The role of D-dimer in relation to the clinical course of patients with COVID-19

In recent times,systemic coagulation,fibrinolysis,and cardio-pulmonary injury has been recognized in patients with COVID-19,the clinical disease state caused by infection of the novel coronavirus,SARS-CoV-2.While originally believed to be a primary lower respiratory infection,as more cases are identified,treated,and examined,hematologic complications are being identified as a significant driver of morbidity and mortality associated with the disease.Elevated D-dimer levels(>1μg/ml)on hospital admission have been identified as being associated with increased mortality[1],and levels greater than 2μg/ml predict fatal outcomes in patients[2].Alongside these results,there is also a greater risk of thrombotic events in COVID-19 patients,with risk increasing to as high as 31%[3],and pulmonary embolism risk increases proportionately alongside this[4].Whilst understanding of the pathophysiology is incomplete,there is clearly a component of coagulative disorder in these patients.D-dimer could prove a valuable tool to identify patients who are likely to have poorer outcomes and allow for prophylactic treatment and monitoring of secondary complications(Fig.1).     

Could cancer and infection be adverse effects of mesenchymal stromal cell therapy?

Multipotent mesenchymal stromal cells [also referred to as mesenchymal stem cells(MSCs)] are a heterogeneous subset of stromal cells. They can be isolated from bone marrow and many other types of tissue. MSCs are currently being tested for therapeutic purposes(i.e., improving hematopoietic stem cell engraftment, managing inflammatory diseases and regenerating damaged organs). Their tropism for tumors and inflamed sites and their context-dependent potential for producing trophic and immunomodulatory factors raises the question as to whether MSCs promote cancer and/or infection. Thisarticle reviews the effect of MSCs on tumor establishment, growth and metastasis and also susceptibility to infection and its progression. Data published to date shows a paradoxical effect regarding MSCs, which seems to depend on isolation and expansion, cells source and dose and the route and timing of administration. Cancer and infection may thus be adverse or therapeutic effects arising form MSC administration.     

Effect of mixed infection on TB dynamics

Poor living conditions,overcrowding and strain diversity are some of the factors that influence mixed infection in Tuberculosis (TB) at the population level.We formulate a mathematical model for mixed infection in TB using nonlinear ordinary differential equa-tions where such factors were represented as probabilities of acquiring mixed infection.A qualitative analysis of the model shows that it exhibits multiple endemic equilibria and backward bifurcation for certain parameter values.The reactivation rate and trans-mission rate of individuals with mixed infection were of importance as well as the prob-abilities for latent individuals to acquire mixed infection.We calculate the prevalence of mixed infection from the model and the effect of mixed infection on TB incidence,TB prevalence and Mycobacterium tuberculosis (MTB) infection rate.Numerical simu-lations show that mixed infection may explain high TB incidences in areas which have a high strain diversity,poor living conditions and are overcrowded even without HIV.     

New Gene Variants Associated with the Risk of Chronic HBV Infection

Some patients with chronic hepatitis B virus(HBV) infection failed to clear HBV, even persistently continue to produce antibodies to HBV. Here we performed a two stage genome wide association study in a cohort of Chinese patients designed to discover single nucleotide variants that associate with HBV infection and clearance of HBV. The first stage involved genome wide exome sequencing of 101 cases(HBsAg plus anti-HBs positive) compared with 102 control patients(antiHBs positive, HBsAg negative). Over 80% of individual sequences displayed 209 sequence coverage. Adapters,uncertain bases [10% or low-quality base calls([50%) were filtered and compared to the human reference genome hg19. In the second stage, 579 chronic HBV infected cases and 439 HBV clearance controls were sequenced with selected genes from the first stage. Although there were no significant associated gene variants in the first stage, two significant gene associations were discovered when the two stages were assessed in a combined analysis. One association showed rs506121-‘‘T' allele [within the dedicator of cytokinesis 8(DOCK8) gene] was higher in chronic HBV infection group than that in clearance group(P = 0.002, OR = 0.77, 95% CI [0.65, 0.91]). The second association involved rs2071676—A allele within the Carbonic anhydrase(CA9) gene that was significantly elevated in chronic HBV infection group compared to the clearance group(P = 0.0003, OR = 1.35, 95% CI [1.15, 1.58]). Upon replication these gene associations would suggest the influence of DOCK8 and CA9 as potential risk genetic factors in the persistence of HBV infection.     

