Adaptations to fasting in the American mink (<Emphasis Type="Italic">Mustela vison</Emphasis>): nitrogen metabolism

The aim of this study was to investigate the adaptations of protein metabolism to seasonal fasting in an actively wintering boreal carnivore. Fifty farm-bred male American minks Mustela vison were divided into a fed control group and four experimental groups fasted for 2, 3, 5 or 7 days. The responses of nitrogen metabolism to wintertime food deprivation were determined by measuring the rate of weight loss, the tissue total protein concentrations and the plasma amino acid, urea, ammonia, uric acid and total protein levels. The mink has relatively poor adaptations to food deprivation, as it is not able to prolong phase II of fasting with fat as the major metabolic fuel. Instead, the species has to derive a part of its energy requirements from the breakdown of body proteins. The end product of protein catabolism—urea— accumulates in its circulation, and the mink may not be able to recycle urea-N. Although the mink can still have a high body fat percent at the end of the 7-day fast, it appears to enter phase III of fasting with stimulated proteolysis during this period.     

Enhanced vascular permeability facilitates entry of plasma HDL and promotes macrophage-reverse cholesterol transport from skin in mice

Reverse cholesterol transport (RCT) pathway from macrophage foam cells initiates when HDL particles cross the endothelium, enter the interstitial fluid, and induce cholesterol efflux from these cells. We injected [³H]cholesterol-loaded J774 macrophages into the dorsal skin of mice and measured the transfer of macrophage-derived [³H]cholesterol to feces [macrophage-RCT (m-RCT)]. Injection of histamine to the macrophage injection site increased locally vascular permeability, enhanced influx of intravenously administered HDL, and stimulated m-RCT from the histamine-treated site. The stimulatory effect of histamine on m-RCT was abolished by prior administration of histamine H1 receptor (H1R) antagonist pyrilamine, indicating that the histamine effect was H1R-dependent. Subcutaneous administration of two other vasoactive mediators, serotonin or bradykinin, and activation of skin mast cells to secrete histamine and other vasoactive compounds also stimulated m-RCT. None of the studied vasoactive mediators affected serum HDL levels or the cholesterol-releasing ability of J774 macrophages in culture, indicating that acceleration of m-RCT was solely due to increased availability of cholesterol acceptors in skin. We conclude that disruption of the endothelial barrier by vasoactive compounds enhances the passage of HDL into interstitial fluid and increases the rate of RCT from peripheral macrophage foam cells, which reveals a novel tissue cholesterol-regulating function of these compounds.     

Leukemia Prediction Using Sparse Logistic Regression

We describe a supervised prediction method for diagnosis of acute myeloid leukemia (AML) from patient samples based on flow cytometry measurements. We use a data driven approach with machine learning methods to train a computational model that takes in flow cytometry measurements from a single patient and gives a confidence score of the patient being AML-positive. Our solution is based on an regularized logistic regression model that aggregates AML test statistics calculated from individual test tubes with different cell populations and fluorescent markers. The model construction is entirely data driven and no prior biological knowledge is used. The described solution scored a 100% classification accuracy in the DREAM6/FlowCAP2 Molecular Classification of Acute Myeloid Leukaemia Challenge against a golden standard consisting of 20 AML-positive and 160 healthy patients. Here we perform a more extensive validation of the prediction model performance and further improve and simplify our original method showing that statistically equal results can be obtained by using simple average marker intensities as features in the logistic regression model. In addition to the logistic regression based model, we also present other classification models and compare their performance quantitatively. The key benefit in our prediction method compared to other solutions with similar performance is that our model only uses a small fraction of the flow cytometry measurements making our solution highly economical.     

Prosthetic crowns and other clinical risk indicators of caries among old-old Swedish adults: findings from the KEOHS Project. Kungsholmen Elders Oral Health Study

Objectives: The Kungsholmen Elders Oral Health Study (KEOHS) evaluated the oral health status of generally healthy, community‐dwelling persons over the age of 80 living in Kungsholmen, Sweden. This paper explored possible clinical risk indicators of coronal and root caries among the KEOHS subjects. Design: In this cross‐sectional study, dentate KEOHS subjects received a caries assessment using defined visual, tactile criteria. Setting: Examinations were carried out in two local clinics by standardized examiners. Subjects: One hundred twenty‐nine dentate persons were examined. Main Outcome Measures: The examination identified decayed and filled surfaces, prosthetic crowns, and missing teeth. Results: More root than coronal surfaces had untreated decay, and secondary root caries contributed the greatest number of decayed surfaces. Ninety percent of the examined dentate subjects had at least one prosthetic crown. Root surfaces exposed to crown margins were more likely to have caries than root surfaces not so exposed, particularly among women. The presence of untreated coronal caries (yes/no) was positively associated with having untreated root caries and an intermediate number (14–20) of teeth, but inversely associated with having 4+ prosthetic crowns. Active root caries (yes/no) was positively associated with having untreated coronal caries, 14–20 teeth, and 4+ prosthetic crowns. Nearly 20% of identified root lesions were present at or below the gingival margin, and most (88%) were secondary caries associated with crown margins (65%) or other restorations (23%). Conclusions: Our findings suggest that some dental characteristics, including the presence of prosthetic crowns, are risk indicators for the presence of untreated coronal and root caries.     

