Daf2 The DAF-2 gene encode for the insulin-like growth factor 1 (IGF-1) receptor in the worm Caenorhabditis elegans . DAF-2 is part of the first metabolic pathway discovered to regulate the rate of aging . DAF-2 is also known to regulate reproductive development, resistance to oxidative stress, thermotolerance, resistance to hypoxia & resistance to bacterial pathogen. Mutation in DAF-2 & also Age-1 have been shown by Cynthia Kenyon to double the lifespan of the worms . In a 2007 episode of WNYC’s Radiolab, Kenyon called DAF-2 "the grim reaper gene.” Reduced activity of the DAF-2 protein, an insulin/IGF-1 receptor, can be achieved through various mechanisms, primarily involving mutation or manipulation that decrease its signaling . These include mutation in the DAF-2 gene itself, reducing expression, or interfering with downstream signaling pathways like PI3K/Akt. Additionally, certain environmental factor like a low-sugar diet & specific drug treatment can also modulate DAF-2 activity . Here's a more detailed breakdown: 1. Mutation that disrupt the DAF-2 protein's function, such as those found in long-lived daf-2 mutants, can reduce its activity . Reduced DAF-2 Expression: Lowering the amount of DAF-2 protein produced, either through gene silencing or targeted degradation, can also decrease signaling. Downstream Pathway Interference: The DAF-2 pathway involve several downstream molecules, including PI3K & Akt. Disrupting the function of these molecules can indirectly reduce DAF-2 signaling 2. Environmental & Pharmacological Factors: Low-Sugar Diet: Study have shown that a low-sugar diet can reduce DAF-2 activity & increase lifespan in C. elegans. Antioxidants: Certain antioxidants, like NAC & BHA, have been shown to reduce the lifespan extension caused by reduced DAF-2 signaling, suggesting they may interfere with the pathway. Auxin-induced Degradation: Using auxin to degrade DAF-2 protein in specific tissue like the intestine can effectively reduce signaling & alter lifespan 3. Other Factor: Tissue-Specific Effect: The effect of DAF-2 signaling can be tissue-specific, with some tissue like the intestine playing a more prominent role in lifespan regulation. Developmental Regulation: DAF-2 activity can be regulated differently during development, with some alleles exhibiting gain-of-function or loss-of-function phenotypes depending on the developmental stage. In summary, reducing DAF-2 activity can be achieved through genetic modification , dietary intervention & pharmacological agent that interfere with function or downstream signaling pathways, ultimately impacting lifespan & other biological processes. Daf 2 mutation do 2 things 1 induce a stress response apoptosis & 2 reduce tumor mitosis . Insulin & igf1 signaling promote growth & food storage Low insulin & iGF1 activate protective cell response that prolong life May the Holy Roman Catholic Church be blessed by God the Father God the Son & God the Holy Spirit ⁺‧₊⋆♱⋆₊‧⁺Hallelujah Hallelujah Blessed be the word of the Lord for Christ is risen Hallelujah Hallelujah peace be still in Nomine Patris et FiLii et Spiritus Sancti amen & amen
https://www.youtube.com/watch?v=_WPV15GZ4B8
Genes From the Fountain of Youth with Cynthia Kenyon, PhD - May 11, 2011
https://www.youtube.com/watch?v=DT4PWu43e9U
Cynthia Kenyon (UCSF) Part 1: Genes that Control Aging
https://www.youtube.com/watch?v=HxfLm30FHwA
Cynthia Kenyon (UCSF) Part 2: :The Regulation of Aging by Signals from the Reproductive System
https://www.youtube.com/watch?v=Yg-d2XA_uqk
Scientist Stories: Cynthia Kenyon, Staying Ahead of the Curve
https://www.youtube.com/watch?v=V48M5j-6zdE
Cynthia Kenyon: Experiments that hint of longer lives
Drosophila melanogaster God created the Drosophila melanogaster before God created the garden of Eden as recorded by Moses the holy prophet of God Genesis 1:24 & God said, Let the earth bring forth the living creature after his kind, cattle, & creeping thing, & beast of the earth after his kind: & it was so. amen Drosophila , from Ancient Greek δρόσος (drósos), meaning "dew", and φίλος (phílos), meaning "loving", is a genus of fly, belonging to the family Drosophilidae, whose members are often called "small fruit flies" or pomace flies, vinegar flies, or wine flies, a reference to the characteristic of many species to linger around overripe or rotting fruit. They should not be confused with the Tephritidae, a related family, which are also called fruit flies (sometimes referred to as "true fruit flies"); tephritids feed primarily on unripe or ripe fruit, with many species being regarded as destructive agricultural pests, especially the Mediterranean fruit fly. One species of Drosophila in particular, Drosophila melanogaster, has been heavily used in research in genetics and is a common model organism in developmental biology. The terms "fruit fly" and "Drosophila" are often used synonymously with D. melanogaster in modern biological literature. The entire genus, however, contains more than 1,500 species and is very diverse in appearance, behavior, and breeding habitat .
