This document summarizes a research study that examined the effects of the relaxation response on gene expression. The study found that one session of relaxation response activated distinct temporal patterns of gene expression. Specifically, it found upregulation of genes related to energy metabolism and downregulation of pro-inflammatory genes. It also found greater effects on these pathways in long-term practitioners of relaxation response compared to short-term practitioners or novices. The study provides early evidence that relaxation response can induce prolonged changes at the genetic level that oppose effects of chronic stress.
Hair Genesis Hair Loss Treatment - A natural solution to Male Pattern Baldnes...nikkisve
A natural solution to hair loss in both Men and Women for thinning hair and male pattern baldness. DHT blocking ingredients, clinically researched and backed by double blind placebo studies. Proven to regrow hair and thicken hair without dangerous ingredients.
Hair Genesis Hair Loss Treatment - A natural solution to Male Pattern Baldnes...nikkisve
A natural solution to hair loss in both Men and Women for thinning hair and male pattern baldness. DHT blocking ingredients, clinically researched and backed by double blind placebo studies. Proven to regrow hair and thicken hair without dangerous ingredients.
Zinc supplementation may reduce the risk of hepatocellular carcinoma using bi...caijjournal
Hepatocellular carcinoma (HCC) is a primary liver cancer with poor survival rates. Gene expression data
of HCC are investigated to screen target genes and core genes, which are employed to propose a new
strategy for the treatment of HCC. New concepts such as gene data streams, gene characteristic strength
(CS), gene impact factor (GIF) and gene force (GF) are proposed. Together with gene community network
(GCN), a novel algorithm, that is, called gene force algorithm (GFA), is presented to screen feature genes,
target genes and core genes. The fifteen target genes are obtained, which can be divided into three
clustering sets including HAMP Cluster = {HAMP, Trans, AQP4, VIPR1}, MT Cluster ={MT1H, MT1B,
MT1G, MT1E, MTIL, RNAHP, DNASE1L3} and GPC3 Cluster ={GPC3}. The core genes of each clusters
are HAMP, Metallothionein genes (MTs) and GPC3 respectively, where MTs is a general name for a group
of metallothionein genes. According to the relationship between the three core genes and the metals
including copper, iron and zinc, a treatment strategy for HCC is proposed, namely, "Supplement Zinc after
surgery" for HCC patients. The proposed treatment method can be used to regulate the expression levels of
HCC core genes.
Radiation and Radiation toxins are responsible for causing severe pathology and toxicity following moderate and high doses of radiation including cytotoxicity - necrosis, apoptosis, neurotoxicity, cardiotoxicity, profuse hemorrhage, and disruption of blood homeostasis.
ABSTRACT- Neurodegenerative diseases (NDDs) are traditionally defined as disorders with selective loss of neurons and distinct involvement of functional systems defining clinical presentation. Alzheimer’s Disease, being one of the most detrimental Neurodegenerative diseases, an irreversible, progressive brain disorder with changes in nerve cells resulting in their death and furthermore leading to the loss of intellectual and cognitive abilities. Despite the commercial availability of few drugs, Alzheimer’s disease is the sixth leading causes of death globally and the major public health concern, owing to a constraining coercion for action against it. For the same, many drug targets were identified of which one among the most potential one’s is the Microtubule- associated Tau protein that contributes to the pathological lesions of Alzheimer’s disease, the Neurofibrillary Tangles or Paired Helical Filaments. Believing that preventing the formation of these pathological lesions, the Neurofibrillary Tangles, is much more a prominent strategy, in the present study, two approaches one approach plying compounds belonging to the class of Cannabinoids and the other approach employing a set of small molecules were used, with the help of Bioinformatics tools, such as Discovery Studio in designing the therapeutic molecules that can obliquely and potentially combat against these Neurofibrillary Tangles or NFTs and actuate to reduce their content in neurons, which might result in an improved communication and thereby enhancing the condition of the diseased person.
Key-words- Alzheimer’s disease, Cannabinoids, Cognitive abilities, Discovery Studio, Neurofibrillary Tangles, Tau protein
DOI:10.21276/ijlssr.2016.2.4.11
ABSTRACT- Every year more than 13 million deaths worldwide are due to environmental pollutants, and
approximately 24% of diseases are caused by environmental exposures that might be averted through preventive
measures. Out of all these environmental chemicals, effects of air pollution is responsible for death of 3.3 million people
prematurely worldwide - a figure that could double by 2050 if emissions continue to rise at the current rate. Increasing
number of evidences has linked environmental pollutants with epigenetic variations, including changes in DNA
methylation status, histone modifications and other factors like incorporation of miRNAs, nucleosome remodeling, etc.
