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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 -
Glomerular Diseases Aug 2021De novo glomerular diseases comprising those both common and unique to transplant may develop in the renal allograft leading to posttransplant proteinuria, hematuria, or... (Review)
Review
BACKGROUND
De novo glomerular diseases comprising those both common and unique to transplant may develop in the renal allograft leading to posttransplant proteinuria, hematuria, or allograft failure. Electron microscopy (EM) is a useful adjunct to the standard light and immunofluorescence microscopy for accurately diagnosing these diseases and subsequently aiding the clinician in initiating appropriate treatments.
SUMMARY
De novo diseases are those new-onset diseases in renal transplantation that are unrelated to the original kidney disease in the recipient. They include virtually any primary or secondary glomerular, tubulointerstitial, or vascular diseases, ranging from subclinical to clinically overt, having acute, subacute, or chronic clinical presentations. This review focuses on common or significant, mainly glomerular, entities, with particular attention to the EM findings. The time of onset, stage, and severity of these diseases may often be modified by the current immunosuppressive protocols and other donor and recipient predisposing characteristics.
KEY MESSAGES
A renal allograft biopsy not only improves our understanding of the pathophysiology but also provides diagnostic accuracy prognostic information, and potential for reversibility. In some cases, the biopsy leads to detection of unsuspected or clinically asymptomatic de novo diseases in the setting of other concomitant rejection processes, infection, or toxicity, which can dictate appropriate therapy. Routine EM in transplant kidney biopsies is a valuable modality in recognizing fully developed or early/subtle features of evolving de novo diseases, often during the subclinical phases, in "for cause" or surveillance/protocol allograft biopsies.
PubMed: 36751493
DOI: 10.1159/000517124 -
Annals of Translational Medicine May 2021With the exponential increase of worldwide obesity, the number of bariatric surgery (BaS) procedures have equally risen. The surgical management of obesity has been... (Review)
Review
With the exponential increase of worldwide obesity, the number of bariatric surgery (BaS) procedures have equally risen. The surgical management of obesity has been widely established as the standard of care for sustained weight reduction, resolution, and improvement of associated comorbidities. However, BaS itself can have postoperative deleterious effects, including gastroesophageal reflux disease (GERD) and upper gastrointestinal motility disorders. The modified anatomy resulting from BaS, due to either a restrictive or hypoabsorptive component, gives this disorder a multifactorial etiology. The overall management of GERD should focus on three primordial approaches: Non-surgical, endoluminal, and surgical. Even in the absence of GERD following primary or secondary BaS, said disorder should be closely monitored and therapy should be catered in a case-by-case approach. Consequently, treatment strategies have been developed on this principle as to adequately resolve GERD. Despite the presence of multiple and suitable treatment modalities, the operating surgeon should perform them in the best interest of the patient. Short-, medium-, and long-term outcomes should be taken into consideration prior to proceed with any type of preferred management option. This article herein presents an update on the surgical management of GERD following BaS and current practical innovations.
PubMed: 34164533
DOI: 10.21037/atm-20-5890 -
ACS Applied Materials & Interfaces Nov 2021Biocatalysts hold great promise in chemical and electrochemical reactions. However, biocatalysts are prone to inhospitable physiochemical conditions. Encapsulating... (Review)
Review
Biocatalysts hold great promise in chemical and electrochemical reactions. However, biocatalysts are prone to inhospitable physiochemical conditions. Encapsulating biocatalysts into a synthetic host matrix can improve their stability and activity, and broaden their operational conditions. In this Review, we summarize the emerging de novo approaches to encapsulating biocatalysts into synthetic matrixes. Here, de novo means that embedding of biocatalysts and construction of matrixes take place simultaneously. We discuss the advantages and limitations of the de novo approach. On the basis of the nature of the biocatalysts and the synthetic frameworks, we specifically focus on two aspects: (1) encapsulation of enzymes (in vitro) in metal-organic frameworks and (2) encapsulation of microbial electrocatalysts (in vivo) on the electrode. For both cases, we discuss how the encapsulation improves biocatalysts' performance (stability, viability, activity, and etc.). We also highlight the benefit of encapsulation in facilitating the transport of charge carriers in microbial electrocatalysis.
PubMed: 34352175
DOI: 10.1021/acsami.1c09708 -
Frontiers in Plant Science 2023Plants, unlike animals, possess a unique developmental plasticity, that allows them to adapt to changing environmental conditions. A fundamental aspect of this... (Review)
Review
Plants, unlike animals, possess a unique developmental plasticity, that allows them to adapt to changing environmental conditions. A fundamental aspect of this plasticity is their ability to undergo postembryonic organogenesis. This requires the presence of regulators that trigger and mediate specific spatiotemporal changes in developmental programs. The phytohormone cytokinin has been known as a principal regulator of plant development for more than six decades. In shoot organogenesis and shoot regeneration, cytokinins are the prime candidates for the signal that determines shoot identity. Both processes of shoot apical meristem development are accompanied by changes in gene expression, cell fate reprogramming, and the switching-on of the shoot-specific homeodomain regulator, WUSCHEL. Current understanding about the role of cytokinins in the shoot regeneration will be discussed.
