Combinatorial Roles of Heparan Sulfate Proteoglycans and Heparan Sulfates in Caenorhabditis elegans Neural Development

Heparan sulfate proteoglycans (HSPGs) play critical roles in the development and adult physiology of all metazoan organisms. Most of the known molecular interactions of HSPGs are attributed to the structurally highly complex heparan sulfate (HS) glycans. However, whether a specific HSPG (such as syndecan) contains HS modifications that differ from another HSPG (such as glypican) has remained largely unresolved. Here, a neural model in C. elegans is used to demonstrate for the first time the relationship between specific HSPGs and HS modifications in a defined biological process in vivo. HSPGs are critical for the migration of hermaphrodite specific neurons (HSNs) as genetic elimination of multiple HSPGs leads to 80% defect of HSN migration. The effects of genetic elimination of HSPGs are additive, suggesting that multiple HSPGs, present in the migrating neuron and in the matrix, act in parallel to support neuron migration. Genetic analyses suggest that syndecan/sdn-1 and HS 6-O-sulfotransferase, hst-6, function in a linear signaling pathway and glypican/lon-2 and HS 2-O-sulfotransferase, hst-2, function together in a pathway that is parallel to sdn-1 and hst-6. These results suggest core protein specific HS modifications that are critical for HSN migration. In C. elegans, the core protein specificity of distinct HS modifications may be in part regulated at the level of tissue specific expression of genes encoding for HSPGs and HS modifying enzymes. Genetic analysis reveals that there is a delicate balance of HS modifications and eliminating one HS modifying enzyme in a compromised genetic background leads to significant changes in the overall phenotype. These findings are of importance with the view of HS as a critical regulator of cell signaling in normal development and disease

Rescaling multipartite entanglement measures for mixed states

A relevant problem regarding entanglement measures is the following: Given an arbitrary mixed state, how does a measure for multipartite entanglement change if general local operations are applied to the state? This question is nontrivial as the normalization of the states has to be taken into account. Here we answer it for pure-state entanglement measures which are invariant under determinant 1 local operations and homogeneous in the state coefficients, and their convex-roof extension which quantifies mixed-state entanglement. Our analysis allows to enlarge the set of mixed states for which these important measures can be calculated exactly. In particular, our results hint at a distinguished role of entanglement measures which have homogeneous degree 2 in the state coefficients.Comment: Published version plus one important reference (Ref. [39]

Emergent complex neural dynamics

A large repertoire of spatiotemporal activity patterns in the brain is the basis for adaptive behaviour. Understanding the mechanism by which the brain's hundred billion neurons and hundred trillion synapses manage to produce such a range of cortical configurations in a flexible manner remains a fundamental problem in neuroscience. One plausible solution is the involvement of universal mechanisms of emergent complex phenomena evident in dynamical systems poised near a critical point of a second-order phase transition. We review recent theoretical and empirical results supporting the notion that the brain is naturally poised near criticality, as well as its implications for better understanding of the brain

Breakdown of a perturbed Z_N topological phase

We study the robustness of a generalized Kitaev's toric code with Z_N degrees of freedom in the presence of local perturbations. For N=2, this model reduces to the conventional toric code in a uniform magnetic field. A quantitative analysis is performed for the perturbed Z_3 toric code by applying a combination of high-order series expansions and variational techniques. We provide strong evidences for first- and second-order phase transitions between topologically-ordered and polarized phases. Most interestingly, our results also indicate the existence of topological multi-critical points in the phase diagram.Comment: 27 pages, 10 figure

The SOCS-Box of HIV-1 Vif Interacts with ElonginBC by Induced-Folding to Recruit Its Cul5-Containing Ubiquitin Ligase Complex

The HIV-1 viral infectivity factor (Vif) protein recruits an E3 ubiquitin ligase complex, comprising the cellular proteins elongin B and C (EloBC), cullin 5 (Cul5) and RING-box 2 (Rbx2), to the anti-viral proteins APOBEC3G (A3G) and APOBEC3F (A3F) and induces their polyubiquitination and proteasomal degradation. In this study, we used purified proteins and direct in vitro binding assays, isothermal titration calorimetry and NMR spectroscopy to describe the molecular mechanism for assembly of the Vif-EloBC ternary complex. We demonstrate that Vif binds to EloBC in two locations, and that both interactions induce structural changes in the SOCS box of Vif as well as EloBC. In particular, in addition to the previously established binding of Vif's BC box to EloC, we report a novel interaction between the conserved Pro-Pro-Leu-Pro motif of Vif and the C-terminal domain of EloB. Using cell-based assays, we further show that this interaction is necessary for the formation of a functional ligase complex, thus establishing a role of this motif. We conclude that HIV-1 Vif engages EloBC via an induced-folding mechanism that does not require additional co-factors, and speculate that these features distinguish Vif from other EloBC specificity factors such as cellular SOCS proteins, and may enhance the prospects of obtaining therapeutic inhibitors of Vif function

Looking Good: Mediatisation and International NGOs

Many international NGOs value those parts of their work that are suited to media representation: campaigning, advocacy, projects that produce the right sort of images. In this article I make three points about this change. First, those parts of the NGO most reliant on media – such as the campaign desk – may be becoming more powerful. This can change the internal dynamics of NGOs. Second, the increasing use of media means that NGOs, like other organisations, hold themselves accountable in new ways. Third, NGOs may appear to look more and more like media organisations. These changes have received relatively little attention in the literature on NGOs, though they reflect a broader set of debates about the role of media in society. Using a case analysis of an international NGO, I suggest that the concept of mediatisation might be a useful way to understand some of the changes observed in the NGO sector

Expert perspectives on global biodiversity loss and its drivers and impacts on people

Despite substantial progress in understanding global biodiversity loss, major taxonomic and geographic knowledge gaps remain. Decision makers often rely on expert judgement to fill knowledge gaps, but are rarely able to engage with sufficiently large and diverse groups of specialists. To improve understanding of the perspectives of thousands of biodiversity experts worldwide, we conducted a survey and asked experts to focus on the taxa and freshwater, terrestrial, or marine ecosystem with which they are most familiar. We found several points of overwhelming consensus (for instance, multiple drivers of biodiversity loss interact synergistically) and important demographic and geographic differences in specialists’ perspectives and estimates. Experts from groups that are underrepresented in biodiversity science, including women and those from the Global South, recommended different priorities for conservation solutions, with less emphasis on acquiring new protected areas, and provided higher estimates of biodiversity loss and its impacts. This may in part be because they disproportionately study the most highly threatened taxa and habitats

Declining resilience of ecosystem functions under biodiversity loss

The composition of species communities is changing rapidly through drivers such as habitat loss and climate change, with potentially serious consequences for the resilience of ecosystem functions on which humans depend. To assess such changes in resilience, we analyse trends in the frequency of species in Great Britain that provide key ecosystem functions-specifically decomposition, carbon sequestration, pollination, pest control and cultural values. For 4,424 species over four decades, there have been significant net declines among animal species that provide pollination, pest control and cultural values. Groups providing decomposition and carbon sequestration remain relatively stable, as fewer species are in decline and these are offset by large numbers of new arrivals into Great Britain. While there is general concern about degradation of a wide range of ecosystem functions, our results suggest actions should focus on particular functions for which there is evidence of substantial erosion of their resilience