2020年3月23日 星期一

An Update on the Coronavirus

As all kinds of news and information are being exposed to people, a clear comprehension must be made, particularly about what the coronavirus (COVID-19) really is, its pervasiveness and effects on the worldwide population, as well as potential post-infectious diseases.

To make it easy for all to understand, the virus is often being commonly referred to as the “coronavirus” or “COVID-19.” However, that is not the case. COVID-19 is the abbreviation for the term “coronavirus disease 2019”. The virus that causes all this chaos, meanwhile, is coined the name “severe acute respiratory syndrome coronavirus 2” (SARS-CoV-2). This virus, which is similar to the SARS-CoV in many aspects, differs in some major structures. Anyway, both of them are types of coronaviruses, and in this article, let’s still refer to the SARS-CoV-2 as the coronavirus, for the sake of concision. 

Typical coronavirus symptoms include coughing, fever, and shortness of breath. Since such symptoms are not indicative of lung infection, or pneumonia, people who are infected with the coronavirus very often do not have pneumonia. The majority of COVID-19 cases, in fact, are mild and only a small percentage of patients will require hospitalization. It is true, however, that COVID-19 can lead to pneumonia for some patients, especially those over the age of 60 and those with pre-existing lung diseases, such as asthma, emphysema, or any form of fibrosis, which make them prone to the development of pneumonia. This explains why the number of deaths in Italy soar above that of many other countries (Italy has an elderly population of roughly 23%).

According to the statistics provided by the World Health Organization (WHO), currently over 99,027 patients have recovered from the COVID-19 infection. However, multiple sources, such as doctors from Taiwan and Hong Kong, suggest that there are roughly 3%-5% of chances for patients who recovered from the coronavirus infection to be found with post-infectious diseases, most likely pulmonary fibrosis. Pulmonary fibrosis is a condition in which the lungs become scarred and tissues around and between the alveoli thickens over time, in this case, due to the repairing of the lungs after the coronavirus infection. Fibroblasts, which are responsible for the repairing of the lungs, tend to synthesize abundant amounts of extracellular matrix (this phenomenon is also called exaggerated ECM production), thus induces scarring and organ failure. This makes it more difficult for oxygen to pass into bloodstreams in the lungs, and the thickened alveoli results in a weakened lung capacity.

While it's too early to establish long-term effects of the disease, several scans released by a Hong Kong hospital have revealed "patterns similar to frosted glass [in the patients’ lungs], suggesting there was organ damage” (Fig.1). What appears in these patients’ CT scans are "ground glass," a phenomenon in which fluid builds up in lungs and presents itself as white patches. 

The coronavirus pandemic is still in its heights, and frankly, there are not much that we can do about. However, it is no longer something that we can underestimate or underrate. Despite no evidence in proving its effects against the prevention of the coronavirus, masks can prevent droplet transmissions and therefore should be wore, at least in crowded and confined spaces. Wash hands and use alcohol disinfectants after handling public objects and before eating. Most importantly, keep yourself healthy no matter what. 


Fig.1 CT scans of patients reveal the accumulation of fluids in lungs after the SARS-CoV-2 infection


Reference:

“False Claim: Doctors Offer Advice for Preventing COVID-19, Symptoms like Coughing and Fever Indicate Pulmonary Fibrosis, Fibrosis Is Detectable by Holding Your Breath for 10 Seconds, Drinking Water Every 15 Minutes Repels Coronavirus.” Reuters, Thomson Reuters, 17 Mar. 2020, www.reuters.com/article/uk-factcheck-covid-advice-self-test-drin/false-claim-doctors-offer-advice-for-preventing-covid-19-symptoms-like-coughing-and-fever-indicate-pulmonary-fibrosis-fibrosis-is-detectable-by-holding-your-breath-for-10-seconds-drinking-water-every-15-minutes-repels-coronavirus-idUSKBN2142B6.
Bostock, Bill. “Those Who Recover From Coronavirus Can Be Left With Reduced Lung Function, Say Doctors.” ScienceAlert, 14 Mar. 2020, www.sciencealert.com/even-those-who-recover-from-corona-can-be-left-gasping-for-breath-afterwards.
G M-K Tse, K-F To, et al. Pulmonary pathological features in coronavirus associated severe acute respiratory syndrome (SARS). NCBI, 2004.
Ryan T. Kendall, Carol A. Feghali-Bostwick. Fibroblasts in fibrosis: novel roles and mediators. NCBI, 2014.

