scholarly journals A large-scale transgenic RNAi screen identifies transcription factors that modulate myofiber size in Drosophila

PLoS Genetics ◽  
2021 ◽  
Vol 17 (11) ◽  
pp. e1009926
Author(s):  
Flavia A. Graca ◽  
Natalie Sheffield ◽  
Melissa Puppa ◽  
David Finkelstein ◽  
Liam C. Hunt ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Skeletal Muscles ◽  
Large Scale ◽  
Body Wall ◽  
Glycolytic Enzymes ◽  
Developmental Growth ◽  
Transcriptional Changes ◽  
Atrophy And Hypertrophy ◽  
Underlying Mechanisms

Myofiber atrophy occurs with aging and in many diseases but the underlying mechanisms are incompletely understood. Here, we have used >1,100 muscle-targeted RNAi interventions to comprehensively assess the function of 447 transcription factors in the developmental growth of body wall skeletal muscles in Drosophila. This screen identifies new regulators of myofiber atrophy and hypertrophy, including the transcription factor Deaf1. Deaf1 RNAi increases myofiber size whereas Deaf1 overexpression induces atrophy. Consistent with its annotation as a Gsk3 phosphorylation substrate, Deaf1 and Gsk3 induce largely overlapping transcriptional changes that are opposed by Deaf1 RNAi. The top category of Deaf1-regulated genes consists of glycolytic enzymes, which are suppressed by Deaf1 and Gsk3 but are upregulated by Deaf1 RNAi. Similar to Deaf1 and Gsk3 overexpression, RNAi for glycolytic enzymes reduces myofiber growth. Altogether, this study defines the repertoire of transcription factors that regulate developmental myofiber growth and the role of Gsk3/Deaf1/glycolysis in this process.

Inflammatory Biomarkers in Atrial Fibrillation

2019 ◽  
Vol 26 (5) ◽  
pp. 837-854 ◽  
Author(s):  
Effimia Zacharia ◽  
Nikolaos Papageorgiou ◽  
Adam Ioannou ◽  
Gerasimos Siasos ◽  
Spyridon Papaioannou ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Plasma Levels ◽  
Large Scale ◽  
Inflammatory Biomarkers ◽  
Inflammatory Pathways ◽  
Inflammatory State ◽  
Anti Inflammatory ◽  
Underlying Mechanisms

During the last few years, a significant number of studies have attempted to clarify the underlying mechanisms that lead to the presentation of atrial fibrillation (AF). Inflammation is a key component of the pathophysiological processes that lead to the development of AF; the amplification of inflammatory pathways triggers AF, and, in tandem, AF increases the inflammatory state. Indeed, the plasma levels of several inflammatory biomarkers are elevated in patients with AF. In addition, the levels of specific inflammatory biomarkers may provide information regarding to the AF duration. Several small studies have assessed the role of anti-inflammatory treatment in atrial fibrillation but the results have been contradictory. Large-scale studies are needed to evaluate the role of inflammation in AF and whether anti-inflammatory medications should be routinely administered to patients with AF.

scholarly journals Co-option of the Limb Patterning Program in Cephalopod Lens Development

2021 ◽  
Author(s):  
Stephanie Neal ◽  
Kyle J. McCulloch ◽  
Francesca Napoli ◽  
Christina M. Daly ◽  
James H. Coleman ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Wnt Signaling ◽  
Functional Significance ◽  
Limb Development ◽  
Lens Development ◽  
Limb Patterning ◽  
Regulatory Relationship ◽  
Radial Patterning ◽  
Underlying Mechanisms

AbstractAcross the Metazoa, similar genetic programs are found in the development of analogous, independently evolved, morphological features. The functional significance of this reuse and the underlying mechanisms of co-option remain unclear. Here we identify the co-option of the canonical bilaterian limb pattering program redeployed during cephalopod lens development, a functionally unrelated structure. We show radial expression of transcription factorsSP6-9/sp1, Dlx/dll, Pbx/exd, Meis/hth, and aPrdlhomolog in the squidDoryteuthis pealeii, similar to expression required inDrosophilalimb development. We assess the role of Wnt signaling in the cephalopod lens, a positive regulator in the developing limb, and find the regulatory relationship reversed, with ectopic Wnt signaling leading to lens loss. This regulatory divergence suggests that duplication of SP6-9 in cephalopods may mediate this co-option. These results suggest that the limb network does not exclusively pattern appendage outgrowth but is performing a more universal developmental function: radial patterning.

scholarly journals The Malmö Offspring Study (MOS): design, methods and first results

2020 ◽  
Author(s):  
Louise Brunkwall ◽  
Daniel Jönsson ◽  
Ulrika Ericson ◽  
Sophie Hellstrand ◽  
Cecilia Kennbäck ◽  
...  
Keyword(s):  
Chronic Disease ◽  
Large Scale ◽  
Risk Scores ◽  
Oral Microbiota ◽  
Dietary Recall ◽  
Three Generations ◽  
First Results ◽  
Underlying Mechanisms ◽  
Rich Data

