scholarly journals Evolution of a cytoplasmic determinant: evidence for the biochemical basis of functional evolution of the novel germ line regulator oskar

2021 ◽  
Author(s):  
Leo Blondel ◽  
Savandara Besse ◽  
Emily L Rivard ◽  
Guillem Ylla ◽  
Cassandra G Extavour
Keyword(s):  
Rna Binding ◽  
Germ Line ◽  
Critical Role ◽  
Binding Potential ◽  
Physical Interaction ◽  
Sequence Evolution ◽  
Biochemical Basis ◽  
Evolutionary Changes ◽  
Rapid Divergence ◽  
History Of

Abstract Germ line specification is essential in sexually reproducing organisms. Despite their critical role, the evolutionary history of the genes that specify animal germ cells is heterogeneous and dynamic. In many insects, the gene oskar is required for the specification of the germ line. However, the germ line role of oskar is thought to be a derived role resulting from co-option from an ancestral somatic role. To address how evolutionary changes in protein sequence could have led to changes in the function of Oskar protein that enabled it to regulate germ line specification, we searched for oskar orthologs in 1565 publicly available insect genomic and transcriptomic datasets. The earliest-diverging lineage in which we identified an oskar ortholog was the order Zygentoma (silverfish and firebrats), suggesting that oskar originated before the origin of winged insects. We noted some order-specific trends in oskar sequence evolution, including whole gene duplications, clade-specific losses, and rapid divergence. An alignment of all known 379 Oskar sequences revealed new highly conserved residues as candidates that promote dimerization of the LOTUS domain. Moreover, we identified regions of the OSK domain with conserved predicted RNA binding potential. Furthermore, we show that despite a low overall amino acid conservation, the LOTUS domain shows higher conservation of predicted secondary structure than the OSK domain. Finally, we suggest new key amino acids in the LOTUS domain that may be involved in the previously reported Oskar-Vasa physical interaction that is required for its germ line role.

scholarly journals Evolution of a cytoplasmic determinant: evidence for the biochemical basis of functional evolution of a novel germ line regulator

2021 ◽  
Author(s):  
Leo Blondel ◽  
Savandara Besse ◽  
Cassandra G. Extavour
Keyword(s):  
Rna Binding ◽  
Germ Line ◽  
Critical Role ◽  
Binding Potential ◽  
Physical Interaction ◽  
Sequence Evolution ◽  
Biochemical Basis ◽  
Evolutionary Changes ◽  
Rapid Divergence ◽  
History Of

AbstractGerm line specification is essential in sexually reproducing organisms. Despite their critical role, the evolutionary history of the genes that specify animal germ cells is heterogeneous and dynamic. In many insects, the geneoskaris required for the specification of the germ line. However, the germ line role ofoskaris thought to be a derived role resulting from co-option from an ancestral somatic role. To address how evolutionary changes in protein sequence could have led to changes in the function of Oskar protein that enabled it to regulate germ line specification, we searched foroskarorthologs in 1565 publicly available insect genomic and transcriptomic datasets. The earliest-diverging lineage in which we identified anoskarortholog was the order Zygentoma (silverfish and firebrats), suggesting thatoskaroriginated before the origin of winged insects. We noted some order-specific trends inoskarsequence evolution, including whole gene duplications, clade-specific losses, and rapid divergence. An alignment of all known 379 Oskar sequences revealed new highly conserved residues as candidates that promote dimerization of the LOTUS domain. Moreover, we identified regions of the OSK domain with conserved predicted RNA binding potential. Furthermore, we show that despite a low overall amino acid conservation, the LOTUS domain shows higher conservation of predicted secondary structure than the OSK domain. Finally, we suggest new key amino acids in the LOTUS domain that may be involved in the previously reported Oskar-Vasa physical interaction that is required for its germ line role.

Chips with Everything

2017 ◽  
Author(s):  
David Segal
Keyword(s):  
Quantum Computing ◽  
Integrated Circuits ◽  
Critical Role ◽  
Moore’S Law ◽  
Moore's Law ◽  
Silicon Chips ◽  
History Of ◽  
Future Potential ◽  
Digital Computers ◽  
Dna Computer

Chapter 3 highlights the critical role materials have in the development of digital computers. It traces developments from the cat’s whisker to valves through to relays and transistors. Accounts are given for transistors and the manufacture of integrated circuits (silicon chips) by use of photolithography. Future potential computing techniques, namely quantum computing and the DNA computer, are covered. The history of computability and Moore’s Law are discussed.

scholarly journals RNA-binding proteins La and HuR cooperatively modulate translation repression of PDCD4 mRNA

