Use of laboratory-developed assays in global HIV-1 treatment-monitoring and research

There has been a surge in the emergence of HIV-1 drug resistance in Low and Middle-Income Countries (LMICs) due to poor drug-adherence and limited access to viral load testing, the current standard for treatment-monitoring. It is estimated that only 75% of people living with HIV (PLWH) worldwide have access to viral load testing. In LMICs, this figure is below 50%. In a recent WHO survey in mostly LMICs, 21 out of 30 countries surveyed found HIV-1 first-line pre-treatment drug resistance in over 10% of study participants. In the worst-affected regions, up to 68% of infants born to HIV-1 positive mothers were found to harbour first-line HIV-1 treatment resistance. This is a huge public health concern. Greater access to treatment-monitoring is required in LMICs if the UNAIDS "third 95" targets are to be achieved by 2030. Here, we review the current challenges of viral load testing and present the case for greater utilization of Laboratory-based assays that quantify intracellular HIV-1 RNA and/or DNA to provide broader worldwide access to HIV-1 surveillance, drug-resistance monitoring, and cure-research

Corrosion and Electrochemical Properties of Laser-Shock-Peening-Treated Stainless Steel AISI 304L in VVER Primary Water Environment

Laser Shock Peening (LSP) is a surface treatment technique for metallic materials. It induces plastic deformation at the surface of up to around 1 mm in depth. This process introduces residual stresses that lead to strain hardening, and potentially improvements in fatigue, stress corrosion cracking (SCC) and general corrosion behaviour in many, but not all, corrosive media. In this paper, two specimens made of AISI 304L stainless steel, one LSP-treated and one un-treated, were tested at 280 °C and 8 MPa in VVER (or PWR) primary circuit water chemistry using in situ Electrochemical Impedance Spectroscopy (EIS). This experiment serves to qualify the influence of LSP on the changes in corrosion behaviour in high-temperature, high-density water. The residual stress (RS) measurement of the surface showed a compression RS. Before LSP treatment, RS at the surface was 52.2 MPa in the rolling direction 0°RD and 10.42 MPa in the transverse rolling direction 90°RD. After the treatment, surface RS was −175.27 MPa and −183.51 MPa for Scan and TScan directions, respectively. The effect of compressive RS at the surface was studied and showed an increase in corrosion rate. The analysis of oxide layer by SEM revealed differences between LSP-treated and untreated AISI 304L specimens and their connection to corrosion rates

Stability and dynamics of polycomb target sites in Drosophila development.

Polycomb-group (PcG) and Trithorax-group proteins together form a maintenance machinery that is responsible for stable heritable states of gene activity. While the best-studied target genes are the Hox genes of the Antennapedia and Bithorax complexes, a large number of key developmental genes are also Polycomb (Pc) targets, indicating a widespread role for this maintenance machinery in cell fate determination. We have studied the linkage between the binding of PcG proteins and the developmental regulation of gene expression using whole-genome mapping to identify sites bound by the PcG proteins, Pc and Pleiohomeotic (Pho), in the Drosophila embryo and in a more restricted tissue, the imaginal discs of the third thoracic segment. Our data provide support for the idea that Pho is a general component of the maintenance machinery, since the majority of Pc targets are also associated with Pho binding. We find, in general, considerable developmental stability of Pc and Pho binding at target genes and observe that Pc/Pho binding can be associated with both expressed and inactive genes. In particular, at the Hox complexes, both active and inactive genes have significant Pc and Pho binding. However, in comparison to inactive genes, the active Hox genes show reduced and altered binding profiles. During development, Pc target genes are not simply constantly associated with Pc/Pho binding, and we identify sets of genes with clear differential binding between embryo and imaginal disc. Using existing datasets, we show that for specific fate-determining genes of the haemocyte lineage, the active state is characterised by lack of Pc binding. Overall, our analysis suggests a dynamic relationship between Pc/Pho binding and gene transcription. Pc/Pho binding does not preclude transcription, but levels of Pc/Pho binding change during development, and loss of Pc/Pho binding can be associated with both stable gene activity and inactivity

ChIP-Chip Designs to Interrogate the Genome of Xenopus Embryos for Transcription Factor Binding and Epigenetic Regulation

Chromatin immunoprecipitation combined with genome tile path microarrays or deep sequencing can be used to study genome-wide epigenetic profiles and the transcription factor binding repertoire. Although well studied in a variety of cell lines, these genome-wide profiles have so far been little explored in vertebrate embryos. genome. In particular, a whole-genome microarray design was used to identify active promoters by close proximity to histone H3 lysine 4 trimethylation. A second microarray design features these experimentally derived promoter regions in addition to currently annotated 5′ ends of genes. These regions truly represent promoters as shown by binding of TBP, a key transcription initiation factor. embryos

p53-mediated neurodegeneration in the absence of the nuclear protein Akirin2.

Proper gene regulation is critical for both neuronal development and maintenance as the brain matures. We previously demonstrated that Akirin2, an essential nuclear protein that interacts with transcription factors and chromatin remodeling complexes, is required for the embryonic formation of the cerebral cortex. Here we show that Akirin2 plays a mechanistically distinct role in maintaining healthy neurons during cortical maturation. Restricting Akirin2 loss to excitatory cortical neurons resulted in progressive neurodegeneration via necroptosis and severe cortical atrophy with age. Comparing transcriptomes from Akirin2-null postnatal neurons and cortical progenitors revealed that targets of the tumor suppressor p53, a regulator of both proliferation and cell death encoded b

Author Correction: Development of a sensitive, quantitative assay with broad subtype specificity for detection of total HIV-1 nucleic acids in plasma and PBMC

Correction to: Scientific Reports https://doi.org/10.1038/s41598-021-03016-1, published online 28 January 202

Established non-union of an operatively managed trans-scaphoid perilunate fracture dislocation progressing to spontaneous union

Perilunate dislocations and fracture dislocations represent uncommon and unusual injuries that are often missed at initial presentation and diagnosed late in up to 25% of cases. Prompt open reduction, carpal stabilisation and ligamentous repair is required to reduce the risk of complications. We report a case of an established scaphoid non-union in an operatively managed perilunate fracture dislocation that spontaneously united almost 2 years after the initial injury, just before a planned revision scaphoid fixation with bone grafting. This case highlights the importance of initial clinical assessment together with appropriate radiographs and follow-up of these injuries post-operatively, especially when complications such as non-union arise

Nucleonic resonance excitations with linearly polarized photon in γp→ωp\gamma p\to \omega p

In this work, an improved quark model approach to the $\omega$ meson photo-production with an effective Lagrangian is presented. The {\it t}-channel {\it natural}-parity exchange is taken into account through the Pomeron exchange, while the {\it unnatural}-parity exchange is described by the $\pi^0$ exchange. With a very limited number of parameters, the available experimental data in the low energy regime can be consistently accounted for. We find that the beam polarization observables show sensitivities to some {\it s}-channel individual resonances in the $SU(6)\otimes O(3)$ quark model symmetry limit. Especially, the two resonances $P_{13}(1720)$ and $F_{15}(1680)$, which belong to the representation $[{\bf 56, ^2 8}, 2, 2, J]$, have dominant contributions over other excited states. Concerning the essential motivation of searching for "missing resonances" in meson photo-production, this approach provides a feasible framework, on which systematic investigations can be done.Comment: 16 pages, Revtex, 9 eps figures, to appear in PR