AbstractAs cardio metabolic disease manifestations tend to cluster in families there is a need to better understand the underlying mechanisms in order to further develop preventive strategies. In fact, genetic markers used in genetic risk scores, important as they are, will not be able alone to explain these family clusters. Therefore, the search goes on for the so called missing heritability to better explain these associations. Shared lifestyle and social conditions in families, but also early life influences may be of importance. Gene-environmental interactions should be explored. In recent years interest has grown for the role of diet-microbiota associations, as microbiota patterns may be shared by family members. In the Malmö Offspring Study that started in 2013, we have so far been able to examine about 4700 subjects (18–71 years) representing children and grandchildren of index subjects from the first generation, examined in the Malmö Diet Cancer Study during 1991 to 1996. This will provide rich data and opportunities to analyse family traits of chronic disease across three generations. We will provide extensive genotyping and phenotyping including cardiovascular and respiratory function, as well as markers of glucose metabolism. In addition, also cognitive function will be assessed. A 4-day online dietary recall will be conducted and gut as well as oral microbiota analysed. The ambition is to provide one of the first large-scale European family studies with individual data across three generations, which could deepen our knowledge about the role of family traits for chronic disease and its underlying mechanisms.

scholarly journals The Impact of Idealized Terrain on Upstream Tropical Cyclone Track

2018 ◽  
Vol 75 (11) ◽  
pp. 3887-3910 ◽  
Author(s):  
Kuan-Chieh Huang ◽  
Chun-Chieh Wu
Keyword(s):  
Large Scale ◽  
Inner Core ◽  
Wrf Model ◽  
Weather Research And Forecasting ◽  
Core Dynamics ◽  
Underlying Mechanisms ◽  
Channeling Effect ◽  
The Impact ◽  
Steering Current

Abstract Tropical cyclones (TCs) encountering the terrain of Taiwan usually experience prominent track deflection, resulting in uncertainty in TC track forecasts. The underlying mechanisms of TC deflection are examined to better understand the pattern of TC tracks under various flow regimes. In this study, idealized experiments are carried out utilizing the Advanced Research version of the Weather Research and Forecasting (WRF) Model. This study investigates the motion of a TC that is deflected southward while moving westward toward an idealized terrain similar to Taiwan. An analysis of both the flow asymmetries and the potential vorticity tendency (PVT) demonstrates that horizontal advection contributes to the southward movement of the TC. The track deflection is examined in two separate time periods, with different mechanisms leading to the southward movement. Changes in the background flow induced by the terrain first cause the large-scale steering current to push the TC southward while the TC is still far from the terrain. As the TC approaches the idealized topography, the role of the inner-core dynamics becomes important, and the TC terrain-induced channeling effect results in further southward deflection. Asymmetries in the midlevel flow also develop during this period, in part associated with the effect of vertical momentum transport. The combination of the large-scale environmental flow, the low-level channeling effect, and asymmetries in the midlevel flow all contribute to the southward deflection of the TC track.

scholarly journals Mechanisms Affecting the Biosynthesis and Incorporation Rate of Selenocysteine

Molecules ◽  
2021 ◽  
Vol 26 (23) ◽  
pp. 7120
Author(s):  
Jing-Jing Peng ◽  
Shi-Yang Yue ◽  
Yu-Hui Fang ◽  
Xiao-Ling Liu ◽  
Cheng-Hua Wang
Keyword(s):  
Large Scale ◽  
Translation Termination ◽  
Scientific Basis ◽  
Inorganic Selenium ◽  
Key Enzyme ◽  
The Operating Mechanism ◽  
Underlying Mechanisms ◽  
Action Modes ◽  
Functional Mechanisms

Selenocysteine (Sec) is the 21st non-standard proteinogenic amino acid. Due to the particularity of the codon encoding Sec, the selenoprotein synthesis needs to be completed by unique mechanisms in specific biological systems. In this paper, the underlying mechanisms for the biosynthesis and incorporation of Sec into selenoprotein were comprehensively reviewed on five aspects: (i) the specific biosynthesis mechanism of Sec and the role of its internal influencing factors (SelA, SelB, SelC, SelD, SPS2 and PSTK); (ii) the elements (SECIS, PSL, SPUR and RF) on mRNA and their functional mechanisms; (iii) the specificity (either translation termination or translation into Sec) of UGA; (iv) the structure–activity relationship and action mechanism of SelA, SelB, SelC and SelD; and (v) the operating mechanism of two key enzyme systems for inorganic selenium source flow before Sec synthesis. Lastly, the size of the translation initiation interval, other action modes of SECIS and effects of REPS (Repetitive Extragenic Palindromic Sequences) that affect the incorporation efficiency of Sec was also discussed to provide scientific basis for the large-scale industrial fermentation for the production of selenoprotein.

scholarly journals Integrated High-Throughput Small RNA and Transcriptome Sequencing Unveil The Shape-Dependent Toxicity of Nano-Alumina in Rat Astrocytes

