The rare pediatric embryonal tumors retinoblastoma, medulloblastoma and neuroblastoma derive from neuroectodermal tissue and share similar histopathological features despite different anatomical locations and diverse clinical outcomes. As metabolism can reflect genetic and histological features, we investigated whether the metabolism of embryonal tumors reflects their similar histology, shared developmental and neural origins, or tumor location. We undertook metabolic profiling on 50 retinoblastoma, 39 medulloblastoma and 70 neuroblastoma using high resolution magic angle spinning magnetic resonance spectroscopy (1H-MRS). Mean metabolite concentrations identified several metabolites that were significantly different between the tumor groups including taurine, hypotaurine, glutamate, glutamine, GABA, phosphocholine, N-acetylaspartate, creatine, glycine and myoinositol, p < 0.0017. Unsupervised multivariate analysis found that each tumor group clustered separately, with a unique metabolic profile, influenced by their underlying clinical diversity. Taurine was notably high in all tumors consistent with prior evidence from embryonal tumors. Retinoblastoma and medulloblastoma were more metabolically similar, sharing features associated with the central nervous system (CNS). Neuroblastoma had features consistent with neural tissue, but also contained significantly higher myoinositol and altered glutamate-glutamine ratio, suggestive of differences in the underlying metabolism of embryonal tumors located outside of the CNS. Despite the histological similarities and shared neural metabolic features, we show that individual neuroectodermal derived embryonal tumors can be distinguished by tissue metabolic profile. Pathway analysis suggests the alanine-aspartate-glutamate and taurine-hypotaurine metabolic pathways may be the most pertinent pathways to investigate for novel therapeutic strategies. This work strengthens our understanding of the biology and metabolic pathways underlying neuroectodermal derived embryonal tumors of childhood.

Non-small cell lung cancer (NSCLC) is associated with high morbidity and mortality, leading the understanding the pathogenesis paramount. Recent studies suggest that long non-coding RNAs (lncRNAs) play an important role in NSCLC. We conducted a systematic review to examine the relationship between lncRNAs and NSCLC.

The association of hemodynamics with cognitive impairment and white matter lesions (WMLs) has come to the foreground in recent years. Six hundred eighty-nine elderly participants aged ≥60 years were eligible enrolled. After an average of 5.4 years follow-up, there was a significant decline in Mini-Mental State Examination (MMSE) scores and increases in total white matter hyperintensities (WMH), periventricular (P)WMH, and deep (D)WMH (P < 0.001). The participants were grouped by the tertiles of carotid mean wall shear stress (WSS). The decline in MMSE scores and the increases in total WMH, PWMH, and DWMH decreased from the lowest group to the highest group. There were significant differences between each group comparison (all P <0.05). Mean WSS was an independent and significant factor for the changes in MMSE scores, total WMH, PWMH, and DWMH after adjustment for confounders (P <0.001). The risk of developing cognitive impairment was higher in the lowest (hazard ratio: 2.753; 95% CI: 1.945 to 3.895; P < 0.001) and intermediate (hazard ratio: 1.531; 95% CI: 1.084 to 2.162; P = 0.015) groups than in the highest group after adjustment for confounders. Similar associations were yielded between peak WSS and the changes in MMSE scores, total WMH, PWMH, and DWMH. Our results indicated that carotid WSS is an independent factor for the progression of cognitive impairment and WMLs in the elderly. Low WSS significantly deteriorates the progression of cognitive impairment and WMLs.

