Refine
Has Fulltext
- yes (58)
Is part of the Bibliography
- yes (58)
Year of publication
Document Type
- Journal article (56)
- Doctoral Thesis (1)
- Report (1)
Keywords
- CML (2)
- Neisseria gonorrhoeae (2)
- Translational research (2)
- cancer (2)
- deadwood enrichment (2)
- gene regulation (2)
- management (2)
- next generation sequencing (2)
- reactive electrophilic species (2)
- remote sensing (2)
- salt stress (2)
- saproxylic beetles (2)
- survival (2)
- (classical and atypical) Werner syndrome (1)
- 12-oxo-phytodienoic acid (1)
- ABCG2 (1)
- ABL gene (1)
- ADHD (1)
- Abstimmbare Laser (1)
- Agent (1)
- Aging (1)
- Alpha therapy (1)
- Alzheimer's disease (1)
- Arthropod (1)
- Autoimmune diseases (1)
- B cell malignancies (1)
- B cells (1)
- BCOR (1)
- BCORL1 (1)
- BCR‐ABL (1)
- BETA-Diversität (1)
- BETA-Multifunktionalität (1)
- BRAF(V600E) mutation (1)
- Biodiversität (1)
- Biologie (1)
- Biomarker (1)
- Bone marrow transplantantation (1)
- Breast-tumors (1)
- COVID-19 (1)
- COX-2 (1)
- CXCR4 (1)
- Cancer (1)
- Cancer genetics (1)
- Cardiovascular risk factors (1)
- Cardiovascular risk prediction (1)
- Carotid intima-media thickness (CIMT) (1)
- Carotid segment (1)
- Carotid ultrasound (1)
- Chronic myeloid leukaemia (1)
- Cognitive control (1)
- DFB-Laser (1)
- EZH1 (1)
- EZH2 (1)
- EZH2 differentiation trichostatin (1)
- Exercise (1)
- Expression (1)
- Factor receptor (1)
- Forschungsstation Fabrikschleichach (1)
- GRAID (1)
- Graft-versus-leukemia (1)
- H3K27me3 (1)
- HLA-E matching (1)
- HSTC outcome (1)
- HUWE1 (1)
- Halbleiterlaser (1)
- Hippocampus (1)
- Human Physiome (1)
- Imatinib (1)
- Immunologie (1)
- In-vivo (1)
- Inhibitor (1)
- LASP1 (1)
- LND (1)
- LNE (1)
- Laserarray (1)
- Lymantria dispar (1)
- M1/M2 macrophages (1)
- MFM (1)
- MIZ1 (1)
- MYC (1)
- Medical research (1)
- Molecularly targeted therapy (1)
- N170 (1)
- NFATc1 (1)
- NHX1 (1)
- NaCl transport (1)
- Neurotrophic factors (1)
- Nude-mice (1)
- Organische Chemie (1)
- P100 (1)
- PTCL (1)
- Pou2af1 (1)
- Prediction (1)
- Regulatory-cells (1)
- Rheumatoid arthritis (1)
- Risk factors (1)
- Salt Overly Sensitive pathway (1)
- Selective attention (1)
- Sentinel-1 (1)
- Staphylococcus aureus (1)
- Suppression (1)
- T cell differentiation (1)
- T cells (1)
- T-cell non-Hodgkin's lymphomas (1)
- TH1-induced senescence (1)
- TH17 cells (1)
- Tissue (1)
- Tumor-necrosis-factor (1)
- VAL66MET polymorphism (1)
- Vascular plasticity (1)
- Waldökosystem (1)
- Working memory (1)
- abscisic acid (ABA) (1)
- accessibility (1)
- acquired thermotolerance (1)
- acquisition (1)
- activation (1)
- acute leukemia (AL) (1)
- acute myeloid leukemia (1)
- adhesion dynamics (1)
- adolescents (1)
- adrenal cancer (1)
- adrenocortical carcinoma (1)
- amino acid transporter (1)
- anaemia (1)
- aneurysmal subarachnoid haemorrhage (1)
- antibodies (1)
- apolipoprotein-E4 (1)
- arabidopsis-thaliana (1)
- arterial stiffening (1)
- assembly mechanisms (1)
- association (1)
- atherosclerosis (1)
- autotoxicity (1)
- bcl-2 associated athanogene protein 3 (1)
- beech forest (1)
- beetle (1)
- beta diversity (1)
- beta-multifunctionality (1)
- biodiversity (1)
- bipartite metabolism (1)
- bipolar disorder (1)
- bird communities (1)
- bisulfite pyrosequencing (1)
- body size (1)
- bohemian forest ecosystem (1)
- brain (1)
- brain computer interface (1)
- breakpoint (1)
- breast cancer (1)
- broadleaf tree species (1)
- calcification (1)
- calcium signaling (1)
- cancer-targeted IL-12 (1)
- canopy herbivory (1)
- carotid artery disease (1)
- cell death (1)
- children (1)
- chronic myelogenous leukemia (1)
- chronic myeloid leukemia (1)
- chronic phase (1)
- coatings (1)
- colorectal cancer (1)
- community‐weighted mean (1)
- conservation (1)
- containment (1)
- crowded housing (1)
- cytogenetic response (1)
- cytosolic pH (1)
- cytotoxic T cells (1)
- cytotoxicity (1)
- data pool (1)
- dead-wood enrichment (1)
- deadwood (1)
- defoliation severity (1)
- detoxification (1)
- dfb-laser (1)
