פרסומים

Novel experimental approaches such as fate-mapping and single-cell analysis have brought fresh insight into monocyte development and function over the past decade and helped redefine the monocyte field. Monocytes are now known to consist of multiple subsets generated through distinct developmental pathways with diverse functional specializations. Their fates under homeostatic conditions include the accumulation in peripheral reservoirs and the engraftment into certain resident macrophage pools. Under pathological conditions, monocytes acquire inflammatory effector functions, but can also develop regulatory properties essential for tissue repair. Importantly, monocytes recruited during inflammation are often functionally distinct from resident macrophages or conventional dendritic cells. Here we outline emerging concepts in monocyte heterogeneity, emergency monopoiesis, and trained immunity and discuss how these bring new perspectives to monocyte research.

The first event of the channelrhodopsin-2 (ChR2) photocycle, i.e. trans-to-cis photoisomerization, is studied by means of quantum mechanics/molecular mechanics, taking into account the flexible retinal environment in the ground state. By treating the chromophore at the ab initio multiconfigurational level of theory, we can rationalize the experimental findings based on pump–probe spectroscopy, explaining the different and more complex scenario found for ChR2 in comparison to other rhodopsins. In particular, we find that depending on the hydrogen bonding pattern, different excited states are involved, hence making it possible to suggest one pattern as the most productive. Moreover, after photoisomerization the structure of the first photocycle intermediate, P5001, is characterized by simulating the infrared spectrum and compared to available experimental data. This was obtained by extensive molecular dynamics, where the chromophore is described by a semi-empirical method based on density functional theory. The results clearly identify which counterion is responsible for accepting the proton from the retinal Schiff base: the side chain of the glutamic acid E123.

FtsZ proteins of the FtsZ1 and FtsZ2 families play important roles in the initiation and progression of plastid division in plants and green algae. Arabidopsis possesses a single FTSZ1 member and two FTSZ2 members, FTSZ2-1 and FTSZ2-2. The contribution of these to chloroplast division and partitioning has been mostly investigated in leaf mesophyll tissues. Here, we assessed the involvement of the three FtsZs in plastid division at earlier stages of chloroplast differentiation. To this end, we studied the effect of the absence of specific FtsZ proteins on plastids in the vegetative shoot apex, where the proplastid-to-chloroplast transition takes place. We found that the relative contribution of the two major leaf FtsZ isoforms, FtsZ1 and FtsZ2-1, to the division process varies with cell lineage and position within the shoot apex. While FtsZ2-1 dominates division in the L1 and L3 layers of the shoot apical meristem (SAM), in the L2 layer, FtsZ1 and FtsZ2-1 contribute equally toward the process. Depletion of the third isoform, FtsZ2-2, generally resulted in stronger effects in the shoot apex than those observed in mature leaves. The implications of these findings, along with additional observations made in this work, to our understanding of the mechanisms and regulation of plastid proliferation in the shoot apex are discussed.

Abstract Ecosystem evapotranspiration (ET) can approach annual precipitation (P) often leaving a residual [P-ET], referred to as an ecosystem water yield (WYe). Using a mobile lab, we estimate ET and WYe, in paired forest and nonforest (shrub or grassland) sites along the precipitation gradient (285?755 mm a?1) in Israel. WYe was 69 mm in the dry sites and was further reduced by ?51 mm by forestation. Both WYe and the impact of forestation increased in the wetter sites, with forestation reducing WYe by >200 mm, equivalent to ?30% of the local P. This was associated with increase in ET by a factor of 2.2 and 1.8 in the forest and nonforest sites, respectively, along the rainfall gradient. Losses in WYe due to forestation approached a maximum of ?200 mm above P ? 500 mm, but the forest WYe could vary between ?300 mm at P?=?900 mm and ?100 mm at P?=?500 mm (with equivalent change in WYe between 500 and 300 mm in the nonforest sites), reflecting the increasing ?hydrological cost? associated with vegetation ET and the expected climate change in these regions. The results quantify the interactions of land use and climate on ecosystem ET, indicating that in dry climates, afforestation impact on WYe varies significantly across small spatial scales and can reduce WYe with significant impacts on local hydrology. Such impact may be diminished by management (e.g., plant species, thinning, and grazing) but should also consider the trade-offs with other ecosystem services (e.g., carbon sequestration, soil protection, and surface cooling).