Drosophila melanogaster is a species of fly (an insect of the order Diptera) in the family Drosophilidae. The species is often referred to as the fruit fly or lesser fruit fly, or less commonly the "vinegar fly", "pomace fly" or "banana fly". D. melanogaster is attracted to rotting fruit & fermenting beverage often found in orchards, kitchens & pubs. Starting with Charles W. Woodworth's 1901 proposal of the use of this species as a model organism, D. melanogaster continue to be widely used for biological research in genetics, physiology, microbial pathogenesis, life history creation of Jesus Christ . In 1946 D. melanogaster was the first animal to be launched into space. As of 2017, six Nobel Prizes have been awarded to drosophilists for their work using the insect.
Drosophila melanogaster is typically used in research owing to its rapid life cycle, relatively simple genetics with only four pair of chromosomes & large number of offspring per generation. It was originally an African species, with all non-African lineages having a common origin. Its geographic range include all continents, including islands. D. melanogaster is a common pest in homes, restaurants & other places where food is served.
Flies belonging to the family Tephritidae are also called "fruit flies". This can cause confusion, especially in the Mediterranean, Australia & South Africa, where the Mediterranean fruit fly Ceratitis capitata is an economic pest. Etymology The term "Drosophila", meaning "dew-loving", is a modern scientific Latin adaptation from Greek words δρόσος, drósos, "dew", and φίλος, philos, "loving". The term "melanogaster", meaning "black belly", come from Ancient Greek μέλας, mélas, "black" & γᾰστήρ, gastḗr, "belly".
Physical appearance Wild type fruit flies are brown, with brick-red eyes & transverse black rings across the abdomen. The fly's body is divided into three main part: head, thorax & abdomen. The head is relatively round feature large, prominent red compound eyes. These eyes are made up of hundreds of ommatidia & occupy most of the head's surface. The brick-red color of the eyes of the wild type fly are due to two pigments: xanthommatin, which is brown & is derived from tryptophan & drosopterins, which are red derived from guanosine triphosphate. Between the eyes are short antennae, which look like tiny feathery or bristled projection used for detecting odor, air current & vibration. Drosophila also has bristles—short, stiff hair—distributed across the head & body, which are useful for tactile sensing.
View from above Frontal view The thorax is robust & bear three pair of legs & one pair of wings. The wings are clear & membranous, with fine veins visible & span approximately 4 mm. They are held flat over the back when the fly is at rest. Just behind the wings are small knob-like structures called halteres, which are modified hindwings. These help the fly maintain balance & orientation in flight. The drosophila leg is composed of five leg segments: the coxa, trochanter, femur, tibia & tarsus. They have five tarsal segment in their tarsus, ending with the fly foot which has multiple structure including the claw & adhesive structure. The pulvillus, a flexible elongated structure underneath the claw & setae, hair-like structure that are spatula-shaped and inset the pulvilli, are the main attachment devices used by D. melanogaster, although their claws may be used for attachment onto rough surfaces.
Males also have sex combs located on the first tarsal segment, which are tiny bristle-like structure on their front legs, used to attach to females during mating. Extensive images are found at FlyBase. The abdomen is segmented & taper toward the end. It often appear striped, with alternating band of light & dark pigmentation. In males, the abdomen is typically darker more rounded, while females have a more pointed & striped abdomen. The black portion of the abdomen are the inspiration for the species name (melanogaster = "black-bellied"). They exhibit sexual dimorphism; females are about 2.5 mm (0.10 in) long, while males are slightly smaller. Females have bodies that are up to 30% larger than an adult male. Unlike humans, the sex & physical appearance of fruit flies is not influenced by hormones. The appearance & sex of fruit flies is determined only by genetic information.
