Pathogen-sugar interactions revealed by universal saturation transfer analysis

Many pathogens exploit host cell-surface glycans. However, precise analyses of glycan ligands binding with heavily modified pathogen proteins can be confounded by overlapping sugar signals and/or compounded with known experimental constraints. Universal saturation transfer analysis (uSTA) builds on existing nuclear magnetic resonance spectroscopy to provide an automated workflow for quantitating protein-ligand interactions. uSTA reveals that early-pandemic, B-origin-lineage severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike trimer binds sialoside sugars in an "end-on" manner. uSTA-guided modeling and a high-resolution cryo-electron microscopy structure implicate the spike N-terminal domain (NTD) and confirm end-on binding. This finding rationalizes the effect of NTD mutations that abolish sugar binding in SARS-CoV-2 variants of concern. Together with genetic variance analyses in early pandemic patient cohorts, this binding implicates a sialylated polylactosamine motif found on tetraantennary N-linked glycoproteins deep in the human lung as potentially relevant to virulence and/or zoonosis

Female chromosome X mosaicism is age-related and preferentially affects the inactivated X chromosome

To investigate large structural clonal mosaicism of chromosome X, we analysed the SNP microarray intensity data of 38,303 women from cancer genome-wide association studies (20,878 cases and 17,425 controls) and detected 124 mosaic X events42Mb in 97 (0.25%) women. Here we show rates for X-chromosome mosaicism are four times higher than mean autosomal rates; X mosaic events more often include the entire chromosome and participants with X events more likely harbour autosomal mosaic events. X mosaicism frequency increases with age (0.11% in 50-year olds; 0.45% in 75-year olds), as reported for Y and autosomes. Methylation array analyses of 33 women with X mosaicism indicate events preferentially involve the inactive X chromosome. Our results provide further evidence that the sex chromosomes undergo mosaic events more frequently than autosomes, which could have implications for understanding the underlying mechanisms of mosaic events and their possible contribution to risk for chronic diseases

Detectable clonal mosaicism and its relationship to aging and cancer

In an analysis of 31,717 cancer cases and 26,136 cancer-free controls from 13 genome-wide association studies, we observed large chromosomal abnormalities in a subset of clones in DNA obtained from blood or buccal samples. We observed mosaic abnormalities, either aneuploidy or copy-neutral loss of heterozygosity, of >2 Mb in size in autosomes of 517 individuals (0.89%), with abnormal cell proportions of between 7% and 95%. In cancer-free individuals, frequency increased with age, from 0.23% under 50 years to 1.91% between 75 and 79 years (P = 4.8 × 10(-8)). Mosaic abnormalities were more frequent in individuals with solid tumors (0.97% versus 0.74% in cancer-free individuals; odds ratio (OR) = 1.25; P = 0.016), with stronger association with cases who had DNA collected before diagnosis or treatment (OR = 1.45; P = 0.0005). Detectable mosaicism was also more common in individuals for whom DNA was collected at least 1 year before diagnosis with leukemia compared to cancer-free individuals (OR = 35.4; P = 3.8 × 10(-11)). These findings underscore the time-dependent nature of somatic events in the etiology of cancer and potentially other late-onset diseases

IUGS reclassification of the high-Mg and picritic volcanic rocks

The 1989 IUGS classification of the igneous rocks for the high-Mg and picritic volcanic rocks has been revised. Instead of an 18 wt % MgO minimum limit being applied for all high-Mg and picritic volcanic rocks, that is now applicable only to the high-Mg rocks such as komatiite and meimechite. The minimum MgO requirement for picrite is reduced to 12 wt %. The SiO2 former boundary figure between boninite and komatiite–meimechite–picrite, which was 53 wt %, is reduced to 52 wt %, and the total alkali content for komatiite and meimechite is increased to 2% and for picrite to 3%

Metacarbonatite or marble? — the case of the carbonate, pyroxenite, calcite–apatite rock complex at Borra, Eastern Ghats, India

Carbonatites are often of economic importance, which raises the problem of distinguishing carbonatites from limestones when either are metamorphosed to high-grade marbles. They can be of similar appearance, particularly those from the Proterozoic and Archaean of the Indian Subcontinent. This study also contributes to solving the problem of determining the frequency of alkaline and carbonatitic magmatism during the early history of the Earth. The mineral assemblage of apatite–magnetite–phlogopite–calcite is common to marbles of both carbonatite and limestone origin. If pyrochlore is present that identifies the rock as carbonatite; if anorthite, fassaite, scapolite or spinel then it was formerly a limestone. If these minerals are absent, then trace element analysis can supply the critical Sr and REE data, which are both normally high in carbonatitic rocks and low in former limestones. These distinguishing factors are applied to the metamorphic carbonate, pyroxenite, calcite–apatite rock complex at Borra, Eastern Ghats, India, which has been variously interpreted as formerly a carbonatite and as a limestone. The evidence shows that the Borra rocks are meta-sedimentary