Most patients with KIT D816V(+) advanced systemic mastocytosis (SM) are characterized by somatic mutations in additional genes. We sought to clarify the prognostic impact of such mutations. Genotype ...and clinical characteristics of 70 multi-mutated KIT D816V(+) advanced SM patients were included in univariate and multivariate analyses. The most frequently identified mutated genes were TET2 (n=33 of 70 patients), SRSF2 (n=30), ASXL1 (n=20), RUNX1 (n=16) and JAK2 (n=11). In univariate analysis, overall survival (OS) was adversely influenced by mutations in SRSF2 (P<0.0001), ASXL1 (P=0.002) and RUNX1 (P=0.03), but was not influenced by mutations in TET2 or JAK2. In multivariate analysis, SRSF2 and ASXL1 remained the most predictive adverse indicators concerning OS. Furthermore, we found that inferior OS and adverse clinical characteristics were significantly influenced by the number of mutated genes in the SRSF2/ASXL1/RUNX1 (S/A/R) panel (P<0.0001). In conclusion, the presence and number of mutated genes within the S/A/R panel are adversely associated with advanced disease and poor survival in KIT D816V(+) SM. On the basis of these findings, inclusion of molecular markers should be considered in upcoming prognostic scoring systems for patients with SM.
The contribution of molecular alterations in bone marrow mesenchymal stromal cells (BM-MSC) to the pathogenesis of acute myeloid leukemia (AML) is poorly understood. Thus we assessed genome-wide ...genetic, transcriptional and epigenetic alterations in BM-MSC derived from AML patients (AML BM-MSC). Whole-exome sequencing (WES) of AML BM-MSC samples from 21 patients revealed a non-specific pattern of genetic alterations in the stromal compartment. The only mutation present in AML BM-MSC at serial time points of diagnosis, complete remission and relapse was a mutation in the PLEC gene encoding for cytoskeleton key player Plectin in one AML patient. Healthy donor controls did not carry genetic alterations as determined by WES. Transcriptional profiling using RNA sequencing revealed deregulation of proteoglycans and adhesion molecules as well as cytokines in AML BM-MSC. Moreover, KEGG pathway enrichment analysis unravelled deregulated metabolic pathways and endocytosis in both transcriptional and DNA methylation signatures in AML BM-MSC. Taken together, we report molecular alterations in AML BM-MSC suggesting global changes in the AML BM microenvironment. Extended investigations of these altered niche components may contribute to the design of niche-directed therapies in AML.
Red clover (
L.), a key perennial pastoral species used globally, can strengthen pastural mixes to withstand increasingly disruptive weather patterns from climate change. Breeding selections can be ...refined for this purpose by obtaining an in-depth understanding of key functional traits. A replicated randomized complete block glasshouse pot trial was used to observe trait responses critical to plant performance under control (15% VMC), water deficit (5% VMC) and waterlogged conditions (50% VMC) in seven red clover populations and compared against white clover. Twelve morphological and physiological traits were identified as key contributors to the different plant coping mechanisms displayed. Under water deficit, the levels of all aboveground morphological traits decreased, highlighted by a 41% decrease in total dry matter and 50% decreases in both leaf number and leaf thickness compared to the control treatment. An increase in root to shoot ratio indicated a shift to prioritizing root maintenance by sacrificing shoot growth, a trait attributed to plant water deficit tolerance. Under waterlogging, a reduction in photosynthetic activity among red clover populations reduced several morphological traits including a 30% decrease in root dry mass and total dry matter, and a 34% decrease in leaf number. The importance of root morphology for waterlogging was highlighted with low performance of red clover: there was an 83% decrease in root dry mass compared to white clover which was able to maintain root dry mass and therefore plant performance. This study highlights the importance of germplasm evaluation across water stress extremes to identify traits for future breeding programs.
Polymyalgia rheumatica is the second most frequent inflammatory rheumatic disease in people aged over 50 years, after rheumatoid arthritis. It is characterized by pain and morning stiffness in the ...region of the shoulders, hip girdle and neck. It can be associated with giant cell arteritis (CGA). Treatment with glucocorticoids is indispensable. The duration of treatment varies and often exceeds 1 year. The additive administration of methotrexate is an option for saving glucocorticoids. The biologicals tocilizumab or secukinumab are very promising alternatives. The course of treatment should be closely monitored for inflammation parameters, glucocorticoid side effects, pain, visual acuity, depression, activities of daily living and especially related to functions of the upper extremities. The geriatric assessment plays an important role in the management of this condition.
Motivated by growing considerations of the scale, severity, and risks associated with human exposure to indoor particulate matter, this work reviewed existing literature to: (i) identify ...state‐of‐the‐art experimental techniques used for personal exposure assessment; (ii) compare exposure levels reported for domestic/school settings in different countries (excluding exposure to environmental tobacco smoke and particulate matter from biomass cooking in developing countries); (iii) assess the contribution of outdoor background vs indoor sources to personal exposure; and (iv) examine scientific understanding of the risks posed by personal exposure to indoor aerosols. Limited studies assessing integrated daily residential exposure to just one particle size fraction, ultrafine particles, show that the contribution of indoor sources ranged from 19% to 76%. This indicates a strong dependence on resident activities, source events and site specificity, and highlights the importance of indoor sources for total personal exposure. Further, it was assessed that 10–30% of the total burden of disease from particulate matter exposure was due to indoor‐generated particles, signifying that indoor environments are likely to be a dominant environmental factor affecting human health. However, due to challenges associated with conducting epidemiological assessments, the role of indoor‐generated particles has not been fully acknowledged, and improved exposure/risk assessment methods are still needed, together with a serious focus on exposure control.
