The authors show that the diverse mutations in
CALR
that occur in nonmutated
JAK2
myeloproliferative diseases all introduce frameshift mutations that alter the C-terminal part of the protein and ...affect its distribution within cells.
The myeloproliferative neoplasms are chronic myeloid cancers that are characterized by the overproduction of mature blood cells, and that may evolve into acute myeloid leukemia.
1
,
2
In addition to chronic myeloid leukemia with the
BCR-ABL
fusion gene, the three most common myeloproliferative neoplasms are essential thrombocythemia, polycythemia vera, and myelofibrosis.
Many patients with a
BCR-ABL–
negative myeloproliferative neoplasm carry a Janus kinase 2 (
JAK2
) V617F mutation.
3
–
6
The
JAK2
V617F mutation or
JAK2
exon 12 mutations are found in most patients with polycythemia vera,
7
,
8
whereas the
JAK2
V617F mutation is found in only 50 to 60% of . . .
Arginine methyltransferases critically regulate cellular homeostasis by modulating the functional outcome of their substrates. The protein arginine methyltransferase 5 (PRMT5) is an enzyme involved ...in growth and survival pathways promoting tumorigenesis. However, little is known about the biologic function of PRMT5 and its therapeutic potential in multiple myeloma (MM). In the present study, we identified and validated PRMT5 as a new therapeutic target in MM. PRMT5 is overexpressed in patient MM cells and associated with decreased progression-free survival and overall survival. Either genetic knockdown or pharmacological inhibition of PRMT5 with the inhibitor EPZ015666 significantly inhibited growth of both cell lines and patient MM cells. Furthermore, PRMT5 inhibition abrogated NF-κB signaling. Interestingly, mass spectrometry identified a tripartite motif-containing protein 21 TRIM21 as a new PRMT5-partner, and we delineated a TRIM21-dependent mechanism of NF-κB inhibition. Importantly, oral administration of EPZ015666 significantly decreased MM growth in a humanized murine model of MM. These data both demonstrate the oncogenic role and prognostic relevance of PRMT5 in MM pathogenesis, and provide the rationale for novel therapies targeting PRMT5 to improve patient outcome.
Extreme environmental events can strongly affect coastal marine ecosystems but are typically unpredictable. Reliable data on benthic community conditions before such events are rarely available, ...making it difficult to measure their effects. At the end of October 2018, a severe storm hit the Ligurian coast (NW Mediterranean) producing damages to coastal infrastructures. Thanks to recent data collected just before the event on two Posidonia oceanica seagrass meadows hit by the storm, it has been possible to assess the impact of the event on one of the most valuable habitats of the Mediterranean Sea. By means of seagrass cover and depth data gathered along four depth transects positioned within the two meadows in areas differently exposed to the storm waves, and by using models (WW3® + SWAN + XBeach 1D) to evaluate wave height and bed shear stress, we showed that meadows experienced erosion and burial phenomena according to exposure. Paradoxically, meadows in good conditions suffered more damage as compared to those already suffering from previous local anthropogenic impacts. Besides the direct effect of waves in terms of plant uprooting, a major loss of P. oceanica was due to sediment burial in the deepest parts of the meadows. Overall, the loss of living P. oceanica cover amounted to about 50%. Considering that previous research showed that the loss of the original surface of P. oceanica meadows in 160 years due to anthropogenic pressures was similarly around 50%, the present study documented that an extreme environmental event can generate in a single day a loss of natural capital equal to that produced gradually by more than a century of human impact.
Display omitted
•Extreme weather events may affect severely the submerged benthic habitats.•Posidonia oceanica meadows halved their living cover.•The loss of P. oceanica in one day equate that lost in 160 years by human impact.
Abstract
This study aimed to measure changes in different properties of skeletal muscles and evaluate their contribution and relationship to changes in functional performance after pulmonary ...rehabilitation (PR) in patients with chronic obstructive pulmonary disease (COPD). COPD outpatients attending 5 weeks of conventional PR were recruited. Functional performance 5-repetitions sit-to-stand (5STS), and 4-m gait speed (4mGS), and muscle function (maximal isometric strength, power, force control, and relative concentric and eccentric activation during 5STS) were assessed after PR and 3 months of follow-up. Twenty patients (71 years; 52% of predicted FEV
1
) completed the study. 4mGS and relative concentric activation during 5STS decreased respectively by 7.7% and 26% between the beginning of PR and follow-up. Quadriceps strength, power, and force control improved by 10.4%, 27.3%, and 15.2%, respectively, from the beginning of PR to follow-up the relative eccentric activation during 5STS explained 31% of the variance in 4mGS changes. In conclusion, functional performance appeared to decline after conventional PR, whereas several properties of skeletal muscles were maintained at follow-up in COPD outpatients. Of note, eccentric contractions might play a role in the improvement of functional performance. Therefore, future studies with interventional design should include eccentric training in PR programs during clinical COPD practice.
