Condensed tannins (CT) may affect ruminal biohydrogenation of dietary polyunsaturated fatty acids. A feeding experiment was conducted with 24 Holstein cows to evaluate whether diets containing CT ...from different forage legumes can increase polyunsaturated fatty acids, especially n-3 fatty acid content in milk and cheese, without affecting negatively their physicochemical and sensorial properties. Cows were assigned to 4 treatment groups (n=6) for 52 d, divided into 2 periods: a control period (CoP) and an experimental period (ExP). During the CoP, cows received a basal diet composed of hay, corn silage, ExtruLin (Trinova Handel & Marketing AG, Wangen, Switzerland), concentrate, and alfalfa (AF) in a ratio of 45:25:5:7:18. In the ExP, in 3 of the 4 groups AF was replaced by either sainfoin (SF; 19% CT in dry matter) or 1 of 2 cultivars of birdsfoot trefoil Polom (BP), 3% CT; Bull (BB), 5% CT. At the end of each period, milk was collected on 3 consecutive days and analyzed for milk gross composition and fatty acid profile and was processed to Gruyère-type cheese. A trained panel assessed the sensory quality of raw milk and cheese using discriminative and descriptive tests. This experimental design consisting of AF in both the CoP and ExP allowed us to quantify effects due to lactation stage and experimental diets. In both the CoP and ExP, dry matter intake and milk yield did not differ among treatment groups. From the CoP to the ExP, milk urea content was reduced by 23% with SF, remained unchanged with BP, and tended to increase with AF and BB. The odor of the raw BB milk was judged to be different from AF milk. With SF, switching from the CoP to the ExP resulted in a 17% increase of the 18:3n-3 proportion in milk and cheese lipids. In BP cheese, the increase was 3%, whereas it tended to decrease in BB cheese. Additionally, the 20:5n-3 and 22:5n-3 proportions tended to increase in SF cheese from the CoP to the ExP. Compared with the AF cheeses, cheeses from cows fed CT-containing legumes were judged harder and tended to be less adhesive to the palate. In addition, SF and BP cheeses had less rind. In conclusion, feeding SF compared with BB and BP increased the content of 18:3n-3 in the milk and the cheese without a negative effect on flavor of the cheese. Despite a similar CT content, the 2 birdsfoot trefoil cultivars had opposite effects on milk urea and 18:3n-3 deposition, suggesting that, besides the content, the chemical structure may have had an important effect on the CT efficacy.
The leukemogenic CALM-AF10 fusion protein is found in patients with immature acute myeloid and T-lymphoid malignancies. CALM-AF10 leukemias display abnormal H3K79 methylation and increased HOXA ...cluster gene transcription. Elevated expression of HOXA genes is critical for leukemia maintenance and progression; however, the precise mechanism by which CALM-AF10 alters HOXA gene expression is unclear. We previously determined that CALM contains a CRM1-dependent nuclear export signal (NES), which is both necessary and sufficient for CALM-AF10-mediated leukemogenesis. Here, we find that interaction of CALM-AF10 with the nuclear export receptor CRM1 is necessary for activating HOXA gene expression. We show that CRM1 localizes to HOXA loci where it recruits CALM-AF10, leading to transcriptional and epigenetic activation of HOXA genes. Genetic and pharmacological inhibition of the CALM-CRM1 interaction prevents CALM-AF10 enrichment at HOXA chromatin, resulting in immediate loss of transcription. These results provide a comprehensive mechanism by which the CALM-AF10 translocation activates the critical HOXA cluster genes. Furthermore, this report identifies a novel function of CRM1: the ability to bind chromatin and recruit the NES-containing CALM-AF10 transcription factor.
The angiotensin-converting enzyme (ACE) inhibitory activity and the concentration of the 2 ACE-inhibiting tripeptides Val-Pro-Pro (VPP) and Ile-Pro-Pro (IPP) were studied during cheese ripening in 7 ...Swiss cheese varieties. The semi-hard cheeses Tilsiter, Appenzeller 1/4 fat, Tête de Moine, and Vacherin fribourgeois and the extra-hard and hard cheeses Berner Hobelkäse, Le Gruyère, and Emmentaler were investigated. Three loaves of each variety manufactured in different cheese factories were purchased at the beginning of commercial ripeness and investigated at constant intervals until the end of the usual sale period. Good agreement was found between ACE-inhibitory activity and the total concentration of VPP and IPP at advanced ripening stages. In most of the investigated varieties ACE-inhibitory activity and the concentration of the 2 tripeptides initially increased during the study period. A decline in the concentration of VPP and IPP was obtained toward the end of the investigated period for Tilsiter and Gruyère. The ratio of VPP/IPP decreased during ripening in all varieties with the exception of Emmentaler. However, large variations were observed among the cheese varieties as well as the individual loaves of the same variety. Chemical characterization of the investigated cheeses revealed that qualitative differences in the proteolysis pattern, not quantitative differences in the degree of proteolysis, are responsible for the observed variations in the concentrations of VPP and IPP. The presence of Lactobacillus helveticus in the starter culture was associated with elevated concentrations of VPP and IPP. The results of the present study show that concentrations of VPP and IPP above 100mg/kg are attainable in semi-hard cheese varieties after ripening periods of about 4 to 7 mo and that stable concentrations of the 2 antihypertensive tripeptides can be expected over several weeks of cheese ripening.
