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LIM-domain proteins have been shown to be associated with heart development and diseases. Systematic studies of LIM family members at the genome-wide level, which are crucial to further understand their functions in cardiac hypertrophy, are currently lacking. Here, 70 LIM genes were identified and characterised in mice. The expression patterns of LIM genes differ greatly during cardiac development and in the case of hypertrophy. Both Crip2 and Xirp2 are differentially expressed in cardiac hypertrophy and during heart failure. In addition, the hypertrophic state of cardiomyocytes is controlled by the relative expression levels of Crip2 and Xirp2. This study provides a foundation for further understanding of the special roles of LIM proteins in mammalian cardiac development and hypertrophy.

Background and aims Liver regeneration after extreme hepatocyte loss occurs through transdifferentiation of biliary epithelial cells (BECs), which includes dedifferentiation of BECs into bipotential progenitor cells (BPPCs) and subsequent redifferentiation into nascent hepatocytes and BECs. Although multiple molecules and signaling pathways have been implicated to play roles in the BEC-mediated liver regeneration, mechanisms underlying the dedifferentiation-redifferentiation transition and the early phase of BPPC redifferentiation that is pivotal for both hepatocyte and BEC directions remain largely unknown. Approach and results The zebrafish extreme liver damage model, genetic mutation, pharmacological inhibition, transgenic lines, whole-mount and fluorescent in situ hybridizations and antibody staining, single-cell RNA sequencing, quantitative real-time PCR, and heat shock-inducible overexpression were used to investigate roles and mechanisms of farnesoid X receptor (FXR; encoded by nuclear receptor subfamily 1, group H, member 4 [nr1h4]) in regulating BPPC redifferentiation. The nr1h4 expression was significantly up-regulated in response to extreme liver injury. Genetic mutation or pharmacological inhibition of FXR was ineffective to BEC-to-BPPC dedifferentiation but blocked the redifferentiation of BPPCs to both hepatocytes and BECs, leading to accumulation of undifferentiated or less-differentiated BPPCs. Mechanistically, induced overexpression of extracellular signal-related kinase (ERK) 1 (encoded by mitogen-activated protein kinase 3) rescued the defective BPPC-to-hepatocyte redifferentiation in the nr1h4 mutant, and ERK1 itself was necessary for the BPPC-to-hepatocyte redifferentiation. The Notch activities in the regenerating liver of nr1h4 mutant attenuated, and induced Notch activation rescued the defective BPPC-to-BEC redifferentiation in the nr1h4 mutant. Conclusions FXR regulates BPPC-to-hepatocyte and BPPC-to-BEC redifferentiations through ERK1 and Notch, respectively. Given recent applications of FXR agonists in the clinical trials for liver diseases, this study proposes potential underpinning mechanisms by characterizing roles of FXR in the stimulation of dedifferentiation-redifferentiation transition and BPPC redifferentiation.

The Wnt signaling pathway is an evolutionarily conserved signaling pathway that plays essential roles in embryonic development, organogenesis, and many other biological activities. Both Wnt proteins and DIX proteins are important components of Wnt signaling. Systematic studies of Wnt and DIX families at the genome-wide level may provide a comprehensive landscape to elucidate their functions and demonstrate their relationships, but they are currently lacking. In this report, we describe the correlations between mouse Wnt and DIX genes in family expansion, molecular evolution, and expression levels in cardiac hypertrophy at the genome-wide scale. We observed that both the Wnt and DIX families underwent more expansion than the overall average in the evolutionarily early stage. In addition, mirrortree analyses suggested that Wnt and DIX were co-evolved protein families. Collectively, these results would help to elucidate the evolutionary characters of Wnt and DIX families and demonstrate their correlations in mediating cardiac hypertrophy.

Sepsis‑induced myocardial dysfunction is one of the features of multiple organ dysfunction in sepsis, which is associated with extremely high mortality and is characterized by impaired myocardial compliance. To date, there are few effective treatment options available to cure sepsis. Tannic acid (TA) is reportedly protective during sepsis; however, the underlying mechanisms by which TA protects against septic heart injury remain elusive. The present study investigated the potential effects and underlying mechanisms of TA in alleviating lipopolysaccharide (LPS)‑induced H9C2 cardiomyocyte cell apoptosis. H9C2 cells were treated with LPS (15 µg/ml), TA (10 µM) and TA + LPS; control cells were treated with medium only. Apoptosis was measured using flow cytometry, reverse transcription‑quantitative PCR (RT‑qPCR) and western blot analysis. Additionally, the levels of cellular reactive oxygen species (ROS), malondialdehyde and nicotinamide adenine dinucleotide phosphate were evaluated. Western blotting and RT‑qPCR were also employed to detect the expression levels of endoplasmic reticulum (ER) stress‑associated functional proteins. The present findings demonstrated that TA reduced the degree of LPS‑induced H9C2 cell injury, including inhibition of ROS production and ER stress (ERS)‑associated apoptosis. ERS‑associated functional proteins, including activating transcription factor 6, protein kinase‑like ER kinase, inositol‑requiring enzyme 1, spliced X box‑binding protein 1 and C/EBP‑homologous protein were suppressed in response to TA treatment. Furthermore, the expression levels of ERS‑associated apoptotic proteins, including c‑Jun N‑terminal kinase, Bax, cytochrome c, caspase‑3, caspase‑12 and caspase‑9 were reduced following treatment with TA. Additionally, the protective effects of TA on LPS‑induced H9C2 cells were partially inhibited following treatment with the ROS inhibitor N‑acetylcysteine, which demonstrated that ROS mediated ERS‑associated apoptosis and TA was able to decrease ROS‑mediated ERS‑associated apoptosis. Collectively, the present findings demonstrated that the protective effects of TA against LPS‑induced H9C2 cell apoptosis may be associated with the amelioration of ROS‑mediated ERS. These findings may assist the development of potential novel therapeutic methods to inhibit the progression of myocardial cell injury.