Mediterranean marine biodiversity has received only a fraction of the attention accorded to its terrestrial counterpart, despite the great cultural and economic importance that the sea has been ...having for the Mediterranean countries. A rough estimate of more than 8500 species of macroscopic marine organisms should live in the Mediterranean Sea, corresponding to somewhat between 4% and 18% of the world marine species. This is a conspicuous figure if one considers that the Mediterranean Sea is only 0.82% in surface area and 0.32% in volume as compared to the world ocean. The high biodiversity of the Mediterranean Sea may be explained by historical (its tradition of study dates older than for almost any other sea), paleogeographic (its tormented geological history through the last 5 my has been determining the occurrence of distinct biogeographic categories), and ecological (its variety of climatic and hydrologic situations within a single basin has probably no equals in the world) reasons. Present-day Mediterranean biodiversity is undergoing rapid alteration under the combined pressure of climate change and human impact, but protection measures, either for species or ecosystems, are still scarce. To understand the role and patterns of Mediterranean marine biodiversity, marine ecological research should: first, re-value those scientific areas currently unfashionable with funding agencies (systematics, biogeography and taxonomy); second, start monitoring biodiversity with a long-term approach at a whole Mediterranean scale, possibly through an internationally co-ordinated network of marine protected areas.
To evaluate the adherence to treatment and efficacy of an eccentric-based training (ECC) program on peripheral muscle function and functional exercise capacity in patients with chronic obstructive ...pulmonary disease (COPD).
Prospective, assessor-blinded, randomized controlled trial.
The cardiopulmonary rehabilitation unit of a tertiary subacute referral center.
Thirty (N=30) stable inpatients (mean age 68±8 years; FEV
44±18% of predicted) with COPD were included in the study.
Inpatients were randomly assigned to 4 weeks of a combined endurance and resistance ECC (n=15) or conventional training (CON; n=15).
Quadriceps peak torque (PT) was the primary outcome measure for muscle function. Rate of force development (RFD), muscle activation and quality (quadriceps PT/leg lean mass), 6-min walk distance (6MWD), 4-meter gait speed (4mGS), 10-meter gait speed, 5-repetition sit-to-stand (5STS), dyspnea rate, and mortality risk were the secondary outcomes. Evaluations were performed at baseline and repeated after 4 weeks and 3 months of follow-up.
Quadriceps PT, RFD, and muscle quality improved by 17±23% (P<.001), 19±24%, and 16±20% (both P<.05) within the ECC group. Besides, a significant between-group difference for RFD (56±94 Nm/s, P=.038) was found after training. Both groups showed clinically relevant improvements in 6MWD, 4mGS, dyspnea rate, and mortality risk, with no significant differences between groups.
Combined endurance and resistance ECC improved lower limbs muscle function compared with CON in inpatients with COPD. In contrast, ECC did not further improve functional performance, dyspnea, and mortality risk. ECC may be of particular benefit to effect on skeletal muscle function in patients with COPD.
A rapid visual assessment (RVA) approach for the characterization and assessment of the integrity of coralligenous reefs was applied in 21 stations subjected to different levels of anthropogenic ...pressure, along the French Mediterranean coasts. The reefs were characterized from both the geomorphologic and bionomic (biotic cover, conspicuous species richness, canopy-forming species, etc.) points of view, and their health status was estimated through the COARSE (COralligenous Assessment by ReefScape Estimate) index. The sensitivity of the COARSE index and the robustness of the RVA approach to observer biases were analyzed. Results showed that most coralligenous reefs were characterized by (sub) vertical cliffs or platforms with variable slope, usually dominated by biotic facies with Paramuricea clavata and/or Eunicella cavolini in healthy stations, or by algal associations or facies of impoverishment in the most impacted situations. The overall quality scores of the COARSE index generally reflected the putative level of stress of the sampling stations; differences due to observer biases resulted negligible. Coupling the RVA approach with the COARSE index proved an effective protocol for both the characterization and the evaluation of coralligenous reefs: the former is achieved by the analysis of the whole complexity of this habitat, the latter provides for the first time an indication of sea-floor integrity, differently from previous indices that aim at estimating water quality.
