The Case for Improving U.S. Computer Science Education

Despite the growing use of computers and software in every facet of our economy, not until recently has computer science education begun to gain traction in American school systems. The current focus on improving science, technology, engineering, and mathematics (STEM) education in the U.S. school system has disregarded differences within STEM fields. Indeed, the most important STEM field for a modern economy is not only one that is not represented by its own initial in "STEM" but also the field with the fewest number of high school students taking its classes and by far has the most room for improvement—computer science

The Curse of Windfall Income: How Foreign Aid and Natural Resource Dependence Constrains Growth

Literature exists on two ‘curses,’ the natural resource curse and the curse of foreign aid, which limit growth in developing nations. At their core, both the natural resources curse and the curse of aid derive from the same root cause- the curse of windfall income. The windfall curse is a macroeconomic side-effect that negates the positive effects of unearned capital by raising domestic prices and lowering competitiveness. While windfall income creates growth in a countries service sector, it represses growth in the manufacturing sector. These trends help explain the inability of both foreign aid and natural resources to fuel sustained growth in windfall income-dependent economies

Crystal structures of asymmetric ClpX hexamers reveal nucleotide-dependent motions in a AAA+ protein-unfolding machine

ClpX is a AAA+ machine that uses the energy of ATP binding and hydrolysis to unfold native proteins and translocate unfolded polypeptides into the ClpP peptidase. The crystal structures presented here reveal striking asymmetry in ring hexamers of nucleotide-free and nucleotide-bound ClpX. Asymmetry arises from large changes in rotation between the large and small AAA+ domains of individual subunits. These differences prevent nucleotide binding to two subunits, generate a staggered arrangement of ClpX subunits and pore loops around the hexameric ring, and provide a mechanism for coupling conformational changes caused by ATP binding or hydrolysis in one subunit to flexing motions of the entire ring. Our structures explain numerous solution studies of ClpX function, predict mechanisms for pore elasticity during translocation of irregular polypeptides, and suggest how repetitive conformational changes might be coupled to mechanical work during the ATPase cycle of ClpX and related molecular machines.National Institutes of Health (U.S.) (Grant number AI-15706

Signaling through the primary cilium

© 2018 Wheway, Nazlamova and Hancock. The presence of single, non-motile "primary" cilia on the surface of epithelial cells has been well described since the 1960s. However, for decades these organelles were believed to be vestigial, with no remaining function, having lost their motility. It wasn't until 2003, with the discovery that proteins responsible for transport along the primary cilium are essential for hedgehog signaling in mice, that the fundamental importance of primary cilia in signal transduction was realized. Little more than a decade later, it is now clear that the vast majority of signaling pathways in vertebrates function through the primary cilium. This has led to the adoption of the term "the cells's antenna" as a description for the primary cilium. Primary cilia are particularly important during development, playing fundamental roles in embryonic patterning and organogenesis, with a suite of inherited developmental disorders known as the "ciliopathies" resulting from mutations in genes encoding cilia proteins. This review summarizes our current understanding of the role of these fascinating organelles in a wide range of signaling pathways

Maternal condition but not corticosterone is linked to brood sex ratio adjustment in a passerine bird

