פרסומים

BACKGROUND: A devastating condition that leads to trauma-related morbidity, multiple rib fractures, remain a serious unmet clinical need. Systemic administration of mesenchymal stem cells (MSCs) has been shown to regenerate various tissues. We hypothesized that parathyroid hormone (PTH) therapy would enhance MSC homing and differentiation, ultimately leading to bone formation that would bridge rib fractures. METHODS: The combination of human MSCs (hMSCs) and a clinically relevant PTH dose was studied using immunosuppressed rats. Segmental defects were created in animals’ fifth and sixth ribs. The rats were divided into four groups: a negative control group, in which animals received vehicle alone; the PTH-only group, in which animals received daily subcutaneous injections of 4 mug/kg teriparatide, a pharmaceutical derivative of PTH; the hMSC-only group, in which each animal received five injections of 2 x 106 hMSCs; and the hMSC + PTH group, in which animals received both treatments. Longitudinal in vivo monitoring of bone formation was performed biweekly using micro-computed tomography (muCT), followed by histological analysis. RESULTS: Fluorescently-dyed hMSCs were counted using confocal microscopy imaging of histological samples harvested 8 weeks after surgery. PTH significantly augmented the number of hMSCs that homed to the fracture site. Immunofluorescence of osteogenic markers, osteocalcin and bone sialoprotein, showed that PTH induced cell differentiation in both exogenously administered cells and resident cells. muCT scans revealed a significant increase in bone volume only in the hMSC + PTH group, beginning by the 4th week after surgery. Eight weeks after surgery, 35% of ribs in the hMSC + PTH group had complete bone bridging, whereas there was complete bridging in only 6.25% of ribs (one rib) in the PTH-only group and in none of the ribs in the other groups. Based on the muCT scans, biomechanical analysis using the micro-finite element method demonstrated that the healed ribs were stiffer than intact ribs in torsion, compression, and bending simulations, as expected when examining bone callus composed of woven bone. CONCLUSIONS: Administration of both hMSCs and PTH worked synergistically in rib fracture healing, suggesting this approach may pave the way to treat multiple rib fractures as well as additional fractures in various anatomical sites.

Enteropathogenic Escherichia coli (EPEC) is a leading cause of severe intestinal disease and infant mortality in developing countries. Virulence is mediated by a type three secretion system (T3SS) causing the hallmark lesions of attaching and effacing (AE) and actin-rich pedestal formation beneath the infecting bacteria on the apical surface of enterocytes. EPEC is a human-specific pathogen whose pathogenesis cannot be studied in animal models. We therefore established an EPEC infection model in human gut xenografts in SCID mice and used it to study the role of T3SS in the pathogenesis of the disease. Following EPEC O127:H6 strain E2348/69 infection, T3SS-dependent AE lesions and pedestals were demonstrated in all infected xenografts. We report here the development of T3SS-dependent intestinal thrombotic microangiopathy (iTMA) and ischemic enteritis in approximately 50% of infected human gut xenografts. Using species-specific CD31 immunostaining, we showed that iTMA was limited to the larger human-mouse chimeric blood vessels which are located between the muscularis mucosa and circular muscular layer of the human gut. These blood vessels were massively invaded by bacteria which adhered to and formed pedestals on endothelial cells and aggregated with mouse neutrophils in the lumen. We conclude that endothelial infection, iTMA and ischemic enteritis might be central mechanisms underlying severe EPEC-mediated disease.

 The insect antennae receive olfactory information from the environment. In some insects it was shown that the antennal responsiveness is dynamically regulated by circadian clocks. However, it is unknown how general this phenomenon is and what functions it serves. Circadian regulation in honeybee workers is particularly interesting in this regard because they show natural task-related chronobiological plasticity. Forager bees show strong circadian rhythms in behavior and brain gene expression, whereas nurse bees tend brood around-the-clock and have attenuated circadian rhythms in activity and whole brain gene expression. Here we tested the hypothesis that there is task-related plasticity in circadian rhythms of antennal responsiveness to odorants in worker honeybees. We used electroantennogram (EAG) to measure the antennal responsiveness of nurses and foragers to general odorants and pheromones around the day. The capacity to track 10 Hz odorant pulses varied with time-of-day for both task-groups, but with different phases. The antennal pulse-tracking capacity was higher during the subjective day for the day-active foragers whereas it was better during the night for around-the-clock active nurses. The task-related phases of pulse-tracking rhythms were similar for all the tested stimuli. We also found evidence for circadian rhythms in the EAG response magnitude of foragers, but not of nurses. To the best of our knowledge, these results provide the first evidence for circadian regulation of antennal olfactory responsiveness and odorant pulse tracking capacity in bees, or any other hymenopteran insect. Importantly, our study shows for the first time that the circadian phase of olfactory responsiveness may be socially regulated. 

