Showing papers by "University of Kiel published in 2000"
TL;DR: In this article, the authors provide microscopic evidence for a structured consortium of archaea and sulphate-reducing bacteria, which are identified by fluorescence in situ hybridization using specific 16S rRNA-targeted oligonucleotide probes.
Abstract: A large fraction of globally produced methane is converted to CO2 by anaerobic oxidation in marine sediments. Strong geochemical evidence for net methane consumption in anoxic sediments is based on methane profiles, radiotracer experiments and stable carbon isotope data. But the elusive microorganisms mediating this reaction have not yet been isolated, and the pathway of anaerobic oxidation of methane is insufficiently understood. Recent data suggest that certain archaea reverse the process of methanogenesis by interaction with sulphate-reducing bacteria. Here we provide microscopic evidence for a structured consortium of archaea and sulphate-reducing bacteria, which we identified by fluorescence in situ hybridization using specific 16S rRNA-targeted oligonucleotide probes. In this example of a structured archaeal-bacterial symbiosis, the archaea grow in dense aggregates of about 100 cells and are surrounded by sulphate-reducing bacteria. These aggregates were abundant in gas-hydrate-rich sediments with extremely high rates of methane-based sulphate reduction, and apparently mediate anaerobic oxidation of methane.
2,679 citations
University College London1, University of Oxford2, Sapienza University of Rome3, Catholic University of the Sacred Heart4, University of Tartu5, University of Kiel6, Trinity College, Dublin7, University of Palermo8, University of Cagliari9, University of Plymouth10, Newcastle University11, Aristotle University of Thessaloniki12, Charles University in Prague13, University of Chicago14, University of Calabria15, Hebrew University of Jerusalem16, University of Copenhagen17, University of Baghdad18, University of Pavia19, University of Urbino20, University of Hamburg21
TL;DR: There has been substantial back-migration into the Near East, there was a founder effect or bottleneck associated with the Last Glacial Maximum, 20,000 years ago, and a way to account for multiple dispersals of common sequence types is suggested.
Abstract: Founder analysis is a method for analysis of nonrecombining DNA sequence data, with the aim of identification and dating of migrations into new territory. The method picks out founder sequence types in potential source populations and dates lineage clusters deriving from them in the settlement zone of interest. Here, using mtDNA, we apply the approach to the colonization of Europe, to estimate the proportion of modern lineages whose ancestors arrived during each major phase of settlement. To estimate the Palaeolithic and Neolithic contributions to European mtDNA diversity more accurately than was previously achievable, we have now extended the Near Eastern, European, and northern-Caucasus databases to 1,234, 2,804, and 208 samples, respectively. Both back-migration into the source population and recurrent mutation in the source and derived populations represent major obstacles to this approach. We have developed phylogenetic criteria to take account of both these factors, and we suggest a way to account for multiple dispersals of common sequence types. We conclude that (i) there has been substantial back-migration into the Near East, (ii) the majority of extant mtDNA lineages entered Europe in several waves during the Upper Palaeolithic, (iii) there was a founder effect or bottleneck associated with the Last Glacial Maximum, 20,000 years ago, from which derives the largest fraction of surviving lineages, and (iv) the immigrant Neolithic component is likely to comprise less than one-quarter of the mtDNA pool of modern Europeans.
965 citations
TL;DR: Findings indicate that LAMP-2 is critical for autophagy, and this theory is further substantiated by the finding that human Lamp-2 deficiency causing Danon's disease is associated with the accumulation of autophagic material in striated myocytes.
Abstract: Lysosome-associated membrane protein-2 (LAMP-2) is a highly glycosylated protein and an important constituent of the lysosomal membrane Here we show that LAMP-2 deficiency in mice increases mortality between 20 and 40 days of age The surviving mice are fertile and have an almost normal life span Ultrastructurally, there is extensive accumulation of autophagic vacuoles in many tissues including liver, pancreas, spleen, kidney and skeletal and heart muscle In hepatocytes, the autophagic degradation of long-lived proteins is severely impaired Cardiac myocytes are ultrastructurally abnormal and heart contractility is severely reduced These findings indicate that LAMP-2 is critical for autophagy This theory is further substantiated by the finding that human LAMP-2 deficiency causing Danon's disease is associated with the accumulation of autophagic material in striated myocytes
860 citations
TL;DR: The increase in sea level from the last glacial maximum has been derived from a siliciclastic system on the tectonically stable Sunda Shelf in Southeast Asia, and the record generally confirms sea-level reconstructions from coral reefs.
Abstract: The increase in sea level from the last glacial maximum has been derived from a siliciclastic system on the tectonically stable Sunda Shelf in Southeast Asia. The time from 21 to 14 thousand calendar years before the present has been poorly covered in other records. The record generally confirms sea-level reconstructions from coral reefs. The rise of sea level during meltwater pulse 1A was as much as 16 meters within 300 years (14.6 to 14.3 thousand years ago).