- different imatinib dose regimens (1)
- differentiation (1)
- digestive system (1)
- disability (1)
- dispersal ability (1)
- dissection (1)
- distant metastases (1)
- diversity (1)
- drug discovery (1)
- early applied higher imatinib dosages (1)
- early respiratory-failure (1)
- elderly (1)
- environmental filtering (1)
- enzyme-linked immunoassays (1)
- epigenetics (1)
- epigenomic landscapes (1)
- epithelial cells (1)
- evidence‐based medicine (1)
- ex vivo expansion (1)
- extinction risk (1)
- fear conditioning (1)
- fire (1)
- focal adhesions (1)
- follicular T helper cells (1)
- force (1)
- forest (1)
- forest biodiversity (1)
- forest conservation (1)
- forest ecosystem science (1)
- forest management (1)
- forest physiognomy (1)
- forestry (1)
- functional traits (1)
- gene-expression (1)
- genome-wide association (1)
- geographic information science (1)
- germinal center (1)
- glycophyte Arabidopsis (1)
- guard cell (1)
- guidelines (1)
- gypsy moth (1)
- habitat heterogeneity (1)
- halophyte Thellungiella/Eutrema (1)
- health care service research (1)
- hearing impairment (1)
- heart (1)
- heart failure (1)
- heat shock response (1)
- heat stress (1)
- hematopoietic stem cell transplantation (HSCT) (1)
- host cells (1)
- human leukocyte antigen-E (HLA-E) (1)
- humanized mice (1)
- humoral immunity (1)
- hybrid messenger RNA (1)
- immune cells (1)
- immunocytokine (1)
- immunohistochemistry (1)
- immunotherapy (1)
- impact (1)
- in vivo polycomb (1)
- independence (1)
- insect decline (1)
- insect disturbance (1)
- integrative management strategy (1)
- intra-annual time-series (1)
- intracerebral haemorrhage (1)
- ion transport (1)
- isothiocyanates (1)
- jasmonates (1)
- kidneys (1)
- land sharing (1)
- land use (1)
- laser array (1)
- leaf response (1)
- learning (1)
- limited mobility (1)
- loss-of-function (1)
- lowland beech forests (1)
- lymph node dissection (1)
- lymphadenectomy (1)
- lymphocyte activation (1)
- machine learning (1)
- macrophages (1)
- major depressive disorder (1)
- managing big data (1)
- medial prefrontal cortex (mPFC) (1)
- medicine (1)
- memory B cells (1)
- memory consolidation and extinction (1)
- messenger RNA (1)
- meta-analysis (1)
- methylation array (1)
- migrants (1)
- migration (1)
- model (1)
- molecular subtypes (1)
- mood disorder (1)
- morphometry (1)
- muscular-dystrophy (1)
- mustard oil bomb (1)
- myopathy (1)
- natural disturbance (1)
- near-infrared spectroscopy (1)
- networks (1)
- neurotrophic factor gene (1)
- neutral processes (1)
- neutrophils (1)
- nilotinib (1)
- no correlation (1)
- older patients (1)
- osmotic effects (1)
- papillary (1)
- patient blood management (1)
- pediatric adrenocortical adenoma (1)
- pediatric adrenocortical cancer (1)
- pediatric adrenocortical tumor (1)
- pharmacology (1)
- phytoprostanes (1)
- plant composition (1)
- plants (1)
- polymerase-chain-reaktion (1)
- polyneuropathy (1)
- posttranscriptional regulation (1)
- precursor cells (1)
- premature aging (1)
- prognostic factors (1)
- protein aggregation (1)
- psychiatry (1)
- radioiodine therapy (1)
- red blood cell transfusion (1)
- red lists (1)
- redox homeostasis (1)
- refugees (1)
- regional species pool (1)
- remote sensing‐enabled essential biodiversity variables (1)
- repositories (1)
- reproducible science (1)
- respiratory infection (1)
- restoration strategy (1)
- review (1)
- rhabdomyosarcoma (1)
- risk stratification (1)
- sRNA (1)
- saproxylic organisms (1)
- saproxylic species (1)
- seasonality (1)
- segmental progeria (1)
- semiconductor lasers (1)
- sequence variations (1)
- service infrastructure (1)
- shock response (1)
- signal transduction (1)
- skeletal myopathy (1)
- soil (1)
- species traits (1)
- species turnover (1)
- spiders (1)
- standards (1)
- stomata (1)
- stress (1)
- sulforaphane (1)
- sun exposure (1)
- surgery (1)
- tension (1)
- therapy (1)
- thermotolerance (1)
- time series (1)
- tissue morphogenesis (1)
- traction (1)
- transcranial magnetic stimulation (TMS) (1)
- transcription deficiency (1)
