Synthetic genomics: potential and limitations

Technologies to synthetically assemble chromosome sized fragments of DNA as well as to enable making thousands of simultaneous changes to existing genomes are now available. These capacities are collectively termed synthetic genomics. The implications of synthetic genomics extend beyond the limited pathway and gene engineering of the past to include the engineering or whole metabolisms, regulatory networks, and even ecosystems. However, in order for those potentials to be met, certain limitations and barriers must be overcome. These barriers no longer include DNA modification and assembly, but instead are based in the limited organisms that many synthetic genomics methods function in, and the limited software for designing custom genomic sequences.     

The potential of nucleic acid repair in functional genomics

Chimeric RNA/DNA oligonucleotides have been used successfully to correct point and frameshift mutations in cells as well as in animal and plant models. This approach is one of several nucleic acid repair technologies that will help elucidate the function of newly discovered genes. Understanding the mechanisms by which these different technologies direct gene alteration is essential for progress in their application to functional genomics.     

Role of genomics in the potential restoration of the American chestnut

The development of genomic tools will enhance traditional tree breeding technologies leading to more certain and timely recovery of the American chestnut, a keystone heritage tree of the eastern United States. Major efforts are being made in gene discovery, genetic marker development, construction of a BAC-based physical map, and DNA transformation technology. A strategy of map-based cloning, association genetics, and genetic engineering, combined with traditional and marker-assisted backcross breeding is proposed for the long-term genetic restoration of this iconic tree species.     

Exploration of antimicrobial and antioxidant potential of newly synthesized 2,3-disubstituted quinazoline-4(3H)-ones

A series of 2-(chloromethyl)-3-(4-methyl-6-oxo-5-[(E)-phenyldiazenyl]-2-thioxo-5,6-dihydropyrimidine-1(2H)-yl)quinazoline-4(3H)-ones 9a-j was synthesized by treating 2-(chloroacetyl)amino benzoic acid with 3-amino-6-methyl-5-[(E)-phenyldiazenyl]-2-thioxo-2,5-dihydropyrimidine-4(3H)-one 8a-j and was screened for in vitro antibacterial activities against a representative panel of Gram-positive and Gram-negative bacteria. The compounds were synthesized in excellent yields and the structures were corroborated on the basis of IR, ¹H NMR, Mass and elemental analysis data. All the synthesized compounds elicited the potent inhibitory action against all the tested bacterial stains. Furthermore, in order to explore the antioxidant potential of newly synthesized compounds, the free radical scavenging activity measurement were performed by the 1,1-diphenyl-2-picryl-hydrazyl (DPPH) assay method. It is revealed from the antioxidant screening results that the compounds 9c and f manifested profound antioxidant potential.     

Biotechnological potential of antimicrobial peptides from flowers

Flowers represent a relatively unexplored source of antimicrobial peptides of biotechnological potential. This review focuses on flower-derived defense peptide classes with inhibitory activity towards plant pathogens. Small cationic peptides display diverse activities, including inhibition of digestive enzymes and bacterial and/or fungal inhibition. Considerable research is ongoing in this area, with natural crop plant defense potentially improved through the application of transgenic technologies. In this report, comparisons were made of peptide tertiary structures isolated from diverse flower species. A summary is provided of molecular interactions between flower peptides and pathogens, which include the role of membrane proteins and lipids. Research on these peptides is contributing to our understanding of pathogen resistance mechanisms, which will, given the perspectives for plant genetic modification, contribute long term to plant genetic improvement for increased resistance to diverse pathogens.     

Seeing is believing: the impact of structural genomics on antimicrobial drug discovery

Over the past decade, the availability of complete microbial genome sequences has led to changes in the strategies that are used to search for novel anti-infectives. However, despite the identification of many new potential drug targets, novel antimicrobial agents have been slow to emerge from these efforts. In part, this reflects the long discovery and development times that are needed to bring new drugs to market and the bottlenecks at the stages of identifying good lead compounds and optimizing these leads into drug candidates. Structural genomics will hopefully provide opportunities to overcome these bottlenecks and populate the antimicrobial pipeline.     

