How Lemmings on Wheels Can Make a U-Turn Through Social Inclusion and Democracy

The challenge is (a) to balance both centralised control to preserve the global commons and (b) to involve people in policy making so that they feel culturally engaged and committed to the policy. Dictatorships and forms of World government from above to support the global commons are no more of an answer than forms of liberal democracy that do not engage people in between national elections. Passive voting does not help people in diverse democracies to engage in thinking through ‘if then scenarios’ about their social, economic and environmental future.     

A Systems Approach for Engaging Groups in Global Complexity: Capacity Building Through an Online Course

Sustainability is not simply about changing practices but more centrally about agreeing to change practices together. To achieve such an end, groups need to improve processes for making complex decisions together. An online course was designed and tested linking students in the United States and in Australia. Students engaged in a re-enactment of deliberations based on Hasan Ozbekhan’s “Predicament of Mankind,” which was constructed originally under assignment from the founders of the Club of Rome in 1970. This re-enactment included contemporary research for examples of a set of 49 continuous critical problems of mankind, asynchronous clarification of these problems using a wiki, pair-wise construction of a systems view of problems assessed to be of highest priority by the class, narrative analysis of the structure, and creative suggestions for resolving the systems problem based on resources available today. This report comments on the strengths and challenges identified in an initial application of an approach for building collaborative and systems thinking skills through an online course in a general education curriculum. Findings are particularly meaningful for contemporary policy makers as well as online educators.     

Antibodies to human serum amyloid P component eliminate visceral amyloid deposits

Accumulation of amyloid fibrils in the viscera and connective tissues causes systemic amyloidosis, which is responsible for about one in a thousand deaths in developed countries. Localized amyloid can also have serious consequences; for example, cerebral amyloid angiopathy is an important cause of haemorrhagic stroke. The clinical presentations of amyloidosis are extremely diverse and the diagnosis is rarely made before significant organ damage is present. There is therefore a major unmet need for therapy that safely promotes the clearance of established amyloid deposits. Over 20 different amyloid fibril proteins are responsible for different forms of clinically significant amyloidosis and treatments that substantially reduce the abundance of the respective amyloid fibril precursor proteins can arrest amyloid accumulation. Unfortunately, control of fibril-protein production is not possible in some forms of amyloidosis and in others it is often slow and hazardous. There is no therapy that directly targets amyloid deposits for enhanced clearance. However, all amyloid deposits contain the normal, non-fibrillar plasma glycoprotein, serum amyloid P component (SAP). Here we show that administration of anti-human-SAP antibodies to mice with amyloid deposits containing human SAP triggers a potent, complement-dependent, macrophage-derived giant cell reaction that swiftly removes massive visceral amyloid deposits without adverse effects. Anti-SAP-antibody treatment is clinically feasible because circulating human SAP can be depleted in patients by the bis-d-proline compound CPHPC, thereby enabling injected anti-SAP antibodies to reach residual SAP in the amyloid deposits. The unprecedented capacity of this novel combined therapy to eliminate amyloid deposits should be applicable to all forms of systemic and local amyloidosis.     

Genetic history of an archaic hominin group from Denisova Cave in Siberia

Using DNA extracted from a finger bone found in Denisova Cave in southern Siberia, we have sequenced the genome of an archaic hominin to about 1.9-fold coverage. This individual is from a group that shares a common origin with Neanderthals. This population was not involved in the putative gene flow from Neanderthals into Eurasians; however, the data suggest that it contributed 4-6% of its genetic material to the genomes of present-day Melanesians. We designate this hominin population 'Denisovans' and suggest that it may have been widespread in Asia during the Late Pleistocene epoch. A tooth found in Denisova Cave carries a mitochondrial genome highly similar to that of the finger bone. This tooth shares no derived morphological features with Neanderthals or modern humans, further indicating that Denisovans have an evolutionary history distinct from Neanderthals and modern humans.     

