Research progress of neoantigen-based dendritic cell vaccines in pancreatic cancer

The mutation of the crucial genes such as tumor suppressors or oncogenes plays an important role in the initiation and development of tumors. The non-synonymous mutations in the tumor cell genome will produce non-autologous proteins (neoantigen) to activate the immune system by activating CD4+ and CD8+ T cells. Neoantigen-based peptide vaccines have exhibited exciting therapeutic effects in treating various cancers alone or in combination with other therapeutic strategies. Furthermore, antigen-loaded DC vaccines are more powerful in inducing stronger immune responses than vaccines generated by antigens and adjuvants. Therefore, neoantigen-based dendritic cell (DC) vaccines could achieve promising effects in combating some malignant tumors. In this review, we summarized and discussed the recent research progresses of the neoantigen, neoantigen-based vaccines, and DC-based vaccine in pancreatic cancers (PCs). The combination of the neoantigen and DC-based vaccine in PC was also highlighted. Therefore, our work will provide more detailed evidence and novel opinions to promote the development of a personalized neoantigen-based DC vaccine for PC

Cell patterning via optimized dielectrophoretic force within hexagonal electrodes in vitro for skin tissue engineering

Abstract(#br)Tissue reconstruction through in vitro cell seeding is a popular method for tissue engineering. In this paper, we proposed a thin-layer structure consisting of multiple hexagons for the regeneration of skin tissue. Cells could be seeded and cultured within the structure via dielectrophoresis (DEP) actively. A thin layer of the structure was fabricated with biocompatible medical-grade stainless steel via precise laser cutting. The fabricated layers were stacked together to form a 3D electrode pair, which could be used to generate a 3D electric field. Thus, the suspended cells within the structure could be patterned via DEP manipulation. The input voltage was examined and optimized to ensure cell viability and patterning efficiency during the DEP manipulation process. As soon..

Mapping the Distribution of Water Resource Security in the Beijing-Tianjin-Hebei Region at the County Level under a Changing Context

The Beijing-Tianjin-Hebei (Jingjinji) region is the most densely populated region in China and suffers from severe water resource shortage, with considerable water-related issues emerging under a changing context such as construction of water diversion projects (WDP), regional synergistic development, and climate change. To this end, this paper develops a framework to examine the water resource security for 200 counties in the Jingjinji region under these changes. Thus, county-level water resource security is assessed in terms of the long-term annual mean and selected typical years (i.e., dry, normal, and wet years), with and without the WDP, and under the current and projected future (i.e., regional synergistic development and climate change). The outcomes of such scenarios are assessed based on two water-crowding indicators, two use-to-availability indicators, and one composite indicator. Results indicate first that the water resources are distributed unevenly, relatively more abundant in the northeastern counties and extremely limited in the other counties. The water resources are very limited at the regional level, with the water availability per capita and per unit gross domestic product (GDP) being only 279/290 m3 and 46/18 m3 in the current and projected future scenarios, respectively, even when considering the WDP. Second, the population carrying capacity is currently the dominant influence, while economic development will be the controlling factor in the future for most middle and southern counties. This suggests that significant improvement in water-saving technologies, vigorous replacement of industries from high to low water consumption, as well as water from other supplies for large-scale applications are greatly needed. Third, the research identifies those counties most at risk to water scarcity and shows that most of them can be greatly relieved after supplementation by the planned WDP. Finally, more attention should be paid to the southern counties because their water resources are not only limited but also much more sensitive and vulnerable to climate change. This work should benefit water resource management and allocation decisions in the Jingjinji region, and the proposed assessment framework can be applied to other similar problems.This study is supported by the National Key Research and Development Program of China (2016YFC0401401) and the National Natural Science Foundation of China (51609256, 51609122, 51522907, 51739011, and 51569026). Partial support is also from the Young Elite Scientists Sponsorship Program by the China Association for Science and Technology (2017QNRC001

S100A4 Knockout Sensitizes Anaplastic Thyroid Carcinoma Cells Harboring BRAFV600E/Mt to Vemurafenib

