Dengue!!

                      Carica papaya L ..... a solution to Aedes aegypti carrier of  Flaviviridae family virus

C. papaya leaves extracts against Dengue fever. The secondary metabolite of plants origin makes up a vast repository of compounds with a wide range of biological activities. There have been many reports of higher plant extracts possessing relatively good potential to inhibit viruses (Van Den Berghe, 1978). Many plants extracts including Spilanthes calva, Sterculia guttata, Balanites aegyptiaca, Vitex negundo, Solanum xanthocarpum, Artemisia annua, Fagonia indica, Nerium indicum, Trigonella foenum, in different solvents have been reported to exhibit activity against Aedes aegypti L., a vector of dengue fever.

C. papaya contains two important biologically active compounds vis: chymopapain and papain which are widely used for digestive disorders. It showed that papaya-derived papain, caricain, chymopapain, and glycine endopeptidase can improve acidic pH conditions and pepsin degradation. Other active compounds of C. papaya are lipase, or CPL, a hydrolase, which is tightly bonded to the water-insoluble fraction of crude papain and is thus considered as a “naturally immobilized” biocatalyst. According to the folk medicine, papaya latex can cure dyspepsia and also applicable for external burns and scalds. Seeds and fruits are excellent antihelminthic and anti-amoebic. Dried and pulverized leaves are sold for making tea, also the leaf decoction is administered as a purgative for horses and used for the treatment of genito-urinary system. Unripe and semi- ripe papaya fruits are ingested or applied on the uterus to cause abortion. However, the consumption of unripe and semi-ripe papaya fruits could be unsafe during pregnancy, but consumption of ripe fruits during pregnancy causes no risk.

It is reported that the plant extracts of Quercus lusitanica have maximum activity against DENV-2 Replication of Dengue virus. It is also reported that the methyle gallate of plant origin interacts with herpes simplex virus proteins and alters the adsorption and penetration of the virion. It is observed that Gastrodia elata B1 has effect on the multiplication cycle of Dengue virus serotype 2. It is reported that two compounds 1-beta-D-ribofuranosyl-3-ethynyl-[1,2,4]triazole (ETAR) and 1-beta-Dribofuranosyl-4-ethynyl[1,3]imidazole (IM18), significantly reduced replication of dengue virus serotype 2 (DENV-2) in cultured Vero cells and a noval trypsin Kazal-type inhibitor from Aedes aegyptihas thrombin coagulant inhibitory activity.

The latex, ripe fruits, unripe fruits, seeds, seeds juice, root, leaves, flower and stem bark of C. papaya are used as antimicrobial, anthelmentic, antimalarial, antifungal, anti-amoebic, hepatoprotective, male and female antifertility, immunomodulatory and against histminergic. This case report shows the activity of C. papaya leaves extracts against Dengue fever.

PhD USA

Applying to PhD Programs in the USA

Finding a School, Taking the GRE / TOEFL, and writing Personal Statements

In October last year, I had to start thinking about my future. Since I was already a year into my master’s studies, I had to determine what I wanted my future to be like. We often think about those things but when the crunch sets in, the reality does hit us hard. Decisions need to be made! The options were to further pursue my education or try to get a job in the field of sport and exercise psychology back home in Sarajevo, Bosnia and Herzegovina. A realization that there is a very slight chance of finding my ideal job back home, combined with my desire to continue to learn more about the field I fell in love with during my master’s studies, made me come up with a decision to apply to PhD programs in the field of sport and exercise psychology in the US. This decision,  came after much contemplation. Not to mention, it was a big bite to chew considering I only had a few months to take the GRE and complete the application process. For those who are thinking of applying to PhD programs in the US, I would have to advise you to make this decision long before the application deadline. Application deadlines in the US are earlier than most of the ones in Europe. In my experience, most PhD program application deadlines are either December 1stor January 15th. Additionally, I had to continue working on my master’s studies, so my academic life during the months of applying to PhD programs became very challenging. I realized that what I had learned in my master’s program had given me the skills to be able to juggle all of those things at once.

In order to select the schools and programs I was going to apply to, I talked to some of my current mentors. They gave me a great guidance as to which schools/programs fit my future career goals. I also investigated potential mentors at various schools in order to identify those with whom I had a desire to work. That helped my selection process in terms of what schools I was going to apply to. I chose those programs that had well-established sport psychology programs, which had ongoing research that fully fit my research interests.

