Large-scale network organization in the avian forebrain: a connectivity matrix and theoretical analysis

Many species of birds, including pigeons, possess demonstrable cognitive capacities, and some are capable of cognitive feats matching those of apes. Since mammalian cortex is laminar while the avian telencephalon is nucleated, it is natural to ask whether the brains of these two cognitively capable taxa, despite their apparent anatomical dissimilarities, might exhibit common principles of organisation on some level. Complementing recent investigations of macro-scale brain connectivity in mammals, including humans and macaques, we here present the first large-scale wiring diagram for the forebrain of a bird. Using graph theory, we show that the pigeon telencephalon is organised along similar lines to that of a mammal. Both are modular, small-world networks with a connective core of hub nodes that includes prefrontal-like and hippocampal structures. These hub nodes are, topologically speaking, the most central regions of the pigeon's brain, as well as being the most richly connected, implying a crucial role in information flow. Overall, our analysis suggests that indeed, despite the absence of cortical layers and close to 300 million years of separate evolution, the connectivity of the avian brain conforms to the same organisational principles as the mammalian brain

The Partial Information Decomposition of Generative Neural Network Models

In this work we study the distributed representations learnt by generative neural network models. In particular, we investigate the properties of redundant and synergistic information that groups of hidden neurons contain about the target variable. To this end, we use an emerging branch of information theory called partial information decomposition (PID) and track the informational properties of the neurons through training. We find two differentiated phases during the training process: a first short phase in which the neurons learn redundant information about the target, and a second phase in which neurons start specialising and each of them learns unique information about the target. We also find that in smaller networks individual neurons learn more specific information about certain features of the input, suggesting that learning pressure can encourage disentangled representations

Heavy-light decay constants from clover heavy quark action in QCD with two flavors of dynamical quarks

We present results on an analysis of the decay constants f_B and f_Bs with two flavours of sea quark. The calculation has been carried out on 3 different bare gauge couplings and 4 sea quark masses at each gauge coupling, with m_pi/m_rho ranging from 0.8 to 0.6. We employ the Fermilab formalism to perform calculations with heavy quarks whose mass is in the range of the b-quark. A detailed comparison with a quenched calculation using the same action is made to elucidate the effects due to the sea quarks.Comment: Contribution to Lattice 99 (Heavy Quarks). Latex file, uses espcrc2.sty and epsf.sty. 3 pages, 3 encapsulated postscript figure

The political and scientific challenges in evaluating compulsory drug treatment centers in Southeast Asia

BACKGROUND: In Vietnam, like many countries in Southeast Asia, the commonly used approach of center-based compulsory drug treatment (CCT) has been criticized on human rights ground. Meanwhile, community-based voluntary methadone maintenance treatment (MMT) has been implemented for nearly a decade with promising results. Reform-minded leaders have been seeking empirical evidence of the costs and effectiveness associated with these two main treatment modalities. Conducting evaluations of these treatments, especially where randomization is not ethical, presents challenges. The aim of this paper is to discuss political challenges and methodological issues when conducting cost-effectiveness studies within the context of a non-democratic Southeast Asian country. METHODS: A retrospective analysis of the political and scientific challenges that were experienced in the study design, sample size determination, government approval and ethics approvals, participant recruitment, data collection, and determination of sources, and quantification of cost and effectiveness data was undertaken. As a consequence of the non-randomized design, analysis of patient characteristics for both treatment types was undertaken to identify the magnitude of baseline group differences. Concordance between self-reported heroin use and urine drug testing was undertaken to determine the reliability of self-report data in a politically challenging environment. RESULTS: We demonstrate that conducting research around compulsory treatment in a non-democratic society is feasible, yet it is politically challenging and requires navigation between science and politics. We also demonstrate that engagement with the government decision makers in the research conception, implementation, and dissemination of the results increases the likelihood of research evidence being considered for change in a contentious drug policy area. CONCLUSIONS: Local empirical evidence on the comparative cost-effectiveness of CCT and MMT in a Southeast Asian setting is critical to consideration of more holistic, humane, and effective drug-dependence treatment approaches, but the garnering of such evidence is very challenging.Thu Vuong, Nhu Nguyen , Giang Le, Marian Shanahan, Robert Ali and Alison Ritte

Disruption of PCNA-lamins A/C interactions by prelamin A induces DNA replication fork stalling

