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The New Phytologist Jun 2018Contents Summary 1334 I. Introduction 1334 II. Regeneration-initial cell: the origin of regeneration 1335 III. Acquiring regeneration competency: the essential... (Review)
Review
Contents Summary 1334 I. Introduction 1334 II. Regeneration-initial cell: the origin of regeneration 1335 III. Acquiring regeneration competency: the essential intermediate step for hormone-induced regeneration 1335 IV. Hormonal induction of stem cell regulators: the program for de novo establishment of apical meristems 1337 V. Conclusions and perspectives 1337 Acknowledgements 1338 Author contributions 1338 References 1338 SUMMARY: High cellular plasticity confers remarkable regeneration capacity to plants. Based on the activity of stem cells and their regulators, higher plants are capable of regenerating new individuals. De novo organogenesis exemplifies the regeneration of the whole plant body and is exploited widely in agriculture and biotechnology. In this Tansley insight article, we summarize recent advances that facilitate our understanding of the molecular mechanisms underlying de novo organogenesis. According to our current knowledge, this process can be divided into three steps, including activation of regeneration-initial cells, acquisition of competency and de novo establishment of apical meristems. The functions of stem cells and their regulators are critical to de novo organogenesis, whereas auxin and cytokinin act as triggers and linkers between different steps.
Topics: Meristem; Organogenesis; Plant Cells; Plant Growth Regulators; Regeneration; Stem Cells
PubMed: 29574802
DOI: 10.1111/nph.15106 -
Case Reports in Transplantation 2022Allograft membranous glomerulopathy can be a recurrent or de novo disease. Both instead have different underlying immune pathophysiology and disease pattern. While the...
Allograft membranous glomerulopathy can be a recurrent or de novo disease. Both instead have different underlying immune pathophysiology and disease pattern. While the introduction of ANTI-PLAR2 and THS7A brought new insights into the management of Immune/primary MN, the treatment of de novo MN is not clear. Relapsing de novo MN in a kidney transplant was rarely reported. Here, we present a case of relapsing de novo MN without evidence of rejection and a gratifying response to rituximab.
PubMed: 35547830
DOI: 10.1155/2022/6754520 -
Clinical Medicine Insights. Oncology 2020It is estimated that approximately 154000 women in the United States have stage IV breast cancer (BC). A subset of this group has metastatic disease at presentation,... (Review)
Review
It is estimated that approximately 154000 women in the United States have stage IV breast cancer (BC). A subset of this group has metastatic disease at presentation, known as de novo stage IV disease. De novo stage IV BC accounts for approximately 6% of all BC diagnoses in the United States. Traditionally, stage IV BC patients are treated with primary systemic therapy with a palliative intent reserving possible locoregional treatment (LRT) as last resort. There has been a lot of interest in the role of LRT in de novo stage IV BC for the past decade with mixed conclusions. Although this review is not intended to be a comprehensive overview of all literature regarding this topic to date, we will review the recent findings in literature focusing on the studies with larger sample sizes to investigate the role of LRT in de novo stage IV BC.
PubMed: 32994701
DOI: 10.1177/1179554920942440 -
Journal of Neurosurgery Feb 2019Incidence rates of de novo aneurysm formation and recurrence after clip ligation remain controversial. In this meta-analysis, the authors provide data on pooled annual... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
Incidence rates of de novo aneurysm formation and recurrence after clip ligation remain controversial. In this meta-analysis, the authors provide data on pooled annual incidence rates and the association of patient characteristics with time to formation of de novo aneurysms and time to recurrence after clipping.
METHODS
A search of the literature up to June 15, 2016, on PubMed and a systematic review were performed. The association of age, aneurysm rupture status, aneurysm multiplicity, and anatomical location with time to recurrence or formation of de novo aneurysm was estimated using multivariable Cox proportional-hazards models. Kaplan-Meier estimates (event-free survival curves) are shown. Pooled annualized incidence rates of recurrent and de novo aneurysms were estimated using Poisson regression. Proportions of aneurysms and average follow-up times are displayed as bubble plots with LOESS smoothers weighted for study size.
RESULTS
Of the 7606 articles screened, 92 were included in the study. Case reports on 101 patients with recurrent aneurysms and 132 patients with de novo aneurysms were analyzed. Long-term follow-up studies on de novo aneurysm formation included 13,723 patients with 101,378 patient-years of follow-up; studies on aneurysm recurrence included 5922 patients with 31,055 patient-years of follow-up. Mean time to recurrence was 12.9 ± 6.6 years (mean ± standard deviation), and mean time to de novo formation was 9.3 ± 6.1 years. No association with sex, aneurysm location, and initial rupture could be shown. De novo aneurysms occurred later in patients with multiplicity of aneurysms at diagnosis (HR 0.63, p = 0.03) and in patients with increasing age (HR per 10 yrs 0.88, p = 0.06). Pooled annualized incidence rates were 0.35% for de novo aneurysms and 0.13% for recurrent aneurysms.
