Multicellular Mathematical Modelling of Mesendoderm Formation in Amphibians.

The earliest cell fate decisions in a developing embryo are those associated with establishing the germ layers. The specification of the mesoderm and endoderm is of particular interest as the mesoderm is induced from the endoderm, potentially from an underlying bipotential group of cells, the mesendoderm. Mesendoderm formation has been well studied in an amphibian model frog, Xenopus laevis, and its formation is driven by a gene regulatory network (GRN) induced by maternal factors deposited in the egg. We have recently demonstrated that the axolotl, a urodele amphibian, utilises a different topology in its GRN to specify the mesendoderm. In this paper, we develop spatially structured mathematical models of the GRNs governing mesendoderm formation in a line of cells. We explore several versions of the model of mesendoderm formation in both Xenopus and the axolotl, incorporating the key differences between these two systems. Model simulations are able to reproduce known experimental data, such as Nodal expression domains in Xenopus, and also make predictions about how the positional information derived from maternal factors may be interpreted to drive cell fate decisions. We find that whilst cell-cell signalling plays a minor role in Xenopus, it is crucial for correct patterning domains in axolotl.

Torque-angle-velocity Relationships and Muscle Performance of Professional and Youth Soccer Players.

Soccer matches consist of a variety of different activities, including repeated sprints. Time to attain velocity (TTAV), load range (LR) and the torque-angle-velocity relationship (TAV3D) represent an important measurement of muscle performance, however there are few related studies. The aim of this study was to compare these outcomes between soccer players of different age category. 17 professional (PRO) and 17 under-17 (U17) soccer players were assessed for concentric knee flexion/extension at 60, 120 and 300°/s. For the extensor muscles, differences were found in favor of the U17 group for TTAV and LR outcomes at 120°/s, however, the PRO group maintained higher torques in both movement directions in comparison to the U17 in TAV3D evaluation. These results suggest that muscle performance of the PRO group is more efficient than the U17 group.

Two different network topologies yield bistability in models of mesoderm and anterior mesendoderm specification in amphibians.

Understanding the Gene Regulatory Networks (GRNs) that underlie development is a major question for systems biology. The establishment of the germ layers is amongst the earliest events of development and has been characterised in numerous model systems. The establishment of the mesoderm is best characterised in the frog Xenopus laevis and has been well studied both experimentally and mathematically. However, the Xenopus network has significant differences from that in mouse and humans, including the presence of multiple copies of two key genes in the network, Mix and Nodal. The axolotl, a urodele amphibian, provides a model with all the benefits of amphibian embryology but crucially only a single Mix and Nodal gene required for the specification of the mesoderm. Remarkably, the number of genes within the network is not the only difference. The interaction between Mix and Brachyury, two transcription factors involved in the establishment of the endoderm and mesoderm respectively, is not conserved. While Mix represses Brachyury in Xenopus, it activates Brachyury in axolotl. Thus, whilst the topology of the networks in the two species differs, both are able to form mesoderm and endoderm in vivo. Based on current knowledge of the structure of the mesendoderm GRN we develop deterministic models that describe the time evolution of transcription factors in a single axolotl cell and compare numerical simulations with previous results from Xenopus. The models are shown to have stable steady states corresponding to mesoderm and anterior mesendoderm, with the in vitro model showing how the concentration of Activin can determine cell fate, while the in vivo model shows that ß-catenin concentration can determine cell fate. Moreover, our analysis suggests that additional components must be important in the axolotl network in the specification of the full range of tissues.

Effects of a single whole body cryotherapy (-110°C) bout on neuromuscular performance of the elbow flexors during isokinetic exercise.

It has been demonstrated that body cooling may decrease neuromuscular performance. However, the effect of a single session of whole body cryotherapy (-110°C) on neuromuscular performance has not been well documented. Thus, the aim of this study was to evaluate the effects of a single exposure of WBC on elbow flexor neuromuscular performance. Thirteen physically active, healthy young men (age=27.9±4.2 years, mass=79.4±9.7 kg, height=176.7±5.2 cm) were randomly exposed to 2 different experimental conditions separated by a minimum of 72 h: 1) whole body cryotherapy- 3 min at -110°C; 2) control- 3 min at 21°C. All subjects were tested for maximal isokinetic elbow flexion at 60°.s(-1) 30 min before and 10 min after each condition. There were no significant differences in peak torque, average power, total work or muscle activity between conditions. Peak torque was lower at post-test compared to pre-test in both conditions (F=6.58, p=0.025). However, there were no differences between pre-test and post-test for any other variables. These results indicate that strength specialists, athletic trainers and physical therapists might utilize whole body cryotherapy before training or rehabilitation without compromising neuromuscular performance of the elbow flexors.

