scholarly journals Genetic variation in dopamine availability modulates the self-reported level of action control in a sex-dependent manner

2019 ◽  
Vol 14 (7) ◽  
pp. 759-768
Author(s):  
Caroline Schlüter ◽  
Larissa Arning ◽  
Christoph Fraenz ◽  
Patrick Friedrich ◽  
Marlies Pinnow ◽  
...  
Keyword(s):  
Dopaminergic System ◽  
Action Control ◽  
Emotional Control ◽  
Control Mechanisms ◽  
Dependent Manner ◽  
Genetic Components ◽  
Functional Differences ◽  
Widespread Phenomenon ◽  
Amygdala Volume ◽  
Insight Into

Abstract Although procrastination is a widespread phenomenon with significant influence on our personal and professional life, its genetic foundation is somewhat unknown. An important factor that influences our ability to tackle specific goals directly instead of putting them off is our ability to initiate cognitive, motivational and emotional control mechanisms, so-called metacontrol. These metacontrol mechanisms have been frequently related to dopaminergic signaling. To gain deeper insight into the genetic components of procrastination, we examined whether genetically induced differences in the dopaminergic system are associated with interindividual differences in trait-like procrastination, measured as decision-related action control (AOD). Analyzing the data of 278 healthy adults, we found a sex-dependent effect of TH genotype on AOD. Interestingly, only in women, T-allele carriers showed lower AOD values and were therefore more likely to procrastinate. Additionally, we investigated whether differences in the morphology and functional connectivity of the amygdala that were previously associated with AOD happen to be related to differences in the TH genotype and thus to differences in the dopaminergic system. However, there was no significant amygdala volume or connectivity difference between the TH genotype groups. Therefore, this study is the first to suggest that genetic, anatomical and functional differences affect trait-like procrastination independently.

The Structural and Functional Signature of Action Control

2018 ◽  
Vol 29 (10) ◽  
pp. 1620-1630 ◽  
Author(s):  
Caroline Schlüter ◽  
Christoph Fraenz ◽  
Marlies Pinnow ◽  
Patrick Friedrich ◽  
Onur Güntürkün ◽  
...  
Keyword(s):  
Resting State ◽  
Significant Negative Correlation ◽  
Action Control ◽  
Anterior Cingulate ◽  
Control Mechanisms ◽  
Dorsal Anterior Cingulate Cortex ◽  
Action Orientation ◽  
Interindividual Differences ◽  
Amygdala Volume ◽  
Resting State Connectivity

Individuals differ in their ability to initiate self- and emotional-control mechanisms. These differences have been explicitly described in Kuhl’s action-control theory. Although interindividual differences in action control make a major contribution to our everyday life, their neural foundation remains unknown. Here, we measured action control in a sample of 264 healthy adults and related interindividual differences in action control to variations in brain structure and resting-state connectivity. Our results demonstrate a significant negative correlation between decision-related action orientation (AOD) and amygdala volume. Further, we showed that the functional resting-state connectivity between the amygdala and the dorsal anterior cingulate cortex was significantly associated with AOD. Specifically, stronger functional connectivity was associated with higher AOD scores. These findings are the first to show that interindividual differences in action control, namely AOD, are based on the anatomical architecture and functional network of the amygdala.

scholarly journals Selective packaging of mitochondrial proteins into extracellular vesicles prevents the release of mitochondrial DAMPs

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Kiran Todkar ◽  
Lilia Chikhi ◽  
Véronique Desjardins ◽  
Firas El-Mortada ◽  
Geneviève Pépin ◽  
...  
Keyword(s):  
Extracellular Vesicles ◽  
Mitochondrial Proteins ◽  
Control Mechanisms ◽  
Mitochondrial Content ◽  
Sorting Nexin ◽  
Inflammatory Conditions ◽  
Selective Targeting ◽  
Molecular Patterns ◽  
Damage Associated Molecular Patterns ◽  
Insight Into

AbstractMost cells constitutively secrete mitochondrial DNA and proteins in extracellular vesicles (EVs). While EVs are small vesicles that transfer material between cells, Mitochondria-Derived Vesicles (MDVs) carry material specifically between mitochondria and other organelles. Mitochondrial content can enhance inflammation under pro-inflammatory conditions, though its role in the absence of inflammation remains elusive. Here, we demonstrate that cells actively prevent the packaging of pro-inflammatory, oxidized mitochondrial proteins that would act as damage-associated molecular patterns (DAMPs) into EVs. Importantly, we find that the distinction between material to be included into EVs and damaged mitochondrial content to be excluded is dependent on selective targeting to one of two distinct MDV pathways. We show that Optic Atrophy 1 (OPA1) and sorting nexin 9 (Snx9)-dependent MDVs are required to target mitochondrial proteins to EVs, while the Parkinson’s disease-related protein Parkin blocks this process by directing damaged mitochondrial content to lysosomes. Our results provide insight into the interplay between mitochondrial quality control mechanisms and mitochondria-driven immune responses.