- transcripts (1)
- transplantation states genes (1)
- transposable elements (1)
- treatment response (1)
- trophic position (1)
- tumor heterogeneity (1)
- tumor-infiltrating lymphocytes (1)
- tunable laser (1)
- ubiquitination (1)
- unfolded protein response (1)
- verbal fluency task (1)
- windthrow (1)
- wood‐inhabiting fungi (1)
- β-diversity (1)
Institute
- Theodor-Boveri-Institut für Biowissenschaften (20)
- Medizinische Klinik und Poliklinik II (9)
- Pathologisches Institut (7)
- Julius-von-Sachs-Institut für Biowissenschaften (6)
- Medizinische Klinik und Poliklinik I (5)
- Institut für Humangenetik (4)
- Klinik und Poliklinik für Psychiatrie, Psychosomatik und Psychotherapie (4)
- Institut für Geographie und Geologie (3)
- Institut für Klinische Epidemiologie und Biometrie (3)
- Institut für Molekulare Infektionsbiologie (3)
Sonstige beteiligte Institutionen
EU-Project number / Contract (GA) number
- 229289 (1)
- 288566 (1)
- 834709 (1)
- ZAM 5-85018031 (1)
The impact of imatinib dose on response rates and survival in older patients with chronic myeloid leukemia in chronic phase has not been studied well. We analyzed data from the German CML-Study IV, a randomized five-arm treatment optimization study in newly diagnosed BCR-ABL-positive chronic myeloid leukemia in chronic phase. Patients randomized to imatinib 400 mg/day (IM400) or imatinib 800 mg/day (IM800) and stratified according to age (≥65 years vs. <65 years) were compared regarding dose, response, adverse events, rates of progression, and survival. The full 800 mg dose was given after a 6-week run-in period with imatinib 400 mg/day. The dose could then be reduced according to tolerability. A total of 828 patients were randomized to IM400 or IM800. Seven hundred eighty-four patients were evaluable (IM400, 382; IM800, 402). One hundred ten patients (29 %) on IM400 and 83 (21 %) on IM800 were ≥65 years. The median dose per day was lower for patients ≥65 years on IM800, with the highest median dose in the first year (466 mg/day for patients ≥65 years vs. 630 mg/day for patients <65 years). Older patients on IM800 achieved major molecular remission and deep molecular remission as fast as younger patients, in contrast to standard dose imatinib with which older patients achieved remissions much later than younger patients. Grades 3 and 4 adverse events were similar in both age groups. Five-year relative survival for older patients was comparable to that of younger patients. We suggest that the optimal dose for older patients is higher than 400 mg/day. ClinicalTrials.gov identifier: NCT00055874
T-cell lymphomas are highly heterogeneous and their prognosis is poor under the currently available therapies. Enhancers of zeste homologue 1 and 2 (EZH1/2) are histone H3 lysine-27 trimethyltransferases (H3K27me3). Despite the rapid development of new drugs inhibiting EZH2 and/or EZH1, the molecular interplay of these proteins and the impact on disease progression and prognosis of patients with T-cell lymphomas remains insufficiently understood. In this study, EZH1/2 mutation status was evaluated in 33 monomorphic epitheliotropic intestinal T-cell lymphomas by next generation sequencing and EZH1/2 and H3K27me3 protein expression levels were detected by immunohistochemistry in 46 T-cell lymphomas. Correlations with clinicopathologic features were analyzed and survival curves generated. No EZH1 mutations and one (3%) EZH2 missense mutation were identified. In univariable analysis, high EZH1 expression was associated with an improved overall survival (OS) and progression-free survival (PFS) whereas high EZH2 and H3K27me3 expression were associated with poorer OS and PFS. Multivariable analysis revealed EZH1 (hazard ratio (HR) = 0.183; 95% confidence interval (CI): 0.044–0.767; p = 0.020;) and EZH2 (HR = 8.245; 95% CI: 1.898–35.826; p = 0.005) to be independent, divergent prognostic markers for OS. In conclusion, EZH1/2 protein expression had opposing effects on the prognosis of T-cell lymphoma patients.
