Pulmonary Embolism


Pulmonary embolism (PE) is a blockage of the pulmonary artery (or one of its branches), usually when a venous thrombus (blood clot from a vein), becomes dislodged from its site of formation and embolizes to the arterial blood supply of one of the lungs. This process is termed thromboembolism.
Symptoms may include difficulty breathing, pain in the chest during breathing, and in more severe cases collapse, circulatory instability and sudden death. Treatment, usually, is with anticoagulant medication, such as heparin and warfarin, and rarely (in severe cases) with thrombolysis or surgery. In other, rarer forms of pulmonary embolism, material other than a blood clot is responsible; this may include fat or bone (usually in association with significant trauma), air (often when diving), clumped tumor cells, and amniotic fluid (affecting mothers during childbirth).


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Clinical presentation

Symptoms of PE are sudden-onset dyspnea (shortness of breath), tachypnea (rapid breathing), chest pain of "pleuritic" nature (worsened by breathing), cough, hemoptysis (coughing up blood), and may aid in the diagnosis. More severe cases can include signs such as pleural rub, cyanosis (blue discoloration, usually of the lips and fingers), collapse, and circulatory instability. About 15% of all cases of sudden death are attributable to PE.

Risk factors

The most common sources of embolism are proximal leg deep venous thrombosis (DVTs) or pelvic vein thromboses. Any risk factor for DVT also increases the risk that the venous clot will dislodge and migrate to the lung circulation, which happens in up to 15% of all DVTs. The conditions are generally regarded as a continuum termed venous thromboembolism (VTE).


The development of thrombosis is classically due to a group of causes named Virchow's triad (alterations in blood flow, factors in the vessel wall and factors affecting the properties of the blood). Often, more than one risk factor is present.
  1. Alterations in blood flow: immobilization (after surgery, injury or long-distance air travel), pregnancy (also procoagulant), obesity (also procoagulant)
  2. Factors in the vessel wall: of limited direct relevance in VTE
  3. Factors affecting the properties of the blood (procoagulant state):
  • Estrogen-containing hormonal contraception
  • Genetic thrombophilia (factor V Leiden, prothrombin mutation G20210A, protein C deficiency, protein S deficiency, antithrombin deficiency, hyperhomocysteinemia and plasminogen/fibrinolysis disorders).
  • Acquired thrombophilia (antiphospholipid syndrome, nephrotic syndrome, paroxysmal nocturnal hemoglobinuria)

Rna to Protein Lecture

Total Hip Replacement Surgery

Hip replacement, also hip arthroplasty, is a surgical procedure in which the hip joint is replaced by a prosthetic implant. Such joint replacement orthopaedic surgery generally is conducted to relieve arthritis pain or fix severe physical joint damage as part of the hip fracture treatment.


There are several different incisions, defined by their relation to the gluteus medius. The approaches are posterior (Moore), lateral (Hardinge or Liverpool), antero-lateral (Watson-Jones), anterior (Smith-Petersen) and greater trochanter osteotomy. There is no compelling evidence in the literature for any particular approach, but consensus of professional opinion favours either modified anterio-lateral (Hardinge) or posterior approach.

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There are several different incisions, defined by their relation to the gluteus medius. The approaches are posterior (Moore), lateral (Hardinge or Liverpool), antero-lateral (Watson-Jones), anterior (Smith-Petersen) and greater trochanter osteotomy. There is no compelling evidence in the literature for any particular approach, but consensus of professional opinion favours either modified anterio-lateral (Hardinge) or posterior approach.

  • The posterior (Moore) approach accesses the joint through the back, taking piriformis muscle and the short external rotators off the femur. This approach gives excellent access to the acetabulum and preserves the hip abductors. Critics cite a higher dislocation rate although repair of capsule and SERs negates this risk.
  • The lateral approach is also commonly used for hip replacement. The approach requires elevation of the hip abductors (gluteus medius and gluteus minimus) in order to access the joint. The abductors may be lifted up by osteotomy of the greater trochanter and reapplying it afterwards using cables (as per Charnley),[citation needed] or may be divided at their tendinous portion, or through the functional tendon (as per Hardinge) and repaired using sutures.

  • The anterolateral approach develops the interval between the tensor fasciae latae and the gluteus medius.
  • The anterior approach utilises an interval between the sartorius and tensor fascia latae.