835 citations
TL;DR: In this paper, both chartist and fundamentalist strategies are considered with agents switching between both behavioural variants according to observed differences in pay-offs. But, the authors do not consider the effect of market makers on price changes.
Abstract: The finding of clustered volatility and ARCH effects is ubiquitous in financial data. This paper presents a possible explanation for this phenomenon within a multi-agent framework of speculative activity. In the model, both chartist and fundamentalist strategies are considered with agents switching between both behavioural variants according to observed differences in pay-offs. Price changes are brought about by a market maker reacting to imbalances between demand and supply. Most of the time, a stable and efficient market results. However, its usual tranquil performance is interspersed by sudden transient phases of destabilisation. An outbreak of volatility occurs if the fraction of agents using chartist techniques surpasses a certain threshold value, but such phases are quickly brought to an end by stabilising tendencies. Formally, this pattern can be understood as an example of a new type of dynamic behaviour known as "on-off intermittency" in physics literature. Statistical analysis of simulated time ...
740 citations
TL;DR: The problem of off label and unlicensed drug prescribing in children is a European problem that requires European action and is likely to affect children throughout Europe.
Abstract: Objective: To determine the extent of use of unlicensed and off label drugs in children in hospital in five European countries. Design: Prospective study of drugs administered to children in general paediatric medical wards over four weeks. Setting: Children9s wards in five hospitals (one each in the United Kingdom, Sweden, Germany, Italy, and the Netherlands). Subjects: Children aged 4 days to 16 years admitted to general paediatric medical wards. Main outcome measure: Proportion of drugs that were used in an unlicensed or off label manner. Results: 2262 drug prescriptions were administered to 624 children in the five hospitals. Almost half of all drug prescriptions (1036; 46%) were either unlicensed or off label. Of these 1036, 872 were off label and 164 were unlicensed. Over half of the patients (421; 67%) received an unlicensed or off label drug prescription. Conclusions: Use of off label or unlicensed drugs to treat children is widespread. This problem is likely to affect children throughout Europe and requires European action. Key messages Many drugs are not tested in children, which means that they are not specifically licensed for use in children Licensed drugs are often prescribed outside the terms of the product license (off label) in relation to age, indication, dose of frequency, route of administration, or formulation Over two thirds (67%) of 624 children admitted to wards in five European hospitals received drugs prescribed in an unlicensed or off label manner 39% of the 2262 drug prescriptions given to children were off label The problem of off label and unlicensed drug prescribing in children is a European problem that requires European action
737 citations
TL;DR: It is shown that the dominant RN- mutation in purebred Hampshire pigs carries a nonconservative substitution (R200Q) in the PRKAG3 gene, which encodes a muscle-specific isoform of the regulatory gamma subunit of adenosine monophosphate-activated protein kinase (AMPK).
Abstract: A high proportion of purebred Hampshire pigs carries the dominant RN- mutation, which causes high glycogen content in skeletal muscle. The mutation has beneficial effects on meat content but detrimental effects on processing yield. Here, it is shown that the mutation is a nonconservative substitution (R200Q) in the PRKAG3 gene, which encodes a muscle-specific isoform of the regulatory gamma subunit of adenosine monophosphate-activated protein kinase (AMPK). Loss-of-function mutations in the homologous gene in yeast (SNF4) cause defects in glucose metabolism, including glycogen storage. Further analysis of the PRKAG3 signaling pathway may provide insights into muscle physiology as well as the pathogenesis of noninsulin-dependent diabetes mellitus in humans, a metabolic disorder associated with impaired glycogen synthesis.
736 citations
TL;DR: Although CYC remains essential in the treatment of WG, it was administered as briefly as possible and under close surveillance to avoid permanent CYC-related morbidity, which can lead to serious therapeutic problems in chronic relapsing WG.
Abstract: Objective To examine the outcome in 155 consecutive patients with Wegener's granulomatosis (WG) followed up for a median of 7 years. Methods Treatment was adapted to the activity and extent of disease, with regular evaluation by an interdisciplinary team accompanied by group education about vasculitis. Results The estimated median survival time was 21.7 years (95% confidence interval [95% CI] 15.60-27.86). Twenty-two patients died; 19 deaths were attributable to WG and/or its treatment. Significant predictors of survival at diagnosis were age >50 years (hazard ratio [HR] 5.45, 95% CI 1.97-15.02), kidney involvement with impaired renal function (HR 5.42, 95% CI 1.76-16.68), and lung involvement (HR 3.75, 95% CI 1.26-11.16). At some stage, 142 patients received prednisone and cyclophosphamide (CYC), usually as daily CYC plus mesna as uroprotection, 50 patients received trimethoprim/sulfamethoxazole, and 45 received methotrexate. Complete remission was achieved in 83 of the 155 patients. One or more relapses occurred in 99 patients after either complete or partial remission. CYC-induced cystitis and myelodysplastic syndrome occurred in 17 and 11 patients, respectively. A cumulative dose of 100 gm or more of CYC resulted in a 2-fold greater risk of CYC-related morbidity than with lower CYC doses. Serious infections occurred in 41 patients. Conclusion An interdisciplinary approach to the care of 155 WG patients resulted in a median survival of >21 years. Kidney or lung involvement at diagnosis was predictive of a >3-fold higher mortality. Although CYC remains essential in the treatment of WG, it was administered as briefly as possible and under close surveillance to avoid permanent CYC-related morbidity, which can lead to serious therapeutic problems in chronic relapsing WG.
