פרסומים

Agroholdings have become a major player in Russian agriculture in less than two decades. Nevertheless, there is no legal definition of agroholding as an organisation, and no statistical information on agroholdings as a distinct category is collected. Only informal definitions exist, which regard agroholdings as groupings of agricultural enterprises linked into a single management network. The numerous publications on Russian agroholdings are mostly based on limited or sporadic data. This is the first study that assembles a full list of more than 1,000 agroholdings in Russia and analyses the corresponding data from official sources. The study examines the role of agroholdings in Russian agriculture and estimates some performance measures. We group all agricultural enterprises (corporate farms in their own right) in Russia into agroholding members and independent, non-member farms, and perform a comparative analysis of the two distinct organisational forms that are at the focus of Russian agricultural policy.

Nanomaterials are now being used in a wide variety of biomedical applications. Medical and health-related issues, however, have raised major concerns, in view of the potential risks of these materials against tissue, cells, and/or organs and these are still poorly understood. These particles are able to interact with the body in countless ways, and they can cause unexpected and hazardous toxicities, especially at cellular levels. Therefore, undertaking in vitro and in vivo experiments is vital to establish their toxicity with natural tissues. In this review, we discuss the underlying mechanisms of nanotoxicity and provide an overview on in vitro characterizations and cytotoxicity assays, as well as in vivo studies that emphasize blood circulation and the in vivo fate of nanomaterials. Our focus is on understanding the role that the physicochemical properties of nanomaterials play in determining their toxicity.

Salivary glands play essential roles in normal upper gastrointestinal tract function and oral health via saliva production. There are three types of salivary glands; the submandibular gland and parotid gland, which secrete serous saliva, and the sublingual gland secretes mucous saliva in mice [1]. Therefore, salivary gland dysfunction due to atrophy of acinar cells caused by Sjogren's syndrome, radiation therapy for head and neck cancer, and aging and saliva reduction, and results in xerostomia (dry mouth syndrome), causes various clinical problems in oral health and influences overall bodily health [2]. Xerostomia induces various clinical problems in oral health, such as dental decay, bacterial infection, and disorders of mastication and swallowing, which result in a general reduction in the quality of life [3]. Current standard to cure xerostomia are symptomatic treatments, such as the administration of artificial saliva substitutes and sialogogues, and the administration of parasympathetic stimulation drugs, including pilocarpine and cevimeline [4]. In salivary gland regenerative therapy, stem cell transplantation, which expressed c-kit and Sca-1 as stem cell markers and exhibit high proliferative capacities [5,6], and gene modification for water channel aquaporin-1 (AQP1) and Interleukin-17 (IL-17) receptor antibody is performed to restore the damaged acinar tissue and recover the flow of saliva [7,8]. Salivary glands arise from the organ germ, which is induced by reciprocal epithelial and mesenchymal stem cell interactions during embryonic development [9]. In this two decades, advances in developmental biology have led to break-through in regeneration of functional bioengineered organ in vitro by using embryonic organ-inductive potential stem cells. Recently, regeneration of fully functional salivary gland as a next-generation organ regeneration has been reported after the transplantation of bioengineered salivary gland germ developed by using embryonic organ-inductive potential stem cells as well as iPS cells [10,11]. In 2013, we demonstrated the fully functional salivary gland regeneration by recapitulating the embryonic morphogenesis. The bioengineered salivary gland organ germ, which was reconstituted by our Organ Germ Method using organ-inductive potential stem cells derived from submandibular gland germs of ED 13.5 mice [12], showed reciprocal epithelial and mesenchymal interactions in in vitro organ culture. Following the orthotopic transplantation, the bioengineered germ develops into a mature salivary gland via acinar formations with a myoepithelium and innervation. The bioengineered salivary gland produces saliva in response to the pilocarpine administration and gustatory stimulation by citrate, protected against bacterial infection and restores normal swallowing function in a mouse model. This study provides a proofof- concept for bioengineered salivary gland regeneration. The next breakthrough first reported in 2008 was the emergence of an organoid as a mini-organ that was generated by inducing body patterning and a subsequent organ-forming field formation in pluripotent stem cells [13]. Organoids are useful to recapitulate the process of organogenesis, which are strictly regulated by morphogen signalling and transcriptional networks. To date, multiple types of organoids, including the retina, pituitary gland, liver, and lung have been successfully generated in vitro. Our colleagues identified a specific combination of two transcription factors, Sox9 and Foxc1, are responsible for the differentiation of mouse ES cells-derived oral ectodermal region into the salivary gland rudiment in a threedimensional organoid culture system [11]. The induced salivary gland rudiment showed a similar morphologies and gene expression profiles to those of the embryonic salivary gland rudiment of normal mice. Following orthotopic transplantation into salivary glands-defected mice, the induced salivary gland germ exhibited characteristics of mature salivary glands including histological morphologies, nerve innervation and saliva secretion. This study is the first report of the fully functional organ regeneration by using organoid, demonstrating the potential of salivary gland organ regeneration from pluripotent stem cells for an additional organ replacement regenerative therapy. As part of regenerative medicine, the autogenous transplantation of stem cells, including bone marrow, and tissue sheets such as skin, cornea, and cardiac muscle, has already been applied clinically through cell and tissue transplantation therapies. The progress made in the past two decades has been remarkable, paving the way for possible future organ replacement regenerative therapies. There remains a critical issue as to whether next-generation organ regenerative therapy can be adopted as a novel clinical therapy for patients of the loss of organ function. The bioengineered salivary gland organ germ by using both embryonic organ-inductive potential stem cells and pluripotent stem cells can grow where salivary grand should be in oral cavity and produce the saliva in response to various taste stimulations. These works indicate the potentials for clinical application of salivary gland organ regeneration. Applying knowledge of these basic research will enable the regeneration of salivary gland organ in the next decades.

