Showing papers by "University of Gothenburg published in 2002"

Osmotic Stress Signaling and Osmoadaptation in Yeasts

Abstract: The ability to adapt to altered availability of free water is a fundamental property of living cells. The principles underlying osmoadaptation are well conserved. The yeast Saccharomyces cerevisiae is an excellent model system with which to study the molecular biology and physiology of osmoadaptation. Upon a shift to high osmolarity, yeast cells rapidly stimulate a mitogen-activated protein (MAP) kinase cascade, the high-osmolarity glycerol (HOG) pathway, which orchestrates part of the transcriptional response. The dynamic operation of the HOG pathway has been well studied, and similar osmosensing pathways exist in other eukaryotes. Protein kinase A, which seems to mediate a response to diverse stress conditions, is also involved in the transcriptional response program. Expression changes after a shift to high osmolarity aim at adjusting metabolism and the production of cellular protectants. Accumulation of the osmolyte glycerol, which is also controlled by altering transmembrane glycerol transport, is of central importance. Upon a shift from high to low osmolarity, yeast cells stimulate a different MAP kinase cascade, the cell integrity pathway. The transcriptional program upon hypo-osmotic shock seems to aim at adjusting cell surface properties. Rapid export of glycerol is an important event in adaptation to low osmolarity. Osmoadaptation, adjustment of cell surface properties, and the control of cell morphogenesis, growth, and proliferation are highly coordinated processes. The Skn7p response regulator may be involved in coordinating these events. An integrated understanding of osmoadaptation requires not only knowledge of the function of many uncharacterized genes but also further insight into the time line of events, their interdependence, their dynamics, and their spatial organization as well as the importance of subtle effects.

Interleukin-6-deficient mice develop mature-onset obesity.

Abstract: The immune-modulating cytokine interleukin-6 (IL-6) is expressed both in adipose tissue and centrally in hypothalamic nuclei that regulate body composition. We investigated the impact of loss of IL-6 on body composition in mice lacking the gene encoding IL-6 (Il6-/- mice) and found that they developed mature-onset obesity that was partly reversed by IL-6 replacement. The obese Il6-/- mice had disturbed carbohydrate and lipid metabolism, increased leptin levels and decreased responsiveness to leptin treatment. To investigate the possible mechanism and site of action of the anti-obesity effect of IL-6, we injected rats centrally and peripherally with IL-6 at low doses. Intracerebroventricular, but not intraperitoneal IL-6 treatment increased energy expenditure. In conclusion, centrally acting IL-6 exerts anti-obesity effects in rodents.

Autologous Chondrocyte Transplantation Biomechanics and Long-Term Durability

Abstract: We evaluated the durability of autologous chondrocyte transplantation grafts in 61 patients treated for isolated cartilage defects on the femoral condyle or the patella and followed up for a mean of 7.4 years (range, 5 to 11). Durability was determined by comparing the clinical status at the long-term follow-up with that found 2 years after the transplantation. After 2 years, 50 of the 61 patients had good or excellent clinical results, and 51 of 61 had good or excellent results at 5 to 11 years later. Grafted areas from 11 of the patients were evaluated with an electromechanical indentation probe during a second-look arthroscopy procedure (mean follow-up, 54.3 months; range, 33 to 84); stiffness measurements were 90% or more of those of normal cartilage in eight patients. Eight of twelve 2-mm biopsy samples taken from these patients showed hyaline characteristics with safranin O staining and a homogeneous appearance in polarized light. Three fibrous and eight hyaline biopsy specimens stained positive to aggrecan and to cartilage oligomeric matrix protein. Hyaline-like specimens stained positive for type II collagen, and fibrous, for type I collagen. Autologous chondrocyte transplantation for the treatment of articular cartilage injuries has a durable outcome for as long as 11 years.

