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It is highly conserved process of posttranscriptional gene silencing by which double stranded RNA (dsRNA) causes sequence-specific degradation of mRNA sequences.
dsRNA-induced gene silencing (RNAi) is reported in a wide range of eukaryotes ranging from worms, insects, mammals and plants.
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What are small ncRNAs?
micro RNA (miRNA)
short interfering RNA (siRNA)
Properties of small non-coding RNA:
Involved in silencing mRNA transcripts.
Called “small” because they are usually only about 21-24 nucleotides long.
Synthesized by first cutting up longer precursor sequences (like the 61nt one that Lee discovered).
Silence an mRNA by base pairing with some sequence on the mRNA.
Discovery of siRNA?
The first small RNA:
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development of the worm C. elegans.
Two small transcripts of lin-4 (22nt and 61nt) were found to be complementary to a sequence in the 3' UTR of lin-14.
Because lin-4 encoded no protein, she deduced that it must be these transcripts that are causing the silencing by RNA-RNA interactions.
Types of RNAi ( non coding RNA)
MiRNA
Length (23-25 nt)
Trans acting
Binds with target MRNA in mismatch
Translation inhibition
Si RNA
Length 21 nt.
Cis acting
Bind with target Mrna in perfect complementary sequence
Piwi-RNA
Length ; 25 to 36 nt.
Expressed in Germ Cells
Regulates trnasposomes activity
MECHANISM OF RNAI:
First the double-stranded RNA teams up with a protein complex named Dicer, which cuts the long RNA into short pieces.
Then another protein complex called RISC (RNA-induced silencing complex) discards one of the two RNA strands.
The RISC-docked, single-stranded RNA then pairs with the homologous mRNA and destroys it.
THE RISC COMPLEX:
RISC is large(>500kD) RNA multi- protein Binding complex which triggers MRNA degradation in response to MRNA
Unwinding of double stranded Si RNA by ATP independent Helicase
Active component of RISC is Ago proteins( ENDONUCLEASE) which cleave target MRNA.
DICER: endonuclease (RNase Family III)
Argonaute: Central Component of the RNA-Induced Silencing Complex (RISC)
One strand of the dsRNA produced by Dicer is retained in the RISC complex in association with Argonaute
ARGONAUTE PROTEIN :
1.PAZ(PIWI/Argonaute/ Zwille)- Recognition of target MRNA
2.PIWI (p-element induced wimpy Testis)- breaks Phosphodiester bond of mRNA.)RNAse H activity.
MiRNA:
The Double-stranded RNAs are naturally produced in eukaryotic cells during development, and they have a key role in regulating gene expression .
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Cancer cell metabolism: special Reference to Lactate PathwayAADYARAJPANDEY1
Normal Cell Metabolism:
Cellular respiration describes the series of steps that cells use to break down sugar and other chemicals to get the energy we need to function.
Energy is stored in the bonds of glucose and when glucose is broken down, much of that energy is released.
Cell utilize energy in the form of ATP.
The first step of respiration is called glycolysis. In a series of steps, glycolysis breaks glucose into two smaller molecules - a chemical called pyruvate. A small amount of ATP is formed during this process.
Most healthy cells continue the breakdown in a second process, called the Kreb's cycle. The Kreb's cycle allows cells to “burn” the pyruvates made in glycolysis to get more ATP.
The last step in the breakdown of glucose is called oxidative phosphorylation (Ox-Phos).
It takes place in specialized cell structures called mitochondria. This process produces a large amount of ATP. Importantly, cells need oxygen to complete oxidative phosphorylation.
If a cell completes only glycolysis, only 2 molecules of ATP are made per glucose. However, if the cell completes the entire respiration process (glycolysis - Kreb's - oxidative phosphorylation), about 36 molecules of ATP are created, giving it much more energy to use.
IN CANCER CELL:
Unlike healthy cells that "burn" the entire molecule of sugar to capture a large amount of energy as ATP, cancer cells are wasteful.
Cancer cells only partially break down sugar molecules. They overuse the first step of respiration, glycolysis. They frequently do not complete the second step, oxidative phosphorylation.
This results in only 2 molecules of ATP per each glucose molecule instead of the 36 or so ATPs healthy cells gain. As a result, cancer cells need to use a lot more sugar molecules to get enough energy to survive.
Unlike healthy cells that "burn" the entire molecule of sugar to capture a large amount of energy as ATP, cancer cells are wasteful.
Cancer cells only partially break down sugar molecules. They overuse the first step of respiration, glycolysis. They frequently do not complete the second step, oxidative phosphorylation.
This results in only 2 molecules of ATP per each glucose molecule instead of the 36 or so ATPs healthy cells gain. As a result, cancer cells need to use a lot more sugar molecules to get enough energy to survive.
introduction to WARBERG PHENOMENA:
WARBURG EFFECT Usually, cancer cells are highly glycolytic (glucose addiction) and take up more glucose than do normal cells from outside.