These entire mechanisms are likely to play important roles in disease aetiology, and their modifications, thus providing
further understanding of disease aetiology, as well as biomarkers for these exposures to environmental chemicals and/or
prediction of the risk for the disease. In this, we had tried to summarize the different epigenetic alterations related to
environmental chemical exposures, and propose the probable mechanisms of action behind such epigenetic changes. We
will also focus onopportunities, challenges and further directions for future epidemiology research in environmental
epigenomics. Further studies are needed in this regard to solve methodological and practical challenges, including
uncertainties about stability over time of epigenomic changes induced by the environment, tissue specificity of epigenetic
alterations, validation of laboratory methods, and adaptation of bioinformatic and biostatistical methods to
high-throughput epigenomics. Moreover, there are several reports of epigenetic modifications arising from environmental
chemical exposures, but most have not been directly linked to disease endpoints. Key-words- Environmental chemicals, Epigenetics, Disease susceptibility
Zinc supplementation may reduce the risk of hepatocellular carcinoma using bi...caijjournal
Hepatocellular carcinoma (HCC) is a primary liver cancer with poor survival rates. Gene expression data
of HCC are investigated to screen target genes and core genes, which are employed to propose a new
strategy for the treatment of HCC. New concepts such as gene data streams, gene characteristic strength
(CS), gene impact factor (GIF) and gene force (GF) are proposed. Together with gene community network
(GCN), a novel algorithm, that is, called gene force algorithm (GFA), is presented to screen feature genes,
target genes and core genes. The fifteen target genes are obtained, which can be divided into three
clustering sets including HAMP Cluster = {HAMP, Trans, AQP4, VIPR1}, MT Cluster ={MT1H, MT1B,
MT1G, MT1E, MTIL, RNAHP, DNASE1L3} and GPC3 Cluster ={GPC3}. The core genes of each clusters
are HAMP, Metallothionein genes (MTs) and GPC3 respectively, where MTs is a general name for a group
of metallothionein genes. According to the relationship between the three core genes and the metals
including copper, iron and zinc, a treatment strategy for HCC is proposed, namely, "Supplement Zinc after
surgery" for HCC patients. The proposed treatment method can be used to regulate the expression levels of
HCC core genes.
Radiation and Radiation toxins are responsible for causing severe pathology and toxicity following moderate and high doses of radiation including cytotoxicity - necrosis, apoptosis, neurotoxicity, cardiotoxicity, profuse hemorrhage, and disruption of blood homeostasis.
ABSTRACT- Neurodegenerative diseases (NDDs) are traditionally defined as disorders with selective loss of neurons and distinct involvement of functional systems defining clinical presentation. Alzheimer’s Disease, being one of the most detrimental Neurodegenerative diseases, an irreversible, progressive brain disorder with changes in nerve cells resulting in their death and furthermore leading to the loss of intellectual and cognitive abilities. Despite the commercial availability of few drugs, Alzheimer’s disease is the sixth leading causes of death globally and the major public health concern, owing to a constraining coercion for action against it. For the same, many drug targets were identified of which one among the most potential one’s is the Microtubule- associated Tau protein that contributes to the pathological lesions of Alzheimer’s disease, the Neurofibrillary Tangles or Paired Helical Filaments. Believing that preventing the formation of these pathological lesions, the Neurofibrillary Tangles, is much more a prominent strategy, in the present study, two approaches one approach plying compounds belonging to the class of Cannabinoids and the other approach employing a set of small molecules were used, with the help of Bioinformatics tools, such as Discovery Studio in designing the therapeutic molecules that can obliquely and potentially combat against these Neurofibrillary Tangles or NFTs and actuate to reduce their content in neurons, which might result in an improved communication and thereby enhancing the condition of the diseased person.
