What causes genes to mutate?

What causes genes to mutate?

•      Ionising radiation – X Rays, UV light

•      Chemicals –from cigarettes, plastic processing, pollutants,

•      Virus infection – papilloma virus, HBV, etc.

•      Hereditary predisposition – Some families are more susceptible to getting certain cancers. you can’t inherit cancer

Silent: If abase substitution occurs in the third position of the codon there is a good chance that a synonymous codon will be generated. Thus the amino acid sequence encoded by the gene is not changed and the mutation is said to be silent.

Missence: When base substitution results in the generation of a codon that specifies a different amino acid and hence leads to a different polypeptide sequence. Depending on the type of amino acid substitution the missense mutation is either conservative or non-conservative.

Nonsense: When a base substitution results in a stop codon ultimately truncating translation and most likely leading to a non-functional protein.

Aneuploidies- Is the presence of an abnormal number of chromosomes in a cell, for example a human cell having 45 or 47 chromosomes instead of the usual 46. It does not include a difference of one or more complete sets of chromosomes.

Mutated Cancer Genes
Oncogenes	Oncosuppressors
Genes that positively contribute to cancer, they need to be more active. They usually push proliferation, inhibit apoptosis, block differentiation, make stemness.	genes that need to be inactivated to contribute to cancer. They usually inhibit proliferation, induce apoptosis, induce differentiation

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RBC Life cycle

Red Blood Cell Life Cycle

1. RBC are produced in the BM from
precursors. This is when Hb is
produced. RBC production is
stimulated by EPO released from
the kidney cells

2. Mature RBC are released in the
circulation where they function
for 120 days

3. Old RBC are recognized and
phagocytized by macrophages in
the spleen (Hemocatheretic
function)

4. The content of the RBC is
recycled: Hb à aa

5. Heme à Protoporphirin + Fe

6. protoporphyrin is recycled or
metabolized by liver (bilirubin)
and excreted in the gut
(stercobilin) or urin (Urobilin)

7. Iron is transported by transferrin
and/or conserved in the protein
ferritin

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Acid base disorder

Acid base disorder 

Effects on cell compartmentalisation induced by changes of ionisation state of molecules.

Metabolic acids:

Anaerobic metabolism of glucose to lactate and pyruvate.

Anaerobic metabolism of fatty acids.

Oxidation of suplphur-containing amino acids (Cys and Met) and cationic amino acids (Arg and Lys).

Chemical buffers (intracellular and extracellular)

- Bicarbonate system (seconds).

- Phosphate system.

- Protein buffer system.

Physiological regulation:

- Respiratory control - the brain stem respiratory centres (1-3 minutes). Changes alveolar ventilation.

- Renal mechanisms (hours; up to a whole  day).

Its biological significance lies on the fact that can eliminate buffer hydrogen ions.

Major buffer system of blood plasma (around 70% of buffering capacity).

Not a very efficient system – pKa not within ideal range to buffer pH 7.4

Importance comes from two other features:

High concentrations in the blood.

Open system – excretion of CO2 from the lungs and reabsorption of HCO3- in the kidney.

**!!Remember to stay positive like to proton!!**

Interesting article on pains of arthritis! I am learning about *COOL*

PURPOSE OF REVIEW:

An increasing number of patients with rheumatoid arthritis (RA) are using cannabis to treat their symptoms, although systematic studies regarding efficacy in RA are lacking. Within this review we will give an overview on the overall effects of cannabinoids in inflammation and why they might be useful in the treatment of RA.

RECENT FINDINGS:

Peripherally, cannabinoids show anti-inflammatory effects by activating cannabinoid type 2 receptors (CB2) which decrease cytokine production and immune cell mobilization. In contrast, cannabinoid type 1 receptor (CB1) activation on immune cells is proinflammatory while CB1 antagonism provides anti-inflammatory effects by increasing β2-adrenergic signaling in the joint and secondary lymphoid organs. In addition, the nonpsychotropic cannabinoid, cannabidiol (CBD) demonstrated antiarthritic effects independent of cannabinoid receptors. In addition to controlling inflammation, cannabinoids reduce pain by activating central and peripheral CB1, peripheral CB2 receptors and CBD-sensitive noncannabinoid receptor targets.

SUMMARY:

Cannabinoids might be a suitable treatment for RA, but it is important to target the right receptors in the right place. For clinical studies, we propose a combination of a CB2 agonist to decrease cytokine production, a peripheral CB1 antagonist to prevent detrimental CB1 signaling and to support anti-inflammatory effects of CB2 via activation of β2-adrenergic receptors and CBD to induce cannabinoid-receptor-independent anti-inflammatory effects.

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Starting 3rd Year! Exciting!!