Lolium perenne L. (perennial ryegrass) is the most important pasture grass species in temperate regions of the world. However, its growth is restricted in summer dry environments. Germplasm screening ...can be used to identify accessions or individual plants for incorporation into breeding programs for drought tolerance. We selected nine perennial ryegrass accessions from different global origins and from a range of climatic and environmental conditions. In addition, the perennial ryegrass cultivar 'Grasslands Impact' was chosen as a reference. The accessions were grown for 360 days in a controlled environment through six consecutive drought stress and recovery cycles. We observed intraspecific differences in drought stress responsiveness for shoot biomass and survival from the third stress cycle. An accession from Norway had 50% more shoot dry matter than the next best-performing accession after six drought cycles. Compared with the reference cultivar 'Grasslands Impact', shoot dry matter of the accession from Norway was more than seven times higher after six drought cycles, indicating superior performance of this ecotype under drought stress. Drought tolerance was characterized by osmotic adjustment and higher relative leaf water content at low soil moisture levels. Furthermore, the findings of this study identify solute potential as an early predictor of drought stress tolerance. These intraspecific differences can be used in breeding programs for the development of drought-tolerant perennial ryegrass cultivars.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Pyroxenite layers embedded within peridotite represent widespread lithological mantle heterogeneities and are potential components in the mantle source of many oceanic basalts. They can be generated ...by a variety of magmatic and metamorphic processes. However, in most natural samples (especially in ultramafic massifs), their primary characteristics are partially or completely erased by later processes (e.g. metamorphism, metasomatism or partial melting). Here we investigate a suite of pyroxenites from the External Liguride Jurassic ophiolites (Northern Apennines, Italy). These are spinel-bearing websterites and clinopyroxenites, partially recrystallized under plagioclase-facies conditions, and occur as centimetre-scale layers parallel to the tectonite foliation of their host peridotites. The pyroxenites have bulk-rock Mg-numbers from 74 to 88 and display rather constant light rare earth element (LREE) depletion relative to middle REE (MREE) (La sub(N)/Sm sub(N) = 0.15-0.35), but variable MREE-heavy REE (HREE) fractionation, with some having markedly positive HREE slopes (Sm sub(N)/Yb sub(N)=0.30-0.96). The HREE enrichment, coupled with high Zr and Sc contents in clinopyroxene porphyroclasts from spinel-bearing domains, provides strong evidence that garnet was present in the precursor mineral assemblages. Mass-balance calculations suggest that the pyroxenites originally contained up to about 40vol. % garnet, indicating that they originated by segregation of melts at relatively high pressure (P>1.5GPa). The parental melts of the pyroxenites have reacted to some extent with the host peridotite during mantle infiltration. Lack of olivine in the primary mineral assemblage and the presence of orthopyroxene-rich rims along the contact with the wall-rock peridotites suggest that the pyroxenites crystallized from silica-rich melts. These probably had REE patterns and Sr-Nd isotope compositions similar to those of enriched mid-ocean ridge basalt. We propose that the pyroxenites originated from melts derived from a hybrid eclogite-bearing peridotite source, which subsequently reacted with their host peridotite to form 'secondary pyroxenites'. The existence of such pyroxenites has been invoked in current models of basalt petrogenesis. During later decompression, the pyroxenites experienced recrystallization at spinel-facies conditions, at 1.2-1.5GPa and minimum temperatures of 950-1000 degree C, and partial re-equilibration in the low-pressure plagioclase facies. The latter event is dated by internal Sm-Nd isochrons at 178 ( plus or minus 8) Ma and is associated with Mesozoic exhumation during extension of the Tethys lithosphere.
Trifolium
is the most used pastoral legume genus in temperate grassland systems, and a common feature in meadows and open space areas in cities and parks. Breeding of
Trifolium
spp. for pastoral ...production has been going on for over a century. However, the breeding targets have changed over the decades in response to different environmental and production pressures. Relatively small gains have been made in
Trifolium
breeding progress.
Trifolium
breeding programmes aim to maintain a broad genetic base to maximise variation. New Zealand is a global hub in
Trifolium
breeding, utilising exotic germplasm imported by the Margot Forde Germplasm Centre. This article describes the history of
Trifolium
breeding in New Zealand as well as the role and past successes of utilising genebanks in forage breeding. The impact of germplasm characterisation and evaluation in breeding programmes is also discussed. The history and challenges of
Trifolium
breeding and its effect on genetic gain can be used to inform future pre-breeding decisions in this genus, as well as being a model for other forage legumes.
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