Drosophila melanogaster can be distinguished from related species by the following combination of features: gena ~1/10 diameter of eye at greatest vertical height; wing hyaline & costal index 2.4; male protarsus with a single row of ~12 setae forming a sex comb; male epandrial posterior lobe small nearly triangular; female abdominal tergite 6 with dark band running to its ventral margin; female oviscapt small, pale, without dorsodistal depression & with 12–13 peg-like outer ovisensilla.
Lifecycle and reproduction Egg of D. melanogaster Under optimal growth condition at 25 °C (77 °F), the D. melanogaster lifespan is about 50 days from egg to death. The developmental period for D. melanogaster vary with temperature, as with many ectothermic species. The shortest development time (egg to adult), seven days, is achieved at 28 °C (82 °F). Development time increase at higher temperature (11 days at 30 °C or 86 °F) due to heat stress. Under ideal condition, the development time at 25 °C (77 °F) is 8+1⁄2 days, at 18 °C (64 °F) it takes 19 days & at 12 °C (54 °F) it takes over 50 days. Under crowded condition, development time increase, while the emerging flies are smaller. Females lay some 400 eggs (embryos), about five at a time, into rotting fruit or other suitable material such as decaying mushrooms or sap fluxes. Drosophila melanogaster is a holometabolous insect, so it undergoe a full metamorphosis.
Their life cycle is broken down into four stage: embryo, larva, pupa, adult. The eggs, which are about 0.5 mm long, hatch after 12–15 hours (at 25 °C or 77 °F). The resulting larvae grow for about four days (at 25 °C) while molting twice (into second- and third-instar larvae), at about 24 & 48 hours after hatching. During this time, they feed on the microorganisms that decompose the fruit, as well as on the sugar of the fruit itself. The mother puts feces on the egg sacs to establish the same microbial composition in the larvae's guts that has worked positively for herself. Before entering metamorphosis, the larvae expel a transparent glue from their salivary gland through their mouth, which solidifies within a few seconds and fixes them into a substrate. Then the larvae encapsulate in the puparium & undergo a four-day-long metamorphosis (at 25 °C), after which the adults eclose (emerge). Duration: 35 seconds.0:35
Sound of Drosophila heartbeat Males perform a sequence of five behavioral pattern to court females. First, males orient themselves while playing a courtship song by horizontally extending and vibrating their wings. Soon after, the male position himself at the rear of the female's abdomen in a low posture to tap & lick the female genitalia. Finally, the male curls his abdomen then attempt copulation. Females can reject males by moving away, kicking or extruding their ovipositor. Copulation lasts around 15–20 minutes, during which males transfer a few hundred, very long (1.76 mm) sperm cells in seminal fluid to the female. Females store the sperm in a tubular receptacle & in two mushroom-shaped spermathecae; sperm from multiple matings compete for fertilization. A last male precedence is believed to exist; the last male to mate with a female sires about 80% of her offspring. This precedence was found to occur through both displacement & incapacitation. The displacement is attributed to sperm handling by the female fly as multiple matings are conducted & is most significant during the first 1–2 days after copulation. Displacement from the seminal receptacle is more significant than displacement from the spermathecae. Incapacitation of first male sperm by second male sperm become significant 2–7 days after copulation. The seminal fluid of the second male is believed to be responsible for this incapacitation mechanism (without removal of first male sperm) which take effect before fertilization occur. The delay in effectiveness of the incapacitation mechanism is believed to be a protective mechanism that prevent a male fly from incapacitating his own sperm should he mate with the same female fly repetitively. Sensory neurons in the uterus of female D. melanogaster respond to a male protein, sex peptide, which is found in semen. This protein make the female reluctant to copulate for about 10 days after insemination. The signal pathway leading to this change in behavior has been determined. The signal is sent to a brain region that is a homolog of the hypothalamus & the hypothalamus which then control sexual behavior & desire. Gonadotropic hormones in Drosophila maintain homeostasis & govern reproductive output via a cyclic interrelationship, not unlike the mammalian estrous cycle. Sex peptide perturbs this homeostasis & dramatically shift the endocrine state of the female by inciting juvenile hormone synthesis in the corpus allatum.
