High expression of NEK2 promotes lung cancer progression and drug resistance and is regulated by mutant EGFR

Molecular and Cellular Biochemistry - An increasing amount of research showed that endothelial cells (ECs) play crucial role in vascular disorders such as atherosclerosis (AS). LncRNA OIP5-AS1 and...     

Genomic insights into the adaptation and evolution of the nautilus,an ancient but evolving “living fossil”

The nautilus, commonly known as a “living fossil,” is endangered and may be at risk of extinction. The lack of genomic information hinders a thorough understanding of its biology and evolution, which can shed light on the conservation of this endangered species. Here, we report the first high-quality chromosome-level genome assembly of Nautilus pompilius. The assembled genome size comprised 785.15 Mb. Comparative genomic analyses indicated that transposable elements (TEs) and large-scale genome reorganizations may have driven lineage-specific evolution in the cephalopods. Remarkably, evolving conserved genes and recent TE insertion activities were identified in N. pompilius, and we speculate that these findings reflect the strong adaptability and long-term survival of the nautilus. We also identified gene families that are potentially responsible for specific adaptation and evolution events. Our study provides unprecedented insights into the specialized biology and evolution of N. pompilius, and the results serve as an important resource for future conservation genomics of the nautilus and closely related species.     

A novel framework for evaluating in situ breeding management strategies in endangered populations

Conservation breeding management aims to reduce inbreeding and maximize the retention of genetic diversity in endangered populations. However, breeding management of wild populations is still rare, and there is a need for approaches that provide data-driven evidence of the likelihood of success of alternative in situ strategies. Here, we provide an analytical framework that uses in silico simulations to evaluate, for real wild populations, (i) the degree of population-level inbreeding avoidance, (ii) the genetic quality of mating pairs, and (iii) the potential genetic benefits of implementing two breeding management strategies. The proposed strategies aim to improve the genetic quality of breeding pairs by splitting detrimental pairs and allowing the members to re-pair in different ways. We apply the framework to the wild population of the Critically Endangered helmeted honeyeater by combining genomic data and field observations to estimate the inbreeding (i.e., pair-kinship) and genetic quality (i.e., Mate Suitability Index) of all mating pairs for seven consecutive breeding seasons. We found no evidence of population-level inbreeding avoidance and that ~91.6% of breeding pairs were detrimental to the genetic health of the population. Furthermore, the framework revealed that neither proposed management strategy would significantly improve the genetic quality or reduce inbreeding of the mating pairs in this population. Our results demonstrate the usefulness of our analytical framework for testing the efficacy of different in situ breeding management strategies and for making evidence-based management decisions.     

Natural variation in cytokinin maintenance improves salt tolerance in apple rootstocks

Plants experiencing salt‐induced stress often reduce cytokinin levels during the early phases of stress‐response. Interestingly, we found that the cytokinin content in the apple rootstock “robusta” was maintained at a high level under salt stress. Through screening genes involved in cytokinin biosynthesis and catabolism, we found that the high expression levels of IPT5b in robusta roots were involved in maintaining the high cytokinin content. We identified a 42 bp deletion in the promoter region of IPT5b, which elevated IPT5b expression levels, and this deletion was linked to salt tolerance in robusta×M.9 segregating population. The 42 bp deletion resulted in the deletion of a Proline Response Element (ProRE), and our results suggest that ProRE negatively regulates IPT5b expression in response to proline. Under salt stress, the robusta cultivar maintains high cytokinin levels as IPT5b expression cannot be inhibited by proline due to the deletion of ProRE, leading to improve salt tolerance.     

伸展素在黄瓜胞壁中的转化及其与羟脯氨酸和异联酪氨酸的关系

用~(14)C-Pro和~3H_2-Tyr离体暗培养黄瓜子叶,发现细胞质、SECW和RCW中的Hyp/Pro和Idt/Tyr都随时间呈线性增加。这两种比值后两者高于前者,而两种比值增加速度之比在胞质部分最大、RCW中最小。表明在胞质和胞壁中都有Pro羟化和Tyr异联化过程,但羟化作用主要发生在胞质中,异联化主要在RCW中。 理化处理(高渗溶液和CHM)和放射性示踪证明胞质中存在HRGP库;它被分泌到胞壁后,先以离子键与壁结合,后转变为共价键与壁结合的伸展素。     

A Water‐Soluble Cu Complex as Molecular Catalyst for Electrocatalytic CO2 Reduction on Graphene‐Based Electrodes

A structurally simple molecular 1,10‐phenanthroline‐Cu complex on a mesostructured graphene matrix that can be active and selective toward CO₂ reduction over H₂ evolution in an aqueous solution is reported. The active sites consist of Cu(I) center in a distorted trigonal bipyramidal geometry, which enables the adsorption of CO₂ with η¹‐COO‐like configuration to commence the catalysis, with a turnover frequency of ≈45 s^?1 at ?1 V versus reversible hydrogen electrode. Using in situ infrared spectroelectrochemical investigation, it is demonstrated that the Cu complex can be reversibly heterogenized near the graphene surface via potential control. An increase of electron density in the complex is observed as a result of the interaction from the electric field, which further tunes the electron distribution in the neighboring CO₂. It is also found that the mesostructure of graphene matrix favored CO₂ reduction on the Cu center over hydrogen evolution by limiting mass transport from the bulk solution to the electrode surface.     

