scholarly journals TMT-Opsins differentially modulate medaka brain function in a context-dependent manner

PLoS Biology ◽  
2021 ◽  
Vol 19 (1) ◽  
pp. e3001012
Author(s):  
Bruno M. Fontinha ◽  
Theresa Zekoll ◽  
Mariam Al-Rawi ◽  
Miguel Gallach ◽  
Florian Reithofer ◽  
...  
Keyword(s):  
Developmental Stages ◽  
Fine Tuning ◽  
Ecological Niches ◽  
Natural Environments ◽  
Dependent Manner ◽  
Peripheral Tissues ◽  
Similar Expression ◽  
Vertebrate Brain ◽  
Complex Interactions ◽  
Starting Point

Vertebrate behavior is strongly influenced by light. Light receptors, encoded by functional opsin proteins, are present inside the vertebrate brain and peripheral tissues. This expression feature is present from fishes to human and appears to be particularly prominent in diurnal vertebrates. Despite their conserved widespread occurrence, the nonvisual functions of opsins are still largely enigmatic. This is even more apparent when considering the high number of opsins. Teleosts possess around 40 opsin genes, present from young developmental stages to adulthood. Many of these opsins have been shown to function as light receptors. This raises the question of whether this large number might mainly reflect functional redundancy or rather maximally enables teleosts to optimally use the complex light information present under water. We focus on tmt-opsin1b and tmt-opsin2, c-opsins with ancestral-type sequence features, conserved across several vertebrate phyla, expressed with partly similar expression in non-rod, non-cone, non-retinal-ganglion-cell brain tissues and with a similar spectral sensitivity. The characterization of the single mutants revealed age- and light-dependent behavioral changes, as well as an impact on the levels of the preprohormone sst1b and the voltage-gated sodium channel subunit scn12aa. The amount of daytime rest is affected independently of the eyes, pineal organ, and circadian clock in tmt-opsin1b mutants. We further focused on daytime behavior and the molecular changes in tmt-opsin1b/2 double mutants, and found that—despite their similar expression and spectral features—these opsins interact in part nonadditively. Specifically, double mutants complement molecular and behavioral phenotypes observed in single mutants in a partly age-dependent fashion. Our work provides a starting point to disentangle the highly complex interactions of vertebrate nonvisual opsins, suggesting that tmt-opsin-expressing cells together with other visual and nonvisual opsins provide detailed light information to the organism for behavioral fine-tuning. This work also provides a stepping stone to unravel how vertebrate species with conserved opsins, but living in different ecological niches, respond to similar light cues and how human-generated artificial light might impact on behavioral processes in natural environments.

scholarly journals TMT-Opsins differentially modulate medaka brain function in a context-dependent manner

2019 ◽  
Author(s):  
Bruno M. Fontinha ◽  
Theresa Zekoll ◽  
Mariam Al-Rawi ◽  
Miguel Gallach ◽  
Florian Reithofer ◽  
...  
Keyword(s):  
Developmental Stages ◽  
Fine Tuning ◽  
Ecological Niches ◽  
Natural Environments ◽  
Time Behavior ◽  
Dependent Manner ◽  
Peripheral Tissues ◽  
Similar Expression ◽  
Vertebrate Brain ◽  
Starting Point

