Microcystins: measuring human exposure and the impact on human health

Abstract

Context: Freshwater cyanobacterial toxins, microcystins, may be a contributing factor to the development of hepatocellular cancer and colorectal cancer.

Objectives: This review summarizes the toxicity data, exposure routes and the methodologies available to determine exposure to elucidate the relationship to liver and colorectal cancer.

Methods: Literature searches were conducted using Medline, PubMed and Web of Science.

Results: There is evidence of human poisonings resulting from exposure to microcystins, however current methods rely on targeted approaches only suitable for acute exposure. No methods exist for the determination of chronic exposure to microcystins.

Conclusions: With the growing evidence of exposure to microcystins and the possible links to cancer, methods to measure medium to long-term human exposure are needed. The identification and validation of candidate biomarkers are key to undertaking urgently required epidemiological studies.     

The endosperm development and the variations of structures of embryo sacs: unravelling the low fecundity of Zephyranthes candida (Amaryllidaceae)

To unravel a low fecundity in Zephyranthes candida (Lindl.) Herb., the development of the endosperm was studied using conventional paraplast section technique. The results show that the endosperm develops normally and comprises four major stages viz. syncytial, cellularization, differentiation and maturation. Both proliferation of antipodal cells and their close contact with the primary endosperm nucleus were observed, which should favor transportation of nutrients and accelerate development of embryo and endosperm. In Z. candida, at least four events of nuclear migration occurred during the course of embryogenesis and endosperm development. The 12.7% structurally and functionally abnormal ovules, along with the 22.3% collapsed and aborted ovules observed accounts for the low fecundity to some extent.     

Testing parameter sensitivities and uncertainty analysis of Biome-BGC model in simulating carbon and water fluxes in broadleaved-Korean pine forests

生态过程模型的发展为研究者在长时间序列和区域尺度的研究提供了便利, 但模型模拟的准确性受到模型自身结构、模型参数估计合理性的影响。敏感性分析能够定量或定性筛选出对模型模拟结果影响较大的敏感参数, 是模型参数校准过程中的重要工具, 也是建模和应用的先决条件。该文以阔叶红松林为研究对象, 采用全局敏感性分析方法——傅里叶幅度灵敏度检验扩展法(EFAST)对Biome-BGC模型的生理生态参数进行了敏感性分析, 分别分析了红松(Pinus koraiensis)和阔叶树的净初级生产力(NPP)、蒸散(ET)对参数变化的敏感性。结果表明: (1)模拟红松NPP的不确定性高于阔叶树, 但二者的模拟ET的不确定性均较小。阔叶树的NPP和ET对生理生态参数的敏感性总体上都小于红松。(2)无论是红松、阔叶或其他植被类型, 模拟NPP均表现出对叶片碳氮比、细根碳氮比、比叶面积(SLA)和冠层截留系数的敏感性, 这4个参数的高敏感性主要是由模型自身结构所决定的, 与植被类型和研究地区的关系较小。对模拟ET而言, 细根与叶片碳分配比、新茎与新叶碳分配比和SLA均是影响红松和阔叶树ET的敏感参数, 但红松ET主要受参数与参数间的二阶或多阶交互作用的间接影响, 而阔叶树ET则主要是受到敏感参数直接效应的影响。(3)除了上述影响红松和阔叶树碳水通量的共性参数外, 诸如核酮糖-1,5-二磷酸羧化酶中叶氮含量、叶片与细根周转率、所有叶面积与投影叶面积之比等也是对模拟结果有影响的重要参数, 但是其敏感程度随物种不同和研究区不同而不同, 所以这类参数可以根据具体情况进行参数本地化, 对于其他不敏感参数则可以采用模型缺省值。     

Effects of global change on key processes of primary production in marine ecosystems

工业革命以来, 不断加剧的人类活动所引起的大气CO₂浓度增加、温度上升等全球变化问题, 正使得海洋生态系统面临着前所未有的压力。该文通过文献计量的方法分析了国内外的研究现状, 简要地回顾了全球变化对海洋生态系统影响研究的发展简史, 并聚焦海洋暖化、海洋酸化和富营养化与缺氧这三个核心研究方向, 重点阐述了它们对海洋生态系统初级生产的关键过程的影响, 总结了已取得的重要进展以及存在的主要问题, 最后提出前沿展望。     

