New, long-lived greenhouse gas found
Perfluorotributylamine (PFTBA) — a novel chemical lurking in the atmosphere, is the most radiatively efficient chemical found to date, breaking all other chemical records for its potential to impact climate.
Management of chilli thrips and mites
Chilli (Capsicum annuum) is one of the important vegetable and commercial spice crops grown throughout the tropics and warm temperate regions of the world.
Although there is a scope to enhance the prod
uctivity of chilli, a number of limiting factors have been attributed for the low productivity, among which, the damage caused by insect pests and mites is of paramount importance.
More than 293 insects and mite species attack the crop in field as well as storage. Amongst these, the thrips, Scirtothrips dorsalis and yellow mite, Polyphagotarsonemus latus are the most important.
Regular menace
These have become regular pests of the crop in traditional chilli growing tracts, known for monocropping resulting in the qualitative and quantitative crop loss.
The indiscriminate use of insecticides has led to insecticide resistance, pest resurgence, environmental pollution besides upsetting the natural ecosystem. Further the presence of pesticide residues in chillies is a major non tariff barrier against export .
Chilli thrips and mites, characterised by relatively short life cycles, can complete several generations on a crop. Adults and nymphs of these pests suck sap from the leaves and growing shoots. Affected leaves curl upwards and downwards resulting in damage called chilli leaf curl or chilli murda complex.
As a result of thrips infestation, leaves become smaller, thickened and brittle. Mite infestation is a characterised by elongation of leaf petiole and clustering of tender leaves at the tip of branches.
Pest management
— Seed treatment with imidacloprid at five grams per kg seed is effective.
— Spray with acaricides such as dicofol at five ml per litre or wettable sulphur three grams per litre or diafenthiuron at one gm per litre or Vertemic at 0.5 ml per litre.
Utilisation of indigenous materials have confirmed that garlic chilli kerosene extract [GCK at 0.5 per cent] +nimbecidine (2.5 ml/lit) can effectively combat the problem.
(Dr. D. N. Kambrekar is Scientist (Agricultural Entomology), Regional Agricultural Research Station, PB.No. 18, Bijapur (UAS, Dharwad), email: kambrekardn@gmail.com, Phone: 08352 230568.)
TB: ‘child-friendly, first-line combination drugs will be available in 2016’
Dr. Mel Spigelman , President and Chief Executive Officer of the Global Alliance for TB Drug Development (TB Alliance) is regarded as one of the world’s leading experts in tuberculosis and TB drug development.
He was instrumental in forging key organisational partnerships and building the pipeline of TB drug candidates when he was the Director of Research & Development at TB Alliance. In an email to R. Prasad , he explained the various facets of paediatric TB drug development. Excerpts:
Is there a greater involvement by drug companies in producing paediatric TB formulations after UNITAID provided a grant of $16.7 million and USAID also contributed funds?
The goal of the grant is to develop first-line TB treatments designed for children, in the proper doses and formulations, but also to help catalyse paediatric TB drug development among pharmaceutical companies through a variety of incentives. More accurately defining the market, clarifying the regulatory pathways for new products, and addressing barriers to entry for manufacturers are all within the scope of our work, and will help bring new partners into the field.
We’ve already engaged and entered into collaborations with interested generic manufacturers, including Svizera, which will help improve access to treatments. It’s also important to note that TB Alliance’s work under this grant will aim to reduce the lag time between adult and paediatric formulations of new drugs, accelerating the availability of new TB drugs in paediatric form. For example, we are working with Janssen to speed up the availability of the paediatric formulation of bedaquiline, which was approved for the treatment of MDR-TB in adults last year.
Has any Indian pharmaceutical company shown interest in developing fixed-dose combination drugs for children?
The current paediatric TB fixed-dosed products sold through the WHO’s Global Drug Facility are produced by Indian pharma companies (Lupin and Macleods). TB Alliance has already entered into an agreement with Svizera to produce new first-line treatments in the doses now recommended by WHO and we are in discussion with other Indian pharmaceutical companies.
Because of their experience, Indian manufacturers are among those for whom we see a likely role in producing new TB drug products for children.
How long will it take to come up with fixed-dose combination drugs for first-line TB drugs? How long will a trial take and how many subjects are needed to test bioavailability?