Key-words- Alzheimer’s disease, Cannabinoids, Cognitive abilities, Discovery Studio, Neurofibrillary Tangles, Tau protein
DOI:10.21276/ijlssr.2016.2.4.11
ABSTRACT- Every year more than 13 million deaths worldwide are due to environmental pollutants, and
approximately 24% of diseases are caused by environmental exposures that might be averted through preventive
measures. Out of all these environmental chemicals, effects of air pollution is responsible for death of 3.3 million people
prematurely worldwide - a figure that could double by 2050 if emissions continue to rise at the current rate. Increasing
number of evidences has linked environmental pollutants with epigenetic variations, including changes in DNA
methylation status, histone modifications and other factors like incorporation of miRNAs, nucleosome remodeling, etc.
These entire mechanisms are likely to play important roles in disease aetiology, and their modifications, thus providing
further understanding of disease aetiology, as well as biomarkers for these exposures to environmental chemicals and/or
prediction of the risk for the disease. In this, we had tried to summarize the different epigenetic alterations related to
environmental chemical exposures, and propose the probable mechanisms of action behind such epigenetic changes. We
will also focus onopportunities, challenges and further directions for future epidemiology research in environmental
epigenomics. Further studies are needed in this regard to solve methodological and practical challenges, including
uncertainties about stability over time of epigenomic changes induced by the environment, tissue specificity of epigenetic
alterations, validation of laboratory methods, and adaptation of bioinformatic and biostatistical methods to
high-throughput epigenomics. Moreover, there are several reports of epigenetic modifications arising from environmental
chemical exposures, but most have not been directly linked to disease endpoints. Key-words- Environmental chemicals, Epigenetics, Disease susceptibility
Integrative bioinformatics analysis of Parkinson's disease related omics dataEnrico Glaab
Presentation on statistical meta analysis of omics data from Parkinson's disease case-control studies. The results are used for a comparative analysis against aging-related omics alterations in the brain and a prioritization of new candidate disease genes using the phenologs approach.
A typical Realization of the process with linear recovery of AldosteroneIJERA Editor
Hypercortisolism as a sign of hypothamamus-pituitary-adrenocortical (HPA) axis overactivity and sleep EEG
changes are frequently observed in depression. Closely related to the
HPA axis is the renin-angiotensin-aldosterone system (RAAS) as 1. adrenocorticotropic hormone (ACTH) is a
common stimulus for cortisol and aldosterone, 2. cortisol release is suppressed by mineralocorticoid receptor
(MR) agonists 3. angiotensin II (ATII) releases CRH and vasopressin from the hypothalamus. The first passage
time and the bounds of the survival functions for the application are also obtained
Effect and maintenance of "EEG-biofeedback rTMS" on mood and working memory ...Amin Asadollahpour Kargar
This is a proposal presented in the 1st IBRO/APRC Iranian Associate School of Cognitive Neuroscience “Functional Human Brain Mapping”, Tehran, Iran, May 22-28, 2015
aimed:
1. To evaluate the effect of EEG-biofeedback rTMS on Mood in major depressed patients compare to EEG biofeedback and rTMS
2. To evaluate the maintenance of EEG-biofeedback rTMS on working memory in major depressed patients compare to EEG biofeedback and rTMS
Methylenetetrahydrofolate Reductase Gene (MTHFR_677CT) Associated with the de...ijsrd.com
Globally, Depression is widespread neuropsychiatric disorders affecting around 5% of the population and has been described as millennia linked with neurobiology showing association with direct neuro-chemicals and biochemical incredible factors, interact with "gene-gene", "gene-environment" as long as a scaffold potential for better exploration. The aetiology of depression is still unknown but believes to be the interaction between gene and environment including some of the other factors responsible for development of depression. The PCR-RFLP analysis of MTHFR (C677T) gene showed 0.45% in CT (heterozygous) genotype in patients of depression in comparison to controls (0.15%), suggesting increased risk of depression in those individuals. However, the odd ratio was also calculated at 95% confidence interval for MTHFR C677T gene which revealed non- significant difference between cases and control, may be because of small sample size.
Voice Assessments for Detecting Patients with Parkinson’s Diseases in Differe...IJECEIAES
Recently, a wide range of speech signal processing algorithms (dysphonia measures) aiming to detect patients with Parkinson’s disease (PD). So we have computed 19 dysphonia measures from sustained vowels collected from 375 voice samples from healthy and people suffer from PD. All the features are analysed and the more relevant ones are selected by the Principal component analysis (PCA) to classify the subjects in 4 classes according to the UPDRS (unified Parkinson’s disease Rating Scale) score. We used kfolds cross validation method with (k=4) validation scheme; 75% for training and 25% for testing, along with the Support Vector Machines (SVM) with its different types of kernels. The best result obtained was 92.5% using the PCA and the linear SVM.