Hi Readers!
As Autumn creeps in the end of summer break is here! After a long restful few months I am happy to come back to university and learn more about medical sciences and trying new experiences! 
A little food for thought and what I am currently working on is what one thing would you do differently than last year? For me I am definitely going to be working on my literature reviews and try to read more science journals in order to get a better understanding and learn the scientific language. 

whats yours? 
Lastly good luck on the new academic year! I hope this year brings new friends, good grades and all round good vibes! 

**REMEMBER TO STAY POSITIVE LIKE A PROTON!!**

Can Treating Gum disease help manage type 2 diabetes?

A new study led by professor Dr. Francesco D' Auito have found out in new research that treating gum disease can have a significant improvement and manageable differences on type 2 diabetes. 

Below are a few experts from the research paper: 

"Gum disease is closely linked to diabetes and it is well known that it can lead to a higher blood glucose level as well as chronic inflammation around the body, which both could promote the development of kidney and vessel damage if sustained for long periods of time.

"This is the first long-term, randomised study to show a substantial benefit of treating gum disease on diabetes control.

"Lowering blood glucose level by 0.6% is the equivalent of prescribing a patient an additional, second blood sugar lowering drug.

what do you think of this exciting news, that I thought I would share with my readers! 

let me know in the comments below!! :)

-Mr. Paracetamol 

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CRISPR - the revolutionary advancement in medicine?

Hi guys! 

Today were going to discuss CRISPR, if you haven't heard of it before its a very simple but powerful tool which can edit genomes. This is really good because it means that scientists can easily alter and edit the genome and its  functions. CRISPR is associated with the protein called cas9 and is a type of enzyme used to catalyses the reaction and cut the DNA strand up. 

I wanted to discuss about CRISPR this week as it has been making waves in the medical community after being deemed unsafe and unethical in genetic editing on children and so called 'designer' babies. 

what are your thoughts? please let me know in the comments below or alternatively email me! I always reply! :) 

hope you all are having a amazing summer! 

From. 
Mr. Paracetamol 

**!!REMEMBER TO STAY POSITIVE LIKE A PROTON!!**

HIV latest developments!

Hi readers! 

HIV also is called Human immunodeficiency virus and when untreated it weakens the immune defense system.

In the news recently two patients were ''cured'' of HIV however in the midst of all the celebrations the harsh realities are compelling for example the treatment was to provide a full bone marrow transplant which is reality is not always possible for multiple reasons such as costs, labor and time for all 40 million HIV suffers in the UK alone. It is also important to note that this HIV cure was in reality to help a type of cancer which was not responding to any chemotherapy or drugs. This HIV cure was more like a positive side effect of the operation carried out. 

Now recently CAR-T TAGS which are a type of cell like receptor which can be altered and used to reprogrammed T cells which can make them stronger at targeting and better fighting HIV. 

Will keep you all updated on more exciting news to come! 

-MR. PARACETAMOL 

NEVER GIVE UP!!

Hi readers!
This week I have had a lot of time to myself to reflect on my life and I have noticed that whenever I had certain obstacles in my path blocking me from reaching my educational goals. That I had two options to give up or to try my very best and work sincerely. come what may as long as you follow these two qualities and try to implement them in your character. Watch how life will fall in to place! 
I wish all of my readers all the best in to what life have to come and I hope you stay with me on my journey! 

Please comment how your spending your summer break:) school starts next month so relax and enjoy it while it lasts! lol after all we earned it! 

Regards, 
-Mr. Paracetamol 

Lets talk about UCAT

Hi guys!

I am currently in the process of applying to medical school in the UK. It has been a long term dream of mine to become a doctor. As part of the application I also had to conduct a medical entrance exam also known as UCAT was previously called UKCAT. 

I spent two hard working months during the summer everyday preparing for the UCAT exam, I was so scared and nervous. I had never done such a strange exam with questions about shapes and fast mental arithmetic and speed reading. 

I got in the 500s which is not great (I know). This has actually taught me a very valuable lesson which I would like to share with you, my fellow readers. That there will always be someone more clever, good looking and better than you. However you can always be the most hard working and that is what I feel I am. Not the brainiest or the most up to date, but hard working definitely! I have faith that my sincerity and pure determination will break all obstacles and my goal to read medicine and become a doctor will be realized! NEVER LOSE HOPE! AS I ALWAYS SAY... 

**STAY POSITIVE LIKE A PROTON!!**

lastly good luck to all of those who are applying this year! :)

-Mr. Paracetamol 

How t cells are transiently retained and controlled in their trafficking through the lymph nodes

How t cells are transiently retained and controlled in their trafficking through the lymph nodes.