Hepatic insulin resistance and increased gluconeogenesis are known therapeutic targets of metformin, but the role of hepatic glycogen in the pathogenesis of diabetes is less clear. Mouse model of neuropeptide Y (NPY) overexpression in noradrenergic neurons (OE-NPYDβH) with a phenotype of late onset obesity, hepatosteatosis, and prediabetes was used to study early changes in glycogen structure and metabolism preceding prediabetes. Furthermore, the effect of the anti-hyperglycemic agent, metformin (300 mg/kg/day/4 weeks in drinking water), was assessed on changes in glycogen metabolism, body weight, fat mass, and glucose tolerance. Glycogen structure was characterized by cytofluorometric analysis in isolated hepatocytes and mRNA expression of key enzymes by qPCR. OE-NPYDβH mice displayed decreased labile glycogen fraction relative to stabile fraction (the intermediate form of glycogen) suggesting enhanced glycogen cycling. This was supported by decreased filling of glucose residues in the 10th outer tier of the glycogen molecule, which suggests accelerated glycogen phosphorylation. Metformin reduced fat mass gain in both genotypes, but glucose tolerance was improved mostly in wild-type mice. However, metformin inhibited glycogen accumulation and normalized the ratio between glycogen structures in OE-NPYDβH mice indicating decreased glycogen synthesis. Furthermore, the presence of glucose residues in the 11th tier together with decreased glycogen phosphorylase expression suggested inhibition of glycogen degradation. In conclusion, structural changes in glycogen of OE-NPYDβH mice point to increased glycogen metabolism, which may predispose them to prediabetes. Metformin treatment normalizes these changes and suppresses both glycogen synthesis and phosphorylation, which may contribute to its preventive effect on the onset of diabetes.

Tissue-mimicking phantoms are widely used for the calibration, evaluation and standardisation of medical imaging systems, and for clinical training. For photoacoustic imaging, tissue-mimicking materials (TMMs) that have tuneable optical and acoustic properties, high stability, and mechanical robustness are highly desired. In this study, gel wax is introduced as a TMM that satisfies these criteria for developing photoacoustic imaging phantoms. The reduced scattering and optical absorption coefficients were independently tuned with the addition of TiO2 and oil-based inks. The frequency-dependent acoustic attenuation obeyed a power law; for native gel wax, it varied from 0.71 dB/cm at 3 MHz to 9.93 dB/cm at 12 MHz. The chosen oil-based inks, which have different optical absorption spectra in the range of 400 to 900 nm, were found to have good photostability under pulsed illumination with photoacoustic excitation light. Optically heterogeneous phantoms that comprised of inclusions with different concentrations of carbon black and coloured inks were fabricated, and multispectral photoacoustic imaging was performed with an optical parametric oscillator and a planar Fabry-Pérot sensor. We conclude that gel wax is well suited as a TMM for multispectral photoacoustic imaging.

Bioluminescence imaging has shown great potential for studying and monitoring disease progression in small animal pre-clinical imaging. However, absolute bioluminescence source recovery through tomographic multi-wavelength measurements is often hindered through the lack of quantitative accuracy and suffers from both poor localisation and quantitative recovery. In this work a method to incorporate a permissible region strategy through not only a priori location (permissible region) but also based on a model of light propagation and hence light sensitivity is developed and tested using both simulations and experimental data. Reconstructions on two different numerical models (a simple slab, and the digital version of a heterogeneous mouse) show an improvement of localisation and recovery of intensity (around 25% for the slab model and around 10% for the digital mouse model). This strategy is also used with experimental data from a phantom gel, which demonstrated an improved recovered tomographic image.

To evaluate the validity of Memorial Sloan-Kettering Cancer Center (MSKCC) and International Extranodal Lymphoma Study Group (IELSG) prognostic scoring systems for Overall Survival (OS) in intracranial Primary CNS lymphoma (PCNSL) of all patients diagnosed at a single center.

MRI measures of network integrity may be useful disease markers in cerebral small vessel disease (SVD). We compared the sensitivity and reproducibility of MRI derived structural and functional network measures in healthy controls and SVD subjects.

Among four crude oil-degrading fungi strains that were isolated from a petroleum-polluted area in the Rumaila oil field, two fungi strains showed high activity in aliphatic hydrocarbon degradation. ITS sequencing and analysis of morphological and biochemical characteristics identified these strains as Penicillium sp. RMA1 and RMA2. Gravimetric and gas chromatography analysis of the crude oil remaining in the culture medium after 14 days of incubation at 30 °C showed that RMA1 and RMA2 degraded the crude oil by 57% and 55%, respectively. These strains reduced surface tension when cultured on crude oil (1% v/v) and exhibited a cell surface hydrophobicity of more than 70%. These results suggested that RMA1 and RMA2 performed effective crude oil-degrading activity and crude oil emulsification. In conclusion, these fungal strains can be used in bioremediation process and oil pollution reduction in aquatic ecosystems.