Effects of partial-body cryotherapy (- 110°C) on muscle recovery between high-intensity exercise bouts.

The aim of this study was to evaluate the effects of a single partial-body cryotherapy bout between training sessions on strength recovery. 12 young men (23.9±5.9 years) were randomly exposed to 2 different conditions separated by 7 days: 1) Partial-body cryotherapy (subjects were exposed to 3 min of partial-body cryotherapy at - 110 °C between 2 high-intensity training sessions); 2) Control (subjects were not exposed to partial-body cryotherapy between 2 high-intensity training sessions). Subjects were exposed to partial-body cryotherapy after the first training session. The 2 knee extension high-intensity training sessions were separated by a 40-min rest interval. Knee extension training consisted of 6 sets of 10 repetitions at 60°.s(-1) for concentric actions and 6 sets of 10 at 180.s(-1) for eccentric actions. The decrease in eccentric peak torque and total work was significantly (p<0.05) less after partial-body cryotherapy (5.6 and 2%, respectively) when compared to control (16 and 11.6%, respectively). However, the decrease in concentric peak torque and total work was not different (p>0.05) between partial-body cryotherapy (9.4 and 6.5%, respectively) and control (7.5 and 5.2%, respectively). These results indicate that the use of partial-body cryotherapy between-training sessions can enhance eccentric muscle performance recovery.

Is exercise-induced muscle damage susceptibility body segment dependent? Evidence for whole body susceptibility.

OBJECTIVE: The current study examined serum CK activity following bench press (BP) and leg press (LP) exercise-induced muscle damage to evaluate agreement of subjects classification as either high (HiR) or normal responders (NoR) between upper and lower body muscle groups. METHODS: Forty-two men performed two resistance exercise bouts (BP and LP) of four sets of maximum repetitions to concentric failure at 10RM, following a random design. RESULTS: Fourteen subjects were classified as HiR after the BP and thirteen subjects after LP, while nine subjects were classified as HiR for both exercises. The analysis revealed good agreement (Kappa=0.528, with SE=0.137 and 95% confidence interval: from 0.259 to 0.798). Additionally, we found a significant moderate correlation (r=0.65, p<0.001) between CK peaks obtained following LP and BP. CONCLUSION: Our results suggest that exercise-induced muscle damage susceptibility is a whole body characteristic and is not body segment dependent. Thus, it may be that genetic or systemic mechanisms explain individual variation in muscle damage susceptibility.

Glacier retreat reorganizes river habitats leaving refugia for Alpine invertebrate biodiversity poorly protected.

Alpine river biodiversity around the world is under threat from glacier retreat driven by rapid warming, yet our ability to predict the future distributions of specialist cold-water species is currently limited. Here we link future glacier projections, hydrological routing methods and species distribution models to quantify the changing influence of glaciers on population distributions of 15 alpine river invertebrate species across the entire European Alps, from 2020 to 2100. Glacial influence on rivers is projected to decrease steadily, with river networks expanding into higher elevations at a rate of 1% per decade. Species are projected to undergo upstream distribution shifts where glaciers persist but become functionally extinct where glaciers disappear completely. Several alpine catchments are predicted to offer climate refugia for cold-water specialists. However, present-day protected area networks provide relatively poor coverage of these future refugia, suggesting that alpine conservation strategies must change to accommodate the future effects of global warming.

B-1 and B-2 cell-derived immunoglobulin M antibodies are nonredundant components of the protective response to influenza virus infection.

