Miracle-dz/UniFAR-FTUs huggingface dataset:
Thermal adaptation in yeast: growth temperatures, membrane lipid, and cytochrome composition of psychrophilic, mesophilic, and thermophilic yeasts

The temperature limits of growth of a number of yeast species were examined, and on this basis the organisms were classified into different thermal categories. The following species were examined: Leucosporidium frigidum and Leucosporidium nivalis, psychrophilic, temperature limits of growth, -2 to 20 degrees C; Canadian lipolytica mesophilic, temperature limits of growth, 5 to 35 degrees Candida parapsilosis and Saccharomyces telluris, thermotolerant, temperature limits of growth, 8 to 42 degrees C; Torulopsis bovina and Candida slooffi, thermophilic, temperature limits of growth, 25 to 45 degrees C and 28 to 45 degrees C, respectively. The membrane lipid and cytochrome composition of mitochrondrial fractions isolated from these yeasts were compared. There was a direct correlation between the growth temperature and the degree of membrane of lipid unsaturation; the lower the temperature, the greater the degree of lipid unsaturation. The membrane lipid composition of the thermophilic yeasts were distinguished by the high percentage (30 to 40%) of saturated fatty acid, as compared with the mesophilic and psychrophilic yeasts. The latter contained approximately 90% unsaturated fatty acid, 55% of which was linolenic acid, C alpha-18:3. Changes in phospholipid composition in relation to temperature were also noted. The respiratory-deficient thermophile, C. slooffi, was characterized by the absence of cardiolipin (sensitivity 0.1 mug of phosphorus) and cytochrome aa3. The absence of conventional mitochondrial structures in this thermophilic microorganism is tentatively suggested although low concentrations of cytochromes b, c, and c1 were detected by low-temperature spectroscopy. On the other hand, the respiratory-competent thermophile, T. bovina, was characterized by a high cardiolipin (25% of the total phospholipid) and cytochrome aa3 content (1 nmol/mg of mitochrondrial protein). Low-temperature spectra showed the presence of one b-type cytochrome in the thermophilic yeasts, two b-type cytochromes in the mesophilic yeasts, and three b-type cytochromes in the psychrophilic yeasts. It was concluded that a knowledge of the properties of the biological membrane is fundamental to an understanding of the ability of a microorganism to grow and reproduce in different temperature environments.
Phospholipids of Animal and Marine Origin: Structure, Function, and Anti-Inflammatory Properties

In this review paper, the latest literature on the functional properties of phospholipids in relation to inflammation and inflammation-related disorders has been critically appraised and evaluated. The paper is divided into three sections: Section 1 presents an overview of the relationship between structures and biological activities (pro-inflammatory or anti-inflammatory) of several phospholipids with respect to inflammation. Section 2 and Section 3 are dedicated to the structures, functions, compositions and anti-inflammatory properties of dietary phospholipids from animal and marine sources. Most of the dietary phospholipids of animal origin come from meat, egg and dairy products. To date, there is very limited work published on meat phospholipids, undoubtedly due to the negative perception that meat consumption is an unhealthy option because of its putative associations with several chronic diseases. These assumptions are addressed with respect to the phospholipid composition of meat products. Recent research trends indicate that dairy phospholipids possess anti-inflammatory properties, which has led to an increased interest into their molecular structures and reputed health benefits. Finally, the structural composition of phospholipids of marine origin is discussed. Extensive research has been published in relation to ω-3 polyunsaturated fatty acids (PUFAs) and inflammation, however this research has recently come under scrutiny and has proved to be unreliable and controversial in terms of the therapeutic effects of ω-3 PUFA, which are generally in the form of triglycerides and esters. Therefore, this review focuses on recent publications concerning marine phospholipids and their structural composition and related health benefits. Finally, the strong nutritional value of dietary phospholipids are highlighted with respect to marine and animal origin and avenues for future research are discussed.
Effects of pathogen exposure on life‐history variation in the gypsy moth (Lymantria dispar)

