Contradictory Effects Research Articles

RUSSIAN SPACE IN THE PROCESS OF HISTORICAL TRANSITIONS (TOWARDS THE DEVELOPMENT AND IMPLEMENTATION OF THE THEORY OF POST-SOVIET SYSTEM TRANSFORMATIONS OF THE ORGANIZATION OF THE SOCIO-ECONOMIC SPACE)

As an object of research in the article, the phenomenon of the Russian space, taken in a long historical retrospective, appears, the subject issues of the study of which are the prerequisites, meanings and content, as well as significant cause-and-effect relationships and the dynamics of its transformations. It is shown that the processes of acquisition and development (colonization) of the country’s space took many centuries, took place in different directions, with different intensity and were initially associated with special motives, extraordinary efforts and contradictory consequences. The cornerstones of the main stages of transformation of the Russian space — pre-revolutionary, Soviet and post-Soviet — are considered. A theoretical understanding of the modern stage is proposed, the deep meaning of which the author associates with the need to remove the main contradiction of the spatial organization of life in the country, due to the abrupt transition of the country «from socialism to the market». The driving forces and limitations of the formation of a new configuration of space are highlighted, the course and content of this transition process are predicted. In the author’s understanding, the ongoing transition is characterized by a complex interweaving of reforms and counter-reforms: the market-federative reversal of the 1990s (with its well-known excesses of reformation radicalism) is opposed by a mechanistic one that ignores the realities of the established market-capitalist system, and therefore counterproductive reproduction of a number of Soviet planning and placement algorithms of public administration. The conceptual approach to the consideration of the organization of the socio-economic space as a large complex dynamic open system and to the interpretation of its transformation processes as systemic transformations is substantiated. The deep Russian features of state participation in the transformation of the socio-economic space are revealed, the requirements for the current state regional policy are formulated.

Effects of Long-Term Straw Management and Potassium Fertilization on Crop Yield, Soil Properties, and Microbial Community in a Rice–Oilseed Rape Rotation

The present study aims to assess the influences of long-term crop straw returning and recommended potassium fertilization on the dynamic change in rice and oilseed rape yield, soil properties, bacterial and fungal alpha diversity, and community composition in a rice–oilseed rape system. A long-term (2011–2020) field experiment was carried out in a selected paddy soil farmland in Jianghan Plain, central China. There were four treatments with three replications: NP, NPK, NPS, and NPKS, where nitrogen (N), phosphate (P), potassium (K), and (S) denote N fertilizer, P fertilizer, K fertilizer, and crop straw, respectively. Results showed that long-term K fertilization and crop straw returning could increase the crop yield at varying degrees for ten years. Compared with the NP treatment, the long-term crop straw incorporation with K fertilizer (NPKS treatment) was found to have the best effect, and the yield rates increased by 23.0% and 20.5% for rice and oilseed rape, respectively. The application of NPK fertilizer for ten years decreased the bacterial and fungal alpha diversity and the relative abundance of dominant bacterial and fungal taxa, whereas continuous straw incorporation had a contradictory effect. NPKS treatment significantly increased the relative abundance of some copiotrophic bacteria (Firmicutes, Gemmatimonadetes, and Proteobacteria) and fungi (Ascomycota). Available K, soil organic matter, dissolved organic carbon, and easily oxidized organic carbon were closely related to alterations in the composition of the dominant bacterial community; easily oxidized organic carbon, dissolved organic carbon, and slowly available K were significantly correlated with the fungal community. We conclude that long-term crop straw returning to the field accompanied with K fertilizer should be employed in rice-growing regions to achieve not only higher crop yield but also the increase in soil active organic carbon and available K content and the improvement of the biological quality of farmland.

The development of children’s prospective memory: Lessons for developmental science

AbstractThe study of children’s prospective memory has gained new momentum over the past 20 years and is now an active area of research in cognitive development. Yet, this resurgence has been accompanied by significant challenges that offer important lessons and insights for other areas of developmental science. In this article, I provide an overview and theoretical accounts of the development of children’s prospective memory. I then describe three puzzling findings that remain unresolved in children’s development of this kind of memory: (1) the contradictory effects of delay length on prospective memory performance, (2) why reminders sometimes fail to improve prospective memory performance, and (3) why parent reports and behavioral measures of prospective memory might fail to correlate. I discuss how each challenge can be applied broadly to other areas of children’s development. I conclude by highlighting challenges and opportunities as the field moves forward.

