פרסומים

This chapter investigates the relationship between prolonged exposure to political violence (EPV) and post-traumatic stress symptoms (PTSS) among Palestinian adolescents. It also examines the moderating effect of participants’ age, gender, and parental socialization styles on the relationship between EPV and PTSS. A systematic cluster random sample of 2, 934 Palestinian adolescents aged 14 to 19 years living in the West Bank and East Jerusalem responded to self-administered questionnaires. Multiple regression analysis showed a positive relationship between levels of EPV and of PTSS. Girls showed higher levels of PTSS than boys. Hostile and rejecting parenting styles, strict discipline, and negative evaluation from parents correlated positively with high PTSS, whereas intimate and loving parenting correlated with low levels of PTSS, supporting the hypotheses presented here. The chapter discusses the importance of intimate and loving parenting styles as a possible protective factor for mitigating the effects of political violence on children.

Delivery of drugs through oral mucosa enables bypass of the gastrointestinal tract and “first pass“ metabolism in the liver and the gut. Thus, a higher and less variable bioavailability can be obtained. Mechanisms of this administration route for cannabidiol were investigated in the current research in pigs. Results show that cannabidiol has substantially low permeability rate over 8 h through oral mucosa and accumulates significantly within it. Furthermore, following the removal of the delivery device, residual prolongation of release from the oral mucosa into systemic blood circulation continues for several hours. This method of delivery enabled acquisition of clinically relevant plasma levels of cannabidiol. The absorption profile indicates that cannabidiol, as well as other lipophilic molecules, should be delivered through oral mucosa for systemic absorption from a device that conceals the drug and prevents its washout by the saliva flow and subsequent ingestion into gastrointestinal tract. © 2020 Elsevier B.V.

Delivery of drugs through oral mucosa enables bypass of the gastrointestinal tract and "first pass" metabolism in the liver and the gut. Thus, a higher and less variable bioavailability can be obtained. Mechanisms of this administration route for cannabidiol were investigated in the current research in pigs. Results show that cannabidiol has substantially low permeability rate over 8 h through oral mucosa and accumulates significantly within it. Furthermore, following the removal of the delivery device, residual prolongation of release from the oral mucosa into systemic blood circulation continues for several hours. This method of delivery enabled acquisition of clinically relevant plasma levels of cannabidiol. The absorption profile indicates that cannabidiol, as well as other lipophilic molecules, should be delivered through oral mucosa for systemic absorption from a device that conceals the drug and prevents its washout by the saliva flow and subsequent ingestion into gastrointestinal tract.

Delivery of drugs through oral mucosa enables bypass of the gastrointestinal tract and "first pass" metabolism in the liver and the gut. Thus, a higher and less variable bioavailability can be obtained. Mechanisms of this administration route for cannabidiol were investigated in the current research in pigs. Results show that cannabidiol has substantially low permeability rate over 8 h through oral mucosa and accumulates significantly within it. Furthermore, following the removal of the delivery device, residual prolongation of release from the oral mucosa into systemic blood circulation continues for several hours. This method of delivery enabled acquisition of clinically relevant plasma levels of cannabidiol. The absorption profile indicates that cannabidiol, as well as other lipophilic molecules, should be delivered through oral mucosa for systemic absorption from a device that conceals the drug and prevents its washout by the saliva flow and subsequent ingestion into gastrointestinal tract.

Delivery of drugs through oral mucosa enables bypass of the gastrointestinal tract and "first pass" metabolism in the liver and the gut. Thus, a higher and less variable bioavailability can be obtained. Mechanisms of this administration route for cannabidiol were investigated in the current research in pigs. Results show that cannabidiol has substantially low permeability rate over 8 h through oral mucosa and accumulates significantly within it. Furthermore, following the removal of the delivery device, residual prolongation of release from the oral mucosa into systemic blood circulation continues for several hours. This method of delivery enabled acquisition of clinically relevant plasma levels of cannabidiol. The absorption profile indicates that cannabidiol, as well as other lipophilic molecules, should be delivered through oral mucosa for systemic absorption from a device that conceals the drug and prevents its washout by the saliva flow and subsequent ingestion into gastrointestinal tract.