We have studied the role of secreted immunoglobulin (Ig)M in protection from infection with influenza virus and delineated the relative contributions of B-1 versus B-2 cell-derived IgM in this process. Mice deficient in secreted IgM but capable of expressing surface IgM and secreting other Ig classes show significantly reduced virus clearance and survival rates compared with wild-type controls. Irradiation chimeras in which only either B-1 or B-2 cells lack the ability to secrete IgM show mortality rates similar to those of mice in which neither B-1 nor B-2 cells secrete IgM. Dependence on both sources of IgM for survival is partially explained by findings in allotype chimeras that broadly cross-reactive B-1 cell-derived natural IgM is present before infection, whereas virus strain-specific, B-2 cell-derived IgM appears only after infection. Furthermore, lack of IgM secreted from one or both sources significantly impairs the antiviral IgG response. Reconstitution of chimeras lacking B-1 cell-derived IgM only with IgM-containing serum from noninfected mice improved both survival rates and serum levels of virus-specific IgG. Thus, virus-induced IgM must be secreted in the presence of natural IgM for efficient induction of specific IgG and for immune protection, identifying B-1 and B-2 cell-derived IgM antibodies as nonredundant components of the antiviral response.

Effects of age and rest interval on strength recovery.

The purpose of this study was to compare the effect of two different rest intervals between sets of isokinetic knee extension exercise on peak torque (PT), and Total Work (TW) between untrained younger and older men. Seventeen young men (24.22+/-2.58 yrs) and 20 older men (66.85+/-4.02 yrs) performed 3 sets of 10 unilateral isokinetic knee extension repetitions at 60 degrees /s. The rest intervals between sets were 1 and 2 min. There was a significant decline in PT when 1 and 2 min rest intervals were used for young men, but not when a 2 min rest interval was applied for old men. There was also a significant decline in TW among the 3 sets when 1 and 2 min rest intervals were applied for young men, whereas the decline in TW in older men occurred only between the 2(nd) and 3(rd) sets. PT and TW in the 3(rd) set were significant greater following a 2 min rest interval than a 1 min rest in both young and older men. The present study indicated that non-resistance trained young men may require longer rest interval to recover full PT and TW when compared to older men.

Gender muscle recovery during isokinetic exercise.

The purpose of this study was to examine the effect of two between set rest intervals (RI) on isokinetic knee extension peak torque (PT) produced by sedentary women and men. Seventeen young women (27.18 ± 4.05 yrs) and 16 young men (26.75 ± 4.73 yrs) performed 3 sets of 10 unilateral isokinetic knee extension at 60° and 180°/s. The RI between sets was 60 and 120 s, counterbalanced across 2 testing days. Statistical evaluation of the data was performed using a 3-way mixed factor ANOVA (gender x rest interval x sets). Males and females exhibited decreases (p<0.05) in PT with 120 s RI at 60°/s. There was no significant decline in PT in the female group during both RI at 180°/s. Men showed a significant decrease in PT only with 60 s RI. Young women and men require more than 120 s of RI to recover full PT at 60°/s. However, full quadriceps's muscle strength recovery can be attained with a 60 and 120 s at 180°/s in women, but in men only with a 120 s at the same velocity.

Silicon Isotopic Composition in Large Meteoritic SiC Particles and 22Na Origin of 22Ne.

Large silicon carbide (SiC) particles extracted from acid-insoluble residues of carbonaceous chondrites are isotopically anomalous in both silicon and carbon and contain isotopically extreme noble gases. These particles are thought to have originated in mass outflows from red giant stars and to have existed in the interstellar medium at the time the solar system formed from an interstellar cloud. Calculations show that the silicon isotope correlations in those large SiC particles can be generated only in the most massive carbon stars. Consequently, the almost pure neon-22 ((22)Ne) in those particles must be interpreted as the condensation of radioactive sodium-22 ((22)Na) in the particles as they flowed away from the stars. The (22)Na is produced through proton capture by (21)Ne at the base of the surface convection zone. Neon-22 does not exist abundantly in helium shells hot enough to burn magnesium, which is necessary to establish the measured silicon isotopic composition.

Call types of the Rana pipiens complex in Illinois.

The presence of western, eastern, and northern call types of the Rana pipiens complex in Illinois supports evidence from the western United States that this complex can no longer be regarded as one species.

Immunity to avian influenza A viruses.

