Influence of wiring cost on the large-scale architecture of human cortical connectivity

In the past two decades some fundamental properties of cortical connectivity have been discovered: small-world structure, pronounced hierarchical and modular organisation, and strong core and rich-club structures. A common assumption when interpreting results of this kind is that the observed structural properties are present to enable the brain's function. However, the brain is also embedded into the limited space of the skull and its wiring has associated developmental and metabolic costs. These basic physical and economic aspects place separate, often conflicting, constraints on the brain's connectivity, which must be characterized in order to understand the true relationship between brain structure and function. To address this challenge, here we ask which, and to what extent, aspects of the structural organisation of the brain are conserved if we preserve specific spatial and topological properties of the brain but otherwise randomise its connectivity. We perform a comparative analysis of a connectivity map of the cortical connectome both on high- and low-resolutions utilising three different types of surrogate networks: spatially unconstrained (‘random’), connection length preserving (‘spatial’), and connection length optimised (‘reduced’) surrogates. We find that unconstrained randomisation markedly diminishes all investigated architectural properties of cortical connectivity. By contrast, spatial and reduced surrogates largely preserve most properties and, interestingly, often more so in the reduced surrogates. Specifically, our results suggest that the cortical network is less tightly integrated than its spatial constraints would allow, but more strongly segregated than its spatial constraints would necessitate. We additionally find that hierarchical organisation and rich-club structure of the cortical connectivity are largely preserved in spatial and reduced surrogates and hence may be partially attributable to cortical wiring constraints. In contrast, the high modularity and strong s-core of the high-resolution cortical network are significantly stronger than in the surrogates, underlining their potential functional relevance in the brain

Coupled dark matter-dark energy in light of near Universe observations

Cosmological analysis based on currently available observations are unable to rule out a sizeable coupling among the dark energy and dark matter fluids. We explore a variety of coupled dark matter-dark energy models, which satisfy cosmic microwave background constraints, in light of low redshift and near universe observations. We illustrate the phenomenology of different classes of dark coupling models, paying particular attention in distinguishing between effects that appear only on the expansion history and those that appear in the growth of structure. We find that while a broad class of dark coupling models are effectively models where general relativity (GR) is modified --and thus can be probed by a combination of tests for the expansion history and the growth of structure--, there is a class of dark coupling models where gravity is still GR, but the growth of perturbations is, in principle modified. While this effect is small in the specific models we have considered, one should bear in mind that an inconsistency between reconstructed expansion history and growth may not uniquely indicate deviations from GR. Our low redshift constraints arise from cosmic velocities, redshift space distortions and dark matter abundance in galaxy voids. We find that current data constrain the dimensionless coupling to be |xi|<0.2, but prospects from forthcoming data are for a significant improvement. Future, precise measurements of the Hubble constant, combined with high-precision constraints on the growth of structure, could provide the key to rule out dark coupling models which survive other tests. We shall exploit as well weak equivalence principle violation arguments, which have the potential to highly disfavour a broad family of coupled models.Comment: 34 pages, 6 figures; changes to match published versio

Rhomboid family member 2 regulates cytoskeletal stress-associated Keratin 16.

Keratin 16 (K16) is a cytoskeletal scaffolding protein highly expressed at pressure-bearing sites of the mammalian footpad. It can be induced in hyperproliferative states such as wound healing, inflammation and cancer. Here we show that the inactive rhomboid protease RHBDF2 (iRHOM2) regulates thickening of the footpad epidermis through its interaction with K16. K16 expression is absent in the thinned footpads of irhom2-/- mice compared with irhom2+/+mice, due to reduced keratinocyte proliferation. Gain-of-function mutations in iRHOM2 underlie Tylosis with oesophageal cancer (TOC), characterized by palmoplantar thickening, upregulate K16 with robust downregulation of its type II keratin binding partner, K6. By orchestrating the remodelling and turnover of K16, and uncoupling it from K6, iRHOM2 regulates the epithelial response to physical stress. These findings contribute to our understanding of the molecular mechanisms underlying hyperproliferation of the palmoplantar epidermis in both physiological and disease states, and how this 'stress' keratin is regulated

