Interplay between Allee effects and collective movement in metapopulations

Population growth can be positively or negatively dependent on density. Therefore, the distribution pattern of individuals in a patchy environment can greatly affect the growth of each subpopulation and thereby of the metapopulation. When population growth presents positive density‐dependence (Allee effect), the distribution pattern becomes crucial, as small populations have an increased extinction risk. The way in which individuals move between patches largely determines the distribution pattern and thereby the population dynamics. Collective movement, in particular, should be expected to increase the potential number of colonisers and therefore the probability of colonising success. Here, we use mathematical modelling (differential equations and stochastic simulations) to study how collective movement can influence metapopulation dynamics when Allee effects are at stake. The models are inspired by the two‐spotted spider mite, a phytophagous pest of recognised agricultural importance. This sub‐social mite displays trail laying/following behaviour that can provoke collective movement. Moreover, experimental evidence suggests that it is subject to Allee effects. In the first part of this study we present a single‐species population growth model incorporating Allee effects, and study its properties. In the second part, this growth model is integrated into a larger simulation model consisting of a set of interconnected patches, in which the individuals move from one patch to the other either independently or collectively. Our results show that collective movement is more advantageous than independent dispersal only when Allee effects are present and strong enough. Furthermore they provide a theoretical framework that allows the quantification of the interplay between Allee effects and collective movement.     

Acute effects of dynamic stretching exercise on power output during concentric dynamic constant external resistance leg extension

The purpose of the present study was to clarify the acute effect of dynamic stretching exercise on muscular performance during concentric dynamic constant external resistance (DCER, formally called isotonic) muscle actions under various loads. Concentric DCER leg extension power outputs were measured in 12 healthy male students after 2 types of pretreatment. The pretreatments were: (a) dynamic stretching treatment including 2 types of dynamic stretching exercises of leg extensors and the other 2 types of dynamic stretching exercises simulating the leg extension motion (2 sets of 15 times each with 30-second rest periods between sets; total duration: about 8 minutes), and (b) nonstretching treatment by resting for 8 minutes in a sitting position. Loads during measurement of the power output were set to 5, 30, and 60% of the maximum voluntary contractile (MVC) torque with isometric leg extension in each subject. The power output after the dynamic stretching treatment was significantly (p < 0.05) greater than that after the nonstretching treatment under each load (5% MVC: 468.4 +/- 102.6 W vs. 430.1 +/- 73.0 W; 30% MVC: 520.4 +/- 108.5 W vs. 491.0 +/- 93.0 W; 60% MVC: 487.1 +/- 100.6 W vs. 450.8 +/- 83.7 W). The present study demonstrated that dynamic stretching routines, such as dynamic stretching exercise of target muscle groups and dynamic stretching exercise simulating the actual motion pattern, significantly improve power output with concentric DCER muscle actions under various loads. These results suggested that dynamic stretching routines in warm-up protocols enhance power performance because common power activities are carried out by DCER muscle actions under various loads.     

Multienergetic verification of dynamic wedge angles in medical accelerators using multichannel linear array

Background

The aim of the modern radiotherapy is to get a homogenous dose distribution in PTV, which is obtained by using for example physical or dynamic wedges. The using of a physical wedge has provided such isodose distributions but their use resulted in detrimental dosimetric consequences, for example beam hardening effects and practical consequences of filter handling or possible misalignment. Linear accelerators are now equipped with collimator jaws systems and controlled by modern computers and it is possible to generate wedge shaped isodose distributions dynamically. Because of a more comfortable use of a dynamic wedge, there are alternatives to the standard physical wedge. During the treatment, different segments of the treatment field can be exposed to the primary beam at different intervals of time. This process of shrinking the field while modulating the collimator jaw velocity and dose rate creates the desired wedge-shaped isodose gradient across the treatment field. Dynamic wedges can replace physical wedges but they need more precise dosimetry and quality control procedures.

Aim

The aim of this study was to perform a multienergetic verification of dynamic wedge angles using the multichannel detector PTW LA48 linear array.