Adiponectin negatively regulates pigmentation, Wnt/β-catenin and HGF/c-Met signalling within human scalp hair follicles ex vivo.

Adiponectin reportedly stimulates proliferation and elongation of human scalp hair follicles (HFs) ex vivo. In the current study, we investigated how adiponectin oligomers produced by perifollicular dermal white adipose tissue (dWAT), a potent source of adiponectin isoforms, influence human HF proliferation and pigmentation. To do so, we treated microdissected, organ-cultured HFs in the presence or absence of dWAT with a recombinant human adiponectin oligomer mix, or inhibited dWAT-derived adiponectin using a neutralizing antibody. Multiplex qPCR (Fluidigm) revealed that adiponectin oligomers downregulated pigmentation genes KITLG, PMEL and TYRP1 and Wnt genes AXIN2, LEF1 and WNT10B. In situ hybridization showed that adiponectin downregulated AXIN2 and LEF1, and up-regulated DKK1 within the dermal papilla (DP), a highly unusual transcriptional profile for a putative hair growth-promoting agent. Adiponectin oligomers also downregulated protein expression of the HGF receptor c-Met within the matrix and DP. However, adiponectin did not alter hair matrix keratinocyte proliferation within 48h ex vivo, irrespective of the presence/absence of dWAT; HF pigmentation (Masson-Fontana histochemistry, tyrosinase activity) was also unchanged. In contrast, neutralizing adiponectin isoforms within HF + dWAT increased proliferation, melanin content and tyrosinase activity but resulted in fewer melanocytes and melanocytic dendrites, as assessed by gp100 immunostaining. These seemingly contradictory effects suggest that adiponectin exerts complex effects upon human HF biology, likely in parallel with the pro-pigmentation effects of dWAT- and DP-derived HGF. Our data suggest that dWAT-derived ratios of adiponectin isoforms and the cleaved, globular version of adiponectin may in fact determine how adiponectin impacts upon follicular pigmentation and growth.

CEACAM1 - A Promising Biomarker for Melanoma

Abstract Malignant melanoma is the third most common skin cancer, but it also remains the most aggressive. Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) is a promising diagnostic and prognostic biomarker for melanoma, because its expression is important for tumour development. This review aims at highlighting the most recent discoveries regarding CEACAM1 and its correlation to the diagnosis and prognosis of malignant melanoma. National Library of Medicine (NIH) PubMed was used for selecting articles published between 2004-2021, based on their relevance and novelty. With its multiple and somewhat contradictory effects, CEACAM1 seems to influence melanoma invasion, migration, immunomodulation and tumour suppression, serving as a useful diagnostic biomarker and target for therapy. While the incidence of malignant melanoma has been increasing over the last decades without signs of prognosis improvement, it is crucial that new biomarkers for diagnosis and detection of metastatic progression are discovered, and CEACAM1 might be a viable option.

P.0071 Do not judge a rat by its (forced) swimming: exploring the contradictory affective behavioural effects of chronic adolescent HU-210 exposure

P.0071 Do not judge a rat by its (forced) swimming: exploring the contradictory affective behavioural effects of chronic adolescent HU-210 exposure

The Influence of Sonication Processing Conditions on Electrical and Mechanical Properties of Single and Hybrid Epoxy Nanocomposites Filled with Carbon Nanoparticles.

