Communicable Diseases Flashcards
the scary diseases that ANY of us can contract, and WHY...! (83 cards)
1
Q
What is a pathogen?
A
- This is a microorganism that can causes diseases in other organisms, acting as the host
2
Q
Explain the bacteria that causes disease…
A
Undergoes binary fission by means of reproduction, damaging cells through toxins released.
* PROKARYOTES
* Reletivly large, compared to the virus
3
Q
Explain the fungi that causes disease
A
- Grows into structures of micellium as main-body structures, that may grow into mushrooms.
- Produces reproductive hyphae, releases spores in the atmosphere to reproduce across environment
- Hyphae = releases extracellular digestive enzymes (cellulase) causing additional decay
4
Q
Explain the Viruses that causes disease
A
- Invade organism cells, using genetic machinery to manufacture more copies of same virus
- Host cell will burst, cusing cell damage, relasesing many more viruses to invade further cells
- NON-LIVING, according to M.R.S G.R.E.N
Movement, Respiration, Sensitivity, Growth, Reproduction, Excretion and Nutrition.
5
Q
Explain the Protists that causes disease
A
- These enter host’s cell, and will feed with the available nutrition to grow and reproduce
- Normally carried with vectors, and transfered through fluids/contact
e.g Plasmodium via Mosquitoes…….
6
Q
How does Ring Rot come about?
A
- Occurs in PLANTS
- Caused by BACTERIA
- Ring of decay around vascular tissues in potatoes/tomatoes, alongside leaf wilting
7
Q
How does Tobacco Mosaic Virus come about?
A
- Occurs in PLANTS
- Caused by VIRUSES
- Leaf discolouration in mosaic-like pattern in many plants.
8
Q
How does Blight come about?
A
- Occurs in PLANTS
- Caused by PROTISTS
- Chlorosis and browning of plant tissues in potatoe tubers, alongside leaf wilting
9
Q
How does Black Sigatoka come about?
A
- Occurs in PLANTS (bananas mostly)
- Caused by FUNGI
- causing leafing spots on bananas, significantly reducing yeilds
10
Q
How does Athlete’s Foot come about?
A
- Occurs in ANIMALS (human mostly)
- Caused by FUNGI
- Redness, Itching and flaking of growth between toes in feet.
11
Q
How does Ring Worm come about?
A
- Occurs in ANIMALS
- Caused by FUNGI
- Ring-shaped growth with spores erupting through the skin, causing rashes in mammals
12
Q
How does Influenza come about?
A
- Occurs in ANIMALS
- Caused by VIRUS
- attacking respiratory system, causes muscle pains and headache in humans
13
Q
How does Bacterial Meningitis come about?
A
- Occurs in ANIMALS
- Caused by BACTERIA
- infection of the meninges, being membranes surrounding brain and nerves , may become inflamed/swollen
14
Q
How does HIV come about?
A
- Occurs in ANIMALS
- Caused by VIRUS
- **destroys the immune system by attacking WBCs, compromising immune response ** in humans
- Becomes AIDS when developed for a while, becoming much more susceptible to many other diseases
15
Q
What makes HIV a more unique virus to many?
A
- This is a RETROVIRUS!
- Will contain RNA rather than DNA, like a regular virus
- Will have enzyme Reverse Transriptase, to convert single stranded RNA genome to DNA when injected into host cell’s machinery
16
Q
Why would Bacteria and Fungi thrive more in vascular tissue, in a plant?
A
- Abundant supplyof water (xylem) and sugar+nutrients (phloem)
- Will MASSIVLEY aid for optimal growth in these organisms
17
Q
How does Malaria come about?
A
- A parasite in the bloodstream that can cause headaches and repeating episodes of fever - comas and even DEATH
- Protist = Plasmodium Falciparum
18
Q
How does Tuberculosis (TB) come about?