683 citations
TL;DR: A faunal record of sea-surface temperature (SST) variations off West Africa documents a series of abrupt, millennial-scale cooling events, which punctuated the Holocene warm period, documenting a strong, in-phase link between millennial- scale variations in high- and low-latitude climate during the Hololithic.
Abstract: A faunal record of sea-surface temperature (SST) variations off West Africa documents a series of abrupt, millennial-scale cooling events, which punctuated the Holocene warm period These events evidently resulted from increased southward advection of cooler temperate or subpolar waters to this subtropical location or from enhanced regional upwelling The most recent of these events was the Little Ice Age, which occurred between 1300 to 1850 AD, when subtropical SSTs were reduced by 3° to 4°C These events were synchronous with Holocene changes in subpolar North Atlantic SSTs, documenting a strong, in-phase link between millennial-scale variations in high- and low-latitude climate during the Holocene
677 citations
The Breast Cancer Research Foundation1, Oregon Health & Science University2, University of Düsseldorf3, University of Kiel4, St Mary's Hospital5, Maastricht University Medical Centre6, Utrecht University7, Erasmus University Rotterdam8, University of Iowa9, University of Oulu10, University of Florida11, St George's Hospital12, Osaka City University13, Ludwig Institute for Cancer Research14, Royal Victoria Infirmary15, University of Newcastle16
TL;DR: The susceptibility gene (CYLD) has been identified by detecting germline mutations in 21 cylindromatosis families and somatic mutations in 1 sporadic and 5 familialcylindromas, all mutations predict truncation or absence of the encoded protein.
Abstract: Familial cylindromatosis is an autosomal dominant genetic predisposition to multiple tumours of the skin appendages. The susceptibility gene (CYLD) has previously been localized to chromosome 16q and has the genetic attributes of a tumour-suppressor gene (recessive oncogene). Here we have identified CYLD by detecting germline mutations in 21 cylindromatosis families and somatic mutations in 1 sporadic and 5 familial cylindromas. All mutations predict truncation or absence of the encoded protein. CYLD encodes three cytoskeletal-associated-protein-glycine-conserved (CAP-GLY) domains, which are found in proteins that coordinate the attachment of organelles to microtubules. CYLD also has sequence homology to the catalytic domain of ubiquitin carboxy-terminal hydrolases (UCH).
644 citations
TL;DR: TRAM-34 (1-[(2-chlorophenyl)diphenylmethyl]-1H-pyrazole) inhibits the cloned and the native IKCa1 channel in human T lymphocytes with a K(d) of 20-25 nM and is 200- to 1,500-fold selective over other ion channels, suggesting that TRAM- 34 and related compounds may hold therapeutic promise as immunosuppressants.
Abstract: The antimycotic clotrimazole, a potent inhibitor of the intermediate-conductance calcium-activated K(+) channel, IKCa1, is in clinical trials for the treatment of sickle cell disease and diarrhea and is effective in ameliorating the symptoms of rheumatoid arthritis. However, inhibition of cytochrome P450 enzymes by clotrimazole limits its therapeutic value. We have used a rational design strategy to develop a clotrimazole analog that selectively inhibits IKCa1 without blocking cytochrome P450 enzymes. A screen of 83 triarylmethanes revealed the pharmacophore for channel block to be different from that required for cytochrome P450 inhibition. The "IKCa1-pharmacophore" consists of a (2-halogenophenyl)diphenylmethane moiety substituted by an unsubstituted polar pi-electron-rich heterocycle (pyrazole or tetrazole) or a -CN group, whereas cytochrome P450 inhibition absolutely requires the imidazole ring. A series of pyrazoles, acetonitriles, and tetrazoles were synthesized and found to selectively block IKCa1. TRAM-34 (1-[(2-chlorophenyl)diphenylmethyl]-1H-pyrazole) inhibits the cloned and the native IKCa1 channel in human T lymphocytes with a K(d) of 20-25 nM and is 200- to 1,500-fold selective over other ion channels. Using TRAM-34, we show that blocking IKCa1 in human lymphocytes, in the absence of P450-inhibition, results in suppression of mitogen-stimulated [(3)H]thymidine incorporation of preactivated lymphocytes with EC(50)-values of 100 nM-1 microM depending on the donor. Combinations of TRAM-34 and cyclosporin A are more effective in suppressing lymphocyte mitogenesis than either compound alone. Our studies suggest that TRAM-34 and related compounds may hold therapeutic promise as immunosuppressants.
