Abstract 131: Differential Regulation of Pitx2 Expression in Pulmonary Vein Muscle Sleeves and Left Atrium with Aging: Implication for Pulmonary Vein Triggers

2012 ◽  
Vol 111 (suppl_1) ◽  
Author(s):  
Johnson Wong ◽  
Div Verma ◽  
Craig Selzman ◽  
Huei-sheng Vincent Chen

Introduction: Pitx2, Paired-like homeodomain transcription factor 2, is a homeobox transcription factor that regulates left-right asymmetry during cardiogenesis. Pitx2 insufficiency in the left atrium (LA) has been linked to LA remodeling and arrhythmogenesis in age-related atrial fibrillation (AF). However, the main triggers for AF reside in pulmonary vein muscle sleeves (PVs). Whether Pitx2 insufficiency in PVs also plays a pathogenic role in generating trigger foci remains to be determined. Also, changes in Pitx2 expression in PVs with age remain unclear. We use qRT-PCR and Illumina microarrays to determine age-related changes in Pitx2 expression of PVs in wild type (WT) & heterozygous Pitx2cnull+/- mice, and in humans with or without AF. Methods: PV and LA regions were obtained from 1-23 month-old WT and Pitx2cnull+/- mice. Human PVs were obtained from ~110D human fetal hearts (E110D aborted fetus), two groups of adult donor hearts [20-30s year-old (yo) and 40-50 yo] and two patients with persistent AF. These tissues were used for genetic expression analysis. Results: Pitx2c expression decreases slightly with age in mouse LA and PV tissues. The expression levels of Pitx2c of Pitx2cnull+/- mice in LA are consistently at 55.2±10.5% of WT but at near-equal levels in PVs over four different age groups. In contrast, during human development, Pitx2 expression in PV muscle sleeves first decreases from ~E110D to ~30 yo but increases from 30 to 50 yo. In patients with AF, Pitx2 expression in PVs is only lower by 15% while HCN4 expression is higher by 13.5% when compared to control PVs at >50 yo. Expressions of type 2 Ryanodine receptors and calsequestrin in human PVs increase with age but decrease by ~30% with AF, suggesting impaired calcium handling abilities may play more significant roles than Pitx2 in the generation of PV triggers of AF. Conclusions: Genetic analysis of Pitx2c expression in PV muscle sleeves and LA tissues of WT and Pitx2cnull+/- mice revealed differential expression patterns. In human PVs, Pitx2 expression shows a regulation pattern with age distinct from that in mice, and genes linked to intracellular calcium handling may play a more important role than Pitx2 in generating trigger foci in PVs to initiate AF.

Cells ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1611
Author(s):  
Nur Fathiah Abdul Abdul Sani ◽  
Ahmad Imran Zaydi Amir Amir Hamzah ◽  
Zulzikry Hafiz Abu Abu Bakar ◽  
Yasmin Anum Mohd Mohd Yusof ◽  
Suzana Makpol ◽  
...  

The mechanism of cognitive aging at the molecular level is complex and not well understood. Growing evidence suggests that cognitive differences might also be caused by ethnicity. Thus, this study aims to determine the gene expression changes associated with age-related cognitive decline among Malay adults in Malaysia. A cross-sectional study was conducted on 160 healthy Malay subjects, aged between 28 and 79, and recruited around Selangor and Klang Valley, Malaysia. Gene expression analysis was performed using a HumanHT-12v4.0 Expression BeadChip microarray kit. The top 20 differentially expressed genes at p < 0.05 and fold change (FC) = 1.2 showed that PAFAH1B3, HIST1H1E, KCNA3, TM7SF2, RGS1, and TGFBRAP1 were regulated with increased age. The gene set analysis suggests that the Malay adult’s susceptibility to developing age-related cognitive decline might be due to the changes in gene expression patterns associated with inflammation, signal transduction, and metabolic pathway in the genetic network. It may, perhaps, have important implications for finding a biomarker for cognitive decline and offer molecular targets to achieve successful aging, mainly in the Malay population in Malaysia.


2021 ◽  
Vol 12 ◽  
Author(s):  
Adrienne R. Henderson ◽  
Qi Wang ◽  
Bessie Meechoovet ◽  
Ashley L. Siniard ◽  
Marcus Naymik ◽  
...  

