Tools for Remote Exploration: A Lithium (Li) Dedicated Spectral Library of the Fregeneda-Almendra Aplite-Pegmatite Field

The existence of diagnostic features in the visible and infrared regions makes it possible to use reflectance spectra not only to identify mineral assemblages but also for calibration and classification of satellite images, considering lithological and/or mineral mapping. For this purpose, a consistent spectral library with the target spectra of minerals and rocks is needed. Currently, there is big market pressure for raw materials including lithium (Li) that has driven new satellite image applications for Li exploration. However, there are no reference spectra for petalite (a Li mineral) in large, open spectral datasets. In this work, a spectral library was built exclusively dedicated to Li minerals and Li pegmatite exploration through satellite remote sensing. The database includes field and laboratory spectra collected in the Fregeneda-Almendra region (Spain-Portugal) from (i) distinct Li minerals (spodumene, petalite, lepidolite); (ii) several Li pegmatites and other outcropping lithologies to allow satellite-based lithological mapping; (iii) areas previously misclassified as Li pegmatites using machine learning algorithms to allow comparisons between these regions and the target areas. Ancillary data include (i) sample location and coordinates, (ii) sample conditions, (iii) sample color, (iv) type of face measured, (v) equipment used, and for the laboratory spectra, (vi) sample photographs, (vii) continuum removed spectra files, and (viii) statistics on the main absorption features automatically extracted. The potential future uses of this spectral library are reinforced by its major advantages: (i) data is provided in a universal file format; (ii) it allows users to compare field and laboratory spectra; (iii) a large number of complementary data allow the comparison of shape, asymmetry, and depth of the absorption features of the distinct Li minerals

Reduced protein expression of the phosphodiesterases PDE4A4 and PDE4A8 in AIP mutation positive somatotroph adenomas

© 2018 Type 4 phosphodiesterases (PDE4s) of the large PDE enzyme superfamily have unique specificity for cAMP and may, therefore, be relevant for somatotroph tumorigenesis. Somatotroph adenomas typically overexpress PDEs probably as part of a compensatory mechanism to reduce cAMP levels. The rat PDE4A5 isoform (human homolog PDE4A4) interacts with the AIP protein, coded by a tumour suppressor gene mutated in a subgroup of familial isolated pituitary adenomas (FIPAs). PDE4A8 is the closest related isoform of PDE4A4. We aimed to evaluate the expression of both PDE4A4 and PDE4A8 in GH cells of AIP-mutated adenomas and compare their expression with that in GH cells from sporadic AIP-mutation negative GH-secreting adenomas, where we had shown previously that both PDE4A4 and PDE4A8 isoforms had been over-expressed. Confocal immunofluorescence analysis showed that both PDE4A8 and PDE4A4 had lower expression in AIP-mutated somatotropinoma samples compared to sporadic GH-secreting tumours (P < 0.0001 for both). Based on the association of low PDE4A4 and PDE4A8 expression with germline AIP-mutations positive samples we suggest that lack of AIP hinders the upregulation of PDE4A8 and PDE4A4 protein seen in sporadic somatotrophinomas. These data point to a unique disturbance of the cAMP-PDE pathway in AIP-mutation positive adenomas, which may help to explain their well-described poor response to somatostatin analogues.Grant sponsor: NIH RO1-GM58553 to GBB, The Bolger Prostate Cancer Research Fund to GBB, and the National Cancer Institute of the National Institutes of Health to the University of Alabama at Birmingham Comprehensive Cancer Center under award number P30 CA013148 (for generation of monoclonal antibodies

An insight into the sialome of Simulium guianense (DIPTERA:SIMulIIDAE), the main vector of River Blindness Disease in Brazil

<p>Abstract</p> <p>Background</p> <p>Little is known about the composition and function of the saliva in black flies such as <it>Simulium guianense</it>, the main vector of river blindness disease in Brazil. The complex salivary potion of hematophagous arthropods counteracts their host's hemostasis, inflammation, and immunity.</p> <p>Results</p> <p>Transcriptome analysis revealed ubiquitous salivary protein families--such as the Antigen-5, Yellow, Kunitz domain, and serine proteases--in the <it>S. guianense </it>sialotranscriptome. Insect-specific families were also found. About 63.4% of all secreted products revealed protein families found only in <it>Simulium</it>. Additionally, we found a novel peptide similar to kunitoxin with a structure distantly related to serine protease inhibitors. This study revealed a relative increase of transcripts of the SVEP protein family when compared with <it>Simulium vittatum </it>and <it>S. nigrimanum </it>sialotranscriptomes. We were able to extract coding sequences from 164 proteins associated with blood and sugar feeding, the majority of which were confirmed by proteome analysis.</p> <p>Conclusions</p> <p>Our results contribute to understanding the role of <it>Simulium </it>saliva in transmission of <it>Onchocerca volvulus </it>and evolution of salivary proteins in black flies. It also consists of a platform for mining novel anti-hemostatic compounds, vaccine candidates against filariasis, and immuno-epidemiologic markers of vector exposure.</p

