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Hypothetically, what is the smallest functional form of human?

Hypothetically, what is the smallest functional form of human?


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Since the my first encounter with doraemon manga, I've been wondering many things, one of them is the small light.

Assuming we had an instrument, such as small light, which enabled people to grow and shrink as they wanted to, what would be the smallest and the most compact functional form of a person?

First, I can rule out that we couldn't be as small as an atom because we couldn't be function as human being if we were compressed into 1 atom. So did 1 molecule. and so did 1 cell.

Second, you need more than 1 cell to construct organs, i.e. I couldn't imagine an eye which consists only several atoms or molecules.

Therefore, there should be a limit to the the size of human organs in order to fully retain their functions and thence, there should also be a limit to the minimum size of human organs.

What are the limits of size of each of human organs?

What are the limits of size of human then?


This question is for Doctor Frankenstein!

The answer would depend on what you would accept to consider being a human.

  • Does it still need to be able to make simple calculation in order to be a human? Yes, because otherwise we would have lost some functions. But then you may ask…
  • Does it need to have big enough hands in order to fulfill the social function of hand shaking.
  • Does it has to be attractive to the other sex?
  • Does it need a heart or is it fine if oxygen diffusion through tissue only is enough for this creature to live?

I guess that if you change the number of cells you will necessarily change the functionality. I am not saying that small guys are not as functional as big guys. For example, big guys are better runner, while small guys are better climber.

  • Are we allowed to shrink the cells to have minimal sized cells?
  • Are we allowed to shorten the DNA in order to shrink the cells?

Notes:

  • There are approximatively 200 different cell types in a human
    • My reference is not a peer-reviewed article (ref). Wikipedia lists cell types and it doesn't seem to go over 200. However, it is important to realize that it probably very much depend on how you define cell types.
  • Terminologica Anatomica lists over 7,500 names parts of the human body
  • There are 13 or 14 (depending on the gender) gland types
  • This article provides an estimation of the number of cells in the human body
  • Here (wikipedia) is a discussion on the concept of the minimal cell
  • Here and here (biology.SE) are discussions on the minimum number of genes/amino acid to sustain life
  • Here (biology.SE) is a discussion on which species has been found to have the smallest genome

Cell Atlas Study Reveals New Insights into Human Biology

The first analysis of the physical arrangement of proteins in cells has been published in Science, revealing that a large portion of human proteins can be found in more than one location in a given cell.

Using the Sweden-based Cell Atlas, researchers examined the spatial distribution of the human proteome that correspond to the majority of protein-coding genes, and they described in unprecedented detail the distribution of proteins to the various organelles and substructures of the human body’s smallest unit, the cell.

Within a cell, the organelles create partitions that form an enclosed environment for chemical reactions tailored to fulfill specific functions in the cell. Since these functions are tightly linked to specific sets of proteins, knowing the subcellular location of the human proteome is key knowledge for understanding the function and underlying mechanisms of the human cell.

The study was led by Emma Lundberg, associate professor at KTH Royal Institute of Technology and responsible for the High Content Microscopy facility at the Science for Life Laboratory (SciLifeLab) in Stockholm, Sweden. The team generated more than 100,000 images to systematically resolve the spatial distribution of human proteins in cultivated cell lines, and map them to cellular compartments and substructures with single cell resolution.

The Cell Atlas is the result of more than 10 years of research within the Human Protein Atlas program, and was launched in December 2016. The article in Science describes the detailed analysis of hundreds of thousands of images created as part of this international effort, which also involved groups in the UK, China, South Korea, India, Denmark, and Germany.

“Only by studying the molecular components of the body’s smallest functional unit – the cell – can we reach a full understanding of human biology,” says KTH Professor Mathias Uhlén, director of the Human Protein Atlas. “The Cell Atlas provides researchers with new knowledge that facilitates functional exploration of individual proteins and their role in human biology and disease.”

The published article also includes a comparative study performed by Kathryn Lilley, director of the Cambridge Centre for Proteomics, at Cambridge University, UK, which enabled the antibody-based immunofluorescence (IF) microscopy analysis to be validated by an alternative mapping strategy that used mass spectrometry.

A total of 12,003 proteins targeted by 13,993 antibodies were classified into one or several of 30 cellular compartments and substructures, altogether defining the proteome of 13 major organelles. The organelles with the largest proteomes were the nucleus and its substructures, such as bodies and speckles (6,930), and the cytosol (4,279).

Interestingly, about one-half of the proteins are found in more than one compartment revealing a shared pool of proteins in functionally unrelated parts of the cell. Lundberg says:

The Cell Atlas is an open access resource that can be used by researchers around the world to study proteins or organelles of interest, Lundberg says. “The Atlas enables systems biology and cell modeling applications, and it is also a highly valuable resource for machine learning applications in image pattern recognition.”