While the basic principles of immunity to the influenza A viruses are probably similar for all vertebrates, detailed understanding is based largely on experiments in laboratory mice. Elements of the innate response limit early virus replication, although high pathogenicity strains can trigger effusive cytokine/chemokine production and lethal shock. Virus clearance is normally mediated via CD8+ effector T cells but, in their absence, the class-switched antibody response can ultimately achieve the same goal. Protection against reinfection is optimally provided by antibody (IgG and IgA) specific for the homologous viral haemagglutinin, and priming against the neuraminidase and the low abundance, conserved M2 protein can also have an effect. Influenza virus-specific plasma cells and CD8+ T cells persist in the long term and the recall of the CD8+ T cell response can lead to earlier virus clearance. The characteristics of the aging immune system and possible, novel vaccine strategies are also considered.

Pluto's Interaction With Energetic Heliospheric Ions.

Pluto energies of a few kiloelectron volts and suprathermal ions with tens of kiloelectron volts and above. We measure this population using the Pluto Energetic Particle Spectrometer Science Investigation (PEPSSI) instrument on board the New Horizons spacecraft that flew by Pluto in 2015. Even though the measured ions have gyroradii larger than the size of Pluto and the cross section of its magnetosphere, we find that the boundary of the magnetosphere is depleting the energetic ion intensities by about an order of magnitude close to Pluto. The intensity is increasing exponentially with distance to Pluto and reaches nominal levels of the interplanetary medium at about 190R P distance. Inside the wake of Pluto, we observe oscillations of the ion intensities with a periodicity of about 0.2 hr. We show that these can be quantitatively explained by the electric field of an ultralow-frequency wave and discuss possible physical drivers for such a field. We find no evidence for the presence of plutogenic ions in the considered energy range.

Initial results from the New Horizons exploration of 2014 MU69, a small Kuiper Belt object.

The Kuiper Belt is a distant region of the outer Solar System. On 1 January 2019, the New Horizons spacecraft flew close to (486958) 2014 MU69, a cold classical Kuiper Belt object approximately 30 kilometers in diameter. Such objects have never been substantially heated by the Sun and are therefore well preserved since their formation. We describe initial results from these encounter observations. MU69 is a bilobed contact binary with a flattened shape, discrete geological units, and noticeable albedo heterogeneity. However, there is little surface color or compositional heterogeneity. No evidence for satellites, rings or other dust structures, a gas coma, or solar wind interactions was detected. MU69's origin appears consistent with pebble cloud collapse followed by a low-velocity merger of its two lobes.

Human dendritic cells pulsed with specific lipopeptides stimulate autologous antigen-specific T cells without the addition of exogenous maturation factors.

SUMMARY: Serum-free culture conditions to generate immature human monocyte-derived DC (Mo-DC) were optimized, and the parameters that influence their maturation after exposure to lipopeptides containing CD4(+) and CD8(+) T-cell epitopes were examined. The lipopeptides contained a single CD4(+) helper T-cell epitopes, one of a number of human leucocyte antigen (HLA)-A2-restricted cytotoxic T-cell epitope and the lipid Pam2Cys. To ensure complete maturation of the Mo-DC, we examined (i) the optimal lipopeptide concentration, (ii) the optimal Mo-DC density and (iii) the appropriate period of exposure of the Mo-DC to the lipopeptides. The results showed that a high dose of lipopeptide (30 microm) was no more efficient at upregulating maturation markers on Mo-DC than a low dose (6 microm). There was an inverse relationship between Mo-DC concentration and the mean fluorescence intensity of maturation markers. In addition, at the higher cell concentrations, the chemotactic capacity of the Mo-DC towards a cognate ligand, CCL21, was reduced. Thus, high cell concentrations during lipopeptide exposure were detrimental to Mo-DC maturation and function. The duration of exposure of Mo-DC to the lipopeptides had little effect on phenotype, although Mo-DC exposed to lipopeptides for 48 rather than 4 h showed an increased ability to stimulate autologous peripheral blood mononuclear cells to release interferon-gamma in the absence of exogenous maturation factors. These findings reveal conditions for generating mature antigen-loaded DC suitable for targeted immunotherapy.

Mechanomyographic responses of the superficial quadriceps femoris muscles to incremental isometric muscle actions.