Asymmetric cytokinin signaling opposes gravitropism in roots

Plants depend on gravity to provide the constant landmark for downward root growth and upward shoot growth. The phytohormone auxin and its cell‐to‐cell transport machinery are central determinants ensuring gravitropic growth. Statolith sedimentation toward gravity is sensed in specialized cells. This positional cue is translated into the polar distribution of PIN auxin efflux carriers at the plasma membrane, leading to asymmetric auxin distribution and consequently, differential growth and organ bending. While we have started to understand the general principles of how primary organs execute gravitropism, we currently lack basic understanding of how lateral plant organs can defy gravitropic responses. Here we briefly review the establishment of the oblique gravitropic set point angle in lateral roots and particularly discuss the emerging role of asymmetric cytokinin signaling as a central anti‐gravitropic signal. Differential cytokinin signaling is co‐opted in gravitropic lateral and hydrotropic primary roots to counterbalance gravitropic root growth.     

Extracellular vesicle‐mediated crosstalk between NPCE cells and TM cells result in modulation of Wnt signalling pathway and ECM remodelling

Primary open‐angle glaucoma is a leading cause of irreversible blindness, often associated with increased intraocular pressure. Extracellular vesicles (EVs) carry a specific composition of proteins, lipids and nucleotides have been considered as essential mediators of cell‐cell communication. Their potential impact for crosstalk between tissues responsible for aqueous humour production and out‐flow is largely unknown. The study objective was to investigate the effects of EVs derived from non‐pigmented ciliary epithelium (NPCE) primary cells on the expression of Wnt proteins in a human primary trabecular meshwork (TM) cells and define the mechanism underlying exosome‐mediated regulation that signalling pathway. Consistent with the results in TM cell line, EVs released by both primary NPCE cells and NPCE cell line showed diminished pGSK3β phosphorylation and decreased cytosolic levels of β‐catenin in primary TM cells. At the molecular level, we showed that NPCE exosome treatment downregulated the expression of positive GSKβ regulator‐AKT protein but increased the levels of GSKβ negative regulator‐PP2A protein in TM cells. NPCE exosome protein analysis revealed 584 miRNAs and 182 proteins involved in the regulation of TM cellular processes, including WNT/β‐catenin signalling pathway, cell adhesion and extracellular matrix deposition. We found that negative modulator of Wnt signalling miR‐29b was abundant in NPCE exosomal samples and treatment of TM cells with NPCE EVs significantly decreased COL3A1 expression. Suggesting that miR‐29b can be responsible for decreased levels of WNT/β‐catenin pathway. Overall, this study highlights a potential role of EVs derived from NPCE cells in modulating ECM proteins and TM canonical Wnt signalling.     

Emperipolesis mediated by CD8+ T cells correlates with biliary epithelia cell injury in primary biliary cholangitis

Primary biliary cholangitis (PBC) is an autoimmune disease characterized by chronic destruction of the bile ducts. A major unanswered question regarding the pathogenesis of PBC is the precise mechanisms of small bile duct injury. Emperipolesis is one of cell‐in‐cell structures that is a potential histological hallmark associated with chronic hepatitis B. This study aimed to clarify the pathogenesis and characteristics of emperipolesis in PBC liver injury. Sixty‐six PBC patients, diagnosed by liver biopsy combined with laboratory test, were divided into early‐stage PBC (stages I and II, n = 39) and late‐stage PBC (stages III and IV, n = 27). Emperipolesis was measured in liver sections stained with haematoxylin‐eosin. The expressions of CK19, CD3, CD4, CD8, CD20, Ki67 and apoptosis of BECs were evaluated by immunohistochemistry or immunofluorescence double labelling. Emperipolesis was observed in 62.1% of patients with PBC, and BECs were predominantly host cells. The number of infiltrating CD3⁺ and CD8⁺ T cells correlated with the advancement of emperipolesis (R² = 0.318, P < .001; R² = 0.060, P < .05). The cell numbers of TUNEL‐positive BECs and double staining for CK19 and Ki67 showed a significant positive correlation with emperipolesis degree (R² = 0.236, P < .001; R² = 0.267, P < .001). We conclude that emperipolesis mediated by CD8⁺ T cells appears to be relevant to apoptosis of BEC and thus may aggravate the further injury of interlobular bile ducts.     