Graphene nanoplatelets (GNP) and carbon nanotubes (CNT) are used to enhance electrical and mechanical properties of epoxy-based nanocomposites. Despite the evidence of synergetic effects in the hybrid GNP-CNT-epoxy system, there is still a lack of studies that focus on the influence of different dispersion methods on the final properties of these ternary systems. In the present work, direct and indirect ultrasonication methods were used to prepare single- and hybrid-filled GNP-CNT-epoxy nanocomposites, varying the amplitude and time of sonication in order to investigate their effect on electrical and thermomechanical properties. Impedance spectroscopy was combined with rheology and electron microscopy to show that high-power direct sonication tends to degrade electrical conductivity in GNP-CNT-epoxy nanocomposites due to damage caused in the nanoparticles. CNT-filled samples were mostly benefitted by low-power direct sonication, achieving an electrical conductivity of 1.3 × 10−3 S·m−1 at 0.25 wt.% loading, while indirect sonication was not able to properly disperse the CNTs and led to a conductivity of 1.6 ± 1.3 × 10−5. Conversely, specimens filled with 2.5 wt. % of GNP and processed by indirect sonication displayed an electrical conductivity that is up to 4 orders of magnitude higher than when processed by direct sonication, achieving 5.6 × 10−7 S·m−1. The introduction of GNP flakes improved the dispersion state and conductivity in hybrid specimens processed by indirect sonication, but at the same time impaired these properties for high-power direct sonication. It is argued that this contradictory effect is caused by a selective localization of shorter CNTs onto GNPs due to strong π-π interactions when direct sonication is used. Dynamic mechanical analysis showed that the addition of nanofillers improved epoxy’s storage modulus by up to 84%, but this property is mostly insensitive to the different processing parameters. Decrease in crosslinking degree and presence of residual solvent confirmed by Fourier-transform infrared spectroscopy, however, diminished the glass transition temperature of the nanocomposites by up to 40% when compared to the neat resin due to plasticization effects.

Contrasting responses of soybean aphids, primary parasitoids, and hyperparasitoids to forest fragments and agricultural landscape structure

Primary parasitoid species, usually Hymenopteran wasp species, contribute to pest regulation services in agroecosystems by parasitizing crop pests and reducing their abundance. However, this positive effect can be limited if primary parasitoids themselves are parasitized by secondary parasitoids, also known as hyperparasitoids. These trophic dynamics that influence pest regulation take place within the context of changes to agricultural landscape structure including loss of natural habitat and landscape simplification. Therefore, there is great interest in understanding how landscape structure influences pest, primary parasitoid, and hyperparasitoid dynamics. We investigated how the structure of agricultural landscapes in Southern Quebec affects primary and hyperparasitism rates of soybean aphid (Aphis glycines). We found that pests, primary parasitoids, and hyperparasitoids responded in contrasting ways to landscape structure. While aphid abundances and hyperparasitoid rates increased with increasing distance-from-forest in soybean fields and as the proportion of forest in the surrounding landscape decreased, primary parasitoid rates showed the opposite trends. Relationships with forest fragment size and isolation were complex, with contrasting positive, negative, and neutral effects across the three groups. Finally, wider fields consistently had lower aphid abundances, primary parasitoid rates, and hyperparasitoid rates. Our results highlight the complexity of the trophic dynamics that underlie pest regulation and how changes to landscape structure can lead to conflicting and contradictory effects on pest regulation.

Phosphorus sorption and desorption characteristics of soils as affected by biochar

Knowledge of phosphorus (P) sorption and desorption properties of different soils can help predict the availability of added P, which is of importance in terms of managing soil fertility problems and P environmental impacts. As biochar has become widely utilized as an amendment in agricultural soils over the past decades, the present study mainly aims at investigating the effect of wheat straw-derived biochars produced at 300 °C (B300) and 600 °C (B600) on P sorption and desorption via batch experiments in four soil samples with a dissimilar reaction. The sampled soils were incubated with B300 and B600 at three rates of 0%, 3%, and 6% (w/w) for 90 days. Isotherm equations were also applied to evaluate which model presents the best fit of the predicted data with experimental results. The results revealed that in the acidic soils (pH 4.6 and 6.0) P sorption decreased, whereas P desorbability increased with increasing biochar pyrolysis temperature and application rates compared to the untreated soils. A similar trend was observed for soil with a pH of 7.4 following biochars addition excluding, the sample that initially received 200 mg P L−1 at a 6% rate of B600 treatment. Reduction of P sorption in another alkaline soil (pH 8.3) upon biochar addition was evident at lower concentrations of added P and was markedly following B300 addition at the application rate of 6%. In this soil (pH 8.3), P desorbability decreased with increasing biochar pyrolysis temperature and application rates. Fits of isotherm equations showed that Freundlich and Langmuir equations did describe P sorption in most of the studied soils. The Langmuir equation did not sufficiently describe P retention data. However, the Freundlich equation showed satisfactory fits to most of the retention data. As sorption and retention isotherms failed to coincide, hysteresis was observed for all the studied soils which was most predominant for the alkaline soil (pH 8.3) following B600 addition at the rate of 6%. This study presents insight into the contradictory effects of biochars on P dynamics in different soil types and it emphasizes the importance of considering the impact of biochar pyrolysis temperature, application rates, soil properties, and initial P concentration when applying biochar as a soil amendment for agricultural P management. All this can bear implications for further studies on biochar utilization and soil P sorption and desorption characteristics.

