马尾松R2R3-MYB基因特征及进化和表达分析

MYB类转录因子在植物生长发育、代谢、应答生物胁迫和非生物胁迫的响应等生物过程发挥重要作用。为探究马尾松R2R3-MYB基因结构及功能,该研究以转录组数据为研究区域,从中筛选获得了17个马尾松R2R3-MYB基因,利用生物信息学对基因进行理化性质、系统进化树等分析,同时利用荧光定量PCR技术分析基因的组织特异性以及在花发育时期和非生物胁迫下的表达模式。结果表明：(1)17个PmMYBs亚细胞定位于细胞核,均无跨膜结构,且均含有Motif1、Motif2保守基序。系统发育进化树将马尾松PmMYBs划分为9个亚家族,且与火炬松、白云杉等裸子针叶植物关系较近。(2)17个基因均属于组成型表达,但在不同组织的表达量不同;所有基因均参与了花发育和非生物胁迫,不同基因在花发育不同时期的表达存在差异,有7个基因可能参与了雌雄性状转变;大部分基因响应非生物胁迫上调表达,但响应胁迫的时间存在差异;少数基因在胁迫中下调表达,尤其是PmMYB11基因在所有胁迫中均明显下调表达。该研究较系统地分析了马尾松R2R3-MYB基因的结构特征、系统进化及其在花发育时期和非生物胁迫下的表达模式,为深入探究马尾松R2R3...     

The structure of Crimean-Congo hemorrhagic fever virus Gc is revealed; many more still need an answer

Highlights
1. The structure of glycoprotein Gc, responsible for mediating membrane fusion between cell and CCHFV, is revealed, but many more mysteries remain.
2. Why do only antibodies against Gc have neutralizing effect, but not the one against Gn?
3. Why can NAbs against Gc only be protective in the animals in preventive settings, but not in the therapeutic administration?     

Discovery of novel DNA viruses in small mammals from Kenya

Emergence and re-emergence of infectious diseases of wildlife origin have led pre-emptive pathogen surveillances in animals to be a public health priority. Rodents and shrews are among the most numerically abundant vertebrate taxa and are known as natural hosts of important zoonotic viruses. Many surveillance programs focused more on RNA viruses. In comparison, much less is known about DNA viruses harbored by these small mammals. To fill this knowledge gap, tissue specimens of 232 animals including 226 rodents, five shrews and one hedgehog were collected from 5 counties in Kenya and tested for the presence of DNA viruses belonging to 7 viral families by PCR. Diverse DNA sequences of adenoviruses, adeno-associated viruses, herpesviruses and polyomaviruses were detected. Phylogenetic analyses revealed that most of these viruses showed distinction from previously described viruses and formed new clusters. Furthermore, this is the first report of the discovery and full-length genome characterization of a polyomavirus in Lemniscomys species. This novel polyomavirus, named LsPyV KY187, has less than 60% amino acid sequence identity to the most related Glis glis polyomavirus 1 and Sciurus carolinensis polyomavirus 1 in both large and small T-antigen proteins and thus can be putatively allocated to a novel species within Betapolyomavirus. Our findings help us better understand the genetic diversity of DNA viruses in rodent and shrew populations in Kenya and provide new insights into the evolution of those DNA viruses in their small mammal reservoirs. It demonstrates the necessity of ongoing pathogen discovery studies targeting rodent-borne viruses in East Africa.     

Infection and pathogenesis of the Delta variant of SARS-CoV-2 in Rhesus macaque

Highlights
1. Delta variant of SARS-CoV-2 can effectively infect the Rhesus macaque.
2. The Delta variant grows faster than the early strain isolated from Wuhan in late 2019.
3. The shedding pattern, viral load and disease severity of Delta variant are similar with the early strain isolated from Wuhan in late 2019.
4. This study supports the attributed rapid disease spread of the Delta variant.     