There is evidence of offspring sex ratio adjustment in a range of species, but the potential mechanisms remain largely unknown. Elevated maternal corticosterone (CORT) is associated with factors that can favour brood sex ratio adjustment, such as reduced maternal condition, food availability and partner attractiveness. Therefore, the steroid hormone has been suggested to play a key role in sex ratio manipulation. However, despite correlative and causal evidence CORT is linked to sex ratio manipulation in some avian species, the timing of adjustment varies between studies. Consequently, whether CORT is consistently involved in sex-ratio adjustment, and how the hormone acts as a mechanism for this adjustment remains unclear. Here we measured maternal baseline CORT and body condition in free-living blue tits (Cyanistes caeruleus) over three years and related these factors to brood sex ratio and nestling quality. In addition, a non-invasive technique was employed to experimentally elevate maternal CORT during egg laying, and its effects upon sex ratio and nestling quality were measured. We found that maternal CORT was not correlated with brood sex ratio, but mothers with elevated CORT fledged lighter offspring. Also, experimental elevation of maternal CORT did not influence brood sex ratio or nestling quality. In one year, mothers in superior body condition produced male biased broods, and maternal condition was positively correlated with both nestling mass and growth rate in all years. Unlike previous studies maternal condition was not correlated with maternal CORT. This study provides evidence that maternal condition is linked to brood sex ratio manipulation in blue tits. However, maternal baseline CORT may not be the mechanistic link between the maternal condition and sex ratio adjustment. Overall, this study serves to highlight the complexity of sex ratio adjustment in birds and the difficulties associated with identifying sex biasing mechanisms

Genome defence in hypomethylated developmental contexts

Retrotransposons constitute around 40% of the mammalian genome and their aberrant activation can have wide ranging detrimental consequences, both throughout development and into somatic lineages. DNA methylation is one of the major epigenetic mechanisms in mammals, and is essential in repressing retrotransposons throughout mammalian development. Yet during normal mouse embryonic development some cell lineages become extensively DNA hypomethylated and it is not clear how these cells maintain retrotransposon silencing in a globally hypomethylated genomic context. In this thesis I determine that hypomethylation in multiple contexts results in the consistent activation of only one gene in the mouse genome - Tex19.1. Thus if a generic compensatory mechanism for loss of DNA methylation exists in mice, it must function through this gene. Tex19.1-/- mice de-repress retrotransposons in the hypomethylated component of the placenta and in the mouse germline, and have developmental defects in these tissues. In this thesis I examine the mechanism of TEX19.1 mediated genome defence and the developmental consequences upon its removal. I show that TEX19.1 functions in repressing retrotransposons, at least in part, through physically interacting with the transcriptional co-repressor, KAP1. Tex19.1-/- ES cells have reduced levels of KAP1 bound retrotransposon chromatin and reduced levels of the repressive H3K9me3 modification at these loci. Furthermore, these subsets of retrotransposon loci are de-repressed in Tex19.1-/- placentas. Thus, my data indicates that mouse cells respond to hypomethylation by activating expression of Tex19.1, which in turn augments compensatory, repressive histone modifications at retrotransposon sequences, thereby helping developmentally hypomethylated cells to maintain genome stability. I next aimed to further elucidate the role of Tex19.1 in the developing hypomethylated placenta. I determine that Tex19.1-/- placental defects precede intrauterine growth restriction of the embryo and that alterations in mRNA abundance in E12.5 Tex19.1-/- placentas is likely in part due to genic transcriptional changes. De-repression of LINE- 1 is evident in these placentas and elements of the de-repressed subfamily are associated with significantly downregulated genes. If retrotransposon de-repression is contributing to developmental defects by interfering with gene expression remains to be determined, however I identify a further possible mechanism leading to placental developmental defects. I determine that Tex19.1-/- placentas have an increased innate immune response and I propose that this is contributing to the developmental defects observed. Developmental defects and retrotransposon de-repression are also observed in spermatogenesis in Tex19.1-/- testes, the molecular basis for which is unclear. I therefore investigate the possibility that the TEX19.1 interacting partners, the E3 ubiquitin ligase proteins, may be contributing to the phenotypes observed in Tex19.1- /- testes. I show that repression of MMERVK10C in the testes is dependent on UBR2, alongside TEX19.1. Furthermore, I have identified a novel role for the TEX19.1 interacting partner, UBR5, in spermatogenesis, whose roles are distinct from those of TEX19.1. The work carried out during the course of this thesis provides mechanistic insights into TEX19.1 mediated genome defence and highlights the importance of protecting the genome from aberrant retrotransposon expression