E-cadherin and cell adhesion: a role in architecture and function in the pancreatic islet

Background/Aims: The efficient secretion of insulin from beta-cells requires extensive intra-islet communication. The cell surface adhesion protein epithelial (E)-cadherin (ECAD) establishes and maintains epithelial tissues such as the islets of Langerhans. In this study, the role of ECAD in regulating insulin secretion from pseudoislets was investigated. Methods: The effect of an immuno-neutralising ECAD on gross morphology, cytosolic calcium signalling, direct cell-to-cell communication and insulin secretion was assessed by fura-2 microfluorimetry, Lucifer Yellow dye injection and insulin ELISA in an insulin-secreting model system. Results: Antibody blockade of ECAD reduces glucose-evoked changes in [Ca2+](i) and insulin secretion. Neutralisation of ECAD causes a breakdown in the glucose-stimulated synchronicity of calcium oscillations between discrete regions within the pseudoislet, and the transfer of dye from an individual cell within a cell cluster is attenuated in the absence of ECAD ligation, demonstrating that gap junction communication is disrupted. The functional consequence of neutralising ECAD is a significant reduction in insulin secretion. Conclusion: Cell adhesion via ECAD has distinct roles in the regulation of intercellular communication between beta-cells within islets, with potential repercussions for insulin secretion. Copyright (C) 2007 S. Karger AG, Basel

Sr-Nd isotope geochemistry of the early Precambrian sub-alkaline mafic igneous rocks from the southern Bastar craton, Central India

Sr–Nd isotope data are reported for the early Precambrian sub-alkaline mafic igneous rocks of the southern Bastar craton, central India. These mafic rocks are mostly dykes but there are a few volcanic exposures. Field relationships together with the petrological and geochemical characteristics of these mafic dykes divide them into two groups; Meso-Neoarchaean sub-alkaline mafic dykes (BD1) and Paleoproterozoic (1.88 Ga) sub-alkaline mafic dykes (BD2). The mafic volcanics are Neoarchaean in age and have very close geochemical relationships with the BD1 type. The two groups have distinctly different concentrations of high-field strength (HFSE) and rare earth elements (REE). The BD2 dykes have higher concentrations of HFSE and REE than the BD1 dykes and associated volcanics and both groups have very distinctive petrogenetic histories. These rocks display a limited range of initial 143Nd/144Nd but a wide range of apparent initial 87Sr/86Sr. Initial 143Nd/144Nd values in the BD1 dykes and associated volcanics vary between 0.509149 and 0.509466 and in the BD2 dykes the variation is between 0.510303 and 0.510511. All samples have positive εNd values the BD1 dykes and associated volcanics have εNd values between +0.3 and +6.5 and the BD2 dykes between +1.9 to +6.0. Trace element and Nd isotope data do not suggest severe crustal contamination during the emplacement of the studied rocks. The positive εNd values suggest their derivation from a depleted mantle source. Overlapping positive εNd values suggest that a similar mantle source tapped by variable melt fractions at different times was responsible for the genesis of BD1 (and associated volcanics) and BD2 mafic dykes. The Rb–Sr system is susceptible to alteration and resetting during post-magmatic alteration and metamorphism. Many of the samples studied have anomalous apparent initial 87Sr/86Sr suggesting post-magmatic changes of the Rb–Sr system which severely restricts the use of Rb–Sr for petrogenetic interpretation

Inconsistent boundaries

Research on this paper was supported by a grant from the Marsden Fund, Royal Society of New Zealand.Mereotopology is a theory of connected parts. The existence of boundaries, as parts of everyday objects, is basic to any such theory; but in classical mereotopology, there is a problem: if boundaries exist, then either distinct entities cannot be in contact, or else space is not topologically connected (Varzi in Noûs 31:26–58, 1997). In this paper we urge that this problem can be met with a paraconsistent mereotopology, and sketch the details of one such approach. The resulting theory focuses attention on the role of empty parts, in delivering a balanced and bounded metaphysics of naive space.PostprintPeer reviewe