As far as the actual application process, it would be an understatement to say that it was challenging. I found myself overwhelmed. There was too much information, too many rules. I was lucky to have a sister who had recently earned her PhD in the US, so she was able to advise me on many things and what to focus on. One helpful thing  was first choosing the programs I was going to apply to, and then organizing the required information into folders and files, collecting information from schools’ and programs’ websites. That way, I was able to start collecting the necessary documentation and preparing for the GRE simultaneously. Another tip is to also start studying for the GRE early, and schedule an appointment to take it as early as possible.. Moreover, depending on the closest city where one can take this exam, the computer-based option may not be possible, but only the paper-based one.  My advice, take the computer-based GRE, as that gives you a little more privacy when taking the exam. I obtained a Kaplan GRE book to prepare for the exam. This book was helpful and provided me with practice exams which I had taken to prepare for the real thing.

If you are a non-native English speaker, you may also have to take a TOEFL exam.. I had TOEFL exam scores from when I was applying to the Erasmus Mundus program, so I reported those scores: which are valid for two years. All scores, GRE and TOEFL, have to be reported officially by the testing company. However, you can report up to 4 free scores at the end of the exam (both GRE and TOEFL), so try to decide what schools you are applying to before then. 

During the application process, I realized that many schools require very similar things. Once you get a hang of it with a couple of schools, it becomes easier. Of course, some programs ask for specific things, so those were a bit of a curve ball. However, I have to strongly advise you on asking your professors or other associates for their recommendation letters as early as possible. They are very busy people, so do give them time. It is your responsibility to remind them about recommendation letter deadlines (yes, let’s face it, we are not the most important people in their lives)!! Most schools have their applications online now, so you can upload necessary documentation instead of mailing it. Some documents, i.e. official transcripts, will have to be mailed, though. If you are planning on pursuing additional education after your current program, it is a good idea to pay attention to how well you are doing in your classes. Schools ask for official transcripts so they do care about your grades, as should you probably. :)

I also invested some time in finding good tips for writing strong letters of purpose/personal statements. They all seem to agree on one thing: use specific examples of how you accomplished something that would make you a suitable candidate for that program. Do not shy away from using some personal stories about yourself, as long as they make a point you are trying to emphasize. Additionaly, do not put everything you can possibly put about yourself in a personal statement: choose wisely. Think about what makes you different from many other candidates.

After  finishing with the application process, I felt like a heavy stone has been lifted from my shoulders. I had invested a lot of time and energy into this process, so I sincerely hope it will pay off. Luckily, I will keep busy while waiting for decisions from my prospective programs, as I have to work on my master’s thesis. Good luck to everyone who is applying and I hope this information will be helpful to you!

Adisa Haznadar is a second year master student in sport and exercise psychology at the University of Thessaly in Greece. She completed her Bachelor in Psychology (2009) at the University of Sarajevo, Bosnia and Herzegovina. Her area of interest and current research area are psychological skills and their implementation; mainly self-talk.


a link to understand the procedure...
http://aegedu.com/blog/how-to-apply-for-phd-usa/

A scope for the cancer treatment.

Loss of Tumor-Suppressor and DNA-Maintenance Proteins

                                                             

A study reported in the recent issue of Nature Genetics demonstrates that loss of the tumor-suppressor protein p53, coupled with elimination of the DNA-maintenance protein ATR .The study provides supportive evidence for the use of inhibitors of ATR in cancer treatment. 

A research at the University of Pennsylvania School of Medicine. The findings highlight the fact that day-to-day maintenance mandatory to keep proliferative tissues like skin and intestines functional is about more than just regeneration, a stem cell-based process that forms the basis of tissue renewal.

Whereas loss of ATR causes DNA damage, the job of p53 is to monitor cells for such damage and either stimulate the early demise of such cells or prevent their replication, the housekeeping part of the equation. The findings indicate that as messy as things can become in the absence of a DNOne of the majortenance protein like ATR, failing to remove resulting damaged cells by also deleting p53, is worse. "Because the persistence of damaged cells in the absence of p53 prevents appropriate tissue renewal, these and other studies have underscored the importance not only of maintaining competent stem cells, but also of eliminating what gets in the way of regeneration.

The finding of an analog,  is what happens to trees during the changing seasons."In springtime, leaves are new and undamaged. But as the summer wears on, the effects of various influences - insects, drought, and disease - cause them to lose the pristine qualities they once had. However, the subsequent fall of these leaves presents a unique opportunity for regeneration later on, a chance to rejuvenate from anew without pre-existing obstacles. Similarly, by suppressing the accumulation of damaged cells in tissues, p53 permits more efficient tissue renewal when ATR is deleted". 

