Abstract
A large variation in the severity of disease symptoms is one of the key open questions in coronavirus disease 2019 (COVID-19) pandemics. The fact that only a small subset of people infected ...with severe acute respiratory syndrome coronavirus 2 develops severe disease suggests that there have to be some predisposing factors, but biomarkers that reliably predict disease severity have not been found so far. Since overactivation of the immune system is implicated in a severe form of COVID-19 and the immunoglobulin G (IgG) glycosylation is known to be involved in the regulation of different immune processes, we evaluated the association of interindividual variation in IgG N-glycome composition with the severity of COVID-19. The analysis of 166 severe and 167 mild cases from hospitals in Spain, Italy and Portugal revealed statistically significant differences in the composition of the IgG N-glycome. The most notable difference was the decrease in bisecting N-acetylglucosamine in severe patients from all three cohorts. IgG galactosylation was also lower in severe cases in all cohorts, but the difference in galactosylation was not statistically significant after correction for multiple testing.
Glycans attached to immunoglobulin G (IgG) directly affect this antibody effector functions and regulate inflammation at several levels. The composition of IgG glycome changes significantly with age. ...In women, the most notable change coincides with the perimenopausal period. Aiming to investigate the effect of estrogen on IgG glycosylation, we analysed IgG and total serum glycomes in 36 healthy premenopausal women enrolled in a randomized controlled trial of the gonadotropin-releasing hormone analogue (GnRH
AG
) leuprolide acetate to lower gonadal steroids to postmenopausal levels and then randomized to transdermal placebo or estradiol (E
2
) patch. The suppression of gonadal hormones induced significant changes in the IgG glycome, while E
2
supplementation was sufficient to prevent changes. The observed glycan changes suggest that depletion of E
2
primarily affects B cell glycosylation, while liver glycosylation stays mostly unchanged. To determine whether previously identified IgG GWAS hits
RUNX1
,
RUNX3
,
SPINK4
, and
ELL2
are involved in downstream signaling mechanisms, linking E
2
with IgG glycosylation, we used the FreeStyle 293-F transient system expressing IgG antibodies with stably integrated CRISPR/dCas9 expression cassettes for gene up- and downregulation.
RUNX3
and
SPINK4
upregulation using dCas9-VPR resulted in a decreased IgG galactosylation and, in the case of
RUNX3
, a concomitant increase in IgG agalactosylation.
Unplanned change in response to a crisis presents a unique opportunity for organization learning. During the COVID-19 pandemic, registered nurses (RN) experienced workplace change at a pace that is ...unprecedented in recent decades. The purpose of this qualitative study was to contribute to organizational learning through analysis of nurses’ experiences within a 3-tiered model of nursing redeployment. Three key themes emerged that highlight the importance of relationships and working conditions during periods of rapid change, and the potential impact of unplanned change on longer-term RN career planning.
Since 1950, the global urban population grew from 746 million to almost 4 billion and is expected to reach 6.4 billion by mid-century. Almost 90% of this increase will take place in Asia and Africa ...and disproportionately in urban slums. In this context, concerns about the amplification of several neglected tropical diseases (NTDs) are warranted and efforts towards achieving effective mass drug administration (MDA) coverage become even more important. This narrative review considers the published literature on MDA implementation for specific NTDs and in-country experiences under the ENVISION and END in Africa projects to surface features of urban settings that challenge delivery strategies known to work in rural areas. Discussed under the thematics of governance, population heterogeneity, mobility and community trust in MDA, these features include weak public health infrastructure and programs, challenges related to engaging diverse and dynamic populations and the limited accessibility of certain urban settings such as slums. Although the core components of MDA programs for NTDs in urban settings are similar to those in rural areas, their delivery may need adjustment. Effective coverage of MDA in diverse urban populations can be supported by tailored approaches informed by mapping studies, research that identifies context-specific methods to increase MDA coverage and rigorous monitoring and evaluation.
We present an unbiased orbit solution and mass determination of the components of the eclipsing binary NY Vir as a critical test for the formation scenarios of subdwarf B stars. We obtained ...high-resolution time series VLT/UVES spectra and high-speed multicolour VLT/ULTRACAM photometric observations of NY Vir, a rapidly pulsating subdwarf B star in a short period eclipsing binary. Combining the radial velocity curve obtained from the VLT/UVES spectra with the VLT/ULTRACAM multicolour lightcurves, we determined numerical orbital solutions for this eclipsing binary. Due to the large number of free parameters and their strong correlations, no unique solution could be found, only families of solutions. We present three solutions of equal statistical significance, two of which are compatible with the primary having gone through a core He-flash and a common-envelope phase described by the \(\alpha\)-formalism. These two models have an sdB primary of 0.466 \msol and 0.389 \msol, respectively. Finally, we report the detection of the Rossiter-McLaughlin effect for NY Vir.
To determine the extent to which genetic and epigenetic factors contribute to variations in glycosylation of immunoglobulin G (IgG) in humans.
76 N-glycan traits in circulating IgG were analyzed by ...UPLC in 220 monozygotic and 310 dizygotic twin pairs from TwinsUK. A classical twin study design was used to derive the additive genetic, common and unique environmental components defining the variance in these traits. Epigenome-wide association analysis was performed using the Illumina 27k chip.
51 of the 76 glycan traits studied have an additive genetic component (heritability, h (2) ) ≥ 0.5. In contrast, 12 glycan traits had a low genetic contribution (h(2)<0.35). We then tested for association between methylation levels and glycan levels (P<2 x10(-6)). Among glycan traits with low heritability probe cg08392591 maps to a CpG island 5' from the ANKRD11 gene, a p53 activator on chromosome 16. Probe cg26991199 maps to the SRSF10 gene involved in regulation of RNA splicing and particularly in regulation of splicing of mRNA precursors upon heat shock. Among those with high heritability we found cg13782134 (mapping to the NRN1L gene) and cg16029957 mapping near the QPCT gene to be array-wide significant. The proportion of array-wide epigenetic associations was significantly larger (P<0.005) among glycans with low heritability (42%) than in those with high heritability (6.2%).
Glycome analyses might provide a useful integration of genetic and non-genetic factors to further our understanding of the role of glycosylation in both normal physiology and disease.
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