Rapid isolation and resolution immune evasion and viral fitness across contemporary SARS-CoV-2 variants

From late 2020 the world observed the rapid emergence of many distinct SARS-CoV-2 variants. At the same time, pandemic responses coalesced into significant global vaccine roll-out that have now significantly lowered Covid-19 hospital and mortality rates in the developed world. Over this period, we developed a rapid platform (R-20) for viral isolation and characterisation using primary remnant diagnostic swabs. This combined with quarantine testing and genomics surveillance, enabled the rapid isolation and characterisation of all major SARS-CoV-2 variants (all variants of concern and 6 variants of interest) globally with a 4-month period. This platform facilitated viral variant isolation and enabled rapid resolution of variant phenotype by allowing determining end point viral titers from primary nasopharyngeal swabs and through ranking of evasion of neutralising antibodies. In late 2021, when the Delta variant was dominating, Omicron rapidly emerged. Using this platform, we isolated and tested the first cases of this variant within Australia. In this setting we observed Omicron to diverge from other variants at two levels: Firstly, it ranks at the mots evasive to neutralisation antibodies compared to all VOCs and major VUIs. Secondly, it no longer engages TMPRSS2 during the late stages of fusion.

Mental, Physical and Socio-Economic Status of Adults Living in Spain during the Late Stages of the State of Emergency Caused by COVID-19

Research has shown that the confinement measures implemented to curb the spread of COVID-19 can have negative effects on people’s lives at multiple levels. The objective of this cross-sectional study was to better understand the mental, physical, and socio-economic status of adults living in Spain during the late stages of the state of emergency caused by COVID-19. Five hundred and forty-four individuals responded to an online survey between 3 June and 30 July 2020. They were asked to report data about their mental and physical health, financial situation, and satisfaction with the information received about the pandemic. Means, percentages, t-test, ANOVAs, and logistic regressions were computed. A third of the participants reported symptoms of anxiety, depression, and stress, and worries about their health and the future. Participants also described mild levels of fatigue and pain during lockdown (66%), and a reduction in household income (39%). Respondents that were female, younger, single, and with lower levels of education reported experiencing a greater impact of the COVID-19 pandemic. The data showed that the negative effects of lockdown were present in the late stages of the state of emergency. The findings can be used to contribute to the development of programs to prevent or mitigate the negative impact of confinement measures.

Relationship between Diversity and Stability of a Karst Plant Community

The relationships among species diversity, functional diversity, functional redundancy, and community stability are central to community and ecosystem ecology. This paper examines plant communities at different stages of vegetation restoration in the Guizhou karst plateau to study the relationship among functional diversity, functional redundancy, and stability of plant communities. The most important results include the following. (1) Species diversity (SD), functional redundancy (FR), and stability (STB) gradually increased with restoration, and there were significant differences among the different stages; functional diversity (FD) increased at first and then decreased, and reached the highest level at the tree irrigation stage. (2) Plant height (PLH) and specific leaf area (SLA) were functional traits that affected the diversity and stability of the plant community, and PLH was positively correlated with plant community diversity and stability, while SLA was negatively correlated with plant community diversity and stability. (3) During the community recovery, FD and FR interacted to maintain stability. In the early and late stages of recovery, the effect of functional redundancy on stability was greater than that of functional diversity, but it was the opposite in the middle stages. (4) The tree irrigation stage is the likely point at which the species diversity of plant communities in karst areas reached saturation, and the growth rate of functional redundancy after species diversity saturation was greater than that before saturation.

The impact of invisible-spreaders on COVID-19 transmission and work resumption

The global impact of coronavirus disease 2019 (COVID-19) is unprecedented, and many control and prevention measures have been implemented to test for and trace COVID-19. However, invisible-spreaders, who are associated with nucleic acid detection and asymptomatic infections, have received insufficient attention in the current COVID-19 control efforts. In this paper, we analyze the time series infection data for Italy, Germany, Brazil, India and Sweden since the first wave outbreak to address the following issues through a series of experiments. We conclude that: 1) As of June 1, 2020, the proportion of invisible-spreaders is close to 0.4% in Sweden, 0.8% in early Italy and Germany, and 0.4% in the middle and late stages. However, in Brazil and India, the proportion still shows a gradual upward trend; 2) During the spread of this pandemic, even a slight increase in the proportion of invisible-spreaders could have large implications for the health of the community; and 3) On resuming work, the pandemic intervention measures will be relaxed, and invisible-spreaders will cause a new round of outbreaks.

