Mini-chromosome maintenance complexes form a filament to remodel DNA structure and topology.

Deregulation of mini-chromosome maintenance (MCM) proteins is associated with genomic instability and cancer. MCM complexes are recruited to replication origins for genome duplication. Paradoxically, MCM proteins are in excess than the number of origins and are associated with chromatin regions away from the origins during G1 and S phases. Here, we report an unusually wide left-handed filament structure for an archaeal MCM, as determined by X-ray and electron microscopy. The crystal structure reveals that an α-helix bundle formed between two neighboring subunits plays a critical role in filament formation. The filament has a remarkably strong electro-positive surface spiraling along the inner filament channel for DNA binding. We show that this MCM filament binding to DNA causes dramatic DNA topology change. This newly identified function of MCM to change DNA topology may imply a wider functional role for MCM in DNA metabolisms beyond helicase function. Finally, using yeast genetics, we show that the inter-subunit interactions, important for MCM filament formation, play a role for cell growth and survival

The clinical effect of a strategy called transcystic gallbladder-preserving cholecystolithotomy based on endoscopic retrograde cholangiopancreatography for cholecystolithiasis: A retrospective study from a single center

BackgroundCholedocholithiasis complicated with cholecystolithiasis is a common disease. This study explores a novel strategy, called ERCP-based transcystic gallbladder-preserving cholecystolithotomy, for the simultaneous removal of common bile duct stones and gallbladder stones.MethodsFrom December 2018 to June 2021, all patients with cholecystolithiasis and common bile duct stones who met the criteria for gallbladder preservation in our hospital were included in the study and prospectively followed up.ResultsWe included 48 patients, including 20 patients with acute biliary pancreatitis. All patients successfully underwent ERCP to remove common bile duct stones. One patient had gallbladder perforation during gallbladder-preserving cholecystolithotomy. The guide wire successfully entered the gallbladder, and the transpapillary gallbladder metal-covered stent was successfully placed in 44 patients. The technical success rate was 91.67% (44/48). All stones were removed in 34 patients, for a clinical success rate of 77.27% (34/44). The total postoperative complication rate was 6.25% (3/48), with 2 cases of pancreatitis (4.17%) and 1 case of cholangitis (2.08%). Three patients were lost to follow-up. Among the 31 patients who were followed up for a mean of 27 months (6–40), 5 patients (16.13%) experienced gallstone recurrence. The recurrence rates at 12 months, 18 months, 24 months, 30 months and 36 months were 0%, 3.23%, 6.45%, 12.9%, and 16.13%, respectively.ConclusionFor patients with cholecystolithiasis and common bile duct stones, ERCP-based transcystic gallbladder-preserving cholecystolithotomy without gallbladder incision can preserve gallbladder structure, and this procedure is safe and feasible for the protection of gallbladder function.Clinical trial registration: The study was registered in the Chinese Clinical Trial Registry, and the registry number is ChiCTR1900028006

The Principal Genetic Determinants for Nasopharyngeal Carcinoma in China Involve the HLA Class I Antigen Recognition Groove

Nasopharyngeal carcinoma (NPC) is an epithelial malignancy facilitated by Epstein-Barr Virus infection. Here we resolve the major genetic influences for NPC incidence using a genome-wide association study (GWAS), independent cohort replication, and high-resolution molecular HLA class I gene typing including 4,055 study participants from the Guangxi Zhuang Autonomous Region and Guangdong province of southern China. We detect and replicate strong association signals involving SNPs, HLA alleles, and amino acid (aa) variants across the major histocompatibility complex-HLA-A, HLA –B, and HLA -C class I genes (PHLA-A-aa-site-62 = 7.4×10−29; P HLA-B-aa-site-116 = 6.5×10−19; P HLA-C-aa-site-156 = 6.8×10−8 respectively). Over 250 NPC-HLA associated variants within HLA were analyzed in concert to resolve separate and largely independent HLA-A, -B, and -C gene influences. Multivariate logistical regression analysis collapsed significant associations in adjacent genes spanning 500 kb (OR2H1, GABBR1, HLA-F, and HCG9) as proxies for peptide binding motifs carried by HLA- A*11:01. A similar analysis resolved an independent association signal driven by HLA-B*13:01, B*38:02, and B*55:02 alleles together. NPC resistance alleles carrying the strongly associated amino acid variants implicate specific class I peptide recognition motifs in HLA-A and -B peptide binding groove as conferring strong genetic influence on the development of NPC in China

Mechanical Properties and Microstructure of High-Strength Lightweight Concrete Incorporating Graphene Oxide

The increasing demand for high-strength lightweight concrete (HSLWC) with excellent mechanical properties has inspired the development of nanomaterials in fundamentally solving brittleness and cracking. This work investigated the effects of graphene oxide (GO) on the mechanical properties and microstructure of HSLWC, including the workability, density, compressive strength in different curing regimes, splitting tensile strength, flexural strength, modulus of elasticity and scanning electron microscopy (SEM). Six groups of mixtures were mixed with GO aqueous solution at a dosage of 0.00%, 0.02%, 0.04%, 0.05%, 0.06%, and 0.08% by weight of cement, respectively, and dispersed by ultrasound for 30 min. The test results showed that adding a low volume of GO to the specimens could slightly increase the density, rationally reduce the slump, and significantly improve the mechanical properties. The maximum increase in compressive strength, splitting tensile strength, modulus of elasticity and flexural strength of HSLWC with GO at 28 days was by 24%, 17%, 15%, 20%, respectively, as compared with HSLWC without GO. Simultaneously, the SEM results showed that GO could not only fill nano-scale pores, but also regulate the formation and growth of flower-like crystals, which was an important factor for the further improvement of properties. The research results provided a potential new pathway to improve the mechanical properties of HSLWC

Evaluating soil nutrients of Dacrydium pectinatum in China using machine learning techniques

Abstract Background The accurate estimation of soil nutrient content is particularly important in view of its impact on plant growth and forest regeneration. In order to investigate soil nutrient content and quality for the natural regeneration of Dacrydium pectinatum communities in China, designing advanced and accurate estimation methods is necessary. Methods This study uses machine learning techniques created a series of comprehensive and novel models from which to evaluate soil nutrient content. Soil nutrient evaluation methods were built by using six support vector machines and four artificial neural networks. Results The generalized regression neural network model was the best artificial neural network evaluation model with the smallest root mean square error (5.1), mean error (− 0.85), and mean square prediction error (29). The accuracy rate of the combined k-nearest neighbors (k-NN) local support vector machines model (i.e. k-nearest neighbors -support vector machine (KNNSVM)) for soil nutrient evaluation was high, comparing to the other five partial support vector machines models investigated. The area under curve value of generalized regression neural network (0.6572) was the highest, and the cross-validation result showed that the generalized regression neural network reached 92.5%. Conclusions Both the KNNSVM and generalized regression neural network models can be effectively used to evaluate soil nutrient content and quality grades in conjunction with appropriate model variables. Developing a new feasible evaluation method to assess soil nutrient quality for Dacrydium pectinatum, results from this study can be used as a reference for the adaptive management of rare and endangered tree species. This study, however, found some uncertainties in data acquisition and model simulations, which will be investigated in upcoming studies