Dynamic changes of CSF sPDGFRβ during ageing and AD progression and associations with CSF ATN biomarkers

Background Loss of brain capillary pericyte is involved in the pathologies and cognitive deficits in Alzheimer’s disease (AD). The role of pericyte in early stage of AD pathogenesis remains unclear. Methods We investigated the dynamic changes of soluble platelet-derived growth factor receptor β (sPDGFRβ) in cerebrospinal fluid (CSF), a marker of brain pericyte injury, in transition from normal ageing to early AD in a cognitively unimpaired population aged 20 to 90 years. Association between sPDGFRβ and ATN biomarkers were analyzed. Results In lifetime, CSF sPDGFRβ continually increased since age of 20 years, followed by the increases of phosphorylated tau-181 (P-tau181) and total tau (T-tau) at the age of 22.2 years and 31.7 years, respectively; CSF Aβ42 began to decline since the age of 39.6 years, indicating Aβ deposition. The natural trajectories of biomarkers suggest that pericyte injury is an early event during transition from normal status to AD, even earlier than Aβ deposition. In AD spectrum, CSF sPDGFRβ was elevated in preclinical stage 2 and participants with suspected non-AD pathophysiologies. Additionally, CSF sPDGFRβ was positively associated with P-tau181 and T-tau independently of Aβ42, and significantly strengthened the effects of Aβ42 on P-tau181, suggesting that pericyte injury accelerates Aβ-mediated tau hyperphosphorylation. Conclusions Our results suggest that pericyte injury contributes to AD progression in the early stage in an Aβ-independent pathway. Recovery of pericyte function would be a target for prevention and early intervention of AD.

Dynamic Changes of Endogenic or Exogenic β-Carboline Alkaloid Harmine in Different Mammals and Human in vivo at Developmental and Physiological States

ObjectiveSeveral β-carboline alkaloids (βCBs), such as harmine, harmaline, harmane, and nor-harmane, are effective for Alzheimer’s disease mouse models. They can be found in some plants, common foodstuffs, and blank plasma of various mammals. However, whether these compounds in mammals are exogenous or endogenous remain unclear.MethodsThe exposure levels of βCBs and of neurotransmitters in plasma and tissues of pup rats, aging rats, mice of different physiological states, and healthy volunteers were detected by using UPLC-MS/MS. Plasma and tissue samples from 110 newborn rats up to 29 days old at 11 sampling points were collected and were analyzed to determine the concentration variation of βCBs in the developmental phase of newborn rats. The plasma of rats aged 2 to 18 months was used to detect the variation trend of βCBs and with some neurotransmitters. The plasma samples of normal C57BL/6 mice, APP/PS1 double transgenic mice, and scopolamine-induced memory impairment mice were collected and were analyzed to compare the difference of βCBs in different physiological states. The exposure levels of βCBs such as harmine, harmaline, and harmane in plasma of 550 healthy volunteers were also detected and analyzed on the basis of gender, race, and age.ResultsResults showed that harmine was the main compound found in rats, mice, and human, which can be detected in a newborn rat plasma (0.16 ± 0.03 ng/ml) and brain (0.33 ± 0.14 ng/g) without any exogenous consumption. The concentration of harmine in rat plasma showed a decreasing trend similar to the exposure levels of neurotransmitters such as 5-hydroxytryptamine, acetylcholine chloride, glutamic acid, tyrosine, and phenylalanine during the growth period of 18 months. The harmine exposure in rats and human indicates high dependence on the physiological and pathological status such as aging, gender, and race.ConclusionThe dynamic changes of harmine exposure in different animals and human, in vivo, at developmental and physiological states indicate that harmine is a naturally and widely distributed endogenous substance in different mammals and human. In addition to exogenous ingestion, spontaneous synthesis might be another important source of harmine in mammals, which should be verified by further experiment.

Communication Pattern Changes Along With Declined IGF1 of Immune Cells in COVID-19 Patients During Disease Progression

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes the coronavirus disease 2019 (COVID-19) pandemic, represents a global crisis. Most patients developed mild/moderate symptoms, and the status of immune system varied in acute and regulatory stages. The crosstalk between immune cells and the dynamic changes of immune cell contact is rarely described. Here, we analyzed the features of immune response of paired peripheral blood mononuclear cell (PBMC) samples from the same patients during acute and regulatory stages. Consistent with previous reports, both myeloid and T cells turned less inflammatory and less activated at recovery phase. Additionally, the communication patterns of myeloid-T cell and T-B cell are obviously changed. The crosstalk analysis reveals that typical inflammatory cytokines and several chemokines are tightly correlated with the recovery of COVID-19. Intriguingly, the signal transduction of metabolic factor insulin-like growth factor 1 (IGF1) is altered at recovery phase. Furthermore, we confirmed that the serum levels of IGF1 and several inflammatory cytokines are apparently dampened after the negative conversion of SARS-CoV-2 RNA. Thus, these results reveal several potential detection and therapeutic targets that might be used for COVID-19 recovery.