A systematic review of the incidence of biological and technical complications in implant dentistry reported in prospective longitudinal studies of at least 5 years

Abstract: Objective: To systematically review the incidence of biological and technical complications in implant therapy reported in prospective longitudinal studies of at least 5 years. Methods: A MEDLINE search was conducted for prospective longitudinal studies with follow-up periods of at least 5 years. Screening and data abstraction were performed independently by multiple reviewers. The types of complications assessed were as follows: implant loss, sensory disturbance, soft tissue complications, peri-implantitis, bone loss ≥2.5 mm, implant fracture and technical complications related to implant components and suprastructures. Results: The search provided 1310 titles and abstracts, out of which 159 were selected for full-text analysis. Finally, 51 studies were included. Meta analysis of these studies indicated that implant loss prior to functional loading is to be expected to occur in about 2.5% of all implants placed in implant therapy including more than one implant and when routine procedures are used. Implant loss during function occurs in about 2–3% of implants supporting fixed reconstructions, while in overdenture therapy >5% of the implants can be expected to be lost during a 5-year period. Few studies (41% of those included) reported data on the incidence of persisting sensory disturbance >1 year following implant surgery. Most of the studies that provided such data reported on the absence or a low incidence (1–2%) of this complication beyond this interval. A higher incidence of soft tissue complications was reported for patients treated with implants supporting overdentures. There is limited information regarding the occurrence of peri-implantitis and implants exhibiting bone loss ≥2.5 mm. Implant fracture is a rare complication and occurs in <1% of all implants during a 5-year period. The incidence of technical complications related to implant components and suprastructures was higher in overdentures than in fixed reconstructions. Conclusion: Implant loss was most frequently described (reported in about 100% of studies), while biological complications were considered in only 40–60% and technical complications in only 60–80% of the studies. This observation indicates that data on the incidence of biological and technical complications may be underestimated and should be interpreted with caution.

Subendothelial retention of atherogenic lipoproteins in early atherosclerosis.

Abstract: Complications of atherosclerosis are the most common cause of death in Western societies. Among the many risk factors identified by epidemiological studies, only elevated levels of lipoproteins containing apolipoprotein (apo) B can drive the development of atherosclerosis in humans and experimental animals even in the absence of other risk factors. However, the mechanisms that lead to atherosclerosis are still poorly understood. We tested the hypothesis that the subendothelial retention of atherogenic apoB-containing lipoproteins is the initiating event in atherogenesis. The extracellular matrix of the subendothelium, particularly proteoglycans, is thought to play a major role in the retention of atherogenic lipoproteins. The interaction between atherogenic lipoproteins and proteoglycans involves an ionic interaction between basic amino acids in apoB100 and negatively charged sulphate groups on the proteoglycans. Here we present direct experimental evidence that the atherogenicity of apoB-containing low-density lipoproteins (LDL) is linked to their affinity for artery wall proteoglycans. Mice expressing proteoglycan-binding-defective LDL developed significantly less atherosclerosis than mice expressing wild-type control LDL. We conclude that subendothelial retention of apoB100-containing lipoprotein is an early step in atherogenesis.

Self reported cannabis use as a risk factor for schizophrenia in Swedish conscripts of 1969: historical cohort study

Abstract: Objectives: An association between use of cannabis in adolescence and subsequent risk of schizophrenia was previously reported in a follow up of Swedish conscripts. Arguments were raised that this association may be due to use of drugs other than cannabis and that personality traits may have confounded results. We performed a further analysis of this cohort to address these uncertainties while extending the follow up period to identify additional cases. Design: Historical cohort study. Setting: 1969-70 survey of Swedish conscripts (>97% of the country's male population aged 18-20). Participants: 50 087 subjects: data were available on self reported use of cannabis and other drugs, and on several social and psychological characteristics. Main outcome measures: Admissions to hospital for ICD-8/9 schizophrenia and other psychoses, as determined by record linkage. Results: Cannabis was associated with an increased risk of developing schizophrenia in a dose dependent fashion both for subjects who had ever used cannabis (adjusted odds ratio for linear trend of increasing frequency 1.2, 95% confidence interval 1.1 to 1.4, P 50 times was 6.7 (2.1 to 21.7) in the cannabis only group. Similar results were obtained when analysis was restricted to subjects developing schizophrenia after five years after conscription, to exclude prodromal cases. Conclusions: Cannabis use is associated with an increased risk of developing schizophrenia, consistent with a causal relation. This association is not explained by use of other psychoactive drugs or personality traits relating to social integration. #### What is already known about this topic What is already known about this topic Use of cannabis has been associated with an increased risk of developing schizophrenia Alternative explanations for this association include confounding by personality or by use of other drugs such as amphetamines, and use of cannabis as a form of self medication secondary to the disorder #### What this study adds What this study adds Self reported cannabis use is associated with an increased risk of subsequently developing schizophrenia, consistent with a causal relation This association is not explained by sociability personality traits, or by use of amphetamines or other drugs Self medication with cannabis is an unlikely explanation for the association observed

