Ligand selectivity in stabilising tandem parallel folded G-quadruplex motifs in human telomeric DNA sequences

Biophysical studies of ligand interactions with three human telomeric repeat sequences (d(AGGG(TTAGGG)n, n = 3, 7 and 11)) show that an oxazole-based ‘click’ ligand, which induces parallel folded quadruplexes, preferentially stabilises longer telomeric repeats providing evidence for selectivity in binding at the interface between tandem quadruplex motifs

The VISCACHA survey -- VII. Assembly history of the Magellanic Bridge and SMC Wing from star clusters

The formation scenario of the Magellanic Bridge during an encounter between the Large and Small Magellanic Clouds $\sim200\,$Myr ago, as proposed by $N$-body models, would be imprinted in the chemical enrichment and kinematics of its stars, and sites of ongoing star formation along its extension. We present an analysis of 33 Bridge star clusters using photometry obtained with the SOAR 4-m telescope equipped with adaptive optics for the VISCACHA survey. We performed a membership selection and derived self-consistent ages, metallicities, distances and reddening values via statistical isochrone fitting, as well as tidal radii and integrated masses from structure analysis. Two groups are clearly detected: 13 well-studied clusters older than the Bridge, with $0.5-6.8\,$Gyr and $\rm{[Fe/H]}<-0.6\,$dex; and 15 clusters with $-0.5\,$dex, probably formed in-situ. The old clusters follow the overall age and metallicity gradients of the SMC, whereas the younger ones are uniformly distributed along the Bridge. The main results are as follows: $(i)$ we derive ages and metallicities for the first time for 9 and 18 clusters, respectively; $(ii)$ we detect two metallicity dips in the age-metallicity relation of the Bridge at $\sim 200\,$Myr and $1.5\,$Gyr ago for the first time, possibly chemical signatures of the formation of the Bridge and Magellanic Stream; $(iii)$ we estimate a minimum stellar mass for the Bridge of $3-5 \times 10^5\,M_\odot$; $(iv)$ we confirm that all the young Bridge clusters at $\rm{RA} < 3^h$ are metal-rich $\rm{[Fe/H]} \sim -0.4\,$dex.Comment: 15 pages, 13 figures + appendix. Accepted for publication in MNRA

Capturing protest in urban environments:The ‘police kettle’ as a territorial strategy

‘Kettling’ has emerged in recent decades as an established, if controversial, tactic of public order policing. Departing from a historical emphasis on dispersal, kettling instead acts to contain protesters within a police cordon for sustained periods of time. This article elaborates upon the spatial and temporal logics of kettling by investigating the conditions of is historical emergence. We argue that kettling should be understood as a territorial strategy that co-evolved in relation to forms of disruptive protest. Whereas techniques of crowd dispersal serve to diffuse a unified collective, ‘kettling’ aims to capture the volatile intensities of public dissent and exhaust its political energies. Drawing on police manuals, media coverage, accounts from activists and expert interviews, we show how the ‘kettle’ re-territorializes protest by acting on its spatio-temporal and affective constitution. By fabricating an inner outside of the urban milieu, freezing the time of collective mobilization and inducing debilitating affects such as fear and boredom, kettling intervenes into the scene of political subjectification that each congregation of protesting bodies seeks to fashion

Formation of a G-quadruplex at the BCL2 major breakpoint region of the t(14;18) translocation in follicular lymphoma

The t(14;18) translocation in follicular lymphoma is one of the most common chromosomal translocations. Most breaks on chromosome 18 are located at the 3′-UTR of the BCL2 gene and are mainly clustered in the major breakpoint region (MBR). Recently, we found that the BCL2 MBR has a non-B DNA character in genomic DNA. Here, we show that single-stranded DNA modeled from the template strand of the BCL2 MBR, forms secondary structures that migrate faster on native PAGE in the presence of potassium, due to the formation of intramolecular G-quadruplexes. Circular dichroism shows evidence for a parallel orientation for G-quadruplex structures in the template strand of the BCL2 MBR. Mutagenesis and the DMS modification assay confirm the presence of three guanine tetrads in the structure. 1H nuclear magnetic resonance studies further confirm the formation of an intramolecular G-quadruplex and a representative model has been built based on all of the experimental evidence. We also provide data consistent with the possible formation of a G-quadruplex structure at the BCL2 MBR within mammalian cells. In summary, these important features could contribute to the single-stranded character at the BCL2 MBR, thereby contributing to chromosomal fragility

Interactive Effect of Combined Intermittent and Sustained Hypoxia and High-Fat Diet on the Colonic Mucosal Microbiome and Host Gene Expression in Mice

Purpose: Gut dysbiosis can cause cardiometabolic disease. Gut dysbiosis can be independently caused by high-fat diet (HFD) and intermittent hypoxia (IH; characterizing obstructive sleep apnea), but the interactive effect of combined intermittent and sustained hypoxia (IH+SH) (characterizing obesity hypoventilation syndrome) and HFD on gut dysbiosis is unclear. We aimed to investigate the interactive effect of a combination of IH and SH and HFD on proximal colonic microbiota and colonic gene expression pattern. Methods: Male mice (n=16) were randomly received four different combinations of diet (normal versus HFD) and oxygen conditions (normoxia versus IH+SH) for 4 weeks. Bacterial DNA and mucosal epithelial cell RNA from proximal colon were collected for analysis of adherent microbiome and host’s gene expression analysis. Results: HFD during IH+SH (22.6 ± 5.73; SD) led to greater Firmicutes: Bacteroidetes ratio than HFD during normoxia (5.89 ± 1.19; p=0.029). HFD significantly decreased microbial diversity as compared to normal diet, but the addition of IH+SH to HFD mildly reversed such effects. When compared to HFD during normoxia, HFD with combination of IH+SH resulted in changes to host mucosal gene expression for apical junctional complexes and adhesion molecules. Specifically, when compared to HFD during normoxia, HFD during IH+SH led to upregulation of Claudin 2 and Syk (tight junction dysfunction and increased mucosal permeability), while the barrier promoting claudin 4 was downregulated. Conclusion: HFD during combined IH and SH causes greater gut dysbiosis and potentially adverse changes in colonic epithelial transcriptome than HFD during normoxia. The latter changes are suggestive of impaired gut barrier function. © 2022 Mashaqi et al.Open access journalThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]