The Great Unlearning

The Great Unlearning is a conceptual exploration: sifting through experiences and objects to overcome psychological pain, expectations of society, individual upbringing, and outside influences in an ongoing quest for authenticity. To both embrace personal history and honor loved ones while letting go of lingering negativity is challenging. Using objects culled from my life, examining the past, and incorporating items gathered along my path through nature, the work seeks personal healing while promoting the power of all people to break from indoctrination, group think, and mob mentality to make better choices to live a satisfying and peaceful existence…hopefully in a democratic free society

mTORC1 pathway activity biases cell fate choice

Pluripotent stem cells can differentiate into distinct cell types but the intracellular pathways controlling cell fate choice are not well understood. The social amoeba Dictyostelium discoideum is a simplified system to study choice preference as proliferating amoebae enter a developmental cycle upon starvation and differentiate into two major cell types, stalk and spores, organised in a multicellular fruiting body. Factors such as acidic vesicle pH predispose amoebae to one fate. Here we show that the mechanistic target of rapamycin complex 1 (mTORC1) pathway has a role in cell fate bias in Dictyostelium. Inhibiting the mTORC1 pathway activity by disruption of Rheb (activator Ras homolog enriched in brain), or treatment with the mTORC1 inhibitor rapamycin prior to development, biases cells to a spore cell fate. Conversely activation of the pathway favours stalk cell differentiation. The Set1 histone methyltransferase, responsible for histone H3 lysine4 methylation, in Dictyostelium cells regulates transcription at the onset of development. Disruption of Set1 leads to high mTORC1 pathway activity and stalk cell predisposition. The ability of the mTORC1 pathway to regulate cell fate bias of cells undergoing differentiation offers a potential target to increase the efficiency of stem cell differentiation into a particular cell type

Management objectives of Queensland fisheries: Putting the horse before the cart

A review of future management arrangements for the Queensland East Coast Trawl fishery was undertaken in 2010 to develop a management plan for the next 10 years. A key question raised at the start of the review process was: what should the management plan achieve? As with fisheries management in most countries, multiple management objectives were implicit in policy statements, but were poorly specified in some areas (particularly social objectives) and strongly identified in others (e.g., an objective of sustainability). As a start to the management review process, an analysis of what objectives the management system should aim to achieve was undertaken. A review of natural resource management objectives employed internationally was used to develop a candidate list, and the objectives most relevant to the fishery were short-listed by a scientific advisory group. Additional objectives specific to Queensland fisheries management, but not identified in the international review, were also identified and incorporated into the objective set. The relative importance of the different objectives to different stakeholder groups was assessed using the Analytic Hierarchy Process. As with other studies, the relative importance of the different objectives varied both within and between the different stakeholder groups, although general trends in preferences were observed

Targets downstream of Cdk8 in Dictyostelium development.

RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are.BACKGROUND: Cdk8 is a component of the mediator complex which facilitates transcription by RNA polymerase II and has been shown to play an important role in development of Dictyostelium discoideum. This eukaryote feeds as single cells but starvation triggers the formation of a multicellular organism in response to extracellular pulses of cAMP and the eventual generation of spores. Strains in which the gene encoding Cdk8 have been disrupted fail to form multicellular aggregates unless supplied with exogenous pulses of cAMP and later in development, cdk8- cells show a defect in spore production. RESULTS: Microarray analysis revealed that the cdk8- strain previously described (cdk8-HL) contained genome duplications. Regeneration of the strain in a background lacking detectable gene duplication generated strains (cdk8-2) with identical defects in growth and early development, but a milder defect in spore generation, suggesting that the severity of this defect depends on the genetic background. The failure of cdk8- cells to aggregate unless rescued by exogenous pulses of cAMP is consistent with a failure to express the catalytic subunit of protein kinase A. However, overexpression of the gene encoding this protein was not sufficient to rescue the defect, suggesting that this is not the only important target for Cdk8 at this stage of development. Proteomic analysis revealed two potential targets for Cdk8 regulation, one regulated post-transcriptionally (4-hydroxyphenylpyruvate dioxygenase (HPD)) and one transcriptionally (short chain dehydrogenase/reductase (SDR1)). CONCLUSIONS: This analysis has confirmed the importance of Cdk8 at multiple stages of Dictyostelium development, although the severity of the defect in spore production depends on the genetic background. Potential targets of Cdk8-mediated gene regulation have been identified in Dictyostelium which will allow the mechanism of Cdk8 action and its role in development to be determined.Published versio

Imaging With the Past: Revealing the Complexity of Chimaeroid Pelvic Musculature Anatomy and Development

Chondrichthyans are now widely adopted as models for examining the development and evolution of the stem gnathostome body plan. The fins of some cartilaginous fish are recognized for their plesiomorphic form and mode of muscular development, i.e., epithelial extension. Despite detailed molecular and descriptive examinations of these developmental mechanisms, there has been little contemporary examination of the ontogeny and morphology of the musculature in chondrichthyans including that of the paired fins. This gap represents a need for further examination of the developmental morphology of these appendicular musculatures to gain insight into their evolution in gnathostomes. The elephant shark is a Holocephalan, the sister group of all other chondrichthyans (Holocephali: Callorhinchus milii). Here, we use nano-CT imaging and 3D reconstructions to describe the development of the pelvic musculature of a growth series of elephant shark embryos. We also use historical descriptions from the nineteenth century and traditional dissection methods to describe the adult anatomy. This combined approach, using traditional methods and historical knowledge with modern imaging techniques, has enabled a more thorough examination of the anatomy and development of the pelvic musculature revealing that chimaeroid musculatures are more complex than previously thought. These data, when compared to extant and extinct sister taxa, are essential for interpreting and reconstructing fossil musculatures as well as understanding the evolution of paired fins

