80 research outputs found
VerhaltensauffÀlligkeiten transgener MÀuse mit defizienter kooperativer DNA-Bindung des Transkriptionsfaktors STAT1
Zytokine spielen in der Pathogenese
der humanen Depression eine zentrale Rolle; dafĂŒr sprechen
die Beobachtung depressiver Reaktionen als klinische
Nebenwirkung im Zu- sammenhang mit einer
Interferon-α-Therapie und die erhöhten Serumspiegel einiger
inflammatorischer Zytokine bei Depressionserkrankten. In der
vorliegenden Arbeit wurde die Bedeutung der kooperativen
DNA-Bindung des Transkriptionsfaktor STAT1 (Signaltransduktor
und Aktivator der Transkription 1) fĂŒr die Entstehung einer
Depres- sion untersucht. Der Austausch eines kritischen
AminosÀurerestes in der amino- terminalen ProteindomÀne
(F77A) bewirkt ĂŒber eine Inhibition der Tetramerbildung und
eine reduzierte Tyrosin-Dephosphorylierung von STAT1 eine
Suppression der tran- skriptionellen Aktivierung von
Interferon-Îł-responsiven Zielgenen, wie dem mig1-Gen. In
Verhaltensexperimenten unter Verwendung eines
Knockin-Mausmodells zeigten homozygote transgene
STAT1F77A/F77A-MÀuse einen depressionsassoziierten PhÀnotyp
im Forced-Swim-Test ohne besondere AuffÀlligkeiten in
lokomotions- und angstprĂŒ- fenden Testreihen. Der
STAT1F77A/F77A-Genotyp besitzt einen protektiven Effekt auf
das Ăberleben nach intraperitonealer
Lipopolysaccharid-(LPS)-Injektion der transgenen MĂ€use und
bewirkte eine verstÀrkte BeeintrÀchtigung des
Krankheitsverhaltens in einem frĂŒhen Stadium mit verkĂŒrzter
Rekonvaleszenzsphase. Zusammenfassend bewirkt die fehlende
kooperative DNA-Bindung von STAT1 einen
depressionsassoziierten PhÀ- notyp mit gleichzeitigem
Ăberlebensvorteil nach isolierter LPS-Gabe. Diese
unerwarteten Resultate sprechen dafĂŒr, dass Interferon-Îł, im
strikten Gegensatz zu Typ-I-Interferonen, antidepressiogene
Effekte ausĂŒbt und dass diese ĂŒber STAT1 vermittelt
werden
Counteracting effects of nutrient composition (Si:N) on export flux under artificial upwelling
To keep global warming below 1.5°C, technologies that remove carbon from the atmosphere will be needed. Ocean artificial upwelling of nutrient-rich water stimulates primary productivity and could enhance the biological carbon pump for natural CO2 removal. Its potential may depend on the Si availability in the upwelled water, which regulates the abundance of diatoms that are key carbon exporters. In a mesocosm experiment, we tested the effect of nutrient composition (Si relative to N) in artificially upwelled waters on export quantity and quality in a subtropical oligotrophic environment. Upwelling led to a doubling of exported particulate matter and increased C:N ratios to well beyond Redfield (9.5 to 11.1). High Si availability stimulated this carbon over-consumption further, resulting in a temporary ~5-fold increase in POC export and ~30% increase in C:N ratios compared to Si-scarce upwelling. Whilst the biogenic Si ballast of the export flux increased more than 3.5-fold over the Si:N gradient, these heavier particles did not sink faster. On the contrary, sinking velocity decreased considerably under high Si:N, most likely due to reduced particle size. Respiration rates remained similar across all treatments indicating that biogenic Si did not protect particles against microbial degradation. Si availability thus influenced key processes of the biological carbon pump in counteracting ways by increasing the export magnitude and associated C:N ratios but decreasing the efficiency of carbon transfer to depth. These opposing effects need to be considered when evaluating the potential of artificial upwelling as negative emission technology
Spatial association of lemming burrows with landforms in the Swedish subarctic mountains : implications for periglacial feature stability
Burrowing mammals often have considerable geomorphological impacts, and their
tunneling activities may decrease the stability of landforms. We document the spatial
distribution of Norwegian lemming burrows in a subarctic alpine meadow to
determine the preferred locations for burrow entrances and to examine the potential
for burrowing to decrease the stability of periglacial landforms at the site. Burrow
entrances were disproportionately common into the base and sides of landforms
(.68% of burrows), probably reflecting the lower energetic cost of moving soil
horizontally, rather than vertically, out of burrows. Most burrow entrances (.60%)
were also located under large rocks, which probably improve burrow stability by
providing a firm ceiling to the entrance. Field observations show that these burrows
are relatively stable, as only 3% were associated with any signs of increased erosion
