Nature and Limits of Science

Science is a public domain and is free from any social or political situation.

The scientific advances made by a country have global impact. For instance: polio vaccine. Scientific research also helps in the betterment of one country through research project grants that can be granted to the needy from various research institutions across the globe. For example, BCPB (British Counsel for Prevention of Blindness) has granted a Trachoma Research Funding Project to Tumaini University, Tanzania, Africa .Also along with the advantages, it has certain limitations as well. All research is funded, and any situation that affects a country’s financial situation as a whole will have its effect on research. Scientific findings are reported back to the community and will be subject to discussion, which may also result in a change in research policies.

GLOBAL WARMING: Fact or Myth?

 

INTRODUCTION:

In the year 2009, more than 200 countries participated in a climate control conference held in Copenhagen for discussing the threats posed to the environment by global warming. The representatives of the countries along with more than 2,500 scientists from several countries were of the opinion that global warming is a major threat to the environment and the future of human population because of pollution and greenhouse gases in particular. Despite of that many scientists were debating that whether this climate change was caused due to human activities or the natural process in the universe and is affecting earth’s climate. There are several natural factors that determine earth’s environment, such as the orbit and degree of tilt determine the warming and cooling of earth. Moreover volcanic eruptions were a cause of global warming in the prehistoric era but due to reduction in these eruptions lately life forms produced on earth. The fact cannot be ignored that after the industrial revolution, the warming of the earth has increased by 35% due to greenhouse gas emission (Edwards 2010).

Greenhouse gases are those gases which trap the heat in the atmosphere and emit radiation which affects the temperature of the surroundings. Greenhouse gases involves several gases produced naturally or by human activities such as carbon dioxide (CO²), Methane (CH⁴), Nitrous oxide (N²O), and other fluorinated gases etc (USEPA 2011).   Although scientists believe that natural process have also caused a variable change in earth’s atmosphere but it has been caused mainly due to human activities emitting greenhouse gases, deforestation, emission of aerosols etc (Mohr 2005 & Mitchell 2010).

The scientists had predicted about the changes in temperature in the coming decade as the atmosphere of earth is continuously changing naturally but studies showed that the climate and temperature of the earth has increases at a much higher rate than the scientists predicted and is still accelerating which can have disastrous consequences such as floods, extreme weather and mass extinction of species, skin diseases and other epidemics etc. (Meinshausen et al, 2009).  

Human activities have emitted a lot of carbon dioxide in the earth’s atmosphere. A study showed that the natural carbon sinks of the nature, where carbon was absorbed and diminished, have been disrupted by human activities. According to a report by US National Oceanic and Atmospheric Administration (NOAA), the concentration of carbon dioxide alone in the environment has elevated up to 19 billion tones since past four years. And after carbon dioxide, it is methane whose concentration has been increased considerable in the past few years (Greenhouse Gas, 2011).

The graph below shows an increment in the amount and concentration of greenhouse gases such as methane, carbon dioxide, nitrous oxide etc. over a decade.

MAJOR THREATS POSED BY GLOBAL WARMING:

Even a small rise in the global temperature can give rise to extreme situations because the entire environment is interconnected with each other. Several factors such as, water currents, rainfall, wind, intensity of sunlight, atmospheric pressure, presence of debris in the atmosphere etc  are connected with each other and together form the weather of the earth. If any of these factors in misbalanced it can pose major threats to environment. According to various researches and studies it has been concluded that if the atmospheric temperature increases, it can lead to increase in the sea level by 0.09 - 0.88 m (Stanford Solar Center 2008) because of the melting of glaciers and polar ice caps, increase in storms, floods, drought and other such abrupt changes in the climate and if it is nor brought under control, then by the end of this century we can expect to see a raise of 7 °F in earth’s climate. Global warming is a serious threat posed to the earth’s environment and can have severe effects which can ultimately lead to the extinction of several wildlife and other species including human being from the face of earth (Edwards, 2010). It also poses a major threat to human health because it can result in the spreading of diseases such as malaria and other epidemic due to poor air quality and living conditions. Greenhouse gases are also a major cause of atmospheric pollution causing breathing problems and asthma. The depletion of ozone layer can allow the UV lights to enter into earth’s atmosphere and can give rise to visual and skin related diseases such as skin cancer. There have been several cases of skin cancer reported in the United States due to radiation of the sun   (Stanford Solar Center 2008).

