Differential regulation of cell functions by CSD peptide subdomains

Background

In fibrotic lung diseases, expression of caveolin-1 is decreased in fibroblasts and monocytes. The effects of this deficiency are reversed by treating cells or animals with the caveolin-1 scaffolding domain peptide (CSD, amino acids 82–101 of caveolin-1) which compensates for the lack of caveolin-1. Here we compare the function of CSD subdomains (Cav-A, Cav-B, Cav-C, Cav-AB, and Cav-BC) and mutated versions of CSD (F92A and T90A/T91A/F92A).

Methods

Migration toward the chemokine CXCL12 and the associated expression of F-actin, CXCR4, and pSmad 2/3 were studied in monocytes from healthy donors and SSc patients. Fibrocyte differentiation was studied using PBMC from healthy donors and SSc patients. Collagen I secretion and signaling were studied in fibroblasts derived from the lung tissue of healthy subjects and SSc patients.

Results

Cav-BC and CSD at concentrations as low as 0.01 μM inhibited the hypermigration of SSc monocytes and TGFβ-activated Normal monocytes and the differentiation into fibrocytes of SSc and Normal monocytes. While CSD also inhibited the migration of poorly migrating Normal monocytes, Cav-A (and other subdomains to a lesser extent) promoted the migration of Normal monocytes while inhibiting the hypermigration of TGFβ-activated Normal monocytes. The effects of versions of CSD on migration may be mediated in part via their effects on CXCR4, F-actin, and pSmad 2/3 expression. Cav-BC was as effective as CSD in inhibiting fibroblast collagen I and ASMA expression and MEK/ERK signaling. Cav-C and Cav-AB also inhibited collagen I expression, but in many cases did not affect ASMA or MEK/ERK. Cav-A increased collagen I expression in scleroderma lung fibroblasts. Full effects on fibroblasts of versions of CSD required 5 μM peptide.

Conclusions

Cav-BC retains most of the anti-fibrotic functions of CSD; Cav-A exhibits certain pro-fibrotic functions. Results obtained with subdomains and mutated versions of CSD further suggest that the critical functional residues in CSD depend on the cell type and readout being studied. Monocytes may be more sensitive to versions of CSD than fibroblasts and endothelial cells because the baseline level of caveolin-1 in monocytes is much lower than in these other cell types.     

Genomic Basis of Circannual Rhythm in the European Corn Borer Moth

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Early‐breeding females experience greater telomere loss

Annual reproductive success is often highest in individuals that initiate breeding early, yet relatively few individuals start breeding during this apparently optimal time. This suggests that individuals, particularly females who ultimately dictate when offspring are born, incur costs by initiating reproduction early in the season. We hypothesized that increases in the ageing rate of somatic cells may be one such cost. Telomeres, the repetitive DNA sequences on the ends of chromosomes, may be good proxies of biological wear and tear as they shorten with age and in response to stress. Using historical data from a long‐term study population of dark‐eyed juncos (Junco hyemalis), we found that telomere loss between years was greater in earlier breeding females, regardless of chronological age. There was no relationship between telomere loss and the annual number of eggs laid or chicks that reached independence. However, telomere loss was greater when temperatures were cooler, and cooler temperatures generally occur early in the season. This suggests that environmental conditions could be the primary cause of accelerated telomere loss in early breeders.     

KIF14 promotes tumor progression and metastasis and is an independent predictor of poor prognosis in human gastric cancer

The kinesin family member 14 (KIF14) is a potential oncogene and is involved in the metastasis of various cancers. Nevertheless, its function in gastric cancer (GC) remains poorly defined. The expression of KIF14 was examined in GC cell lines and a clinical cohort of GC specimens by qPCR, western blotting and immunohistochemistry (IHC) staining. The relationship between KIF14 expression and the clinicopathological features was analyzed. The effect of KIF14 on cell proliferation, colony formation, invasion and migration were investigated in vitro and in vivo. The expression of KIF14 was significantly increased in the GC tissues and cell lines. High KIF14 expression was associated with tumor stage, tumor-node-metastasis (TNM) stage and metastasis. KIF14 was an independent prognostic factor for the overall survival of GC, and a higher expression of KIF14 predicted a poorer survival. KIF14 silencing resulted in attenuated proliferation, invasion and migration in human gastric cancer cells, whereas KIF14 ectopic expression facilitated these biological abilities. Notably, the depressed expression of KIF14 inhibited Akt phosphorylation, while overexpressed KIF14 augmented Akt phosphorylation. Additionally, there was a significant correlation between the expression of KIF14 and p?Akt in GC tissues. Importantly, the proliferation, invasion and migration of the GC cells, which was promoted by KIF14 overexpression, was abolished by the Akt inhibitor MK-2206, while Akt overexpression greatly rescued the effects induced by KIF14 knockdown. Our findings are the first to demonstrate that KIF14 is overexpressed in GC, is correlated with poor prognosis and plays a crucial role in the progression and metastasis of GC.     

我国涉天鹅属鸟类死亡案件分析及防控对策研究

我国有分布的天鹅属所有种(Cygnusspp.)均为国家Ⅱ级重点保护野生动物,根据中华人民共和国刑法,非法猎捕、杀害珍贵濒危野生动物构成刑事犯罪。然而,天鹅死亡案件仍时有发生。本文分析2000至2016年有统计的我国天鹅死亡案件发现,每年11月至翌年1月是涉天鹅案件的高发时期;毒杀为致死主因;案件多发生于我国行政区划交界处。因此,应于迁徙越冬季节重点加强高案发地点的侦查监管;加强克百威(呋喃丹)为代表的高毒农药管控;建立迁徙季节多地区执法联动机制。     

东亚-澳大利西亚候鸟迁飞区中杓鹬 的迁徙追踪

追踪候鸟的迁徙活动是全面认识其生活史年周期的重要途径。中杓鹬(Numeniusphaeopus)在全球广泛分布,但在东亚-澳大利西亚候鸟迁飞区的迁徙活动一直缺乏追踪研究。2018年2月,在澳大利亚西北部的布鲁姆为捕捉到的中杓鹬成鸟佩戴平台发射终端或全球定位系统-全球移动通讯系统追踪器,以确定其迁徙日程、迁徙路线以及迁徙停歇地和繁殖地的地理位置。我们从成功追踪的7只个体获取了6 378条精度高于1 km的位点数据。分析结果表明,在春季,中杓鹬的迁徙时长为(36±4)d,其间在1～3个迁徙停歇地的停留日期为(23±2)d,从越冬地到繁殖地的迁徙距离为(9 795±346)km(n=7)。追踪的中杓鹬在俄罗斯东部和中部区域繁殖,不同个体的繁殖地纬度相近而经度范围较广。在秋季,中杓鹬的迁徙时长为(90±27)d,相比春季迁徙时长更长;其间,在2～4个迁徙停歇地停留(79±29)d,从繁殖地到越冬地的迁徙距离为(10 101±520)km(n=5)。无论在春季还是秋季迁徙,迁徙停歇地广泛分布于东亚、东南亚沿海及内陆区域。大部分个体春季和秋季的迁徙路线相近,成功追踪的个体均在秋季返回了上一年的越冬地,这表明中杓鹬对越冬地具有很高的忠诚度。