פרסומים

book review

The single-epithelial cell layer of the gut mucosa serves as an essential barrier between the host and luminal microflora and plays a major role in innate immunity against invading pathogens. Nuclear factor kB (NF-kB), a central component of the cellular signaling machinery, regulates immune response and inflammation. NF-kB proteins are activated by signaling pathways downstream to microbial recognition receptors and cytokines receptors. Highly regulated NF-kB activity in intestinal epithelial cells (IEC) is essential for normal gut homeostasis; dysregulated activity has been linked to a number of disease states, including inflammatory bowel diseases (IBD) such as Crohns Disease (CD). Our aim was to visualize and quantify spatial and temporal dynamics of NF-kB activity in steady state and inflamed human gut. Lentivirus technology was used to transduce the IEC of human gut xenografts in SCID mice with a NF-kB luminescence reporter system. NF-kB signaling was visualized and quantified using low resolution, intravital imaging of the whole body and high resolution, immunofluorescence microscopic imaging of the tissues. We show that NF-kB is activated in select subset of IEC with low leaky NF-kB activity. These unique inflammatory epithelial cells are clustered in the gut into discrete hotspots of NF-kB activity that are visible in steady state and selectively activated by systemic LPS and human TNFa; or luminal bacteria. The presence of inflammatory hotspots in the normal and inflamed gut might explain the patchy mucosal lesions characterizing CD and thus could have important implications for diagnosis and therapy.Competing Interest StatementThe authors have declared no competing interest.

Worldwide demand for tef (Eragrostis tef) as a functional food for human consumption is increasing, thanks to its nutritional benefits and gluten-free properties. As a result, tef in now grown outside its native environment in Ethiopia and thus information is required regarding plant nutrition demands in these areas, as well as resulting grain health-related composition. In the current work, two tef genotypes were grown in Israel under irrigation in two platforms, plots in the field and pots in a greenhouse, with four and five nitrogen treatments, respectively. Nutritional and health-related quality traits were analyzed, including mineral content, fatty acid composition, hydrophilic and lipophilic antioxidative capacity, total phenolic content and basic polyphenolic profile. Our results show that tef genotypes differ in their nutritional composition, e.g. higher phenolic contents in the brown compared to the white genotype. Additionally, nitrogen availability positively affected grain fatty acid composition and iron levels in both experiments, while negatively affecting total phenolics in the field trials. To conclude, nitrogen fertilization is crucial for crop growth and productivity, however it also implicates nutritional value of the grains as food. These effects should be considered when fertilizing tef with nitrogen, to optimize both crop productivity and nutritional effects.

Worldwide demand for tef (Eragrostis tef) as a functional food for human consumption is increasing, thanks to its nutritional benefits and gluten-free properties. As a result, tef in now grown outside its native environment in Ethiopia and thus information is required regarding plant nutrition demands in these areas, as well as resulting grain health-related composition. In the current work, two tef genotypes were grown in Israel under irrigation in two platforms, plots in the field and pots in a greenhouse, with four and five nitrogen treatments, respectively. Nutritional and health-related quality traits were analyzed, including mineral content, fatty acid composition, hydrophilic and lipophilic antioxidative capacity, total phenolic content and basic polyphenolic profile. Our results show that tef genotypes differ in their nutritional composition, e.g. higher phenolic contents in the brown compared to the white genotype. Additionally, nitrogen availability positively affected grain fatty acid composition and iron levels in both experiments, while negatively affecting total phenolics in the field trials. To conclude, nitrogen fertilization is crucial for crop growth and productivity, however it also implicates nutritional value of the grains as food. These effects should be considered when fertilizing tef with nitrogen, to optimize both crop productivity and nutritional effects.

Leaf nitrogen concentration often is higher in leguminous plants, which associate with dinitrogen-fixing bacteria, compared with nonlegume plants. However, the range of nitrogen concentrations in legumes is wide, likely related to the range of nitrogen fixation strategies. We evaluated how carbon and nitrogen allocation to roots, stems and leaves is influenced by the type of strategy of nitrogen fixation regulation. We grew herbaceous annual legumes (Medicago truncatula, Hymenocarpos circinnatus and Vicia palaestina) under two nitrogen availability treatments (none/sufficient), with and without bacterial inoculation. We found facultative downregulation of the rate of nitrogen fixation when nitrogen was available in H. circinnatus, and an obligate similar fixation rate in both nitrogen treatments in M. truncatula and V. palaestina. Uninoculated plants invested more biomass in roots and contained lower nitrogen concentrations. However, nitrogen concentration in the entire plant and in the leaves was lower and more plastic in the species with a facultative fixation strategy, whereas species with an obligate fixation strategy also maintained high nitrogen concentrations. Our results suggest a suite of functional traits associated with the strategies of allocation and symbiotic nitrogen fixation. This suite of traits probably shapes successional and functional niches of different leguminous species in specious plant communities.

From soda cans to space rockets, thin-walled cylindrical shells are abundant, offering exceptional load carrying capacity at relatively low weight. However, the actual load at which any shell buckles and collapses is very sensitive to imperceptible defects and cannot be predicted, which challenges the of such structures. Consequently, probabilistic descriptions in terms of empirical design rules are used and designing reliable structures requires the use of conservative strength estimates. We introduce a nonlinear description where finite-amplitude perturbations trigger buckling. Drawing from the analogy between imperfect shells which buckle and imperfect pipe flow which becomes turbulent, we experimentally show that lateral probing of cylindrical shells reveals their strength nondestructively. A new ridge-tracking method is applied to commercial cylinders with a hole showing that when the location where buckling nucleates is known we can accurately predict the buckling load of each individual shell, within ±5%. Our study provides a new promising framework to understand shell buckling, and more generally, imperfection-sensitive instabilities.