Impact of Scotland’s comprehensive, smoke-free legislation on stroke

<p>Background: Previous studies have reported a reduction in acute coronary events following smoke-free legislation. Evidence is lacking on whether stroke is also reduced. The aim was to determine whether the incidence of stroke, overalland by sub-type, fell following introduction of smoke-free legislation across Scotland on 26 March 2006.</p> <p>Methods and Findings: A negative binomial regression model was used to determine whether the introduction of smokefree legislation resulted in a step and/or slope change in stroke incidence. The model was adjusted for age-group, sex, socioeconomic deprivation quintile, urban/rural residence and month. Interaction tests were also performed. Routine hospital administrative data and death certificates were used to identify all hospital admissions and pre-hospital deaths due to stroke (ICD10 codes I61, I63 and I64) in Scotland between 2000 and 2010 inclusive. Prior to the legislation, rates of all stroke, intracerebral haemorrhage and unspecified stroke were decreasing, whilst cerebral infarction was increasing at 0.97% per annum. Following the legislation, there was a dramatic fall in cerebral infarctions that persisted for around 20 months. No visible effect was observed for other types of stroke. The model confirmed an 8.90% (95% CI 4.85, 12.77, p,0.001) stepwise reduction in cerebral infarction at the time the legislation was implemented, after adjustment for potential cofounders.</p> <p>Conclusions: Following introduction of national, comprehensive smoke-free legislation there was a selective reduction in cerebral infarction that was not apparent in other types of stroke.</p&gt

Population Genetics of Franciscana Dolphins (Pontoporia blainvillei): Introducing a New Population from the Southern Edge of Their Distribution

Due to anthropogenic factors, the franciscana dolphin, Pontoporia blainvillei, is the most threatened small cetacean on the Atlantic coast of South America. Four Franciscana Management Areas have been proposed: Espiritu Santo to Rio de Janeiro (FMA I), São Paulo to Santa Catarina (FMA II), Rio Grande do Sul to Uruguay (FMA III), and Argentina (FMA IV). Further genetic studies distinguished additional populations within these FMAs. We analyzed the population structure, phylogeography, and demographic history in the southernmost portion of the species range. From the analysis of mitochondrial DNA control region sequences, 5 novel haplotypes were found, totalizing 60 haplotypes for the entire distribution range. The haplotype network did not show an apparent phylogeographical signal for the southern FMAs. Two populations were identified: Monte Hermoso (MH) and Necochea (NC)+Claromecó (CL)+Río Negro (RN). The low levels of genetic variability, the relative constant size over time, and the low levels of gene flow may indicate that MH has been colonized by a few maternal lineages and became isolated from geographically close populations. The apparent increase in NC+CL+RN size would be consistent with the higher genetic variability found, since genetic diversity is generally higher in older and expanding populations. Additionally, RN may have experienced a recent split from CL and NC; current high levels of gene flow may be occurring between the latter ones. FMA IV would comprise four franciscana dolphin populations: Samborombón West+Samborombón South, Cabo San Antonio+Buenos Aires East, NC+CL+Buenos Aires Southwest+RN and MH. Results achieved in this study need to be taken into account in order to ensure the long-term survival of the species.Fil: Gariboldi, María Constanza. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Maimónides. Área de Investigaciones Biomédicas y Biotecnológicas. Centro de Estudios Biomédicos, Biotecnológicos, Ambientales y de Diagnóstico; ArgentinaFil: Tunez, Juan Ignacio. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Luján; ArgentinaFil: Dejean, Cristina Beatriz. Universidad Maimónides. Área de Investigaciones Biomédicas y Biotecnológicas. Centro de Estudios Biomédicos, Biotecnológicos, Ambientales y de Diagnóstico; Argentina. Universidad de Buenos Aires. Facultad de Filosofía y Letras. Instituto de Ciencias Antropológicas. Sección Antropología Biológica; ArgentinaFil: Failla, Mauricio. Fundación Cethus; ArgentinaFil: Vitullo, Alfredo Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Maimónides. Área de Investigaciones Biomédicas y Biotecnológicas. Centro de Estudios Biomédicos, Biotecnológicos, Ambientales y de Diagnóstico; ArgentinaFil: Negri, Maria Fernanda. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Museo Argentino de Ciencias Naturales ; ArgentinaFil: Cappozzo, Humberto Luis. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Maimónides. Área de Investigaciones Biomédicas y Biotecnológicas. Centro de Estudios Biomédicos, Biotecnológicos, Ambientales y de Diagnóstico; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Museo Argentino de Ciencias Naturales ; Argentin

Population Structure and Modern Human Origins

This paper reviews statistical methods for inferring population his-tory from mitochondrial mismatch distributions and extends them to the case of geographically structured populations. Inference is based on a geographically structured version of the coalescent algorithm that allows for temporal variation in population size, in the number of subdivisions, and in the rate of migration between subdivisions. Confidence regions are inferred under several models of population history. If the pattern in mitochondrial DNA reflects population growth rather than selection, then the confidence regions reject the multiregional hypothesis of modern human origins more strongly than has previously been possible. They do not reject the replacement hypothesis

Shedding a Light on the Challenges of Adolescents and Young Adults with Rhabdomyosarcoma.