Deficiency of Macf1 in osterix expressing cells decreases bone formation by Bmp2/Smad/Runx2 pathway

Microtubule actin cross‐linking factor 1 (Macf1) is a spectraplakin family member known to regulate cytoskeletal dynamics, cell migration, neuronal growth and cell signal transduction. We previously demonstrated that knockdown of Macf1 inhibited the differentiation of MC3T3‐E1 cell line. However, whether Macf1 could regulate bone formation in vivo is unclear. To study the function and mechanism of Macf1 in bone formation and osteogenic differentiation, we established osteoblast‐specific Osterix (Osx) promoter‐driven Macf1 conditional knockout mice (Macf1^f/fOsx‐Cre). The Macf1^f/fOsx‐Cre mice displayed delayed ossification and decreased bone mass. Morphological and mechanical studies showed deteriorated trabecular microarchitecture and impaired biomechanical strength of femur in Macf1^f/fOsx‐Cre mice. In addition, the differentiation of primary osteoblasts isolated from calvaria was inhibited in Macf1^f/fOsx‐Cre mice. Deficiency of Macf1 in primary osteoblasts inhibited the expression of osteogenic marker genes (Col1, Runx2 and Alp) and the number of mineralized nodules. Furthermore, deficiency of Macf1 attenuated Bmp2/Smad/Runx2 signalling in primary osteoblasts of Macf1^f/fOsx‐Cre mice. Together, these results indicated that Macf1 plays a significant role in bone formation and osteoblast differentiation by regulating Bmp2/Smad/Runx2 pathway, suggesting that Macf1 might be a therapeutic target for bone disease.     

Leaf size of woody dicots predicts ecosystem primary productivity

A key challenge in ecology is to understand the relationships between organismal traits and ecosystem processes. Here, with a novel dataset of leaf length and width for 10 480 woody dicots in China and 2374 in North America, we show that the variation in community mean leaf size is highly correlated with the variation in climate and ecosystem primary productivity, independent of plant life form. These relationships likely reflect how natural selection modifies leaf size across varying climates in conjunction with how climate influences canopy total leaf area. We find that the leaf size?primary productivity functions based on the Chinese dataset can predict productivity in North America and vice‐versa. In addition to advancing understanding of the relationship between a climate‐driven trait and ecosystem functioning, our findings suggest that leaf size can also be a promising tool in palaeoecology for scaling from fossil leaves to palaeo‐primary productivity of woody ecosystems.     

Mouse Sertoli cells isolation by lineage tracing and sorting

Sertoli cells play a key role in spermatogenesis by supporting the germ cells throughout differentiation. The isolation of Sertoli cells is essential to study their functions. However, the close contact of Sertoli cells with other testicular cell types and the high proliferation of contaminating cells are obstacles to obtain pure primary cultures. Current rodent Sertoli cell isolation protocols result in enriched, rather than pure Sertoli cells. Therefore, novel approaches are necessary to improve the purity of Sertoli cell primary cultures. The goal of this study is to obtain pure mouse Sertoli cells using lineage tracing and fluorescence‐activated cell sorting (FACS). We bred the Amh‐Cre mouse line with tdTomato line to generate mice constitutively expressing red fluorescence specifically in Sertoli cells. Primary cultures of Sertoli cells isolated from prepubertal mice showed that 79% of cells expressed tdTomato, as evaluated by fluorescence microscopy and flow cytometry; however, nearly all adherent cells were positive for vimentin. Most of the tomato‐negative cells expressed α‐smooth muscle actin (α‐SMA), a peritubular myoid cell marker, but double‐negative populations were also present. These findings suggest that vimentin lacks Sertoli cell‐specificity and that α‐SMA is not adequate to identify all of the contaminating cells. Upon FACS sorting; however, virtually 100% of the cells were tdTomato positive, expressed vimentin, but not α‐SMA. Prepubertal mice yielded a higher number of Sertoli cells compared to adults, but both could be adequately sorted. In conclusion, our study shows that lineage tracing and sorting is an efficient strategy for acquiring pure populations of murine Sertoli cells.