Comparing Basal Area Diameter Distributions Estimated by Tree Species and for the Entire Stock in a Mixed Stand

Summary

Analysis of the role of mobility-lifetime products in the performance of amorphous silicon p-i-n solar cells

An analytical model of an amorphous silicon p-i-n solar cell is presented to describe its photovoltaic behavior under short-circuit conditions. It has been developed from the analysis of numerical simulation results. These results reproduce the experimental illumination dependence of short-circuit resistance, which is the reciprocal slope of the I(V) curve at the short-circuit point. The recombination rate profiles show that recombination in the regions of charged defects near the p-i and i-n interfaces should not be overlooked. Based on the interpretation of the numerical solutions, we deduce analytical expressions for the recombination current and short-circuit resistance. These expressions are given as a function of an effective ¿¿ product, which depends on the intensity of illumination. We also study the effect of surface recombination with simple expressions that describe its influence on current loss and short-circuit resistance.

Antigen presentation in the lung: dendritic cells and macrophages.

Antigen presentation is a required prime event before T-cell activation can occur. Cells which constitutively express major histocompatibility antigen class I or II are responsible for presenting antigens. These are essentially alveolar macrophages (AM) residing mostly in the air spaces, and dendritic cells (DC), which create a tight surveillance network just below the epithelial cells of the airways and in the loose connective tissue around the vessels or in the pleura. AM are poor antigen presenting cells compared to DC. AM when encountering foreign particles or organisms may, however, influence the degree of activity or maturation of neighbouring DC, by releasing cytokines. Thus, we will describe how the innate immune processes may influence specific immunity and perhaps Th1 and Th2 differentiation. Following the description of the differences in phenotype and functions of AM and DC, we will provide data showing that in some pathological conditions, such as sarcoidosis, AM can acquire some specificities of DC.

Localization of HLA-A2.1-restricted T cell epitopes in the circumsporozoite protein of Plasmodium falciparum.

Localization of human MHC class I-restricted T cell epitopes in the circumsporozoite (CS) protein of the human parasite Plasmodium falciparum is an important objective in the development of antimalarial vaccines. To this purpose, we synthesized a series of overlapping synthetic 20-mer peptides, spanning the entire sequence of the 7G8 CS molecule except for the central repeat B cell domain. The P.f.CS peptides were first tested for their ability to bind to the human MHC class I HLA-A2.1 molecule on T2, a human cell line. Subsequently, the use of a series of shorter peptide analogues allowed us to determine the optimal A2.1 binding sequence present in several of the 20-mers. Binding P.f.CS peptides were further tested for their capacity to activate PBL from HLA-A2.1+ immune donors living in a malaria-endemic area. Specific IFN-gamma production was detected in the supernatant of cultures of PBL from exposed individuals. Cytotoxic T cell lines and clones were derived from the PBL of one responder, and their activity was shown to be HLA-A2.1-restricted and specific for the peptide 334-342 of the CS protein. In addition, double transgenic HLA-A2.1 x human beta 2-microglobulin mice were immunized with peptide 1-10 of the CS protein. T cells derived from immune lymph nodes displayed a peptide-specific HLA-A2.1-restricted cytolytic activity after one in vitro stimulation.

Die Behandlung von Acetabulumfrakturen bei geriatrischen Patienten mittels modifizierter Kabelcerclage und primärer Hüfttotalprothese. Erste Ergebnisse [Treatment of acetabular fractures in the elderly with primary total hip arthroplasty and modified cerclage. Early results]

This prospective study addresses early results of the treatment of acute acetabular fractures in elderly patients by total hip arthroplasty and cerclage wiring.Fifteen patients with an average age of 81 years were treated at our institution between February 1998 and December 2000. There were two transverse fractures, eight T-shaped fractures, two transverse fractures with associated posterior wall fracture, two posterior column fractures with associated posterior wall fracture, and one fracture of both columns. Treatment consisted of cerclage wiring of the fracture and primary non-cemented total hip replacement.All of the patients were followed for a mean of 36 months. Although there was one patient with three hip dislocations during the first 10 months after the operation, we found an excellent or good result for the entire group. During this relatively short follow-up period, we have not found a radiological loss of fracture reduction of more than 1 mm or a cup migration of more than 3.2 mm. All of the fractures healed and no loosening of the implant was evident.Primary total hip arthroplasty combined with internal fixation is a valid treatment option for acetabular fractures in the elderly. Preliminary results are convincing, but a bigger patient population and a longer follow-up time are necessary before we are able to draw final conclusions.

