scholarly journals Small RNA-Mediated De Novo Silencing of Ac/Ds Transposons Is Initiated by Alternative Transposition in Maize

Genetics ◽  
2020 ◽  
Vol 215 (2) ◽  
pp. 393-406 ◽  
Author(s):  
Dafang Wang ◽  
Jianbo Zhang ◽  
Tao Zuo ◽  
Meixia Zhao ◽  
Damon Lisch ◽  
...  
Keyword(s):  
Defense Mechanisms ◽  
De Novo ◽  
Inverted Repeats ◽  
Small Interfering Rnas ◽  
Major Fraction ◽  
First Case ◽  
Transposon Silencing ◽  
Alternative Transposition ◽  
Interfering Rna ◽  
Eukaryotic Genomes

Although transposable elements (TEs) comprise a major fraction of many higher eukaryotic genomes, most TEs are silenced by host defense mechanisms. The means by which otherwise active TEs are recognized and silenced remains poorly understood. Here we analyzed two independent cases of spontaneous silencing of the active maize Ac/Ds transposon system. This silencing is initiated by alternative transposition, a type of aberrant transposition event that engages the termini of two nearby separate TEs. Alternative transposition during DNA replication can generate Composite Insertions that contain inverted duplications of the transposon sequences. We show that the inverted duplications of two Composite Insertions are transcribed to produce double-stranded RNAs that trigger the production of two distinct classes of small interfering RNAs: a 24-nt class complementary to the TE terminal inverted repeats and noncoding subterminal regions, and a 21- to 22-nt class corresponding to the TE transcribed regions. Plants containing these small interfering RNA-generating Composite Insertions exhibit decreased levels of Ac transcript and heritable repression of Ac/Ds transposition. Further, we demonstrate that Composite Insertions can heritably silence otherwise active elements in trans. This study documents the first case of transposon silencing induced by alternative transposition and may represent a general initiating mechanism for silencing of DNA transposons.

scholarly journals siRNA-mediated de novo silencing of Ac/Ds transposons is initiated by alternative transposition in maize

2020 ◽  
Author(s):  
Dafang Wang ◽  
Jianbo Zhang ◽  
Tao Zuo ◽  
Damon Lisch ◽  
Meixia Zhao ◽  
...  
Keyword(s):  
Transposable Elements ◽  
Defense Mechanisms ◽  
De Novo ◽  
Inverted Repeats ◽  
Small Interfering Rnas ◽  
Major Fraction ◽  
First Case ◽  
Transposon Silencing ◽  
Alternative Transposition ◽  
Eukaryotic Genomes

AbstractAlthough Transposable Elements (TEs) comprise a major fraction of many higher eukaryotic genomes, most TEs are silenced by host defense mechanisms. The means by which otherwise active TEs are recognized and silenced remains poorly understood. Here we analyzed two independent cases of spontaneous silencing of the active maize Ac/Ds transposon system. This silencing was initiated by Alternative Transposition (AT), a type of aberrant transposition event that engages the termini of two nearby separate TEs. AT during DNA replication can generate Composite Insertions (CIs) that contain inverted duplications of the transposon sequences. We show that the inverted duplications of two CIs are transcribed to produce dsRNAs that trigger the production of two distinct classes of siRNAs: a 24-nt class complementary to the TE terminal inverted repeats (TIRs) and non-coding sub-terminal regions, and a 21-22 nt class corresponding to the TE transcribed regions. Plants containing these siRNA-generating CIs exhibit decreased levels of Ac transcript and heritable repression of Ac/Ds transposition. This study documents the first case of TE silencing attributable to transposon self-initiated AT and may represent a general initiating mechanism for silencing of DNA transposons.Article summaryTransposable Elements (TEs) are often silenced by their hosts, but how TEs are initially recognized for silencing remains unclear. Here we describe two independent loci that induce de novo heritable silencing of maize Ac/Ds transposons. Plants containing these loci produce dsRNA and Ac-homologous small interfering RNAs, and exhibit decreased levels of Ac transcript and heritable repression of Ac/Ds transposition. We show that these loci comprise inverted duplications of TE sequences generated by Alternative Transposition coupled with DNA re-replication. This study documents the first case of transposon silencing induced by AT and may represent a general initiating mechanism for TE silencing.

