פרסומים

BACKGROUND: The dorsal domain of the neural tube is an excellent model to investigate the generation of complexity during embryonic development. It is a highly dynamic and multifaceted region being first transiently populated by prospective neural crest (NC) cells that sequentially emigrate to generate most of the peripheral nervous system. Subsequently, it becomes the definitive roof plate (RP) of the central nervous system. The RP, in turn, constitutes a patterning center for dorsal interneuron development. The factors underlying establishment of the definitive RP and its segregation from NC and dorsal interneurons are currently unknown. RESULTS: We performed a transcriptome analysis at trunk levels of quail embryos comparing the dorsal neural tube at premigratory NC and RP stages. This unraveled molecular heterogeneity between NC and RP stages, and within the RP itself. By implementing these genes, we asked whether Notch signaling is involved in RP development. First, we observed that Notch is active at the RP-interneuron interface. Furthermore, gain and loss of Notch function in quail and mouse embryos, respectively, revealed no effect on early NC behavior. Constitutive Notch activation caused a local downregulation of RP markers with a concomitant development of dI1 interneurons, as well as an ectopic upregulation of RP markers in the interneuron domain. Reciprocally, in mice lacking Notch activity, both the RP and dI1 interneurons failed to form and this was associated with expansion of the dI2 population. CONCLUSIONS: Collectively, our results offer a new resource for defining specific cell types, and provide evidence that Notch is required to establish the definitive RP, and to determine the choice between RP and interneuron fates, but not the segregation of RP from NC.

Interest in CBG (cannabigerol) has been growing in the past few years, due to its anti-inflammatory properties and other therapeutic benefits. Here we report the synthesis of three new CBG derivatives (HUM-223, HUM-233 and HUM-234) and show them to possess anti-inflammatory and analgesic properties. In addition, unlike CBG, HUM-234 also prevents obesity in mice fed a high-fat diet (HFD). The metabolic state of the treated mice on HFD is significantly better than that of vehicle-treated mice, and their liver slices show significantly less steatosis than untreated HFD or CBG-treated ones from HFD mice. We believe that HUM-223, HUM-233 and HUM-234 have the potential for development as novel drug candidates for the treatment of inflammatory conditions, and in the case of HUM-234, potentially for obesity where there is a huge unmet need.

Interest in CBG (cannabigerol) has been growing in the past few years, due to its anti-inflammatory properties and other therapeutic benefits. Here we report the synthesis of three new CBG derivatives (HUM-223, HUM-233 and HUM-234) and show them to possess anti-inflammatory and analgesic properties. In addition, unlike CBG, HUM-234 also prevents obesity in mice fed a high-fat diet (HFD). The metabolic state of the treated mice on HFD is significantly better than that of vehicle-treated mice, and their liver slices show significantly less steatosis than untreated HFD or CBG-treated ones from HFD mice. We believe that HUM-223, HUM-233 and HUM-234 have the potential for development as novel drug candidates for the treatment of inflammatory conditions, and in the case of HUM-234, potentially for obesity where there is a huge unmet need.

Typical murine models of allergic inflammation are induced by the combination of ovalbumin and aluminum hydroxide. However, accumulating evidence indicates that, in models of asthma and atopic dermatitis, allergic inflammation can be generated in the absence of aluminum hydroxide. Moreover, co-administration of Staphylococcus aureus enterotoxin B with ovalbumin can enhance inflammation. The objective of this study was to establish a rapid and mast cell-dependent murine model of allergic inflammation by inducing allergic peritonitis using ovalbumin and S. aureus enterotoxin B. Allergic peritonitis was induced in C57BL/6 mice by subcutaneous sensitization and intraperitoneal challenge with ovalbumin and S. aureus enterotoxin B. Disease characteristics were assessed by flow cytometry, enzyme-linked immunosorbent assay (ELISA), trypan blue exclusion and colorimetric assays. The time-course of the allergic peritonitis revealed a peak of peritoneal inflammation 48 h after challenge, as assessed by total cells and eosinophil counts. The decrease of cell numbers started 96 h post-challenge, with complete clearance within 168 h. Moreover, significantly higher levels of tryptase and increased vascular permeability were found 30 min following challenge. Allergic inflammation induction by ovalbumin and S. aureus enterotoxin B was impaired in mast cell-deficient mice and partially restored by mice reconstitution with bone marrow-derived mast cells, indicating the mast cell role in this model. We present a novel model of allergic peritonitis that is mast cell-dependent, simple and robust. Moreover, the use of S. aureus enterotoxin B better resembles human allergic inflammation, which is known to be characterized by the colonization of S. aureus.

Typical murine models of allergic inflammation are induced by the combination of ovalbumin and aluminum hydroxide. However, accumulating evidence indicates that, in models of asthma and atopic dermatitis, allergic inflammation can be generated in the absence of aluminum hydroxide. Moreover, co-administration of Staphylococcus aureus enterotoxin B with ovalbumin can enhance inflammation. The objective of this study was to establish a rapid and mast cell-dependent murine model of allergic inflammation by inducing allergic peritonitis using ovalbumin and S. aureus enterotoxin B. Allergic peritonitis was induced in C57BL/6 mice by subcutaneous sensitization and intraperitoneal challenge with ovalbumin and S. aureus enterotoxin B. Disease characteristics were assessed by flow cytometry, enzyme-linked immunosorbent assay (ELISA), trypan blue exclusion and colorimetric assays. The time–course of the allergic peritonitis revealed a peak of peritoneal inflammation 48 h after challenge, as assessed by total cells and eosinophil counts. The decrease of cell numbers started 96 h post-challenge, with complete clearance within 168 h. Moreover, significantly higher levels of tryptase and increased vascular permeability were found 30 min following challenge. Allergic inflammation induction by ovalbumin and S. aureus enterotoxin B was impaired in mast cell-deficient mice and partially restored by mice reconstitution with bone marrow-derived mast cells, indicating the mast cell role in this model. We present a novel model of allergic peritonitis that is mast cell-dependent, simple and robust. Moreover, the use of S. aureus enterotoxin B better resembles human allergic inflammation, which is known to be characterized by the colonization of S. aureus.