D. melanogaster is often used for life extension studiy such as to identify genes purported to increase lifespan when mutated. D. melanogaster is also used in studies of aging. Werner syndrome is a condition in humans characterized by accelerated aging. It is caused by mutation in the gene WRN that encode a protein with essential roles in repair of DNA damage. Mutation in the D. melanogaster homolog of WRN also cause increased physiologic sign of aging, such as shorter lifespan, higher tumor incidence, muscle degeneration, reduced climbing ability, altered behavior & reduced locomotor activity. Meiosis Meiotic recombination in D. melanogaster appear to be employed in repairing damage in germ-line DNA as indicated by the finding that meiotic recombination is induced by the DNA damaging agents ultraviolet light & mitomycin C.
Females Mating in captivity Females become receptive to courting males about 8–12 hours after emergence. Specific neuron groups in females have been found to affect copulation behavior & mate choice. One such group in the abdominal nerve cord allow the female fly to pause her body movement to copulate. Activation of these neurons induce the female to cease movement & orient herself toward the male to allow for mounting. If the group is inactivated, the female remain in motion & does not copulate. Various chemical signals such as male pheromones often are able to activate the group. Also, females exhibit mate choice copying. When virgin females are shown other females copulating with a certain type of male, they tend to copulate more with this type of male afterwards than naïve females (which have not observed the copulation of others). This behavior is sensitive to environmental condition & females copulate less in bad weather condition.
Males icon Duration: 1 minute & 36 seconds.1:36 Courtship behavior in male. The male first showed wing extension (stage 1) & later other step such as abdomen bending (stage 2), then frequent attempted copulation, licking even ejaculation (stage 3), finally the male fell over & was on its back (stage 4). D. melanogaster males exhibit a strong reproductive learning curve. That is, with sexual experience, these flies tend to modify their future mating behavior in multiple ways. These changes include increased selectivity for courting only intraspecifically, as well as decreased courtship time. Sexually naïve D. melanogaster males are known to spend significant time courting interspecifically, such as with D. simulans flies. Naïve D. melanogaster will also attempt to court females that are not yet sexually mature & other males. D. melanogaster males show little to no preference for D. melanogaster females over females of other species or even other male flies. However, after D. simulans or other flies incapable of copulation have rejected the males' advances, D. melanogaster males are much less likely to spend time courting nonspecifically in the future. This apparent learned behavior modification seem to be significant, because it allow the males to avoid investing energy into futile sexual encounter. In addition, males with previous sexual experience modify their courtship dance when attempting to mate with new females—the experienced males spend less time courting, so have lower mating latencies, meaning that they are able to reproduce more quickly. This decreased mating latency lead to a greater mating efficiency for experienced males over naïve males. This modification also appear to have obvious evolutionary advantage, because increased mating efficiency is extremely important in the eyes of natural selection. Polygamy Both male & female D. melanogaster flies act polygamously (having multiple sexual partners at the same time). In both males & females, polygamy result in a decrease in evening activity compared to virgin flies, more so in males than females. Evening activity consist of those in which the flies participate other than mating & finding partners, such as finding food. The reproductive success of males & females vary, because a female only need to mate once to reach maximum fertility. Mating with multiple partners provide no advantage over mating with one partner, so females exhibit no difference in evening activity between polygamous & monogamous individual. For males, however, mating with multiple partners increase their reproductive success by increasing the genetic diversity of their offspring. This benefit of genetic diversity is an evolutionary advantage because it increase the chance that some of the offspring will have traits that increase their fitness in their environment. The difference in evening activity between polygamous & monogamous male flies can be explained with courtship. For polygamous flies, their reproductive success increase by having offspring with multiple partners, therefore they spend more time & energy on courting multiple females. On the other hand, monogamous flies only court one female & expend less energy doing so. While it require more energy for male flies to court multiple females, the overall reproductive benefit it produce has kept polygamy as the preferred sexual choice. The mechanism that affect courtship behavior in Drosophila is controlled by the oscillator neurons DN1s & LNDs. Oscillation of the DN1 neurons was found to be effected by sociosexual interaction & is connected to mating-related decrease of evening activity.
