FMRF-NH2-related neuropeptides in Biomphalaria spp., intermediate hosts for schistosomiasis: Precursor organization and immunohistochemical localization

Freshwater snails of the genus Biomphalaria serve as intermediate hosts for the digenetic trematode Schistosoma mansoni, the etiological agent for the most widespread form of intestinal schistosomiasis. As neuropeptide signaling in host snails can be altered by trematode infection, a neural transcriptomics approach was undertaken to identify peptide precursors in Biomphalaria glabrata, the major intermediate host for S. mansoni in the Western Hemisphere. Three transcripts that encode peptides belonging to the FMRF-NH2-related peptide (FaRP) family were identified in B. glabrata. One transcript encoded a precursor polypeptide (Bgl-FaRP1; 292 amino acids) that included eight copies of the tetrapeptide FMRF-NH2 and single copies of FIRF-NH2, FLRF-NH2, and pQFYRI-NH2. The second transcript encoded a precursor (Bgl-FaRP2; 347 amino acids) that comprised 14 copies of the heptapeptide GDPFLRF-NH2 and 1 copy of SKPYMRF-NH2. The precursor encoded by the third transcript (Bgl-FaRP3; 287 amino acids) recapitulated Bgl-FaRP2 but lacked the full SKPYMRF-NH2 peptide. The three precursors shared a common signal peptide, suggesting a genomic organization described previously in gastropods. Immunohistochemical studies were performed on the nervous systems of B. glabrata and B. alexandrina, a major intermediate host for S. mansoni in Egypt. FMRF-NH2-like immunoreactive (FMRF-NH2-li) neurons were located in regions of the central nervous system associated with reproduction, feeding, and cardiorespiration. Antisera raised against non-FMRF-NH2 peptides present in the tetrapeptide and heptapeptide precursors labeled independent subsets of the FMRF-NH2-li neurons. This study supports the participation of FMRF-NH2-related neuropeptides in the regulation of vital physiological and behavioral systems that are altered by parasitism in Biomphalaria

Ultrafast carrier relaxation in GaN, In_(0.05)Ga_(0.95)N and an In_(0.05)Ga_(0.95)/In_(0.15)Ga_(0.85)N Multiple Quantum Well

Room temperature, wavelength non-degenerate ultrafast pump/probe measurements were performed on GaN and InGaN epilayers and an InGaN multiple quantum well structure. Carrier relaxation dynamics were investigated as a function of excitation wavelength and intensity. Spectrally-resolved sub-picosecond relaxation due to carrier redistribution and QW capture was found to depend sensitively on the wavelength of pump excitation. Moreover, for pump intensities above a threshold of 100 microJ/cm2, all samples demonstrated an additional emission feature arising from stimulated emission (SE). SE is evidenced as accelerated relaxation (< 10 ps) in the pump-probe data, fundamentally altering the re-distribution of carriers. Once SE and carrier redistribution is completed, a slower relaxation of up to 1 ns for GaN and InGaN epilayers, and 660 ps for the MQW sample, indicates carrier recombination through spontaneous emission.Comment: submitted to Phys. Rev.

Reexamining nonstandard interaction effects on supernova neutrino flavor oscillations

Several extensions of the standard electroweak model allow new four-fermion interactions (nu_a nu_b * ff) with strength eps_ab*G_F, where (a,b) are flavor indices. We revisit their effects on flavor oscillations of massive (anti)neutrinos in supernovae, in order to achieve, in the region above the protoneutron star, an analytical treatment valid for generic values of the neutrino mixing angles (omega,phi,psi)=(theta_12,theta_13,theta_23). Assuming that eps_ab<<1, we find that the leading effects on the flavor transitions occurring at high (H) and low (L) density along the supernova matter profile can be simply embedded through the replacements phi-->phi+eps_H and omega-->omega+eps_L, respectively, where eps_H and eps_L are specific linear combinations of the eps_ab's. Similar replacements hold for eventual oscillations in the Earth matter. From a phenomenological point of view, the most relevant consequence is a possible uncontrolled bias (phi-->phi+eps_H) in the value of the mixing angle phi inferred by inversion of supernova neutrino data. Such a drawback, however, does not preclude the discrimination of the neutrino mass spectrum hierarchy (direct or inverse) through supernova neutrino oscillations.Comment: Text clarified, one figure added. To appear in PR

Spatial regulation of the glycocalyx component podocalyxin is a switch for prometastatic function

