Upchurchdillon4103

As an emerging technology, cryo-electron microscopy (cryo-EM) has attracted more and more research interests from both structural biology and computer science, because many challenging computational tasks are involved in the processing of cryo-EM images. An important image processing step is to cluster the 2D cryo-EM images according to their projection angles, then the cluster mean images are used for the subsequent 3D reconstruction. However, cryo-EM images are quite noisy and denoising them is not easy, because the noise is a complicated mixture from samples and hardware. In this study, we design an effective cryo-EM image denoising model, CDAE, i.e., a cascade of denoising autoencoders. The new model comprises stacked blocks of deep neural networks to reduce noise in a progressive manner. Each block contains a convolutional autoencoder, pre-trained by simulated data of different SNRs and fine-tuned by target data set. We assess this new model on three simulated test sets and a real data set. CDAE achieves very competitive PSNR (peak signal-to-noise ratio) in the comparison of the state-of-the-art image denoising methods. Moreover, the denoised images have significantly enhanced clustering results compared to original image features or high-level abstraction features obtained by other deep neural networks. Both quantitative and visualized results demonstrate the good performance of CDAE for the noise reduction in clustering single-particle cryo-EM images.Cystic Fibrosis (CF) is a lethal autosomal recessive disease caused by mutations in the gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR). The most common mutation is the deletion of phenylalanine residue at position 508 (ΔF508). Here we report the production of CFTR-ΔF508 rabbits by CRISPR/Cas9-mediated gene editing. After microinjection and embryo transfer, 77 kits were born, of which five carried the ΔF508 mutation. To confirm the germline transmission, one male ΔF508 founder was bred with two wild-type females and produced 16 F1 generation kits, of which six are heterozygous ΔF508/WT animals. Our work adds CFTR-ΔF508 rabbits to the toolbox of CF animal models for biomedical research.The purple sea urchin Strongylocentrotus purpuratus has been used for over 150 years as a model organism in developmental biology. Using this model species, scientists have been able to describe, in detail, the mechanisms of cell cycle control and cell adhesion, fertilization, calcium signaling, cell differentiation, and death. Massive parallel sequencing of the sea urchin genome enabled the deciphering of the main components of gene regulatory networks during the activation of embryonic signaling pathways. This knowledge helped to extrapolate aberrations in somatic cells that may lead to diseases, including cancer in humans. Furthermore, since many, if not all, developmental signaling pathways were shown to be controlled by non-coding RNAs (ncRNAs), the sea urchin organism represents an attractive experimental model. In this review, we discuss the main discoveries in the genetics, genomics, and transcriptomics of sea urchins during embryogenesis with the main focus on the role of ncRNAs. This information may be useful for comparative studies between different organisms, and may help identify new regulatory networks controlled by ncRNAs.Cassava is crucial for food security of millions of people in sub-Saharan Africa. The crop has great potential to contribute to African development and is increasing its income-earning potential for small-scale farmers and related value chains on the continent. Therefore, it is critical to increase cassava production, as well as its quality attributes. Technological innovations offer great potential to drive this envisioned change. This paper highlights genomic tools and resources available in cassava. The paper also provides a glimpse of how these resources have been used to screen and understand the pattern of cassava genetic diversity on the continent. Here, we reviewed the approaches currently used for phenotyping cassava traits, highlighting the methodologies used to link genotypic and phenotypic information, dissect the genetics architecture of key cassava traits, and identify quantitative trait loci/markers significantly associated with those traits. Additionally, we examined how knowledge acquired is utilized to contribute to crop improvement. We explored major approaches applied in the field of molecular breeding for cassava, their promises, and limitations. We also examined the role of national agricultural research systems as key partners for sustainable cassava production.Background Congenital adrenal hyperplasia (CAH) is a group of autosomal recessive disorders encompassing enzyme deficiencies in the adrenal steroidogenesis pathway that leads to impaired cortisol biosynthesis. 21-hydroxylase deficiency (21-OHD) is the most common type of CAH. Severe cases of 21-OHD may result in death during the neonatal or infancy periods or sterility in later life. The early detection and timely treatment of 21-OHD are essential. This study aimed to summarize the clinical and genotype characteristics of 21-OHD patients detected by neonatal screening in Nanjing, Jiangsu province of China from 2000 to 2019. Methods Through a retrospective analysis of medical records, the clinical presentations, laboratory data, and molecular characteristics of 21-OHD patients detected by neonatal screening were evaluated. Results Of the 1,211,322 newborns who were screened, 62 cases were diagnosed with 21-OHD with an incidence of 119858. 