scholarly journals Control of microtubule dynamics using an optogenetic microtubule plus end–F-actin cross-linker

2017 ◽  
Vol 217 (2) ◽  
pp. 779-793 ◽  
Author(s):  
Rebecca C. Adikes ◽  
Ryan A. Hallett ◽  
Brian F. Saway ◽  
Brian Kuhlman ◽  
Kevin C. Slep
Keyword(s):  
Blue Light ◽  
Actin Binding ◽  
Cross Linking ◽  
Dependent Manner ◽  
Exclusion Zone ◽  
Actin Networks ◽  
Drosophila Melanogaster S2 Cells ◽  
Actin Binding Domain ◽  
Specific Factors ◽  
Insight Into

We developed a novel optogenetic tool, SxIP–improved light-inducible dimer (iLID), to facilitate the reversible recruitment of factors to microtubule (MT) plus ends in an end-binding protein–dependent manner using blue light. We show that SxIP-iLID can track MT plus ends and recruit tgRFP-SspB upon blue light activation. We used this system to investigate the effects of cross-linking MT plus ends and F-actin in Drosophila melanogaster S2 cells to gain insight into spectraplakin function and mechanism. We show that SxIP-iLID can be used to temporally recruit an F-actin binding domain to MT plus ends and cross-link the MT and F-actin networks. Cross-linking decreases MT growth velocities and generates a peripheral MT exclusion zone. SxIP-iLID facilitates the general recruitment of specific factors to MT plus ends with temporal control enabling researchers to systematically regulate MT plus end dynamics and probe MT plus end function in many biological processes.

scholarly journals Maternal GALNT2 Variations Affect Blood Pressure, Atherogenic Index, and Fetal Growth, Depending on BMI in Gestational Diabetes Mellitus

2021 ◽  
Vol 12 ◽  
Author(s):  
Linbo Guan ◽  
Ping Fan ◽  
Xinghui Liu ◽  
Mi Zhou ◽  
Yujie Wu ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Blood Pressure ◽  
Gestational Diabetes ◽  
Gestational Diabetes Mellitus ◽  
Fetal Growth ◽  
Atherogenic Index ◽  
Dependent Manner ◽  
Nucleotide Polymorphisms ◽  
Genetic Associations ◽  
Genetic Components

BackgroundGALNT2 is a GalNAc transferase that regulates serum lipid fractions, insulin signaling, and lipogenesis. Genetic variants are implicated in the pathogenesis of gestational diabetes mellitus (GDM). The objective of this study was to investigate the association of GALNT2 rs2144300 and rs4846914 single nucleotide polymorphisms (SNPs) with the risk of GDM and related traits.MethodsTwo SNPs were genotyped, and clinical and metabolic parameters were determined in 461 GDM patients and 626 control subjects. Genetic associations with related traits were also analyzed.ResultsThe genotype distributions of the two SNPs in GDM patients were similar to those in normal controls. However, significant differences were noted across the three groups of genotypes with respect to the examined variables in subjects in a BMI-dependent manner. The rs4846914 and rs2144300 SNPs of GALNT2 were significantly associated with systolic blood pressure and/or diastolic blood pressure levels in nonobese GDM patients and atherogenic index (AI) in overweight/obese GDM patients. The rs4846914 SNP was also associated with fetal growth in overweight/obese GDM patients, and apo A1 and pregnancy weight gain in overweight/obese control women (all P<0.05).ConclusionsThe two polymorphisms in the GALNT2 gene are associated with variations in blood pressure, atherogenic index, and fetal growth in GDM, depending on BMI, but not with GDM. Our findings highlight a link between related phenotypes in GDM mothers and their fetuses and the genetic components.

scholarly journals Fc-dependent depletion of tumor-infiltrating regulatory T cells co-defines the efficacy of anti–CTLA-4 therapy against melanoma

2013 ◽  
Vol 210 (9) ◽  
pp. 1695-1710 ◽  
Author(s):  
Tyler R. Simpson ◽  
Fubin Li ◽  
Welby Montalvo-Ortiz ◽  
Manuel A. Sepulveda ◽  
Katharina Bergerhoff ◽  
...  
Keyword(s):  
T Cells ◽  
Cytotoxic T Lymphocyte ◽  
Tumor Regression ◽  
Cell Activity ◽  
Dependent Manner ◽  
Antitumor Effector ◽  
Tumor Environment ◽  
In Trans ◽  
Immunomodulatory Therapies ◽  
Insight Into

Treatment with monoclonal antibody specific for cytotoxic T lymphocyte–associated antigen 4 (CTLA-4), an inhibitory receptor expressed by T lymphocytes, has emerged as an effective therapy for the treatment of metastatic melanoma. Although subject to debate, current models favor a mechanism of activity involving blockade of the inhibitory activity of CTLA-4 on both effector (T eff) and regulatory (T reg) T cells, resulting in enhanced antitumor effector T cell activity capable of inducing tumor regression. We demonstrate, however, that the activity of anti–CTLA-4 antibody on the T reg cell compartment is mediated via selective depletion of T reg cells within tumor lesions. Importantly, T reg cell depletion is dependent on the presence of Fcγ receptor–expressing macrophages within the tumor microenvironment, indicating that T reg cells are depleted in trans in a context-dependent manner. Our results reveal further mechanistic insight into the activity of anti-CTLA-4–based cancer immunotherapy, and illustrate the importance of specific features of the local tumor environment on the final outcome of antibody-based immunomodulatory therapies.

scholarly journals Progression from remodeling to hibernation of ribosomes in zinc-starved mycobacteria

2020 ◽  
Vol 117 (32) ◽  
pp. 19528-19537
Author(s):  
Yunlong Li ◽  
Jamie H. Corro ◽  
Christopher D. Palmer ◽  
Anil K. Ojha
Keyword(s):  
Zinc Concentration ◽  
Specific Protein ◽  
Zinc Binding ◽  
Free Form ◽  
Dependent Manner ◽  
Drug Resistant ◽  
Zinc Depletion ◽  
Cellular Zinc ◽  
Mouse Lungs ◽  
Insight Into

Zinc starvation in mycobacteria leads to remodeling of ribosomes, in which multiple ribosomal (r-) proteins containing the zinc-binding CXXC motif are replaced by their motif-free paralogues, collectively called C− r-proteins. We previously reported that the 70S C− ribosome is exclusively targeted for hibernation by mycobacterial-specific protein Y (Mpy), which binds to the decoding center and stabilizes the ribosome in an inactive and drug-resistant state. In this study, we delineate the conditions for ribosome remodeling and hibernation and provide further insight into how zinc depletion induces Mpy recruitment to C− ribosomes. Specifically, we show that ribosome hibernation in a batch culture is induced at an approximately two-fold lower cellular zinc concentration than remodeling. We further identify a growth phase in which the C− ribosome remains active, while its hibernation is inhibited by the caseinolytic protease (Clp) system in a zinc-dependent manner. The Clp protease system destabilizes a zinc-bound form of Mpy recruitment factor (Mrf), which is stabilized upon further depletion of zinc, presumably in a zinc-free form. Stabilized Mrf binds to the 30S subunit and recruits Mpy to the ribosome. Replenishment of zinc to cells harboring hibernating ribosomes restores Mrf instability and dissociates Mpy from the ribosome. Finally, we demonstrate zinc-responsive binding of Mpy to ribosomes inMycobacterium tuberculosis(Mtb) and show Mpy-dependent antibiotic tolerance of Mtb in mouse lungs. Together, we propose that ribosome hibernation is a specific and conserved response to zinc depletion in both environmental and pathogenic mycobacteria.

Exploratory Studies on the Control of High-Speed Flows With Magnetogasdynamics

2002 ◽  
Author(s):  
Datta V. Gaitonde
Keyword(s):  
Flow Control ◽  
High Speed ◽  
Three Dimensional ◽  
Experimental Investigations ◽  
Control Mechanisms ◽  
Ground Testing ◽  
Simulation Efficiency ◽  
The Status ◽  
Physical Phenomena ◽  
Insight Into

Magnetogasdynamics (MGD) has the potential to lift many of the constraints presently inhibiting sustained hypersonic flight and affordable access to space. Given the difficulty of ground-testing under the expected harsh conditions, numerical methods can provide insight into the physical phenomena, and thus complement experimental investigations in the development of future concepts. This paper describes the status of an effort to develop a high-fidelity, fully three-dimensional method to explore MGD flow control in complex configurations. The theoretical model includes several non-ideal effects and takes recourse to a blend of first principles and phenomenological approaches to enhance simulation efficiency. Boundary conditions are summarized and sample verification exercises are presented. Exploratory calculations on a reentry vehicle and flow-through scramjet flowpath with MGD-bypass demonstrate the versatility of the approach and yield insight into dominant flow control mechanisms.

scholarly journals Novel molecular components involved in callose-mediated Arabidopsis defense against Salmonella enterica and Escherichia coli O157:H7

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Paula Rodrigues Oblessuc ◽  
Cleverson Carlos Matiolli ◽  
Maeli Melotto
Keyword(s):  
Escherichia Coli ◽  
Pseudomonas Syringae ◽  
Salmonella Enterica ◽  
Plant Pathogens ◽  
Dependent Manner ◽  
Callose Deposition ◽  
E Coli ◽  
Genetic Components ◽  
Ros Burst ◽  
Sa Signaling

Abstract Background Food contamination with Salmonella enterica and enterohemorrhagic Escherichia coli is among the leading causes of foodborne illnesses worldwide and crop plants are associated with > 50% of the disease outbreaks. However, the mechanisms underlying the interaction of these human pathogens with plants remain elusive. In this study, we have explored plant resistance mechanisms against these enterobacteria and the plant pathogen Pseudomonas syringae pv. tomato (Pst) DC3118, as an opportunity to improve food safety. Results We found that S. enterica serovar Typhimurium (STm) transcriptionally modulates stress responses in Arabidopsis leaves, including induction of two hallmark processes of plant defense: ROS burst and cell wall modifications. Analyses of plants with a mutation in the potentially STm-induced gene EXO70H4 revealed that its encoded protein is required for stomatal defense against STm and E. coli O157:H7, but not against Pst DC3118. In the apoplast however, EXO70H4 is required for defense against STm and Pst DC3118, but not against E. coli O157:H7. Moreover, EXO70H4 is required for callose deposition, but had no function in ROS burst, triggered by all three bacteria. The salicylic acid (SA) signaling and biosynthesis proteins NPR1 and ICS1, respectively, were involved in stomatal and apoplastic defense, as well as callose deposition, against human and plant pathogens. Conclusions The results show that EXO70H4 is involved in stomatal and apoplastic defenses in Arabidopsis and suggest that EXO70H4-mediated defense play a distinct role in guard cells and leaf mesophyll cells in a bacteria-dependent manner. Nonetheless, EXO70H4 contributes to callose deposition in response to both human and plant pathogens. NPR1 and ICS1, two proteins involved in the SA signaling pathway, are important to inhibit leaf internalization and apoplastic persistence of enterobacteria and proliferation of phytopathogens. These findings highlight the existence of unique and shared plant genetic components to fight off diverse bacterial pathogens providing specific targets for the prevention of foodborne diseases.

scholarly journals Interaction between Polycomb and SSX Proteins in Pericentromeric Heterochromatin Function and Its Implication in Cancer

Cells ◽  
2020 ◽  
Vol 9 (1) ◽  
pp. 226
Author(s):  
Simone Johansen ◽  
Morten Frier Gjerstorff
Keyword(s):  
Immune Deficiency ◽  
Tumor Biology ◽  
Pericentromeric Heterochromatin ◽  
Control Mechanisms ◽  
Malignant Cells ◽  
Polycomb Proteins ◽  
The Stability ◽  
Polycomb Bodies ◽  
Insight Into ◽  
Cancer Testis

The stability of pericentromeric heterochromatin is maintained by repressive epigenetic control mechanisms, and failure to maintain this stability may cause severe diseases such as immune deficiency and cancer. Thus, deeper insight into the epigenetic regulation and deregulation of pericentromeric heterochromatin is of high priority. We and others have recently demonstrated that pericentromeric heterochromatin domains are often epigenetically reprogrammed by Polycomb proteins in premalignant and malignant cells to form large subnuclear structures known as Polycomb bodies. This may affect the regulation and stability of pericentromeric heterochromatin domains and/or the distribution of Polycomb factors to support tumorigeneses. Importantly, Polycomb bodies in cancer cells may be targeted by the cancer/testis-related SSX proteins to cause derepression and genomic instability of pericentromeric heterochromatin. This review will discuss the interplay between SSX and Polycomb factors in the repression and stability of pericentromeric heterochromatin and its possible implications for tumor biology.

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