scholarly journals Epigenetic conflict on a degenerating Y chromosome increases mutational burden in Drosophila males

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Kevin H.-C. Wei ◽  
Lauren Gibilisco ◽  
Doris Bachtrog
Keyword(s):  
Y Chromosome ◽  
Early Development ◽  
Defense Mechanisms ◽  
De Novo ◽  
Genome Integrity ◽  
Selfish Dna ◽  
Mutational Burden ◽  
Y Chromosomes ◽  
Genome Wide ◽  
Eukaryotic Genomes

Abstract Large portions of eukaryotic genomes consist of transposable elements (TEs), and the establishment of transcription-repressing heterochromatin during early development safeguards genome integrity in Drosophila. Repeat-rich Y chromosomes can act as reservoirs for TEs (‘toxic’ Y effect), and incomplete epigenomic defenses during early development can lead to deleterious TE mobilization. Here, we contrast the dynamics of early TE activation in two Drosophila species with vastly different Y chromosomes of different ages. Zygotic TE expression is elevated in male embryos relative to females in both species, mostly due to expression of Y-linked TEs. Interestingly, male-biased TE expression diminishes across development in D. pseudoobscura, but remains elevated in D. miranda, the species with the younger and larger Y chromosome. The repeat-rich Y of D. miranda still contains many actively transcribed genes, which compromise the formation of silencing heterochromatin. Elevated TE expression results in more de novo insertions of repeats in males compared to females. This lends support to the idea that the ‘toxic’ Y chromosome can create a mutational burden in males when genome-wide defense mechanisms are compromised, and suggests a previously unappreciated epigenetic conflict on evolving Y chromosomes between transcription of essential genes and silencing of selfish DNA.

scholarly journals Broad noncoding transcription suggests genome surveillance by RNA polymerase V

2020 ◽  
Vol 117 (48) ◽  
pp. 30799-30804
Author(s):  
Masayuki Tsuzuki ◽  
Shriya Sethuraman ◽  
Adriana N. Coke ◽  
M. Hafiz Rothi ◽  
Alan P. Boyle ◽  
...  
Keyword(s):  
Rna Polymerase ◽  
De Novo ◽  
Genome Integrity ◽  
Biological Functions ◽  
Pol V ◽  
Low Levels ◽  
Interfering Rna ◽  
Eukaryotic Genomes ◽  
Transcribed Sequences ◽  
Pervasive Transcription

Eukaryotic genomes are pervasively transcribed, yet most transcribed sequences lack conservation or known biological functions. InArabidopsis thaliana, RNA polymerase V (Pol V) produces noncoding transcripts, which base pair with small interfering RNA (siRNA) and allow specific establishment of RNA-directed DNA methylation (RdDM) on transposable elements. Here, we show that Pol V transcribes much more broadly than previously expected, including subsets of both heterochromatic and euchromatic regions. At already established RdDM targets, Pol V and siRNA work together to maintain silencing. In contrast, some euchromatic sequences do not give rise to siRNA but are covered by low levels of Pol V transcription, which is needed to establish RdDM de novo if a transposon is reactivated. We propose a model where Pol V surveils the genome to make it competent to silence newly activated or integrated transposons. This indicates that pervasive transcription of nonconserved sequences may serve an essential role in maintenance of genome integrity.

scholarly journals Epigenetic conflict on a degenerating Y chromosome increases mutational burden in Drosophila males

2020 ◽  
Author(s):  
Kevin H.-C. Wei ◽  
Lauren Gibilisco ◽  
Doris Bachtrog
Keyword(s):  
Y Chromosome ◽  
Early Development ◽  
Defense Mechanisms ◽  
De Novo ◽  
Genome Integrity ◽  
Selfish Dna ◽  
Mutational Burden ◽  
Y Chromosomes ◽  
Genome Wide ◽  
Eukaryotic Genomes