Assessment of immunomolecular_expression_and_prognostic_role_of_tlr7_among_pa...dr.Ihsan alsaimary
Dr. ihsan edan abdulkareem alsaimary
PROFESSOR IN MEDICAL MICROBIOLOGY AND MOLECULAR IMMUNOLOGY
ihsanalsaimary@gmail.com
mobile : 009647801410838
university of basrah - college of medicine - basrah -IRAQ
Model Attribute Check Company Auto PropertyCeline George
In Odoo, the multi-company feature allows you to manage multiple companies within a single Odoo database instance. Each company can have its own configurations while still sharing common resources such as products, customers, and suppliers.
Honest Reviews of Tim Han LMA Course Program.pptxtimhan337
Personal development courses are widely available today, with each one promising life-changing outcomes. Tim Han’s Life Mastery Achievers (LMA) Course has drawn a lot of interest. In addition to offering my frank assessment of Success Insider’s LMA Course, this piece examines the course’s effects via a variety of Tim Han LMA course reviews and Success Insider comments.
The Roman Empire A Historical Colossus.pdfkaushalkr1407
The Roman Empire, a vast and enduring power, stands as one of history's most remarkable civilizations, leaving an indelible imprint on the world. It emerged from the Roman Republic, transitioning into an imperial powerhouse under the leadership of Augustus Caesar in 27 BCE. This transformation marked the beginning of an era defined by unprecedented territorial expansion, architectural marvels, and profound cultural influence.
The empire's roots lie in the city of Rome, founded, according to legend, by Romulus in 753 BCE. Over centuries, Rome evolved from a small settlement to a formidable republic, characterized by a complex political system with elected officials and checks on power. However, internal strife, class conflicts, and military ambitions paved the way for the end of the Republic. Julius Caesar’s dictatorship and subsequent assassination in 44 BCE created a power vacuum, leading to a civil war. Octavian, later Augustus, emerged victorious, heralding the Roman Empire’s birth.
Under Augustus, the empire experienced the Pax Romana, a 200-year period of relative peace and stability. Augustus reformed the military, established efficient administrative systems, and initiated grand construction projects. The empire's borders expanded, encompassing territories from Britain to Egypt and from Spain to the Euphrates. Roman legions, renowned for their discipline and engineering prowess, secured and maintained these vast territories, building roads, fortifications, and cities that facilitated control and integration.
The Roman Empire’s society was hierarchical, with a rigid class system. At the top were the patricians, wealthy elites who held significant political power. Below them were the plebeians, free citizens with limited political influence, and the vast numbers of slaves who formed the backbone of the economy. The family unit was central, governed by the paterfamilias, the male head who held absolute authority.
Culturally, the Romans were eclectic, absorbing and adapting elements from the civilizations they encountered, particularly the Greeks. Roman art, literature, and philosophy reflected this synthesis, creating a rich cultural tapestry. Latin, the Roman language, became the lingua franca of the Western world, influencing numerous modern languages.
Roman architecture and engineering achievements were monumental. They perfected the arch, vault, and dome, constructing enduring structures like the Colosseum, Pantheon, and aqueducts. These engineering marvels not only showcased Roman ingenuity but also served practical purposes, from public entertainment to water supply.
2024.06.01 Introducing a competency framework for languag learning materials ...Sandy Millin
http://sandymillin.wordpress.com/iateflwebinar2024
Published classroom materials form the basis of syllabuses, drive teacher professional development, and have a potentially huge influence on learners, teachers and education systems. All teachers also create their own materials, whether a few sentences on a blackboard, a highly-structured fully-realised online course, or anything in between. Despite this, the knowledge and skills needed to create effective language learning materials are rarely part of teacher training, and are mostly learnt by trial and error.
Knowledge and skills frameworks, generally called competency frameworks, for ELT teachers, trainers and managers have existed for a few years now. However, until I created one for my MA dissertation, there wasn’t one drawing together what we need to know and do to be able to effectively produce language learning materials.
This webinar will introduce you to my framework, highlighting the key competencies I identified from my research. It will also show how anybody involved in language teaching (any language, not just English!), teacher training, managing schools or developing language learning materials can benefit from using the framework.