Arsenic and Cadmium Accumulation in Soil as Affected by Continuous Organic Fertilizer Application: Implications for Clean Production

As and Cd in soil can be assimilated and accumulated by vegetables and can be subsequently ingested by humans. Contradictory effects of organic fertilizer application on As and Cd accumulation in soil have been reported in previous studies. An eight-year greenhouse study was conducted on a sandy loam soil in Beijing, China to investigate the effects of organic fertilizer application rate on soil properties, and As and Cd accumulation in soil. The contamination risk of pak choi grown after eight years’ application of organic fertilizer was also evaluated. Soil organic carbon increased 3.0–3.8 times with low, medium and high rates of fertilizer application in 2018 compared to the initial soil. Organic fertilizer application significantly increased soil nutrients and microbial biomass while it mildly affected soil pH. The bioavailability of As/Cd has decreased after eight years’ application of organic fertilizer. Pak choi crop harvested from all three treatments in 2018 did not pose a threat to human health, even for life-time consumption. Soil total As content significantly decreased with organic fertilizer application, mainly due to the lower As content in the applied fertilizer than that in soil. Continuous application of clean organic fertilizer can be adopted to reduce the contamination risk of highly contaminated soil in the soil–plant system.

Factors Influencing Technical Efficiency in the EU Dairy Farms

This paper aims to analyse the technical efficiency (TE) of dairy farms and find its determinants. To accomplish this problem, the Stochastic Frontier Analysis was applied. The data were obtained from the Farm Accountancy Data Network database for dairy farms (TF15-45—Specialist dairying) for 2004–2019. Dairy farms were divided into four clusters according to their physical size (number of livestock units per farm) and economic size (standard output per farm). The largest farms by physical and economic size are located in Denmark and Cyprus. The smallest, in comparison, are in Bulgaria, Croatia, Latvia, Lithuania, Austria, Poland, Romania, and Slovenia. Farms in the EU are relatively technically efficient, i.e., they use their resources efficiently to produce maximum output (production). However, they have the potential to achieve better economic results and be more competitive, as the size of farms’ is not fully optimised. The abolition of the milk quota can be considered a factor in improving technical efficiency, as the indicator is higher after the abolition. New and old member states have almost comparable technical efficiency levels (the p-value of the t-test is 0.463), with old members having slightly higher level TE. Subsidies have contradictory effects on TE. Farm efficiency with higher subsidies per cow is higher for farms with €51–100/cow. However, as subsidies increase, TE decreases. Only the group of farms with the highest subsidies has a higher TE. More diversified farms are more technically efficient than specialised farms. Milk yield did not influence the analysed indicator. The analysis results can serve the stakeholders as a tool for modelling future agricultural policy, as the European farms are very heterogenous and show different conditions and economic outcomes.

Toll-like Receptor-3 Ligation Induces Pro-Survival Signaling in Pediatric Acute Lymphoblastic Leukemia

