Asymmetrical Macromolecular Complex Formation of Lysophosphatidic Acid Receptor 2 (LPA2) Mediates Gradient Sensing in Fibroblasts

Chemotactic migration of fibroblasts toward growth factors relies on their capacity to sense minute extracellular gradients and respond to spatially confined receptor-mediated signals. Currently, mechanisms underlying the gradient sensing of fibroblasts remain poorly understood. Using single-particle tracking methodology, we determined that a lysophosphatidic acid (LPA) gradient induces a spatiotemporally restricted decrease in the mobility of LPA receptor 2 (LPA₂) on chemotactic fibroblasts. The onset of decreased LPA₂ mobility correlates to the spatial recruitment and coupling to LPA₂-interacting proteins that anchor the complex to the cytoskeleton. These localized PDZ motif-mediated macromolecular complexes of LPA₂ trigger a Ca²⁺ puff gradient that governs gradient sensing and directional migration in response to LPA. Disruption of the PDZ motif-mediated assembly of the macromolecular complex of LPA₂ disorganizes the gradient of Ca²⁺ puffs, disrupts gradient sensing, and reduces the directional migration of fibroblasts toward LPA. Our findings illustrate that the asymmetric macromolecular complex formation of chemoattractant receptors mediates gradient sensing and provides a new mechanistic basis for models to describe gradient sensing of fibroblasts.     

Significant Improvement in Dynamic Visual Acuity after Cataract Surgery: A Promising Potential Parameter for Functional Vision

Purpose

Dynamic visual acuity (DVA) is a relatively independent parameter for evaluating the ability to distinguish details of a moving target. The present study has been designed to discuss the extent to which age-related cataract impacts DVA in elderly individuals and to determine whether it could be restored after bilateral phacoemulsification combined with intraocular lens implantation surgery.

Methods

Twenty-six elderly cataract patients scheduled for binocular cataract surgery and 30 elderly volunteers without cataract were enrolled in the study. DVA at 15, 30, 60 and 90 degree per second (dps) was assessed, and velocity-dependent visual acuity decreases between consecutive speed levels were calculated.

Results

Compared with the control group, the patient group exhibited significantly worse DVA performance at all speed levels (p<0.001), and the decreases in velocity-dependent visual acuity were more serious in the patient group at the intervals of 0–15 dps (p<0.001), 15–30 dps (p = 0.007) and 30–60 dps (p = 0.008). Postoperatively, DVA performance at every speed level in the patient group clearly improved (p<0.001) and recovered to levels compatible to the control group. The decrease in visual acuity with increasing speed was less pronounced than during the preoperative phase (p_{0–15 dps} = 0.001, p_{15–30 dps}<0.001 and p_{30–60 dps} = 0.001) and became similar to that of the control group. The postoperative visual benefit regarding DVA was more pronounced than the improvement in static visual acuity (p_{15 dps} = 0.001 and p<0.001 at 30 dps, 60 dps and 90 dps).

Conclusions

The impact of age-related cataract on DVA was more severe than its effects on static visual acuity. After cataract surgery, not only static vision of the patients was restored markedly, but also the dynamic vision. DVA could be an important adjunct to the current evaluation system of functional vision, thereby meriting additional attention in clinical assessment.     

Inhibition of polo-like kinase 1 (PLK1) facilitates reactivation of gamma-herpesviruses and their elimination

Both Kaposi’s sarcoma-associated herpesvirus (KSHV) and Epstein-Barr virus (EBV) establish the persistent, life-long infection primarily at the latent status, and associate with certain types of tumors, such as B cell lymphomas, especially in immuno-compromised individuals including people living with HIV (PLWH). Lytic reactivation of these viruses can be employed to kill tumor cells harboring latently infected viral episomes through the viral cytopathic effects and the subsequent antiviral immune responses. In this study, we identified that polo-like kinase 1 (PLK1) is induced by KSHV de novo infection as well as lytic switch from KSHV latency. We further demonstrated that PLK1 depletion or inhibition facilitates KSHV reactivation and promotes cell death of KSHV-infected lymphoma cells. Mechanistically, PLK1 regulates Myc that is critical to both maintenance of KSHV latency and support of cell survival, and preferentially affects the level of H3K27me3 inactive mark both globally and at certain loci of KSHV viral episomes. Furthremore, we recognized that PLK1 inhibition synergizes with STAT3 inhibition to efficiently induce KSHV reactivation. We also confirmed that PLK1 depletion or inhibition yields the similar effect on EBV lytic reactivation and cell death of EBV-infected lymphoma cells. Lastly, we noticed that PLK1 in B cells is elevated in the context of HIV infection and caused by HIV Nef protein to favor KSHV/EBV latency.     