Background/Aims: Anaplastic thyroid cancer (ATC), with 25% BRAFV600E mutation, is one of the most lethal human malignancies that currently has no effective therapy. Vemurafenib, a BRAFV600E inhibitor, has shown promise in clinical trials, including ATC patients, but is being hampered by the acquisition of drug resistance. Therefore, combination therapy that includes BRAFV600E inhibition and avoids resistance is a clinical need. Methods: ATC cell lines 8505C (BRAFV600E/mt), SW1736 (BRAFV600E/mt), KAT18 (BRAFV600E/wt) and Cal-62(BRAFV600E/wt) cells were used in the study. The ability of S100A knockout or /and in combination with the BRAF inhibitor vemurafenib on growth, apoptosis, invasion and apoptosis in ATC cells in vitro was demonstrated by MTT and BrdUrd incorporation assay, Annexin-V-FITC staining analyzed by flow cytometry, Transwell migration and Matrigel invasion assay. S100A4,pERK1/2, pAKT and pROCK1/2 protein was detected by western blot assay; Small molecule inhibitors of Y27632, U0126, MK-2206 and constitutively active forms of pCDNA-Myc-pERK, pCMV6-HA-Akt, pCMV-RhoA were employed, and the mechanistic studies were performed. We assessed the efficiency of in vivo combination treatment with S100A4 knockout and Vemurafenib on tumors. Results: S100A4 knockout induced apoptosis and reduced proliferation by inactivation of pAKT and pERK signals, and inhibited invasion and migration by inactivation of pAKT and RhoA/ROCK1/2 signals in 8505C or Cal-62 cells in vitro, and vice versa in SW1736 and KAT18 cells. Vemurafenib did not affect apoptosis of both 8505C and SW1736 cells, but reduced proliferation via arresting cell cycle, and promoted cell migration and invasion in vitro. Combination treatment with S100A4 knockdown and vemurafenib reduced cell proliferation, migration and invasion in vitro compared to the S100A4 knockdown or Vemurafenib alone. Vemurafenib treatment resulted in a transient inhibition of pERK expression and gradually activation of pAKT expression, but quickly recovery from ERK1/2 activation inhibition by vemurafenib treatment in 4 h for SW1736 and 8505C cells. Combined treatment completely inhibited ERK1/2 and AKT activation during 48 h. In an in vivo mouse model of SW1736 and 8505C, vemurafenib treatment alone did not significantly inhibit tumor growth in both of the tumors, but inhibited tumor growth in combined groups. Conclusion: Our results show S100A4 knockout alone inhibits ATC cells (rich endogenous S100A4) survival and invasion, regardless of the BRAFV600E status, and potentiates the effect of vemurafenib on tumor regression in vitro and in vivo. In addition, S100A4 knockout potently inhibits the recovery from ERK1/2 activation inhibition and the AKT activation following vemurafenib treatment and reversed the vemurafenib resistance. This therapeutic combination may be of benefit in patients with ATC

Comparative analysis of physiological variations and genetic architecture for cold stress response in soybean germplasm

Soybean (Glycine max L.) is susceptible to low temperatures. Increasing lines of evidence indicate that abiotic stress-responsive genes are involved in plant low-temperature stress response. However, the involvement of photosynthesis, antioxidants and metabolites genes in low temperature response is largely unexplored in Soybean. In the current study, a genetic panel of diverse soybean varieties was analyzed for photosynthesis, chlorophyll fluorescence and leaf injury parameters under cold stress and control conditions. This helps us to identify cold tolerant (V100) and cold sensitive (V45) varieties. The V100 variety outperformed for antioxidant enzymes activities and relative expression of photosynthesis (Glyma.08G204800.1, Glyma.12G232000.1), GmSOD (GmSOD01, GmSOD08), GmPOD (GmPOD29, GmPOD47), trehalose (GmTPS01, GmTPS13) and cold marker genes (DREB1E, DREB1D, SCOF1) than V45 under cold stress. Upon cold stress, the V100 variety showed reduced accumulation of H2O2 and MDA levels and subsequently showed lower leaf injury compared to V45. Together, our results uncovered new avenues for identifying cold tolerant soybean varieties from a large panel. Additionally, we identified the role of antioxidants, osmo-protectants and their posttranscriptional regulators miRNAs such as miR319, miR394, miR397, and miR398 in Soybean cold stress tolerance

