Hepatitis C virus quasispecies and pseudotype analysis from acute infection to chronicity in HIV-1 co-infected individuals

HIV-1 infected patients who acquire HCV infection have higher rates of chronicity and liver disease progression than patients with HCV mono-infection. Understanding early events in this pathogenic process is important. We applied single genome sequencing of the E1 to NS3 regions and viral pseudotype neutralization assays to explore the consequences of viral quasispecies evolution from pre-seroconversion to chronicity in four co-infected individuals (mean follow up 566 days). We observed that one to three founder viruses were transmitted. Relatively low viral sequence diversity, possibly related to an impaired immune response, due to HIV infection was observed in three patients. However, the fourth patient, after an early purifying selection displayed increasing E2 sequence evolution, possibly related to being on suppressive antiretroviral therapy. Viral pseudotypes generated from HCV variants showed relative resistance to neutralization by autologous plasma but not to plasma collected from later time points, confirming ongoing virus escape from antibody neutralization

Do User (Browse and Click) Sessions Relate to Their Questions in a Domain-Specific Collection?

We seek to improve information retrieval in a domain-specific collection by clustering user sessions from a click log and then classifying later user sessions in real-time. As a preliminary step, we explore the main assumption of this approach: whether user sessions in such a site are related to the question that they are answering. Since a large class of machine learning algorithms use a distance measure at the core, we evaluate the suitability of common machine learning distance measures to distinguish sessions of users searching for the answer to same or different questions. We found that two distance measures work very well for our task and three others do not. As a further step, we then investigate how effective the distance measures are when used in clustering. For our dataset, we conducted a user study where we had multiple users answer the same set of questions. This data, grouped by question, was used as our gold standard for evaluating the clusters produced by the clustering algorithms. We found that the observed difference between the two classes of distance measures affected the quality of the clusterings, as expected. We also found that one of the two distance measures that worked well to differentiate sessions, worked significantly better than the other when clustering. Finally, we discuss why some distance metrics performed better than others in the two parts of our work

The Li Overabundance of J37: Diffusion or Accretion?

In September 2002 the discovery of a super Li-rich F-dwarf (J37) in NGC 6633, an iron poor analogue of the better studied Hyades and Praecepe open clusters, was announced. This unique star was thought to be the smoking gun for the action of diffusion, models of which predict a narrow ”Li-peak” at approximately the correct temperature. However, with more detailed studies into J37s abundance pattern this star provides firm evidence for the accretion of planetesimals or other material from the circumstellar environment of new born stars. Thanks to the specific predictions made about the behaviour of Be abundances, (the most striking of which being no Be in super-Li-rich dwarfs subject to diffusion) the opposing diffu-sion/accretion predictions can be tested. Initial modelling of the Be line indicates that J37 is as Be rich as it is Li rich; log N(Be) = 2.25 ± 0.25, and so is broadly consistent with an accretion-fuelled enhancement. However, that both Li and Be are enhanced by much more than the iron-peak elements (as determined in previous studies) suggests that diffusion also plays a role in increasing the abundances of Li and Be specifically. Furthermore, a new data set from the UVES/UT2 combination has allowed the elemental abundance of Iron to be measured, and the set of preliminary stellar parameters determined; Teff ∼ 7340 K, log g ∼ 4.1, microturbulence ∼ 4.3 kms− 1, [Fe/H] ∼ 0.50. This again provides distinct evidence for the effects of accretion in J37 and requires a new synthesis of the Be doublet

Beryllium Enhancement as Evidence for Accretion in a Lithium-Rich F Dwarf

The early F dwarf star ``J37\u27\u27 in the open cluster NGC6633 shows an unusual pattern of photospheric abundances, including an order of magnitude enhancement of lithium and iron-peak elements, but an under-abundance of carbon. As a consequence of its thin convection zone these anomalies have been attributed to either radiative diffusion or the accretion of hydrogen-depleted material. By comparing high resolution VLT/UVES spectra of J37 (and other F stars in NGC 6633) with syntheses of the Be ii doublet region at 3131 Ang, we establish that J37 also has a Be abundance (A(Be)=3.0+/-0.5) that is at least ten times the cosmic value. This contradicts radiative diffusion models that produce a Li over-abundance, as they also predict photospheric Be depletion. Instead, since Be is a highly refractory element, it supports the notion that J37 is the first clear example of a star that has accreted volatile-depleted material with a composition similar to chondritic meteorites, although some diffusion may be necessary to explain the low C and O abundances

iPLA2-VIA is Required for Healthy Aging of Neurons, Muscle, and the Female Germline in Drosophila melanogaster

Neurodegenerative disease (ND) is a growing health burden worldwide, but its causes and treatments remain elusive. Although most cases of ND are sporadic, rare familial cases have been attributed to single genes, which can be investigated in animal models. We have generated a new mutation in the calcium-independent phospholipase A2 (iPLA2) VIA gene CG6718, the Drosophila melanogaster ortholog of human PLA2G6/PARK14, mutations in which cause a suite of NDs collectively called PLA2G6-associated neurodegeneration (PLAN). Our mutants display age-related loss of climbing ability, a symptom of neurodegeneration in flies. Although phospholipase activity commonly is presumed to underlie iPLA2VIA function, locomotor decline in our mutants is rescued by a transgene carrying a serine-to-alanine mutation in the catalytic residue, suggesting that important functional aspects are independent of phospholipase activity. Additionally, we find that iPLA2-VIA knockdown in either muscle or neurons phenocopies locomotor decline with age, demonstrating its necessity in both neuronal and non-neuronal tissues. Furthermore, RNA in situ hybridization shows high endogenous iPLA2-VIA mRNA expression in adult germ cells, and transgenic HA-tagged iPLA2-VIA colocalizes with mitochondria there. Mutant males are fertile with normal spermatogenesis, while fertility is reduced in mutant females. Mutant female germ cells display age-related mitochondrial aggregation, loss of mitochondrial potential, and elevated cell death. These results suggest that iPLA2-VIA is critical for mitochondrial integrity in the Drosophila female germline, which may provide a novel context to investigate its functions with parallels to PLAN