Otto Heinrich Warburg (; 8 October 1883 – 1 August 1970) In 1931 was awarded the Nobel Prize in Physiology for his "discovery of the nature and mode of action of the respiratory enzyme.
WARNBURG EFFECT : cancer cells under aerobic (well-oxygenated) conditions to metabolize glucose to lactate (aerobic glycolysis) is known as the Warburg effect. Warburg made the observation that tumor slices consume glucose and secrete lactate at a higher rate than normal tissues.
The role of reliable data collection systems for improved livestock genetics in Burundi: Experience from ILRI ADGG program
1. Better lives through livestock
The role of reliable data collection systems for
improved livestock genetics in Burundi:
Experience from ILRI ADGG program
Workshop on sustainable development of Burundi's dairy sector--Partners of the regional integrated
agricultural development in the great lakes (PRDAIGL) project workshop, Burundi, 2–3 November 2022
Julie Ojango, Chinyere Ekine-Dzivenu.
Livestock Genetics
International Livestock Research Institute (ILRI)
3. 3
Challenges facing dairy producers in Africa
• Farmers do not have access to
productive and adapted livestock
seedstock that best suit their
production systems
• Access to various services and inputs is
inadequate, hence gains in
productivity in one generation cannot
be sustained in the next one
• Farmers have very limited access to
information to enable them extract
optimum benefits for their dairy
enterprises
• No systematic and sustainable
breeding or selection taking place
Huge differences in productivity in the different farming
systems
4. 4
Consequences of low production levels
Methane emission per kilogram of milk is
about 4 times higher in the top herds than
in herds that produce an average of 2000 kg
of milk
5. 5
Addressing the challenges
facing small holder livestock (dairy) systems
through innovative application
of ICT and genomic technology
What is the African Genetic Gain Program about ?
6. 6
ADGG’s Innovative Approach and
Objectives • Establish/Revamp National livestock
Performance Recording Centers (DPRCs) or
Platforms for herd and cow data management
• Develop & scale ICT platforms to capture herd,
cow level & other related data & link it to
DPRCs & other databases
• Develop a pipeline for genomic evaluations to
identify genetically superior bulls & cows for
propagation using Artificial Insemination and
natural mating
• Establish a digital farmer extension and
feedback system using genomic and
performance data for improved herd
management
• Establish private-public partnerships to
sustainably resource recording, genetic
evaluation and digital extension at county &
regional levels
7. 7
ADGG’s innovative approach
o Digital platforms for on-farm
performance tracking
o Decision-support and Farmer-to-Farmer
performance benchmarking
o Smart use of records & genomics tools
for selection and AI service delivery
Accelerate on-farm
genetic gains
• Milk Yield
• Milk composition
• Weight
• Reproductive
Performance
• Heat tolerance
• Survival rates
• Lactation persistency
• Mastitis incidences
• Disease tolerance
• Methane emission
• Adaptability Indices
o Target appropriate genotypes to
the agro-ecology
o Use young bulls with a focus on
production & adaptation
o Local feed/fodder resource use
efficiency
Genotypes adapted to
local agro-ecology
Economically and
Environmentally relevant
Traits
Adapted, and
Genetically
superior "seed”
animals for local
production
systems
Accelerate on-farm
genetic gains
9. •Farming systems characteristics
•Characteristics of dairy animals on
farms
•Monitor animal performance
•Monitor use of technologies (eg
Artificial Insemination, vaccination)
•Service providers
Data capture
Country Data platforms
Data Extraction
API Management
System Administration
Data Validation
DATA PLATFORM
Data Feedback
systems
•Customized data summaries
•Genomic evaluation
•Customized indexes for animal
selection
Analytics
•Managing reproduction
•Managing calves at different stages
•Using livestock data for decisions
•Managing animal health
E-Learning tools
• i-Cow
• Interherd +
Other data bases
The ADGG Platform
The ADGG landing page: https://portal.adgg.ilri.org/
An agile, robust, flexible & scalable system
10. 10
Breeds reared in different regions
Useful data summaries for
informed decision making by
different stakeholders :
Example from Tanzania
11. 11
Cont’d - Useful data summaries for decision making by different
stakeholders
14. 14
• ILRI director general, Jimmy Smith (left) and Minister for Livestock and
Fisheries Luhaga Mpina (2nd to left) present the award for best bull at
a special bull and cow show at the Nane Nane exhibition center in
Dodoma, Tanzania, June 2019. Photo ILR
Milestones &
Achievements
• Ethiopia First dairy animal parade
held on Tuesday March 30, 2020,
Fikiru Regessa, State Minister of
Agriculture (extreme left), Selam
Meseret ADGG Ethiopia National
Coordinator (middle), and Asrat Tera,
Director General of National Animal
Genetics Institute (NAGII) Ethiopia.
16. Index for selecting seed animals
developed using results from genomic
evaluation to improve milk production
without increasing body weight
• In 2018, about 5600 animals sampled
• GeneSeek Genomic Profiler (GGP) Bovine 50K used for genotyping
• 40581 SNPs imputed to high density
• In 2022 an additional 3000 animals sampled for genotyping per
country
17. Objective: Evaluate changes in genetic
parameters for milk yield and estimate
breeding values for milk production
under heat stress conditions.