This article has been republished from materials provided by the KTH. Note: material may have been edited for length and content. For further information, please contact the cited source.


Bile Pigments: Origin and Formation | Digestive Juice | Human | Biology

In this article we will discuss about:- 1. Origin and Formation of Bile Pigments 2. Chemistry and Varieties of Bile Pigments 3. Circulation and Fate.

Origin and Formation of Bile Pigments:

The old and worn-out red blood cells disintegrate and are removed from the circulation by the cells of the reticuloendothelial system the bone-marrow appears to be the most active site. Haemoglobin is released and by degradation, opening of the porphyrin ring system occurs. The degraded compound is known as verdohaemoglobin or choleglobin. In the next stage it is broken down into protein and haem. Protein is broken down into amino acids which enter the general amino acid pool of the body.

The iron present in the haem remains stored in the body as apoferritin, ferritin and haemosiderin which help in the formation of new haemoglobin. The rest of the haem is converted into yellow pigment bilirubin which is oxidised into green pigment biliverdin or the green pigment biliverdin is formed first which by reduction forms the yellow pigment bilirubin. Biliverdin reductase is the enzyme which catalyses the reduction of biliverdin to bilirubin. These are also derived to some extent from myohaemoglobin.

A schematic representation of bile pigment formation is given below in the Fig. 9.26. It does not represent proved steps of the reactions, but only attempts to summarise the facts and supplies possible pathways.

The oxidation and reduction take place by transference of hydrogen from the substrate and NAD/NADH or NADP/NADPH system. The bilirubin then probably combines with albumin of the plasma. When it enters the liver cells, plasma albumin is separated from bilirubin. In the liver cells and to lesser extent in kidney cells it is conjugated with glucuronic acid (UDP glucuronic acid) and forms monoglucuronide and diglucuronide.

In hepatic bile these are bound in addition with protein and in gall-bladder bile with lipoprotein, cholesterol and bile acids. The reaction is catalised by glucuronyl transferase. Some bilirubin is also esterified by sulphuric acid as bilirubin sulphate.

Chemistry and Varieties of Bile Pigments:

A number of pigments are present in bile. The two chief pigments are bilirubin (golden-yellow) and biliverdin (green). Bilirubin (C33H36N4O6) is the chief pigment of human and carnivorous bile. Biliverdin (C33H36N4O8) is the oxidation product of bilirubin. It is present chiefly in the bile of birds and of herbivorous animals.

Biliprasin is supposed to be an intermediate product formed during oxidation of bilirubin into biliverdin. Bilicyanin (blue), bilifuscin (red) and choletelin (yellow) are three other pigments formed by the successive oxidation of biliverdin. They are found in the gall-stones. The bile pigments are porphyrin compounds and constitute about 15 – 20% of the total solids of the liver bile. [They can be detected by Gmelin’s test.]

Circulation and Fate of Bile Pigments:

Liver (Kupffer cells), spleen and bone-marrow, being the chief seats of the reticulo-endothelial system, take the main part in bilirubin formation. Blood leaving the spleen and bone-marrow has a much higher bilirubin content than the arterial blood. Normal blood serum contains traces of bilirubin which on the average amounts to about 0.5 – 0.8 unit. It is to be noted that bilirubin, as it is present in blood (haemobilirubin), is not the same as that present in bile (cholebilirubin). Haemobilirubin remains combined with serum albumin and cholebilirubin remains in combination with glucuronic acid.

The main differences between the two bilirubins are summarised below in table 9.3:

Van Den Bergh Reaction:

This test helps in detection of bile pigment in blood serum.

There are three types of reactions:

Two types of solutions are used:

Sulphanilic acid (0.1 gm), concentrated HCI (1.5 ml), distilled water—(100 ml).

Sodium nitrate (0.5 gm) and water (100 ml).

25ml of No. I solution is mixed with 0.75 ml of No. II solution—Diazo reagent. 1 ml of serum is taken in a small test-tube.

To it equal amount of Diazo reagent is added and any one of the following reactions may occur:

i. Immediate or Prompt:

A bluish-violet colour immediately appears (within 10 – 30 sec).

Reddish colour appears which gradually becomes violet and this takes from 5-15 minutes or even half an hour.

A reddish colour appears promptly and after much longer time becomes violet.

At first 1 ml of serum is treated with 2 ml of 95% alcohol. It is shaken and centrifuged. 1 ml of supernatant fluid is taken and to it 0.25 ml of Diazo reagent is added. A reddish-violet colour appears immediately.

In Jaundice there is excessive accumulation of bile pigments in blood which causes yellowish discoloura­tion of skin, mucous membrane and conjunctiva.

There are three types of jaundice:

1. Obstructive Jaundice:

Van den Bergh test is direct and prompt.

2. Haemolytic Jaundice:

Van den Bergh test is indi­rect.