or landform instability. Therefore, in contrast to some previous studies, and despite
burrowing being concentrated on landforms, we suggest that these rodents have little
direct impact on landform integrity at this site.South African National Research Foundation and the Swedish International Development Cooperation Agency. South African National Antarctic Program. DST-NRF Centre of Excellence for Invasion Biology.http://instaar.colorado.edu/AAAR/index.phphb2016Geography, Geoinformatics and Meteorolog
The benefit of adjuvant radiotherapy after breast conserving surgery in older patients with low risk breast cancer- a meta- analysis of randomized trials
Purpose/Objective(s): It is currently unclear whether patients with low risk breast cancer receiving adjuvant endocrine therapy need adjuvant radiation therapy after breast conserving surgery. The data of randomized trials are available. Materials/Methods: In a database search 5 randomized trials including in total 3766 mostly elderly patients with early stage breast cancer treated either with adjuvant endocrine therapy or with endocrine therapy and additional whole breast radiation after breast conserving surgery were identified. Published hazard ratios for time to local recurrence were the basis of our meta-analysis. Meta-analysis of the effect sizes on local recurrence was performed using a random effects model based on parameter estimates of log hazard ratios in Cox models and their standard errors. Furthermore, overall survival was examined. Results: Adjuvant hormone therapy alone in mostly older patients with low risk breast cancer resulted in significantly shorter time to local relapse compared to radiation therapy combined with hormone therapy (Hazard Ratio: 6.8, 95% CI: 4.23-10.93, p < 0.0001). There was no significant difference for overall survival. Conclusion: Additional radiation therapy to hormone therapy did improve local relapse in breast cancer patients but did not show significant impact on overall survival
Kinship and familiarity mitigate costs of social conflict between Seychelles warbler neighbors
Because virtually all organisms compete with others in their social environment, mechanisms that reduce conflict between interacting individuals are crucial for the evolution of stable families, groups, and societies. Here, we tested whether costs of social conflict over territorial space between Seychelles warblers (Acrocephalus sechellensis) are mitigated by kin-selected (genetic relatedness) or mutualistic (social familiarity) mechanisms. By measuring longitudinal changes in individualsâ body mass and telomere length, we demonstrated that the fitness costs of territoriality are driven by a complex interplay between relatedness, familiarity, local density, and sex. Physical fights were less common at territory boundaries shared between related or familiar males. In line with this, male territory owners gained mass when living next to related or familiar males and also showed less telomere attrition when living next to male kin. Importantly, these relationships were strongest in high-density areas of the population. Males also had more rapid telomere attrition when living next to unfamiliar male neighbors, but mainly when relatedness to those neighbors was also low. In contrast, neither kinship nor familiarity was linked to body mass or telomere loss in female territory owners. Our results indicate that resolving conflict over territorial space through kin-selected or mutualistic pathways can reduce both immediate energetic costs and permanent somatic damage, thus providing an important mechanism to explain fine-scale population structure and cooperation between different social units across a broad range of taxa
Hakai is required for stabilization of core components of the m6A mRNA methylation machinery
N6-methyladenosine (m6A) is the most abundant internal modification on mRNA which influences most steps of mRNA metabolism and is involved in several biological functions. The E3 ubiquitin ligase Hakai was previously found in complex with components of the m6A methylation machinery in plants and mammalian cells but its precise function remained to be investigated. Here we show that Hakai is a conserved component of the methyltransferase complex in Drosophila and human cells. In Drosophila, its depletion results in reduced m6A levels and altered m6A-dependent functions including sex determination. We show that its ubiquitination domain is required for dimerization and interaction with other members of the m6A machinery, while its catalytic activity is dispensable. Finally, we demonstrate that the loss of Hakai destabilizes several subunits of the methyltransferase complex, resulting in impaired m6A deposition. Our work adds functional and molecular insights into the mechanism of the m6A mRNA writer complex
