The Arp2/3 Complex, UNC-115/abLIM, and UNC-34/Enabled Regulate Axon Guidance and Growth Cone Filopodia Formation in Caenorhabditis Elegans

Background While many molecules involved in axon guidance have been identified, the cellular and molecular mechanisms by which these molecules regulate growth cone morphology during axon outgrowth remain to be elucidated. The actin cytoskeleton of the growth cone underlies the formation of lamellipodia and filopodia that control growth cone outgrowth and guidance. The role of the Arp2/3 complex in growth cone filopodia formation has been controversial, and other mechanisms of growth cone filopodia formation remain to be described. Results Here we show that mutations in genes encoding the Arp2/3 complex (arx genes) caused defects in axon guidance. Analysis of developing growth cones in vivo showed that arx mutants displayed defects in filopodia and reduced growth cone size. Time-lapse analysis of growth cones in living animals indicated that arx mutants affected the rate of growth cone filopodia formation but not filopodia stability or length. Two other actin modulatory proteins, UNC-115/abLIM and UNC-34/Enabled, that had been shown previously to affect axon guidance had overlapping roles with Arp2/3 in axon guidance and also affected the rate of filopodia initiation but not stability or length. Conclusion Our results indicate that the Arp2/3 complex is required cell-autonomously for axon guidance and growth cone filopodia initiation. Furthermore, they show that two other actin-binding proteins, UNC-115/abLIM and UNC-34/Enabled, also control growth cone filopodia formation, possibly in parallel to Arp2/3. These studies indicate that, in vivo, multiple actin modulatory pathways including the Arp2/3 complex contribute to growth cone filopodia formation during growth cone outgrowth

The Arp2/3 complex, UNC-115/abLIM, and UNC-34/Enabled regulate axon guidance and growth cone filopodia formation in Caenorhabditis elegans

<p>Abstract</p> <p>Background</p> <p>While many molecules involved in axon guidance have been identified, the cellular and molecular mechanisms by which these molecules regulate growth cone morphology during axon outgrowth remain to be elucidated. The actin cytoskeleton of the growth cone underlies the formation of lamellipodia and filopodia that control growth cone outgrowth and guidance. The role of the Arp2/3 complex in growth cone filopodia formation has been controversial, and other mechanisms of growth cone filopodia formation remain to be described.</p> <p>Results</p> <p>Here we show that mutations in genes encoding the Arp2/3 complex (<it>arx </it>genes) caused defects in axon guidance. Analysis of developing growth cones <it>in vivo </it>showed that <it>arx </it>mutants displayed defects in filopodia and reduced growth cone size. Time-lapse analysis of growth cones in living animals indicated that <it>arx </it>mutants affected the rate of growth cone filopodia formation but not filopodia stability or length. Two other actin modulatory proteins, UNC-115/abLIM and UNC-34/Enabled, that had been shown previously to affect axon guidance had overlapping roles with Arp2/3 in axon guidance and also affected the rate of filopodia initiation but not stability or length.</p> <p>Conclusion</p> <p>Our results indicate that the Arp2/3 complex is required cell-autonomously for axon guidance and growth cone filopodia initiation. Furthermore, they show that two other actin-binding proteins, UNC-115/abLIM and UNC-34/Enabled, also control growth cone filopodia formation, possibly in parallel to Arp2/3. These studies indicate that, <it>in vivo</it>, multiple actin modulatory pathways including the Arp2/3 complex contribute to growth cone filopodia formation during growth cone outgrowth.</p

Monte Carlo inference and maximization for phrase-based translation

Recent advances in statistical machine translation have used beam search for approximate NP-complete inference within probabilistic translation models. We present an alternative approach of sampling from the posterior distribution defined by a translation model. We define a novel Gibbs sampler for sampling translations given a source sentence and show that it effectively explores this posterior distribution. In doing so we overcome the limitations of heuristic beam search and obtain theoretically sound solutions to inference problems such as finding the maximum probability translation and minimum expected risk training and decoding.

