Four New C19-Diterpenoid Alkaloids from Aconitum nagarum Stapf

Four new aconitine-type C₁₉-diterpenoid alkaloids, were isolated from the roots of Aconitum nagarum Stapf which were named as nagarutines A–D ( 1–4 ), together with eleven known compounds ( 5–15 ). The structures of the compounds were identified by IR, HR-ESI-MS, 1D and 2D NMR spectra. All compounds were tested for the inhibitory effect on LPS induced NO production in RAW 264.7 macrophages, compound 7 showed moderate anti-inflammatory activity effect and Inhibition rate is about 44.50%.     

Applying single-cell highly multiplexed secretome proteomics to characterize immunotherapeutic products and predict clinical responses

Genetically and phenotypically identical immune cell populations can be highly heterogenous in terms of their immune functions and protein secretion profiles. The microfluidic chip-based single-cell highly multiplexed secretome proteomics enables characterization of cellular heterogeneity of immune responses at different cellular and molecular layers. Increasing evidence has demonstrated that polyfunctional T cells that simultaneously produce 2+ proteins per cell at the single-cell level are key effector cells that contribute to the development of potent and durable cellular immunity against pathogens and cancers. The functional proteomic technology offers a wide spectrum of cellular function assessment and can uniquely define highly polyfunctional cell subsets with cytokine signatures from live individual cells. This high-dimensional single-cell analysis provides deep dissection into functional heterogeneity and helps identify predictive biomarkers and potential correlates that are crucial for immunotherapeutic product design optimization and personalized immunotherapy development to achieve better clinical outcomes.     

Structural insight into chitin perception by chitin elicitor receptor kinase 1 of Oryza sativa

Plants have developed innate immune systems to fight against pathogenic fungi by monitoring pathogenic signals known as pathogen-associated molecular patterns (PAMP) and have established endo symbiosis with arbuscular mycorrhizal (AM) fungi through recognition of mycorrhizal (Myc) factors. Chitin elicitor receptor kinase 1 of Oryza sativa subsp. Japonica (OsCERK1) plays a bifunctional role in mediating both chitin-triggered immunity and symbiotic relationships with AM fungi. However, it remains unclear whether OsCERK1 can directly recognize chitin molecules. In this study, we show that OsCERK1 binds to the chitin hexamer ((NAG)₆) and tetramer ((NAG)₄) directly and determine the crystal structure of the OsCERK1-(NAG)₆ complex at 2 Å. The structure shows that one OsCERK1 is associated with one (NAG)₆. Upon recognition, chitin hexamer binds OsCERK1 by interacting with the shallow groove on the surface of LysM2. These structural findings, complemented by mutational analyses, demonstrate that LysM2 is crucial for recognition of both (NAG)₆ and (NAG)₄. Altogether, these findings provide structural insights into the ability of OsCERK1 in chitin perception, which will lead to a better understanding of the role of OsCERK1 in mediating both immunity and symbiosis in rice.     

BmCaspase-8-like regulates autophagy by suppressing BmDREDD-mediated cleavage of BmATG6

Autophagy plays an important role in tissue remodeling during insect development. The interplay between autophagy-related (ATG) proteins and caspases regulates the autophagic activity of ATGs, thereby modulating the process of autophagy. Our previous study characterized BmCaspase-8-like (BmCasp8L) as a caspase suppressor that inhibits apoptosis and immune signaling by suppressing the activation of death-related ced-3/Nedd2-like caspase (DREDD), a caspase-8 homolog in silkworm. In this study, we explored the regulatory role of BmCasp8L in autophagy. We found that the expression of Bmcasp8l increased from the late spinning stage to the pupa stage in the posterior silk gland (PSG), correlating with the expression patterns of Bmatg8 and Bmatg6. RNA interference-mediated downregulation of BmCasp8L expression significantly decreased starvation-induced autophagic influx as determined by the levels of BmATG8–phosphatidylethanolamine and the percentage of cells displaying punctate enhanced green fluorescent protein-BmATG8. Conversely, the overexpression of BmCasp8L significantly increased autophagic influx. We also found that BmCasp8L underwent autophagic degradation induced by starvation and that it was colocalized with BmATG8. Lastly, we demonstrated that BmDREDD attenuated autophagy and BmCasp8L suppressed BmDREDD-mediated cleavage of BmATG6. Taken together, our results demonstrated that BmCasp8L is a novel proautophagic molecule which suppresses BmDREDD-mediated cleavage of BmATG6 and is a target for autophagy.     

