The prognostic value of MKL1 in predicting breast cancer immune infiltrates and chemosensitivity

Megakaryocytic leukemia 1 (MKL1) acts as a transcription factor in the regulation of the immune system and is associated with cancer biology. However, its function in the infiltrating immune cells in breast cancer has not been explored. Our study aimed to analyze the expression of MKL1 in The Cancer Genome Atlas (TCGA) breast cancer dataset. The aim of this study was to evaluate the correlations between MKL1 expression, infiltrating immune cells, and immune control genes. Enriched signaling pathways and drug sensitivity analyses were also performed. Our results indicate that high MKL1 expression could predict better survival in breast cancer patients. MKL1 expression was associated with the expression and function of different immune cells, including T cells, B cells, natural killer (NK) cells, macrophages, neutrophils and dendritic cells (DCs). The chromatin modifying enzymes, cellular senescence, epigenetic regulation of gene expression, estrogen-dependent gene expression, and chromosome maintenance were differentially enriched in MKL1 low expression phenotype. Patients in the high MKL1 expression group showed sensitivity to paclitaxel, while those in the low expression group showed potential sensitivity for cisplatin and docetaxel. In conclusion, MKL1 might act as a potential biomarker of prognostic value for immune infiltration and drug sensitivity in breast cancer

Analysis of Intermediate Hosts and Susceptible Animals of SARS-CoV-2 by Computational Methods

COVID-19, a disease caused by SARS-CoV-2 that produces major symptoms of pneumonia, has been a disaster worldwide. The traceability of SARS-CoV-2 and the discovery of susceptible animal species is crucial to halt viral transmission and explore the mechanism of cross-species transmission. We selected 82 representative ACE2 sequences from the 1000 sequences with the closest homology to the hACE2 protein. All selected ACE2 proteins were subjected to homology modeling. Potential natural and intermediate hosts, as well as animal species susceptible to SARS-CoV-2, were analyzed systematically by calculation of the binding free energy of ACE2 protein to the RBD of SARS-CoV-2. Primates, some wild Felidae, civets, goats, spotted hyenas and golden hamsters are susceptible to SARS-CoV-2 and may be potential intermediate hosts, whereas pangolins, birds and reptiles are unlikely to be intermediate hosts. Mice, rats and guinea pig are not susceptible to SARS-CoV-2. Given their possible susceptibility, non-human primates, goats and golden hamsters could potentially be used as experimental models to examine SARS-CoV-2 infection without transgenesis. Herein, possible candidates for the natural and intermediate hosts of SARS-CoV-2 are suggested, to provide guidance for subsequent studies

Energy deficiency promotes rhythmic foraging behavior by activating neurons in paraventricular hypothalamic nucleus

BackgroundDysregulation of feeding behavior leads to a variety of pathological manifestations ranging from obesity to anorexia. The foraging behavior of animals affected by food deficiency is not fully understood.MethodsHome-Cage system was used to monitor the behaviors. Immunohistochemical staining was used to monitor the trend of neuronal activity. Chemogenetic approach was used to modify neuronal activity.ResultsWe described here a unique mouse model of foraging behavior and unveiled that food deprivation significantly increases the general activities of mice with a daily rhythmic pattern, particularly foraging behavior. The increased foraging behavior is potentiated by food cues (mouthfeel, odor, size, and shape) and energy deficit, rather than macronutrient protein, carbohydrate, and fat. Notably, energy deficiency increases nocturnal neuronal activity in paraventricular hypothalamic nucleus (PVH), accompanying a similar change in rhythmic foraging behavior. Activating neuronal activity in PVH enhances the amplitude of foraging behavior in mice. Conversely, inactivating neuronal activity in PVH decreases the amplitude of foraging behavior and impairs the rhythm of foraging behavior.DiscussionThese results illustrate that energy status and food cues regulate the rhythmic foraging behavior via PVH neuronal activity. Understanding foraging behavior provides insights into the underlying mechanism of eating-related disorders

Plant biosystems design research roadmap 1.0

Human life intimately depends on plants for food, biomaterials, health, energy, and a sustainable environment. Various plants have been genetically improved mostly through breeding, along with limited modification via genetic engineering, yet they are still not able to meet the ever-increasing needs, in terms of both quantity and quality, resulting from the rapid increase in world population and expected standards of living. A step change that may address these challenges would be to expand the potential of plants using biosystems design approaches. This represents a shift in plant science research from relatively simple trial-and-error approaches to innovative strategies based on predictive models of biological systems. Plant biosystems design seeks to accelerate plant genetic improvement using genome editing and genetic circuit engineering or create novel plant systems through de novo synthesis of plant genomes. From this perspective, we present a comprehensive roadmap of plant biosystems design covering theories, principles, and technical methods, along with potential applications in basic and applied plant biology research. We highlight current challenges, future opportunities, and research priorities, along with a framework for international collaboration, towards rapid advancement of this emerging interdisciplinary area of research. Finally, we discuss the importance of social responsibility in utilizing plant biosystems design and suggest strategies for improving public perception, trust, and acceptance