A
- Occurs in ANIMALS
- Caused by BACTERIA
- Killing cells in the entire body, mainly affecting respiratory systems (lungs…)
19
Q
Give and explain the methods of Direct Transmissions of disease
A
- Physical Contact: direct touching involved my ANY means; stopped by Condoms, Disinfectant, Sterilising equipments
- Feacal/Oral: Consuming anything with pathogens; stopped by Sewage Treatment, Cooked and Washed meats
- Droplets: Pathogens carried in air via drops; stopped by “Catch it - Kill it -Bin it”, tissues when sneezing
- Spore Transmission: Fungal/pathogenic spores carried in air; stopped by masks when needed, wash skin after soil contact
20
Q
Give and explain the methods of Indirect Transmissions of disease
A
- Vector Transmission: another organism used to gain entry into primary host, without harming this organism; stopped byKilling potential vector organisms, vaccinations, sterilising vectors
- Fungal Spores: airborne transission carried in the air; stopped by Condoms, Disinfectant, Sterilising equipments
- Leaf Distribution: Infected leaf shedding falls to soil, able to reproduce, and infect other plants ; stopped by Incinerating infected leaves/entire plant before shedding
21
Q
How does Malaria infect an individual?
A
- A female anopheles mosquito will suck blood of infected person
- Will also pick up gammetes of plasmodiumin the bloodstream
- Plasmodium will be nurtured and develop in mosquitotes salivary glands
- Another person is bitten
- Inside the liver, the parasites invade liver cells and multiply asexually to form more parasites.
- After maturing, the liver cells burst, releasing many parasites back into the bloodstream.
- The parasites (plasmodium falciparium) then invade erythrocytes, where they continue to multiply and cause the symptoms of malaria.
and cycle starts over!!
22
Q
What are Passive Defences in organsims?
A
- These are defences in place BEFORE a pathogen infection has taken place, preventing initial entry of said pathogen!!
23
Q
What are Active Defences in organisms?
A
- These are defences in place AFTER a pathogen infection has taken place, preventing internal speading of said pathogen, using ENERGY, and CHEMICALS (mostly….)
24
Q
What is a way to remeber Plant Physical Defences?
A
- LST CW BC = Lost Cow Back!
= Ligin, Stomata, Tylose, Cellulose, Waxy Cuticle, Bark, CALLOSE,
25
How can we describe **CALLOSE** and **TYLOSE?**
1. ***CALLOSE*** = **Large polysaccharide, blocking sieve end-wall plates**, as such polymers will block pathogen = spread decrease!
2. ***TYLOSE*** = **Baloon-Like swelling of toxic chemicals, filling/blocking xylem cavity**, containing Terpenes, also toxic to pathogens
26
What is a way to remeber **Plant Chemical Defences?**
1. **P.A.T.H.O.D.** = **say how it is read**
= **Phenols** (tanins that kill insects), **Alkeniods** (caffine, cocaine = bitter taste!), **Terpeniods** (antibacterial oils) , **Hydrolictic** Enzymes (degrading pathogen cell wall), **Defensive** Proteins (inhibiting ion channel transport), **Oxidative** Reagents (highly reactive oxygen molecules damaging pathogens)
27
Another means of ***Active defence***? *(plants...)*
***NECROSIS!***
**Another programmed cell death**, due to *untreatable site of infection*
***Killings infected cells*** = Stoppping pathogen spead through *stopping water/nutrient access to reproduce*
28
Define what is meant by ***parasite***
This is an organism that **lives inside a host organism**, **feeding and using nutrients** from this organism, while **harming this host organism**
29
Suggest reasons for **possible rapid spread of pathogens** (e.g. Fungi)?
1. **Vectors/Infected individuals moving** over a large geographical area
2. **Lack of resistance/Immunity** from the pathogen
3. **Overpopulation/Overcrowding** in a small area
4. Fungal spores / larger distances
30
Why would protsist ***Plasmodium*** use erythrocytes as part of life cycle?
1. To **avoid any foreign recognition** from the immune system
2. To **complete** its life cycle
3. Provides a **source of nutrients** to grow and nourish
31
What *chemical* processes will take place during **Blood Clotting?**
1. **Abrasion to skin** will cause opening to pathogens!
2. ***Exposed Collagen*** will bind to ***platelets***, to release ***12 Clotting Factors + Ca2 ions***
3. ***Inactive Thrombokinase*** will become ***Active Thrombokinase*** = important enzyme for next step
4. THEN ***Prothrombin*** becomes ***Active Thrombin*** = another enzyme inportant for next step
5. THENN ***Soluable Fibrinogen*** becomes ***Insoluable Fibrin*** = big player in "fish netting" of RBCs.
6. THENNN ***RBCs and Platelets are all trapped in a fat clump***, **drying up** and becoming **solid**.......
## Footnote
Thrombin becomes active when certain amino acids are removed from the active site: REALLY COOL!
