On the statistical significance of primary structural features found in DNA-protein interaction sites

Probabilities of occurrence for a number of the symmetries and other sequence regularities found in DNA-protein interaction site sequences have been calculated for segments of random DNA sequence. Results show that many of the symmetrical and repetitive features seen in these interaction sites are likely to have occurred by chance. Other features are so unlikely to have occurred by chance that they are probably involved in the DNA-protein interaction processes.     

JQ-1 ameliorates schistosomiasis liver granuloma in mice by suppressing male and female reproductive systems and egg development of Schistosoma japonicum

Schistosomiasis is a serious and widespread parasitic disease caused by infection with Schistosoma. Because the parasite’s eggs are primarily responsible for schistosomiasis dissemination and pathogenesis, inhibiting egg production is a potential approach to control the spread and severity of the disease. The bromodomain and extra-terminal (BET) proteins represent promising targets for the development of epigenetic drugs against Schistosoma. JQ-1 is a selective inhibitor of the BET protein family. In the present study, JQ-1 was applied to S. japonicum in vitro. By using laser confocal scanning microscopy and EdU incorporation assays, we showed that application of JQ-1 to worms in vitro affected egg laying and the development of both the male and female reproductive systems. JQ-1 also inhibited the expression of the reproductive-related genes SjPlk1 and SjNanos1 in S. japonicum. Mice infected with S. japonicum were treated with JQ-1 during egg granuloma formation. JQ-1 treatment significantly reduced the size of the liver granulomas and levels of serum alanine aminotransferase and aspartate aminotransferase in mice and suppressed both egg laying and the development of male and female S. japonicum reproductive systems in vivo. Moreover, the mRNA expression levels of some proinflammatory cytokines were decreased in the parasites. Our findings suggest that JQ-1 treatment attenuates S. japonicum egg–induced hepatic granuloma due at least in part to suppressing the development of the reproductive system and egg production of S. japonicum. These findings further suggest that JQ-1 or other BET inhibitors warrant additional study as a new approach for the treatment or prevention of schistosomiasis.     

Guidelines for model adaptation: A study of the transferability of a general seagrass ecosystem Dynamic Bayesian Networks model

In general, it is not feasible to collect enough empirical data to capture the entire range of processes that define a complex system, either intrinsically or when viewing the system from a different geographical or temporal perspective. In this context, an alternative approach is to consider model transferability, which is the act of translating a model built for one environment to another less well‐known situation. Model transferability and adaptability may be extremely beneficial—approaches that aid in the reuse and adaption of models, particularly for sites with limited data, would benefit from widespread model uptake. Besides the reduced effort required to develop a model, data collection can be simplified when transferring a model to a different application context. The research presented in this paper focused on a case study to identify and implement guidelines for model adaptation. Our study adapted a general Dynamic Bayesian Networks (DBN) of a seagrass ecosystem to a new location where nodes were similar, but the conditional probability tables varied. We focused on two species of seagrass (Zostera noltei and Zostera marina) located in Arcachon Bay, France. Expert knowledge was used to complement peer‐reviewed literature to identify which components needed adjustment including parameterization and quantification of the model and desired outcomes. We adopted both linguistic labels and scenario‐based elicitation to elicit from experts the conditional probabilities used to quantify the DBN. Following the proposed guidelines, the model structure of the general DBN was retained, but the conditional probability tables were adapted for nodes that characterized the growth dynamics in Zostera spp. population located in Arcachon Bay, as well as the seasonal variation on their reproduction. Particular attention was paid to the light variable as it is a crucial driver of growth and physiology for seagrasses. Our guidelines provide a way to adapt a general DBN to specific ecosystems to maximize model reuse and minimize re‐development effort. Especially important from a transferability perspective are guidelines for ecosystems with limited data, and how simulation and prior predictive approaches can be used in these contexts.     

Single-cell transcriptomic atlas of primate cardiopulmonary aging

Aging is a major risk factor for many diseases,especially in highly prevalent cardiopulmonary comorbidities and infectious diseases including Coronavirus Diseas...     