AbstractVertebrate behavior is strongly influenced by light. Light receptors, encoded by functional Opsin proteins, are present inside the vertebrate brain and peripheral tissues. This expression feature is present from fishes to human and appears to be particularly prominent in diurnal vertebrates. Despite their conserved widespread occurrence, the non-visual functions of Opsins are still largely enigmatic. This is even more apparent when considering the high number of Opsins. Teleosts possess around 40 Opsin genes, present from young developmental stages to adulthood. Many of these Opsins have been shown to function as light receptors. This raises the question, if this large number might mainly reflect functional redundancy or rather maximally enables teleosts to optimally use the complex light information present under water. We focus on tmt-opsin1b and tmt-opsin2, c-Opsins with ancestral-type sequence features, conserved across several vertebrate phyla, expressed with partly similar expression in non-rod, non-cone, non-RGCs brain tissues and a similar spectral sensitivity. The characterization of the single mutants revealed age- and light-dependent behavioral changes, as well as an impact on the levels of the preprohormone sst1b and the voltage-gated sodium channel subunit scn12aa. The amount of day-time rest is affected independently of eyes, pineal and the circadian clock in tmt-opsin1b mutants. We further focused on day-time behavior and the molecular changes in tmt-opsin1b/2 double mutants, and revealed that – despite their similar expression and spectral features– these Opsins interact in part non-additively. Specifically, double mutants complement molecular and (age-dependently) behavioral phenotypes observed in single mutants.Our work provides a starting point to disentangle the highly complex interactions of vertebrate non-visual Opsins, suggesting that tmt-opsin-expressing cells together with other visual and non-visual Opsins provide detailed light information to the organism for behavioral fine-tuning. This work also provides a stepping stone to unravel how vertebrate species with conserved Opsins, but in different ecological niches respond to similar light cues and how human generated artificial light might impact on behavioral processes in natural environments.

scholarly journals Mosquito indolergic receptors belong to an ancient and functionally conserved Dipteran gene lineage

2020 ◽  
Author(s):  
R. Jason Pitts ◽  
Shan Ju Shih ◽  
Jonathan D. Bohbot
Keyword(s):  
Developmental Stages ◽  
Expression System ◽  
Transcript Abundance ◽  
Ecological Niches ◽  
Natural Environments ◽  
Resource Exploitation ◽  
Vector Surveillance ◽  
Control Programs ◽  
Indolic Compounds ◽  
Gene Structures

AbstractDiptera is a megadiverse group of flies with sophisticated chemical detection systems, which exploits an incredible variety of ecological niches. Among the vast array of odorants in natural environments, indoles stand out as playing crucial roles in mediating fly behavior. In mosquitoes, indolic compounds are detected by an ancient class of conserved indolergic Odorant Receptors (indolORs). In this study, we have identified a set of 92 putative indolOR genes encoded in the genomes of Nematoceran and Brachyceran flies, resolved their phylogenetic relationships, and defined conserved elements in their gene structures. Further, we have quantified indolOR transcript abundance in the antennae of the housefly, Musca domestica, and have characterized MdomOR30a as a skatole receptor using a heterologous expression system. The presence of indolORs in species operating in different ecological contexts suggests that indoles act as pleiotropic signals for resource exploitation at multiple developmental stages. Further characterization of indolORs will impact our understanding of insect chemical ecology and will provide targets for the development of novel odor-based tools that can be integrated into existing vector surveillance and control programs.

scholarly journals Decoding the temporal nature of brain GR activity in the NFκB signal transition leading to depressive-like behavior

2021 ◽  
Author(s):  
Young-Min Han ◽  
Min Sun Kim ◽  
Juyeong Jo ◽  
Daiha Shin ◽  
Seung-Hae Kwon ◽  
...  
Keyword(s):  
Inhibitory Action ◽  
Time Course ◽  
Molecular Mechanisms ◽  
Late Phase ◽  
Fine Tuning ◽  
Dependent Manner ◽  
Middle Phase ◽  
Temporal Shift

AbstractThe fine-tuning of neuroinflammation is crucial for brain homeostasis as well as its immune response. The transcription factor, nuclear factor-κ-B (NFκB) is a key inflammatory player that is antagonized via anti-inflammatory actions exerted by the glucocorticoid receptor (GR). However, technical limitations have restricted our understanding of how GR is involved in the dynamics of NFκB in vivo. In this study, we used an improved lentiviral-based reporter to elucidate the time course of NFκB and GR activities during behavioral changes from sickness to depression induced by a systemic lipopolysaccharide challenge. The trajectory of NFκB activity established a behavioral basis for the NFκB signal transition involved in three phases, sickness-early-phase, normal-middle-phase, and depressive-like-late-phase. The temporal shift in brain GR activity was differentially involved in the transition of NFκB signals during the normal and depressive-like phases. The middle-phase GR effectively inhibited NFκB in a glucocorticoid-dependent manner, but the late-phase GR had no inhibitory action. Furthermore, we revealed the cryptic role of basal GR activity in the early NFκB signal transition, as evidenced by the fact that blocking GR activity with RU486 led to early depressive-like episodes through the emergence of the brain NFκB activity. These results highlight the inhibitory action of GR on NFκB by the basal and activated hypothalamic-pituitary-adrenal (HPA)-axis during body-to-brain inflammatory spread, providing clues about molecular mechanisms underlying systemic inflammation caused by such as COVID-19 infection, leading to depression.

