Species by Environment Interactions Affect Pyrrolizidine Alkaloid Expression in Senecio jacobaea, Senecio aquaticus, and Their Hybrids

We examined the effects of water and nutrient availability on the expression of the defense pyrrolizidine alkaloids (PAs) in Senecio jacobaea and S. aquaticus. Senecio jacobaea, and S. aquaticus are adapted to different natural habitats, characterized by differing abiotic conditions and different selection pressures from natural enemies. We tested if PA concentration and diversity are plastic over a range of water and nutrient treatments, and also whether such plasticity is dependent on plant species. We also tested the hypothesis that hybridization may contribute to PA diversity within plants, by comparing PA expression in parental species to that in artificially generated F1 hybrids, and also in later generation natural hybrids between S. jacobaea and S. aquaticus. We showed that total PA concentration in roots and shoots is not dependent on species, but that species determines the pattern of PA diversification. Pyrrolizidine alkaloid diversity and concentration are both dependent on environmental factors. Hybrids produce a putatively novel PA, and this PA is conserved in natural hybrids, that are backcrossed to S. jacobaea. Natural hybrids that are backcrossed several times to S. jacobaea are with regard to PA diversity significantly different from S. jacobaea but not from S. aquaticus, while F1 hybrids are in all cases more similar to S. jacobaea. These results collectively suggest that PA diversity is under the influence of natural selection

Fitness consultations in routine care of patients with type 2 diabetes in general practice: an 18-month non-randomised intervention study

<p>Abstract</p> <p>Background</p> <p>Increasing physical activity is a cornerstone in the treatment of type 2 diabetes and in general practice it is a challenge to achieve long-term adherence to this life style change. The aim of this study was to investigate in a non-randomised design whether the introduction of motivational interviewing combined with fitness tests in the type 2 diabetes care programme was followed by a change in cardio-respiratory fitness expressed by VO_2max, muscle strength of upper and lower extremities, haemoglobin A_1c(HbA_1c) and HDL-cholesterol.</p> <p>Methods</p> <p>Uncontrolled 18-month intervention study with follow-up and effect assessment every 3 months in a primary care unit in Denmark with six general practitioners (GPs). Of 354 eligible patients with type 2 diabetes, 127 (35.9%) were included. Maximum work capacity was tested on a cycle ergometer and converted to VO_2max. Muscle strength was measured with an arm curl test and a chair stand test. The results were used in a subsequent motivational interview conducted by one of the GPs. Patients were encouraged to engage in lifestyle exercise and simple home-based self-managed exercise programmes. Data were analysed with mixed models.</p> <p>Results</p> <p>At end of study, 102 (80.3%) participants remained in the intervention. Over 18 months, VO_2maxincreased 2.5% (p = 0.032) while increases of 33.2% (p < 0.001) and 34.1% (p < 0.001) were registered for the arm curl test and chair stand test, respectively. HDL-cholesterol increased 8.6% (p < 0.001), but HbA_1cremained unchanged (p = 0.57) on a low level (6.8%). Patients without cardiovascular disease or pain from function limitation increased their VO_2maxby 5.2% (p < 0.0001) and 7.9% (p = 0.0008), respectively.</p> <p>Conclusions</p> <p>In this 18-month study, participants who had repeated fitness consultations, including physical testing and motivational interviewing to improve physical activity, improved VO_2max, muscle strength, and lipid profile. Our results indicate that physical testing combined with motivational interviewing is feasible in a primary health care setting. Here, a fitness consultation tailored to the individual patient, his/her comorbidities and conditions in the local area can be incorporated into the diabetes programme to improve patients' muscle strength and cardio-respiratory fitness.</p

The activating mutation R201C in GNAS promotes intestinal tumourigenesis in Apc(Min/+) mice through activation of Wnt and ERK1/2 MAPK pathways.

