Experimental evidence of delocalized states in random dimer superlattices

We study the electronic properties of GaAs-AlGaAs superlattices with intentional correlated disorder by means of photoluminescence and vertical dc resistance. The results are compared to those obtained in ordered and uncorrelated disordered superlattices. We report the first experimental evidence that spatial correlations inhibit localization of states in disordered low-dimensional systems, as our previous theoretical calculations suggested, in contrast to the earlier belief that all eigenstates are localized.Comment: 4 pages, 5 figures. Physical Review Letters (in press

Electronic structure and vertical transport in random dimer GaAs-Al_xGa_(1-x)As superlattices

We report a systematic study of several GaAs-AlxGa1-xAs semiconductor superlattices grown by molecular-beam epitaxy specifically designed to explore the existence of extended states in random dimer superlattices. We have confirmed our previous results [V. Bellani et al., Phys. Rev. Lett. 82, 2159 (1999)] with much additional evidence that allows us to lay claim to a clear-cut experimental verification of the presence of extended states in random dimer superlattices due to the short-range correlations (dimers) that inhibit the localization effects of the disorder

Functional over-redundancy and high functional vulnerability in global fish faunas on tropical reefs

When tropical systems lose species, they are often assumed to be buffered against declines in functional diversity by the ability of the species-rich biota to display high functional redundancy: i.e., a high number of species performing similar functions. We tested this hypothesis using a ninefold richness gradient in global fish faunas on tropical reefs encompassing 6,316 species distributed among 646 functional entities (FEs): i.e., unique combinations of functional traits. We found that the highest functional redundancy is located in the Central Indo-Pacific with a mean of 7.9 species per FE. However, this overall level of redundancy is disproportionately packed into few FEs, a pattern termed functional over-redundancy (FOR). For instance, the most speciose FE in the Central Indo-Pacific contains 222 species (out of 3,689) whereas 38% of FEs (180 out of 468) have no functional insurance with only one species. Surprisingly, the level of FOR is consistent across the six fish faunas, meaning that, whatever the richness, over a third of the species may still be in overrepresented FEs whereas more than one third of the FEs are left without insurance, these levels all being significantly higher than expected by chance. Thus, our study shows that, even in high-diversity systems, such as tropical reefs, functional diversity remains highly vulnerable to species loss. Although further investigations are needed to specifically address the influence of redundant vs. vulnerable FEs on ecosystem functioning, our results suggest that the promised benefits from tropical biodiversity may not be as strong as previously thought

Capacitance-conductance investigation on the phase transitions in Ga nanoparticles

We have reported on coupled capacitance-conductance measurements on Ga nanoparticles embedded in vitreous matrices. The melting of nanoparticles was clearly detected as an abrupt increase in the capacitance vs. temperature scans. The influence of the embedding matrix and of the frequency of the applied field on the dielectric response was checked. The presence of a hysteresis cycle between melting and solidification has been detected. The technique allows the identification of the various solid phases of confined Ga

Plate tectonics drive tropical reef biodiversity dynamics

The Cretaceous breakup of Gondwana strongly modified the global distribution of shallow tropical seas reshaping the geographic configuration of marine basins. However, the links between tropical reef availability, plate tectonic processes and marine biodiversity distribution patterns are still unknown. Here, we show that a spatial diversification model constrained by absolute plate motions for the past 140 million years predicts the emergence and movement of diversity hotspots on tropical reefs. The spatial dynamics of tropical reefs explains marine fauna diversification in the Tethyan Ocean during the Cretaceous and early Cenozoic, and identifies an eastward movement of ancestral marine lineages towards the Indo-Australian Archipelago in the Miocene. A mechanistic model based only on habitat-driven diversification and dispersal yields realistic predictions of current biodiversity patterns for both corals and fishes. As in terrestrial systems, we demonstrate that plate tectonics played a major role in driving tropical marine shallow reef biodiversity dynamics

Clinical use of polymerase chain reaction performed on peripheral blood and bone marrow samples for the diagnosis and monitoring of visceral leishmaniasis in HIV-infected and HIV-uninfected patients: a single-center, 8-year experience in Italy and review of the literature