Parkinson’s disease (PD) is the second most common age-related neurodegenerative disease. It is presently only accurately diagnosed at an advanced stage by a series of motor deficits, which are predated by a litany of non-motor symptoms manifesting over years or decades. Aberrant epigenetic modifications exist across a range of diseases and are non-invasively detectable in blood as potential markers of disease. We performed comparative analyses of the methylome and transcriptome in blood from PD patients and matched controls. Our aim was to characterize DNA methylation and gene expression patterns in whole blood from PD patients as a foundational step toward the future goal of identifying molecular markers that could predict, accurately diagnose, or track the progression of PD. We found that differentially expressed genes (DEGs) were involved in the processes of transcription and mitochondrial function and that PD methylation profiles were readily distinguishable from healthy controls, even in whole-blood DNA samples. Differentially methylated regions (DMRs) were functionally varied, including near transcription factor nuclear transcription factor Y subunit alpha (NFYA), receptor tyrosine kinase DDR1, RING finger ubiquitin ligase (RNF5), acetyltransferase AGPAT1, and vault RNA VTRNA2-1. Expression quantitative trait methylation sites were found at long non-coding RNA PAX8-AS1 and transcription regulator ZFP57 among others. Functional epigenetic modules were highlighted by IL18R1, PTPRC, and ITGB2. We identified patterns of altered disease-specific DNA methylation and associated gene expression in whole blood. Our combined analyses extended what we learned from the DEG or DMR results alone. These studies provide a foundation to support the characterization of larger sample cohorts, with the goal of building a thorough, accurate, and non-invasive molecular PD biomarker.


Development ◽  
1999 ◽  
Vol 126 (14) ◽  
pp. 3253-3262 ◽  
Author(s):  
B.W. Bisgrove ◽  
J.J. Essner ◽  
H.J. Yost

The embryonic midline is crucial for the development of embryonic pattern including bilateral symmetry and left-right asymmetry. In zebrafish, lefty1 (lft1) and lefty2 (lft2) have distinct midline expression domains along the anteroposterior axis that overlap with the expression patterns of the nodal-related genes cyclops and squint. Altered expression patterns of lft1 and lft2 in zebrafish mutants that affect midline development suggests different upstream pathways regulate each expression domain. Ectopic expression analysis demonstrates that a balance of lefty and cyclops signaling is required for normal mesendoderm patterning and goosecoid, no tail and pitx2 expression. In late somite-stage embryos, lft1 and lft2 are expressed asymmetrically in the left diencephalon and left lateral plate respectively, suggesting an additional role in laterality development. A model is proposed by which the vertebrate midline, and thus bilateral symmetry, is established and maintained by antagonistic interactions among co-expressed members of the lefty and nodal subfamilies of TGF-beta signaling molecules.


2021 ◽  
Vol 12 ◽  
Author(s):  
Charly Gilbert ◽  
Caroline Lefeuvre ◽  
Laurence Preisser ◽  
Adeline Pivert ◽  
Raffaella Soleti ◽  
...  

SARS-CoV-2 coronavirus infection induces heterogeneous symptoms, ranging from asymptomatic to lethal forms. Severe forms usually occur in the elderly and/or individuals with comorbidities. Children generally remain asymptomatic to primary infection, suggesting that they may have an effective local innate immune response. IFN-I and -III have non-redundant protective roles against SARS-CoV-2, although sometimes damaging the host. The expression and role of anti-viral peptides during SARS-CoV-2 infection have thus far been little studied. We aimed to identify the innate immune molecules present at the SARS-CoV-2 entry point. We analyzed the mRNA levels of type I (IFN-α and -β) and type III (IFN-λ1-3) interferons and selected antiviral peptides (i.e., β-defensins 1-3, α-defensins [HNP1-3, HD5] pentraxin-3, surfactant protein D, the cathelicidin LL-37 and interleukin-26) in nasopharyngeal swabs from 226 individuals of various ages, either infected with SARS-CoV-2 (symptomatic or asymptomatic) or negative for the virus. We observed that infection induced selective upregulation of IFN-λ1 expression in pediatric subjects (≤15 years), whereas IFN-α, IFN-β, IFN-λ2/λ3, and β-defensin 1-3 expression was unaffected. Conversely, infection triggered upregulation of IFN-α, IFN-β, IFN-λ2/λ3, and β-defensin 1-3 mRNA expression in adults (15-65 years) and the elderly (≥ 65 years), but without modulation of IFN-λ1. The expression of these innate molecules was not associated with gender or symptoms. Expression of the interferon-stimulated genes IFITM1 and IFITM3 was upregulated in SARS-CoV-2-positive subjects and reached similar levels in the three age groups. Finally, age-related differences in nasopharyngeal innate immunity were also observed in SARS-CoV-2-negative subjects. This study shows that the expression patterns of IFN-I/-III and certain anti-viral molecules in the nasopharyngeal mucosa of SARS-CoV-2-infected subjects differ with age and suggests that susceptibility to SARS-CoV-2 may be related to intrinsic differences in the nature of mucosal anti-viral innate immunity.


