Advances in Basic Theory Research of Mongolian Medicine and Prospects of Its Combination with Systems Biology Research

This paper sorted out the relevant literature on the basic theory of Mongolian medicine,explored the research methods and ideas of the basic theory of Mongolian medicine,and elaborated the idea of combining systems biology to study part of the basic theory of Mongolian medicine.Through searching classic works and research papers in academic journals,this paper sorted out and summarized the research progress of the basic theory of Mongolian medicine and the existing problems in the current research,analyzed its characteristics,combined with systems biology methods to systematically explain some content in the basic theory,reveal its scientific connotation,and provide a basis for further research.

新加坡生物学主流教材习题的特征探析及启示--以《Biology Matters》为例

以新加坡Biology Matters生物学教材习题为研究对象,分析得出其具有“绘图作答,提高学生形象思维能力”,“情境多样,注重学生对现象的解释”,“联系生活,强调知识解决实际问题”,“探讨伦理,引导学生承担社会责任”“分层设问,培养学生思维的逻辑性”等特征,希望对我国生物学测评试题的命制具有一定的启示意义。

Systems biology unravels interferon responses to respiratory virus infections

Interferon production is an important defence against viral replication and its activation is an attractive therapeutic target. However, it has long been known that viruses perpetually evolve a multitude of strategies to evade these host immune responses. In recent years there has been an explosion of information on virusinduced alterations of the host immune response that have resulted from data-rich omics technologies. Unravelling how these systems interact and determining the overall outcome of the host response to viral infection will play an important role in future treatment and vaccine development. In this review we focus primarily on the interferon pathway and its regulation as well as mechanisms by which respiratory RNA viruses interfere with its signalling capacity.

Omics Studies and Systems Biology Perspective towards Abiotic Stress Response in Plants

Plant abiotic stress responses are vital yield-restricting aspect in agriculture. Recent technology in plant biology allows research of such stress responses at a molecular scale in plants. Network analysis provides in-depth knowledge regarding omics information visualisation as it reduces the intrinsic intricacy of such data. The use of integrated functional genomics helps to understand the relationship between the genomic profile and the phenotypic profile in different environmental conditions of an organism. Plants’ responses to abiotic stress are often considered as a complex process. Systems biology approaches allow visualising and understanding how plant life works to overcome abiotic stress. The combination of integrated functional genomics along with bioinformatics will put a hand in additional in-depth research knowledge on stress tolerance to plants by exploiting available genetic information and continuously improving techniques and strategies. Most of the omics technologies are high throughput with very rapid data generation rates and humongous outputs. These technologies have made noticeable contributions to the modern-day improvements in our knowledge of plant biology. So, in this review, omics studies and the system biology approach towards abiotic stress tolerance in plants are highlighted.

Engineering DNA Materials for Sustainable Data Storage Using a DNA Movable-Type System

DNA molecules are green materials with great potential for high-density and long-term data storage.However,the current data-writing process of DNA data storage via DNA synthesis suffers from high costs and the production of hazards,limiting its practical applications.Here,we developed a DNA movable-type storage system that can utilize DNA fragments pre-produced by cell factories for data writing.In this system,these pre-generated DNA fragments,referred to herein as“DNA movable types,”are used as basic writing units in a repetitive way.The process of data writing is achieved by the rapid assembly of these DNA movable types,thereby avoiding the costly and environmentally hazardous process of de novo DNA synthesis.With this system,we successfully encoded 24 bytes of digital information in DNA and read it back accurately by means of high-throughput sequencing and decoding,thereby demonstrating the feasibility of this system.Through its repetitive usage and biological assembly of DNA movable-type fragments,this system exhibits excellent potential for writing cost reduction,opening up a novel route toward an economical and sustainable digital data-storage technology.

Comparative systems biology between human and animal models based on next-generation sequencing methods

Animal models provide myriad benefits to both experimental and clinical research.Unfortunately,in many situations,they fall short of expected results or provide contradictory results.In part,this can be the result of traditional molecular biological approaches that are relatively inefficient in elucidating underlying molecular mechanism.To improve the efficacy of animal models,a technological breakthrough is required.The growing availability and application of the high-throughput methods make systematic comparisons between human and animal models easier to perform.In the present study,we introduce the concept of the comparative systems biology,which we define as“comparisons of biological systems in different states or species used to achieve an integrated understanding of life forms with all their characteristic complexity of interactions at multiple levels”.Furthermore,we discuss the applications of RNA-seq and ChIP-seq technologies to comparative systems biology between human and animal models and assess the potential applications for this approach in the future studies.