32
Outline the **Skin's details** on primary defence....
* **Upper Layer = Epidermis Layer**, with layer of **cells underneath**
* Most cells are ***Keratinocytes, produced by mitosis from base-layer Multipotent Adult Stem Cells***
* As such cells approach surface, they undergo **Keratinisation** = ***Cytpolasm slowly replaced by Keratin Protien, drying out.....***
* Keratinised **DEAD CELL SURFACE LAYER** becomes very surface of skin!
*HENCE, BEING MAIN PRIMARY DEFENCE OF HUMANS!*
33
What makes the skin surface a **good primary defence**
**Keratin-Tough Epidermis**= Keratinocyes provide a very tough outer barrier to pathogens to penetrate
**Non-Living cells** = no cyloplasm; no chemical reactions; less susceptible to pathogenic infection on skin!
34
What is an **Enzyme Cascade?**
* An enzymatic cascade is **a sequence of successive activation reactions involving enzymes**, characterized by a **series stemming from an initial stimulus.**
* The **product** of each **preceding reaction catalyzes and is consumed in the next reaction**, and so forth......
35
*WHERE* and *WHY* are the **Mucus Membranes** found?
1. Found in: *Ears, Lungs, Genitals and Digestive System*
2. These all have **very thin membranes that means pathogens can enter much more easily**, into the body
3. Hence, at airways, epithelial tissue has ***GOBLET CELLS*** that **secretes the mucus**, to ***TRAP*** said pathogens
4. At epithelial tissue, we also have ***Ciliated cells***, that have ***Cilia***, to **waft bands of mucus away from the lungs!!**
36
How does **Inflammation Response** take place?
* Pathogen enters via **wound site!**
* ***Mast Cells*** will **detect and recognise** foreign pathogens invading tissue, releasing ***Histamines*** in response
* Histamines will cause ***VASODILATION*** in nearby blood vessels, **causing neutrophils and erythrocytes to leak out**
* ***ERYTHROCYTES*** = causes the **redness and swelling**, due to more concentrated in a **smaller** location
* ***MACROPHAGES*** = Releases **cytokines** to initiate **tissue repair**
| (can be paired with *specific* immune response....)
37
How does the Lymphatic Sytem help with Inflammation?
* Main Role: **Drains away waste fluids** from site of injuries!
* Such fluid will drain to nearby **Lymph Nodes**, containing **Lymphocytes** (can have***Lymph Node Swelling*** during sudden ***surge of lymphocyes activity and numbers!!)***
38
What does Lymph Fluid consist of?
* Contains fluid that **CAN NOT be absorbed back into the cappileries!!!**
* Consists of *Fats, Protiens, Damaged/Cancerous cells, Pathogens and Lymphocytes*
39
What are some other *secret* primary defences?
1. **TEARS:** Contains enzymes, providing killing of some pathogens in the eyes
2. **WAX:** At ear canal, ca trap entering pathogens
3. **REPRODUCTIVE:** Mucus plug walls in the cervix, also trapping pathogens!
40
Some expulsive forces to remove pathogens by Reflex Actions?
* SNEEZING!
* COUGHING!
* VOMITING!
All are methods to urgently remove disturbances/toxins/irritation inflicted by PATHOGENS!!
41
What are ***Secondary Non-Specific Defences?***
* These are defences that are used when a **pathogen has already entered the bloodstream**
* These still remain as **NOT SPECIFIC to antigens**, but forigen pathogens as a **whole...**
42
What are Antigens?
* These are **protiens on plasma membrane** that are **chemical markers for immune system** to recognise if **self or foriegn** cell
43
What are ***Opsonins?***
## Footnote
***BE SURE TO CHECK THIS LIL BIT OUT!!!!!***
1. These are **protien molecule that attach to antigens on pathogen surface**
2. Type of **UNIVERSAL ANTIBODY** that is **NON-SPECIFIC**, allowing a phagocytic cell to **easily bind, engulf and digest** the pathogen.
3. Hence, are able to bind to a **RANGE of antigens of differing pathogens**, (but not ALL...)
## Footnote
***RELEASED BY PHAGOCYTES!!!!!!!!!!!!!!***
44
What is ***Opsoninisation?***
The act of **Opsonins binding to antigens on the pathogen** surfaces.......