AbstractLarge portions of eukaryotic genomes consist of transposable elements (TEs), and the establishment of transcription-repressing heterochromatin during early development safeguards genome integrity in Drosophila. Repeat-rich Y chromosomes can act as reservoirs for TEs (‘toxic’ Y effect), and incomplete epigenomic defenses during early development can lead to deleterious TE mobilization. Here, we contrast the dynamics of early TE activation in two Drosophila species with vastly different Y chromosomes of different age. Zygotic TE expression is elevated in male embryos relative to females in both species, mostly due to expression of Y-linked TEs. Interestingly, male-biased TE misexpression diminishes across development in D. pseudoobscura, but remains elevated in D. miranda, the species with the younger and larger Y chromosome. The repeat-rich Y of D. miranda still contains many actively transcribed genes, which compromise the formation of silencing heterochromatin. Elevated TE expression results in more de novo insertions of repeats in males compared to females. This lends support to the idea that the ‘toxic’ Y chromosome can create a mutational burden in males when genome-wide defense mechanisms are compromised, and suggests a previously unappreciated epigenetic conflict on evolving Y chromosomes between transcription of essential genes and silencing of selfish DNA.

scholarly journals Endovascular repair of de novo post-stenotic aortic coarctation aneurysms with complex collateral supply: two cases with long and medium term follow-up

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Omar Abdel-Hadi ◽  
John Thomson ◽  
Simon J. McPherson
Keyword(s):  
Stent Graft ◽  
Endovascular Repair ◽  
Aortic Coarctation ◽  
De Novo ◽  
Aortic Aneurysms ◽  
Medium Term ◽  
First Case ◽  
Case Presentations ◽  
Selective Embolisation

Abstract Purpose To report the technical details and outcomes of the endovascular repair of two cases of de novo post-stenotic aortic coarctation aneurysms complicated by complex collateral supply. Case presentations Two patients with thoracic aortic aneurysms complicated by complex aneurysm sac collaterals distal to a previously untreated thoracic aortic coarctation have been treated at our institution. Open surgical intervention was deemed to carry a high risk of haemorrhage due to the degree and complexity of arterial collateralisation. In the first case, selective embolisation of collateral vasculature was performed prior to successful exclusion of the aneurysm with a thoracic endovascular stent-graft and then balloon-expandable stent dilatation of the coarctation stenosis. In the second case, the additional technique of using a jailed sheath within the aneurysm sac allowed for selective embolisation of previously inconspicuous collaterals after deployment of the stent-graft and stent combination. Results Technical success was achieved in both patients with successful occlusion of the aneurysm, with no recorded complications or aneurysm sac perfusion in the long and medium term follow up periods respectively. Conclusion De novo post stenotic aortic coarctation aneurysms are rare. Endovascular repair is a safe and durable technique that provides a less invasive alternative to open surgical repair. The use of a jailed sheath allows for complete selective embolisation of complex collaterals avoiding a type II aneurysm endoleak.

Enhanced accumulation of pinosylvin stilbenes and related gene expression in Pinus strobus after infection of pine wood nematode

2021 ◽  
Author(s):  
Hwan-Su Hwang ◽  
Jung Yeon Han ◽  
Yong Eui Choi
Keyword(s):  
Transcription Factors ◽  
Defense Mechanisms ◽  
De Novo ◽  
Pinus Strobus ◽  
Pine Wilt Disease ◽  
Monomethyl Ether ◽  
Bursaphelenchus Xylophilus ◽  
Nematicidal Activity ◽  
Dependent Manner ◽  
Pine Wood

