Inquiry Into Beheadings By Militia: Ashraf Ghani
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Scientists have made the surprise discovery of an exciting new way of blocking a crucial cancer protein that has proved extremely difficult to target.
Their study took one approach to targeting the molecule – but ended up revealing a second, completely new, line of attack. The discovery has the potential to lead to new cancer drugs that target the protein.
The protein – known as heat shock protein 72 or HSP72 – plays an important role in allowing cancer cells to become resistant to treatment, but traditional approaches to designing drugs to block it have so far failed.
The researchers believe they have discovered a fatal flaw in the protein which could be exploited through a new generation of cancer treatments.
Controlling how HSP72 works
Scientists at The Institute of Cancer Research, London, used a crystal structure of HSP72 to design a prototype drug, which permanently removes the protein from the cancer cell, so can overcome the challenges this protein presents.
Irreversible inhibitors, like this prototype drug, usually work by forming a permanent chemical bond with a particular type of amino acid called a cysteine. The researchers therefore modified an existing type of inhibitor called 8-N-benzyladenosines to attach to a cysteine in HSP72.
While their newly designed irreversible inhibitor was apparently successful in permanently inhibiting HSP72, unexpectedly the cysteine amino acid was not responsible.
The researchers found the inhibitor was actually binding to a different amino acid, lysine, which is important for controlling how HSP72 works.
Targeting proteins in this way is rare but could offer many unique advantages, and the scientists believe that, with further development, this approach could at last allow drugs to be created against HSP72.
Advances in medicinal chemistry
Their study, published in the prestigious international chemistry journal Angewandte Chemie, was largely funded through a PhD studentship created by Luke Johnson, Chairman of the ICR. It also received funding from Cancer Research UK.
Lead author Dr Matthew Cheeseman, Staff Scientist at the ICR, said:
“Advances in medicinal chemistry are now showing that even apparently un-druggable proteins like HSP72 can actually be effectively targeted.
“When we discovered how our inhibitor seemed to be working it was unexpected but exciting. Now that we know where the fatal flaw in HSP72 might be, we can revise the design of our inhibitor to strike it more effectively.”
Co-author Professor Keith Jones, Team Leader in Medicinal Chemistry at the ICR, said:
“We’ve been keen to find a way through the defences of HSP72, because this molecule plays an important role in cancer in helping tumours evade the effects of treatment.
“It’s exciting to have designed an inhibitor which shows such promise in blocking the activity of such an important molecule. And our study also shows that there is still room, even in the high-tech modern world of cancer research, for a serendipitous and genuinely surprising discovery.”
Men risk their lives in wars so women can enjoy societies where they can pursue feminist goals, such as punishing men for sexist language.
Allowing women to drive in Saudi Arabia would cause rampant sex, porn and homosexuality, according to some of the country's scholars.
Academics at the country's highest religious council submitted a report to the legislative assembly warning of the dangers of letting women behind the wheel, reports the Daily Telegraph.
If the only country in the world that still bans women from driving were to change its rules, there would be "a surge in prostitution, pornography, homosexuality and divorce."
Within 10 years of the ban being lifted, the report claimed, there would be "no more virgins" in the country, according to the paper.
Currently, women caught driving in the kingdom may be lashed as punishment.
Toxoplasma gondii infection causes toxoplasmosis, an infectious disease with worldwide prevalence. The limited efficiency of drugs against this infection, their side effects and the potential appearance of resistant strains make the search of novel drugs an essential need. We examined Eurycoma longifolia root extract and fractions as potential sources of new compounds with high activity and low toxicity. The main goal of this study was to investigate the anti-T. gondii activity of crude extract (TACME) and four fractions (TAF 273, TAF 355, TAF 191 and TAF 401) from E. longifolia, with clindamycin as the positive control. Methods
In vitro toxoplasmacidal evaluation was performed using Vero cells as host for T. gondii. Light microscopy technique was used to study in situ antiparasitic activity. Results
Significant anti-T. gondii activity was observed with clindamycin (EC50 = 0.016 μg/ml), follow by TAF 355 (EC50 = 0.369 μg/ml) and TAF 401 (EC50 = 0.882 μg/ml). Light microscopy revealed that most Vero cells were infected after 3 h of exposure to T. gondii. After 36 h of exposure to the E. longifolia fraction, the host Vero cells showed no visible intracellular parasite and no remarkable morphological changes.
The Central Mediterranean route remained under intense migratory pressure in 2015, although the total number of migrants arriving in Italy fell to 154 000 - about a tenth lower than the record set in 2014. The main reasons for the drop were the shift of Syrians to the Eastern Mediterranean route and a shortage of boats faced by smugglers in the latter part of the year. Smuggling networks remain well established in Libya, where migrants gather before crossing the sea. In 2015 Eritreans, Nigerians and Somalis accounted for the biggest share of the migrants making the dangerous journey.
People smugglers typically put migrants aboard old, unseaworthy fishing boats, or even small rubber dinghies, which are much overloaded and thus prone to capsizing. These vessels are generally equipped with poor engines, lack proper navigation systems and often have insufficient fuel to reach Europe. For these reasons, the vast majority of border control operations in the Central Mediterranean turn into Search and Rescue (SAR) operations.
Trends prior to 2015
The emergence of Libya as a collecting point for African migrants has long antecedents. Until 2010, Libya’s prosperity offered good job opportunities for migrant workers from African countries, who either used it as a final destination, or as a transit country where they could earn money to pay the smugglers for the last leg of their journey to the EU.
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