CONTRIBUTION OF GREENHOUSE GASES IN GLOBAL WARMING:

Greenhouse gases play a major role in global warming. Green house gases such as methane, nitrous oxide and chlorofluorocarbons even if found in low concentrations, can give rise to major issues because even though they are lower in concentration but their each molecule can absorb high amount of infrared radiation as compared to molecules of other gases. According to a study, it was observed that greenhouse gases have caused about 43% of elevation in radiative forces and therefore pose a major threat to environment. (Lashof & Ahuja, 1990)

We know that our atmosphere is made up of 78% nitrogen and 21% oxygen along with water vapor and several other gases contributing the rest. These other gases which include argon, carbon dioxide, neon, helium, methane, hydrogen, nitrous oxide and ozone are the cause of global warming and greenhouse gas issues.  Natural and various human activities lead to the emission of greenhouse gases (carbon dioxide, methane, nitrous oxide and fluorinated gases which includes fluorine, chlorine and bromine). These gases trap the atmospheric heat and emit radiation and their increased concentration in the atmosphere which can lead to global warming. (Greenhouse Gas, 2011)   

Why are they called “greenhouse” and how do they cause global warming:

The earth absorbs the heat in the daytime and radiated it in the space during the night except some amount which is used to maintain earth’s atmosphere. These specific gases do not allow the earth to radiate the heat back in the space and trap it in the earth’s atmosphere making the atmosphere of the earth warmer than required and converting the earth into something which can be compared to a green house. That is why these gases are called ‘greenhouse gases”.  (Greenhouse Gas, 2011)

The emission of greenhouse gases has resulted into a variable depletion of ozone layer found in the atmosphere which protects the atmosphere from harmful ultraviolet radiation. With the depletion of atmospheric ozone, the UV rays can easily penetrate into earth's atmosphere causing elevation in earth's atmosphere. The green house gases are one of the primary reasons for ozone depletion because when they move above to the stratosphere, they do not get washed away by rainfall but instead they react with atmospheric ozone and react with it to destroy it. The scientists have estimated that with a decrease on one percent atmospheric ozone, there will be an increase of about two percent in the penetration of UV light in the earth’s atmosphere. (Greenhouse Gas, 2011)

Although, certain scientists debate that these changes in earth’s atmosphere are not caused by human activities, but are seen due to natural changes such as cloud cover. They also suggest that increased level of carbon dioxide and other greenhouse gases are the result of warming of earth, changes in the solar system and radiation of the sun and human activities are not the potential cause of global warming because earth’s atmosphere is continuously changing over the years (Edwards, 2010).

CONCLUSION:

There are certain reports by the workers who claim the temperature of the earth is not increasing but dropping eventually, the increase in the level of carbon dioxide is due to natural changes in earth’s environment, activity of the sun and global warming is a myth. But the reports from Intergovernmental Panel on Climate Change (IPCC) support the fact that global warming is a result of human activities which produce factors such as greenhouse gases, aerosols, debris etc. which continue to deplete the earth’s covering and this theory is the result of a research conducted on the CO₂ trapped in the ice. Although there is not much reports of the opinion that global warming is not driven by human activities and most of the studies support the human driven theory of climate change. It is evident that human activities have increased the level of atmospheric pollution and given rise to environmental problems such as deforestation, pollution of water reservoirs such as rivers and increase in the carbon dioxide level by burning of fossil fuels etc. In the end, no matter what factors are responsible for global warming, it is our duty to keep our planet pollution free and reduce the emission of harmful gases and byproducts which whether or not harm the environment, do harm human health.

Model of E.coli replication fork

A replication fork is formed during the replication of the DNA and is initiated by the enzyme helicase which breaks the hydrogen bond formed between the nucleotides thus separating the strands. The two strands will act as a template for leading and lagging strand, during replication. In the leading strand, replication is carried out in 3’ to 5’ direction allowing the new strand to be synthesized 5’ to 3’. The DNA polymerase continuously reads and adds nucleotides to the growing strand. In the lagging strand, the replication fork moves in 5’ to 3’ direction and the growing strand is synthesized 3’ to 5’. Since DNA polymerase catalyzes the polymerization of dNTPs only in the 5′ to 3′ direction, therefore the enzyme primase reads the DNA and adds short segments of RNA to it. DNA polymerase lengthens the segments and Okazaki fragments are formed which are joined by DNA ligase. Thus with the help of leading and lagging strand the replication form moves forward till the total DNA is replicated.