2020年3月21日 星期六

Motor Proteins: Cytoskeleton Filament Motor Proteins


Motor proteins are proteins that transform chemical energy into mechanical work. They are divided into three categories: cytoskeleton filaments motor proteins, nucleic acid motor proteins, and rotary motor proteins. In this article, we will talk in-depth about cytoskeleton filament motor proteins.

Cytoskeleton filament motor protein


Cytoskeleton filament motor proteins are motor proteins that associate and move along cytoskeleton filaments. This includes myosins, kinesins, and dyneins.

Myosin


Myosins are motor proteins that move along microfilaments; thus, they are also called actin motor proteins (because they interact with the actin of microfilaments). Myosins hydrolyze ATP as the source of energy and use it to propel their movements toward the plus end of an actin filament.

There are as many as 18 types of myosins that are known. Myosin II, for instance, is responsible for generating muscle contraction and dividing a cell during cytokinesis. Myosin V is involved in vesicle and organelle transport. Myosin XI is involved in cytoplasmic streaming, wherein movement along  microfilament networks in the cell allows organelles and cytoplasm to stream in a particular direction.

The movement of myosin is characterized by a release of actin during every cycle. What does this mean? Take muscle-contracting myosin II as an example. Myosin attaches to an actin component, moves once, and then dissociates from the actin. It then attaches again onto actin. This is the cycle of myosin movement.

Kinesin


Kinesins associate and move along microtubules, involving in the anterograde movement [1], which directs the transport of cargoes toward the plus end of microtubules. However, kinesins can also travel toward the minus-end, depending on whether the kinesin has an N-terminal or a C-terminal cargo-binding region. Anyway, just keep in mind the relationship between kinesin and anterograde transport.

Kinesins are primarily involved in the separation of chromosomes during cell division and also the shuttling of mitochondria, Golgi bodies, and vesicles within eukaryotic cells.

Unlike the movements of myosins, kinesins are rather highly processive. This means that kinesins move a great deal of “steps” before dissociating their carriages. Recall the shape of a kinesin [click]. The two heavy chains that attach to the microtubule function like legs, “walking” on the microtubule for a cycle of as much as hundreds of steps, while the two light chains attach to vesicles or organelles like hands.

Dynein


Dyneins move along microtubules through the retrograde movement. Dyneins are larger and more complex than kinesin and myosin motors, composing of two or three heavy chains and a large and variable number of associated light chains. Dyneins move toward the minus end of microtubules, where the nucleus locates.

There are mainly two types of dyneins. Axonemal dyneins facilitate the beating of cilia and flagella by sliding microtubules. Cytoplasmic dyneins facilitate the transport of intracellular cargos. 15 types of axonemal dynein are presently discovered, but only two cytoplasmic forms are known.

Summary


Myosin – microfilament - muscle contraction - cytokinesis (microfilament)
Kinesin – microtubule - anterograde - separation of chromosome - transport
Dynein – microtubule – retrograde - beating of flagella and cilia - transport








Reference:

Lodish H, Berk A, Zipursky SL, et al. Molecular Cell Biology, 4th edition. W. H. Freeman, 2000.
Berg JM, Tymoczko JL, Stryer L. Biochemistry, 5th edition. W. H. Freeman, 2002.
Anatoly B. Kolomeisky. Motor Proteins and Molecular Motors: How to Operate Machines at Nanoscale. NCBI, 2013.