Mating system shifts a species’ range

Understanding the ecological and evolutionary mechanisms that shape a species’ range is an important goal in evolutionary biology. Evidence indicates that mating system is an effective predictor of the global range of native species or naturalized alien plants, but the mechanisms underlying this predictability are not elaborated. Here, we develop a theoretical model to account for the ranges of plants under different mating systems based on migration‐selection processes (an idea proposed by Haldane). The model includes alternation of gametophyte and sporophyte generations in one life cycle and the dispersal of haploid pollen and diploid seeds as vectors for gene flow. We show that the interaction between selfing rates and gametophytic selection determines the role of mating system in shaping a species’ range. Selfing restricts the species’ range under gametophytic selection in nonrandom mating systems, but expands the species’ range under the absence of gametophytic selection in any mating system. Gametophytic selection slightly restricts the species’ range in random mating. Both logarithmic and logistic models of population demography yield similar conclusions in the case of fixed or evolving genetic variance. The theory also helps to explain a broader relationship between mating system and range size following biological invasion or plant naturalization.     

microRNA-33-3p involved in selenium deficiency-induced apoptosis via targeting ADAM10 in the chicken kidney

Selenium (Se) deficiency induces typical clinical and pathological changes and causes various pathological responses at the molecular level in several different chicken organs; the kidney is one of the target organs of Se deficiency. To explore the mechanisms that underlie the effects of microRNA-33-3p (miR-33-3p) on Se deficiency-induced kidney apoptosis, 60 chickens were randomly divided into two groups (30 chickens per group). We found that Se deficiency increased the expression of miR-33-3p in the chicken kidney. A disintegrin and metalloprotease domain 10 (ADAM10) was verified to be a target of miR-33-3p in the chicken kidney. The overexpression of miR-33-3p decreased the expression levels of β-catenin, cyclinD1, T-cell factor (TCF), c-myc, survivin, and Bcl-2; it increased the expression levels of E-cadherin, Bak, Bax, and caspase-3; and it increased the number of chicken kidney cells in the G0/G1 phase. In addition, Se deficiency caused the ultrastructure of the kidney to develop apoptotic characteristics. The results of flow cytometry analysis and AO/EB staining showed that the number of apoptotic chicken kidney cells increased in the miR-33-3p mimic group. All these results suggest that Se deficiency-induced cell cycle arrest and apoptosis in vivo and in vitro in the chicken kidney via the regulation of miR-33-3p, which targets ADAM10.     

LncRNA MEG3 negatively modified osteosarcoma development through regulation of miR-361-5p and FoxM1

This study was aimed to figure out whether long noncoding RNA MEG3/miR-361-5p/FoxM1 signaling would contribute to improved proliferation and metastasis of osteosarcoma cells. We altogether collected 204 pairs of osteosarcoma tissues and adjacent normal tissues, and obtained four human osteosarcoma cell lines. Then pcDNA3.1-MEG3, si-MEG3, miR-361-5p mimic, miR-361-5p inhibitor, pcDNA3.1-FoxM1, si-FoxM1, and negative control (NC) were, respectively, transfected into the osteosarcoma cells. Furthermore, real time polymerase chain reaction was utilized to determine the mRNA expressions of maternally expressed gene 3 (MEG3) and miR-361-5p, and western blot analysis was applied for determining the FoxM1 expression. Besides, dual luciferase reporter gene assay was adopted to verify if MEG3 can be directly targeted by miR-361-5p. Finally, 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide, colony formation assay, flow cytometry, wound healing assay, and transwell assay were conducted to investigate the influence of MEG3, miR-361-5p, and FoxM1 expressions on the viability, proliferation, apoptosis, migration, and invasion of osteosarcoma cells. MEG3 and miR-361-5p were observed to be significantly downregulated within both osteosarcoma tissues and cell lines, whereas FoxM1 was upregulated in osteosarcoma tissues and cell lines (p < 0.05). MEG3 directly bound to miR-361-5p, and significantly upgraded its expression (p < 0.05). The upregulated MEG3 and miR-361-5p or the downregulated FoxM1 appeared to substantially inhibit proliferation, migration, and invasion of osteosarcoma cells (p < 0.05). Finally, the proliferation, migration, invasion, and motility of osteosarcoma cells within the miR-NC + pcDNA3.1-FoxM1 group and pcDNA + pcDNA-FoxM1 group were markedly promoted when compared with the miR-361-5p mimic group and pcDNA3.1-MEG3 group (p < 0.05). The MEG3/miR-361-5p/FoxM1 axis could potentially serve as therapeutic targets or diagnostic biomarkers for osteosarcoma.     