以材料“创造”土地？——中国城市化进程的一个重要特征

中国快速城市化进程的一个重要特征是以土地为载体,通过大量投入钢铁、水泥等建材大规模修建城市建筑和基础设施,创造出大量的城市生产和生活空间。利用1985—2010年中国省级行政单元城市建成区总面积、城市居住用地总面积、城市住宅总面积和城市住宅建筑材料总使用量等数据,识别城市扩张模式,揭示中国城市化进程中土地、建筑面积及其构筑材料三者间的关系。研究表明2000年是中国城市扩张的重要分界点,2000年之前中国各省份的城市建成区总面积、城市住宅总面积和城市住宅建筑材料总使用量均较小且省份间差异不大,2000年之后三者迅速增长且省份间差异逐渐扩大。在地区尺度上,三者均呈现东部地区最高、中部次之、西部最低的特点,地区内部差异则表现为东部地区最大、西部次之、中部最小的特征。大多数省份的城市住宅总面积及其构筑材料总量随着城市建成区的扩张而增长,表明城市在发展初期以扩大建成区和水平扩张为主。随着城市化水平的不断提高,城市内部空间重组和用地置换导致高层建筑逐步替代了原有的单层或低矮建筑,城市扩张的方向由依赖土地的水平扩张转向以大量使用建筑材料为基础的垂直扩张,使得许多省份的城市住宅总面积逐渐超过辖区内居住用地总面积。这种以建筑材料"创造"出更多"土地"的城市垂直扩张在满足人们对城市生产和生活空间需求的同时,有利于节约土地资源和保护生态空间,但需要以消耗更多的建筑材料并承担建筑材料在开采、制造、运输、使用和废弃过程中所造成的环境影响为代价。     

Derivation and characterization of human embryonic stem cell lines from poor quality embryos

Poor quality embryos discarded from in vitro fertilization （IVF） laboratories are good sources for deriving human embryonic stem cell （hESC） lines. In this study, 166 poor quality embryos donated from IVF centers on day 3 were cultured in a blastocyst medium for 2 days, and 32 early blastocysts were further cultured in a blastocyst optimum culture medium for additional 2 days so that the inner cell masses （ICMs） could be identified and isolated easily. The ICMs of 17 blastocysts were isolated by a mechanical method, while those of the other 15 blastocysts were isolated by immunosurgery. All isolated ICMs were inoculated onto a feeder layer for subcultivation. The rates of ICM attachment, primary ICM colony formation and the efficiency of hESC derivation were similar between the ICMs isolated by the two methods （P〉0.05）. As a result, four new hESC lines were established. Three cell lines had normal karyotypes and one had an unbalanced Robertsonian translocation. All cell lines showed normal hESC characteristics and had the differentiation ability. In conclusion, we established a stable and effective method for hESC isolation and culture, and it was confirmed that the mechanical isolation was an effective method to isolate ICMs from poor embryos. These results further indicate that hESC lines can be derived from poor quality embryos discarded by IVF laboratories.     

The effect of plant growth regulators, nitric oxide, nitrate, nitrite and light on the germination of dimorphic seeds of Suaeda salsa under saline conditions

Suaeda salsa, a leaf succulent shrub in the family Chenopodiaceae, is one of the most important halophytes in China. Suaeda salsa produces dimorphic seeds (soft brown seeds and hard black seeds). Seeds of S. salsa were collected from the coastal salt flats near Huanghua City, China. Experiments were conducted to determine the salinity-alleviating effect of plant growth regulators, nitric oxide, nitrate, nitrite and light on the germination of dimorphic seeds of S. salsa. Brown seeds had a higher germination rate than black seeds in all experiments. Black seeds were more sensitive to salt in the absence of light in comparison to brown seeds. Brown seeds absorbed water more quickly in comparison to black seeds and were found to be more tolerant of salt stress. Our results showed that 1-aminocyclopropane-1-carboxylate (ACC, the immediate precursor of ethylene), nitrite, GA₄ and BA improved seed germination in the presence of salt. However, nitrate, GA₁, GA₃ failed to alleviate salt stress. ABA inhibited seed germination and seedling growth. Possible mechanisms involved in the alleviation of salt stress in S. salsa seeds and the ecological adaptation of the seeds to the environment are discussed.     