Burkholderia cenocepacia is an opportunistic bacterium that can thrive in different environments, including the amino acid-rich mucus of the cystic fibrosis (CF) lung. B. cenocepacia responds to the nutritional conditions that mimic the CF sputum by increasing flagellin expression and swimming motility. Individual amino acids also induce swimming but not flagellin expression. Here, we show that modulation of the second messenger cyclic dimeric guanosine monophosphate (c-di-GMP) levels by the PAS-containing c-di-GMP phosphodiesterase, BCAL1069 (CdpA), regulates the swimming motility of B. cenocepacia K56-2 in response to CF sputum nutritional conditions. Heterologous expression of WspR, a diguanylate cyclase, in B. cenocepacia K56-2 caused an increase in c-di-GMP levels and reduced swimming motility but did not affect flagellin expression or flagellar biosynthesis. After insertional mutagenesis of 12 putative genes encoding c-di-GMP metabolizing enzymes, one mutant of the locus BCAL1069 (cdpA), exhibited decreased swimming motility independent of flagellin expression in CF sputum nutritional conditions and an increase in intracellular c-di-GMP levels. The reduced swimming motility phenotype of the BCAL1069 mutant was observed in the presence of arginine and glutamate, but not of histidine, phenylalanine, or proline. The B. cenocepacia CdpA was also found to be involved in regulation of protease activity but not in biofilm formation. Altogether, these results highlight a role of B. cenocepacia BCAL1069 (CdpA) in sensing the nutritional conditions of the CF sputum and eliciting a pathogenic response that includes swimming motility toward amino acids and an increase in protease activity.

Despite its study since the 1960's, very little is known about the post-translational regulation of the multiple catalytic activities performed by protein disulfide isomerase (PDI), the primary protein folding catalyst of the cell. This work identifies a functional role for the highly conserved CxxC-flanking residues Lys57 and Lys401 of human PDI in vitro. Mutagenesis studies have revealed these residues as modulating the oxidoreductase activity of PDI in a pH-dependent manner. Non-conservative amino acid substitutions resulted in enzyme variants upwards of 7-fold less efficient. This attenuated activity was found to translate into a 2-fold reduction of the rate of electron shuttling between PDI and the intraluminal endoplasmic reticulum oxidase, ERO1α, suggesting a functional significance to oxidative protein folding. In light of this, the possibility of lysine acetylation at residues Lys57 and Lys401 was assessed by in vitro treatment using acetylsalicylic acid (aspirin). A total of 28 acetyllysine residues were identified, including acLys57 and acLys401. The kinetic behavior of the acetylated protein form nearly mimicked that obtained with a K57/401Q double substitution variant providing an indication that acetylation of the active site-flanking lysine residues can act to reversibly modulate PDI activity.

Diabetes mellitus is a global health problem representing the fifth leading cause of mortality and a major risk factor for cardiovascular diseases. In the last years, we reported an association among urinary trypsin inhibitor (UTI), a small proteoglycan that plays pleiotropic roles in many inflammatory processes, and both type 1 and 2 diabetes and developed a method for its direct quantitation and structural characterization.

This article describes the analysis of volatile compounds in fermented materials used for salmon fish sauce production via gas chromatography/mass spectrometry (GC/MS). Ten types of fish sauces were produced from raw salmon materials, including various proportions of flesh, viscera, inedible portion (heads, fins, and backbones), and soft roe, by mixing them with salt and allowing them to ferment for up to three months. The volatile compounds were captured by a solid-phase microextraction method and then applied to GC/MS for separation and identification of the compounds in the fish sauce products. The number of volatile compounds identified in the starting materials varied from 15 to 29 depending on the ingredients. The number of compounds in the final fish sauce products was reduced by 3.4-94.7% of that in the original material. The retention times and names of the identified compounds, as well as their relative peak areas, are provided in a Microsoft Excel Worksheet.

