Three-dimensional reconstruction of individual helical nano-filament structures from atomic force microscopy topographs

Atomic force microscopy, AFM, is a powerful tool that can produce detailed topographical images of individual nano-structures with a high signal-to-noise ratio without the need for ensemble averaging. However, the application of AFM in structural biology has been hampered by the tip-sample convolution effect, which distorts images of nano-structures, particularly those that are of similar dimensions to the cantilever probe tips used in AFM. Here we show that the tip-sample convolution results in a feature-dependent and non-uniform distribution of image resolution on AFM topographs. We show how this effect can be utilised in structural studies of nano-sized upward convex objects such as spherical or filamentous molecular assemblies deposited on a flat surface, because it causes ‘magnification’ of such objects in AFM topographs. Subsequently, this enhancement effect is harnessed through contact-point based deconvolution of AFM topographs. Here, the application of this approach is demonstrated through the 3D reconstruction of the surface envelope of individual helical amyloid filaments without the need of cross-particle averaging using the contact- deconvoluted AFM topographs. Resolving the structural variations of individual macromolecular assemblies within inherently heterogeneous populations is paramount for mechanistic understanding of many biological phenomena such as amyloid toxicity and prion strains. The approach presented here will also facilitate the use of AFM for high-resolution structural studies and integrative structural biology analysis of single molecular assemblies

Optimal Pandemic Influenza Vaccine Allocation Strategies for the Canadian Population

BACKGROUND: The world is currently confronting the first influenza pandemic of the 21(st) century. Influenza vaccination is an effective preventive measure, but the unique epidemiological features of swine-origin influenza A (H1N1) (pH1N1) introduce uncertainty as to the best strategy for prioritization of vaccine allocation. We sought to determine optimal prioritization of vaccine distribution among different age and risk groups within the Canadian population, to minimize influenza-attributable morbidity and mortality. METHODOLOGY/PRINCIPAL FINDINGS: We developed a deterministic, age-structured compartmental model of influenza transmission, with key parameter values estimated from data collected during the initial phase of the epidemic in Ontario, Canada. We examined the effect of different vaccination strategies on attack rates, hospitalizations, intensive care unit admissions, and mortality. In all scenarios, prioritization of high-risk individuals (those with underlying chronic conditions and pregnant women), regardless of age, markedly decreased the frequency of severe outcomes. When individuals with underlying medical conditions were not prioritized and an age group-based approach was used, preferential vaccination of age groups at increased risk of severe outcomes following infection generally resulted in decreased mortality compared to targeting vaccine to age groups with higher transmission, at a cost of higher population-level attack rates. All simulations were sensitive to the timing of the epidemic peak in relation to vaccine availability, with vaccination having the greatest impact when it was implemented well in advance of the epidemic peak. CONCLUSIONS/SIGNIFICANCE: Our model simulations suggest that vaccine should be allocated to high-risk groups, regardless of age, followed by age groups at increased risk of severe outcomes. Vaccination may significantly reduce influenza-attributable morbidity and mortality, but the benefits are dependent on epidemic dynamics, time for program roll-out, and vaccine uptake

Genus Two Partition and Correlation Functions for Fermionic Vertex Operator Superalgebras I

We define the partition and $n$-point correlation functions for a vertex operator superalgebra on a genus two Riemann surface formed by sewing two tori together. For the free fermion vertex operator superalgebra we obtain a closed formula for the genus two continuous orbifold partition function in terms of an infinite dimensional determinant with entries arising from torus Szeg\"o kernels. We prove that the partition function is holomorphic in the sewing parameters on a given suitable domain and describe its modular properties. Using the bosonized formalism, a new genus two Jacobi product identity is described for the Riemann theta series. We compute and discuss the modular properties of the generating function for all $n$-point functions in terms of a genus two Szeg\"o kernel determinant. We also show that the Virasoro vector one point function satisfies a genus two Ward identity.Comment: A number of typos have been corrected, 39 pages. To appear in Commun. Math. Phy

South Africa - CGIAR Partnership Results in New Maize Varieties with 30 to 50 percent higher yields

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On the Relationship between the Uniqueness of the Moonshine Module and Monstrous Moonshine

We consider the relationship between the conjectured uniqueness of the Moonshine Module, ${\cal V}^\natural$, and Monstrous Moonshine, the genus zero property of the modular invariance group for each Monster group Thompson series. We first discuss a family of possible $Z_n$ meromorphic orbifold constructions of ${\cal V}^\natural$ based on automorphisms of the Leech lattice compactified bosonic string. We reproduce the Thompson series for all 51 non-Fricke classes of the Monster group $M$ together with a new relationship between the centralisers of these classes and 51 corresponding Conway group centralisers (generalising a well-known relationship for 5 such classes). Assuming that ${\cal V}^\natural$ is unique, we then consider meromorphic orbifoldings of ${\cal V}^\natural$ and show that Monstrous Moonshine holds if and only if the only meromorphic orbifoldings of ${\cal V}^\natural$ give ${\cal V}^\natural$ itself or the Leech theory. This constraint on the meromorphic orbifoldings of ${\cal V}^\natural$ therefore relates Monstrous Moonshine to the uniqueness of ${\cal V}^\natural$ in a new way.Comment: 53 pages, PlainTex, DIAS-STP-93-0