3. Toxic or Infective Jaundice: (Where there is Paren­chymatous Liver Damage):

Van den Bergh test is delayed direct or biphasic.

After passing through the hepatic cells, conju­gated bilirubin and biliverdin enter bile channels and then into the intestine along with bile.

In the intestine following changes take place:

Bilirubin mesobilirubin mesobilirubinogen stercobilinogen. On being exposed to air stercobilinogen is further oxidised into yellowish-brown stercobilin and is responsible for the normal colour of the faeces. About half the amount of total bile pigments is excreted in the fae­ces, which varies from 40 – 280 mgm per day.

The remaining part of stercobilinogen is reab­sorbed from the intestine and is carried back to liv­er. Under normal conditions, this reabsorbed sterco­bilinogen is almost fully re-excreted in the bile. A trace of stercobilinogen may fail to pass through the liver, and is excreted in the urine. This excretory product is named as urobilinogen which is quickly oxidised into urobilin by the air after the urine is voided (Fig. 9.27).

It is believed that some urobilinogen passes directly to the kidney escaping the liver for excretion (not shown in Fig. 9.27). Urobilinogen is identical with stercobilinogen and urobilin is identical with stercobilin. Normally faecal excretion of bile pigments varies from 50 – 250 mgm per day, only 1-2 mgm being excreted through urine.

When liver is damaged, urobilinogen reabsorbed from the intestine, fails to pass through the liver cells and appears in the urine in a larger amount. Under such conditions, urine contains considerable amounts of urobilinogen and urobilin. Presence of urobilinogen in urine in excess, therefore, indicates functional deficiency of liver.


BIO 140 - Human Biology I - Textbook

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Chapter 38

Skeletal Muscle

  • Describe the layers of connective tissues packaging skeletal muscle
  • Explain how muscles work with tendons to move the body
  • Identify areas of the skeletal muscle fibers
  • Describe excitation-contraction coupling

The best-known feature of skeletal muscle is its ability to contract and cause movement. Skeletal muscles act not only to produce movement but also to stop movement, such as resisting gravity to maintain posture. Small, constant adjustments of the skeletal muscles are needed to hold a body upright or balanced in any position. Muscles also prevent excess movement of the bones and joints, maintaining skeletal stability and preventing skeletal structure damage or deformation. Joints can become misaligned or dislocated entirely by pulling on the associated bones muscles work to keep joints stable. Skeletal muscles are located throughout the body at the openings of internal tracts to control the movement of various substances. These muscles allow functions, such as swallowing, urination, and defecation, to be under voluntary control. Skeletal muscles also protect internal organs (particularly abdominal and pelvic organs) by acting as an external barrier or shield to external trauma and by supporting the weight of the organs.

Skeletal muscles contribute to the maintenance of homeostasis in the body by generating heat. Muscle contraction requires energy, and when ATP is broken down, heat is produced. This heat is very noticeable during exercise, when sustained muscle movement causes body temperature to rise, and in cases of extreme cold, when shivering produces random skeletal muscle contractions to generate heat.

Each skeletal muscle is an organ that consists of various integrated tissues. These tissues include the skeletal muscle fibers, blood vessels, nerve fibers, and connective tissue. Each skeletal muscle has three layers of connective tissue (called &ldquomysia&rdquo) that enclose it and provide structure to the muscle as a whole, and also compartmentalize the muscle fibers within the muscle (Figure 1). Each muscle is wrapped in a sheath of dense, irregular connective tissue called the epimysium , which allows a muscle to contract and move powerfully while maintaining its structural integrity. The epimysium also separates muscle from other tissues and organs in the area, allowing the muscle to move independently.

Figure 1: Bundles of muscle fibers, called fascicles, are covered by the perimysium. Muscle fibers are covered by the endomysium.

Inside each skeletal muscle, muscle fibers are organized into individual bundles, each called a fascicle , by a middle layer of connective tissue called the perimysium . This fascicular organization is common in muscles of the limbs it allows the nervous system to trigger a specific movement of a muscle by activating a subset of muscle fibers within a bundle, or fascicle of the muscle. Inside each fascicle, each muscle fiber is encased in a thin connective tissue layer of collagen and reticular fibers called the endomysium . The endomysium contains the extracellular fluid and nutrients to support the muscle fiber. These nutrients are supplied via blood to the muscle tissue.

In skeletal muscles that work with tendons to pull on bones, the collagen in the three tissue layers (the mysia) intertwines with the collagen of a tendon. At the other end of the tendon, it fuses with the periosteum coating the bone. The tension created by contraction of the muscle fibers is then transferred though the mysia, to the tendon, and then to the periosteum to pull on the bone for movement of the skeleton. In other places, the mysia may fuse with a broad, tendon-like sheet called an aponeurosis , or to fascia, the connective tissue between skin and bones. The broad sheet of connective tissue in the lower back that the latissimus dorsi muscles (the &ldquolats&rdquo) fuse into is an example of an aponeurosis.