TL;DR: The present state of knowledge in sialobiology, with an emphasis on my personal experience in this research area, is outlined including a discussion of necessary future work in this fascinating field of cell biology.
Abstract: Sialic acids are one of the most important molecules of life, since they occupy the terminal position on macromolecules and cell membranes and are involved in many biological and pathological phenomena. The structures of sialic acids, comprising a family of over 40 neuraminic acid derivatives, have been elucidated. However, many aspects of the regulation of their metabolism at the enzyme and gene levels, as well as of their functions remain mysterious. Sialic acids play a dual role, not only are they indispensable for the protection to and adaptation of life, but are also utilised by life-threatening infectious microorganisms. In this article the present state of knowledge in sialobiology, with an emphasis on my personal experience in this research area, is outlined including a discussion of necessary future work in this fascinating field of cell biology.
University of Leicester1, Estonian Biocentre2, University of Belgrade3, University of Porto4, University of Cambridge5, Guardia Civil6, Complutense University of Madrid7, University of Ferrara8, Umeå University9, Pompeu Fabra University10, Trinity College, Dublin11, University of Oslo12, Instituto Nacional de Saúde Dr. Ricardo Jorge13, Leiden University Medical Center14, Katholieke Universiteit Leuven15, Russian Academy16, University of Kiel17, Medical University of Łódź18, Edith Cowan University19, Humboldt University of Berlin20, University of Oxford21, National Academy of Sciences of Ukraine22, University of Rome Tor Vergata23, The Cyprus Institute of Neurology and Genetics24, Pasteur Institute25, University of Tartu26, La Trobe University27, Memorial Sloan Kettering Cancer Center28, University of Copenhagen29, University of Ljubljana30, Boğaziçi University31
TL;DR: These patterns retain a strong signal of expansion from the Near East but also suggest that the demographic history of Europe has been complex and influenced by other major population movements, as well as by linguistic and geographic heterogeneities and the effects of drift.
Abstract: Clinal patterns of autosomal genetic diversity within Europe have been interpreted in previous studies in terms of a Neolithic demic diffusion model for the spread of agriculture; in contrast, studies using mtDNA have traced many founding lineages to the Paleolithic and have not shown strongly clinal variation. We have used 11 human Y-chromosomal biallelic polymorphisms, defining 10 haplogroups, to analyze a sample of 3,616 Y chromosomes belonging to 47 European and circum-European populations. Patterns of geographic differentiation are highly nonrandom, and, when they are assessed using spatial autocorrelation analysis, they show significant clines for five of six haplogroups analyzed. Clines for two haplogroups, representing 45% of the chromosomes, are continentwide and consistent with the demic diffusion hypothesis. Clines for three other haplogroups each have different foci and are more regionally restricted and are likely to reflect distinct population movements, including one from north of the Black Sea. Principal-components analysis suggests that populations are related primarily on the basis of geography, rather than on the basis of linguistic affinity. This is confirmed in Mantel tests, which show a strong and highly significant partial correlation between genetics and geography but a low, nonsignificant partial correlation between genetics and language. Genetic-barrier analysis also indicates the primacy of geography in the shaping of patterns of variation. These patterns retain a strong signal of expansion from the Near East but also suggest that the demographic history of Europe has been complex and influenced by other major population movements, as well as by linguistic and geographic heterogeneities and the effects of drift.
TL;DR: The c-Jun N-terminal kinases and p38 kinases constitute together with extracellular signal-regulated kinases (ERKs) the family of MAP kinases, and there is raising evidence that JNKs are potent effectors of apoptosis or degeneration of neurons in vitro and in the brain.
TL;DR: In this paper, the effects of lichens on their mineral substrates can be attributed to both physical and chemical processes, such as hyphal penetration, expansion and contraction of lichen thallus, swelling action of the organic and inorganic salts originating from lichen activity.
Abstract: The evidence presented by numerous investigations of the interface between lichens and their rock substrates strongly suggests that the weathering of minerals can be accelerated by the growth of at least some lichen species. The effects of lichens on their mineral substrates can be attributed to both physical and chemical processes. The physical effects are reflected by the mechanical disruption of rocks caused by hyphal penetration, expansion and contraction of lichen thallus, swelling action of the organic and inorganic salts originating from lichen activity. Lichens also have significant impact in the chemical weathering of rocks by the excretion of various organic acids, particularly oxalic acid, which can effectively dissolve minerals and chelate metallic cations. As a result of the weathering induced by lichens, many rock-forming minerals exhibit extensive surface corrosion. The precipitation of poorly ordered iron oxides and amorphous alumino-silica gels, the neoformation of crystalline metal oxalates and secondary clay minerals have been frequently identified in a variety of rocks colonized by lichens in nature. For a better understanding of the impacts of lichens on environments, further work on the comprehensive involvement of the lichen effects on weathering of natural rocks, deterioration of building stones and stonework, and formation of primitive soils should be carried out.
TL;DR: Here a biochemical method based on aspartic acid racemization in dentine provides the most accurate estimates of age, followed by special morphological dental and skeletal methods.
