Metabolic dynamics and physiological adaptation of Panax ginseng during development

Being an essential Oriental medicinal plant, ginseng (Panax ginseng Meyer) is a slow-growing perennial herb-accumulating pharmaceutically active metabolites such as ginsenosides in roots during growth. However, little is known about how ginseng plants survive in the harsh environments such as winter cold and summer heat for a longer period and accumulates those active metabolites as the plant grows. To understand the metabolic kinetics in both source and sink organs such as leaves and roots of ginseng plant, respectively, and to assess the changes in ginsenosides biosynthesis during ginseng growth, we investigated the metabolic profiles from leaves and roots of 1-, 4-, and 6-year-old field-grown ginseng plants. Using an integrated non-targeted metabolomic approach, we identified in total 348 primary and secondary metabolites, which provided us for the first time a global metabolomic assessment of ginseng during growth, and morphogenesis. Strikingly, the osmoprotectants and oxidized chemicals were highly accumulated in 4- and 6-year-old ginseng leaves suggested that ginseng develop a wide range of metabolic strategies to adapt unfavorable conditions as they mature. In 6-year-old plants, ginsenosides were decreased in leaves but increased in roots up to 1.2- to sixfold, supporting the view that there is a long-distance transport of ginsenosides from leaves to roots as ginseng plants mature. Our findings provide insights into the metabolic kinetics during the development of ginseng plant and this could complement the pharmacological importance of ginseng and its compounds according to their age

Exome sequencing of Finnish isolates enhances rare-variant association power.

Exome-sequencing studies have generally been underpowered to identify deleterious alleles with a large effect on complex traits as such alleles are mostly rare. Because the population of northern and eastern Finland has expanded considerably and in isolation following a series of bottlenecks, individuals of these populations have numerous deleterious alleles at a relatively high frequency. Here, using exome sequencing of nearly 20,000 individuals from these regions, we investigate the role of rare coding variants in clinically relevant quantitative cardiometabolic traits. Exome-wide association studies for 64 quantitative traits identified 26 newly associated deleterious alleles. Of these 26 alleles, 19 are either unique to or more than 20 times more frequent in Finnish individuals than in other Europeans and show geographical clustering comparable to Mendelian disease mutations that are characteristic of the Finnish population. We estimate that sequencing studies of populations without this unique history would require hundreds of thousands to millions of participants to achieve comparable association power

Neuronal differentiation of hair-follicle-bulge-derived stem cells co-cultured with mouse cochlear modiolus explants

Stem-cell-based repair of auditory neurons may represent an attractive therapeutic option to restore sensorineural hearing loss. Hair-follicle-bulge-derived stem cells (HFBSCs) are promising candidates for this type of therapy, because they (1) have migratory properties, enabling migration after transplantation, (2) can differentiate into sensory neurons and glial cells, and (3) can easily be harvested in relatively high numbers. However, HFBSCs have never been used for this purpose. We hypothesized that HFBSCs can be used for cell-based repair of the auditory nerve and we have examined their migration and incorporation into cochlear modiolus explants and their subsequent differentiation. Modiolus explants obtained from adult wild-type mice were cultured in the presence of EF1α-copGFP-transduced HFBSCs, constitutively expressing copepod green fluorescent protein (copGFP). Also, modiolus explants without hair cells were co-cultured with DCX-copGFP-transduced HFBSCs, which demonstrate copGFP upon doublecortin expression during neuronal differentiation. Velocity of HFBSC migration towards modiolus explants was calculated, and after two weeks, co-cultures were fixed and processed for immunohistochemical staining. EF1α-copGFP HFBSC migration velocity was fast: 80.5 ± 6.1 μm/h. After arrival in the explant, the cells formed a fascicular pattern and changed their phenotype into an ATOH1-positive neuronal cell type. DCX-copGFP HFBSCs became green-fluorescent after integration into the explants, confirming neuronal differentiation of the cells. These results show that HFBSC-derived neuronal progenitors are migratory and can integrate into cochlear modiolus explants, while adapting their phenotype depending on this micro-environment. Thus, HFBSCs show potential to be employed in cell-based therapies for auditory nerve repair

