Biomolecular self-assembly under extreme Martian mimetic conditions

The recent discovery of subsurface water on Mars has challenged our understanding of the natural limits of life. The presence of magnesium perchlorate (Mg(ClO4)2) on the Martian surface raises the possibility that it may also be present in this subsurface lake. Given that the subsurface lakes on Earth, such as Lake Vostok and Lake Whillans, are capable of harbouring surprising amounts of life, these new findings raise interesting possibilities for how biomolecules might self-assemble in this environment on Mars. Here we investigate the self-association and hydration of the amino acid glycine in aqueous Mg(ClO4)2 at 25°C and −20°C using neutron diffraction with hydrogen isotope substitution and subsequent analysis with empirical potential structure refinement to yield a simulated box of atoms consistent with the scattering data. We find that although the highly chaotropic properties of Mg(ClO4)2 disrupt the hydration and hydrogen bonding ability of the amino acid, as well as the bulk water structure, glycine molecules are nonetheless still able to self-associate. This occurs more readily at lower temperature, where clusters of up to three molecules are observed, allowing us to speculate that the formation of biological molecules is possible in the Martian environment

Transnuclear TRP1-Specific CD8 T Cells with High or Low Affinity TCRs Show Equivalent Antitumor Activity

We have generated, via somatic cell nuclear transfer, two independent lines of transnuclear (TN) mice, using as nuclear donors CD8 T cells, sorted by tetramer staining, that recognize the endogenous melanoma antigen TRP1. These two lines of nominally identical specificity differ greatly in their affinity for antigen (TRP1(high) or TRP1(low)) as inferred from tetramer dissociation and peptide responsiveness. Ex vivo-activated CD8 T cells from either TRP1(high) or TRP1(low) mice show cytolytic activity in 3D tissue culture and in vivo, and slow the progression of subcutaneous B16 melanoma. Although naïve TRP1(low) CD8 T cells do not affect tumor growth, upon activation these cells function indistinguishably from TRP1(high) cells in vivo, limiting tumor cell growth and increasing mouse survival. The anti-tumor effect of both TRP1(high) and TRP1(low) CD8 T cells is enhanced in RAG-deficient hosts. However, tumor outgrowth eventually occurs, likely due to T cell exhaustion. The TRP1 TN mice are an excellent model for examining the functional attributes of T cells conferred by TCR affinity, and they may serve as a platform for screening immunomodulatory cancer therapies

The Contribution of Pre-Existing Depression to the Acute Cognitive Sequelae of Mild Traumatic Brain Injury

Frontotemporal abnormalities and cognitive dysfunction, especially in verbal memory and information processing speed, occur in both mild traumatic brain injury (mTBI) and depression. Study 1 investigated the effect of depression on cognitive performance in a sample at risk of sustaining mTBI.Seventy-eight male undergraduates completed the Depression Anxiety Stress Scales (DASS), Digit Symbol Substitution Test (DSS), Hopkins Verbal Learning Test (HVLT), and Speed of Comprehension Test. A oneway analysis of covariance (using the top 25% and bottom 25% of DASS Depression subscale scorers) showed that HVLT recognition was significantly worse in the high scorers. Study 2 examined the effects of injury type and pre-existing depression on cognitive performance in a prospective emergency department sample (within 24 hours of injury). Fifty-eight participants with mTBI (29 with depression, 29 without depression) and 47 control participants (18 with depression, 29 without depression) completed the DSS, HVLT, and Speed of Comprehension Test. Participants with mTBI performed worse than controls (uninjured and orthopaedic-injured participants) on all tests. Participants with depression did not perform worse than participants without depression on the tests. However, there was a significant univariate interaction for HVLT recognition, participants in the mTBI group with depression exhibited worse recognition compared to participants without depression. Since word recognition was impaired in participants who were more depressed in both samples, this suggests that it is a consistent finding. More importantly, the results of Study 2 indicate that depression may interact with mTBI to impair word recognition during the acute phase after head injury