Biological screening of herbal drugs: Introduction and Need for
Phyto-Pharmacological Screening, New Strategies for evaluating
Natural Products, In vitro evaluation techniques for Antioxidants, Antimicrobial and Anticancer drugs. In vivo evaluation techniques
for Anti-inflammatory, Antiulcer, Anticancer, Wound healing, Antidiabetic, Hepatoprotective, Cardio protective, Diuretics and
Antifertility, Toxicity studies as per OECD guidelines
Welcome to TechSoup New Member Orientation and Q&A (May 2024).pdfTechSoup
In this webinar you will learn how your organization can access TechSoup's wide variety of product discount and donation programs. From hardware to software, we'll give you a tour of the tools available to help your nonprofit with productivity, collaboration, financial management, donor tracking, security, and more.
Adversarial Attention Modeling for Multi-dimensional Emotion Regression.pdf
RR and gene expression
1.
2. Brief Background
Authors: Manoj Bhasin, Jeffery Dusek, Bei-Hung Chang,
Marie Joseph, John Denninger, Gregory Fricchione, Herbert
Benson, Towia Libermann
Published: May 2013
Grant Funding: H75/CCH123424 and R01 DP000339 from
the Centers for Disease Control and Prevention (CDC) (HB),
RO1 AT006464-01 from the National Center for
Complementary and Alternative Medicine (NCCAM)(HB),
M01 RR01032 from the NCRR, National Institutes of Health
(The Harvard-Thorndike GCRC). These grant funders had
“no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript.”
Conflicts of Interest: None.
3. Relaxation Response (RR)
This is the opposite response of the stress response (better
known as “flight or fight” response) which produces specific
psychological and physiological reactions in the mind and body. This
response often activates the parasympathetic nervous system whereas
the stress response activates the sympathetic nervous system. Over
time, over heightened activity of the sympathetic nervous system can
activate the inflammatory response and lead to chronic disease where
as the activation of the parasympathetic response is responsible for
helping to bring the body and mind into a state of equilibrium and
health.
The RR is activated by (1) focusing on a word, prayer, phrase,
sound, or movement, and (2) “disregarding everyday thoughts”
Examples of activities that activate RR: meditation, yoga,
movement practices, biofeedback, breathing exercises, progressive
muscle relaxation
Physiological changes associated with RR activation:
biochemical changes; < oxygen consumption, CO2 elimination, blood
pressure, heart and respiratory rate, and norepinephrine
responsiveness, >heart rate variability, and changes in cortical and
subcortical brain regions
4. Previous Research,
Purpose of This Study
Previous Research Findings:
Activation of the RR has shown to be an effective therapeutic
intervention to counteract stress associated with hypertension,
anxiety, aging, diabetes, rheumatoid arthritis, and insomnia;
however, the cellular evidence for this effect has not been fully
defined.
Previous study by authors established changes in genetic
expression with a similar design, specific with genes associated
with oxygen phosphorylation, antigen processing/presentation,
and apoptosis with short and long term practitioners when
compared to novices
This same previous study also found psychobiological changes
only in long term practitioners during one session of RR
What is unique for this Research?
It is examining acute genetic changes within one RR session and how
the length of previous practices affects this genetic expression.
5. Hypotheses of Study
(1) One Relaxation Response session for both short and
long-term practitioners would make specific changes in gene
expression that would be linked specific biological
pathways in comparison to a control group with no
experience
(2) More significant genetic changes would be found in long
term practitioners of Relaxation Response sessions in
comparison to short term practitioners of RR.
6. Study Sample
Study enrolled 26 healthy subjects with no previous
formal RR activation experience (ie. no formal practices of
RR) which were considered the control group, Novices (N1).
These subjects then took 8 weeks of RR training and then
became the first comparison as Short-term Practitioners (N2)
A second group of 26 healthy subjects with prior practices
in RR (4-20 years experience) were to compared with the
Novice (N1) group and Short-term Practitioners (N2). This
group was named Long-term Practitioners (M).
All subjects were recruited within Boston, MA
7. N1 (control group): Listened to a 20 minute Health
Education CD on first visit
N2 (control group which became N2) and M: Listened to
20 minute RR activating CD
Blood samples (to be used for gene expression profiles) and
biological measurements were taken before the session (T0),
after the session (T1) and 15 minutes after the session was
complete.
