Tidal interactions - crude body model in dynamical investigations

The paper presents results of investigations of small bodies dynamics in a vicinity of giant planets. We used the most simple body model: gravitationally bounded, rotating contact binary affected by the tidal force acting from a planet. Spin variations of such binaries were extensively studied during planetary close encounters. Two main types of dynamical behaviour were observed: (i) huge but interim fluctuations of the angular velocity and (ii) permanent changes of a rotation during a close approach. The first type is observed mainly for fast rotators, while the second one was encountered in a population of slowly spinning objects with periods longer than 12 hours. Conclusions on usability of such crude physical body models in dynamical investigations and a comparison to previous results were attached. The results allow us to formulate a thesis explaining the phenomenon of creation of the extremely slow rotators and an observational excess of such type of objects

Interdisciplinary Teaching Using Satellite Images as a Way to Introduce Remote Sensing in Secondary School

This article aims to meet two needs: (i) the need for skilled workers and students in the area of remote sensing and (ii) the need to make school science interesting for students. This article addresses both needs by proposing a project for high school students entitled "the Colors of Earth". The main aim for students was to distinguish between different types of land cover via the creation of various false color band compositions from the satellite Sentinel-2. Achieving this goal requires knowledge from various subjects and enables their practical application via work performed using real data. The project was presented to 39 high-school teachers and 184 high-school students (K-9 and K-10) in the summer semester of the 2019/2020 school year, and their opinions about the project were collected. Overall, both students and teachers judged the project to be interesting, worth introducing to the school, and capable of influencing student opinions of science. In addition, introducing remote sensing elements during pre-university education can help meet the demands for students and workers to study Earth observation

Dissecting the molecular basis of PfCRT-mediated antimalarial drug resistance

The protozoan parasite Plasmodium falciparum is responsible for the deadliest form of malaria, which causes 584,000 fatalities annually and whose complications include coma, anemia, respiratory distress, and renal failure. Although malaria eradication efforts were hindered by the rise of chloroquine (CQ) resistance (CQR), CQ continues to be clinically deployed in resistance-free regions. CQR is primarily mediated by mutations in the P. falciparum chloroquine resistance transporter (pfcrt) gene, which also modulates parasite susceptibility to first-line artemisinin-based combination therapies (ACTs). In certain geographical regions (e.g. Africa), mutant pfcrt alleles display considerable fitness costs and have undergone attrition in the absence of CQ pressure. Surveillance of resistant field isolates presently centers on the PfCRT mutation K76T, ubiquitous among CQ-resistant parasites and always accompanied by ≥3 additional mutations. Despite the global adoption of K76T as a molecular marker of CQR, the contributions of this and other mutations to P. falciparum drug resistance versus fitness had not been previously defined. AIMS: We aimed to address the following: (1) Do PfCRT mutations beyond PfCRT K76T directly contribute to CQR? (2) Do PfCRT mutations contribute to parasite fitness during the pathogenic asexual blood stage? (3) Are there predictable mutational paths in the evolution of pfcrt-mediated drug resistance? (4) How do PfCRT mutations impact current antimalarials, including the first-line ACTs? APPROACH: Using zinc finger nucleases, we generated isogenic, pfcrt-modified blood-stage P. falciparum parasites encoding wild-type (CQ-sensitive) or variant PfCRT haplotypes. Variants included a combinatorial library of alleles harboring 1-4 mutations comprising the simplest CQ-resistant haplotype (Ecu1110). Additional genetic dissections of full-length or partial pfcrt alleles encompassed the most common variants found in Africa and Asia, including a unique fitness-neutral mutant allele (Cam734) that has undergone expansion in Southeast Asia. Parasite antimalarial drug susceptibility was determined using IC50-based (cytostatic) assays or parasite survival-based (cytocidal) assays and was combined with data from flow cytometric parasite growth competition assays to computationally model mutant pfcrt evolution. To further define the biochemical impacts of PfCRT mutations, our studies leveraged metabolomic, heme fractionation, and drug transport studies. RESULTS: Key findings emerging from our studies included the following: (1) PfCRT K76T is insufficient for CQR and an inaccessible first mutational step in pfcrt evolution; (2) Alongside proliferation rates, parasite resistance gains dictate a constrained pfcrt mutational landscape and predict important roles for the active metabolites of CQ and amodiaquine in guiding pfcrt evolution; (3) To various degrees, PfCRT polymorphisms beyond K76T increase the potency of both the artemisinin and partner drug components of first-line ACT regimens; (4) Emerging PfCRT mutations (e.g. A144F) directly contribute to the enhanced fitness of pfcrt alleles and are necessary for multidrug resistance, independent of K76T. CONCLUSIONS: Our studies uncovered multiple pleiotropic contributions of PfCRT mutations to antimalarial drug resistance, countering earlier dogma that non-K76T mutations are merely compensatory. Evolutionary modeling revealed parasites’ ability to navigate constrained mutational landscapes and evolve drug resistance via rare mutational bursts. These results collectively highlight the capacity of PfCRT to acquire novel mutations that successfully balance parasite multidrug resistance with the essential role of PfCRT in maintaining digestive vacuole physiology. Our studies are of direct relevance to the regional recommendations of antimalarials, whose activity is influenced by, and in certain cases enhanced against, pfcrt-mutant parasites

