Localization of Human RNase Z Isoforms: Dual Nuclear/Mitochondrial Targeting of the ELAC2 Gene Product by Alternative Translation Initiation

RNase Z is an endonuclease responsible for the removal of 3′ extensions from tRNA precursors, an essential step in tRNA biogenesis. Human cells contain a long form (RNase ZL) encoded by ELAC2, and a short form (RNase ZS; ELAC1). We studied their subcellular localization by expression of proteins fused to green fluorescent protein. RNase ZS was found in the cytosol, whereas RNase ZL localized to the nucleus and mitochondria. We show that alternative translation initiation is responsible for the dual targeting of RNase ZL. Due to the unfavorable context of the first AUG of ELAC2, translation apparently also starts from the second AUG, whereby the mitochondrial targeting sequence is lost and the protein is instead routed to the nucleus. Our data suggest that RNase ZL is the enzyme involved in both, nuclear and mitochondrial tRNA 3′ end maturation

Status of Muon Collider Research and Development and Future Plans

The status of the research on muon colliders is discussed and plans are outlined for future theoretical and experimental studies. Besides continued work on the parameters of a 3-4 and 0.5 TeV center-of-mass (CoM) energy collider, many studies are now concentrating on a machine near 0.1 TeV (CoM) that could be a factory for the s-channel production of Higgs particles. We discuss the research on the various components in such muon colliders, starting from the proton accelerator needed to generate pions from a heavy-Z target and proceeding through the phase rotation and decay ($\pi \to \mu \nu_{\mu}$) channel, muon cooling, acceleration, storage in a collider ring and the collider detector. We also present theoretical and experimental R & D plans for the next several years that should lead to a better understanding of the design and feasibility issues for all of the components. This report is an update of the progress on the R & D since the Feasibility Study of Muon Colliders presented at the Snowmass'96 Workshop [R. B. Palmer, A. Sessler and A. Tollestrup, Proceedings of the 1996 DPF/DPB Summer Study on High-Energy Physics (Stanford Linear Accelerator Center, Menlo Park, CA, 1997)].Comment: 95 pages, 75 figures. Submitted to Physical Review Special Topics, Accelerators and Beam

Patterns with Bounded Treewidth

We show that any parameter of patterns that is an upper bound for the treewidth of appropriate encodings of patterns as relational structures, if restricted to a constant, allows the membership problem for pattern languages to be solved in polynomial time. Furthermore, we identify a new such parameter, called the scope coincidence degree

Identification of proteins involved in neural progenitor cell targeting of gliomas

<p>Abstract</p> <p>Background</p> <p>Glioblastoma are highly aggressive tumors with an average survival time of 12 months with currently available treatment. We have previously shown that specific embryonic neural progenitor cells (NPC) have the potential to target glioma growth in the CNS of rats. The neural progenitor cell treatment can cure approximately 40% of the animals with malignant gliomas with no trace of a tumor burden 6 months after finishing the experiment. Furthermore, the NPCs have been shown to respond to signals from the tumor environment resulting in specific migration towards the tumor. Based on these results we wanted to investigate what factors could influence the growth and progression of gliomas in our rodent model.</p> <p>Methods</p> <p>Using microarrays we screened for candidate genes involved in the functional mechanism of tumor inhibition by comparing glioma cell lines to neural progenitor cells with or without anti-tumor activity. The expression of candidate genes was confirmed at RNA level by quantitative RT-PCR and at the protein level by Western blots and immunocytochemistry. Moreover, we have developed <it>in vitro </it>assays to mimic the antitumor effect seen <it>in vivo</it>.</p> <p>Results</p> <p>We identified several targets involved in glioma growth and migration, specifically CXCL1, CD81, TPT1, Gas6 and AXL proteins. We further showed that follistatin secretion from the NPC has the potential to decrease tumor proliferation. <it>In vitro </it>co-cultures of NPC and tumor cells resulted in the inhibition of tumor growth. The addition of antibodies against proteins selected by gene and protein expression analysis either increased or decreased the proliferation rate of the glioma cell lines <it>in vitro</it>.</p> <p>Conclusion</p> <p>These results suggest that these identified factors might be useful starting points for performing future experiments directed towards a potential therapy against malignant gliomas.</p

Effectiveness and acceptability of progestogens in combined oral contraceptives – a systematic review

BACKGROUND: The progestogen component of oral contraceptives (OCs) has undergone changes since it was recognized that their chemical structure can influence the spectrum of minor adverse and beneficial effects. METHODS: The objective of this review was to evaluate currently available low-dose OCs containing ethinylestradiol and different progestogens in terms of contraceptive effectiveness, cycle control, side effects and continuation rates. The Cochrane Controlled Trials Register, MEDLINE and EMBASE databases were searched. Randomized trials reporting clinical outcomes were considered for inclusion and were assessed for methodological quality and validity. RESULTS: Twenty–two trials were included in the review. Eighteen were sponsored by pharmaceutical companies and in only 5 there was an attempt for blinding. Most comparisons between different interventions included one to three trials, involving usually less than 500 women. Discontinuation was less with second-generation progestogens compared to first–generation (RR 0.79; 95% CI 0.69–0.91). Cycle control appeared to be better with second-compared to first-generation progestogens for both, mono-and triphasic preparations (RR 0.69; 95% CI 0.52–0.91) and (RR 0.61; 95% CI 0.43–0.85), respectively. Intermenstrual bleeding was less with third- compared to second-generation pills (RR 0.71; 95% CI 0.55–0.91). Contraceptive effectiveness of gestodene (GSD) was comparable to that of levonorgestrel (LNG), and had similar pattern of spotting, breakthrough bleeding and absence of withdrawal bleeding). Drospirenone (DRSP) was similar compared to desogestrel (DSG) regarding contraceptive effectiveness, cycle control and side effects. CONCLUSION: The third- and second-generation progestogens are preferred over first generation in all indices of acceptability. Current evidence suggests that GSD is comparable to LNG in terms of contraceptive effectiveness and for most cycle control indices. GSD is also comparable to DSG. DRSP is comparable to DSG. Future research should focus on independently conducted well designed randomized trials comparing particularly the third- with second-generation progestogens

Duration of female parental care and their survival in the little auk Alle alle - are these two traits linked?

Desertion of offspring before its independence by one of the parents is observed in a number of avian species with bi-parental care but reasons for this strategy are not fully understood. This behaviour is particularly intriguing in species where bi-parental care is crucial to raise the brood successfully. Here, we focus on the little auk, Alle alle, a small seabird with intensive bi-parental care, where the female deserts the brood at the end of the chick rearing period. The little auk example is interesting as most hypotheses to explain desertion of the brood by females (e.g. “re-mating hypothesis”, “body condition hypothesis”) have been rejected for this species. Here, we analysed a possible relationship between the duration of female parental care over the chick and her chances to survive to the next breeding season. We performed the study in two breeding colonies on Spitsbergen with different foraging conditions – more favourable in Hornsund and less favourable in Magdalenefjorden. We predicted that in Hornsund females would stay for shorter periods of time with the brood and would have higher survival rates in comparison with birds from Magdalenefjorden. We found that indeed in less favourable conditions of Magdalenefjorden, females stay longer with the brood than in the more favourable conditions of Hornsund. Moreover, female survival was negatively affected by the length of stay in the brood. Nevertheless, duration of female parental care over the chick was not related to their parental efforts, earlier in the chick rearing period, and survival of males and females was similar. Thus, although females brood desertion and winter survival are linked, the relationship is not straightforward