Ultracold atoms and the Functional Renormalization Group
We give a self-contained introduction to the physics of ultracold atoms using
functional integral techniques. Based on a consideration of the relevant length
scales, we derive the universal effective low energy Hamiltonian describing
ultracold alkali atoms. We then introduce the concept of the effective action,
which generalizes the classical action principle to full quantum status and
provides an intuitive and versatile tool for practical calculations. This
framework is applied to weakly interacting degenerate bosons and fermions in
the spatial continuum. In particular, we discuss the related BEC and BCS
quantum condensation mechanisms. We then turn to the BCS-BEC crossover, which
interpolates between both phenomena, and which is realized experimentally in
the vicinity of a Feshbach resonance. For its description, we introduce the
Functional Renormalization Group approach. After a general discussion of the
method in the cold atoms context, we present a detailed and pedagogical
application to the crossover problem. This not only provides the physical
mechanism underlying this phenomenon. More generally, it also reveals how the
renormalization group can be used as a tool to capture physics at all scales,
from few-body scattering on microscopic scales, through the finite temperature
phase diagram governed by many-body length scales, up to critical phenomena
dictating long distance physics at the phase transition. The presentation aims
to equip students at the beginning PhD level with knowledge on key physical
phenomena and flexible tools for their description, and should enable to embark
upon practical calculations in this field.Comment: 73 pages, 32 figures. Lecture notes for the 49th Schladming Winter
School `Physics at all scales: The Renormalization Group' (to appear in the
proceedings
The comorbidity and co-medication profile of patients with progressive supranuclear palsy
BackgroundProgressive supranuclear palsy (PSP) is usually diagnosed in elderly. Currently, little is known about comorbidities and the co-medication in these patients.ObjectivesTo explore the pattern of comorbidities and co-medication in PSP patients according to the known different phenotypes and in comparison with patients without neurodegenerative disease.MethodsCross-sectional data of PSP and patients without neurodegenerative diseases (non-ND) were collected from three German multicenter observational studies (DescribePSP, ProPSP and DANCER). The prevalence of comorbidities according to WHO ICD-10 classification and the prevalence of drugs administered according to WHO ATC system were analyzed. Potential drug-drug interactions were evaluated using AiDKlinik (R).ResultsIn total, 335 PSP and 275 non-ND patients were included in this analysis. The prevalence of diseases of the circulatory and the nervous system was higher in PSP at first level of ICD-10. Dorsopathies, diabetes mellitus, other nutritional deficiencies and polyneuropathies were more frequent in PSP at second level of ICD-10. In particular, the summed prevalence of cardiovascular and cerebrovascular diseases was higher in PSP patients. More drugs were administered in the PSP group leading to a greater percentage of patients with polypharmacy. Accordingly, the prevalence of potential drug-drug interactions was higher in PSP patients, especially severe and moderate interactions.ConclusionsPSP patients possess a characteristic profile of comorbidities, particularly diabetes and cardiovascular diseases. The eminent burden of comorbidities and resulting polypharmacy should be carefully considered when treating PSP patients
Measures of infection prevention and incidence of SARS-CoV-2 infections in cancer patients undergoing radiotherapy in Germany, Austria and Switzerland
Abstract
Purpose
COVID-19 infection has manifested as a major threat to both patients and healthcare providers around the world. Radiation oncology institutions (ROI) deliver a major component of cancer treatment, with protocols that might span over several weeks, with the result of increasing susceptibility to COVID-19 infection and presenting with a more severe clinical course when compared with the general population. The aim of this manuscript is to investigate the impact of ROI protocols and performance on daily practice in the high-risk cancer patients during this pandemic.