Every skeletal muscle is also richly supplied by blood vessels for nourishment, oxygen delivery, and waste removal. In addition, every muscle fiber in a skeletal muscle is supplied by the axon branch of a somatic motor neuron, which signals the fiber to contract. Unlike cardiac and smooth muscle, the only way to functionally contract a skeletal muscle is through signaling from the nervous system.

Skeletal Muscle Fibers

Because skeletal muscle cells are long and cylindrical, they are commonly referred to as muscle fibers. Skeletal muscle fibers can be quite large for human cells, with diameters up to 100 &mum and lengths up to 30 cm (11.8 in) in the Sartorius of the upper leg. During early development, embryonic myoblasts, each with its own nucleus, fuse with up to hundreds of other myoblasts to form the multinucleated skeletal muscle fibers. Multiple nuclei mean multiple copies of genes, permitting the production of the large amounts of proteins and enzymes needed for muscle contraction.

Some other terminology associated with muscle fibers is rooted in the Greek sarco, which means &ldquoflesh.&rdquo The plasma membrane of muscle fibers is called the sarcolemma , the cytoplasm is referred to as sarcoplasm , and the specialized smooth endoplasmic reticulum, which stores, releases, and retrieves calcium ions (Ca ++ ) is called the sarcoplasmic reticulum (SR) (Figure 2). As will soon be described, the functional unit of a skeletal muscle fiber is the sarcomere, a highly organized arrangement of the contractile myofilaments actin (thin filament) and myosin (thick filament), along with other support proteins.

Figure 2: A skeletal muscle fiber is surrounded by a plasma membrane called the sarcolemma, which contains sarcoplasm, the cytoplasm of muscle cells. A muscle fiber is composed of many fibrils, which give the cell its striated appearance.

The Sarcomere

The striated appearance of skeletal muscle fibers is due to the arrangement of the myofilaments of actin and myosin in sequential order from one end of the muscle fiber to the other. Each packet of these microfilaments and their regulatory proteins, troponin and tropomyosin (along with other proteins) is called a sarcomere .

Watch the video linked to below to learn more about macro- and microstructures of skeletal muscles. (a) What are the names of the &ldquojunction points&rdquo between sarcomeres? (b) What are the names of the &ldquosubunits&rdquo within the myofibrils that run the length of skeletal muscle fibers? (c) What is the &ldquodouble strand of pearls&rdquo described in the video? (d) What gives a skeletal muscle fiber its striated appearance?

The sarcomere is the functional unit of the muscle fiber. The sarcomere itself is bundled within the myofibril that runs the entire length of the muscle fiber and attaches to the sarcolemma at its end. As myofibrils contract, the entire muscle cell contracts. Because myofibrils are only approximately 1.2 &mum in diameter, hundreds to thousands (each with thousands of sarcomeres) can be found inside one muscle fiber. Each sarcomere is approximately 2 &mum in length with a three-dimensional cylinder-like arrangement and is bordered by structures called Z-discs (also called Z-lines, because pictures are two-dimensional), to which the actin myofilaments are anchored (Figure 3). Because the actin and its troponin-tropomyosin complex (projecting from the Z-discs toward the center of the sarcomere) form strands that are thinner than the myosin, it is called the thin filament of the sarcomere. Likewise, because the myosin strands and their multiple heads (projecting from the center of the sarcomere, toward but not all to way to, the Z-discs) have more mass and are thicker, they are called the thick filament of the sarcomere.

Figure 3: The sarcomere, the region from one Z-line to the next Z-line, is the functional unit of a skeletal muscle fiber.

The Neuromuscular Junction

Another specialization of the skeletal muscle is the site where a motor neuron&rsquos terminal meets the muscle fiber&mdashcalled the neuromuscular junction (NMJ) . This is where the muscle fiber first responds to signaling by the motor neuron. Every skeletal muscle fiber in every skeletal muscle is innervated by a motor neuron at the NMJ. Excitation signals from the neuron are the only way to functionally activate the fiber to contract.

Every skeletal muscle fiber is supplied by a motor neuron at the NMJ. Watch the video linked to below to learn more about what happens at the NMJ. (a) What is the definition of a motor unit? (b) What is the structural and functional difference between a large motor unit and a small motor unit? (c) Can you give an example of each? (d) Why is the neurotransmitter acetylcholine degraded after binding to its receptor?

Excitation-Contraction Coupling

All living cells have membrane potentials, or electrical gradients across their membranes. The inside of the membrane is usually around -60 to -90 mV, relative to the outside. This is referred to as a cell&rsquos membrane potential. Neurons and muscle cells can use their membrane potentials to generate electrical signals. They do this by controlling the movement of charged particles, called ions, across their membranes to create electrical currents. This is achieved by opening and closing specialized proteins in the membrane called ion channels. Although the currents generated by ions moving through these channel proteins are very small, they form the basis of both neural signaling and muscle contraction.