Pathogen- and Host-Directed Antileishmanial Effects Mediated by Polyhexanide (PHMB)

BACKGROUND:Cutaneous leishmaniasis (CL) is a neglected tropical disease caused by protozoan parasites of the genus Leishmania. CL causes enormous suffering in many countries worldwide. There is no licensed vaccine against CL, and the chemotherapy options show limited efficacy and high toxicity. Localization of the parasites inside host cells is a barrier to most standard chemo- and immune-based interventions. Hence, novel drugs, which are safe, effective and readily accessible to third-world countries and/or drug delivery technologies for effective CL treatments are desperately needed. METHODOLOGY/PRINCIPAL FINDINGS:Here we evaluated the antileishmanial properties and delivery potential of polyhexamethylene biguanide (PHMB; polyhexanide), a widely used antimicrobial and wound antiseptic, in the Leishmania model. PHMB showed an inherent antileishmanial activity at submicromolar concentrations. Our data revealed that PHMB kills Leishmania major (L. major) via a dual mechanism involving disruption of membrane integrity and selective chromosome condensation and damage. PHMB's DNA binding and host cell entry properties were further exploited to improve the delivery and immunomodulatory activities of unmethylated cytosine-phosphate-guanine oligodeoxynucleotides (CpG ODN). PHMB spontaneously bound CpG ODN, forming stable nanopolyplexes that enhanced uptake of CpG ODN, potentiated antimicrobial killing and reduced host cell toxicity of PHMB. CONCLUSIONS:Given its low cost and long history of safe topical use, PHMB holds promise as a drug for CL therapy and delivery vehicle for nucleic acid immunomodulators

Activation of Type 1 Cannabinoid Receptor (CB1R) promotes neurogenesis in murine subventricular zone cell cultures

The endocannabinoid system has been implicated in the modulation of adult neurogenesis. Here, we describe the effect of type 1 cannabinoid receptor (CB1R) activation on self-renewal, proliferation and neuronal differentiation in mouse neonatal subventricular zone (SVZ) stem/progenitor cell cultures. Expression of CB1R was detected in SVZ-derived immature cells (Nestin-positive), neurons and astrocytes. Stimulation of the CB1R by (R)-(+)-Methanandamide (R-m-AEA) increased self-renewal of SVZ cells, as assessed by counting the number of secondary neurospheres and the number of Sox2+/+ cell pairs, an effect blocked by Notch pathway inhibition. Moreover, R-m-AEA treatment for 48 h, increased proliferation as assessed by BrdU incorporation assay, an effect mediated by activation of MAPK-ERK and AKT pathways. Surprisingly, stimulation of CB1R by R-m-AEA also promoted neuronal differentiation (without affecting glial differentiation), at 7 days, as shown by counting the number of NeuN-positive neurons in the cultures. Moreover, by monitoring intracellular calcium concentrations ([Ca2+](i)) in single cells following KCl and histamine stimuli, a method that allows the functional evaluation of neuronal differentiation, we observed an increase in neuronal-like cells. This proneurogenic effect was blocked when SVZ cells were co-incubated with R-m-AEA and the CB1R antagonist AM 251, for 7 days, thus indicating that this effect involves CB1R activation. In accordance with an effect on neuronal differentiation and maturation, R-m-AEA also increased neurite growth, as evaluated by quantifying and measuring the number of MAP2-positive processes. Taken together, these results demonstrate that CB1R activation induces proliferation, self-renewal and neuronal differentiation from mouse neonatal SVZ cell cultures.Fundacao para a Ciencia e a Tecnologia - Portugal [POCTI/SAU-NEU/68465/2006, PTDC/SAU-NEU/104415/2008, PTDC/SAU-NEU/101783/2008, POCTI/SAU-NEU/110838/2009]; Fundacao Calouste Gulbenkian [96542]; Fundacao para a Ciencia e Tecnologiainfo:eu-repo/semantics/publishedVersio

Origin and history of Phoxinus (Cyprinidae) introductions in the Douro basin (Iberian Peninsula): an update inferred from genetic data