Biology Fact-Sheet on ‘Fragile X Syndrome’

CHARECTERISTICS

Fragile X syndrome is an X-linked dominant disorder causing mental and emotional disabilities. This disorder is heritable and can be passed from one generation to another. The persons suffering from this disorder show phenotypes like prominent ears, long face, autism and behavioral problems (Fragile X Syndrome). It is called “fragile X syndrome” because the affected X chromosomes are narrowed at the end when observed under high resolution microscope. (Fragile X Syndrome, 2007)

 Since the gene causing is present on the X chromosome, the number of affected males is higher than the number of affected females. It is so because, males have only one X chromosome present (XY chromosome) while females have two X chromosomes (XX chromosomes). Most of the females with fragile X syndrome have one normal X chromosome and one defective X chromosome but they have only one functional copy of X chromosome. During protein formation cell randomly chooses only one X chromosome for translation, therefore sometimes females with a defective X chromosome also have normal phenotype. Where as in males the X chromosome is always utilized in protein formation and the disorder is expressed. (Fragile X Syndrome)

CAUSES

It is caused by the mutation in a gene that encodes for the Fragile X Mental Retardation Protein (FMRP) required for the brain to carry out normal functions. Due to the transcriptional silencing of the Fragile X Mental Retardation 1 (FMR1) gene the expression is inhibited. (Garber 2008)

The promoter region of the FMR1 gene consists of a repeated CGG sequence. A normal FMR1 gene has about 6 to 40 CGG repeats where a mutated FMR1 may have more than 200 repeats. The number of repeats vary from person to person.  A mutation ranging from 55 to 200 repeats is called “Premutation” where as a mutation with more than 200 repeats in a gene is known as “Full Mutation” and the phenomenon is called as methylation. (Fragile X Syndrome)

 Due to extended CGG repeats in the untranslated 5′- region the gene is inactivated and production of FMRP is halted. FMRP is a protein which selectively binds to RNA and carries out the negative regulation of protein synthesis in neuronal dendrites (Hagerman 2005). When FMRP is not present, the transcripts regulated by FMRP are over translated resulting in the abundance of proteins. The protein abundance reduces the synaptic strength due to trafficking of AMPA receptor (α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor). Because AMPA receptors get inhibited, the synaptic transmission to the Central Nervous System is reduced leading to synaptic plasticity and mental abnormalities. Because synaptic plasticity is responsible for learning and memory, its alteration results into fragile X syndrome. (Garber 2008)

TREATMENT

There are several ongoing research projects funded by National Institute of Child Health and Human Development (NICHD), which aim to find a suitable cure for this disorder. NICHD has established three research centers across the country for the treatment of Fragile X Disorder.  The disorder can be determined by carryings genetic testing. In order to find the treatment, the research is carried out on several model analogous to human brain the possible outcomes are discussed as follows: (Fragile X Syndrome)

1.    Production of certain chemical in the brain that repairs the mutated, extended FMR1 gene.
2.    A drug that initiates reverse methylation.
3.    Replacing the mutated FMR1 gene with a normal gene.
4.    To introduce FMRP artificially into brain via pills or injections.
5.    To find a substitute for FMRP that carries out similar function.

Bradford micro-assay

Bradford micro-assay is a technique which is used to determine the total protein concentration in an unknown sample. The presence of protein is determined by a dye named, Comassie Brilliant Blue G250 (Bradford Reagent) which favorably binds to the basic amino acid residues like arginine and lysine. Upon binding, the dye turns blue in the presence of protein or may appear brown in color if the protein is absent in the solution. The quantity of protein is analyzed with the help of a spectrophotometer which measures the quantity of protein by measuring its transmission properties. To analyze the quantity of protein, a standard curve with known amount of protein content is prepared first. The standard curve is a smooth line and by locating the value obtained from unknown sample, we will get the value of the protein content in the unknown sample.


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Use of OLIGONUCLEOTIDES as anti viral drugs

Antibiotics are widely used against a wide spectrum of microorganisms but they are not effective on the viruses because viruses are not living and they become active only through the viral transcript. Therefore a different class of drugs known as antiviral drugs is meant for the treatment of viral diseases. Most of the antiviral drugs are the analogues of nucleosides lacking hydroxyl groups, which get incorporated in the viral genome when the viral DNA replicates itself. The double stranded DNA created after replication is inactive due to the presence of nucleoside analogues and the virus is not able to grow. (Mindel 1983)

Conventional antiviral drugs do not destroy the virus but only inhibits their growth by halting the replication. But there is a significant risk associated with these drugs because the nucleoside analogues may also inhibit the replication of cellular DNA.  (Soundararajan 2009)

Therefore there is a requirement of a drug molecule that acts only on the specific target and selectively inhibits the gene expression. There has been an ongoing research on the usage of oligonucleotide as antiviral in antisense and RNA interference against pathogenic RNA viruses. Oligonucleotide as antiviral therapeutics has proved to be effective in this direction and has shown high target specificity so far.  (Lopez-Fraga 2008)