  • The double incision surgery and minimally invasive surgery seeks to reduce soft tissue damage through reducing the size of the incision. However component positioning accuracy is impaired and surgeons using these approaches are advised to use computer guidance systems

T helper cell lymphocyte

T helper cells (also known as effector T cells or Th cells) are a sub-group of lymphocytes (a type of white blood cell or leukocyte) that plays an important role in establishing and maximizing the capabilities of the immune system. These cells are unusual in that they have no cytotoxic or phagocytic activity; they cannot kill infected host (also known as somatic) cells or pathogens, and without other immune cells they would usually be considered useless against an infection. Th cells are involved in activating and directing other immune cells, and are particularly important in the immune system. They are essential in determining B cell antibody class switching, in the activation and growth of cytotoxic T cells, and in maximizing bactericidal activity of phagocytes such as macrophages. It is this diversity in function and their role in influencing other cells that gives T helper cells their name.

Mature Th cells are believed to always express the surface protein CD4. T cells expressing CD4 are also known as CD4+ T cells. CD4+ T cells are generally treated as having a pre-defined role as helper T cells within the immune system, although there are known rare exceptions. For example, there are sub-groups of suppressor T cells, natural killer T cells, and cytotoxic T cells that are known to express CD4 (although cytotoxic examples have been observed in extremely low numbers in specific disease states, they are usually considered non-existent). All of the latter CD4+ T cell groups are not considered T helper cells, and are beyond the scope of this article.