T cell receptors recognise foreign antigens, then convey the message to the nucleus to induce a response.  The body produces many T cells, each with specific TCRs on its surface through the recombination of the genes that encode the receptors, before it has encountered complementary antigens.  By having a surplus of T cells carrying different TCRs, the body is able to mount a fast response once an intruder is detected.  Furthermore, there are thousands of identical TCRs on the surface of a T cell, which increases the likelihood of binding when an antigen is encountered.  The antigens that TCRs bind are small peptide fragments, or epitopes, displayed by MHC molecules on the surface of cells.  Cytotoxic T lymphocyte TCRs recognise epitopes displayed by MHC class I molecules on the surface of almost every cell in the body, so it can distinguish between ‘self’-antigens and foreign antigens (viral-infected cells), as well as being sensitive to the amount of self-antigen presented (increased number of self-antigens in malignant cells).  Helper T cell and inflammatory T cell TCRs recognise epitopes displayed by MHC class II molecules on the surface of antigen-presenting immune cells, including:  macrophages that engulf foreign particles such as bacteria; dendritic cells that present antigen to T cells; and B cells that produce antibodies.  The binding of the epitope to the TCR involves a T cell surface glycoprotein:  CD8 on cytotoxic T lymphocytes, and CD4 on helper T cells and inflammatory T cells (as shown in the picture to the left).  The CD8 and CD4 surface glycoproteins recognise MHC class I and II molecules, respectively.  The binding of a TCR to an epitope can result in a signal being sent to the nucleus to induce a response.

T cell migration within and between peripheral tissues and secondary lymphoid organs is essential for proper functioning of adaptive immunity. While active T cell migration within a tissue is fairly slow, blood vessels and lymphatic vessels (LVs) serve as speedy highways that enable T cells to travel rapidly over long distances. The molecular and cellular mechanisms of T cell migration out of blood vessels have been intensively studied over the past 30 years. By contrast, less is known about T cell trafficking through the lymphatic vasculature. This migratory process occurs in one manner within lymph nodes (LNs), where recirculating T cells continuously exit into efferent lymphatics to return to the blood circulation. In another manner, T cell trafficking through lymphatics also occurs in peripheral tissues, where T cells exit the tissue by means of afferent lymphatics, to migrate to draining LNs and back into blood. In this review, we highlight how the anatomy of the lymphatic vasculature supports T cell trafficking and review current knowledge regarding the molecular and cellular requirements of T cell migration through LVs

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PCR a guide

PCR a guide 

The results of a PCR reaction are usually visualized (made visible) using Gel electrophoresis is a technique in which fragments of DNA are pulled through a gel matrix by an electric current, and it separates DNA fragments according to size. A standard, or DNA ladder, is typically included so that the size of the fragments in the PCR sample can be determined.

DNA fragments of the same length form a "band" on the gel, which can be seen by eye if the gel is stained with a DNA-binding dye. For example, a PCR reaction producing a 400400400 base pair (bp) fragment would look like this on a gel:

Using PCR, a DNA sequence can be amplified millions or billions of times, producing enough DNA copies to be analyzed using other techniques. For instance, the DNA may be visualized by gel electrophoresis, sent for or digested with restriction enzymes and into a plasmid.

PCR is used in many research labs, and it also has practical applications in forensics, genetic testing, and diagnostics. For instance, PCR is used to amplify genes associated with genetic disorders from the DNA of patients (or from fetal DNA, in the case of prenatal testing). PCR can also be used to test for a bacterium or DNA virus in a patient's body: if the pathogen is present, it may be possible to amplify regions of its DNA from a blood or tissue sample.

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Antibiotic – a substance produced by living organisms with activity against bacteria.

Antibiotic – a substance produced by living organisms with activity against bacteria.

Intrinsic resistance refers to resistance which is an inherent and unchanging property of a particular organism. • Acquired resistance refers to the appearance of resistance in organisms which were initially susceptible to a particular antibiotic.

Low level resistance: when an organism becomes resistant to the normal clinical dose of the antibiotic but may be treated by the use of higher doses. • High level resistance: when an organism becomes resistant to the highest clinically achievable dose of the antibiotic, i.e. it is no longer treatable with that antibiotic.

Resistance mechanisms fall into four main categories: 1. Modification of the target site 2. Metabolic bypass (reduced physiological importance of the target site) 3. Decreased drug accumulation in the bacterial cell 4. Antibiotic inactivation

1. Modification of target site • Occurs primarily through mutation. • Example: Streptomycin resistance in E.coli 1) Streptomycin inhibits protein synthesis by binding to the bacterial ribosome. 2) High level resistant E. coli have been found with a mutation at the Lys42 or Lys87 positions of the S12 ribosomal protein. 3) Mutations in rRNA genes have also been found to cause streptomycin resistance.

