Prediction of amino acid pairs sensitive to mutations in the spike protein from SARS related coronavirus

In this study, we analyzed the amino acid pairs affected by mutations in two spike proteins from human coronavirus strains 229E and OC43 by means of random analysis in order to gain some insight into the possible mutations in the spike protein from SARS-CoV. The results demonstrate that the randomly unpredictable amino acid pairs are more sensitive to the mutations. The larger is the difference between actual and predicted frequencies, the higher is the chance of mutation occurring. The effect induced by mutations is to reduce the difference between actual and predicted frequencies. The amino acid pairs whose actual frequencies are larger than their predicted frequencies are more likely to be targeted by mutations, whereas the amino acid pairs whose actual frequencies are smaller than their predicted frequencies are more likely to be formed after mutations. These findings are identical to our several recent studies, i.e. the mutations represent a process of degeneration inducing human diseases.     

Spironolactone Attenuates Bleomycin-Induced Pulmonary Injury Partially via Modulating Mononuclear Phagocyte Phenotype Switching in Circulating and Alveolar Compartments

Background

Recent experimental studies provide evidence indicating that manipulation of the mononuclear phagocyte phenotype could be a feasible approach to alter the severity and persistence of pulmonary injury and fibrosis. Mineralocorticoid receptor (MR) has been reported as a target to regulate macrophage polarization. The present work was designed to investigate the therapeutic potential of MR antagonism in bleomycin-induced acute lung injury and fibrosis.

Methodology/Principal Findings

We first demonstrated the expression of MR in magnetic bead-purified Ly6G-/CD11b+ circulating monocytes and in alveolar macrophages harvested in bronchoalveolar lavage fluid (BALF) from C57BL/6 mice. Then, a pharmacological intervention study using spironolactone (20mg/kg/day by oral gavage) revealed that MR antagonism led to decreased inflammatory cell infiltration, cytokine production (downregulated monocyte chemoattractant protein-1, transforming growth factor β1, and interleukin-1β at mRNA and protein levels) and collagen deposition (decreased lung total hydroxyproline content and collagen positive area by Masson’ trichrome staining) in bleomycin treated (2.5mg/kg, via oropharyngeal instillation) male C57BL/6 mice. Moreover, serial flow cytometry analysis in blood, BALF and enzymatically digested lung tissue, revealed that spironolactone could partially inhibit bleomycin-induced circulating Ly6C^hi monocyte expansion, and reduce alternative activation (F4/80+CD11c+CD206+) of mononuclear phagocyte in alveoli, whereas the phenotype of interstitial macrophage (F4/80+CD11c-) remained unaffected by spironolactone during investigation.

Conclusions/Significance

The present work provides the experimental evidence that spironolactone could attenuate bleomycin-induced acute pulmonary injury and fibrosis, partially via inhibition of MR-mediated circulating monocyte and alveolar macrophage phenotype switching.     

Identification of a novel coronavirus from a beluga whale by using a panviral microarray

The emergence of viruses such as severe acute respiratory syndrome coronavirus and Nipah virus has underscored the role of animal reservoirs in human disease and the need for reservoir surveillance. Here, we used a panviral DNA microarray to investigate the death of a captive beluga whale in an aquatic park. A highly divergent coronavirus, tentatively named coronavirus SW1, was identified in liver tissue from the deceased whale. Subsequently, the entire genome of SW1 was sequenced, yielding a genome of 31,686 nucleotides. Phylogenetic analysis revealed SW1 to be a novel virus distantly related to but most similar to group III coronaviruses.     

Identification and molecular mapping of a resistance gene to powdery mildew from the synthetic wheat line M53

Powdery mildew disease caused by Blumeria graminis f. sp. tritici (Bgt) is an economically important disease in wheat worldwide. The identification of germplasms resistant to the disease can not only facilitate the breeding of resistant cultivars, but can also broaden the diversity of resistance genes. The Mexican M53 is a synthetic hexaploid wheat line developed at the International Maize and Wheat Improvement Center (CIMMYT) from the cross between Triticum durum and Aegilops tauschii249. Infection of M53 with 15 different pathogen races revealed that the resistance in M53 was race-dependent and effective against the majority of the tested Bgt races, including the race 15 predominant in the Beijing wheat growing area. Inoculation of the parents of M53 with the race 15 demonstrated that M53 and Ae. tauschii249 were resistant, whereas T. durum was susceptible. The inoculation of three segregating F₂ populations developed from the crosses between M53 and three susceptible Chinese wheat cultivars with the race 15 showed that the resistant gene in M53 segregated in a single dominant manner. Amplified fragment length polymorphism (AFLP) and simple sequence repeat (SSR) markers were used to map the gene in a segregating F₂ population consisting of 213 lines developed from the cross Wan7107 × M53. Two closely linked AFLP markers, Apm109 and Apm161, were identified to flank the gene with genetic distances of 1.0 cM and 3.0 cM, respectively. The recognized gene was assigned to the long arm of chromosome 5D as determined by three linked SSR markers, Xwmc289b, Xgwm583, and Xgwm292, and by the physical mapping of Apm109 using Chinese Spring nullisomic–tetrasomic and ditelosomic stocks. The resistance gene identified in M53, temporarily designated as Pm-M53, could be used in local wheat-breeding programs to improve powdery mildew resistance.     

miR-194-5p negatively regulates the proliferation and differentiation of rabbit skeletal muscle satellite cells

Molecular and Cellular Biochemistry - Skeletal muscle satellite cells (SMSCs), also known as a multipotential stem cell population, play a crucial role during muscle growth and regeneration. In...