The incidence and severity of respiratory diseases in commercial broiler chicken flocks have increased recently in India because of intensification of the broiler industry. Viral population are predominant in respiratory tract infections and they pose continuous economic burden to poultry industry by causing severe economic losses through decreased productivity [1], [2]. To understand viral metagenome of poultry associated with respiratory infections, we performed DNA virome sequencing and data analysis of broilers from 8 districts of Gujarat State in India. We report high quality sequencing reads and highly abundant DNA viral population present in the infected broiler birds. The raw sequencing data used to perform metagenomic analysis is available in the Sequence Read Archive (SRA) under the BioProject No. PRJNA322592 and Accession No. MAUZ00000000, MAVA00000000, MAVB00000000, MAVC00000000, MAVD00000000, MAVE00000000, MAVF00000000, MAVG00000000 (https://www.ncbi.nlm.nih.gov/bioproject/?term=PRJNA322592).

Stress perfusion cardiac magnetic resonance (CMR) has been proposed as an important gatekeeper for invasive coronary angiography (ICA) and percutaneous coronary interventions (PCI) in patients evaluated for possible coronary artery disease (CAD) (Fihn et al., 2012; Montalescot et al., 2013) [1], [2]. Several meta-analyses have evaluated the accuracy of stress perfusion CMR to diagnose CAD at the vessel level (Danad et al., 2017; Dai et al., 2016; Jiang et al., 2016; Takx et al., 2015; Li et al., 2015; Desai and Jha, 2013; Jaarsma et al. 2012; Hamon et al., 2010; Nandalur et al. 2007) [3], [4], [5], [6], [7], [8], [9], [10], [11]. However, they included in the same analysis studies with different definitions of significant CAD (i.e. fractional flow reserve [FFR] < 0.75 and < 0.80 or coronary stenosis ≥ 50% and ≥ 70%), magnetic field strength (1.5 or 3 Tesla [T]), and study protocol (integration or not of late gadolinium enhancement [LGE] into stress perfusion protocol). Data of 34 studies (6091 arteries) have been pooled with the aim of analyzing the accuracy of stress perfusion CMR for the diagnosis of ischemic heart disease at the vessel level according to different definitions of significant CAD, magnetic field strength and study protocol (Arnold et al., 2010; Bettencourt et al., 2013; Cheng et al., 2007; Chiribiri et al., 2013; Cury et al., 2006; De Mello et al., 2012; Donati et al., 2010; Ebersberger et al., 2013; Gebker et al., 2008; Greulich et al., 2015; Hussain et al., 2016; Ishida et al., 2005, 2003; Kamiya et al., 2014; Kitagawa et al., 2008; Klein et al., 2008; Klem et al., 2006; Klumpp et al., 2010; Krittayaphong et al., 2009; Lockie et al., 2011; Ma et al., 2012; Merkle et al., 2007; Meyer et al., 2008; Mor-Avi et al., 2008; Pan et al., 2015; Papanastasiou et al., 2016; Pons Lladó et al., 2004; Sakuma et al., 2005; Salerno et al., 2014; Scheffel et al., 2010; van Werkhoven et al., 2010; Walcher et al., 2013; Watkins et al., 2009; Yun et al., 2015) [12-45]. This article describes data related article titled "Diagnostic Performance of Stress Perfusion Cardiac Magnetic Resonance for the Detection of Coronary Artery Disease" (Kiaos et al., submitted for publication) [46].

Retinoic acid (RA) is a metabolite of vitamin A and has important roles in development, differentiation, and reproduction. Activin has been shown to regulate the RA pathway and affect granulosa cell (GC) proliferation, suggesting that RA is important for early follicle development. However, little is known about the effects of RA on GC functions, particularly steroidogenesis, during the early follicle stage. The aim of this study was to investigate the effects of all-trans-RA (atRA) on progesterone production in immature rat GCs cultured without gonadotropin. Our results demonstrated that atRA enhanced progesterone production by upregulating the levels of steroidogenic acute regulatory protein (StAR) and cytochrome P450scc (Cyp11a1) mRNAs, but not 3β-hydroxysteroid dehydrogenase mRNA in immature rat GCs. Additionally, analysis of the mechanisms through which atRA upregulated StAR and Cyp11a1 mRNAs revealed that atRA enhanced intracellular cAMP accumulation and phosphorylation of cAMP response-element binding protein (CREB). In addition, H-89, an inhibitor of protein kinase A (PKA), abolished the stimulatory effects of atRA, indicating that atRA enhanced progesterone synthesis through cAMP/PKA signaling. In conclusion, our data demonstrated that atRA has a crucial role in progesterone synthesis in rat GCs during the early follicle stage.