Detection of mutations associated with resistance to rifampicin and isoniazid in Mycobacterium tuberculosis by polymerase chain reaction-ligase detection reaction

Mycobacterium tuberculosis （MTB） infection remains a serious infectious disease worldwide, causing 8.8 million new infections and 1.45 million deaths in 2010 [1]. The emergence of drug-resistant strains of MTB poses a significant threat to the control of the disease globally. Multidrugresistant MTB （MDR-TB）, defined as being resistant to at least rifampicin （RMP） and isoniazid （1NH）,     

Structural Basis of Glycan Recognition in Globally Predominant Human P[8] Rotavirus

Rotavirus(RV)causes acute gastroenteritis in infants and children worldwide.Recent studies showed that glycans such as histo-blood group antigens(HBGAs)function as cell attachment factors affecting RV host susceptibility and prevalence.P[8]is the predominant RV genotype in humans,but the structural basis of how P[8]RVs interact with glycan ligands remains elusive.In this study,we characterized the interactions between P[8]VP8~*s and glycans which showed that VP8~*,the RV glycan binding domain,recognized both mucin core 2 and H type 1 antigens according to the ELISA-based oligosaccharide binding assays.Importantly,we determined the structural basis of P[8]RV-glycans interaction from the crystal structures of a Rotateq P[8]VP8~*in complex with core 2 and H type 1 glycans at 1.82.3 ?,respectively,revealing a common binding pocket and similar binding mode.Structural and sequence analysis demonstrated that the glycan binding site is conserved among RVs in the P[Ⅱ]genogroup,while genotype-specific amino acid variations determined different glycan binding preference.Our data elucidated the detailed structural basis of the interactions between human P[8]RVs and different host glycan factors,shedding light on RV infection,epidemiology,and development of anti-viral agents.     

Using the SELDI ProteinChip System to Detect Changes in Protein Expression in Vero Cells after Infection

Human herpes simplex virus 1 (HSV-l) causes facial, ocular, and encephalitic disease and is associated with latent infection and cancer. Here, we developed a means of studying the pathogenesis of HSV-l infection at the protein level by using the SELDI Protein Chip to detect changes of protein expression in Vero cells cultured in vitro. After infection with HSV-l and culture for 12, 24 or 48 h, cells were harvested and lysed. IMAC3 arrays were applied to SELDI-TOF-MS to detect proteomic differences before and after infection. The chip detected a series of differentially expressed protein peaks. Interestingly, both peaks at 16 912 Da and 17 581 Da corresponded precisely with the molecular mass of ISG 15, which may participate in antiviral activity during the process of infection. Thus, the results we obtained can serve as a basis to study the pathogenesis of HSV-1 and the interaction between the virus and its host. In addition, they can help in the discovery of new therapeutic targets for treatment of HSV-l infection.     

Dynamic changes of [Ca~(2 )]_i in cerebellar granule cells exposed to pulsed electric fields

Intracellular free Ca2 concentration ([Ca2 ]i) in embryonic chick cerebellar granule cells loaded with fluo-3/AM and exposed to a single pulsed electric field was investigated using a confocal laser scanning microscope and fluorescent microscope equipped with CCD video imaging system. The results showed that [Ca2 ]i increased immediately and rose to the peak rapidly as the cells exposed to a single pulsed electric field. The amplitude and rate of the increases of [Ca2 ]i depend on the intensity of external electric field. In the presence of Ca2 chelant EGTA or Ca2 channels blocker La3 in the pulsation solutions, the increase of [Ca2 ]i was still observable. It was also observed that [Ca2 ]i of different intracellular areas in the cell elevated simultaneously while the peak of the increase of [Ca2 ]i in the poles of the cell preceded to the peak in its somata and recovered to a plateau within a short time.     

Polyomavirus interaction with the DNA damage response

Viruses are obligate intracellular parasites that subvert cellular metabolism and pathways to mediate their own replication—normally at the expense of the host cell. Polyomaviruses are a group of small DNA viruses, which have long been studied as a model for eukaryotic DNA replication. Polyomaviruses manipulate host replication proteins, as well as proteins involved in DNA maintenance and repair, to serve as essential cofactors for productive infection. Moreover, evidence suggests that polyomavirus infection poses a unique genotoxic threat to the host cell. In response to any source of DNA damage, cells must initiate an effective DNA damage response(DDR) to maintain genomic integrity, wherein two protein kinases, ataxia telangiectasia mutated(ATM) and ATM- and Rad3-related(ATR), are major regulators of DNA damage recognition and repair. Recent investigation suggests that these essential DDR proteins are required for productive polyomavirus infection. This review will focus on polyomaviruses and their interaction with ATMand ATR-mediated DNA damage responses and the effect of this interaction on host genomic stability.     

