The yeast P5 type ATPase, Spf1, regulates manganese transport into the endoplasmic reticulum

The endoplasmic reticulum (ER) is a large, multifunctional and essential organelle. Despite intense research, the function of more than a third of ER proteins remains unknown even in the well-studied model organism Saccharomyces cerevisiae. One such protein is Spf1, which is a highly conserved, ER localized, putative P-type ATPase. Deletion of SPF1 causes a wide variety of phenotypes including severe ER stress suggesting that this protein is essential for the normal function of the ER. The closest homologue of Spf1 is the vacuolar P-type ATPase Ypk9 that influences Mn2+ homeostasis. However in vitro reconstitution assays with Spf1 have not yielded insight into its transport specificity. Here we took an in vivo approach to detect the direct and indirect effects of deleting SPF1. We found a specific reduction in the luminal concentration of Mn2+ in ∆spf1 cells and an increase following it’s overexpression. In agreement with the observed loss of luminal Mn2+ we could observe concurrent reduction in many Mn2+-related process in the ER lumen. Conversely, cytosolic Mn2+-dependent processes were increased. Together, these data support a role for Spf1p in Mn2+ transport in the cell. We also demonstrate that the human sequence homologue, ATP13A1, is a functionally conserved orthologue. Since ATP13A1 is highly expressed in developing neuronal tissues and in the brain, this should help in the study of Mn2+-dependent neurological disorders

LHC and lepton flavour violation phenomenology of a left-right extension of the MSSM

We study the phenomenology of a supersymmetric left-right model, assuming minimal supergravity boundary conditions. Both left-right and (B-L) symmetries are broken at an energy scale close to, but significantly below the GUT scale. Neutrino data is explained via a seesaw mechanism. We calculate the RGEs for superpotential and soft parameters complete at 2-loop order. At low energies lepton flavour violation (LFV) and small, but potentially measurable mass splittings in the charged scalar lepton sector appear, due to the RGE running. Different from the supersymmetric 'pure seesaw' models, both, LFV and slepton mass splittings, occur not only in the left- but also in the right slepton sector. Especially, ratios of LFV slepton decays, such as Br(${\tilde\tau}_R \to \mu \chi^0_1$)/Br(${\tilde\tau}_L \to \mu \chi^0_1$) are sensitive to the ratio of (B-L) and left-right symmetry breaking scales. Also the model predicts a polarization asymmetry of the outgoing positrons in the decay $\mu^+ \to e^+ \gamma$, A ~ [0,1], which differs from the pure seesaw 'prediction' A=1$. Observation of any of these signals allows to distinguish this model from any of the three standard, pure (mSugra) seesaw setups.Comment: 43 pages, 17 figure

Astrobiological Complexity with Probabilistic Cellular Automata

Search for extraterrestrial life and intelligence constitutes one of the major endeavors in science, but has yet been quantitatively modeled only rarely and in a cursory and superficial fashion. We argue that probabilistic cellular automata (PCA) represent the best quantitative framework for modeling astrobiological history of the Milky Way and its Galactic Habitable Zone. The relevant astrobiological parameters are to be modeled as the elements of the input probability matrix for the PCA kernel. With the underlying simplicity of the cellular automata constructs, this approach enables a quick analysis of large and ambiguous input parameters' space. We perform a simple clustering analysis of typical astrobiological histories and discuss the relevant boundary conditions of practical importance for planning and guiding actual empirical astrobiological and SETI projects. In addition to showing how the present framework is adaptable to more complex situations and updated observational databases from current and near-future space missions, we demonstrate how numerical results could offer a cautious rationale for continuation of practical SETI searches.Comment: 37 pages, 11 figures, 2 tables; added journal reference belo

Paving (through) Amazonia: Neoliberal Urbanism and the Reperipheralization of Roraima

This paper examines the neoliberal reshaping of infrastructure provision in Brazil's extreme north since the mid-1990s, when roadway investments resulted in unprecedented regional connectivity. The BR-174 upgrade, the era's most important project, marked a transition from resource-based developmentalism to free-market transnationalism. Primarily concerned with urban competitiveness, the federal government funded the trunk roadway's paving to facilitate manufacturing exports from Manaus. While an effort was made to minimize deforestation, planners sidelined development implications in adjacent Roraima. The state's urban system has thus experienced reperipheralization and intensified primacy. Market-led growth now compounds the inheritance of hierarchical centralism and ongoing governmental neglect. Our study shows a vast territory dependent on primate cities for basic goods and services. Travelling with Roraimans from bypassed towns, we detected long-distance passenger transportation and surface logistics with selective routes. Heterogeneous Roraiman (im)mobilities comprise middle-class tourism and heightened consumerism as well as informal mobility tactics and transnational circulations of precarious labor. The paper exhorts neoliberal urbanism research to look beyond both Euro America's metropoles and their Global South counterparts. Urbanization dynamics in Brazil's extreme north demonstrate that market-disciplined investments to globalize cities produce far-reaching spatial effects. These are felt even by functionally-articulated-yet-marginalized peripheries in ostensibly remote locations

