Full-length TDP-43 and its C-terminal domain form filamentsin vitrohaving non-amyloid properties

Accumulation of ubiquitin-positive, tau- and α-synuclein-negative intracellular inclusions of TDP-43 in the central nervous system represents the major hallmark correlated to amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration with ubiquitin-positive inclusions (FTLD-U). Such inclusions have variably been described as amorphous aggregates or more structured deposits having amyloid properties. Here we have purified full-length TDP-43 (FL TDP-43) and its C-terminal domain (Ct TDP-43) to investigate the morphological, structural and tinctorial features of aggregates formed in vitro by them at pH 7.4 and 37 °C. AFM images indicate that both protein variants show a tendency to form filaments. Moreover, we show that both FL TDP-43 and Ct TDP-43 filaments possess a largely disordered secondary structure, as ascertained by far-UV circular dichroism and Fourier transform infra-red spectroscopy, do not bind Congo red and induce a very weak increase of thioflavin T fluorescence, indicating the absence of a clear amyloid-like signature

Extreme Energy Cosmic Rays: Bottom-up vs. Top-down scenarii

We present an overview on extreme energy cosmic rays (EECR) and the fundamental physics connected with them. The top-down and bottom-up scenarii are contrasted. We summarize the essential features underlying the top-down scenarii for EECR, namely, the lifetime and the mass {\bf imposed} to the heavy relics whatever they be: topological and non-topological solitons, X-particles, cosmic defects, microscopic black-holes, fundamental strings. An unified formula for the quantum decay rate of all these objects was provided in hep-ph/0202249. The key point in the top-down scenarii is the necessity to {\bf adjust} the lifetime of the heavy object to the age of the universe. The natural lifetimes of such heavy objects are, however, microscopic times associated to the GUT energy scale (sim 10^{-28} sec. or shorter); such heavy objects could have been abundantly formed by the end of inflation and it seems natural they decayed shortly after being formed. The arguments produced to {\bf fine tune} the relics lifetime to the age of the universe are critically analyzed. The annihilation scenario (`Wimpzillas') is analyzed too. Top-down scenarii based on networks of topological defects are strongly disfavored at the light of the recent CMB anisotropy observations. We discuss the acceleration mechanisms of cosmic rays,their possible astrophysical sources and the main open physical problems and difficulties in the context of bottom-up scenarii, and we conclude by outlining the expectations from future observatories like EUSO and where the theoretical effort should be placed.Comment: LaTex, 16 pages, 2 .eps figures. The annihilation scenario (Wimpzillas) is included and the discussion on gamma ray bursts improved. Based on lectures at the Fourth International Workshop on `New Worlds in Astroparticle Physics' in Faro, Portugal, September 2002, at the 9th Course on Astrofundamental Physics of the Chalonge School, Palermo, Italia, September 2002 and at the SOWG EUSO meeting, Roma, Italia, November 200

Integrable models: from dynamical solutions to string theory

We review the status of integrable models from the point of view of their dynamics and integrability conditions. Some integrable models are discussed in detail. We comment on the use it is made of them in string theory. We also discuss the Bethe Ansatz solution of the SO(6) symmetric Hamiltonian with SO(6) boundary. This work is especially prepared for the seventieth anniversaries of Andr\'{e} Swieca (in memoriam) and Roland K\"{o}berle.Comment: 24 pages, to appear in Brazilian Journal of Physic

Scoping review on vector-borne diseases in urban areas : transmission dynamics, vectorial capacity and co-infection