2. Metabolic bypass Reduces the importance of the antibiotic target site by providing an alternative pathway. Examples include: Methicillin resistance in staphylococci - due to the possession of an alternate penicillin binding protein (PBP2). Vancomycin resistance in enterococci - due to the possession of the vanA gene cluster which synthesises a modified pentapeptide building block for cell wall synthesis.

3. Decreased drug accumulation Can be achieved in one of two ways: 1. Prevent uptake of the drug by the cell 2. Active efflux of the drug from the cell Limited uptake • Responsible for a lot of intrinsic resistance, e.g. penicillins do not easily cross the outer membrane of Gram negative cells; Mycobacteria are impermeable to many drugs. • Alteration in outer membrane proteins can lead to low level resistance to several classes of drugs: • 1) Loss of D2 porin in Pseudomonas aeruginosa leads to imipenem resistance • 2) Altered porin expression in Salmonella has been associated with combined low level resistance to βlactams, aminoglycosides, chloramphenicol, tetracyclines, trimethoprim and quinolones.

Active efflux • The best studied example is tetracycline resistance – found in a wide range of both Gram positive and Gram negative bacteria. • It depends on the presence of an inner membrane protein (tet). This forms a multimer spanning the membrane and binds the drug in the presence of Mg2+, leading to its export from the cell in an energy dependent manner.

4. Antibiotic inactivation • This is the most commonly encountered mechanism of drug resistance. • Resistance can be achieved in one of two types of reaction: I. Hydrolysis of the antibiotic molecule e.g. β-lactamases II. Addition of groups to the antibiotic molecule e.g. chloramphenicol acetyl-transferase The genes for these enzymes are often associated with transposons and plasmids.

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Mycology (continued)

Mycology continued

Mycology is the branch of biology concerned with the study of fungi, including their genetic and biochemical properties, their taxonomy and their use to humans as a source for tinder, medicine, food, and entheogens, as well as their dangers, such as toxicity or infection.

Concerned with diagnosis, management, and prevention of fungal diseases or mycoses • Mycoses are among the most difficult diseases to diagnose and treat – Signs of mycoses are often missed or misinterpreted – Fungi are often resistant to some antifungal agents
Diagnosis of invasive fungal disease (IFD) is challenging because current diagnostic methods lack sensitivity and specificity, or take too long to yield a result to be clinically useful. Such limitations have consequences; delayed diagnosis leads to delayed treatment. Speed to diagnosis is a key risk factor in patient outcomes (Barnes 2008). Diagnosis of fungal infection is further complicated by problematic developments in the field of medical mycology. First and foremost is the loss of senior mycology experts in the field who were trained in classical mycology, which has created crises-level problems in clinical mycology (Steinbach et al. 2003). This problem has been compounded over the last 30 years as the spectrum of fungi-causing infections has exploded owing to AIDS and the use of highly immunosuppressive agents for treatment of a variety of diseases. These patients are susceptible to infections from fungi rarely seen, or never reported as a human pathogen, which can cause identification problems for even the most experienced mycologists. Whereas mycologists in the past needed to be able to identify ∼50 commonly encountered fungi, and ∼300 total fungi that were pathogenic for humans, the number of potential fungal pathogens is likely many times what is described in textbooks, and will continue to grow as the severely immunosuppressed patient population continues to grow 

Diagnosis of fungal infection has relied primarily on methods such as direct microscopic examination of clinical samples, histopathology, and culture. Such approaches are dependent on personnel with relatively high levels of specific mycology training. The growth in the number of fungi that clinical mycologists must identify has forced investigators to develop and apply new methods for fungal identification that go beyond classical phenotypic methods. As a consequence, there is an increased emphasis on the use of molecular methods and antigen detection as surrogates for culture in diagnosis of fungal diseases.

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my notes on Compare and contrast different general approaches for laboratory diagnosis of viral infections.

my notes on Compare and contrast different general approaches for laboratory diagnosis of viral infections.

Microscopy • Time-consuming • Not high throughput • Poor sensitivity • Poor specificity • Subjective • Training • When justifiable? • What samples? • What stains?

Microscopy Unstained preparations: “Wet prep” – Amoeba – Trichomonas vaginalis • Dark-ground illumination for syphilis – Motile spirochaetes
Microscopy Stained preparations- • Gram-stain • Acridine orange • Acid-fast stain – Ziehl-Neelsen • Fluorescence – Direct, e.g. auramine – Immunofluorescence

Factors limiting usefulness of bacteriological investigations • wrong sample – e.g. saliva instead of sputum • delay in transport / inappropriate storage – e.g. CSF • overgrowth by contaminants – e.g. blood cultures • insufficient sample / sampling error – e.g. in mycobacterial disease • patient has received antibiotics

Advantages of Solid Media • isolation of single clonal colonies – get bacterium in pure culture • identify by colonial morphology • quantification by colonyforming units • Organism available for further tests such as susceptibility testing

