A New Operation on Sequences: the Boustrouphedon Transform

A generalization of the Seidel-Entringer-Arnold method for calculating the alternating permutation numbers (or secant-tangent numbers) leads to a new operation on integer sequences, the Boustrophedon transform.Comment: very minor change: corrected typo in author list. June 24 2002: correction to a proof; additional reference

Comparing Infrared Star-Formation Rate Indicators with Optically-Derived Quantities

We examine the UV reprocessing efficiencies of warm dust and polycyclic aromatic hydrocarbons (PAHs) through an analysis of the mid- and far-infrared surface luminosity densities of 85 nearby H$\alpha$-selected star-forming galaxies detected by the volume-limited KPNO International Spectroscopic Survey (KISS). Because H$\alpha$ selection is not biased toward continuum-bright objects, the KISS sample spans a wide range in stellar masses ($10^8$-$10^{12}\rm{M}_\odot$), as well as H$\alpha$ luminosity ($10^{39}$-$10^{43}\rm{ergs/s}$), mid-infrared 8.0$\mu$m luminosity ($10^{41}$-$10^{44}\rm{ergs/s}$), and [Bw-R] color (-.1-2.2). We find that mid-infrared polycyclic aromatic hydrocarbon (PAH) emission in the Spitzer IRAC 8.0$\mu$m band correlates with star formation, and that the efficiency with which galaxies reprocess UV energy into PAH emission depends on metallicity. We also find that the relationship between far-infrared luminosity in the Spitzer MIPS 24$\mu$m band pass and H$\alpha$-measured star-formation rate varies from galaxy to galaxy within our sample; we do not observe a metallicity dependence in this relationship. We use optical colors and established mass-to-light relationships to determine stellar masses for the KISS galaxies; we compare these masses to those of nearby galaxies as a confirmation that the volume-limited nature of KISS avoids strong biases. We also examine the relationship between IRAC 3.6$\mu$m luminosity and galaxy stellar mass, and find a color-dependent correlation between the two.Comment: 15 pages, 10 figure

Stabilizing the Retromer Complex in a Human Stem Cell Model of Alzheimer's Disease Reduces TAU Phosphorylation Independently of Amyloid Precursor Protein.

Developing effective therapeutics for complex diseases such as late-onset, sporadic Alzheimer's disease (SAD) is difficult due to genetic and environmental heterogeneity in the human population and the limitations of existing animal models. Here, we used hiPSC-derived neurons to test a compound that stabilizes the retromer, a highly conserved multiprotein assembly that plays a pivotal role in trafficking molecules through the endosomal network. Using this human-specific system, we have confirmed previous data generated in murine models and show that retromer stabilization has a potentially beneficial effect on amyloid beta generation from human stem cell-derived neurons. We further demonstrate that manipulation of retromer complex levels within neurons affects pathogenic TAU phosphorylation in an amyloid-independent manner. Taken together, our work demonstrates that retromer stabilization is a promising candidate for therapeutic development in AD and highlights the advantages of testing novel compounds in a human-specific, neuronal system

Evolution of electron transfer out of the cell: comparative genomics of six Geobacter genomes

Background: Geobacter species grow by transferring electrons out of the cell - either to Fe(III)-oxides or to manmade substances like energy-harvesting electrodes. Study of Geobacter sulfurreducens has shown that TCA cycle enzymes, inner-membrane respiratory enzymes, and periplasmic and outer-membrane cytochromes are required. Here we present comparative analysis of six Geobacter genomes, including species from the clade that predominates in the subsurface. Conservation of proteins across the genomes was determined to better understand the evolution of Geobacter species and to create a metabolic model applicable to subsurface environments. Results: The results showed that enzymes for acetate transport and oxidation, and for proton transport across the inner membrane were well conserved. An NADH dehydrogenase, the ATP synthase, and several TCA cycle enzymes were among the best conserved in the genomes. However, most of the cytochromes required for Fe(III)-reduction were not, including many of the outer-membrane cytochromes. While conservation of cytochromes was poor, an abundance and diversity of cytochromes were found in every genome, with duplications apparent in several species. Conclusions: These results indicate there is a common pathway for acetate oxidation and energy generation across the family and in the last common ancestor. They also suggest that while cytochromes are important for extracellular electron transport, the path of electrons across the periplasm and outer membrane is variable. This combination of abundant cytochromes with weak sequence conservation suggests they may not be specific terminal reductases, but rather may be important in their heme-bearing capacity, as sinks for electrons between the inner-membrane electron transport chain and the extracellular acceptor

