TGF-β isoforms inhibit hepatitis C virus propagation in transforming growth factor beta/SMAD protein signalling pathway dependent and independent manners

Transforming growth factor beta (TGF-β) plays an important role in the viral liver disease progression via controlling viral propagation and mediating inflammation-associated responses. However, the antiviral activities and mechanisms of TGF-β isoforms, including TGF-β1, TGF-β2 and TGF-β3, remain unclear. Here, we demonstrated that all of the three TGF-β isoforms were increased in Huh7.5 cells infected by hepatitis C virus (HCV), but in turn, the elevated TGF-β isoforms could inhibit HCV propagation with different potency in infectious HCV cell culture system. TGF-β isoforms suppressed HCV propagation through interrupting several different stages in the whole HCV life cycle, including virus entry and intracellular replication, in TGF-β/SMAD signalling pathway–dependent and TGF-β/SMAD signalling pathway–independent manners. TGF-β isoforms showed additional anti-HCV activities when combined with each other. However, the elevated TGF-β1 and TGF-β2, not TGF-β3, could also induce liver fibrosis with a high expression of type I collagen alpha-1 and α-smooth muscle actin in LX-2 cells. Our results showed a new insight into TGF-β isoforms in the HCV-related liver disease progression.     

Down-regulated LINC00115 inhibits prostate cancer cell proliferation and invasion via targeting miR-212-5p/FZD5/Wnt/β-catenin axis

Prostate cancer is the second most frequent malignancy in men worldwide, and its incidence is increasing. Therefore, it is urgently required to clarify the underlying mechanisms of prostate cancer. Although the long non-coding RNA LINC00115 was identified as an oncogene in several cancers, the expression and function of LINC00115 in prostate cancer have not been explored. Our results showed that LINC00115 was significantly up-regulated in prostate cancer tissues, which was significantly associated with a poor prognosis for prostate cancer patients. Functional studies showed that knockdown LINC00115 inhibited cell proliferation and invasion. In addition, LINC00115 served as a competing endogenous RNA (ceRNA) through sponging miR-212-5p to release Frizzled Family Receptor 5 (FZD5) expression. The expression of miR-212-5p was noticeably low in tumour tissues, and FZD5 expression level was down-regulated with the knockdown of LINC00115. Knockdown LINC00115 inhibited the Wnt/β‑catenin signalling pathway by inhibiting the expression of FZD5. Rescue experiments further showed that LINC00115 inhibits prostate cancer cell proliferation and invasion via targeting miR-212-5p/ FZD5/ Wnt/β-catenin axis. The present study provided clues that LINC00115 may be a promising novel therapeutic target for prostate cancer patients.     

Modulation of physiological performance by temperature and salinity in the sugar kelp Saccharina latissima

The sugar kelp Saccharina latissima experiences a wide range of environmental conditions along its geographical and vertical distribution range. Temperature and salinity are two critical drivers influencing growth, photosynthesis and biochemical composition. Moreover, interactive effects might modify the results described for single effects. In shallow water coastal systems, exposure to rising temperatures and low salinity are expected as consequence of global warming, increased precipitation and coastal run‐off. To understand the acclimation mechanisms of S. latissima to changes in temperature and salinity and their interactions, we performed a mechanistic laboratory experiment in which juvenile sporophytes from Brittany, France were exposed to a combination of three temperatures (0, 8 and 15°C) and two salinity levels (20 and 30 psu (practical salinity units)). After a temperature acclimation of 7 days, sporophytes were exposed to low salinity (20 psu) for a period of 11 days. Growth, and maximal quantum yield of photosystem II (Fv/Fm), pigments, mannitol content and C:N ratio were measured over time. We report for the first time in S. latissima a fivefold increase in the osmolyte mannitol in response to low temperature (0°C) compared to 8 and 15°C that may have ecological and economic implications. Low temperatures significantly affected all parameters, mostly in a negative way. Chlorophyll a, the accessory pigment pool, growth and Fv/Fm were significantly lower at 0°C, while the de‐epoxidation state of the xanthophyll cycle was increased at both 0 and 8°C compared to 15°C. Mannitol content and growth decreased with decreased salinity; in contrast, pigment content and Fv/Fm were to a large extent irresponsive to salinity. In comparison to S. latissima originating from an Arctic population, despite some reported differences, this study reveals a remarkably similar impact of temperature and salinity variation, reflecting the large degree of adaptability in this species.     