Recent progress in livestock genomics and potential impact on breeding programs

Most of the major livestock breeding organizations in the world are actively involved in using the emerging tools for genome analysis to obtain a better understanding of the molecular architecture of their favourite production traits. This is bound to generate a considerable amount of novel biological information that will provide a competitive advantage to those that have access to it. At present, the preferred avenue to exploit this information is via marker-assisted selection (MAS), and several breeding organisations are starting to implement MAS in breeding programs. However, it seems unlikely that the exploitation of genomics information will be limited to MAS in the future. Even though it is difficult to anticipate the ultimate impact of genomics on animal production, it would be very surprising if it were not to revolutionize this industry as it is already revolutionizing the biomedical and plant breeding industries.     

Gene expression-based chemical genomics identifies potential therapeutic drugs in hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is an aggressive tumor with a poor prognosis. Currently, only sorafenib is approved by the FDA for advanced HCC treatment; therefore, there is an urgent need to discover candidate therapeutic drugs for HCC. We hypothesized that if a drug signature could reverse, at least in part, the gene expression signature of HCC, it might have the potential to inhibit HCC-related pathways and thereby treat HCC. To test this hypothesis, we first built an integrative platform, the "Encyclopedia of Hepatocellular Carcinoma genes Online 2", dubbed EHCO2, to systematically collect, organize and compare the publicly available data from HCC studies. The resulting collection includes a total of 4,020 genes. To systematically query the Connectivity Map (CMap), which includes 6,100 drug-mediated expression profiles, we further designed various gene signature selection and enrichment methods, including a randomization technique, majority vote, and clique analysis. Subsequently, 28 out of 50 prioritized drugs, including tanespimycin, trichostatin A, thioguanosine, and several anti-psychotic drugs with anti-tumor activities, were validated via MTT cell viability assays and clonogenic assays in HCC cell lines. To accelerate their future clinical use, possibly through drug-repurposing, we selected two well-established drugs to test in mice, chlorpromazine and trifluoperazine. Both drugs inhibited orthotopic liver tumor growth. In conclusion, we successfully discovered and validated existing drugs for potential HCC therapeutic use with the pipeline of Connectivity Map analysis and lab verification, thereby suggesting the usefulness of this procedure to accelerate drug repurposing for HCC treatment.     

多肽配体技术在植物功能基因组学中的应用前景

人工智能配体或适配体(Aptamer)技术是近年来兴起的一项特异性极强的基因干扰技术。通过人工合成特异的智能配体结合靶基因的蛋白产物, 达到特异干扰靶基因的生物学功能, 这是人工智能配体技术的基本设想。文章综述了多肽配体(Peptide aptamer)技术在基因功能验证中的主要进展, 着重阐明它在植物基因功能验证和作物抗病毒育种中的应用前景, 并提出克服该技术主要风险对策。     

Evaluation of the antimicrobial potential of immune sera

The inhibiting activity of blood sera obtained from 20 volunteers immunized with the multi-component vaccine "PYOPOL", 25 nonimmune donors and 7 lots of human antistaphylococcal immunoglobulin with respect to Staphylococcus aureus, Escherichia coli, Proteus vulgaris and Pseudomonas aeruginosa has been studied in the liquid nutrient medium with the use an automated microbiological analyzer. The sera of donors immunized with the vaccine "PYOPOL" have been found to possess high antimicrobial activity, comparable with the definite concentration of the antiseptic agent "Myramistin". The proposed method may be recommended for the evaluation of the bacteriostatic activity of different immuno- biological preparations.     

用非常规培养方法提高乳酸菌产酸率的研究

以德氏乳酸杆菌为研究对象,考察了八种有机溶剂分别加入培养基对细菌生长及产酸的影响。结果表明,采用油醇和三辛胺混合溶剂时,既能降低对细胞生长的毒性,又保持了较强的萃取能力。对悬浮细胞发酵和萃取整合的方法和固定化细胞发酵和萃取整合的方法进行了比较,表明这两种方法均较常规培养方法提高乳酸产率60％以上。     

Peptidomics and genomics analysis of novel antimicrobial peptides from the frog,Rana nigrovittata