Disadvantages of Cultivation • Sensitivity – Only 0.1% microbes are cultivable! • Specificity – Overgrowth – Selective medium • Relevance – Multiple isolates • Conditions – Atmosphere – Temperature – Time • Slow • Infection risk

dentification of Bacteria • Morphology • Growth requirements • Biochemistry • Enzymes • Antigens • Molecular typing • Maldi-Tof
Non-cultural diagnostic methods • Antigen detection (Serology) – e.g. latex agglutination, direct immunofluorescence • Antibody detection (Serology) – e. g. agglutination tests, ELISA, indirect immunofluorescence, lateral flow assays, gamma interferon assays • Molecular methods – Polymerase Chain Reaction (PCR) – Hybridisation (microarrays, luminex) – Whole genome sequencing

Susceptibility tests • on solid media – disc diffusion technique • in liquid media – minimum inhibitory concentration (MIC) test • Breakpoint methods • E-test
Antimicrobial agents impregnated into filter paper disc – Control on same plate – Control on different plate • Break points • MIC’s • MBC’s


Susceptibility Testing Problems • Organism in tissues – drug penetration • Microbial biofilms • Mixed cultures • Adverse affect on normal flora • Microbial agent interactions • Selective toxicity • Too slow!

*!!REMEMBER TO STAY POSITIVE LIKE A PROTON!!**

Serology my introduction

serology Introduction 

SEROLOGICAL DIAGNOSIS OF INFECTIOUS DISEASES 
•The scientific study of blood sera and their effects 
•Subdivision of immunology concerned with in-vitro Ag-Ab reaction 
•Concerned with the laboratory study of the activities of the component of serum that contribute to immunity. 

METHODS OF DETECTION OF ANTIBODIES Immuno-precipitation Assays = detect antibodies in solution = qualitative indication of the presence of antibodies = end-point is visual flocculation of the antigen and antibody in suspension

METHODS OF DETECTION OF ANTIBODIES Immunofluorescence = requires use of microscope equipped to provide ultraviolet illumination or an instrument capable of irradiating the assay with UV light and detecting resulting fluorescence with a fluorometer

IMMUNOFLUORESCENCE 
These are Ag-Ab reactions in which Ab or anti-human immunoglobulin is labelled with fluorescein. 
Fluorescein is a dye which emits greenish fluorescence under UV light. 
There are two ways for this test; 
Direct immunofluorescence (detect antigen with labelled antibody),
Indirect immunofluorescence (detect antibody with labelled anti-human immunoglobulin).

METHODS OF DETECTION OF ANTIBODIES Enzyme Immunoassay = the most sensitive = usually indirect assay that depends on the use of an antihuman IgG or IgM antibody conjugate = the antibody conjugate (if present) is made to attach to enzyme which catalyzes conversion of the substrate to a colored product which will then be read with the use of a spectrophotometer

ENZYME-LINKED IMMUNO SORBENT ASSAY (ELISA) 
This technique is ; 
Very sensitive 
 Does not require specialized equipment
  Avoid the hazards of radioactivity. 
The method depends on conjugation of an enzyme to either Ag or Ab, then substrate is added as a quantitative measure of enzyme activity.

ELISA  Indirect ELISA: 
 In this test an enzyme- labelled anti-human Ig is used to detect the presence of specific Abs in patients’ sera. 
 Known Ag is fixed by adsorption onto a plastic surface. 
 The serum sample is added (if specific Ab is present, it will bind the fixed Ag).
 Wash 
 Add the enzyme-labelled antihuman Ig 
 wash the excess 
 add the substrate, then quantitatively measure for the degree of colour change.

TO IMPROVE SPECIFICITY – WESTERN OR IMMUNOBLOTTING
 Separation of antigens by gel electrophoresis 
 Antigens blotted onto nitrocellulose
 Antigens printed directly onto nitrocellulose 
 Strips of separated antigens on nitrocellulose reacted with serum
 Washed
 React with anti-human conjugate 
 Washed
 Colour detected with substrate

SEROLOGICAL DIAGNOSIS OF INFECTIOUS DISEASES = HIV • Laboratory diagnosis of HIV infection Western Blot Testing = interpretation of result 
 no bands, negative 
 in order to be interpreted as positive a minimum of 3 bands directed against the following antigens must be present : p24, p31, gp41 or gp120/160 
 CDC criteria require 2 bands of the following : p24, gp41 or gp120/160

ROLE OF SEROLOGY IN MICROBIAL DIAGNOSTICS 
 Generally considered as the back-up when cultivation is not appropriate
 Organisms too slow to grow 
 Organism cannot be grown  Organism to hazardous to grow
 Imprecise compared to isolation
 Antigens may cross-react with those of other organisms
 Antigens may be shared between organisms (lateral gene transfer)