Somatically acquired, activating mutations of GNAS, the gene encoding the stimulatory G-protein Gsalpha subunit, have been identified in kidney, thyroid, pituitary, leydig cell, adrenocortical and, more recently, in colorectal tumours, suggesting that mutations such as R201C may be oncogenic in these tissues. To study the role of GNAS in intestinal tumourigenesis, we placed GNAS R201C under the control of the A33-antigen promoter (Gpa33), which is almost exclusively expressed in the intestines. The GNAS R201C mutation has been shown to result in the constitutive activation of Gsalpha and adenylate cyclase and to lead to the autonomous synthesis of cyclic adenosine monophosphate (cAMP). Gpa33(tm1(GnasR201C)Wtsi/+) mice showed significantly elevated cAMP levels and a compensatory upregulation of cAMP-specific phosphodiesterases in the intestinal epithelium. GNAS R201C alone was not sufficient to induce tumourigenesis by 12 months, but there was a significant increase in adenoma formation when Gpa33(tm1(GnasR201C)Wtsi/+) mice were bred onto an Apc(Min/+) background. GNAS R201C expression was associated with elevated expression of Wnt and extracellular signal-regulated kinase 1/2 mitogen-activated protein kinase (ERK1/2 MAPK) pathway target genes, increased phosphorylation of ERK1/2 MAPK and increased immunostaining for the proliferation marker Ki67. Furthermore, the effects of GNAS R201C on the Wnt pathway were additive to the inactivation of Apc. Our data strongly suggest that activating mutations of GNAS cooperate with inactivation of APC and are likely to contribute to colorectal tumourigenesis

An evaluation of family physicians' educational needs and experiences in health promotion and disease prevention in Poland and Lithuania - a qualitative study

Reikšminiai žodžiai: Ligų prevencija; Sveikatos stiprinimas; Šeimos gydytojai; Šeimos gydytojų rengimas; Šeimos gydytojų švietimo poreikiai; Disease prevention; Family physicians; Family physicians educational needs; Health promotion; Training of family physician

Diffractive Dijet Production at sqrt(s)=630 and 1800 GeV at the Fermilab Tevatron

We report a measurement of the diffractive structure function $F_{jj}^D$ of the antiproton obtained from a study of dijet events produced in association with a leading antiproton in $\bar pp$ collisions at $\sqrt s=630$ GeV at the Fermilab Tevatron. The ratio of $F_{jj}^D$ at $\sqrt s=630$ GeV to $F_{jj}^D$ obtained from a similar measurement at $\sqrt s=1800$ GeV is compared with expectations from QCD factorization and with theoretical predictions. We also report a measurement of the $\xi$ ($x$-Pomeron) and $\beta$ ($x$ of parton in Pomeron) dependence of $F_{jj}^D$ at $\sqrt s=1800$ GeV. In the region $0.035<\xi<0.095$, $|t|<1$ GeV$^2$ and $\beta<0.5$, $F_{jj}^D(\beta,\xi)$ is found to be of the form $\beta^{-1.0\pm 0.1} \xi^{-0.9\pm 0.1}$, which obeys $\beta$-$\xi$ factorization.Comment: LaTeX, 9 pages, Submitted to Phys. Rev. Letter

A Study of B0 -> J/psi K(*)0 pi+ pi- Decays with the Collider Detector at Fermilab

We report a study of the decays B0 -> J/psi K(*)0 pi+ pi-, which involve the creation of a u u-bar or d d-bar quark pair in addition to a b-bar -> c-bar(c s-bar) decay. The data sample consists of 110 1/pb of p p-bar collisions at sqrt{s} = 1.8 TeV collected by the CDF detector at the Fermilab Tevatron collider during 1992-1995. We measure the branching ratios to be BR(B0 -> J/psi K*0 pi+ pi-) = (8.0 +- 2.2 +- 1.5) * 10^{-4} and BR(B0 -> J/psi K0 pi+ pi-) = (1.1 +- 0.4 +- 0.2) * 10^{-3}. Contributions to these decays are seen from psi(2S) K(*)0, J/psi K0 rho0, J/psi K*+ pi-, and J/psi K1(1270)

Cigarette smoke exposure inhibits extracellular MMP-2 (gelatinase A) activity in human lung fibroblasts