Both neurons and skeletal muscle cells are electrically excitable, meaning that they are able to generate action potentials. An action potential is a special type of electrical signal that can travel along a cell membrane as a wave. This allows a signal to be transmitted quickly and faithfully over long distances.

Although the term excitation-contraction coupling confuses or scares some students, it comes down to this: for a skeletal muscle fiber to contract, its membrane must first be &ldquoexcited&rdquo&mdashin other words, it must be stimulated to fire an action potential. The muscle fiber action potential, which sweeps along the sarcolemma as a wave, is &ldquocoupled&rdquo to the actual contraction through the release of calcium ions (Ca ++ ) from the SR. Once released, the Ca ++ interacts with the shielding proteins, forcing them to move aside so that the actin-binding sites are available for attachment by myosin heads. The myosin then pulls the actin filaments toward the center, shortening the muscle fiber.

In skeletal muscle, this sequence begins with signals from the somatic motor division of the nervous system. In other words, the &ldquoexcitation&rdquo step in skeletal muscles is always triggered by signaling from the nervous system (Figure 4).

Figure 4: At the NMJ, the axon terminal releases ACh. The motor end-plate is the location of the ACh-receptors in the muscle fiber sarcolemma. When ACh molecules are released, they diffuse across a minute space called the synaptic cleft and bind to the receptors.

The motor neurons that tell the skeletal muscle fibers to contract originate in the spinal cord, with a smaller number located in the brainstem for activation of skeletal muscles of the face, head, and neck. These neurons have long processes, called axons, which are specialized to transmit action potentials long distances&mdash in this case, all the way from the spinal cord to the muscle itself (which may be up to three feet away). The axons of multiple neurons bundle together to form nerves, like wires bundled together in a cable.

Signaling begins when a neuronal action potential travels along the axon of a motor neuron, and then along the individual branches to terminate at the NMJ. At the NMJ, the axon terminal releases a chemical messenger, or neurotransmitter , called acetylcholine (ACh) . The ACh molecules diffuse across a minute space called the synaptic cleft and bind to ACh receptors located within the motor end-plate of the sarcolemma on the other side of the synapse. Once ACh binds, a channel in the ACh receptor opens and positively charged ions can pass through into the muscle fiber, causing it to depolarize , meaning that the membrane potential of the muscle fiber becomes less negative (closer to zero.)

As the membrane depolarizes, another set of ion channels called voltage-gated sodium channels are triggered to open. Sodium ions enter the muscle fiber, and an action potential rapidly spreads (or &ldquofires&rdquo) along the entire membrane to initiate excitation-contraction coupling.

Things happen very quickly in the world of excitable membranes (just think about how quickly you can snap your fingers as soon as you decide to do it). Immediately following depolarization of the membrane, it repolarizes, re-establishing the negative membrane potential. Meanwhile, the ACh in the synaptic cleft is degraded by the enzyme acetylcholinesterase (AChE) so that the ACh cannot rebind to a receptor and reopen its channel, which would cause unwanted extended muscle excitation and contraction.

Propagation of an action potential along the sarcolemma is the excitation portion of excitation-contraction coupling. Recall that this excitation actually triggers the release of calcium ions (Ca ++ ) from its storage in the cell&rsquos SR. For the action potential to reach the membrane of the SR, there are periodic invaginations in the sarcolemma, called T-tubules (&ldquoT&rdquo stands for &ldquotransverse&rdquo). You will recall that the diameter of a muscle fiber can be up to 100 &mum, so these T-tubules ensure that the membrane can get close to the SR in the sarcoplasm. The arrangement of a T-tubule with the membranes of SR on either side is called a triad (Figure 5). The triad surrounds the cylindrical structure called a myofibril , which contains actin and myosin.

Figure 5: Narrow T-tubules permit the conduction of electrical impulses. The SR functions to regulate intracellular levels of calcium. Two terminal cisternae (where enlarged SR connects to the T-tubule) and one T-tubule comprise a triad&mdasha &ldquothreesome&rdquo of membranes, with those of SR on two sides and the T-tubule sandwiched between them.

The T-tubules carry the action potential into the interior of the cell, which triggers the opening of calcium channels in the membrane of the adjacent SR, causing Ca ++ to diffuse out of the SR and into the sarcoplasm. It is the arrival of Ca ++ in the sarcoplasm that initiates contraction of the muscle fiber by its contractile units, or sarcomeres.

Chapter Review

Skeletal muscles contain connective tissue, blood vessels, and nerves. There are three layers of connective tissue: epimysium, perimysium, and endomysium. Skeletal muscle fibers are organized into groups called fascicles. Blood vessels and nerves enter the connective tissue and branch in the cell. Muscles attach to bones directly or through tendons or aponeuroses. Skeletal muscles maintain posture, stabilize bones and joints, control internal movement, and generate heat.