Investment in host defences against pathogens may lead to trade‐offs with host fecundity. When such trade‐offs arise from genetic correlations, rates of phenotypic change by natural selection may be affected. However, genetic correlations between host survival and fecundity are rarely quantified. To understand trade‐offs between immune responses to baculovirus exposure and fecundity in the gypsy moth (Lymantria dispar), we estimated genetic correlations between survival probability and traits related to fecundity, such as pupal weight. In addition, we tested whether different virus isolates have different effects on male and female pupal weight. To estimate genetic correlations, we exposed individuals of known relatedness to a single baculovirus isolate. To then evaluate the effect of virus isolate on pupal weight, we exposed a single gypsy moth strain to 16 baculovirus isolates. We found a negative genetic correlation between survival and pupal weight. In addition, virus exposure caused late‐pupating females to be identical in weight to males, whereas unexposed females were 2–3 times as large as unexposed males. Finally, we found that female pupal weight is a quadratic function of host mortality across virus isolates, which is likely due to trade‐offs and compensatory growth processes acting at high and low mortality levels, respectively. Overall, our results suggest that fecundity costs may strongly affect the response to selection for disease resistance. In nature, baculoviruses contribute to the regulation of gypsy moth outbreaks, as pathogens often do in forest‐defoliating insects. We therefore argue that trade‐offs between host life‐history traits may help explain outbreak dynamics.
Optimal Demand Response from Home Energy Management System: Modeling and Benefits for Distribution Networks

The increasing levels of renewable generation and the electrification of transport and heating as parts of the movement towards low-carbon energy systems to cope with climate change will place significant challenges on the electricity system to facilitate the way towards future low carbon energy systems in a cost effective way and ensure secure power delivery. New solutions and higher levels of flexibility are required than currently exist in order to reduce the integration costs of low carbon generation and demand technologies. Price-based demand response in residential sector is considered as one of these potential solutions. However, a certain level of automation is required to reduce both the uncertainty in the consumer response and the complexity for consumers to react to the price signal. This thesis presents a comprehensive and general residential optimization-based Automated Demand Response (ADR). The modelling of home appliances has been extensively developed to include all the classifications proposed in the literature, namely, deferrable and thermal in addition to new groups of critical and fully curtailable loads. The operations of the appliances are controlled in response to dynamic price signals to reduce the consumer? s electricity bill whilst minimizing the daily volume of curtailed energy and therefore considering the user? s comfort level. To avoid shifting most portion of consumer demand towards the least price intervals, which could create network issues due to loss of diversity, higher prices are applied when the consumer? s demand goes beyond a power threshold level. The arising mixed integer nonlinear optimization problem is solved in an iterative manner rolling throughout the day to follow the changes in the anticipated price signals and the variations in the controller inputs while information is updated. The results from different case studies show the effectiveness of the proposed controller to minimize the household? s daily electricity bill while preserving comfort level as well as preventing creation of new least-price peaks.This thesis also proposes a two-stage distribution-planning framework to assess the benefits of the proposed ADR models in response to a location-specific time of use Distribution Use of Systems Charge (DUoSC) on the required investments to connect future low-carbon technologies. The network investments and the satisfaction of consumers in terms of energy curtailment are both quantified. The first stage aims to generate location-specific time of use price signals for all users in the network, which represents their contributions in future network investments due to congestion and security constraints. The second stage relates to a group of ADR controllers at residential premises that aims to minimise the daily energy payment whilst maximising consumer comfort in response to the corresponding price signal produced from the first stage.
Maintenance of adrenergic vascular tone by MMP transactivation of the EGFR requires PI3K and mitochondrial ATP synthesis.

AIMS G-protein-coupled receptors (GPCRs) modulate vascular tone, at least in part, via matrix metalloproteinase (MMP) transactivation of the epidermal growth factor receptor (EGFR). We previously have identified novel signalling pathways downstream of the EGFR suggestive of mitogen-activated protein kinase and mitochondrial redox control of vascular tone. In the present study, we examined whether MMP modulation of vascular tone involves phosphoinositide 3-kinase (PI3K) and mitochondrial ATP synthesis. METHODS AND RESULTS To determine whether PI3K is required for the maintenance of adrenergic vascular tone, we first constricted rat small mesenteric arteries with phenylephrine (PE) and then perfused with PI3K inhibitors, LY294002 and wortmannin, both of which produced a dose-dependent vasodilatation. Next, to investigate whether MMPs modulate PI3K activity, we cultured rat aortic vascular smooth muscle cells (VSMCs) and stimulated them with GPCR agonists such as PE and angiotensin II. Inhibition of MMPs (by GM6001) or EGFR (by AG1478) or suppressing the expression of MMP-2 or MMP-7 or the EGFR by small interfering RNA blunted the PI3K phosphorylation of Akt induced by PE. Further, in VSMCs, PI3K inhibitors reduced the PE-induced increase in ATP synthesis and glucose transporter-4 translocation, an effect that was also observed with MMP and the EGFR inhibitors. Further, the PE-induced increase in ATP synthesis activated MMP-7 by mechanisms involving purinergic (P2X) receptors and calcium. CONCLUSION These data suggest that the maintenance of adrenergic vascular tone by the MMP-EGFR pathway requires PI3K activation and ATP synthesis. Further, our data support the view that elevated levels of GPCR agonists exaggerate the MMP transactivation of EGFR response and contribute to enhanced vascular tone and development of cardiovascular disease such as hypertension.
Transcription and alternative splicing of telomerase reverse transcriptase in benign and malignant breast tumours and in adjacent mammary glandular tissues: implications for telomerase activity

