פרסומים

Skip to Next Section Post-surgical implant-associated spinal infection is a devastating complication commonly caused by Staphylococcus aureus. Biofilm formation is thought to reduce penetration of antibiotics and immune cells, contributing to chronic and difficult-to-treat infections. A rabbit model of a posterior-approach spinal surgery was created, in which bilateral titanium pedicle screws were interconnected by a plate at the level of lumbar vertebra L6 and inoculated with a methicillin-resistant S. aureus (MRSA) bioluminescent strain. In vivo whole-animal bioluminescence imaging (BLI) and ex vivo bacterial cultures demonstrated a peak in bacterial burden by day 14, when wound dehiscence occurred. Structures suggestive of biofilm, visualized by scanning electron microscopy, were evident up to 56 days following infection. Infection-induced inflammation and bone remodeling were also monitored using 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) and computed tomography (CT). PET imaging signals were noted in the soft tissue and bone surrounding the implanted materials. CT imaging demonstrated marked bone remodeling and a decrease in dense bone at the infection sites. This rabbit model of implant-associated spinal infection provides a valuable preclinical in vivo approach to investigate the pathogenesis of implant-associated spinal infections and to evaluate novel therapeutics.

Heavy precipitation events (HPEs) can lead to natural hazards (e.g. floods and debris flows) and contribute to water resources. Spatiotemporal rainfall patterns govern the hydrological, geomorphological, and societal effects of HPEs. Thus, a correct characterisation and prediction of rainfall patterns is crucial for coping with these events. Information from rain gauges is generally limited due to the sparseness of the networks, especially in the presence of sharp climatic gradients. Forecasting HPEs depends on the ability of weather models to generate credible rainfall patterns. This paper characterises rainfall patterns during HPEs based on high-resolution weather radar data and evaluates the performance of a high-resolution, convection-permitting Weather Research and Forecasting (WRF) model in simulating these patterns. We identified 41 HPEs in the eastern Mediterranean from a 24-year radar record using local thresholds based on quantiles for different durations, classified these events into two synoptic systems, and ran model simulations for them. For most durations, HPEs near the coastline were characterised by the highest rain intensities; however, for short durations, the highest rain intensities were found for the inland desert. During the rainy season, the rain field's centre of mass progresses from the sea inland. Rainfall during HPEs is highly localised in both space (less than a 10 km decorrelation distance) and time (less than 5 min). WRF model simulations were accurate in generating the structure and location of the rain fields in 39 out of 41 HPEs. However, they showed a positive bias relative to the radar estimates and exhibited errors in the spatial location of the heaviest precipitation. Our results indicate that convection-permitting model outputs can provide reliable climatological analyses of heavy precipitation patterns; conversely, flood forecasting requires the use of ensemble simulations to overcome the spatial location errors.

Heavy precipitation events (HPEs) can lead to natural hazards (e.g. floods and debris flows) and contribute to water resources. Spatiotemporal rainfall patterns govern the hydrological, geomorphological, and societal effects of HPEs. Thus, a correct characterisation and prediction of rainfall patterns is crucial for coping with these events. Information from rain gauges is generally limited due to the sparseness of the networks, especially in the presence of sharp climatic gradients. Forecasting HPEs depends on the ability of weather models to generate credible rainfall patterns. This paper characterises rainfall patterns during HPEs based on high-resolution weather radar data and evaluates the performance of a high-resolution, convection-permitting Weather Research and Forecasting (WRF) model in simulating these patterns. We identified 41 HPEs in the eastern Mediterranean from a 24-year radar record using local thresholds based on quantiles for different durations, classified these events into two synoptic systems, and ran model simulations for them. For most durations, HPEs near the coastline were characterised by the highest rain intensities; however, for short durations, the highest rain intensities were found for the inland desert. During the rainy season, the rain field’s centre of mass progresses from the sea inland. Rainfall during HPEs is highly localised in both space (less than a 10 km decorrelation distance) and time (less than 5 min). WRF model simulations were accurate in generating the structure and location of the rain fields in 39 out of 41 HPEs. However, they showed a positive bias relative to the radar estimates and exhibited errors in the spatial location of the heaviest precipitation. Our results indicate that convection-permitting model outputs can provide reliable climatological analyses of heavy precipitation patterns; conversely, flood forecasting requires the use of ensemble simulations to overcome the spatial location errors.

Humean Supervenience is the view that (a) there are a plurality of fundamental beings, (b) there are no inexplicable constraints on modal space, and hence the fundamental nature of each such being is independent of those of all the rest and of the fundamental relations in which it stands to the rest, (c) the fundamental beings stand in no fundamental causal or nomic relations, and hence (d) the distribution of any causal or nomic relations in which they do stand globally supervenes on their fundamental natures and the non‐nomic, non‐causal fundamental relations in which they stand. If Humean Supervenience is true, then as A.J. Ayer put it, it's just one damn thing after another. Radical Pluralism is the view that Humean Supervenience is true, and, moreover, that none of the fundamental beings stands in any fundamental relations at all. If Radical Pluralism is true, then, as William James puts it, the world's pieces are held together by nothing more than conjunction: it's just one damn