Abstract: Age estimation in cadavers, human remains and living individuals may clarify issues with significant legal and social ramifications for individuals as well as for the community. In such cases methods for estimating age should fulfil the following specific demands: (1) they must have been presented to the scientific community, as a rule by publication in peer-reviewed journals, (2) clear information concerning accuracy of age estimation by the method should be available, (3) the methods need to be sufficiently accurate and (4) in cases of age estimation in living individuals principles of medical ethics and legal regulations have to be considered. We have identified and summarized the methods that essentially fulfil these specific demands. In childhood and adolescence morphological methods based on the radiological examination of dental and skeletal development are to be recommended. In adulthood, the accuracy of most morphological methods is much reduced. Here a biochemical method based on aspartic acid racemization in dentine provides the most accurate estimates of age, followed by special morphological dental and skeletal methods. The choice of method has to take account of the individual circumstances of each case. Most methods require either the consultation of specialised and trained scientists or an adequate calibration by the “user”. Very few attempts have been made to find common standardisation, calibration and evaluation procedures or to develop means of quality assurance for methods of age estimation. Efforts in these directions are necessary to guarantee quality standards and adequate answers to the important legal and social issue of age estimation in forensic medicine.
TL;DR: Evaluating the performance of several state-of-the-art heuristics from the literature on the basis of a standard set of test instances and point out to the most promising procedures is presented.
TL;DR: Subcutaneous treatment with rhuIL-10 over 28 days induced a fully reversible, dose-dependent decrease in hemoglobin and thrombocyte counts but no clinically significant side effects and up to 8 μg/kg of rhu IL-10 was well tolerated.
TL;DR: This work purified antimicrobial activity from supernatants of the A549 lung epithelial cell line, previously stimulated with PA bacteria, by subsequent high performance liquid chromatography and revealed it to be identical with human beta-defensin-2 (hBD-2).
Abstract: Cultured lung epithelial cells release antibacterial activity upon contact with Pseudomonas aeruginosa (PA), which is impaired in cystic fibrosis (CF). In order to identify the factors responsible for killing PA by a biochemical approach, we purified antimicrobial activity from supernatants of the A549 lung epithelial cell line, previously stimulated with PA bacteria, by subsequent high performance liquid chromatography. NH(2)-terminal sequencing of a major bactericidal compound revealed it to be identical with human beta-defensin-2 (hBD-2). A mucoid phenotype of PA, but not two nonmucoid PA strains, high concentrations (> 10 microg/ml) of PA lipopolysaccharide, tumor necrosis factor alpha, and interleukin (IL)-1beta, but not IL-6, dose-dependently induced hBD-2 messenger RNA in cultured normal bronchial, tracheal, as well as normal and CF-derived nasal epithelial cells. Genomic analysis of hBD-2 revealed a promoter region containing several putative transcription factor binding sites, including nuclear factor (NF) kappaB, activator protein (AP)-1, AP-2, and NF-IL-6, known to be involved in the regulation of inflammatory responses. Thus, hBD-2 represents a major inducible antimicrobial factor released by airway epithelial cells either on contact with mucoid PA or by endogenously produced primary cytokines. Therefore, it might be important in lung infections caused by mucoid PA, including those seen in patients with CF.
TL;DR: The identification of a specific population of neurons whose firing properties change suddenly and synchronously following axotomy, and whose activity is associated with tactile allodynia, provides a powerful vehicle for defining the specific cascade of cellular and molecular events that underlie neuropathic pain.
Abstract: We examined the relation between ectopic afferent firing and tactile allodynia in the Chung model of neuropathic pain. Transection of the L5 spinal nerve in rats triggered a sharp, four- to six-fold increase in the spontaneous ectopic discharge recorded in vivo in sensory axons in the ipsilateral L5 dorsal root (DR). The increase, which was not yet apparent 16 h postoperatively, was complete by 24 h. This indicates rapid modification of the electrical properties of the neurons. Only A-neurons, primarily rapidly conducting A-neurons, contributed to the discharge. No spontaneously active C-neurons were encountered. Tactile allodynia in hindlimb skin emerged during precisely the same time window after spinal nerve section as the ectopia, suggesting that ectopic activity in injured myelinated afferents can trigger central sensitization, the mechanism believed to be responsible for tactile allodynia in the Chung model. Most of the spike activity originated in the somata of axotomized DRG neurons; the spinal nerve end neuroma accounted for only a quarter of the overall ectopic barrage. Intracellular recordings from afferent neuron somata in excised DRGs in vitro revealed changes in excitability that closely paralleled those seen in the DR axon recordings in vivo. Corresponding changes in biophysical characteristics of the axotomized neurons were catalogued. Axotomy carried out at a distance from the DRG, in the mid-portion of the sciatic nerve, also triggered increased afferent excitability. However, this increase occurred at a later time following axotomy, and the relative contribution of DRG neuronal somata, as opposed to neuroma endings, was smaller. Axotomy triggers a wide variety of changes in the neurochemistry and physiology of primary afferent neurons. Investigators studying DRG neurons in culture need to be alert to the rapidity with which axotomy, an inevitable consequence of DRG excision and dissociation, alters key properties of these neurons. Our identification of a specific population of neurons whose firing properties change suddenly and synchronously following axotomy, and whose activity is associated with tactile allodynia, provides a powerful vehicle for defining the specific cascade of cellular and molecular events that underlie neuropathic pain.