Much attention has been paid on amphibian peptides for their wide-ranging pharmacological properties, clinical potential, and gene-encoded origin. More than 300 antimicrobial peptides (AMPs) from amphibians have been studied. Peptidomics and genomics analysis combined with functional test including microorganism killing, histamine-releasing, and mast cell degranulation was used to investigate antimicrobial peptide diversity. Thirty-four novel AMPs from skin secretions of Rana nigrovittata were identified in current work, and they belong to 9 families, including 6 novel families. Other three families are classified into rugosin, gaegurin, and temporin family of amphibian AMP, respectively. These AMPs share highly conserved preproregions including signal peptides and spacer acidic peptides, while greatly diversified on mature peptides structures. In this work, peptidomics combined with genomics analysis was confirmed to be an effective way to identify amphibian AMPs, especially novel families. Some AMPs reported here will provide leading molecules for designing novel antimicrobial agents.     

New chitosan derivatives with potential antimicrobial activity

A series of four water-soluble chitosan derivatives differing in molecular mass, hydrophobicity, and charge was synthesized and tested for the intensity of their effects on Gram-negative and Gram-positive bacteria. It was shown that the tested compounds allowed the penetration of ethidium bromide into the bacteria, which showed increased permeability of their cell walls under the effect of chitosans. The tolerance to various chitosan derivatives differed in Gram-negative and Gram-positive bacteria. The Gram-negative bacteria were the most responsive to high-molecular chitosan and the Gram-positive ones, to N-,O-carboxypropylchitosan, whereas high-molecular chitosan had little effect. Research on the correlation between the structure and activity of the studied compounds revealed that depolymerization of chitosan reduced, and introduction of hydrophobic substantives in chitosan molecule significantly enhanced its permeability effect on bacterial cell walls. The obtained results provide a basis for the construction of new chitosan derivatives with antimicrobial activities.     

Next-generation sequencing and its potential impact on food microbial genomics

Recent efforts of researchers to elucidate the molecular mechanisms of biological systems have been revolutionized greatly with the use of high throughput and cost-effective techniques such as next generation sequencing (NGS). Application of NGS to microbial genomics is not just limited to predict the prevalence of microorganisms in food samples but also to elucidate the molecular basis of how microorganisms respond to different food-associated conditions, which in turn offers tremendous opportunities to predict and control the growth and survival of desirable or undesirable microorganisms in food. Concurrently, NGS has facilitated the development of new genome-assisted approaches for correlating genotype and phenotype. The aim of this review is to provide a snapshot of the various possibilities that these new technologies are opening up in area of food microbiology, focusing the discussion mainly on lactic acid bacteria and yeasts associated with fermented food. The contribution of NGS to a system level understanding of food microorganisms is also discussed.     

Exploring potential risk factors of antimicrobial use in beef cattle

Livestock species are major contributors to the increase of antimicrobial (AM) resistance which is a worldwide concern for both human and animal health. The over-use of AM is widely acknowledged, however, unlike pigs, poultry and dairy cattle, knowledge on potential risk factors affecting AM usage (AMU) in beef industry is limited. Hence, this study aimed to investigate the impact of farm, breed, sex and season of arrival of purchased beef cattle on AMU in Italian beef cattle. Data on 1 063 batches were collected from January 2016 to April 2019 from specialised beef fattening farms located in the north of Italy. Information on breed, sex, date of arrival, performance traits and AM agents used on farm was collected, and the treatment incidence 100 (TI100) indexes per batch were calculated using the defined daily dose animal estimated according to Italian summaries of product characteristics. Factors affecting TI100 indexes were investigated using a cross-classified multilevel model. Farms largely differed in terms of AMU. Males had greater AMU than females (P < 0.001), likely due to their higher susceptibility to disease. Statistically significant differences were observed between seasons of arrival with summer and spring having lower TI100 indexes than winter and autumn (P < 0.001). Indeed, winter is commonly linked to an increase in respiratory diseases in beef cattle. Finally, the TI100it indexes tended to be different among breeds with Blonde d'Aquitaine and Limousine having greater AMU compared to the other breeds. Results of this study provided valuable information on potential risk factors of AMU in beef production which may be useful to address its reduction. For instance, the development of tailored management strategies for specific breeds, targeted approaches to improve the health of males as well as greater care towards batches purchased in winter are possible advice to implement on-farm for a more responsible AM stewardship.