Insights into the structural biology of G-protein coupled receptors impacts drug design for central nervous system neurodegenerative processes

In the last few years, there have been important new insights into the structural biology of G-protein coupled receptors. It is now known that allosteric binding sites are involved in the affinity and selec- tivity of ligands for G-protein coupled receptors, and that signaling by these receptors involves both G-protein dependent and independent pathways. The present review outlines the physiological and pharmacological implications of this perspective for the design of new drugs to treat disorders of the central nervous system. Specifically, new possibilities are explored in relation to allosteric and or- thosteric binding sites on dopamine receptors for the treatment of Parkinson＇s disease, and on muscarinic receptors for Alzheimer＇s disease. Future research can seek to identify ligands that can bind to more than one site on the same receptor, or simultaneously bind to two receptors and form a dimer. For example, the design of bivalent drugs that can reach homo/hetero-dimers of D2 dopa- mine receptor holds promise as a relevant therapeutic strategy for Parkinson＇s disease. Regarding the treatment of Alzheimer＇s disease, the design of dualsteric ligands for mono-oligomeric mus- carinic receptors could increase therapeutic effectiveness by generating potent compounds that could activate more than one signaling pathway.

Developmental systems biology flourishing on new technologies

Organism development is a systems level process. It has benefited greatly from the recent technological advances in the field of systems biology. DNA microarray, phenome, interactome and transcriptome mapping, the new generation of deep sequencing technologies, and faster and better computational and modeling approaches have opened new frontiers for both systems biologists and developmental biologists to reexamine the old developmental biology questions, such as pattern formation, and to tackle new problems, such as stem cell reprogramming. As showcased in the International Developmental Systems Biology Symposium organized by Chinese Academy of Sciences, developmental systems biology is flourishing in many perspectives, from the evolution of developmental systems, to the underlying genetic and molecular pathways and networks, to the genomic, epigenomic and noncoding levels, to the computational analysis and modeling. We believe that the field will continue to reap rewards into the future with these new approaches.

Systems biology applications to study mechanisms of human immunodeficiency virus latency and reactivation

Eradication of human immunodeficiency virus(HIV) in infected individuals is currently not possible because of the presence of the persistent cellular reservoir of latent infection. The identification of HIV latency biomarkers and a better understanding of the molecular mechanisms contributing to regulation of HIV expression might provide essential tools to eliminate these latently infected cells. This review aims at summarizing gene expression profiling and systems biology applications to studies of HIV latency and eradication. Studies comparing gene expression in latently infected and uninfected cells identify candidate latency biomarkers and novel mechanisms of latency control. Studies that profiled gene expression changes induced by existing latency reversing agents(LRAs) highlight uniting themes driving HIV reactivation and novel mechanisms that contribute to regulation of HIV expression by different LRAs. Among the reviewed gene expression studies, the common approaches included identification of differentially expressed genes and gene functional category assessment. Integration of transcriptomic data with other biological data types is presently scarce, and the field would benefit from increased adoption of these methods in future studies. In addition, designing prospective studies that use the same methods of data acquisition and statistical analyses will facilitate a more reliableidentification of latency biomarkers using different model systems and the comparison of the effects of different LRAs on host factors with a role in HIV reactivation. The results from such studies would have the potential to significantly impact the process by which candidate drugs are selected and combined for future evaluations and advancement to clinical trials.

Do GMOs Accumulate Formaldehyde and Disrupt Molecular Systems Equilibria? Systems Biology May Provide Answers