TL;DR: The European Laryngological Society is proposing a classification of different laryngeal endoscopic cordectomies in order to ensure better definitions of postoperative results to facilitate use of the classification in daily practice.
Abstract: The European Laryngological Society is proposing a classification of different laryngeal endoscopic cordectomies in order to ensure better definitions of post-operative results. We chose to keep the word "cordectomy" even for partial resections because it is the term most often used in the surgical literature. The classification comprises eight types of cordectomies: a subepithelial cordectomy (type I), which is resection of the epithelium; a subligamental cordectomy (type II), which is a resection of the epithelium, Reinke's space and vocal ligament; transmuscular cordectomy (type III), which proceeds through the vocalis muscle; total cordectomy (type IV); extended cordectomy, which encompasses the contralateral vocal fold and the anterior commissure (type Va); extended cordectomy, which includes the arytenoid (type Vb); extended cordectomy, which encompasses the subglottis (type Vc); and extended cordectomy, which includes the ventricle (type Vd). Indications for performing those cordectomies may vary from surgeon to surgeon. The operations are classified according to the surgical approach used and the degree of resection in order to facilitate use of the classification in daily practice. Each surgical procedure ensures that a specimen is available for histopathological examination.
TL;DR: This paper analyzed the behavior of N/O and C/O abundance ratios as a function of metallicity as gauged by O/H in large, extant Galactic and extragalactic H II region abundance samples.
Abstract: We analyze the behavior of N/O and C/O abundance ratios as a function of metallicity as gauged by O/H in large, extant Galactic and extragalactic H II region abundance samples. We compile and compare published yields of C, N, and O for intermediate mass and massive stars and choose appropriate yield sets based on analytical chemical evolution models fitted to the abundance data. We then use these yields to compute numerical chemical evolution models that satisfactorily reproduce the observed abundance trends and thereby identify the most likely production sites for carbon and nitrogen. Our results suggest that carbon and nitrogen originate from separate production sites and are decoupled from one another. Massive stars (M > 8 M☉) dominate the production of carbon, while intermediate-mass stars between 4 and 8 M☉, with a characteristic lag time of roughly 250 Myr following their formation, dominate nitrogen production. Carbon production is positively sensitive to metallicity through mass-loss processes in massive stars and has a pseudo-secondary character. Nitrogen production in intermediate mass stars is primary at low metallicity, but when 12 + log(O/H) > 8.3, secondary nitrogen becomes prominent, and nitrogen increases at a faster rate than oxygen—indeed, the dependence is steeper than would be formally expected for a secondary element. The observed flat behavior of N/O versus O/H in metal-poor galaxies is explained by invoking low star formation rates that flatten the age-metallicity relation and allow N/O to rise to observed levels at low metallicities. The observed scatter and distribution of data points for N/O challenge the popular idea that observed intermittent polluting by oxygen is occurring from massive stars following star bursts. Rather, we find most points cluster at relatively low N/O values, indicating that scatter is caused by intermittent increases in nitrogen caused by local contamination by Wolf-Rayet stars or luminous blue variables. In addition, the effect of inflow of gas into galactic systems on secondary production of nitrogen from carbon may introduce some scatter into N/O ratios at high metallicities.
TL;DR: In this article, the authors present some research developments in primitive equation ocean models which could impact the ocean component of realistic global coupled climate models aimed at large-scale, low frequency climate simulations and predictions.
TL;DR: The 14-3-3–Hsp70–precursor protein complex is a bona fide intermediate in the in vivo protein import pathway in plants and indicates an unrecognized selectivity of 14- 3-3 proteins for precursors from mitochondria and plastids in plants in comparison to fungi and animals.
Abstract: Transit sequences of chloroplast-destined precursor proteins are phosphorylated on a serine or threonine residue. The amino acid motif around the phosphorylation site is related to the phosphopeptide binding motif for 14-3-3 proteins. Plant 14-3-3 proteins interact specifically with wheat germ lysate–synthesized chloroplast precursor proteins and require an intact phosphorylation motif within the transit sequence. Chloroplast precursor proteins do not interact with 14-3-3 when synthesized in the heterologous reticulocyte lysate. In contrast, a precursor protein destined for plant mitochondria was found to be associated with 14-3-3 proteins present in the reticulocyte lysate but not with 14-3-3 from wheat germ lysate. This indicates an unrecognized selectivity of 14-3-3 proteins for precursors from mitochondria and plastids in plants in comparison to fungi and animals. The heterooligomeric complex has an apparent size of 200 kD. In addition to the precursor protein, it contains 14-3-3 (probably as a dimer) and a heat shock protein Hsp70 isoform. Dissociation of the precursor complex requires ATP. Protein import experiments of precursor from the oligomeric complex into intact pea chloroplasts reveal three- to fourfold higher translocation rates compared with the free precursor, which is not complexed. We conclude that the 14-3-3–Hsp70–precursor protein complex is a bona fide intermediate in the in vivo protein import pathway in plants.
