Vaccines against toxoplasma gondii : challenges and opportunities

Development of vaccines against Toxoplasma gondii infection in humans is of high priority, given the high burden of disease in some areas of the world like South America, and the lack of effective drugs with few adverse effects. Rodent models have been used in research on vaccines against T. gondii over the past decades. However, regardless of the vaccine construct, the vaccines have not been able to induce protective immunity when the organism is challenged with T. gondii, either directly or via a vector. Only a few live, attenuated T. gondii strains used for immunization have been able to confer protective immunity, which is measured by a lack of tissue cysts after challenge. Furthermore, challenge with low virulence strains, especially strains with genotype II, will probably be insufficient to provide protection against the more virulent T. gondii strains, such as those with genotypes I or II, or those genotypes from South America not belonging to genotype I, II or III. Future studies should use animal models besides rodents, and challenges should be performed with at least one genotype II T. gondii and one of the more virulent genotypes. Endpoints like maternal-foetal transmission and prevention of eye disease are important in addition to the traditional endpoint of survival or reduction in numbers of brain cysts after challenge

Nesfatin-1/NUCB2 as a Potential New Element of Sleep Regulation in Rats.

STUDY OBJECTIVES: Millions suffer from sleep disorders that often accompany severe illnesses such as major depression; a leading psychiatric disorder characterized by appetite and rapid eye movement sleep (REMS) abnormalities. Melanin-concentrating hormone (MCH) and nesfatin-1/NUCB2 (nesfatin) are strongly co - expressed in the hypothalamus and are involved both in food intake regulation and depression. Since MCH was recognized earlier as a hypnogenic factor, we analyzed the potential role of nesfatin on vigilance. DESIGN: We subjected rats to a 72 h-long REMS deprivation using the classic flower pot method, followed by a 3 h-long 'rebound sleep'. Nesfatin mRNA and protein expressions as well as neuronal activity (Fos) were measured by quantitative in situ hybridization technique, ELISA and immunohistochemistry, respectively, in 'deprived' and 'rebound' groups, relative to controls sacrificed at the same time. We also analyzed electroencephalogram of rats treated by intracerebroventricularly administered nesfatin-1, or saline. RESULTS: REMS deprivation downregulated the expression of nesfatin (mRNA and protein), however, enhanced REMS during 'rebound' reversed this to control levels. Additionally, increased transcriptional activity (Fos) was demonstrated in nesfatin neurons during 'rebound'. Centrally administered nesfatin-1 at light on reduced REMS and intermediate stage of sleep, while increased passive wake for several hours and also caused a short-term increase in light slow wave sleep. CONCLUSIONS: The data designate nesfatin as a potential new factor in sleep regulation, which fact can also be relevant in the better understanding of the role of nesfatin in the pathomechanism of depression

A time predefined variable depth search for nurse rostering

This paper presents a variable depth search for the nurse rostering problem. The algorithm works by chaining together single neighbourhood swaps into more effective compound moves. It achieves this by using heuristics to decide whether to continue extending a chain and which candidates to examine as the next potential link in the chain. Because end users vary in how long they are willing to wait for solutions, a particular goal of this research was to create an algorithm that accepts a user specified computational time limit and uses it effectively. When compared against previously published approaches the results show that the algorithm is very competitive

Nano-Architecture of nitrogen-doped graphene films synthesized from a solid CN source

New synthesis routes to tailor graphene properties by controlling the concentration and chemical configuration of dopants show great promise. Herein we report the direct reproducible synthesis of 2-3% nitrogen-doped ‘few-layer’ graphene from a solid state nitrogen carbide a-C:N source synthesized by femtosecond pulsed laser ablation. Analytical investigations, including synchrotron facilities, made it possible to identify the configuration and chemistry of the nitrogen-doped graphene films. Auger mapping successfully quantified the 2D distribution of the number of graphene layers over the surface, and hence offers a new original way to probe the architecture of graphene sheets. The films mainly consist in a Bernal ABA stacking three-layer architecture, with a layer number distribution ranging from 2 to 6. Nitrogen doping affects the charge carrier distribution but has no significant effects on the number of lattice defects or disorders, compared to undoped graphene synthetized in similar conditions. Pyridinic, quaternary and pyrrolic nitrogen are the dominant chemical configurations, pyridinic N being preponderant at the scale of the film architecture. This work opens highly promising perspectives for the development of self-organized nitrogen-doped graphene materials, as synthetized from solid carbon nitride, with various functionalities, and for the characterization of 2D materials using a significant new methodology

Spin transport and spin torque in antiferromagnetic devices

Ferromagnets are key materials for sensing and memory applications. In contrast, antiferromagnets which represent the more common form of magnetically ordered materials, have found less practical application beyond their use for establishing reference magnetic orientations via exchange bias. This might change in the future due to the recent progress in materials research and discoveries of antiferromagnetic spintronic phenomena suitable for device applications. Experimental demonstration of the electrical switching and detection of the Néel order open a route towards memory devices based on antiferromagnets. Apart from the radiation and magnetic-field hardness, memory cells fabricated from antiferromagnets can be inherently multilevel, which could be used for neuromorphic computing. Switching speeds attainable in antiferromagnets far exceed those of ferromagnetic and semiconductor memory technologies. Here we review the recent progress in electronic spin-transport and spin-torque phenomena in antiferromagnets that are dominantly of the relativistic quantum mechanical origin. We discuss their utility in pure antiferromagnetic or hybrid ferromagnetic/antiferromagnetic memory devices

Integrins as therapeutic targets: lessons and opportunities.