The importance of helper T cells can be seen from HIV, a virus that infects cells that are CD4+ (including helper T cells). Towards the end of an HIV infection the number of functional CD4+ T cells falls, which leads to the symptomatic stage of infection known as the acquired immune deficiency syndrome (AIDS). There are also rare disorders, probably genetic in etiology, that result in the absence or dysfunction of CD4+ T cells. These disorders produce similar symptoms, and many of these are fatal (see T-Lymphocytopenia).
Activation of naïve helper T cells
Following T cell development, matured, naïve (meaning they have never been exposed to the antigen to which they can respond) T cells leave the thymus and begin to spread throughout the body, including the lymph nodes. Like all T cells, they express the T cell receptor/CD3 complex. The T cell receptor (TcR) consists of both constant and variable regions, the latter of which determines what antigen the T cell can respond to. CD4+ T cells have TcRs with an affinity for Class II MHC, and it is believed that CD4 is involved in determining MHC affinity during maturation in the thymus. Class II MHC proteins are generally only found on the surface of professional antigen-presenting cells (APCs). Professional antigen presenting cells are primarily dendritic cells, macrophages and B cells, although dendritic cells are the only cell group that expresses MHC Class II constitutively (at all times). Some APCs also bind native (or unprocessed) antigens to their surface, such as follicular dendritic cells, but unprocessed antigens do not interact with T cells and are not involved in their activation. The antigens that bind to MHC proteins are always short peptides, 8-10 amino acids long for MHC Class I, and up to 25 or so for MHC Class II.
Recognition (Signal 1)
During an immune response, professional antigen-presenting cells (APCs) endocytose (absorb) foreign material (typically bacteria or viruses), which undergoes processing, then travel from the infection site to the lymph nodes. Once at the lymph nodes, the APC begins to present antigen peptides that are bound to Class II MHC, allowing CD4+ T cells that express specific TcR's against the peptide/MHC complex to activate.
When a Th cell encounters and recognises the antigen on an APC, the TcR-CD3 complex binds strongly to the peptide-MHC complex present on the surface of professional APC's. CD4, a co-receptor of the TCR complex, also binds to a different section of the MHC molecule. These interactions bring these proteins closer together, allowing the intracellular kinases present on the TcR, CD3 and CD4 proteins to activate each other via phosphorylation. With the assistance of a phosphatase present on the intracellular section of CD45 (common leukocyte antigen), these molecules activate the major biochemical pathways in the cytosol of the Th cell. These active pathways are known as Signal 1 of T cell activation, as it is the first and primary pro-activation signal in a Th cell. Upon subsequent encounters with a given antigen, memory T cells are re-activated using the same TCR pathways.
The binding of the antigen-MHC to the TCR complex and CD4 may also help the APC and the Th cell adhere during Th cell activation, but the integrin protein LFA-1 on the T cell and ICAM on the APC are the primary molecules of adhesion in this cell interaction.
It is unknown what role the relatively bulky extracellular region of CD45 plays during cell interactions, but CD45 has various isoforms that change in size depending on the Th cell's activation and maturation status. For example, CD45 shortens in length following Th activation (CD45RA+ to CD45RO+), but whether this change in length influences activation is unknown. It has been proposed that the larger CD45RA+ may decrease the accessibility of the T cell receptor for the antigen-MHC molecule, thereby necessitating an increase in the affinity (and specificity) of the T cell for activation. Once the activation has occurred however, CD45 shortens, allowing easier interactions and activation as an effector T helper cell.
Verification (Signal 2)
Having received the first TcR/CD3 signal, the naïve T cell must activate a second independent biochemical pathway, known as Signal 2. This verification step is a protective measure to ensure that a T cell is responding to a foreign antigen. If this second signal is not present during initial antigen exposure, the T cell presumes that it is auto-reactive. This results in the cell becoming anergic (anergy is generated from the unprotected biochemical changes of Signal 1). Anergic cells will not respond to any antigen in the future, even if both signals are present later on. These cells are generally believed to circulate throughout the body with no value until they apoptose at the end of their lifespan.
The second signal involves an interaction between CD28 on the CD4+ T cell and the proteins CD80 (B7.1) or CD86 (B7.2) on the professional APCs. Both CD80 and CD86 activate the CD28 receptor. These proteins are also known as co-stimulatory molecules.
Although the verification stage is necessary for the activation of naïve helper T cells, the importance of this stage is best demonstrated during the similar activation mechanism of CD8+ cytotoxic T cells. As naïve CD8+ T cells have no true bias towards foreign sources, these T cells must rely on the activation of CD28 for confirmation that they recognise a foreign antigen (as CD80/CD86 is only expressed by active APC's). CD28 plays an important role in decreasing the risk of T cell auto-immunity against host antigens.
Once the naïve T cell has both pathways activated, the biochemical changes induced by Signal 1 are altered, allowing the cell to activate instead of anergise. The second signal is then obsolete; only the first signal is necessary for future activation. This is also true for memory T cells, which is one example of learned immunity. Faster responses occur upon reinfection because memory T cells have already undergone confirmation and can produce effector cells much sooner.
Proliferation
Once both stimulatory signals are active within the helper T cell, the cell then allows itself to proliferate. It achieves this by releasing a potent T cell growth factor called interleukin-2 (IL-2). Activated T cells also produce the alpha sub-unit of the IL-2 receptor (CD25 or IL-2R), enabling a fully functional receptor that can bind with IL-2, which in turn activates the T cell's proliferation pathways.
In this case, the released IL-2 binds to same T cell's IL-2 receptors to allow itself to proliferate. The phenomenon of cells releasing cytokines to alter their own behaviour is known as auto-regulation (or autocrine stimulation). It should be noted that this is not the only function of IL-2 release (e.g. NK-cells also begin to proliferate when getting in contact with IL-2), and that IL-2 can also bind to other T cells in the area (paracrine stimulation).
Maturation After many cell generations, the Th cell's progenitors differentiate into effector Th cells, memory Th cells, and suppressor Th cells.
  • Effector Th cells secrete cytokines, proteins or peptides that stimulate or interact with other leukocytes, including Th cells.
  • Memory Th cells retain the antigen affinity of the originally activated T cell, and are used to act as later effector cells during a second immune response (e.g. if there is re-infection of the host at a later stage).
  • Suppressor T cells do not promote immune function, but act to decrease it instead. Despite their low numbers during an infection, these cells are believed to play an important role in the self-limitation of the immune system; they have been shown to prevent the development of various auto-immune diseases.
The production of IL-2 by helper T cells is also necessary for the proliferation of activated CD8+ T cells. Without helper T cell interactions, CD8+ T cells do not proliferate and eventually become anergic. This cross-reliance on helper T cells is another way the immune system tries to prevent T cell-mediated auto-immune disease.