Abstract Pine wood nematodes (PWNs: Bursaphelenchus xylophilus) infect pine trees and cause serious pine wilt disease. Eastern white pine (Pinus strobus) has resistance to PWN. However, the detailed defense mechanisms of P. strobus against PWN are not well known. When P. strobus plants were infected with PWNs, the accumulation of stilbenoids, dihydropinosylvin monomethyl ether (DPME) and pinosylvin monomethyl ether (PME), were increased remarkably. DPME and PME had the high nematicidal activity. Interestingly, the nematicidal activity of the two compounds was resulted in a developmental stage-dependent manner. PME was more toxic to adult PWNs than juveniles, whereas DPME was found more toxic to juvenile PWNs than the adults. The genes involved in PME and DPME biosynthesis such as phenylalanine ammonia-lyase (PAL), 4-coumarate-CoA ligase (4CL), pinosylvin synthase (STS), and pinosylvin O-methyltransferase (PMT) were isolated using de novo sequencing of the transcriptome in P. strobus. In addition, transcription factors (bHLH, MYB and WRKY) related to stilbene biosynthesis were isolated. qPCR analyses of the selected genes (PAL, 4CL, STS, and PMT) including transcription factors (bHLH, MYB and WRKY) revealed that the expression level of the selected genes highly enhanced after PWN infection. Our results suggest that pinosylvin-type stilbenoid biosynthesis is highly responsive to PWN infection and plays an important role in PWN resistance of P. strobus trees.

scholarly journals Pustular Rash in Crohn’s Patient on Ustekinumab Raises Concern for Drug-Induced Paradoxical Psoriasis

2021 ◽  
pp. 662-666
Author(s):  
Mitra Barahimi ◽  
Scott Lee ◽  
Kindra Clark-Snustad
Keyword(s):  
Side Effect ◽  
De Novo ◽  
Pustular Psoriasis ◽  
Initial Weight ◽  
Drug Induced ◽  
Clinical Recurrence ◽  
Potential Side Effect ◽  
First Case ◽  
Tnf Antagonist ◽  
Subcorneal Pustular Dermatosis

We report the case of a 51-year-old male with Crohn’s disease (CD) who developed a reproducible pustular rash after ustekinumab (UST) administration. The patient first presented with a pustular rash on his hands, body, extremities, and scalp starting 5 weeks after his initial weight-based UST induction. The rash resolved spontaneously, then recurred 4 weeks after his first subcutaneous maintenance dose of UST 90 mg. Biopsy of the affected area demonstrated subcorneal pustular dermatosis (SPD). UST was discontinued and the rash resolved. Unfortunately, the patient experienced clinical recurrence of CD, and given prior failure of multiple CD medications, UST was restarted with premedication. Two weeks after UST re-induction, the rash recurred, though less severe. Given improvement in CD symptoms, UST was continued and the rash managed with topical corticosteroids. This is the first case of drug-induced SPD associated with UST. One case report has previously described de novo pustular psoriasis associated with UST in a patient with CD and enteropathic arthritis. Notably, SPD and pustular psoriasis can be histologically indistinguishable. The development of a paradoxical psoriasiform rash is thought to be one of the few dose and duration dependent side effects of TNF-antagonist therapy but has not previously been established as a side effect of UST. This case demonstrates a new potential side effect of UST.

Computational study for suppression of CD25/IL-2 interaction

2020 ◽  
Vol 0 (0) ◽  
Author(s):  
Moein Dehbashi ◽  
Zohreh Hojati ◽  
Majid Motovali-bashi ◽  
Mazdak Ganjalikhani-Hakemi ◽  
Akihiro Shimosaka ◽  
...  
Keyword(s):  
Small Molecules ◽  
Cancer Progression ◽  
Immune Escape ◽  
De Novo ◽  
Computational Study ◽  
Treg Cells ◽  
Homology Search ◽  
Small Interfering Rnas

AbstractCancer recurrence presents a huge challenge in cancer patient management. Immune escape is a key mechanism of cancer progression and metastatic dissemination. CD25 is expressed in regulatory T (Treg) cells including tumor-infiltrating Treg cells (TI-Tregs). These cells specially activate and reinforce immune escape mechanism of cancers. The suppression of CD25/IL-2 interaction would be useful against Treg cells activation and ultimately immune escape of cancer. Here, software, web servers and databases were used, at which in silico designed small interfering RNAs (siRNAs), de novo designed peptides and virtual screened small molecules against CD25 were introduced for the prospect of eliminating cancer immune escape and obtaining successful treatment. We obtained siRNAs with low off-target effects. Further, small molecules based on the binding homology search in ligand and receptor similarity were introduced. Finally, the critical amino acids on CD25 were targeted by a de novo designed peptide with disulfide bond. Hence we introduced computational-based antagonists to lay a foundation for further in vitro and in vivo studies.