The integrins are a large family of cell adhesion molecules that are essential for the regulation of cell growth and function. The identification of key roles for integrins in a diverse range of diseases, including cancer, infection, thrombosis and autoimmune disorders, has revealed their substantial potential as therapeutic targets. However, so far, pharmacological inhibitors for only three integrins have received marketing approval. This article discusses the structure and function of integrins, their roles in disease and the chequered history of the approved integrin antagonists. Recent advances in the understanding of integrin function, ligand interaction and signalling pathways suggest novel strategies for inhibiting integrin function that could help harness their full potential as therapeutic targets

A review of combined advanced oxidation technologies for the removal of organic pollutants from water

Water pollution through natural and anthropogenic activities has become a global problem causing short-and long-term impact on human and ecosystems. Substantial quantity of individual or mixtures of organic pollutants enter the surface water via point and nonpoint sources and thus affect the quality of freshwater. These pollutants are known to be toxic and difficult to remove by mere biological treatment. To date, most researches on the removal of organic pollutants from wastewater were based on the exploitation of individual treatment process. This single-treatment technology has inherent challenges and shortcomings with respect to efficiency and economics. Thus, application of two advanced treatment technologies characterized with high efficiency with respect to removal of primary and disinfection by-products in wastewater is desirable. This review article focuses on the application of integrated technologies such as electrohydraulic discharge with heterogeneous photocatalysts or sonophotocatalysis to remove target pollutants. The information gathered from more than 100 published articles, mostly laboratories studies, shows that process integration effectively remove and degrade recalcitrant toxic contaminants in wastewater better than single-technology processing. This review recommends an improvement on this technology (integrated electrohydraulic discharge with heterogeneous photocatalysts) viz-a-vis cost reduction in order to make it accessible and available in the rural and semi-urban settlement. Further recommendation includes development of an economic model to establish the cost implications of the combined technology. Proper monitoring, enforcement of the existing environmental regulations, and upgrading of current wastewater treatment plants with additional treatment steps such as photocatalysis and ozonation will greatly assist in the removal of environmental toxicants

Multi-messenger observations of a binary neutron star merger

On 2017 August 17 a binary neutron star coalescence candidate (later designated GW170817) with merger time 12:41:04 UTC was observed through gravitational waves by the Advanced LIGO and Advanced Virgo detectors. The Fermi Gamma-ray Burst Monitor independently detected a gamma-ray burst (GRB 170817A) with a time delay of ~1.7 s with respect to the merger time. From the gravitational-wave signal, the source was initially localized to a sky region of 31 deg2 at a luminosity distance of 40+8-8 Mpc and with component masses consistent with neutron stars. The component masses were later measured to be in the range 0.86 to 2.26 Mo. An extensive observing campaign was launched across the electromagnetic spectrum leading to the discovery of a bright optical transient (SSS17a, now with the IAU identification of AT 2017gfo) in NGC 4993 (at ~40 Mpc) less than 11 hours after the merger by the One- Meter, Two Hemisphere (1M2H) team using the 1 m Swope Telescope. The optical transient was independently detected by multiple teams within an hour. Subsequent observations targeted the object and its environment. Early ultraviolet observations revealed a blue transient that faded within 48 hours. Optical and infrared observations showed a redward evolution over ~10 days. Following early non-detections, X-ray and radio emission were discovered at the transient’s position ~9 and ~16 days, respectively, after the merger. Both the X-ray and radio emission likely arise from a physical process that is distinct from the one that generates the UV/optical/near-infrared emission. No ultra-high-energy gamma-rays and no neutrino candidates consistent with the source were found in follow-up searches. These observations support the hypothesis that GW170817 was produced by the merger of two neutron stars in NGC4993 followed by a short gamma-ray burst (GRB 170817A) and a kilonova/macronova powered by the radioactive decay of r-process nuclei synthesized in the ejecta

A bi-objective model for the location and optimization configuration of kitchen waste transfer stations

202506 bcrcVersion of RecordOthersNational Natural Science Foundation of China; National Key Research and Development Program of China; 2019 Guangdong Special Support Talent Program—Innovation and Entrepreneurship Leading Team (China); 2018 Guangzhou Leading Innovation Team Program (China); the Science and Technology Development Fund (Macau SAR); the Fundamental Research Funds for the Central UniversitiesPublishedC

mTOR: from growth signal integration to cancer, diabetes and ageing

In all eukaryotes, the target of rapamycin (TOR) signalling pathway couples energy and nutrient abundance to the execution of cell growth and division, owing to the ability of TOR protein kinase to simultaneously sense energy, nutrients and stress and, in metazoans, growth factors. Mammalian TOR complex 1 (mTORC1) and mTORC2 exert their actions by regulating other important kinases, such as S6 kinase (S6K) and Akt. In the past few years, a significant advance in our understanding of the regulation and functions of mTOR has revealed the crucial involvement of this signalling pathway in the onset and progression of diabetes, cancer and ageing.National Institutes of Health (U.S.)Howard Hughes Medical InstituteWhitehead Institute for Biomedical ResearchJane Coffin Childs Memorial Fund for Medical Research (Postdoctoral Fellowship)Human Frontier Science Program (Strasbourg, France