An integrated encyclopedia of DNA elements in the human genome.

The human genome encodes the blueprint of life, but the function of the vast majority of its nearly three billion bases is unknown. The Encyclopedia of DNA Elements (ENCODE) project has systematically mapped regions of transcription, transcription factor association, chromatin structure and histone modification. These data enabled us to assign biochemical functions for 80% of the genome, in particular outside of the well-studied protein-coding regions. Many discovered candidate regulatory elements are physically associated with one another and with expressed genes, providing new insights into the mechanisms of gene regulation. The newly identified elements also show a statistical correspondence to sequence variants linked to human disease, and can thereby guide interpretation of this variation. Overall, the project provides new insights into the organization and regulation of our genes and genome, and is an expansive resource of functional annotations for biomedical research.

Immune and stress responses covary with melanin-based coloration in the barn swallow

Eumelanin and pheomelanin are the main endogenous pigments in animals and melanin-based coloration has multiple functions. Melanization is associated with major life-history traits, including immune and stress response, possibly because of pleiotropic effects of genes that control melanogenesis. The net effects on pheo- versus eumelanization and other life-history traits may depend on the antagonistic effects of the genes that trigger the biosynthesis of either melanin form. Covariation between melanin-based pigmentation and fitness traits enforced by pleiotropic genes has major evolutionary implications particularly for socio-sexual communication. However, evidence from non-model organisms in the wild is limited to very few species. Here, we tested the hypothesis that melanin-based coloration of barn swallow (Hirundo rustica) throat and belly feathers covaries with acquired immunity and activation of the hypothalamic-pituitary-adrenal (HPA) axis, as gauged by corticosterone plasma levels. Individuals of both sexes with darker brownish belly feathers had weaker humoral immune response, while darker males had higher circulating corticosterone levels only when parental workload was experimentally reduced. Because color of belly feathers depends on both eu- and pheomelanin, and its darkness decreases with an increase in the concentration of eu- relative to pheomelanin, these results are consistent with our expectation that relatively more eu- than pheomelanized individuals have better immune response and smaller activation of the HPA-axis. Covariation of immune and stress response arose for belly but not throat feather color, suggesting that any function of color as a signal of individual quality or of alternative life-history strategies depends on plumage region.

Evolution of the P-type II ATPase gene family in the fungi and presence of structural genomic changes among isolates of Glomus intraradices.

BACKGROUND: The P-type II ATPase gene family encodes proteins with an important role in adaptation of the cell to variation in external K+, Ca2+ and Na2+ concentrations. The presence of P-type II gene subfamilies that are specific for certain kingdoms has been reported but was sometimes contradicted by discovery of previously unknown homologous sequences in newly sequenced genomes. Members of this gene family have been sampled in all of the fungal phyla except the arbuscular mycorrhizal fungi (AMF; phylum Glomeromycota), which are known to play a key-role in terrestrial ecosystems and to be genetically highly variable within populations. Here we used highly degenerate primers on AMF genomic DNA to increase the sampling of fungal P-Type II ATPases and to test previous predictions about their evolution. In parallel, homologous sequences of the P-type II ATPases have been used to determine the nature and amount of polymorphism that is present at these loci among isolates of Glomus intraradices harvested from the same field. RESULTS: In this study, four P-type II ATPase sub-families have been isolated from three AMF species. We show that, contrary to previous predictions, P-type IIC ATPases are present in all basal fungal taxa. Additionally, P-Type IIE ATPases should no longer be considered as exclusive to the Ascomycota and the Basidiomycota, since we also demonstrate their presence in the Zygomycota. Finally, a comparison of homologous sequences encoding P-type IID ATPases showed unexpectedly that indel mutations among coding regions, as well as specific gene duplications occur among AMF individuals within the same field. CONCLUSION: On the basis of these results we suggest that the diversification of P-Type IIC and E ATPases followed the diversification of the extant fungal phyla with independent events of gene gains and losses. Consistent with recent findings on the human genome, but at a much smaller geographic scale, we provided evidence that structural genomic changes, such as exonic indel mutations and gene duplications are less rare than previously thought and that these also occur within fungal populations.