Methods
We addressed the incidence of positive COVID-19 cases in both patients and health care workers (HCW), in addition to the protective measures adopted in ROIs in Germany, Austria and Switzerland using a specific questionnaire.
Results
The results of the questionnaire showed that a noteworthy number of ROIs were able to complete treatment in SARS-CoVâ2 positive cancer patients, with only a short interruption. The ROIs reported a significant decrease in patient volume that was not impacted by the circumambient disease incidence, the type of ROI or the occurrence of positive cases. Of the ROIs 16.5% also reported infected HCWs. About half of the ROIs (50.5%) adopted a screening program for patients whereas only 23.3% also screened their HCWs. The range of protective measures included the creation of working groups, instituting home office work and protection with face masks.
Regarding the therapeutic options offered, curative procedures were performed with either unchanged or moderately decreased schedules, whereas palliative or benign radiotherapy procedures were more often shortened. Most ROIs postponed or cancelled radiation treatment for benign indications (88.1%). The occurrence of SARS-CoVâ2 infections did not affect the treatment options for curative procedures. Non-university-based ROIs seemed to be more willing to change their treatment options for curative and palliative cases than university-based ROIs.
Conclusion
Most ROIs reported a deep impact of SARS-CoVâ2 infections on their work routine. Modification and prioritization of treatment regimens and the application of protective measures preserved a well-functioning radiation oncology service and patient care
Peri-operative red blood cell transfusion in neonates and infants: NEonate and Children audiT of Anaesthesia pRactice IN Europe: A prospective European multicentre observational study
BACKGROUND: Little is known about current clinical practice concerning peri-operative red blood cell transfusion in neonates and small infants. Guidelines suggest transfusions based on haemoglobin thresholds ranging from 8.5 to 12âgâdl-1, distinguishing between children from birth to day 7 (week 1), from day 8 to day 14 (week 2) or from day 15 (â„week 3) onwards. OBJECTIVE: To observe peri-operative red blood cell transfusion practice according to guidelines in relation to patient outcome. DESIGN: A multicentre observational study. SETTING: The NEonate-Children sTudy of Anaesthesia pRactice IN Europe (NECTARINE) trial recruited patients up to 60 weeks' postmenstrual age undergoing anaesthesia for surgical or diagnostic procedures from 165 centres in 31 European countries between March 2016 and January 2017. PATIENTS: The data included 5609 patients undergoing 6542 procedures. Inclusion criteria was a peri-operative red blood cell transfusion. MAIN OUTCOME MEASURES: The primary endpoint was the haemoglobin level triggering a transfusion for neonates in week 1, week 2 and week 3. Secondary endpoints were transfusion volumes, 'delta haemoglobin' (preprocedure - transfusion-triggering) and 30-day and 90-day morbidity and mortality. RESULTS: Peri-operative red blood cell transfusions were recorded during 447 procedures (6.9%). The median haemoglobin levels triggering a transfusion were 9.6 [IQR 8.7 to 10.9] gâdl-1 for neonates in week 1, 9.6 [7.7 to 10.4] gâdl-1 in week 2 and 8.0 [7.3 to 9.0] gâdl-1 in week 3. The median transfusion volume was 17.1 [11.1 to 26.4] mlâkg-1 with a median delta haemoglobin of 1.8 [0.0 to 3.6] gâdl-1. Thirty-day morbidity was 47.8% with an overall mortality of 11.3%. CONCLUSIONS: Results indicate lower transfusion-triggering haemoglobin thresholds in clinical practice than suggested by current guidelines. The high morbidity and mortality of this NECTARINE sub-cohort calls for investigative action and evidence-based guidelines addressing peri-operative red blood cell transfusions strategies. TRIAL REGISTRATION: ClinicalTrials.gov, identifier: NCT02350348
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