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Frontiers in Immunology 2019The prevalence, pathogenesis, predictors, and natural course of patients with recurrent glomerulonephritis (GN) occurring after kidney transplantation remains... (Review)
Review
The prevalence, pathogenesis, predictors, and natural course of patients with recurrent glomerulonephritis (GN) occurring after kidney transplantation remains incompletely understood, including whether there are differences in the outcomes and advances in the treatment options of specific GN subtypes, including those with GN. Consequently, the treatment options and approaches to recurrent disease are largely extrapolated from the general population, with responses to these treatments in those with recurrent or GN post-transplantation poorly described. Given a greater understanding of the pathogenesis of GN and the development of novel treatment options, it is conceivable that these advances will result in an improved structure in the future management of patients with recurrent or GN. This review focuses on the incidence, genetics, characteristics, clinical course, and risk of allograft failure of patients with recurrent or GN after kidney transplantation, ascertaining potential disparities between "high risk" disease subtypes of IgA nephropathy, idiopathic membranous glomerulonephritis, focal segmental glomerulosclerosis, and membranoproliferative glomerulonephritis. We will examine in detail the management of patients with high risk GN, including the pre-transplant assessment, post-transplant monitoring, and the available treatment options for disease recurrence. Given the relative paucity of data of patients with recurrent and GN after kidney transplantation, a global effort in collecting comprehensive in-depth data of patients with recurrent and GN as well as novel trial design to test the efficacy of specific treatment strategy in large scale multicenter randomized controlled trials are essential to address the knowledge deficiency in this disease.
Topics: Glomerulonephritis; Glomerulonephritis, IGA; Glomerulosclerosis, Focal Segmental; Graft Survival; Humans; Kidney Failure, Chronic; Kidney Transplantation; Recurrence; Risk Factors; Transplantation, Homologous
PubMed: 31475005
DOI: 10.3389/fimmu.2019.01944 -
Proteins Oct 2022Membrane transport proteins, which include transporters and channels, are delicate protein machineries that mediate the exchange of a variety of substances across... (Review)
Review
Membrane transport proteins, which include transporters and channels, are delicate protein machineries that mediate the exchange of a variety of substances across biomembranes. Accumulated structural and functional knowledge allows for the de novo design of transport proteins with new structures that do not exist in nature. Analysis based on these novel proteins provides new insights into the principles that govern protein assembly, conformational change, and substrate recognition. Here, we review the advances in the de novo design of transporters and channels over recent years and highlight the challenges and opportunities in this field.
Topics: Biological Transport; Carrier Proteins; Membrane Transport Proteins
PubMed: 35305033
DOI: 10.1002/prot.26336 -
Breast (Edinburgh, Scotland) Oct 2023Information of brain metastasis (BM) in de novo stage IV breast cancer is lacking, which is an unavoidable problem and dilemma in practice. Understanding the current...
OBJECTIVES
Information of brain metastasis (BM) in de novo stage IV breast cancer is lacking, which is an unavoidable problem and dilemma in practice. Understanding the current situation is helpful for the clinical cognition and decision-making.
METHODS
We retrospectively analyzed the clinical and survival information of de novo stage IV breast cancer with BM between 2015 and 2019 from the Surveillance, Epidemiology, and End Results (SEER) database. Multivariable logistic and Cox regression analyses were performed to identify predictors of BM and factors associated with all-cause mortality in de novo stage IV breast cancer, respectively. Overall survival (OS) was calculated using Kaplan-Meier and log-rank tests.
RESULTS
Our cohort consisted of 1366 patients with BM in de novo stage IV breast cancer, with an incidence of 8.38% in patients with metastatic disease to any distant site. Incidence was highest among patients with metastatic disease with HR-HER2+ (12.95%) and HR-HER2- (13.40%) subtypes. The higher the number of extracranial metastases, the higher the BM incidence. The median OS was 12.0 (95%CI: 10.426-13.574) months in BM group; it was longest in HR + HER2+ (19.0[95%CI: 11.793-26.207] months), and shortest in HR-HER2- (7.0 [95%CI:5.354-8.646] months). Marital status, subtype, and abundance of metastatic sites influenced morbidity and OS of BM in de novo stage IV breast cancer.
CONCLUSIONS
Population-based estimates of the incidence and prognosis for patients with BM in de novo stage IV breast cancer were closely associated with subtype and metastatic burden. These findings may be helpful in developing diagnostic strategies, especially for brain screening.
