A Conceptual Cortical Surface Atlas

Volumetric, slice-based, 3-D atlases are invaluable tools for understanding complex cortical convolutions. We present a simple scheme to convert a slice-based atlas to a conceptual surface atlas that is easier to visualize and understand. The key idea is to unfold each slice into a one-dimensional vector, and concatenate a succession of these vectors – while maintaining as much spatial contiguity as possible – into a 2-D matrix. We illustrate our methodology using a coronal slice-based atlas of the Rhesus Monkey cortex. The conceptual surface-based atlases provide a useful complement to slice-based atlases for the purposes of indexing and browsing

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

Concurrence of form and function in developing networks and its role in synaptic pruning

A fundamental question in neuroscience is how structure and function of neural systems are related. We study this interplay by combining a familiar auto-associative neural network with an evolving mechanism for the birth and death of synapses. A feedback loop then arises leading to two qualitatively different types of behaviour. In one, the network structure becomes heterogeneous and dissasortative, and the system displays good memory performance; furthermore, the structure is optimised for the particular memory patterns stored during the process. In the other, the structure remains homogeneous and incapable of pattern retrieval. These findings provide an inspiring picture of brain structure and dynamics that is compatible with experimental results on early brain development, and may help to explain synaptic pruning. Other evolving networks—such as those of protein interactions—might share the basic ingredients for this feedback loop and other questions, and indeed many of their structural features are as predicted by our model.We are grateful for financial support from the Spanish MINECO (project of Excellence: FIS2017-84256-P) and from “Obra Social La Caixa”

New approaches to measuring anthelminthic drug efficacy: parasitological responses of childhood schistosome infections to treatment with praziquantel

By 2020, the global health community aims to control and eliminate human helminthiases, including schistosomiasis in selected African countries, principally by preventive chemotherapy (PCT) through mass drug administration (MDA) of anthelminthics. Quantitative monitoring of anthelminthic responses is crucial for promptly detecting changes in efficacy, potentially indicative of emerging drug resistance. Statistical models offer a powerful means to delineate and compare efficacy among individuals, among groups of individuals and among populations.; We illustrate a variety of statistical frameworks that offer different levels of inference by analysing data from nine previous studies on egg counts collected from African children before and after administration of praziquantel.; We quantify responses to praziquantel as egg reduction rates (ERRs), using different frameworks to estimate ERRs among population strata, as average responses, and within strata, as individual responses. We compare our model-based average ERRs to corresponding model-free estimates, using as reference the World Health Organization (WHO) 90 % threshold of optimal efficacy. We estimate distributions of individual responses and summarize the variation among these responses as the fraction of ERRs falling below the WHO threshold.; Generic models for evaluating responses to anthelminthics deepen our understanding of variation among populations, sub-populations and individuals. We discuss the future application of statistical modelling approaches for monitoring and evaluation of PCT programmes targeting human helminthiases in the context of the WHO 2020 control and elimination goals

Towards neuro-inspired symbolic models of cognition: linking neural dynamics to behaviors through asynchronous communications

A computational architecture modeling the relation between perception and action is proposed. Basic brain processes representing synaptic plasticity are first abstracted through asynchronous communication protocols and implemented as virtual microcircuits. These are used in turn to build mesoscale circuits embodying parallel cognitive processes. Encoding these circuits into symbolic expressions gives finally rise to neuro-inspired programs that are compiled into pseudo-code to be interpreted by a virtual machine. Quantitative evaluation measures are given by the modification of synapse weights over time. This approach is illustrated by models of simple forms of behaviors exhibiting cognition up to the third level of animal awareness. As a potential benefit, symbolic models of emergent psychological mechanisms could lead to the discovery of the learning processes involved in the development of cognition. The executable specifications of an experimental platform allowing for the reproduction of simulated experiments are given in “Appendix”

Rh-POP Pincer Xantphos Complexes for C-S and C-H Activation. Implications for Carbothiolation Catalysis