2020 ◽  
pp. jbc.RA120.014894
Author(s):  
Ravi Kumar ◽  
Dipak Kumar Poria ◽  
Partho Sarothi Ray
Keyword(s):  
Inflammatory Response ◽  
Chronic Inflammation ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Critical Role ◽  
Regulation Of Gene Expression ◽  
Mrna Translation ◽  
Suppressor Gene ◽  
Cooperative Action ◽  
Translation Repression

Post-transcriptional regulation of gene expression plays a critical role in controlling the inflammatory response. An uncontrolled inflammatory response results in chronic inflammation, often leading to tumorigenesis. Programmed cell death 4 (PDCD4) is a pro-inflammatory tumor-suppressor gene which helps to prevent the transition from chronic inflammation to cancer. PDCD4 mRNA translation is regulated by an interplay between the oncogenic microRNA miR-21 and the RNA-binding protein (RBP) HuR in response to LPS stimulation, but the role of other regulatory factors remain unknown. Here we report that the RBP Lupus antigen (La) interacts with the 3’UTR of PDCD4 mRNA and prevents miR-21-mediated translation repression. While LPS causes nuclear-cytoplasmic translocation of HuR, it enhances cellular La expression. Remarkably, La and HuR were found to bind cooperatively to the PDCD4 mRNA and mitigate miR-21-mediated translation repression. The cooperative action of La and HuR reduced cell proliferation and enhanced apoptosis, reversing the pro-oncogenic function of miR-21. Together, these observations demonstrate a cooperative interplay between two RBPs, triggered differentially by the same stimulus, which exerts a synergistic effect on PDCD4 expression and thereby helps maintain a balance between inflammation and tumorigenesis.

scholarly journals Transcriptional coregualtor NUPR1 maintains tamoxifen resistance in breast cancer cells

2021 ◽  
Vol 12 (2) ◽  
Author(s):  
Lingling Wang ◽  
Jiashen Sun ◽  
Yueyuan Yin ◽  
Yanan Sun ◽  
Jinyi Ma ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Critical Role ◽  
Endocrine Resistance ◽  
Autophagic Flux ◽  
Physical Interaction ◽  
Premature Senescence ◽  
Breast Cancers ◽  
Transcriptional Coregulator

AbstractTo support cellular homeostasis and mitigate chemotherapeutic stress, cancer cells must gain a series of adaptive intracellular processes. Here we identify that NUPR1, a tamoxifen (Tam)-induced transcriptional coregulator, is necessary for the maintenance of Tam resistance through physical interaction with ESR1 in breast cancers. Mechanistically, NUPR1 binds to the promoter regions of several genes involved in autophagy process and drug resistance such as BECN1, GREB1, RAB31, PGR, CYP1B1, and regulates their transcription. In Tam-resistant ESR1 breast cancer cells, NUPR1 depletion results in premature senescence in vitro and tumor suppression in vivo. Moreover, enforced-autophagic flux augments cytoplasmic vacuolization in NUPR1-depleted Tam resistant cells, which facilitates the transition from autophagic survival to premature senescence. Collectively, these findings suggest a critical role for NUPR1 as a transcriptional coregulator in enabling endocrine persistence of breast cancers, thus providing a vulnerable diagnostic and/or therapeutic target for endocrine resistance.

Friends of Rose Canyon

2018 ◽  
Vol 95 (3) ◽  
pp. 2-20 ◽  
Author(s):  
Andrew Wiese
Keyword(s):  
Open Space ◽  
Critical Role ◽  
First Century ◽  
Grassroots Politics ◽  
History Of ◽  
University City ◽  
Participant Observer ◽  
The Rose

Place-based activism has played a critical role in the history of urban and environmental politics in California. This article explores the continuing significance of environmental place making to grassroots politics through a case study of Friends of Rose Canyon, an environmental group in San Diego. Based in the fast-growing University City neighborhood, Friends of Rose Canyon waged a long, successful campaign between 2002 and 2018 to prevent construction of a bridge in the Rose Canyon Open Space Park in their community. Using historical and participant observer methodologies, this study reveals how twenty-first-century California urbanites claimed and created meaningful local places and mobilized effective politics around them. It illuminates the critical role of individual activists; suggests practical, replicable strategies for community mobilization; and demonstrates the significant impact of local activism at the urban and metropolitan scales.

