The generalized identification of truly interfacial molecules (ITIM) algorithm for nonplanar interfaces

We present a generalized version of the ITIM algorithm for the identification of interfacial molecules, which is able to treat arbitrarily shaped interfaces. The algorithm exploits the similarities between the concept of probe sphere used in ITIM and the circumsphere criterion used in the α-shapes approach, and can be regarded either as a reference-frame independent version of the former, or as an extended version of the latter that includes the atomic excluded volume. The new algorithm is applied to compute the intrinsic orientational order parameters of water around a dodecylphosphocholine and a cholic acid micelle in aqueous environment, and to the identification of solvent-reachable sites in four model structures for soot. The additional algorithm introduced for the calculation of intrinsic density profiles in arbitrary geometries proved to be extremely useful also for planar interfaces, as it allows to solve the paradox of smeared intrinsic profiles far from the interface. © 2013 American Institute of Physics

Visual responses of neurons in the middle temporal area of new World Monkeys after lesions of striate cortex

In primates, lesions of striate cortex (V1) result in scotomas in which only rudimentary visual abilities remain. These aspects of vision that survive V1 lesions have been attributed to direct thalamic pathways to extrastriate areas, including the middle temporal area (MT). However, studies in New World monkeys and humans have questioned this interpretation, suggesting that remnants of V1 are responsible for both the activation of MT and residual vision. We studied the visual responses of neurons in area MT in New World marmoset monkeys in the weeks after lesions of V1. The extent of the scotoma in each case was estimated by mapping the receptive fields of cells located near the lesion border and by histological reconstruction. Two response types were observed among the cells located in the part of MT that corresponds, in visuotopic coordinates, to the lesioned part of V1. Many neurons (62%) had receptive fields that were displaced relative to their expected location, so that they represented the visual field immediately surrounding the scotoma. This may be a consequence of a process analogous to the reorganization of the V1 map after retinal lesions. However, another 20% of the cells had receptive fields centered inside the scotoma. Most of these neurons were strongly direction-selective, similar to normal MT cells. These results show that MT cells differ in their responses to lesioning of V1 and that only a subpopulation of MT neurons can be reasonably linked to residual vision and blindsight

Fates and Travel Times of Denmark Strait Overflow Water in the Irminger Basin*

The Denmark Strait Overflow (DSO) supplies about one-third of the North Atlantic Deep Water and is critical to global thermohaline circulation. Knowledge of the pathways of DSO through the Irminger Basin and its transformation there is still incomplete, however. The authors deploy over 10 000 Lagrangian particles at the Denmark Strait in a high-resolution ocean model to study these issues. First, the particle trajectories show that the mean position and potential density of dense waters cascading over the Denmark Strait sill evolve consistently with hydrographic observations. These sill particles transit the Irminger Basin to the Spill Jet section (65.25°N) in 5–7 days and to the Angmagssalik section (63.5°N) in 2–3 weeks. Second, the dense water pathways on the continental shelf are consistent with observations and particles released on the shelf in the strait constitute a significant fraction of the dense water particles recorded at the Angmagssalik section within 60 days (~25%). Some particles circulate on the shelf for several weeks before they spill off the shelf break and join the overflow from the sill. Third, there are two places where the water density following particle trajectories decreases rapidly due to intense mixing: to the southwest of the sill and southwest of the Kangerdlugssuaq Trough on the continental slope. After transformation in these places, the overflow particles exhibit a wide range of densities

Exposure to pesticides and risk of amyotrophic lateral sclerosis: a population-based case-control study

A few epidemiologic studies have suggested an association of agricultural work and pesticidesexposure with a severe degenerative disease of the motor neurons, amyotrophic lateral sclerosis(ALS), though conflicting results have also been provided. We investigated through a populationbasedcase-control study the possible relation between overall occupational exposure to pesticidesand ALS risk in the northern Italy municipality of Reggio Emilia. By administering a questionnaire,we investigated occupational history and leisure-time habits of the 41 ALS patients diagnosed in the1995-2006 period, and of 82 age- and sex-matched randomly sampled population controls. Morecases than controls were found to have been exposed to pesticides for at least six months (31.7% vs13.4%, respectively), in all cases within the occupational environment. In a conditional logistic regressionmodel, we found an excess ALS risk associated with exposure to pesticides, with a relativerisk of 3.6 (95% confidence interval 1.2-10.5). Such association persisted after inclusion in the statisticalanalysis of potential confounders. Despite the limited statistical stability of the risk estimates,these results appear to indicate that occupational exposure to pesticides is a risk factor for ALS,suggesting the need to further investigate this issue