Unmyelinated tactile afferents signal touch and project to insular cortex

Abstract: There is dual tactile innervation of the human hairy skin: in addition to fast-conducting myelinated afferent fibers, there is a system of slow-conducting unmyelinated (C) afferents that respond to light touch. In a unique patient lacking large myelinated afferents, we found that activation of C tactile (CT) afferents produced a faint sensation of pleasant touch. Functional magnetic resonance imaging (fMRI) analysis during CT stimulation showed activation of the insular region, but not of somatosensory areas S1 and S2. These findings identify CT as a system for limbic touch that may underlie emotional, hormonal and affiliative responses to caress-like, skin-to-skin contact between individuals.

Helicobacter pylori SabA adhesin in persistent infection and chronic inflammation.

Abstract: Helicobacter pylori adherence in the human gastric mucosa involves specific bacterial adhesins and cognate host receptors. Here, we identify sialyl-dimeric-Lewis x glycosphingolipid as a receptor for H. pylori and show that H. pylori infection induced formation of sialyl-Lewis x antigens in gastric epithelium in humans and in a Rhesus monkey. The corresponding sialic acid-binding adhesin (SabA) was isolated with the "retagging" method, and the underlying sabA gene (JHP662/HP0725) was identified. The ability of many H. pylori strains to adhere to sialylated glycoconjugates expressed during chronic inflammation might thus contribute to virulence and the extraordinary chronicity of H. pylori infection.

Multiple Glassy States in a Simple Model System

Abstract: Experiments, theory, and simulation were used to study glass formation in a simple model system composed of hard spheres with short-range attraction ("sticky hard spheres"). The experiments, using well-characterized colloids, revealed a reentrant glass transition line. Mode-coupling theory calculations and molecular dynamics simulations suggest that the reentrance is due to the existence of two qualitatively different glassy states: one dominated by repulsion (with structural arrest due to caging) and the other by attraction (with structural arrest due to bonding). This picture is consistent with a study of the particle dynamics in the colloid using dynamic light scattering.

The marine ecosystem of Kongsfjorden, Svalbard

Abstract: Kongsfjorden is a glacial fjord in the Arctic (Svalbard) that is influenced by both Atlantic and Arctic water masses and harbours a mixture of boreal and Arctic flora and fauna. Inputs from large tidal glaciers create steep environmental gradients in sedimentation and salinity along the length of this fjord. The glacial inputs cause reduced biomass and diversity in the benthic community in the inner fjord. Zooplankton suffers direct mortality from the glacial outflow and primary production is reduced because of limited light levels in the turbid, mixed inner waters. The magnitude of the glacial effects diminishes towards the outer fjord. Kongsfjorden is an important feeding ground for marine mammals and seabirds. Even though the fjord contains some boreal fauna, the prey consumed by upper trophic levels is mainly Arctic organisms. Marine mammals constitute the largest top-predator biomass, but seabirds have the largest energy intake and also export nutrients and energy out of the marine environment. Kongsfjorden has received a lot of research attention in the recent past. The current interest in the fjord is primarily based on the fact that Kongsfjorden is particularly suitable as a site for exploring the impacts of possible climate changes, with Atlantic water influx and melting of tidal glaciers both being linked to climate variability. The pelagic ecosystem is likely to be most sensitive to the Atlantic versus Arctic influence, whereas the benthic ecosystem is more affected by long-term changes in hydrography as well as changes in glacial runoff and sedimentation. Kongsfjorden will be an important Arctic monitoring site over the coming decades and a review of the current knowledge, and a gap analysis, are therefore warranted. Important knowledge gaps include a lack of quantitative data on production, abundance of key prey species, and the role of advection on the biological communities in the fjord.