Safety assessment of genetically modified organisms (GMOs) is a contentious topic. Proponents of GMOs assert that GMOs are safe since the FDA’s policy of substantial equivalence considers GMOs “equivalent” to their non-GMO counterparts, and argue that genetic modification (GM) is simply an extension of a “natural” process of plant breeding, a form of “genetic modification”, though done over longer time scales. Anti-GMO activists counter that GMOs are unsafe since substantial equivalence is unscientific and outdated since it originates in the 1970s to assess safety of medical devices, which are not comparable to the complexity of biological systems, and contend that targeted GM is not plant breeding. The heart of the debate appears to be on the methodology used to determine criteria for substantial equivalence. Systems biology, which aims to understand complexity of the whole organism, as a system, rather than just studying its parts in a reductionist manner, may provide a framework to determine appropriate criteria, as it recognizes that GM, small or large, may affect emergent properties of the whole system. Herein, a promising computational systems biology method couples known perturbations on five biomolecules caused by the CP4 EPSPS GM of Glycine max L. (soybean), with an integrative model of C1 metabolism and oxidative stress (two molecular systems critical to plant function). The results predict significant accumulation of formaldehyde and concomitant depletion of glutathione in the GMO, suggesting how a “small” and single GM creates “large” and systemic perturbations to molecular systems equilibria. Regulatory agencies, currently reviewing rules for GMO safety, may wish to adopt a systems biology approach using a combination of in silico, computational methods used herein, and subsequent targeted experimental in vitro and in vivo designs, to develop a systems understanding of “equivalence” using biomarkers, such as formaldehyde and glutathione, which predict metabolic disruptions, towards modernizing the safety assessment of GMOs.

In-Silico Analysis &In-Vivo Results Concur on Glutathione Depletion in Glyphosate Resistant GMO Soy, Advancing a Systems Biology Framework for Safety Assessment of GMOs

This study advances previous efforts towards development of computational systems biology, in silico, methods for biosafety assessment of genetically modified organisms (GMOs). C1 metabolism is a critical molecular system in plants, fungi, and bacteria. In our previous research, critical molecular systems of C1 metabolism were identified and modeled using CytoSolve?, a platform for in silico analysis. In addition, multiple exogenous molecular systems affecting C1 metabolism such as oxidative stress, shikimic acid metabolism, glutathione biosynthesis, etc. were identified. Subsequent research expanded the C1 metabolism computational models to integrate oxidative stress, suggesting glutathione (GSH) depletion. Recent integration of data from the EPSPS genetic modification of Soy, also known as Roundup Ready Soy (RRS), with C1 metabolism predicts similar GSH depletion and HCHO accumulation in RRS. The research herein incorporates molecular systems of glutathione biosynthesis and glyphosate catabolism to expand the extant in silico models of C1 metabolism. The in silico results predict that Organic Soy will have a nearly 250% greater ratio of GSH and GSSG, a measure of glutathione levels, than in RRS that are glyphosate-treated glyphosate-resistant Soy versus the Organic Soy. These predictions also concur with in vivo greenhouse results. This concurrence suggests that these in silico models of C1 metabolism may provide a viable and validated platform for biosafety assessment of GMOs, and aid in selecting rational criteria for informing in vitro and in vivo efforts to more accurately decide in the problem formulation phase whose parameters need to be assessed so that conclusion on “substantial equivalence” or material difference of a GMO and its non-GMO counterpart can be drawn on a well-grounded basis.

An Effective Numerical Calculation Method for Multi-Time-Scale Mathematical Models in Systems Biology

The improvements of high-throughput experimental devices such as microarray and mass spectrometry have allowed an effective acquisition of biological comprehensive data which include genome, transcriptome, proteome, and metabolome (multi-layered omics data). In Systems Biology, we try to elucidate various dynamical characteristics of biological functions with applying the omics data to detailed mathematical model based on the central dogma. However, such mathematical models possess multi-time-scale properties which are often accompanied by time-scale differences seen among biological layers. The differences cause time stiff problem, and have a grave influence on numerical calculation stability. In the present conventional method, the time stiff problem remained because the calculation of all layers was implemented by adaptive time step sizes of the smallest time-scale layer to ensure stability and maintain calculation accuracy. In this paper, we designed and developed an effective numerical calculation method to improve the time stiff problem. This method consisted of ahead, backward, and cumulative algorithms. Both ahead and cumulative algorithms enhanced calculation efficiency of numerical calculations via adjustments of step sizes of each layer, and reduced the number of numerical calculations required for multi-time-scale models with the time stiff problem. Backward algorithm ensured calculation accuracy in the multi-time-scale models. In case studies which were focused on three layers system with 60 times difference in time-scale order in between layers, a proposed method had almost the same calculation accuracy compared with the conventional method in spite of a reduction of the total amount of the number of numerical calculations. Accordingly, the proposed method is useful in a numerical analysis of multi-time-scale models with time stiff problem.

Systems Biology: The take, input, vision, concerns and hopes

Systems Biology is a relatively new branch of biology that brings together an interdisciplinary team of scientist, computer engineers and mathematicians. Biomedicine can gain much from the input of Systems Biology. The object and aims of this article centre on clarification and direction for Systems Biology, notably in regard to human health and disease.