Background. To overcome some of the limitations of conventional microbiologic techniques, polymerase chain reaction (PCR)–based assays are proposed as useful tools for the diagnosis of visceral leishmaniasis. Patients and methods. A comparative study using conventional microbiologic techniques (i.e., serologic testing, microscopic examination, and culture) and a Leishmania species–specific PCR assay, using peripheral blood and bone marrow aspirate samples as templates, was conducted during an 8-year period. The study cohort consisted of 594 Italian immunocompetent (adult and pediatric) and immunocompromised (adult) patients experiencing febrile syndromes associated with hematologic alterations and/or hepatosplenomegaly. Identification of the infecting protozoa at the species level was directly obtained by PCR of peripheral blood samples, followed by restriction fragment–length polymorphism analysis of the amplified products, and the results were compared with those of isoenzyme typing of Leishmania species strains from patients, which were isolated in vitro. Results. Sixty-eight patients (11.4%) had a confirmed diagnosis of visceral leishmaniasis. Eleven cases were observed in human immunodeficiency virus (HIV)–uninfected adults, 20 cases were observed in HIV-infected adults, and the remaining 37 cases were diagnosed in HIV-uninfected children. In the diagnosis of primary visceral leishmaniasis, the sensitivities of the Leishmania species–specific PCR were 95.7% for bone marrow aspirate samples and 98.5% for peripheral blood samples versus sensitivities of 76.2%, 85.5%, and 90.2% for bone marrow aspirate isolation, serologic testing, and microscopic examination of bone marrow biopsy specimens, respectively. None of 229 healthy blood donors or 25 patients with imported malaria who were used as negative control subjects had PCR results positive for Leishmania species in peripheral blood samples (i.e., specificity of Leishmania species– specific PCR, 100%). PCR and restriction fragment–length polymorphism analysis for Leishmania species identification revealed 100% concordance with isoenzyme typing in the 19 patients for whom the latter data were available. Conclusions. PCR assay is a highly sensitive and specific tool for the diagnosis of visceral leishmaniasis in both immunocompetent and immunocompromised patients and can be reliably used for rapid parasite identification at the species level

Identification of small molecules uncoupling the Notch : Jagged interaction through an integrated high-throughput screening

Notch signaling plays an important role in several cellular functions including growth, differentiation, cell fate determination and stemness. Increased Notch activity has been linked to several types of cancers. Activation of Notch signaling is triggered by the interaction of Notch receptors (Notch1-4) with 5 different ligands (Jagged1-2 and Dll1-3-4) expressed on the neighbouring cells. Currently, indirect approaches to inhibit Notch signalling are based on the inhibition of the key step of Notch activation catalyzed by the \u3b3-Secretase and thereby affect several different \u3b3-Secretase substrates; conversely direct strategies get advantage of antibody-based drugs. The evidence that Jagged-mediated Notch activation plays a key role in cancer cell biology and the interplay with the surrounding microenvironment prompted us to develop a strategy to directly inhibit Notch activation by uncoupling its interaction with the Jagged, using an unprecedented approach based on small molecules. We set-up a screening strategy based on: protein::protein docking of crystallographic structures of Notch1 with Jagged1; comparative modelling of the Notch2:Jagged2 complex, based on the Notch1::Jagged1 complex; in silico high-throughput screening directed to Notch2 interaction surface of a virtual chemical library containing a large variety of molecules commercially available. The predicted pharmacological activity of the selected compounds was validated in vitro by a gene reporter and a viability assay. This approach led to the successful identification of two candidates with different anti-proliferative potency and efficacy. This represents the first step towards the rational identification of candidate molecules for the development of entirely novel drugs directed to inhibit Notch signaling in cancer

Nutrient limitation, bioenergetics and stoichiometry: A new model to predict elemental fluxes mediated by fishes

Energy flow and nutrient cycling dictate the functional role of organisms in ecosystems. Fishes are key vectors of carbon (C), nitrogen (N) and phosphorus (P) in aquatic systems, and the quantification of elemental fluxes is often achieved by coupling bioenergetics and stoichiometry. While nutrient limitation has been accounted for in several stoichiometric models, there is no current implementation that permits its incorporation into a bioenergetics approach to predict ingestion rates. This may lead to biased estimates of elemental fluxes.Here, we introduce a theoretical framework that combines stoichiometry and bioenergetics with explicit consideration of elemental limitations. We examine varying elemental limitations across different trophic groups and life stages through a case study of three trophically distinct reef fishes. Further, we empirically validate our model using an independent database of measured excretion rates.Our model adequately predicts elemental fluxes in the examined species and reveals species‐ and size‐specific limitations of C, N and P. In line with theoretical predictions, we demonstrate that the herbivore Zebrasoma scopas is limited by N and P, and all three fish species are limited by P in early life stages. Further, we show that failing to account for nutrient limitation can result in a greater than twofold underestimation of ingestion rates, which leads to severely biased excretion rates.Our model improved predictions of ingestion, excretion and egestion rates across all life stages, especially for fishes with diets low in N and/or P. Due to its broad applicability, its reliance on many parameters that are well‐defined and widely accessible, and its straightforward implementation via the accompanying r‐package fishflux, our model provides a user‐friendly path towards a better understanding of ecosystem‐wide nutrient cycling in the aquatic biome.A free Plain Language Summary can be found within the Supporting Information of this article.A free Plain Language Summary can be found within the Supporting Information of this article.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/162691/5/fec13618_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/162691/4/fec13618-sup-0002-AppendixS1.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/162691/3/fec13618-sup-0001-Summary.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/162691/2/fec13618-sup-0003-AppendixS2.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/162691/1/fec13618.pd