Protective Microbiota: From Localized to Long-Reaching Co-Immunity

Resident microbiota do not just shape host immunity, they can also contribute to host protection against pathogens and infectious diseases. Previous reviews of the protective roles of the microbiota have focused exclusively on colonization resistance localized within a microenvironment. This review shows that the protection against pathogens also involves the mitigation of pathogenic impact without eliminating the pathogens (i.e., “disease tolerance”) and the containment of microorganisms to prevent pathogenic spread. Protective microorganisms can have an impact beyond their niche, interfering with the entry, establishment, growth, and spread of pathogenic microorganisms. More fundamentally, we propose a series of conceptual clarifications in support of the idea of a “co-immunity,” where an organism is protected by both its own immune system and components of its microbiota

The Resonant Dynamical Evolution of Small Body Orbits Among Giant Planets

Mean motion resonances (MMRs) can lead either to chaotic or regular motion. We report on a numerical experiment showing that even in one of the most chaotic regions of the Solar System - the region of the giant planets, there are numerous bands where MMRs can stabilize orbits of small bodies in a time span comparable to their lifetimes. Two types of temporary stabilization were observed: short period ($\sim10^{4}$ years) when a body was in a MMR with only one planet and long period (over $10^{5}$ years) when a body is located in overlapping MMRs with two or three planets. The experiment showed that the Main Belt region can be enriched by cometary material in its pre-active state due to temporary resonant interactions between small bodies and giant planets.Comment: 8 pages, 6 figure

Evolution of Fitness Cost-Neutral Mutant PfCRT Conferring P. falciparum 4-Aminoquinoline Drug Resistance Is Accompanied by Altered Parasite Metabolism and Digestive Vacuole Physiology

Southeast Asia is an epicenter of multidrug-resistant Plasmodium falciparum strains. Selective pressures on the subcontinent have recurrently produced several allelic variants of parasite drug resistance genes, including the P. falciparum chloroquine resistance transporter (pfcrt). Despite significant reductions in the deployment of the 4-aminoquinoline drug chloroquine (CQ), which selected for the mutant pfcrt alleles that halted CQ efficacy decades ago, the parasite pfcrt locus is continuously evolving. This is highlighted by the presence of a highly mutated allele, Cam734 pfcrt, which has acquired the singular ability to confer parasite CQ resistance without an associated fitness cost. Here, we used pfcrt-specific zinc-finger nucleases to genetically dissect this allele in the pathogenic setting of asexual blood-stage infection. Comparative analysis of drug resistance and growth profiles of recombinant parasites that express Cam734 or variants thereof, Dd2 (the most common Southeast Asian variant), or wild-type pfcrt, revealed previously unknown roles for PfCRT mutations in modulating parasite susceptibility to multiple antimalarial agents. These results were generated in the GC03 strain, used in multiple earlier pfcrt studies, and might differ in natural isolates harboring this allele. Results presented herein show that Cam734-mediated CQ resistance is dependent on the rare A144F mutation that has not been observed beyond Southeast Asia, and reveal distinct impacts of this and other Cam734-specific mutations on CQ resistance and parasite growth rates. Biochemical assays revealed a broad impact of mutant PfCRT isoforms on parasite metabolism, including nucleoside triphosphate levels, hemoglobin catabolism and disposition of heme, as well as digestive vacuole volume and pH. Results from our study provide new insights into the complex molecular basis and physiological impact of PfCRT-mediated antimalarial drug resistance, and inform ongoing efforts to characterize novel pfcrt alleles that can undermine the efficacy of first-line antimalarial drug regimens

Staphylococcus aureus small colony variants impair host immunity by activating host cell glycolysis and inducing necroptosis