BACKGROUND: Exposure to cigarette smoke is considered a major risk factor for the development of lung diseases, since its causative role has been assessed in the induction and maintenance of an inflamed state in the airways. Lung fibroblasts can contribute to these processes, due to their ability to produce proinflammatory chemotactic molecules and extracellular matrix remodelling proteinases. Among proteolytic enzymes, gelatinases A and B have been studied for their role in tissue breakdown and mobilisation of matrix-derived signalling molecules. Multiple reports linked gelatinase deregulation and overexpression to the development of inflammatory chronic lung diseases such as COPD. METHODS: In this study we aimed to determine variations in the gelatinolytic pattern of human lung fibroblasts (HFL-1 cell line) exposed to cigarette smoke extract (CSE). Gelatinolytic activity levels were determined by using gelatin zymography for the in-gel detection of the enzymes (proenzyme and activated forms), and the subsequent semi-quantitative densitometric evaluation of lytic bands. Expression of gelatinases was evaluated also by RT-PCR, zymography of the cell lysates and by western blotting. RESULTS: CSE exposure at the doses used (1–10%) did not exert any significant cytotoxic effects on fibroblasts. Zymographic analysis showed that CSE exposure resulted in a linear decrease of the activity of gelatinase A. Control experiments allowed excluding a direct inhibitory effect of CSE on gelatinases. Zymography of cell lysates confirmed the expression of MMP-2 in all conditions. Semi-quantitative evaluation of mRNA expression allowed assessing a reduced transcription of the enzyme, as well as an increase in the expression of TIMP-2. Statistical analyses showed that the decrease of MMP-2 activity in conditioned media reached the statistical significance (p = 0.0031 for 24 h and p = 0.0012 for 48 h), while correlation analysis showed that this result was independent from CSE cytotoxicity (p = 0.7833 for both exposures). CONCLUSION: Present work describes for the first time that, apart well characterized proinflammatory responses, human lung fibroblasts may react to CSE with a significant reduction of extracellular MMP-2 lytic activity. Therefore, fibroblasts may actively participate to the alteration of the proteolysis/antiproteolysis balance, which reflects the defective repair of the extracellular matrix. Such event should provide a further contribution to the maintenance of the inflamed state in the lungs

Establishment of a Replicating Plasmid in Rickettsia prowazekii

Rickettsia prowazekii, the causative agent of epidemic typhus, grows only within the cytosol of eukaryotic host cells. This obligate intracellular lifestyle has restricted the genetic analysis of this pathogen and critical tools, such as replicating plasmid vectors, have not been developed for this species. Although replicating plasmids have not been reported in R. prowazekii, the existence of well-characterized plasmids in several less pathogenic rickettsial species provides an opportunity to expand the genetic systems available for the study of this human pathogen. Competent R. prowazekii were transformed with pRAM18dRGA, a 10.3 kb vector derived from pRAM18 of R. amblyommii. A plasmid-containing population of R. prowazekii was obtained following growth under antibiotic selection, and the rickettsial plasmid was maintained extrachromosomally throughout multiple passages. The transformant population exhibited a generation time comparable to that of the wild type strain with a copy number of approximately 1 plasmid per rickettsia. These results demonstrate for the first time that a plasmid can be maintained in R. prowazekii, providing an important genetic tool for the study of this obligate intracellular pathogen

The effects of an extensive exercise programme on the progression of Mild Cognitive Impairment (MCI): study protocol for a randomised controlled trial

Background Exercise interventions to prevent dementia and delay cognitive decline have gained considerable attention in recent years. Human and animal studies have demonstrated that regular physical activity targets brain function by increasing cognitive reserve. There is also evidence of structural changes caused by exercise in preventing or delaying the genesis of neurodegeneration. Although initial studies indicate enhanced cognitive performance in patients with mild cognitive impairment (MCI) following an exercise intervention, little is known about the effect of an extensive, controlled and regular exercise regimen on the neuropathology of patients with MCI. This study aims to determine the effects of an extensive exercise programme on the progression of MCI. Methods/design This randomised controlled clinical intervention study will take place across three European sites. Seventy-five previously sedentary patients with a clinical diagnosis of MCI will be recruited at each site. Participants will be randomised to one of three groups. One group will receive a standardised 1-year extensive aerobic exercise intervention (3 units of 45 min/week). The second group will complete stretching and toning (non-aerobic) exercise (3 units of 45 min/week) and the third group will act as the control group. Change in all outcomes will be measured at baseline (T0), after six months (T1) and after 12 months (T2). The primary outcome, cognitive performance, will be determined by a neuropsychological test battery (CogState battery, Trail Making Test and Verbal fluency). Secondary outcomes include Montreal Cognitive Assessment (MoCA), cardiovascular fitness, physical activity, structural changes of the brain, quality of life measures and measures of frailty. Furthermore, outcome variables will be related to genetic variations on genes related to neurogenesis and epigenetic changes in these genes caused by the exercise intervention programme. Discussion The results will add new insights into the prevailing notion that exercise may slow the rate of cognitive decline in MCI