scholarly journals The rare hemoglobin variant Hb Mizuho: report of a Swiss family and literature review

2021 ◽  
Author(s):  
Linet Njue ◽  
Cesare Medri ◽  
Peter Keller ◽  
Miriam Diepold ◽  
Behrouz Mansouri Taleghani ◽  
...  
Keyword(s):  
Literature Review ◽  
Hemolytic Anemia ◽  
De Novo ◽  
Clinical History ◽  
Molecular Techniques ◽  
De Novo Mutation ◽  
First Case ◽  
History Of ◽  
Transfusion Dependency ◽  
Unstable Hemoglobin

AbstractHb Mizuho is a very rare unstable hemoglobin; here, we describe the clinical history of three Swiss family members with Hb Mizuho together with a systematic review of the previously six published cases. The clinical history of the adult woman we report here is unique since this is the first Hb Mizuho presenting with Moyamoya complications and the first case reported with long-term erythrocyte exchange. The literature review showed that Hb Mizuho was mainly reported as a de novo mutation, with the exception of children descended from known cases. All published patients with this unstable hemoglobin showed severe hemolytic anemia with the exception of one; all were regularly transfused. Patients with higher HbF levels might require fewer transfusions. All patients underwent splenectomy at a median age of 4 years and had variable clinical improvement; some achieved complete resolution of transfusion dependency after splenectomy. Iron overload in Hb Mizuho patients seems to be mainly attributed to transfusions and has less to do with ineffective erythropoiesis. Diagnosis might be challenging; a normal hemoglobin electrophoresis should not rule out the diagnosis of unstable hemoglobin in patients with otherwise unexplained hemolytic anemia. This series shows the enormous utility of using molecular techniques for diagnosis.

Gordon syndrome caused by a CUL3 mutation in a patient with short stature in Korea: a case report

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Ji Hong Park ◽  
Ji Hyun Kim ◽  
Yo Han Ahn ◽  
Hee Gyung Kang ◽  
Il Soo Ha ◽  
...  
Keyword(s):  
Metabolic Acidosis ◽  
Short Stature ◽  
De Novo ◽  
Plasma Renin ◽  
Endocrine Function ◽  
First Case ◽  
Pseudohypoaldosteronism Type Ii ◽  
Stimulation Tests ◽  
Severity Of The Disease ◽  
Potassium Gradient

Abstract Objectives: Gordon syndrome (GS), also known as pseudohypoaldosteronism type II, is a rare tubular disease characterized by hypertension, hyperkalemia, and metabolic acidosis. Its causative genes are CUL3, KLHL3, WNK1, and WNK4, and they are associated with varying severity of the disease. Herein, we report the first case of GS caused by a CUL3 mutation in a patient with short stature in Korea.Case presentation: A 7-year-old boy had hypertension, metabolic acidosis, and persistent hyperkalemia, which were initially detected during the evaluation of short stature. He was born small for gestational age at late preterm gestation. Laboratory test findings showed hyperkalemia with low trans-tubular potassium gradient, hyperchloremic metabolic acidosis with a normal anion gap, and low plasma renin levels. Genetic analysis revealed a heterozygous de novo mutation in the CUL3 gene (c.1377+1G > C in intron 9). Thus, a diagnosis of GS was made. The results of the endocrine function test (including growth hormone stimulation tests) were normal. After thiazide treatment, the patient’s electrolyte levels were normalized. However, he presented with persistent hypertension and short stature.Conclusions: GS should be considered in children with short stature, hypertension, and hyperkalemia, and early treatment may reduce complications.

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