scholarly journals Regulation of Wnt Signaling by FOX Transcription Factors in Cancer

Cancers ◽  
2021 ◽  
Vol 13 (14) ◽  
pp. 3446
Author(s):  
Stefan Koch
Keyword(s):  
Transcription Factors ◽  
Wnt Signaling ◽  
Wnt Pathway ◽  
Treatment Options ◽  
Wnt Signaling Pathway ◽  
Tissue Homeostasis ◽  
Fine Tuning ◽  
Dependent Manner ◽  
Forkhead Box ◽  
Signaling Activity

Aberrant activation of the oncogenic Wnt signaling pathway is a hallmark of numerous types of cancer. However, in many cases, it is unclear how a chronically high Wnt signaling tone is maintained in the absence of activating pathway mutations. Forkhead box (FOX) family transcription factors are key regulators of embryonic development and tissue homeostasis, and there is mounting evidence that they act in part by fine-tuning the Wnt signaling output in a tissue-specific and context-dependent manner. Here, I review the diverse ways in which FOX transcription factors interact with the Wnt pathway, and how the ectopic reactivation of FOX proteins may affect Wnt signaling activity in various types of cancer. Many FOX transcription factors are partially functionally redundant and exhibit a highly restricted expression pattern, especially in adults. Thus, precision targeting of individual FOX proteins may lead to safe treatment options for Wnt-dependent cancers.

scholarly journals WD40-repeat 47, a microtubule-associated protein, is essential for brain development and autophagy

2017 ◽  
Vol 114 (44) ◽  
pp. E9308-E9317 ◽  
Author(s):  
Meghna Kannan ◽  
Efil Bayam ◽  
Christel Wagner ◽  
Bruno Rinaldi ◽  
Perrine F. Kretz ◽  
...  
Keyword(s):  
Corpus Callosum ◽  
Brain Development ◽  
Brain Connectivity ◽  
Neuronal Morphology ◽  
Dependent Manner ◽  
Wd40 Repeat ◽  
Starting Point ◽  
Neuronal Regulation ◽  
The Family ◽  
Cervical Ganglion

The family of WD40-repeat (WDR) proteins is one of the largest in eukaryotes, but little is known about their function in brain development. Among 26 WDR genes assessed, we found 7 displaying a major impact in neuronal morphology when inactivated in mice. Remarkably, all seven genes showed corpus callosum defects, including thicker (Atg16l1, Coro1c, Dmxl2, and Herc1), thinner (Kif21b and Wdr89), or absent corpus callosum (Wdr47), revealing a common role for WDR genes in brain connectivity. We focused on the poorly studied WDR47 protein sharing structural homology with LIS1, which causes lissencephaly. In a dosage-dependent manner, mice lacking Wdr47 showed lethality, extensive fiber defects, microcephaly, thinner cortices, and sensory motor gating abnormalities. We showed that WDR47 shares functional characteristics with LIS1 and participates in key microtubule-mediated processes, including neural stem cell proliferation, radial migration, and growth cone dynamics. In absence of WDR47, the exhaustion of late cortical progenitors and the consequent decrease of neurogenesis together with the impaired survival of late-born neurons are likely yielding to the worsening of the microcephaly phenotype postnatally. Interestingly, the WDR47-specific C-terminal to LisH (CTLH) domain was associated with functions in autophagy described in mammals. Silencing WDR47 in hypothalamic GT1-7 neuronal cells and yeast models independently recapitulated these findings, showing conserved mechanisms. Finally, our data identified superior cervical ganglion-10 (SCG10) as an interacting partner of WDR47. Taken together, these results provide a starting point for studying the implications of WDR proteins in neuronal regulation of microtubules and autophagy.

scholarly journals Phospholipid flippases enable precursor B cells to flee engulfment by macrophages