2013 ◽  
Vol 18 (3) ◽  
pp. 158-168 ◽  
Author(s):  
Emily Frankenberg ◽  
Katharina Kupper ◽  
Ruth Wagner ◽  
Stephan Bongard

This paper reviews research on young migrants in Germany. Particular attention is given to the question of how Germany’s history of migration, immigration policies, and public attitude toward migrants influence the transcultural adaptation of children and adolescents from different ethnic backgrounds. We combine past research with the results of new empirical studies in order to shed light on migrants’ psychological and sociocultural adaptation. Studies comparing young migrants and their German peers in terms of psychological well-being, life satisfaction, and mental health outcome suggest higher rates of emotional and behavioral problems among migrants of most age groups. With regard to adolescent populations between the ages of 14 and 17 years, however, the existence of differences between migrants and natives appears to be less clear. Research has also yielded inconsistent findings regarding the time trajectory of transcultural adaptation among adolescents. The coincidence of acculturation and age-related change is discussed as a possible source of these inconsistencies. Further, we provide an overview of risk and protective factors such as conflicting role expectations and ethnic discrimination, which may cause heightened vulnerability to adverse adaptation outcomes in some groups. Large-scale studies have repeatedly shown migrants of all age groups to be less successful within the German school system, indicating poor sociocultural adaptation. Possible explanations, such as the idiosyncrasies of the German school system, are presented. Our own studies contribute to the understanding of young migrants’ adaptation process by showing that it is their orientation to German culture, rather than the acculturation strategy of integration, that leads to the most positive psychological and sociocultural outcomes. The paper concludes by discussing implications for future cross-cultural research on young migrants and by suggesting recommendations for multicultural policies.


Author(s):  
A. E. Chernikova ◽  
Yu. P. Potekhina

Introduction. An osteopathic examination determines the rate, the amplitude and the strength of the main rhythms (cardiac, respiratory and cranial). However, there are relatively few studies in the available literature dedicated to the influence of osteopathic correction (OC) on the characteristics of these rhythms.Goal of research — to study the influence of OC on the rate characteristics of various rhythms of the human body.Materials and methods. 88 adult osteopathic patients aged from 18 to 81 years were examined, among them 30 men and 58 women. All patients received general osteopathic examination. The rate of the cranial rhythm (RCR), respiratory rate (RR) heart rate (HR), the mobility of the nervous processes (MNP) and the connective tissue mobility (CTM) were assessed before and after the OC session.Results. Since age varied greatly in the examined group, a correlation analysis of age-related changes of the assessed rhythms was carried out. Only the CTM correlated with age (r=–0,28; p<0,05) in a statistically significant way. The rank dispersion analysis of Kruskal–Wallis also showed statistically significant difference in this indicator in different age groups (p=0,043). With the increase of years, the CTM decreases gradually. After the OC, the CTM, increased in a statistically significant way (p<0,0001). The RCR varied from 5 to 12 cycles/min in the examined group, which corresponded to the norm. After the OC, the RCR has increased in a statistically significant way (p<0,0001), the MNP has also increased (p<0,0001). The initial heart rate in the subjects varied from 56 to 94 beats/min, and in 15 % it exceeded the norm. After the OC the heart rate corresponded to the norm in all patients. The heart rate and the respiratory rate significantly decreased after the OC (р<0,0001).Conclusion. The described biorhythm changes after the OC session may be indicative of the improvement of the nervous regulation, of the normalization of the autonomic balance, of the improvement of the biomechanical properties of body tissues and of the increase of their mobility. The assessed parameters can be measured quickly without any additional equipment and can be used in order to study the results of the OC.