The accumulation of prelamin A is linked to disruption of cellular homeostasis, tissue degeneration and aging. Its expression is implicated in compromised genome stability and increased levels of DNA damage, but to date there is no complete explanation for how prelamin A exerts its toxic effects. As the nuclear lamina is important for DNA replication we wanted to investigate the relationship between prelamin A expression and DNA replication fork stability. In this study we report that the expression of prelamin A in U2OS cells induced both mono-ubiquitination of proliferating cell nuclear antigen (PCNA) and subsequent induction of Pol η, two hallmarks of DNA replication fork stalling. Immunofluorescence microscopy revealed that cells expressing prelamin A presented with high levels of colocalisation between PCNA and γH2AX, indicating collapse of stalled DNA replication forks into DNA double-strand breaks. Subsequent protein-protein interaction assays showed prelamin A interacted with PCNA and that its presence mitigated interactions between PCNA and the mature nuclear lamina. Thus, we propose that the cytotoxicity of prelamin A arises in part, from it actively competing against mature lamin A to bind PCNA and that this destabilises DNA replication to induce fork stalling which in turn contributes to genomic instability

Full QCD light hadron spectrum from the CP-PACS

We report on an on-going two-flavor full QCD study on CP-PACS using an RG-improved gauge action and a tadpole-improved SW quark action. Runs are made for three lattice spacings $a^{-1}\approx 0.9$, 1.3, and 2.5 GeV on $12^3\times24$, $16^3\times32$, and $24^3\times48$ lattices. Four sea quark masses having $m_{\rm PS}/m_{\rm V} \approx 0.8$--0.6 are simulated, for each of which hadron masses are evaluated for valence quark masses corresponding to $m_{\rm PS}/m_{\rm V} \approx 0.8$--0.5. Results for hadron and light quark masses are presented and compared with those obtained in quenched QCD.Comment: LATTICE98(spectrum), 3 pages, 3 figure

Light hadron spectrum and quark masses in QCD with two flavors of dynamical quarks

We present updated results of the CP-PACS calculation of the light hadron spectrum in $N_{\rm f}=2$ full QCD. Simulations are made with an RG-improved gauge action and a tadpole-improved clover quark action for sea quark masses corresponding to $m_{\rm PS}/m_{\rm V} \approx 0.8$--0.6 and the lattice spacing $a=0.22$--0.09 fm. A comparison of the full QCD spectrum with new quenched results, obtained with the same improved action, shows clearly the existence of sea quark effects in vector meson masses. Results for light quark masses in $N_{\rm f}=2$ QCD are also presented.Comment: Latex 3 pages, 6 PostScript figures, Talk presented at LATTICE99(QCD Spectrum and Quark Masses

Heavy Quarkonia from Anisotropic and Isotropic Lattices

We report on recent results for the spectrum of heavy quarkonia. Using coarse and anisotropic lattices we achieved an unprecedented control over statistical and systematic errors for higher excited states such as exotic hybrid states. In a parallel study on isotropic lattices we also investigate the effect of two dynamical flavours on the spin structure of charmonium and bottomonium for several symmetric lattices.Comment: LATTICE'99 (heavy quarks), 3 pages, 3 figure

Prelamin A Accumulation Attenuates Rac1 Activity and Increases the Intrinsic Migrational Persistence of Aged Vascular Smooth Muscle Cells

Vascular smooth muscle cell (VSMC) motility is essential during both physiological and pathological vessel remodeling. Although ageing has emerged as a major risk factor in the development of cardiovascular disease, our understanding of the impact of ageing on VSMC motility remains limited. Prelamin A accumulation is known to drive VSMC ageing and we show that presenescent VSMCs, that have accumulated prelamin A, display increased focal adhesion dynamics, augmented migrational velocity/persistence and attenuated Rac1 activity. Importantly, prelamin A accumulation in proliferative VSMCs, induced by depletion of the prelamin A processing enzyme FACE1, recapitulated the focal adhesion, migrational persistence and Rac1 phenotypes observed in presenescent VSMCs. Moreover, lamin A/C-depleted VSMCs also display reduced Rac1 activity, suggesting that prelamin A influences Rac1 activity by interfering with lamin A/C function at the nuclear envelope. Taken together, these data demonstrate that lamin A/C maintains Rac1 activity in VSMCs and prelamin A disrupts lamin A/C function to reduce Rac1 activity and induce migrational persistence during VSMC ageing