2021 ◽  
Author(s):  
Yuanyuan Chen ◽  
Li Dong ◽  
Fuchang Deng ◽  
Yaqiang Cao ◽  
Yuanzheng Fu ◽  
...  
Keyword(s):  
Large Scale ◽  
Ex Vivo ◽  
Critical Role ◽  
Ether Lipid ◽  
Global Market ◽  
Alumina Nanoparticles ◽  
Toxic Response ◽  
Nano Alumina ◽  
Underlying Mechanisms

Abstract Background The large-scale applications of alumina nanoparticles (Al2O3-NPs), one of the most important NPs in the global market, is causing severe damages to the environment and human health. Our previous research has revealed a critical role of nanoparticle morphology (e.g., flake and rod) in determining the toxic potencies of Al2O3-NPs, where nanorods demonstrated a significantly stronger toxic response than that of nanoflakes. However, their underlying mechanisms have not been completely elucidated yet. In the present study, we evaluated and compared the potential toxicological mechanisms of two shapes of γ-Al2O3-NPs (flake versus rod) by measuring miRNAs and mRNAs profiles of astrocytes in rat cerebral cortex, ex vivo. Results Totals of 269 mRNAs and 122 miRNAs, 180 mRNAs and 116 miRNAs were differentially expressed after nanoflakes or nanorods exposure, respectively. Among them, 55 miRNAs (e.g., miR-760-5p, miR-326-3p, and miR-35) and 105 mRNAs (e.g., Kdm4d, Wdr62, and Rps6) showed the same trend between the two shapes. These miRNAs and mRNAs were mainly involved in apoptosis, inflammatory pathways (e.g., NF-kappa B), carcinogenic pathways (e.g., MAPK, p53, Notch, Rap1, and Ras), and cellular lipid metabolisms (e.g., glycerolipid metabolism, sphingolipid, and ether lipid metabolism). However, the remaining miRNAs and mRNAs either showed an opposite trend or only changed by a particular shape. Nanorods could specifically alter the changes of PI3K/Akt, AMPK and TNF pathways, cell cycle, and cellular senescence, while nanoflakes caused the changes of Toll and lmd signaling pathways. Conclusions In this study, we demonstrate that the toxicity of nanorods might be stronger than that of nanoflakes. And this study also demonstrates the critical role of morphology in nanotoxicity of nano-alumina and reveals its potential biomolecular mechanisms.

scholarly journals Complex Roles of Neutrophils during Arboviral Infections

Cells ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 1324
Author(s):  
Abenaya Muralidharan ◽  
St Patrick Reid
Keyword(s):  
Viral Replication ◽  
Large Scale ◽  
Viral Pathogenesis ◽  
Complex Nature ◽  
Effective Protection ◽  
Wide Range ◽  
The World ◽  
Underlying Mechanisms ◽  
A Site

Arboviruses are known to cause large-scale epidemics in many parts of the world. These arthropod-borne viruses are a large group consisting of viruses from a wide range of families. The ability of their vector to enhance viral pathogenesis and transmission makes the development of treatments against these viruses challenging. Neutrophils are generally the first leukocytes to be recruited to a site of infection, playing a major role in regulating inflammation and, as a result, viral replication and dissemination. However, the underlying mechanisms through which neutrophils control the progression of inflammation and disease remain to be fully understood. In this review, we highlight the major findings from recent years regarding the role of neutrophils during arboviral infections. We discuss the complex nature of neutrophils in mediating not only protection, but also augmenting disease pathology. Better understanding of neutrophil pathways involved in effective protection against arboviral infections can help identify potential targets for therapeutics.

Response Interference as a Mechanism Underlying Implicit Measures

2008 ◽  
Vol 24 (4) ◽  
pp. 218-225 ◽  
Author(s):  
Bertram Gawronski ◽  
Roland Deutsch ◽  
Etienne P. LeBel ◽  
Kurt R. Peters
Keyword(s):  
Task Performance ◽  
Psychological Research ◽  
Implicit Measures ◽  
Mediation Model ◽  
Response Interference ◽  
Relevant Evidence ◽  
Moderated Mediation Model ◽  
Stimulus Features ◽  
Underlying Mechanisms

Over the last decade, implicit measures of mental associations (e.g., Implicit Association Test, sequential priming) have become increasingly popular in many areas of psychological research. Even though successful applications provide preliminary support for the validity of these measures, their underlying mechanisms are still controversial. The present article addresses the role of a particular mechanism that is hypothesized to mediate the influence of activated associations on task performance in many implicit measures: response interference (RI). Based on a review of relevant evidence, we argue that RI effects in implicit measures depend on participants’ attention to association-relevant stimulus features, which in turn can influence the reliability and the construct validity of these measures. Drawing on a moderated-mediation model (MMM) of task performance in RI paradigms, we provide several suggestions on how to address these problems in research using implicit measures.

Sign in / Sign up

Export Citation Format

Share Document