Cryo-EM structure of the fatty acid reductase LuxC–LuxE complex provides insights into bacterial bioluminescence

The discovery of reduced flavin mononucleotide and fatty aldehydes as essential factors of light emission facilitated study of bacterial luminescence. Although the molecular mechanisms underlying bacterial luminescence have been studied for more than 60 years, the structure of the bacterial fatty acid reductase complex remains unclear. Here, we report the cryo-EM structure of the Photobacterium phosphoreum fatty acid reductase complex LuxC–LuxE to a resolution of 2.79 Å. We show that the active site Lys238/Arg355 pair of LuxE is >30 Å from the active site Cys296 of LuxC, implying that catalysis relies on a large conformational change. Furthermore, mutagenesis and biochemical experiments support that the L-shaped cleft inside LuxC plays an important role in substrate binding and reaction. We obtained a series of mutants with significantly improved activity as measured by in vitro bioluminescence assays and demonstrated that the double mutant W111A/F483K displayed the highest activity (370% of the WT). Our results indicated that the activity of LuxC significantly affects the bacterial bioluminescence reaction. Finally, we expressed this mutated lux operon in Escherichia coli but observed that the in vivo concentrations of ATP and NADPH limited the enzyme activity; thus, we conclude that the luminous intensity mainly depends on the level of metabolic energy.     

Effects of Luteolin on Human Breast Cancer Using Gene Expression Array: Inferring Novel Genes

Taraxacum officinale (dandelion) is often used in traditional Chinese medicine for the treatment of cancer; however, the downstream regulatory genes and signaling pathways mediating its effects on breast cancer remain unclear. The present study aimed to explore the effects of luteolin, the main biologically active compound of T. officinale, on gene expression profiles in MDA-MB-231 and MCF-7 breast cancer cells. The results revealed that luteolin effectively inhibited the proliferation and motility of the MDA-MB-231 and MCF-7 cells. The mRNA expression profiles were determined using gene expression array analysis and analyzed using a bioinformatics approach. A total of 41 differentially expressed genes (DEGs) were found in the luteolin-treated MDA-MB-231 and MCF-7 cells. A Gene Ontology analysis revealed that the DEGs, including AP2B1, APP, GPNMB and DLST, mainly functioned as oncogenes. The human protein atlas database also found that AP2B1, APP, GPNMB and DLST were highly expressed in breast cancer and that AP2B1 (cut-off value, 75%) was significantly associated with survival rate (p = 0.044). In addition, a Kyoto Encyclopedia of Genes and Genomes pathway analysis revealed that the DEGs were involved in T-cell leukemia virus 1 infection and differentiation. On the whole, the findings of the present study provide a scientific basis that may be used to evaluate the potential benefits of luteolin in human breast cancer. Further studies are required, however, to fully elucidate the role of the related molecular pathways.     

SARS-CoV-2 envelope protein causes acute respiratory distress syndrome (ARDS)-like pathological damages and constitutes an antiviral target

Cytokine storm and multi-organ failure are the main causes of SARS-CoV-2-related death. However, the origin of excessive damages caused by SARS-CoV-2 remains largely unknown. Here we show that the SARS-CoV-2 envelope (2-E) protein alone is able to cause acute respiratory distress syndrome (ARDS)-like damages in vitro and in vivo. 2-E proteins were found to form a type of pH-sensitive cation channels in bilayer lipid membranes. As observed in SARS-CoV-2-infected cells, heterologous expression of 2-E channels induced rapid cell death in various susceptible cell types and robust secretion of cytokines and chemokines in macrophages. Intravenous administration of purified 2-E protein into mice caused ARDS-like pathological damages in lung and spleen. A dominant negative mutation lowering 2-E channel activity attenuated cell death and SARS-CoV-2 production. Newly identified channel inhibitors exhibited potent anti-SARS-CoV-2 activity and excellent cell protective activity in vitro and these activities were positively correlated with inhibition of 2-E channel. Importantly, prophylactic and therapeutic administration of the channel inhibitor effectively reduced both the viral load and secretion of inflammation cytokines in lungs of SARS-CoV-2-infected transgenic mice expressing human angiotensin-converting enzyme 2 (hACE-2). Our study supports that 2-E is a promising drug target against SARS-CoV-2.Subject terms: Cell death, Molecular biology     