Torus n-Point Functions for R\mathbb{R}-graded Vertex Operator Superalgebras and Continuous Fermion Orbifolds

We consider genus one n-point functions for a vertex operator superalgebra with a real grading. We compute all n-point functions for rank one and rank two fermion vertex operator superalgebras. In the rank two fermion case, we obtain all orbifold n-point functions for a twisted module associated with a continuous automorphism generated by a Heisenberg bosonic state. The modular properties of these orbifold n-point functions are given and we describe a generalization of Fay's trisecant identity for elliptic functions.Comment: 50 page

Quantification of amyloid fibril polymorphism by nano-morphometry reveals the individuality of filament assembly

Amyloid fibrils are highly polymorphic structures formed by many different proteins. They provide biological function but also abnormally accumulate in numerous human diseases. The physicochemical principles of amyloid polymorphism are not understood due to lack of structural insights at the single-fibril level. To identify and classify different fibril polymorphs and to quantify the level of heterogeneity is essential to decipher the precise links between amyloid structures and their functional and disease associated properties such as toxicity, strains, propagation and spreading. Employing gentle, force-distance curve-based AFM, we produce detailed images, from which the 3D reconstruction of individual filaments in heterogeneous amyloid samples is achieved. Distinctive fibril polymorphs are then classified by hierarchical clustering, and sample heterogeneity is objectively quantified. These data demonstrate the polymorphic nature of fibril populations, provide important information regarding the energy landscape of amyloid self-assembly, and offer quantitative insights into the structural basis of polymorphism in amyloid populations

Spatial distribution, inter-annual variability and influence of abiotic factors on molluscan assemblages collected with otter trawl in the northen Alborán Sea

Molluscs constitute one of the most diverse and best represented invertebrate groups in the marine environment. In the northern sectors of the Alborán Sea and Gulf of Cádiz 1200 spp. of the 1800 spp. occurring in the Mediterranean Sea, have been found so far highlighting the importance of this area for the european molluscan fauna (Gofas et al., 2011). Molluscs are also the second group in abundance and biomass in demersal fisheries and an important component of soft-bottom benthic communities, including ecologically important and/or commercial mollusc species that are also exposed to an increasing trawling impact (Snelgrove, 1998; Kaiser & De Groot, 1999). Previous studies on molluscs of the Alborán Sea has primarily focused on those from infralittoral habitats, with few studies focussing on the composition, structure and dynamics of circalittoral and bathyal molluscan assemblages ( Rueda et al., 2015). The study of soft bottom molluscan assemblages where trawling fishing fleet operates is important for improving the fisheries evaluation and management, as well as the implementation of ecosystemic and biodiversity conservation measures in the context of the new Marine Strategy Framework Directive. In the present study, the distribution and inter-annual variability of molluscan assemblages of circalittoral and bathyal soft bottoms of the Alborán Sea have been analyzed as well as the relationships of fauna with different environmental variables. Samples were collected in 190 otter trawl hauls performed between “Punta Europa” and “Cabo de Gata”, including the Alborán Ridge, at depths from 30 to 800 m during four MEDITS-ES trawl surveys in spring between 2012 and 2015. Several environmental variables from the water column (temperature and salinity) and sediment samples were taken where each haul was performed in order to elucidate their relationships with the molluscan assemblages. Abundances of each species (individuals . h-1) of each haul and trawl survey were pooled in a matrix for performing multivariate methods in order to contrast molluscan assemblages of different sites and years. The Bray-Curtis similarity index was then used to perform non-parametric multidimensional scaling ordinations (nMDS). A fourth root transformation pretreatment was applied on the quantitative data in order to minimize the contribution of the most abundant species to the analyses. Analyses of similarities (ANOSIM) were carried out for statistical comparisons of groups of samples according to different factors (e.g. year, location). Analyses of similitude percentage (SIMPER) were used to identify those species that contributed to the similarity and dissimilarity between groups of samples according to factors. These multivariate analyses were executed using the PRIMER v6 (Plymouth Routines in Multivariate Ecological Research). Average values of abundance of molluscs (N), species richness (S), Shannon-Wiener diversity index (H’: log2), evenness index (J’) and taxonomic distinctness index (Δ*) were calculated for each sample group. Statistical differences between these values were tested with the non-parametric Kruskal-Wallis using SPSS software. The relationships between environmental variables and molluscs abundance in the different hauls were only studied for the 2014 trawl survey using a correspondence canonical analysis (CCA). The statistical significance of the adjusted CCA was assessed using a Monte Carlo permutation test. Prior to this, the environmental variables were screened and those which presented a correlation higher than 0.9 (after a Spearman correlation analysis) were not further considered. These analyses were executed using the R software. Three main molluscan assemblages were detected and belonged to the: I) Continental Shelf (30-200 m); II) Upper Continental Slope (201-350 m), and III) Middle Continental Slope (351-800 m). The multivariate analyses revealed geographical differences within the Alborán Sea, being these differences more acute between the Alborán Island, mainly in the shallower assemblages (30-200 m and 201-350 m) and the remaining locations considered. These differences were due to a lower abundance in the island of species that were dominant in the continental margin, such as Alloteuthis media, Sepietta oweniana and Turritella communis and a higher abundance in the island of species that were less abundant in the continental margin, such as Neopycnodonte cochlear, Arca tetragona, Loligo forbesii and Sepia orbignyana. No significant differences of the abundance, biomass, species richness and diversity index were detected in the assemblages over the four years. Nevertheless, significant abundance declines of A. media, S. oweniana, and increases of N. cochlear were detected in the continental shelf over the years as well as abundance declines of Bathypolipus sponsalis and Galeodea rugosa in the slope assemblages. Regarding the environmental variables, the shallower assemblage (30-200 m) showed a significantly higher temperature, lower salinity and wider variety of sediment types than the others, with a predominance of sandy mud textures followed by muddy sand. As depth increases the sedimentary heterogeneity decreases, with dominant muddy sediments. Depth, temperature and mud percentage were the key variables that better explained the variability of the molluscan assemblage in the CCA. In conclusions: (1) Acute geographical differences occurred between the Alborán Island and the locations of the continental margin, due to its location far from the continental influence and, therefore, with lower fisheries activity and a less muddy and more bioclastic sediment, (2) Inter-annual trends in the abundance, biomass, species richness and diversity of assemblages were not detected, but some species displayed inter-annual changes due to biological aspects or accidental catch of gregarious species and (3) depth and some sedimentological variables displayed the most significant relationships with the molluscan assemblages, as previously observed for other invertebrate assemblages in the Alborán Sea