Stimulating the immune system to attack cancer is a promising approach, even for the control of advanced cancers. Several cytokines that promote interferon-γ-dominated immune responses show antitumor activity, with interleukin 12 (IL-12) being of major importance. Here, we used an antibody-IL-12 fusion protein (NHS-IL12) that binds histones of necrotic cells to treat human sarcoma in humanized mice. Following sarcoma engraftment, NHS-IL12 therapy was combined with either engineered IL-7 (FcIL-7) or IL-2 (IL-2MAB602) for continuous cytokine bioavailability. NHS-IL12 strongly induced innate and adaptive antitumor immunity when combined with IL-7 or IL-2. NHS-IL12 therapy significantly improved survival of sarcoma-bearing mice and caused long-term remissions when combined with IL-2. NHS-IL12 induced pronounced cancer cell senescence, as documented by strong expression of senescence-associated p16\(^{INK4a}\) and nuclear translocation of p-HP1γ, and permanent arrest of cancer cell proliferation. In addition, this cancer immunotherapy initiated the induction of myogenic differentiation, further promoting the hypothesis that efficient antitumor immunity includes mechanisms different from cytotoxicity for efficient cancer control in vivo.
Aim: Despite increasing interest in β-diversity, that is the spatial and temporal turnover of species, the mechanisms underlying species turnover at different spatial scales are not fully understood, although they likely differ among different functional groups. We investigated the relative importance of dispersal limitations and the environmental filtering caused by vegetation for local, multi-taxa forest communities differing in their dispersal ability, trophic position and body size.
Location: Temperate forests in five regions across Germany.
Methods: In the inter-region analysis, the independent and shared effects of the regional spatial structure (regional species pool), landscape spatial structure (dispersal limitation) and environmental factors on species turnover were quantified with a 1-ha grain across 11 functional groups in up to 495 plots by variation partitioning. In the intra-region analysis, the relative importance of three environmental factors related to vegetation (herb and tree layer composition and forest physiognomy) and spatial structure for species turnover was determined.
Results: In the inter-region analysis, over half of the explained variation in community composition (23% of the total explained 35%) was explained by the shared effects of several factors, indicative of spatially structured environmental filtering. Among the independent effects, environmental factors were the strongest on average over 11 groups, but the importance of landscape spatial structure increased for less dispersive functional groups. In the intra-region analysis, the independent effect of plant species composition had a stronger influence on species turnover than forest physiognomy, but the relative importance of the latter increased with increasing trophic position and body size.
Main conclusions: Our study revealed that the mechanisms structuring assemblage composition are associated with the traits of functional groups. Hence, conservation frameworks targeting biodiversity of multiple groups should cover both environmental and biogeographical gradients. Within regions, forest management can enhance β-diversity particularly by diversifying tree species composition and forest physiognomy.
Chronic myeloid leukaemia (CML) is a clonal myeloproliferative stem cell disorder characterized by the constitutively active BCR‐ABL tyrosine kinase. The LIM and SH3 domain protein 1 (LASP1) has recently been identified as a novel BCR‐ABL substrate and is associated with proliferation, migration, tumorigenesis and chemoresistance in several cancers. Furthermore, LASP1 was shown to bind to the chemokine receptor 4 (CXCR4), thought to be involved in mechanisms of relapse. In order to identify potential LASP1‐mediated pathways and related factors that may help to further eradicate minimal residual disease (MRD), the effect of LASP1 on processes involved in progression and maintenance of CML was investigated. The present data indicate that not only overexpression of CXCR4, but also knockout of LASP1 contributes to proliferation, reduced apoptosis and migration as well as increased adhesive potential of K562 CML cells. Furthermore, LASP1 depletion in K562 CML cells leads to decreased cytokine release and reduced NK cell‐mediated cytotoxicity towards CML cells. Taken together, these results indicate that in CML, reduced levels of LASP1 alone and in combination with high CXCR4 expression may contribute to TKI resistance.