Skeletal muscle fibers are long, multinucleated cells. The membrane of the cell is the sarcolemma the cytoplasm of the cell is the sarcoplasm. The sarcoplasmic reticulum (SR) is a form of endoplasmic reticulum. Muscle fibers are composed of myofibrils. The striations are created by the organization of actin and myosin resulting in the banding pattern of myofibrils.


Compounds and Molecules

A compound is a unique substance that consists of two or more elements combined in fixed proportions. This means that the composition of a compound is always the same. The smallest particle of most compounds in living things is called a molecule .

Figure 3.2.4 A molecule of water consists of one atom of oxygen and two atoms of hydrogen connected by covalent bonds.

Consider water as an example. A molecule of water always contains one atom of oxygen and two atoms of hydrogen. The composition of water is expressed by the chemical formula H2O. A model of a water molecule is shown in Figure 3.2.4.

What causes the atoms of a water molecule to “stick” together? The answer is chemical bonds. A chemical bond is a force that holds together the atoms of molecules. Bonds in molecules involve the sharing of electrons among atoms. New chemical bonds form when substances react with one another. A chemical reaction is a process that changes some chemical substances into others. A chemical reaction is needed to form a compound, and another chemical reaction is needed to separate the substances in that compound.


Current policy status

Current federal policy in the form of NIH guidelines and recommendations put forth by various scientific organizations take into consideration ethical concerns and recent advancements in research and technology.

In September 2015, the NIH placed a temporary moratorium on funding research in which human pluripotent cells are introduced into nonhuman vertebrate animals prior to the gastrulation stage of embryonic development. During gastrulation the three germ layers, or three main tissue layers that ultimately give rise to all the cells and tissues of the body, are formed. When human pluripotent cells are introduced early on into animal embryos, the human cells have a chance of incorporating all through the organism, says Carrie Wolinetz, the associate director for science policy at NIH. "You have less control over where they [pluripotent cells] are going to go," she said.

Wolinetz noted that the ethical concerns regarding human-animal chimeras have not really changed much over the years. "People are really worried about integration of human cells into the germline and into the brain," she said. Though she characterized the idea of an animal having human cognition as a "science fiction scenario," Wolinetz emphasized the need to make sure that the integration of human cells into an animal brain does not cause changes in the animal's behavior and cognition that affect its welfare or cause any kind of distress.

In August 2016, following workshops and discussions with researchers and animal welfare experts, the NIH published proposed changes to its current guidelines. The ethical concerns detailed above formed much of the basis for these guidelines. The NIH proposed the establishment of a steering committee that would provide oversight for funding decisions involving certain types of research. According to a blog post authored by Wolinetz, the first type involves research in which "human pluripotent cells are introduced into nonhuman vertebrate embryos, up through the end of gastrulation stage, with the exception of nonhuman primates, which would only be considered after the blastocyst stage." The second involves areas of research in which "human cells are introduced into postgastrulation nonhuman mammals (excluding rodents), where there could be either a substantial contribution or a substantial functional modification to the animal brain by the human cells."

In addition, the NIH proposed changes to the current human stem cell guidelines.

In speaking about the proposed changes, Wolinetz told Live Science that they constitute a "recognition that science has moved beyond where the guidelines [initially] started."


The Human Protein Project and Cell Atlas

The Cell Atlas is part of the Human Protein Atlas project, which was initiated in 2003 by Professor Mathias Uhlén and is funded by the Knut and Alice Wallenberg Foundation. Primarily based in Sweden, the Human Protein Atlas project involves the joint efforts of KTH Royal Institute of Technology in Stockholm, Uppsala University, Uppsala Akademiska University Hospital and, more recently, Science for Life Laboratory, which is based in both Uppsala and Stockholm. Formal collaborations are with groups in India, South Korea, Japan, China, Germany, France, Switzerland, USA, Canada, Denmark, Finland, the Netherlands, Spain and Italy.


1.1: Levels of Organization of the Human Organism

All living and non-living things are made of one or more unique substances called elements, the smallest unit of which is the atom, (for example, the element oxygen (O) is made of O atoms, carbon (C) is made of C atoms and hydrogen (H) is made of H atoms. Atoms combine to form molecules. Molecules can be small (for example, O2, oxygen gas, which has 2 atoms of the element O CO2, carbon dioxide, which has 1 atom of C and 2 of O), medium (for example, C6H12O6, glucose, which has 6 atoms of C, 12 of H, and 6 of O) or large (for example molecules called proteins are made of hundreds of atoms of C, H, and O with other elements such as nitrogen (N). Molecules are the building blocks to all structures in the human body.

