Critical role of extracellular vesicles in modulating the cellular effects of cytokines

Under physiological and pathological conditions, extracellular vesicles (EVs) are present in the extracellular compartment simultaneously with soluble mediators. We hypothesized that cytokine effects may be modulated by EVs, the recently recognized conveyors of intercellular messages. In order to test this hypothesis, human monocyte cells were incubated with CCRF acute lymphoblastic leukemia cell line-derived EVs with or without the addition of recombinant human TNF, and global gene expression changes were analyzed. EVs alone regulated the expression of numerous genes related to inflammation and signaling. In combination, the effects of EVs and TNF were additive, antagonistic, or independent. The differential effects of EVs and TNF or their simultaneous presence were also validated by Taqman assays and ELISA, and by testing different populations of purified EVs. In the case of the paramount chemokine IL-8, we were able to demonstrate a synergistic upregulation by purified EVs and TNF. Our data suggest that neglecting the modulating role of EVs on the effects of soluble mediators may skew experimental results. On the other hand, considering the combined effects of cytokines and EVs may prove therapeutically useful by targeting both compartments at the same time.     

福田红树林桐花树和秋茄的生长过程研究

对深圳福田红树林群落两个优势种桐花树（Ａｅｇｉｃｅｒａｓｃｏｒｎｉｃｕｌａｔｕｍ）和秋茄（Ｋａｎｄｅｌｉ－ａｃａｎｄｅｌ）进行横剖树干解析，研究这两个树种的胸径、地径、树高、材积生长量的年变化规律及形数年变化规律，结果为：胸径、地径、树高、材积生长量呈镊合状曲线态；其年生长量一般在其最大值的５０％～９８％之间；各种平均生长量随年龄的增加而平缓地增加，近峰值而未及，可见两树种有相当长的成熟及衰老期，它们的现存年龄为２０ａ左右；两树种的基部形数不随年龄的增加而呈规律性的变化，很难确定其经验形数值     

A specific requirement for PDGF-C in palate formation and PDGFR-alpha signaling

PDGF-C is a member of the platelet-derived growth factor (PDGF) family, which signals through PDGF receptor (PDGFR) alphaalpha and alphabeta dimers. Here we show that Pdgfc(-/-) mice die in the perinatal period owing to feeding and respiratory difficulties associated with a complete cleft of the secondary palate. This phenotype was less severe than that of Pdgfra(-/-) embryos. Pdgfc(-/-) Pdgfa(-/-) embryos developed a cleft face, subepidermal blistering, deficiency of renal cortex mesenchyme, spina bifida and skeletal and vascular defects. Complete loss of function of both ligands, therefore, phenocopied the loss of PDGFR-alpha function, suggesting that both PDGF-A and PDGF-C signal through PDGFR-alpha to regulate the development of craniofacial structures, the neural tube and mesodermal organs. Our results also show that PDGF-C signaling is a new pathway in palatogenesis, different from, and independent of, those previously implicated.     

Heritable germline epimutation of MSH2 in a family with hereditary nonpolyposis colorectal cancer

Epimutations in the germline, such as methylation of the MLH1 gene, may contribute to hereditary cancer syndrome in human, but their transmission to offspring has never been documented. Here we report a family with inheritance, in three successive generations, of germline allele-specific and mosaic hypermethylation of the MSH2 gene, without evidence of DNA mismatch repair gene mutation. Three siblings carrying the germline methylation developed early-onset colorectal or endometrial cancers, all with microsatellite instability and MSH2 protein loss. Clonal bisulfite sequencing and pyrosequencing showed different methylation levels in different somatic tissues, with the highest level recorded in rectal mucosa and colon cancer tissue, and the lowest in blood leukocytes. This mosaic state of germline methylation with different tissue distribution could act as the first hit and provide a mechanism for genetic disease inheritance that may deviate from the mendelian pattern and be overlooked in conventional leukocyte-based genetic diagnosis strategy.     

Reputed rat scotophobin prepared by a solid-phase procedure shown invalid by comparison with a product derived from a classical synthesis on the basis of physical and biological properties

Zusammenfassung Eine Synthese von Scotophobin mit klassischen Methoden ergab ein Produkt, das sich vom natürlichen Peptid hinsichtlich seiner biologischen, chromatographischen und physiologischen Eigenschaften unterschied. Es wird daraus gefolgert, dass die für das natürliche Produkt vorgeschlagene Strukturformel nicht korrekt ist.     

The synthesis of a peptide having the structure attributed to a sound habituating material.

A peptide isolated from rats habituated to a sound stimulus has been given the structure (see article) Glu-Ala-Gly-Tyr-Ser-Lys-OH. A synthesis of this compound afforded a product that different from the natural material on the basis of chromatographic and physiological comparisons. The proposed sequence must therefore be in error.     

双酚A对微小小环藻的毒性效应

以微小小环藻(Cyclotella caspia)为测试藻种,研究了不同浓度的双酚A对微小小环藻的急性毒性效应。在双酚A(4,6,8,10,12 mg/L)作用下,藻细胞生长受到不同程度的抑制;藻细胞叶绿素a含量随着双酚A浓度的增加呈下降趋势;藻细胞SOD活性随着双酚A浓度和作用时间的变化基本呈现为从诱导到抑制的动态过程;4~6 mg/L双酚A对藻细胞形态影响不大,8~12 mg/L双酚A可导致藻细胞不易分裂,细胞体积增大,细胞内含物增多,细胞器受到不同程度的破坏。