlights the importance of assessing and understanding infection dynamics on individual units. The lack of influence of the cow and quarter factors measured in this study suggests that herd and management factors may be more influential

Protease activity measurement in milk as a diagnostic test for clinical mastitis in dairy cows

Due to the increasing use of automated milking systems, automated detection of clinical mastitis is becoming more important. Various in- or on-line diagnostic tests are in use, but generally suffer from false mastitis alerts. In this study, we explored a new diagnostic approach based on measurement of protease activity using fluorogenic protease substrates, which can be performed on site, at high speed, and at low costs. Samples from cows with clinical mastitis submitted for bacteriological culture at the University Farm Animal Practice were collected during several months and kept at -20°C until protease activity measurement. A reference set of milk samples from clinically healthy cows were collected on 9 different farms and were tested for protease activity directly and after freezing at -20°C to allow for comparison with the samples from clinical cases. The protease activity in mastitic milk samples was significantly higher than in samples from healthy animals. Based on 71 clinical mastitis samples and 180 milk samples from clinically healthy quarters, the area under the receiver-operating characteristic curve was estimated to be between 0.88 and 0.90, and at a threshold of 38 fluorescence per minute the test had a specificity of 0.99 at a sensitivity of 0.58. Protease activity measured in fresh milk from clinically healthy cows was significantly associated with somatic cell count and parity, but not with electrical conductivity, whereas protease activity in milk that had been frozen was statistically significantly associated with all 3 parameters. This study indicates that protease activity measurement as a stand-alone test can be used for detecting mastitis samples, using milk samples that have been frozen. Because protease activity acts in part on a different biological mechanism than somatic cell count or electrical conductivity, this test may increase the accuracy of mastitis diagnosis in combination with currently available in- or on-line tests in automated milking systems