The neutral Rh­(I)–Xantphos complex [Rh­(κ³-_P,O,P-Xantphos)­Cl]_<i>n</i>, <b>4</b>, and cationic Rh­(III) [Rh­(κ³-_P,O,P-Xantphos)­(H)₂]­[BAr^F₄], <b>2a</b>, and [Rh­(κ³-_P,O,P-Xantphos-3,5-C₆H₃(CF₃)₂)­(H)₂]­[BAr^F₄], <b>2b</b>, are described [Ar^F = 3,5-(CF₃)₂C₆H₃; Xantphos = 4,5-bis­(diphenylphosphino)-9,9-dimethylxanthene; Xantphos-3,5-C₆H₃(CF₃)₂ = 9,9-dimethylxanthene-4,5-bis­(bis­(3,5-bis­(trifluoromethyl)­phenyl)­phosphine]. A solid-state structure of <b>2b</b> isolated from C₆H₅Cl solution shows a κ¹-chlorobenzene adduct, [Rh­(κ³-_P,O,P-Xantphos-3,5-C₆H₃(CF₃)₂)­(H)₂(κ¹-ClC₆H₅)]­[BAr^F₄], <b>3</b>. Addition of H₂ to <b>4</b> affords, crystallographically characterized, [Rh­(κ³-_P,O,P-Xantphos)­(H)₂Cl], <b>5</b>. Addition of diphenyl acetylene to <b>2a</b> results in the formation of the C–H activated metallacyclopentadiene [Rh­(κ³-_P,O,P-Xantphos)­(ClCH₂Cl)­(σ,σ-(C₆H₄)­C­(H)CPh)]­[BAr^F₄], <b>7</b>, a rare example of a crystallographically characterized Rh–dichloromethane complex, alongside the Rh­(I) complex <i>mer</i>-[Rh­(κ³-_P,O,P-Xantphos)­(η²-PhCCPh)]­[BAr^F₄], <b>6</b>. Halide abstraction from [Rh­(κ³-_P,O,P-Xantphos)­Cl]_<i>n</i> in the presence of diphenylacetylene affords <b>6</b> as the only product, which in the solid state shows that the alkyne binds perpendicular to the κ³-POP Xantphos ligand plane. This complex acts as a latent source of the [Rh­(κ³-_P,O,P-Xantphos)]⁺ fragment and facilitates <i>ortho</i>-directed C–S activation in a number of 2-arylsulfides to give <i>mer</i>-[Rh­(κ³-_P,O,P-Xantphos)­(σ,κ¹-Ar)­(SMe)]­[BAr^F₄] (Ar = C₆H₄COMe, <b>8</b>; C₆H₄(CO)­OMe, <b>9</b>; C₆H₄NO₂, <b>10</b>; C₆H₄CNCH₂CH₂O, <b>11</b>; C₆H₄C₅H₄N, <b>12</b>). Similar C–S bond cleavage is observed with allyl sulfide, to give <i>fac</i>-[Rh­(κ³-_P,O,P-Xantphos)­(η³-C₃H₅)­(SPh)]­[BAr^F₄], <b>13</b>. These products of C–S activation have been crystallographically characterized. For <b>8</b> in situ monitoring of the reaction by NMR spectroscopy reveals the initial formation of <i>fac</i>-κ³-<b>8</b>, which then proceeds to isomerize to the <i>mer</i>-isomer. With the <i>para</i>-ketone aryl sulfide, 4-SMeC ₆H₄COMe, C–H activation <i>ortho</i> to the ketone occurs to give <i>mer</i>-[Rh­(κ³-_P,O,P-Xantphos)­(σ,κ¹-4-(COMe)­C₆H₃SMe)­(H)]­[BAr^F₄], <b>14</b>. The temporal evolution of carbothiolation catalysis using <i>mer</i>-κ³-<b>8</b>, and phenyl acetylene and 2-(methylthio)­acetophenone substrates shows initial fast catalysis and then a considerably slower evolution of the product. We suggest that the initially formed <i>fac</i>-isomer of the C–S activation product is considerably more active than the <i>mer</i>-isomer (i.e., <i>mer</i>-<b>8</b>), the latter of which is formed rapidly by isomerization, and this accounts for the observed difference in rates. A likely mechanism is proposed based upon these data

Network Structure Implied by Initial Axon Outgrowth in Rodent Cortex: Empirical Measurement and Models

