Retrograde semaphorin-plexin signalling drives homeostatic synaptic plasticity.

Homeostatic signalling systems ensure stable but flexible neural activity and animal behaviour. Presynaptic homeostatic plasticity is a conserved form of neuronal homeostatic signalling that is observed in organisms ranging from Drosophila to human. Defining the underlying molecular mechanisms of neuronal homeostatic signalling will be essential in order to establish clear connections to the causes and progression of neurological disease. During neural development, semaphorin-plexin signalling instructs axon guidance and neuronal morphogenesis. However, semaphorins and plexins are also expressed in the adult brain. Here we show that semaphorin 2b (Sema2b) is a target-derived signal that acts upon presynaptic plexin B (PlexB) receptors to mediate the retrograde, homeostatic control of presynaptic neurotransmitter release at the neuromuscular junction in Drosophila. Further, we show that Sema2b-PlexB signalling regulates presynaptic homeostatic plasticity through the cytoplasmic protein Mical and the oxoreductase-dependent control of presynaptic actin. We propose that semaphorin-plexin signalling is an essential platform for the stabilization of synaptic transmission throughout the developing and mature nervous system. These findings may be relevant to the aetiology and treatment of diverse neurological and psychiatric diseases that are characterized by altered or inappropriate neural function and behaviour

New record of blunthead pufferfish, Sphoeroides pachygaster (Muller & Troschel, 1848 (Tetraodontiformes: Tetraodontidae) from Indian water along with DNA barcode and some biological aspects

Blunthead pufferfish, Sphoeroides pachygaster (Muller and Troschel 1848) was recorded for the first time in Indian seas. A single female specimen of S. pachygaster was caught in bottom trawl operation at 263 – 310 m depth of the Eastern Arabian Sea. Morphometric and meristic description are presented in detail and compared with the pertinent records available elsewhere. The specimen collected was fully matured with Gonado Somatic Index (GSI) of 17.9 %. Gonad occupied two-third of the abdominal cavity, ova diameters ranged between 0.45 and 0.6 mm and the absolute fecundity estimated was 0.238 million eggs. Histological studies revealed that, this species performs single spawning strategy and it is the first information on the reproduction of S. pachygaster in India. Available reports on the occurrence of this species indicated distribution in the Mediterranean Sea, Atlantic, Indian and Pacific Oceans; however, the present record confirms its distribution in the Arabian Sea. Wide variations in the meristic counts among the specimens of this species collected from various locations are also discussed. Molecular analysis of the present specimen using Mitochondrial 16S rRNA gene sequences, confirmed the identity as S. pachygaster with intra specific divergence of 00.0 – 0.04 %. This report is the first well documented, confirmed record and re-description of S. pachygaster from the Indian Ocean, which documents a new addition to the family, Tetraodontidae of the Indian ichthyofauna

Semaphorin-1a Is Required for Aedes aegypti Embryonic Nerve Cord Development

Although mosquito genome projects have uncovered orthologues of many known developmental regulatory genes, extremely little is known about mosquito development. In this study, the role of semaphorin-1a (sema1a) was investigated during vector mosquito embryonic ventral nerve cord development. Expression of sema1a and the plexin A (plexA) receptor are detected in the embryonic ventral nerve cords of Aedes aegypti (dengue vector) and Anopheles gambiae (malaria vector), suggesting that Sema1a signaling may regulate mosquito nervous system development. Analysis of sema1a function was investigated through siRNA-mediated knockdown in A. aegypti embryos. Knockdown of sema1a during A. aegypti development results in a number of nerve cord phenotypes, including thinning, breakage, and occasional fusion of the longitudinal connectives, thin or absent commissures, and general distortion of the nerve cord. Although analysis of Drosophila melanogaster sema1a loss-of-function mutants uncovered many similar phenotypes, aspects of the longitudinal phenotypes differed between D. melanogaster and A. aegypti. The results of this investigation suggest that Sema1a is required for development of the insect ventral nerve cord, but that the developmental roles of this guidance molecule have diverged in dipteran insects

Southeast Asia and the Politics of Vulnerability

The economic and political crises that have recently engulfed the countries of Southeast Asia provide a stark reminder of just how difficult the challenge of sustained regional development remains. In retrospect, the hyperbole that surrounded the 'East Asian miracle' looks overblown, and testimony to the manner in which rhetoric can outstrip reality, especially in the minds of international investors. Certainly, some observers had questioned the depth and resilience of capitalist development in Southeast Asia, but in the years immediately prior to 1997 such analyses tended to be in the minority. Now, of course, it is painfully obvious that much of Southeast Asia's economic and political development was extremely fragile. When seen in historical context, this outcome should not have been surprising since the countries of modern Southeast Asia, both as independent nations and as colonies of various imperial powers, have been highly vulnerable to the actions of powerful external political and economic forces. This paper will examine the economic bases and the political consequences of this vulnerablity, both domestically and at a regional level. I argue that the recent crisis has served as an unwelcome reminder of just how constrained, dependent and vulnerable the Southeast Asia region's development prospects remain, a situation that is exacerbated by, and which contributes to, domestic political crises