B cell precursor acute lymphoblastic leukemia (B-ALL) is the most common cancer in children, with a peak age of incidence of 2-5 years. In the majority of pediatric cases, B-ALL is initiated in utero, with full transformation from pre-leukemia to leukemia being driven by additional oncogenic events acquired in early childhood. Surprisingly, common in utero genetic events lead to the expansion of pre-leukemic clones in >1% of all newborns, yet only 1 in 100 of these infants go on to develop clinically overt leukemia in their lifetime. This suggests the presence of certain protective and/or non-protective mechanisms that influence the fate of pre-leukemic clones.While several epidemiological studies of early-life infection indicate a consequent increased risk for ALL, protective effects of infection exposure against ALL have also been reported. An infectious agent responsible for pro- or anti-leukemic effects has not been identified and a mechanistic explanation for the seemingly contradictory effects of early-life infection has not been defined. We have previously reported the ability of immune stimulation with infection-associated toll-like receptor (TLR) agonists to reduce pre-leukemic cell burden and delay leukemia onset in the Eμ-RET transgenic mouse model of hyperdiploid B-ALL. We observed that while TLR9 (CpG) and TLR7/8 (R848) ligands were effective at reducing viable pre-leukemic and leukemic cells, a TLR3 ligand (PolyI:C) appeared to have an opposite effect. In this study, we further investigate the potential pro-leukemic effect of TLR3 ligands (pathogenic dsRNA) on abnormal BCP cell behavior.Purified pre-leukemic or leukemic cells from Eu-ret mice were treated in vitro with TLR agonists and cell viability was assessed after 48 hours. In contrast to the reduced viability observed after exposure to TLR7/8 (R848) and TLR9 (CpG) ligands, a ~1.5-fold increase in viable cell recovery, compared to untreated cells, was observed after treatment with PolyI:C (p <0.05). Since PolyI:C binds other receptors in addition to TLR3, we then assessed PolyA:U, a synthetic dsRNA molecule signaling exclusively through TLR3. Treatment of purified pre-leukemic and leukemic cells with PolyA:U lead to an increase in viable cell recovery compared to untreated cells (p < 0.01), implicating TLR3 as the relevant receptor. This viable cell recovery correlated with reduced apoptosis and an increased proliferation index in PolyA:U treated samples.To assess the relevance of this TLR-induced activity for clinical B-ALL, we evaluated the responses of patient-derived B-ALL samples. A similar survival benefit was observed with primary B-ALL samples treated with TLR3, but not other TLR ligands. Consistent with observations from primary murine leukemia, CpG and R848 were able to induce in vitro killing of human leukemia cells, while PolyA:U promoted increased leukemia cell viability.As the overall outcome of early-life infection will also involve TLR-induce immune responses, we next assessed the effect of TLR3 agonists in the presence of immune effector cells. Bulk splenocytes from 1- to 12-week-old Eu-RET mice were cultured in the presence or absence of TLR agonists and viable cell recovery after 48 hours measured. In the presence of immune effector cells, the impact of pro-survival TLR3 signalling was diminished in an age-dependent manner, implicating neonatal immunity in the abnormal pro-leukemic response induced by TLR3 ligation.Overall, our results reveal previously unrecognized pro-survival signalling through TLR3 that could contribute to an early-life infection-driven progression of B-ALL. We are currently exploring the signaling pathway(s) responsible for this effect and evaluating the immune variables that influence pre-leukemia cell fate in vivo. This study will significantly enhance our mechanistic understanding of immune-mediated modification of B-ALL progression induced by early-life infection exposure. DisclosuresNo relevant conflicts of interest to declare.

PECULIARITIES OF CLASSIFICATION AND USE OF NON-TARIFF REGULATION MEASURES

Purpose. The purpose of the research is to conduct a systematic study of existing classifications of measures of non-tariff regulation of foreign economic activity and analysis of the dynamics of the use of specific methods of non-tariff regulation in Ukraine and the world. Design/methodology/approach. The study examined the hypothesis of the lack of a single unified classification of measures of non-tariff regulation of foreign economic activity on the basis of a study of the most commonly used classifications in Ukraine and in the world, determining their common and distinctive features. In order to achieve the purpose of the research, general scientific methods of scientific knowledge were used: analysis and synthesis, theoretical generalization, formalization, observation, systematization. Findings. It is found out that there are many classifications for non-tariff regulation, but the most common are classifications of the World Trade Organization and the United Nations Conference on Trade and Development (UNCTAD), but the last one is more popular and used for formation of a global database on dynamics of non-tariff regulation measures applying. In addition, the current classification of non-tariff regulation measures of the World Trade Organization deserves attention, it contains up-to-date information on the dynamics of the use of existing and initiated non-tariff regulation measures by WTO members. The hypothesis of the absence of a single unified classification of measures of non-tariff regulation of foreign economic activity based on a study of the most commonly used classifications in Ukraine and in the world, their common and distinctive features can be considered proven, as evidenced by the results of the study and generalized conclusions. Practical implications. The studied classifications are of great practical importance, as they allow international market participants to monitor the use of non-tariff regulation measures. The hold analysis showed that among all non-tariff regulation measures in 2021, most countries in the world used technical measures related to imports, in particular, sanitary and phytosanitary measures (A) - 29750, technical barriers to trade) - 25772, as well as exports-related measures - 7804, quantitative restrictions - 6438. The same can be said about Ukrainian practice of non-tariff regulation measures usage. Originality/value. It is established that the UNCTAD classification is the most comprehensive and suitable for the purposes of economic analysis. The impact of non-tariff measures on trade as well as on welfare is less clear than the impact of tariff restrictions. On the one hand, non-tariff measures often restrict trade flows, which has a negative impact on welfare. On the other hand, there are a number of non-tariff measures, the application of which contributes to the growth of welfare by ensuring the highest quality of goods offered on the market, which is an independent value for consumers. The use of non-tariff instruments should be treated with caution, as they are not devoid of dualism and may have contradictory consequences, as well as provoke a similar response from partner countries.