Fractional exhaled nitric oxide (FeNO) were collected at the
3 time points, which helps to assess physiological effects of
RR (such as reduction in blood pressure) and has shown
that RR typical increases FeNO levels which can influence
immune system responses.
Methods
9. Techniques
RNA was isolated from peripheral blood mononuclear cells
(PBMCs) in blood samples
Real-time FeNO (exhaled) was measured with a rapid response
chemoluminescent Nitric Oxide Analyzer before each session
Transcriptional Profiling: Done by Affymetrix human genome
high throughput array plates. These plates contained 96 arrays
and 22,000 transcripts. Array images were analyzed with dChip.
Types of Gene Analyses: The purpose was to identify RR
affected genes/sets of genes with a hierarchy of bioinformatic
techniques including Individual Gene Analysis, Gene Ontology
(GO) enrichment analysis, Gene Set Enrichment Analysis,
Pathways and Interactive network analysis, Systems Biology
analysis
10. Results Explained
RR leads to qualitative and quantitative temporal transcriptome changes:
Individual Gene Analysis
RR elicits distinct temporal patterns of differential gene expression: Self-
Organizing Map (SOM) Analysis
RR progressively affected energy metabolism and inflammation pathways:
Canonical pathways: Gene Set Enrichment Analysis (GSEA)
Upregulated Progressive changes induced by RR are linked to energy
production in mitochondria: Systems Biology Analysis
Upregulated Long-term changes induced by RR are linked to telomerase
stability and maintenance: Systems Biology Analysis
Progressive and Long-term Downregulated gene expression changes induced
by RR are linked to alteration of NF-kB-dependent pathways: Systems Biology
Analysis
Immune response and telomere maintenance related pathways are affected
among Long-term RR practitioners: GSEA
RR affected pathways are correlated with Fractional exhaled Nitric Oxide
(FeNO) levels : Correlation Analysis
11. Results
Across Group:
At T (0): Greatest differentiated genes between N1 vs. N2
At T (1): Greatest differentiated genes between N1 vs. M
At T (2): Greatest differentiated genes between N1 vs. M
What about Within Groups, what is the greatest differentiation?
17. Results: FeNO Gene Regulation
Table S3: Correlation analysis of NO levels and Selected 10 pathways affected progressively or only in long term manner
by RR (Bold).
The correlation analysis was performed both by comparing FeNO and gene expression levels at particular time point (e.g.
T0, T1, T2) as well as changes in gene expression and FeNO levels within a group. The significance of the correlation
was determined on the basis of P value (P < 0.05) and FDR (<25%). The positive and negative correlations between
FeNO and gene expression levels are indicated by red and green color respectively.
!"#$%"&'
!" !# !$
%&' ' () *+, ) +!+- (. &/+0!&/(123!&3456+6
%&' ' (. !32(6+' - 04+- ' (10!78 05 "9": "9#; "9""< "9"# "9"# "9#=
%&' ' (>02/+0>(. ) 6>4&(>3- !20>!+3-
%&' ' (0- !+' &- (123>&66+- ' (0- /(12&6&- !0!+3- "9"< "9"$ "9"<
*+3>02!0(2&40(10!78 05 " "9"$ "9"= "9"< "9#
*+3>02!0(+4; (10!78 05 "9""< "9""<
*+3>02!0(- ?%*(10!78 05
*+3>02!0(. +!3>73- /2+0(10!78 05
*+3>02!0(6!2&66(10!78 05 " "9""< "9"@ "9"# "9#$
*+3>02!0(!- ?2$(10!78 05 "9"# "9#$ "9"< "9#@
1ABCDE ?/2 1ABCDE ?/2 1ABCDE ?/2 1ABCDE ?/2 1ABCDE ?/2 1ABCDE ?/2 1ABCDE ?/2 1ABCDE?/2
!$F!#
. GHIJDK
1GABCDE
!#F!"
- #GHIJDK- $GHIJDK
!$F!" !$F!# !$F!" !$F!# !#F!" !$F!"
19. Discussion: Inflammation Relationships
Significant research has shown that activation of the RR can reduce chronic stress
and promote wellness and these authors have provided some of the first evidence of
prolonged gene level changes that are opposite of the transcriptional changes that
accompany chronic stress.
This research specifically looked at transient transcriptome changes in temporal
analysis because it focuses on indentifying genes affected by RR at time points and
reduces the likelihood of false positives.
