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.

ABO blood type,diabetes and risk of gastrointestinal cancer in northern China

AIM:To explore the potential risk factors related to gastrointestinal cancer in northern China.METHODS:A total of 3314 cases of gastrointestinal cancer(esophageal,gastric,pancreatic and biliary) and 2223 controls(including healthy individuals,glioma and thyroid cancer) were analyzed by case-control study.Multivariable logistic regression analysis was applied to evaluate the association between different cancers and hepatitis B surface antigen,sex,age,blood type,diabetes,or family history of cancer.RESULTS:Type 2 diabetes was significantly associated with gastric,biliary and pancreatic cancer with an OR of 2.0-3.0.Blood type B was significantly associated with esophageal cancer [odd ratio(OR) = 1.53,95% confidence interval(CI) = 1.10-2.14] and biliary cancer(OR = 1.49,95% CI = 1.09-2.05).The prevalence of type 2 diabetes was significantly higher in gastric,biliary and pancreatic cancers compared with other groups,with ORs ranging between 2.0 and 3.0.Family history of cancer was strongly associated with gastrointestinal compared with other cancers.CONCLUSION:Blood type B individuals are susceptible to esophageal and biliary cancer.Type 2 diabetes is significantly associated with gastric,biliary and especially pancreatic cancer.

PRMT5 regulates Golgi apparatus structure through methylation of the golgin GM130

Golgi 仪器(GA ) 的维护结构和功能取决于 Golgi 矩阵蛋白质。象 golgin 和掌握家庭的成员的 phosphorylation 那样的 Golgi 蛋白质的 posttranslational 修正为决定 Golgi 建筑学是重要的。包括 golgin-84 的一些 Golgi 蛋白质也被知道是 methylated，但是 golgin methylation 的功能仍然保持不清楚。这里，我们证明蛋白质精氨酸 methyltransferase (PRMT5 ) 5 本地化到 GA 和形式建筑群，几个部件在拴住的 GA 带子形成和泡包含了。PRMT5 在 Golgi 带子形成与 PRMT5 原因缺点的 golgin GM130，和弄空交往。而且，在 GM130 的 PRMT5 甲醇化物 N 终端精氨酸，和如此的精氨酸 methylation 为 GA 显得批评带子形成。我们的调查结果揭示 GM130 的 PRMT5 依赖的精氨酸 methylation 由控制 GA 建筑学的维护的分子的机制。

Understanding biological functions through molecular networks

染色体序列并且分子的网络的随后的高产量的印射的结束允许我们从网络观点学习生物学。试验性、统计、数学的当模特儿的途径被采用了学习分子的网络的结构，函数和动力学，并且开始揭示各种各样的网络性质的重要连接到生物系统的函数。与这些功能的连接一致，一个网络的进化选择是显然基于功能，而非直接在网络的结构上。动态模块化是分子的网络的突出的特征之一。利用如此的一个特征可以通过过程特定的模块化的网络的建设简化基于网络的生物研究并且提供连接 genotypic 变化到复杂特点或疾病的功能、机械学的卓见，它是可能的是在理解建筑群人疾病的下一个波浪的一条关键途径。与 ready-to-use 网络分析和当模特儿的工具的开发，网络途径在不久的将来将被灌输进日常生物研究。

Smad2 mediates Activin/Nodal signaling in mesendoderm differentiation of mouse embryonic stem cells

尽管发信号的 Activin/Nodal 调整人的胚胎的茎(ES ) 的 pluripotency 细胞，这个发信号怎么在老鼠 ES 细胞行动，仍然保持大部分不清楚。调查这，我们证实了房间拥有活跃调停 Smad2 的 Activin/Nodal 发信号的那老鼠 ES 并且发现调停 Smad2 的 Activin/Nodal 发信号为自强维护是非必需的，但是向 mesendoderm 系为合适的区别被要求。到进内在的机制的获得卓见，联系 Smad2 的基因被染色体宽的染色质 immunoprecipitation 薄片分析识别。结果证明在 Smad2 绑定和 Activin/Nodal 发信号调整之间有 transcriptional 关联，并且发展相关的基因在 Smad2 固定的目标之中被充实。我们进一步在 Activin/Nodal-Smad2 小径下游地行动的老鼠 ES 房间的 mesendoderm 区别作为一个关键播放器识别了 Tapbp。一起拿，我们的调查结果建议发信号的调停 Smad2 的 Activin/Nodal 通过相应发展管理者表示的直接调整安排鼠标 ES 房间的 mesendoderm 系承诺。

Transgenic expression of DwMYB2 impairs iron transport from root to shoot in Arabidopsis thaliana