Rhabdomyosarcoma (RMS) is a typical tumour of childhood but can occur at any age. Several studies have reported that adolescent and young adult (AYA) patients with RMS have poorer survival than do younger patients. This review discusses the specific challenges in AYA patients with pediatric-type RMS, exploring possible underlying factors which may influence different outcomes. Reasons for AYA survival gap are likely multifactorial, and might be related to differences in tumor biology and intrinsic aggressiveness, or differences in clinical management (that could include patient referral patterns, time to diagnosis, enrolment into clinical trials, the adequacy and intensity of treatment), as well as patient factors (including physiology and comorbidity that may influence treatment tolerability, drug pharmacokinetics and efficacy). However, improved survival has been reported in the most recent studies for AYA patients treated on pediatric RMS protocols. Different strategies may help to further improve outcome, such as supporting trans-age academic societies and national/international collaborations; developing specific clinical trials without upper age limit; defining integrated and comprehensive approach to AYA patients, including the genomic aspects; establishing multidisciplinary tumor boards with involvement of both pediatric and adult oncologists to discuss all pediatric-type RMS patients; developing dedicated projects with specific treatment recommendations and registry/database

Comparison of depression and anxiety symptom networks in reporters and non-reporters of lifetime trauma in two samples of differing severity

Background: Reported trauma is associated with differences in the course and outcomes of depression and anxiety. However, no research has explored the association between reported trauma and patterns of clinically relevant symptoms of both depression and anxiety. / Methods: We used network analysis to investigate associations between reported trauma and depression and anxiety symptom interactions in affected individuals from the Genetic Links to Anxiety and Depression (GLAD) Study (n = 17720), and population volunteers from the UK Biobank (n = 11120). Participants with current moderate symptoms of depression or anxiety were grouped into reporters and non-reporters of lifetime trauma. Networks of 16 depression and anxiety symptoms in the two groups were compared using the network comparison test. / Results: In the GLAD Study, networks of reporters and non-reporters of lifetime trauma did not differ on any metric. In the UK Biobank, the symptom network of reporters had significantly greater density (7.80) than the network of non-reporters (7.05). / Limitations: The data collected in the GLAD Study and the UK Biobank are self-reported with validated or semi-validated questionnaires. / Conclusions: Reported lifetime trauma was associated with stronger interactions between symptoms of depression and anxiety in population volunteers. Differences between reporters and non-reporters may not be observed in individuals with severe depression and/or anxiety due to limited variance in the presentation of disorder

Brachytherapy for rhabdomyosarcoma: Survey of international clinical practice and development of guidelines.

BACKGROUND AND PURPOSE: The purpose of this study was to address the lack of published data on the use of brachytherapy in pediatric rhabdomyosarcoma by describing current practice as starting point to develop consensus guidelines. MATERIALS AND METHODS: An international expert panel on the treatment of pediatric rhabdomyosarcoma comprising 24 (pediatric) radiation oncologists, brachytherapists and pediatric surgeons met for a Brachytherapy Workshop hosted by the European paediatric Soft tissue Sarcoma Study Group (EpSSG). The panel's clinical experience, the results of a previously distributed questionnaire, and a review of the literature were presented. RESULTS: The survey indicated the most common use of brachytherapy to be in combination with tumor resection, followed by brachytherapy as sole local therapy modality. HDR was increasingly deployed in pediatric practice, especially for genitourinary sites. Brachytherapy planning was mostly by 3D imaging based on CT. Recommendations for patient selection, treatment requirements, implant technique, delineation, dose prescription, dose reporting and clinical management were defined. CONCLUSIONS: Consensus guidelines for the use of brachytherapy in pediatric rhabdomyosarcoma have been developed through multicenter collaboration establishing the basis for future work. These have been adopted for the open EpSSG overarching study for children and adults with Frontline and Relapsed RhabdoMyoSarcoma (FaR-RMS)

CAR-T cell. the long and winding road to solid tumors

Adoptive cell therapy of solid tumors with reprogrammed T cells can be considered the "next generation" of cancer hallmarks. CAR-T cells fail to be as effective as in liquid tumors for the inability to reach and survive in the microenvironment surrounding the neoplastic foci. The intricate net of cross-interactions occurring between tumor components, stromal and immune cells leads to an ineffective anergic status favoring the evasion from the host's defenses. Our goal is hereby to trace the road imposed by solid tumors to CAR-T cells, highlighting pitfalls and strategies to be developed and refined to possibly overcome these hurdles