Material and methods

The measurements of angle value of dynamic wedges were performed for Clinac 2300 C/D accelerators (Varian). The accelerator was equipped with the EDW option for 6 MV and 15 MV photon beams. In this case, 7 wedge angle values were used: 10°, 15°, 20°, 25°, 30°, 45° and 60°. The dynamic wedges are realized by continuous movement of one collimator jaw. The field size is gradually reduced until the collimator is almost completely closed or the field increases, while the beam is on. The measurements were divided in two steps: in the first step, the dynamic wedges were verified with the recommended values and in the second step there the planned and measured angles of dynamic wedges were compared. Measurements were made by means of LA48 linear array of ionization chambers (PTW). The results of the measurements were compared with the reference profile produced by the treatment planning system ECLIPSE 8.5 (Varian).

Results

The results showed differences between measured and calculated angle of dynamic wedges. The differences were observed for both energies in the case of a small angle value. For energies 6 MV and 15 MV, almost all percentage difference between the measured and calculated profile was lower than 5%. The biggest difference was observed in the first step of measurements when the angle of Dynamic Wedge was verified. The comparison between the planned and measured angle value of Dynamic Wedge showed the difference between 0.1% and 4.5%.The difference for 6 MV for the angle value of 10° in orientation IN was 1.1% and for energy 15 MV in the same case the difference was 3.8%. Thinner wedges exhibit less difference.

Conclusion

It is necessary to provide comprehensive quality control procedure for enhanced dynamic wedges. Verification measurements should be an obligatory procedure in the recommendation for the testing of medical accelerators. These results are the preliminary results to provide measurements in other Polish Cancer Centres.     

Image fusion for dynamic contrast enhanced magnetic resonance imaging

Background  

Multivariate imaging techniques such as dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) have been shown to provide valuable information for medical diagnosis. Even though these techniques provide new information, integrating and evaluating the much wider range of information is a challenging task for the human observer. This task may be assisted with the use of image fusion algorithms.     

Interplay between Structure-Specific Endonucleases for Crossover Control during Caenorhabditis elegans Meiosis

The number and distribution of crossover events are tightly regulated at prophase of meiosis I. The resolution of Holliday junctions by structure-specific endonucleases, including MUS-81, SLX-1, XPF-1 and GEN-1, is one of the main mechanisms proposed for crossover formation. However, how these nucleases coordinately resolve Holliday junctions is still unclear. Here we identify both the functional overlap and differences between these four nucleases regarding their roles in crossover formation and control in the Caenorhabditis elegans germline. We show that MUS-81, XPF-1 and SLX-1, but not GEN-1, can bind to HIM-18/SLX4, a key scaffold for nucleases. Analysis of synthetic mitotic defects revealed that MUS-81 and SLX-1, but not XPF-1 and GEN-1, have overlapping roles with the Bloom syndrome helicase ortholog, HIM-6, supporting their in vivo roles in processing recombination intermediates. Taking advantage of the ease of genetic analysis and high-resolution imaging afforded by C. elegans, we examined crossover designation, frequency, distribution and chromosomal morphology in single, double, triple and quadruple mutants of the structure-specific endonucleases. This revealed that XPF-1 functions redundantly with MUS-81 and SLX-1 in executing crossover formation during meiotic double-strand break repair. Analysis of crossover distribution revealed that SLX-1 is required for crossover suppression at the center region of the autosomes. Finally, analysis of chromosome morphology in oocytes at late meiosis I stages uncovered that SLX-1 and XPF-1 promote meiotic chromosomal stability by preventing formation of chromosomal abnormalities. We propose a model in which coordinate action between structure-specific nucleases at different chromosome domains, namely MUS-81, SLX-1 and XPF-1 at the arms and SLX-1 at the center region, exerts positive and negative regulatory roles, respectively, for crossover control during C. elegans meiosis.     

