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991.
Anja Ulmer Klaus Dietz Isabelle Hodak Bernhard Polzer Sebastian Scheitler Murat Yildiz Zbigniew Czyz Petra Lehnert Tanja Fehm Christian Hafner Stefan Schanz Martin R?cken Claus Garbe Helmut Breuninger Gerhard Fierlbeck Christoph A. Klein 《PLoS medicine》2014,11(2)
Background
Sentinel lymph node spread is a crucial factor in melanoma outcome. We aimed to define the impact of minimal cancer spread and of increasing numbers of disseminated cancer cells on melanoma-specific survival.Methods and Findings
We analyzed 1,834 sentinel nodes from 1,027 patients with ultrasound node-negative melanoma who underwent sentinel node biopsy between February 8, 2000, and June 19, 2008, by histopathology including immunohistochemistry and quantitative immunocytology. For immunocytology we recorded the number of disseminated cancer cells (DCCs) per million lymph node cells (DCC density [DCCD]) after disaggregation and immunostaining for the melanocytic marker gp100. None of the control lymph nodes from non-melanoma patients (n = 52) harbored gp100-positive cells. We analyzed gp100-positive cells from melanoma patients by comparative genomic hybridization and found, in 45 of 46 patients tested, gp100-positive cells displaying genomic alterations. At a median follow-up of 49 mo (range 3–123 mo), 138 patients (13.4%) had died from melanoma. Increased DCCD was associated with increased risk for death due to melanoma (univariable analysis; p<0.001; hazard ratio 1.81, 95% CI 1.61–2.01, for a 10-fold increase in DCCD + 1). Even patients with a positive DCCD ≤3 had an increased risk of dying from melanoma compared to patients with DCCD = 0 (p = 0.04; hazard ratio 1.63, 95% CI 1.02–2.58). Upon multivariable testing DCCD was a stronger predictor of death than histopathology. The final model included thickness, DCCD, and ulceration (all p<0.001) as the most relevant prognostic factors, was internally validated by bootstrapping, and provided superior survival prediction compared to the current American Joint Committee on Cancer staging categories.Conclusions
Cancer cell dissemination to the sentinel node is a quantitative risk factor for melanoma death. A model based on the combined quantitative effects of DCCD, tumor thickness, and ulceration predicted outcome best, particularly at longer follow-up. If these results are validated in an independent study, establishing quantitative immunocytology in histopathological laboratories may be useful clinically. Please see later in the article for the Editors'' Summary 相似文献992.
Bernd Gröttrup Helmut Heinsen Katrin Marcus Helmut E. Meyer Young Mok Park Lea T. Grinberg 《Proteomics》2014,14(11):1305-1307
The HUPO Brain Proteome Project (HUPO BPP) held its 20th workshop in Yokohama, Japan, September 15, 2013. The focus of the autumn workshop was on new insights and prospects of neurodegenerative diseases. 相似文献
993.
Giuseppe Villani Igor Shevelev Eleonora Orlando Helmut Pospiech Juhani E. Syvaoja Enni Markkanen Ulrich Hubscher Nicolas Tanguy Le Gac 《PloS one》2014,9(4)
DNA polymerase ε (pol ε) is believed to be the leading strand replicase in eukaryotes whereas pols λ and β are thought to be mainly involved in re-synthesis steps of DNA repair. DNA elongation by the human pol ε is halted by an abasic site (apurinic/apyrimidinic (AP) site). We have previously reported that human pols λ, β and η can perform translesion synthesis (TLS) of an AP site in the presence of pol ε. In the case of pol λ and β, this TLS requires the presence of a gap downstream from the product synthetized by the ε replicase. However, since these studies were conducted exclusively with a linear DNA template, we decided to test whether the structure of the template could influence the capacity of the pols ε, λ, β and η to perform TLS of an AP site. Therefore, we have investigated the replication of damaged “minicircle” DNA templates. In addition, replication of circular DNA requires, beyond DNA pols, the processivity clamp PCNA, the clamp loader replication factor C (RFC), and the accessory proteins replication protein A (RPA). Finally we have compared the capacity of unmodified versus monoubiquitinated PCNA in sustaining TLS by pols λ and η on a circular template. Our results indicate that in vitro gap-directed TLS synthesis by pols λ and β in the presence of pol ε, RPA and PCNA is unaffected by the structure of the DNA template. Moreover, monoubiquitination of PCNA does not affect TLS by pol λ while it appears to slightly stimulate TLS by pol η. 相似文献
994.