Deg proteases are involved in protein quality control in prokaryotes. Of the three Arabidopsis () homologs, Deg1, Deg5, and Deg8, located in the thylakoid lumen, Deg1 forms a homohexamer, whereas Deg5 and Deg8 form a heterocomplex. Both Deg1 and Deg5-Deg8 were shown separately to degrade photosynthetic proteins during photoinhibition. To investigate whether Deg1 and Deg5-Deg8 are redundant, a full set of Arabidopsis knockout mutants were generated and their phenotypes were compared. Under all conditions tested, mutants were affected more than the wild type and and mutants. Moreover, overexpression of Deg5-Deg8 could only partially compensate for the loss of Deg1. Comparative proteomics of mutants revealed moderate up-regulation of thylakoid proteins involved in photoprotection, assembly, repair, and housekeeping and down-regulation of those that form photosynthetic complexes. Quantification of protein levels in the wild type revealed that Deg1 was 2-fold more abundant than Deg5-Deg8. Moreover, recombinant Deg1 displayed higher in vitro proteolytic activity. Affinity enrichment assays revealed that Deg1 was precipitated with very few interacting proteins, whereas Deg5-Deg8 was associated with a number of thylakoid proteins, including D1, OECs, LHCBs, Cyt , and NDH subunits, thus implying that Deg5-Deg8 is capable of binding substrates but is unable to degrade them efficiently. This work suggests that differences in protein abundance and proteolytic activity underlie the differential importance of Deg1 and Deg5-Deg8 protease complexes observed in vivo.

The present disclosure provides cannabinoid-loaded formulations, as well as processes for their prepn. [on SciFinder(R)]

High-quality patterns were successfully prepared by inkjet-printing WO3-PEDOT:PSS composites on different substrates including the rigid FTO glass and most importantly, on flexible PEDOT:PSS/Ag grid/PET. Excellent electrochromic performances can be achieved, including large optical modulation (85.7% optical contrast at the wavelength of 633 nm on FTO glass substrate), fast switching speed (coloration/bleaching time of 2.4/0.8 s on the PEDOT:PSS/Ag grid/PET substrate), instantaneous coloration efficiency (68.8 cm2 C−1) and good cycling stability (up to 10,000 cycles). The effects of the applied potential window during electrochemical evaluation on the electrochromic performances were analyzed in detail. The printed electrochromics films on PEDOT:PSS/Ag grid/PET showed the best electrochemical stability, in agreement with its superior conductivity and transmittance at 633 nm of 0.6 Ω/sq and 66%, respectively. It sustained transmittance modulation of about 75.5% and 53.1% of its first cycle recorded contrast at 633 nm, after being subjected to 1000 and 5000 cycles, respectively, and maintained good electrochemical stability up to 10,000 cycles. Moreover, a robust mechanical stability was also achieved by the printed films on flexible PEDOT:PSS/Ag grid/PET substrate. The film maintained a transmittance modulation of 85.8% of its original contrast after 5000 bending cycles at a curvature radius of 1 cm. The inkjet-printed WO3 nanocomposite based flexible electrochromic displays exhibited excellent electrochromic performance, making it a promising candidate for energy efficient displays, e-books, e-cards and multifunctional electronic devices.