BACKGROUND: Transmission dynamics, vectorial capacity, and co-infections have substantial impacts on vector-borne diseases (VBDs) affecting urban and suburban populations. Reviewing key factors can provide insight into priority research areas and offer suggestions for potential interventions. MAIN BODY: Through a scoping review, we identify knowledge gaps on transmission dynamics, vectorial capacity, and co-infections regarding VBDs in urban areas. Peer-reviewed and grey literature published between 2000 and 2016 was searched. We screened abstracts and full texts to select studies. Using an extraction grid, we retrieved general data, results, lessons learned and recommendations, future research avenues, and practice implications. We classified studies by VBD and country/continent and identified relevant knowledge gaps. Of 773 articles selected for full-text screening, 50 were included in the review: 23 based on research in the Americas, 15 in Asia, 10 in Africa, and one each in Europe and Australia. The largest body of evidence concerning VBD epidemiology in urban areas concerned dengue and malaria. Other arboviruses covered included chikungunya and West Nile virus, other parasitic diseases such as leishmaniasis and trypanosomiasis, and bacterial rickettsiosis and plague. Most articles retrieved in our review combined transmission dynamics and vectorial capacity; only two combined transmission dynamics and co-infection. The review identified significant knowledge gaps on the role of asymptomatic individuals, the effects of co-infection and other host factors, and the impacts of climatic, environmental, and socioeconomic factors on VBD transmission in urban areas. Limitations included the trade-off from narrowing the search strategy (missing out on classical modelling studies), a lack of studies on co-infections, most studies being only descriptive, and few offering concrete public health recommendations. More research is needed on transmission risk in homes and workplaces, given increasingly dynamic and mobile populations. The lack of studies on co-infection hampers monitoring of infections transmitted by the same vector. CONCLUSIONS: Strengthening VBD surveillance and control, particularly in asymptomatic cases and mobile populations, as well as using early warning tools to predict increasing transmission, were key strategies identified for public health policy and practice

Self-gravity as an explanation of the fractal structure of the interstellar medium

The gas clouds of the interstellar medium have a fractal structure, the origin of which has generally been thought to lie in turbulence. The energy of turbulence could come from galactic rotation at large-scale, then cascade down to be dissipated on small-scales by viscosity; it has been suggested that such turbulence helps to prevent massive molecular clouds from collapsing in response to their own gravity. Here we show that, on the contrary, self-gravity itself may be the dominant factor in making clouds fractal. We develop a field-theory approach to the structure of clouds, assuming them to be isothermal, and with only gravitational interactions; we find that the observed fractal dimension of the clouds arise naturally from this approach. Although this result does not imply that turbulence is not important, it does demonstrate that the fractal structure can be understood without it.Comment: Latex file, four pages and two colour figures in .cps files. To appear in Nature, 5 September 199

Identification and Phylogenetic Analysis of Tityus pachyurus and Tityus obscurus Novel Putative Na+-Channel Scorpion Toxins

Background: Colombia and Brazil are affected by severe cases of scorpionism. In Colombia the most dangerous accidents are caused by Tityus pachyurus that is widely distributed around this country. In the Brazilian Amazonian region scorpion stings are a common event caused by Tityus obscurus. The main objective of this work was to perform the molecular cloning of the putative Na+-channel scorpion toxins (NaScTxs) from T. pachyurus and T. obscurus venom glands and to analyze their phylogenetic relationship with other known NaScTxs from Tityus species. Methodology/Principal Findings: cDNA libraries from venom glands of these two species were constructed and five nucleotide sequences from T. pachyurus were identified as putative modulators of Na+-channels, and were named Tpa4, Tpa5, Tpa6, Tpa7 and Tpa8; the latter being the first anti-insect excitatory b-class NaScTx in Tityus scorpion venom to be described. Fifteen sequences from T. obscurus were identified as putative NaScTxs, among which three had been previously described, and the others were named To4 to To15. The peptides Tpa4, Tpa5, Tpa6, To6, To7, To9, To10 and To14 are closely related to the a-class NaScTxs, whereas Tpa7, Tpa8, To4, To8, To12 and To15 sequences are more related to the b-class NaScTxs. To5 is possibly an arthropod specific toxin. To11 and To13 share sequence similarities with both a and b NaScTxs. By means of phylogenetic analysis using the Maximum Parsimony method and the known NaScTxs from Tityus species, these toxins were clustered into 14 distinct groups. Conclusions/Significance: This communication describes new putative NaScTxs from T. pachyurus and T. obscurus and their phylogenetic analysis. The results indicate clear geographic separation between scorpions of Tityus genus inhabiting the Amazonian and Mountain Andes regions and those distributed over the Southern of the Amazonian rainforest. Based on the consensus sequences for the different clusters, a new nomenclature for the NaScTxs is proposed