Prokaryote phylogeny based on ribosomal proteins and aminoacyl tRNA synthetases by using the compositional distance approach

1 Introduction The systematics of prokaryotes has been a chal-lenge in microbiology as there are too few morpho-logical characteristics that can be used for classifica-tion[1]. A major breakthrough took place in the 1970s when Carl Woese[2] and coworkers aligned the small subunit ribosomal RNA (SSU rRNA) sequences to infer phylogenetic relations. The recognition of Ar-chaea as a third domain of life in addition to Bacteria and Eukarya and the support to the endosymbiotic origin of chlor…     

枯草芽孢杆菌BS2对葡萄灰霉病菌抑菌机制的初步探索

对葡萄灰霉病菌的生防枯草芽孢杆菌BS2菌液成分及胞外蛋白的抑菌机制进行了初步研究,BS2对葡萄灰霉病菌具有较好的拮抗作用,其菌液成分和胞外蛋白经20°C-120°C处理后,抑菌效果存在差异。BS2的菌液成分及胞外蛋白对灰霉病菌的产孢、萌发和菌丝的生长等方面均具有较好的抑制作用,且对灰霉病菌菌丝的原生质有囊泡和颗粒化现象。由此分析,BS2抑菌活性物质是多种成分共同作用的结果,抑菌物质中含有对温度敏感的高分子蛋白质,且抑菌机制也是从多方面共同起作用。     

木霉(Trichoderma spp.)对三种引起大棚蔬菜病害病原菌的影响

通过木霉属(Trichoderma) 3菌株与双鸭山蔬菜大棚中的黄瓜枯萎病菌(FusariumoxysporumSchlecht.f.cucumerinum)、黄瓜果腐病菌(PhytophthoracapsiciLeonian)、菜豆叶枯病菌(Cladosporiumsp .)的对峙培养试验,结果表明:绿色木霉1(TrichodermaviridePers.exGray 1)可作为双鸭山蔬菜大棚中的黄瓜枯萎病、黄瓜果腐病、菜豆叶枯病3种病害的生物防治拮抗菌加以利用,该拮抗菌对菜豆叶枯病菌抑制效果最好;绿色木霉2 (Tricho dermaviride 2 )对黄瓜果腐病菌抑制效果最好;而哈茨木霉(TrichodermaharzianumRifai)对以上3种病原菌都有抑制效果,对菜豆叶枯病菌抑制效果最好。从试验结果还可看出,绿色木霉2对黄瓜枯萎病菌和菜豆叶枯病菌的生长有促进作用。     

Phylogenetic diversity of bacterial endophytes of Panax notoginseng with antagonistic characteristics towards pathogens of root-rot disease complex

Endophytes play an important role in protection of host plants from infection by phytopathogens. Endophytic bacteria were isolated from five different parts (root, stem, petiole, leaf and seed) of Panax notoginseng and evaluated for antagonistic activity against Fusarium oxysporum, Ralstonia sp. and Meloidogyne hapla, three major pathogens associated with root-rot disease complex of P. notoginseng. From 1000 endophytic bacterial strains evaluated in vitro, 104 strains exhibited antagonistic properties against at least one of these three pathogens. Phylogenetic analyses of their 16S rRNA gene sequences showed that these 104 antagonistic bacteria belong to four clusters: Firmicutes, Proteobacteria, Actinobacteria and Bacteroidetes/Chlorobi. Members of the Firmicutes, in particular the Bacillus spp., were predominant in all analyzed tissues. The root was the main reservoir for antagonistic bacteria. Of the 104 antagonists, 51 strains showed antagonistic activities to one pathogen only, while 43 and 10 displayed the activities towards two and all three pathogens, respectively. The most dominant species in all tissues were Bacillus amyloliquefaciens subsp. plantarum and Bacillus methylotrophicus, which were represented by eight strains with broad antagonistic spectrum to the all three test pathogens of root-rot disease complex of P. notoginseng.     

An important role of a BAHD acyl transferase-like protein in plant innate immunity

Salicylic acid (SA) is an important regulator of plant resistance to biotrophic and hemi-biotrophic pathogens. The enhanced pseudomonas susceptibility 1 ( eps1 ) mutant in Arabidopsis thaliana is hypersusceptible to both virulent and avirulent strains of the bacterial pathogen Pseudomonas syringae . Through positional cloning, the EPS1 gene was isolated and found to encode a novel member of the BAHD acyltransferase superfamily. Pathogen-induced accumulation of SA and expression of pathogenesis-related ( PR ) genes were compromised in the eps1 mutant. SA could induce PR1 gene expression and restore disease resistance in the eps1 mutant. These results suggest that EPS1 functions upstream of SA and may be involved directly in synthesis of a precursor or a regulatory molecule for SA biosynthesis. Mutations of EPS1 or other genes important for SA accumulation or signaling conferred enhanced resistance to the necrotrophic fungal pathogens Botrytis cinerea and Alternaria brassicicola in the Nossen-0 background but had little effect in the Columbia-0 background. These results suggest that there is natural variation among Arabidopsis ecotypes with respect to the antagonistic cross-talk between defense signaling pathways against various types of microbial pathogens.     