The extinction of species is a non‐random process, and understanding why some species are more likely to go extinct than others is critical for conservation efforts. Functional trait‐based approaches offer a promising tool to achieve this goal. In forests, deadwood‐dependent (saproxylic) beetles comprise a major part of threatened species, but analyses of their extinction risk have been hindered by the availability of suitable morphological traits.
To better understand the mechanisms underlying extinction in insects, we investigated the relationships between morphological features and the extinction risk of saproxylic beetles. Specifically, we hypothesised that species darker in colour, with a larger and rounder body, a lower mobility, lower sensory perception and more robust mandibles are at higher risk.
We first developed a protocol for morphological trait measurements and present a database of 37 traits for 1,157 European saproxylic beetle species. Based on 13 selected, independent traits characterising aspects of colour, body shape, locomotion, sensory perception and foraging, we used a proportional‐odds multiple linear mixed‐effects model to model the German Red List categories of 744 species as an ordinal index of extinction risk.
Six out of 13 traits correlated significantly with extinction risk. Larger species as well as species with a broad and round body had a higher extinction risk than small, slim and flattened species. Species with short wings had a higher extinction risk than those with long wings. On the contrary, extinction risk increased with decreasing wing load and with higher mandibular aspect ratio (shorter and more robust mandibles).
Our study provides new insights into how morphological traits, beyond the widely used body size, determine the extinction risk of saproxylic beetles. Moreover, our approach shows that the morphological characteristics of beetles can be comprehensively represented by a selection of 13 traits. We recommend them as a starting point for functional analyses in the rapidly growing field of ecological and conservation studies of deadwood.
Community-acquired (CA) Staphylococcus aureus cause various diseases even in healthy individuals. Enhanced virulence of CA-strains is partly attributed to increased production of toxins such as phenol-soluble modulins (PSM). The pathogen is internalized efficiently by mammalian host cells and intracellular S. aureus has recently been shown to contribute to disease. Upon internalization, cytotoxic S. aureus strains can disrupt phagosomal membranes and kill host cells in a PSM-dependent manner. However, PSM are not sufficient for these processes. Here we screened for factors required for intracellular S. aureus virulence. We infected escape reporter host cells with strains from an established transposon mutant library and detected phagosomal escape rates using automated microscopy. We thereby, among other factors, identified a non-ribosomal peptide synthetase (NRPS) to be required for efficient phagosomal escape and intracellular survival of S. aureus as well as induction of host cell death. By genetic complementation as well as supplementation with the synthetic NRPS product, the cyclic dipeptide phevalin, wild-type phenotypes were restored. We further demonstrate that the NRPS is contributing to virulence in a mouse pneumonia model. Together, our data illustrate a hitherto unrecognized function of the S. aureus NRPS and its dipeptide product during S. aureus infection.
Werner Syndrome (WS) is an adult‐onset segmental progeroid syndrome. Bisulfite pyrosequencing of repetitive DNA families revealed comparable blood DNA methylation levels between classical (18 WRN‐mutant) or atypical WS (3 LMNA‐mutant and 3 POLD1‐mutant) patients and age‐ and sex‐matched controls. WS was not associated with either age‐related accelerated global losses of ALU, LINE1, and α‐satellite DNA methylations or gains of rDNA methylation. Single CpG methylation was analyzed with Infinium MethylationEPIC arrays. In a correspondence analysis, atypical WS samples clustered together with the controls and were clearly separated from classical WS, consistent with distinct epigenetic pathologies. In classical WS, we identified 659 differentially methylated regions (DMRs) comprising 3,656 CpG sites and 613 RefSeq genes. The top DMR was located in the HOXA4 promoter. Additional DMR genes included LMNA, POLD1, and 132 genes which have been reported to be differentially expressed in WRN‐mutant/depleted cells. DMRs were enriched in genes with molecular functions linked to transcription factor activity and sequence‐specific DNA binding to promoters transcribed by RNA polymerase II. We propose that transcriptional misregulation of downstream genes by the absence of WRN protein contributes to the variable premature aging phenotypes of WS. There were no CpG sites showing significant differences in DNA methylation changes with age between WS patients and controls. Genes with both WS‐ and age‐related methylation changes exhibited a constant offset of methylation between WRN‐mutant patients and controls across the entire analyzed age range. WS‐specific epigenetic signatures occur early in life and do not simply reflect an acceleration of normal epigenetic aging processes.
Introduction:
Evidence from a number of open-label, uncontrolled studies has suggested that rituximab may benefit patients with autoimmune diseases who are refractory to standard-of-care. The objective of this study was to evaluate the safety and clinical outcomes of rituximab in several standard-of-care-refractory autoimmune diseases (within rheumatology, nephrology, dermatology and neurology) other than rheumatoid arthritis or non-Hodgkin’s lymphoma in a real-life clinical setting.