Higgs boson production in photon-photon collision at ILC: a comparative study in different little Higgs models

We study the process \gamma\gamma->h->bb_bar at ILC as a probe of different little Higgs models, including the simplest little Higgs model (SLH), the littlest Higgs model (LH), and two types of littlest Higgs models with T-parity (LHT-I, LHT-II). Compared with the Standard Model (SM) prediction, the production rate is found to be sizably altered in these little Higgs models and, more interestingly, different models give different predictions. We find that the production rate can be possibly enhanced only in the LHT-II for some part of the parameter space, while in all other cases the rate is suppressed. The suppression can be 10% in the LH and as much as 60% in both the SLH and the LHT-I/LHT-II. The severe suppression in the SLH happens for a large \tan\beta and a small m_h, in which the new decay mode h->\eta\eta (\eta is a light pseudo-scalar) is dominant; while for the LHT-I/LHT-II the large suppression occurs when f and m_h are both small so that the new decay mode h->A_H A_H is dominant. Therefore, the precision measurement of such a production process at the ILC will allow for a test of these models and even distinguish between different scenarios.Comment: Version in JHEP (h-g-g & h-gamma-gamma expressions added

Whale, whale, everywhere: increasing abundance of western South Atlantic humpback whales (Megaptera novaeangliae) in their wintering grounds

The western South Atlantic (WSA) humpback whale population inhabits the coast of Brazil during the breeding and calving season in winter and spring. This population was depleted to near extinction by whaling in the mid-twentieth century. Despite recent signs of recovery, increasing coastal and offshore development pose potential threats to these animals. Therefore, continuous monitoring is needed to assess population status and support conservation strategies. The aim of this work was to present ship-based line-transect estimates of abundance for humpback whales in their WSA breeding ground and to investigate potential changes in population size. Two cruises surveyed the coast of Brazil during August-September in 2008 and 2012. The area surveyed in 2008 corresponded to the currently recognized population breeding area; effort in 2012 was limited due to unfavorable weather conditions. WSA humpback whale population size in 2008 was estimated at 16,410 (CV = 0.228, 95% CI = 10,563–25,495) animals. In order to compare abundance between 2008 and 2012, estimates for the area between Salvador and Cabo Frio, which were consistently covered in the two years, were computed at 15,332 (CV = 0.243, 95% CI = 9,595–24,500) and 19,429 (CV = 0.101, 95% CI = 15,958–23,654) whales, respectively. The difference in the two estimates represents an increase of 26.7% in whale numbers in a 4-year period. The estimated abundance for 2008 is considered the most robust for the WSA humpback whale population because the ship survey conducted in that year minimized bias from various sources. Results presented here indicate that in 2008, the WSA humpback whale population was at least around 60% of its estimated pre-modern whaling abundance and that it may recover to its pre-exploitation size sooner than previously estimated.Publisher PDFPeer reviewe

Questionnaire Hearing Handicap Inventory for the Elderly - Screening version (HHIE-S): sensitivity and specificity study

