Malaria parasites Genetic fingerprints

Genetic fingerprints can track drug resistance in malaria parasites :

Resistance to the frontline malaria drug artemisinin can be identified by surveying the genomes of malaria parasite populations, a worldwide research collaboration has shown.

Genetic fingerprinting has been able to detect strains of drug-resistant malaria parasites in Western Cambodia.

The effectiveness of artemisinin – this key drug against malaria – is weakening, threatening hundreds of thousands of lives. It is a major objective of the World Health Organization to stop the spread of malaria parasites that are resistant to drugs.

The team, led by researchers at the University of Oxford and the Wellcome Trust Sanger Institute, discovered multiple strains of the malaria-causing parasite Plasmodium falciparum that appear to be rapidly expanding throughout the local parasite population in Western Cambodia, a known hotspot for drug resistance. These strains have emerged recently and are all artemisinin-resistant.

The scientists were able to characterise distinct genetic patterns or 'fingerprints' for each of the strains, showing the approach offers a rapid and novel way to detect and track the global emergence of drug resistance. Their findings provide deep insights into how resistance emerges and is maintained by certain parasite populations.

The international group used new genome sequencing technologies to investigate how genetic monitoring of malaria on a large scale could be used to track drug resistance. They sequenced the entire DNA of malaria parasites in over 800 samples from Africa and from South East Asia.

'Our survey of genetic variation showed that Western Cambodian malaria parasites had a population structure that was strikingly different to those of the other countries we analysed,' says Professor Dominic Kwiatkowski, senior author of the paper from the University of Oxford and the Wellcome Trust Sanger Institute near Cambridge. 'Different not just from countries in Africa, but also different from malaria parasite populations in neighbouring Thailand, Vietnam, and even Eastern Cambodia.

 

Artemisinin resistance is an emergency which could derail all the good work of global malaria control in recent years. We desperately need methods to track it in order to contain it, and molecular fingerprinting provides this.

Professor Nicholas White

 

'Initially, we thought our findings might be just an anomaly. But when we investigated further we found three distinct sub-populations of drug-resistant parasites that differ not only from the susceptible parasites, but also from one another. It is as if there are different ethnic groups of artemisinin-resistant parasites inhabiting the same region.'

One important benefit of this genetic approach is that, even without knowing the precise genetic causes of drug resistance, researchers are able to quickly identify resistant strains – an important step towards effective worldwide surveillance.

'Public health authorities need rapid and efficient ways to genetically detect drug-resistant parasites in order to track their emergence and spread,' says Dr Olivo Miotto, first author of the paper from Oxford University, Mahidol University in Thailand, and the MRC Centre for Genomics and Global Health. 'Our approach allows us to identify emerging populations of artemisinin-resistant parasites, and monitor their spread and evolution in real time. This knowledge will play a key role in informing strategic health planning and malaria elimination efforts.'

Western Cambodia appears to be a hotspot for the emergence of drug resistance, but it is not fully known why. Resistance to other malaria drugs, namely chloroquine and sulfadoxine/pyrimethamine, first developed in Southeast Asia before spreading to Africa. This study offers new leads that the consortium will be pursuing as to why drug resistance arises more readily in some locations when compared with others.

'Whilst we have not yet identified the precise mechanism of action or resistance to artemisinin, this research represents substantial progress in that direction,' says Professor Nicholas White of Oxford University and Mahidol University. 'It also provides an important insight into why antimalarial drug resistance (previously to chloroquine and antifols, and now to artemisinin) arises in Western Cambodia.'

He adds: 'Artemisinin resistance is an emergency which could derail all the good work of global malaria control in recent years. We desperately need methods to track it in order to contain it, and molecular fingerprinting provides this.'

Fingerprinting offers a new tool for monitoring public health threat For Malaria Parasite drug resistance : 26Oct 2013

Fingerprinting offers a new tool for monitoring public health threat For Malaria Parasite drug resistance : 26Oct 2013

Resistance to the frontline antimalarial drug, artemisinin, can be identified and tracked by analysing the genetic fingerprint of parasite populations, a study published online today in ‘Nature Genetics’ demonstrates.
The effectiveness of this key drug is weakening, threatening hundreds of thousands of lives, and new methods of tracking resistance are vital for understanding how it could be contained.

An international team of researchers used new genetic sequencing technologies to analyse the whole genetic make-up, or genomes, of samples of the malaria-causing parasite Plasmodium falciparum. They discovered multiple strains of the parasite that seem to be rapidly expanding throughout the local parasite population in Western Cambodia, a known hotspot for drug resistance. These strains have emerged recently and are all resistant to artemisinin.

