Photodynamic therapy of prostate cancer by means of 5-aminolevulinic acid-induced protoporphyrin IX - In vivo experiments on the dunning rat tumor model

Objective: In order to expand the use of photodynamic therapy (PDT) in the treatment of prostate carcinoma (PCA), the aim of this study was to evaluate PDT by means of 5-aminolevulinic acid (5-ALA)-induced protoporphyrin IX ( PPIX) in an in vivo tumor model. Methods: The model used was the Dunning R3327 tumor. First of all, the pharmacokinetics and the localization of PPIX were obtained using fluorescence measurement techniques. Thereafter, PDT using 150 mg 5-ALA/kg b.w.i.v. was performed by homogenous irradiation of the photosensitized tumor (diode laser lambda = 633 nm). The tumors necrosis was determined histopathologically. Results: The kinetics of PPIX fluorescence revealed a maximum intensity in the tumor tissue within 3 and 4.5 h post-application of 5-ALA. At this time, specific PPIX fluorescence could be localized selectively in the tumor cells. The PDT-induced necrosis (n = 18) was determined to be 94 B 12% (range 60-100%), while the necrosis of the controls ( n = 12) differs significantly (p < 0.01), being less than 10%. Conclusion: These first in vivo results demonstrate the effective potential of 5-ALA-mediated PDT on PCA in an animal model. Copyright (C) 2004 S. Karger AG, Basel

Histometric data obtained by in vivo confocal laser scanning microscopy in patients with systemic sclerosis

BACKGROUND: It would be a benefit if time-saving, non-invasive methods could give hints for diagnosing systemic sclerosis. To investigate the skin of patients with systemic sclerosis using confocal laser scanning microscopy in vivo and to develop histometric parameters to describe characteristic cutaneous changes of systemic sclerosis observed by this new technique, we conducted an exploratory study. MATERIALS AND METHODS: Fifteen patients with systemic sclerosis treated with extracorporal photopheresis were compared with 15 healthy volunteers and 10 patients with other disorders also treated with extracorporal photopheresis. All subjects were investigated using confocal laser scanning microscopy in vivo. RESULTS: Micromorphologic characteristics of skin of patients with systemic sclerosis and measuring parameters for melanisation, epidermal hypotrophy, and fibrosis for dislocation of capillaries by collagen deposits in the papillary dermis were evaluated. An interesting finding was an increased thickness of the tissue in the dermal papillae superior to the first dermal papilla vessel. It was also possible to reproduce characteristic histologic features by confocal laser scanning microscopy in vivo. Histometric parameters for fibrosis and vascular features developed in this study showed significant differences in patients with systemic sclerosis compared to controls. CONCLUSIONS: Although the predominant histopathological features in systemic sclerosis are findings of the reticular dermis and the subcutis, and in histopathological investigation the epidermis seems to remain unaffected by the disease, we have demonstrate some characteristic differences in the epidermis and papillary dermis by confocal laser scanning microscopy in vivo. Some of them have not been described so far. However, to use this technique as a tool for diagnosis and/or staging of systemic sclerosis, further studies are needed investigating the sensitivity and specificity of the histometric parameters developed in this study

Integrated global assessment of the natural forest carbon potential

Forests are a substantial terrestrial carbon sink, but anthropogenic changes in land use and climate have considerably reduced the scale of this system1. Remote-sensing estimates to quantify carbon losses from global forests2–5 are characterized by considerable uncertainty and we lack a comprehensive ground-sourced evaluation to benchmark these estimates. Here we combine several ground-sourced6 and satellitederived approaches2,7,8 to evaluate the scale of the global forest carbon potential outside agricultural and urban lands. Despite regional variation, the predictions demonstrated remarkable consistency at a global scale, with only a 12% difference between the ground-sourced and satellite-derived estimates. At present, global forest carbon storage is markedly under the natural potential, with a total deficit of 226 Gt (model range = 151–363 Gt) in areas with low human footprint. Most (61%, 139 Gt C) of this potential is in areas with existing forests, in which ecosystem protection can allow forests to recover to maturity. The remaining 39% (87 Gt C) of potential lies in regions in which forests have been removed or fragmented. Although forests cannot be a substitute for emissions reductions, our results support the idea2,3,9 that the conservation, restoration and sustainable management of diverse forests offer valuable contributions to meeting global climate and biodiversity targets.EEA Santa CruzFil: Mo, Lidong. Institute of Integrative Biology. ETH Zurich (Swiss Federal Institute of Technology); SuizaFil: Zohner, Constantin M. Institute of Integrative Biology. ETH Zurich (Swiss Federal Institute of Technology); SuizaFil: Reich, Peter B. University of Minnesota. Department of Forest Resources; Estados UnidosFil: Reich, Peter B. Western Sydney University. Hawkesbury Institute for the Environment; Australia.Fil: Reich, Peter B. University of Michigan. Institute for Global Change Biology; Estados UnidosFil: Liang, Jingjing. Purdue University. Department of Forestry and Natural Resources; Estados UnidosFil: de-Miguel, Sergio. University of Lleida. Department of Agricultural and Forest Sciences and Engineering; EspañaFil: de-Miguel, Sergio. Joint Research Unit CTFC - AGROTECNIO – CERCA; EspañaFil: Nabuurs, Gert-Jan. Wageningen University and Research; Países BajosFil: Renner, Susanne S. Washington University. Department of Biology; Estados UnidosFil: van den Hoogen, Johan. Institute of Integrative Biology. ETH Zurich (Swiss Federal Institute of Technology); SuizaFil: Araza, Arnan. Wageningen University and Research; Países BajosFil: Herold, Martin. Helmholtz GFZ German Research Centre for Geosciences. Remote Sensing and Geoinformatics Section; Alemania.Fil: Peri, Pablo Luis. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Santa Cruz; Argentina.Fil: Peri, Pablo Luis. Universidad Nacional de la Patagonia Austral.; Argentina.Fil: Peri, Pablo Luis. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina.Fil: Crowther, Thomas W. Institute of Integrative Biology. ETH Zurich (Swiss Federal Institute of Technology); Suiz