Pediatric Hypothermia: An Ambiguous Issue.

Hypothermia in pediatrics is mainly about small body size. The key thermal factor here is the large surface-to-volume ratio. Although small mammals, including human infants and children, are adapted to higher heat losses through their elevated metabolic rate and thermogenic capacity, they are still at risk of hypothermia because of a small regulatory range and an impending metabolic exhaustion. However, some small mammalian species (hibernators) use reduced metabolic rates and lowered body temperatures as adaptations to impaired energy supply. Similar to nature, hypothermia has contradictory effects in clinical pediatrics as well: In neonates, it is a serious risk factor affecting respiratory adaptation in term and developmental outcome in preterm infants. On the other hand, it is an important self-protective response to neonatal hypoxia and an evidence-based treatment option for asphyxiated babies. In children, hypothermia first enabled the surgical repair of congenital heart defects and promotes favorable outcome after ice water drowning. Yet, it is also a major threat in various prehospital and clinical settings and has no proven therapeutic benefit in pediatric critical care. All in all, pediatric hypothermia is an ambiguous issue whose harmful or beneficial effects strongly depend on the particular circumstances.

The role of systemic inflammatory cells in meningiomas.

The aim of this review is to describe the inflammatory systemic cell infiltrate and its role in pathophysiology and prognostic implications of meningiomas. Articles from PubMed describing inflammation and immune cells in meningioma were systematically selected and reviewed. Infiltrating inflammatory cells are common in meningiomas and correlate with tumor behavior and peritumoral edema. The immune cell infiltrate mainly comprised macrophages, CD4 + T cells of the Th1 and Th2 subtype, CD8 + cytotoxic T cells, mast cells, and to a lesser degree B cells. The polarization of macrophages to M1 or M2 states, as well as the differentiation of T-helper cells to Th1 or Th2 subsets, is of prognostic value, but whether or not the presence of macrophages is associated with the degree of malignancy of the tumor is controversial. The best documented immunosuppressive and tumor-promoting mechanism is the expression of programmed cell death protein 1 (PD-1/PD-1L) which is found on both tumor cells and tumor-infiltrating immune cells. The immune cell infiltration varies between different meningiomas. It contributes to a microenvironment with potential contradictory effects on tumor growth and edema. The immune mechanisms are potential therapeutic targets provided that their effects can be comprehensively understood.

Saturation Season: Inclusivity, Queerness, and Aesthetics in the New Media Practices of Brockhampton

ABSTRACT Following the self-release of their Saturation album trilogy in 2017, American hip-hop group Brockhampton broke through to an international audience. The period of the trilogy’s release – known as “Saturation Season” – is notable for the large body of creative content the group produced and released online. In this article, the authors demonstrate how the group’s new media practices query the boundaries that separate amateurs and professionals, consumers and producers, and fans and artists, raising a range of questions concerning digitalization, (social) inclusion, and the democratization of culture. Emphasis is placed on exploring the contradictory effects of the digital turn in popular music.