Low genetic diversity and population connectivity fuel vulnerability to climate change for the Tertiary relict pine Pinus bungeana

Endemic species are important components of regional biodiversity and hold the key to understanding local adaptation and evolutionary processes that shape species distributions. This study investigated the biogeographic history of a relict conifer Pinus bungeana Zucc. ex Endl. confined to central China. We examined genetic diversity in P. bungeana using genotyping-by-sequencing and chloroplast and mitochondrial DNA markers. We performed spatial and temporal inference of recent genetic and demographic changes, and dissected the impacts of geography and environmental gradients on population differentiation. We then projected P. bungeana's risk of decline under future climates. We found extremely low nucleotide diversity (average π 0.0014), and strong population structure (global F_ST 0.234) even at regional scales, reflecting long-term isolation in small populations. The species experienced severe bottlenecks in the early Pliocene and continued to decline in the Pleistocene in the western distribution, whereas the east expanded recently. Local adaptation played a small (8%) but significant role in population diversity. Low genetic diversity in fragmented populations makes the species highly vulnerable to climate change, particularly in marginal and relict populations. We suggest that conservation efforts should focus on enhancing gene pool and population growth through assisted migration within each genetic cluster to reduce the risk of further genetic drift and extinction.     

A proposito del llamado micetoma maduro-micosico del pulmon

Conclusiones Se efectúa el estudio de 5 observaciones del llamado Micetoma maduromicósico de pulmón en sus aspectos, histopatológico, micológico y clínico.Todas ellas pertenecen a mujeres y configuraron el cuadro de cavidad bronquial empastada, anotando el predominio de su localización en el lóbulo superior izquierdo.Se señala la uniformidad de los caracteres morfológicos que presenta la masa miceliana llamada grano en todos los casos estudiados, en los cuales no fué posible individualizar la existencia de órganos de fructificación que permitiéran una clasificación, cuando más no fuera, genérica del hongo observado.Se critica la aplicación del término Micetoma para éstos casos con igual criterio que el clásico, que supone una enfermedad micótica primitiva, razón por la cual se prefiere hablar de cavidad con contenido micótico o maduromicótico.En el único caso que se logró cultivar al hongo parásito, el estudio micológico del mismo permitió aislar una especie del GéneroAspergillua con caracteres morfológicos sumamente atípicos.

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Summary The author presents the study of five observations of the so-called Maduromycosis-mycetoma of the lungs in their clinical, histopathologic and mycologic aspects.The pathologic features in all these cases have been found in bronchial cavities of women, situated in the upper lobe of the lung. A compact mycelial mass, the grain, filled up these cavities.In one of the five cases a fungus was cultivated which was classified as belonging to the GenusAspergillus Michelii, with abnormal and atypical features.Short criticism is presented about the concept Maduromycosis mycetoma of the lung, applied by authors designating this process.

     

Evidence for the presence of β-lactamase inStreptomyces glaucescens and its inhibition by sodium clavulanate

Streptomyces glaucescens is shown to possess -lactamase activity which is inhibitable by clavulanate. This is important in regard to its use as a cloning host for enzymes of \-lactam biosynthesis.     

一例智力低下患者7q~ 标记染色体的来源鉴定

以人类染色体显微切割、PCR技术构建的现有人类染色体特异性和染色体区带特异性探针池作为绘画探针,采用正向染色体绘画技术,结合染色体筛查方法,查明了一例7q~ 标记染色体患者的染色体附加片段来源于3q26→3qter。确定该患者的核型为46,XX,-7, der(7)t(7;3)(7pter→7q32::3q26→3qter)。应用这个策略,能够快速有效地鉴定标记染色体的来源。     

Incorporating an Asymptotic Parameter into the Weibull Model to Describe Plant Disease Progress

The Weibull model is a flexible growth model that describes both general population growth and plant disease progress. However, lack of an asymptotic parameter has limited its wider application. In the present study, an asymptotic parameter K was introduced into the original Weibull model, written as; y = K {1 − exp [− ( t − a ) ^c ]}, in which a , b , c and K are location, scale, shape, and asymptotic parameters, respectively, y is the proportion of disease and t is time. A wide range of simulated disease progress data sets were generated using logistic, Gompertz and monomolecular models by specifying different parameter values, and fitted to both original and modified Weibull models. The modified model provided statistically better fits for all data than the original model. The modified model can thus improve the curve-fitting ability of the original model which often failed to converge, especially when the asymptote is less than 1.0. Actual disease progress data on wheat leaf rust and tomato root rot with different asymptotic values were also used to compare the original and modified Weibull models. The modified model provided a statistically better fit than the original model, and model estimates of asymptotic parameter K were nearly identical to the actual disease maxima reflecting the characteristics of the host-pathosystem. Comparison of logistic, Gompertz, and Weibull models including parameter K by fitting to the observed data on wheat leaf rust and tomato root rot revealed the applicability of the modified Weibull model, which in a majority of cases provided a statistically superior fit.