Harboring a large number of endemic species, the Alps and the Western Carpathians are considered as major centers of biodiversity. Nonetheless, the general opinion until the turn of the millennium was that both Central European mountain regions did not provide suitable habitat during the Last Glacial Maximum, but were colonized later from southern refuges. However, recent molecular genetic studies provide new evidence for peripheral Alpine refuges. We studied the phylogeography of the calciphilous land snail O. dolium across its distribution in the Alps and the Western Carpathians to assess the amount of intraspecific differentiation and to detect potential glacial refuges. A partial sequence of the mitochondrial COI was analyzed in 373 specimens from 135 sampling sites, and for a subset of individuals, partial sequences of the mitochondrial 16S and the nuclear histone H3 and H4 were sequenced. A molecular clock analysis was combined with a reconstruction of the species’ geographic range history to estimate how its lineages spread in the course of time. In order to obtain further information on the species’ past distribution, we also screened its extensive Pleistocene fossil record. The reconstruction of geographic range history suggests that O. dolium is of Western Carpathian origin and diversified already around the Miocene-Pliocene boundary. The fossil record supports the species’ presence at more than 40 sites during the last glacial and earlier cold periods, most of them in the Western Carpathians and the Pannonian Basin. The populations of O. dolium display a high genetic diversity with maximum intraspecific p-distances of 18.4% (COI) and 14.4% (16S). The existence of various diverged clades suggests the survival in several geographically separated refuges. Moreover, the sequence patterns provide evidence of multiple migrations between the Alps and the Western Carpathians. The results indicate that the Southern Calcareous Alps were probably colonized only during the Holocene. 相似文献
995.
Thorsten Müller Andreas Schrötter Christina Loosse Kathy Pfeiffer Carsten Theiss Marion Kauth Helmut E. Meyer Katrin Marcus 《Biochimica et Biophysica Acta - Proteins and Proteomics》2013,1834(1):387-394
The ternary complex consisting of AICD/FE65/TIP60 is thought to play a role in gene expression and was suggested to have a crucial impact in Alzheimer's disease. AICD is the intracellular subdomain of the amyloid precursor protein (APP) and able to bind the adapter protein FE65 and the histone acetyltransferase TIP60 setting up a nuclear dot-like phenotype. Within this work we readdressed the generation of the complex as a function of its compartments. Subsequently, we studied the proteome of AFT expressing cells vs. controls and identified Stathmin1 significantly down-regulated in AFT cells. Stathmin1 functions as an important regulatory protein of microtubule dynamics and was found associated with neurofibrillary tangles in brains of Alzheimer's disease patients. We validated our results using an independent label-free mass spectrometry based method using the same cell culture model. In a reversal model with diminished APP expression, caused by simultaneous knock-down of all three members of the APP family, we further confirmed our results, as Stathmin1 was regulated in an opposite fashion. We hypothesize that AICD-dependent deregulation of Stathmin1 causes microtubule disorganization, which might play an important role for the pathophysiology of Alzheimer's disease. 相似文献
996.
