A Novel CCR5 Mutation in Sooty Mangabeys Reveals SIVsmm Infection of CCR5-null Natural Hosts: Examining the Potential Roles of Alternative Entry Pathways in HIV and SIV Infection

Natural hosts of SIV, such as sooty mangabeys (SM), maintain high levels of virus replication, but do not typically develop CD4+ T cell loss and immunodeficiency. Understanding the virus/host relationship in natural hosts will enable better understanding of pathogenic HIV infection of humans. Host cell targeting in vivo is an important determinant of pathogenesis, and is defined mainly by expression of coreceptors used by the virus for entry, in conjunction with CD4. Established dogma holds that, with rare exceptions, SIV uses CCR5 for entry. However, SM and other natural hosts express extremely low CCR5 levels on CD4+ T cells. I identified a novel SM-CCR5 mutant allele containing a two base-pair deletion (CCR5-d2) that results in a non-functional protein. Using PCR screening and direct sequence confirmation in a large captive SM colony, I found an allelic frequency of 26% for CCR5-d2, along with 3% for a previously-described CCR5-d24 null allele. Notably, SM-CCR5-d2 was also present in West African wild-living SM. Approximately 8% of captive SM were homozygous for CCR5-null alleles. Surprisingly, SIVsmm infection was not significantly less prevalent in SM lacking functional CCR5 compared to CCR5-expressing animals, and CCR5-null animals displayed high-level viremia. Primary PBMC from SM were permissive for SIVsmm replication in both the absence and presence of CCR5 in vitro. Pseudotype virions carrying Envs from both CCR5-null and wild-type infected SM used CXCR6 and GPR15 efficiently for entry in transfected cells, suggesting likely alternative entry molecules. In preliminary studies using human cells, I found that CD4+ T cell expression of CXCR6 and GPR15 was predominantly on central and effector memory subsets, although expression patterns on SM cells will require antibodies that can detect SM proteins. This finding challenges the long-standing notion that CCR5 is the exclusive coreceptor used for SIV entry in vivo, and reveals that SIVsmm can infect target cells in vivo using non-CCR5 entry pathways. Since CD4/coreceptor interactions determine viral tropism and cell targeting, these results suggest that infection in natural host SM may involve target cells defined by the distribution and use of alternative coreceptors CXCR6 and GPR15. Combined with restricted expression of CCR5 on critical target cells previously described, alternative coreceptor-dependent targeting may allow virus replication in more expendable cells without loss of immune cell homeostasis. We hypothesize that SM natural hosts may have evolved to restrict expression of CXCR6 and GPR15, in addition to CCR5, to dispensable cell subsets, thus allowing for high viral replication without causing disease. Future studies comparing CXCR6 and GPR15 expression profiles in natural and non-natural hosts will be of importance in determining the role of alternative coreceptors in natural hosts in vivo

An assessment of anxiety levels in dyslexic students in higher education

Background: It has long been hypothesized that children with learning disabilities, including dyslexia, may be highly vulnerable to emotional consequences such as anxiety. However, research has centred on school aged children. Aims: The present study aimed to clarify these findings with dyslexic students in higher education. Samples: 16 students with dyslexia were compared to 16 students with no history of learning difficulties. Methods: Students were asked to complete a verbal questionnaire concerning trait anxiety levels. They were then told that they would be given a timed reading test and their state anxiety levels were measured using the State‐Trait Anxiety Inventory (STAI; Spielberger, Gorsuch, & Lushene, 1983). Finally their reading was assessed using the Test of Word Reading Efficiency (Torgesen, Wagner & Rashotte, 1999). Results: Dyslexic students showed slower reading speeds than controls. They also had higher levels of state anxiety and elevated levels of academic and social, but not appearance anxiety. Conclusions: Dyslexic students in higher education show anxiety levels that are well above what is shown by students without learning difficulties. This anxiety is not limited to academic tasks but extends to many social situations. It is proposed that assessment of emotional well‐being should form part of the assessment of need for dyslexic students entering higher education

Influence of Host Gender on Infection Rate, Density and Distribution of the Parasitic Fungus, Hesperomyces virescens, on the Multicolored Asian Lady Beetle, Harmonia axyridis

