Multifunctional Eu-doped NaGd(MoO4)(2) nanoparticles functionalized with poly(L-lysine) for optical and MRI imaging

A method for the synthesis of non-aggregated and highly uniform Eu3+ doped NaGd(MoO4)(2) nanoparticles is reported for the first time. The obtained particles present tetragonal structure, ellipsoidal shape and their size can be varied by adjusting the experimental synthesis parameters. These nanoparticles, which were coated with citrate anions and functionalised with PLL, have also been developed in order to improve their colloidal stability in physiological medium (2-(N-morpholino) ethanesulfonic acid, MES). A study of the luminescent dynamics of the samples as a function of the Eu doping level has been conducted in order to find the optimum nanophosphors, whose magnetic relaxivity and cell viability have also been evaluated for the first time for this system, in order to assess their suitability as multifunctional probes for optical (in vitro) and magnetic bioimaging applications

The corticomuscular response to experimental pain via blood flow occlusion when applied to the ipsilateral and contralateral leg during an isometric force task

Blood flow occlusion (BFO) has been previously used to investigate physiological responses to muscle ischemia, showing increased perceptual effort (RPE) and pain along with impaired neuromuscular performance. However, at present, it is unclear how BFO alters corticomuscular activities when either applied to the exercising or nonexercising musculature. The present study therefore set out to assess the corticomuscular response to these distinct BFO paradigms during an isometric contraction precision task. In a repeated measures design, fifteen participants (age = 27.00 ± 5.77) completed 15 isometric contractions across three experimental conditions; no occlusion (CNTRL), occlusion of the contralateral (i.e., nonexercising) limb (CON-OCC), and occlusion of the ipsilateral (i.e., exercising) limb (IPS-OCC). Measures of force, electroencephalographic (EEG), and electromyographic (EMG) were recorded during contractions. We observed that IPS-OCC broadly impaired force steadiness, elevated EMG of the vastus lateralis, and heightened RPE and pain. IPSI-OCC also significantly decreased corticomuscular coherence during the early phase of contraction and decreased EEG alpha activity across the sensorimotor and temporoparietal regions during the middle and late phases of contraction compared with CNTRL. By contrast, CON-OCC increased perceived levels of pain (but not RPE) and decreased EEG alpha activity across the prefrontal cortex during the middle and late phases of contraction, with no changes observed for EMG and force steadiness. Together, these findings highlight distinctive psychophysiological responses to experimental pain via BFO showing altered cortical activities (CON-OCC) and altered cortical, corticomuscular, and neuromuscular activities (IPS-OCC) when applied to the lower limbs during an isometric force precision task

Sphingosine 1-phosphate modulates antigen capture by murine langerhans cells via the S1P2 receptor subtype

Dendritic cells (DCs) play a pivotal role in the development of cutaneous contact hypersensitivity (CHS) and atopic dermatitis as they capture and process antigen and present it to T lymphocytes in the lymphoid organs. Recently, it has been indicated that a topical application of the sphingolipid sphingosine 1-phosphate (S1P) prevents the inflammatory response in CHS, but the molecular mechanism is not fully elucidated. Here we indicate that treatment of mice with S1P is connected with an impaired antigen uptake by Langerhans cells (LCs), the initial step of CHS. Most of the known actions of S1P are mediated by a family of five specific G protein-coupled receptors. Our results indicate that S1P inhibits macropinocytosis of the murine LC line XS52 via S1P2 receptor stimulation followed by a reduced phosphatidylinositol 3-kinase (PI3K) activity. As down-regulation of S1P2 not only diminished S1P-mediated action but also enhanced the basal activity of LCs on antigen capture, an autocrine action of S1P has been assumed. Actually, S1P is continuously produced by LCs and secreted via the ATP binding cassette transporter ABCC1 to the extracellular environment. Consequently, inhibition of ABCC1, which decreased extracellular S1P levels, markedly increased the antigen uptake by LCs. Moreover, stimulation of sphingosine kinase activity, the crucial enzyme for S1P formation, is connected not only with enhanced S1P levels but also with diminished antigen capture. These results indicate that S1P is essential in LC homeostasis and influences skin immunity. This is of importance as previous reports suggested an alteration of S1P levels in atopic skin lesions

Growth and structure analysis of tungsten oxide nanorods using environmental TEM

WO3 nanorods targeted for applications in electric devices were grown from a tungsten wire heated in an oxygen atmosphere inside an environmental transmission electron microscope, which allowed the growth process to be observed to reveal the growth mechanism of the WO3 nanorods. The initial growth of the nanorods did not consist of tungsten oxide but rather crystal tungsten. The formed crystal tungsten nanorods were then oxidized, resulting in the formation of the tungsten oxide nanorods. Furthermore, it is expected that the nanorods grew through cracks in the natural surface oxide layer on the tungsten wire

Integrated Analysis of Germline and Tumor DNA Identifies New Candidate Genes Involved in Familial Colorectal Cancer