One of the significant challenges to the development of new paediatric TB treatments is the need for additional clarity on what is needed for such a product to receive approval by the various regulatory authorities around the world. These studies can take 6 to 18 months to complete. The quantity and scope of these studies required for regulatory approval can vary by country. We are working to collect that information and disseminate it widely, so that those with the capacity to work in this space have a clear understanding of what needs to be done, how to do it, and what regulators need to see to make approval decisions.
That said, we expect that the first wave of new, simpler, fixed-dose combinations for children will be available in 2016, fulfilling a significant need.
Since we need several dosages to cater to different weight bands, will the cost of drug development increase?
Fixed-dose combinations of current first-line TB treatments are weight-banded for both adults and children. The improved first-line TB treatments for children that will be made available as a result of this grant will be weight-banded as well. Dose-ranging studies are underway for the small group of newborns for whom this information is not already available. Dispersible tablets allow the same tablet to be dissolved in water or other liquid; different amounts are then given for each of the different weight groups, which is a cost-effective means of delivery.
When will the first-line, fixed-dose combination drugs become available?
Our goal is to have optimised formulations of existing first-line treatment for children available to be sold through a global procurement agency by 2016, with a phased market rollout to follow.
Are there attempts to produce child-friendly second-line drugs? Can combination drugs be produced for such drugs?
There are a number of obstacles to developing fixed-dose combinations of the current second-line drugs for children, including the fact that not all the second-line TB drugs are administered the same way. Kanamycin and capreomycin are delivered via injection, for example. While many groups advocate for drug developers to develop child-friendly formulations of the current second-line drugs, in the long run, we need new drugs to treat MDR-TB. Only then can we shorten the long treatment time (up to two years) and avoid the many toxicities that are associated with today’s MDR-TB treatments. Compared with adults, children respond better to second-line treatment. With the development of new regimens for the treatment of drug-resistant TB with hopefully new drugs to which there is no pre-existent resistance, combination products will become readily available for treatment of what is now considered drug-resistant TB.
How long would it take and how many children are needed to undertake bioavailability of fixed-dose combination drug trials?
The number of children to be enrolled and the timeline for either a bioavailability or bioequivalence study are agreed upon between the manufacturer and the regulatory authority reviewing the product for market authorisation/approval.
The child-friendly combination drugs are for <5 five years. But do we know the disease burden in this age group?
For clarification, child-friendly TB products are limited to children under 30 kg which limits the use of the drugs by weight and not by age. Depending on the region of the world, median weights for different age groups can vary. Children five years and under are a critical group, since they are most susceptible to becoming sick and dying from TB; however, all children need improved TB treatment.
Determining the actual number of paediatric patients, including those who are younger than five years, is a challenge, given the overall challenges in diagnosing paediatric TB.
However, as part of this grant and in conjunction with other groups such as WHO, we are working to develop a better estimate of this cohort than has previously been available.
Full interview online
( The Correspondent is a recipient of the 2013 REACH Lilly MDR-TB Partnership National Media Fellowship for Reporting on TB. )
Is keeping animals in captivity slavery?
First it was the argument that the human foetus should be considered a person. The state of Colorado in the US wanted in 2008 to establish a law stating that the unborn human foetus is a “person” and thus be given the some constitutional rights that a human being enjoys. The state of Mississippi went a step further to say that the term ‘person’ should apply to every human being from the moment of fertilization, and hence anyone who aborts such a life should be termed illegal and punished. The motive behind these was to overturn the US Supreme Court’s 1973 decision of the right to abortion. Both the Colorado and Mississippi moves were rejected in their legislatures, but the story is not over. The “Personhood Bill”, introduced last month in the state of Georgia, wishes to declare the “one-cell human embryo” (even before implantation) to be a person and should be given the right to life.
Now, the matter has gone beyond us humans. The journal Science reports in its December 6, 2013 issue that the Boston lawyer Steven Wise, who has founded the “Non-human Rights Project” (NhRP), has filed lawsuits that want the New York courts to declare that chimpanzees and other great apes are persons, and therefore all such apes in captivity — be they in research labs, zoos or personal farms — be freed. He claims that not only chimpanzees but even dolphins have cognition. Using the discovery that great apes and dolphins possess a sense of “self awareness” as the basis, Wise argues that keeping these animals in captivity is tantamount to slavery and hence illegal. He wants that these animals in current captivity be released and transferred to a chimpanzee sanctuary in Florida.