在植物，铁举起和动态平衡紧被调整从土壤保证它的吸收并且在房间避免过量铁。涉及这个过程的许多基因在过去的几年期间被识别了，但是有在整个植物铁交通国王和分配的基因规定未解决的许多问题遗体。MYB 抄写因素包含约 50 氨基酸的双人脚踏车重复 DNA 有约束力的主题(R) 并且涉及植物开发，荷尔蒙发信号和新陈代谢的许多方面的规定。这里，我们报导在 Arabidopsis thaliana 的兰花 R2R3-MYB 基因 DwMYB2 的宫外的表示授与转基因的植物超敏性熨缺乏。在 DwMYB2 转基因的植物，在根的铁内容在野类型的根与那相比更高是双重的，当颠倒在射击是真的时。在根和射击的铁内容的这不平衡建议到射击的从根的铁的 translocation 被 DwMYB2 的表示在转基因的植物影响。一致地，基因薄片和反向的抄写聚合酶链反应分析表明铁螯的 reductase 基因， AtFRO2，和铁 transporter 基因， AtIRT1 和 AtIRT2，当象 AtIREG1， AtFRD3 和 NRAMP1 那样的另外的潜在的铁运输 ers 是下面调整的时，由 DwMYB2 表示是起来调整的。另外， ers 和抄写因素也是的几通常认为的肽运输的表示在 35S::DwMYB2 改变了转基因的线。这些数据提供我们卓见进整个植物 translocation 尽管 heterologous 基因被表示，在植物为铁动态平衡熨并且识别候选人基因。

Transgenic analyses of TGIF family proteins in Drosophila imply their role in cell growth

TG-interacting factors （TGIFs） belong to a family of TALE-homeodomain proteins including TGIF, TGIF2, and TGIF2LX/Y （TGIF2 like on X or Y chromosome） in human. They potentially play important functions in various tissues during development. Mutations in TGIF are frequently associated with malformation of forebrain and facial structures; TGIF2 proteins are over-expressed in many ovarian cancer cell lines; and TGIF2LX/Y are specifically expressed in adult testis. The molecular functions of these proteins have been investigated mostly in cultured cells. TGIF and TGIF2 have been found as transcriptional repressors that modulate TGF-beta signaling. However these findings are far from sufficient to explain their mutant phenotypes or expression patterns, and the functions of TGIF2LX/Y have never been reported. Here we use Drosophila as a model system to explore the functions of TGIF family proteins in vivo. We observed in fly tissues such as fat body, epithelia, and neuronal cells, that expressing human TGIF2 or human TGIF2LX generally inhibited cell growth in size and number. Co-expressing Drosophila Myc, Cyclin E, or human c-MycS partially rescued the growth inhibition induced by human TGIFs, whereas activated insulin pathway signaling did not. Taken together, we provide in vivo evidence for the potential functions of human TGIF2 and TGIF2LX in growth control. Additionally, we confirmed that Drosophila TGIFs are transcriptional activators by assaying their activities in spermatogenesis.

The tea plant CsLHT1 and CsLHT6 transporters take up amino acids, as a nitrogen source, from the soil of organic tea plantations

Organic tea is more popular than conventional tea that originates from fertilized plants.Amino acids inorganic soils constitute a substantial pool nitrogen(N)available for plants.However,the amino-acid contents in soils of tea plantations and how tea plants take up these amino acids remain largely unknown.In this study,we show that the amino-acid content in the soil of an organic tea plantation is significantly higher than that of a conventional tea plantation.Glutamate,alanine,valine,and leucine were the most abundant amino acids in the soil of this tea plantation.When 15 N-glutamate was fed to tea plants,it was efficiently absorbed and significantly increased the contents of other amino acids in the roots.We cloned seven CsLHT genes encoding amino-acid transporters and found that the expression of CsLHT1,CsLHT2,and CsLHT6 in the roots significantly increased upon glutamate feeding.Moreover,the expression of CsLHT1 or CsLHT6 in a yeast amino-acid uptake-defective mutant,22Δ10α,enabled growth on media with amino acids constituting the sole N source.Amino-acid uptake assays indicated that CsLHT1 and CsLHT6 are H^(+)-dependent high-and low-affinity amino-acid transporters,respectively.We further demonstrated that CsLHT1 and CsLHT6 are highly expressed in the roots and are localized to the plasma membrane.Moreover,overexpression of CsLHT1 and CsLHT6 in Arabidopsis significantly improved the uptake of exogenously supplied 15 N-glutamate and 15 N-glutamine.Taken together,our findings are consistent with the involvement of CsLHT1 and CsLHT6 in amino-acid uptake from the soil,which is particularly important for tea plants grown inorganic tea plantations.

