What have we learned about the kallikrein-kinin and renin-angiotensin systems in neurological disorders?

The kallikrein-kinin system(KKS) is an intricate endogenous pathway involved in several physiological and pathological cascades in the brain. Due to the pathological effects of kinins in blood vessels and tissues, their formation and degradation are tightly controlled. Their components have been related to several central nervous system diseases such as stroke, Alzheimer's disease, Parkinson's disease, multiple sclerosis, epilepsy and others. Bradykinin and its receptors(B1R and B2R) may have a role in the pathophysiology of certain central nervous system diseases. It has been suggested that kinin B1R is up-regulated in pathological conditions and has a neurodegenerative pattern, while kinin B2R is constitutive and can act as a neuroprotective factor in many neurological conditions. The renin angiotensin system(RAS) is an important blood pressure regulator and controls both sodium and water intake. AngⅡ is a potent vasoconstrictor molecule and angiotensin converting enzyme is the major enzyme responsible for its release. AngⅡ acts mainly on the AT1 receptor, with involvement in several systemic and neurological disorders. Brain RAS has been associated with physiological pathways, but is also associated with brain disorders. This review describes topics relating to the involvement of both systems in several forms of brain dysfunction and indicates components of the KKS and RAS that have been used as targets in several pharmacological approaches.     

Systematic genome editing of the genes spanning an entire chromosome by CRISPR/Cas9 in a vertebrate——zebrafish (Danio rerio)

正Deciphering the biological functions of each gene in the genome is fundamental for understanding the molecular mechanisms underlying normal development, physiology,and behavior, as well as diseases. One common approach to determine gene function is to disrupt individual genes and assess the consequences. Zebrafish (Danio rerio) has been gaining popularity as a model organism to analyze gene function. This is particularly true in China, as the number of     

Nitrogen in global animal production and management options for improving nitrogen use efficiency

Animal production systems convert plant protein into animal protein. Depending on animal species, ration and management, between 5% and 45 % of the nitrogen (N) in plant protein is converted to and deposited in animal protein. The other 55%-95% is excreted via urine and feces, and can be used as nutrient source for plant (= often animal feed) production. The estimated global amount of N voided by animals ranges between 80 and 130 Tg N per year, and is as large as or larger than the global annual N fertilizer consumption. Cattle (60%), sheep (12%) and pigs (6%) have the largest share in animal manure N production. The conversion of plant N into animal N is on average more efficient in poultry and pork production than in dairy production, which is higher than in beef and sheep production. However, differences within a type of animal production system can be as large as differences between types of animal production systems, due to large effects of the genetic potential of animals, animal feed and management. The management of animals and animal feed, together with the genetic potential of the animals, are key factors to a high efficiency of conversion of plant protein into animal protein. The efficiency of the conversion of N from animal manure, following application to land, into plant protein ranges between 0 and 60%, while the estimated global mean is about 15%. The other 40%-100% is lost to the wider environment via NH3 volatilization, denitrification, leaching and run-off in pastures or during storage and/or following application of the animal manure to land. On a global scale, only 40%-50% of the amount of N voided is collected in barns, stables and paddocks, and only half of this amount is recycled to crop land. The N losses from animal manure collected in barns, stables and paddocks depend on the animal manure management system. Relative large losses occur in confined animal feeding operations, as these often lack the land base to utilize the N from animal manure effectively. Losses will be relatively low when all manure are collected rapidly in water-tight and covered basins, and when they are subsequently applied to the land in proper amounts and at the proper time, and using the proper method (low-emission techniques). There is opportunity for improving the N conversion in animal production systems by improving the genetic production potential of the herd, the composition of the animal feed, and the management of the animal manure. Coupling of crop and animal production systems, at least at a regional scale, is one way to high N use efficiency in the whole system. Clustering of confined animal production systems with other intensive agricultural production systems on the basis of concepts from industrial ecology with manure processing is another possible way to improve N use efficiency.     

COP9 signalosome: Discovery,conservation, activity,and function

The COP9 signalosome(CSN)is a conserved protein complex,typically composed of eight subunits(designated as CSN1 to CSN8)in higher eukaryotes such as plants and animals,but of fewer subunits in some lower eukaryotes such as yeasts.The CSN complex is originally identified in plants from a genetic screen for mutants that mimic light-induced photomorphogenic development when grown in the dark.The CSN complex regulates the activity of cullin-RING ligase(CRL)families of E3 ubiquitin ligase complexes,and play critical roles in regulating gene expression,cell proliferation,and cell cycle.This review aims to summarize the discovery,composition,structure,and function of CSN in the regulation of plant development in response to external(light and temperature)and internal cues(phytohormones).     