Colorectal cancer (CRC) shows aggregation in some families but no alterations in the known hereditary CRC genes. We aimed to identify new candidate genes which are potentially involved in germline predisposition to familial CRC. An integrated analysis of germline and tumor whole-exome sequencing data was performed in 18 unrelated CRC families. Deleterious single nucleotide variants (SNV), short insertions and deletions (indels), copy number variants (CNVs) and loss of heterozygosity (LOH) were assessed as candidates for first germline or second somatic hits. Candidate tumor suppressor genes were selected when alterations were detected in both germline and somatic DNA, fulfilling Knudson's two-hit hypothesis. Somatic mutational profiling and signature analysis were also performed. A series of germline-somatic variant pairs were detected. In all cases, the first hit was presented as a rare SNV/indel, whereas the second hit was either a different SNV (3 genes) or LOH affecting the same gene (141 genes). BRCA2, BLM, ERCC2, RECQL, REV3L and RIF1 were among the most promising candidate genes for germline CRC predisposition. The identification of new candidate genes involved in familial CRC could be achieved by our integrated analysis. Further functional studies and replication in additional cohorts are required to confirm the selected candidates

ProtozoaDB: dynamic visualization and exploration of protozoan genomes

ProtozoaDB (http://www.biowebdb.org/protozoadb) is being developed to initially host both genomics and post-genomics data from Plasmodium falciparum, Entamoeba histolytica, Trypanosoma brucei, T. cruzi and Leishmania major, but will hopefully host other protozoan species as more genomes are sequenced. It is based on the Genomics Unified Schema and offers a modern Web-based interface for user-friendly data visualization and exploration. This database is not intended to duplicate other similar efforts such as GeneDB, PlasmoDB, TcruziDB or even TDRtargets, but to be complementary by providing further analyses with emphasis on distant similarities (HMM-based) and phylogeny-based annotations including orthology analysis. ProtozoaDB will be progressively linked to the above-mentioned databases, focusing in performing a multi-source dynamic combination of information through advanced interoperable Web tools such as Web services. Also, to provide Web services will allow third-party software to retrieve and use data from ProtozoaDB in automated pipelines (workflows) or other interoperable Web technologies, promoting better information reuse and integration. We also expect ProtozoaDB to catalyze the development of local and regional bioinformatics capabilities (research and training), and therefore promote/enhance scientific advancement in developing countries

Oncogenic driver mutations predict outcome in a cohort of head and neck squamous cell carcinoma (HNSCC) patients within a clinical trial

234 diagnostic formalin-fixed paraffin-embedded (FFPE) blocks from homogeneously treated patients with locally advanced head and neck squamous cell carcinoma (HNSCC) within a multicentre phase III clinical trial were characterised. The mutational spectrum was examined by next generation sequencing in the 26 most frequent oncogenic drivers in cancer and correlated with treatment response and survival. Human papillomavirus (HPV) status was measured by p16INK4a immunohistochemistry in oropharyngeal tumours. Clinicopathological features and response to treatment were measured and compared with the sequencing results. The results indicated TP53 as the most mutated gene in locally advanced HNSCC. HPV-positive oropharyngeal tumours were less mutated than HPV-negative tumours in TP53 (p < 0.01). Mutational and HPV status influences patient survival, being mutated or HPV-negative tumours associated with poor overall survival (p < 0.05). No association was found between mutations and clinicopathological features. This study confirmed and expanded previously published genomic characterization data in HNSCC. Survival analysis showed that non-mutated HNSCC tumours associated with better prognosis and lack of mutations can be identified as an important biomarker in HNSCC. Frequent alterations in PI3K pathway in HPV-positive HNSCC could define a promising pathway for pharmacological intervention in this group of tumours

Collaborative database to track Mass Mortality Events in the Mediterranean Sea

Anthropogenic climate change, and global warming in particular, has strong and increasing impacts on marine ecosystems (Poloczanska et al., 2013; Halpern et al., 2015; Smale et al., 2019). The Mediterranean Sea is considered a marine biodiversity hotspot contributing to more than 7% of world\u2019s marine biodiversity including a high percentage of endemic species (Coll et al., 2010). The Mediterranean region is a climate change hotspot, where the respective impacts of warming are very pronounced and relatively well documented (Cramer et al., 2018). One of the major impacts of sea surface temperature rise in the marine coastal ecosystems is the occurrence of mass mortality events (MMEs). The first evidences of this phenomenon dated from the first half of \u201980 years affecting the Western Mediterranean and the Aegean Sea (Harmelin, 1984; Bavestrello and Boero, 1986; Gaino and Pronzato, 1989; Voultsiadou et al., 2011). The most impressive phenomenon happened in 1999 when an unprecedented large scale MME impacted populations of more than 30 species from different phyla along the French and Italian coasts (Cerrano et al., 2000; Perez et al., 2000). Following this event, several other large scale MMEs have been reported, along with numerous other minor ones, which are usually more restricted in geographic extend and/or number of affected species (Garrabou et al., 2009; Rivetti et al., 2014; Marb\ue0 et al., 2015; Rubio-Portillo et al., 2016, authors\u2019 personal observations). These events have generally been associated with strong and recurrent marine heat waves (Crisci et al., 2011; Kersting et al., 2013; Turicchia et al., 2018; Bensoussan et al., 2019) which are becoming more frequent globally (Smale et al., 2019). Both field observations and future projections using Regional Coupled Models (Adloff et al., 2015; Darmaraki et al., 2019) show the increase in Mediterranean sea surface temperature, with more frequent occurrence of extreme ocean warming events. As a result, new MMEs are expected during the coming years. To date, despite the efforts, neither updated nor comprehensive information can support scientific analysis of mortality events at a Mediterranean regional scale. Such information is vital to guide management and conservation strategies that can then inform adaptive management schemes that aim to face the impacts of climate change