Abstract The role of bitter taste—one of the few basic taste modalities—is commonly assumed to signal toxicity and alert animals against consuming harmful compounds. However, it is known that some toxic compounds are not bitter and that many bitter compounds have negligible toxicity while having important health benefits. Here we apply a quantitative analysis of the chemical space to shed light on the bitterness-toxicity relationship. Using the BitterDB dataset of bitter molecules, The BitterPredict prediction tool, and datasets of toxic compounds, we quantify the identity and similarity between bitter and toxic compounds. About 60% of the bitter compounds have documented toxicity and only 56% of the toxic compounds are known or predicted to be bitter. The LD50 value distributions suggest that most of the bitter compounds are not very toxic, but there is a somewhat higher chance of toxicity for known bitter compounds compared to known nonbitter ones. Flavonoids and alpha acids are more common in the bitter dataset compared with the toxic dataset. In contrast, alkaloids are more common in the toxic datasets compared to the bitter dataset. Interestingly, no trend linking LD50 values with the number of activated bitter taste receptors (TAS2Rs) subtypes is apparent in the currently available data. This is in accord with the newly discovered expression of TAS2Rs in several extra-oral tissues, in which they might be activated by yet unknown endogenous ligands and play non-gustatory physiological roles. These results suggest that bitter taste is not a very reliable marker for toxicity, and is likely to have other physiological roles. © 2017 IUBMB Life, 69(12):938–946, 2017

BACKGROUND: Food banks seeking to rescue and redistribute highly nutritious perishable foods to simultaneously alleviate food insecurity and reduce food waste often encounter practical, ethical, and political dilemmas. OBJECTIVES: We present a case study of "Leket Israel," an Israeli food bank that uses an effective large-scale logistical model for the rescue and redistribution of perishable food and discuss the challenges and solutions it offers. RESULTS: The organization operates in a rich country plagued with poverty and inequality, where the government passively encourages nongovernmental organizations to respond to the serious and growing problem of food insecurity. Operating under a business-to-business model, Leket Israel distributes food via intermediary nonprofit organizations (NPOs), enriching the food they provide with fresh produce. Food is obtained through an Agricultural Gleaning project, Self-Growing Farm project, and Meal Rescue project. The partnering NPOs then distribute the food to people in need. Although the rescue and redistribution of highly perishable food is more costly and complex than acquiring, storing, and distributing dried and staple foods and it requires specialized knowledge and infrastructure in order to maintain rigorous safety standards, it improves the nutritional quality of the aid. In 2015, Leket Israel distributed 15 217 389 kg of food, 90% of which was fruit and vegetables, to 180 partnering NPOs nationwide, reaching an estimated 175 000 recipients. CONCLUSION: "Leket Israel" offers a valuable model that can be studied and emulated by international nutrition scientists, practitioners, and policy makers who are seeking to reduce food insecurity and food waste in other countries.

The promise of social network technology for learning purposes has been heavily debated, with proponents highlighting its transformative and opponents its distracting potential. However, little is known about the actual, everyday use of ubiquitous social network sites for learning and study purposes in secondary schools. In the present work, we present findings from two survey studies on representative samples of Israeli, Hebrew-speaking teenagers (N1 = 206 and N2 = 515) which explored the scope, characteristics and reasons behind such activities. Study 1 shows that these can be described best as online knowledge sharing, that is: the up- and downloading of knowledge and knowledge sources to social network-based peer groups. Findings were replicated in study 2 to further support the claim that school-related knowledge sharing is common and widespread and entails different types of knowledge. Findings from study 2 furthermore show that sharing is mainly motivated by prosocial motives, as well as expectations for future reciprocation. Sharing is predicted by individual differences, such as gender, collectivist values, mastery goal orientations and academic self-efficacy. Relations between competitive-individualist values and sharing are more complex, and are, among others, moderated by expectations for future benefits. Implications for educational practices and for learning are discussed.

Nearly all bone fractures in humans can deteriorate into a non-union fracture, often due to formation of fibrotic tissue. Cranial allogeneic bone grafts present a striking example: although seemingly attractive for craniofacial reconstructions, they often fail due to fibrosis at the host-graft junction, which physically prevents the desired bridging of bone between the host and graft and revitalization of the latter. In the present study we show that intermittent treatment with recombinant parathyroid hormone-analogue (teriparatide) modulates neovascularization feeding in the graft surroundings, consequently reducing fibrosis and scar tissue formation and facilitates osteogenesis. Longitudinal inspection of the vascular tree feeding the allograft has revealed that teriparatide induces formation of small-diameter vessels in the 1st week after surgery; by the 2nd week, abundant formation of small-diameter blood vessels was detected in untreated control animals, but far less in teriparatide-treated mice, although in total, more blood capillaries were detected in the animals that were given teriparatide. By that time point we observed expression of the profibrogenic mediator TGF-beta in untreated animals, but negligible expression in the teriparatide-treated mice. To evaluate the formation of scar tissue, we utilized a magnetization transfer contrast MRI protocol to differentiate osteoid tissue from scar tissue, based on the characterization of collagen fibers. Using this method we found that significantly more bone matrix was formed in animals given teriparatide than in control animals. Altogether, our findings show how teriparatide diminishes scarring, ultimately leading to superior bone graft integration.

A previous multi-locus lineage (MLL) analysis of SSR-microsatellite data of old olive trees in the southeast Mediterranean area had shown the predominance of the Souri cultivar (MLL1) among grafted trees. The MLL analysis had also identified an MLL (MLL7) that was more common among rootstocks than other MLLs. We here present a comparison of the MLL combinations MLL1 (scion)/MLL7 (rootstock) and MLL1/MLL1 in order to investigate the possible influence of rootstock on scion phenotype.