Loss of Corticostriatal Mu-Opioid Receptors in α-Synuclein Transgenic Mouse Brains

Ultrastructural, neurochemical, and molecular alterations within the striatum are associated with the onset and progression of Parkinson’s disease (PD). In PD, the dopamine-containing neurons in the substantia nigra pars compacta (SNc) degenerate and reduce dopamine-containing innervations to the striatum. The loss of striatal dopamine is associated with enhanced corticostriatal glutamatergic plasticity at the early stages of PD. However, with disease progression, the glutamatergic corticostriatal white matter tracts (WMTs) also degenerate. We analyzed the levels of Mu opioid receptors (MORs) in the corticostriatal WMTs, as a function of α-Synuclein (α-Syn) toxicity in transgenic mouse brains. Our data show an age-dependent loss of MOR expression levels in the striatum and specifically, within the caudal striatal WMTs in α-Syn tg mouse brains. The loss of MOR expression is associated with degeneration of the myelinated axons that are localized within the corticostriatal WMTs. In brains affected with late stages of PD, we detect evidence confirming the degeneration of myelinated axons within the corticostriatal WMTs. We conclude that loss of corticostriatal MOR expression is associated with degeneration of corticostriatal WMT in α-Syn tg mice, modeling PD.

Trends in the Prevalence and Progression of Diabetic Retinopathy Associated with Hyperglycemic Disorders during Pregnancy in Japan

The aim of this study was to determine the prevalence and progression of diabetic retinopathy (DR) with hyperglycemic disorders during pregnancy (HDPs) in Japan between 2013 and 2018 using two cohorts. The patients with HDPs were classified as those with pre-existing DM (pexD), gestational DM (GDM), and overt DM (ODM). Cohort 1 was obtained from the health claims database whose diseases were classified by the International Classification of Diseases-10. Cohort 2 was derived from a retrospective, multicenter analysis of the medical records of 225 patients from 10 ophthalmological institutions. In Cohort 1, there were 5268 patients with an HDP prevalence of 8.4%. Among them, 73 of 1139 patients had pexD (6.4%) and 61 of 4129 patients with GDM (1.5%) had DR; the overall prevalence of DR was 2.5%. In Cohort 2, 36 of 225 patients (16.0%) had DR, and 149 patients were followed at the early and late stages of pregnancy. Moreover, 10 of the 102 patients with pexD (9.8%) and two of five patients with ODM (40.0%) had a progression of DR. In conclusion, the prevalence and progression of DR in patients with pexD is lower than previously reported. More attention should be given to pexD and ODM.

Mapping prion pathology in mice using quantitative imaging: an MRI study

Human prion diseases are fatal neurodegenerative disorders which cause cognitive impairment and neurological deficits. Additional measures of tissue status are necessary for improving the sensitivity and specificity of clinical diagnosis as in many cases clinical forms of prion disease are commonly mistaken for other forms of dementia. To that effect, we developed a set of quantitative magnetic resonance-based tools, including magnetic resonance spectroscopy (MRS), magnetization transfer ratio (MTR) and quantitative T1 and T2 imaging to study the course of the disease in an animal model of prion disease. Using in vivo MTR, significant changes were detected in the cortex and thalamus of late-stage prion -infected mice as compared to littermates. In addition, we found a significant increase of MTR in thalamus and cortex of 80 dpi healthy mice when compared with 160 dpi healthy mice suggestive of changes occurring during the development of the brain. Using quantitative T2 mapping, significantly higher values were measured in thalamus of prion mice at all stages of the disease (T2=40ms) while T1 was found to be significantly higher in cortex (T1=1.89s) and hippocampus, albeit only in late-stage prion mice as compared to aged-matched controls (T1=1.67s). Using quantitative MRS significant changes were detected in glutamate (Glu) and myo-inositol (Ins) at all stages of prion disease when compared with the control group. NAA, Cr, Lactate and Lipids were only found to be significantly different at early and late stages of the disease while Taurine (Tau) was only significantly increased in the asymptomatic stage without any significant change at early and late stages of the disease. These changes in MRI and MRS signals, which precede clinical signs of disease, could provide insights into the pathogenesis of this disease and may enable early detection of pathology.