Review: Contact sport-related chronic traumatic encephalopathy in the elderly: clinical expression and structural substrates.

A. Costanza, K. Weber, S. Gandy, C. Bouras, P. R. Hof, P. Giannakopoulos and A. Canuto (2011) Neuropathology and Applied Neurobiology37, 570-584 Contact sport-related chronic traumatic encephalopathy in the elderly: clinical expression and structural substrates Professional boxers and other contact sport athletes are exposed to repetitive brain trauma that may affect motor functions, cognitive performance, emotional regulation and social awareness. The term of chronic traumatic encephalopathy (CTE) was recently introduced to regroup a wide spectrum of symptoms such as cerebellar, pyramidal and extrapyramidal syndromes, impairments in orientation, memory, language, attention, information processing and frontal executive functions, as well as personality changes and behavioural and psychiatric symptoms. Magnetic resonance imaging usually reveals hippocampal and vermis atrophy, a cavum septum pellucidum, signs of diffuse axonal injury, pituitary gland atrophy, dilated perivascular spaces and periventricular white matter disease. Given the partial overlapping of the clinical expression, epidemiology and pathogenesis of CTE and Alzheimer's disease (AD), as well as the close association between traumatic brain injuries (TBIs) and neurofibrillary tangle formation, a mixed pathology promoted by pathogenetic cascades resulting in either CTE or AD has been postulated. Molecular studies suggested that TBIs increase the neurotoxicity of the TAR DNA-binding protein 43 (TDP-43) that is a key pathological marker of ubiquitin-positive forms of frontotemporal dementia (FTLD-TDP) associated or not with motor neurone disease/amyotrophic lateral sclerosis (ALS). Similar patterns of immunoreactivity for TDP-43 in CTE, FTLD-TDP and ALS as well as epidemiological correlations support the presence of common pathogenetic mechanisms. The present review provides a critical update of the evolution of the concept of CTE with reference to its neuropathological definition together with an in-depth discussion of the differential diagnosis between this entity, AD and frontotemporal dementia.

SEPT4, a p53 target gene product, implicates p 53 in the regulation of exocytosis