Reconstruction and Dynamics of the Human Intestinal Microbiome Observed In Situ

The human gut microbiome has primarily been studied through the use of fecal samples,a practice that has generated vital knowledge on the composition and functional capacities of gastrointestinal microbial communities.However,this reliance on fecal materials limits the investigation of microbial dynamics in other locations along the gastrointestinal tract(in situ),and the infrequent availability of fecal samples prevents analysis at finer temporal scales(e.g.,hours).In our study,we utilized colonic transendoscopic enteral tubing,a technology originally developed for fecal microbiota transplantation,to sample the ileocecal microbiome twice daily;metagenomic and metatranscriptomic analyses were then conducted on these samples.A total of 43 ileocecal and 28 urine and fecal samples were collected from five healthy volunteers.The ileocecal and fecal microbiomes,as profiled in the five volunteers,were found to be similar in metagenomic profiling,yet their active genes(metatranscriptome)were found to be highly distinct.Both microbiomes were perturbed after laxative exposure;over time,they exhibited reduced dissimilarity to their pre-treatment state,thereby demonstrating resilience as an innate property of the gut microbiome,although they did not fully recover within our observation time window.Sampling of the ileocecal microbiome during the day and at night revealed the existence of diurnal rhythms in a series of bacterial species and functional pathways,particularly those related to short-chain fatty acid production,such as Propionibacterium acnes and coenzyme A biosynthesis Ⅱ.Autocorrelation analysis and fluctuations decomposition further indicated the significant periodicity of the diurnal oscillations.Metabolomic profiling in the fecal and urine samples mirrored the perturbance and recovery in the gut microbiome,indicating the crucial contribution of the gut microbiome to many key metabolites involved in host health.This study provides novel insights into the human gut microbiome and its inner resilience and diurnal rhythms,as well as the potential consequences of these to the host.

Instability of Nucleic Acids in Airborne Microorganisms under Far Infrared Radiation

Emergence of zoonotic-human pathogens is proven to be a lethal threat to public health, and RNA virus including influenza viruses, severe acute respiratory syndrome coronavirus, middle east respiratory syndrome coronavirus, and COVID-19, plays a pivotal role. As those viruses as airborne microorganisms spread mainly by tiny airborne particles, it is important to de-active those airborne particles before their entry into human bodies. In this study, we investigated the effect of far infrared (FIR) radiation on inhibition of airborne microorganisms. The result confirmed that double stand DNA from airborne microorganisms containing RNA viruses was stable under mild FIR radiation. However, single strand RNA from them was found to be sensitive to FIR radiation, indicating that RNA virus in airborne particles is instable under FIR radiation. Based on this observation, two models on usage of FIR radiation to prevent RNA virus transmission by air and cure RNA virus infection were proposed. Then, this study suggests that FIR radiation has the potential to be a cheap, convenient, and efficient method in clinic to treat RNA virus.

Inaugural Editorial:Seed Biology

Seed is the most important reproductive organ in plant.Since its first emergence approximately 370 million years ago,seed plant had overwhelming advantage to non-seed plants in reproduction,spreading and colonization in terrestrial land.Beside its essential function in the sexual reproduction of plants,seed is the most economically important agricultural product,offering necessity food for human and wildlife,nutritious feed for livestock.Seeds and grains also provide massive amount of raw materials for manufactured goods,such as coffee,starch,and oil.Seeds also play a pivotal role in development of fruits which supplement significant portion of food and nutrition for human and wildlife.

Haem Oxygenase 1 is a potential target for creating etiolated/albino tea plants (Camellia sinensis) with high theanine accumulation

Theanine content is highly correlated with sensory quality and health benefits of tea infusion.The tender shoots of etiolated and albino tea plants contain higher theanine than the normal green tea plants and are valuable materials for high quality green tea processing.However,why these etiolated or albino tea plants can highly accumulate theanine is largely unknown.In this study,we observed an Arabidopsis etiolated mutant hy1–100(mutation in Haem Oxygenase 1,HO1)that accumulated higher levels of glutamine(an analog of theanine).We therefore identified CsHO1 in tea plants and found CsHO1 is conserved in amino acid sequences and subcellular localization with its homologs in other plants.Importantly,CsHO1 expression in the new shoots was much lower in an etiolated tea plants‘Huangkui’and an albino tea plant‘Huangshan Baicha’than that in normal green tea plants.The expression levels of CsHO1 were negatively correlated with theanine contents in these green,etiolated and albino shoots.Moreover,CsHO1 expression levels in various organs and different time points were also negatively correlated with theanine accumulation.The hy1–100 was hypersensitive to high levels of theanine and accumulated more theanine under theanine feeding,and these phenotypes were rescued by the expression of CsHO1 in this mutant.Transient knockdown CsHO1 expression in the new shoots of tea plant using antisense oligonucleotides(asODN)increased theanine accumulation.Collectively,these results demonstrated CsHO1 negatively regulates theanine accumulation in tea plants,and that low expression CsHO1 likely contributes to the theanine accumulation in etiolated/albino tea plants.