IMGs Have Played Critical Role In History of U.S. Psychiatry

2002 ◽  
Vol 37 (21) ◽  
pp. 18-44
Author(s):  
David Milne
Keyword(s):  
Critical Role ◽  
History Of

scholarly journals CHEK2∗1100delC Mutation and Risk of Prostate Cancer

2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Victoria Hale ◽  
Maren Weischer ◽  
Jong Y. Park
Keyword(s):  
Prostate Cancer ◽  
Current Knowledge ◽  
Prostate Cancer Screening ◽  
Critical Role ◽  
Prostate Cancer Risk ◽  
Conclusive Evidence ◽  
Increased Risk ◽  
History Of ◽  
Cancer Studies

Although the causes of prostate cancer are largely unknown, previous studies support the role of genetic factors in the development of prostate cancer.CHEK2plays a critical role in DNA replication by responding to double-stranded breaks. In this review, we provide an overview of the current knowledge of the role of a genetic variant, 1100delC, ofCHEK2on prostate cancer risk and discuss the implication for potential translation of this knowledge into clinical practice. Currently, twelve articles that discussedCHEK2∗1100delC and its association with prostate cancer were identified. Of the twelve prostate cancer studies, five studies had independent data to draw conclusive evidence from. The pooled results of OR and 95% CI were 1.98 (1.23–3.18) for unselected cases and 3.39 (1.78–6.47) for familial cases, indicating thatCHEK2∗1100delC mutation is associated with increased risk of prostate cancer. Screening for CHEK2∗1100delC should be considered in men with a familial history of prostate cancer.

scholarly journals A dark clue to seesaw and leptogenesis in a pseudo-Dirac singlet doublet scenario with (non)standard cosmology

2021 ◽  
Vol 2021 (3) ◽  
Author(s):  
Partha Konar ◽  
Ananya Mukherjee ◽  
Abhijit Kumar Saha ◽  
Sudipta Show
Keyword(s):  
Dark Matter ◽  
Thermal History ◽  
Direct Detection ◽  
Critical Role ◽  
Mass Term ◽  
Baryon Asymmetry ◽  
Dark Sector ◽  
Lepton Asymmetry ◽  
History Of ◽  
The Universe

Abstract We propose an appealing alternative scenario of leptogenesis assisted by dark sector which leads to the baryon asymmetry of the Universe satisfying all theoretical and experimental constraints. The dark sector carries a non minimal set up of singlet doublet fermionic dark matter extended with copies of a real singlet scalar field. A small Majorana mass term for the singlet dark fermion, in addition to the typical Dirac term, provides the more favourable dark matter of pseudo-Dirac type, capable of escaping the direct search. Such a construction also offers a formidable scope to radiative generation of active neutrino masses. In the presence of a (non)standard thermal history of the Universe, we perform the detailed dark matter phenomenology adopting the suitable benchmark scenarios, consistent with direct detection and neutrino oscillations data. Besides, we have demonstrated that the singlet scalars can go through CP-violating out of equilibrium decay, producing an ample amount of lepton asymmetry. Such an asymmetry then gets converted into the observed baryon asymmetry of the Universe through the non-perturbative sphaleron processes owing to the presence of the alternative cosmological background considered here. Unconventional thermal history of the Universe can thus aspire to lend a critical role both in the context of dark matter as well as in realizing baryogenesis.

AMPK blocks chromatin activation and consequent R-loop formation to protect genome stability following acute starvation

2021 ◽  
Author(s):  
Bing Sun ◽  
McLean Sherrin ◽  
Richard Roy
Keyword(s):  
Dna Damage ◽  
Genome Stability ◽  
Germ Line ◽  
Critical Role ◽  
Significant Proportion ◽  
Loop Formation ◽  
C Elegans ◽  
Chromatin Activation ◽  
Acute Starvation

Abstract During periods of starvation organisms must modify both gene expression and metabolic pathways to adjust to the energy stress. We previously reported that C. elegans that lack AMPK have transgenerational reproductive defects that result from abnormally elevated H3K4me3 levels in the germ line following recovery from acute starvation1. Here we show that H3K4me3 is dramatically increased at promoters, driving aberrant transcription elongation that results in the accumulation of R-loops in the starved AMPK mutants. DRIP-seq analysis demonstrated that a significant proportion of the genome was affected by R-loop formation with a dramatic expansion in the number of R-loops at numerous loci, most pronounced at the promoter-TSS regions of genes in the starved AMPK mutants. The R-loops are transmissible into subsequent generations, likely contributing to the transgenerational reproductive defects typical of these mutants following starvation. Strikingly, AMPK null germ lines show considerably more RAD-51 foci at sites of R-loop formation, potentially sequestering it from its critical role at meiotic breaks and/or at sites of induced DNA damage. Our study reveals a previously unforeseen role of AMPK in maintaining genome stability following starvation, where in its absence R-loops accumulate, resulting in reproductive compromise and DNA damage hypersensitivity.

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