Ty3 requires yeast La homologous protein for wild-type frequencies of transposition

The Saccharomyces cerevisiae retrovirus-like element Ty3 inserts specifically into the initiation sites of genes transcribed by RNA polymerase III (pol III). A strain with a disruption of LHP1, which encodes the homologue of autoantigen La protein, was recovered in a screen for mutants defective in Ty3 transposition. Transposition into a target composed of divergent tRNA genes was decreased eightfold. In lhp1 mutants, Ty3 polyproteins were produced at wild-type levels, assembled into virus-like particles (VLPs) and processed efficiently. The amount of cDNA associated with these particles was about half the amount in a wild-type control at early times, but approached the wild-type level after 48 h of induction. Ty3 integration was examined at two genomic tRNA gene families and two plasmid-borne tRNA promoters. Integration was significantly decreased at one of the tRNA gene families, but was only slightly decreased at the second tRNA gene family. These findings suggest that Lhp1p contributes to Ty3 cDNA synthesis, but might also act at a target-specific step, such as integration.     

Unusual plasmodium malariae-like parasites in southeast Asia

During malaria surveys in Myanmar, 2 peculiar forms of Plasmodium malariae-like parasites were found. The morphologies of their early trophozoite stages were distinct from that of the typical P. malariae, resembling instead that of Plasmodium vivax, var. minuta, reported by Emin, and Plasmodium tenue, reported by Stephens, both in 1914. Two polymerase chain reaction (PCR)-based diagnoses, which target the same regions in the small subunit ribosomal RNA (SSUrRNA) genes, indicated that these parasites were new variant forms of P. malariae and that they could be separated into 2 genetic types that correlated with the 2 morphological types. Sequence analysis of the SSUrRNA and the circumsporozoite protein genes revealed that they were distinct both from each other and from other known P. malariae isolates and that the P. tenue-like type was closer to a monkey quartan malaria parasite, Plasmodium brasilianum. These results illustrate that the microscopic appearance of human P. malariae parasites may be more varied than previously assumed and suggest the value of molecular tools in the evaluation of malaria morphological variants.     

The upper dentition and face of Pondaungia cotteri from central Myanmar

A specimen of Pondaungia from the late middle Eocene Pondaung Formation in central Myanmar includes maxillary fragments and parts of the dentition, some hitherto undocumented, including the upper central incisor, canine, premolars and molars. Pondaungia has a large spatulate I1 closely resembling that of crown anthropoids. It possesses a stout projecting upper canine (like anthropoids) but differs from that tooth of crown anthropoids in lacking a strong mesial groove. There are three upper premolars of which P2 is distinctly smaller than P3 or P4. P3 has a buccolingually oriented mesial profile and an inflated distal profile resembling that of parapithecids and crown anthropoids. The distolingual molar cusp is a hypocone and is not homologus with the "pseudohypocone" of notharctines because the cusp is neither twinned with the protocone nor attached to a Nannopithex-fold. Pondaungia has a stout zygomatic root with a strongly demarcated muscle scar for the superficial masseter situated well above the occlusal plane. The inferior orbital margin is not preserved but the inflated suborbital region allows for the inference that the orbit was small. This specimen is not sufficiently well preserved to identify if there was postorbital closure. However, a specimen of the frontal bone of Amphipithecus shows that its orbital septum was absent or poorly developed. If, as commonly supposed, Pondaungia andAmphipithecus are sister taxa, postorbital closure was probably absent in Pondaungia. The large incisors, molars with poorly developed crests and thick enamel, together with the stoutly developed and strong dorsal component of the force vector of the superficial masseter muscle suggest that Pondaungia had a diet low in fiber, but that included hard food objects like nuts or seeds. The present material adds to the structural similarities between Pondaungia and anthropoids, but whether these similarities are due to shared descent or functional and adaptive convergence remains unresolved.     