The glycocalyx component and sialomucin podocalyxin (PODXL) is required for normal tissue development by promoting apical membranes to form between cells, triggering lumen formation. Elevated PODXL expression is also associated with metastasis and poor clinical outcome in multiple tumor types. How PODXL presents this duality in effect remains unknown. We identify an unexpected function of PODXL as a decoy receptor for galectin-3 (GAL3), whereby the PODXL-GAL3 interaction releases GAL3 repression of integrin-based invasion. Differential cortical targeting of PODXL, regulated by ubiquitination, is the molecular mechanism controlling alternate fates. Both PODXL high and low surface levels occur in parallel subpopulations within cancer cells. Orthotopic intraprostatic xenograft of PODXL-manipulated cells or those with different surface levels of PODXL define that this axis controls metastasis in vivo. Clinically, interplay between PODXL-GAL3 stratifies prostate cancer patients with poor outcome. Our studies define the molecular mechanisms and context in which PODXL promotes invasion and metastasis

PURA syndrome : clinical delineation and genotype-phenotype study in 32 individuals with review of published literature

Background De novo mutations in PURA have recently been described to cause PURA syndrome, a neurodevelopmental disorder characterised by severe intellectual disability (ID), epilepsy, feeding difficulties and neonatal hypotonia. Objectives T o delineate the clinical spectrum of PURA syndrome and study genotype-phenotype correlations. Methods Diagnostic or research-based exome or Sanger sequencing was performed in individuals with ID. We systematically collected clinical and mutation data on newly ascertained PURA syndrome individuals, evaluated data of previously reported individuals and performed a computational analysis of photographs. We classified mutations based on predicted effect using 3D in silico models of crystal structures of Drosophila-derived Pur-alpha homologues. Finally, we explored genotypephenotype correlations by analysis of both recurrent mutations as well as mutation classes. Results We report mutations in PURA (purine-rich element binding protein A) in 32 individuals, the largest cohort described so far. Evaluation of clinical data, including 22 previously published cases, revealed that all have moderate to severe ID and neonatal-onset symptoms, including hypotonia (96%), respiratory problems (57%), feeding difficulties (77%), exaggerated startle response (44%), hypersomnolence (66%) and hypothermia (35%). Epilepsy (54%) and gastrointestinal (69%), ophthalmological (51%) and endocrine problems (42%) were observed frequently. Computational analysis of facial photographs showed subtle facial dysmorphism. No strong genotype-phenotype correlation was identified by subgrouping mutations into functional classes. Conclusion We delineate the clinical spectrum of PURA syndrome with the identification of 32 additional individuals. The identification of one individual through targeted Sanger sequencing points towards the clinical recognisability of the syndrome. Genotype-phenotype analysis showed no significant correlation between mutation classes and disease severity.Peer reviewe

A parametric study on the dynamic response of planar multibody systems with multiple clearance joints

A general methodology for dynamic modeling and analysis of multibody systems with multiple clearance joints is presented and discussed in this paper. The joint components that constitute a real joint are modeled as colliding bodies, being their behavior influenced by geometric and physical properties of the contacting surfaces. A continuous contact force model, based on the elastic Hertz theory together with a dissipative term, is used to evaluate the intra-joint contact forces. Furthermore, the incorporation of the friction phenomenon, based on the classical Coulomb’s friction law, is also discussed. The suitable contact-impact force models are embedded into the dynamics of multibody systems methodologies. An elementary mechanical system is used to demonstrate the accuracy and efficiency of the presented approach, and to discuss the main assumptions and procedures adopted. Different test scenarios are considered with the purpose of performing a parametric study for quantifying the influence of the clearance size, input crank speed and number of clearance joints on the dynamic response of multibody systems with multiple clearance joints. Additionally, the total computation time consumed in each simulation is evaluated in order to test the computational accuracy and efficiency of the presented approach. From the main results obtained in this study, it can be drawn that clearance size and the operating conditions play a crucial role in predicting accurately the dynamic responses of multibody systems.Fundação para a Ciência e a Tecnologia (FCT

Structural and morphological analysis of zinc incorporated non-stoichiometric hydroxyapatite nano powders

ABSTRACT In this study, Zn incorporated non-stoichiometric hydroxyapatite (nHAp) was synthesized via precipitation method and effect of the incorporation of Zn (fraction: 2, 4, 6 and 8 mol-%) on the microstructure of nHAp was studied by XRD, FTIR analysis and SEM-EDS techniques. The formation of nHAp was confirmed by XRD and FTIR those showed that no secondary phase was formed through the Zn incorporation. The SEM studies also revealed that particles were formed in nano-metric size (30-60 nm). It was found that crystallite and particle size of Zn incorporated nHAp gradually decreased up to 6 mol-%, and started to increase while the Zn fraction reached up to the 8 mol-% and hence the morphology of the aggregated products was also changed. It can be concluded that the incorporation of Zn cations cause to form nHAp phase. Furthermore, the nHAp microstructure has deviated from stoichiometric condition by incorporation of more Zn cations