Emerging roles and therapeutic potentials of sphingolipids in pathophysiology:emphasis on fatty acyl heterogeneity

Sphingolipids not only exert structural roles in cellular membranes,but also act as signaling molecules in various physiological and pathological processes.A myriad of studies have shown that abnormal levels of sphingolipids and their metabolic enzymes are associated with a variety of human diseases.Moreover,blood sphingolipids can also be used as biomarkers for disease diagnosis.This review summarizes the biosynthesis,metabolism,and pathological roles of sphingolipids,with emphasis on the biosynthesis of ceramide,the precursor for the biosynthesis of complex sphingolipids with different fatty acyl chains.The possibility of using sphingolipids for disease prediction,diagnosis,and treatment is also discussed.Targeting endogenous ceramides and complex sphingolipids along with their specific fatty acyl chain to promote future drug development will also be discussed.

GreenPhos,a universal method for in-depth measurement of plant phosphoproteomes with high quantitative reproducibility

Protein phosphorylation regulates a variety of important cellular and physiological processes in plants.In-depth profiling of plant phosphoproteomes has been more technically challenging than that of animal phosphoproteomes.This is largely due to the need to improve protein extraction efficiency from plant cells,which have a dense cell wall,and to minimize sample loss resulting from the stringent sample clean-up steps required for the removal of a large amount of biomolecules interfering with phosphopeptide purification and mass spectrometry analysis.To this end,we developed a method with a streamlined workflow for highly efficient purification of phosphopeptides from tissues of various green organisms including Arabidopsis,rice,tomato,and Chlamydomonas reinhardtii,enabling in-depth identification with high quantitative reproducibility of about 11000 phosphosites,the greatest depth achieved so far with single liquid chromatography-mass spectrometry(LC-MS)runs operated in a data-dependent acquisition(DDA)mode.The mainstay features of the method are the minimal sample loss achieved through elimination of sample clean-up before protease digestion and of desalting before phosphopeptide enrichment and hence the dramatic increases of time-and cost-effectiveness.The method,named GreenPhos,combined with single-shot LC-MS,enabled in-depth quantitative identification of Arabidopsis phosphoproteins,including differentially phosphorylated spliceosomal proteins,at multiple time points during salt stress and a number of kinase substrate motifs.GreenPhos is expected to serve as a universal method for purification of plant phosphopeptides,which,if samples are further fractionated and analyzed by multiple LC-MS runs,could enable measurement of plant phosphoproteomes with an unprecedented depth using a given mass spectrometry technology.

Erratum to “Lipidome Atlas of the Developing Heart Uncovers Dynamic Membrane Lipid Attributes Underlying Cardiac Structural and Metabolic Maturation”

Main Text In the Research Article“Lipidome Atlas of the Developing Heart Uncovers Dynamic Membrane Lipid Attributes Underlying Cardiac Structural and Metabolic Maturation”[1],there was an error in Fig.2B.The authors mistakenly repeated the chord diagram designated for P7 with that from P1.The figure amendment did not affect the in-text discussion of the figure,which was focused on changes between P0 and P21,and did not alter the conclusion.Figure 2B has now been corrected in the PDF and HTML(full text).

The retromer component SNX6 interacts with dynactin p150Glued and mediates endosome-to-TGN transport

retromer 是调停的蛋白质建筑群后退到 trans-Golgi 网络(TGN ) 的从内涵体的 transmembrane 货物的运输。它由 Vps26， Vps29 和 Vps35 的货物选择 subcomplex 和排序 nexins (SNX ) 的膜绑定上衣 subcomplex 组成。以前的研究作为第二 SNX 的候选人作为 SNX subcomplex，和 SNX5/6 的部件之一识别了 SNX1/2。联系 retromer 的货物怎么被分子的马达认出并且搬运，大部分是未知的。在这研究，我们发现了一个 SNX1/2 的 dimerization 搭挡， SNX6，与 dynein/dynactin 马达建筑群的 p150Glued 子单元交往。我们 SNX6 是 retromer 的一个部件的现在的证据，和到联系膜的 retromer 的马达建筑群的那招募要求 SNX6-p150Glued 相互作用。在从内涵体在一些 CI-MPR 检索从内涵体和结果排序结构到 TGN 的 tubulovesicular 的形成和分开的 SNX6-p150Glued 相互作用原因失败的混乱。这些观察显示除了 SNX1/2，与 dynein/dynactin 建筑群联合的 SNX6 驾驶形成和运动管状后退中介。