A rapid cellular FRET assay of polyglutamine aggregation identifies a novel inhibitor

Many neurodegenerative diseases, including tauopathies, Parkinson's disease, amyotrophic lateral sclerosis, and the polyglutamine diseases, are characterized by intracellular aggregation of pathogenic proteins. It is difficult to study modifiers of this process in intact cells in a high-throughput and quantitative manner, although this could facilitate molecular insights into disease pathogenesis. Here we introduce a high-throughput assay to measure intracellular polyglutamine protein aggregation using fluorescence resonance energy transfer (FRET). We screened over 2800 biologically active small molecules for inhibitory activity and have characterized one lead compound in detail. Y-27632, an inhibitor of the Rho-associated kinase p160ROCK, diminished polyglutamine protein aggregation (EC(50) congruent with 5 microM) and reduced neurodegeneration in a Drosophila model of polyglutamine disease. This establishes a novel high-throughput approach to study protein misfolding and aggregation associated with neurodegenerative diseases and implicates a signaling pathway of previously unrecognized importance in polyglutamine protein processing.     

An Integrated Global Analysis of Compartmentalized HRAS Signaling

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Trauma and Poor Mental Health in Relation to Economic Status: The Case of Cambodia 35 Years Later

Background

Cambodia is one of the poorest countries in south-east Asia and is still emerging from the events of the Khmer Rouge reign. It has been suggested that the atrocities experienced by the Cambodian population can explain why Cambodia continues to lag behind its neighbours in economic outcomes. The purpose of this study is to investigate whether there is an association between exposure to past trauma and/or current poor mental health and current economic status in Cambodia.

Method

A newly conducted survey performed in two regions (north-west and south-east Cambodia) collected information on trauma exposure, psychiatric symptoms, self-rated health outcomes and socio-economic information for 3200 persons aged 18–60. Economic outcomes were measured as household debt and poverty status and whether the respondent was economically inactive. All models were analysed using logistic regression.

Results

No association was found between high exposure to conflict-related or civilian trauma and any economic outcomes save for a negative association between civilian trauma and poverty in the south-east. Current post-traumatic stress was related solely to poverty status. All other measures of current mental health status, however, were found to be strongly negatively associated with all measures of economic status. Thus, mental health interventions could potentially be utilised in poverty reduction strategies, but greater efficacy is likely to be achieved by targeting current mental health status rather than previous trauma exposure.     

A cellular trafficking signal in the SIV envelope protein cytoplasmic domain is strongly selected for in pathogenic infection

The HIV/SIV envelope glycoprotein (Env) cytoplasmic domain contains a highly conserved Tyr-based trafficking signal that mediates both clathrin-dependent endocytosis and polarized sorting. Despite extensive analysis, the role of these functions in viral infection and pathogenesis is unclear. An SIV molecular clone (SIVmac239) in which this signal is inactivated by deletion of Gly-720 and Tyr-721 (SIVmac239ΔGY), replicates acutely to high levels in pigtail macaques (PTM) but is rapidly controlled. However, we previously reported that rhesus macaques and PTM can progress to AIDS following SIVmac239ΔGY infection in association with novel amino acid changes in the Env cytoplasmic domain. These included an R722G flanking the ΔGY deletion and a nine nucleotide deletion encoding amino acids 734–736 (ΔQTH) that overlaps the rev and tat open reading frames. We show that molecular clones containing these mutations reconstitute signals for both endocytosis and polarized sorting. In one PTM, a novel genotype was selected that generated a new signal for polarized sorting but not endocytosis. This genotype, together with the ΔGY mutation, was conserved in association with high viral loads for several months when introduced into naïve PTMs. For the first time, our findings reveal strong selection pressure for Env endocytosis and particularly for polarized sorting during pathogenic SIV infection in vivo.     

Two new Kirschsteiniothelia species with Dendryphiopsis anamorphs cluster in Kirschsteiniotheliaceae fam. nov

Two new Kirschsteiniothelia species are proposed in this study; both were collected on decaying wood from Chiang Mai and Chiang Rai provinces in northern Thailand. The taxa were isolated and the morphological characters are described and illustrated. ITS, LSU and SSU combined sequence analysis showed taxa of Kirschsteiniothelia separating into three lineages: (i) K. elaterascus grouped within Morosphaeriaceae (Pleosporales); (ii) K. maritima clustered with Mytilinidion spp. as a sister group in the Mytilinidiaceae clade; and (iii) the two new Kirschsteiniothelia species, which produce Dendryphiopsis anamorphs in culture, clustered with K. aethiops (the generic type) and the anamorph D. atra. The new family Kirschsteiniotheliaceae is introduced to accommodate taxa grouping with K. aethiops. K. elaterascus is transferred to Morosphaeria (Morosphaeriaceae) and a new genus Halokirschteiniothelia is introduced to accommodate K. maritima (Mytilinidiaceae).