Detection of clustered DNA lesions: Biological and clinical applications

Humans are daily exposed to background radiation and various sources of oxidative stress. My research has focused in the last 12 years on the effects of ionizing radiation on DNA, which is considered as the key target of radiation in the cell. Ionizing radiation and endogenous cellular oxidative stress can also induce closely spaced oxidatively induced DNA lesions called "clusters" of DNA damage or locally multiply damage sites, as first introduced by John Ward. I am now interested in the repair mechanisms of clustered DNA damage, which is considered as the most difficult for the cell to repair. A main part of my research is devoted to evaluating the role of clustered DNA damage in the promotion of carcinogenesis in vitro and in vivo . Currently in my laboratory, there are two main ongoing projects. (1) Study of the role of BRCA1 and DNA-dependent protein kinase catalytic subunit repair proteins in the processing of clustered DNA damage in human cancer cells. For this project, we use several tumor cell lines, such as breast cancer cell lines MCF-7 and HCC1937 (BRCA1 deficient) and human glioblastoma cells MO59J/K; and (2) Possible use of DNA damage clusters as novel cancer biomarkers for prognostic and therapeutic applications related to modulation of oxidative stress. In this project human tumor and mice tissues are being used.     

Information engineering infrastructure for life sciences and its implementation in China

Biological data,represented by the data from omics platforms,are accumulating exponentially.As some other data-intensive scientific disciplines such as high-energy physics,climatology,meteorology,geology,geography and environmental sciences,modern life sciences have entered the information-rich era,the era of the 4th paradigm.The creation of Chinese information engineering infrastructure for pan-omics studies(CIEIPOS) has been long overdue as part of national scientific infrastructure,in accelerating the further development of Chinese life sciences,and translating rich data into knowledge and medical applications.By gathering facts of current status of international and Chinese bioinformatics communities in collecting,managing and utilizing biological data,the essay stresses the significance and urgency to create a ’data hub’ in CIEIPOS,discusses challenges and possible solutions to integrate,query and visualize these data.Another important component of CIEIPOS,which is not part of traditional biological data centers such as NCBI and EBI,is omics informatics.Mass spectroscopy platform was taken as an example to illustrate the complexity of omics informatics.Its heavy dependency on computational power is highlighted.The demand for such power in omics studies is argued as the fundamental function to meet for CIEIPOS.Implementation outlook of CIEIPOS in hardware and network is discussed.     

Offshore wave energy generation devices: Impacts on ocean bio-environment

As the crisis of petroleum-based energy is aggravating and the carbon emission is elevating, the search and exploitation of renewable energy sources such as solar, wind and oceanic powers, are of global interest and underway in some developed countries. In western countries pioneering the oceanic energy utilization, wave is currently an attractive energy source due to the predictability and the ease to be absorbed into power grid. As wave-energy generators (WEGs) and the associated devices interact with the surrounding environment, they would have impacts on the biological components within the ecosystem in the vicinity of WEGs. However, the environmental effects of offshore WEGs on local fauna and flora have yet to be evaluated in a comprehensive way. This article discusses several aspects, including influence of offshore WEGs on marine macrofaunal communities, interactions between offshore WEGs and biofouling organisms, impacts of offshore WEGs on marine birds and of electromagnetic fields (EMFs) on marine animals as well as “artificial reef” effects. If precaution is taken with the planning and construction of offshore WEGs, and environmental monitoring is performed with operation of these devices, marine wave energy can become a desirable alternative to fossil fuels.     

Recent Advances in Biological Control of Pest Insects by Using Viruses in China

Insect viruses are attractive as biological control agents and could be a feasible alternative to chemical insecticides in the management of insect infestations. This review describes recent advances in the development of wild-type and genetically modified viruses as insecticides. A new strategy of application of insect viruses in China is reviewed. Also, the assessment of biosafety of genetically modified Helicoverpa armigera Nucleopolyhedovirus (HearNPV) is emphasized as a case-study.     