CONCLUSIONS
Despite low reported annual incidence rates, the cumulative risk of 9.6%-22% for aneurysm recurrence or de novo formation 20 years after clip ligation warrants lifelong follow-up. Screening at 5, 10, and 20 years would detect 30.8% (95% CI 23.3%-37.6%), 64.2% (95% CI 55.9%-70.9%), and 95.9% (95% CI 90.9%-97.9%) of de novo aneurysms. Screening for recurrent aneurysms at 10, 15, and 20 years would detect 36.6% (95% CI 26.5%-45.4%), 65.3% (95% CI 54.7%-73.5%), and 95.1% (95% CI 85.8%-96.6%) of lesions.
Topics: Humans; Incidence; Intracranial Aneurysm; Kaplan-Meier Estimate; Ligation; Postoperative Complications; Proportional Hazards Models; Recurrence
PubMed: 30797217
DOI: 10.3171/2018.10.JNS181281 -
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 -
Chemistry, An Asian Journal May 2017The importance of carbohydrates is evident by their essential role in all living systems. Their syntheses have attracted attention from chemists for over a century. Most... (Review)
Review
The importance of carbohydrates is evident by their essential role in all living systems. Their syntheses have attracted attention from chemists for over a century. Most chemical syntheses in this area focus on the preparation of carbohydrates from naturally occurring monosaccharides. De novo chemical synthesis of carbohydrates from feedstock starting materials has emerged as a complementary method for the preparation of diverse mono- and oligosaccharides. In this review, the history of de novo carbohydrate synthesis is briefly discussed and particular attention is given to methods that address the formation of glycosidic bonds for potential de novo synthesis of oligosaccharides. Almost all methods of this kind involve the formation of dihydropyran intermediates. Recent progress in forming dihydropyrans by Achmatowicz rearrangement, hetero-Diels-Alder cycloaddition, ring-closing metathesis, and other methods is also elaborated.
Topics: Molecular Structure; Monosaccharides; Oligosaccharides; Pyrans
PubMed: 28319359
DOI: 10.1002/asia.201700212 -
Journal of Gastrointestinal Cancer Dec 2022Patient care, newer immunosuppressive medications, and advances in surgical technique, have resulted in significant prolongation of survival after liver transplantation...
PURPOSE
Patient care, newer immunosuppressive medications, and advances in surgical technique, have resulted in significant prolongation of survival after liver transplantation in recent years. However, as life expectancy increased and the early mortality rates have decreased, different problems have evolved due to chronic immunosuppressive therapy. The aim of the present study is to evaluate patients who were transplanted and then developed de novo malignancies, in terms of the type of malignancies and the follow-up period.
METHODS
The study was conducted on 2814 patients who received liver transplantation between 2008 and 2020 in Inonu University Liver Transplant Institute. In total, the data of 23 patients were evaluated retrospectively.
RESULTS
Non-melanoma skin cancer was the most common de novo malignancy (21.7%), followed by gynecological cancers (17.3%). The interval between the time of transplantation until the development of de novo malignancy was 36 (6-75) months. The median follow-up period after the diagnoses of the de novo malignancies was 4.11 years. One, 3-, 5-year survival rates of patients after the diagnoses of de novo malignancies were 69.6%, 56.5%, and 41.9%; respectively.
CONCLUSION
Non-melanotic skin cancers were the most common de novo cancers in liver transplant recipients. A strict surveillance program is very important in the follow-up of liver transplant recipients.