RGS1 silencing inhibits the inflammatory response and angiogenesis in rheumatoid arthritis rats through the inactivation of Toll-like receptor signaling pathway

Emerging evidence shows that rheumatoid arthritis (RA) progression can be induced by the activation of Toll-like receptor (TLR) signaling pathway. Regulator of G-protein signaling 1 (RGS1) is observed to be a candidate biomarker for arthritis. Accordingly, the present study aims to determine the potential effects of RGS1 mediating TLR on RA. A rat model of collagen-induced arthritis (CIA) was established to mimic the features of RA by injection of bovine type II collagen. The rats with CIA were treated with short hairpin RNA (shRNA) against RGS1 or TLR pathway activator Poly I:C to elucidate the role of RGS1 in RA progression. The inflammatory factors were measured, and the thoracic gland and spleen indexes as well as the vascular density were determined. The expression levels of RGS1, TLR3, vascular endothelial growth factor (VEGF), metalloproteinase-2 (MMP-2), MMP-9, and interleukin 1 receptor-associated kinase-4 (IRAK4) were determined. RGS1 was robustly increased in RA. The TLR signaling pathway was suppressed by RGS1 silencing. shRNA-mediated depletion of RGS1 was shown to significantly enhance thoracic gland index and inhibit the serum levels of TNF-α, IL-1β, and IL-17, spleen index, vascular density, and the expression levels of TLR3, VEGF, MMP-2, MMP-9, and IRAK4. However, when the rats with CIA were treated with Poly I:C, the trend of effects was opposite. These findings highlight that functional suppression of RGS1 inhibits the inflammatory response and angiogenesis by inactivating the TLR signaling pathway in rats with CIA, thereby providing a novel therapeutic target for RA treatment.     

BI1 alleviates cardiac microvascular ischemia-reperfusion injury via modifying mitochondrial fission and inhibiting XO/ROS/F-actin pathways

Pathogenesis of cardiac microvascular ischemia-reperfusion (IR) injury is associated with excessive mitochondrial fission. However, the upstream mediator of mitochondrial fission remains obscure. Bax inhibitor 1 (BI1) is linked to multiple mitochondrial functions, and there have been no studies investigating the contribution of BI1 on mitochondrial fission in the setting of cardiac microvascular IR injury. This study was undertaken to establish the action of BI1 on the cardiac microvascular reperfusion injury and figure out whether BI1 sustained endothelial viability via inhibiting mitochondrial fission. Our observation indicated that BI1 was downregulated in reperfused hearts and overexpression of BI1 attenuated microvascular IR injury. Mechanistically, reperfusion injury elevated the levels of xanthine oxidase (XO), an effect that was followed by increased reactive oxygen species (ROS) production. Subsequently, oxidative stress mediated F-actin depolymerization and the latter promoted mitochondrial fission. Aberrant fission caused mitochondrial dysfunction and ultimately activated mitochondrial apoptosis in cardiac microvascular endothelial cells. By comparison, BI1 overexpression repressed XO expression and thus neutralized ROS, interrupting F-actin-mediated mitochondrial fission. The inhibitory effect of BI1 on mitochondrial fission sustained endothelial viability, reversed endothelial barrier integrity, attenuated the microvascular inflammation response, and maintained microcirculation patency. Altogether, we conclude that BI1 is essential in maintaining mitochondrial homeostasis and alleviating cardiac microvascular IR injury. Deregulated BI1 via the XO/ROS/F-actin pathways plays a causative role in the development of cardiac microvascular reperfusion injury.