The developmental mechanisms by which the network organization of the adult cortex is established are incompletely understood. Here we report on empirical data on the development of connections in hamster isocortex and use these data to parameterize a network model of early cortical connectivity. Using anterograde tracers at a series of postnatal ages, we investigate the growth of connections in the early cortical sheet and systematically map initial axon extension from sites in anterior (motor), middle (somatosensory) and posterior (visual) cortex. As a general rule, developing axons extend from all sites to cover relatively large portions of the cortical field that include multiple cortical areas. From all sites, outgrowth is anisotropic, covering a greater distance along the medial/lateral axis than along the anterior/posterior axis. These observations are summarized as 2-dimensional probability distributions of axon terminal sites over the cortical sheet. Our network model consists of nodes, representing parcels of cortex, embedded in 2-dimensional space. Network nodes are connected via directed edges, representing axons, drawn according to the empirically derived anisotropic probability distribution. The networks generated are described by a number of graph theoretic measurements including graph efficiency, node betweenness centrality and average shortest path length. To determine if connectional anisotropy helps reduce the total volume occupied by axons, we define and measure a simple metric for the extra volume required by axons crossing. We investigate the impact of different levels of anisotropy on network structure and volume. The empirically observed level of anisotropy suggests a good trade-off between volume reduction and maintenance of both network efficiency and robustness. Future work will test the model's predictions for connectivity in larger cortices to gain insight into how the regulation of axonal outgrowth may have evolved to achieve efficient and economical connectivity in larger brains

Measuring macroscopic brain connections in vivo

Decades of detailed anatomical tracer studies in non-human animals point to a rich and complex organization of long-range white matter connections in the brain. State-of-the art in vivo imaging techniques are striving to achieve a similar level of detail in humans, but multiple technical factors can limit their sensitivity and fidelity. In this review, we mostly focus on magnetic resonance imaging of the brain. We highlight some of the key challenges in analyzing and interpreting in vivo connectomics data, particularly in relation to what is known from classical neuroanatomy in laboratory animals. We further illustrate that, despite the challenges, in vivo imaging methods can be very powerful and provide information on connections that is not available by any other means

Finding a Needle in the Virus Metagenome Haystack - Micro-Metagenome Analysis Captures a Snapshot of the Diversity of a Bacteriophage Armoire

Viruses are ubiquitous in the oceans and critical components of marine microbial communities, regulating nutrient transfer to higher trophic levels or to the dissolved organic pool through lysis of host cells. Hydrothermal vent systems are oases of biological activity in the deep oceans, for which knowledge of biodiversity and its impact on global ocean biogeochemical cycling is still in its infancy. In order to gain biological insight into viral communities present in hydrothermal vent systems, we developed a method based on deep-sequencing of pulsed field gel electrophoretic bands representing key viral fractions present in seawater within and surrounding a hydrothermal plume derived from Loki's Castle vent field at the Arctic Mid-Ocean Ridge. The reduction in virus community complexity afforded by this novel approach enabled the near-complete reconstruction of a lambda-like phage genome from the virus fraction of the plume. Phylogenetic examination of distinct gene regions in this lambdoid phage genome unveiled diversity at loci encoding superinfection exclusion- and integrase-like proteins. This suggests the importance of fine-tuning lyosgenic conversion as a viral survival strategy, and provides insights into the nature of host-virus and virus-virus interactions, within hydrothermal plumes. By reducing the complexity of the viral community through targeted sequencing of prominent dsDNA viral fractions, this method has selectively mimicked virus dominance approaching that hitherto achieved only through culturing, thus enabling bioinformatic analysis to locate a lambdoid viral “needle" within the greater viral community “haystack". Such targeted analyses have great potential for accelerating the extraction of biological knowledge from diverse and poorly understood environmental viral communities

Epidemiology and interactions of Human Immunodeficiency Virus - 1 and Schistosoma mansoni in sub-Saharan Africa.

Human Immunodeficiency Virus-1/AIDS and Schistosoma mansoni are widespread in sub-Saharan Africa and co-infection occurs commonly. Since the early 1990s, it has been suggested that the two infections may interact and potentiate the effects of each other within co-infected human hosts. Indeed, S. mansoni infection has been suggested to be a risk factor for HIV transmission and progression in Africa. If so, it would follow that mass deworming could have beneficial effects on HIV-1 transmission dynamics. The epidemiology of HIV in African countries is changing, shifting from urban to rural areas where the prevalence of Schistosoma mansoni is high and public health services are deficient. On the other side, the consequent pathogenesis of HIV-1/S. mansoni co-infection remains unknown. Here we give an account of the epidemiology of HIV-1 and S. mansoni, discuss co-infection and possible biological causal relationships between the two infections, and the potential impact of praziquantel treatment on HIV-1 viral loads, CD4+ counts and CD4+/CD8+ ratio. Our review of the available literature indicates that there is evidence to support the hypothesis that S. mansoni infections can influence the replication of the HIV-1, cell-to-cell transmission, as well as increase HIV progression as measured by reduced CD4+ T lymphocytes counts. If so, then deworming of HIV positive individuals living in endemic areas may impact on HIV-1 viral loads and CD4+ T lymphocyte counts.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