Visualization of SpoVAEa protein dynamics in dormant spores of Bacillus cereus and dynamic changes in their germinosomes and SpoVAEa during germination

Bacillus cereus spores, like most Bacillus spores, can survive for years depending on their specific structure, and germinate when their surroundings become suitable. Spore germination proteins play an important role in the initiation of germination. Because germinated spores lose the extreme resistance of the dormant state, more information related to the function of germination proteins could be useful to develop new strategies to control B. cereus spores. Prior work has shown that: i) the channel protein SpoVAEa exhibits high frequency movement in the outer leaflet of the inner membrane (IM) in dormant spores of B. subtilis; ii) the dynamics of germinosome formation in developing spores of B. cereus indicate that the formation of germinosome foci is slower than foci formation of germinant receptor GerR and scaffold protein GerD. However, the dynamics of movement of SpoVAEa in B. cereus spores, and the complete behavior of the germinosome in germinated spores of B. cereus are still unclear. In this study, we found that the SpoVAEa fluorescent foci in dormant spores of B. cereus redistribute at a lower frequency than in B. subtilis, and likely colocalize with GerD in dormant spores. Our results further indicate that: i) overexpression of GerR(A-C-B)-SGFP2 and SpoVAEa-SGFP2 with GerD-mScarlet-I from a plasmid leads to more heterogeneity and lower efficiency of spore germination in B. cereus; ii), germinosome foci composed of GerR(A-C-B)-SGFP2 and GerD-mScarlet-I were lost prior to the phase transition in germination; and iii) GerD-mScarlet-I foci spread out but continued to exist beyond the phase transition of B. cereus spores.

Dynamic Changes in Groundwater Level under Climate Changes in the Gnangara Region, Western Australia

The groundwater-dependent ecosystem in the Gnangara region is confronted with great threats due to the decline in groundwater level since the 1970s. The aim of this study is to apply multiple trend analysis methods at 351 monitoring bores to detect the trends in groundwater level using spatial, temporal and Hydrograph Analysis: Rainfall and Time Trend models, which were applied to evaluate the impacts of rainfall on the groundwater level in the Gnangara region, Western Australia. In the period of 1977–2017, the groundwater level decreased from the Gnangara’s edge to the central-north area, with a maximum trend magnitude of −0.28 m/year. The groundwater level in 1998–2017 exhibited an increasing trend in December–March and a decreasing trend in April–November with the exception of September when compared to 1978–1997. The rainfall + time model based on the cumulative annual residual rainfall technique with a one-month lag during 1990–2017 was determined as the best model. Rainfall had great impacts on the groundwater level in central Gnangara, with the highest impact coefficient being 0.00473, and the impacts reduced gradually from the central area to the boundary region. Other factors such as pine plantation, the topography and landforms, the Tamala Limestone formation, and aquifer groundwater abstraction also had important influences on the groundwater level.

Research on Cavitation Characteristics of Two-Throat Nozzle Submerged Jet

Ship fouling not only increases ship resistance and fuel consumption but is equally a type of biological invasion, which causes severe ecological damage. Submerged cavitation jet cleaning is an environmentally friendly, high-efficiency, and energy-saving cleaning method. The nozzle structure has an essential influence on the cleaning effect. Thus, a two-throat nozzle was designed for application in submerged cavitation jet cleaning. To investigate the cavitation characteristics of the two-throat nozzle, a high-speed photographic visualization experiment and an erosion experiment concerning the submerged cavitation jet were carried out in this study. The frame-difference method (FDM) was used to analyze the dynamic changes in the cavitation cloud in a single period. The dynamic changes in the cavitation cloud and the characteristics of the submerged cavitation jet were investigated under different inlet pressures. The sample mass loss and the macroscopic and microscopic changes in surface morphology were used to evaluate the cavitation intensity of the two-throat nozzle submerged jet. The experimental results demonstrate that the two-throat nozzle has a good cavitation effect, and the cavitation cloud of the submerged jet has obvious periodicity. With the increase in inlet pressure, the length, width, and area of the cavitation cloud continue to increase, and the shedding frequency of the cavitation cloud continues to decrease. The intensity of cavitation erosion is related to target distance and impact time. There is an appropriate target distance by which to achieve the optimal cavitation effect. The collapse of cavitation bubbles near the sample surface is related to the erosion distribution on the sample surface. Moreover, the magnitude of the absolute values of the root-mean-square surface roughness and surface skewness increase with cavitation intensity. The results in this paper are helpful for a better understanding of the cavitation characteristics of the two-throat nozzle submerged jet.

Whole-Tissue Deconvolution and scRNAseq Analysis Identify Altered Endometrial Cellular Compositions and Functionality Associated With Endometriosis

The uterine lining (endometrium) exhibits a pro-inflammatory phenotype in women with endometriosis, resulting in pain, infertility, and poor pregnancy outcomes. The full complement of cell types contributing to this phenotype has yet to be identified, as most studies have focused on bulk tissue or select cell populations. Herein, through integrating whole-tissue deconvolution and single-cell RNAseq, we comprehensively characterized immune and nonimmune cell types in the endometrium of women with or without disease and their dynamic changes across the menstrual cycle. We designed metrics to evaluate specificity of deconvolution signatures that resulted in single-cell identification of 13 novel signatures for immune cell subtypes in healthy endometrium. Guided by statistical metrics, we identified contributions of endometrial epithelial, endothelial, plasmacytoid dendritic cells, classical dendritic cells, monocytes, macrophages, and granulocytes to the endometrial pro-inflammatory phenotype, underscoring roles for nonimmune as well as immune cells to the dysfunctionality of this tissue.

Face-Specific Pupil Contagion in Infants

Pupil contagion is the phenomenon in which an observer’s pupil-diameter changes in response to another person’s pupil. Even chimpanzees and infants in early development stages show pupil contagion. This study investigated whether dynamic changes in pupil diameter would induce changes in infants’ pupil diameter. We also investigated pupil contagion in the context of different faces. We measured the pupil-diameter of 50 five- to six-month-old infants in response to changes in the pupil diameter (dilating/constricting) of upright and inverted faces. The results showed that (1) in the upright presentation condition, dilating the pupil diameter induced a change in the infants’ pupil diameter while constricting the pupil diameter did not induce a change, and (2) pupil contagion occurred only in the upright face presentation, and not in the inverted face presentation. These results indicate the face-inversion effect in infants’ pupil contagion.