Hierarchical biomechanics: student engagement activities with a focus on biological physics

Hierarchical structure and mechanics are crucial in biological systems as they allow for smaller molecules, such as proteins and sugars, to be used in the construction of large scale biological structures exhibiting properties such as structural support functionality. By exploring the fundamental principles of structure and mechanics at the macroscale, this general theme provides a clear insight into how physics can be applied to the complex questions of biology. With a focus on biopolymer networks and hydrogels, we present a series of interactive activities which cover a range of biophysical concepts at an introductory level, such as viscoelasticity, biological networks and ultimately, hierarchical biomechanics. These activities enable us to discuss multidisciplinary science with a general audience and, given the current trends of research science, this conceptualisation of science is vital for the next generation of scientists

Black Hole Interaction Energy

The interaction energy between two black holes at large separation distance is calculated. The first term in the expansion corresponds to the Newtonian interaction between the masses. The second term corresponds to the spin-spin interaction. The calculation is based on the interaction energy defined on the two black holes initial data. No test particle approximation is used. The relation between this formula and cosmic censorship is discussed.Comment: 18 pages, 2 figures, LaTeX2

Chronology Protection and Non-Naked Singularity

We test the chronology protection conjecture in classical general relativity by investigating finitely vicious space-times. First we present singularity theorems in finitely vicious space-times by imposing some restrictions on the chronology violating sets. In the theorems we can refer to the location of an occurring singularity and do not assume any asymptotic conditions such as the existence of null infinities. Further introducing the concept of a non-naked singularity, we show that a restricted class of chronology violations cannot arise if all occurring singularities are the non-naked singularities. Our results suggest that the causal feature of the occurring singularities is the key to prevent the appearance of causality violation.Comment: 17 pages including 3 eps figures. Accepted for publication in Classical and Quantum Gravit

Post-vaccine epidemiology of serotype 3 pneumococci identifies transformation inhibition through prophage-driven alteration of a non-coding RNA

Background: The respiratory pathogen Streptococcus pneumoniae (the pneumococcus) is a genetically diverse bacterium associated with over 101 immunologically distinct polysaccharide capsules (serotypes). Polysaccharide conjugate vaccines (PCVs) have successfully eliminated multiple targeted serotypes, yet the mucoid serotype 3 has persisted despite its inclusion in PCV13. This capsule type is predominantly associated with a single globally disseminated strain, GPSC12 (clonal complex 180).Methods: A genomic epidemiology study combined previous surveillance datasets of serotype 3 pneumococci to analyse the population structure, dynamics, and differences in rates of diversification within GPSC12 during the period of PCV introductions. Transcriptomic analyses, whole genome sequencing, mutagenesis, and electron microscopy were used to characterise the phenotypic impact of loci hypothesised to affect this strain's evolution.Results: GPSC12 was split into clades by a genomic analysis. Clade I, the most common, rarely underwent transformation, but was typically infected with the prophage phi OXC141. Prior to the introduction of PCV13, this Glade's composition shifted towards a phi OXC141-negative subpopulation in a systematically sampled UK collection. In the post-PCV13 era, more rapidly recombining non-Clade I isolates, also phi OXC141-negative, have risen in prevalence. The low in vitro transformation efficiency of a Clade I isolate could not be fully explained by the similar to 100-fold reduction attributable to the serotype 3 capsule. Accordingly, prophage phi OXC141 was found to modify csRNA3, a non-coding RNA that inhibits the induction of transformation. This alteration was identified in -30% of all pneumococci and was particularly common in the unusually clonal serotype 1 GPSC2 strain. RNA-seq and quantitative reverse transcriptase PCR experiments using a genetically tractable pneumococcus demonstrated the altered csRNA3 was more effective at inhibiting production of the competence-stimulating peptide pheromone. This resulted in a reduction in the induction of competence for transformation.Conclusion: This interference with the quorum sensing needed to induce competence reduces the risk of the prophage being deleted by homologous recombination. Hence the selfish prophage-driven alteration of a regulatory RNA limits cell-cell communication and horizontal gene transfer, complicating the interpretation of post-vaccine population dynamics