Methods:
Patients who received rituximab having shown an inadequate response to standard-of-care had their safety and clinical outcomes data retrospectively analysed as part of the German Registry of Autoimmune Diseases. The main outcome measures were safety and clinical response, as judged at the discretion of the investigators.
Results:
A total of 370 patients (299 patient-years) with various autoimmune diseases (23.0% with systemic lupus erythematosus, 15.7% antineutrophil cytoplasmic antibody-associated granulomatous vasculitides, 15.1% multiple sclerosis and 10.0% pemphigus) from 42 centres received a mean dose of 2,440 mg of rituximab over a median (range) of 194 (180 to 1,407) days. The overall rate of serious infections was 5.3 per 100 patient-years during rituximab therapy. Opportunistic infections were infrequent across the whole study population, and mostly occurred in patients with systemic lupus erythematosus. There were 11 deaths (3.0% of patients) after rituximab treatment (mean 11.6 months after first infusion, range 0.8 to 31.3 months), with most of the deaths caused by infections. Overall (n = 293), 13.3% of patients showed no response, 45.1% showed a partial response and 41.6% showed a complete response. Responses were also reflected by reduced use of glucocorticoids and various immunosuppressives during rituximab therapy and follow-up compared with before rituximab. Rituximab generally had a positive effect on patient well-being (physician’s visual analogue scale; mean improvement from baseline of 12.1 mm)
Donor CD4\(^+\)Foxp3\(^+\) regulatory T cells (T reg cells) suppress graft-versus-host disease (GvHD) after allogeneic hematopoietic stem cell transplantation (HCT allo-HCT]). Current clinical study protocols rely on the ex vivo expansion of donor T reg cells and their infusion in high numbers. In this study, we present a novel strategy for inhibiting GvHD that is based on the in vivo expansion of recipient T reg cells before allo-HCT, exploiting the crucial role of tumor necrosis factor receptor 2 (TNFR2) in T reg cell biology. Expanding radiation-resistant host T reg cells in recipient mice using a mouse TNFR2-selective agonist before allo-HCT significantly prolonged survival and reduced GvHD severity in a TNFR2-and T reg cell-dependent manner. The beneficial effects of transplanted T cells against leukemia cells and infectious pathogens remained unaffected. A corresponding human TNFR2-specific agonist expanded human T reg cells in vitro. These observations indicate the potential of our strategy to protect allo-HCT patients from acute GvHD by expanding T reg cells via selective TNFR2 activation in vivo.
Soil salinity is an increasingly global problem which hampers plant growth and crop yield. Plant productivity depends on optimal water-use efficiency and photosynthetic capacity balanced by stomatal conductance. Whether and how stomatal behavior contributes to salt sensitivity or tolerance is currently unknown. This work identifies guard cell-specific signaling networks exerted by a salt-sensitive and salt-tolerant plant under ionic and osmotic stress conditions accompanied by increasing NaCl loads.
We challenged soil-grown Arabidopsis thaliana and Thellungiella salsuginea plants with short- and long-term salinity stress and monitored genome-wide gene expression and signals of guard cells that determine their function.
Arabidopsis plants suffered from both salt regimes and showed reduced stomatal conductance while Thellungiella displayed no obvious stress symptoms. The salt-dependent gene expression changes of guard cells supported the ability of the halophyte to maintain high potassium to sodium ratios and to attenuate the abscisic acid (ABA) signaling pathway which the glycophyte kept activated despite fading ABA concentrations.
Our study shows that salinity stress and even the different tolerances are manifested on a single cell level. Halophytic guard cells are less sensitive than glycophytic guard cells, providing opportunities to manipulate stomatal behavior and improve plant productivity.
Acute myeloid leukemia (AML) is characterized by recurrent genetic events. The BCL6 corepressor (BCOR) and its homolog, the BCL6 corepressor-like 1 (BCORL1), have been reported to be rare but recurrent mutations in AML. Previously, smaller studies have reported conflicting results regarding impacts on outcomes. Here, we retrospectively analyzed a large cohort of 1529 patients with newly diagnosed and intensively treated AML. BCOR and BCORL1 mutations were found in 71 (4.6%) and 53 patients (3.5%), respectively. Frequently co-mutated genes were DNTM3A, TET2 and RUNX1. Mutated BCORL1 and loss-of-function mutations of BCOR were significantly more common in the ELN2017 intermediate-risk group. Patients harboring loss-of-function mutations of BCOR had a significantly reduced median event-free survival (HR = 1.464 (95%-Confidence Interval (CI): 1.005–2.134), p = 0.047), relapse-free survival (HR = 1.904 (95%-CI: 1.163–3.117), p = 0.01), and trend for reduced overall survival (HR = 1.495 (95%-CI: 0.990–2.258), p = 0.056) in multivariable analysis. Our study establishes a novel role for loss-of-function mutations of BCOR regarding risk stratification in AML, which may influence treatment allocation.