GOOD THINGS ABOUT SEROLOGY 
 Cheap 
 Easy to automate 
 Good for population screening 
 Can be used for several specimen types 
 Serum 
 CSF
 Synovial fluid 
 Milk 
 Can be used for retrospective diagnosis 
 Sensitive if used 10-14 days post-infection

BAD THINGS ABOUT SEROLOGY
 Poor for acute infection 
 Often require repeat samples 
 Poor if the infection is endemic 
 Poor for determination of reinfection or relapse 
 Specificity variable (depending upon antigen) 
 Vaccination can complicate results 
 Early treatment can interfere with development of positive response 
 Risk of dealing with blood samples (bloodborne pathogens)

**!!REMEMBER TO STAY POSITIVE LIKE A PROTON!!**

What are Zoonoses?

Zoonoses: Infections acquired from animals. By direct contact. Indirect contact by vector. Indirect contact through environmental contamination.

Zoonosis refers to diseases that can be passed from animals to humans. They are sometimes called zoonotic diseases. Animals can carry harmful germs, such as bacteria, fungi, parasites, and viruses. These are then shared with humans and cause illness
Animals can carry harmful germs, such as bacteria, fungi, parasites, and viruses. 

These are then shared with humans and cause illness. Zoonotic diseases range from mild to severe, and some can even be fatal.

Before the introduction of new hygiene regulations around 100 years ago, zoonotic diseases such as bovine tuberculosis, bubonic plague, and glanders caused millions of deaths. They are still a major problem in developing countries.

Rabies
Rabies is a disease that affects the nervous system of mammals. It is usually caused by a virus and is transmitted if an infected animal bites a person or other animal.
Rabies is almost always fatal once symptoms appear. However, rabies vaccines exist and are commonly available.

Lyme Disease
Lyme disease and Rocky Mountain spotted fever
Lyme disease is transmitted through tick bites. Symptoms can range from mild to severe, but it can be treated using antibiotics.
Dengue, malaria, and chikungunya
These are mosquito-borne diseases and are more common in certain areas, such as the Caribbean.
Symptoms include fever, vomiting, and headaches. It is vital to treat these conditions as soon as possible, as they can be fatal.

Salmonella infection
Salmonella is often caused by handling reptiles or amphibians that carry Salmonella, or by handling baby chicks or ducks.
The illness usually lasts for between 4 and 7 days, and symptoms include diarrhea, fever, and abdominal cramps. People can usually recover without medical treatment, although conservative measures are recommended.
E. coli infection
This infection is often caused by touching infected animals or handling contaminated food. Cows also have E. coli germs on their udders.

**!!REMEMBER TO STAY POSITIVE LIKE A PROTON!!**

How microorganisms enter a host and how they damage host cells with exotoxins?

How microorganisms enter a host and how they damage host cells with exotoxins?

To cause disease most pathogens must: 
 gain access to the host 
 gain access to the tissue
 evade host defences 
 damage the host tissue 

• Some microbes cause disease without invading the body • Portals of entry - gaining entrance to the human body (and other hosts) through several avenues
Adhesins/ligands bind to receptors on host cells
The host cell cytoskeleton provides the mechanism: • Actin is used:  to penetrate host cells  to move through and between host cells
Invasins – Salmonella alters host actin to enter a host cell
Use actin to move from one cell to the next – Listeria
Cadherin: bridges membrane junctions
Exotoxins 

• Antibodies: 
 provide immunity to exotoxins • Inactivated exotoxins: 
 can no longer cause disease 
 can still stimulate the body to produce exotoxins 

• These altered exotoxins are called toxoids 
 toxoids (as vaccines) stimulate antitoxin production (immunity) 
 Vaccines – stimulate antitoxin production
Exotoxins 

• Are named on the basis of many characteristics: 
 neurotoxins - nerve cells 
 cardiotoxins - heart cells
 hepatotoxins - liver cells 
 leukotoxins - leukocytes 
 enterotoxins - the lining of the gastrointestinal tract 
 cytotoxins - a wide variety of cells diphtheria toxin (cause of diphtheria) botulinum toxin (Clostridium botulinum) vibrio enterotoxin (Vibrio cholerae)

**REMEMBER TO STAY POSITIVE LIKE A PROTON!!**

viral infections

viral infections 

A virus (from the Latin virus meaning toxin or poison) is a sub-microscopic infectious agent that is unable to grow or reproduce outside a host cell.”
Acute virus infection:
Following host entry the virus multiplies and spreads rapidily. and contact with the virus activates host immune responses. Hosts immune mechanisms overcome and eliminate virus. The hosts retains immunological virus and virus survival dependent on rapid dissemination and susceptible hosts aviabliliy.