Quantitative Proteomic Analysis of Bi Zhong Xiao Decoction Against Collagen-induced Arthritis Rats in the Early and Late Stages

Background: Rheumatoid arthritis (RA) is a chronic, progressive, systemic autoimmune inflammatory disease. Bi Zhong Xiao decoction (BZXD) performs multiple functions for rheumatoid arthritis (RA) treatment for decades. In this study, we aimed to study the protein alterations of BZXD in the early and late stages of RA.Methods: Sprague-Dawley rats were randomly divided into the Control, collagen-induced arthritis (CIA) and BZXD groups. Clinical assessment, paw thickness, weight changes and serum inflammatory cytokine levels were used to evaluate anti-inflammatory effects. Histopathological tests were performed to assess the improvement of inflammation and synovial hyperplasia. Moreover, we analyzed the proteins profiling of synovial tissue samples with different time intervals after BZXD treatment by Isobaric Tag for Relative Absolute (ITRAQ) quantitative proteomics technology. To further explore the interrelationships among differentially expressed proteins (DEPs), we used DAVID Bioinformatics Resources v6.8 and STRING 11.0 for bioinformatics analysis. Besides, western blot was exerted to verify related proteins.Results: In our study, BZXD ameliorated joint inflammation, suppressed the pathological changes in arthrosis of CIA rats. The proteomic analysis demonstrated that CIA rats were mainly involved in two significant pathways (the focal adhesion and the ECM-receptor interaction) in the early stage. BZXD down-regulated the expression of proteins involved in these pathways, such as CAV1, CHAD, COL3A1, COL5A2, COL6A1 and COL6A5. Additionally, BZXD exerts anti-inflammatory effects in the late stage mainly by increasing the expression of FASN, and affecting fatty acid metabolism.Conclusion: BZXD exerts therapeutic effects on RA through multi-pathways in the early and late stages. This work may provide proteomic clues for treating RA by BZXD.

Morphological characteristic of premature infants’s kidneys with opened Ductus Arteriosis (by the autopsy).

Background. Kidney has protracted nephrogenesis and depend on hemodynamic changes on the highest level in support of natural transition to extrauterine circulation. Fetal communications like Ductus Arteriosus take part in the shunting from the aorta to the pulmonary artery. Increase of this shunting of the blood leads to hyperperfusion with hypoxic changes of some development systems of organs with protracted morphogenesis so like kidneys. Objective. To determine the features of postnatal morphogenesis of the kidneys in premature infants with a gestational age of 25 to 35 weeks on the background of an open ductus arteriosus. Methods. 21 autopsy material premature infant’s kidney which were fixed by 10%-formalin and then were subjected to the standard histological procedures. Slides were stained by hematoxylin and eosin. We used the complex of histological and morphometric methods. There were created 3-demenshional models of kidney’s fragments. We carried out biometrical and statistical analysis. Results. During our research it was determines that the changes of the volume of the functional parenchyma of the kidney and the diameter of the Ductus Arteriosus became in inverse relationship. The wider the duct the smaller the volume of the functional parenchyma because of atrophic and necrotic changes during the late stages of glomerulo- and tubulogenesis. These changes could be distinguished by the quantitative density of development on three germinate layers of the cortex of kidney. Сonclusion. Summing up, it determined the retardation of glomerulogenesis particularly superficial area of the cortex because of the opened Ductus Arteriosus.