Re-framing Prostitution in Indonesia: A Critical Systemic Approach

This study applies critical systems thinking as a process to respond to and offer recommendations to address prostitution policy in Indonesia. The article addresses social, economic and environmental aspects of prostitution. The analysis centres on the way in which prostitution is framed by the different interest groups in Indonesia, and highlights the current crisis in policy-making praxis in Indonesia. The article develops a case for systemic policy praxis, and aims to: (1) Make a case for re-framing the issue of prostitution in the sense that it addresses the ‘capabilities’ prostituted women and children ought to have (see Sen in Development as freedom, Oxford University Press, Oxford, 1999 and Nussbaum in Women and human development: the capabilities approach, Cambridge University Press, Cambridge 2000). (2) Re-frame the policy response to prostitution to address life chances and human dignity. (3) Assert that the lack of attention to a just and fair human rights for all is due to a policy-making gap where ‘systemic intervention’ is required to restore human dignity.     

Diversity, stability and resilience of the human gut microbiota

Trillions of microbes inhabit the human intestine, forming a complex ecological community that influences normal physiology and susceptibility to disease through its collective metabolic activities and host interactions. Understanding the factors that underlie changes in the composition and function of the gut microbiota will aid in the design of therapies that target it. This goal is formidable. The gut microbiota is immensely diverse, varies between individuals and can fluctuate over time - especially during disease and early development. Viewing the microbiota from an ecological perspective could provide insight into how to promote health by targeting this microbial community in clinical treatments.     

Abundant gene conversion between arms of palindromes in human and ape Y chromosomes

Eight palindromes comprise one-quarter of the euchromatic DNA of the male-specific region of the human Y chromosome, the MSY. They contain many testis-specific genes and typically exhibit 99.97% intra-palindromic (arm-to-arm) sequence identity. This high degree of identity could be interpreted as evidence that the palindromes arose through duplication events that occurred about 100,000 years ago. Using comparative sequencing in great apes, we demonstrate here that at least six of these MSY palindromes predate the divergence of the human and chimpanzee lineages, which occurred about 5 million years ago. The arms of these palindromes must have subsequently engaged in gene conversion, driving the paired arms to evolve in concert. Indeed, analysis of MSY palindrome sequence variation in existing human populations provides evidence of recurrent arm-to-arm gene conversion in our species. We conclude that during recent evolution, an average of approximately 600 nucleotides per newborn male have undergone Y-Y gene conversion, which has had an important role in the evolution of multi-copy testis gene families in the MSY.     

Inhibition of mTOR induces autophagy and reduces toxicity of polyglutamine expansions in fly and mouse models of Huntington disease

Huntington disease is one of nine inherited neurodegenerative disorders caused by a polyglutamine tract expansion. Expanded polyglutamine proteins accumulate abnormally in intracellular aggregates. Here we show that mammalian target of rapamycin (mTOR) is sequestered in polyglutamine aggregates in cell models, transgenic mice and human brains. Sequestration of mTOR impairs its kinase activity and induces autophagy, a key clearance pathway for mutant huntingtin fragments. This protects against polyglutamine toxicity, as the specific mTOR inhibitor rapamycin attenuates huntingtin accumulation and cell death in cell models of Huntington disease, and inhibition of autophagy has the converse effects. Furthermore, rapamycin protects against neurodegeneration in a fly model of Huntington disease, and the rapamycin analog CCI-779 improved performance on four different behavioral tasks and decreased aggregate formation in a mouse model of Huntington disease. Our data provide proof-of-principle for the potential of inducing autophagy to treat Huntington disease.     

The European dimension for the mouse genome mutagenesis program

The European Mouse Mutagenesis Consortium is the European initiative contributing to the international effort on functional annotation of the mouse genome. Its objectives are to establish and integrate mutagenesis platforms, gene expression resources, phenotyping units, storage and distribution centers and bioinformatics resources. The combined efforts will accelerate our understanding of gene function and of human health and disease.