Comparison of dosimetric characteristics of physical and enhanced dynamic wedges

BackgroundWedge filters can be used as missing tissue compensators or wedge pairs to alter the shape of isodose curves so that two beams can be angled with a small hinge angle at a target volume without creating a hotspot.AimIn this study the dosimetric properties of Varian Enhanced Dynamic Wedge (EDW) and physical wedges (PW) were analyzed and compared.Materials and methodsIonometric measurements of open field output factor, physical wedge output factor, physical wedge factor and EDW factor for photon beams were carried out. A 3D scanning water phantom was used to scan depth dose and profiles for open and PW fields. The 2D ionization matrix was used to measure profiles of physical and EDW wedges. The isodose curves of physical and EDW angles were obtained using a therapy verification film.Results and discussionThe PW output factors of photons were compared with the open field output factors. The physical and EDW factors were compared. The difference in percentage depth dose for open and PW fields was observed for both photon beams. The measured isodose plots for physical and EDW were compared.ConclusionThe wedge field output factor increases with field size and wedge angle compared to that of the open field output factor. The number of MU to deliver a particular dose with the EDW field is less than that of the PW field due to a change in wedge factor. The dosimetric characteristics, like profile and isodose of EDW, closely match with that of the PW.     

Interplay between lipids and viral glycoproteins during hemolysis and fusion by influenza virus

Since mixtures of lipids alone are known to elicit membrane fusion without participation of fusion proteins, the role of viral lipids in the so-called virus-induced hemolysis and cell fusion has been investigated, using as a model the fowl plague virus (influenza A/FPV/Rostock/H7N1). The experiments were planned in a way that allowed quantitative modification of viral lipids without changing envelope glycoproteins. Under the conditions employed, cholesterol oxidase of Nocardia erythropolis and phospholipase C of Bacillus cereus were shown to completely modify their substrates in the virus without altering virus-associated hemagglutinating and neuraminidase activities. It was found with such enzyme treatment that virus-induced hemolysis and cell fusion are greatly influenced by cholesterol and phospholipids of the envelope. It became clear, that hemolysis and fusion are differently dependent on the nature of lipid components even though mediated by the same viral glycoproteins.     

Interplay between synaptonemal complex, homologous recombination, and centromeres during mammalian meiosis

The intimate synapsis of homologous chromosome pairs (homologs) by synaptonemal complexes (SCs) is an essential feature of meiosis. In many organisms, synapsis and homologous recombination are interdependent: recombination promotes SC formation and SCs are required for crossing-over. Moreover, several studies indicate that initiation of SC assembly occurs at sites where crossovers will subsequently form. However, recent analyses in budding yeast and fruit fly imply a special role for centromeres in the initiation of SC formation. In addition, in budding yeast, persistent SC–dependent centromere-association facilitates the disjunction of chromosomes that have failed to become connected by crossovers. Here, we examine the interplay between SCs, recombination, and centromeres in a mammal. In mouse spermatocytes, centromeres do not serve as SC initiation sites and are invariably the last regions to synapse. However, centromeres are refractory to de-synapsis during diplonema and remain associated by short SC fragments. Since SC–dependent centromere association is lost before diakinesis, a direct role in homolog segregation seems unlikely. However, post–SC disassembly, we find evidence of inter-centromeric connections that could play a more direct role in promoting homolog biorientation and disjunction. A second class of persistent SC fragments is shown to be crossover-dependent. Super-resolution structured-illumination microscopy (SIM) reveals that these structures initially connect separate homolog axes and progressively diminish as chiasmata form. Thus, DNA crossing-over (which occurs during pachynema) and axis remodeling appear to be temporally distinct aspects of chiasma formation. SIM analysis of the synapsis and crossover-defective mutant Sycp1^−/− implies that SCs prevent unregulated fusion of homolog axes. We propose that SC fragments retained during diplonema stabilize nascent bivalents and help orchestrate local chromosome reorganization that promotes centromere and chiasma function.     