Cells without ATR that remain uncleared appears to be block tissue regeneration either by effectively refusing to relinquish space to undamaged cells, or by secreting signals that halt regeneration until they have been removed.
These results came as something of a surprise. Prior studies pairing DNA-repair mutations with p53 mutations always led to a partial rescue of the DNA repair mutation. It was thought that,this happens because p53 loss helps cells with just a little DNA damage to continue to contribute to the tissue.

But the result was opposite,absence of p53 did not rescue the tissue degeneration caused by ATR loss, it made it much worse. This result suggested that allowing mutant cells without ATR to persist is more harmful to tissues than eliminating them in the first place.It is thought that this could be because the ATR mutation produces much more damage than most other DNA-repair defects. 

It was found that that cells missing both ATR and p53 have more DNA damage than those missing either gene alone. As a large fraction of human cancers have p53 mutations, he says, "p53-deficient tumors might be particularly susceptible to ATR inhibition." Indeed, clinical trials already are underway involving an ATR partner protein called Chk1.So the study provided with the potential use of ATR/Chk1 inhibitors in cancer treatment.

Molecules Recognise Each Other!

How Individual Molecules Recognise Each Other?

If one thinks that there are thousands of times more molecules forming our body than stars in the universe it is astonishing how all these molecules can work together in such an organised and efficient way. How can our muscles contract to make us walk? How can food be metabolised every day? How can we use specific drugs to relieve pain?




To work as a perfect machine, our body ultimately relies on the capability of each little part (molecule) to know a specific function and location out of countless possibilities. To do this, molecules carry information in different ways. The key to understanding all biological processes is recognition. Each molecule has a unique composition and shape that allows it to interact with other molecules. 
A number of molecules can recognise each other and transfer information exactly in a way, they can either be "right handed" (D) or "left handed" (L). This property called "chirality" is a spectacular way to store information: a chiral molecule can recognise molecules that have the same chirality (same "handedness", L to L or D to D) and discriminate the ones of different chirality (L to D and D to L). 

Probably one of the most exciting mysteries of Nature is why the building blocks of life, i.e. amino acids (the building blocks of proteins) are exclusively present in the chiral L form and sugars (which constitute DNA) are all in the D form. Once more, the reason for this preference is "historical", but this time goes back millions of years till the origins of the biological world. Researchers think that current life forms could not exist without the uniform chirality ("homochirality") of these blocks, because biological processes need the efficiency in recognition achieved with homochiral substances. In other words, the separation of molecules by chirality was the crucial process during the Archean Era when life first emerged.

It has been seen that two molecule, let say (diphenylalanine, the core recognition motif of Alzheimer amyloid polypeptide) of the same chirality can form structures (pairs, chains) while molecules of different chirality discriminate and cannot form stable structures.
As it occurs when you shake the hand of your friend, the fact that the two homochiral hands are complementary by shape is not enough, you both have to dynamically adapt and adjust your hands to reach a better fit, a comfortable situation. This dynamic mechanism of how two molecules "shake hands" and recognise each other by mutually induced conformational changes at the single molecule level. 
We live in houses, wear clothes and read books made of chiral cellulose. Most of the molecules that mediate the processes of life like hormones, antibodies and receptors are chiral. Fifty of the top hundred best-selling drugs worldwide are chiral... there is lot more to know, to understand , to emphasis the big and key term that is "LIFE" ....

Ants use antibiotics as weed killers!!

A mixed community of actinomycetes(Bacteria) produce multiple antibiotics for the fungus farming  Acromyrmex octospinosus(ant)                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        Attine ants live in an intensely studied tripartite mutualism with the fungus Leucoagaricus gongylophorus, which provides food to the ants, and with antibiotic-producing actinomycete bacteria. One hypothesis suggests that bacteria from the genus Pseudonocardia are the sole, co-evolved mutualists of attine ants and are transmitted vertically by the queens. A recent study identified a Pseudonocardia-produced antifungal, named dentigerumycin, associated with the lower attine Apterostigma dentigerum consistent with the idea that co-evolved Pseudonocardia make novel antibiotics. An alternative possibility is that attine ants sample actinomycete bacteria from the soil, selecting and maintaining those species that make useful antibiotics.Acromyrmex octospinosus was recently shown to produce the well-known antifungal candicidin. Candicidin production is widespread in environmental isolates of Streptomyce                                                                                                                                                                                                                 Actinomycetes from A. octospinosus garden worker ants and, in a single colony of ants, identified a Pseudonocardia and a Streptomyces species that produce antifungals in laboratory culture. The Streptomyces species, which is named S4, contains candicidin biosynthesis genes and produces candicidin, consistent with a report on antifungal-producing actinomycetes associated with A. octospinosus. The actinomycetes studied in this work were isolated from A. octospinosus ants from one region, whereas the previous study used A. octospinosus ants collected from the other. However, despite this geographic separation, the candicidin-producing Streptomyces strains identified in the two studies show 99% 16 S rDNA sequence identity suggesting that candicidin-producing Streptomycesare common mutualists of A. octospinosus. Candicidin-producing Streptomyces are widespread in the environment and attine ants most likely acquire them selectively from the soil.                                                                                                                                                              