Plasmid Cloning animation


Process by which a plasmid is used to import recombinant DNA into a host cell for cloning.
Many diseases are caused by gene alterations. Our understanding of genetic diseases was greatly increased by information gained from DNA cloning. In DNA cloning, a DNA fragment that contains a gene of interest is inserted into a cloning vector or plasmid.

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The plasmid carrying genes for antibiotic resistance, and a DNA strand, which contains the gene of interest, are both cut with the same restriction endonuclease. The plasmid is opened up and the gene is freed from its parent DNA strand. They have complementary "sticky ends." The opened plasmid and the freed gene are mixed with DNA ligase, which reforms the two pieces as recombinant DNA.
This recombinant DNA stew is allowed to transform a bacterial culture, which is then exposed to antibiotics. All the cells except those which have been encoded by the plasmid DNA recombinant are killed, leaving a cell culture containing the desired recombinant DNA.

DNA cloning allows a copy of any specific part of a DNA (or RNA) sequence to be selected among many others and produced in an unlimited amount. This technique is the first stage of most of the genetic engineering experiments: production of DNA libraries, PCR, DNA sequencing, et al.

Single Nucleotide Polymorphism (SNP) Animation


A single nucleotide polymorphism (SNP, pronounced snip), is a DNA sequence variation occurring when a single nucleotide - A, T, C, or G - in the genome (or other shared sequence) differs between members of a species (or between paired chromosomes in an individual). For example, two sequenced DNA fragments from different individuals, AAGCCTA to AAGCTTA, contain a difference in a single nucleotide. In this case we say that there are two alleles : C and T. Almost all common SNPs have only two alleles. For a variation to be considered a SNP, it must occur in at least 1% of the population.
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Within a population, SNPs can be assigned a minor allele frequency - the lowest allele frequency at a locus that is observed in a particular population. This is simply the lesser of the two allele frequencies for single nucleotide polymorphisms[1]. It is important to note that there are variations between human populations, so a SNP allele that is common in one geographical or ethnic group may be much rarer in another. In the past, single nucleotide polymorphisms with a minor allele frequency of less than or equal to 1% (or 0.5%, etc.) were given the title "SNP," an unwieldy definition. With the advent of modern bioinformatics and a better understanding of evolution, this definition is no longer necessary.
Single nucleotide polymorphisms may fall within coding sequences of genes, non-coding regions of genes, or in the intergenic regions between genes. SNPs within a coding sequence will not necessarily change the amino acid sequence of the protein that is produced, due to degeneracy of the genetic code. A SNP in which both forms lead to the same polypeptide sequence is termed synonymous (sometimes called a silent mutation) - if a different polypeptide sequence is produced they are non-synonymous. SNPs that are not in protein-coding regions may still have consequences for gene splicing, transcription factor binding, or the sequence of non-coding RNA.

Variations in the DNA sequences of humans can affect how humans develop diseases and respond to pathogens, chemicals, drugs, vaccines, and other agents. However, their greatest importance in biomedical research is for comparing regions of the genome between cohorts (such as with matched cohorts with and without a disease).
The study of single nucleotide polymorphisms is also important in crop and livestock breeding programs (see genotyping). See SNP genotyping for details on the various methods used to identify SNPs

Blood Vascular System

The blood and lymphatic vascular systems are classified as specialized connective tissue.
The main functions of the blood are to transport oxygen, nutrients and hormones to the tissues and to collect the waste products (carbon dioxide and waste metabolites) for removal from the body via the excretory system.



The cardiovascular system consists of the:
  • Heart (muscular pump)
  • Pulmonary circulation (system of blood vessels to and from the lungs)
  • Systemic circulation (system of blood vessels bringing blood to and from all the other organs of the body).
  • Arteries are classified into two main groups:
  • Conducting (Elastic Arteries).
  • These are large arteries closest to the heart (aorta, renal artery) with very high blood pressure and flow (320mm/sec in the aorta).
Distributing (Muscular Arteries).
These are smaller diameter arteries with a slower blood flow.
The arteries lead to smaller vessels, the arterioles, which lead to the capillaries. The capillaries are present in the form of microcirculation networks (capillary beds) in the organs and tissues. Exchange of metabolites and transport through the vessel wall is only possible in the capillaries, as only here the blood flow is sufficiently reduced (about 0.3mm/sec) and the vessel wall sufficiently thin.
On the return route to the heart the blood flows in venules, small veins and large veins.