Apolipoprotein-E4 (APOE-E4) is a major genetic risk factor for developing Alzheimer’s disease (AD). The verbal fluency task (VFT), especially the subtask category fluency, has shown to provide a good discrimination between cognitively normal controls and subjects with AD. Interestingly, APOE-E4 seems to have no effect on the behavioral performance during a VFT in healthy elderly. Thus, the purpose of the present study was to reveal possible compensation mechanisms by investigating the effect of APOE-E4 on the hemodynamic response in non-demented elderly during a VFT by using functional near-infrared spectroscopy (fNIRS). We compared performance and hemodynamic response of high risk APOE-E4/E4, -E3/E4 carriers with neutral APOE-E3/E3 non-demented subjects (N = 288; 70–77 years). No difference in performance was found. APOE-E4/E4, -E3/E4 carriers had a decreased hemodynamic response in the right inferior frontal junction (IFJ) with a corresponding higher response in the left middle frontal gyrus (MFG) during category fluency. Performance was correlated with the hemodynamic response in the MFG. We assume a compensation of decreased IFJ brain activation by utilizing the MFG during category fluency and thus resulting in no behavioral differences between APOE-groups during the performance of a VFT.
Effects of climate change‐induced events on forest ecosystem dynamics of composition, function and structure call for increased long‐term, interdisciplinary and integrated research on biodiversity indicators, in particular within strictly protected areas with extensive non‐intervention zones. The long‐established concept of forest supersites generally relies on long‐term funds from national agencies and goes beyond the logistic and financial capabilities of state‐ or region‐wide protected area administrations, universities and research institutes.
We introduce the concept of data pools as a smaller‐scale, user‐driven and reasonable alternative to co‐develop remote sensing and forest ecosystem science to validated products, biodiversity indicators and management plans. We demonstrate this concept with the Bohemian Forest Ecosystem Data Pool, which has been established as an interdisciplinary, international data pool within the strictly protected Bavarian Forest and Šumava National Parks and currently comprises 10 active partners. We demonstrate how the structure and impact of the data pool differs from comparable cases.
We assessed the international influence and visibility of the data pool with the help of a systematic literature search and a brief analysis of the results. Results primarily suggest an increase in the impact and visibility of published material during the life span of the data pool, with highest visibilities achieved by research conducted on leaf traits, vegetation phenology and 3D‐based forest inventory.
We conclude that the data pool results in an efficient contribution to the concept of global biodiversity observatory by evolving towards a training platform, functioning as a pool of data and algorithms, directly communicating with management for implementation and providing test fields for feasibility studies on earth observation missions.
Electrophilic oxylipins trigger a heat-shock-like response in the absence of heat through the canonical heat-shock transcription factor A1, thereby helping to cope with stresses associated with protein damage.Abiotic and biotic stresses are often characterized by an induction of reactive electrophile species (RES) such as the jasmonate 12-oxo-phytodienoic acid (OPDA) or the structurally related phytoprostanes. Previously, RES oxylipins have been shown massively to induce heat-shock-response (HSR) genes including HSP101 chaperones. Moreover, jasmonates have been reported to play a role in basal thermotolerance. We show that representative HSR marker genes are strongly induced by RES oxylipins through the four master regulator transcription factors HSFA1a, b, d, and e essential for short-term adaptation to heat stress in Arabidopsis. When compared with Arabidopsis seedlings treated at the optimal acclimation temperature of 37 A degrees C, the exogenous application of RES oxylipins at 20 A degrees C induced a much weaker induction of HSP101 at both the gene and protein expression levels which, however, was not sufficient to confer short-term acquired thermotolerance. Moreover, jasmonate-deficient mutant lines displayed a wild-type-like HSR and were not compromised in acquiring thermotolerance. Hence, the OPDA- and RES oxylipin-induced HSR is not sufficient to protect seedlings from severe heat stress but may help plants to cope better with stresses associated with protein unfolding by inducing a battery of chaperones in the absence of heat.