The use of auxins to improve the vase life of cut flowers is very limited. Previous studies demonstrated that a pulse treatment of Red Cestrum (Cestrum elegansSchlecht.) cut flowers with 2,4-dichlorophenoxyacetic acid (2,4-D) significantly reduced floret bud abscission, whereas 1-naphthaleneacetic acid (NAA) was ineffective. This difference resulted, at least in part, from the higher acropetal transport capability of 2,4-D compared to that of NAA. The present research focused on examining the factors affecting the acropetal transport, and hence the efficacy of the two auxins in reducing floret bud abscission of Red Cestrum cut flowers. We assumed that the differential acropetal transport capability of the two auxins results from the difference in their dissociation constants (pKa), with values of 2.75 and 4.23 for 2,4-D and NAA, respectively, which affects their pH-dependent physicochemical properties. Thus, increasing the pH of the pulsing solution above the pKa of both auxins might improve their acropetal movement. Indeed, the results of the present research show that raising the pH of the pulsing solution to pH 7.0 and above improved the efficacy of the two auxins in reducing floret bud abscission, with a higher effect on 2,4-D than that on NAA. Raising the pH of the pulsing solution decreased the adsorption and/or uptake of the two auxins by the cells adjacent to the xylem vessels, leading to an increase in their acropetal transport. The high pH of the pulsing solution increased the dissociation and hence decreased the lipophilicity of the auxin molecules, leading to improved acropetal movement. This effect was corroborated by the significant reduction in their 1-octanol/water partition coefficient (K-OW) values with the increase in the pH. A significant increase in theCeIAA1transcript level was obtained in response to 2,4-D pulsing at pH 7.0 and 8.25 and to NAA pulsing at pH 8.25, indicating that the acropetally transported auxins were taken up by the cells under these conditions. Our data suggest that raising the pH of the pulsing solution would significantly contribute to the increased efficacy of auxins in improving the vase life of cut flowers.

This paper is a faithful description of the author’s career as a scientist, which often intersected that of Yves Couder. The emphasis of this paper is a true description of how the science that the author has been associated with really came about. Included are brief descriptions of the science associated with the research paths described. It is hoped that this rather accurate account may be amusing for the senior scientists among us and educational (and possibly useful) for younger scientists.

Rangelands are a dominant anthropogenic land use and a main driver of natural habitat loss worldwide. Land sharing, the integration of agricultural production and biodiversity conservation, may provide a platform for managing rangelands to fulfill multiple ecosystem services. However, livestock grazing can greatly affect biodiversity and little is known about its effects on providers of focal ecosystem services, such as pollinators. We investigated the effect of cattle grazing on bee communities and their foraging and nesting resources in Mediterranean rangelands. Specifically, we explored the effect of moderate cattle grazing on flowering plant abundance, species richness and composition, the diversity of nesting substrates, and consequently, the possible effects on wild bee and honey bee foraging activity, species diversity, and community composition. We conducted field research in the Mediterranean rangelands of Israel during the main bee activity season, in the spring of 2012 and 2013, comparing paired cattle-grazed and ungrazed areas. The availability of floral and nesting resources for bees was unaffected or positively affected by grazing. Similarly, wild bee abundance, species richness, and composition were not affected by grazing, but were instead shaped by spatiotemporal factors. Nor was honey bee activity level impaired by grazing. The foraging preferences of bees, as well as flower species composition and peak bloom differed between grazed and ungrazed areas. Therefore, in our studied rangelands, grazing had its main effect on the foraging choices of honey bees and wild bees, rather than on their abundance and diversity. Moreover, our results indicate the potentially important role of ungrazed patches in increasing nectar and pollen diversity and availability in rangelands for both honey bees and wild bees in the spring. Hence, maintaining a mosaic of moderately grazed and ungrazed patches is expected to provide the greatest benefits for wild bee conservation and honey bee activity in Mediterranean rangelands. Our findings support the notion of rangeland sharing by cattle and bees in Mediterranean ecosystems under moderate grazing intensities, mimicking the coexistence of honey bees, wild bees, and cattle in Mediterranean ecosystems on an evolutionary timescale.

We develop a range-separated stochastic resolution of identity (RS-SRI) approach for the four-index electron repulsion integrals, where the larger terms (above a predefined threshold) are treated using a deterministic RI and the remaining terms are treated using a SRI. The approach is implemented within a second-order Green’s function formalism with an improved O(N3) scaling with the size of the basis set, N. Moreover, the RS approach greatly reduces the statistical error compared to the full stochastic version [T. Y. Takeshita et al., J. Chem. Phys. 151, 044114 (2019)], resulting in computational speedups of ground and excited state energies of nearly two orders of magnitude, as demonstrated for hydrogen dimer chains and water clusters.

