Evidence for calpains in cancer metastasis

Metastatic dissemination represents the final stage of tumor progression as well as the principal cause of cancer-associated deaths. Calpains are a conserved family of calcium-dependent cysteine proteinases with ubiquitous or tissue-specific expression. Accumulating evidence indicates a central role for calpains in tumor migration and invasion via participating in several key processes, including focal adhesion dynamics, cytoskeletal remodeling, epithelial-to-mesenchymal transition, and apoptosis. Activated after the increased intracellular calcium concentration () induced by membrane channels and extracellular or intracellular stimuli, calpains induce the limited cleavage or functional modulation of various substrates that serve as metastatic mediators. This review covers established literature to summarize the mechanisms and underlying signaling pathways of calpains in cancer metastasis, making calpains attractive targets for aggressive tumor therapies.     

Retracted: Prelamin A overexpression promotes detrusor calcification/aging in urinary incontinence via prelamin A accumulation

Urinary incontinence (UI) is known as a distressing condition particularly among older adults, and negatively associated with health-related quality of life in both males and females. Prelamin A accumulation has been found in all progeroid laminopathies and is obviously linked to cell and organism aging. Therefore, this study was expected to investigate the effect of prelamin A on detrusor on UI. Prelamin A expression in clinical and animal samples was detected. To investigate the degree of prelamin A accumulation and detrusor calcification/aging, the detrusor cells were subcultured separately into low and high passage. The low-passage subculture cells were treated with transfection of overexpressed prelamin A plasmid, and transfection of overexpressed prelamin A plasmid and application of farnesyl transferase inhibitor (FTIs) H-9279, respectively. Zmpste24, Icmt and lamin A/C expression were detected to explore how prelamin A affected detrusor calcification/aging. Prelamin A was overexpressed in aged detrusor cells, indicating prelamin A expression was positively related to the age of subjects. The degree of prelamin A accumulation and detrusor calcification/aging was higher in aged rats and high passage subculture cells. Zmpste24, Icmt and lamin A/C were poorly expressed in cells transfected with overexpressed prelamin A, as well as cell proliferation activity decreased and calcium deposition and apoptotic rate increased. Furthermore, we also found that the effect of overexpressed prelamin A was lost when cells were treated with H-9279. These findings provide evidence that prelamin A overexpression impairs degradation of its farnesylated form, thus causing prelamin A accumulation which induces detrusor calcification/aging in UI.     

Multi‐year stigmatic pollen‐load sampling reveals temporal stability in interspecific pollination of flowers in a subalpine meadow

Co‐flowering plants may commonly experience interspecific pollination. It remains unknown, however, whether interspecific pollination is a largely stochastic process or consistent enough over years to exert selection for traits that can reduce interspecific pollination or ameliorate its deleterious effects on reproduction. To assess the likelihood of this precondition being met, stigmatic pollen loads on 17–34 insect‐pollinated plant species over three consecutive years were scored in a subalpine meadow in southwestern China. Plant species varied significantly in the amount and proportion of heterospecific pollen (HP) on stigmas. Both the number of HP species and the proportion of the pollen load that was HP for each recipient species correlated positively between years (reflected in pairwise correlations for all year‐by‐year combinations). Although inter‐annual variation was smaller for conspecific pollen (CP) than for HP loads, species tended to experience either consistently high or consistently low HP proportions across years. We found that species with higher stigmatic HP proportions generally experienced lower proportional variation in stigmatic HP, an unexpected result if high HP loads are the result of rare stochastic events. The novel finding of between‐year consistency in stigmatic loads of heterospecific pollen suggests that adaption to stigmatic loads of HP is possible, and two divergent strategies may have evolved: HP avoidance and HP tolerance. The observation of temporally consistent differences among species in levels of HP supports the idea that natural selection may be operating either to increase tolerance or to minimize arrival of heterospecific pollen on stigmas in co‐flowering plants. Such adaptations may be important for the maintenance of high levels of local plant diversity in biodiversity hotspots such as our study area.     