Both pancreatic intraepithelial neoplasia (PanIN), a frequent precursor of pancreatic cancer, and intraductal papillary mucinous neoplasm (IPMN), a less common precursor, undergo several phases of molecular conversions and finally develop into highly malignant solid tumors with negative effects on the quality of life. We approached this long-standing issue by examining the following PanIN/IPMN cell lines derived from mouse models of pancreatic cancer: Ptf1a-Cre; KrasG12D; p53f/+ and Ptf1a-Cre; KrasG12D; and Brg1f/f pancreatic ductal adenocarcinomas (PDAs). The mRNA from these cells was subjected to a cap analysis of gene expression (CAGE) to map the transcription starting sites and quantify the expression of promoters across the genome. Two RNA samples extracted from three individual subcutaneous tumors generated by the transplantation of PanIN or IPMN cancer cell lines were used to generate libraries and Illumina Seq, with four RNA samples in total, to depict discrete transcriptional network between IPMN and PanIN. Moreover, in IPMN cells, the transcriptome tended to be enriched for suppressive and inhibitory biological processes. In contrast, the transcriptome of PanIN cells exhibited properties of stemness. Notably, the proliferation capacity of the latter cells in culture was only minimally constrained by well-known chemotherapy drugs such as GSK690693 and gemcitabine. The various transcriptional factor network systems detected in PanIN and IPMN cells reflect the distinct molecular profiles of these cell types. Further, we hope that these findings will enhance our mechanistic understanding of the characteristic molecular alterations underlying pancreatic cancer precursors. These data may provide a promising direction for therapeutic research.

Because of its superior coherent and optical properties at room temperature, the nitrogen-vacancy (N-V) center in diamond has become a promising quantum probe for nanoscale quantum sensing. However, the application of N-V-containing nanodiamonds to quantum sensing suffers from their relatively short spin coherence times. Here we demonstrate energy-efficient protection of N-V spin coherence in nanodiamonds using concatenated continuous dynamical decoupling, which exhibits excellent performance with a less-stringent microwave-power requirement. When this is applied to nanodiamonds in living cells, we are able to extend the spin coherence time by an order of magnitude to the T1 limit of 30μs. Further analysis demonstrates concomitant improvements of sensing performance, which shows that our results provide an important step toward in vivo quantum sensing using N-V centers in nanodiamond.

Traumatic brain injury (TBI) is one of the main causes of death in young people for which currently no efficacious treatment exists. Recently, we have reported that mice with mild-TBI with a specific injury in the insula showed elevated levels of a little investigated N-acyl amino acid, N-oleoylglycine (OlGly). N-acyl amino acids have recently experienced an increased interest because of their important biological activities. They belong to the endocannabinoidome family of lipids with structural similarities with the endocannabinoids (eCBs). The aim of this study was to test the neuroprotective and antihyperalgesic actions of OlGly in a model of mouse mild-TBI (mTBI) and its effect on levels of eCBs and N-acylethanolamines at the end of treatment. Following mTBI, mice were administered a daily injection of OlGly (10-50-100 mg/kg i.p.) for 14 days. Treatment with OlGly normalized motor impairment and behavior in the light/dark box test, ameliorated TBI-induced thermal hyperalgesia and mechanical allodynia, and normalized aggressiveness and depression. Moreover, levels of eCBs and some N-acylethanolamines underwent significant changes 60 days after TBI, especially in the prefrontal cortex and hypothalamus, and OlGly reversed some of these changes. In conclusion, our findings reveal that OlGly ameliorates the behavioral alterations associated with mTBI in mice, while concomitantly modulating eCB and eCB-like mediator tone. © 2020 American Chemical Society.