Associations of type 2 diabetes with common variants in PPARD and the modifying effect of vitamin D among middle-aged and elderly Chinese

Background

Previous studies have identified that variants in peroxisome proliferator-activated receptor PPAR-δ (PPARD), a target gene of vitamin D, were significantly associated with fasting glucose and insulin sensitivity in European populations. This current study sought to determine (1) whether the genetic associations of PPARD variants with type 2 diabetes and its related traits could be replicated in Chinese Han population, and (2) whether the associations would be modified by the effect of vitamin D status.

Methods and Findings

We genotyped 9 tag single nucleotide polymorphisms (SNPs) that cover the gene of PPARD (rs2267664, rs6902123, rs3798343, rs2267665, rs2267668, rs2016520, rs2299869, rs1053049, and rs9658056) and tested their associations with type 2 diabetes risk and its related traits, including fasting glucose, insulin and HbA1c in 3,210 Chinese Hans. Among the 9 PPARD tag SNPs, rs6902123 was significantly associated with risk of type 2 diabetes (odds ratio 1.75 [95%CI 1.22–2.53]; P = 0.0025) and combined type 2 diabetes and impaired fasting glucose (IFG) (odds ratio 1.47 [95%CI 1.12–1.92]; P = 0.0054). The minor C allele of rs6902123 was associated with increased levels of fasting glucose (P = 0.0316) and HbA1c (P = 0.0180). In addition, we observed that vitamin D modified the effect of rs6902123 on HbA1c (P for interaction = 0.0347).

Conclusions/Significance

Our findings demonstrate that common variants in PPARD contribute to the risk of type 2 diabetes in Chinese Hans, and provided suggestive evidence of interaction between 25(OH)D levels and PPARD-rs6902123 on HbA1c.     

不同强度运动对大鼠心肌细胞凋亡的影响

通过比较不同强度负荷运动中大鼠心肌细胞的凋亡及其相关基因B细胞淋巴瘤-2(Bcl-2)表达变化的实验研究,试图找出它们之间相互关系的一般规律,为训练制定合理的、适宜的运动负荷提供理论依据.采用8周龄雄性SD大鼠30只,随机分为安静对照组(NC)、中等强度运动组(ME)和大强度运动组(HE),测定心肌细胞的凋亡指数和相关基因B细胞淋巴瘤-2,采用HE染色法观察心肌细胞.结果表明:中等强度运动组和大强度运动组的心肌都有细胞凋亡现象.中等强度运动组的心肌细胞凋亡指数显著升高且差异具有显著性意义(P<0.05),不同强度运动组差异无统计学意义.3组均有Bcl-2表达,中等强度运动组和安静对照组相比具有极显著性差异(P<0.01),大强度运动组和安静对照组相比有显著性差异(P<0.05),大强度运动组表达显著低于中等强度运动组(P<0.05).不适宜的运动负荷会造成大鼠心肌细胞凋亡增加,并且可能参与心肌的损害过程.     

Phase II trial of hu14.18-IL2 for patients with metastatic melanoma

Phase I testing of the hu14.18-IL2 immunocytokine in melanoma patients showed immune activation, reversible toxicities, and a maximal tolerated dose of 7.5?mg/m²/day. In this phase II study, 14 patients with measurable metastatic melanoma were scheduled to receive hu14.18-IL2 at 6?mg/m²/day as 4-h intravenous infusions on Days 1, 2, and 3 of each 28?day cycle. Patients with stable disease (SD) or regression following cycle 2 could receive two additional treatment cycles. The primary objective was to evaluate antitumor activity and response duration. Secondary objectives evaluated adverse events and immunologic activation. All patients received two cycles of treatment. One patient had a partial response (PR) [1 PR of 14 patients?=?response rate of 7.1?%; confidence interval, 0.2?C33.9?%], and 4 patients had SD and received cycles 3 and 4. The PR and SD responses lasted 3?C4?months. All toxicities were reversible and those resulting in dose reduction included grade 3 hypotension (2 patients) and grade 2 renal insufficiency with oliguria (1 patient). Patients had a peripheral blood lymphocytosis on Day 8 and increased C-reactive protein. While one PR in 14 patients met protocol criteria to proceed to stage 2 and enter 16 additional patients, we suspended stage 2 due to limited availability of hu14.18-IL2 at that time and the brief duration of PR and SD. We conclude that subsequent testing of hu14.18-IL2 should involve melanoma patients with minimal residual disease based on compelling preclinical data and the confirmed immune activation with some antitumor activity in this study.     

Influence of introduced arbuscular mycorrhizal fungi and phosphorus sources on plant traits,soil properties,and rhizosphere microbial communities in organic legume-flax rotation

Plant and Soil - We identify P management strategies combining arbuscular mycorrhizal fungal (AMF) inoculation with rock phosphate or composted manure for intensive organic grain-production...