BACKGROUND: Implantation failure remains an unsolved obstacle in reproductive medicine. Previous studies have indicated that estrogen responsiveness, specifically by estrogen receptor alpha (ER$\alpha$), is crucial for proper implantation. There is an utmost need for a reliable in vitro model that mimics the events in the uterine wall during the implantation process for studying the regulatory mechanisms governing the process. The current two-dimensional and hydrogel-based in vitro models provide only short-term endometrial cell culture with partial functionality. RESULTS: Endometrial biopsies showed an increase in E-cadherin expression on the typical window of implantation of fertile women, compared to negligible expression in recurrent implantation failure (RIF) patients. These clinical results indicated E-cadherin as a marker for receptivity. Three-dimensional (3D) macroporous alginate scaffolds were the base for epithelial endometrial cell-seeding and long-term culture under hormone treatment that mimicked a typical menstrual cycle. The RL95-2 epithelial cell culture in macroporous scaffolds was viable for 3 weeks and showed increased E-cadherin levels in response to estrogen. Human choriocarcinoma (JAR) spheroids were used as embryo models, seeded onto cell constructs and successfully adhered to the RL95-2 cell culture. Moreover, a second model of HEC-1A with low ER$\alpha$ levels, showed lower E-cadherin expression and no JAR attachment. E-cadherin expression and JAR attachment were recovered in HEC-1A cells that were transfected with ER$\alpha$ plasmid. CONCLUSIONS: We present a novel model that enables culturing endometrial cells on a 3D matrix for 3 weeks under hormonal treatment. It confirmed the importance of ER$\alpha$ function and E-cadherin for proper implantation. This platform may serve to elucidate the regulatory mechanisms controlling the implantation process, and for screening and evaluating potential novel therapeutic strategies for RIF.

Implantation failure remains an unsolved obstacle in reproductive medicine. Previous studies have indicated that estrogen responsiveness, specifically by estrogen receptor alpha (ER?), is crucial for proper implantation. There is an utmost need for a reliable in vitro model that mimics the events in the uterine wall during the implantation process for studying the regulatory mechanisms governing the process. The current two-dimensional and hydrogel-based in vitro models provide only short-term endometrial cell culture with partial functionality.\\ Endometrial biopsies showed an increase in E-cadherin expression on the typical window of implantation of fertile women, compared to negligible expression in recurrent implantation failure (RIF) patients. These clinical results indicated E-cadherin as a marker for receptivity. Three-dimensional (3D) macroporous alginate scaffolds were the base for epithelial endometrial cell-seeding and long-term culture under hormone treatment that mimicked a typical menstrual cycle. The RL95-2 epithelial cell culture in macroporous scaffolds was viable for 3 weeks and showed increased E-cadherin levels in response to estrogen. Human choriocarcinoma (JAR) spheroids were used as embryo models, seeded onto cell constructs and successfully adhered to the RL95-2 cell culture. Moreover, a second model of HEC-1A with low ER? levels, showed lower E-cadherin expression and no JAR attachment. E-cadherin expression and JAR attachment were recovered in HEC-1A cells that were transfected with ER? plasmid.\\ We present a novel model that enables culturing endometrial cells on a 3D matrix for 3 weeks under hormonal treatment. It confirmed the importance of ER? function and E-cadherin for proper implantation. This platform may serve to elucidate the regulatory mechanisms controlling the implantation process, and for screening and evaluating potential novel therapeutic strategies for RIF.

A novel hypothesis is presented to explain the pathogenesis of the multifactorial autoimmune disorder rheumatic fever (RF). It involves a synergistic interaction among streptococcal toxins, their cell wall components, M protein, immune complexes, complement components, cationic histones. These agents can act with cationic histones released by neutrophils during NETosis and bacteriolysis and can function as opsonic agents possessing properties similar to antibodies. Cationic histones can interact by strong electrostatic forces with negatively- charged domains on immune complexes and complement components. This allows their deposition and endocytosis in the myocardium, the heart valves, and in the joints. However, the main cause of cell and tissue damage observed in RF is due to a synergism among the plethora of pro-inflammatory substances released by activated neutrophils and macrophages. Cell damage may be mitigated to some extent by anionic heparins, heparinoids, and by anti-inflammatory drugs such as corticosteroids which counteract neutrophils and macrophage chemotaxis induced by cytokines.

 Recent studies have pointed out that highly cationic histones released by PMNs netosis may be major agents in autoimmune lupus since they have high affinity to various kidney sites and can be expected to play a key role in autoimmune glomerular disease.Similarly to antibodies, cationic peptides such a nuclear histone can also act as potent opsonic agents capable of binding by strong electrostatic forces to negatively charged domains in immune complexes and in complement components resulting in their endocytosis and deposition in various parts of the kidney. It is also proposed that to prevent such events, highly anionic heparin and heparinoids, may be effective drugs since these may effectively neutralize histones activities but provided that agents such as steroids, methotrexate and colchicine, all potent inhibitors of neutrophils functions, and antibodies to TH1 cytokines be essential to treat nephritis and to prevent kidney failure. However, the main cause of kidney damage is eventually caused by the plethora of toxic pro inflammatory agents delivered by activated neutrophils and macrophages.