Topics: Humans; Female; Breast Neoplasms; Retrospective Studies; Brain Neoplasms; Brain; Cognition; Prognosis; Neoplasm Metastasis
PubMed: 37499376
DOI: 10.1016/j.breast.2023.07.005 -
Nature Ecology & Evolution Jun 2023Genes and translated open reading frames (ORFs) that emerged de novo from previously non-coding sequences provide species with opportunities for adaptation. When... (Review)
Review
Genes and translated open reading frames (ORFs) that emerged de novo from previously non-coding sequences provide species with opportunities for adaptation. When aberrantly activated, some human-specific de novo genes and ORFs have disease-promoting properties-for instance, driving tumour growth. Thousands of putative de novo coding sequences have been described in humans, but we still do not know what fraction of those ORFs has readily acquired a function. Here, we discuss the challenges and controversies surrounding the detection, mechanisms of origin, annotation, validation and characterization of de novo genes and ORFs. Through manual curation of literature and databases, we provide a thorough table with most de novo genes reported for humans to date. We re-evaluate each locus by tracing the enabling mutations and list proposed disease associations, protein characteristics and supporting evidence for translation and protein detection. This work will support future explorations of de novo genes and ORFs in humans.
Topics: Humans; Open Reading Frames; Exons
PubMed: 36928843
DOI: 10.1038/s41559-023-02014-y -
Journal of Chemical Information and... Feb 2022Nowadays, machine learning and deep learning approaches are widely utilized for generative chemistry and computer-aided drug design and discovery such as de novo peptide... (Review)
Review
Nowadays, machine learning and deep learning approaches are widely utilized for generative chemistry and computer-aided drug design and discovery such as de novo peptide and protein design, where target-specific peptide-based/protein-based therapeutics have been suggested to cause fewer adverse effects than the traditional small-molecule drugs. In light of current advancements in deep learning techniques, generative adversarial network (GAN) algorithms are being leveraged to a wide variety of applications in the process of generative chemistry and computer-aided drug design and discovery. In this review, we focus on the up-to-date developments for de novo peptide and protein design research using GAN algorithms in the interdisciplinary fields of generative chemistry, machine learning, deep learning, and computer-aided drug design and discovery. First, we present various studies that investigate GAN algorithms to fulfill the task of de novo peptide and protein design in the drug development pipeline. In addition, we summarize the drawbacks with respect to the previous studies in de novo peptide and protein design using GAN algorithms. Finally, we depict a discussion of open challenges and emerging problems for future research.
Topics: Artificial Intelligence; Machine Learning; Neural Networks, Computer; Peptides; Proteins
PubMed: 35128926
DOI: 10.1021/acs.jcim.1c01361 -
Frontiers in Cell and Developmental... 2022In cycling cells, new centrioles are assembled in the vicinity of pre-existing centrioles. Although this canonical centriole duplication is a tightly regulated process... (Review)
Review
In cycling cells, new centrioles are assembled in the vicinity of pre-existing centrioles. Although this canonical centriole duplication is a tightly regulated process in animal cells, centrioles can also form in the absence of pre-existing centrioles; this process is termed centriole formation. centriole formation is triggered by the removal of all pre-existing centrioles in the cell in various manners. Moreover, overexpression of polo-like kinase 4 (Plk4), a master regulatory kinase for centriole biogenesis, can induce centriole formation in some cell types. Under these conditions, structurally and functionally normal centrioles can be formed . While centriole formation is normally suppressed in cells with intact centrioles, depletion of certain suppressor proteins leads to the ectopic formation of centriole-related protein aggregates in the cytoplasm. It has been shown that centriole formation also occurs naturally in some species. For instance, during the multiciliogenesis of vertebrate epithelial cells, massive centriole amplification occurs to form numerous motile cilia. In this review, we summarize the previous findings on centriole formation, particularly under experimental conditions, and discuss its regulatory mechanisms.