Fractal Dimensions and Scaling Laws in the Interstellar Medium and Galaxy Distributions: a new Field Theory Approach

We develop a field theoretical approach to the cold interstellar medium (ISM) and large structure of the universe. We show that a non-relativistic self- gravitating gas in thermal equilibrium with variable number of atoms or fragments is exactly equivalent to a field theory of a scalar field phi(x) with exponential self-interaction. We analyze this field theory perturbatively and non-perturbatively through the renormalization group(RG).We show scaling behaviour (critical) for a continuous range of the physical parameters as the temperature. We derive in this framework the scaling relation M(R) \sim R^{d_H} for the mass on a region of size R, and Delta v \sim R^\frac12(d_H -1) for the velocity dispersion. For the density-density correlations we find a power-law behaviour for large distances \sim |r_1 - r_2|^{2D - 6}.The fractal dimension D turns to be related with the critical exponent \nu by D = 1/ \nu. Mean field theory yields \nu = 1/2, D = 2. Both the Ising and the mean field values are compatible with the present ISM observational data:1.4\leq D \leq 2. We develop a field theoretical approach to the galaxy distribution considering a gas of self-gravitating masses on the FRW background, in quasi-thermal equi- librium. We show that it exhibits scaling behaviour by RG methods. The galaxy correlations are computed without assuming homogeneity. We find \sim r^{D-3} $. The theory allows to compute the three and higher density correlators without any assumption.We find that the connected N-points density scales as r_1^{N(D-3)}, when$ r_1 >> r_i

Large sub-clonal variation in <i>Phytophthora infestans</i> from recent severe late blight epidemics in India

Abstract The population structure of the Phytophthora infestans populations that caused the recent 2013–14 late blight epidemic in eastern India (EI) and northeastern India (NEI) was examined. The data provide new baseline information for populations of P. infestans in India. A migrant European 13_A2 genotype was responsible for the 2013–14 epidemic, replacing the existing populations. Mutations have generated substantial sub-clonal variation with 24 multi-locus genotypes (MLGs) found, of which 19 were unique variants not yet reported elsewhere globally. Samples from West Bengal were the most diverse and grouped alongside MLGs found in Europe, the UK and from neighbouring Bangladesh but were not linked directly to most samples from south India. The pathogen population was broadly more aggressive on potato than on tomato and resistant to the fungicide metalaxyl. Pathogen population diversity was higher in regions around the international borders with Bangladesh and Nepal. Overall, the multiple shared MLGs suggested genetic contributions from UK and Europe in addition to a sub-structure based on the geographical location within India. Our data indicate the need for improved phytosanitary procedures and continuous surveillance to prevent the further introduction of aggressive lineages of P. infestans into the country

Histone Deacetylase 3 Depletion in Osteo/Chondroprogenitor Cells Decreases Bone Density and Increases Marrow Fat

Histone deacetylase (Hdac)3 is a nuclear enzyme that contributes to epigenetic programming and is required for embryonic development. To determine the role of Hdac3 in bone formation, we crossed mice harboring loxP sites around exon 7 of Hdac3 with mice expressing Cre recombinase under the control of the osterix promoter. The resulting Hdac3 conditional knockout (CKO) mice were runted and had severe deficits in intramembranous and endochondral bone formation. Calvarial bones were significantly thinner and trabecular bone volume in the distal femur was decreased 75% in the Hdac3 CKO mice due to a substantial reduction in trabecular number. Hdac3-CKO mice had fewer osteoblasts and more bone marrow adipocytes as a proportion of tissue area than their wildtype or heterozygous littermates. Bone formation rates were depressed in both the cortical and trabecular regions of Hdac3 CKO femurs. Microarray analyses revealed that numerous developmental signaling pathways were affected by Hdac3-deficiency. Thus, Hdac3 depletion in osterix-expressing progenitor cells interferes with bone formation and promotes bone marrow adipocyte differentiation. These results demonstrate that Hdac3 inhibition is detrimental to skeletal health