Evolution from a respiratory ancestor to fill syntrophic and fermentative niches: comparative fenomics of six Geobacteraceae species

<p>Abstract</p> <p>Background</p> <p>The anaerobic degradation of organic matter in natural environments, and the biotechnical use of anaerobes in energy production and remediation of subsurface environments, both require the cooperative activity of a diversity of microorganisms in different metabolic niches. The <it>Geobacteraceae </it>family contains members with three important anaerobic metabolisms: fermentation, syntrophic degradation of fermentation intermediates, and anaerobic respiration.</p> <p>Results</p> <p>In order to learn more about the evolution of anaerobic microbial communities, the genome sequences of six <it>Geobacteraceae </it>species were analyzed. The results indicate that the last common <it>Geobacteraceae </it>ancestor contained sufficient genes for anaerobic respiration, completely oxidizing organic compounds with the reduction of external electron acceptors, features that are still retained in modern <it>Geobacter </it>and <it>Desulfuromonas </it>species. Evolution of specialization for fermentative growth arose twice, via distinct lateral gene transfer events, in <it>Pelobacter carbinolicus </it>and <it>Pelobacter propionicus</it>. Furthermore, <it>P. carbinolicus </it>gained hydrogenase genes and genes for ferredoxin reduction that appear to permit syntrophic growth via hydrogen production. The gain of new physiological capabilities in the <it>Pelobacter </it>species were accompanied by the loss of several key genes necessary for the complete oxidation of organic compounds and the genes for the <it>c</it>-type cytochromes required for extracellular electron transfer.</p> <p>Conclusion</p> <p>The results suggest that <it>Pelobacter </it>species evolved parallel strategies to enhance their ability to compete in environments in which electron acceptors for anaerobic respiration were limiting. More generally, these results demonstrate how relatively few gene changes can dramatically transform metabolic capabilities and expand the range of environments in which microorganisms can compete.</p

Bub2 regulation of cytokinesis and septation in budding yeast

<p>Abstract</p> <p>Background</p> <p>The mitotic exit network (MEN) is required for events at the end of mitosis such as degradation of mitotic cyclins and cytokinesis. Bub2 and its binding partner Bfa1 act as a GTPase activating protein (GAP) to negatively regulate the MEN GTPase Tem1. The Bub2/Bfa1 checkpoint pathway is required to delay the cell cycle in response to mispositioned spindles. In addition to its role in mitotic exit, Tem1 is required for actomyosin ring contraction.</p> <p>Results</p> <p>To test the hypothesis that the Bub2 pathway prevents premature actin ring assembly, we compared the timing of actin ring formation in wild type, <it>bub2Δ</it>, <it>mad2Δ</it>, and <it>bub2Δmad2Δ </it>cells both with and without microtubules. There was no difference in the timing of actin ring formation between wild type and mutant cells in a synchronized cell cycle. In the presence of nocodazole, both <it>bub2Δ </it>and <it>mad2Δ </it>cells formed rings after a delay of the same duration. Double mutant <it>bub2Δmad2Δ </it>and <it>bfa1Δmad2Δ </it>cells formed rings at the same time with and without nocodazole. To determine if Bub2 has an effect on actomyosin ring contraction through its regulation of Tem1, we used live cell imaging of Myo1-GFP in a <it>bub2Δ </it>strain. We found a significant decrease in the total time of contraction and an increase in rate of contraction compared to wild type cells. We also examined myosin contraction using Myo1-GFP in cells overexpressing an epitope tagged Bub2. Surprisingly, overexpression of Bub2 also led to a significant increase in the rate of contraction, as well as morphological defects. The chained cell phenotype caused by Bub2 overexpression could be rescued by co-overexpression of Tem1, and was not rescued by deletion of <it>BFA1</it>.</p> <p>Conclusion</p> <p>Our data indicate that the Bub2 checkpoint pathway does not have a specific role in delaying actin ring formation. The observed increase in the rate of myosin contraction in the <it>bub2Δ </it>strain provides evidence that the MEN regulates actomyosin ring contraction. Our data suggest that the overexpression of the Bub2 fusion protein acts as a dominant negative, leading to septation defects by a mechanism that is Tem1-dependent.</p