Massive migration from the steppe is a source for Indo-European languages in Europe

We generated genome-wide data from 69 Europeans who lived between 8,000-3,000 years ago by enriching ancient DNA libraries for a target set of almost four hundred thousand polymorphisms. Enrichment of these positions decreases the sequencing required for genome-wide ancient DNA analysis by a median of around 250-fold, allowing us to study an order of magnitude more individuals than previous studies and to obtain new insights about the past. We show that the populations of western and far eastern Europe followed opposite trajectories between 8,000-5,000 years ago. At the beginning of the Neolithic period in Europe, ~8,000-7,000 years ago, closely related groups of early farmers appeared in Germany, Hungary, and Spain, different from indigenous hunter-gatherers, whereas Russia was inhabited by a distinctive population of hunter-gatherers with high affinity to a ~24,000 year old Siberian6 . By ~6,000-5,000 years ago, a resurgence of hunter-gatherer ancestry had occurred throughout much of Europe, but in Russia, the Yamnaya steppe herders of this time were descended not only from the preceding eastern European hunter-gatherers, but from a population of Near Eastern ancestry. Western and Eastern Europe came into contact ~4,500 years ago, as the Late Neolithic Corded Ware people from Germany traced ~3/4 of their ancestry to the Yamnaya, documenting a massive migration into the heartland of Europe from its eastern periphery. This steppe ancestry persisted in all sampled central Europeans until at least ~3,000 years ago, and is ubiquitous in present-day Europeans. These results provide support for the theory of a steppe origin of at least some of the Indo-European languages of Europe

G2019S mutation in the leucine-rich repeat kinase 2 gene is not associated with multiple system atrophy

Multiple system atrophy (MSA) is characterized clinically by Parkinsonism, cerebellar dysfunction, and autonomic impairment. Multiple mutations in the LRRK2 gene are associated with parkinsonian disorders, and the most common one, the G2019S mutation, has been found in ∼1% of sporadic cases of Parkinsonism. In a well-characterized cohort of 136 subjects with probable MSA and 110 neurologically evaluated control subjects, none carried the G2019S mutation. We conclude that the G2019S mutation in the LRRK2 gene is unlikely to be associated with MSA. © 2007 Movement Disorder SocietyPeer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/56014/1/21343_ftp.pd

A Re-Appraisal of the Early Andean Human Remains from Lauricocha in Peru

The discovery of human remains from the Lauricocha cave in the Central Andean highlands in the 1960’s provided the first direct evidence for human presence in the high altitude Andes. The skeletons found at this site were ascribed to the Early to Middle Holocene and represented the oldest known population of Western South America, and thus were used in several studies addressing the early population history of the continent. However, later excavations at Lauricocha led to doubts regarding the antiquity of the site. Here, we provide new dating, craniometric, and genetic evidence for this iconic site. We obtained new radiocarbon dates, generated complete mitochondrial genomes and nuclear SNP data from five individuals, and re-analyzed the human remains of Lauricocha to revise the initial morphological and craniometric analysis conducted in the 1960’s. We show that Lauricocha was indeed occupied in the Early to Middle Holocene but the temporal spread of dates we obtained from the human remains show that they do not qualify as a single contemporaneous population. However, the genetic results from five of the individuals fall within the spectrum of genetic diversity observed in pre-Columbian and modern Native Central American populations

Concept of the Munich/Augsburg Consortium Precision in Mental Health for the German Center of Mental Health

The Federal Ministry of Education and Research (BMBF) issued a call for a new nationwide research network on mental disorders, the German Center of Mental Health (DZPG). The Munich/Augsburg consortium was selected to participate as one of six partner sites with its concept “Precision in Mental Health (PriMe): Understanding, predicting, and preventing chronicity.” PriMe bundles interdisciplinary research from the Ludwig-Maximilians-University (LMU), Technical University of Munich (TUM), University of Augsburg (UniA), Helmholtz Center Munich (HMGU), and Max Planck Institute of Psychiatry (MPIP) and has a focus on schizophrenia (SZ), bipolar disorder (BPD), and major depressive disorder (MDD). PriMe takes a longitudinal perspective on these three disorders from the at-risk stage to the first-episode, relapsing, and chronic stages. These disorders pose a major health burden because in up to 50% of patients they cause untreatable residual symptoms, which lead to early social and vocational disability, comorbidities, and excess mortality. PriMe aims at reducing mortality on different levels, e.g., reducing death by psychiatric and somatic comorbidities, and will approach this goal by addressing interdisciplinary and cross-sector approaches across the lifespan. PriMe aims to add a precision medicine framework to the DZPG that will propel deeper understanding, more accurate prediction, and personalized prevention to prevent disease chronicity and mortality across mental illnesses. This framework is structured along the translational chain and will be used by PriMe to innovate the preventive and therapeutic management of SZ, BPD, and MDD from rural to urban areas and from patients in early disease stages to patients with long-term disease courses. Research will build on platforms that include one on model systems, one on the identification and validation of predictive markers, one on the development of novel multimodal treatments, one on the regulation and strengthening of the uptake and dissemination of personalized treatments, and finally one on testing of the clinical effectiveness, utility, and scalability of such personalized treatments. In accordance with the translational chain, PriMe’s expertise includes the ability to integrate understanding of bio-behavioral processes based on innovative models, to translate this knowledge into clinical practice and to promote user participation in mental health research and care