Rosalind Franklin Was Born #OTD In 1920. Her Work Was Instrumental In The Discovery Of The Structure

Plantibodies and Plant-Derived Edible Vaccines

Throughout history, humans have used plants in the treatment of disease. This includes more traditional methods involving direct consumption with minimal preparation involved and the extraction of compounds for use in modern pharmaceuticals. One of the more recent methods of using plants in medicine involves the synthesis and application of plantibodies and plant produced antigens. These are recombinant antibodies and antigens respectively, which have been produced by a genetically modified plant (1, 2).        

Antibodies are a diverse set of proteins which serve the purpose of aiding the body in eliminating foreign pathogens. They are secreted by effector B lymphocytes which are a type of white blood cell that circulate throughout the body. An antigen is a molecule or a component of a molecule, such as a protein or carbohydrate, which can stimulate an immune response. The human body is capable of producing around 1012  different types of antibodies, each of which can bind to a specific antigen or a small group of related motifs (3). When an antibody encounters the antigen of a foreign pathogen to which it has high affinity, it binds to it which can disable it or alert the immune system for its destruction (4).

Figure 1: Each type of antibody has the ability to bind to a specific antigen or group of antigens with high affinity.

Plants do not normally produce antibodies and thus must be genetically modified to produce plantibodies as well as foreign protein antigens. Plantibodies produced in this manner function the same way as the antibodies native to the human body (1). The main ways to do this are to stably integrate foreign DNA into a host cell and place it into a plant embryo resulting in a permanent change of the nuclear genome, or to induce transient gene expression of the specified protein (5). In both cases, the genetic material introduced to the plant codes for the protein of choice. Several of the methods used to induce permanent transgene expression include agrobacterium-mediated transformation, particle bombardment using a gene gun, or the transformation of organelles such as chloroplasts. Transient transgene expression can be done using plant viruses as viral vectors or agroinfiltration (2). Once the genetic material has been inserted, the specified protein is produced via the plant endomembrane and secretory systems, after which it can be recovered through purification of the plant tissue to be used for injection (1). The production of these proteins can also be directed to specific organs of the plant such as the seeds using targeting signals (2). Stable integration techniques are generally used for more large scale production and when the gene in question has a high level of expression, while transient techniques are used to produce a greater yield in the short term (5).

Figure 2: A gene gun being used to introduce genetic material into the leaves of a plant.

Now how can plantibodies and plant produced antigens help us as humans? The primary purpose of producing plantibodies is for the treatment of disease via immunotherapy. Immunotherapy is a method of treatment in which one’s immune response to a particular disease is enhanced. Specific plantibodies can be produced in order to target a particular disease and then be applied to patients via injection as a means of treatment (6). Doing so provides a boost to the number of antibodies against the targeted disease in the patient’s body which helps to enhance their immune system response against it. An example of this is CaroRx, the first clinically tested plantibody which has the ability to bind to Streptococcus mutans. CaroRx has been shown to be effective in the treatment of tooth decay caused by this species of bacteria (1). More recently, a plantibody known as ZMapp has shown potential in the treatment of Ebola. A study by Qiu et al showed that when administered up to 5 days after the onset of the disease, 100% of rhesus macaques that were administered the drug were shown to have recovered from its effects while all of the control group animals perished as a result of the disease (7). In addition, it has been experimentally administered to some humans who later recovered from the disease, although its role in their recovery was not fully ascertained (8).

Plant produced antigens on the other hand can be used to produce oral vaccines (9). Vaccines are typically biological mixtures containing a weakened pathogen and its antigens. Injection of this results in priming of the body’s adaptive immune system against the particular pathogen so that it can more easily recognize and respond to the threat in the future (4). By producing the antigens of targeted pathogens in plants through transgenic expression, edible vaccines can be created if the plant used is safe to eat. Tobacco, potato, and tomato plants have typically been used in past attempts to create them, showing success in both animal studies and a number of human trials. The advantages of using an oral vaccine include ease of administration and lower costs since specialised personel are not required for administration (9). In addition, oral vaccines are more effective in providing immunity against pathogens at mucosal surfaces as they can be directly applied to the gastrointestinal tract (1). The primary issue with the usage of oral vaccines is that protein antigens must avoid degradation in the stomach and intestines before they can reach the targeted sites in the body. Several solutions to this dilemma include using other biological structures such as liposomes and proteasomes as a means of delivery. This helps to prevent the proteins from being degraded by digestive enzymes and the acidic environment of the stomach before they can reach their destination (1, 9).