2018 ◽  
Vol 115 (48) ◽  
pp. 12212-12217 ◽  
Author(s):  
Katsumori Segawa ◽  
Yuichi Yanagihashi ◽  
Kyoko Yamada ◽  
Chigure Suzuki ◽  
Yasuo Uchiyama ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
B Cells ◽  
B Cell ◽  
Developmental Stages ◽  
Peritoneal Macrophages ◽  
Dependent Manner ◽  
Wild Type ◽  
Immature B Cells ◽  
T Lymphoma ◽  
Precursor B Cells

ATP11A and ATP11C, members of the P4-ATPases, are flippases that translocate phosphatidylserine (PtdSer) from the outer to inner leaflet of the plasma membrane. Using the W3 T lymphoma cell line, we found that Ca2+ ionophore-induced phospholipid scrambling caused prolonged PtdSer exposure in cells lacking both the ATP11A and ATP11C genes. ATP11C-null (ATP11C−/y) mutant mice exhibit severe B-cell deficiency. In wild-type mice, ATP11C was expressed at all B-cell developmental stages, while ATP11A was not expressed after pro−B-cell stages, indicating that ATP11C−/y early B-cell progenitors lacked plasma membrane flippases. The receptor kinases MerTK and Axl are known to be essential for the PtdSer-mediated engulfment of apoptotic cells by macrophages. MerTK−/− and Axl−/− double deficiency fully rescued the lymphopenia in the ATP11C−/y bone marrow. Many of the rescued ATP11C−/y pre-B and immature B cells exposed PtdSer, and these cells were engulfed alive by wild-type peritoneal macrophages, in a PtdSer-dependent manner. These results indicate that ATP11A and ATP11C in precursor B cells are essential for rapidly internalizing PtdSer from the cell surface to prevent the cells’ engulfment by macrophages.

scholarly journals A novel measurement-based procedure for dynamic equivalents of electric power systems for stability studies using improved sine cosine algorithm

2019 ◽  
Vol 70 (6) ◽  
pp. 454-464
Author(s):  
Omar Benmiloud ◽  
Salem Arif
Keyword(s):  
Power Systems ◽  
Dynamic Properties ◽  
Specific Area ◽  
Pattern Search ◽  
Fine Tuning ◽  
Large Power ◽  
Area Of Interest ◽  
Starting Point ◽  
Sine Cosine Algorithm ◽  
Dynamic Equivalent

Abstract Dynamic equivalent (DE) is an important process of multi-area interconnected power systems. It allows to perform stability assessment of a specific area (area of interest) at minimum cost. This study is intended to investigate the dynamic equivalent of two relatively large power systems. The fourth-order model of synchronous generators with a simplified excitation system is used as equivalent to the group of generators in the external system. To improve the accuracy of the estimated model, the identification is carried in two stages. First, using the global search Sine Cosine Algorithm (SCA) to find a starting set values, then this set is used as starting point for the fine-tuning made through the Pattern Search (PS) algorithm. To increase the reliability of the model’s parameters, two disturbances are used to avoid the identification based on a specific event. The developed program is applied on two standard power systems, namely, the New England (NE) system and the Northeast Power Coordinating Council (NPCC) system. Simulation results confirm the ability of the optimized model to preserve the main dynamic properties of the original system with accuracy.

scholarly journals Gene expression profiling identifies pathways involved in seeds maturation of Jatropha curcas

2019 ◽  
Author(s):  
Fatemeh Maghuly ◽  
Tamas Deak ◽  
Klemens Vierlinger ◽  
Stephan Pabinger ◽  
Hakim Tafer ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Seed Development ◽  
Jatropha Curcas ◽  
Molecular Mechanisms ◽  
Seed Quality ◽  
Developmental Stages ◽  
Seed Maturation ◽  
Nutrient Mobilization ◽  
Starting Point ◽  
Maturation Stages