Unlike the soft bottom meiofauna, meiofauna associated to hard substrata is poorly studied, despite its ecological relevance. Since communities of hard substrata are usually characterized by species ...with different life cycles and strategies from those of soft bottom assemblages, information on hard substrata meiofauna is still needed. In this study, sessile macrobenthos and the associated meiofaunal assemblages of two sites of Portofino (NW Mediterranean) were investigated in two seasons at three different depths on both sub-vertical and inclined reefs. The study aimed to assess the abundance, diversity and composition of the meiofauna and the factors structuring its assemblages. Moreover, as meiofauna is known to be dependent upon the substrate characteristics, the study investigated whether the meiofaunal patterns could be related to the sessile macrobenthos structure and composition, and to which extent. Macroalgae dominated the sessile macrobenthic assemblages, while Nematoda and Copepoda were the main meiofaunal groups. Meiofaunal higher-taxa richness and diversity resulted very high, due to the large number of different microhabitats offered by macroalgae. Macrobenthic assemblages were dominated by Rodophyta and Ochrophyta in summer, the latter dramatically collapsing in winter. The meiofaunal abundance and composition changed significantly with the season, consistently with the sessile macrobenthic assemblages, and resulted strongly correlated with Ochrophyta. Shaping the meiofaunal assemblages, macroalgae appeared to act as ecosystem engineer for the meiofauna.
•Macroalgae dominated macrobenthic assemblages, Nematoda and Copepoda the meiofauna.•Meiofaunal diversity was high, due to the many habitats offered by sessile macrobenthos.•Meiofaunal abundance and community structure resulted related to Ochrophyta.•Sessile macrobenthos acted as ecosystem engineer for the associated meiofauna.
More than 60 marine non-indigenous species (NIS) have been removed from previous lists and 84 species have been added, bringing the total to 986 alien species in the Mediterranean 775 in the eastern ...Mediterranean (EMED), 249 in the central Mediterranean (CMED), 190 in the Adriatic Sea (ADRIA) and 308 in the western Mediterranean (WMED). There were 48 new entries since 2011 which can be interpreted as approximately one new entry every two weeks. The number of alien species continues to increase, by 2-3 species per year for macrophytes, molluscs and polychaetes, 3-4 species per year for crustaceans, and 6 species per year for fish. The dominant group among alien species is molluscs (with 215 species), followed by crustaceans (159) and polychaetes (132). Macrophytes are the leading group of NIS in the ADRIA and the WMED, reaching 26-30% of all aliens, whereas in the EMED they barely constitute 10% of the introductions. In the EMED, molluscs are the most species-rich group, followed by crustaceans, fish and polychaetes. More than half (54%) of the marine alien species in the Mediterranean were probably introduced by corridors (mainly Suez). Shipping is blamed directly for the introduction of only 12 species, whereas it is assumed to be the most likely pathway of introduction (via ballasts or fouling) of another 300 species. For approximately 100 species shipping is a probable pathway along with the Suez Canal and/or aquaculture. Approximately 20 species have been introduced with certainty via aquaculture, while >50 species (mostly macroalgae), occurring in the vicinity of oyster farms, are assumed to be introduced accidentally as contaminants of imported species. A total of 18 species are assumed to have been introduced by the aquarium trade. Lessepsian species decline westwards, while the reverse pattern is evident for ship-mediated species and for those introduced with aquaculture. There is an increasing trend in new introductions via the Suez Canal and via shipping.
In this case series study, we aimed to evaluate the feasibility of a subacute rehabilitation program for mechanically ventilated patients with severe consequences of COVID-19 infection. Data were ...retrospectively collected from seven males (age 37–61 years) who were referred for inpatient rehabilitation following the stay in the ICU (14–22 days). On admission, six patients were still supported by mechanical ventilation. All patients were first placed in isolation in a special COVID unit for 6–22 days. Patients attended 11–24 treatment sessions for the duration of rehabilitation stay (13–27 days), including 6–20 sessions in the COVID unit. The treatment included pulmonary and physical rehabilitation. The initially nonventilated patient was discharged prematurely due to gallbladder problems, whereas all six mechanically ventilated patients were successfully weaned off before transfer to a COVID-free unit where they stayed for 7–19 days. At discharge, all patients increased limb muscle strength and thigh circumference, reduced activity-related dyspnea, regained functional independence and reported better quality of life. Rehabilitation plays a vital role in the recovery of seriously ill post-COVID-19 patients. Facilities should develop and implement plans for providing multidisciplinary rehabilitation treatments in various settings to recover functioning and prevent the development of long-term consequences of the COVID-19 disease.
PDF