Hydrodynamics of galactic dark matter

We consider simple hydrodynamical models of galactic dark matter in which the galactic halo is a self-gravitating and self-interacting gas that dominates the dynamics of the galaxy. Modeling this halo as a sphericaly symmetric and static perfect fluid satisfying the field equations of General Relativity, visible barionic matter can be treated as ``test particles'' in the geometry of this field. We show that the assumption of an empirical ``universal rotation curve'' that fits a wide variety of galaxies is compatible, under suitable approximations, with state variables characteristic of a non-relativistic Maxwell-Boltzmann gas that becomes an isothermal sphere in the Newtonian limit. Consistency criteria lead to a minimal bound for particle masses in the range $30 \hbox{eV} \leq m \leq 60 \hbox{eV}$ and to a constraint between the central temperature and the particles mass. The allowed mass range includes popular supersymmetric particle candidates, such as the neutralino, axino and gravitino, as well as lighter particles ($m\approx$ keV) proposed by numerical N-body simulations associated with self-interactive CDM and WDM structure formation theories.Comment: LaTeX article style, 16 pages including three figures. Final version to appear in Classical and Quantum Gravit

Oral chondroitin sulfate and prebiotics for the treatment of canine Inflammatory Bowel Disease: a randomized, controlled clinical trial

BACKGROUND Canine inflammatory bowel disease (IBD) is a chronic enteropathy of unknown etiology, although microbiome dysbiosis, genetic susceptibility, and dietary and/or environmental factors are hypothesized to be involved in its pathogenesis. Since some of the current therapies are associated with severe side effects, novel therapeutic modalities are needed. A new oral supplement for long-term management of canine IBD containing chondroitin sulfate (CS) and prebiotics (resistant starch, β-glucans and mannaoligosaccharides) was developed to target intestinal inflammation and oxidative stress, and restore normobiosis, without exhibiting any side effects. This double-blinded, randomized, placebo-controlled trial in dogs with IBD aims to evaluate the effects of 180 days administration of this supplement together with a hydrolyzed diet on clinical signs, intestinal histology, gut microbiota, and serum biomarkers of inflammation and oxidative stress. RESULTS Twenty-seven client-owned biopsy-confirmed IBD dogs were included in the study, switched to the same hydrolyzed diet and classified into one of two groups: supplement and placebo. Initially, there were no significant differences between groups (p > 0.05) for any of the studied parameters. Final data analysis (supplement: n = 9; placebo: n = 10) showed a significant decrease in canine IBD activity index (CIBDAI) score in both groups after treatment (p < 0.001). After treatment, a significant decrease (1.53-fold; p < 0.01) in histologic score was seen only in the supplement group. When groups were compared, the supplement group showed significantly higher serum cholesterol (p < 0.05) and paraoxonase-1 (PON1) levels after 60 days of treatment (p < 0.01), and the placebo group showed significantly reduced serum total antioxidant capacity (TAC) levels after 120 days (p < 0.05). No significant differences were found between groups at any time point for CIBDAI, WSAVA histologic score and fecal microbiota evaluated by PCR-restriction fragment length polymorphism (PCR-RFLP). No side effects were reported in any group. CONCLUSIONS The combined administration of the supplement with hydrolyzed diet over 180 days was safe and induced improvements in selected serum biomarkers, possibly suggesting a reduction in disease activity. This study was likely underpowered, therefore larger studies are warranted in order to demonstrate a supplemental effect to dietary treatment of this supplement on intestinal histology and CIBDAI