Helmut Rosemeyer Eva-Maria Stürenberg Piet Herdewijn 《Nucleosides, nucleotides & nucleic acids》2013,32(8-9):995-999
Four different series of nucleolipids or bola-nucleolipids were synthesized or re-synthesized. Most of the compounds were studied with respect to their gelation properties toward either water or aromatic, hetero-aromatic, and aliphatic hydrocarbons. Bola-nucleolipids 6 and 7 do not gelate any solvent tested, neither as sole additive nor by adding up to 10 wt% of a 1:1 mixture. The nucleolipid 22 carrying the antiviral acyclovir as a head group proved to be a potent organogelator for aromatic hydrocarbons such as toluene, but not for hetarenes, aliphatic hydrocarbons or water. The mono-tailed nucleolipid 24 exhibits excellent organogelator properties for both aromatic and aliphatic hydrocarbons. These were studied as a function of concentration and temperature. 相似文献
997.
Helmut Rosemeyer Natalya Ramzaeva Matthias Zulauf Horst Thomas Yaoming Chen Cathrin Mittelbach 《Nucleosides, nucleotides & nucleic acids》2013,32(7-9):1447-1451
Abstract Conformational analyses of the sugar moieties of a series of 7-(8)- substituted 7-deazapurine-2′-deoxynucleosides on the basis of vicinal [H,H] coupling constants is presented using the PSEUROT 6.0 program. 相似文献
998.
999.
Bos E SantAnna C Gnaegi H Pinto RF Ravelli RB Koster AJ de Souza W Peters PJ 《Journal of structural biology》2011,175(1):62-72
Cryo-ultramicrotomy can be used to obtain ultrathin cryo-sections from cryo-fixed or aldehyde-fixed cryo-protected vitreous biologic samples. For immuno-gold EM, cryo-sections are retrieved from the cryo-chamber on a droplet of a pick-up solution (paste-like and almost frozen) to which the sections attach. The sections are then placed on an EM specimen grid at room temperature. This procedure compromises the ultrastructure, resulting in folds, holes, and loss of the original material. In this paper we show the critical influence of humidity, stretching, and relief of compression during thawing of the sections. We show a new lift-up hinge device for semi-automated retrieval of cryo-sections that results in significantly improved section quality. This approach was also applied successfully to vitreous sections from high pressure frozen samples. An important advance is that these vitreous cryo-sections can now successfully be post-fixed and immunolabelled after thawing; this allows cryo-EM comparison with adjacent ribbons of sections still in the frozen hydrated state. These findings call for technical innovations aiming at automated cryo-ultramicrotomy in a fully controlled environment for improved localization of proteins within their 'close to native' cellular context and correlative electron cryo-tomography of consecutive ribbons of sections of one frozen hydrated sample. 相似文献
1000.
Gunda Thöming Birgit Pölitz Angela Kühne Helmut Saucke 《Agricultural and Forest Entomology》2011,13(2):121-130
- 1 A method for area‐wide risk assessment of pea moth infestation in commercial pea‐growing areas based on spatial and temporal analyses of pea moth abundance and the phenological distribution of pea fields was investigated.
- 2 In a commercial pea‐growing region in Saxony, Germany, all pea fields were identified, mapped and characterized, recording the pea plant phenology, pea moth flight and larval infestation of each field in the years 2006–2008.
- 3 The relationship between pea moth flight and pea plant phenology was studied in detail in small‐scale field experiments in Hesse, Germany, using different pea cultivars and sowing dates.
- 4 In the study area, the abundance of Cydia nigricana Fabricius (Lepidoptera: Tortricidae) in organic green peas increased linearly with the pea‐cropping area of the previous year in the surroundings of the current fields according to the continuous abundance index.
- 5 Considering solely the early flowering period (= early pea sowing dates) of the organic green peas, we calculated that a minimum distance of the current pea field to the nearest pea field of the previous year of 500 m was necessary to significantly reduce pea moth flight and larval infestation.
- 6 In small‐scale field experiments, a correlation between pea moth flight and larval investation, as well as the importance of the pea flower for the pea moth occurrence, was demonstrated.
- 7 The spatio‐temporal findings are discussed in relation to the development of a coincidence avoidance strategy in pea‐growing areas.