It is suspected that with upregulation of gene sets with RR for oxidation might
improve efficiency of oxidation-reduction reactions and reduce oxidative stress.
Upregulation of the ATP synthase pathway with RR can play an important role in
understanding the biological supportive evidence of RR.
Critical pro-inflammatory transcriptor factors were downregulated by RR thus
having an influential effect on the inflammatory response, which can reduce
oxidative stress, insulin resistance, and apoptosis.
Psychological stress can cause chronic mitochondrial oxidative stress that can lead
to metabolic syndrome and activate NF-kB (pro-inflammatory factor) which can
make this worse.
Understanding the NF-kB relationship in inflammation is important for
understanding the molecular/cellular mechanisms for health benefits for RR.
20. Long term RR practice helped to upregulate pathways associated with gene
stability especially with telemere packing, telemere maintenance, and tight
junction interaction. Since telemere breakdown can affect mitochondria function
and lead to apoptosis.
The psychological stress is linked to deregulated immune system function and
DNA repair that may be influenced by RR and thus RR may be able to reverse
stress related transcriptome changes.
RR practice may create mitochondrial resiliency or mitochondrial reserve capacity
which can create cellular benefits in relationship to health and reducing
psychological stress and chronic disease.
Mitochondria are considered the energy powerhouse of a cell and also „master
regulators of danger signaling‟ to help protect cellular health and life of an
organism.
Certain mitochondria also experience differential reserve capacity to help work
with the different pathogenic effects of oxidative stress. Mitochondrial reserve
capacity and resiliency begins to fail when there is high cellular metabolic
demands, which contributes to high disease vulnerability.
The Future of This Research:
To continue to clinically define the in-depth cellular/molecular
pathways and genetic connections related to RR with secondary
biochemical testing.
Discussion: Mitochondria Relationships
21. Reference
Bhasin M., Dusek J., Chang B., Joseph M., Denninger J., Fricchione G.,
Benson H., Libermann T. (2013). Relaxation response induces temporal
transcriptome changes in energy metabolism, insulin secretion, and
inflammatory pathways. Retreived from PlosOne on March 6, 2014:
http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.
0062817
Editor's Notes
Why did I choose this research?Previous cardiovascular medicine research with a great interest in inflammation and what reverses the inflammatory process that can lead to chronic disease. I have approached this from Traditional Chinese Medicine looking at emotional, mental, physical, and spiritual components and this research allows me to approach it from physiological and genetic approaches and make larger and deeper connections.
Stress Response: highly activated by our fears, anxiety, the unknown, frustration, excesses, overwork, etc…..sound familiar?Relaxation Response: turns down the stress response and takes us into that happy medium where we can cope, understand, comprehend, listen, work well with others, and make good choices, and our immune system has the ability to respond correctly to maintain equilibrium and thus we process well on emotional, mental, physical, and spiritual levels.
RR training included: diaphragmatic breathing, body scan, mantra repetition, mindfulness meditation while ignoring intrusive thoughts20 minute CD was listened to once a day
Affymetrix human genomehigh throughput arrays plates with 96 arrays (HT U133A),containing more than 22,000 transcripts, were used. Scannedarray images were analyzed by dChip [31]. The raw probe leveldata were normalized using the smoothing-spline invariant setmethod, and the signal value for each transcript was summarizedusing the PM-only based signal modeling algorithm in which thesignal value corresponds to the absolute level of expression of atranscriptData analysis for identifying RR affected genes and gene setswas conducted first based on individual genes then on biologicallyrelated gene sets using a hierarchy of bioinformatics techniquesdescribed below and outlined in Figure 1. We then conductedcorrelation analysis to examine whether the gene expression of RR affected gene sets are associated with the changes in biologicalmeasurement, FeNO.
At T0: The greatest amount of differentiated genes happened with the comparison between N1 (novices) vs N2 (short-term)At T1: The greatest amount of differentiated genes occurred with the comparison between N1 (novices) vs M (long-term)At T3: The greatest amount of differentiated genes occurred with the comparison between N1 vs M.Figure 1. Individual gene-based differential expression analysis. Differentially expressed genes identified by 3 across-group comparisons(N1 vs. N2, N1 vs. M, and N2 vs. M) at T0, T1 and T2. Venn diagrams depict the overlap of genes identified by these 3 comparisons at each time point.B) Heat map of genes that were significantly differentially expressed comparing N1 vs. N2 and N1 vs. M at T1 and T2 (marked with arrow in Venndiagrams). Gene expression is shown with a pseudocolor scale (21 to 1) with red color denoting increased and green color denoting decreased foldchange in gene expression. The rows represent the genes and columns represent subjects in N1, N2 and M groups at T0, T1 and T2. Differentiallyexpressed genes identified by 3 within-group comparisons at different time points (T0 vs. T1, T0 vs. T2 and T1 vs. T2). Venn diagrams depict theoverlap of genes identified by the 3 comparisons within each group.