The novel BackHome system offers individuals with disabilities a range of useful services available via brain-computer interfaces (BCIs), to help restore their independence. This is the time such technology is ready to be deployed in the real world, that is, at the target end users’ home. This has been achieved by the development of practical electrodes, easy to use software, and delivering telemonitoring and home support capabilities which have been conceived, implemented, and tested within a user-centred design approach. The final BackHome system is the result of a 3-year long process involving extensive user engagement to maximize effectiveness, reliability, robustness, and ease of use of a home based BCI system. The system is comprised of ergonomic and hassle-free BCI equipment; one-click software services for Smart Home control, cognitive stimulation, and web browsing; and remote telemonitoring and home support tools to enable independent home use for nonexpert caregivers and users. BackHome aims to successfully bring BCIs to the home of people with limited mobility to restore their independence and ultimately improve their quality of life.
Background:
Recent decades have seen a rise in the incidence of well-differentiated (mainly papillary) thyroid carcinoma around the world. In Germany, the age-adjusted incidence of well-differentiated thyroid carcinoma in 2010 was 3.5 per 100 000 men and 8.7 per 100 000 women per year.
Method:
This review is based on randomized, controlled trials and multicenter trials on the treatment of well-differentiated thyroid carcinoma that were retrieved by a selective literature search, as well as on three updated guidelines issued in the past two years.
Results:
The recommended extent of surgical resection depends on whether the tumor is classified as low-risk or high-risk, so that papillary microcar cinomas, which carry a highly favorable prognosis, will not be overtreated. More than 90% of localized, well-differentiated thyroid carcinomas can be cured with a combination of surgery and radioactive iodine therapy. Radio active iodine therapy is also effective in the treatment of well-differentiated thyroid carcinomas with distant metastases, yielding a 10-year survival rate of 90%, as long as there is good iodine uptake and the tumor goes into remission after treatment; otherwise, the 10-year survival rate is only 10%. In the past two years, better treatment options have become available for radioactive-iodine-resistant thyroid carcinoma. Phase 3 studies of two different tyrosine kinase inhibitors have shown that either one can markedly prolong progression-free survival, but not overall survival. Their more common clinically significant side effects are hand-foot syndrome, hypertension, diarrhea, proteinuria, and weight loss.
Conclusion:
Slow tumor growth, good resectability, and susceptibility to radioactive iodine therapy lend a favorable prognosis to most cases of well-differentiated thyroid carcinoma. The treatment should be risk-adjusted and interdisciplinary, in accordance with the current treatment guidelines. Even metastatic thyroid carcinoma has a favorable prognosis as long as there is good iodine uptake. The newly available medical treatment options for radioactive-iodine-resistant disease need to be further studied.
Cord blood hematopoietic stem cells (CB-HSCs) are an outstanding source for transplantation approaches. However, the amount of cells per donor is limited and culture expansion of CB-HSCs is accompanied by a loss of engraftment potential. In order to analyze the molecular mechanisms leading to this impaired potential we profiled global and local epigenotypes during the expansion of human CB hematopoietic stem and progenitor cells (HPSCs). Human CB-derived CD34+ cells were cultured in serum-free medium together with SCF, TPO, FGF, with or without Igfbp2 and Angptl5 (STF/STFIA cocktails). As compared to the STF cocktail, the STFIA cocktail maintains in vivo repopulation capacity of cultured CD34+ cells. Upon expansion, CD34+ cells genome-wide remodel their epigenotype and depending on the cytokine cocktail, cells show different HK4me3 and H3K27me3 levels. Expanding cells without Igfbp2 and Angptl5 leads to higher global H3K27me3 levels. ChIPseq analyses reveal a cytokine cocktail-dependent redistribution of H3K27me3 profiles. Inhibition of the PRC2 component EZH2 counteracts the culture-associated loss of NOD scid gamma (NSG) engraftment potential. Collectively, our data reveal chromatin dynamics that underlie the culture-associated loss of engraftment potential. We identify PRC2 component EZH2 as being involved in the loss of engraftment potential during the in vitro expansion of HPSCs.
The expression of T-cell-associated serine proteinase 1 (MTSP-1) in vivo during Leishmania major infection was analyzed in genetically resistant C57BL/6 mice and in genetically susceptible BALB/c mice. Using a monoclonal antibody as well as an RNA probe specific for MTSP-1 to stain tissue sections, we found T cells expressing MTSP-1 in skin lesions and spleens of mice of both strains. In skin lesions, MTSP-1-positive T cells could be detected as early as 3 days after infection. Most importantly, the frequency of T cells expressing MTSP-1 was significantly higher in susceptible BALB/c mice than in resistant C57BL/6 mice. These findings suggest that MTSP-1 is associated with disease-promoting T cells and that it may be an effector molecule involved in the pathogenesis of cutaneous leishmaniasis.