The Pseudonocardia species P1, isolated from the same colony as Streptomyces S4, showed relatively weak antifungal activity that was only observed in cultures grown on solid growth medium. This made it difficult to purify enough of the compound for analysis and identification. Using a genome scanning approach we identified a biosynthetic gene cluster for a polyene antifungal in Pseudonocardia P1 and then isolated and identified this antifungal using LC-MS/MS. This combined chemical and genomic approach provides a powerful tool for identifying and isolating new antibiotics and confirmed that Pseudonocardia P1 produces a polyene antifungal that was tentatively named NYSTATIN P1. This compound is markedly different from the antifungal dentigerumycin produced by Pseudonocardia associated with the lower attine ant species A. dentigerum although it is notable that both Pseudonocardia strains are making previously unknown antifungals, consistent with the idea that the Pseudonocardia mutualists co-evolved with attine ants. There was no detection of any compounds in extracts from Pseudonocardia P1 agar plates and mycelium that matched the isotopic mass of dentigerumycin. However, since the biosynthetic gene cluster for this compound is not known, it wasn't possible exclude the possibility that this strain also has the ability to make dentigerumycin.

Taken together, this work provides the first direct evidence that individual leaf-cutting ant colonies have access to multiple antifungals via the diversity of hosted actinomycetes and increases the number of known antifungals used by attine ants to three. This work also provides evidence to support the two current possibilities for the identity and acquisition of mutualistic bacteria,Pseudonocardia co-evolution, and the environmental acquisition of useful actinomycetes. This strongly suggests that both possibilities apply, at least in the attine species A. octospinosus. Careful experimental work will be needed in order to demonstrate that multiple compounds are in fact produced and confer benefits in vivo. It is interesting that the only two antifungal compounds to be isolated and identified from A. octospinosus colonies so far are polyenes, which are active against dimorphic fungi, yeasts (Candida) and molds (Escovopsis), but which apparently do not kill the fungal cultivar. The isolation of a nystatin-like polyene from a leaf-cutting ant-associated Pseudonocardia species that some Pseudonocardia bacteria associated with attine ants have non-specific antibiotic properties that inhibit a range of fungi and are not targeted specifically at Escovopsis.

The advantage to the ants of deploying two antifungals is not clear. Polyene antifungals are thought to work by interacting hydrophobically with ergosterol in the fungal cell membrane and forming channels that increase membrane permeability, but this may not be their only mechanism of action, and there may therefore be some advantage to the ants in using more than one. However, as fungi do not develop resistance to polyene antifungals (at least in a clinical setting), it is unlikely that resistance is the basis for any such advantage. Nevertheless, as candicidin and nystatin are not antibacterial, neither of these compounds is likely to be involved in competition amongst the bacteria for host resources. Thus, the identities of these two antifungal compounds are consistent with the longstanding hypothesis that these actinomycete associates of leaf-cutting ants can be mutualists of the ant and the attine fungus, provided that the compounds are applied correctly by the ant.                                                                                                                                                                                                    So the conclusion is:-

A combined genomic and chemical approach that has proven useful for the identification of a new antifungal associated with Acromyrmex ants, this time produced by their Pseudonocardiamutualist. This approach should stimulate further chemical ecology studies of insect fungiculture systems, which are widespread in nature and which are likely to use symbiotic antibiotic-producing bacteria to protect their fungal partners.There is also a evidence that supports both of the possibilities proposed to explain the mutualism between actinomycetes and attine ants-co-evolution of Pseudonocardia with attine ants and environmental sampling by the ants of useful antibiotic-producing bacteria. Thus it is  proposed that these possibilities are not mutually exclusive and that both are likely to apply to both attine ants and other systems of insect fungiculture.