Arterial blood in the Systemic Circulation is richly oxygenated, whereas the venous blood has little oxygen. In the Pulmonary Circulation the arterial blood is poorly oxygenated, whereas the venous blood, are highly oxygenated (having replenished its oxygen supplies in the lungs).


Benign Fibroadenoma Tumors

Definition

Fibroadenoma of the breast is a benign (noncancerous) tumor.

Causes, incidence, and risk factors

Fibroadenoma is the most common benign tumor of the breast and the most common breast tumor in women less than 30 years of age. Fibroadenomas are usually found as solitary lumps, but about 10-15% of women have multiple lumps that may affect both breasts.

Black women tend to develop fibroadenomas more frequently and at an earlier age than white women. The cause of fibroadenoma is not known.


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Symptoms



Lumps may be moveable, painless, firm, or rubbery, with well-defined borders
May grow in size, especially during pregnancy
Often get smaller after menopause (if not taking hormones)

Signs and tests

The following may be performed to gain information about a breast lump:

Physical examination
Mammogram
Breast Ultrasound
Fine needle aspiration
Biopsy (needle or open)
Treatment

A biopsy is needed to get a definitive diagnosis. Women in their teens or early 20s may not need a biopsy if the lump goes away on its own.
If a biopsy indicates that the lump is a fibroadenoma, the lump may be left in place or removed, depending on the patient and the lump. If left in place, it may be watched over time with physical examinations, mammograms, and ultrasounds.
The lump may be surgically removed at the time of an open biopsy (this is called an excisional biopsy). The decision depends on the features of the lump and the patient's preferences.
Alternative treatments include removing the lump with a needle, and destroying the lump without removing it (such as by freezing, in a process called cryoablation).
Expectations (prognosis)

The outlook is excellent, although patients with fibroadenoma have a slightly higher risk of breast cancer later. Lumps that are not removed should be periodically monitored by physical examinations and imaging, following the recommendations of the doctor.

Complications

If the lump is left in place for observation, removal may be needed at a later time if the lump changes, grows, or persists.
Cancer may be found in the lump (very rare) and require further treatment.
Biopsy or removal may result in bleeding or scarring.
Calling your health care provider

Patients should contact their health care provider if they feel a new breast lump, if a known lump changes, or if they note changes in the breast that aren’t affected by the menstrual cycle. Women should perform regular breast self exam and undergo breast screening as recommended by their health care provider.

Brain


Brainstem - The lower extension of the brain where it connects to the spinal cord. Neurological functions located in the brainstem include those necessary for survival (breathing, digestion, heart rate, blood pressure) and for arousal (being awake and alert).
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Most of the cranial nerves come from the brainstem. The brainstem is the pathway for all fiber tracts passing up and down from peripheral nerves and spinal cord to the highest parts of the brain.
Cerebellum - The portion of the brain (located at the back) which helps coordinate movement (balance and muscle coordination). Damage may result in ataxia which is a problem of muscle coordination. This can interfere with a person's ability to walk, talk, eat, and to perform other self care tasks.
Frontal Lobe - Front part of the brain; involved in planning, organizing, problem solving, selective attention, personality and a variety of "higher cognitive functions" including behavior and emotions.
The anterior (front) portion of the frontal lobe is called the prefrontal cortex. It is very important for the "higher cognitive functions" and the determination of the personality.
The posterior (back) of the frontal lobe consists of the premotor and motor areas. Nerve cells that produce movement are located in the motor areas. The premotor areas serve to modify movements.
The frontal lobe is divided from the parietal lobe by the central culcus.
Occipital Lobe - Region in the back of the brain which processes visual information. Not only is the occipital lobe mainly responsible for visual reception, it also contains association areas that help in the visual recognition of shapes and colors. Damage to this lobe can cause visual deficits.
Parietal Lobe - One of the two parietal lobes of the brain located behind the frontal lobe at the top of the brain.
Parietal Lobe, Right - Damage to this area can cause visuo-spatial deficits (e.g., the patient may have difficulty finding their way around new, or even familiar, places).
Parietal Lobe, Left - Damage to this area may disrupt a patient's ability to understand spoken and/or written language.
The parietal lobes contain the primary sensory cortex which controls sensation (touch, pressure). Behind the primary sensory cortex is a large association area that controls fine sensation (judgment of texture, weight, size, shape).
Temporal Lobe - There are two temporal lobes, one on each side of the brain located at about the level of the ears. These lobes allow a person to tell one smell from another and one sound from another. They also help in sorting new information and are believed to be responsible for short-term memory.
Right Lobe - Mainly involved in visual memory (i.e., memory for pictures and faces). Left Lobe - Mainly involved in verbal memory (i.e., memory for words and names).