The scientists were able to characterise distinct genetic patterns, or 'fingerprints', for each of the strains, showing the approach offers a rapid and novel way to detect and track the global emergence of drug resistance. Their findings provide important insights into how resistance emerges and is maintained by certain parasite populations.

A major objective of the World Health Organization is to stop the spread of malaria parasites resistant to leading drugs. Researchers from 23 institutions across South-east Asia, Africa, the USA and the UK sequenced parasite genomes from more than 800 malaria samples from Africa and South-east Asia with the aim of investigating how the large-scale genetic monitoring of malaria could identify and track drug resistance.

"Our survey of genetic variation showed that Western Cambodian malaria parasites had a population structure that was strikingly different to those of the other countries we analysed. Different not just from countries in Africa, but also different from malaria parasite populations in neighbouring Thailand, Vietnam, and even Eastern Cambodia," says Professor Dominic Kwiatkowski, senior author of the paper from the Wellcome Trust Sanger Institute and University of Oxford.

"Initially, we thought our findings might be just an anomaly. But when we investigated further we found three distinct sub-populations of drug-resistant parasites that differ not only from the susceptible parasites but also from one another. It is as if there are different ethnic groups of artemisinin-resistant parasites inhabiting the same region."

One important benefit of this genetic approach is that, even without knowing the precise genetic causes of drug resistance, researchers are able to quickly identify resistant strains - an important step towards identifying molecular markers to enable effective worldwide surveillance.

Dr Olivo Miotto, first author of the paper from Oxford University, Mahidol University in Thailand, and the MRC Centre for Genomics and Global Health, said: "Public health authorities need rapid and efficient ways to genetically detect drug-resistant parasites in order to track their emergence and spread. Our approach allows us to identify emerging populations of artemisinin-resistant parasites, and monitor their spread and evolution in real time. This knowledge will play a key role in informing strategic health planning and malaria elimination efforts."

Western Cambodia seems to be a hotspot for the emergence of drug resistance, but it is not fully known why. Resistance to other malaria drugs, namely chloroquine and sulfadoxine/pyrimethamine, first developed in South-east Asia before spreading to Africa. This study offers new leads regarding why drug resistance arises more readily in some locations than in others, which the consortium will be pursuing.

"While we have not yet identified the precise mechanism of action or resistance to artemisinin, this research represents substantial progress in that direction. It also provides an important insight into why antimalarial drug resistance (previously to chloroquine and antifols, and now to artemisinin) arises in Western Cambodia," said Professor Nicholas White, Director of the Wellcome Trust-Mahidol University-Oxford Tropical Medicine Research Programme in Thailand.

"Artemisinin resistance is an emergency which could derail all the good work of global malaria control in recent years. We desperately need methods to track it in order to contain it, and molecular fingerprinting provides this."

In the longer term, the findings provide an important resource for exploring the underlying mechanisms of resistance. Several genetic variations were discovered in genes that are suspected to play a part in drug resistance, notably those that code transporter proteins and those implicated in DNA repair. These findings provide a rich resource for researchers investigating the molecular mechanism of drug resistance.

"This research demonstrates the value of collaborative working to survey the genetic landscape of malaria across the globe," added Dr Abdoulaye Djimdé from the Malaria Research and Training Centre, University of Science, Techniques and Technologies of Bamako, Mali and the Sanger Institute. "Continuing global genetic surveillance and investigation will help us to identify the emergence of further resistant strains and improve our understanding of how they arise and spread."

There were an estimated 219 million cases of malaria in 2010 and an estimated 660 000 deaths. The World Health Organization Global Plan for Artemisinin Resistance Containment is a call to action that outlines measures to protect the value of artemisinin-based combination therapies for Plasmodium falciparum malaria.