Topics: Humans; Liver Transplantation; Retrospective Studies; Incidence; Neoplasms; Immunosuppressive Agents; Skin Neoplasms; Risk Factors
PubMed: 34778909
DOI: 10.1007/s12029-021-00749-0 -
Translational Cancer Research Aug 2020Despite recent advances in multimodality treatments such as endocrine therapy, chemotherapy, molecularly targeted therapy, and radiation therapy, it is still very... (Review)
Review
Despite recent advances in multimodality treatments such as endocrine therapy, chemotherapy, molecularly targeted therapy, and radiation therapy, it is still very difficult to cure stage IV breast cancer patients completely. The traditional role of radiation therapy for these patients has been a palliative treatment strategy that aims to control tumor progression and suppress tumor related symptoms. Recently, several non-randomized retrospective studies on stage IV breast cancer have revealed that locoregional radiation therapy (LRRT) might confer a survival benefit. However, there is no high level evidence to support the impact of LRRT on survival among patients with metastatic disease so far. This article aimed to summarize the literature and to discuss whether treating the primary lesion with radiation therapy could improve clinical survival outcomes among stage IV breast cancer patients. The issue of patient selection will be discussed because not all stage IV breast cancer patients could benefit from LRRT. This article also explores the clinical evidence regarding LRRT for metastatic disease across various cancers such as prostate, uterine cervical, non-small-cell lung, and head and neck cancers. Many retrospective trials have shown the impact of locoregional treatment (LRT) on survival in metastatic breast cancer. However, since the backgrounds of patients treated with LRRT are quite different from those of patients who did not receive LRRT and the treatment consists of surgery and/or radiation therapy, the role of radiation therapy alone remains unclear. Several reports investigated prognostic factors to detect the benefits of LRRT, which still remains conflicting and no consensus exists. However, selected patients with metastatic disease with better performance status, low tumor burden, and estrogen receptor positivity should be considered for the addition of radiation therapy delivered to the primary site. To explore proper decision-making regarding LRRT, further prospective randomized trials are eagerly awaited.
PubMed: 35117877
DOI: 10.21037/tcr.2020.02.54 -
Molecular Genetics & Genomic Medicine Mar 2019Osteogenesis imperfecta (OI) is a rare genetic bone fragility disorder. In the current study, differences between the genotypes and phenotypes of de novo and inherited...
BACKGROUND
Osteogenesis imperfecta (OI) is a rare genetic bone fragility disorder. In the current study, differences between the genotypes and phenotypes of de novo and inherited collagen-related OI were investigated.
METHODS
A comparative analysis was performed of the genotypes and phenotypes of 146 unrelated inherited and de novo collagen I OI cases from Estonia, Ukraine, and Vietnam. Mutational analysis of the subjects and all available parents were performed with Sanger sequencing.
RESULTS
Results showed that 56.16% of the OI cases were caused by de novo pathogenic variants. The proportion of OI types OI1, OI4, and OI3 among subjects with inherited OI was 45.31%, 46.88%, and 7.81%, respectively. Among subjects with de novo OI, the proportions of OI types (OI1, OI4, and OI3) were almost equal. Both inherited and de novo OI pathogenic variants occurred more often in the COL1A1 gene than in the COL1A2. The majority of de novo cases were missense pathogenic variants, whereas inherited OI was mostly caused by loss of function pathogenic variants.
CONCLUSION
In summary, there were significant differences between the phenotypes and genotypes of subjects with de novo and inherited OI. These findings may promote the further understanding of OI etiology, and assist with diagnostics procedures, as well as with family planning.
Topics: Adolescent; Collagen Type I; Collagen Type I, alpha 1 Chain; Female; Humans; Male; Mutation; Osteogenesis Imperfecta
PubMed: 30675999
DOI: 10.1002/mgg3.559 -
Protein Science : a Publication of the... Jun 2023De novo protein design enhances our understanding of the principles that govern protein folding and interactions, and has the potential to revolutionize biotechnology...
De novo protein design enhances our understanding of the principles that govern protein folding and interactions, and has the potential to revolutionize biotechnology through the engineering of novel protein functionalities. Despite recent progress in computational design strategies, de novo design of protein structures remains challenging, given the vast size of the sequence-structure space. AlphaFold2 (AF2), a state-of-the-art neural network architecture, achieved remarkable accuracy in predicting protein structures from amino acid sequences. This raises the question whether AF2 has learned the principles of protein folding sufficiently for de novo design. Here, we sought to answer this question by inverting the AF2 network, using the prediction weight set and a loss function to bias the generated sequences to adopt a target fold. Initial design trials resulted in de novo designs with an overrepresentation of hydrophobic residues on the protein surface compared to their natural protein family, requiring additional surface optimization. In silico validation of the designs showed protein structures with the correct fold, a hydrophilic surface and a densely packed hydrophobic core. In vitro validation showed that 7 out of 39 designs were folded and stable in solution with high melting temperatures. In summary, our design workflow solely based on AF2 does not seem to fully capture basic principles of de novo protein design, as observed in the protein surface's hydrophobic vs. hydrophilic patterning. However, with minimal post-design intervention, these pipelines generated viable sequences as assessed experimental characterization. Thus, such pipelines show the potential to contribute to solving outstanding challenges in de novo protein design.
Topics: Furylfuramide; Protein Engineering; Proteins; Amino Acid Sequence; Protein Folding
PubMed: 37165539
DOI: 10.1002/pro.4653