Characteristics of actute virus disease:
-normally rapid onset.
-symptoms often corresponds with peak viral multiplication.
-often fever and mygalia (from activation of immune response)
-vary in servity from one individual to another.
-Resolve rapidly once the innate immune response develops.

Acute viral infections are serve public health problems.
-usually associated with epidemics
-short incubation period
-delay in indentifibile symptoms until the virus has already spread.
-Acute infections occur in crowded places e.g schools, militariy, nursing homes.

EXAMPLE OF ACUTE VIRAL INFECTION:
RHINOVIRUSES (INFLUENZA)
-common cold often caused by rhinoviruses more than 110 serological types. killed by gastric acid and replicated at 33'C.
-Bind to ICAM-1 on epithelial cell surface and are not easily removed by muco-ciliary secretions.
-enter host cells by translocation
-Lyse host cells after replication and spread to neighbouring cells leading to progressive and extensive damage.
Pathogenesis of the common cold:
-debris from lysed cells provokes a strong inflammatory response
-increased secretion of fluids from lamina propria leads to runny nose and sneezing.
-Phagocytes migrate to to site of infection.
-Release of inflammatory mediators leads to blocked nose and mild fever
-Symptoms are restricted to the upper part of the respiratory tract as these viruses multiply optimal at 33'C and less at 37'C.

Immunity to rhinoviruses
-Rhinoviruses recognises by immune system specific mucosal response -IgA ect rather than humoral response
-immune response quickly clears the infection leading to rapid recovery. (couple of days)
-Immune memory of the infection is retained but is not long lasting as for systematic virus infection.
-frequent reoccurrence of the common cold is due to the larger number >100 of serological distinct strains of rhinoviruses.
EXAMPLE OF ACUTE VIRAL INFECTION: ENTEROVIRUSES.  (MEASLES)

**REMEMBER TO STAY POSITIVE LIKE A PROTON!!**  

positive and negative T cell selection in the thymus.

positive and negative T cell selection in the thymus

 A lymphoid organ is situated in the neck of vertebrates which produces T-lymphocytes for 
the immune system. The human thymus becomes much smaller at the approach of puberty.  

Cortex – immature thymocytes, epithelial cells and scattered macrophages.
Medulla- mature thymocytes, epithelial cells, macrophages and dendritic cells.
T Cell development  in the thymus: 
Step 1: T- cell progenitors develop in the bone marrow and migrate to the thymus-  T cell precursors rearranges its t cells receptor genes in the thymus. 

Step 2: positive and negative selection in the thymus- Immature T cells that recognise self MHC receive signals for survival. Those that interact strongly with self antigen are removed from the repertoire. 

Step 3: Mature T cells migrate to the peripheral lymphoid organs- Mature T cells encounter foreign antigens in the peripheral lymphoid organs are activated. 

Step 4: Activated T cells migrate  to sites of infection- Activated T cells proliferate and eliminate infection. 

T cells move through a number of different developmental stages classified by expression of CD4 and CD8 on their cell surface: They are:
• DN (CD4-8-)
• DP (CD4+8+)
• CD4SP or CD8SP




T cell precursors proliferate extensively in the thymus, but most die there. 95% of thymocytes die by apoptosis before reaching the medulla. Some die due to NEGLECT. 
NEGLECT – no TCR-MHC interaction = NO SURVIVAL SIGNAL
• Positive selection of thymocytes: development of the self MHC-restricted T cell repertoire.  The MHC type of the thymic stroma selects a repertoire of mature T cells that can recognize foreign antigens presented by the same MHC type- self restriction. 
• Only thymocytes whose TCR interact with self-peptide: self-MHC complexes weakly can survive and mature.
• Those that do not recognize the MHC molecules are killed by apoptosis (death by neglect) 
Positive selection is mediated by MHC:peptide on thymic epithelial cells 
Peptides role in positive selection: 
• Peptides presented in the thymus are self –peptides derived from widely expressed 
• Self-peptides presented cause stabilisation of MHC on epithelial cells 
• Self-peptides presented on epithelial cells influence the specificity of the T cells that are selected
• Some self peptides are better than other at positive selection
• Different peptides result in different T cell repertoires
Positive selection coordinates the expression of CD4 or CD8 with the specificity of the T-cell receptor and the potential effector functions of the T cell. This is known as lineage commitment

The Double positive (DP) thymocytes
• DPs initially express low levels of abTCR 
• 10-30% of TCRs recognise cortical epithelial cells expressing ‘self peptide’ presented by ‘self MHC’ – POSITIVE SELECTION
• Positive selection acts on a repertoire of T-cell receptors with inherent specificity for self MHC molecules.
Negative selection removes thymocytes that are capable of strongly binding with "self" MHC peptides. Thymocytes that survive positive selection migrate towards the boundary of the cortex and medulla in the thymus.The remaining cells exit the thymus as immature naïve T cells.