Mineralization of the Callorhinchus Vertebral Column (Holocephali; Chondrichthyes)

Members of the Chondrichthyes (Elasmobranchii and Holocephali) are distinguished by their largely cartilaginous endoskeletons, which comprise an uncalcified core overlain by a mineralized layer; in the Elasmobranchii (sharks, skates, rays) most of this mineralization takes the form of calcified polygonal tiles known as tesserae. In recent years, these skeletal tissues have been described in ever increasing detail in sharks and rays, but those of Holocephali (chimaeroids) have been less well-studied, with conflicting accounts as to whether or not tesserae are present. During embryonic ontogeny in holocephalans, cervical vertebrae fuse to form a structure called the synarcual. The synarcual mineralizes early and progressively, anteroposteriorly and dorsoventrally, and therefore presents a good skeletal structure in which to observe mineralized tissues in this group. Here, we describe the development and mineralization of the synarcual in an adult and stage 36 elephant shark embryo (Callorhinchus milii). Small, discrete, but irregular blocks of cortical mineralization are present in stage 36, similar to what has been described recently in embryos of other chimaeroid taxa such as Hydrolagus, while in Callorhinchus adults, the blocks of mineralization are more irregular, but remain small. This differs from fossil members of the holocephalan crown group (Edaphodon), as well as from stem group holocephalans (e.g., Symmorida, Helodus, Iniopterygiformes), where tesserae are notably larger than in Callorhinchus and show similarities to elasmobranch tesserae, for example with respect to polygonal shape

PARP regulates nonhomologous end joining through retention of Ku at double-strand breaks

Poly ADP-ribosylation polymerases are necessary for recruitment and/or retention of Ku at double-strand breaks during nonhomologous end-joining DNA repair

Early to Middle Bronze Age agricultural terraces in north-east England : morphology, dating and cultural implications

Terracing is found widely in the Mediterranean and in other hilly and mountainous regions of the world. Yet while archaeological attention to these ‘mundane' landscape features has grown, they remain understudied, particularly in Northern Europe. Here, the authors present a multidisciplinary study of terraces in the Breamish Valley, Northumberland. The results date their construction to the Early to Middle Bronze Age, when they were built by cutting back the hillside, stone clearance and wall construction. Environmental evidence points to their use for cereal cultivation. The authors suggest that the construction and use of these terraces formed part of an Early to Middle Bronze Age agricultural intensification, which may have been both demographically and culturally driven

Control of Cyclin C Levels during Development of Dictyostelium

Background: Cdk8 and its partner cyclin C form part of the mediator complex which links the basal transcription machinery to regulatory proteins. The pair are required for correct regulation of a subset of genes and have been implicated in control of development in a number of organisms including the social amoeba Dictyostelium discoideum. When feeding, Dictyostelium amoebae are unicellular but upon starvation they aggregate to form a multicellular structure which develops into a fruiting body containing spores. Cells in which the gene encoding Cdk8 has been deleted fail to enter aggregates due to a failure of early gene expression.Principal Findings: We have monitored the expression levels of cyclin C protein during development and find levels decrease after the multicellular mound is formed. This decrease is triggered by extracellular cAMP that, in turn, is working in part through an increase in intracellular cAMP. The loss of cyclin C is coincident with a reduction in the association of Cdk8 with a high molecular weight complex in the nucleus. Overexpression of cyclin C and Cdk8 lead to an increased rate of early development, consistent with the levels being rate limiting.Conclusions: Overall these results show that both cyclin C and Cdk8 are regulated during development in response to extracellular signals and the levels of these proteins are important in controlling the timing of developmental processes. These findings have important implications for the role of these proteins in controlling development, suggesting that they are targets for developmental signals to regulate gene expression.</p

Differential Roles of the PKC Novel Isoforms, PKCδ and PKCε, in Mouse and Human Platelets

Background Increasing evidence suggests that individual isoforms of protein kinase C (PKC) play distinct roles in regulating platelet activation. Methodology/Principal Findings In this study, we focus on the role of two novel PKC isoforms, PKCδ and PKCε, in both mouse and human platelets. PKCδ is robustly expressed in human platelets and undergoes transient tyrosine phosphorylation upon stimulation by thrombin or the collagen receptor, GPVI, which becomes sustained in the presence of the pan-PKC inhibitor, Ro 31-8220. In mouse platelets, however, PKCδ undergoes sustained tyrosine phosphorylation upon activation. In contrast the related isoform, PKCε, is expressed at high levels in mouse but not human platelets. There is a marked inhibition in aggregation and dense granule secretion to low concentrations of GPVI agonists in mouse platelets lacking PKCε in contrast to a minor inhibition in response to G protein-coupled receptor agonists. This reduction is mediated by inhibition of tyrosine phosphorylation of the FcRγ-chain and downstream proteins, an effect also observed in wild-type mouse platelets in the presence of a PKC inhibitor. Conclusions These results demonstrate a reciprocal relationship in levels of the novel PKC isoforms δ and ε in human and mouse platelets and a selective role for PKCε in signalling through GPVI