Lipoarabinomannan and related glycoconjugates: structure, biogenesis and role in Mycobacterium tuberculosis physiology and host–pathogen interaction

Approximately one third of the world's population is infected with Mycobacterium tuberculosis, the causative agent of tuberculosis. This bacterium has an unusual lipid-rich cell wall containing a vast repertoire of antigens, providing a hydrophobic impermeable barrier against chemical drugs, thus representing an attractive target for vaccine and drug development. Apart from the mycolyl–arabinogalactan–peptidoglycan complex, mycobacteria possess several immunomodulatory constituents, notably lipomannan and lipoarabinomannan. The availability of whole-genome sequences of M. tuberculosis and related bacilli over the past decade has led to the identification and functional characterization of various enzymes and the potential drug targets involved in the biosynthesis of these glycoconjugates. Both lipomannan and lipoarabinomannan possess highly variable chemical structures, which interact with different receptors of the immune system during host–pathogen interactions, such as Toll-like receptors-2 and C-type lectins. Recently, the availability of mutants defective in the synthesis of these glycoconjugates in mycobacteria and the closely related bacterium, Corynebacterium glutamicum, has paved the way for host–pathogen interaction studies, as well as, providing attenuated strains of mycobacteria for the development of new vaccine candidates. This review provides a comprehensive account of the structure, biosynthesis and immunomodulatory properties of these important glycoconjugates

PDX1 DNA methylation distinguishes two subtypes of pancreatic neuroendocrine neoplasms with a different prognosis

DNA methylation is a crucial epigenetic mechanism for gene expression regulation and cell differentiation. Furthermore, it was found to play a major role in multiple pathological processes, including cancer. In pancreatic neuroendocrine neoplasms (PNENs), epigenetic deregulation is also considered to be of significance, as the most frequently mutated genes have an important function in epigenetic regulation. However, the exact changes in DNA methylation between PNENs and the endocrine cells of the pancreas, their likely cell-of-origin, remain largely unknown. Recently, two subtypes of PNENs have been described which were linked to cell-of-origin and have a different prognosis. A difference in the expression of the transcription factor PDX1 was one of the key molecular differences. In this study, we performed an exploratory genome-wide DNA methylation analysis using Infinium Methylation EPIC arrays (Illumina) on 26 PNENs and pancreatic islets of five healthy donors. In addition, the methylation profile of the PDX1 region was used to perform subtyping in a global cohort of 83 PNEN, 2 healthy alpha cell and 3 healthy beta cell samples. In our exploratory analysis, we identified 26,759 differentially methylated CpGs and 79 differentially methylated regions. The gene set enrichment analysis highlighted several interesting pathways targeted by altered DNA methylation, including MAPK, platelet-related and immune system-related pathways. Using the PDX1 methylation in 83 PNEN, 2 healthy alpha cell and 3 healthy beta cell samples, two subtypes were identified, subtypes A and B, which were similar to alpha and beta cells, respectively. These subtypes had different clinicopathological characteristics, a different pattern of chromosomal alterations and a different prognosis, with subtype A having a significantly worse prognosis compared with subtype B (HR 0.22 [95% CI: 0.051–0.95], p = 0.043). Hence, this study demonstrates that several cancer-related pathways are differently methylated between PNENs and normal islet cells. In addition, we validated the use of the PDX1 methylation status for the subtyping of PNENs and its prognostic importance

Selection for efficient translation initiation biases codon usage at second amino acid position in secretory proteins

The definition of a typical sec-dependent bacterial signal peptide contains a positive charge at the N-terminus, thought to be required for membrane association. In this study the amino acid distribution of all Escherichia coli secretory proteins were analysed. This revealed that there was a statistically significant bias for lysine at the second codon position (P2), consistent with a role for the positive charge in secretion. Removal of the positively charged residue P2 in two different model systems revealed that a positive charge is not required for protein export. A well-characterized feature of large amino acids like lysine at P2 is inhibition of N-terminal methionine removal by methionyl amino-peptidase (MAP). Substitution of lysine at P2 for other large or small amino acids did not affect protein export. Analysis of codon usage revealed that there was a bias for the AAA lysine codon at P2, suggesting that a non-coding function for the AAA codon may be responsible for the strong bias for lysine at P2 of secretory signal sequences. We conclude that the selection for high translation initiation efficiency maybe the selective pressure that has led to codon and consequent amino acid usage at P2 of secretory proteins

Frb 20210405i:a nearby Fast Radio Burst localised to sub-arcsecond precision with MeerKAT

