Metabolomic profiling of amoebic and pyogenic liver abscesses: an in vitro NMR study

Pus samples obtained from 109 patients with liver abscess were examined by NMR spectroscopy. To our knowledge this is the first report on metabolic profiling of liver abscesses. Fifty metabolites were identified by combination of one (1D) and two-dimensional (2D) NMR spectra. Metabolic derangements were evaluated for differentiation between amoebic (ALA) and pyogenic liver abscess (PLA). The NMR results indicate that aspartate, asparagine and galactose, integral components of lipoproteophophoglycans (LPG) of the cell wall of Entamoeba histolytica are metabolic biomarkers of ALA. On the other hand, acetate, propionate, butyrate, succinate and formate, the fermentation products the facultative anaerobes are significantly prevalent in PLA. The NMR based metabolic profile of ALA and PLA are evaluated taking polymerase chain reaction (PCR) and bacterial culture as gold standard method. However, when NMR results were compared with culture and PCR methods, a correct diagnosis of 94.11% in ALA (n?=?85) and 100% in PLA (n?=?10) cases were observed. NMR spectroscopy in conjunction with PCR and culture can expedite in differentiating ALA from PLA.     

Microbial deracemisation of aromatic β-hydroxy acid esters

Aromatic β-hydroxy acid esters were found to undergo deracemisation using whole cells of Candida parapsilosis. The conditions for the deracemisation reaction were optimised where 75% isolated yield and >95% enantiomeric excess of the product was achieved. The effect of electron donating as well as electron withdrawing groups present in the standard substrate, ethyl 3-hydroxy 3-phenyl propionate was studied to establish the generality of the reaction. The enantiomeric excess of the product remains high (>95%) irrespective of the different substituents in the para position but substitution at the ortho position obstructs the process. Similarly, ethyl and methyl esters of the standard substrate undergo deracemisation reaction giving high ee of the product, but the benzyl ester of the standard substrate did not undergo deracemisation.     

Black and white with some shades of grey: the diverse responses of inducible metabolic pathways in Escherichia coli

The metabolic pathways for many sugars are inducible. This process has been extensively studied in the case of Escherichia coli lactose metabolism. It has long been known that gratuitous induction of the lac operon with non‐metabolizable lactose analogues generates an all‐or‐nothing response, where some cells express the lac genes at a maximal rate and others not at all. However, the response to lactose itself is graded, where all cells express the lac genes in proportion to lactose concentrations. The mechanisms generating these distinct behaviours in lactose metabolism have been a topic of many studies. Despite this large body of work, little is known about how other pathways respond to their cognate sugars. An article of Molecular Microbiology investigated the response of eight metabolic pathways in E. coli to their cognate sugars at single‐cell resolution. The authors demonstrate that these pathways exhibit diverse responses, ranging from graded to all‐or‐nothing responses and combinations thereof. Remarkably, they were able to interpret these responses using a simple mathematical model and identify the mechanisms likely giving rise to each.     

Effect of different arginine methylations on the thermodynamics of Tat peptide binding to HIV-1 TAR RNA

RNA-binding proteins are an important class of mediators that regulate cell function and differentiation. Methylation of arginine, a post-translational modification (PTM) found in these proteins, can modulate their function. Arginine can be monomethylated or dimethylated, depending on the type of methyl transferases involved. This paper describes a comparative study of the thermodynamics of unmodified and modified Tat peptide interaction with TAR RNA, where the peptide is methylated at epsilon (?) and eta (η) nitrogen atoms of guanidinium group of arginine side chain at position 52 or 53. The results indicate that monomethylation of arginine at epsilon (?) nitrogen atom enhances binding affinity, owing to a more favourable enthalpy component which overrides the less favourable entropy change. In contrast, monomethylation of arginine residue at η nitrogen results in reduced binding affinity originating exclusively from a less favourable enthalpy change leaving entropic component unaffected. However, in case of simultaneous methylation at ? and η positions, the binding parameters remain almost unaffected, when compared to the unmodified peptide. In case of symmetric dimethylation at η position the observed enthalpy change of the binding was found to be smaller than the values obtained for the unmodified peptide. Asymmetric dimethylation at η position showed the most reduced binding affinities owing to less favourable enthalpy changes. These results provide insights that enable elucidation of the biological outcome of arginine methylation as PTMs that regulate protein function, and will contribute to our understanding of how these PTMs are established in vitro and in vivo.     

Mesenchymal stem cells as living anti-inflammatory therapy for COVID-19 related acute respiratory distress syndrome

Coronavirus disease 2019(COVID-19), a pandemic disease caused by the severe acute respiratory syndrome coronavirus 2(SARS-Co V2), is growing at an exponential rate worldwide. Manifestations of this disease are heterogeneous; however, advanced cases often exhibit various acute respiratory distress syndrome-like symptoms, systemic inflammatory reactions, coagulopathy, and organ involvements. A common theme in advanced COVID-19 is unrestrained immune activation, classically referred to as a "cytokine storm", as well as deficiencies in immune regulatory mechanisms such as T regulatory cells. While mesenchymal stem cells(MSCs) themselves are objects of cytokine regulation, they can secrete cytokines to modulate immune cells by inducing antiinflammatory regulatory Treg cells, macrophages and neutrophils; and by reducing the activation of T and B cells, dendritic and nature killer cells. Consequently, they have therapeutic potential for treating severe cases of COVID-19. Here we discuss the unique ability of MSCs, to act as a "living antiinflammatory", which can "rebalance" the cytokine/immune responses to restore equilibrium. We also discuss current MSC trials and present different concepts for optimization of MSC therapy in patients with COVID-19 acute respiratory distress syndrome.     

Fabrication of polyaniline/graphene oxide composites for implementation in humidity sensing

This work reports the measurement of impedance variations under various humidity conditions at frequency ranges between 100 Hz and 5 MHz. An electrochemical polymerization process has been used in the synthesis including varying the mass ratios of graphene oxide (GO) in polyaniline. An electrochemical deposition method has been used to produce a sample film on an indium tin oxide glass slide. The percentage relative humidity (RH%) of the samples has been estimated to be 20–90%. Impedance and humidity had an inverse relationship, i.e. the impedance value decreased with an increase in humidity. In contrast with platinum capacitive humidity sensors (HS), the GO-based HS had a sensitivity of 75–99%, which was ~10-fold more than that of traditional sensors. With three different parameter weight % of GO, the frequency range have been 100 Hz to 5 MHz and RH% has been found to 20–90%. The HS showed a fast response and recovery time. Therefore, GO appears to be a useful material for building HS with high sensitivity for a comprehensive approach.