45
What are some activity differences between **Neutrophils** and **Macrophages?**
1. **Macrophages**: Engulfs pathogens, but *not FULLY digesting*
Antigens on digested pathogens are **conserevd**, and used for **protien complex on plasma membrane**
Becomes ***antigen presenting cell***, presenting antigens for **antibody production in Lymphocytes**
2. **Neutrophils:** *100% killing* , undergoes the good and proper **engulfing and digesting of pathogens**, containing ***lysosomes of hydrolyctic enzymes*** to do so!
46
What are some physical differences between **Neutrophils** and **Macrophages?**
1. **Macrophages**: ***Larger*** in size, lasts for ***3 months***, ***irregular outer membrane shape***, engulfs up to ***100*** pathogens
2. **Neutrophils:** ***Smaller*** in size, ***Multi-Lobed nucleus***, ***smoother outer membrane shape***, lasting for a **few days with consumption of up to 20** pathogens.
47
What is a **Monocyte** and a **Phagosome**?
1. **Monocyte** = This is the **IMMATURE VERSION** of a *Macrophage*, as it travels inactive in the bloodstream (more adolecscent in the life cycle)
2. **Phagosome** = The large vauole/vesicle that *surrounds pathogens* when engulfed
48
How do **Neutrophils** engulf and digest pathogens?
* They contain *many Lysosomes*, that contain **Hydrolyctic Enzymes, that will break down the structure of the pathogen**, destroying it
* Waste products will be expelled via *excocytosis*
49
Why does the **macrophages also antigen-presetning cells**, and not *neutrophils*?
| and WHY ANTIGEN **PRESENTING**, and not just ANTIGEN....
* This is because **macrophages are larger in size, with a much longer lifespan** than neutrophils *(despite both phagocytes)*
* This will mean that they will be **able to carry antigen-presetning much longer, for the lymphocytes to produce antibodies for same antigen!**
## Footnote
If a sole antigen, macrophage will be recognised by **immune response as foreign**, and will be **attacked**, and we do NOT want thia to happen
50
4 Main ways Phagocytes are adapted to their function!
1. ***Well Developed Cytoskeleton*** = Easily **changes shape to engulf and digest pathogens** + important **lysosome transportation** network
2. ***Many mitochondria*** = ATP **releases energy** for cell movements + endo/exocytosis
3. ***Multi-LObed Nucleus (neutrophils specific)*** = Able to **squeeze through cell layers in tissue** to reach infected locations
4. ***Many Ribossomes*** = Efficient **protiensynthesis to make lysozyme enzymes + antigen-presenting!**
51
Where are the phagocytes made??
**IN THE BONE MARROW!!!!**
52
What are Hydrolyctic Enzymes?
Enzymes using **water molecules to break down most chemical bonds** in *biological* structues (ester/peptide/Hydrogen....)
53
Describe how a Neutrophil can undergo phagocytosis!
- **Chemicals released** by pathogens as well as chemicals released by the body cells under attack **attract neurtophills via chemotaxis** to the site where the pathogen are located
- Neutrophills **move towards pathogens**, Which **may have antibodies attached** to their surface antigens
- Neutrophills have **receptor molecules** on their surface that recognise antibody molecule and attatch to them
- Once attached to the **pathogen the cell surface membrane of the neurtophill extends out engulfing the pathogen** and trapping the pathogen with a phagosome
- This part of the process is known as ***endocytosis***
- The neutrophill releases digestive enzymes into the vacuole, **becoming phagolysosome to occur**
- These **enzymes destroy the pathogens structure**
- After killing and digesting the pathogens the neutrophill die (eventually)
54
What is a **Lymphocyte?**
* This is a *WBC* with **a round, whole nucleus, found mostly in the lymphatic nodes/vessels**
* Undergoes **SPECIFIC IMMUNE RESPONSE**, capable of recognising **specific antigens**!
55
What are **Cytokines?**
1. These are **cell-signalling chemicals heavily involved in immune response** (but *not quite* hormones)
2. Use to signall **to other WBCs, to carry out certain immune responses**
56
What are the **different types of Cytokines**?
