A Small Family of Elements with Long Inverted Repeats is Located Near Sites of Developmentally Regulated DNA Rearrangement in \u3cem\u3eTetrahymena thermophila\u3c/em\u3e

Extensive DNA rearrangement occurs during the development of the somatic macronucleus from the germ line micronucleus in ciliated protozoans. The micronuclear junctions and the macronuclear product of a developmentally regulated DNA rearrangement in Tetrahymena thermophila, Tlr1, have been cloned. The intrachromosomal rearrangement joins sequences that are separated by more than 13 kb in the micronucleus with the elimination of moderately repeated micronucleus-specific DNA sequences. There is a long, 825-bp, inverted repeat near the micronuclear junctions. The inverted repeat contains two different 19-bp tandem repeats. The 19-bp repeats are associated with each other and with DNA rearrangements at seven locations in the micronuclear genome. Southern blot analysis is consistent with the occurrence of the 19-bp repeats within pairs of larger repeated sequences. Another family member was isolated. The 19-mers in that clone are also in close proximity to a rearrangement junction. We propose that the 19-mers define a small family of developmentally regulated DNA rearrangements having elements with long inverted repeats near the junction sites. We discuss the possibility that transposable elements evolve by capture of molecular machinery required for essential cellular functions

Engaging Older Youth: Program and City-Level Strategies to Support Sustained Participation in Out-of-School Time

With support from The Wallace Foundation, the Harvard Family Research Project and P/PV conducted a study of almost 200 out-of-school-time (OST) programs in six cities to better understand how they promote sustained participation among older youth.The resulting data indicated that two of the most important practices distinguishing high-retention programs were: ample leadership opportunities for youth and high levels of staff efforts to keep informed about participants' lives outside the programs. The study also compares and contrasts effective practices for middle school- versus high school-aged youth, noting the shortcomings of "one-size-fits-all" strategies. Finally, Engaging Older Youth details the influence of city-level OST initiatives on programs and identifies the types of city-level services that likely support participation

Interferon signaling patterns in peripheral blood lymphocytes may predict clinical outcome after high-dose interferon therapy in melanoma patients

<p>Abstract</p> <p>Background</p> <p>High-dose Interferon (HDI) therapy produces a clinical response and achieves relapse-free survival in 20-33% of patients with operable high risk or metastatic melanoma. However, patients may develop significant side effects frequently necessitating dose reduction or discontinuation of therapy. We recently showed that peripheral blood lymphocytes (PBL) from some melanoma patients have impaired interferon (IFN) signaling which could be restored with high concentrations of IFN. This exploratory study evaluated IFN signaling in PBL of melanoma patients to assess whether the restoration of PBL IFN signaling may predict a beneficial effect for HDI in melanoma patients.</p> <p>Methods</p> <p>PBL from 14 melanoma patients harvested on Day 0 and Day 29 of neoadjuvant HDI induction therapy were analyzed using phosflow to assess their interferon signaling patterns through IFN-α induced phosphorylation of STAT1-Y701.</p> <p>Results</p> <p>Patients who had a clinical response to HDI showed a lower PBL interferon signaling capacity than non-responders at baseline (Day 0). Additionally, clinical responders and patients with good long-term outcome showed a significant increase in their PBL interferon signaling from Day 0 to Day 29 compared to clinical non-responders and patients that developed metastatic disease. The differences in STAT1 activation from pre- to post- HDI treatment could distinguish between patients who were inclined to have a favorable or unfavorable outcome.</p> <p>Conclusion</p> <p>While the sample size is small, these results suggest that interferon signaling patterns in PBL correlate with clinical responses and may predict clinical outcome after HDI in patients with melanoma. A larger confirmatory study is warranted, which may yield a novel approach to select patients for HDI therapy.</p

Diversity, differentiation, and linkage disequilibrium: prospects for association mapping in the malaria vector anopheles arabiensis