TL;DR: In this paper, the authors investigated the safety and efficacy of using 0.1% tacrolimus ointment for long-term treatment of atopic dermatitis and found that up to 1 year of ointments use was safe and effective.
Abstract: Objective To investigate the safety and efficacy of using 0.1% tacrolimus ointment for long-term treatment of atopic dermatitis. Design Open-label, noncomparative study with 6 to 12 months of follow-up. Settings Outpatient departments in 30 study centers in 11 European countries. Patients We enrolled 316 patients aged 18 years and older with moderate to severe atopic dermatitis, 200 for 6 months and 116 for 12 months; 77.5% of patients completed the study. Intervention Twice-daily application of 0.1% tacrolimus ointment on all affected skin. Visits were scheduled on day 1; after 1, 2, and 4 weeks of treatment; and monthly thereafter. Main Outcome Measures Safety assessments included monitoring of adverse events, clinical laboratory values, and tacrolimus blood concentrations. Efficacy end points included a combined score (modified Eczema Area and Severity Index) and an investigator's global assessment. Results Local irritation, adverse events such as burning sensation (47% of patients), pruritus (24% of patients), and erythema (12% of patients) were common but tended to occur only when initiating treatment. Laboratory values showed no marked changes over time. Systemic absorption was minimal, with the maximum tacrolimus blood concentration being less than 1 ng/mL in 76% of patients. All efficacy end points showed improvement. The mean (SD) modified Eczema Area and Severity Index score was 23.7 (12.6) at day 1, 13.5 (11.3) at week 1, 6.1 (9.2) at month 6, and 6.1 (8.1) at month 12. Marked or excellent improvement or clearance of disease was reported in 54%, 81%, and 86% of patients at week 1, month 6, and month 12, respectively. Conclusion Up to 1 year of tacrolimus ointment use was safe and effective in patients with atopic dermatitis.
TL;DR: It is demonstrated that afferent feedback from ankle extensors is of significant importance for the activation of these muscles in the stance phase of human walking.
Abstract: In the cat, the basic walking pattern is generated by a spinal network that is under the control of supraspinal structures (Grillner, 1981; Armstrong, 1988). In addition, sensory feedback from the skin and the moving muscles has repeatedly been shown to play a significant role in the regulation of the network activity and the locomotor movements. Graham Brown (1914) demonstrated that cats with supracollicular lesions of the brainstem are able to adjust their locomotion to the speed and slope of the treadmill at which they are walking. Furthermore, Grillner & Rossignol (1978) demonstrated in spinalised cats that changes in the hip position have a significant effect on the timing and amplitude of the locomotor bursts. Several recent studies have demonstrated a resetting of the locomotion movements in the cat by stimulation of different afferents such as group Ib afferents (Conway et al. 1987) and the afferents involved in flexor reflexes (FRA afferents; Schomburg et al. 1998). This indicates that the sensory feedback mediated by these afferents is closely integrated into the activity of the spinal network generating the locomotion. Several studies have demonstrated a positive contribution of feedback activity in group I afferents to the locomotor activity, either relatively directly or via an effect on the spinal locomotor network (Gossard et al. 1994; McCrea, 1998; Pearson et al. 1998; Hiebert & Pearson, 1999). Other studies have shown that the basic muscle activation profile in the stance phase of walking is not substantially altered by short latency afferent input in the very early part of stance whereas a significant sensory contribution later in stance was argued (Gorassini et al. 1994). Group II afferents also activate a group of interneurones in the midlumbar region, which are believed to be closely integrated into the spinal locomotor circuitry and thereby to add significantly to the generation of the locomotor activity (Edgley et al. 1988).
It is still unclear to what extent a spinal network is involved in the generation of human walking and whether sensory feedback to the spinal cord plays a similarly significant role in human muscle activation as in the cat. In large parts of the stance phase of human walking, the ankle extensors undergo eccentric contractions, which make the large and fast conducting muscle afferents from these muscles increase their discharge strongly (e.g. Prochazka, 1995). Through monosynaptic or polysynaptic projections, muscle afferents might, therefore, be expected to make a significant contribution to the activation of the muscle ankle extensors in the stance phase of walking. Consequently, several studies have attempted to evaluate the contribution of muscle afferent feedback to the EMG activity during walking by measuring stretch reflex activity in different phases of the walking cycle (Yang et al. 1991; Sinkjaer et al. 1996, 1999). However, such data only provide evidence of the significance of the muscle afferents in the generation of the correction of possible unexpected external perturbations of the gait, but do not reveal much about the involvement of the muscle afferent activity in generating the EMG activity during unperturbed movements.