Genome Scan for Parent-of-Origin QTL Effects on Bovine Growth and Carcass Traits

Parent-of-origin effects (POE) such as genomic imprinting influence growth and body composition in livestock, rodents, and humans. Here, we report the results of a genome scan to detect quantitative trait loci (QTL) with POE on growth and carcass traits in Angus × Brahman cattle crossbreds. We identified 24 POE–QTL on 15 Bos taurus autosomes (BTAs) of which six were significant at 5% genome-wide (GW) level and 18 at the 5% chromosome-wide (CW) significance level. Six QTL were paternally expressed while 15 were maternally expressed. Three QTL influencing post-weaning growth map to the proximal end of BTA2 (linkage region of 0–9 cM; genomic region of 5.0–10.8 Mb), for which only one imprinted ortholog is known so far in the human and mouse genomes, and therefore may potentially represent a novel imprinted region. The detected QTL individually explained 1.4 ∼ 5.1% of each trait’s phenotypic variance. Comparative in silico analysis of bovine genomic locations show that 32 out of 1,442 known mammalian imprinted genes from human and mouse homologs map to the identified QTL regions. Although several of the 32 genes have been associated with quantitative traits in cattle, only two (GNAS and PEG3) have experimental proof of being imprinted in cattle. These results lend additional support to recent reports that POE on quantitative traits in mammals may be more common than previously thought, and strengthen the need to identify and experimentally validate cattle orthologs of imprinted genes so as to investigate their effects on quantitative traits

Self-induced Floquet magnons in magnetic vortices

Driving condensed matter systems with periodic electromagnetic fields can result in exotic states not found in equilibrium. Termed Floquet engineering, such periodic driving applied to electronic systems can tailor quantum effects to induce topological band structures and control spin interactions. However, Floquet engineering of magnon band structures in magnetic systems has proven challenging so far. Here, we present a class of Floquet states in a magnetic vortex that arise from nonlinear interactions between the vortex core and microwave magnons. Floquet bands emerge through the periodic oscillation of the core, which can be initiated by either driving the core directly or pumping azimuthal magnon modes. For the latter, the azimuthal modes induce core gyration through nonlinear interactions, which in turn renormalizes the magnon band structure. This represents a self-induced mechanism for Floquet band engineering and offers new avenues to study and control nonlinear magnon dynamics

JaxPruner: A concise library for sparsity research

This paper introduces JaxPruner, an open-source JAX-based pruning and sparse training library for machine learning research. JaxPruner aims to accelerate research on sparse neural networks by providing concise implementations of popular pruning and sparse training algorithms with minimal memory and latency overhead. Algorithms implemented in JaxPruner use a common API and work seamlessly with the popular optimization library Optax, which, in turn, enables easy integration with existing JAX based libraries. We demonstrate this ease of integration by providing examples in four different codebases: Scenic, t5x, Dopamine and FedJAX and provide baseline experiments on popular benchmarks.Comment: Jaxpruner is hosted at http://github.com/google-research/jaxprune

Overexpression of Panax ginseng sesquiterpene synthase gene confers tolerance against Pseudomonas syringae pv. tomato in Arabidopsis thaliana

Sesquiterpenes are an abundant group belonging to the terpenoid family, with a C15 structure comprise of three isoprene units. Many sesquiterpenes are volatile compounds and it act as chemical messenger in plant signalling, particularly in the defense mechanism against biotic and abiotic stresses. Panax ginseng Meyer is important medicinal herbs with various reported pharmacological efficacies in which its triterpenoid saponins, called ginsenosides, were mostly studied. However, there have been few studies on volatile sesquiterpenes compounds regulation on P. ginseng. As slow-growing perennial plant, P. ginseng received many kind of stresses during its cultivation. The pathogen attack is one of the most devastated perturbation for ginseng yield. Thus, we aimed to analyze P. ginseng STS gene (PgSTS) expressions in ginseng organs as well as mono-, sesquiterpenes contents from ginseng seedlings treated with elicitors. qRT-PCR and GC-MS analysis showed that two elicitors- salicylic acid (SA) and methyl jasmonate (MeJA) triggered PgSTS expression at different time points and significantly induced mono-, sesquiterpene yield. Overexpression of PgSTS in Arabidopsis also induced high terpene content and conferred tolerance against Pseudomonas syringae pv. tomato infection. These results suggested that PgSTS transcripts are involved in terpenoid biosynthesis in response to environmental stress mediated by MeJA and SA elicitors; thus, generate tolerance against pathogen attack

A highly potent antibody effective against SARS-CoV-2 variants of concern.