2020年3月14日 星期六

Cytoskeleton: Microfilament, Intermediate Filament, and Microtubule


The cytoskeleton is a network of fibers that extends throughout the cytoplasm and aids the structures and activities of a cell. It is responsible for maintaining the shape of a cell, anchoring organelles and vesicles, assisting intracellular transport, and manipulating the plasma membrane to form food vacuoles and phagocytic vesicles. In this article, we will differentiate the three kinds of cytoskeletons- microtubule, microfilament, and intermediate filament- and make a clear comparison between them.

Microtubule


Microtubules are hollow fibers composed of a single type of globular (round) protein, called tubulin. Tubulin is a dimer formed by two closely related polypeptides, α-tubulin and β-tubulin, and it polymerizes (connects together) to form microtubules.

Microtubule is a polar structure, which is important because polarity gives molecules directionality, and microtubule uses this property to direct its movements as it rapidly assembles and disassembles to a certain direction in the cell. The specific mechanism regarding microtubule’s extension and shrinkage is rather complicated, however, and it will be mentioned in another article (Microtubule and Dynamic Instability).

Microtubule plays a very important role in many cellular processes. It forms the structural support of a cell with microfilament and intermediate filament. It also makes up the internal structure of cilia and flagella, in a “9+2” arrangement [click to understand more]. It provides a platform for intracellular transport and is also involved in the formation of spindles and the separation of eukaryotic chromosomes during cell division (mitosis and meiosis).

Microfilament


Microfilaments are thin solid rods composed of globular proteins called actin. Actin subunits form a twisted double chain that results in the shape of a microfilament. Microfilaments, like microtubules, are polar molecules.

Microfilament networks are found just inside the plasma membrane (cortical microfilament) of cells, stabilizing the outer cytoplasmic layer (cortex) of the cell. This is also the reason why cells can form pseudopodia or conduct phagocytic activities. Microfilaments also interact with motor proteins called myosin that bring about the contraction of muscle cells.

Intermediate filament


Intermediate filaments are composed of a variety of proteins, differing from the single-polymer microtubule and microfilament. The type of protein that polymerizes into intermediate filament depends on different cell types, but they share a common structural organization (meaning that they are constructed based on the same principle). Intermediate filaments only provide structural support in a cell.

Intermediate filaments are apolar, meaning that they do not have distinct plus and minus ends like microtubules and microfilaments do. Thus, they are assembled end to end (sort of like DNAs) and both ends are equivalent.

Here are some examples of intermediate filaments to give you a better picture:
  • Types I and II intermediate filaments consist of two groups of keratins that are responsible for the production of hair, nails, and horns.
  • Type IV intermediate filament proteins include three neurofilament (NF) proteins that support the structures of long, thin axons.
  •  Type V intermediate filament proteins are the nuclear lamins, which are components of the nuclear envelope, holding the nucleus in place.


Structural support


Microtubules, along with intermediate filament and microfilament, provide a cell’s structural support. Microtubules, being hollow tubes, act as girders (橫樑) that resist compression and maintain a cell’s dome shape. Microfilaments, which are solid rods, bear tensions exerted on the cell (hold the cell’s shape so the cell would not stretch when being pulled by a force). It is also responsible for the change in cell shape (phagocytosis, etc.). The job of intermediate filaments is to reinforce the shape of a cell and fix the position of certain organelles. Unlike microtubule and microfilament, which assembles and disassembles, the intermediate filament is often fixed in position, so it secures the structure of the cell and keeps organelles such as the nucleus in place.


An overview of the organization of microtubules and microfilaments in an animal cell. Intermediate filaments are not indicated, but keep in mind that they provide structural support for the cell, so their organization should be close to that of microtubules.
The general building of microtubules and microfilaments. Intermediate filaments are not shown, because they varied in composition. However, their structures as solid rods are similar to that of micofilaments. 








Reference:

Campbell, et al. Biology: A Global Approach. 11th ed., Pearson, 2017.
Cooper GM. The Cell: A Molecular Approach. 2nd ed., 2000.
Lodish H, Berk A, Zipursky SL, et al. Molecular Cell Biology. 4th ed., W. H. Freeman, 2000.