Working with animals is vital for knowledge. The reaction of the scientific community has been strong and shocked. Some of them have argued that they care very much about animal welfare and offer them all possible forms of help and comfort, treat them ethically and protect them. But going beyond animal welfare and assigning them rights akin to what humans have would harm research. Anatomist Susan Larson of Stony Brook, NY is quoted as saying: “Everything I do with these animals I have done on myself. I understand that animal rights activists don’t want these animals mistreated, but they are hampering our ability to study them before they become extinct”. Dr. Stephen Ross of the Fisher Center for the Study and Conservation of Apes, of the Chicago zoo says: “I think these animals should have some rights to be comfortable and live in an engaging environment, but you don’t need personhood to do that. We want to make things better for chimps. We just disagree on how to get there”.
Defining personhood
We shall wait to see what courts have to say on this and on the definition of cognition and “personhood”. Wikipedia defines cognition to imply learning, memory, reasoning, problem solving and decision making. Philosophers and logicians have long thought about what defines a person and, in my opinion, the one that captures the idea best is the one proposed by the contemporary philosopher Professor Thomas White. He wants the following attributes as necessary for personhood: to be alive, be aware, feel positive and negative sensations, have emotions, have a sense of self, have control own behaviour, recognize other persons, and have cognitive abilities (see my earlier column of 24-11-2011).
Given the above attributes to cognition and personhood, chimpanzees come close and so do dolphins to some extent. As it turns out, The New York courts have dismissed the Wise petitions on chimps, but he will appeal. But the larger question still looms; as science progresses and we discover and understand more and more animals with some (if not all) of these attributes of personhood, we may face the accusation of practising slavery. Dr Alexandra Horwitz of Barnard College, Columbia University NY runs a dog cognition lab and has recently shown that the domestic dog has some limits to understand and to oppose inequity. But a dog treated unfairly but yet offered greater rewards chooses the latter! And cows have cognitive ability even if it is just domain- specific (meaning familiarity with the neighbourhood).
Science way well declare that even a pea-sized brain may be sufficient for some aspects of cognition — we may then move from “ self awareness” as the criterion of personhood to cognition (even feeling of pain /happiness) as the basis for animal rights and argue that keeping pets is slavery! It may not come to that yet, since in our minds, as Orwell said, some animals are more equal than others.
Where then do we draw a line on “personhood”? Will we relax the White criteria one after another? In that event, is it not better to turn vegetarian, and stick the plants for food.
All I hope is that nobody revives J.C. Bose’s romantic notion that plants too have cognitive abilities; then we are all done for — humans, apes, dogs, cats, big fish or small fish!
D. BALASUBRAMANIAN
When patience, passion and perseverance pay
Dr. Frederick Sanger, twice Nobel Prize winner, died on November 19
Biochemistry was at its nascent stage around the 1930s and nobody knew whether proteins had a structure or were they colloids. Dr Frederick Sanger charted the less travelled path and laid new rules for arriving at the full structure of proteins.
He rated himself as a very ordinary human being and believed that one need not be brilliant to discover but must have patience, passion and perseverance. Dr. Sanger moved away from conventional natural product chemistry and did most of his work with paper chromatography to separate, purify, and characterise the degradation products.
As amino acids and fragments of proteins were colourless, he developed a chemical reagent FDNB (Known as Sanger Reagent) which on reacting would selectively label one end and gave a yellow spot on paper and the label remained even after degrading the labelled peptide with acid. He worked on insulin for eight years before publishing the results with just two students. For the first time he established that proteins are linked together in a specific way with an amino group at one end and carboxyl group at another. To date there is no exception to this linkage. This opened up the way for molecular medicine and could explain the molecular basis of many diseases; most well-known among them being sickle cell anaemia and thalassaemia, to name a few. Dr.Sanger won the Nobel Prize for developing methods to sequence proteins in the year 1958.