Policy Instruments for Environmental and Natural Resource Management

Abstract: As Thomas Sterner points out, the economic 'toolkit' for dealing with environmental problems has become formidable. It includes taxes, charges, permits, deposit-refund systems, labeling, and other information disclosure mechanisms. Though not all these devices are widely used, empirical application has started within some sectors, and we are beginning to see the first systematic efforts at an advanced policy design that takes due account of market-based incentives. Sterner‘s book encourages more widespread and careful use of economic policy instruments. Intended primarily for application in developing and transitional countries, the book compares the accumulated experiences of the use of economic policy instruments in the U.S. and Europe, as well as in select rich and poor countries in Asia, Africa, and Latin America. Ambitious in scope, the book discusses the design of instruments that can be employed in a wide range of contexts, including transportation, industrial pollution, water pricing, waste, fisheries, forests, and agriculture. Policy Instruments for Environmental and Natural Resource Management is deeply rooted in economics but also informed by perspectives drawn from political, legal, ecological, and psychological research. Sterner notes that, in addition to meeting requirements for efficiency, the selection and design of policy instruments must satisfy criteria involving equity and political acceptability. He is careful to distinguish between the well-designed plans of policymakers and the resulting behavior of society. A copublication of Resources for the Future, the World Bank, and the Swedish International Development Cooperation Agency (Sida).

Pericytes and the Pathogenesis of Diabetic Retinopathy

Abstract: Pericytes provide vascular stability and control endothelial proliferation. Pericyte loss, microaneurysms, and acellular capillaries are characteristic for the diabetic retina. Platelet-derived growth factor (PDGF)-B is involved in pericyte recruitment, and brain capillaries of mice with a genetic ablation of PDGF-B show pericyte loss and microaneurysms. We investigated the role of capillary coverage with pericytes in early diabetic retinopathy and the contribution to proliferative retinopathy using mice with a single functional allele of PDGF-B (PDGF-B(+/-) mice). As assessed by quantitative morphometry of retinal digest preparations, pericyte numbers in nondiabetic PDGF-B(+/-) mice were reduced by 30% compared with wild-type mice, together with a small but significant increase in acellular capillaries. Pericyte numbers were reduced by 40% in diabetic wild-type mice compared with nondiabetic wild-type controls. Pericyte numbers were decreased by 50% in diabetic PDGF-B(+/-) mice compared with nondiabetic wild-type littermates, and the incidence of acellular capillaries was increased 3.5-fold when compared with nondiabetic PDGF-B(+/-) mice. To investigate the effect of pericyte loss in the context of ongoing angiogenesis, we subjected mice to hypoxia-induced proliferative retinopathy. As a result, PDGF-B(+/-) mice developed twice as many new blood vessels as their wild-type littermates. We conclude that retinal capillary coverage with pericytes is crucial for the survival of endothelial cells, particularly under stress conditions such as diabetes. At high vascular endothelial growth factor levels, such as those in the retinopathy of prematurity model, pericyte deficiency leads to reduced inhibition of endothelial proliferation in vivo.

A new method for large scale isolation of kidney glomeruli from mice.

Abstract: Here we report a new isolation method for mouse glomeruli. The method is fast and simple and allows for the isolation of virtually all glomeruli present in the adult mouse kidney with minimal contamination of nonglomerular cells. Mice were perfused through the heart with magnetic 4.5- micro m diameter Dynabeads. Kidneys were minced into small pieces, digested by collagenase, filtered, and collected using a magnet. The number of glomeruli retrieved from one adult mouse was 20,131 +/- 4699 (mean +/- SD, n = 14) with a purity of 97.5 +/- 1.7%. The isolated glomeruli retained intact morphology, as confirmed by light and electron microscopy, as well as intact mRNA integrity, as confirmed by Northern blot analysis. The method was applicable also to newborn mice, which allows for the isolation of immature developmental stage glomeruli. This method makes feasible transcript profiling and proteomic analysis of the developing, healthy and diseased mouse glomerulus.

