פרסומים

The endocannabinoid (eCB) system, including its receptors, ligands, and their metabolizing enzymes, plays an important role in bone physiology. Skeletal cannabinoid type 1 (CB1) receptor signaling transmits retrograde signals that restrain norepinephrine (NE) release, thus transiently stimulating bone formation following an acute challenge, suggesting a feedback circuit between sympathetic nerve terminals and osteoblasts. To assess the effect of chronic in vivo occurrence of this circuit, we characterized the skeletal phenotype of mice with a conditional deletion of the CB1 receptor in adrenergic/noradrenergic cells, including sympathetic nerves. Whereas the deletion of the CB1 receptor did not affect bone mass accrual in the distal femoral metaphysis and in vertebral bodies of young, 12-week-old mice, it substantially increased bone mass in aged, 35-week-old mutant mice as compared to wild-type controls. Contrary to our expectations, specific deficiency of the CB1 receptor in sympathetic neurons led to a markedly increased bone mass phenotype, associated with an enhanced bone formation rate and reduced osteoclastogenesis. Mechanistically, the reduced skeletal eCB 'tone' in the null mice did not reflect in increased sympathetic tone and reduced bone formation, suggesting that constitutive genetic inactivation of sympathetic CB1 receptor disrupts the negative feedback loop between eCBs and NE signaling in bone.

We present here a newly developed software package named Artifact GeoMorph Toolbox 3-D (AGMT3-D). It is intended to provide archaeologists with a simple and easy-to-use tool for performing 3-D landmarks-based geometric morphometric shape analysis on 3-D digital models of archaeological artifacts. It requires no prior knowledge of programming or proficiency in statistics. AGMT3-D consists of a data-acquisition procedure for automatically positioning 3-D models in space and fitting them with grids of 3-D semi-landmarks. It also provides a number of analytical tools and procedures that allow the processing and statistical analysis of the data, including generalized Procrustes analysis, principal component analysis, a warp tool, automatic calculation of shape variabilities and statistical tests. It provides an output of quantitative, objective and reproducible results in numerical, textual and graphic formats. These can be used to answer archaeologically significant questions relating to morphologies and morphological variabilities in artifact assemblages. Following the presentation of the software and its functions, we apply it to a case study addressing the effects of different types of raw material on the morphologies and morphological variabilities present in an experimentally produced Acheulian handaxe assemblage. The results show that there are statistically significant differences between the mean shapes and shape variabilities of handaxes produced on flint and those produced on basalt. With AGMT3-D, users can analyze artifact assemblages and address questions that are deducible from the morphologies and morphological variabilities of material culture assemblages. These questions can relate to issues of, among others, relative chronology, cultural affinities, tool function and production technology. AGMT3-D is aimed at making 3-D landmarks-based geometric morphometric shape analysis more accessible to archaeologists, in the hope that this method will become a tool commonly used by archaeologists.

Agritourism attractions are a commonly chosen alternative in farm diversification. Some attractions are based on active farms, while others are based on rural ambience. We model and estimate the agritourism attraction market as a differentiated-goods market based on Israeli market data and simulate different scenarios. We show that total welfare increases when attractions are based on rural ambience rather than on active farms. We also show that an indirect support scheme has a stronger impact on total welfare than a direct scheme.

A program about Aleksandr Solzhenitsyn, marking the 100th anniversary of his birth.

While desired for the cure of allergy, regulatory immune cell subsets and nonclassical Th2-biased inflammatory mediators in the tumour microenvironment can contribute to immune suppression and escape of tumours from immunological detection and clearance. A key aim in the cancer field is therefore to design interventions that can break immunological tolerance and halt cancer progression, whereas on the contrary allergen immunotherapy exactly aims to induce tolerance. In this position paper, we review insights on immune tolerance derived from allergy and from cancer inflammation, focusing on what is known about the roles of key immune cells and mediators. We propose that research in the field of AllergoOncology that aims to delineate these immunological mechanisms with juxtaposed clinical consequences in allergy and cancer may point to novel avenues for therapeutic interventions that stand to benefit both disciplines.

The Neurospora crassa Mps One Binder (MOB) proteins MOB2A and MOB2B physically interact with the Nuclear Dbf2 Related (NDR) kinase COT1 and have been shown to have overlapping functions in various aspects of asexual development. Here, we identified two N. crassa MOB2A residues, Tyr117 and Tyr119, which are potentially phosphorylated. Using phosphomimetic mob-2a mutants we have been able to establish that apart from their previously described roles, MOB2A/B are involved in additional developmental processes. Enhanced conidial germination, accompanied by conidial agglutination, in the phosphomimetic mutants indicated that MOB2A is a negative regulator of germination. Thick-section imaging of perithecia revealed slow maturation and a lack of asci alignment in the mutant strains demonstrating a role for MOB2A in sexual development. We demonstrate that even though MOB2A and MOB2B have some overlapping functions, MOB2B cannot compensate for the roles MOB2A has in conidiation and germination. Altering Tyr residues 117 and 119 impaired the physical interactions between MOB2A and COT1, most likely contributing to some of the observed effects. As cot-1 and the phosphomimetic mutants share an extragenic suppressor (gul-1), we concluded that at least some of the effects imposed by altering Tyr117 and Tyr119 are mediated by the NDR kinase.

