Zika Virus Growth in Human Kidney Cells Is Restricted by an Elevated Glucose Level

Mosquito-borne Zika virus (ZIKV) became a real threat to human health due to the lack of vaccine and effective antiviral treatment. The virus has recently been responsible for a global outbreak leading to millions of infected cases. ZIKV complications were highlighted in adults with Guillain–Barré syndrome and in newborns with increasing numbers of congenital disorders ranging from mild developmental delays to fatal conditions. The ability of ZIKV to establish a long-term infection in diverse organs including the kidneys has been recently documented but the consequences of such a viral infection are still debated. Our study aimed to determine whether the efficiency of ZIKV growth in kidney cells relates to glucose concentration. Human kidney HK-2 cells were infected with different ZIKV strains in presence of normal and high glucose concentrations. Virological assays showed a decrease in viral replication without modifying entry steps (viral binding, internalization, fusion) under high glucose conditions. This decrease replication was associated with a lower virus progeny and increased cell viability when compared to ZIKV-infected HK-2 cells in normal glucose concentration. In conclusion, we showed for the first time that an elevated glucose level influences ZIKV replication level with an effect on kidney cell survival.     

Adventitial Tertiary Lymphoid Organs as Potential Source of MicroRNA Biomarkers for Abdominal Aortic Aneurysm

Abdominal aortic aneurysm (AAA) is an inflammatory disease associated with marked changes in the cellular composition of the aortic wall. This study aims to identify microRNA (miRNA) expression in aneurysmal inflammatory cells isolated by laser microdissection from human tissue samples. The distribution of inflammatory cells (neutrophils, B and T lymphocytes, mast cells) was evaluated in human AAA biopsies. We observed in half of the samples that adventitial tertiary lymphoid organs (ATLOs) with a thickness from 0.5 to 2 mm were located exclusively in the adventitia. Out of the 850 miRNA that were screened by microarray in isolated ATLOs (n = 2), 164 miRNAs were detected in ATLOs. The three miRNAs (miR-15a-3p, miR-30a-5p and miR-489-3p) with the highest expression levels were chosen and their expression quantified by RT-PCR in isolated ATLOs (n = 4), M1 (n = 2) and M2 macrophages (n = 2) and entire aneurysmal biopsies (n = 3). Except for the miR-30a-5p, a similar modulation was found in ATLOs and the two subtypes of macrophages. The modulated miRNAs were then evaluated in the plasma of AAA patients for their potential as AAA biomarkers. Our data emphasize the potential of miR-15a-3p and miR-30a-5p as biomarkers of AAA but also as triggers of ATLO evolution. Further investigations will be required to evaluate their targets in order to better understand AAA pathophysiology.     

Alteration of the Route to Menaquinone towards Isochorismate-Derived Metabolites

Chorismate and isochorismate constitute branch-point intermediates in the biosynthesis of many aromatic metabolites in microorganisms and plants. To obtain unnatural compounds, we modified the route to menaquinone in Escherichia coli. We propose a model for the binding of isochorismate to the active site of MenD ((1R,2S, 5S,6S)-2-succinyl-5-enolpyruvyl-6-hydroxycyclohex-3-ene-1-carboxylate (SEPHCHC) synthase) that explains the outcome of the native reaction with α-ketoglutarate. We have rationally designed variants of MenD for the conversion of several isochorismate analogues. The double-variant Asn117Arg–Leu478Thr preferentially converts (5S,6S)-5,6-dihydroxycyclohexa-1,3-diene-1-carboxylate (2,3-trans-CHD), the hydrolysis product of isochorismate, with a >70-fold higher ratio than that for the wild type. The single-variant Arg107Ile uses (5S,6S)-6-amino-5-hydroxycyclohexa-1,3-diene-1-carboxylate (2,3-trans-CHA) as substrate with >6-fold conversion compared to wild-type MenD. The novel compounds have been made accessible in vivo (up to 5.3 g L⁻¹). Unexpectedly, as the identified residues such as Arg107 are highly conserved (>94 %), some of the designed variations can be found in wild-type SEPHCHC synthases from other bacteria (Arg107Lys, 0.3 %). This raises the question for the possible natural occurrence of as yet unexplored branches of the shikimate pathway.     