中药源芽孢杆菌抗病原真菌菌株的筛选与鉴定

从20种中药中分离纯化得到48株芽孢杆菌,其中25株对10种植物病原菌中至少一种具有拮抗作用,7株抗菌谱较广,其中1株广谱抗菌能力极强。25株有抗性菌株经纯化培养对其进行菌体菌落形态观察和生理生化特征鉴定,其中8株芽孢杆菌被初步鉴定为枯草芽孢杆菌,3株被初步鉴定为蜡样芽孢杆菌,1株被初步鉴定为纳豆芽孢杆菌,1株被初步鉴定为地衣芽孢杆菌,发现两种可能对芽孢杆菌有抑制作用的中药。     

Isolation and characterization of protease overproducing mutants of Trichoderma harzianum

Several Trichoderma strains have been reported to be effective in controlling plant diseases, and the action of fungal hydrolytic enzymes is considered as the main mechanism involved in the antagonistic process. Strain Trichoderma harzianum T334 is a potential biocontrol agent against plant pathogenic fungi with the ability to produce low levels of proteases constitutively. To improve its fungal antagonistic capacity, mutagenetic program was undertaken for the construction of protease overproducing derivates. The mutant strains were obtained by means of UV-irradiation and were selected for p-fluorophenyl-alanine resistance or altered colony morphology. It was revealed by means of specific chromogenic protease substrates that both trypsin-like and chymotrypsin-like protease secretion was elevated in most of the mutant strains. The profiles of isoenzymes were different between the mutants and the wild-type strain, when examined by gel filtration chromatography. Certain mutants proved to be better antagonists against plant pathogens in in vitro antagonism experiments. This study suggests the possibility of using mutants with improved constitutive extracellular protease secretion against plant pathogenic fungi.     

Diversity and antagonistic potential of bacteria associated with bryophytes from nutrient-poor habitats of the Baltic Sea Coast

Very little is known about the interaction of bryophytes with bacteria. Therefore, we analyzed bacteria associated with three bryophyte species, Tortula ruralis, Aulacomnium palustre, and Sphagnum rubellum, which represent typical moss species of three nutrient-poor plant communities at the southern Baltic Sea coast in Germany. By use of two cultivation-independent techniques, denaturing gradient gel electrophoresis and single-strand conformation polymorphism analysis of the 16S ribosomal DNA, a high degree of moss specificity was found for associated bacterial communities. This specificity could be further evidenced by a cultivation-dependent approach for the following parameters: (i) plate counts of bacteria on R2A medium, (ii) proportion of antagonistic isolates, (iii) antagonistic activity as well as spectrum against pathogens, and (iv) diversity and richness of antagonistic isolates. The proportion of isolates with antagonistic activity against the pathogenic model fungus Verticillium dahliae was highest for S. rubellum (31%), followed by A. palustre (17%) and T. ruralis (5%). A high percentage (99%) of moss-associated antagonistic bacteria produced antifungal compounds. The high recovery of antagonistic isolates strongly suggests that bryophytes represent an ecological niche which harbors a diverse and hitherto largely uncharacterized microbial population with yet unknown and untapped potential biotechnological applications, e.g., for biological control of plant pathogens.     

Modulation of anti-pathogenic activity in canine-derived Lactobacillus species by carbohydrate growth substrate

AIMS: To investigate the effect of various carbon sources on the production of extracellular antagonistic compounds against two Escherichia coli strains and Salmonella enterica serotype Typhimurium by three canine-derived lactobacilli strains. METHODS AND MATERIALS: Cell-free preparations, pH neutralized, were used in antibiotic disc experiments as an initial screening. The bacteria/carbohydrate combinations that showed inhibition of the growth of those pathogens, were further investigated in batch co-culture experiments. The cell-free supernatants of the cultures, that decreased the population number of the pathogens in the co-culture experiments to log CFU ml-1 相似文献   

Expression of a small RNA, BS203 RNA, from the yocI-yocJ intergenic region of Bacillus subtilis genome

We isolated and characterized a novel small RNA from Bacillus subtilis. We termed this molecule BS203 RNA from the length of its mature form (203 nt) and located the corresponding gene at the yocI-yocJ intergenic region on the B. subtilis genome. Northern blotting revealed that it is transcribed in vegetative growing cells and that the amount of BS203 RNA decreased in the middle of the vegetative phase. A computer-aided prediction of the BS203 RNA secondary structure revealed three characteristic stem-loop structures. Despite active expression during the vegetative phase, growth of the knockout mutant was not affected by depletion of BS203 RNA. A phylogenetic comparison of the sequence of the BS203 RNA with other Bacillus species including B. cereus and B. halodurans C-125, or Clostridium perfringens suggests that the sequence is unique to Bacillus subtilis.