Skin homeostasis is constantly challenged by environmental factors, affecting its delicate redox balance. The skin is also home to a wide variety of bacterial species, including Staphylococci. The cutaneous redox state is governed by the Nrf2-keap1 pathway, which is responsible for the induction of phase II cytoprotective enzymes, thus sustaining a healthy oxidative state. As part of normal metabolism, both bacteria and cutaneous tissue emit copious amounts of volatile organic compounds (VOCs), one subgroup of which are aldehydes. $\alpha$,$\beta$-unsaturated aldehydes are known activators of Nrf2-keap1 pathway by direct oxidation of the keap1 protein. However, we did not encounter reports of Nrf2 activation by saturated or aromatic aldehydes, neither bacteria nor skin-derived. We hypothesized that non-$\alpha$,$\beta$-unsaturated aldehydes derived from skin or cutaneous bacteria may act as Nrf2-keap1 pathway activators and therefore afford protection against environmental insults. The saturated aldehydes nonanal and decanal (known skin metabolites) and the aromatic aldehyde benzaldehyde (known skin and Staphylococcus epidermidis metabolite) were shown to induce the Nrf2-keap1 pathway in human keratinocytes. We also identified a newly described aromatic aldehyde, 3-furaldehyde (3-FA), emitted from S. aureus and S. epidermidis cultures, which also activated the pathway. Moreover, Nrf2-keap1 induction led to a significant protection against UVB-induced apoptosis. The mechanism involved in this activation has been partially elucidated. This work emphasizes the importance of cutaneous bacteria, as well as healthy skin lipid peroxidation processes in the maintenance and regulation of the cellular antioxidant response, namely with regard to coping with environmental stressors.

Objective: Improving symptomology and cognitive deficits in neurodevelopmental disorders is a crucial
challenge. We examined whether neurostimulation protocols, which have been shown to yield long-term
effects when combined with cognitive training, could benefit children with Attention-deficit/hyperactiv
ity-disorder (ADHD), the most common neurodevelopmental disorder in childhood.
Methods: We used a randomized double-blind active-controlled crossover study of 19 unmedicated children
with ADHD, who received either anodal transcranial direct current stimulation (tDCS) over the left
dorsolateral prefrontal cortex (dlPFC) or random noise stimulation (tRNS) over the bilateral dlPFC, while
completing executive functions training.
Results: For our primary outcome, tRNS yielded a clinical improvement as indicated by the reduced
ADHD rating-scale score from baseline, and in comparison to the changes observed in tDCS. The effect
of brain stimulation one week after completion of treatment yielded further improvement, suggesting
a neuroplasticity-related effect. Finally, tRNS improved working memory compared to tDCS, and a larger
tRNS effect on ADHD rating-scale was predicted for those who showed the greatest improvement in
working memory.
Conclusions: We found that our intervention can have a lasting effect, rather than a merely immediate
effect as was shown for in previous medical interventions in ADHD.
Significance: Our results provide a promising direction toward a novel intervention in ADHD.