 It utilizes complementary oligonucleotide sequence that inhibits gene transcription either by catalytic degradation of mRNA or binding to mRNA sites for translation. It is different from the optimal approach in being specific because the optimal approach aims at total inhibition of the viral genome. (Spurgersa 2007)

Oligonucleotides in RNA interference (RNAI)

The double stranded small interfering RNA (siRNA) have been used in the mammalian cells for gene silencing. They are about 21 nucleotides in length and generated by the cleavage of long dsRNA by RNase class III riboendonuclease proteins, also known as Dicer. The Dicer generated siRNAs are incorporated into the RNA-induced silencing complex (RISC). RISC is activated by the action of Argonaute 2 (AGO2). After getting activated, the siRNA cleaves the sense strand of targeted RNA and generates a complementary sequence to the mRNA. The endonuclease present in the RISC complex, cleaves mRNA which is then degraded by intracellular proteins and does not gets translated. The RISC complex is recovered at the end of the process. (Lopez-Fraga 2008)

Another method of gene silencing involves micro RNAs (miRNA) which are produced in the cell as a separate species and posses some complementary sequences. They are about 21 nucleotides long non coding RNAs that bind to the mRNA and translation is inhibited leading to degradation of mRNA. (Lopez-Fraga 2008)

The RNAi based antiviral therapy is analogous to this naturally occurring process. Its aim to silence the targeted viral gene without harming the cellular genes and it can be achieved either by transfecting the cell with synthetic siRNA or short hairpin RNA (shRNA) resembling miRNA. There has been a sufficient progress in achieving the stability, drug resistance, toxicity, and cost of siRNA therapy. There are several other advantages associated with siRNA therapy like, they have short pharmacological development time period, very specific in action, can be easily synthesized and a broad spectrum of pathogens could be targeted. These findings support siRNA being used as an antiviral therapy for the treatment of highly pathogenic viruses. (Lopez-Fraga 2008)

Oligonucleotides in Antisense Technology

The antisense technology is not dependent on the host cell mechanism but it is a simple technique where the antisense oligonucleotide combines to the mRNA and inhibits the translation of viral transcript. The analogous antisense oligonucleotides are synthesized artificially and they consist of nuclease activity. Their binding capacity is much higher than the oligonucleotides naturally occurring in the cell. This avoids the binding of the analogue to cellular gene. The analogue is about 20 to 25 nucleotides in length and with 10 to 100% modified bases for effective and specific binding.  (A New Generation of Antiviral Drugs). They are chemically modified and purified to maintain the stability and keep them safe from the exonuclease activity. (Khan 1993)

One of the example of antisense technology is vaccine against Enterovirus and Rhinovirus which are pathogenic viruses and cause several diseases. Antisense antiviral therapy has proved to be very effective in the treatment as no effective treatment was available earlier. Single stranded DNA like antisense compound called, Peptide-conjugated phosphorodiamidate morpholino oligomers   (PPMO) was used. It can easily enter the cell and is specific for internal ribosome entry site (IRES) sequence which is the target sequence against human rhinovirus. The IRES sequence is highly conserved (about 99%) in the Enterovirus and Rhinovirus so it is a good target for a drug. The results showed that PPMO was highly efficient against broad variety of Enterovirus and Rhinovirus.  (Stone 2008)

There are several advantages associated with antisense antiviral therapy like , they do not depend upon the host machinery for functioning, they are very specific in action, can be used against a wide variety of pathogens and several diseases such as, HIV, Hepatitis C, Influenza etc. The main concern in the application of antisense antiviral therapy is to maintain its stability in the cell and prevent from degradation, method of delivery and maintain their bioavailabity. Therefore they are first chemically modified before transfection. The success of PPMO vaccine against Enterovirus and Rhinovirus supports the fact that antisense antiviral therapy can be uses as potential drug again undruggable pathogenic viruses. (A New Generation of Antiviral Drugs)

Forces stabilizing the nucleic acid structure

The forces responsible for stabilizing nucleic acid structures include non-covalent intramolecular interactions between the bases, magnitude of the Gibbs free energy and the thermodynamic relationships between enthalpy and entropy changes.

Two different forces and interactions govern the stability, including: 1) Occuring in the plane of the bases (horizontal); most commonly hydrogen bonds; b) Occuring perpendicular to the base planes or "base stacking" effects; these are stabilized by London dispersion forces and the hydrophobic effect. 1. Under the influence of a hydrogen bond, the H becomes more electropositive and becomes a better donor. 2. Stacking is a diffusion controlled, additive, and stabilized by two separate forces: hydrophobic effect and London dispersion forces.