Sleep complaints predict coronary artery disease mortality in males: a 12-year follow-up study of a middle-aged Swedish population.

Abstract: . Mallon L, Broman J-E, Hetta J (University Hospital, Uppsala, and Falun Hospital, Falun; and Institute of Clinical Neuroscience, Goteborg; Sweden). Sleep complaints predict coronary artery disease mortality in males: a 12-year follow-up study of a middle-aged Swedish population. J Intern Med 2002; 251: 207–216. Objectives. Only a few prospective surveys have been performed to investigate the relationship between sleep complaints and coronary artery disease (CAD) mortality. This study was conducted to determine whether sleep complaints in a middle-aged population predicted total mortality and CAD mortality. Design. A population-based prospective study. Setting. The County of Dalarna, Sweden. Subjects and methods. In 1983, a random sample of 1870 subjects aged 45–65 years responded to a postal questionnaire (response rate 70.2%) including questions about sleep complaints and various diseases. Mortality data for the period 1983–95 were collected, and Cox proportional hazard analyses were used to examine the mortality risks. Results. At 12-year follow-up 165 males (18.2%) and 101 females (10.5%) had died. After adjustment for a wide range of important putative risk factors, difficulties initiating sleep (DIS) were related to CAD death in males [relative risk (RR), 3.1; 95% confidence interval (CI), 1.5–6.3; P < 0.01], but not in females. Short or long sleep duration did not influence risk of CAD mortality or total mortality for either gender. Depression in males increased the risk of death attributed to CAD (RR, 3.0; 95% CI, 1.1–8.4; P < 0.05) and total mortality (RR, 2.2; 95% CI, 1.1–4.5; P < 0.05). Conclusion. These results provide evidence that there is an association between difficulties falling asleep and CAD mortality in males.

Bacterial strategies for overcoming host innate and adaptive immune responses

Abstract: In higher organisms a variety of host defense mechanisms control the resident microflora and, in most cases, effectively prevent invasive microbial disease. However, it appears that microbial organisms have coevolved with their hosts to overcome protective host barriers and, in selected cases, actually take advantage of innate host responses. Many microbial pathogens avoid host recognition or dampen the subsequent immune activation through sophisticated interactions with host responses, but some pathogens benefit from the stimulation of inflammatory reactions. This review will describe the spectrum of strategies used by microbes to avoid or provoke activation of the host's immune response as well as our current understanding of the role this immunomodulatory interference plays during microbial pathogenesis.

English discourse particles

Abstract: There are few aspects of language which are more problematic than its discourse particles. The present study of discourse particles draws upon data from the London-Lund Corpus to show how the methods and tools of corpora can sharpen their description. The first part of the book provides a picture of the state of the art in discourse particle studies and introduces the theory and methodology for the analysis in the second part of the book. Discourse particles are analysed as elements which have been grammaticalised and as a result have certain properties and uses. The importance of linguistic and contextual cues such as text type, position in the discourse, prosody and collocation for analysing discourse particles is illustrated. The following chapters deal with specific discourse particles ( now , oh, just, sort of, and that sort of thing, actually ) on the basis of their empirical analysis in the London-Lund Corpus. Examples and extended extracts from many different text types are provided to illustrate what discourse particles are doing in discourse.

The problem of chronic refractory angina - Report from the ESC Joint Study Group on the Treatment of Refractory Angina

Abstract: It has been recognized that there is a group of patients with severe disabling angina and coronary artery disease who are refractory to conventional forms of treatment. Although this issue has already been debated at the level of the National Societies, we felt that it was appropriate to also tackle it at the European level. This is particularly important in view of the rapid pace of growth of this problem and the lack of a standardized approach. This has encouraged the development of a variety of treatments that vary considerably in terms of cost-effectiveness and safety and require proper validation procedures. The aim of this paper is to draw attention to the problem and start a process that will lead to improvement and harmonization of the care of patients with refractory angina.