Scapegoating -- attributing inordinate blame for a negative outcome to a target individual or group -- is considered an important driver of discrimination by psychologists, but has received little attention by economists. This paper helps fill the gap by providing evidence for scapegoating in a natural setting. Using data on three million driving tests held in Israel, I find that an increase in the number of unrelated traffic accident fatalities leads driving testers to discriminate against out-group students. Scapegoating characterizes all groups of testers -- Jewish and Arab, male and female -- and works to increase ethnic in-group bias and decrease gender out-group bias.

SCLC is frequently associated with paraneoplastic syndromes, including dermatomyositis. Patients with malignancy-associated dermatomyositis express a specific autoantibody pattern usually positive for anti-transcription intermediary factor 1-γ (TIF1-γ), suggesting anti-TIF1-γ plays a role in development of malignancy-associated dermatomyositis. We present a case of a patient with SCLC, paraneoplastic dermatomyositis, positive anti-TIF1-γ, and a point mutation in TIF1-γ coding gene, with prominent clinical response to chemoradiation. We suggest that this point mutation is pathogenic, providing evidence for the development of paraneoplastic dermatomyositis through immune cross-reactivity.

Can you efficiently look for something even without knowing what it looks like? According to theories of visual search, the answer is no: A template of the search target must be maintained in an active state to guide search for potential locations of the target. Here, we tested the need for an active template by assessing a case in which this template is improbable: the search for a familiar face among unfamiliar ones when the identity of the target face is unknown. Because people are familiar with hundreds of faces, an active guiding template seems unlikely in this case. Nevertheless, participants (35 Israelis and 33 Germans) were able to guide their search as long as extrafoveal processing of the target features was possible. These results challenge current theories of visual search by showing that guidance can rely on long-term memory and extrafoveal processing rather than on an active search template.

Can you efficiently look for something even without knowing what it looks like? According to theories of visual search, the answer is no: A template of the search target must be maintained in an active state to guide search for potential locations of the target. Here, we tested the need for an active template by assessing a case in which this template is improbable: the search for a familiar face among unfamiliar ones when the identity of the target face is unknown. Because people are familiar with hundreds of faces, an active guiding template seems unlikely in this case. Nevertheless, participants (35 Israelis and 33 Germans) were able to guide their search as long as extrafoveal processing of the target features was possible. These results challenge current theories of visual search by showing that guidance can rely on long-term memory and extrafoveal processing rather than on an active search template.

Plant pathogens challenge our efforts to maximize crop production due to their ability to rapidly develop resistance to pesticides. Fungal biocontrol agents have become an important alternative to chemical fungicides, due to environmental concerns related to the latter. Here we review the complex modes of action of biocontrol agents in general and epiphytic yeasts belonging to the genus Pseudozyma specifically and P. aphidis in particular. Biocontrol agents act through multiple direct and indirect mechanisms, which are mainly based on their secretions. We discuss the direct modes of action, such as antibiosis, reactive oxygen species-producing, and cell wall-degrading enzyme secretions which can also play a role in mycoparasitism. In addition, we discuss indirect modes of action, such as hyperbiotrophy, induced resistance and growth promotion based on the secretion of effectors and elicitors from the biocontrol agent. Due to their unique characteristics, epiphytic yeasts hold great potential for use as biocontrol agents, which may be more environmentally friendly than conventional pesticides and provide a way to reduce our dependency on fungicides based on increasingly expensive fossil fuels. No less important, the complex mode of action of Pseudozyma-based biocontrol agents can also reduce the frequency of resistance developed by pathogens to these agents.