In the present study, a portable device was used to unload the ankle extensors in the stance phase of walking (Andersen & Sinkjaer, 1995). The idea was that if the muscle afferents contributed significantly to the background EMG, unloading of the ankle extensors would diminish the firing of the muscle afferents from the ankle extensors and thereby reduce the background EMG. Unloading of the ankle extensors did indeed reduce the soleus EMG at a latency of around 64 ms. The reduction of EMG activity was still present when transmission in Ia afferents was blocked by ischaemia and when transmission in the antagonist nerve was blocked by local anaesthesia. On this basis group Ib and/or group II afferents are suggested to make a significant contribution to the extensor EMG activity in the stance phase of human walking.
TL;DR: On the basis of their molecular structures, hemocyanins are used as model systems to understand the substrate-active-site interaction between catecholoxidases and tyrosinases.
TL;DR: In this paper, the main flow of the Kuroshio Current was inferred to re-enter the Okinawa Trough at ∼7.3 calendar (cal.) kyr BP, leading to abrupt changes in sedimentation rate, remarkably increased abundance of Pulleniatina obliquiloculata, increased sea surface temperature (SST) and depth of thermocline (DOT).
Journal Article•
TL;DR: A durable resin bond strength to yttrium-oxide-partially-stabilized zirconia ceramic (YPSZ) was achieved only after air abrasion of YPSZ and using one of two resin composites containing a special phosphate monomer.
Abstract: Purpose The aim of this in vitro study was to evaluate the long-term bond strength of adhesive bonding systems to yttrium-oxide-partially-stabilized zirconia ceramic (YPSZ). Materials and methods Plexiglas tubes filled with resin composite were bonded to industrially manufactured zirconia ceramic disks (96% ZrO2 stabilized by 4% Y2O3). After air abrading the ceramic and ultrasonic cleansing, groups of 16 samples were bonded in an alignment apparatus using 7 different bonding methods. Subgroups of 8 bonded samples were tested for tensile strength following storage in distilled water at 37 degrees C either for 3 days or 2 years. In addition, the 2-year samples were thermocycled 37,500 times. The statistical analyses were conducted with the Kruskal-Wallis test followed by multiple pair-wise comparison of the groups using the Wilcoxon rank sum test. Results A moderate to relatively high initial bond strength was achieved by air abrasion alone, the additional use of a silane, or acrylizing the YPSZ surface in combination with a conventional bis-GMA resin composite. However, these methods failed spontaneously over storage time. The use of the bis-GMA resin composite after tribochemical silica coating of YPSZ and the use of a polyacid-modified resin composite after air abrasion of YPSZ resulted in a high initial bond strength which decreased significantly over storage time. A durable resin bond strength to YPSZ was achieved only after air abrasion of YPSZ and using one of two resin composites containing a special phosphate monomer. Conclusion A durable bond strength to YPSZ was achieved only by using resin composites containing a special adhesive monomer.
TL;DR: It is concluded that ET(IT) patients have abnormalities of their upper limb function compatible with cerebellar disease, and patients with more advanced ET show abnormalities of Cerebellar functions.
Abstract: The cerebellum is assumed to play a major role in the pathophysiology of essential tremor (ET). As intention tremor is considered one of the classical features of cerebellar disease, we have assessed a large group of patients with ET for the semiology of the tremor and have performed objective quantitative analysis of a grasping movement in patients with ET, cerebellar disease and a normal control group. We found 25% of the patients to have a moderate or severe kinetic tremor with clear-cut features of a classical intention tremor. Another 33% of the patients had a mild intentional component of their kinetic tremor. Patients with intention tremor (ET(IT)) did not differ from those with predominant postural tremor (ET(PT)) with respect to alcohol sensitivity of the tremor and the frequency of a family history. ET(IT) patients were older and more often showed head and trunk involvement. The onset of this intention tremor has been assessed retrospectively. It was found to begin at a randomly distributed time interval after the onset of the postural tremor, but older patients had a shorter time to development of intention tremor. Quantitative accelerometry of postural tremor showed similar tremor frequencies in both patient groups, but ET(IT) patients had a slightly larger tremor amplitude. Quantitative analysis of a grasping movement using an infrared-camera system was performed in two subgroups of the patients with ET(PT) and ET(IT) and control groups with cerebellar disease or normal subjects. The intention tremor could be quantified objectively as an increased amplitude of curvature during the deceleration and target phase of the movement. The amplitude measurements of intention tremor were clearly abnormal and of comparable magnitude for ET(PT) and cerebellar disease. Additionally, the patients with ET(IT) had a significantly slowed grasping movement during the deceleration and target period. Hypermetria was significantly increased for the patients with ET(IT) and cerebellar disease. We conclude that intention tremor is a feature of ET. ET(IT) patients have abnormalities of their upper limb function compatible with cerebellar disease. This suggests that patients with more advanced ET show abnormalities of cerebellar functions.