中国森林生态系统林冠层降雨截留特征

森林生态系统作为陆地生态系统的主体,其发达的林冠层通过调节降水量、改变降水强度等深刻影响着流域全过程水文通量及水分输出。以中国广泛开展的典型森林降雨再分配过程的年尺度监测数据为基础,揭示中国不同类型森林生态系统的降雨再分配及林冠层降雨截留特征,阐明森林生态系统林冠层截留特征与降雨、植被要素的关系。结果表明:我国不同森林生态系统年穿透雨量处于141.4-2450.0 mm之间,年穿透雨率为36.3%-92.3%。5种典型森林生态系统多年平均穿透雨量((445.3±252.9)-(1230.6±479.6) mm)占同期多年平均降雨量的(72.6±9.2)%-(77.4±8.9)%。不同森林生态系统年树干茎流量介于0-508.2 mm之间,占同期年降雨量的0-25.8%。5种典型森林生态系统树干茎流量多年平均值((9.8±17.3)-(87.8±81.6) mm)占同期多年平均降雨量的(1.4±1.9)%-(5.4±4.6)%。不同森林生态系统林冠层年降雨截留范围在25.7-812.9 mm之间,占年降雨量的4.2%-55.6%。5种典型森林生态系统多年平均林冠截留量((154.2±81.6)-(392.2±203.5) mm)占同期年平均降雨量的(18.7±7.4)%-(25.9±8.3)%。进一步分析表明,我国森林生态系统穿透雨量、树干茎流量和林冠层截留量随观测区年降雨量的增加而呈显著增大(P<0.05),年穿透雨率、年树干茎流率随年降雨量的增加呈显著线性上升趋势(P<0.05),而年林冠截留率与年降雨量呈显著的负相关关系(P<0.01),降雨量、叶面积指数是深刻影响森林生态系统林冠层降雨截留率等特征的重要因素。整体上,不同类型森林生态系统林冠截留降雨能力存在明显差异,林冠层截留率突出表现为:落叶林大于常绿林、针叶林大于阔叶林。     

Barley GRIK1‐SnRK1 kinases subvert a viral virulence protein to upregulate antiviral RNAi and inhibit infection

Viruses often usurp host machineries for their amplification, but it remains unclear if hosts may subvert virus proteins to regulate viral proliferation. Here, we show that the 17K protein, an important virulence factor conserved in barley yellow dwarf viruses (BYDVs) and related poleroviruses, is phosphorylated by host GRIK1‐SnRK1 kinases, with the phosphorylated 17K (P17K) capable of enhancing the abundance of virus‐derived small interfering RNAs (vsiRNAs) and thus antiviral RNAi. Furthermore, P17K interacts with barley small RNA‐degrading nuclease 1 (HvSDN1) and impedes HvSDN1‐catalyzed vsiRNA degradation. Additionally, P17K weakens the HvSDN1‐HvAGO1 interaction, thus hindering HvSDN1 from accessing and degrading HvAGO1‐carried vsiRNAs. Importantly, transgenic expression of 17K phosphomimetics (17K^5D), or genome editing of SDN1, generates stable resistance to BYDV through elevating vsiRNA abundance. These data validate a novel mechanism that enhances antiviral RNAi through host subversion of a viral virulence protein to inhibit SDN1‐catalyzed vsiRNA degradation and suggest new ways for engineering BYDV‐resistant crops.     

Erdheim Chester disease in a patient with Burkitt lymphoma: a case report and review of literature

Background

Erdheim Chester disease (ECD) is a rare, non-Langerhans cell histiocytosis characterized by widespread tissue infiltration by CD68-positive, CD1a-negative foamy histiocytes. ECD can be difficult to identify, and diagnosis relies on the presence of histiocytes with certain histologic and immunophenotypic features in an appropriate clinical and radiologic setting. Clinical signs and symptoms are variable depending on which organ systems are involved. Most patients have at least skeletal involvement with bone pain as well as fatigue. Other common manifestations include diabetes insipidus, cardiac, periaortic, or retro-orbital infiltration/fibrosis, kidney impairment, xanthelasmas, among others.

Case presentation

Herein, we describe a case of BRAF-mutation positive ECD in a patient with Burkitt lymphoma, and we review recent literature.

Conclusion

Underlying BRAF and other MAPK pathway mutations are identified in approximately 50% of cases of ECD, which aids in diagnosis as well as enables novel targeted treatments. ECD patients have an increased risk of myeloid neoplasms; however, unlike other histiocytoses, an association with lymphoproliferative disorders has not been recognized.