Vagus-nerve stimulation for the treatment of epilepsy

Abstract: Summary Vagus-nerve stimulation (VNS) is now an accepted treatment for patients with refractory epilepsy. There have been many studies suggesting that VNS affects the brain in such areas as the thalamus and other limbic structures. In addition, there is some evidence that norepinephrine is important in the prophylactic antiseizure effects of VNS. The efficacy of VNS has been established for partial seizure types, even in refractory patients who did not respond to surgical treatment for epilepsy. There are also data, from open-label studies, that suggest efficacy in other seizure types. Therefore, VNS seems to be a broad-spectrum treatment for epilepsy. Improvement is not immediate but increases over 18–24 months of treatment. Most studies report subjective improvements in various quality-of-life measurements during treatment with VNS—objective trials have confirmed this observation. Side-effects are mainly stimulation related and reversible and they tend to decrease over time. They are generally mild to moderate and seldom necessitate the removal of the device. No idiosyncratic side-effects have been reported in 12 years of experience, and VNS does not interact with antiepileptic drugs. Most adverse events are predictable and related to the specific stimulation regimen. VNS does not have cognitive and systemic side-effects and can, therefore, be a valuable treatment approach even for patients who have poor tolerance of antiepileptic drugs.

Models of white matter injury: comparison of infectious, hypoxic-ischemic, and excitotoxic insults.

Abstract: White matter damage (WMD) in preterm neonates is strongly associated with adverse outcome. The etiology of white matter injury is not known but clinical data suggest that ischemia-reperfusion and/or infection-inflammation are important factors. Furthermore, antenatal infection seems to be an important risk factor for brain injury in term infants. In order to explore the pathophysiological mechanisms of WMD and to better understand how infectious agents may affect the vulnerability of the immature brain to injury, numerous novel animal models have been developed over the past decade. WMD can be induced by antenatal or postnatal administration of microbes (E. coli or Gardnerella vaginalis), virus (border disease virus) or bacterial products (lipopolysaccharide, LPS). Alternatively, various hypoperfusion paradigms or administration of excitatory amino acid receptor agonists (excitotoxicity models) can be used. Irrespective of which insult is utilized, the maturational age of the CNS and choice of species seem critical. Generally, lesions with similarity to human WMD, with respect to distribution and morphological characteristics, are easier to induce in gyrencephalic species (rabbits, dogs, cats and sheep) than in rodents. Recently, however, models have been developed in rats (PND 1-7), using either bilateral carotid occlusion or combined hypoxia-ischemia, that produce predominantly white matter lesions. LPS is the infectious agent most often used to produce WMD in immature dogs, cats, or fetal sheep. The mechanism whereby LPS induces brain injury is not completely understood but involves activation of toll-like receptor 4 on immune cells with initiation of a generalized inflammatory response resulting in systemic hypoglycemia, perturbation of coagulation, cerebral hypoperfusion, and activation of inflammatory cells in the CNS. LPS and umbilical cord occlusion both produce WMD with quite similar distribution in 65% gestational sheep. The morphological appearance is different, however, with a more pronounced infiltration of inflammatory cells into the brain and focal microglia/macrophage ("inflammatory WMD") in response to LPS compared to hypoperfusion evoking a more diffuse microglial response usually devoid of cellular infiltrates ("ischemic WMD"). Furthermore, low doses of LPS that by themselves have no adverse effects in 7-day-old rats (maturation corresponding to the near term human fetus), dramatically increase brain injury to a subsequent hypoxic-ischemic challenge, implicating that bacterial products can sensitize the immature CNS. Contrary to this finding, other bacterial agents like lipoteichoic acid were recently shown to induce tolerance of the immature brain suggesting that the innate immune system may respond differently to various ligands, which needs to be further explored.

Dental treatment, dental fear and behaviour management problems in children with severe enamel hypomineralization of their permanent first molars.