The Expected Impacts of Climate Change on the Ocean Economy

The ocean is critically important to our global economy. Collectively, it is estimated that ocean-based industries and activities contribute hundreds of millions of jobs and approximately US $2.5 trillion to the global economy each year, making it the world’s seventh-largest economy when compared with national gross domestic products. In addition, the nonmarket services and benefts provided by the global ocean are signifcant and may in fact far exceed the value added by market-based goods and services. • Climate change is altering ocean climate, chemistry, circulation, sea level and ice distribution. Collectively, these system changes have critical impacts on the habitats, biological productivities and species assemblages that underpin many of the economic benefts of the sea. • Swift efforts to reduce anthropogenic greenhouse gas emissions are needed to maintain a robust ocean economy. The recent Intergovernmental Panel on Climate Change report estimates that climate-induced declines in ocean health will cost the global economy$428 billion/year by 2050 and $1.98 trillion/year by 2100. • Climate change is reducing the productivities and changing the spatial distributions of economically important marine species and their habitats. All countries stand to gain signifcant benefts relative to a business-as-usual trajectory by implementing climate-adaptive fsheries management reforms that address both changes in species’ distributions and productivities due to climate change. Many countries could maintain or improve profts and catches into the future with effective adaptation. • The potential of marine aquaculture (mariculture) is likely to remain high under climate change and, with careful planning, mariculture could offset losses in food and income from capture fsheries in those countries that will experience losses in that sector. Expanding the potential for marine aquaculture will require enhancing technical capac�ities, defning best practices, easing undue regulatory bur�dens, increasing access to credit and insurance, breeding stocks for faster growth and improving feed technology. • The combined effects of ocean warming and acidifcation result in predictions of negative impacts on coral reef cover and tourism values for all countries, with magnitudes dependent on the strength of climate change. For a high emissions scenario (Representative Concentration Pathway 8.5), coral cover is expected to decline by 72–87%, causing on-reef tourism values to decrease by over 90% in 2100. • Climate change impacts will differ by country and sector and solutions must be context-specifc. By exploring climate change impacts at the country level for fsheries, aquaculture and reef tourism, countries can assess what they stand to gain or lose due to climate change and understand how they might capitalise on these predictions to inform their investments and actions. • Implementing certain key strategies will help build socio�ecological resilience to climate change and ensure the continued, or improved, provision of functions and ser�vices from the ocean, especially for the most vulnerable coastal nations. These strategies include the following: – A focus on equity. Climate change is likely to cause and exacerbate global inequities, reducing resilience and thereby likely worsening outcomes under all climate change scenarios. It will thus be profoundly important to examine the equity implications of all new and existing management decisions across all three sectors. Looking forward. The future of the ocean economy is expected to drastically change given climate change, and the nature and magnitude of these changes can be highly variable. Each of these three sectors will need to work to understand risks and anticipate changes, and build precautionary and adaptive strategies into their management decisions. – Co-operating across boundaries. As suitable habitats shift and change, marine species will move across jurisdictional boundaries and regional, national and international cooperative agreements will be necessary to ensure that these species are well-managed, and that the benefts are fairly distributed during and after the transitions

Large-scale instability in interacting dark energy and dark matter fluids

If dark energy interacts with dark matter, this gives a new approach to the coincidence problem. But interacting dark energy models can suffer from pathologies. We consider the case where the dark energy is modelled as a fluid with constant equation of state parameter w. Non-interacting constant-w models are well behaved in the background and in the perturbed universe. But the combination of constant w and a simple interaction with dark matter leads to an instability in the dark sector perturbations at early times: the curvature perturbation blows up on super-Hubble scales. Our results underline how important it is to carefully analyze the relativistic perturbations when considering models of coupled dark energy. The instability that we find has been missed in some previous work where the perturbations were not consistently treated. The unstable mode dominates even if adiabatic initial conditions are used. The instability also arises regardless of how weak the coupling is. This non-adiabatic instability is different from previously discovered adiabatic instabilities on small scales in the strong-coupling regime.Comment: 15 pages, 5 figures. New reference; published versio

Large-scale instability in interacting dark energy and dark matter fluids

If dark energy interacts with dark matter, this gives a new approach to the coincidence problem. But interacting dark energy models can suffer from pathologies. We consider the case where the dark energy is modelled as a fluid with constant equation of state parameter w. Non-interacting constant-w models are well behaved in the background and in the perturbed universe. But the combination of constant w and a simple interaction with dark matter leads to an instability in the dark sector perturbations at early times: the curvature perturbation blows up on super-Hubble scales. Our results underline how important it is to carefully analyze the relativistic perturbations when considering models of coupled dark energy. The instability that we find has been missed in some previous work where the perturbations were not consistently treated. The unstable mode dominates even if adiabatic initial conditions are used. The instability also arises regardless of how weak the coupling is. This non-adiabatic instability is different from previously discovered adiabatic instabilities on small scales in the strong-coupling regime.Comment: 15 pages, 5 figures. New reference; published versio