Clone-specific responses in leaf phenolics of willows exposed to enhanced UVB radiation and drought stress

The effects of enhanced UVB radiation and drought stress on willow secondary phenolics were studied using the leaves of 8‐week‐old micropropagated plantlets from interspecific hybrids (Salix myrsinites L. ×S. myrsinifolia Salisb.) and pure species (S. myrsinifolia). The plantlets were subjected for 4 weeks to two levels of UVB radiation (ambient, enhanced) and two levels of watering (well‐watered, drought‐stressed) according to a 2 × 2 factorial design. Enhanced UVB radiation increased the total concentration of flavonoids and phenolic acids in all plantlets, while the total concentration of salicylates remained unaffected. Drought stress reduced the total concentration of salicylates and phenolic acids in S. myrsinifolia plantlets, while in hybrids only phenolic acids were affected. The response of phenolic acids to enhanced UVB in drought‐stressed plantlets was different from that in well‐watered ones, indicating that drought stress limited the accumulation of phenolic acids under enhanced UVB radiation. Flavonoids increased in response to enhanced UVB radiation in drought‐stressed plantlets, although drought caused serious physiological stress on growth. There were significant differences between hybrid and S. myrsinifolia plantlets with respect to the composition of phenolics and between families and clones with respect to their concentration. In addition, the response of salicylates, flavonoids and phenolic acids to enhanced UVB and drought stress was clone‐specific, which may indicate that climatic changes will alter the genetic composition of northern forests.     

A rare sugar xylitol. Part II: biotechnological production and future applications of xylitol

Xylitol is the first rare sugar that has global markets. It has beneficial health properties and represents an alternative to current conventional sweeteners. Industrially, xylitol is produced by chemical hydrogenation of d-xylose into xylitol. The biotechnological method of producing xylitol by metabolically engineered yeasts, Saccharomyces cerevisiae or Candida, has been studied as an alternative to the chemical method. Due to the industrial scale of production, xylitol serves as an inexpensive starting material for the production of other rare sugars. The second part of this mini-review on xylitol will look more closely at the biotechnological production and future applications of the rare sugar, xylitol.     

Quantitative determination of dehydroepiandrosterone fatty acyl esters in human female adipose tissue and serum using mass spectrometric methods

Dehydroepiandrosterone-fatty acyl esters (DHEA-FAE) are naturally occurring water-insoluble metabolites of DHEA, which are transported in plasma exclusively by lipoproteins. To find out whether DHEA, like estradiol, might be stored in adipose tissue in FAE form, we set up a mass spectrometric method to quantify DHEA-FAE and free DHEA in human adipose tissue and serum. The method consists of chromatographic purification steps and final determination of hydrolyzed DHEA-FAE and free DHEA, which was carried out by gas chromatography-mass spectrometry (GC-MS) or liquid chromatography-tandem mass spectrometry (LC-MS/MS). Our results showed that no detectable amounts of DHEA-FAE could be found in adipose tissue although 32-178 pmol/g of free DHEA were determined by GC-MS and LC-MS/MS. The DHEA-FAE concentrations in serum quantified by GC-MS were 1.4±0.7 pmol/ml in premenopausal women (n=7), and 0.9±0.4 pmol/ml in postmenopausal women (n=5). Correspondingly, the free DHEA concentrations were 15.2±6.3 pmol/ml and 6.8±3.0 pmol/ml. In addition, the mean proportions of DHEA-FAE of total DHEA (DHEA-FAE+free DHEA) in serum were 8.6% and 11.2% in pre- and postmenopausal women, respectively. Serum DHEA-FAE concentration was below quantification limit for LC-MS/MS (signal-to-noise ratio, S/N=10), while free DHEA concentrations varied between 5.8 and 23.2 pmol/ml. In conclusion, the proportion of DHEA-FAE of total DHEA in serum was approximately 9%. However, in contrast to our previous findings for estradiol fatty acid esters in adipose tissue which constituted about 80% of total estradiol (esterified+free), the proportion of DHEA-FAE of total DHEA was below 5%. Four to ten times higher concentrations of free DHEA were quantified in adipose tissue compared to those in serum.