He now decided to focus on RNA sequencing. Though he was a Nobel laureate, nobody seemed to want to join his group! He was not willing to go back to protein sequencing even though there were many who wanted to join him for protein work! Ultimately he got a technician, Bob Barrel, a school pass out, who agreed to join him. Such was his ability to pick up talents. Later George Brownlee joined and thus began the journey of RNA and DNA sequencing in the 1960s.Interestingly, he had bright ideas even while sequencing proteins but many had to be forcefully abandoned as they were not in keeping with the safety norms. But he used the same ideas for DNA sequencing using DNA polymerase and its property brilliantly and in arrived at the full sequence of Phi X 174, a bacteriophage, which was the first DNA-based genome to be sequenced. The method came to be called the Plus Minus method. He once again shared the Nobel Prize for this work in the year 1980.
He opened up a new window of opportunity and improved his method by introducing the so-called dideoxy method. This helped in developing an automated DNA sequencer and enabled the whole human genome project to be completed .Ability to sequence a whole human genome in a day will be a routine diagnostic tool and personalised medicine will soon become a reality.
As a researcher I was very fascinated by the work of Dr. Sanger and applied for research under him in 1978. Later I met him when I had invited him to deliver a talk in 1980 at Imperial College, London, where I was the Biochemical Society president. The announcement of the Nobel Prize in 1980 made me worry but he honoured his commitment and rehearsed the Nobel Lecture on December 4, 1980. I was elated and we made a hand sketch of him and posted it all over the campus. He was so touched by the poster that he took the original one and displayed it in his house.
On his arrival there was a huge crowd to talk to him and I knew I may not be able to talk to him. Then came the next surprise when he called me and explained why he was unable to accommodate me. Even more surprising to me was the keen interest he continued to take in my work on Ubiquitin. We chatted for how long I cannot remember but time stood still and I was mesmerised. He made me feel so important that the memory of this meeting remained etched in my memory forever. I was truly surprised when he said that he will retire at the age of 65 and would pursue rose gardening.On the day of the lecture, the auditorium at Imperial College was jam packed and I had the pleasure of introducing my hero to the audience. I requested Prof. Hartley, his long term associate to say a few words. Joking Prof Hartley said, if Dr. Sanger went to heaven, God would ask him why he did not complete sequencing complex carbohydrates! For that was the only area he left untouched.
Dr. Sanger, you live through those who came in contact with you and will continue to affect humanity through your contributions to personalized medicine.
KRISHNAMOORTHY KANNAN
( The author is Professor, University School of Biotechnology, GGS Indraprastha University, New Delhi and a former Vice Chancellor, Nagaland University. kkannan@ipu.ac.in)
Could Picasso, Matisse or Andy Warhol, with their magnificently inexact representations of the real world possibly offer anything to the empiricism of neuroscience?
Neuroscientist Patrick Cavanagh, director of the Vision Sciences Laboratory, Department of Psychology, Harvard University believes that these very distortions, artistic “short-cuts” and deliberate “mistakes” reveal the artists’ intuitive mastery over key principles of visual cognition. And it is this skill that enables them to so effectively portray the impressions they intend to.
Vision takes up a third of the cerebral cortex, and each of the 30 billion neurons that make up the visual system analyse a small portion of the world for colour, movement and orientation. So powerful is this visual computational device that the brain often needs just a ‘hint’ at forms to construct images, which it retrieves largely from ‘stored information,’ Prof Cavanagh said. The visual brain guesses, makes assumptions and constructs a story. “Artists must deal with these processes of inference,” not so much with real physics.
Artists reveal that our visual brain uses a “reduced physics” to see the real world, often relying on memory and inference rather than true physics, to quickly and efficiently form perceptions, said Prof Cavanagh at a lecture at the Indian Institute of Science (IISc) on ‘The artist as neuroscientist’ earlier this week. And in doing so they have, beginning with cave painters, created a record of “40,000 years of experiments in vision,” he said. “They are the original neuroscientists.”
The economy of line drawings, or the high-contrast format of pop art are spectacular examples of artists discovering principals and shortcuts that the visual brain uses to create an image, he told his audience at IISc’s faculty hall.
Artists also appear to have known for centuries another curious fact about our visual brain that scientific experiments have only recently established: we have little understanding of how reflections, mirrors and shadows work.
“In a painting almost any reflection will do… The pattern only needs to match the average properties of natural scenes.” And so the most impossible reflections are entirely accepted by viewers.
These undetected errors, he said, “are the ones that tell us which rules of physics actually count for visual perception. As artists find the rules they can break without penalty, they act as research neuroscientists and we have to only look to their paintings to uncover and appreciate their discoveries.”