It All Adds Up: Connecting Home and School through Family Math

Considered a core component of children’s foundational cognitive development, early mathematics experiences can support children’s long-term academic success. Teachers and families alike share the common goal of wanting children to succeed developmentally, socially, and academically. Given the importance of early mathematics to academic success in all subjects, children need and deserve to build a robust knowledge of early math concepts in their earliest years. In this chapter, we consider the approach of the Young Mathematicians (YM) project at EDC, which for the past ten years, has partnered with families, teachers, and early childhood programs in richly diverse communities with large populations of students of color, linguistically minoritized students, and students living in poverty, to support math learning across home and school environments. We illustrate some of our fun early learning games that engage teachers and families alike and are freely available in multiple languages for anyone to use. We discuss how our close collaboration with families and teachers has informed our approach to equity and report on some of the positive results from our research. Finally, we reflect on ways we can all improve how we are partnering with families and teachers to create equitable and supportive learning communities

Polyglutamine-expanded androgen receptor interferes with TFEB to elicit autophagy defects in SBMA.

Macroautophagy (hereafter autophagy) is a key pathway in neurodegeneration. Despite protective actions, autophagy may contribute to neuron demise when dysregulated. Here we consider X-linked spinal and bulbar muscular atrophy (SBMA), a repeat disorder caused by polyglutamine-expanded androgen receptor (polyQ-AR). We found that polyQ-AR reduced long-term protein turnover and impaired autophagic flux in motor neuron-like cells. Ultrastructural analysis of SBMA mice revealed a block in autophagy pathway progression. We examined the transcriptional regulation of autophagy and observed a functionally significant physical interaction between transcription factor EB (TFEB) and AR. Normal AR promoted, but polyQ-AR interfered with, TFEB transactivation. To evaluate physiological relevance, we reprogrammed patient fibroblasts to induced pluripotent stem cells and then to neuronal precursor cells (NPCs). We compared multiple SBMA NPC lines and documented the metabolic and autophagic flux defects that could be rescued by TFEB. Our results indicate that polyQ-AR diminishes TFEB function to impair autophagy and promote SBMA pathogenesis

Risk perception, safer sex practices and PrEP enthusiasm: Barriers and facilitators to oral HIV pre-exposure prophylaxis in Black African and Black Caribbean women in the UK

Objectives: UK Black African/Black Caribbean women remain disproportionately affected by HIV. Although oral pre-exposure prophylaxis (PrEP) could offer them an effective HIV prevention method, uptake remains limited. This study examined barriers and facilitators to PrEP awareness and candidacy perceptions for Black African/Black Caribbean women to help inform PrEP programmes and service development. Methods: Using purposive sampling through community organisations, 32 in-depth, semi-structured interviews were conducted with Black African/Black Caribbean women living in London and Glasgow between June and August 2018. Participants (aged 19–63) included women of varied HIV statuses to explore perceptions of sexual risk and safer sex, sexual health knowledge and PrEP attitudes. A thematic analysis guided by the Social Ecological Model was used to explore how PrEP perceptions intersected with wider safer sex understandings and practices. Results: Four key levels of influence shaping safer sex notions and PrEP candidacy perceptions emerged: personal, interpersonal, perceived environment and policy. PrEP-specific knowledge was low and some expressed distrust in PrEP. Many women were enthusiastic about PrEP for others but did not situate PrEP within their own safer sex understandings, sometimes due to difficulty assessing their own HIV risk. Many felt that PrEP could undermine intimacy in their relationships by disrupting the shared responsibility implicit within other HIV prevention methods. Women described extensive interpersonal networks that supported their sexual health knowledge and shaped their interactions with health services, though these networks were influenced by prevailing community stigmas. Conclusions: Difficulty situating PrEP within existing safer sex beliefs contributes to limited perceptions of personal PrEP candidacy. To increase PrEP uptake in UK Black African/Black Caribbean women, interventions will need to enable women to advance their knowledge of PrEP within the broader context of their sexual health and relationships. PrEP service models will need to include trusted ‘non-sexual health-specific’ community services such as general practice