Hesperomyces virescens Thaxter (Laboulbeniales: Laboulbeniaceae) is a parasitic fungus that infects lady beetles (Coleoptera: Coccinellidae) via horizontal transmission between adults at overwintering and feeding sites. The differential behavior of male and female hosts could have profound effects on intensity of infection and positioning of fungus on the host's integument. The influence of host gender on infection rate, density and distribution of this parasite on the multicolored Asian lady beetle, Harmonia axyridis (Pallas) (Coleoptera: Coccinellidae), was determined at a feeding site. Adult H. axyridis were sampled from pecan, Carya illinoinensis (Wangenh.) K. Koch, trees in northern Mississippi, USA, during summer and early fall 2003–2004. Results indicated that the behavior of male or female beetles on pecan trees had only a limited effect on the intensity of infection. When averaged over the entire season, the percentage of H. axyridis infected with H. virescens was not influenced by host gender. In 2003, a seasonal average of 54 and 39% of males and females, respectively, were infected; whereas in 2004, 36 and 41% of male and female beetles, respectively, were infected. The percentage of males infected with H. virescens was correlated with the number of males captured at the site in 2003; infection rate decreased as male abundance increased. Infection rate did not correlate with female abundance in 2003 or male or female abundance in 2004. Host gender had a considerable effect on the density and distribution of the fungus. Hesperomyces virescens mature thalli were denser on male rather than female beetles. Also, thallus density was often greatest on the elytra, meso- and metathorax, and abdomen of males and elytra of females, than on other body parts, in 2003. In 2003 and 2004, approximately 59 and 97% and 67 and 96% of males and females, respectively, had mature thalli distributed on the elytra. Prevalence of H. virescens thalli on the dorsum of H. axyridis females suggests that mating behavior is important in fungal transmission. However, prevalence of thalli on the dorsum of H. axyridis males suggests that behaviors other than mating contribute to the transmission of H. virescens onto male beetles. Spread of H. virescens ascospores from infected to uninfected H. axyridis adults of different generations, at feeding sites, might be vital to maintaining stable populations of the fungus

Learn to Fly Test Setup and Concept of Operations

The NASA Learn-to-Fly (L2F) project recently completed a series of flight demonstrations of its learning algorithm for flight control at Fort A. P. Hill in Virginia. This paper discusses the test setup and concept of operations (ConOps) used by the L2F team. Unmanned airframe demonstrators for testing the research algorithms included a modified commercial off-the-shelf subscale powered airplane, plus four gliders two of which had an unconventional configuration and were fabricated using a rapid prototyping technique. Avionics system similarities and differences between the test aircraft are described, as well as ground testing in preparation for flight. The ConOps discussion includes the development of a tethered helium balloon drop launch technique for the glider demonstrators. This launch method was chosen for its potential to be inexpensive and allow for rapid turn-around for multiple glider launches but it also presented challenges, such as balloon tether avoidance, high angle of attack, low dynamic pressure initial conditions, and susceptibility to winds. A remotely piloted approach employing high-end hobbyist radio controlled (R/C) hardware was used for the powered demonstrator. This approach accommodated the interaction between the R/C flight system and the research flight control computer, engaging the L2F algorithm at varying initial conditions and artificially reducing the aircraft stability to stress the algorithm

Limited Transmission of the Ectoparasitic Fungus Hesperomyces virescens

The ectoparasitic fungus Hesperomyces virescens Thaxter (Ascomycota: Laboulbeniales) commonly infects the invasive lady beetle Harmonia axyridis (Pallas) and several other aphidophagous lady beetles in North America and Europe. We tested the hypothesis that bodily contact between adults of different lady beetle species supports horizontal transmission of H. virescens. We used laboratory assays to determine whether H. axyridis or Olla v-nigrum (Mulsant) harboring H. virescens (i.e., source beetles) transmit the fungus to noninfected target beetles H. axyridis, O. v-nigrum, Coccinella septempunctata L., Coleomegilla maculata (De Geer), or Hippodamia convergens Guerin-Meneville. Results indicate that intraspecific transmission (i.e., for the source beetles H. axyridis and O. v-nigrum) was common but interspecific transmission (i.e., from source H. axyridis or O. v-nigrum to target species) was low. Interspecific transmission occurred at low rates from H. axyridis to both C. septempunctata and O. v-nigrum and from O. v-nigrum to both C. septempunctata and H. convergens. Based upon our laboratory assays of forced pairings/groupings of source and target beetles, we predict that horizontal transmission of H. virescens between species of aphidophagous coccinellids is possible but likely rare

