Author: Hazelnut-of-Life

>>>INHIBITORS OF PROTEASES<<<

As stated in Zinsser Microbioloby book, many viral proteins are synthesized in the form of precursors that must be cleaved in order to yield the functional proteins required. Often, such as in the case of picornaviruses, the togaviruses, and the retroviruses, these cleavages are effected by highly specific virus-encoded proteases that are prime targets for interference with virus multiplication. In particular, the three-dimensional structure of the HIV protease, which cleaves both the gag and env protein precursors has been solved at the atomic level by x-ray crystallographic analysis; strenuous efforts are now being made, with the use of computer modeling, to design inhibitors of it. This approach is also promising for viruses like the coronaviruses, the paramyxoviruses, and the orthomyxoviruses in which envelope glycoproteins such as the fusion proteins and the hemagglutinins must be cleaved to permit these viruses to infect cells effectively. These cleavages, which occur in basic amino acid sequences are carried out by host proteases that are often referred to as trypsin-like. In the case of influenza virus it has been shown that peptidyl chloroalkyl ketones ( which bind covalently to the substrate-binding sites of proteolytic enzymes ) strongly inhibit virus multiplication when they contain a palmityl residue, as wel as at least two adjacent amino acids (e.g. , palmityl-fluorophenylalanine-alanine-lysine-arginine-chloroethylketone)

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As stated in Zinsser Microbiology book, viruses are encapsidated segments of genetic material, and like other genetic systems, viral genomes are not invariate but are subject to change by mutation. Spontaneous mutations occur constantly in the course of virus multiplication, and while many mutations are lethal, others are not. Mutant virus strains can also be generated in the laboratory as a result of mutagenesis, and it is from mutagenized virus populations that mutant isolation is usually undertaken.

>>Mutants with Other Commonly Observed Phenotypes:

1. Plaque-size Mutants
2. Host-Range Mutants
3. Drug-Resistant Mutants
4. Enzyme-Deficient Mutants
5. Neutralization Escape Mutants

>>Genetic Interactions Among Viruses:

Under conditions of multiple infection, cells may become infected with two or more virus particles with different genomes. If they are sufficiently closely related-that is, if they belong to the same genus-they can interact genetically.

1. Recombination. Viruses must be reasonably closely related for recombination to occur; only viruses within the same genus recombine.
2. Genome Segment Reassortment. Recombination proceeds not by classic recombination involving breakage and reformation and covalent bonds but by simple reassortment of segments into new genomic sets.
3. Multiplicity Reactivation. Viruses that contain double-stranded DNA frequently exhibit multiplicity reactivation after being subjected to UV radiation. Recognized by the fact that the frequency of viral survivors increase sharply with multiplicities of infection above 1.
4. Complementation. Infection of cells at restrictive temperatures with two virus mutants that bear temperature-sensitive mutations in different genes and neither of which can multiply alone. It plays a major role in permitting the survival of viruses with genomes that contain damaged or nonfunctional genes.
5. Phenotypic Mixing and Phenotypic Masking. Represent a special case of complementation. When two closely related viruses, infect the same cell, the two types of progeny genomes may become encapsidated not only by their own capsids but also by hybrid capsids.
6. Suppression. Reversal of mutant phenotypes can occur by several mechanisms. The most obvious obvious is simple reversion, that is back mutation at the nucleotide of the original mutation.

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Each year, new strains of influenza virus cause millions to miss work or classes. From where or what do these and other “emerging viruses” arise?

Three processes contribute to the emergence of viral diseases:

1. An existing virus can evolve and cause disease in individuals who had developed immunity to the ancestral virus.>>>For example, annual or biennial influenza episodes are caused by virus that have evolved into new genetic strains. The “new model” is different enough from last year’s virus that the human immune system must develop defenses as though it were responding to the virus for the first time. Between flu outbreaks, the evolving viruses are maintained within other animal hosts, especially ducks and other water fowl.
2. An existing virus can spread from one host species to another. For example, monkeypox virus, which causes pocking of the host’s skin, spread from African monkeys to Asian monkeys in the 1950s, when monkeys from those two continents were transported together under crowded conditions to laboratories that were using the animals to develop and test polio vaccines. The World Health Organization documented the first cases of monkeypox in humans in forest villages of Zaire (in Central Africa) in the 1970s. It is likely that humans did not acquire the virus directly from monkeys, but rather from squirrels and other game animals that had harbored the virus without becoming ill.
3. An existing virus can disseminate from a small population to become more widespread. >>>The hantavirus that made news in 1993 was not really a new virus, even to humans. Small rodents called deer mice are the reservoirs for the virus, and it is probable that occasional infections of humans in the southwestern U.S. have occurred for decades. Indeed, to the Navajo, mice are taboo, bearers of strange illness. In 1993, the population of deer mice exploded after a wet year increased their food supply. Humans became infected when they inhaled dust containing hantavirus deposited in the urine and feces of deer mice.