Staphylococcus aureus small colony variants (SCVs) are frequently associated with chronic infection, yet they lack expression of many virulence determinants associated with the pathogenicity of wild-type strains. We found that both wild-type S. aureus and a ΔhemB SCV prototype potently activate glycolysis in host cells. Glycolysis and the generation of mitochondrial reactive oxygen species were sufficient to induce necroptosis, a caspase-independent mechanism of host cell death that failed to eradicate S. aureus and instead promoted ΔhemB SCV pathogenicity. To support ongoing glycolytic activity, the ΔhemB SCV induced over a 100-fold increase in the expression of fumC, which encodes an enzyme that catalyses the degradatin of fumarate, an inhibitor of glycolysis. Consistent with fumC-dependent depletion of local fumarate, the ΔhemB SCV failed to elicit trained immunity and protection from a secondary infectious challenge in the skin. The reliance of the S. aureus SCV population on glycolysis accounts for much of its role in the pathogenesis of S. aureus skin infection

Visualization of Murine Intranasal Dosing Efficiency Using Luminescent Francisella tularensis: Effect of Instillation Volume and Form of Anesthesia

Intranasal instillation is a widely used procedure for pneumonic delivery of drugs, vaccine candidates, or infectious agents into the respiratory tract of research mice. However, there is a paucity of published literature describing the efficiency of this delivery technique. In this report we have used the murine model of tularemia, with Francisella tularensis live vaccine strain (FTLVS) infection, to evaluate the efficiency of pneumonic delivery via intranasal dosing performed either with differing instillation volumes or different types of anesthesia. FTLVS was rendered luminescent via transformation with a reporter plasmid that constitutively expressed the Photorhabdus luminescens lux operon from a Francisella promoter. We then used an IVIS Spectrum whole animal imaging system to visualize FT dissemination at various time points following intranasal instillation. We found that instillation of FT in a dose volume of 10 µl routinely resulted in infection of the upper airways but failed to initiate infection of the pulmonary compartment. Efficient delivery of FT into the lungs via intranasal instillation required a dose volume of 50 µl or more. These studies also demonstrated that intranasal instillation was significantly more efficient for pneumonic delivery of FTLVS in mice that had been anesthetized with inhaled (isoflurane) vs. parenteral (ketamine/xylazine) anesthesia. The collective results underscore the need for researchers to consider both the dose volume and the anesthesia type when either performing pneumonic delivery via intranasal instillation, or when comparing studies that employed this technique

Numerical modelling of Kuiper belt objects’ dynamics – limitations

AbstractThe investigation of KBOs’ dynamics is based on numerical orbital integrations on extremly long time scales due to orbital evolution of particles. The evolution of KBOs to JFCs needs a time-span of order of 109years. Such a long time of integration affects errors. So the question arises what is the boundary of an integration time to distinguish the physical solution from numerical noise and what it depends on. This paper presents numerical integrations of less than 150 massless test particles in the model of the Solar System which consists of 4 giant planets and the central mass. For each test particle computations were repeated at least twice on different computers and using two different methods of integration. The results show that an increase of errors in a solution depends on the eccentricity and the inclination of an orbit. The estimated maximum time-span of integration is of the order of 10 million years for highly elliptic orbits (e 0.6) and up to 125 million years for quasi-circular orbits (for particular model of the Solar System with orbits of massless objects outside Neptune's orbit). After long time-span of integration (120-130 Myrs) the solution can be completely chaotic. It cannot be stated unequivocally that this is one of the possible particle's paths or that this is just a numerical noise. So a different way of studying KBOs’ and SP comets’ dynamical evolution is needed. The integration of equations of motion between particular phases of objects which are considered as comets in different phases of their lives (KBOs − Centaurs − Comets − possibly extinct Comets) could be the new way of studying the dynamical evolution of SP comets.</jats:p

Idea of an Intelligent Building - Development Prospects

An ever-increasing number of offices as also residential buildings are being realised by designers and investors in accordance with the concept of an intelligent building. Houses of the new generation are being constructed. This is possible thanks to dynamic progress in the development of computer and microprocessor engineering techniques. Putting into reality the idea of the'intelligent building'will become one of the most interesting assignments of Polish building industry in the rapidly approaching XXI century. The term'intelligent building'first appeared in the eighties. The idea behind this conception is aspiring to create a friendly, work supporting, effective environment. The revolution in telecommunications and information technology along with change in the standards of office work, have caused computer networks and modem systems of automation and protection, to invade buildings. From the technical point of view, an intelligent building is an object in which all the subsystems co-operate with each other, forming a friendly environment for man. For users of an intelligent building, the most important issue is realisation of the following aims: object management which includes both control of human resources and automation systems in the building and also efficient management of the building space in such a way that the costs of its utilisation are minimised. The possibility of optional installation of modern systems and equipment should be facilitated by the architecture itself. Therefore, the specifics of all the building elements should be taken into account right at the designing stage. The following features characterise an intelligent building: integration of telecommunication systems in the building, central management and supervision system and utilisation of structural cabling as the carrier of signals controlling most of the systems in the building. Presently, there is no building in Poland that could be characterised by the three features mentioned