1970 ◽  
Vol 4 (2) ◽  
pp. 74-77
Author(s):  
Rukshana Ahmed ◽  
Shamim Ara

Pathological changes in the prostate gland occur commonly with advancing age including inflammation, atrophy, hyperplasia and carcinoma and a change in volume is also evident. Estimation of volume of prostate may be useful in a variety of clinical settings. A cross-sectional descriptive study was designed to see the changes in volume of the prostate with advancing age and done in the Department of Anatomy, Dhaka Medical College, Dhaka from August 2006 to June 2007. The study was performed on 70 post-mortem human prostates collected from the unclaimed dead bodies that were under examination in the Department of Forensic Medicine, Dhaka Medical College, Dhaka. The samples were divided into three age groups; group A (10-20 years), group B (21-40 years) and group C (41-70 years). Volume of the sample was measured by using the ellipsoid formula. The mean ± SD volume of prostate was 7.68 ± 3.64 cm3 in group A, 10.61 ± 3.99 cm3 in group B and 15.40 ± 6.31 cm3 in group C. Mean difference in volume between group A and group C, group B and group C were statistically significant (p<0.001). Statistically significant positive correlation was found between age and volume of prostate (r = + 0.579, p < 0.001). Key Words: Prostate; volume; Bangladeshi. DOI: 10.3329/imcj.v4i2.6501Ibrahim Med. Coll. J. 2010; 4(2): 74-77


2019 ◽  
Vol 1 (8) ◽  
pp. 42-50
Author(s):  
A. V. Budkevich ◽  
L. B. Ivanov ◽  
G. R. Novikova ◽  
G. M. Dzhanumova

According to the authors, rationing the age-related EEG parameters in children should be based on personal psychical characteristics. A comparative analysis of personal psychical characteristics and electroencephalographic data was carried out in 300 apparently healthy children aged 3-15 years. According to this principle, two subgroups of conditionally healthy children in each age group were singled out: 1) with an immature attention function and 2) with an increased anxious background that do not reach the pathological level. Registration and analysis of EEG was performed by the Neurokariograf computer complex (MBN, Moscow) using mathematical processing methods.The EEG interpretation was based on the principle of assessing the functional state of a child's brain using a three-component model according to: 1) wakefulness level and its dissociation, 2) severity of signs of the EEG neurotic pattern, 3) directionality of formation of traits of the system-functional brain organization (severity of signs functional hypofrontality).lt was found the presence of EEG signs was indicative of a lower level of wakefulness in children with an immature function of attention in all age groups, compared with the indicators of the average population of group and children with an increased background of anxiety. Children with an increased background of anxiety have a tendency to prevalence and excessive spatial synchronization of the alpha rhythm. ln healthy children, the fact of a decrease in wakefulness and the presence of signs of anxiety in the clinic and in EEG patterns indicates individual personalities and should not be considered as pathology.


Author(s):  
Khuan Seow ◽  
Nadia Caidi

Canada has an aging population with the fastest growing age groups (80 and 45-64 years old) vulnerable to age-related diseases such as Alzheimer’s disease. Caregiving responsibilities often fall to the family members of the afflicted without much attention and consideration being placed on the information needs of these caregivers. We call for a better understanding of these caregivers' information needs and uses by social policy makers as well as information providers.La population du Canada a tendance à vieillir considérablement, avec la hausse la plus rapide dans les groupes d’âge (80 et 45 à 64 ans). Les personnes âges sont très vulnérables à toute sorte de maladies, telles que la maladie d’Alzheimer. La responsabilité revient souvent aux membres de la famille qui doivent prendre soin des personnes atteintes de cette maladie. Or, nous ne connaissons que peu de chose sur les besoins en information des personnes qui prennent soin de ces malades de l’Alzheimer : qui sont-ils ? Quelles sont leurs sources... 


2018 ◽  
Author(s):  
Foyzul Rahman ◽  
Sabrina Javed ◽  
Ian Apperly ◽  
Peter Hansen ◽  
Carol Holland ◽  
...  

Age-related decline in Theory of Mind (ToM) may be due to waning executive control, which is necessary for resolving conflict when reasoning about others’ mental states. We assessed how older (OA; n=50) versus younger adults (YA; n=50) were affected by three theoretically relevant sources of conflict within ToM: competing Self-Other perspectives; competing cued locations and outcome knowledge. We examined which best accounted for age-related difficulty with ToM. Our data show unexpected similarity between age groups when representing a belief incongruent with one’s own. Individual differences in attention and motor response speed best explained the degree of conflict experienced through conflicting Self-Other perspectives. However, OAs were disproportionately affected by managing conflict between cued locations. Age and spatial working memory were most relevant for predicting the magnitude of conflict elicited by conflicting cued locations. We suggest that previous studies may have underestimated OA’s ToM proficiency by including unnecessary conflict in ToM tasks.


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