Association mapping is a widely applied method for elucidating the genetic basis of phenotypic traits. However, factors such as linkage disequilibrium and levels of genetic diversity influence the power and resolution of this approach. Moreover, the presence of population subdivision among samples can result in spurious associations if not accounted for. As such, it is useful to have a detailed understanding of these factors before conducting association mapping experiments. Here we conducted whole-genome sequencing on 24 specimens of the malaria mosquito vector, Anopheles arabiensis, to further understanding of patterns of genetic diversity, population subdivision and linkage disequilibrium in this species. We found high levels of genetic diversity within the An. arabiensis genome, with ~800,000 high-confidence, single- nucleotide polymorphisms detected. However, levels of nucleotide diversity varied significantly both within and between chromosomes. We observed lower diversity on the X chromosome, within some inversions, and near centromeres. Population structure was absent at the local scale (Kilombero Valley, Tanzania) but detected between distant populations (Cameroon vs. Tanzania) where differentiation was largely restricted to certain autosomal chromosomal inversions such as 2Rb. Overall, linkage disequilibrium within An. arabiensis decayed very rapidly (within 200 bp) across all chromosomes. However, elevated linkage disequilibrium was observed within some inversions, suggesting that recombination is reduced in those regions. The overall low levels of linkage disequilibrium suggests that association studies in this taxon will be very challenging for all but variants of large effect, and will require large sample sizes

Brief Note: Discovery of the Federally Endangered Freshwater Mussel, Epioblasma obliquata obliquata (Rafinesque, 1820) (Unionidae), in Ohio

Author Institution: Department of Life and Earth Sciences, Otterbein College ; Division of Natural Areas and Preserves, Ohio Department of Natural ResourcesDiscovery of the purple catspaw, Epioblasma obliquata obliquata, in Killbuck Creek, Coshocton County, OH, is reported. This subspecies of unionid mollusc was thought to have been extirpated from the state in the mid to late 1800s and was known only from two nonreproductive populations in Kentucky and Tennessee. The mussel was thought to be on the verge of extinction. Fifteen living and 23 dead specimens of this subspecies were collected in September 1994 from Killbuck Creek. This is the largest known population of this rare subspecies and it is the only known population to currently support breeding individuals. It is threatened by soil erosion resulting from agricultural land-use practices such as clearing of the stream banks for farm fields and cattle grazing and by muskrat predation

A diverse portfolio of novel drug discovery efforts for Alzheimer's disease: Meeting report from the 11th International Conference on Alzheimer's Drug Discovery, 27-28 September 2010, Jersey City, NJ, USA

While Alzheimer's disease researchers continue to debate the underlying cause(s) of the disease, most agree that a diverse, multi-target approach to treatment will be necessary. To this end, the Alzheimer's Drug Discovery Foundation (ADDF) recently hosted the 11th International Conference on Alzheimer's Drug Discovery to highlight the array of exciting efforts from the ADDF's funded investigators

The position of authenticity within extant models of personality.

The aim of the current study was to explore where authenticity, derived from the humanistic tradition of psychology, was positioned within a number of extant models of personality. Exploratory and Confirmatory Factor Analysis of data from four samples (total N = 1286) suggested that authenticity can be considered as loading on the Honesty–Humility factor of personality. These findings are discussed in terms of the wider theoretical overlaps between Honesty–Humility and psychological functioning as emphasised by the humanistic tradition of psychology

Acceptorless Amine Dehydrogenation and Transamination Using Pd-Doped Hydrotalcites

The acceptorless dehydrogenation of acyclic secondary amines is a highly desirable but still elusive catalytic process. Here we report the synthesis, characterization, and activity of Pd-doped hydrotalcites (Pd-HTs) for acceptorless dehydrogenation of both primary and secondary amines (cyclic and acyclic). These multifunctional catalysts comprise Brønsted basic and Lewis acidic surface sites that stabilize Pd in 0, 2 + , and 4 + oxidation states. Pd speciation and corresponding catalytic performance is a strong function of metal loading. High activity is observed for the dehydrogenation of secondary aliphatic amines to imines, and N-heterocycles, such as indoline, 1,2,3,4-tetrahydroquinoline, and piperidine, to aromatic compounds. Oxidative transamination of primary amines is achieved using low Pd loading (0.5 mol %), without the need for oxidants. The relative yields of secondary imines afforded are consistent with trends for calculated free energy of reaction, while yields for transamination products correspond to the electrophilicity of primary imine intermediates. Reversible amine dehydrogenation and imine hydrogenation determine the relative selectivity for secondary imine/amine products. Poisoning tests evidence that Pd-HTs operate heterogeneously, with negligible metal leaching. Catalysts retain over 90% of activity over six reuse cycles, but do suffer some selectivity loss, attributed to changes of Pd phases