Emerging roles of transforming growth factor β signaling in wet age-related macular degeneration

Age-related macular degeneration (AMD) is one of the major causes of irreversible blindness among aging populations in developed countries and can be classified as dry or wet according to its progression.Wet AMD,which is characterized by angiogenesis on the choroidal membrane,is uncommonly seen but more severe.Controlling or completely inhibiting the factors that contribute to the progression of events that lead to angiogenesis may be an effective strategy for treating wet AMD.Emerging evidence has shown that transforming growth factor-β(TGF-β) signaling plays a significant role in the progression of wet AMD.In this review,we described the roles of and changes in TGF-β signaling in the development of AMD and discussed the mechanisms of the TGF-β superfamily in choroidal neovascularization (CNV) and wet AMD,including the modulation of angiogenesis-related factors,inflammation,vascular fibrosis,and immune responses,as well as cross-talk with other signaling pathways.These remarkable findings indicate that TGF-β signaling is a potential target for wet AMD treatment.     

Glyoxylate Reductase Isoform 1 is Localized in the Cytosol and Not Peroxisomes in Plant Cells

Glyoxylate reductase (GLYR) is a key enzyme in plant metabolism which catalyzes the detoxification of both photorespiratory glyoxylate and succinic semialdehdye, an intermediate of the γ-aminobutyrate (GABA) pathway. Two isoforms of GLYR exist in plants, GLYR1 and GLYR2, and while GLYR2 is known to be localized in plastids, GLYR1 has been reported to be localized in either peroxisomes or the cytosol. Here, we reappraised the intracellular localization of GLYR1 in Arabidopsis thaliana L. Heynh (ecotype Lansberg erecta) using both transiently-transformed suspension cells and stably-transformed plants, in combination with fluorescence microscopy. The results indicate that GLYR1 is localized exclusively to the cytosol regardless of the species, tissue and/or cell type, or exposure of plants to environmental stresses that would increase flux through the GABA pathway. Moreover, the C-terminal tripeptide sequence of GLYR1, -SRE, despite its resemblance to a type 1 peroxisomal targeting signal, is not sufficient for targeting to peroxisomes. Collectively, these results define the cytosol as the intracellular location of GLYR1 and provide not only important insight to the metabolic roles of GLYR1 and the compartmentation of the GABA and photorespiratory pathways in plant cells, but also serve as a useful reference for future studies of proteins proposed to be localized to peroxisomes and/or the cytosol.     

Longevity of animals under reactive oxygen species stress and disease susceptibility due to global warming

The world is projected to experience an approximate doubling of atmospheric CO_2 concentration in the next decades. Rise in atmospheric CO_2 level as one of the most important reasons is expected to contribute to raise the mean global temperature 1.4 ℃-5.8 ℃ by that time. A survey from 128 countries speculates that global warming is primarily due to increase in atmospheric CO_2 level that is produced mainly by anthropogenic activities. Exposure of animals to high environmental temperatures is mostly accompanied by unwanted acceleration of certain biochemical pathways in their cells. One of such examples is augmentation in generation of reactive oxygen species(ROS) and subsequent increase in oxidation of lipids, proteins and nucleic acids by ROS. Increase in oxidation of biomolecules leads to a state called as oxidative stress(OS). Finally, the increase in OS condition induces abnormality in physiology of animals under elevated temperature. Exposure of animals to rise in habitat temperature is found to boost the metabolism of animals and a very strong and positive correlation exists between metabolism and levels of ROS and OS. Continuous induction of OS is negatively correlated with survivability and longevity and positively correlated with ageing in animals. Thus, it can be predicted that continuous exposure of animals to acute or gradual rise in habitat temperature due to global warming may induce OS, reduced survivability and longevity in animals in general and poikilotherms in particular. A positive correlation between metabolism and temperature in general and altered O_2 consumption at elevated temperature in particular could also increase the risk of experiencing OS in homeotherms. Effects of global warming on longevity of animals through increased risk of protein misfolding and disease susceptibility due to OS as the cause or effects or both also cannot be ignored. Therefore, understanding the physiological impacts of global warming in relation to longevity of animals will become very crucial challenge to biologists of the present millennium.     

Pharmacokinetics and toxicology of therapeutic proteins: Advances and challenges

Significant progress has been made in understanding pharmacokinetics (PK),pharmacodynamics (PD),as well as toxicity profiles of therapeutic proteins in animals and humans,which have been in commercial development for more than three decades.However,in the PK arena,many fundamental questions remain to be resolved.Investigative and bioanalytical tools need to be established to improve the translation of PK data from animals to humans,and from in vitro assays to in vivo readouts,which would ultimately lead to a higher success rate in drug development.In toxicology,it is known,in general,what studies are needed to safely develop therapeutic proteins,and what studies do not provide relevant information.One of the major complicating factors in nonclinical and clinical programs for therapeutic proteins is the impact of immunogenicity.In this review,we will highlight the emerging science and technology,as well as the challenges around the pharmacokinetic-and safety-related issues in drug development of mAbs and other therapeutic proteins.     

