Linking genetic, metabolic, and phenotypic diversity among Saccharomyces cerevisiae strains using multi-omics associations.

Background: The selection of bioengineering platform strains and engineering strategies to improve the stress resistance of Saccharomyces cerevisiae remains a pressing need in bio-based chemical production. Thus, a systematic effort to exploit genotypic and phenotypic diversity to boost yeast's industrial value is still urgently needed.

Results: We analyzed 5,400 growth curves obtained from 36 S.

Close to the Edge: Growth Restrained by the NAD(P)H/ATP Formation Flux Ratio.

Most fermentative microorganisms grow well-under anaerobic conditions managing a balanced redox and appropriate energy metabolism, but a few species do exist in which cells have to cope with inadequate energy recovery or capture and/or redox balancing. Two cases of these species, i.e.

Physiological effects of over-expressing compartment-specific components of the protein folding machinery in xylose-fermenting Saccharomyces cerevisiae.

Background: Efficient utilization of both glucose and xylose is necessary for a competitive ethanol production from lignocellulosic materials. Although many advances have been made in the development of xylose-fermenting strains of Saccharomyces cerevisiae, the productivity remains much lower compared to glucose. Previous transcriptional analyses of recombinant xylose-fermenting strains have mainly focused on central carbon metabolism.

Engineering yeast hexokinase 2 for improved tolerance toward xylose-induced inactivation.

Hexokinase 2 (Hxk2p) from Saccharomyces cerevisiae is a bi-functional enzyme being both a catalyst and an important regulator in the glucose repression signal. In the presence of xylose Hxk2p is irreversibly inactivated through an autophosphorylation mechanism, affecting all functions. Consequently, the regulation of genes involved in sugar transport and fermentative metabolism is impaired.

Crystal structure of a benzimidazole hepatitis C virus inhibitor free and in complex with the viral RNA target.

The crystal structure of 8-((dimethylamino)methyl)-1-(3-(dimethylamino)propyl)-1,7,8,9-tetrahydrochromeno[5,6-d]imidazol-2-amine (), an inhibitor of the hepatitis C virus internal ribosome entry site, is described and compared to the structure of the compound in complex with the viral RNA target. Compound crystallized by pentane vapor diffusion into dichloroethane solution. It crystallized in the monoclinic system, P2/c space group with unit cell parameters = 15.

New route to the ergoline skeleton via cyclization of 4-unsubstituted indoles.

A new route to the ergoline skeleton has been developed that does not require prior functionalization of the indole 4-position. The indole nucleus is introduced late in the synthesis to allow for eventual efficient introduction of substituents in this region. Key steps include Negishi coupling of a three-carbon chain to a bromonicotinate ester, Fischer indole synthesis to facilitate incorporation of substituents via phenylhydrazines, and Pd-catalyzed cyclization to form the ergoline C ring.

Dynamic metabolomics differentiates between carbon and energy starvation in recombinant Saccharomyces cerevisiae fermenting xylose.

Background: The concerted effects of changes in gene expression due to changes in the environment are ultimately reflected in the metabolome. Dynamics of metabolite concentrations under a certain condition can therefore give a description of the cellular state with a high degree of functional information. We used this potential to evaluate the metabolic status of two recombinant strains of Saccharomyces cerevisiae during anaerobic batch fermentation of a glucose/xylose mixture.

Structure of a hepatitis C virus RNA domain in complex with a translation inhibitor reveals a binding mode reminiscent of riboswitches.

The internal ribosome entry site (IRES) in the hepatitis C virus (HCV) RNA genome is essential for the initiation of viral protein synthesis. IRES domains adopt well-defined folds that are potential targets for antiviral translation inhibitors. We have determined the three-dimensional structure of the IRES subdomain IIa in complex with a benzimidazole translation inhibitor at 2.

Kinetic modelling reveals current limitations in the production of ethanol from xylose by recombinant Saccharomyces cerevisiae.

Saccharomyces cerevisiae lacks the ability to ferment the pentose sugar xylose that is the second most abundant sugar in nature. Therefore two different xylose catabolic pathways have been heterologously expressed in S. cerevisiae.

An efficient new route to dihydropyranobenzimidazole inhibitors of HCV replication.

A class of dihydropyranobenzimidazole inhibitors was recently discovered that acts against the hepatitis C virus (HCV) in a new way, binding to the IRES-IIa subdomain of the highly conserved 5' untranslated region of the viral RNA and thus preventing the ribosome from initiating translation. However, the reported synthesis of these compounds is lengthy and low-yielding, the intermediates are troublesome to purify, and the route is poorly structured for the creation of libraries. We report a streamlined route to this class of inhibitors in which yields are far higher and most intermediates are crystalline.