Data –phenotype, genotype, weather
Genomic analysis of milk yield and heat tolerance in small holder dairy system of
sub-Saharan Africa
C.C. Ekine-Dzivenu, R. Mrode1, R.D. Oloo, D. Komwihangilo, E. Lyatuu, G. Msuta, J.M. Ojango, A.M. Okeyo
-1
0
1
2
3
4
69 70 71 72 73 74 76 77 78 79 80 81 82
Milk
EBV
THI
65769 55133 59078 63039 51938 59188 59155
Results Antagonistic relationships
between milk yield and thermal
tolerance. Milk production reduced
by 4.16% to 14.42% across THI
groups (heat stress levels).
Reaction norm shows genetic
variations exist between sires,
indicating the possibility to select
animals that perform optimally in
different environments.
Chinyere Ekine-Dzivenu
cekine@cgiar.org
18. Better lives through livestock
Take home message
Current & emerging ICT and genomic tools plus reproductive technologies present
new opportunities for Burundi to hasten genetic gains, hence there is no excuse
any more inaction.
Good afternoon and welcome back from lunch. I will give you more in-depth view of the ADGG data platform building on what Julie presented yesterday.
I would like to start by reminding you of this slide from yesterday that what you cannot measure, you cannot improve.
These are some of the problems facing small holder farmers in Africa ….lack of appropriate animals suited to our production system, in
adequate access to input and services and extension information and also lack of systematic breeding and selection going on
By applying a few changes in the management of their cattle, the small holder farmer can almost double his production
With the low production of our animals we have higher green house gas emission intensity which is leading to the change in the climate that we are seeing in our environment…..you can tell that the rains don’t come when it should come and the dry seasons are longer so if we have more productive animals,
Yesterday, we heard from Julie that in the developed parts of the world where dairy cows are producing a lot of milk, data was key. They had established system for collecting data from farmers and used that to develop the cattle population.
The problem we have in Africa is that we do not have such well established systems but we have ow discovered that we can work around that. Almost everyone has a mobile phone, farmers have mobile phones and we can use this to capture information we need to improve our dairy cattle populations coupled with DNA information form the cow’s hair.
But how do you measure in such fragmented system as ours in sub-Saharan Africa
Maximise productivity er unit land community best seeds production systems….cimmyt seeds to grow under inspection from them. Theny bought back the seed, gave it back to
Perenial fodder……grow what we know will work well……
Persistence,,,,how long deos it last in the cutting or grazing regime
So when ADGG comes into a country
Establish a platform for data recording
Establish ICT platform for capturing the data
Develop pipeline for genomic evaluation for identifying the genetically superior animals
Establish digital farmer feedback and extension system for informed decision making
Establish public private partnerships to keep the system running beyond the program
So ADGG collects data on economically important traits—MY, milk composition, weight, methane emission, heat tolerance, in the production environment of the farmer where the trait will be expressed and couples this information with the DNA information of the farmer to find the star animals that is adapted and genetically superior for breeding
When you open the data platform, this is what you see. The highlighted countries have data on the system. Data on the platform is secure and only people who are authorized to get access to the data can view it.
This platform is structured to capture data, analyze it and give feed back to farmers and other actors in the dairy value chain.
This platforms in can interface with others in other parts of the world and can be expanded to support different livestock species
Different actors can get very useful information for decision making from the platform. For example, for countries the livestock department can see what milk production looks like in the country and the breeds that are in use where
You can filter the data by regions in the country or ward and can see number of farmers and animals registered, category of farmers, gender distribution, breed……etc The ministry for example can use these summaries for informed decision making
This is a dashboard that was developed for one of our partners. So this is for NAIC, can see how semen is distributed in the country and the breed that is nost and least used for example, They can also monitor activities of inseminators to see how well they are performing……what is the rate of pregnancy for each inseminator…….and much more
For farmers, they get feedback on how they are preforming relative to others in their region. Individuals preforming well within district can become champions for influencing other farmers on best practices for improved production. They also get information on the composition of the animals to help manage them appropriate to extract optimum benefit. What we see I the field is that an animal is called a HF but when we look at the DNA profile, it is a crossbred having many more breeds like in this picture. Also, farmers can receive alerts on their mobile devices in the event of an outbreak in their area like here, it says …..
We have developed and constantly refining our selection index f
Another thing that happens when you have data constantly coming into the platform is that you can begin to ask questions and get answers so here we were interested to know whether heatsess was affecting animals in tz in therms of producu=tion and we see that whe the weather becomes hot they mlk procutioon drops. So then we ask another question, can we breed animals that can witstand this stress and still keep producing without being disturbed and we see tha
Developing this platform and providing all this information is a collective effort of many partners, many institutions and the dairy Farmers.
Thank you to everybody who has contributed and enabled us to have data from all types of dairy farmers in Africa all in one portal.