THE NATIONAL BIRD OF INDIA

Natural remedies to treat Chronic Obstructive Pulmonary Disease

Ayurvedic Medicines to cure Coronary Artery Disease

Global Warming Impact on Animals - Part 3

NEW DRUG TO COMBAT SKIN CANCER DEVELOPED

APOBEC- A KEY DEFENSE PROTEIN CAUSES CANCER

APOBEC-2 is a member of the APOBEC family

A recent study conducted by a team of Swiss and Russian scientists led by Sergey Nikolaev at the University of Geneva, Switzerland deciphered that APOBEC, a defense protein that usually functions as protecting agent against viral infection causes cancer in human beings.

APOBEC is a family of intrinsic cellular protein which has the power to modify a single-stranded DNA. Since the viral DNA is being frequently single stranded, the double stranded human DNA cannot be altered.

About 20% of APOBEC mutations arise due to abnormality in the DNA called "double-stranded breaks" where a part of the DNA is in a single-stranded state for a period of time causing multiple mutations. Researchers were able to govern the remaining 80% of APOBEC related mutations. They managed to identify in which direction the replication fork was travelling through the human cells. During the cell division process, the DNA replication starts at a specific location to produce two identical copies from the original DNA. The replication fork is caused by the separation of two original strands and synthesis of the new ones. DNA replication process is a dangerous mutagen when it takes advantage of a weakness during the DNA replication process thereby inducing mutations in our genome.

As a result, new strands are rebuilt as the fork moves along the chromosome. The two strands are replicated in two different mechanisms depending on the direction of the replication fork. Hence the reconstruction of strands is possible only when one of the them are constructed immediately.

Therefore, one strand i.e. the "leading strand" never exists as single stranded DNA whereas the other strand " lagging strand" continues to be single stranded for a period of time. Researchers were able to discover twice as many mutations on the "lagging strand" when compared with "leading strand". Findings suggested that APOBEC takes advantage of the DNA when "lagging strand" remains single and weak.

DNA replication process:

DNA replication process is a process of creating two identical replicas from the original DNA molecule which ensures that the next generation of cells contains the same genetic information.

DNA replication process

Leading strand:

It is one of the two strands which is oriented in 5' to 3' direction travelling towards the replication fork. It is synthesized continuously with no breaks in between.

Lagging strand:

It is a single stranded DNA replicated in 3' to 5' which moves away from the replication fork. It is synthesized discontinuously in fragments known as Okazaki fragments.

Okazaki Fragments:

Okazaki Fragments is a relatively short fragment of DNA which is formed on the lagging template strand during the DNA replication process. In 1968, Reiji Okazaki, a pioneer Japanese molecular biologist along with his wife Tsuneko Okazaki and their colleagues discovered Okazaki fragments while conducting a research on replication of bacteriophage DNA in Escherichia coli.

Some of the encoding members of APOBEC protein family are mentioned below:

• APOBEC3G (A3G): is a single stranded DNA which acts as an effective cellular host defending agent prohibiting the expression of the functional form of the HIV encoded protein Vif. When this wild type of Vif attacks the A3G enzyme, all sorts of host defense advantage provided by A3G gradually diminishes and thereby promoting the emergence of new virulent strains of the HIV virus.A3G acts as a double agent in defense. It can either be an anti-viral factor capable of destroying the virus or it can help diversify viral genomes through gene mutation allowing the virus to be more resistant to drugs.To be more effective, the A3G should be incorporated into the virus.

Protein APOBEC 3G

• APOBEC-1 (A1): It is a cytidine deaminase which is linked with cholesterol control, cancer development and inhibition of viral replication. Levels of A1 is extremely low in the human liver and small intestine but higher in gastrointestinal epithelial cells. A1 is highly expressed in rodents with a wide tissue distribution.
• APOBEC 3A: It is a DNA cytidine deaminase commonly found in human beings, non-human primates and mammals containing antiviral effects. Studies suggests that APOBEC 3A can inhibit activity against parvoviruses, retroviruses, adeno associated virus (AAV), human T-cell leukemia virus type 1 (HTLV-1), foreign DNA and mobility of retrotransposons.

• Activation induced cytidine deaminase: AICDA is an enzyme which creates mutations in DNA by converting cytosine into uracil.

APOBEC Cytidine Deaminase and cancer:

DNA Cytidine deaminase APOBEC3B accounts for multiple human cancers. The researchers discovered that mutations induced by APOBEC3B can be found in many tumorous cells throughout the genome. There are presence of APOBEC mutation pattern in bladder, cervical, breast, head and neck, and lung cancers.