Figure 3: An overview of one method of producing an edible vaccine using a potato plant. A gene coding for the protein of a human pathogen is used in agrobacterium-mediated transformation to produce a transgenic potato plant. The potatoes from this plant can then serve as an edible vaccine against pathogen from which the protein originated.

There are a number of advantages to using these plant based pharmaceuticals. First of all, they can be produced on a large scale at a relatively low cost through agriculture and are convenient for long-term storage due to the resiliency and size of plant seeds (5). There is also a low risk of contamination by mammalian viruses, blood borne pathogens, and oncogenes which can remove the need for expensive removal steps (1). In addition, purification steps can be skipped if the plants used are edible and ethical problems that come with animal production can be avoided (5). The disadvantages include the potential for allergic reactions to plant antigens and contamination by pesticides and herbicides. There is also the possibility of outcrossing of transgenic pollen to weeds or related crops which would lead to non-target crops also expressing the pharmaceutical.This could lead to public concern along with the potential that other species which ingest these plants may be negatively affected (9).  While plantibodies and plant produced antigens have not yet been extensively tested in clinical trials, going forward they represent a new treatment option with great promise.

References

1. Jain P, Pandey P, Jain D, Dwivedi P. Plantibody: An overview. Asian journal of Pharmacy and Life Science. 2011 Jan;1(1):87-94.

2. Stoger E, Sack M, Fischer R, Christou P. Plantibodies: applications, advantages and bottlenecks. Current Opinion in Biotechnology. 2002 Apr 1;13(2):161-166.

3. Alberts B, Johnson A, Lewis J, Raff M, Roberts K, Walter P. Molecular Biology of the Cell. 4th Edition. New York: Garland Science; 2002.

4. Parham P. The immune system. 4th Edition. New York: Garland Science; 2014.

5. Ferrante E, Simpson D. A review of the progression of transgenic plants used to produce plantibodies for human usage. J. Young Invest. 2001;4:1-0.

6. Smith MD. Antibody production in plants. Biotechnology advances. 1996 Dec 31;14(3):267-81.

7. Qiu X, Wong G, Audet J, Bello A, Fernando L, Alimonti JB, Fausther-Bovendo H, Wei H, Aviles J, Hiatt E, Johnson A. Reversion of advanced Ebola virus disease in nonhuman primates with ZMapp. Nature. 2014 Aug 29.

8. Sneed A. Know the Jargon. Scientific american. 2014 Dec 1;311(6):24-24.

9. Daniell H, Streatfield SJ, Wycoff K. Medical molecular farming: production of antibodies, biopharmaceuticals and edible vaccines in plants. Trends in plant science. 2001 May 1;6(5):219-26.

Watching a snowflake grow seems almost magical–the six-sided shape, the symmetry, the way every arm of it grows simultaneously. But it’s science that guides the snowflake, not magic. Snowflakes are ice crystals; their six-sided shape comes from how water molecules fit together. The elaborate structures and branches in a snowflake are the result of the exact temperature and humidity conditions when that part of the snowflake formed. The crystals look symmetric and seem to grow identical arms simultaneously because the temperature and humidity conditions are the same around the tiny forming crystals. And the old adage that no two snowflakes are alike doesn’t hold either. If you can control the conditions well enough, you can grow identical-twin snowflakes! (Video credit: K. Libbrecht)

Archbishop Ussher’s chronology was taken as gospel in the Western world. Until we turned to another book to find the age of the earth, the one that was written in the rocks themselves.

Antibiotic Resistance Will Soon Hit the Tipping Point, Unless We Act

Antibiotic Resistance Will Soon Hit the Tipping Point, Unless We Act

Antibiotic-resistant superbugs are enough of a severe, genuine threat to global populations that the UN has placed the issue on par with the spread of Ebola and HIV. The livestock industry is a major factor contributing to the rapid proliferation of these superbugs, swift action is required.

Evidence suggests women’s ovaries can grow new eggs 

Scientists have uncovered the first evidence that the human ovary may be able to grow new eggs in adulthood.

If confirmed, the discovery would overturn the accepted view that women are born with a fixed number of eggs and that the body has no capacity to increase this supply. Until now this has been the main constraint on the female reproductive lifespan. The findings, if replicated, would raise the prospect of new treatments to allow older women to conceive and for infertility problems in younger women.

The small study, involving cancer patients, showed that ovarian biopsies taken from young women who had been given a chemotherapy drug had a far higher density of eggs than healthy women of the same age.

Prof Evelyn Telfer, who led the work at the University of Edinburgh, said: “This was something remarkable and completely unexpected for us. The tissue appeared to have formed new eggs. The dogma is that the human ovary has a fixed population of eggs and that no new eggs form throughout life.”