Ribosome biogenesis is a significant process in cells. Dysfunction in this process will result in the defects of protein synthesis and consequently cause the development of specific diseases called ribosomopathies. Mutations in ribosome biogenesis protein Rps19, Rpl5, or Rpl11 can lead to hematopoietic defects in human, thus triggering the disease Diamond Blackfan anemia. However, the regulatory mechanisms of ribosome biogenesis in hematopoiesis remain incompletely understood. In this study, we describe a zebrafish mutant cq42, which carries a nonsense mutation in the gene that encodes ribosome biogenesis 2 homolog (Urb2). Urb2 is strongly expressed in the caudal hematopoietic tissue (CHT) during hematopoietic stem cells (HSCs) expanding. Molecular characterization of urb2cq42 larvae suggest that urb2 deficiency notably decrease the population of HSCs in CHT and early T cells in thymus. Further analysis shows that compromised cell proliferation and superfluous apoptosis are observed in the CHT of urb2cq42 mutant. P53 pathway is upregulated in the urb2cq42 larvae and loss-of-function of P53 can fully rescue the hematopoietic defects in urb2cq42 mutant. These data demonstrate that urb2 is essential for HSCs development through the regulation of P53 pathway.

Toll-like receptors (TLRs) are the earliest reported pathogen recognition receptors (PRRs), and these receptors play pivotal roles in the innate immune system. Systematic studies of TLR family at the genome-wide level are important to understand its functions but are currently lacking in the insect lineage. Here, 6 TLR genes were identified and characterized in housefly (Musca domestica). The TLR genes of housefly were classified into five families according to the phylogenetic analysis of insect TLRs. The domain organization analyses indicated that the TLRs were composed by three major components: a leucine-rich repeat (LRR) domain, a transmembrane region (TM) and a Toll/interleukin-1 receptor (TIR) domain. Primary and tertiary structure analysis showed that the ectodomains of arthropod TLRs were longer than that of other phyla or classes. The mRNA expression levels of all 6 TLRs downregulated in the resistant housefly strain. Moreover, the expression levels of 6 TLRs varied between tissue and gender. Additionally, the 3D structures of the TIR domain were highly conserved during evolution. Collectively, these results help elucidate the crucial roles of TLRs in the immune response of housefly and provide a foundation for further understanding of innate immunity of the housefly.

Rho GTPases play essential roles in various life activities. Rho GTPase-activating protein (RhoGAP) and Rho guanine nucleotide exchange factor (RhoGEF) are the main regulators of Rho GTPases. RhoGAP, RhoGEF and Rho make up a molecular switch and exert crucial roles in signaling pathways. The genome-wide studies can provide us a comprehensive information of special protein family, but the genome-wide information of RhoGAP and RhoGEF families are still lacking in the mammal lineage. Here, we report the correlations between mouse RhoGAPs and RhoGEFs in gene quantities, evolution, molecular function, and their expression levels in heart embryonic development and cardiovascular medicine treatment at genome-wide scale. Besides, we find that the 3D structures of RhoGAP domains between different species are highly conserved, but that of RhoGEF domains are variable between species. Our present study contributes to a better understanding of the complex regulation mechanisms of RhoGAP and RhoGEF families.

High throughput plant phenotyping has gained significant interest in the plant science community due to its potential impact in advancing the use of advanced plant genetics for problems ranging from global food security to biomass-based energy crops. While traditional collection of field-based phenotypes is manual, automated remote sensing-based methods can reduce the manual requirements, expand the number of sampled points, and accelerate associations with genotypes. In this preliminary work, we use multiple types of features derived from multi-temporal UAV-based hyperspectral and RGB image data for prediction of sorghum biomass. Considering the nonlinear properties of the spectral input features, multiple layer perception (MLP) neural networks and support vector regression (SVR) are explored for predicting dry biomass. The analysis is conducted on datasets acquired during June-August 2016 over an agricultural test field at the Agronomy Center for Research and Education (ACRE) at Purdue University.

Pseudomonas aeruginosa causes serious acute and chronic infections in humans. Major differences exist in disease pathogenesis, clinical treatment and outcomes between acute and chronic infections. P. aeruginosa acute infection characteristically involves the type III secretion systems (T3SS) while chronic infection is often associated with the formation of biofilms, a major cause of difficulties to eradicate chronic infections. The choice between acute and chronic infection or the switch between them by P. aeruginosa is controlled by regulatory pathways that control major virulence factors and genes associated with biofilm formation. In this study, we characterized a hybrid sensor kinase PA1611 that controls the expression of genes associated with acute and chronic infections in P. aeruginosa PAO1. Expression of PA1611 completely repressed T3SS and swarming motility while it promoted biofilm formation. The protein PA1611 regulates two small RNAs (sRNAs), rsmY and rsmZ which in turn control RsmA. Independent of phosphate relay, PA1611 interacts directly with RetS in vivo. The positive effect of RetS on factors associated with acute infection could presumably be restrained by PA1611 when chronic infection conditions are present. This RetS-PA1611 interaction, together with the known RetS-GacS interaction, may control disease progression and the lifestyle choice of P. aeruginosa.