Photosynthesis


Photosynthesis is the conversion of light energy into chemical energy by living organisms. The raw materials are carbon dioxide and water; the energy source is sunlight; and the end-products are oxygen and (energy rich) carbohydrates, for example sucrose, glucose and starch. This process is arguably the most important biochemical pathway,[1] since nearly all life either directly or indirectly depends on it. It is a complex process occurring in higher plants, phytoplankton, algae, as well as bacteria such as cyanobacteria. Photosynthetic organisms are also referred to as photoautotrophs.

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Photosynthesis uses light energy and carbon dioxide to make triose phospates (G3P). G3P is generally considered the prime end-product of photosynthesis. It can be used as an immediate food nutrient, or combined and rearranged to form disaccharide sugars, such as sucrose and fructose, which can be transported to other cells, or packaged for storage as insoluble polysaccharides such as starch.

A commonly used but slightly simplified equation for photosynthesis is:

6 CO2(g) + 12 H2O(l) + photons → C6H12O6(aq) + 6 O2(g) + 6 H2O(l)
carbon dioxide + water + light energy → glucose + oxygen + water

When written as a word equation the light energy appears above the arrow as it is required for photosynthesis but it is not actually a reactant. Here the monosaccharide glucose is shown as a product, although the actual processes in plants produce disaccharides.

The equation is often presented in introductory chemistry texts in an even more simplified form as:[2]

6 CO2(g) + 6 H2O(l) + photons → C6H12O6(aq) + 6 O2(g)

Photosynthesis occurs in two stages. In the first phase, light-dependent reactions or photosynthetic reactions (also called the Light reactions) capture the energy of light and use it to make high-energy molecules. During the second phase, the light-independent reactions (also called the Calvin-Benson Cycle, and formerly known as the Dark Reactions) use the high-energy molecules to capture carbon dioxide (CO2) and make the precursors of carbohydrates.

In the light reactions, one molecule of the pigment chlorophyll absorbs one photon and loses one electron. This electron is passed to a modified form of chlorophyll called pheophytin, which passes the electron to a quinone molecule, allowing the start of a flow of electrons down an electron transport chain that leads to the ultimate reduction of NADP into NADPH. In addition, it serves to create a proton gradient across the chloroplast membrane; its dissipation is used by ATP Synthase for the concomitant synthesis of ATP. The chlorophyll molecule regains the lost electron by taking one from a water molecule through a process called photolysis, that releases oxygen gas.

In the Light-independent or dark reactions the enzyme RuBisCO captures CO2 from the atmosphere and in a process that requires the newly-formed NADPH, called the Calvin-Benson cycle releases three-carbon sugars, which are later combined to form sucrose and starch.

Photosynthesis may simply be defined as the conversion of light energy into chemical energy by living organisms. It is affected by its surroundings and the rate of photosynthesis is affected by the concentration of carbon dioxide, the intensity of light, and the temperature.

The light energy is converted to chemical energy using the light-dependent reactions. This chemical energy production is more than 90% efficient with only 5-8% of the energy transferred thermally. The products of the light-dependent reactions are ATP from photophosphorylation and NADPH from photoreduction. Both are then utilized as an energy source for the light-independent reactions.

Not all wavelengths of light can support photosynthesis. The photosynthetic action spectrum depends on the type of accessory pigments present. For example, in green plants, the action spectrum resembles the absorption spectrum for chlorophylls and carotenoids with peaks for violet-blue and red light. In red algae, the action spectrum overlaps with the absorption spectrum of phycobilins for blue-green light, which allows these algae to grow in deeper waters that filter out the longer wavelengths used by green plants. The non-absorbed part of the light spectrum is what gives photosynthetic organisms their color (e.g., green plants, red algae, purple bacteria) and is the least effective for photosynthesis in the respective organisms.