Abstract: Summary. Objectives. To assess the demand for restorative treatment, dental anxiety and dental behaviour management problems among children with severe hypomineralization of their first molars (MIH). Design. Case control study. Sample and methods. Data were compiled from the dental records of 32 9-year-old children with severe enamel hypomineralization of their first molars and from 41 controls of the same age group concerning dental health, a number of restorative treatments, use of local anaesthesia and clinical behaviour management problems (BMP). A questionnaire containing specific questions on children’s experiences of dental care and the Children’s Fear Survey Schedule – Dental Subscale (CFSS-DS), was answered by the parents. Results. The children in the study group had undergone dental treatment of their first molars nearly 10 times as often as the children in the control group. Repeated treatments of these teeth at brief intervals were common. The dental treatment was often undertaken without the use of local anaesthesia, and BMP, and dental fear and anxiety (DFA) were more common than in the controls. Conclusions. Children with severe enamel hypomineralization of their first molars had had to undergo a considerable amount of dental treatment. It is reasonable to assume that experiences of pain and discomfort on repeated occasions were related to the occurrence of BMP in patients with MIH. An early treatment planning and prognostication based on increased knowledge of hypomineralized first molars is desirable. Local anaesthesia and other pain-reducing techniques, e.g. sedation, should be used when treating these teeth. Extraction should be considered in cases of extensive disintegration of the crown, in cases of frequently repeated treatments or when pulpal symptoms are hard to cure.

Endothelium-specific platelet-derived growth factor-B ablation mimics diabetic retinopathy.

Abstract: Loss of pericytes from the capillary wall is a hallmark of diabetic retinopathy, however, the pathogenic significance of this phenomenon is unclear. In previous mouse gene knockout models leading to pericyte deficiency, prenatal lethality has so far precluded analysis of postnatal consequences in the retina. We now report that endothelium-restricted ablation of platelet-derived growth factor-B generates viable mice with extensive inter- and intra-individual variation in the density of pericytes throughout the CNS. We found a strong inverse correlation between pericyte density and the formation of a range of retinal microvascular abnormalities strongly reminiscent of those seen in diabetic humans. Proliferative retinopathy invariably developed when pericyte density was <50% of normal. Our data suggest that a reduction of the pericyte density is sufficient to cause retinopathy in mice, implying that pericyte loss may also be a causal pathogenic event in human diabetic retinopathy.

Economic freedom and growth: decomposing the effects

Abstract: Most studies of the relation between economic freedom andgrowth of GDP have found a positive relation One problem inthis area is the choice of economic freedom measure A singlemeasure does not reflect the complex economic environment anda highly aggregated index makes it difficult to draw policyconclusions In this paper we investigate what specific typesof economic freedom measures that are important for growthThe robustness of the results is carefully analysed since thepotential problem with multicollinearity is one of thenegative effects of decomposing an index The results showthat economic freedom does matter for growth This does notmean that increasing economic freedom, defined in generalterms, is good for economic growth since some of thecategories in the index are insignificant and some of thesignificant variables have negative effects

Regulation of σ factor competition by the alarmone ppGpp

Abstract: Many regulons controlled by alternative c factors, including cs and c32, are poorly induced in cells lacking the alarmone ppGpp. We show that ppGpp is not absolutely required for the activity of cs ...

Burden of illness and suicide in elderly people: case-control study

Abstract: Objectives: To study the association between physical illness and suicide in elderly people. Design: Case-control with illness determined from interviews with relatives of people who committed suicide and with control participants and from medical records. Setting: Gothenburg and two surrounding counties (210 703 people aged 65 years and over). Participants: Consecutive records of people who had committed suicide and had undergone forensic examination (46 men, 39 women) and living control participants from the tax register (84 men, 69 women). Main outcome measures: Physical illness rated in 13 organ systems according to the cumulative illness rating scale-geriatrics; serious physical illness (organ category score 3 or 4); overall score for burden of physical illness. Results: Visual impairment (odds ratio 7.0, 95% confidence interval 2.3 to 21.4), neurological disorders (3.8, 1.5 to 9.4), and malignant disease (3.4, 1.2 to 9.8) were associated with increased risk for suicide. Serious physical illness in any organ category was an independent risk factor for suicide in the multivariate regression model (6.4, 2.0 to 20.0). When the sexes were analysed separately, serious physical illness was associated with suicide in men (4.2, 1.8 to 9.5) as was high burden of physical illness (2.8, 1.2 to 6.5). Such associations were not seen in women, possibly because of the small sample size. Conclusions: Visual impairment, neurological disorders, and malignant disease were independently associated with increased risk of suicide in elderly people. Serious physical illness may be a stronger risk factor for suicide in men than in women.