The purpose of this study was to compare the composite and individual relationships for mechanomyographic (MMG) amplitude vs. torque during incremental isometric muscle actions. Ten women and six men (mean age +/- SD = 21.8 +/- 1.6 y) performed isometric leg extension muscle actions at 10-100% of peak isometric torque. Accelerometers were placed over the superficial quadriceps femoris muscles to detect the MMG signals. Polynomial regression analyses were used to determine the composite and individual patterns for MMG amplitude vs. isometric torque. The results indicated that the composite MMG amplitude vs. isometric torque relationships for all subjects combined were quadratic for the vastus lateralis and vastus medialis, and linear for the rectus femoris. The results of the individual analyses for the vastus lateralis revealed that the best fit model was linear for six subjects, quadratic for five subjects, cubic for three subjects, while two subjects exhibited no significant relationship. For the rectus femoris, eight subjects demonstrated linear patterns, six were quadratic, and two were cubic. For the vastus medialis, six subjects demonstrated linear patterns, four were quadratic, four were cubic, and two demonstrated no significant relationship. Examination of the patterns between muscles for each individual subject demonstrated that twelve of the sixteen subjects demonstrated different patterns for MMG amplitude vs. isometric torque for at least two of the three muscles examined. The results indicated there were differences in the patterns of responses for the composite MMG amplitude vs. isometric torque relationships for the three muscles. Furthermore, individual patterns for MMG amplitude frequently differed from the composite patterns, as well as between muscles. The results suggested that, in addition to using composite results of MMG responses, individual subject responses should be examined. Furthermore, caution should be used in generalizing the MMG responses of the quadriceps femoris muscles when examining a single muscle.

Live Attenuated Influenza Vaccines engineered to express the nucleoprotein of a recent isolate stimulate human influenza CD8+ T cells more relevant to current infections.

Live attenuated influenza vaccines (LAIV) induce CD8+ T lymphocyte responses that play an important role in killing virus-infected cells. Despite the relative conservation of internal influenza A proteins, the epitopes recognized by T cells can undergo drift under immune pressure. The internal proteins of Russian LAIVs are derived from the master donor virus A/Leningrad/134/17/57 (Len/17) isolated 60 years ago and as such, some CD8+ T cell epitopes may vary between the vaccine and circulating wild-type strains. To partially overcome this issue, the nucleoprotein (NP) gene of wild-type virus can be incorporated into LAIV reassortant virus, along with the HA and NA genes. The present study compares the human CD8+ T cell memory responses to H3N2 LAIVs with the Len/17 or the wild-type NP using an in vitro model.

Antitumor activity of dual-specific T cells and influenza virus.

Activation and expansion of T cells are important in disease resolution, but tumors do not usually satisfy these immune requirements. Therefore, we employed a novel strategy whereby dual-specific T cells were generated that could respond to both tumor and influenza virus, reasoning that immunization with influenza virus would activate and expand tumor-specific cells, and inhibit tumor growth. Dual-specific T cells were generated by gene modification of influenza virus-specific mouse T cells with a chimeric gene-encoding reactivity against the erbB2 tumor-associated antigen. Dual-specific T cells were demonstrated to respond against both tumor and influenza in vitro, and expanded in vitro in response to influenza to a much greater degree than in response to tumor cells. Following adoptive transfer and immunization of tumor-bearing mice with influenza virus, dual-specific T cells expanded greatly in numbers in the peritoneal cavity and spleen. This resulted in a significant increase in time of survival of mice. However, tumors were not eradicated, which may have been due to the observed poor penetration of tumor by T cells. This is the first demonstration that the potent immunogenic nature of an infectious agent can be utilized to directly impact on T-cell expansion and activity against tumor in vivo.

Introduction of exogenous DNA into Chlamydomonas reinhardtii by electroporation.

The fate of exogenous DNA introduced into Chlamydomonas reinhardtii by electroporation was analyzed. With single and double electrical pulses, plasmids as large as 14 kb were introduced into cells with and without intact cell walls. Within hours after introduction, exogenous plasmid DNA was associated with nuclei isolated from cells; several weeks after introduction, exogenous DNA was stably integrated into the Chlamydomonas genome. These studies establish electroporation as a method for introducing DNA, and potentially other molecules, into C. reinhardtii.