Mechanics of the Formation,Interaction, and Evolution of Membrane Tubular Structures

Membrane nanotubes, also known as membrane tethers, play important functional roles in many cellular processes, such as trafficking and signaling. Although considerable progresses have been made in understanding the physics regulating the mechanical behaviors of individual membrane nanotubes, relatively little is known about the formation of multiple membrane nanotubes due to the rapid occurring process involving strong cooperative effects and complex configurational transitions. By exerting a pair of external extraction upon two separate membrane regions, here, we combine molecular dynamics simulations and theoretical analysis to investigate how the membrane nanotube formation and pulling behaviors are regulated by the separation between the pulling forces and how the membrane protrusions interact with each other. As the force separation increases, different membrane configurations are observed, including an individual tubular protrusion, a relatively less deformed protrusion with two nanotubes on its top forming a V shape, a Y-shaped configuration through nanotube coalescence via a zipper-like mechanism, and two weakly interacting tubular protrusions. The energy profile as a function of the separation is determined. Moreover, the directional flow of lipid molecules accompanying the membrane shape transition is analyzed. Our results provide new, to our knowledge, insights at a molecular level into the interaction between membrane protrusions and help in understanding the formation and evolution of intra- and intercellular membrane tubular networks involved in numerous cell activities.     

ESM-1 promotes adhesion between monocytes and endothelial cells under intermittent hypoxia

Intermittent hypoxia (IH), the key property of obstructive sleep apnea (OSA), is closely associated with endothelial dysfunction. Endothelial-cell-specific molecule-1 (ESM-1, Endocan) is a novel, reported molecule linked to endothelial dysfunction. The aim of this study is to evaluate the effect of IH on ESM-1 expression and the role of ESM-1 in endothelial dysfunction. We found that serum concentration of ESM-1, inter-cellular adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1 (VCAM-1) is significantly higher in patients with OSA than healthy volunteers (p < 0.01). The expression of ESM-1, hypoxia-inducible factor-1 alpha (HIF-1α), and vascular endothelial growth factor (VEGF) was significantly increased in human umbilical vein endothelial cells (HUVECs) by treated IH in a time-dependent manner. HIF-1α short hairpin RNA and vascular endothelial growth factor receptor (VEGFR) inhibitor inhibited the expression of ESM-1 in HUVECs. ICAM-1 and VCAM-1 expressions were significantly enhanced under IH status, accompanied by increased monocyte–endothelial cell adhesion rate ( p < 0.001). Accordingly, ESM-1 silencing decreased the expression of ICAM-1 and VCAM-1 in HUVECs, whereas ESM-1 treatment significantly enhanced ICAM-1 expression accompanied by increasing adhesion ability. ESM-1 is significantly upregulated by the HIF-1α/VEGF pathway under IH in endothelial cells, playing a critical role in enhancing adhesion between monocytes and endothelial cells, which might be a potential target for IH-induced endothelial dysfunction.     

Evaluation of reference genes for quantitative real-time PCR analysis of messenger RNAs and microRNAs in rainbow trout Oncorhynchus mykiss under heat stress

We assessed the expression stability of several messenger (m)RNAs and micro (mi)RNAs from liver and head kidney of rainbow trout Oncorhynchus mykiss using high-throughput RNA sequencing (RNA-seq) and miRNA-seq data. Additionally, four commonly used reference genes and one small non-coding RNA (u6) were also selected to identify ideal reference mRNAs and miRNAs for quantitative real-time (qrt)-PCR analysis of heat stress responses. GeNorm, NormFinder, BestKeeper and comparative ΔC_t were employed for analysis of qrt-PCR data to systematically assess the expression stability of candidate mRNAs and miRNAs and stability was ranked using geometric means. β-actin and ef1-α were the most stably expressed reference mRNAs in liver and head kidney, respectively and ssa-mir-26a-5p and ssa-mir-462b-5p were the most stably expressed miRNAs in these tissues. This is the first identification of appropriate reference mRNAs and miRNAs for qrt-PCR analysis of O. mykiss under heat stress.     

Case of a stronger capability of maize seedlings to use ammonium being responsible for the higher 15N recovery efficiency of ammonium compared with nitrate

Plant and Soil - Biocrusts are important functional units in dryland ecosystems. Regarded as ecosystem engineers, cyanobacteria in biocrusts contribute several major physico-chemical and biological...