AGEING- Is really a threat or it could be slayed out of human race- A KEY QUESTION :)

Reversed the ageing process in mice – now for humans....

It a claim to be a step closer to reversing the ageing process after rejuvenating worn out organs in elderly mice. The experimental treatment developed by researchers at the Dana-Farber Cancer Institute, Harvard Medical School, turned weak and feeble old mice into healthy animals by regenerating their aged bodies.

The surprise recovery of the animals has raised hopes, that it may be possible to achieve a similar feat in humans – or at least to slow down the ageing process.

"This could lead to strategies that enhance the regenerative potential of organs as individuals age and so increase their quality of life. Whether it serves to increase longevity is a question we are not yet in a position to answer."

The ageing process is poorly understood, but it is known , it is caused by many factors. Highly reactive particles called free radicals are made naturally in the body and cause damage to cells, while smoking, ultraviolet light and other environmental factors contribute to ageing.


There is a process called telomere shortening. Most cells in the body contain 23 pairs of chromosomes, which carry our DNA. At the ends of each chromosome is a protective cap called a telomere. Each time a cell divides, the telomeres are snipped shorter, until eventually they stop working and the cell dies or goes into a suspended state called "senescence". The process is behind much of the wear and tear associated with ageing.


 A genetically manipulated mice that lacked an enzyme called telomerase that stops telomeres getting shorter. Without the enzyme, the mice aged prematurely and suffered ailments, including a poor sense of smell, smaller brain size, infertility and damaged intestines and spleens. But when the mice was injections to reactivate the enzyme, it repaired the damaged tissues and reversed the signs of ageing.

"These were severely aged animals, but after a month of treatment they showed a substantial restoration, including the growth of new neurons in their brains," 

Repeating the trick in humans will be more difficult. Mice make telomerase throughout their lives, but the enzyme is switched off in adult humans, an evolutionary compromise that stops cells growing out of control and turning into cancer. Raising levels of telomerase in people might slow the ageing process, but it makes the risk of cancer soar.

DePinho, a scientist in HARVARD MEDICAL SCHOOL said the treatment might be safe in humans if it were given periodically and only to younger people who do not have tiny clumps of cancer cells already living, unnoticed, in their bodies.

David Kipling, who studies ageing at Cardiff University, said: "The goal for human tissue 'rejuvenation' would be to remove senescent cells, or else compensate for the deleterious effects they have on tissues and organs. Although this is a fascinating study, it must be remembered that mice are not little men, particularly with regard to their telomeres, and it remains unclear whether a similar telomerase reactivation in adult humans would lead to the removal of senescent cells."

It is seen that none of mice developed cancer after the treatment. so it has been a big query, whether it extends the lifespan of mice or enables them to live healthier lives into old age.

 "The key question is what might this mean for human therapies against age-related diseases? While there is some evidence that telomere erosion contributes to age-associated human pathology, it is surely not the only, or even dominant, cause, as it appears to be in mice engineered to lack telomerase. Furthermore, there is the ever-present anxiety that telomerase reactivation is a hallmark of most human cancers." .....

UBIQUITIN DEPENDENT RECUITMENT OF HELICASE UPON REPLICATION STRESS TO SUPPRESS HOMOLOGOUS RECOMBINATION

Ubiquitin-dependent recruitment of the Bloom Syndrome helicase upon replication stress is required to suppress homologous recombination

Limiting the levels of homologous recombination (HR) that occur at sites of DNA damage is a major role of BLM helicase. However, very little is known about the mechanisms dictating its relocalization to these sites. Here, we demonstrate that the ubiquitin/SUMO-dependent DNA damage response (UbS-DDR), controlled by the E3 ligases RNF8/RNF168, triggers BLM recruitment to sites of replication fork stalling via ubiquitylation in the N-terminal region of BLM and subsequent BLM binding to the ubiquitin-interacting motifs of RAP80. Furthermore, we show that this mechanism of BLM relocalization is essential for BLM’s ability to suppress excessive/uncontrolled HR at stalled replication forks. Unexpectedly, we also uncovered a requirement for RNF8-dependent ubiquitylation of BLM and PML for maintaining the integrity of PML-associated nuclear bodies and as a consequence the localization of BLM to these structures. Lastly, we identified a novel role for RAP80 in preventing proteasomal degradation of BLM in unstressed cells. Taken together, these data highlight an important biochemical link between the UbS-DDR and BLM-dependent pathways involved in maintaining genome stability.