All living structures are made of cells, which are made of many different molecules. Cells are the smallest independent living thing in the human body. The body is made of many different cell types, each with a particular function, (for example muscle cells contract to move something, and red blood cells carry oxygen). All human cells are made of a cell membrane (thin outer layer) that encloses a jelly-like cellular fluid containing tiny organ-like
structures called organelles. There are many types of organelles, each with a particular function (for example, organelles called mitochondrion provides energy to a cell). Different types of cells contain different amounts and types of organelles, depending on their function, (for example muscle cells use a lot of energy and therefore have many mitochondria while skin cells do not and have few mitochondria).

As in other multicellular organisms, cells in the human body are organized into tissues. A tissue is a group of similar cells that work together to perform a specific function. There are four main tissue types in humans (muscular, epithelial, nervous and connective). An organ is an identifiable structure of the body composed of two or more tissues types (for example, the stomach contains muscular tissue made of muscle cells, which allows it to change its shape, epithelial tissue which lines both the inner and outer surface of the
stomach, nervous tissue which sends and receives signals to and from the stomach and the central nervous system, and connective tissue which binds everything together). Organs often perform a specific physiological function (for example, the stomach helps digest food). An organ system is a group of organs that work together to perform a specific function (for example, the stomach, small and large intestines are all organs of the digestive system, that work together to digest foodstuff, move nutrients into the blood and get rid of waste). The most complex level of organization, the human organism is composed of many organ systems that work together to perform the functions of an
independent individual.

The major levels of organization in the body, from the simplest to the most complex are: atoms, molecules, organelles, cells, tissues, organs, organ systems, and the human organism. See below Figure (PageIndex<1>) .

Figure (PageIndex<1>) Hierarchical levels of organization of the human body from the smallest chemical level to the largest organismal level. Read the description, and examples for each level in the pyramid: Chemical level, Cellular level, Tissue level, Organ level, Organ system level, and Organismal level.

Concepts, Terms, and facts check

Study Questions Write your answer in a sentence form (do not answer using loose words)

1. What is an element?
2. What is an atom?
3. What is a molecule?
4. What is a cell?
5. What is an organelle?
6. What is a tissue?
7. What is an organ?
8. What is an organ system?
9. What is an organism?
10. What are the levels of organization in the human organism (list them from the smallest to the largest)?


Protein Atlas Reveals new Details About Human Cells

Reporting in Science, researchers have created an atlas that aims to show the location of proteins throughout a human cell. The work showed that many of these proteins, essential components of cells that are the functional readout of many coding genes, are located in multiple locations in any given type of cell. Led by Emma Lundberg, an Associate Professor at KTH Royal Institute of Technology in Stockholm, Sweden, this new data has been reported in Science.

The research team has now outlined how proteins are distributed among the organelles and subcellular structures of a cell with unprecedented detail. Our bodies are made up of cells, and in order to carry out the myriad functions for life, cells have highly specialized roles that are dictated by our genomic blueprint. The specificity of cells is built upon the different proteins they express, as such knowing where proteins move or where they are stationed in a cell is an important part of understanding their function. Knowing more about protein function can only aid in our understanding of human disease.

This work was part of an international collaboration that created and analyzed more than 300,000 images, aiming to determine how the proteins of a human cell are organized and distributed. The researchers found protein location at single cell resolution, placing them to the compartments and structures within the cell.

The Cell Atlas is an open access tool that is free to investigators, and is the culmination of over a decade of work undertaken as part of the Human Protein Atlas program. The research report outlines the analysis of hundreds of thousands of images that were made for this effort, which also involved scientists in China, Denmark, Germany, South Korea and India.

"Only by studying the molecular components of the body's smallest functional unit, the cell, can we reach a full understanding of human biology," explained KTH Professor Mathias Uhlen, the Director of the Human Protein Atlas. "The Cell Atlas provides researchers with new knowledge that facilitates functional exploration of individual proteins and their role in human biology and disease."

Accompanying the research is a comparative work performed by Kathryn Lilley, Director of the Cambridge Centre for Proteomics at Cambridge University, UK, which enabled immunofluorescence (IF), a technique that uses antibody staining and microscopy analysis, to validate by an additional mapping tool that used mass spectrometry.

The investigators used 13,993 antibodies to sort 12,003 proteins into one or more of 30 different cellular compartments and organelles, thereby describing the protein makeup of 13 major organelles. Unsurprisingly, the nucleus and its substructures had the largest proteome, made up of 6,930 proteins, followed by the cytosol, with 4,279.

Intriguingly, nearly half of the proteins are not confined to one compartment, but instead appear in multiple places, suggesting that within a cell there is a pool of proteins that have roles in otherwise unrelated parts of the cell.

"The Atlas enables systems biology and cell modeling applications, and it is also a highly valuable resource for machine learning applications in image pattern recognition,&rdquo said Lundberg, who also oversees the High Content Microscopy facility at the Science for Life Laboratory (SciLifeLab).

Learn more about protein localization from the video above, a feature of MIT&rsquos open courseware.