PURPOSE: To investigate the sensitivity and specificity of the questionnaire Hearing Handicap Inventory for the Elderly - Screening version (HHIE-S) in the hearing screening of elderly people who seek for different health care services (audiological clinic and other clinics). METHODS: The hearing of 78 elderly - 23 attended at the Discipline of Geriatrics and Gerontology of the institution who did not, necessarily, have complaints regarding their hearing, and 55 attended at the Audiology Clinic of the same institution with complaints related to the auditory and/or vestibular systems - was assessed. The HHIE-S questionnaire was applied, and its total score was divided into three categories, according to the handicap perception. RESULTS: A statistically significant relationship was found between handicap and degree of hearing loss in both patients from the Audiology Clinic (p=0.009*) and from the Geriatrics Clinic (p=0.002). In the first group, the HHIE-S questionnaire showed low sensitivity (23.5%) and high specificity (73.7%). In the group of patients from the Geriatrics Clinic, the values of sensitivity (94.7%) and specificity (75%) were both high. CONCLUSIONS: There was positive association between the degree of hearing loss and the handicap referred by both groups of subjects. The HHIE-S questionnaire is a hearing screening instrument with high sensitivity and specificity in identifying hearing loss in elderly people that seek health care services that are not specific for attention related to hearing disorders.OBJETIVO: Investigar a sensibilidade e especificidade do questionário Hearing Handicap Inventory for the Elderly - Screening version (HHIE-S) na triagem auditiva de idosos que procuram diferentes serviços de atenção à saúde (clínica audiológica e outras clínicas). MÉTODOS: Foi avaliada a audição de 78 idosos - 23 atendidos na disciplina de Geriatria e Gerontologia da instituição de origem, que não tinham, necessariamente, queixas relacionadas à audição, e 55 atendidos no Ambulatório de Audiologia da mesma instituição, com queixas relacionadas aos sistemas auditivo e/ou vestibular. Foi aplicado o HHIE-S, cujo escore total foi dividido em três categorias, de acordo com a percepção do handicap. RESULTADOS: Houve relação estatisticamente significante entre handicap e grau de perda auditiva no grupo de pacientes do Ambulatório de Audiologia (p=0,009), e no grupo de pacientes do Ambulatório de Geriatria (p=0,002). No primeiro grupo, o questionário HHIE-S revelou baixa sensibilidade (23,5%) e alta especificidade (73,7%). No grupo de pacientes do setor de Geriatria, foram altos os valores de sensibilidade (94,7%) e de especificidade (75%). CONCLUSÕES: Há associação positiva entre o grau de perda auditiva e o handicap referido em ambos os grupos. O questionário HHIE-S é um instrumento de triagem auditiva com alta especificidade e sensibilidade na identificação de perdas auditivas em idosos que procuram serviços de saúde que não são específicos para atendimentos relacionados às alterações auditivas.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Irmandade da Santa Casa de Misericórdia de São PauloUniversidade Federal de São Paulo (UNIFESP)Universidade Federal de São Paulo (UNIFESP) Departamento de FonoaudiologiaUNIFESP, Depto. de FonoaudiologiaSciEL

Genome of the Avirulent Human-Infective Trypanosome—Trypanosoma rangeli

Background: Trypanosoma rangeli is a hemoflagellate protozoan parasite infecting humans and other wild and domestic mammals across Central and South America. It does not cause human disease, but it can be mistaken for the etiologic agent of Chagas disease, Trypanosoma cruzi. We have sequenced the T. rangeli genome to provide new tools for elucidating the distinct and intriguing biology of this species and the key pathways related to interaction with its arthropod and mammalian hosts.  Methodology/Principal Findings: The T. rangeli haploid genome is ,24 Mb in length, and is the smallest and least repetitive trypanosomatid genome sequenced thus far. This parasite genome has shorter subtelomeric sequences compared to those of T. cruzi and T. brucei; displays intraspecific karyotype variability and lacks minichromosomes. Of the predicted 7,613 protein coding sequences, functional annotations could be determined for 2,415, while 5,043 are hypothetical proteins, some with evidence of protein expression. 7,101 genes (93%) are shared with other trypanosomatids that infect humans. An ortholog of the dcl2 gene involved in the T. brucei RNAi pathway was found in T. rangeli, but the RNAi machinery is non-functional since the other genes in this pathway are pseudogenized. T. rangeli is highly susceptible to oxidative stress, a phenotype that may be explained by a smaller number of anti-oxidant defense enzymes and heatshock proteins.  Conclusions/Significance: Phylogenetic comparison of nuclear and mitochondrial genes indicates that T. rangeli and T. cruzi are equidistant from T. brucei. In addition to revealing new aspects of trypanosome co-evolution within the vertebrate and invertebrate hosts, comparative genomic analysis with pathogenic trypanosomatids provides valuable new information that can be further explored with the aim of developing better diagnostic tools and/or therapeutic targets

Bigger, Better, Faster, More at the LHC

Multijet plus missing energy searches provide universal coverage for theories that have new colored particles that decay into a dark matter candidate and jets. These signals appear at the LHC further out on the missing energy tail than two-to-two scattering indicates. The simplicity of the searches at the LHC contrasts sharply with the Tevatron where more elaborate searches are necessary to separate signal from background. The searches presented in this article effectively distinguish signal from background for any theory where the LSP is a daughter or granddaughter of the pair-produced colored parent particle without ever having to consider missing energies less than 400 GeV.Comment: 26 pages, 8 Figures. Minor textual changes, typos fixed and references adde