Thus, emerging viruses are generally not new, but are existing viruses that expand their “host territory” by evolving, by spreading to new host species or by disseminating to a larger proportion of the host species…

Name the ten wealthiest men in the world. Name eight people who have won the Nobel or Pulitzer prize.

How did you do? I didn’t do well either. With the exception of your trivia hounds, none of us remember the headliners of yesterday too well. Surprising how quickly we forget, isn’t it? And what I’ve mentioned above are no second-rate achievements. These are the best in their fields. But the applause dies. Awards tarnish. Achievements are forgotten.

Here’s another quiz. See how you do in this one. Name ten people who have taught you something worthwhile. Name five friends who have helped you in difficult time. Easier? It was for me, too. The lesson? The people who make a difference are not the ones with the credentials, but the ones with the concern.

Greed comes in many forms. Greed for approval. Greed for applause. Greed for status. Greed for the best office, the fastest car, the prettiest date. Greed has many faces, but speaks one language: the language of more. Epicurus noted, “Nothing is enough for the man to whom enough is too little.” And what was that observation`of John D. Rockfeller’s? He was asked, “How much money does it take to satisfy a man?” He answered, “Just a little more.” Wise was the one who wrote, “Whoever loves money never has money enough; whoever loves wealth is never satisfied with his income” (Eccles. 5:10 NIV)

Greed has a growling stomach. Feed it, and you risk more than budget-busting debt. You risk losing purpose.

1. Ecoursem – this website will guide you about self- improvement and some matter of productivity.

2. edX – another website that will help you to engage learning from the best universities of the world.

3. FutureLearn- a digital education platform with free courses and online course categories.

4.Open2Study- a website with undergraduate and postgraduate courses.

5.Saylor.org.- another website with free online courses available globally.

6. Stuvera- website with free online courses, eBooks and many more.

Disability is never simply limitation in social and vocational functioning, never an objectively determinable, pathological clinical entity originating in the bodies of individuals. Rather, defying simple definition, it is an elastic social category shaped and reshaped by cultural values, societal arrangements, public policies, and professional practices. It is always an array of culturally constructed identities and highly mutable social roles.

Cold are the people who have long forgotten how warm human togetherness may be; how much consolation, comfort, encouragement, and just ordinary pleasure one may derive from sharing one’s own lot and one’s hopes with others—“others like me,” or more exactly, others who are “like me” precisely for the reason of sharing my plight, my misery and my dream of happiness; and even more so for the fact of my concern with their plight, their misery, and their dream of happiness.”

The French philosopher Jean-Paul Sartre (1905-1980) had nothing but disdain for the concept of companionship. He saw all people as competitors. According to this view, people are always striving with one another in a kind of continual rivalry.

Competition can be healthy in the worlds of business and athletics. It becomes detrimental, however, when a person’s attitudes and actions become viciously self-serving. Such competition should have no place in marriage or in the church. When spouses try to outdo each other in a career, or in some other endeavor, the marriage may be in trouble. The apostle Peter, in a male-dominated society, admonished men to teat their wives as companions, as “heirs together of the grace of life” (1 Peter 3:7)

When someone starts complaining about people in the church who always try to run things, a competitive spirit may be at the heart of the problem. In Romans 16, Paul saw his fellow believers as companions, not competitors. All Christians, mean and women, are members of God’s family and serve Jesus as co-workers in the greatest of all enterprises. Companions, not competitors-that’s what Christ wants us to be!

When we submit to God’s plans, we can trust our desires. Our assignment is found at the intersection of God’s plan and our pleasures. What do you love to do? What brings you joy? What gives you a sense of satisfaction?

Some long to feed the poor. Other’s enjoy leading the church….Each of us has been made to serve God in a unique way…

The longings of your heart, then, are not incidental; they are critical messages. The desires of your heart are not to be ignored; they are to be consulted. As the wind turns the weather vane, so God uses your passions to turn your life. God is too gracious to ask you to do something you hate.