Preferential regulation of duplicated genes by microRNAs in mammals

Analysis of duplicate genes and predicted microRNA targets in human and mouse shows that microRNAs are important in how the regulatory patterns of mammalian paralogs have evolved

The Cellular Robustness by Genetic Redundancy in Budding Yeast

The frequent dispensability of duplicated genes in budding yeast is heralded as a hallmark of genetic robustness contributed by genetic redundancy. However, theoretical predictions suggest such backup by redundancy is evolutionarily unstable, and the extent of genetic robustness contributed from redundancy remains controversial. It is anticipated that, to achieve mutual buffering, the duplicated paralogs must at least share some functional overlap. However, counter-intuitively, several recent studies reported little functional redundancy between these buffering duplicates. The large yeast genetic interactions released recently allowed us to address these issues on a genome-wide scale. We herein characterized the synthetic genetic interactions for ∼500 pairs of yeast duplicated genes originated from either whole-genome duplication (WGD) or small-scale duplication (SSD) events. We established that functional redundancy between duplicates is a pre-requisite and thus is highly predictive of their backup capacity. This observation was particularly pronounced with the use of a newly introduced metric in scoring functional overlap between paralogs on the basis of gene ontology annotations. Even though mutual buffering was observed to be prevalent among duplicated genes, we showed that the observed backup capacity is largely an evolutionarily transient state. The loss of backup capacity generally follows a neutral mode, with the buffering strength decreasing in proportion to divergence time, and the vast majority of the paralogs have already lost their backup capacity. These observations validated previous theoretic predictions about instability of genetic redundancy. However, departing from the general neutral mode, intriguingly, our analysis revealed the presence of natural selection in stabilizing functional overlap between SSD pairs. These selected pairs, both WGD and SSD, tend to have decelerated functional evolution, have higher propensities of co-clustering into the same protein complexes, and share common interacting partners. Our study revealed the general principles for the long-term retention of genetic redundancy

Fully Convolutional Network Ensembles for White Matter Hyperintensities Segmentation in MR Images

White matter hyperintensities (WMH) are commonly found in the brains of healthy elderly individuals and have been associated with various neurological and geriatric disorders. In this paper, we present a study using deep fully convolutional network and ensemble models to automatically detect such WMH using fluid attenuation inversion recovery (FLAIR) and T1 magnetic resonance (MR) scans. The algorithm was evaluated and ranked 1 st in the WMH Segmentation Challenge at MICCAI 2017. In the evaluation stage, the implementation of the algorithm was submitted to the challenge organizers, who then independently tested it on a hidden set of 110 cases from 5 scanners. Averaged dice score, precision and robust Hausdorff distance obtained on held-out test datasets were 80%, 84% and 6.30mm respectively. These were the highest achieved in the challenge, suggesting the proposed method is the state-of-the-art. In this paper, we provide detailed descriptions and quantitative analysis on key components of the system. Furthermore, a study of cross-scanner evaluation is presented to discuss how the combination of modalities and data augmentation affect the generalization capability of the system. The adaptability of the system to different scanners and protocols is also investigated. A quantitative study is further presented to test the effect of ensemble size. Additionally, software and models of our method are made publicly available. The effectiveness and generalization capability of the proposed system show its potential for real-world clinical practice.Comment: final version in NeuroImag

RECENT CASE NOTES

<p><i>Notes</i>: H-sites and L-sites refer to high-tide-zone sites and low-tide-zone sites, respectively.</p><p>Results of <i>t</i>-test for effects of different stands on aboveground net primary production (ANPP), soil pH, total carbon (TC), organic and inorganic carbon (SOC and SIC, 0–100 cm), and SMBC.</p

FBXO5 acts as a novel prognostic biomarker for patients with cervical cancer

Background: Cervical cancer (CC) remains one of the most common and deadly malignancies in women worldwide. FBXO5, a protein-coding gene, is highly expressed in a variety of primary tumors and promotes tumor progression, however, its role and prognostic value in CC remain largely unknown.Methods: A key differential gene, FBXO5, was screened according to WGCNA based on immunohistochemical assays of clinical samples, multiple analyses of the Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) databases, including survival analysis, tumor mutational burden, GO, KEGG, tumor immune infiltration, and chemotherapeutic drug sensitivity, to explore the expression and prognostic value of FBXO5 in CC. The migration and invasiveness of cervical cancer cells following FBXO5 knockdown and overexpression were examined using wound healing and transwell assays, and the viability of cancer cells was assessed using CCK8 and EdU assays.Results:FBXO5 was discovered to be substantially expressed in CC tissues using data from our CC cohort and the TCGA database, and a survival analysis indicated FBXO5 as a predictive factor for poor overall survival in CC patients. In vitro, CC cells were more inclined to proliferate, migrate, and invade when FBXO5 was upregulated as opposed to when it was knocked down

Integrating high-throughput genetic interaction mapping and high-content screening to explore yeast spindle morphogenesis

A combination of yeast genetics, synthetic genetic array analysis, and high-throughput screening reveals that sumoylation of Mcm21p promotes disassembly of the mitotic spindle

Preferential regulation of stably expressed genes in the human genome suggests a widespread expression buffering role of microRNAs

In this study, we comprehensively explored the stably expressed genes (SE genes) and fluctuant genes (FL genes) in the human genome by a meta-analysis of large scale microarray data. We found that these genes have distinct function distributions. miRNA targets are shown to be significantly enriched in SE genes by using propensity analysis of miRNA regulation, supporting the hypothesis that miRNAs can buffer whole genome expression fluctuation. The expression-buffering effect of miRNA is independent of the target site number within the 3'-untranslated region. In addition, we found that gene expression fluctuation is positively correlated with the number of transcription factor binding sites in the promoter region, which suggests that coordination between transcription factors and miRNAs leads to balanced responses to external perturbations

Transient receptor potential channels’ genes forecast cervical cancer outcomes and illuminate its impact on tumor cells

Introduction: In recent years, there has been a strong association between transient receptor potential (TRP) channels and the development of various malignancies, drug resistance, and resistance to radiotherapy. Consequently, we have investigated the relationship between transient receptor potential channels and cervical cancer from multiple angles.Methods: Patients’ mRNA expression profiles and gene variants were obtained from the TCGA database. Key genes in transient receptor potential channel prognosis-related genes (TRGs) were screened using the least absolute shrinkage and selection operator (LASSO) regression method, and a risk signature was constructed based on the expression of key genes. Various analyses were performed to evaluate the prognostic significance, biological functions, immune infiltration, and response to immunotherapy based on the risk signature.Results: Our research reveals substantial differences between high and low-risk groups in prognosis, tumor microenvironment, tumor mutational load, immune infiltration, and response to immunotherapy. Patients in the high-risk group exhibited poorer prognosis, lower tumor microenvironment scores and reduced response to immunotherapy while showing increased sensitivity to specific targeted drugs. In vitro experiments further illustrated that inhibiting transient receptor potential channels effectively decreased the proliferation, invasion, and migration of cervical cancer cells.Discussion: This study highlights the significant potential of transient receptor potential channels in cervical cancer, emphasizing their crucial role in prognostic prediction and personalized treatment strategies. The combination of TRP inhibitors with immunotherapy and targeted drugs may offer promise for individuals affected by cervical cancer