Cyclic peptide-peptoid hybrids possess improved stability and selectivity over linear peptides and are thus better drug candidates. However, their synthesis is far from trivial and is usually difficult to automate. Here we describe a new rapid and efficient approach for the synthesis of click-based cyclic peptide-peptoid hybrids. Our methodology is based on a combination between easily synthesized building blocks, automated microwave assisted solid phase synthesis and bioorthogonal click cyclization. We proved the concept of this method using the INS peptide, which we have previously shown to activate the HIV-1 integrase enzyme. This strategy enabled the rapid synthesis and biophysical evaluation of a library of cyclic peptide-peptoid hybrids derived from HIV-1 integrase in high yield and purity. The new cyclic hybrids showed improved biological activity and were significantly more stable than the original linear INS peptide. 

 

The currently accepted imaging methods have been a central hurdle to imaging the finer details of tumor behavior in three-dimensional (3D) ex vivo multicellular culture models. In our search for an improved way of imaging tumor behavior in its physiological-like niche, we developed a simple, efficient, and straightforward procedure using standard reagents and imaging equipment that significantly enhanced 3D imaging up to a $\sim$200-micron depth. We tested its efficacy on pancreatic spheroids, prototypes of high-density tissues that are difficult to image. We found we could both save time with this method and extract information about pancreatic tumor spheroids that previously was difficult to obtain. We were able to discern clear differences in the organization of pancreatic tumor spheroids generated from different origins, suggesting cell-specific, inherent, bottom-up organization with a correlation to the level of malignancy. We also examined the dynamic changes in the spheroids at predetermined time points, providing important information related to tissue morphogenesis and its metabolic state. Lastly, this process enabled us to assess a drug vehicle's potential to penetrate dense tumor tissue by improving our view of the inert particles' diffusion in the 3D spheroid. This clearing method, a simple procedure, can open the door to more accurate imaging and reveal more about cancer behavior.

The currently accepted imaging methods have been a central hurdle to imaging the finer details of tumor behavior in three-dimensional (3D) ex vivo multicellular culture models. In our search for an improved way of imaging tumor behavior in its physiological-like niche, we developed a simple, efficient, and straightforward procedure using standard reagents and imaging equipment that significantly enhanced 3D imaging up to a $\sim$200-micron depth. We tested its efficacy on pancreatic spheroids, prototypes of high-density tissues that are difficult to image. We found we could both save time with this method and extract information about pancreatic tumor spheroids that previously was difficult to obtain. We were able to discern clear differences in the organization of pancreatic tumor spheroids generated from different origins, suggesting cell-specific, inherent, bottom-up organization with a correlation to the level of malignancy. We also examined the dynamic changes in the spheroids at predetermined time points, providing important information related to tissue morphogenesis and its metabolic state. Lastly, this process enabled us to assess a drug vehicle's potential to penetrate dense tumor tissue by improving our view of the inert particles' diffusion in the 3D spheroid. This clearing method, a simple procedure, can open the door to more accurate imaging and reveal more about cancer behavior.

Abstract Carbon reserve use is a major drought response in trees, enabling tree survival in conditions prohibiting photosynthesis. However, regulation of starch metabolism under drought at the whole-tree scale is still poorly understood. To this end, we combined measurements of nonstructural carbohydrates (NSC), tree physiology and gene expression. The experiment was conducted outside on olive trees in pots under 90 days of seasonal spring to summer warming. Half of the trees were also subjected to limited water conditions for 28 days. Photosynthesis decreased in dehydrating trees from 19 to 0.5 µmol m-2 s-1 during the drought period. Starch degradation and mannitol production were a major drought response, with mannitol increasing to 71% and 41% out of total NSC in shoots and roots, respectively. We identified the gene family members potentially relevant either to long-term or stress-induced carbon storage. Partitioning of expression patterns among β amylase and starch synthase family members was observed, with three β amylases possibly facilitating the rapid starch degradation under heat and drought. Our results suggest a group of stress-related, starch metabolism genes, correlated with NSC fluctuations during drought and recovery. The daily starch metabolism gene expression was different from the stress-mode starch metabolism pattern, where some genes are uniquely expressed during the stress-mode response.

Small guanosine triphosphatases (GTPases) of the RAS superfamily signal by directly binding to multiple downstream effector proteins. Effectors are defined by a folded RAS-association (RA) domain that binds exclusively to GTP-loaded (activated) RAS, but the binding specificities of most RA domains toward more than 160 RAS superfamily GTPases have not been characterized. Ten RA domain family (RASSF) proteins comprise the largest group of related effectors and are proposed to couple RAS to the proapoptotic Hippo pathway. Here, we showed that RASSF1-6 formed complexes with the Hippo kinase ortholog MST1, whereas RASSF7-10 formed oligomers with the p53-regulating effectors ASPP1 and ASPP2. Moreover, only RASSF5 bound directly to activated HRAS and KRAS, and RASSFs did not augment apoptotic induction downstream of RAS oncoproteins. Structural modeling revealed that expansion of the RASSF effector family in vertebrates included amino acid substitutions to key residues that direct GTPase-binding specificity. We demonstrated that the tumor suppressor RASSF1A formed complexes with the RAS-related GTPases GEM, REM1, REM2, and the enigmatic RASL12. Furthermore, interactions between RASSFs and RAS GTPases blocked YAP1 nuclear localization. Thus, these simple scaffolds link the activation of diverse RAS family small G proteins to Hippo or p53 regulation.