Telomerase activity was determined in 15 breast cancers, 24 benign breast lesions, and 36 breast tissues adjacent to benign or malignant tumours. A positive TRAP (telomeric repeat amplification protocol) signal was detected in 67% of carcinomas and 29% of benign tumours. In five of ten cases, non‐invaded breast tissues adjacent to telomerase‐positive carcinomas also displayed telomerase activity. Conversely, in peritumoural specimens adjacent to benign lesions, telomerase activity was never detected. To investigate the regulatory mechanisms of telomerase activity in breast tissues, the expression of telomerase subunits was assessed, as well as the presence of alternatively spliced variants of human telomerase reverse transcriptase (hTERT). The presence of the hTERT full‐length transcript appeared necessary for telomerase activity in breast carcinomas. Specifically, all telomerase‐positive carcinomas expressed the hTERT full‐length message, together with different combinations of alternatively spliced variants, whereas in telomerase‐negative cancers, the hTERT full‐length transcript was not detectable, or its abundance was markedly lower than that of alternatively spliced variants. Results obtained in benign tumours and normal tissues surrounding carcinomas instead showed that the presence of hTERT full‐length transcript was not sufficient to determine telomerase activity. These findings suggest that in non‐neoplastic tissues there are other mechanisms that suppress telomerase activity downstream from hTERT transcription and mRNA splicing and that such mechanisms have been lost during neoplastic transformation. Copyright © 2002 John Wiley & Sons, Ltd.
Larger testes and higher inhibin B levels in Finnish than in Danish newborn boys.

CONTEXT Recent studies showed that male reproductive health problems, such as cryptorchidism, hypospadias, testicular cancer, and low sperm quality, are more prevalent in Denmark than in Finland. OBJECTIVES We hypothesized that, if fetal testicular dysgenesis contributed to these observations, differences in gonadal development and the hypothalamus-pituitary-testis axis would already be detectable perinatally. Thus, we investigated healthy newborn boys in both countries. DESIGN This was a prospective, longitudinal population-based study. SETTING Two primary obstetric centers were included at the University Hospitals of Copenhagen, Denmark, and Turku, Finland. PARTICIPANTS The participants of the study included 633 Danish and 1044 Finnish boys, born at term with appropriate weight for gestational age. INTERVENTIONS Ultrasound determination of testis size at 0, 3, and 18 months and blood sampling (n = 727) at 3 months were analyzed. MAIN OUTCOME MEASURES Testicular volume and reproductive hormones were measured. RESULTS Testis volume was significantly higher at all ages in Finnish than in Danish boys (medians, 98 vs. 95, 185 vs. 119, and 188 vs. 136 mm(3), respectively; P < 0.00001). Testis growth from birth to 3 months was larger in Finnish than in Danish boys (mean, 75 vs. 26 mm(3); P < 0.0001). Serum hormone levels were higher in Finnish than Danish boys for inhibin B (median, 456 vs. 385 pg/ml; P < 0.0001), FSH (1.33 vs. 1.21 IU/liter; P < 0.036), and SHBG (143 vs. 136 nmol/liter; P < 0.022). Inhibin B was significantly positively correlated to testicular volume (r = 0.25; P < 0.006). CONCLUSIONS The larger testes and higher inhibin B levels most likely represent a bigger volume of seminiferous tubules in Finnish compared with Danish boys. Although this phenomenon may be attributable to a genetic difference between the two countries, it may also reflect environmental factors influencing testicular development.
Combining p53 stabilizers with metformin induces synergistic apoptosis through regulation of energy metabolism in castration-resistant prostate cancer