PubMed: 37662179
DOI: 10.3389/fpls.2023.1239133 -
Biology Jan 2023Protein therapeutics have been widely used to treat hematological disorders. With the advent of de novo protein design, protein therapeutics are not limited to... (Review)
Review
Protein therapeutics have been widely used to treat hematological disorders. With the advent of de novo protein design, protein therapeutics are not limited to ameliorating natural proteins but also produce novel protein sequences, folds, and functions with shapes and functions customized to bind to the therapeutic targets. De novo protein techniques have been widely used biomedically to design novel diagnostic and therapeutic drugs, novel vaccines, and novel biological materials. In addition, de novo protein design has provided new options for treating hematological disorders. Scientists have designed protein switches called Colocalization-dependent Latching Orthogonal Cage-Key pRoteins (Co-LOCKR) that perform computations on the surface of cells. De novo designed molecules exhibit a better capacity than the currently available tyrosine kinase inhibitors in chronic myeloid leukemia therapy. De novo designed protein neoleukin-2/15 enhances chimeric antigen receptor T-cell activity. This new technique has great biomedical potential, especially in exploring new treatment methods for hematological disorders. This review discusses the development of de novo protein design and its biological applications, with emphasis on the treatment of hematological disorders.
PubMed: 36829445
DOI: 10.3390/biology12020166 -
Molecules (Basel, Switzerland) Dec 2022Axially chiral heterobiaryl frameworks are privileged structures in many natural products, pharmaceutically active molecules, and chiral ligands. Therefore, a variety of... (Review)
Review
Axially chiral heterobiaryl frameworks are privileged structures in many natural products, pharmaceutically active molecules, and chiral ligands. Therefore, a variety of approaches for constructing these skeletons have been developed. Among them, de novo synthesis, due to its highly convergent and superior atom economy, serves as a promising strategy to access these challenging scaffolds including C-N, C-C, and N-N chiral axes. So far, several elegant reviews on the synthesis of axially chiral heterobiaryl skeletons have been disclosed, however, atroposelective construction of the heterobiaryl subunits by de novo synthesis was rarely covered. Herein, we summarized the recent advances in the catalytic asymmetric synthesis of the axially chiral heterobiaryl scaffold via de novo synthetic strategies. The related mechanism, scope, and applications were also included.
Topics: Biological Products; Catalysis; Skeleton
PubMed: 36500610
DOI: 10.3390/molecules27238517 -
World Journal of Transplantation Dec 2017The glomerular diseases after renal transplantation can occur ., with no relation to the native kidney disease, or more frequently occur as a recurrence of the original... (Review)
Review
The glomerular diseases after renal transplantation can occur ., with no relation to the native kidney disease, or more frequently occur as a recurrence of the original disease in the native kidney. There may not be any difference in clinical features and histological pattern between glomerular disease and recurrence of original glomerular disease. However, structural alterations in transplanted kidney add to dilemma in diagnosis. These changes in architecture of histopathology can happen due to: (1) exposure to the immunosuppression specifically the calcineurin inhibitors (CNI); (2) in vascular and tubulointerstitial alterations as a result of antibody mediated or cell-mediated immunological onslaught; (3) post-transplant viral infections; (4) ischemia-reperfusion injury; and (5) hyperfiltration injury. The pathogenesis of the glomerular diseases differs with each type. Stimulation of B-cell clones with subsequent production of the monoclonal IgG, particularly IgG3 subtype that has higher affinity to the negatively charged glomerular tissue, is suggested to be included in PGNMID pathogenesis. membranous nephropathy can be seen after exposure to the cryptogenic podocyte antigens. The role of the toxic effects of CNI including tissue fibrosis and the hemodynamic alterations may be involved in the FSGS pathophysiology. The well-known deleterious effects of HCV infection and its relation to MPGN disease are frequently reported. The new concepts have emerged that demonstrate the role of dysregulation of alternative complement pathway in evolution of MPGN that led to classifying into two subgroups, immune complex mediated MPGN and complement-mediated MPGN. The latter comprises of the dense deposit disease and the C3 GN disease. C3 disease is rather rare. Prognosis of diseases varies with each type and their management continues to be empirical to a large extent.
PubMed: 29312858
DOI: 10.5500/wjt.v7.i6.285 -
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 -
Clinical Journal of the American... Aug 2014Glomerular diseases developing in the kidney allograft are more often recurrences of the original disease affecting the native kidneys. However, in an undefined number... (Review)
Review
Glomerular diseases developing in the kidney allograft are more often recurrences of the original disease affecting the native kidneys. However, in an undefined number of cases de novo, glomerular diseases unrelated to the original disease in the native kidneys can develop in the transplanted kidney. The clinical presentation and histologic features of de novo diseases are often similar to those features observed in patients with primary or secondary GN in the native kidneys. However, in transplanted kidneys, the glomerular, vascular, and tubulointerstitial changes are often intertwined with structural abnormalities already present at the time of transplant or caused by antibody- or cell-mediated allograft rejection, immunosuppressive drugs, or superimposed infection (most often of a viral nature). The pathophysiology of de novo glomerular diseases is quite variable. In rare cases of de novo minimal change disease, circulating factors increasing the glomerular permeability likely participate. Maladaptive hemodynamic changes and tissue fibrosis caused by calcineurin inhibitors or other factors may be involved in the pathogenesis of de novo FSGS. The exposure of cryptic podocyte antigens may favor the development of de novo membranous nephropathy. Many cases of de novo membranoproliferative GN are related to hepatitis C virus infection. Patients with Alport syndrome lacking antigenic epitopes in their glomerular basement membrane may develop antibodies against these glomerular basement membrane antigens expressed in the transplanted kidney. Infection may cause acute GN to have a heterogeneous clinical presentation and outcome. De novo pauci-immune GN in renal transplant is rare. Preexisting or acquired intolerance to glucose may, in the long term, cause diabetic nephropathy. The prognosis of de novo diseases depends on the type of GN, the severity of lesions caused by the alloimmune response, or the efficacy of immunosuppressive therapy. In most cases, the management of de novo glomerular diseases is empirical or elusive.
Topics: Animals; Glomerulonephritis; Humans; Kidney Diseases; Kidney Glomerulus; Kidney Transplantation; Risk Factors; Treatment Outcome
PubMed: 24700797
DOI: 10.2215/CJN.12571213