1. ***Monokines:*** *Released by macrophages*, **attracting neutrophils to stimulate B lymphocytes to differentiate and relase specific antibodies**
2. ***Interleukins:*** *Released by T Cells and macrophages* Stimulates **clonal expansion and differentiation of B lymphocytes**
3. ***Interferons:*** **Inhibiting virus replication**, by stimulating **T Killer Cell activity**!
57
What is **Clonal Expansion?**
This is a method of **mitosis** to **rapidly produce lymphocytes in a shorter** given time period
58
What are B lymphocytes Plasma+Memory Cells?
* ***B PLASMA CELLS:*** These will **produce the specific, complamentary antibodies via exocytosis**, at very very large quantities
* ***B MEMORY CELLS:*** Cells that remain in the bloodstream for a **very long period, providing immunity from encountered pathogens and a much faster secondary immune response**
59
How would **B Lymphocytes respond to antigen exposure?**
1. B lymphocytes **encounters anitgen via pathogen or macrophage antigen-presenting cell**
2. *Interleukins* released from T Cells and macrophages will cause **CLONAL EXPANSION**.
3. *Monokines* released from macrophages will cause **CELL DIFFERENTIATION**, into ***plasma and memory cells***
4. Plasma cells die in days due to *ATP energy all used for mass-producing antibodies*, while Memory cells *remain for YEARS!*
## Footnote
***CLONAL EXPANSION = PROLIFERATION!! (hit a 4 if u forget.....)***
60
What are ***T*** **Helper+Killer+Memory+Regulator** cells
1. ***T Helper Cells:*** *Secretes cytokines to stimulate colonal expansion and differentiation* of **B** Cells
2. ***T Killer Cells:*** *Destroys cells infected with viruses, by injecting H2O2*, causing cell lysis (killing away *cell+virus*)
3. ***T Memory Cells:*** Remains *in the blood, casugin a much faster secondary response upon second encounter*!
61
What do T Regulator Cells even do?
* They are **responsible for shutting down immune activity** following removal of pathogen
* Preventing ***AUTOIMMUNITY!***
62
**Mention and state** why do we need the ***3 lines of Defences***?
These are ***PRIMARY NON-SPECIFIC, SECONDARY NON-SPECIFIC AND SPECIFIC DEFENCES***
1. = **Prevents initial pathogen entry** into body/bloodstream
2. = **Short-Term response that can remove pathogen**, but ***NOT*** lead to *longer-term immunity*
3. = Immune response that ***remains SPECIFIC to PARTICULAR ANTIGEN***, leading to *life-long immunity* via *B Memory Cells*!
63
What is a **immunoglobin?**
* Complex protiens **produced by B Plasma Cells**, released in response to an *infection!*
* *Antibodies* can be classified as immunoglobins!
64
How can we describe the **structure of an Antibody?**
1. Consists of *Light polypeptide* (top region) and *Heavy polypeptide chains* (lower region)
4. ***CONSTANT REGION***: Universal region for *overall body of the antibody* and providing *easy binding site for phagocytes*!
5. ***VARIABLE REGION***: Has *specific shape to anigen*, different for *ALL antibodies*, and will bind to the antigen
6. ***HINGE REGION***: Region that allows *antibody flexibility, can bind to more than one antigen per antibody*!
7. ***DISULFIDE BRIDGES***: *Holding polpeptides together* in antibody
65
What are the **main types** of Antibodies?
1. ***Opsonins***: Binds to pathogen antigens;binding sites for phagocytic cells, allowing easly phagocytosis!
2. ***Agglutinins***: Each antibody has *2 binding sites*; will use each "arm" to bind to 2 pathogens each, *clumping together* (easily engulfednd digested) > **agglutination!!**
3. ***Antitoxins***: will bind to *toxic chemicals with antibodies produced by pathogens*, cancelling out toxic effect in the body!
66
What are Primary and Secondary responses?
1. ***PRIMARY***: This is the *first encounter* with pathogen, where *plasma cells first start producing the specific antibodies* for specific pathogen **(SLOWER RESPONSE ,FEWER ANTIBODIES PRODUCED)**
2. ***SECONDARY***: This is the *second encounter* with same pathogen, but *B and T memory cells* with recognise pathogens, stimulating *cytokines to plasma cels to produce many* antibodies **(RAPID RESPONSE, HUGE AMOUNT OF ANTIBODIES)**
67
What is vaccination?