ABSTRACT Since altered energy metabolism is a hallmark of cancer, many drugs targeting metabolic pathways are in active clinical trials. The tumor suppressor p53 is often inactivated in cancer, either through downregulation of protein or loss-of-function mutations. As such, stabilization of p53 is considered as one promising approach to treat those cancers carrying wild type (WT) p53. Herein, SIRT1 inhibitor Tenovin-1 and polo-like kinase 1 (Plk1) inhibitor BI2536 were used to stabilize p53. We found that both Tennovin-1 and BI2536 increased the anti-neoplastic activity of metformin, an inhibitor of oxidative phosphorylation, in a p53 dependent manner. Since p53 has also been shown to regulate metabolic pathways, we further analyzed glycolysis and oxidative phosphorylation upon drug treatments. We showed that both Tennovin-1 and BI2536 rescued metformin-induced glycolysis and that both Tennovin-1 and BI2536 potentiated metformin-associated inhibition of oxidative phosphorylation. Of significance, castration-resistant prostate cancer (CRPC) C4-2 cells show a much more robust response to the combination treatment than the parental androgen-dependent prostate cancer LNCaP cells, indicating that targeting energy metabolism with metformin plus p53 stabilizers might be a valid approach to treat CRPC carrying WT p53.
Intracellular pH regulation in isolated cochlear outer hair cells of the guinea‐pig.

1. The intracellular pH (pHi) regulation mechanisms of the outer hair cell (OHC) isolated from the guinea‐pig were studied using fluorescence ratio imaging microscopy. 2. The OHC pHi in the resting condition was 7.26 +/‐ 0.08 (mean +/‐ S.D., n = 49) when the standard solution buffered with HEPES‐Tris was superfused. 3. Exposure to 25 mM‐NH4+ in the absence of HCO3‐ caused biphasic changes in pHi; a transient increase (7.89 +/‐ 0.14, n = 22) followed by a slow decrease (7.57 +/‐ 0.12; mean +/‐ S.D.). Removal of external NH4+ by introducing the N‐methyl‐D‐glucamine (NMDG+) solution in the absence of HCO3‐ markedly acidified the pHi to 6.38 +/‐ 0.12 with little pHi recovery. Subsequent application of the standard Na+ solution restored the pHi to the initial value. The recovery was inhibited by 0.5 mM‐amiloride but not by 0.3 mM‐DIDS (4,4'‐diisothiocyanatostilbene‐2,2'‐disulphonic acid). 4. In the presence of HCO3‐, removal of both external NH4+ and Na+ promptly caused an intracellular acidification followed by a pHi recovery. The pHi recovery from an acid load was inhibited by 0.3 mM‐DIDS or 10 microM‐NPPB (5‐nitro‐2‐(3‐phenylpropyl‐amino)‐benzoate). However, the pHi in the steady state in the presence or absence of HCO3‐ was not altered by addition of 0.5 mM‐amiloride or NMDG+ solution. 5. The intracellular buffering power obtained from the NH4+ exposure and withdrawal was ‐15.1 +/‐ 8.7 mM (pH unit)‐1 (n = 6) and ‐14.3 +/‐ 5.8 mM (pH unit)‐1, respectively. 6. Replacement of external Cl‐ with gluconate in the HCO3‐ solution increased the pHi from 7.22 +/‐ 0.12 to 7.51 +/‐ 0.20 (n = 6), which was inhibited by 0.3 mM‐DIDS. Moreover, addition of DIDS to the HCO3‐ solution increased the pHi by 0.13 +/‐ 0.08 (n = 8). 7. When the external standard solution buffered with HEPES‐Tris was replaced with the HCO3‐ solution, the basal pHi (7.27 +/‐ 0.10) was promptly acidified to 6.87 +/‐ 0.10 then relaxed slowly to 7.00 +/‐ 0.15 (n = 16). 8. The pHi showed an initial alkalinization and a subsequent slow acidification after the HCO3(‐)‐free standard solution replaced the HCO3‐ solution. The slow acidification was inhibited by low external Cl‐ concentration or by addition of 0.3 mM‐DIDS. (ABSTRACT TRUNCATED AT 400 WORDS)
Minor contribution of biliary excretion in lithium elimination in rats