Perspectives on using multimedia scenarios in a PBL medical curriculum.

Unlabelled: In 1999, the Faculty of Health Sciences at Linköping University, Sweden, started up a process of replacing text-based problem-based learning (PBL) scenarios with web-based multimedia-enhanced scenarios. This article brings together three studies of the results of this process and the experience gained from 10 years of implementation work.

Results And Conclusions: Adding multimedia to PBL scenarios makes them more realistic and thereby more motivating and stimulating for the student to process.

Effects of a problem-based learning rehabilitation program on physical activity in patients with coronary artery disease.

Purpose: To evaluate the effects of a problem-based learning (PBL) rehabilitation program on physical activity.

Methods: We randomized 207 consecutive patients younger than 70 years, with a recent event of coronary artery disease (CAD), to a PBL group (n = 104) or a control group (n = 103). In addition to standard treatment, the PBL patients participated in a 1-year program with 13 sessions in small groups, where learning needs and behavior change were focused upon.

Attenuated cortisol response to a standardized stress test in Lithuanian versus Swedish men: the LiVicordia study.

Cardiovascular mortality rates of middle-aged men are 4 times higher in Lithuania than in Sweden The difference is not explained by standard risk factors, but our previous findings of pronounced psychosocial stress in Lithuanian men offer a possible explanation. We investigated cortisol and cardiovascular reactivity to a standardized laboratory stress test in population-based random samples of 50-year-old men from Vilnius, Lithuania and Linköping, Sweden. Repeated measures analysis of variance showed that cortisol responses differed between cities (p's < .

[Renewed medical education in Linkoping. Problem-based learning, basic science and public health intensified].

A complete undergraduate medical programme in Linköping started 1986. The curriculum was innovative applying problem-based learning, community-orientation, and multi-professional training. After almost 20 years, a revision is implemented to vitalise the original educational principles.

Lectures in problem-based learning--why, when and how? An example of interactive lecturing that stimulates meaningful learning.

Even though opinions differ as to whether lecturing is compatible with problem-based learning (PBL) or not, lectures are still a common form of instruction in PBL curricula. This paper discusses the lecture in the framework of theories of learning in general and the medical problem-based learning tradition in particular. An example of how theories of learning can be implemented in the lecture hall is presented.

Incentives for lifestyle changes in patients with coronary heart disease.

Aim: This paper reports a study exploring how patients in the rehabilitation phase of coronary heart disease experience facilitating and constraining factors related to lifestyle changes of importance for wellbeing and prognosis.

Background: Lifestyle change is important but complex during rehabilitation after a myocardial infarction or angina pectoris. The intentions to perform behaviours and to experience control over facilitators and constraints are important determinants of behaviour.

Effects of a problem-based learning rehabilitation programme on quality of life in patients with coronary artery disease.

Background: The aim of cardiac rehabilitation (CR) is not only physical improvement but also increased quality of life (QoL). A CR programme based upon problem based learning (PBL) philosophy was developed, to achieve and apply new knowledge related to coronary artery disease (CAD). The aim of this paper was to evaluate the impact of the PBL programme on QoL.

[The EDIT project. Problem-based learning on the web challenges students' thinking].

EDIT is short for Educational Development using Information Technology. The EDIT project was initiated by the Faculty of Health Sciences at Linköping University. The aim was to develop web-based scenarios for problem-based learning (PBL).

Effect of problem-based learning on stages of change for exercise behaviour in patients with coronary artery disease.

Background And Purpose: Physical activity plays an important part in preventing coronary artery disease and is targeted in most rehabilitation and education programmes. The aim of the present study was to evaluate stages of change for exercise behaviour in patients with a recent event of coronary artery disease.

Method: A randomized two-group, pre--post-test design was used.

Rehabilitation after coronary heart disease: spouses' views of support.

Background: Family presence decreases mortality and improves psychosocial recovery after a coronary heart disease event. In this situation, spousal support seems important for the recovering partner's self-esteem and mastery. There is inadequate knowledge of how spouses view their supportive roles.

Coronary heart disease: causes and drug treatment--spouses' conceptions.

Background: Spouses are important in the rehabilitation process of their partner after coronary heart disease event. Their knowledge and attitudes have an impact on their support to the partner concerning lifestyle changes and drug treatment after an event.

Aims And Objectives: To explore spouses' conceptions concerning causes of coronary heart disease and drug treatment 1 year after the partner's cardiac event.

Patients' conceptions of coronary heart disease--a phenomenographic analysis.

Readjustment after an event of coronary heart disease (CHD) is defined to comprise cognitive, instrumental and affective components. The cognitive dimension refers to understanding of the disease. Twenty-three patients (<60 years) with CHD were interviewed about the nature of their disease and encouraged to use their own words.