Antagonistic Interplay between MicroRNA-155 and IL-10 during Lyme Carditis and Arthritis

MicroRNA-155 has been shown to play a role in immune activation and inflammation, and is suppressed by IL-10, an important anti-inflammatory cytokine. The established involvement of IL-10 in the murine model of Borrelia burgdorferi-induced Lyme arthritis and carditis allowed us to assess the interplay between IL-10 and miR-155 in vivo. As reported previously, Mir155 was highly upregulated in joints from infected severely arthritic B6 Il10^-/- mice, but not in mildly arthritic B6 mice. In infected hearts, Mir155 was upregulated in both strains, suggesting a role of miR-155 in Lyme carditis. Using B. burgdorferi-infected B6, Mir155^-/-, Il10^-/-, and Mir155^-/- Il10^-/- double-knockout (DKO) mice, we found that anti-inflammatory IL-10 and pro-inflammatory miR-155 have opposite and somewhat compensatory effects on myeloid cell activity, cytokine production, and antibody response. Both IL-10 and miR-155 were required for suppression of Lyme carditis. Infected Mir155^-/- mice developed moderate/severe carditis, had higher B. burgdorferi numbers, and had reduced Th1 cytokine expression in hearts. In contrast, while Il10^-/- and DKO mice also developed severe carditis, hearts had reduced bacterial numbers and elevated Th1 and innate cytokine expression. Surprisingly, miR-155 had little effect on Lyme arthritis. These results show that antagonistic interplay between IL-10 and miR-155 is required to balance host defense and immune activation in vivo, and this balance is particularly important for suppression of Lyme carditis. These results also highlight tissue-specific differences in Lyme arthritis and carditis pathogenesis, and reveal the importance of IL-10-mediated regulation of miR-155 in maintaining healthy immunity.     

Population dynamic consequences of allee effects

We take a well-known dynamic model of an isolated, unstructured population and modify this to include a factor that allows for a reduction in fitness due to declining population sizes, often termed an Allee effect. Analysis of the behaviour of this model is carried out on two fronts - determining the equilibrium values and examining the stability of these equilibria. Our results point to the stabilising effect on population dynamics of the Allee effect and an unexpected increase in stability with increased competition due to the interaction between competitive and Allee effects.     

Intratumoral immunocytokine treatment results in enhanced antitumor effects

Immunocytokines (IC), consisting of tumor-specific monoclonal antibodies fused to the immunostimulatory cytokine interleukin 2 (IL2), exert significant antitumor effects in several murine tumor models. We investigated whether intratumoral (IT) administration of IC provided enhanced antitumor effects against subcutaneous tumors. Three unique ICs (huKS-IL2, hu14.18-IL2, and GcT84.66-IL2) were administered systemically or IT to evaluate their antitumor effects against tumors expressing the appropriate IC-targeted tumor antigens. The effect of IT injection of the primary tumor on a distant tumor was also evaluated. Here, we show that IT injection of IC resulted in enhanced antitumor effects against B16-KSA melanoma, NXS2 neuroblastoma, and human M21 melanoma xenografts when compared to intravenous (IV) IC injection. Resolution of both primary and distant subcutaneous tumors and a tumor-specific memory response were demonstrated following IT treatment in immunocompetent mice bearing NXS2 tumors. The IT effect of huKS-IL2 IC was antigen-specific, enhanced compared to IL2 alone, and dose-dependent. Hu14.18-IL2 also showed greater IT effects than IL2 alone. The antitumor effect of IT IC did not always require T cells since IT IC induced antitumor effects against tumors in both SCID and nude mice. Localization studies using radiolabeled ¹¹¹In-GcT84.66-IL2 IC confirmed that IT injection resulted in a higher concentration of IC at the tumor site than IV administration. In conclusion, we suggest that IT IC is more effective than IV administration against palpable tumors. Further testing is required to determine how to potentially incorporate IT administration of IC into an antitumor regimen that optimizes local and systemic anticancer therapy.     