Dynamic imaging of dendritic cell extension into the small bowel lumen in response to epithelial cell TLR engagement

Cells lining the gastrointestinal tract serve as both a barrier to and a pathway for infectious agent entry. Dendritic cells (DCs) present in the lamina propria under the columnar villus epithelium of the small bowel extend processes across this epithelium and capture bacteria, but previous studies provided limited information on the nature of the stimuli, receptors, and signaling events involved in promoting this phenomenon. Here, we use immunohistochemical as well as dynamic explant and intravital two-photon imaging to investigate this issue. Analysis of CD11c–enhanced green fluorescent protein (EGFP) or major histocompatibility complex CII-EGFP mice revealed that the number of trans-epithelial DC extensions, many with an unusual “balloon” shape, varies along the length of the small bowel. High numbers of such extensions were found in the proximal jejunum, but only a few were present in the terminal ileum. The extensions in the terminal ileum markedly increased upon the introduction of invasive or noninvasive Salmonella organisms, and chimeric mouse studies revealed the key role of MyD88-dependent Toll-like receptor (TLR) signaling by nonhematopoietic (epithelial) elements in the DC extension response. Collectively, these findings support a model in which epithelial cell TLR signaling upon exposure to microbial stimuli induces active DC sampling of the gut lumen at sites distant from organized lymphoid tissues

Essential role of diastolic oscillatory potentials in adrenergic control of guinea pig sino-atrial node discharge

Background: The diastolic oscillatory after-potential Vos and pre-potential ThVos play an essential role in the pacemaker mechanism of sino-atrial node (SAN). The aim of this study was to investigate whether these oscillatory potentials are also involved in adrenergic control of SAN discharge. Methods: Vos and ThVos were visualized by superfusing guinea pig SAN in high [K+]o. The actions of adrenergic agonists on oscillatory potentials were studied by means of a microelectrode technique. Statistical significance was determined by means of Student's paired t-test. Results: In non-spontaneous SAN, norepinephrine (NE) decreased the resting potential into a voltage range ("oscillatory zone") where increasingly larger ThVos appeared and initiated spontaneous discharge. In slowly discharging SAN, NE gradually increased the rate by increasing the amplitude and slope of earlier-occurring ThVos and of Vos until these oscillations fused with initial diastolic depolarization (DD1). In the presence of NE, sudden fast rhythms were initiated by large Vos that entered a more negative oscillatory zone and initiated a large ThVos. Recovery from NE exposure involved the converse changes. The β-adrenergic agonist isoproterenol had similar actions. Increasing calcium load by decreasing high [K+]o, by fast drive or by recovery in Tyrode solution led to growth of Vos and ThVos which abruptly fused when a fast sudden rhythm was induced. Low [Ca2+]o antagonized the adrenergic actions. Cesium (a blocker of If) induced spontaneous discharge in quiescent SAN through ThVos. In spontaneous SAN, Cs+increased Vos and ThVos, thereby increasing the rate. Cs+ did not hinder the positive chronotropic action of NE. Barium increased the rate, as Cs+ did. Conclusion: Adrenergic agonists: (i) initiate SAN discharge by decreasing the resting potential and inducing ThVos; (ii) gradually accelerate SAN rate by predominantly increasing size and slope of earlier and more negative ThVos; (iii) can induce sudden fast rhythms through the abrupt fusion of large Vos with large ThVos; (iv) increase Vos and ThVosby increasing cellular calcium; and (v) do not modify the oscillatory potentials by means of the hyperpolarization-activated current If. The results provide evidence for novel mechanisms by which the SAN dominant pacemaker activity is initiated and enhanced by adrenergic agonists