Ovarian biopsies taken from young women who had been given a particular chemotherapy drug showed that the tissue appeared to have formed new eggs. Photograph: Science Picture Co/Getty Images/Science Faction

‪The first synthesis of aspirin was carried out #OTD in 1897. Here’s a look at how it compares to other painkillers: http://www.compoundchem.com/2014/09/25/painkillers/‬

Who Needs Hard Drives? Scientists Store Film Clip in DNA

In a first, researchers converted a movie into a DNA sequence and inserted it into bacteria. They hope to someday use the technology to record cell behavior.

It was one of the very first motion pictures ever made: a galloping mare filmed in 1878 by the British photographer Eadweard Muybridge, who was trying to learn whether horses in motion ever become truly airborne.

More than a century later, that clip has rejoined the cutting edge. It is now the first movie ever to be encoded in the DNA of a living cell, where it can be retrieved at will and multiplied indefinitely as the host divides and grows.

The advance, reported on Wednesday in the journal Nature by researchers at Harvard Medical School, is the latest and perhaps most astonishing example of the genome’s potential as a vast storage device.

Continue Reading.

The Hubble Space Telescope captured this picture of the wispy remains of a supernova explosion. The dust cloud in the upper center of the picture is the actual supernova remnant. The dense concentration of stars in the lower left is the outskirts of star cluster NGC 1850. Full resolution picture here. More info here. Credit: NASA, ESA, Y.-H. Chu (Academia Sinica, Taipei)

Why do flowers do the thing they do?

Flowers are the reproductive organs of plants. When pollinated, flowers develop into fruits containing seeds. However, producing flowers, fruits, and seeds is not easy. Plants devote lots of resources and energy to grow these specialized organs. Thus, plants tend to synchronize their efforts with a time of year when conditions are best for reproductive success and survival.

“Annuals” are plants that grow from seed, flower, and die in one year. Since annuals need to grow leaves and stems before they flower, most annuals won’t mature enough to flower until mid-summer or later.

“Winter annuals” get a jump-start on reproduction by germinating from seeds in the fall, over-wintering as rosettes of leaves and storing energy which allows them to flower early in the spring.

“Perennial” plants can live for many years and flower multiple times. Perennials have evolved many different flowering strategies. Most flower in mid- to late summer after they have had time to accumulate the resources needed to produce seeds each year.  Others, such as early forest wildflowers, grow for only a short while, blooming before the trees above them leaf out, starving them of light. These plants store energy in underground roots or stems, allowing them to flower early and quickly.

The evolution of such diverse flowering strategies is good for plants that otherwise would have to compete for the same resources at the same time. Its also is nice for us, as we get to enjoy flowers brightening the landscape throughout the growing season.

Giffed by: rudescience  From: this video

Autonomic nervous system

Structure and Function of the Sympathetic and Parasympathetic nervous system

The main function of the autonomic nervous system (ANS) is to assist the body in maintaining a relatively constant internal environment. For example, a sudden increase in systemic blood pressure activates the baroreceptors (those are receptors that detect physical pressure) which in turn modify the activity of the ANS so that the blood pressure is restored to its previous level [1].

The ANS is often regarded as a part of the motor system and is responsible for involuntary action and its effector organs are smooth muscle, cardiac muscle and glands. Another system, the somatic (meaning around the body) nervous system, is responsible for voluntary action in which skeletal muscle is the effector.

The ANS can further be divided into 3 parts: sympathetic, parasympathetic and enteric nervous systems [1][2], with the enteric nervous system sometimes being considered a separate entity [2]. Both parasympathetic and sympathetic nervous systems coexist and work in opposition with each other, ultimately maintaining the correct balance; the activity of one being more active depending on the situation. In a normal resting human, the parasympathetic nervous system dominates, while in a tense and stressful situation, the sympathetic nervous system switches to become dominant.

Figure 1. Structure and function of the central nervous system

This article will be focused on sympathetic and parasympathetic activity from the perspective of:

Anatomy

Biochemical

The sympathetic division provides your “fight or flight” whereas the parasympathetic division helps you to “rest and digest”

Anatomy

Higher centers that control autonomic function include the pons, medulla oblongata and hypothalamus [3].

The pons contains the micturition (urination) and respiratory center.

The medulla oblongata contains the respiratory, cardiac, vomiting, vasomotor and vasodilator centres [4].