NMR-based structural biology enhanced by dynamic nuclear polarization at high magnetic field

Dynamic nuclear polarization (DNP) has become a powerful method to enhance spectroscopic sensitivity in the context of magnetic resonance imaging and nuclear magnetic resonance spectroscopy. We show that, compared to DNP at lower field (400 MHz/263 GHz), high field DNP (800 MHz/527 GHz) can significantly enhance spectral resolution and allows exploitation of the paramagnetic relaxation properties of DNP polarizing agents as direct structural probes under magic angle spinning conditions. Applied to a membrane-embedded K⁺ channel, this approach allowed us to refine the membrane-embedded channel structure and revealed conformational substates that are present during two different stages of the channel gating cycle. High-field DNP thus offers atomic insight into the role of molecular plasticity during the course of biomolecular function in a complex cellular environment.     

The effects of rest interval length on ratings of perceived exertion during dynamic knee extension exercise

The objective of this study was to examine the effects of rest interval length on perceived exertion and during 3 sets of 10 inertial knee extension repetitions. Thirty healthy men (n = 15) and women (n = 15) volunteers were randomly assigned to 1 of 3 groups (1-, 2-, or 3-minute rest interval length) following the establishment of each subject's 1 repetition maximum (1RM) for inertial knee extension exercise. Subjects in each group performed 3 sets of 10 repetitions at 70% of a theoretical 10RM (based on each subject's 1RM), with a 1-, 2-, or 3-minute rest interval between each set. Perceived exertion was recorded, via the Borg category-ratio scale, from each subject after each repetition of each set. The results demonstrated no significant rest interval length effect on perceived exertion across the 3 sets of 10 repetitions. The results revealed a significantly higher perceived exertion value following the first repetition in set 3 as compared to sets 2 and 1 in all groups. The increase in perceived exertion within each set, as described by the slope, was found to be significantly lowest in set 1, as compared to sets 2 and 3. The major findings of this study demonstrate that perceived exertion significantly increases in a similar manner across 3 sets of 10 knee extension repetitions, despite rest interval lengths of 1-3 minutes.     

Interplay between efflux pumps may provide either additive or multiplicative effects on drug resistance

The effects of simultaneous expression of several efflux pumps on antibiotic resistance were investigated in Escherichia coli and Pseudomonas aeruginosa. Several combinations of efflux pumps have been studied: (i) simultaneous expression of a single-component efflux pump, which exports antibiotics into the periplasm, in combination with a multicomponent efflux pump that accomplishes efflux directly into the external medium; (ii) simultaneous expression of two single-component pumps; and (iii) simultaneous expression of two multicomponent pumps. It was found that when efflux pumps of different structural types were combined in the same cell (the first case), the observed antibiotic resistance was much higher than that conferred by each of the pumps expressed singly. Simultaneous expression of pairs of single-component or multicomponent efflux pumps (the second and third cases) did not produce strong increases in antibiotic resistance.     

Interplay between CDC2 kinase and MAP kinase pathway during maturation of mammalian oocytes

Two principal kinases, p34cdc2 kinase and MAP kinase play a pivotal role in maturation of mammalian oocytes. In the porcine and bovine oocytes both kinases are activated around the time of germinal vesicle breakdown (GVBD). Butyrolactone I (BL I), a specific inhibitor of cdk kinases, prevents effectively and reversibly resumption of meiosis in the porcine and bovine oocytes. Neither p34cdc2 kinase nor MAP kinase are activated in oocytes inhibited in the GV stage. The bovine oocytes maintained for 48 h in the medium supplemented with BL I, progress subsequently to metaphase II in 91%, their cumuli expand optimally and after in vitro fertilization they possess two pronuclei. When the cdc2 kinase is blocked in the porcine oocytes by BL I, MAP kinase, activated by okadaic acid treatment, is able to substitute cdc2 kinase and induce GVBD. The histone H1 kinase activity sharply decreases in the metaphase II oocytes treated by BL I and one or two female pronuclei are formed. These data indicate that BL I is a useful tool either for the two step in vitro culture of mammalian oocytes or for their activation in nuclear transfer experiments.