Negative selection of thymocytes: Central Tolerance
• T cells that react strongly (high avidity/strong interaction) with ubiquitous self antigens are deleted in the thymus or become regulatory T cells
• Can occur at the DP or SP stages 
• Can be induced by bone marrow derived antigen-presenting cells in the cortex and medulla such as DCs and macrophages
• thymic medullary epithelial cells can also induce negative selection 

Negative selection is driven by bone marrow derived antigen-presenting cells (DCs and macs) and medullary epithelial cells.

**!!REMEMBER TO STAY POSITIVE LIKE A PROTON!!**

INTERVIEW QUESTIONS

INTERVIEW QUESTIONS 

1.Why do you think it is important for Thames Water to share scientific knowledge among its workforce?

·         Knowledge sharing important because it encourages more connection and collaboration between the workforce.

·         get to know everyone and work in happy environment and be more productive

·         Make everyone knowledgeable about scientific advancements in the field.

·         E.g. from studying the Thames water corporate responsibility and sustainability report suggest that it is important that we share scientific knowledge to help spread awareness of the implications and understanding of how to protect public water supplies and the environment in terms of climate change.

It is important that that employees share their job-related with each other, so that they will be able to perform their job better and eventually lead to higher organization performance. The more knowledgeable individuals are, the more they will be able to innovate. For a company to stay in the game, the employees need to make the most of the knowledge they have- sharing and absorbing it readily.

2.How do you think Thames Water can fulfil its environmental responsibility by sharing scientific knowledge?

·         its written on corporate responsibility and sustainability report. ''responsible and sustainable use of natural resources''.

·         Sending a monthly scientific magazine to all workforce of latest scientific advancements, holding seminars to the public and visiting primary and secondary schools to spread awareness to the general public.

·         creating posters and/or advertising.

Environmentalism is an ideology that evokes the necessity and responsibility of humans to respect, protect and preserve the natural world.* Promoting environmental awareness is a crucial part of being an environmental steward. A way to promote this is by proposing environmentally sustainable and beneficial projects and starting community gardens. As well as constantly educating people. By this way people can understand the economic and biological importance of eliminating the harmful products created by man.

3. What previous experience do you have in teaching or tutoring?

·         very rewarding to tutor people.

·         I have tutored 9 year olds at a elite private school for three years.

·         I am able to explain theories and complex information in a simple and easy to understand and friendly way similarly I way will help my colleagues in understanding.

4. Please give an example when you used your communication skills in teaching or 

tutoring?

·         I helped teach someone how to code and create website as well as buy a website and domain name.

·         I used to be in a computer club.

·         looking for someone with it experience and I know how to use Microsoft office.

Effective communication is the key to human interaction. Whenever I teach, I communicate in a respectful manner. I use a tone that is honest and tactful. When taking on a listening role, I make eye contact and focus on the speaker.

5. How do you see your career progress within the area of teaching?

·         I personally love to teach very rewarding.

·         I like the career prospects and development such as promotional opportunities of career advancement to become of senior instructor &  part of the senior training strategic team.

·         looking to stay with Thames Water for the a long period of time in my life.

·         I can handle responsibility.

Developing my skills as a teacher will not only help you deliver engaging and informative lessons, but it will also help me progress in my teaching career. Continuing professional development (CPD) is a great way of showing employers that I am committed to the company and that I will keep up to date with new approaches of teaching. Personal development way is the best way to learn new skills. And may one day I will have the expertise to have a leadership role.

6. What do you think you will personally bring to the role?

·         I have learned business studies so can help cater to achieve the company goals as well as my scientific understanding.

·         I am determined individual so will try my upmost best to spread the awareness due my duties such as assisting in workshops.

·         I enjoy teaching and open to learn from others.

7. Why are you interested in working  for Thames Water?

·         I like to drink water.

·         I like the career prospects and development such as promotional opportunities of career advancement to become of senior instructor & senior training strategic team.

·          I enjoy the mix of the business and science fields which I have qualifications for both and learned them at A-level.

·         Thames water is the largest water services company in the UK and it will be a privilege to serve the people of the UK providing them with a vital necessity of water.

·        The Thames Water reputation is certainly a key factor, I would be proud to work for a company with such a long history of leadership in the industry.

·        * A friends that works there has told me that the culture supports learning and development and really rewards hard work.

·        * Also my proven track record in teaching and my superb communication skills make me and excellent match for the job requirements.

·        * Also, the role excites me because I love the idea of sharing facts and interacting with people.

**REMEMBER TO STAY POSITIVE LIKE A PROTON!!**