Molecular insights into the transgenerational inheritance of stress memory

There is accumulating evidence to show that environmental stressors can regulate a variety of phenotypes in descendants through germline-mediated epigenetic inheritance. Studies of model organisms exposed to environmental cues(e.g., diet, heat stress, toxins) indicate that altered DNA methylations, histone modifications, or non-coding RNAs in the germ cells are responsible for the transgenerational effects. In addition,it has also become evident that maternal provision could provide a mechanism for the transgenerational inheritance of stress adaptations that result from ancestral environmental cues. However, how the signal of environmentally-induced stress response transmits from the soma to the germline, which may influence offspring fitness, remains largely elusive. Small RNAs could serve as signaling molecules that transmit between tissues and even across generations. Furthermore, a recent study revealed that neuronal mitochondrial perturbations induce a transgenerational induction of the mitochondrial unfolded protein response mediated by a Wnt-dependent increase in mitochondrial DNA levels. Here, we review recent work on the molecular mechanism by which parental experience can affect future generations and the importance of soma-to-germline signaling for transgenerational inheritance.

PRMT5 determines the pattern of polyploidization and prevents liver from cirrhosis and carcinogenesis

Human hepatocellular carcinoma(HCC)occurs almost exclusively in cirrhotic livers.Here,we report that hepatic loss of protein arginine methyltransferase 5(PRMT5)in mice is sufficient to cause cirrhosis and HCC in a clinically relevant way.Furthermore,pathological polyploidization induced by hepatic loss of PRMT5 promotes liver cirrhosis and hepatic tumorigenesis in aged liver.The loss of PRMT5 leads to hyperaccumulation of P21 and endoreplication-dependent formation of pathological mono-nuclear polyploid hepatocytes.PRMT5 and symmetric dimethylation at histone H4 arginine 3(H4R3me2s)directly associate with chromatin of P21 to suppress its transcription.More importantly,loss of P21 rescues the pathological mono-nuclear polyploidy and prevents PRMT5-deficiency-induced liver cirrhosis and HCC.Thus,our results indicate that PRMT5-mediated symmetric dimethylation at histone H4 arginine 3(H4R3me2s)is crucial for preventing pathological polyploidization,liver cirrhosis and tumorigenesis in mouse liver.

Temporospatial inhibition of Erk signaling is required for lymphatic valve formation

Intraluminal lymphatic valves(LVs)and lymphovenous valves(LVs)are critical to ensure the unidirectional flow of lymphatic fluid.Morphological abnormalities in these valves always cause lymph or blood reflux,and result in lymphedema.

Cbl negatively regulates JNK activation and cell death

这里，我们在 neuronal apoptosis 的规定探索 Cbl 蛋白质的角色。在神经原 apoptosis 鈥 ? 神经生长的二个范例，因素(NGF ) 剥夺和 DNA 损坏鈥 ? c-Cbl 和 Cbl-b 的细胞的层次在细胞死亡的发作前掉落了很好。NGF 剥夺也导致了酷氨酸 phosphorylation 的快速的损失(并且很可能，激活) c-Cbl。与 siRNAs 指向 c-Cbl 和 Cbl-b 模仿他们的 loss/inactivation 敏化 neuronal 房间到 NGF 剥夺或 DNA 损坏支持的死亡。Cbl 蛋白质可能由影响 neuronal 死亡的一潜在的机制由发信号的 apoptotic c6 月 N 终端 kinase (JNK ) 的规定。我们证明 Cbl 蛋白质与 JNK 小径部件交往混合的系 kinase (MLK ) 3 并且呸和那 Cbl 蛋白质击倒是足够的增加 JNK 小径活动。而且， c-Cbl 的表示堵住 MLK 的能力发信号到导致 JNK 激活的 kinase 串联的下游的部件并且保护 neuronal 房间免受 MLK 导致的死亡的伤害，然而并非从下游的 JNK 使活跃之物。根据这些调查结果，我们建议 Cbls 由禁止 MLK 的能力激活 JNK 发信号部分地至少在健康神经原压制房间死亡。Apoptotic 刺激导致 Cbl 蛋白质 / 活动的损失，从而在 JNK 激活上并且在房间死亡上移开一个批评刹车。