Current advances of biocontainment strategy in synthetic biology

Synthetic biotechnology has led to the widespread application of genetically modified organisms(GMOs)in biochemistry, bioenergy, and therapy. However, the uncontrolled spread of GMOs may lead to genetic contamination by horizontal gene transfer, resulting in unpredictable biosafety risks. To deal with these challenges, many effective methods have been developed for biocontainment. In this article, we summarize and discuss recent advances in biocontainment strategies from three aspects: DNA replication, transcriptional regulation, and protein translation. We also briefly introduce the efforts in the biocontainment convention, such as the recent publication of the Tianjin Biosecurity Guidelines for the Code of Conduct for Scientists.

Network biology:A promising approach for drug target identification against neurodevelopmental disorders

Biological entities are involved in complicated and complex connections;hence,discovering biological information using network biology ideas is critical.In the past few years,network biology has emerged as an integrative and systems-level approach for understanding and interpreting these complex interactions.Biological network analysis is one method for reducing enormous data sets to clinically useful knowledge for disease diagnosis,prognosis,and treatment.The network of biological entities can help us predict drug targets for several diseases.The drug targets identified through the systems biology approach help in targeting the essential biological pathways that contribute to the progression and development of the disease.The novel strategical approach of system biologyassisted pharmacology coupled with computer-aided drug discovery(CADD)can help drugs fight multifactorial diseases efficiently.In the present review,we have summarized the role and application of network biology for not only unfolding the mechanism of complex neurodevelopmental disorders but also identifying important drug targets for diseases like ADHD,Autism,Epilepsy,and Intellectual Disability.Systems biology has emerged as a promising approach to identifying drug targets and aiming for targeted drug discovery for the precise treatment of neurodevelopmental disorders.

Pollination Biology of the Endangered Herbal Medicines Dendrobium chrysotoxum(Orchidaceae)

Pollination biology studies of the endangered herbal medicines Dendrobium chrysotoxum were conducted in natural pollination conditions using flower observation,pollinator observation and artificial pollination experiments.Populations of D.chrysotoxum with fragrance and nectar were pollinated by Ctenoplectra davidi Valhalla(Hymenoptera:Apidae)species.The floral structure of D.chrysotoxum adapted precisely to its pollinators.Flowers had a low capsule setting(0.17%)under natural conditions.However,compared to open pollination,artificial pollination experiments showed a significant increase in capsule setting,and D.chrysotoxum was cross-compatible and self-compatible,but there was pollinator limitation also.This study will provide important information for the preservation of this endangered species.

Isolation and characterization ofβ-transducin repeat-containing protein ligands screened using a high-throughput screening system

β-transducin repeat-containing protein(β-TrCP)is an F-box protein subunit of the E3 Skp1-Cullin-F box(SCF)type ubiquitin-ligase complex,and provides the substrate specificity for the ligase.To find potent ligands ofβ-TrCP useful for the proteolysis targeting chimera(PROTAC)system usingβ-TrCP in the future,we developed a high-throughput screening system for small moleculeβ-TrCP ligands.We screened the chemical library utilizing the system and obtained several hit compounds.The effects of the hit compounds on in vitro ubiquitination activity of SCFβ-TrCP1 and on downstream signaling pathways were examined.Hit compounds NPD5943,NPL62020-01,and NPL42040-01 inhibited the TNFα-induced degradation of IκBαand its phosphorylated form.Hence,they inhibited the activation of the transcription activity of NF-κB,indicating the effective inhibition ofβ-TrCP by the hit compounds in cells.Next,we performed an in silico analysis of the hit compounds to determine the important moieties of the hit compounds.Carboxyl groups of NPL62020-01 and NPL42040-01 and hydroxyl groups of NPD5943 created hydrogen bonds withβ-TrCP similar to those created by intrinsic target phosphopeptides ofβ-TrCP.Our findings enhance our knowledge of useful small molecule ligands ofβ-TrCP and the importance of residues that can be ligands ofβ-TrCP.

Application of Molecular Biology Technology in Identification of Modern Mongolian Medicine

The application of molecular biology technology in the identification and quality control of Mongolian medicine is increasing gradually,and it provides a new method for identifying fake and inferior products and confused products of Mongolian medicine.In this paper,the application and prospect of molecular biology technology(such as DNA barcoding and PCR molecular identification technique)in the identification of crude Mongolian medicine were reviewed.