Researchers bring order to big data of human biology

The functional genetic network shown is just one of the 144 such networks identified for a diverse set of human tissues and cell types. Credit: (c) Simons Center for Data Analysis

A multi-year study led by researchers from the Simons Center for Data Analysis (SCDA) and major universities and medical schools has broken substantial new ground, establishing how genes work together within 144 different human tissues and cell types in carrying out those tissues' functions.

The paper, to be published online by Nature Genetics on April 27, also demonstrates how computer science and statistical methods may combine to aggregate and analyze very large—and stunningly diverse—genomic 'big-data' collections.

Led by Olga Troyanskaya, deputy director for genomics at SCDA, the team collected and integrated data from about 38,000 genome-wide experiments (from an estimated 14,000 publications). These datasets necessarily contain not only information about cells' RNA/protein functions, but also information from individuals diagnosed with a variety of illnesses.

Using integrative computational analysis, the researchers first isolated the functional genetic interconnections contained in these rich datasets for various tissue types. Then, combining that tissue-specific functional signal with the relevant disease's DNA-based genome-wide association studies (GWAS), the researchers were able to identify statistical associations between genes and diseases that would otherwise be undetectable.

The resulting technique, which they called a 'network-guided association study,' or NetWAS, thus integrates quantitative genetics with functional genomics to increase the power of GWAS and identify genes underlying complex human diseases. And because the technique is completely data-driven, NetWAS avoids bias toward better-studied genes and pathways, permitting discovery of novel associations.

SCDA director Leslie Greengard says, "Olga and her collaborators have demonstrated that extraordinary results can be achieved by merging deep biological insight with state-of-the-art computational methods, and applying them to large-scale, noisy and heterogeneous datasets."

The result of their efforts was 144 functional gene interaction networks for organs as diverse as the kidney, the liver and the whole brain. The paper goes on to describe functional gene disruptions for diseases such as hypertension, diabetes and obesity.

Importantly, while such functional gene interaction networks had already been established in animal models, this feat had not yet been accomplished—and could not have been accomplished without 'big data'— in human tissue. Many human cell types important to disease cannot be studied by traditional direct experimentation, so the ability to instead work with these rich datasets was a critical workaround.

"A key challenge in human biology is that genetic circuits in human tissues and cell types are very difficult to study experimentally," says Troyanskaya, who also is a professor in the computer science department and the Lewis-Sigler Institute for Integrative Genomics at Princeton University. "For example, the podocyte cells in the kidneys that perform the kidney's filtering function cannot be isolated for study in the lab, nor can the function of genes be identified by genome-scale experiments. Yet we need to understand how proteins interact in these cells if we want to understand and treat chronic kidney disease. Our approach mined these big data collections to build a map of how genetic circuits function in the podocyte cells, and in many other disease-relevant tissues and cell types."

These findings have important implications for our understanding of normal gene function, but also for drug use and development: Causal or target genes may be better identified for treatment, and previously unexpected drug interactions and disruptions may be anticipated. "Biomedical researchers can use these networks and the pathways that they uncover to understand drug action and side effects in the context of specific disease-relevant tissues, and to repurpose drugs," Troyanskaya says. "These networks can also be useful for understanding how various therapies work and to help with developing new therapies."

The researchers have also created an online resource so that other scientists may use NetWAS and access the tissue-specific networks. The team created an interactive server, the Genome-scale Integrated Analysis of Networks in Tissues, or GIANT. GIANT allows users to explore the networks, compare how genetic circuits vary across tissues, and analyze data from genetic studies to find genes that cause disease.

Aaron K. Wong, a data scientist at SCDA and formerly a graduate student in the computer science department at Princeton, led the way in creating GIANT. "Our goal was to develop a resource that was accessible to biomedical researchers," he says. "For example, with GIANT, researchers studying Parkinson's disease can search the substantia nigra network, which represents the brain region affected by Parkinson's, to identify new genes and pathways involved in the disease." Wong is one of three co-first authors of the paper.

The paper's other two co-first authors are Arjun Krishnan, a postdoctoral fellow at the Lewis-Sigler Institute and Casey S. Greene, assistant professor of genetics at Dartmouth College, who was a postdoctoral fellow with the Troyanskaya group from 2009 to 2012. Other key collaborators on this study were Emanuela Ricciotti, Garret A. FitzGerald and Tilo Grosser of the pharmacology department and the Institute for Translational Medicine and Therapeutics at the Perelman School of Medicine, University of Pennsylvania Daniel I. Chasman of Brigham and Women's Hospital and Harvard Medical School in Boston and Kara Dolinski at the Lewis-Sigler Institute at Princeton University.

"This is an exciting time in biomedical research, and I believe we are still at the early stages of developing new ways to think about biological networks and their control," Greengard says.


Watch the video: From DNA to protein - 3D (December 2022).