The hypothalamus contains the highest concentration of autonomic centres [4]. It contains several centres that control autonomic activities, including heat loss, heat production and conservation, feeding and satiety, as well as fluid intake [4].

Figure 2. Locations of the autonomic control centres of the brain

All 3 structures receive input from certain sources by stimulation of nerve fibres resulting from chemical changes in blood composition like blood pH, blood glucose level, blood osmolarity and volume [4]. Notably, the hypothalamus receives input from cerebral cortex and the limbic system, a system that helps control emotional behaviour [3].

Autonomic promoter neurons are neurons that are found in the brain stem, hypothalamus or even cerebral hemispheres that project to preganglionic neurons (discussed below), where they form synapses with these neurons (5). Hence, input from the higher centres can be relayed to the motor neurons (preganglionic and then postganglionic neurons) which subsequently innervate different body tissues. Changes in the input from these centres could result in responses in those tissues.

The primary functional unit of the sympathetic and parasympathetic nervous system consists of a 2 neuron motor pathway (Figure 3), containing a preganglionic and postganglionic neurons, arranged in series.(2) The two synapse in peripheral ganglion. This clearly distinguishes autonomic motor nervous system and somatic nervous system. The somatic nervous system project from the CNS directly to innervated tissue without any intervening ganglia.(6)

Figure 3. Diagram showing the primary functional unit of the ANS

Sympathetic nervous system

Sympathetic preganglionic neurons mainly are concentrated in the lateral horn in the thoracic (T1-12) and upper lumbar (L1 &2) segments of the spinal cord (Figure 4).

The preganglionic axons leave the spinal cord in 3 ways:

Through the paravertebral ganglion

The preganglionic axon may synapse with postganglionic neurons in this ganglion or some axon may travel rostrally or caudally within the sympathetic trunk before forming synapse with a postganglionic neurons in a different paravertebral ganglion.

Through the prevertebral ganglion

Some preganglionic axons pass the paravertebral ganglion (no synapse occur) and form synapse with postganglionic neurons in prevertebral ganglion, also known as collateral ganglion.

Directly to the organs without any synapse

Some preganglionic axons pass through the sympathetic trunk (no synapse) and end directly on cells of the adrenal medulla, which are equivalent to postganglionic cell.

Parasympathetic nervous system

The parasympathetic preganglionic neurons are located in several cranial nerve nuclei in the brain stem and some are found in the S3 and S4 segments of the sacral spinal cord (Figure 4). The parasympathetic postganglionic neurons are located in cranial ganglia, including the ciliary ganglion, the pterygopalatine, submandibular ganglia, and the otic ganglion. Other ganglia are present near or in the walls of visceral organs. Similarly, the preganglionic neurons form synapse with the postganglionic neurons in the ganglia.

Figure 4. Anatomy of the ANS and how its nuerons innervate tissues

After knowing how nerves connect from the CNS to PNS and to different organs, we will now consider some of the neurotransmitters that are being released at different nerve terminals. It is the binding of these neurotransmitters to the receptors on the effectors that leads to biochemical and physiological changes. Some of the neurotransmitters in use are:

For the synapse between pre and postganglionic neurons mentioned above, the neurotransmitter that is released by the preganglionic axon terminal, is acetylcholine. The corresponding receptors are found on the postsynaptic membrane of postganglionic nerves and are nicotinic receptors.

Parasympathetic postganglionic nerve terminals also release acetylcholine.

Sympathetic postganglionic nerve terminals release mostly noradrenaline

The adrenal medulla receives direct stimulation from sympathetic preganglionic innervation, releases mainly adrenaline (80%) and some noradrenaline into the blood stream. In this case, both adrenaline and noradrenaline act as hormones as they are transported via blood circulating system to target organs instead of neuronal pathway.

Strangely, for the sympathetic postganglionic nerves that innervate the sweat glands, the nerves release acetylcholine (normally only by parasympathetic postganglionic nerve) instead.

1. H.P.Rang, J.M.Ritter, R.J.Flower GH. RANG & DALE’S Pharmacology. In: 8th ed. ELSEVIER CHURCHILL LIVINGSTONE; 2016. p. 145.

2. Bruce M. Koeppen BAS. BERNE & LEVY PHYSIOLOGY. In: 6th ed. MOSBY ELSEVIER; 2010. p. 218.

3. Cholinergic transmission [Internet]. 2015. Available from: http://www.dartmouth.edu/~rpsmith/Cholinergic_Transmission.html

4. Bruce M. Koeppen BAS. BERNE & LEVY PHYSIOLOGY. In: 6th ed. MOSBY ELSEVIER; 2016. p. 44.