We present the first sub-arcsecond localised Fast Radio Burst (FRB) detected using MeerKAT. FRB 20210405I was detected in the incoherent beam using the MeerTRAP pipeline on 2021 April 05 with a signal to noise ratio of 140.8 and a dispersion measure of 565.17 pc cm$^{-3}$. It was detected while MeerTRAP was observing commensally with the ThunderKAT large survey project, and was sufficiently bright that we could use the ThunderKAT 8s images to localise the FRB. Two different models of the dispersion measure in the Milky Way and halo suggest that the source is either right at the edge of the Galaxy, or outside. This highlights the uncertainty in the Milky Way dispersion measure models, particularly in the Galactic Plane, and the uncertainty of Milky Way halo models. Further investigation and modelling of these uncertainties will be facilitated by future detections and localisations of nearby FRBs. We use the combined localisation, dispersion measure, scattering, specific luminosity and chance coincidence probability information to find that the origin is most likely extra-galactic and identify the likely host galaxy of the FRB: 2MASS J1701249$-$4932475. Using SALT spectroscopy and archival observations of the field, we find that the host is a disk/spiral galaxy at a redshift of $z=0.066$

FRB 20210405I: a nearby Fast Radio Burst localised to sub-arcsecond precision with MeerKAT

We present the first sub-arcsecond localised Fast Radio Burst (FRB) detected using MeerKAT. FRB 20210405I was detected in the incoherent beam using the MeerTRAP pipeline on 2021 April 05 with a signal to noise ratio of 140.8 and a dispersion measure of 565.17 pc cm$^{-3}$. It was detected while MeerTRAP was observing commensally with the ThunderKAT large survey project, and was sufficiently bright that we could use the ThunderKAT 8s images to localise the FRB. Two different models of the dispersion measure in the Milky Way and halo suggest that the source is either right at the edge of the Galaxy, or outside. This highlights the uncertainty in the Milky Way dispersion measure models, particularly in the Galactic Plane, and the uncertainty of Milky Way halo models. Further investigation and modelling of these uncertainties will be facilitated by future detections and localisations of nearby FRBs. We use the combined localisation, dispersion measure, scattering, specific luminosity and chance coincidence probability information to find that the origin is most likely extra-galactic and identify the likely host galaxy of the FRB: 2MASS J1701249$-$4932475. Using SALT spectroscopy and archival observations of the field, we find that the host is a disk/spiral galaxy at a redshift of $z=0.066$.Comment: 15 pages, 4 tables, 10 figures. Accepted to MNRA

Red hot frogs:Identifying the Australian frogs most at risk of extinction

More than a third of the world’s amphibian species are listed as Threatened or Extinct, with a recent assessment identifying 45 Australian frogs (18.4% of the currently recognised species) as ‘Threatened’ based on IUCN criteria. We applied structured expert elicitation to 26 frogs assessed as Critically Endangered and Endangered to estimate their probability of extinction by 2040. We also investigated whether participant experience (measured as a self-assigned categorical score, i.e. ‘expert’ or ‘non-expert’) influenced the estimates. Collation and analysis of participant opinion indicated that eight species are at high risk (>50% chance) of becoming extinct by 2040, with the disease chytridiomycosis identified as the primary threat. A further five species are at moderate–high risk (30–50% chance), primarily due to climate change. Fourteen of the 26 frog species are endemic to Queensland, with many species restricted to small geographic ranges that are susceptible to stochastic events (e.g. a severe heatwave or a large bushfire). Experts were more likely to rate extinction probability higher for poorly known species (those with <10 experts), while non-experts were more likely to rate extinction probability higher for better-known species. However, scores converged following discussion, indicating that there was greater consensus in the estimates of extinction probability. Increased resourcing and management intervention are urgently needed to avert future extinctions of Australia’s frogs. Key priorities include developing and supporting captive management and establishing or extending in-situ population refuges to alleviate the impacts of disease and climate change

Nitrogen doping into titanium dioxide by the sol–gel method using nitric acid

N-doped TiO(2) has been prepared by use of sol-gel systems containing titanium alkoxide, with nitric acid as the nitrogen source. The time needed for gelation of the systems was drastically reduced by ultrasonic irradiation. The peaks assigned to the nitrate and nitrous ions were observed by FT-IR measurement during the sol-gel reaction. The N-doping was confirmed by the observation of N-O peaks in the XPS spectrum of the sample heated at 400 A degrees C. The nitrate ion acted as an oxidizer of the ethanol solvent and titanium species. The TiO(2) became doped with nitrogen oxide species as a result of reduction of nitrate ion incorporated into the dried gel samples. These results indicated that the added nitric acid was reduced during the sol-gel transition and heating process, and the resulting NO species were situated in the titania networks. The UV and visible photocatalytic activity of the samples was confirmed by the degradation of trichloroethylene.ArticleRESEARCH ON CHEMICAL INTERMEDIATES. 37(8):869-881 (2011)journal articl