58 patients were identified with the classical salt-wasting type (SW) 21-OHD and four patients were identified with simple virilizing type (SV) 21-OHD. Amongst these patients, 19 cases patients accepted genetic analysis, and another 40 cases were received from other cities in Eastern China. Eighteen different variants were found in the CYP21A2 gene. The most frequent variants was c.293-13A/C>G (36.29%). The most severe clinical manifestations were caused by large deletions or conversions of CYP21A2. Conclusions This study suggested that neonatal screening effectively leads to the early diagnosis of 21-OHD and reduces fatal adrenal crisis. Our data provide additional information on the occurrence and genotype-phenotype correlation of 21-OHD in the Chinese population which can be used to better inform treatment and improve prognosis.High-temperature stress can cause serious abiotic damage that limits the yield and quality of rice. Heat tolerance (HT) during the flowering stage of rice is a key trait that can guarantee a high and stable yield under heat stress. HT is a complex trait that is regulated by multiple quantitative trait loci (QTLs); however, few underlying genes have been fine mapped and cloned. In this study, the F23 population derived from a cross between Huanghuazhan (HHZ), a heat-tolerant cultivar, and 9311, a heat-sensitive variety, was used to map HT QTLs during the flowering stage in rice. A new major QTL, qHTT8, controlling HT was identified on chromosome 8 using the bulked-segregant analysis (BSA)-seq method. The QTL qHTT8 was mapped into the 3,555,000-4,520,000 bp, which had a size of 0.965 Mb. The candidate region of qHTT8 on chromosome 8 contained 65 predicted genes, and 10 putative predicted genes were found to be associated with abiotic stress tolerance. Furthermore, qRT-PCR was performed to analyze the differential expression of these 10 genes between HHZ and 9311 under high temperature conditions. LOC_Os08g07010 and LOC_Os08g07440 were highly induced in HHZ compared with 9311 under heat stress. Orthologous genes of LOC_Os08g07010 and LOC_Os08g07440 in plants played a role in abiotic stress, suggesting that they may be the candidate genes of qHTT8. Generally, the results of this study will prove useful for future efforts to clone qHTT8 and breed heat-tolerant varieties of rice using marker-assisted selection.Genome architecture plays a pivotal role in gene regulation. The use of high-throughput methods for chromatin profiling and 3-D interaction mapping provide rich experimental data sets describing genome organization and dynamics. These data challenge development of new models and algorithms connecting genome architecture with epigenetic marks. In this review, we describe how chromatin architecture could be reconstructed from epigenetic data using biophysical or statistical approaches. We discuss the applicability and limitations of these methods for understanding the mechanisms of chromatin organization. We also highlight the emergence of new predictive approaches for scoring effects of structural variations in human cells.Previously, a homodiploid goldfish-like fish (2n = 100; GF-L) was spontaneously generated by self-crossing a homodiploid red crucian carp-like fish (2n = 100; RCC-L), which was in turn produced via the distant hybridization of female koi carp (Cyprinus carpio haematopterus, KOC, 2n = 100) and male blunt snout bream (Megalobrama amblycephala, BSB, 2n = 48). The phenotypes and genotypes of RCC-L and GF-L differed from those of the parental species but were similar to diploid red crucian carp (2n = 100; RCC) and goldfish (2n = 100; GF), respectively. We sequenced the complete mitochondrial DNAs (mtDNAs) of the KOC, BSB, RCC-L, GF-L, and subsequent generations produced by self-crossing [the self-mating offspring of RCC-L (RCC-L-F2) to the self-mating offspring of RCC-L-F2 (RCC-L-F3) and the self-mating offspring of GF-L (GF-L-F2)]. Paternal mtDNA fragments were stably embedded in the mtDNAs of both lineages, forming chimeric DNA fragments. Fenebrutinib In addition to these chimeras, several nucleotide positions in the RCC-L aDNA. These evolutionary analyses in mtDNA suggest that GF might have diverged from RCC after RCC diverged from koi carp.Prostate cancer (PC) is one of the most common cancers among men worldwide, and advanced PCs, such as locally advanced PC (LAPC) and castration-resistant PC (CRPC), present the greatest challenges in clinical management. Current indicators have limited capacity to predict the disease course; therefore, better prognostic markers are greatly needed. In this study, we performed a bioinformatic analysis of The Cancer Genome Atlas (TCGA) datasets, including RNA-Seq data from the prostate adenocarcinoma (PRAD; n = 55) and West Coast Dream Team - metastatic CRPC (WCDT-MCRPC; n = 84) projects, to evaluate the transcriptome changes associated with progression-free survival (PFS) for LAPC and CRPC, respectively. We identified the genes whose expression was positively/negatively correlated with PFS. In LAPC, the genes with the most significant negative correlations were ZC2HC1A, SQLE, and KIF11, and the genes with the most significant positive correlations were SOD3, LRRC26, MIR22HG, MEG3, and MIR29B2CHG. In CRPC, the most significant positive correlations were found for BET1, CTAGE5, IFNGR1, and GIMAP6, and the most significant negative correlations were found for CLPB, PRPF19, ZNF610, MPST, and LINC02001. In addition, we performed a gene network interaction analysis using STRINGdb, which revealed a significant relationship between genes predominantly involved in the cell cycle and characterized by upregulated expression in early recurrence. Based on the results, we propose several genes that can be used as potential prognostic markers.