Critical current density: Measurements vs. reality

Different experimental techniques are employed to evaluate the critical current density (Jc), namely transport current measurements and two different magnetisation measurements forming quasi-equilibrium and dynamic critical states. Our technique-dependent results for superconducting YBa 2Cu3O7 (YBCO) film and MgB2 bulk samples show an extremely high sensitivity of Jc and associated interpretations, such as irreversibility fields and Kramer plots, which lose meaning without a universal approach. We propose such approach for YBCO films based on their unique pinning features. This approach allows us to accurately recalculate the magnetic-field-dependent Jc obtained by any technique into the Jc behaviour, which would have been measured by any other method without performing the corresponding experiments. We also discovered low-frequency-dependent phenomena, governing flux dynamics, but contradicting the considered ones in the literature. The understanding of these phenomena, relevant to applications with moving superconductors, can clarify their dramatic impact on the electric-field criterion through flux diffusivity and corresponding measurements. © Copyright EPLA, 2013

The complete reference genome for grapevine (Vitis vinifera L.) genetics and breeding

Grapevine is one of the most economically important crops worldwide. However, the previous versions of the grapevine reference genome consisted of thousands of fragments with missing centromeres and telomeres, which limited the accessibility of the repetitive sequences, the centromeric and telomeric regions, and the inheritance of important agronomic traits in these regions. Here, we assembled a telomere-to-telomere (T2T) gap-free reference genome for the pinot noir cultivar (PN40024) using the PacBio HiFi long reads. The T2T reference genome (PN_T2T) was 69 Mb longer with 9026 more genes identified than the 12X.v2 version (Canaguier et al., 2017). We annotated 67% repetitive sequences, 19 centromeres and 36 telomeres, and incorporated gene annotations of previous versions into the PN_T2T. We detected a total of 377 gene clusters, which showed associations with complex traits, such as aroma and disease resistance. Even though the PN40024 sample had been selfed for nine generations, we still found nine genomic hotspots of heterozygous sites associated with biological processes, such as the oxidation-reduction process and protein phosphorylation. The fully annotated complete reference genome, therefore, provides important resources for grapevine genetics and breeding.This work was supported by the National Natural Science Fund for Excellent Young Scientists Fund Program (Overseas) to Yongfeng Zhou, the National Key Research and Development Program of China(grant2019YFA0906200), the Agricultural Science and Technology Innovation Program (CAAS-ZDRW202101), the Shenzhen Science and Technology Program (grant KQTD2016113010482651), the BMBF funded de.NBI Cloud within the German Network for Bioinformatics Infrastructure (de.NBI). We thank Bianca Frommer, Marie Lahaye, David Navarro-Payá, Marcela K. Tello-Ruiz and Kapeel Chougule for their help in analyzing the RNA-Seq data and in running the gene annotation pipeline. This study is also based upon work from COST Action CA17111 INTEGRAPE and form COST Innovators Grant IG17111 GRAPEDIA, supported by COST (European Cooperation in Science and Technology).ViticultureT2Tgap-fregene clustercentromeretelomerePublishe

A sheep pangenome reveals the spectrum of structural variations and their effects on tail phenotypes

Structural variations (SVs) are a major contributor to genetic diversity and phenotypic variations, but their prevalence and functions in domestic animals are largely unexplored. Here we generated high-quality genome assemblies for 15 individuals from genetically diverse sheep breeds using Pacific Biosciences (PacBio) high-fidelity sequencing, discovering 130.3 Mb nonreference sequences, from which 588 genes were annotated. A total of 149,158 biallelic insertions/deletions, 6531 divergent alleles, and 14,707 multiallelic variations with precise breakpoints were discovered. The SV spectrum is characterized by an excess of derived insertions compared to deletions (94,422 vs. 33,571), suggesting recent active LINE expansions in sheep. Nearly half of the SVs display low to moderate linkage disequilibrium with surrounding single-nucleotide polymorphisms (SNPs) and most SVs cannot be tagged by SNP probes from the widely used ovine 50K SNP chip. We identified 865 population-stratified SVs including 122 SVs possibly derived in the domestication process among 690 individuals from sheep breeds worldwide. A novel 168-bp insertion in the 5' untranslated region (5' UTR) of HOXB13 is found at high frequency in long-tailed sheep. Further genome-wide association study and gene expression analyses suggest that this mutation is causative for the long-tail trait. In summary, we have developed a panel of high-quality de novo assemblies and present a catalog of structural variations in sheep. Our data capture abundant candidate functional variations that were previously unexplored and provide a fundamental resource for understanding trait biology in sheep

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe