scholarly journals The Impact of Melatonin and NLRP3 Inflammasome on the Expression of microRNAs in Aged Muscle

Antioxidants ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 524
Author(s):  
Ramy KA Sayed ◽  
Marisol Fernández-Ortiz ◽  
José Fernández-Martínez ◽  
Paula Aranda Martínez ◽  
Ana Guerra-Librero ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Nlrp3 Inflammasome ◽  
Gastrocnemius Muscle ◽  
Pcr Analysis ◽  
Physiological Mechanisms ◽  
Complex Process ◽  
Regulatory Machinery ◽  
The Impact ◽  
First Time

Muscular aging is a complex process and underlying physiological mechanisms are not fully clear. In recent years, the participation of the NF-kB pathway and the NLRP3 inflammasome in the chronic inflammation process that accompanies the skeletal muscle’s aging has been confirmed. microRNAs (miRs) form part of a gene regulatory machinery, and they control numerous biological processes including inflammatory pathways. In this work, we studied the expression of four miRs; three of them are considered as inflammatory-related miRs (miR-21, miR-146a, and miR-223), and miR-483, which is related to the regulation of melatonin synthesis, among other targets. To investigate the changes of miRs expression in muscle along aging, the impact of inflammation, and the role of melatonin in aged skeletal muscle, we used the gastrocnemius muscle of wild type (WT) and NLRP3-knockout (NLRP3−) mice of 3, 12, and 24 months-old, with and without melatonin supplementation. The expression of miRs and pro-caspase-1, caspase-3, pro-IL-1β, bax, bcl-2, and p53, was investigated by qRT-PCR analysis. Histological examination of the gastrocnemius muscle was also done. The results showed that age increased the expression of miR-21 (p < 0.01), miR-146a, and miR-223 (p < 0.05, for both miRs) in WT mice, whereas the 24-months-old mutant mice revealed decline of miR-21 and miR-223 (p < 0.05), compared to WT age. The lack of NLRP3 inflammasome also improved the skeletal muscle fibers arrangement and reduced the collagen deposits compared with WT muscle during aging. For the first time, we showed that melatonin significantly reduced the expression of miR-21, miR-146a, and miR-223 (p < 0.05 for all ones, and p < 0.01 for miR-21 at 24 months old) in aged WT mice, increased miR-223 in NLRP3− mice (p < 0.05), and induced miR-483 expression in both mice strains, this increase being significant at 24 months of age.

Relationship between big five personality model and abusive supervision

2019 ◽  
Vol 12 (2) ◽  
Author(s):  
Bibi Tahira ◽  
Naveed Saif ◽  
Muhammad Haroon ◽  
Sadaqat Ali
Keyword(s):  
Big Five ◽  
Abusive Supervision ◽  
State Universities ◽  
Big Five Personality ◽  
Big Five Model ◽  
The Impact ◽  
First Time ◽  
Supervisor Behavior ◽  
Moderating Role

The current study tries to understand the diverse nature of relationship between personality Big Five Model (PBFM) and student's perception of abusive supervision in higher education institutions of Khyber Pakhtoonkhwa Pakistan. Data was collected in dyads i.e. (supervisors were asked to rate their personality attributes while student were asked to rate the supervisor behavior) through adopted construct. For this purpose, data was collected from three government state universities and one Private Sector University. The focus was on MS/M.Phill and PhD student and their supervisors of the mentioned universities. After measuring normality and validity regression analysis was conducted to assess the impact of supervisor personality characteristics that leads to abusive supervision. Findings indicate interestingly that except agreeableness other four attributes of (PBFM) are play their role for abusive supervision. The results are novel in the nature as for the first time Neuroticism, openness to experience, extraversion and conscientiousness are held responsible for the abusive supervision. The study did not explore the demographic characteristics, and moderating role of organizational culture, justice and interpersonal deviances to understand the strength of relationship in more detail way. Keywords: Personality big five model, abusive supervision, HEIs

scholarly journals Phenotypic Susceptibility to Bevirimat in Isolates from HIV-1-Infected Patients without Prior Exposure to Bevirimat

2010 ◽  
Vol 54 (6) ◽  
pp. 2345-2353 ◽  
Author(s):  
Nicolas A. Margot ◽  
Craig S. Gibbs ◽  
Michael D. Miller
Keyword(s):  
Recombinant Viruses ◽  
Gag Polyprotein ◽  
New Class ◽  
Major Mutation ◽  
Hiv Drugs ◽  
The Impact ◽  
First Time ◽  
Hiv 1

ABSTRACT Bevirimat (BVM) is the first of a new class of anti-HIV drugs with a novel mode of action known as maturation inhibitors. BVM inhibits the last cleavage of the Gag polyprotein by HIV-1 protease, leading to the accumulation of the p25 capsid-small peptide 1 (SP1) intermediate and resulting in noninfectious HIV-1 virions. Early clinical studies of BVM showed that over 50% of the patients treated with BVM did not respond to treatment. We investigated the impact of prior antiretroviral (ARV) treatment and/or natural genetic diversity on BVM susceptibility by conducting in vitro phenotypic analyses of viruses made from patient samples. We generated 31 recombinant viruses containing the entire gag and protease genes from 31 plasma samples from HIV-1-infected patients with (n = 21) or without (n = 10) prior ARV experience. We found that 58% of the patient isolates tested had a >10-fold reduced susceptibility to BVM, regardless of the patient's ARV experience or the level of isolate resistance to protease inhibitors. Analysis of mutants with site-directed mutations confirmed the role of the V370A SP1 polymorphism (SP1-V7A) in resistance to BVM. Furthermore, we demonstrated for the first time that a capsid polymorphism, V362I (CA protein-V230I), is also a major mutation conferring resistance to BVM. In contrast, none of the previously defined resistance-conferring mutations in Gag selected in vitro (H358Y, L363M, L363F, A364V, A366V, or A366T) were found to occur among the viruses that we analyzed. Our results should be helpful in the design of diagnostics for prediction of the potential benefit of BVM treatment in HIV-1-infected patients.

Reflections from the field (mountain, cityscape and park): walking for management development and links to being-in-the world, belonging and “Ba”

2021 ◽  
Vol ahead-of-print (ahead-of-print) ◽  
Author(s):  
Arthur F. Turner ◽  
Gareth Edwards ◽  
Catherine Latham ◽  
Harriet Shortt
Keyword(s):  
Leadership Development ◽  
Management Development ◽  
Learning And Development ◽  
Content Type ◽  
Personal Story ◽  
The World ◽  
Effective Use ◽  
The Impact ◽  
First Time

PurposeThe purpose of this paper, based on reflections from practice, is to shed light on the realities of using walking as a tool for learning and development. This is done through an initial analysis of longitudinal reflective data spanning seven years and connecting these reflections to the concepts: being-in-the-world, belonging and Ba.Design/methodology/approachThis research takes a practice based phenomenological and reflective approach. The value of this approach is to seek a new understanding, through three distinct conceptual frames, of the effective use of walking within management development.FindingsThe findings connect three conceptual approaches of being-in-the-world, belonging and “Ba” to the practicalities of delivery, thus encouraging practitioners and designers to deeply reflect on the role of walking in management development.Research limitations/implicationsA limitation is that this is largely a personal story exploring the impact of an intuitively developed set of interventions. Despite this, the paper represents a unique and deep interpretation of walking as a mechanism for management development.Practical implicationsThe paper concludes with three recommendations to practitioners wanting to use walking in management development programmes. These are: facilitators need to be familiar with their surroundings; they should look for spaces and places where participants can connect and build relationships; and organisers and sponsors need to recognise how walking not only consolidates knowledge but can help create knowledge too.Originality/valueThis is a unique, seven-year longitudinal study that broadens the theoretical focus of walking as a mechanism for management and leadership development that combines the theoretical lenses of being-in-the-world, belonging and “Ba”, the authors believe, for the first time in research on management development.

scholarly journals The gut microbial metabolite trimethylamine N-oxide aggravates GVHD by inducing M1 macrophage polarization in mice

Blood ◽  
2020 ◽  
Vol 136 (4) ◽  
pp. 501-515 ◽  
Author(s):  
Kunpeng Wu ◽  
Yan Yuan ◽  
Huihui Yu ◽  
Xin Dai ◽  
Shu Wang ◽  
...  
Keyword(s):  
Nlrp3 Inflammasome ◽  
Macrophage Polarization ◽  
Short Chain Fatty Acids ◽  
Inflammasome Activation ◽  
Microbial Metabolites ◽  
M1 Macrophage ◽  
The Impact

Abstract The diversity of the human microbiome heralds the difference of the impact that gut microbial metabolites exert on allogenic graft-versus-host (GVH) disease (GVHD), even though short-chain fatty acids and indole were demonstrated to reduce its severity. In this study, we dissected the role of choline-metabolized trimethylamine N-oxide (TMAO) in the GVHD process. Either TMAO or a high-choline diet enhanced the allogenic GVH reaction, whereas the analog of choline, 3,3-dimethyl-1-butanol reversed TMAO-induced GVHD severity. Interestingly, TMAO-induced alloreactive T-cell proliferation and differentiation into T-helper (Th) subtypes was seen in GVHD mice but not in in vitro cultures. We thus investigated the role of macrophage polarization, which was absent from the in vitro culture system. F4/80+CD11b+CD16/32+ M1 macrophage and signature genes, IL-1β, IL-6, TNF-α, CXCL9, and CXCL10, were increased in TMAO-induced GVHD tissues and in TMAO-cultured bone marrow–derived macrophages (BMDMs). Inhibition of the NLRP3 inflammasome reversed TMAO-stimulated M1 features, indicating that NLRP3 is the key proteolytic activator involved in the macrophage’s response to TMAO stimulation. Consistently, mitochondrial reactive oxygen species and enhanced NF-κB nuclear relocalization were investigated in TMAO-stimulated BMDMs. In vivo depletion of NLRP3 in GVHD recipients not only blocked M1 polarization but also reversed GVHD severity in the presence of TMAO treatment. In conclusion, our data revealed that TMAO-induced GVHD progression resulted from Th1 and Th17 differentiation, which is mediated by the polarized M1 macrophage requiring NLRP3 inflammasome activation. It provides the link among the host choline diet, microbial metabolites, and GVH reaction, shedding light on alleviating GVHD by controlling choline intake.

scholarly journals Chronic opioid pretreatment potentiates the sensitization of fear learning by trauma

2019 ◽  
Vol 45 (3) ◽  
pp. 482-490 ◽  
Author(s):  
Zachary T. Pennington ◽  
Jeremy M. Trott ◽  
Abha K. Rajbhandari ◽  
Kevin Li ◽  
Wendy M. Walwyn ◽  
...  
Keyword(s):  
Basolateral Amygdala ◽  
Traumatic Event ◽  
Fear Learning ◽  
Opioid Use ◽  
Physical Injuries ◽  
Opioid Administration ◽  
The Impact ◽  
First Time ◽  
Considerable Period

AbstractDespite the large comorbidity between PTSD and opioid use disorders, as well as the common treatment of physical injuries resulting from trauma with opioids, the ability of opioid treatments to subsequently modify PTSD-related behavior has not been well studied. Using the stress-enhanced fear learning (SEFL) model for PTSD, we characterized the impact of chronic opioid regimens on the sensitization of fear learning seen following traumatic stress in mice. We demonstrate for the first time that chronic opioid pretreatment is able to robustly augment associative fear learning. Highlighting aversive learning as the cognitive process mediating this behavioral outcome, these changes were observed after a considerable period of drug cessation, generalized to learning about multiple aversive stimuli, were not due to changes in stimulus sensitivity or basal anxiety, and correlated with a marker of synaptic plasticity within the basolateral amygdala. Additionally, these changes were not observed when opioids were given after the traumatic event. Moreover, we found that neither reducing the frequency of opioid administration nor bidirectional manipulation of acute withdrawal impacted the subsequent enhancement in fear learning seen. Given the fundamental role of associative fear learning in the generation and progression of PTSD, these findings are of direct translational relevance to the comorbidity between opioid dependence and PTSD, and they are also pertinent to the use of opioids for treating pain resulting from traumas involving physical injuries.

scholarly journals Protective effect of exogenous hydrogen sulfide on diaphragm muscle fibrosis in streptozotocin-induced diabetic rats

2020 ◽  
Vol 245 (14) ◽  
pp. 1280-1289
Author(s):  
Rui Yang ◽  
Qiang Jia ◽  
Yan Li ◽  
Shomaila Mehmood
Keyword(s):  
Diabetes Mellitus ◽  
Skeletal Muscle ◽  
Hydrogen Sulfide ◽  
Nlrp3 Inflammasome ◽  
Respiratory Function ◽  
Diaphragm Muscle ◽  
Receptor Protein ◽  
Muscle Fibrosis ◽  
First Time ◽  
Oligomerization Domain

Diabetes mellitus has been shown to impair respiratory function. The diaphragm is an important skeletal muscle involved in respiration. Hydrogen sulfide (H2S) is one of the three endogenous gas messengers in mammals, which exhibits anti-fibrotic activity in some types of diabetes-related complications. However, whether and how H2S exerts its anti-fibrotic activity on the diabetic diaphragmatic muscle remains unclear. In this study, we explored the anti-fibrotic activity of exogenous H2S on the diaphragm using a streptozotocin (STZ)-induced diabetic rat model. The results showed that diaphragmatic biomechanical parameters were decreased, whereas the levels of inflammatory cytokines, collagen, and nucleotide-binding oligomerization domain-like receptor protein (NLRP) 3 inflammasome-related protein expression were increased in diabetic diaphragms. This implies that diabetes causes fibrosis of the diaphragm muscle through activation of NLRP3 inflammasome. After supplementation with exogenous H2S, the diaphragmatic biomechanical and pathological alterations were ameliorated and activation of NLRP3 inflammasome was inhibited, followed by a decline in diaphragm muscle inflammation and fibrosis. These results demonstrate for the first time that exogenous H2S effectively attenuates STZ-induced diabetic diaphragm muscle fibrosis, and that the underlying mechanism may be associated with suppression of the NLRP3 inflammasome-mediated inflammatory reaction. Impact statement Diabetes mellitus is a group of chronic metabolic disorders, which causes serious damage to a variety of organs, such as the retina, heart, and skeletal muscle. The diaphragm is an important skeletal muscle involved in respiration in mammals. Fibrosis of the diaphragm muscle affects its contractility, which in turn impairs respiratory function. Accumulating evidence suggests that exogenous hydrogen sulfide (H2S) exhibits anti-fibrotic activity in diabetes mellitus, but whether and how H2S exerts this anti-fibrotic effect in the diabetic diaphragm remains unclear. The current work for the first time reveals that exogenous H2S attenuates hyperglycemia-induced fibrosis of the diaphragm muscle and strengthens diaphragmatic biomechanical properties in diabetes mellitus, and the mechanism may involve the alleviation of collagen deposition by suppression of the nucleotide-binding oligomerization domain-like receptor protein (NLRP) 3 inflammasome-mediated inflammatory reaction. Therefore, H2S supplementation could be used as an efficient targeted therapy against the NLRP3 inflammasome in the diabetic diaphragm.

Spore morphotypes of Thelohania solenopsae (microsporidia) described microscopically and confirmed by PCR of individual spores microdissected from smears by position ablative laser microbeam microscopy

Microbiology ◽  
2004 ◽  
Vol 150 (5) ◽  
pp. 1261-1270 ◽  
Author(s):  
Yuliya Y. Sokolova ◽  
Lacey R. McNally ◽  
James R. Fuxa ◽  
S. Bradleigh Vinson
Keyword(s):  
Life Cycle ◽  
Pcr Analysis ◽  
Red Imported Fire Ant ◽  
Electron Microscopic ◽  
Laser Microbeam ◽  
Laser Pressure Catapulting ◽  
First Time ◽  
Imported Fire Ant ◽  
Ablative Laser

Development of Thelohania solenopsae, a parasite of the red imported fire ant (Solenopsis invicta), until recently was thought to include formation of two types of spores: unicellular meiospores, maturing inside sporophorous vesicles in sets of eight (octospores); and Nosema-like binuclear free spores. Megaspores, discovered in 2001, develop primarily in alates and are morphologically distinct from the two previously known types of spores. The role of megaspores in the T. solenopsae life cycle, as well as their existence, has been questioned. The current research includes light and electron microscopic descriptions of the three major spore morphotypes characteristic of T. solenopsae development. In addition, individual octospores and megaspores were isolated into groups of 8–20 from methanol-fixed and Calcofluor-stained smears of the infected ants for subsequent PCR analysis by the laser pressure catapulting function of a position ablative laser microbeam microscope, a technique applied for the first time to research of microsporidia. The PCR-amplified SSU rDNA nucleotide sequences from octospores and megaspores were identical. This, along with the consistency with which megaspores are detected in infected ants, demonstrates that megaspores are integral to the life cycle of T. solenopsae.

First Time Lucky? Exploring Whether First-Time Offenders Should Be Sentenced More Leniently

2013 ◽  
Vol 77 (2) ◽  
pp. 163-171
Author(s):  
Elaine Freer
Keyword(s):  
Criminal Justice ◽  
Theoretical Basis ◽  
Justice System ◽  
Minority Group ◽  
Criminal Behaviour ◽  
Repeat Offenders ◽  
The Impact ◽  
First Time ◽  
Sentence Reductions

This article explores the normative position and theoretical justifications for sentencing first-time offenders more leniently than repeat offenders, and examines whether such a practice is defensible. Those justifications include a lack of awareness of the gravity of criminal behaviour, a single lapse, that no censure has previously been communicated by the criminal justice system to that person, adolescent-limited offending, the impact of being in a minority group, and non-uniform impact. It examines whether various sentencing philosophies support sentence reductions for first-time offenders, and whether the justifiability of such practices depends on the theoretical basis and aims of sentencing, for instance the role of proportionality and deterrence.

ADF/n-cofilin–dependent actin turnover determines platelet formation and sizing

Blood ◽  
2010 ◽  
Vol 116 (10) ◽  
pp. 1767-1775 ◽  
Author(s):  
Markus Bender ◽  
Anita Eckly ◽  
John H. Hartwig ◽  
Margitta Elvers ◽  
Irina Pleines ◽  
...  
Keyword(s):  
Actin Filament ◽  
Molecular Mechanisms ◽  
Critical Role ◽  
Actin Dynamics ◽  
Complex Process ◽  
First Time ◽  
Late Stages ◽  
Platelet Formation

Abstract The cellular and molecular mechanisms orchestrating the complex process by which bone marrow megakaryocytes form and release platelets remain poorly understood. Mature megakaryocytes generate long cytoplasmic extensions, proplatelets, which have the capacity to generate platelets. Although microtubules are the main structural component of proplatelets and microtubule sliding is known to drive proplatelet elongation, the role of actin dynamics in the process of platelet formation has remained elusive. Here, we tailored a mouse model lacking all ADF/n-cofilin–mediated actin dynamics in megakaryocytes to specifically elucidate the role of actin filament turnover in platelet formation. We demonstrate, for the first time, that in vivo actin filament turnover plays a critical role in the late stages of platelet formation from megakaryocytes and the proper sizing of platelets in the periphery. Our results provide the genetic proof that platelet production from megakaryocytes strictly requires dynamic changes in the actin cytoskeleton.

scholarly journals The Limits to Parapatric Speciation II: Strengthening a Preexisting Genetic Barrier to Gene Flow in Parapatry

2018 ◽  
Author(s):  
Alexandre Blanckaert ◽  
Joachim Hermisson
Keyword(s):  
New Species ◽  
Gene Flow ◽  
Genetic Barrier ◽  
New Mutation ◽  
Genetic Incompatibility ◽  
Complex Process ◽  
Parapatric Speciation ◽  
The Impact ◽  
New Mutations

AbstractParapatric speciation has recently received a lot of attention. By encompassing the whole continuum between allopatric and sympatric scenarios, it includes many potential scenarios for the evolution of new species. Building upon previous work, we investigate how a genetic barrier to gene flow, that relies on a single postzygotic genetic incompatibility, may further evolve. We consider a continent island model with three loci involved in pairwise Dobzhansky-Muller incompatibilities (DMIs). Using a deterministic and analytic approach, we derive the conditions for invasion of a new mutation and its consequences on an already existing genetic barrier to gene flow. We focus on quantifying the impact of the epistasis generated by the new mutation on the genetic barrier. We show that the accumulation of genetic incompatibilities in the presence of gene flow is a complex process, where new mutations can either strengthen or destroy a preexisting barrier. In particular, preexisting polymorphism and incompatibilities do not always facilitate the growth of the genetic barrier by accumulation of further barrier genes. Migration may disrupt the snowball effect (the accelerating rate of DMI accumulation in allopatry) because incompatibilities are directly tested by selection. Our results also show an ambiguous role of gene flow, which can either impede or facilitate the strengthening of the genetic barrier. Overall, our results illustrate how the inclusion of gene flow renders the building of a genetic barrier difficult to analyze.

Sign in / Sign up

Export Citation Format

Share Document