Co-discoverer of DNA

Co-discoverer of DNA
The Nobel Prize winning scientist who co-discovered the structure of DNA 60 years ago has said Ireland cannot be a success in science unless it knows as much as other nations.
Dr James Watson, 86, said the investment made in research in Ireland over the past 40 years is beginning to pay off and there are some very good scientists in the country.
He was asked about comments he made last month in San Diego, where he referred to ignorance being the curse of the Irish. Dr Watson said what he meant was that historically Irish people lacked knowledge. He said that he was not implying that Irish people were stupid.
Ireland just has to be good at technology, he said, and that takes a long time and requires a serious university system. He said it is very important to make science appealing to young people.
Dr Watson, who is now engaged in cancer research, said he is convinced genetics will not lead to the discovery of a cure for cancer, but chemistry will.
On the level of investment in cancer research, he said he does not believe that too much is being spent on it.  Dr Watson said he did not think the future of cancer research is dependent on a big burst of investment in the area. He said what is really limiting the search for a cure for cancer is ideas and intelligent people.  Dr Watson was in Dublin to unveil a new sculpture in the Botanic Gardens in Dublin marking the 60th anniversary since the discovery of the double helix structure of DNA.

human neurons

In 1937, John Zachary Young suggested that the squid giant axon could be used to study neuronal electrical properties. Being larger  human neurons than but similar in nature to human neurons , squid cells were easier to study.  human neurons By inserting electrodes into the giant squid axons, accurate measurements  human neurons  were made of the membrane potential. human neurons The cell membrane of the axon and soma contain voltage-gated ion channels that allow human neurons  the neuron to generate and propagate an electrical signal (an action potential). human neurons  These signals are generated and propagated by charge-carrying ions including sodium (Na+), potassium (K+), chloride (Cl-), and calcium (Ca2+).

There are several stimuli that can activate a neuron leading to electrical activity, including pressure, stretch, chemical transmitters, and changes of the electric potential across the cell membrane. Stimuli cause specific ion-channels within the cell membrane to open, leading to a flow of ions through the cell membrane, changing the membrane potential.

Thin neurons and axons require less metabolic expense to produce and carry action potentials, but thicker axons human neurons  convey impulses more rapidly. To minimize metabolic expense while maintaining rapid conduction, many neurons have insulating sheaths of myelin around their axons. The sheaths are formed by glial cells: oligodendrocytes in the central nervous system and Schwann cells in the peripheral nervous system. The sheath enables action potentials to travel faster than in unmyelinated axons of the same diameter, whilst using less energy. human neurons The myelin sheath in peripheral nerves normally runs along the axon in sections about 1 mm long, punctuated by unsheathed nodes of Ranvier, which contain a high density of voltage-gated ion channels. Multiple sclerosis is a neurological disorder that results from demyelination of axons in the central nervous system.

Some neurons do not generate action potentials, but instead generate a graded electrical signal, which in turn causes graded neurotransmitter release. human neurons  Such nonspiking neurons tend to be sensory neurons or interneurons, because they cannot carry signals long distances.

neurons

Neural coding is concerned with how sensory and other information is represented in the brain by neurons. neurons The main goal of studying neural coding is to characterize the relationship between the stimulus and the individual or ensemble neuronal responses, neurons and the relationships amongst the electrical activities of the neurons within the ensemble. It is thought that neurons can encode both digital and analog information.

second checkpoint is located at the end of G2 phase

   

The second checkpoint is located at the end of G2 phase, triggering the start of the M phase (mitotic phase). In order for this checkpoint to be passed, the cell has to check a number of factors to ensure the cell is ready for mitosis. If this checkpoint is passed, the cell initiates the many molecular processes that signal the beginning of mitosis. The CDKs associated with this checkpoint are activated by phosphorylation of the CDK by the action of a "Maturation promoting factor" (Mitosis Promoting Factor, MPF).

The molecular nature of this checkpoint involves an activating phosphatase, known as Cdc25, which under favorable conditions removes the inhibitory phosphates present within the MPF (term for the cyclin B/CDK1 complex). However, DNA is frequently damaged prior to mitosis, and, to prevent transmission of this damage to daughter cells, the cell cycle is arrested via inactivation of the Cdc25 phosphatase. This is done by the ATM kinase protein which phosphorylates Cdc25 which leads to its ubiquitinylation and destruction.

Human Placental Lactogen example : Estrogen ,Progesterone

Human Placental Lactogen (hPL [Human Chorionic Somatomammotropin]): This hormone is lactogenic and growth-promoting properties. It promotes mammary gland growth in preparation for lactation in the mother. It also regulates maternal glucose, protein, and fat levels so that this is always available to the fetus.

Estrogen: referred to as the "hormone of women" because it stimulates the development of secondary female sex characteristics. It contributes to the woman's mammary gland development in preparation for lactation and stimulates uterine growth to accommodate growing fetus.

Progesterone: necessary to maintain endometrial lining of the uterus during pregnancy. This hormone prevents preterm labor by reducing myometrial contraction. Levels of progesterone are high during pregnancy.