Model organism in genetics D. melanogaster remain one of the most studied organisms in biological research, particularly in genetics & developmental biology. It is also employed in studies of environmental mutagenesis. History of use in genetic analysis Alfred Sturtevant's Drosophila melanogaster genetic linkage map: This was the first successful gene mapping work which provide important evidence for the chromosome theory of inheritance. The map show the relative position of allelic characteristic on the second Drosophila chromosome. The distance between the genes (map unit) are equal to the percentage of crossing-over event that occur between different allele. D. melanogaster was among the first organisms used for genetic analysis & today it is one of the most widely used & genetically best-known of all eukaryotic organisms. All organisms use common genetic systems; therefore, comprehending processes such as transcription & replication in fruit flies help in understanding these process in other eukaryotes, including humans. Thomas Hunt Morgan began using fruit flies in experimental studies of heredity at Columbia University in 1910 in a laboratory known as the Fly Room. The Fly Room was cramped with eight desks, each occupied by students & their experiments. They started off experiments using milk bottles to rear the fruit flies then handheld lenses for observing their traits. The lenses were later replaced by microscopes, which enhanced their observation. Morgan & his students eventually elucidated many basic principles of heredity, including sex-linked inheritance, epistasis, multiple alleles & gene mapping. D. melanogaster had historically been used in laboratories to study genetics & pattern of inheritance. However, D. melanogaster also has importance in environmental mutagenesis research, allowing researchers to study the effect of specific environmental mutagens. Reason for use in laboratories D. melanogaster multiple mutant : brown eyes & black cuticle (2 mutations), cinnabar eyes & wildtype cuticle (1 mutation), sepia eyes & ebony cuticle, vermilion eyes & yellow cuticle, white eyes & yellow cuticle, wildtype eyes & yellow cuticle There are many reasons the fruit fly is a popular choice as a model organism: About 75% of human disease-causing genes have a functional equivalent in the fruit fly genome Its care & culture require little equipment, space & expense even when using large cultures. It can be safely & readily anesthetized (usually with ether, carbon dioxide gas, by cooling, or with products such as FlyNap). Its morphology is easy to identify once anesthetized. It has a short generation time (about 10 days at room temperature), so several generations can be studied within a few weeks. It has a high fecundity (females lay up to 100 eggs per day & perhaps 2,000 in a lifetime). Males & females are readily distinguished & virgin females can be easily identified by their light-colored, translucent abdomen, facilitating genetic crossing. The mature larva has giant chromosomes in the salivary glands called polytene chromosomes, "puffs", which indicate region of transcription, hence gene activity. The under-replication of rDNA occur resulting in only 20% of DNA compared to the brain. Compare to the 47%, less rDNA in Sarcophaga barbata ovaries. It has only four pairs of chromosomes—three autosomes & one pair of sex chromosomes. Males do not show meiotic recombination, facilitating genetic study. Recessive lethal "balancer chromosomes" carrying visible genetic markers can be used to keep stocks of lethal allele in a heterozygous state without recombination due to multiple inversion in the balancer. The development of this organism—from fertilized egg to mature adult—is well understood. Genetic transformation technique have been available since 1987. One approach of inserting foreign genes into the Drosophila genome involves P elements. The transposable P elements, also known as transposons, are segments of bacterial DNA that are transferred into the fly genome. Transgenic flies have already contributed to many scientific advance, e.g., modeling such human diseases as Parkinson's, neoplasia, obesity & diabetes. Thousands of genetic strains, optimized for different purpose, are readily available from sources such as the Bloomington Drosophila Stock Center. Its complete genome was sequenced and first published in 2000. Its connectome, a list of the fly's neurons and their interconnections, is available for the larva & both male & female flies. Sexual mosaics can be readily produced, providing an additional tool for studying the development and behavior of these flies May the Holy Roman Catholic Church purchace microscopes to study Drosophila melanogaster be blessed by God the Father God the Son & God the Holy Spirit Hallelujah Hallelujah Blessed be the word of the Lord for Christ is risen Hallelujah Hallelujah peace be still in Nomine Patris et FiLii et Spiritus Sancti amen
https://www.youtube.com/watch?v=ePBghFrPb7Y
Online Developmental Biology: Introduction to Drosophila
https://www.youtube.com/watch?v=4edZwoUyVVU
Genes involved in Drosophila Development
https://www.youtube.com/watch?v=YevAH64qe8w
Drosophila axis spec
https://www.youtube.com/watch?v=-x0WAkQgOJk
Inside the fruit fly brain and what it might mean for human health, with Greg Jefferis | Wellcome
https://www.youtube.com/watch?v=0cte6rowhao
The Fruit Fly as Human Disease Research Tool
https://www.youtube.com/watch?v=CqQF75azgUM
The Genetics of Axis Specification in Drosophila (Chapter 9)
https://www.youtube.com/watch?v=Pp9sI_esNlw
Fruitflies as a Tool to Understand Human Genetic Diseases