The contents of the 2 antihypertensive peptides Val-Pro-Pro (VPP) and Ile-Pro-Pro (IPP) were determined in 101 samples from 10 different Swiss cheese varieties using HPLC with subsequent triple mass ...spectrometry. In the category of extra hard and hard cheeses, the Protected Denomination of Origin cheeses Berner Alpkäse and Berner Hobelkäse, L’Etivaz à rebibes, Le Gruyère, Sbrinz, Emmentaler (organic and conventional) and in the category of semihard cheeses, the varieties Tilsiter, Appenzeller 14 fat and full fat, Tête de Moine, and Vacherin fribourgeois were screened in the study. The average concentration of the sum of VPP and IPP in the screened cheese varieties varied to a large extent, and substantial variations were obtained for individual samples within the cheese varieties. The lowest average concentration of the 2 tri-petides was found in L’Etivaz à rebibes (n = 3) at 19.1mg/kg, whereas Appenzeller 14 fat (n = 4) contained the greatest concentration at 182.2mg/kg. In individual samples, the total concentration of VPP and IPP varied between 1.6 and 424.5mg/kg. With the exception of a 10-yr-old cheese, VPP was always present at greater concentrations than IPP. Milk pretreatment, cultures, scalding conditions, and ripening time were identified as the key factors influencing the concentration of these 2 naturally occurring bioactive peptides in cheese. The results of the present study show that various traditional cheese varieties contain, on average, similar concentrations of the 2 antihypertensive peptides to the recently developed fermented milk products with blood pressure–lowering property. This may serve as a basis for the development of a functional cheese with blood pressure–lowering property.
To report outcomes of deep sclerectomy (DS) with intraoperative mitomycin C (MMC) application in eyes with previous failed glaucoma surgery (GS) and/or cataract extraction (CE).
Single-surgeon case ...series of 82 eyes of 82 patients undergoing DS with MMC. The patients had previous CE with IOL and/or conjunctival GS and treated intraocular pressure (IOP) >18 mm Hg. MMC (0.2 mg/ml) was applied for 2-3 min before scleral flap dissection. Complete success was defined as IOP between 6 and 21 mm Hg or a reduction of 20% from baseline without medications. Reoperation for glaucoma or related complications, or loss of light perception vision was considered as failure.
Mean follow-up was 57.7 ± 22.4 months with 78% of patients completing the 3-year follow-up. Mean IOP decreased from 24.0 mm Hg (22.3-25.6, 95% confidence intervals) to 13.4 mm Hg (12.0-14.2) at 3 years after surgery (P<0.001). There was a significant decrease in the number of glaucoma medications from 2.0 ± 1 preoperatively, to 0.3 ± 0.7, 3 years after surgery. Kaplan-Meier cumulative success rates were 85.6% at 1 year, 80.0% at 2 years, and 76% at 3 years. At 3 years, IOP was maintained <19 and 15 mm Hg in 83 and 70% of eyes, respectively. Fourteen eyes (17.1%) had complications. Delayed hypotony (IOP <6 mm Hg) was the commonest complication in five eyes (6.1%).
DS with MMC appears to be a safe and effective surgical procedure for eyes with previous intraocular surgery.
Myocilin glaucoma is an autosomal dominant disorder leading to irreversible blindness, but early intervention can minimize vision loss and delay disease progression. The purpose of this study was to ...discuss the benefits of predictive genetic testing in minors for Myocilin mutations associated with childhood onset glaucoma. Three families with Myocilin mutations associated with an age of onset before 18 years and six unaffected at‐risk children were identified. Predictive genetic testing was discussed with the parents and offered for at‐risk minors. Parents opted for genetic testing in half of the cases. None carried the familial mutation. The age of disease onset in the family, the severity of the condition, and the age of the child are all factors that appear to influence the decision of the parent to test their children. Predictive genetic testing for early onset Myocilin glaucoma can facilitate early detection of disease or discharge from routine ophthalmic examinations.
Eye formation is an important quality parameter in the dairy industry for (semi-)hard cheeses in Switzerland. To monitor the formation of eyes in cheese, radiography and, more recently, computed ...tomography (CT) technology, are employed. In the present study, two quality indicators (eye number and total eye volume) are calculated from radiographs by two recent procedures and compared with the results from CT data. The radiograph analysis procedures underestimate both quantifiers systematically and the deviation increases with the number of eyes. In contrast to radiographic data, the distribution of the eye volumes and positions as well as their geometric shape can be calculated from the CT data. These data allowed the observation that the eyes in the considered cheeses accumulate in the centre of the cheese, are predominately of spherical shape and non-spherical eyes can be extracted by a simple geometrical criterion. These findings illustrate the advantages of the CT technology.
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