The role of drug-level monitoring among patients using direct-acting oral anticoagulant (DOAC) is unclear. We aimed to investigate its 'real-life' utilization and effect on clinical management. A review of records of patients who underwent DOAC level testing during 2013-2017. Overall, 212 patients (median age 77 years) underwent 292 DOAC measurements [apixaban (n = 147), rivaroxaban (n = 102), dabigatran (n = 43)]. Monitoring volume increased by 460% during study period. DOAC level testing was performed during routine follow-up in 51 (17.5%) cases, whereas the remaining 241 (82.5%) measurements were performed due to selected clinical circumstances, most commonly: bleeding (n = 60), perioperative status (n = 45), breakthrough thrombosis (n = 37) and renal failure (n = 35). Drug levels were within the expected range in 210 (71.9%), above the expected range in 62 (21.2%) and lower than expected range in 20 (6.8%). In multivariate analysis, older age (P = 0.005), lower glomerular filtration rate (P = 0.001) and lower body mass index (P = 0.006) were associated with DOAC levels above the expected range. Clinical decisions were affected by DOAC monitoring following most (140/241, 58.1%) measurements for which we identified an indication for testing; yet only rarely when monitoring was performed during routine follow-up (7.8%, 4/51) (P < 0.0001). While no benefit of routine DOAC monitoring was observed, drug level measurement has an important role in the management of patients in selected circumstances. Age, body weight and creatinine clearance were found to be significant predictors of drug levels. Future studies are warranted to establish associations between drug levels and outcomes, and better delineate the role of DOAC monitoring.

Successfully cryopreserving cells adhered to a substrate would facilitate the growth of a vital confluent cell culture after thawing while dramatically shortening the post-thaw culturing time. Herein we propose a controlled slow cooling method combining initial directional freezing followed by gradual cooling down to -80°C for robust preservation of cell monolayers adherent to a substrate. Using computer controlled cryostages we examined the effect of cooling rates and dimethylsulfoxide (DMSO) concentration on cell survival and established an optimal cryopreservation protocol. Experimental results show the highest post-thawing viability for directional ice growth at a speed of 30 μm/sec (equivalent to freezing rate of 3.8°C/min), followed by gradual cooling of the sample with decreasing rate of 0.5°C/min. Efficient cryopreservation of three widely used epithelial cell lines: IEC-18, HeLa, and Caco-2, provides proof-of-concept support for this new freezing protocol applied to adherent cells. This method is highly reproducible, significantly increases the post-thaw cell viability and can be readily applied for cryopreservation of cellular cultures in microfluidic devices.

בצעדם הראשון במסע החיפוש, במבוא, מציגים העורכים את המסקנות העולות מהפרקים השונים, ולפיהן השימוש רחב ההיקף בקצבאות הנכות ולחילופין אי השתתפותם של אנשים עם מוגבלות בשוק העבודה הם תולדה של שלושה גורמי עומק מרכזיים: הראשון והעיקרי בהם הוא התמורות שעובר שוק העבודה, ובהן המעבר מכלכלה תעשייתית המבוססת על ייצור לכלכלת שירותים בתר-תעשייתית. לצד גורם ביקוש זה מצביעים העורכים גם על שני של רבים מהאנשים עם מוגבלות )employability( גורמי היצע: פערים ביכולת התעסוקה ובעיות בריאות. ביסוס חזק ומעניין למסקנות אלה ניתן למצוא לאורך כל פרקי הספר, חלקם מדגישים בניתוחם את אחד משלושת הגורמים הללו וחלקם האחר משלבים אותם יחדיו. בסקירה זו אבקש להתמקד במספר פרקים בולטים ורלוונטיים במיוחד. (מתוך המאמר)

 Disaster occurs frequently around the world and is no more considered an isolated event. Thus, disaster management has become a hot issue in urban development and human security. However, selecting suitable measures in disaster preparedness is a complex task. Some mitigation measures, which include making dams and updating building codes, prove ineffective and can themselves become a source of added vulnerability. Therefore, the importance of preparedness cannot be ignored, and the relief distribution aspect needs to be appraised as a measure of disaster preparedness. This study integrates disaster preparedness and response. Many parameters cannot be known before a disaster, while relief demand is a key parameter in disaster preparedness modelling. A decision maker needs to identify the properties of relief demand. Seven influencing factors of relief demand are identified. Then, a facility location model is proposed, and the model results are analysed. The results show that the hub-and-spoke distribution system brings higher social benefits.