Computer Vision and Pattern Recognition 2020

International Journal of Computer Vision -     

Surgery for hepatoblastoma in children

In order to characterize the role of transforming growth factor-alpha (TGF alpha) during hepatocarcinogenesis, liver tissue was examined at 10, 16, and 19 weeks following initial 10-week diethylnitrosamine (50 mg l-1 drinking water) exposure in female Wistar rats. Liver tissue protein extracts were electrophoresed and transferred to nitrocellulose filters. Levels of tissue-derived TGF alpha and epidermal growth factor receptor (EGFr) were assessed using an anti-TGF alpha monoclonal antibody (Ab-1) and an anti-EGFr polyclonal antibody (AB-4), coupled with scanning densitometric quantification. Immunolocalization of TGF alpha was performed in Bouin's-fixed, paraffin-embedded liver tissue sections. The distribution and intensity of TGF alpha immunoreactivity varied according to the degree of dysplasia, severely dysplastic cells being strongly immunoreactive. At week 10, mild hepatocyte dysplasia and perivenular inflammation were evident, together with a corresponding increase in perivenular TGF alpha immunoreactivity. By week 16, foci of moderate to severe dysplasia were observed; at this stage, there was a decrease in perivenular immunoreactivity but a further increase in overall liver tissue TGF alpha levels. Some 'altered foci' and dysplastic nodules showed intense immunoreactivity for TGF alpha. At these time points, immunodetectable liver EGFr was found to decrease significantly in comparison with normal control tissue. TGF alpha immunoreactivity was observed in fully developed carcinomas at week 19, although some tumours were negative by immunohistochemistry. The up-regulation of immunodetectable TGF alpha and the concomitant down-regulation of EGFr demonstrated positive (P < 0.01) and negative (P < 0.001) correlations, respectively, with hepatocyte proliferation indices. These findings suggest that the TGF alpha/EGFr ligand receptor system may be important during tumour promotion and in the stimulation of continued proliferation in hepatocellular carcinomas.     

Performance evaluation of a water/silicone oil two‐phase partitioning bioreactor using Rhodococcus erythropolis T902.1 to remove volatile organic compounds from gaseous effluents

BACKGROUND: In the framework of biological processes used for waste gas treatment, the impact of the inoculum size on the start‐up performance needs to be better evaluated. Moreover, only a few studies have investigated the behaviour of elimination capacity and biomass viability in a two‐phase partitioning bioreactor (TPPB) used for waste gas treatment. Lastly, the impact of ethanol as a co‐substrate remains misunderstood. RESULTS: Firstly, no benefit of inoculation with a high cellular density (>1.5 g L^?1) was observed in terms of start‐up performance. Secondly, the TPPB was monitored for 38 days to characterise its behaviour under several operational conditions. The removal efficiency remained above 63% for an inlet concentration of 7 g isopropylbenzene (IPB) m^?3 and at some time points reached 92% during an intermittent loading phase (10 h day^?1), corresponding to a mean elimination capacity of 4 × 10^?3 g L^?1 min^?1 (240 g m^?3 h^?1) for a mean IPB inlet load of 6.19 × 10^?3 g L^?1 min^?1 (390 g m^?3 h^?1). Under continuous IPB loading, the performance of the TPPB declined, but the period of biomass acclimatisation to this operational condition was shorter than 5 days. The biomass grew to approximately 10 g L^?1 but the cellular viability changed greatly during the experiment, suggesting an endorespiration phenomenon in the bioreactor. It was also shown that simultaneous degradation of IPB and ethanol occurred, suggesting that ethanol improves the biodegradation process without causing oxygen depletion. CONCLUSION: A water/silicone oil TPPB with ethanol as co‐substrate allowed the removal of a high inlet load of IPB during an experiment lasting 38 days. Copyright © 2008 Society of Chemical Industry