Inhibition of ER stress attenuates kidney injury and apoptosis induced by 3-MCPD via regulating mitochondrial fission/fusion and Ca2+ homeostasis

Cell Biology and Toxicology - 3-Chloro-1, 2-propanediol (3-MCPD) is a food-borne toxic substance well-known for more than 40 years that is mainly associated with nephrotoxicity. A better...     

Impact of genetic variants in IL-2RA and IL-2RB on breast cancer risk in Chinese Han women

The expression of IL-2RA and IL-2RB was correlated with breast cancer (BC) progression. However, there is no literature investigating the association of IL-2RA and IL-2RB polymorphisms with BC predisposition among Chinese Han Women. Seven SNPs in IL-2RA and IL-2RB were genotyped by Agena MassARRAY platform among 553 BC patients and 550 healthy controls. Odds ratios (OR) and 95% confidence interval (CI) adjusted for age were calculated for the effect of IL-2RA and IL-2RB variants on BC susceptibility. IL-2RA rs12722498 was a protective factor for BC occurrence (OR?=?0.70, p?=?0.019), especially in subjects with age?≤?52 years (OR?=?0.55, p?=?0.004). IL-2RA rs12569923 (OR?=?9.07, p?=?0.033), IL-2RB rs2281089 (OR?=?0.67, p?=?0.043) and rs9607418 (OR?=?0.59, p?=?0.012) were related to the incidence of estrogen receptor positive (ER?+) BC. IL-2RB rs3218264 (OR?=?1.38, p?=?0.010) and rs9607418 (OR?=?0.56, p?=?0.009) were associated with the risk of developing progesterone receptor positive (PR?+) BC. Rs2281089 (OR?=?1.54, p?=?0.012) and rs1573673 (OR?=?0.72, p?=?0.035) were correlated to Ki-67 level. Moreover, IL-2RB rs2281089 (OR?=?0.72, p?=?0.022) showed a reduced risk of BC metastasis, and IL-2RA rs12722498 (OR?=?0.54, p?=?0.030) had a lower frequency in BC patients with tumor size?>?2 cm. Our study identified the potential effect of genetic variations in IL-2RA and IL-2RB on BC susceptibility and/or BC clinicopathologic indicators among Chinese Han Women.

     

Consumer-driven nutrient release to the water by a small omnivorous fish enhanced ramet production but reduced the growth rate of the submerged macrophyte Vallisneria denseserrulata (Makino) Makino

Small fish are highly associated with submerged macrophytes but may potentially hamper their growth due to nutrient excretion that stimulate growth of phytoplankton and periphyton growth. We conducted a mesocosm experiment to elucidate the effects of the small omnivore Chinese bitterling Acheilognathus macropterus on the growth of phytoplankton, periphyton and the submerged macrophyte Vallisneria denseserrulata. The treatments were fishless as well as low (LF) and high (HF) fish density. We found that the concentrations of nutrients and the phytoplankton biomass increased substantially in both fish treatments, leading to a significantly higher light attenuation compared with the control. Moreover, bitterling substantially enhanced the biomass of periphyton on plant leaves. Consequently, the relative growth rate (RGR) of V. denseserrulata was significantly suppressed in HF, while RGR in the LF treatment did not differ significantly from the controls. However, the bitterling also stimulated the ramet production of V. denseserrulata, significantly. Our results indicate that Chinese bitterling reduce the RGR of V. denseserrulata under high fish density condition. Therefore, the density of Chinese bitterling should be kept low in order to reduce the negative effects of the fish on the RGR of submerged macrophytes (e.g. V. denseserrulata), when restoring lakes by plant transplantation.

     

An inducible constitutive expression system in Bombyx mori mediated by phiC31 integrase

Inducible gene-expression systems play important roles in gene functional assays in the post-genome era. Streptomyces phage-derived phiC31 integrase, which mediates an irreversible site-specific cassette exchange between the phage attachment site (attP) and the bacterial attachment site (attB), provides a promising option for the construction of a controllable gene-expression system. Here, we report a phiC31 integrase-mediated promoter flip system (FLIP) for the inducible expression of target genes in silkworm (Bombyx mori). First, we constructed a FLIP reporter system, in which a BmAct4 promoter with enhanced translational efficiency was flanked by the attB and attP sites in a head-to-head orientation and further linked in a reverse orientation to a DsRed reporter gene. The coexpression of a C-terminal modified phiC31-NLS integrase carrying a simian virus 40 (SV40) nuclear localization signal (NLS) effectively flipped the BmAct4 promoter through an attB/attP exchange, thereby activating the downstream expression of DsRed in a silkworm embryo-derived cell line, BmE. Subsequently, the FLIP system, together with a system continuously expressing the phiC31-NLS integrase, was used to construct binary transgenic silkworm lines. Hybridization between FLIP and phiC31-NLS transgenic silkworm lines resulted in the successful flipping of the BmAct4 promoter, with an approximately 39% heritable transformation efficiency in silkworm offspring, leading to the constitutive and high-level expression of DsRed in silkworms, which accounted for approximately 0.81% of the silkworm pupal weight. Our successful development of the FLIP system offers an effective alternative for manipulating gene expression in silkworms and other lepidopteran species.     

Autophagy in plants: Physiological roles and post‐translational regulation

In eukaryotes, autophagy helps maintain cellular homeostasis by degrading and recycling cytoplasmic materials via a tightly regulated pathway.Over the past few decades, significant progress has been made towards understanding the physiological functions and molecular regulation of autophagy in plant cells. Increasing evidence indicates that autophagy is essential for plant responses to several developmental and environmental cues, functioning in diverse processes such as senescence, male fertility, root meristem maintenance, responses to nutrient starvation,and biotic and abiotic stress. Recent studies have demonstrated that, similar to nonplant systems,the modulation of core proteins in the plant autophagy machinery by posttranslational modifications such as phosphorylation, ubiquitination,lipidation, S-sulfhydration, S-nitrosylation, and acetylation is widely involved in the initiation and progression of autophagy. Here, we provide an overview of the physiological roles and posttranslational regulation of autophagy in plants.     

Targeted sequencing and integrative analysis of 3,195 Chinese patients with neurodevelopmental disorders prioritized 26 novel candidate genes

Neurodevelopmental disorders(NDDs) are a set of complex disorders characterized by diverse and cooccurring clinical symptoms. The genetic contribution in patients with NDDs remains largely unknown.Here, we sequence 519 NDD-related genes in 3,195 Chinese probands with neurodevelopmental phenotypes and identify 2,522 putative functional mutations consisting of 137 de novo mutations(DNMs) in 86 genes and 2,385 rare inherited mutations(RIMs) with 22 X-linked hemizygotes in 13 genes, 2 homozygous mutations in 2 genes and 23 compound heterozygous mutations in 10 genes. Furthermore, the DNMs of16,807 probands with NDDs are retrieved from public datasets and combine in an integrated analysis with the mutation data of our Chinese NDD probands by taking 3,582 in-house controls of Chinese origin as background. We prioritize 26 novel candidate genes. Notably, six of these genes d ITSN1, UBR3, CADM1,RYR3, FLNA, and PLXNA3 d preferably contribute to autism spectrum disorders(ASDs), as demonstrated by high co-expression and/or interaction with ASD genes confirmed via rescue experiments in a mouse model. Importantly, these genes are differentially expressed in the ASD cortex in a significant manner and involved in ASD-associated networks. Together, our study expands the genetic spectrum of Chinese NDDs,further facilitating both basic and translational research.