合成己酸乙酯脂肪酶产生菌的筛选及产酶条件

从２７株脂肪酶产生菌中筛选到能由乙醇和己酸合成己酸乙酯的菌株８株。其中Ｒｈｉｚｏｐｕｓｓｐ．Ｈ－３菌株脂肪酶活力为５０－６０ｕ／ｍｌ,全细胞在有机溶剂中的酯化率可达己酸的９１％。Ｈ３产酶的最适碳源为淀粉或葡萄糖。６％黄豆饼粉加４％蛋白陈复合氮源有利于酶活力的增加。     

Environmental filtering rather than dispersal limitation dominated plant community assembly in the Zoige Plateau

Identifying the mechanisms that underlie the assembly of plant communities is critical to the conservation of terrestrial biodiversity. However, it is seldom measured or quantified how much deterministic versus stochastic processes contribute to community assembly in alpine meadows. Here, we measured the decay in community similarity with spatial and environmental distance in the Zoige Plateau. Furthermore, we used redundancy analysis (RDA) to divide the variations in the relative abundance of plant families into four components to assess the effects of environmental and spatial. Species assemblage similarity liner declined with geographical distance (p < .001, R ² = .6388), and it decreased significantly with increasing distance of total phosphorus (TP), alkali‐hydrolyzable nitrogen (AN), available potassium (AK), nitrate nitrogen (NO₃ ⁺–N), and ammonia nitrogen (NH₄ ⁺–N). Environmental and spatial variables jointly explained a large proportion (55.2%) of the variation in the relative abundance of plant families. Environmental variables accounted for 13.1% of the total variation, whereas spatial variables accounted for 11.4%, perhaps due to the pronounced abiotic gradients in the alpine areas. Our study highlights the mechanism of plant community assembly in the alpine ecosystem, where environmental filtering plays a more important role than dispersal limitation. In addition, a reasonably controlled abundance of Compositae (the family with the highest niche breadth and large niche overlap value with Gramineae and Cyperaceae) was expected to maintain sustainable development in pastoral production. These results suggest that management measures should be developed with the goal of improving or maintaining suitable local environmental conditions.     

Rhizosphere soil bacterial communities and nitrogen cycling affected by deciduous and evergreen tree species

Deciduous and evergreen trees differ in their responses to drought and nitrogen (N) demand. Whether or not these functional types affect the role of the bacterial community in the N cycle during drought remains uncertain. Two deciduous tree species (Alnus cremastogyne, an N₂‐fixing species, and Liquidambar formosana) and two evergreen trees (Cunninghamia lanceolata and Pinus massoniana) were used to assess factors in controlling rhizosphere soil bacterial community and N cycling functions. Photosynthetic rates and biomass production of plants, 16S rRNA sequencing and N‐cycling‐related genes of rhizosphere soil were measured. The relative abundance of the phyla Actinobacteria and Firmicutes was higher, and that of Proteobacteria, Acidobacteria, and Gemmatimondaetes was lower in rhizosphere soil of deciduous trees than that of evergreen. Beta‐diversity of bacterial community also significantly differed between the two types of trees. Deciduous trees showed significantly higher net photosynthetic rates and biomass production than evergreen species both at well water condition and short‐term drought. Root biomass was the most important factor in driving soil bacterial community and N‐cycling functions than total biomass and aboveground biomass. Furthermore, 44 bacteria genera with a decreasing response and 46 taxa showed an increased response along the root biomass gradient. Regarding N‐cycle‐related functional genes, copy numbers of ammonia‐oxidizing bacteria (AOB) and autotrophic ammonia‐oxidizing archaea (AOA), N₂ fixation gene (nifH), and denitrification genes (nirK, nirS) were significantly higher in the soil of deciduous trees than in that of the evergreen. Structural equation models explained 50.2%, 47.6%, 48.6%, 49.4%, and 37.3% of the variability in copy numbers of nifH, AOB, AOA, nirK, and nirS, respectively, and revealed that root biomass had significant positive effects on copy numbers of all N‐cycle functional genes. In conclusion, root biomass played key roles in affecting bacterial community structure and soil N cycling. Our findings have important implications for our understanding of plants control over bacterial community and N‐cycling function in artificial forest ecosystems.