* A method of stimulating an immune response to achieve immunity!
68
What can be contained in vaccines?
1. **Whole, live microorganisms** with similar antigens (copox vs smallpox)
2. **Weakened versions** of the pathogens
3. **Dead version** of pathogen
4. **Antigens only** only!
5. **Harmless version** of toxin!
69
How can vaccines prevent disease spread?
* ***Herd Vaccination:*** almost all population are given vaccine, where disease spread to non-immune hosts is very unlikey *(herd immunity acheived)*
* ***Ring Vaccination:*** Vaccinating people, mostly towns, villages and homes, in the IMMIDIATE VICINITY of new cases or possible occurences of infection with pathogen (Smallpox...)
70
How can we combat an **ever-mutating virus** like influenza?
1. **High-mutation rate: constant change of virus antigens**
2. In order to decrease chance to develop a pandemic of particular strain, most vulnerable people are vaccinated (65+, respiratory issues, weak immune systems)
71
What are 4 types of immunity achieved?
| What are
1. ***Natural*** = Acheived through natural, biological processes *(Natural body infection/Placenta and Breastfeeding in newborns)*
2. ***Artificial*** = Acheived through medical interventions *(Dead-Pathogen Vaccination/Antibody antigens)*
3. ***Active*** = immune system activated and making own antibodies
4. ***Passive*** = antibodies made supplied by another source
72
Why some diseases have **vaccines over others??**
1. Humans being the **main host**
2. Pathogen **mutates** *very* slow
3. Easy to identify **symptoms**
4. Pathogen **not concelased in other cell** in life cycle!
72
Why do we need **to research for new medicines**
* New diseases *emerging* always
* *Non-effective* treatments of some disease
* Antibiotics *less* effective!
73
Main sources of finding **new medicines?**
1. **Accidental findings** = Penicillin discovery
2. **Traditional, herbal medicine** = Poppy Seeds for morphine
3. **Observing Wildlife** = Elephant+Parrot clay eating for toxin treatment
4. **Using plant sources** = Foxgloves = *Digitalis* and Willow tree = *Aspirin*
74
Why should we *sustainably farm* rainforests?
1. **As plants are used for medicine**, we must ensure to **not allow species to be extinct, by removing them!**
2. Species are potential sources for new medicines!
75
What are personalised medicines?
* Where ***we sequence the genes of specific individuals***, and use them to ***create specific, tailored medicine treatment*** to the same patient!!
76
How has the *Human Genome Project* helped with *personalised medicine?*
* Access to a full genetic sequence can help **identify faulty genes in individual, that may give rise to certain diseases!**
77
What is ***Synthetic Biology?***
This is the ***production of new molecules that mimic natural processes***, or the ***use of natural molecules to produce new biological systems***, that ***DO NOT EXIST IN NATURE!!!!***
78
Examples of *Synthetic Biology* taking place!
* *Tomatoes* with ***anthocyanin*** pigment, being ***antioxidants against CHD***
* *Goldent Rice*, a GM Crop, producing ***beta-carotene***, used to produce ***vitamin A to combat blindless*** in children
79
How antibiotics kill bacteria?
| and ***SOMETIMES WILL NOT!***
* They are ***chemicals that inhibits the growth of the bacteria***, allowing them to be managed and killed via immune response!
* BUT, antibiotic resistance is a real deal, so must **COMPLETE COURSES** and **PRESCRIBE WHEN NECESSARY** to reduce this!
80
Describe the shape of *Primary Response curve*!
1. ***Lag time*** = time needed for *clonal selection and expansion of B Lymphocytes*
2. ***Rise*** = *B Plasma cells rapidly divide,* producing *specific antibodies* to pathies
3. ***Fall*** = Plasma cells *eventually die*, and infection *is overcome*
4. ***Rapid Increase+Shorter timespan*** = *B memory cells remain in blood*, giving ***faster secondary response***
81
Why no symptoms felt in upon second infection in *Primary Response curve?*
* **Second immune response is much faster**, with much larger quantity of antibodies produced!
82
How do vaccines lead into Memory Cells?
1. Vaccines **inject antigens**, where **APC presents to T helper cells**
2. **Antigen will bind to T Helper**, releases **cytokines**
3. **B Lymphocytes for clonal selection and expansion**, forming **B memory cells after differnetiation!!**