ESTIMACIÓN BAYESIANA EN EL MODELO DE RIESGOS ADITIVOS

En el "análisis de supervivencia", se estudia el comportamiento de variables que miden el tiempo hasta la ocurrencia de cierto evento de interés, por ejemplo, en medicina puede interesar el tiempo hasta la remisión de determinada enfermedad. Dada la naturaleza del estudio, es usual la presencia de "datos censurados", es decir, en estos casos, se mide la variable durante cierto período de tiempo, durante el cual no se ha observado el evento de interés. En este contexto, se define la "función de riesgo", que se puede expresar en función de las expresiones de las funciones de densidad de probabilidad y de distribución acumulada de la variable en cuestión. Se suelen caracterizar los distintos modelos acorde a la expresión que toma su función de riesgo, siendo el más conocido el modelo de riesgos proporcionales de Cox [1]. Como alternativas, suelen aparecer otros modelos. Uno de ellos es en el cual basamos nuestro estudio: el modelo de riesgos aditivos (o AHM) [1]. Estos modelos (Cox, Aalen) son semi-paramétricos, ya que constan de una componente paramétrica y una no paramétrica. En el caso de AHM, Lin & Ying [3] abordaron el problema de la estimación de la componente paramétrica del modelo. En nuestro trabajo, tratamos a este modelo mediante un enfoque Bayesiano para ambas componentes, basándonos en las ecuaciones descriptas por Lin & Ying para la componente paramétrica. En el caso de la componente no paramétrica, proponemos, extendiendo lo expuesto el año anterior (Riddick, Álvarez [4]), un proceso a priori conjunto, optando por un proceso Gamma. Para ilustrar la eficacia del método, exponemos los resultados obtenidos mediante simulaciones, y en un conjunto de datos asociados a la medicina

Deciphering the Finger Prints of Brain Cancer Glioblastoma Multiforme from Four Different Patients by Using Near Infrared Raman Spectroscopy

To explore the effectiveness of Raman spectra to diagnose brain cancer glioblastoma multiforme (GBM), we investigated the Raman spectra of single cell from four different GBM cell lines developed from four different patients and analyzed the spectra. The Raman spectra of brain cancer (GBM) cells were similar in all these cell lines. The results indicate that Raman spectra can offer the experimental basis for the cancer diagnosis and treatment

INDIGO : better geomagnetic observatories where we need them

The INDIGO project aims to improve the global coverage of digital observatories by deploying digital magnetometer systems in: i) Observatories where existing analog recording equipment is in need of upgrading. ii) Newly established digital observatories. iii) Existing digital observatories for the purpose of quality control and redundancy. In implementing the project and selecting suitable sites, special attention is paid to parts of the Earth devoid of magnetic observatories, increasing the reliability and long-term operation of existing observatories and cost-effective use of local resources. The Poster reviews the current status of the project. We examine the different steps and initiatives taken since the initiation of INDIGO in 2004 and assess their effectiveness in achieving progress towards our aims of improving global coverage and enhanced data quality

Aircraft Configured for Flight in an Atmosphere Having Low Density

An aircraft is configured for flight in an atmosphere having a low density. The aircraft includes a fuselage, a pair of wings, and a rear stabilizer. The pair of wings extends from the fuselage in opposition to one another. The rear stabilizer extends from the fuselage in spaced relationship to the pair of wings. The fuselage, the wings, and the rear stabilizer each present an upper surface opposing a lower surface. The upper and lower surfaces have X, Y, and Z coordinates that are configured for flight in an atmosphere having low density