Figure 2. Temporal genomic expression patterns during one session of RR elicitation. Genes that were differentially expressed eitheracross or within groups comparisons at different time points were used as the seed set of genes for Self-Organizing Map (SOM) analysis. Thesedifferentially expressed genes were partitioned to 18 separate maps according to Pearson correlation coefficient based distance metrics (Figure S2).Selected biologically interesting SOM maps were manually clustered into 4 biologically relevant categories based on the gene expression of N1, N2and M groups at the 3 time points in one session of RR elicitation: Long-term Downregulation; Long-term Upregulation; Progressive Upregulation;and Progressive Downregulation. One representative pattern for each of these 4 biologically relevant categories is shown in the figure. The figuredisplays the box plot of the gene expression with X-axis representing time points and groups, and Y-axis representing scaled gene expression datafrom 21 to +1.
Figure 3. Significantly enriched pathways with progressive patterns identified using gene set enrichment analysis. UpregulatedPathways Downregulated Pathways. The solid dots indicate significantly affected pathways (False Discovery Rate ,25%) identified from acrossgroup comparisons (N1 vs. N2, N1 vs. M and N2 vs. M) at a particular time point (T0, T1 and T2). The asterisks represent significance and directionalityof enrichment (P value,0.09 *, P value,0.05 **, P value,0.01 ***) identified from within group comparisons at different time points (T0 vs. T1, T0 vs.T2, T1 vs. T2). The red and green color asterisks indicate up- and down-regulated enrichment of pathways respectively. The heatmaps depictingrelative expression of selected genes from representative pathways are shown in panels on the right side. Gene expression is shown with a pseudocolor scale (23 to 3) with red and green colors denoting increased and decreased relative expression respectively. Pathways with progressivepatterns were enriched (up- or down- regulated) in N2 and M groups with greater significance of enrichments in M group. Furthermore, increasingenrichment over time within one session of RR elicitation was observed in M group.
Figure 4. Significantly enriched pathways with long-term patterns identified using gene set enrichment analysis. UpregulatedPathwaysDownregulated Pathways. The solid dots indicate significantly affected pathways (False Discovery Rate ,25%) identified from acrossgroup comparisons (N1 vs. N2, N1 vs. M and N2 vs. M) at a particular time point (T0, T1 and T2). The asterisks represent significance and directionalityof enrichment (P value,0.09 *, P value,0.05 **, P value,0.01 ***) identified from within group comparisons at different time points (T0 vs. T1, T0 vs.T2, T1 vs. T2). The red and green color asterisks indicate up- and down-regulated enrichment of pathways respectively. The heatmaps depictingrelative expression of selected genes from representative pathways are shown in panels on the right side. Gene expression is shown with a pseudocolor scale (23 to 3) with red and green colors denoting increased and decreased relative expression respectively. Pathways with long-term patternswere enriched (up- or down- regulated) only in M group. Furthermore, increasing enrichment over time within one session of RR elicitation wasobserved in M group
Figure 5. Interactive network and top focus gene hubs identified from significantly affected pathways. The figure represents the topfocus genes. A) Progressive upregulated Pathways, B) Progressive downregulated Pathways, and C) Integrated network of Long-term and Progressiveaffected pathways. The top focus hubs were identified from complex interactive networks generated from pathways with progressive and long-termpatterns. The focus gene hubs were identified using the bottleneck algorithm for identification of the most interactive molecules with tree liketopological structure. The bottleneck algorithm ranks genes on the basis of significance level with smaller rank indicating increasing confidence. Thepseudocolor scale from red to green represents the bottleneck ranks from 1 to 20.
Oxidative Gene sets and the ATP synthase pathways have central roles in mitochondrial energy mechanics, oxidative phosphorylation, and cell aging---this can prevent an overactive cellular activity expending too much mitochondrial energy.