The number of non-native freshwater fishes in the Iberian Peninsula has been greatly increasing. In this study, individuals of the genus Phoxinus were detected in 18 out of 138 stream sites sampled across the Douro Basin in 2017 and 2018. A total of 26 individuals were barcoded using partial cytochrome c oxidase subunit I (COI) and cytochrome b (cytb) genes for species identification and determination of geographical origin. Molecular data provided the first record of a second Phoxinus species in western Douro (Portugal, Iberian Peninsula), with haplotypes closely matching those found in the Charente River (southern France). This species is suspected to be a recent introduction associated with the use of minnows as live bait by freshwater anglers, which was facilitated by human movements between France and Portugal. Individuals from watercourses in eastern Douro (Spain) were genetically assigned to Phoxinus bigerri, an introduced species previously known for that region, which confirms reports of introduction events from Ebro to Douro Basin probably also related to freshwater angling and facilitated by geographic proximity. The potential ecological impacts of this genus in the region are unknown and need further investigation.We acknowledge Fernando Teixeira, Fernando Miranda, Mario Ferreira, Sara Carona, Jose Pedro RamiAo and Francisco Carvalho for the valuable assistance during fieldwork. We specially thank Maria Filomena MagalhAes for previous fruitful discussions and logistic support. We are grateful to Matthias F. Geiger and Andrea Corral Lou for facilitating genetic data and coordinates of sampling sites. Finally, we appreciate the comments of the three anonymous reviewers that improved the quality of the manuscript. AFF and AGR were supported by the project FRESHING founded by the Portuguese Foundation for Science and Technology (FCT) and COMPETE (PTDC/AAGMAA/2261/2014 - POCI-01-0145-FEDER-356016824). FMSM was supported by the FCT PhD grant SFRH/BD/104703/2014. This study was conducted as part of the projects FRESHING and FRESHCO. The latter is also supported by FCT and COMPETE (PTDC/AGR-FOR/1627/2014 - 04/SAICT/2015) and UID/AGR/04033/2019. Logistic support was also facilitated by the ENVMETAGEN - Capacity Building at InBIO for Research and Innovation Using Environmental Metagenomics project at CIBIO laboratories (668981; EUH2020-WIDESPREAD-2014-2)

Lymphotoxin-β receptor in microenvironmental cells promotes the development of T-cell acute lymphoblastic leukaemia with cortical/mature immunophenotype.

Lymphotoxin-mediated activation of the lymphotoxin-β receptor (LTβR; LTBR) has been implicated in cancer, but its role in T-cell acute lymphoblastic leukaemia (T-ALL) has remained elusive. Here we show that the genes encoding lymphotoxin (LT)-α and LTβ (LTA, LTB) are expressed in T-ALL patient samples, mostly of the TAL/LMO molecular subtype, and in the TEL-JAK2 transgenic mouse model of cortical/mature T-ALL (Lta, Ltb). In these mice, expression of Lta and Ltb is elevated in early stage T-ALL. Surface LTα1 β2 protein is expressed in primary mouse T-ALL cells, but only in the absence of microenvironmental LTβR interaction. Indeed, surface LT expression is suppressed in leukaemic cells contacting Ltbr-expressing but not Ltbr-deficient stromal cells, both in vitro and in vivo, thus indicating that dynamic surface LT expression in leukaemic cells depends on interaction with its receptor. Supporting the notion that LT signalling plays a role in T-ALL, inactivation of Ltbr results in a significant delay in TEL-JAK2-induced leukaemia onset. Moreover, young asymptomatic TEL-JAK2;Ltbr(-/-) mice present markedly less leukaemic thymocytes than age-matched TEL-JAK2;Ltbr(+/+) mice and interference with LTβR function at this early stage delayed T-ALL development. We conclude that LT expression by T-ALL cells activates LTβR signalling in thymic stromal cells, thus promoting leukaemogenesis.Grants from Fundação para a Ciencia e a Tecnologia (PTDC/SAU-OBD/103336/2008 and PEst-OE/EQB/LA0023/2013), Nucleo Regional Sul da Liga Portuguesa Contra o Cancro (NRS/LPCC-Terry Fox) and Fundacao MSD to NRdS; grants from the Sao Paulo Research Foundation (FAPESP 08/10034-1 and 12/12802-1) to JAY; and Plan Cancer Action 29 to ED. MTF (SFRH/BD/75137/2010) MNG (SFRH/BD/80503/2011), and RKK (SFRH/BPD/70718/2010) were recipients of FCT PhD or postdoctoral fellowships. ABS and JAY are supported by PhD and Productivity Fellowships, respectively, from the Brazilian National Council for Scientific and Technological Development (CNPq). NRdS has been supported by FCT Ciencia 2007 and FCT Investigator contracts (IF/00056/2012)