Résumé : Le cancer, qui est responsable d'un quart des décès en Suisse, exhibe un état cellulaire désordonné, qui lui-même, est la conséquence d'un dérèglement des gènes. Le gène le plus fréquemment altéré, dans les cas de cancers humains, est p53. Ce gène encode un facteur de transcription, impliqué dans la régulation de nombreux gènes impliqués dans le cycle cellulaire, l'apoptose ou la différenciation. Notre laboratoire a récemment identifié seize nouveaux gènes, dont l'expression est régulée par p53, parmi lesquels sept4, su jet de cette thèse. La protéine 5EPT4 appartient à la famille des septines, qui est impliquée dans la cytokinèse. Dans ce travail, nous avons confirmé la régulation de l'expression de sept4 par p53 dans des tissus de souris, et étonnamment, seul un des deux promoteurs du gène sept4 est contrôlé par p53. En outre, l'approche immunohistologique nous a permis de supposer une implication de la protéine SEPT4 dans le mécanisme de l'exocytose. Cette hypothèse a été confirmée par l'interaction de SEPT4 avec la protéine syntaxine 1A, et par son activité inhibitrice sur la sécrétion stimulée. En élargissant l'étude de la protéine SEPT4, nous avons découvert que celle-ci avait comme partenaire fonctionnel, la protéine Pinl, une enzyme qui catalyse l'isomérisation cis-trans du lien peptidique précédant une proline. bans ce contexte, nous avons démontré que l'interaction entre ces deux protéines reposait sur le domaine WW de Pinl, un type de domaine reconnaissant les motifs phosphoséryl-prolyl et phosphothréonyl-prolyl. Ce dernier résultat nous a conduit à examiner la phosphorylation de 5EPT4. Nous avons démontré que la partie N-terminale de SEPT4 était phosphorylée par la kinase Cdk5. La co¬expression de Cdk5 et de SEPT4 stimule la dégradation de SEPT4, indépendamment de la voie du protéasome. Ainsi, l'ensemble de nos observations fournissent l'évidence de l'engagement de la protéine SEPT4 dans la régulation de l'exocytose, et soutiennent le rôle de p53 dans le contrôle de l'exocytose, via SEPT4, ce qui constituerait un nouveau rôle fonctionnel pour ce gardien du génome. Summary: Cancer, which is responsible for a quarter of the deaths in Switzerland, exhibits a disordered cellular state, which itself, is the consequence of an altered state of genes. The most frequently altered gene in human cancer is p53. This gene encodes a transcription factor, implicated in the regulation of numerous genes involved in cell cycle, apoptosis or differentiation. Our laboratory has recently identified sixteen new genes whose expression is regulated by p53, amongst them septin 4, which is the subject of this thesis. The SEPT4 protein belongs to the septin family which is implicated in cytokinesis. In the present work, we have confirmed the regulation of sept4 expression by p53 in mouse tissues, and surprisingly, only one of the two sept4 promoters is regulated by p53. In addition, the immunohistologic approach enabled us to suppose a role of SEPT4 in exocytosis. This assumption was confirmed by the interaction of SEPT4 with syntaxin 1A, and by its inhibiting activity on stimulated secretion. By widening the analysis of SEPT4, we identified Pin1 as an interacting protein. Pin1 is an enzyme which catalyzes the cis-trans isomerization of the peptide bond preceding a proline residue. In this context, we showed that the interaction between these two proteins depends on the WW domain of Pin 1. This domain has been shown to function as a phosphoserine- or phosphothreonine¬binding module. This last result prompted us to examine phosphorylation of SEPT4. We demonstrated that the N-terminal portion of SEPT4 was phosphorylated by the Cdk5 kinase. The co-expression of Cdk5 with 5EPT4 stimulates SEPT4 degradation, independently of the proteasome pathway. Thus, these observations provide evidence for the engagement of SEPT4 in the regulation of exocytosis, and supports the role of p53 in the control of exocytosis, via SEPT4, which constitutes a new functional role for this guardian of the genome.

Prevalence, awareness and control of diabetes in the Seychelles and relationship with excess body weight.

BACKGROUND: The evidence for a "diabesity" epidemic is accumulating worldwide but population-based data are still scarce in the African region. We assessed the prevalence, awareness and control of diabetes (DM) in the Seychelles, a rapidly developing country in the African region. We also examined the relationship between body mass index, fasting serum insulin and DM. METHODS: Examination survey in a sample representative of the entire population aged 25-64 of the Seychelles, attended by 1255 persons (participation rate of 80.2%). An oral glucose tolerance test (OGTT) was performed in individuals with fasting blood glucose between 5.6 and 6.9 mmol/l. Diabetes mellitus (DM), impaired fasting glucose (IFG) and impaired glucose tolerance (IGT) were defined along criteria of the ADA. Prevalence estimates were standardized for age. RESULTS: The prevalence of DM was 11.5% and 54% of persons with DM were aware of having DM. Less than a quarter of all diabetic persons under treatment were well controlled for glycemia (HbA1c), blood pressure or LDL-cholesterol. The prevalence of IGT and IFG were respectively 10.4% and 24.2%. The prevalence of excess weight (BMI > or = 25 kg/m2) and obesity (BMI > or = 30 kg/m2) was respectively 60.1% and 25.0%. Half of all DM cases in the population could be attributed to excess weight. CONCLUSION: We found a high prevalence of DM and pre-diabetes in a rapidly developing country in the African region. The strong association between overweight and DM emphasizes the importance of weight control measures to reduce the incidence of DM in the population. High rates of diabetic persons not aware of having DM in the population and insufficient cardiometabolic control among persons treated for DM stress the need for intensifying health care for diabetes.