AutoWM: a novel domain-specific tool for universal multi-/many-core accelerations of the WRF cloud microphysics

Cluster Computing - In large-scale atmospheric simulations, microphysics parameterization often takes a large portion of simulation time and usually consists of dozens of parameterization schemes....     

PRPF6 promotes androgen receptor/androgen receptor-variant 7 actions in castration-resistant prostate cancer cells

Androgen receptor (AR) and its variants play vital roles in development and progression of prostate cancer. To clarify the mechanisms involved in the enhancement of their actions would be crucial for understanding the process in prostate cancer and castration-resistant prostate cancer transformation. Here, we provided the evidence to show that pre-mRNA processing factor 6 (PRPF6) acts as a key regulator for action of both AR full length (AR-FL) and AR variant 7 (AR-V7), thereby participating in the enhancement of AR-FL and AR-V7-induced transactivation in prostate cancer. In addition, PRPF6 is recruited to cis-regulatory elements in AR target genes and associates with JMJD1A to enhance AR-induced transactivation. PRPF6 also promotes expression of AR-FL and AR-V7. Moreover, PRPF6 depletion reduces tumor growth in prostate cancer-derived cell lines and results in significant suppression of xenograft tumors even under castration condition in mouse model. Furthermore, PRPF6 is obviously highly expressed in human prostate cancer samples. Collectively, our results suggest PRPF6 is involved in enhancement of oncogenic AR signaling, which support a previously unknown role of PRPF6 during progression of prostate cancer and castration-resistant prostate cancers.     

Lyciumamide A,a dimer of phenolic amide,protects against NMDA-induced neurotoxicity and potential mechanisms in vitro

Journal of Molecular Histology - Currently, the excessive activation of N-methyl-D-aspartate receptors (NMDARs) is considered to be a crucial mechanism of brain injury. Lycium barbarum A (LyA) is a...     

A formalism for modelling traction forces and cell shape evolution during cell migration in various biomedical processes

The phenomenological model for cell shape deformation and cell migration Chen (BMM 17:1429–1450, 2018), Vermolen and Gefen (BMM 12:301–323, 2012), is extended with the incorporation of cell traction forces and the evolution of cell equilibrium shapes as a result of cell differentiation. Plastic deformations of the extracellular matrix are modelled using morphoelasticity theory. The resulting partial differential differential equations are solved by the use of the finite element method. The paper treats various biological scenarios that entail cell migration and cell shape evolution. The experimental observations in Mak et al. (LC 13:340–348, 2013), where transmigration of cancer cells through narrow apertures is studied, are reproduced using a Monte Carlo framework.

     

A multiscale model for multiple platelet aggregation in shear flow

Biomechanics and Modeling in Mechanobiology - We developed a multiscale model for simulating aggregation of multiple, free-flowing platelets in low–intermediate shear viscous flow, in which...     

国家公园陆地自然生态系统完整性与原真性评价方法探索: 以钱江源国家公园体制试点为例

中国建立国家公园的目的是保护自然生态系统的完整性和原真性, 促进生物多样性保护。国家公园的完整性和原真性评价是国家公园的布局规划、边界范围确定以及功能区划等研究的前提条件。为了评估国家公园自然生态系统完整性和原真性状态, 本文基于陆地自然生态系统的结构和功能, 通过指标筛选、专家咨询、指标量化和建立综合评价模型, 构建了陆地自然生态系统完整性与原真性的评价指标体系及其量化评价方法。该评价方法包括5个自然生态系统完整性指标、5个自然生态系统原真性指标和2个综合评价指标。以浙江省钱江源国家公园体制试点为例, 本文初步评估了其生态系统完整性与原真性状态, 并对评价结果进行了分级。按照本研究的评价方法, 钱江源国家公园体制试点的自然生态系统完整性评价结果为52.83%, 评价等级为较差; 自然生态系统原真性评价结果为87.06%, 评价等级为好。钱江源国家公园体制试点有待关注和提升的指标有保护区域完整性指数(27.00%)和旗舰种适宜生境完整性指数(53.04%)。最后, 本文结合研究区域评价结果对生态系统完整性和原真性领域应关注的问题进行了讨论。该自然生态系统完整性和原真性评价方法可提供一种评价指标覆盖较全面、数据易获取, 且评价结果易被决策者和管理者理解的评价思路。