PubMed: 35445021
DOI: 10.3389/fcell.2022.861864 -
Briefings in Bioinformatics Jan 2018As the advent of next-generation sequencing (NGS) technology, various de novo assembly algorithms based on the de Bruijn graph have been developed to construct... (Review)
Review
As the advent of next-generation sequencing (NGS) technology, various de novo assembly algorithms based on the de Bruijn graph have been developed to construct chromosome-level sequences. However, numerous technical or computational challenges in de novo assembly still remain, although many bright ideas and heuristics have been suggested to tackle the challenges in both experimental and computational settings. In this review, we categorize de novo assemblers on the basis of the type of de Bruijn graphs (Hamiltonian and Eulerian) and discuss the challenges of de novo assembly for short NGS reads regarding computational complexity and assembly ambiguity. Then, we discuss how the limitations of the short reads can be overcome by using a single-molecule sequencing platform that generates long reads of up to several kilobases. In fact, the long read assembly has caused a paradigm shift in whole-genome assembly in terms of algorithms and supporting steps. We also summarize (i) hybrid assemblies using both short and long reads and (ii) overlap-based assemblies for long reads and discuss their challenges and future prospects. This review provides guidelines to determine the optimal approach for a given input data type, computational budget or genome.
Topics: Algorithms; Genome, Human; Genomics; High-Throughput Nucleotide Sequencing; Humans; Software; Whole Genome Sequencing
PubMed: 27742661
DOI: 10.1093/bib/bbw096 -
Plant & Cell Physiology Nov 2022Most cereal crops were domesticated within the last 12,000 years and subsequently spread around the world. These crops have been nourishing the world by supplying a... (Review)
Review
Most cereal crops were domesticated within the last 12,000 years and subsequently spread around the world. These crops have been nourishing the world by supplying a primary energy and nutrient source, thereby playing a critical role in determining the status of human health and sustaining the global population. Here, we review the major challenges of future agriculture and emphasize the utilization of wild germplasm. De novo domestication is one of the most straightforward strategies to manipulate domestication-related and/or other genes with known function, and thereby introduce desired traits into wild plants. We also summarize known causal variations and their corresponding pathways in order to better understand the genetic basis of crop evolution, and how this knowledge could facilitate de novo domestication. Indeed knowledge-driven de novo domestication has great potential for the development of new sustainable crops that have climate-resilient high yield with low resource input and meet individual nutrient needs. Finally, we discuss current opportunities for and barriers to knowledge-driven de novo domestication.
Topics: Humans; Domestication; Crops, Agricultural; Agriculture; Edible Grain; Phenotype
PubMed: 35762778
DOI: 10.1093/pcp/pcac077 -
The Plant Journal : For Cell and... Aug 2022De novo genes are derived from non-coding sequences, and they can play essential roles in organisms. Cultivated peanut (Arachis hypogaea) is a major oil and protein crop...
De novo genes are derived from non-coding sequences, and they can play essential roles in organisms. Cultivated peanut (Arachis hypogaea) is a major oil and protein crop derived from a cross between Arachis duranensis and Arachis ipaensis. However, few de novo genes have been documented in Arachis. Here, we identified 381 de novo genes in A. hypogaea cv. Tifrunner based on comparison with five closely related Arachis species. There are distinct differences in gene expression patterns and gene structures between conserved and de novo genes. The identified de novo genes originated from ancestral sequence regions associated with metabolic and biosynthetic processes, and they were subsequently integrated into existing regulatory networks. De novo paralogs and homoeologs were identified in A. hypogaea cv. Tifrunner. De novo paralogs and homoeologs with conserved expression have mismatching cis-acting elements under normal growth conditions. De novo genes potentially have pluripotent functions in responses to biotic stresses as well as in growth and development based on quantitative trait locus data. This work provides a foundation for future research examining gene birth processes and gene function in Arachis and related taxa.
Topics: Arachis; Evolution, Molecular; Quantitative Trait Loci
PubMed: 35748398
DOI: 10.1111/tpj.15875 -
Yeast (Chichester, England) Sep 2022De novo gene birth is the process by which new genes emerge in sequences that were previously noncoding. Over the past decade, researchers have taken advantage of the... (Review)
Review
De novo gene birth is the process by which new genes emerge in sequences that were previously noncoding. Over the past decade, researchers have taken advantage of the power of yeast as a model and a tool to study the evolutionary mechanisms and physiological implications of de novo gene birth. We summarize the mechanisms that have been proposed to explicate how noncoding sequences can become protein-coding genes, highlighting the discovery of pervasive translation of the yeast transcriptome and its presumed impact on evolutionary innovation. We summarize current best practices for the identification and characterization of de novo genes. Crucially, we explain that the field is still in its nascency, with the physiological roles of most young yeast de novo genes identified thus far still utterly unknown. We hope this review inspires researchers to investigate the true contribution of de novo gene birth to cellular physiology and phenotypic diversity across yeast strains and species.
Topics: Evolution, Molecular; Saccharomyces cerevisiae
PubMed: 35959631
DOI: 10.1002/yea.3810