Biomineralization is a common strategy adopted by organisms to support their body structure. Plants practice significant silicon and calcium based biomineralization in which silicon is deposited as silica in cell walls and intracellularly in various cell-types, while calcium is deposited mostly as calcium oxalate in vacuoles of specialized cells. In this review, we compare cellular processes leading to protein-dependent mineralization in plants, diatoms and sponges (phylum Porifera). The mechanisms of biomineralization in these organisms are inherently different. The composite silica structure in diatoms forms inside the cytoplasm in a membrane bound vesicle, which after maturation is exocytosed to the cell surface. In sponges, separate vesicles with the mineral precursor (silicic acid), an inorganic template, and organic molecules, fuse together and are extruded out. In plants, calcium oxalate precursors are concentrated in a vacuolar vesicle containing a protein matrix which is never exocytosed. Silica deposition in grass silica cells takes place outside the cell membrane when the cells secrete the mineralizing protein into the apoplasm rich with silicic acid (the mineral precursor molecules). Our review infers that the organism complexity and precursor reactivity (calcium and oxalate versus silicic acid) are main driving forces for the evolution of varied mineralization mechanisms.

Many plant viruses are vector-borne and depend on arthropods for transmission between host plants. Begomoviruses, the largest, most damaging and emerging group of plant viruses, infect hundreds of plant species, and new virus species of the group are discovered each year. Begomoviruses are transmitted by members of the whitefly Bemisia tabaci species complex in a persistent-circulative manner. Tomato yellow leaf curl virus (TYLCV) is one of the most devastating begomoviruses worldwide and causes major losses in tomato crops, as well as in many agriculturally important plant species. Different B. tabaci populations vary in their virus transmission abilities; however, the causes for these variations are attributed among others to genetic differences among vector populations, as well as to differences in the bacterial symbionts housed within B. tabaci.Here, we performed discovery proteomic analyses in 9 whitefly populations from both Middle East Asia Minor I (MEAM1, formerly known as B biotype) and Mediterranean (MED, formerly known as Q biotype) species. We analysed our proteomic results on the basis of the different TYLCV transmission abilities of the various populations included in the study. The results provide the first comprehensive list of candidate insect and bacterial symbiont (mainly Rickettsia) proteins associated with virus transmission.Our data demonstrate that the proteomic signatures of better vector populations differ considerably when compared with less efficient vector populations in the 2 whitefly species tested in this study. While MEAM1 efficient vector populations have a more lenient immune system, the Q efficient vector populations have higher abundance of proteins possibly implicated in virus passage through cells. Both species show a strong link of the facultative symbiont Rickettsia to virus transmission.

Diabetic kidney disease (DKD) increases the risk for mortality and is the leading cause of end-stage renal disease. Treatment with sodium-glucose cotransporter 2 inhibitors (SGLT2i) attenuates the progression of DKD, especially in patients with advanced kidney disease. Herein, we show that in diabetes, mTORC1 activity is increased in renal proximal tubule cells (RPTCs) along with enhanced tubule-interstitial fibrosis; this is prevented by SGLT2i. Constitutive activation of mTORC1 in RPTCs induces renal fibrosis and failure and abolishes the renal-protective effects of SGLT2i in diabetes. On the contrary, partial inhibition of mTORC1 in RPTCs prevents fibrosis and the decline in renal function. Stimulation of mTORC1 in RPTCs turns on a pro-fibrotic program in the renal cortex, whereas its inhibition in diabetes reverses the alterations in gene expression. We suggest that RPTC mTORC1 is a critical node that mediates kidney dysfunction in diabetes and the protective effects of SGLT2i by regulating fibrogenesis.

Diabetic kidney disease (DKD) increases the risk for mortality and is the leading cause of end-stage renal disease. Treatment with sodium-glucose cotransporter 2 inhibitors (SGLT2i) attenuates the progression of DKD, especially in patients with advanced kidney disease. Herein, we show that in diabetes, mTORC1 activity is increased in renal proximal tubule cells (RPTCs) along with enhanced tubule-interstitial fibrosis; this is prevented by SGLT2i. Constitutive activation of mTORC1 in RPTCs induces renal fibrosis and failure and abolishes the renal-protective effects of SGLT2i in diabetes. On the contrary, partial inhibition of mTORC1 in RPTCs prevents fibrosis and the decline in renal function. Stimulation of mTORC1 in RPTCs turns on a pro-fibrotic program in the renal cortex, whereas its inhibition in diabetes reverses the alterations in gene expression. We suggest that RPTC mTORC1 is a critical node that mediates kidney dysfunction in diabetes and the protective effects of SGLT2i by regulating fibrogenesis.