Abstract Background: Jatropha curcas, a tropical shrub, is a promising biofuel crop, which produces seeds with a high content of oil and protein. To better understand the development of its seeds to improve Jatropha`s agronomic performance, a two-step approach was performed: 1) generation of the entire transcriptome of six different maturation stages of J. curcas seeds using 454-Roche sequencing of a cDNA library, 2) comparison of transcriptional expression levels in six different developmental stages of seeds using a custom Agilent 8x60K oligonucleotide microarray. Results: A total of 793,875 high-quality reads were assembled into 19,841 unique full-length contigs, of which 13,705 could be annotated with Gene Ontology (GO) terms. Microarray data analysis identified 9,111 probes (out of 57,842 probes), which were differentially expressed between the six developmental stages. The expression results were validated for 70 randomly selected putative genes. Result from cluster analyses showed that transcripts related to sucrose, fatty acid, flavonoid, phenylpropanoid, lignin, hormone biosynthesis were over-represented in the early stage, while lipid storage, seed dormancy and maturation in the late stage. Generally, the expression of the most over-represented transcripts decrease in the last stage of seed maturation. Further, expression analyses of different maturation stages of J. curcas seed showed that most changes in transcript abundance occurred between the two last stages, suggesting that the timing of metabolic pathways during seed maturation in J. curcas is in late stages. The co-expression result showed a high degree of connectivity between genes that play essential role in fatty acid biosynthesis and nutrient mobilization. Furthermore, seed development and hormone pathways are significantly well connected. Conclusion: The obtained results revealed DESs regulating important pathways related to seed maturation, which could contribute to understanding the complex regulatory network during seed development. This study provides detailed information on transcription changes during J. curcas seed development and provides a starting point for a genomic survey of seed quality traits. The current results highlighted specific genes and processes relevant to the molecular mechanisms involved in Jatropha seed development, and it is anticipated that this data can be delivered to other Euphorbiaceae species of economic value.

scholarly journals Conjugated structure of the lawn-grass cover of the urban landscape

2020 ◽  
Vol 10 (212) ◽  
pp. 68-72
Author(s):  
Mikhail Motyl ◽  
◽  
Alexander Romanyuk ◽  
Vladimir Titok
Keyword(s):  
Urban Landscape ◽  
Green Spaces ◽  
Ecological Niches ◽  
Grass Cover ◽  
Urban Green ◽  
Urban Green Spaces ◽  
Native Flora ◽  
Initial Stage ◽  
Unique Object ◽  
Starting Point

The features of the conjugated structure of plants of the lawn-grass cover of the city of Minsk as an unique object of a natural-anthropogenic landscape and a phyto-indicator of the current state of urban green spaces of Belarus are established. The basic composition of 35 species of native flora, which form 10 conjugated groups and reflect diversity of ecological niches, is determined. Their composition and the nature of the bonds indicate a tendency toward xerophytization of the soil cover. The data obtained reflect the initial stage of its transformation and can serve as a starting point for monitoring climate and anthropogenic changes in the structure of urban green spaces.

scholarly journals Fine-tuning citrate synthase flux potentiates and refines metabolic innovation in the Lenski evolution experiment

eLife ◽  
2015 ◽  
Vol 4 ◽  
Author(s):  
Erik M Quandt ◽  
Jimmy Gollihar ◽  
Zachary D Blount ◽  
Andrew D Ellington ◽  
George Georgiou ◽  
...  
Keyword(s):  
Citrate Synthase ◽  
Fine Tuning ◽  
Ecological Niches ◽  
Glta Gene ◽  
Evolutionary Changes ◽  
Before And After ◽  
Evolution Experiment ◽  
History Of ◽  
Second Wave

Evolutionary innovations that enable organisms to colonize new ecological niches are rare compared to gradual evolutionary changes in existing traits. We discovered that key mutations in the gltA gene, which encodes citrate synthase (CS), occurred both before and after Escherichia coli gained the ability to grow aerobically on citrate (Cit+ phenotype) during the Lenski long-term evolution experiment. The first gltA mutation, which increases CS activity by disrupting NADH-inhibition of this enzyme, is beneficial for growth on the acetate and contributed to preserving the rudimentary Cit+ trait from extinction when it first evolved. However, after Cit+ was refined by further mutations, this potentiating gltA mutation became deleterious to fitness. A second wave of beneficial gltA mutations then evolved that reduced CS activity to below the ancestral level. Thus, dynamic reorganization of central metabolism made colonizing this new nutrient niche contingent on both co-opting and overcoming a history of prior adaptation.

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