A meta-analysis of the association between day-care attendance and childhood acute lymphoblastic leukaemia

Background Childhood acute lymphoblastic leukaemia (ALL) may be the result of a rare response to common infection(s) acquired by personal contact with infected individuals. A meta-analysis was conducted to examine the relationship between day-care attendance and risk of childhood ALL, specifically to address whether early-life exposure to infection is protective against ALL

Suitability Of Nitisinone In Alkaptonuria 1 (SONIA 1): an international, multicentre, randomised, open-label, no-treatment controlled, parallel-group, dose-response study to investigate the effect of once daily nitisinone on 24-h urinary homogentisic acid excretion in patients with alkaptonuria after 4 weeks of treatment.

BACKGROUND: Alkaptonuria (AKU) is a serious genetic disease characterised by premature spondyloarthropathy. Homogentisate-lowering therapy is being investigated for AKU. Nitisinone decreases homogentisic acid (HGA) in AKU but the dose-response relationship has not been previously studied. METHODS: Suitability Of Nitisinone In Alkaptonuria 1 (SONIA 1) was an international, multicentre, randomised, open-label, no-treatment controlled, parallel-group, dose-response study. The primary objective was to investigate the effect of different doses of nitisinone once daily on 24-h urinary HGA excretion (u-HGA24) in patients with AKU after 4 weeks of treatment. Forty patients were randomised into five groups of eight patients each, with groups receiving no treatment or 1 mg, 2 mg, 4 mg and 8 mg of nitisinone. FINDINGS: A clear dose-response relationship was observed between nitisinone and the urinary excretion of HGA. At 4 weeks, the adjusted geometric mean u-HGA24 was 31.53 mmol, 3.26 mmol, 1.44 mmol, 0.57 mmol and 0.15 mmol for the no treatment or 1 mg, 2 mg, 4 mg and 8 mg doses, respectively. For the most efficacious dose, 8 mg daily, this corresponds to a mean reduction of u-HGA24 of 98.8% compared with baseline. An increase in tyrosine levels was seen at all doses but the dose-response relationship was less clear than the effect on HGA. Despite tyrosinaemia, there were no safety concerns and no serious adverse events were reported over the 4 weeks of nitisinone therapy. CONCLUSIONS: In this study in patients with AKU, nitisinone therapy decreased urinary HGA excretion to low levels in a dose-dependent manner and was well tolerated within the studied dose range. TRIAL REGISTRATION NUMBER: EudraCT number: 2012-005340-24. Registered at ClinicalTrials.gov: NCTO1828463

ASEAN's unchanged melody? The theory and practice of 'non-interference' in Southeast Asia

This is an Author's Accepted Manuscript of an article published as Jones, Lee. (2010). ASEAN's unchanged melody? The theory and practice of 'non-interference' in Southeast Asia. Pacific Review 23:4, 479-502 as published in PACIFIC REVIEW 2010 © Taylor & Francis, available online at: http://www.tandfonline.com/10.1080/09512748.2010.49599

From low-conflict polity to democratic civil peace: Explaining Zambian exceptionalism

An absence of civil war and other significant sub-state violence makes Zambia an exceptional although not unique case in central-southern Africa. The literature devoted to explaining civil war has grown dramatically in recent years, but while it pays much attention to sub-Saharan Africa only rarely does it investigate counterfactual cases like Zambia. Similarly the growing field of research into post-conflict reconstruction fails to capture the distinct features of persistently low-conflict situations where many of the predisposing conditions for violent conflict might seem to be present. This paper examines Zambia’s experience against a background of general theories that try to explain conflict. It is an “interpretative case study”. The paper proceeds by substantiating Zambia’s claim to a relatively peaceful record and introduces ideas of conflict and conflict theories, before arguing that no single general theory dwelling on just one primary “cause” will suffice to explain Zambian exceptionalism. The precise mix of arguments differs for each one Zambia’s three republican eras, as the potential threats to peace have themselves evolved over the period since independence. The paper’s main theoretical claim is that over time the explanation is both multi-layered and dynamic. That said, certain features do stand out, most notably an inherited political culture that is predisposed against the violent resolution of conflict and continues to insulate the country against social and economic traumas and democratic shortcomings