Controlled diastereoselectivity at the alkene-geometry through selective encapsulation: E-Z photoisomerization of oxazolidinone-functionalized enecarbamates within hydrophobic nano-cavities

Photoisomerization of encapsulated Z-enecarbamates within the hydrophobic chiral cavities of γ-CD showed higher diastereoselectivities in the photoproducts than those obtained in solution. The selective encapsulation of the enecarbamates and the following isomerization process are both diastereoselectively controlled by γ-CD

Dementia diagnosis and referral in general practice: a representative survey of Irish general practitioners

Aims: Most of those with a memory problem or concern over cognition present to their General Practitioner (GP) in the first instance. Despite this, the current diagnostic and referral patterns of Irish GPs remains unclear. Methods: A survey was distributed to three separate cohorts of GPs (n=692) Results: Ninety-Five (14%) responded. Most personally diagnose 1-3 (69%; 65/95) or 4-6 (21%; 20/95) patients with dementia per year. Two-thirds (62%; 59/95) refer >80% of those with possible dementia for further assessment/support, most commonly to support/clarify a diagnosis (71%; 67/95) and most frequently to a geriatrician (79%; 75/95). In half of cases (51%; 48/95), referral is to a professional working as part of an established memory clinic. One-fifth reported receiving dementia-specific postgraduate training (19%; 18/95) and over four-fifths (82%; 78/95) would welcome further training. Discussion: Further attention to the ongoing establishment of memory clinic services and dedicated referral pathways, as well as increasing emphasis on dementia assessment and diagnosis in medical curricula, is warranted

Energy and eventhood: the infrastructural set piece

‘Energy and Eventhood’ considers the relationship between infrastructure and the cinematic set piece. It proposes a working definition of the set piece as a distinctly (and perhaps excessively) effortful passage or sequence, and reflects on the tendency for narrative films to incorporate infrastructural sites and structures—such as bridges, dams and pipelines—into such set pieces. A number of writers on infrastructure, as both a cultural phenomenon and a representational object, have noted the aesthetic challenge of rendering it as visible and locatable; this article examines how that difficulty becomes manifest in the infrastructural set piece. It takes as its case studies Unstoppable (2010) and Night Moves (2013), two films noted for their distinctive rhythmic expressiveness, and each one deploying the convention of the set piece in ways which exemplify and reflect on the resistance of infrastructure to narrative containment

Long‐term anticholinergic, benzodiazepine and Z‐drug use in community‐dwelling older adults: What is the impact on cognitive and neuropsychological performance?

BACKGROUND Long-term use of anticholinergics, benzodiazepines and related drugs (or "Z-drugs") have been associated with cognitive impairment and dementia. However, the relationship of these medications with cognitive function and domain-specific neuropsychological performance in older adults without dementia, is unclear. METHODS 5135 older adults (74.0 ± 8.3 years; 67.4% female) without a diagnosis of dementia were recruited in Ireland to the Trinity-Ulster-Department of Agriculture (TUDA) study. Detailed cognitive and neuropsychological assessment was conducted using the Mini-Mental State Examination (MMSE), Frontal Assessment Battery (FAB) and Repeatable Battery for Assessment of Neuropsychological Status (RBANS). RESULTS A total of 44% (2259 of 5153) used either a potential or definite anticholinergic medication. Overall, 9.7% (n = 500) used a definite anticholinergic medication. Regular benzodiazepine use was reported by 7% (n = 363), whilst 7.5% (n = 387) used a "Z-drug". Use of definite, but not potential anticholinergic medication was associated with poorer performance on all three assessments (β: -0.09; 95% CI: -0.14, -0.03, p = 0.002 for MMSE; β: -0.04; 95% CI: -0.06, -0.02; p < 0.001 for FAB; β: -4.15; 95% CI: -5.64, -2.66; p < 0.001 for RBANS) in addition to all domains of the RBANS. Regular benzodiazepine use was also associated with poorer neuropsychological test performance, especially in Immediate Memory (β: -4.98; 95% CI: -6.81, -3.15; p < 0.001) and Attention (β: -6.81; 95% CI: -8.60, -5.03; p < 0.001) RBANS domains. CONCLUSIONS Regular use of definite anticholinergic medications and benzodiazepines, but not potential anticholinergics or "Z-drugs", was associated with poorer overall and domain-specific neuropsychological performance in older adults