Platelet-rich plasma vs bone marrow aspirate concentrate: An overview of mechanisms of action and orthobiologic synergistic effects

The use of orthobiologics as a novel therapy for the treatment of numerous musculoskeletal disorders has increased considerably over the past decade.Currently,there are multiple alternatives available as suitable treatments;however,the use of autologous blood-derived products such as platelet-rich plasma(PRP),bone marrow aspirate(BMA)and BMA concentrate(BMAC),specifically,is expanding.Although many investigations attempted to demonstrate the effectiveness of these therapies,even with positive results,the literature lacks standardized protocols and overall accuracy in study designs,which leads to variance and difficulty in reproducibility of protocols.The efficacy of PRP for the treatment of cartilage,bone and muscle tissues is well known.Although BMAC has generated optimistic results for the same purposes,its applicability in clinical trials is still relatively recent when compared to PRP.Both products demonstrate the potential to set forth reparative processes,each in their own distinct mechanism.The combination of these biological products has been previously proposed,yet little is known about their synergism.Evidence indicates that growth factor,cytokine,and chemokine profiles seen in both PRP and BMAC vary but are likely to work synergistically to enhance musculoskeletal healing.BMAC products seem to work well without PRP;however,the addition of PRP to BMAC has been shown to act as a rich and natural source of culture medium for stem cells located either peripherally or in the bone marrow itself.Nevertheless,additional variables associated with the use of BMAC and PRP in orthopedics must be further evaluated in order to consolidate the efficacy of this therapeutic strategy.     

Modulation of the MAP kinase signaling cascade by Raf kinase inhibitory protein

Proteins like Rafkinase inhibitory protein (RKIP) that serve as modulators of signaling pathways, either by promoting or inhibiting the formation of productive signaling complexes through protein-protein interactions, have been demonstrated to play an increasingly important role in a number of cell types and organisms. These proteins have been implicated in development as well as the progression of cancer. RKIP is a particularly interesting regulator, as it is a highly conserved, ubiquitously expressed protein that has been shown to play a role in growth and differentiation in a number of organisms and can regulate multiple signaling pathways. RKIP is also the first MAP kinase signaling modulator to be identified as playing a role in cancer metastasis, and identification of the mechanism by which it regulates Raf-1 activation provides new targets for theraoeutic intervention.     

Legume Genomics and Genetics(LGG)

正Legume Genomics and Genetics (ISSN 1925-1580) is an open access and peer-reviewed journal that publishes original research papers in the fields of genomics and genetics of legume plants, which is committed to publishing grain/forage legume studies, as well as research on model legume plants such as Lotus japonicus and Medicago truncatula. The aims are to feature innovative research findings in the basic and applied fields of legume     

Legume Genomics and Genetics(LGG)

正Legume Genomics and Genetics(ISSN 1925-1580)is an open access and peer-reviewed journal that publishes original research papers in the fields of genomics and genetics of legume plants,which is committed to publishing grain/forage legume studies,as well as research on model legume plants such as Lotus japonicus and Medicago truncatula.The aims are to feature innovative research findings in the basic and applied fields of legume     

Legume Genomics and Genetics(LGG)

正Legume Genomics and Genetics(ISSN 1925-1580)is an open access and peer-reviewed journal that publishes original research papers in the fields of genomics and genetics of legume plants,which is committed to publishing grain/forage legume studies,as well as research on model legume plants such as Lotus japonicus and Medicago truncatula.The aims are to feature innovative research findings in the basic and applied fields of legume     

Legume Genomics and Genetics(LGG)

正Legume Genomics and Genetics(ISSN 1925-1580)is an open access and peer-reviewed journal that publishes original research papers in the fields of genomics and genetics of legume plants,which is committed to publishing grain/forage legume studies,as well as research on model legume plants such as Lotus japonicus and Medicago truncatula.The aims are to feature innovative research findings in the basic and applied fields of legume     

Legume Genomics and Genetics(LGG)

正Legume Genomics and Genetics(ISSN 1925-1580)is an open access and peer-reviewed journal that publishes original research papers in the fields of genomics and genetics of legume plants,which is committed to publishing grain/forage legume studies,as well as research on model legume plants such as Lotus japonicus and Medicago truncatula.The aims are to feature innovative research findings in the basic and applied fields of legume