Genome editing reveals dmrt1 as an essential male sex-determining gene in Chinese tongue sole (Cynoglossus semilaevis)

Chinese tongue sole is a marine fish with ZW sex determination. Genome sequencing suggested that the Z-linked dmrt1 is a putative male determination gene, but direct genetic evidence is still lacking. Here we show that TALEN of dmrt1 efficiently induced mutations of this gene. The ZZ dmrt1 mutant fish developed ovary-like testis, and the spermatogenesis was disrupted. The female-related genes foxl2 and cyp19a1a were significantly increased in the gonad of the ZZ dmrt1 mutant. Conversely, the male-related genes Sox9a and Amh were significantly decreased. The dmrt1 deficient ZZ fish grew much faster than ZZ male control. Notably, we obtained an intersex ZW fish with a testis on one side and an ovary on the other side. This fish was chimeric for a dmrt1 mutation in the ovary, and wild-type dmrt1 in the testis. Our data provide the first functional evidence that dmrt1 is a male determining gene in tongue sole

Draft genome sequence of the mulberry tree Morus notabilis

Human utilization of the mulberry–silkworm interaction started at least 5,000 years ago and greatly influenced world history through the Silk Road. Complementing the silkworm genome sequence, here we describe the genome of a mulberry species Morus notabilis. In the 330-Mb genome assembly, we identify 128 Mb of repetitive sequences and 29,338 genes, 60.8% of which are supported by transcriptome sequencing. Mulberry gene sequences appear to evolve ~3 times faster than other Rosales, perhaps facilitating the species’ spread worldwide. The mulberry tree is among a few eudicots but several Rosales that have not preserved genome duplications in more than 100 million years; however, a neopolyploid series found in the mulberry tree and several others suggest that new duplications may confer benefits. Five predicted mulberry miRNAs are found in the haemolymph and silk glands of the silkworm, suggesting interactions at molecular levels in the plant–herbivore relationship. The identification and analyses of mulberry genes involved in diversifying selection, resistance and protease inhibitor expressed in the laticifers will accelerate the improvement of mulberry plants

Fingerprint locating algorithm based on interval-valued fuzzy theory for ubiquitous computing

Locating is one of the important applications for ubiquitous computing,while it is difficult to obtain the accurate location context.This paper proposes an interval-value based fuzzy method to deal with uncertainty for location context.Firstly,a general framework of indoor locating system is described. Its advantages and disadvantages are discussed. Then the interval-valued fuzzy fingerprint locating algorithm is provided. This algorithm includes two phases,the phase of off line database establishing and the phase of online real-time fuzzy locating. An indoor locating experiment is used to verify the accuracy of this algorithm

Regionalizing Streamflow Regime Function through Integrations of Geographical Controls in Mountainous Basins

Flow duration curves (FDCs) that represent streamflow regime function through an empirical relationship between the FDC parameters and basin descriptors are widely adopted for hydrologic applications. However, the applications of this method are highly dependent on the availability of observation data. Hence, it is still of great significance to explore the process controls of underpinning regional patterns on streamflow regimes. In this study, we developed a new regionalization method of FDCs to solve the problem of runoff prediction for ungauged mountainous basins. Five empirical equations (power, exponential, logarithmic, quadratic, and cubic) were used to fit the observed FDCs in the 64 mountainous basins in eastern China, and the power model outperforms other models. Stepwise regression was used to explore the differentiated control of 23 basin descriptors on the 13 percentile flows of FDCs, and seven descriptors remained as independent variables for further developing the regional FDCs. Application results with different combinations of these selected descriptors showed that five indices, i.e., average annual rainfall (P), average elevation (H), average gradient (β), average topographic index (TI), and maximum 7d of annual rainfall (Max7d), were the main control factors of FDCs in these areas. Through the regional method, we found that 95.31% of all the basins have NSE values greater than 0.60 and ε (namely the relative mean square error) values less than 20%. In conclusion, our study can guide runoff predictions to help manage booming demands for water resources and hydropower developments in mountainous areas