Lack of association of cranial lacunae with intracranial hypertension in children with Crouzon syndrome and Apert syndrome: a 3D morphometric quantitative analysis

Purpose Cranial lacunae (foci of attenuated calvarial bone) are CT equivalents ofBcopper beating seen on plain skull radio-graphs in children with craniosynostosis. The qualitative presence of copper beating has not been found to be useful for the diagnosis of intracranial hypertension (IH) in these patients. 3D morphometric analysis (3DMA) allows a more systematic and quantitative assessment of calvarial attenuation. We used 3DMA to examine the relationship between cranial lacunae and IH in children with Crouzon and Apert syndromic craniosynostosis

In situ identification of Palaeoarchaean biosignatures using co-located Perseverance rover analyses: perspectives for in situ Mars science and sample return

The NASA Mars 2020 Perseverance rover is currently exploring Jezero crater, a Noachian locality that once hosted a delta–lake system with high habitability and biosignature preservation potential. Perseverance conducts detailed appraisals of rock targets using a synergistic payload capable of geological characterisation from kilometre to micron scales. The highest-resolution textural and chemical information will be provided by correlated WATSON (imaging), SHERLOC (deep-UV Raman and fluorescence spectroscopy) and PIXL (X-ray lithochemistry) analyses, enabling the distributions of organic and mineral phases within rock targets to be comprehensively established. Herein, we analyse Palaeoarchaean microbial mats from the ~3.42 Ga Buck Reef Chert (Barberton greenstone belt) – considered astrobiological analogues for a putative Martian biosphere – following a WATSON–SHERLOC–PIXL protocol identical to that conducted by Perseverance on Mars during each sampling activities. Correlating deep-UV Raman and fluorescence spectroscopic mapping with X-ray elemental mapping, we show that the Perseverance payload has the capability to detect thermally and texturally mature organic materials of biogenic origin and can highlight organic–mineral interrelationships and elemental co-location at fine spatial scales. We also show that the Perseverance protocol obtains very similar results to high-performance laboratory imaging, Raman spectroscopy and µXRF instruments. This is encouraging for the prospect of detecting micro-scale organic-bearing textural biosignatures on Mars using the correlative micro-analytical approach enabled by WATSON, SHERLOC and PIXL; indeed, laminated, organic-bearing samples such as those studied herein are considered plausible biosignatures for a potential Noachian–Hesperian biosphere and would make compelling targets for sampling during the mission