Surface Plasmon Resonance as a Tool for Ligand Binding Investigation of Engineered GPR17 Receptor, a G Protein Coupled Receptor Involved in Myelination

The aim of this study was to investigate the potential of surface plasmon resonance (SPR) spectroscopy for the measurement of real-time ligand-binding affinities and kinetic parameters for GPR17, a G protein-coupled receptor (GPCR) of major interest in medicinal chemistry as potential target in demyelinating diseases. The receptor was directly captured, in a single-step, from solubilized membrane extracts on the sensor chip through a covalently bound anti-6x-His-antibody and retained its ligand binding activity for over 24h. Furthermore, our experimental setup made possible, after a mild regeneration step, to remove the bound receptor without damaging the antibody, and thus to reuse many times the same chip. Two engineered variants of GPR17, designed for crystallographic studies, were expressed in insect cells, extracted from crude membranes and analyzed for their binding with two high affinity ligands: the antagonist Cangrelor and the agonist Asinex 1. The calculated kinetic parameters and binding constants of ligands were in good agreement with those reported from activity assays and highlighted a possible functional role of the N-terminal residues of the receptor in ligand recognition and binding. Validation of SPR results was obtained by docking and molecular dynamics of GPR17-ligands interactions and by functional in vitro studies. The latter allowed us to confirm that Asinex 1 behaves as GPR17 receptor agonist, inhibits forskolin-stimulated adenylyl cyclase pathway and promotes oligodendrocyte precursor cell maturation and myelinating ability

Dysregulation of the GPR17 receptor in neuroinflammatory diseases: implications for remyelination in multiple sclerosis

Multiple sclerosis (MS) is a chronic immune-mediated disease of the central nervous system, in which inflammation and myelin disruption contribute to impaired in electrical conduction. Oligodendrocyte precursor cells (OPCs) are massively recruited to the site of injury to myelinate damaged axons, but in MS patients remyelination is often ineffective. For this reason, therapeutic strategies aimed at fostering this process could block/delay the development of the disease and the consequent disability. We have previously shown that the membrane receptor GPR17 timely regulates the early stages of OPC differentiation, but, after reaching its highest levels in immature oligodendrocytes, it has to be down-regulated to allow terminal maturation. Any defect in its expression pattern leads to impairment in oligodendrocyte differentiation. Interestingly, overexpression of GPR17 was found in rodent models of cerebral trauma, ischemia and in lysolecithin induced focal demyelination. Instead, little is known about GPR17 in a primary demyelinating disease such as MS. On this basis, aim of this work has been to characterize GPR17 alterations in a murine model of MS and in human post-mortem MS lesions. In spinal cord of mice subjected to experimental autoimmune encephalomyelitis (EAE), we observed a marked and persistent upregulation of GPR17 in the OPCs accumulating at demyelinating lesions. Moreover, fate-mapping experiments with transgenic GPR17iCreERT2-GFP reporter mice showed that this increased pool of proliferating cells is blocked at an intermediate stage of differentiation, and cannot fully complete the myelination process, likely due to unfavourable inflammatory environment. In a similar way, in post-mortem tissues from SPMS patients, many GPR17-positive activated OPCs accumulated at the border of active lesions. In particular, GPR17 was found mainly expressed by hypertrophic cells HLA (human leukocyte antigen or major histocompatibility complex) -positive at within the lesions, suggesting that GPR17 is involved in the reaction to damage in both OPCs and immune cells directly responding to inflammation. We conclude that the coordinated presence of GPR17 at the membrane of these cells at the lesion sites could be exploited as potential new target to support endogenous remyelination through advanced pharmacological approaches