Angular momentum and an invariant quasilocal energy in general relativity

Owing to its transformation property under local boosts, the Brown-York quasilocal energy surface density is the analogue of E in the special relativity formula: E^2-p^2=m^2. In this paper I will motivate the general relativistic version of this formula, and thereby arrive at a geometrically natural definition of an `invariant quasilocal energy', or IQE. In analogy with the invariant mass m, the IQE is invariant under local boosts of the set of observers on a given two-surface S in spacetime. A reference energy subtraction procedure is required, but in contrast to the Brown-York procedure, S is isometrically embedded into a four-dimensional reference spacetime. This virtually eliminates the embeddability problem inherent in the use of a three-dimensional reference space, but introduces a new one: such embeddings are not unique, leading to an ambiguity in the reference IQE. However, in this codimension-two setting there are two curvatures associated with S: the curvatures of its tangent and normal bundles. Taking advantage of this fact, I will suggest a possible way to resolve the embedding ambiguity, which at the same time will be seen to incorporate angular momentum into the energy at the quasilocal level. I will analyze the IQE in the following cases: both the spatial and future null infinity limits of a large sphere in asymptotically flat spacetimes; a small sphere shrinking toward a point along either spatial or null directions; and finally, in asymptotically anti-de Sitter spacetimes. The last case reveals a striking similarity between the reference IQE and a certain counterterm energy recently proposed in the context of the conjectured AdS/CFT correspondence.Comment: 54 pages LaTeX, no figures, includes brief summary of results, submitted to Physical Review

Meson-exchange Model for πN\pi N scattering and γN−>πN\gamma N -> \pi N reaction

An effective Hamiltonian consisting of bare $\Delta \leftrightarrow\pi N$, $\gamma N$ vertex interactions and energy-independent meson-exchange $\pi N \leftrightarrow \pi N, \gamma N$ transition operators is derived by applying a unitary transformation to a model Lagrangian with $N,\Delta,\pi$, $\rho$, $\omega$, and $\gamma$ fields. With appropraite phenomenological form factors and coupling constants for $\rho$ and $\Delta$, the model can give a good description of $\pi N$ scattering phase shifts up to the $\Delta$ excitation energy region. It is shown that the best reproduction of the recent LEGS data of the photon-asymmetry ratios in $\gamma p \rightarrow \pi ^0 p$ reactions provides rather restricted constraints on the coupling strengths $G_E$ of the electric $E2$ and $G_M$ of the magnetic $M1$ transitions of the bare $\Delta \leftrightarrow \gamma N$ vertex and the less well-determined coupling constant $g_{\omega NN}$ of $\omega$ meson. Within the ranges that $G_M = 1.9 \pm 0.05$, $G_E = 0.0 \pm 0.025$, and $7 \leq g_{\omega NN}\leq 10.5$, the predicted differential cross sections and photon-asymmetry ratios are in an overall good agreement with the data of $\gamma p \rightarrow \pi ^0 p$, $\gamma p \rightarrow \pi ^+ n$, and $\gamma n\rightarrow \pi ^- p$ reactions from 180 MeV to the $\Delta$ excitation region. The predicted $M_{1^+}$ and $E_{1^+}$ multipole amplitudes are also in good agreement with the empirical values determined by the amplitude analyses. The constructed effective Hamiltonian is free of the nucleon renormlization problem and hence is suitable for nuclear many-body calculations. We have also shown that the assumptions made in the $K$-matrix method, commonly used in extracting empirically the $\gamma N \rightarrow \Delta$ transition amplitudes from the data, are consistent withComment: 49 pages + 23 Figures, Revte