ZIKA VIRUS - ALARMING THREAT TO PREGNANT WOMEN AND NEW-BORN BABIES

The outbreak of Zika virus in Latin American and Caribbean nations spreads panic among the officials. They have warned women to avoid pregnancy amid concerns over an illness causing severe birth defects. Many countries including Brazil, Columbia, Ecuador, El Salvador and Jamaica recommended delaying of pregnancies until more was known about this malignant disease. The pregnant women may not be aware of the danger from the sting of the mosquito bite followed by fever due to Zika virus until it strikes their unborn child. It is suspected to be the cause of microcephaly or abnormally smaller heads  resulting  in brain damage. US health authorities have issued travel warnings to pregnant women in certain countries like South America, Africa, Oceania and Caribbean. The virus is expected to spread more drastically covering local areas in Barbados, Bolivia, El Salvador, French Guiana, Guadeloupe, Guatemala, Guyana, Haiti, Honduras, Martinique, Mexico, Panama, Paraguay, Puerto Rico, Saint Martin, Suriname, Venezuela, Cape Verde in Africa and Samoa in the South Pacific.

 Baby Jose Wesley being bathed in a bucket, Poco Fundo, Brazil. His microcephalic condition was diagnosed a couple of days after his birth

What is Zika Virus?

Zika virus which is a member of Flaviviridae virus family is a mosquito-borne viral disease transmitted to human beings by Aedes aegypti Mosquitoes. It is interconnected with similar pathogenic vector borne Flavivirus such as dengue, West Nile and Japanese encephalitis producing a comparatively mild febrile viral illness known as Zika fever in humans. The incubation period ranges between 3 to 12 days.

Aedes albopictus

    Aedes aegypti mosquito

Spotlight on Zika Virus:

The virus was first identified in April 1947 when a rhesus monkey living in the Zika forest of Uganda developed an unknown febrile illness. Scientists isolated a new transmissible agent from the sick monkey and named it Zika virus. The vector of Zika virus was finally confirmed in 1948 when the same virus was discovered in an Aedes africanus mosquito trapped in the same forest. Researchers were unable to trace any evidence of human infection with ZIKV until twenty years later when it was isolated from human patients in Nigeria.

In 2007, an outbreak of illness characterized by skin rashes, conjunctivitis and arthralgia was reported on the Yap Island, Federated States of Micronesia, but the outbreak caused only mild illness among 108 confirmed cases.

Since 2015, the current outbreak of Zika virus that began in Brazil has now progressed to other countries in Central and South America and to the Caribbean Islands.

Causes of Outbreak in Brazil:

Local authorities suspected the outbreak was due to a massive influx of foreign visitors attending the 2014 Fifa World Cup combined with large population of Aedes aegypti and A. Albopictus mosquitoes in the region. The virus had previously been existed only in some parts of Africa, Asia and the Pacific.

Counter measures to eradicate virus carrying mosquitoes:

With just few months away before the highly anticipated 2016 Summer Olympics going to be hosted in Rio De Janeiro, Brazil. Brazil's Ministry of health has announced its countermeasures to ensure safety and protection of Olympic athletes as well as spectators from  Zika virus who are expected in the city. Based on their countings that August is relatively a drier month in Brazil, the population of mosquitoes that spreads disease could be much lower than at present. Further steps are put forward by the authorities such as inspecting the facilities four months before the events as well as fumigation. However, the latter will only be implemented in extreme cases to avoid health issues for athletes and audiences. Stadium premises will be swept clean daily.

Risk of local Zika Transmission

Symptoms of Zika Virus:

• Low grade fever
• Skin Rashes and Pruritus (severe itching of the skin)
• Arthralgia (pain in a joint) with possible swollen joints.
• Conjunctivitis (red eyes)
•  Myalgia (Muscle pain)
• Headache
• Asthenia (a chronic respiratory disease)
• Digestive problems like abdominal pain, diarrhea and constipation
• Aphthae (mucous membrane ulcerations- a small ulcer formed in groups in the mouth or on the tongue)

Diagnosis:

Consult a healthcare provider and explain to him in detail how you developed the symptoms and from when and where you contracted the virus? The healthcare provider conducts the necessary blood tests to confirm any virus infection like Zika or other similar viruses like Dengue, chikungunya.

Treatment:

Currently, there is no specific anti-viral treatment or medicine for Zika virus infection available. Patients are advised to take plenty of rest and drink fluids to prevent dehydration.

Travel guidance related to Zika Virus:

Travelers are strongly recommended to protect themselves from mosquito bites by:

• Wear appropriate clothing like long-sleeved shirts and long pants to prevent tick bites and mosquito bites.
• Walk in the center of hiking trails and stay away from wooded and brushy areas with high grass, brush and leaves where the ticks are more active.
• The tsetse fly which lives in the sub-Saharan Africa can contract African sleeping sickness or African trypanosomiasis.
• Prevent tsetse fly bites by wearing neutral -colored clothing since they are more attracted to very bright and dark colors, metallic fabric.
• Avoid bushes during the day time. The tsetse fly usually rests in bushes and will bite if disturbed.
• Apply insect repellants containing Deet, Picaridin, oil of lemon eucalyptus which are safe for pregnant and nursing women, but not advisable for children under the age of 3.
• Avail permethrin treated clothing and gear such as boots, pants, socks and tents to kill or repel insects such as mosquitoes and ticks.
• The tsetse flies are attracted to moving vehicles, so inspect the vehicle for any flies before entering.
• Sleep in " screened-in or air-conditioned rooms."

Countries confirmed with Zika virus cases