Abstract Background: Lithium, which is often used for the treatment of bipolar disorders, is mainly recovered into urine after being orally administered. Due to the fact that it is completely absorbed via the gastrointestinal tract, it remains unknown whether biliary excretion is involved in the lithium disposition. In this study, we examined biliary excretion of lithium in rats and compared these with renal excretion. Materials and methods: After the injection of lithium chloride to femoral vein, plasma levels and excretion into urine and bile of lithium were evaluated. Results: After its intravenous administration as a bolus, the plasma concentration of lithium decreased time-dependently. Until 60 min, 6.47% and 0.694% of injected lithium were excreted into urine and bile, respectively. The biliary clearance of lithium was calculated to be 0.0779 mL/min/kg, and this was 11.3% of the renal clearance. Conclusions: These findings suggest the low ability of the liver to eliminate lithium from plasma in comparison with the kidney in rats.
Changes of the MS functional composite and EDSS during and after treatment of relapses with methylprednisolone in patients with multiple sclerosis

Objectives– The Multiple Sclerosis Functional Composite (MSFC) comprises quantitative functional measures of leg, hand/arm and cognitive function. We examined the responsiveness of the MSFC compared with the Expanded Disability Status Scale (EDSS) during treatment of relapses in patients with multiple sclerosis (MS). Patients and methods– 27 patients received 1000 mg intravenous methylprednisolone (i.v.‐MP) for 5 days, followed by oral methylprednisolone for 14 days. The MSFC and the EDSS‐score were assessed on day 0, before the first corticosteroid treatment, on day 5, after the last course of i.v. MP, and on day 20 after the treatment was finished. Before the first administration of the MSFC, patients were trained for the paced auditory addition test (PASAT) performing three test trials. In order to analyse practice effects, 10 MS patients without an acute exacerbation were tested three times under the same conditions as the treated group. Results– The median EDSS‐score was 2.5 in both groups. On day 5 it remained unchanged in all treated patients, on day 20 a decrease of 0.5 EDSS point occurred in five patients, and in two patients an improvement with a decrease of more than 0.5 point was observed. There was no statistically significant difference between the EDSS‐scores on day 0, 5 and 20. The mean MSFC‐score in the treated group was –0.14 ± 0.63 on day 0, 0.17 ± 0.66 on day 5, and 0.42 ± 0.59 on day 20. On the last study day, 26 patients improved compared with day 0. The differences between the MSFC‐scores at the three points of time were statistically significant for the treated group (P < 0.001), but not for the control group. Conclusion– During and after treatment of relapses in patients with MS, the MSFC appears to be more sensitive in detecting changes in function than the EDSS.
Assessing Gait Patterns of Healthy Adults Climbing Stairs Employing Machine Learning Techniques

So far, stair climbing has not been studied as extensively as gait has, although the significance of the prevention of falling on stairs has been well recognized. Based on acceleration data taken from 25 healthy subjects climbing up and down a set of 13 stairs with an accelerometer placed on the lumbo‐sacral joint, this paper aims to assess gait patterns of younger and older adults climbing stairs using a machine learning approach. A total of 14 gait features were extracted and analyzed. The performance of six representative classification models: Multilayer Perceptron (MLP), KStar, Support Vector Machine (SVM), Naïve Bayesian (NB), C4.5 Decision Trees, and Random Forests were evaluated in terms of their ability to discriminate between younger and older adults climbing up‐ and downstairs. MLP was found to provide the highest accuracy for classification. Accuracy of 95.7% was found for classifying a subject walking either up or down the stairs and an accuracy of 80.6% for classifying whether the subject was younger or older. An evaluation of individual features showed poor performance of classification for younger and older subjects climbing up‐ and downstairs, and in most cases failed to distinguish between the two classes. To access which set of features derived from a triaxial accelerometer can better describe the performance differences between younger and older adults climbing up‐ and downstairs, two feature selection algorithms, sequential feature selection and correlation‐based feature selection, were implemented. Results show that 10 features derived from correlation‐based feature selection were able to produce a 96.8% accuracy for classification between subjects climbing up and down. A subset of seven features achieved a performance of 84.9% accuracy for classification between younger and older subjects.