People who are more religious tend to experience more positive affect and higher levels of life satisfaction. Current explanations for this relation include social support, meaning in life, and more positive emotional experiences. Adding cognitive reappraisal as a new mechanism, we propose that religion consistently trains people to reappraise emotional events, making the devout more effective in applying this emotion regulation practice, which cultivates more positive affect and greater life satisfaction. In two studies, involving Israeli Jewish (N = 288) and American Christian (N = 277) participants, we found that more frequent use of cognitive reappraisal mediated the relationship between religiosity and affective experiences, which in turn, were associated with greater life satisfaction. Religiosity was associated with more frequent cognitive reappraisal (in both samples) and less frequent expressive suppression (in the Christian sample). Cognitive reappraisal mediated the link between religiosity and positive affect (in both samples) as well as negative affect (in the Christian sample). We discuss implications for understanding the link between religion and emotional well-being.

People who are more religious tend to experience more positive affect and higher levels of life satisfaction. Current explanations for this relation include social support, meaning in life, and more positive emotional experiences. Adding cognitive reappraisal as a new mechanism, we propose that religion consistently trains people to reappraise emotional events, making the devout more effective in applying this emotion regulation practice, which cultivates more positive affect and greater life satisfaction. In two studies, involving Israeli Jewish (N = 288) and American Christian (N = 277) participants, we found that more frequent use of cognitive reappraisal mediated the relationship between religiosity and affective experiences, which in turn, were associated with greater life satisfaction. Religiosity was associated with more frequent cognitive reappraisal (in both samples) and less frequent expressive suppression (in the Christian sample). Cognitive reappraisal mediated the link between religiosity and positive affect (in both samples) as well as negative affect (in the Christian sample). We discuss implications for understanding the link between religion and emotional well-being.

Amaranthus is a genus of tropical origin that belongs to the Amaranthaceae. Today it is widely distributed all over the world, with species reaching temperate regions even before man converted some of them into cosmopolitan weeds or domesticates (crops or ornamentals).15 About 60 species are native to the Americas, and about 15 others to Europe, Asia, Africa, and Australia. Most of them are pioneer annuals of naturally open habitats, producing abundant seed. They thrive by constant colonization of sites of disturbed soil, with full sun and little competition. Long natural selection for such a way of life preadaptated certain of the species for success in habitats drastically disturbed by man. Thus, today Amaranthus spp. are best known as noxious weeds (e.g., A. hybridus L., A. retroflexus L., A. spinosus L., A. powellii S. Wats.). However, in tropical and subtropical countries, certain species are grown for grain (A. hypocondriacus L., A. cruentus L., A. caudatus L.), whereas the young plants of others are eaten as pot-herbs (A. dubius Mart., A. tricolor L.). Other species are cultivated as ornamentals for their highly colored inflorescence (A. caudatus L.) or leaves (A. tricolor L.). © 1995 by CRC Press, Inc.

In this article I analyze Van Gennep’s understanding of purity, impurity, and purification and its relationship with ancient Christian texts discussing these subjects. Through this comparison, I show how modern and ancient theories of ritual can illuminate each other, and more specifically, how purification was a problematic and ambivalent concept for both ancient Christian writers and for Van Gennep, making it a fruitful one for investigating the thought of both.

Intensive pond cultivation of Gracilaria may achieve maximal yields by enrichment of seawater with ammonia and CO2. In the present study, we examined the use of organic waste material as a source of ammonia and inorganic carbon. A biofiltration system was constructed, consisting of several fermentation tanks and a fluidized bed reactor for the required bioconversion of organic wastes. Gracilaria conferta was cultured in a 30m2 pond from which seawater was circulated through the biofiltration system for a period of nine months. As compared to the filtered seawater used for water supply, the outlets of the fermentation tanks and the fluidized bed reactor showed significant increases in dissolved inorganic carbon and ammonia concentrations and significant decreases in oxygen concentrations and redox potentials. The most efficient organic waste compound tested had the highest C/N ratio. No significant differences were found between the Gracilaria yields of the control and biofiltration pond systems. These results might contribute a fundamental improvement in the economy of Gracilaria pond cultivation by water recycling through such a biofiltration system. Statement of relevance The system might contribute a fundamental improvement in the economy of Gracilaria pond cultivation.

The heterogeneity of pancreatic ductal adenocarcinoma (PDAC) suggests that successful treatment might rely on simultaneous targeting of multiple genes, which can be achieved by RNA interference-based therapeutic strategies. Here we show a potent combination of microRNA and siRNA delivered by an efficient nanocarrier to PDAC tumors. Using proteomic-microRNA profiles and survival data of PDAC patients from TCGA, we found a novel signature for prolonged survival. Accordingly, we used a microRNA-mimic to increase miR-34a together with siRNA to silence PLK1 oncogene. For in vivo dual-targeting of this combination, we developed a biodegradable amphiphilic polyglutamate amine polymeric nanocarrier (APA). APA-miRNA-siRNA polyplexes systemically administered to orthotopically inoculated PDAC-bearing mice showed no toxicity and accumulated at the tumor, resulting in an enhanced antitumor effect due to inhibition of MYC oncogene, a common target of both miR-34a and PLK1. Taken together, our findings warrant this unique combined polyplex's potential as a novel nanotherapeutic for PDAC.