In an urbanized city, about a third of total electrical consumption is allocated for indoor lighting and air conditioning system in residential and commercial buildings. The majority of the worldwide energy generation comes from burning of non-renewable fossil fuel which is not sustainable in the long run. The use of smart windows technology may catalyze the effort to reduce energy consumption of building and houses. More than 50% of heat entering a building through windows originate from the solar radiation in the near infrared (NIR) region. This candidate smart window material must exhibit dual-band (visible and NIR) modulation that allows selective modulation of NIR heat without affecting visible light transmission. A good electrochromic material in this respect should possess high visible light transmission, high NIR modulation, fast switching between colored and bleached state, and good stability over prolonged usage. In this work, we propose a novel Nd–Mo co-doped SnO2/α-WO3 electrochromic materials (ECs). As compared to the traditional SnO2/α-WO3 ECs, our Nd–Mo co-doped SnO2/α-WO3 ECs exhibits up to 90% visible light transparency (at λ = 600 nm), 62% NIR modulation (at wavelength 1200 nm), high coloration efficiency ($\sim$200 cm2 C−1), fast switching time with only 31% electrochromic performance drop (vs 59% of undoped sample) after up to 1000 reversible cyclic test. The enhanced electrochromic performance comes from the presence of Nd–Mo co-dopants that limit the trapping of Li + ion within α-WO3 framework, reduce the extent of crystallization of α-WO3 layer and enhancement of the electronic conductivity by transferring their excess electron to the conduction band of the SnO2. To the best of the authors' knowledge, the present composition of ECs offers one of the better candidate materials for electrochromic to be used as thermal management layers on smart windows application.

We previously showed that Livin, an inhibitor of apoptosis protein, is specifically cleaved to produce a truncated protein, tLivin, and demonstrated its paradoxical proapoptotic activity. We further demonstrated that mini-tLivin (MTV), a 70 amino acids derivative of tLivin, is a proapoptotic protein as potent as tLivin. Based on these findings, in this study we aimed to develop a venue to target MTV for the treatment of diffuse large B-cell lymphoma (DLBCL). MTV was conjugated to poly (lactide-co-glycolic acid) surface-activated nanoparticles (NPs). In order to target MTV-NPs we also conjugated CD40 ligand (CD40L) to the surface of the NPs and evaluated the efficacy of the bifunctional CD40L-MTV-NPs. In vitro, CD40L-MTV-NPs elicited significant apoptosis of DLBCL cells. In a disseminated mouse model of DLBCL, 37.5% of MTV-NPs treated mice survived at the end of the experiment. Targeting MTV-NPs using CD40L greatly improved survival and 71.4% of these mice survived. CD40L-MTV-NPs also greatly reduced CNS involvement of DLBCL. Only 20% of these mice presented infiltration of lymphoma to the brain in comparison to 77% of the MTV-NPs treated mice. In a subcutaneous mouse model, CD40L-MTV-NPs significantly reduced tumor volume in correlation with significant increased caspase-3 activity. Thus, targeted MTV-NPs suggest a novel approach to overcome apoptosis resistance in cancer.

Two experiments manipulated participants’ familiarity with another person and examined their performance in future understanding of that person’s emotions. To gain familiarity, participants watched several videos of the target sharing experiences and rated her emotions. In the Feedback condition, perceivers learned about the actual emotions the target felt. In the Control condition, perceivers completed identical recognition tasks but did not know the target’s own emotion ratings. Studies (N total= 398; one preregistered) found that the Feedback group was more accurate than the Control in future understanding of the target’s emotions. Results provide a proof-of-concept demonstration that brief preliminary learning about past emotional experiences of another person can give one a more accurate understanding of the person in the future.(PsycInfo Database Record (c) 2021 APA, all rights reserved.

Can oil discovery shocks affect the demand for protectionism? An intertemporal model of Dutch disease indicates that if the tradable sector is politically dominant then an oil discovery can induce protectionism. If the economy is also credit constrained, this effect is intensified upon discovery, but partially reversed when oil revenues start to flow. We test these predictions using 16.2 million, HS-6 level, bilateral tariff rates that cover 5718 products in 155 countries over the period 1988–2012, and data on worldwide discoveries of giant oil and gas fields. Our identification strategy rests on the exogeneity of the timing of discoveries. Our empirical results indicate that an oil discovery increases tariffs during pre-production years and decreases tariffs in the years to follow yet to a lesser extent, most notably in capital scarce economies with a relatively dominant tradable sector. Our baseline estimates indicate that a giant oil field discovery induces a rise of approximately 13% in the average tariff over the course of 10 years; this increase is approximately 2.5 times larger during the pre-production period when the oil discovery represents a pure news shock.