Degradation: A critical challenge for M–N–C electrocatalysts

Atomically dispersed transition metal (M) and nitrogen (N) co-doped carbon (M–N–C) electrocatalysts hold excellent application potentials for several critical reactions required in electrochemical conversion processes and energy storage devices, including oxygen reduction reaction, oxygen evolution reaction, hydrogen evolution reaction, carbon dioxide reduction reaction and nitrogen reduction reaction. Despite significant progress achieved in the past few decades, their commercialization is hindered by their fast degradation. This perspective article outlines the historical development of M–N–C electrocatalysts, the current understanding of their active catalytic sites, and crucial degradation mechanisms. We highlight that many methods used to tailor M–N–C electrocatalysts likely cause contradictory effects on activity and stability. More emphasis is needed to address their degradation issues under industry-relevant working conditions.

Global Constitutionalism and Legal Fragmentation: The Populist Backslide in Central and Eastern Europe

&lt;p&gt;Globalisation has provoked a deep transformation in international law, political affairs and governance with contradictory consequences. It has stimulated the cosmopolitan project of global constitutionalism, transnational integration and the unification of democratic standards. However, it also resulted in the fragmentation of international affairs, the deterioration of constitutional democracy and a feeling of a growing shortage in democracy on national and international levels of governance. Trying to balance the impact of these two opposing trends, the author analyses the positive and negative effects of globalisation on constitutional development regarding such issues as transnational constitutionalisation, democracy and national sovereignty, the changing place of multilayer constitutionalism, the international separation of powers, and the system of global governance in the establishment of transnational constitutional democratic legitimacy. From this point of view, the populist backslide in Central and Eastern Europe (CEE) looks dangerous and unforeseen, but it is a systemic and potentially predictable reaction of global regions on the uneven character of integration, the lack of democratic legitimacy and a new answer to the contortions and dysfunctions of global governance. An adequate response to these challenges could be found in a new concept of constitutional integration based on ongoing dialogue between the transnational and national actors of legal globalisation. This dialogue is possible by using a conflict-mediation strategy, elaborated by international experts, especially, for the deliberation of complex and protracted conflicts, which have no clear practical solutions in the short to medium term.&lt;/p&gt;

Isolation and Characterization of Heparan Sulfate Containing Amyloid Precursor Protein Degradation Products.

Numerous studies indicate that heparan sulfate proteoglycans (HSPGs) participate in a network of complex molecular events involving amyloid precursor protein (APP) processing and formation, oligomerization, intracellular targeting, clearance, and propagation of amyloid β in Alzheimer's disease (AD). A mutual functional interplay between recycling glypican-1 and APP processing has been demonstrated where the HS released from glypican-1 by a Cu/NO-ascorbate-dependent reaction forms a conjugate with APP degradation products and undergoes an endosome-nucleus-autophagosome co-trafficking. HS has been shown to display contradictory and dual effects in AD involving both prevention and promotion of amyloid β formation. It is therefore important to identify the source, detailed structural features as well as factors that favor formation of the neuroprotective forms of HS. Here, a method for isolation and identification of HS-containing APP degradation products has been described. The method is based on isolation of radiolabeled HS followed by identification of accompanying APP degradation products by SDS-PAGE and Western blotting.

Contradictory Effect of Notch1 and Notch2 on Phosphatase and Tensin Homolog and its Influence on Glioblastoma Angiogenesis.

Many genes induce angiogenesis in tumors, and among them, Notch family genes have received particular attention due to their extensive network of connections with other genes active in this function. Suppression of angiogenic signaling has been studied in various cancers, confirming Notch's fundamental and extensive role. According to studies, four Notch genes work independently with many genes such as vascular endothelial growth factor, phosphatase and tensin homolog, Phosphoinositide 3-kinase/Akt, and matrix metalloproteinases, and so many other genes, as well as proteins (such as hypoxia-inducible factor-1 alpha) significantly affect tumor angiogenesis. Notch1 regular activity in a healthy person causes angiogenesis in body tissues, controlled by normal Notch2 activity. However, in many cases of glioblastoma, whether on patients or tumor xenografts or in vivo models, a mutation in one of these two essential genes or at least one of the genes and proteins that affected by them can cause better angiogenesis in hypoxic conditions and lead to become an invasive tumor. In this review, we examined the contrasting activity of Notch1 and Notch2 and the signaling cascade that each generates in the angiogenesis of glioblastoma, the most invasive cancer of the central nervous system.