Peroxisome proliferator-activated receptor gamma is required in mature white and brown adipocytes for their survival in the mouse.

The peroxisome proliferator-activated receptor gamma (PPARgamma) mediates the activity of the insulin-sensitizing thiazolidinediones and plays an important role in adipocyte differentiation and fat accretion. The analysis of PPARgamma functions in mature adipocytes is precluded by lethality of PPARgamma(-/-) fetuses and tetraploid-rescued pups. Therefore we have selectively ablated PPARgamma in adipocytes of adult mice by using the tamoxifen-dependent Cre-ER(T2) recombination system. We show that mature PPARgamma-null white and brown adipocytes die within a few days and are replaced by newly formed PPARgamma-positive adipocytes, demonstrating that PPARgamma is essential for the in vivo survival of mature adipocytes, in addition to its well established requirement for their differentiation. Our data suggest that potent PPARgamma antagonists could be used to acutely reduce obesity.

Circadian clock-dependent and -independent rhythmic proteomes implement distinct diurnal functions in mouse liver.

Diurnal oscillations of gene expression controlled by the circadian clock underlie rhythmic physiology across most living organisms. Although such rhythms have been extensively studied at the level of transcription and mRNA accumulation, little is known about the accumulation patterns of proteins. Here, we quantified temporal profiles in the murine hepatic proteome under physiological light-dark conditions using stable isotope labeling by amino acids quantitative MS. Our analysis identified over 5,000 proteins, of which several hundred showed robust diurnal oscillations with peak phases enriched in the morning and during the night and related to core hepatic physiological functions. Combined mathematical modeling of temporal protein and mRNA profiles indicated that proteins accumulate with reduced amplitudes and significant delays, consistent with protein half-life data. Moreover, a group comprising about one-half of the rhythmic proteins showed no corresponding rhythmic mRNAs, indicating significant translational or posttranslational diurnal control. Such rhythms were highly enriched in secreted proteins accumulating tightly during the night. Also, these rhythms persisted in clock-deficient animals subjected to rhythmic feeding, suggesting that food-related entrainment signals influence rhythms in circulating plasma factors.

The FoxO3a gene is a key negative target of canonical Notch signalling in the keratinocyte UVB response.

Notch signalling has an important role in skin homeostasis, promoting keratinocyte differentiation and suppressing tumorigenesis. Here we show that this pathway also has an essential anti-apoptotic function in the keratinocyte UVB response. Notch1 expression and activity are significantly induced, in a p53-dependent manner, by UVB exposure of primary keratinocytes as well as intact epidermis of both mouse and human origin. The apoptotic response to UVB is increased by deletion of the Notch1 gene or down-modulation of Notch signalling by pharmacological inhibition or genetic suppression of 'canonical' Notch/CSL/MAML1-dependent transcription. Conversely, Notch activation protects keratinocytes against apoptosis through a mechanism that is not linked to Notch-induced cell cycle withdrawal or NF-kappaB activation. Rather, transcription of FoxO3a, a key pro-apoptotic gene, is under direct negative control of Notch/HERP transcription in keratinocytes, and upregulation of this gene accounts for the increased susceptibility to UVB of cells with suppressed Notch signalling. Thus, the canonical Notch/HERP pathway functions as a protective anti-apoptotic mechanism in keratinocytes through negative control of FoxO3a expression.