Control of the ongoing SARS-CoV-2 pandemic is endangered by the emergence of viral variants with increased transmission efficiency, resistance to marketed therapeutic antibodies, and reduced sensitivity to vaccine-induced immunity. Here, we screen B cells from COVID-19 donors and identify P5C3, a highly potent and broadly neutralizing monoclonal antibody with picomolar neutralizing activity against all SARS-CoV-2 variants of concern (VOCs) identified to date. Structural characterization of P5C3 Fab in complex with the spike demonstrates a neutralizing activity defined by a large buried surface area, highly overlapping with the receptor-binding domain (RBD) surface necessary for ACE2 interaction. We further demonstrate that P5C3 shows complete prophylactic protection in the SARS-CoV-2-infected hamster challenge model. These results indicate that P5C3 opens exciting perspectives either as a prophylactic agent in immunocompromised individuals with poor response to vaccination or as combination therapy in SARS-CoV-2-infected individuals

Cause-specific mortality time series analysis: a general method to detect and correct for abrupt data production changes

<p>Abstract</p> <p>Background</p> <p>Monitoring the time course of mortality by cause is a key public health issue. However, several mortality data production changes may affect cause-specific time trends, thus altering the interpretation. This paper proposes a statistical method that detects abrupt changes ("jumps") and estimates correction factors that may be used for further analysis.</p> <p>Methods</p> <p>The method was applied to a subset of the AMIEHS (Avoidable Mortality in the European Union, toward better Indicators for the Effectiveness of Health Systems) project mortality database and considered for six European countries and 13 selected causes of deaths. For each country and cause of death, an automated jump detection method called Polydect was applied to the log mortality rate time series. The plausibility of a data production change associated with each detected jump was evaluated through literature search or feedback obtained from the national data producers.</p> <p>For each plausible jump position, the statistical significance of the between-age and between-gender jump amplitude heterogeneity was evaluated by means of a generalized additive regression model, and correction factors were deduced from the results.</p> <p>Results</p> <p>Forty-nine jumps were detected by the Polydect method from 1970 to 2005. Most of the detected jumps were found to be plausible. The age- and gender-specific amplitudes of the jumps were estimated when they were statistically heterogeneous, and they showed greater by-age heterogeneity than by-gender heterogeneity.</p> <p>Conclusion</p> <p>The method presented in this paper was successfully applied to a large set of causes of death and countries. The method appears to be an alternative to bridge coding methods when the latter are not systematically implemented because they are time- and resource-consuming.</p

The state of health in the European Union (EU-27) in 2019: a systematic analysis for the Global Burden of Disease study 2019

Background: The European Union (EU) faces many health-related challenges. Burden of diseases information and the resulting trends over time are essential for health planning. This paper reports estimates of disease burden in the EU and individual 27 EU countries in 2019, and compares them with those in 2010. Methods: We used the Global Burden of Disease 2019 study estimates and 95% uncertainty intervals for the whole EU and each country to evaluate age-standardised death, years of life lost (YLLs), years lived with disability (YLDs) and disability-adjusted life years (DALYs) rates for Level 2 causes, as well as life expectancy and healthy life expectancy (HALE). Results: In 2019, the age-standardised death and DALY rates in the EU were 465.8 deaths and 20,251.0 DALYs per 100,000 inhabitants, respectively. Between 2010 and 2019, there were significant decreases in age-standardised death and YLL rates across EU countries. However, YLD rates remained mainly unchanged. The largest decreases in age-standardised DALY rates were observed for “HIV/AIDS and sexually transmitted diseases” and “transport injuries” (each -19%). “Diabetes and kidney diseases” showed a significant increase for age-standardised DALY rates across the EU (3.5%). In addition, “mental disorders” showed an increasing age-standardised YLL rate (14.5%). Conclusions: There was a clear trend towards improvement in the overall health status of the EU but with differences between countries. EU health policymakers need to address the burden of diseases, paying specific attention to causes such as mental disorders. There are many opportunities for mutual learning among otherwise similar countries with different patterns of disease