Hepatitis B virus (HBV) affects up to 400 million people worldwide and accounts for approximately one million deaths per year from liver pathologies. Current treatment regimens are effective in suppressing viremia but usually have to be taken indefinitely, warranting research into new therapeutic approaches. Acute HBV infection in adults almost universally results in resolution of viremia, with the exception of immunocompromised persons, suggesting that the immune response can functionally cure or even eradicate HBV infection.

Adamantinomatous craniopharyngiomas (ACPs) are clinically challenging tumours, the majority of which have activating mutations in CTNNB1. They are histologically complex, showing cystic and solid components, the latter comprised of different morphological cell types (e.g. β-catenin-accumulating cluster cells and palisading epithelium), surrounded by a florid glial reaction with immune cells. Here, we have carried out RNA sequencing on 18 ACP samples and integrated these data with an existing ACP transcriptomic dataset. No studies so far have examined the patterns of gene expression within the different cellular compartments of the tumour. To achieve this goal, we have combined laser capture microdissection with computational analyses to reveal groups of genes that are associated with either epithelial tumour cells (clusters and palisading epithelium), glial tissue or immune infiltrate. We use these human ACP molecular signatures and RNA-Seq data from two ACP mouse models to reveal that cell clusters are molecularly analogous to the enamel knot, a critical signalling centre controlling normal tooth morphogenesis. Supporting this finding, we show that human cluster cells express high levels of several members of the FGF, TGFB and BMP families of secreted factors, which signal to neighbouring cells as evidenced by immunostaining against the phosphorylated proteins pERK1/2, pSMAD3 and pSMAD1/5/9 in both human and mouse ACP. We reveal that inhibiting the MAPK/ERK pathway with trametinib, a clinically approved MEK inhibitor, results in reduced proliferation and increased apoptosis in explant cultures of human and mouse ACP. Finally, we analyse a prominent molecular signature in the glial reactive tissue to characterise the inflammatory microenvironment and uncover the activation of inflammasomes in human ACP. We validate these results by immunostaining against immune cell markers, cytokine ELISA and proteome analysis in both solid tumour and cystic fluid from ACP patients. Our data support a new molecular paradigm for understanding ACP tumorigenesis as an aberrant mimic of natural tooth development and opens new therapeutic opportunities by revealing the activation of the MAPK/ERK and inflammasome pathways in human ACP.

Hepatitis C virus (HCV) is a leading cause of liver disease worldwide. Although several HCV protease/polymerase inhibitors were recently approved by U.S. FDA, the combination of antivirals targeting multiple processes of HCV lifecycle would optimize anti-HCV therapy and against potential drug-resistance. Viral entry is an essential target step for antiviral development, but FDA-approved HCV entry inhibitor remains exclusive. Here we identify serotonin 2A receptor (5-HT2AR) is a HCV entry factor amendable to therapeutic intervention by a chemical biology strategy. The silencing of 5-HT2AR and clinically available 5-HT2AR antagonist suppress cell culture-derived HCV (HCVcc) in different liver cells and primary human hepatocytes at late endocytosis process. The mechanism is related to regulate the correct plasma membrane localization of claudin 1 (CLDN1). Moreover, phenoxybenzamine (PBZ), an FDA-approved 5-HT2AR antagonist, inhibits all major HCV genotypes in vitro and displays synergy in combination with clinical used anti-HCV drugs. The impact of PBZ on HCV genotype 2a is documented in immune-competent humanized transgenic mice. Our results not only expand the understanding of HCV entry, but also present a promising target for the invention of HCV entry inhibitor.

To evaluate the efficiency of ovarian tissue heterotopic autografting after vitrification in prepubertal rats.