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New structure of key protein holds clues for better drug design

The scientists working at the Scripps Research Institute (TSRI) have elucidated the molecular structure of  a key protein, which is used extensively in drug design. With this discovery, scientists can now develop to new ways to combat infectious diseases. They have discovered the structure of the protein named A2A adenosine receptor (A2aAR), which is a member of the G-protein-coupled receptor (GPCR) family. Approximately 40 percent of all approved pharmaceutical drugs use this protein as target molecule.

Furthermore, scientists have uncovered the detailed signaling mechanism of the protein A2aAR, helping us understand the inner workings of this proteins. For example, an amino acid of A2aAR acts like a “toggle switch” and controls the signaling processes of the cell membrane. Journal Cell published this path-breaking discovery today. Based on imaging techniques, it can be inferred that shape of proteins changes.

The protein A2aAR and other molecules of the GPCR family are embedded into plasma membrane of human cells. A normal human body contains more than 800 GPCRs and each protein molecule regulates the metabolic functions of the human body. Scientists have reported that the protein A2aAR is associated with the regulation of blood flow and inflammation. The harmful effects of caffeine are also alleviated by the protein A2aAR. For treating Parkinson’s disease, A2aAR is a relatively new target. Moreover, the protein A2aAR is reported to be a relatively new target in the treatment of cancer.

In recent years, X-ray crystallography has been used to determine the three-dimensional structure of A2aAR protein in previous studies. The X-ray images show that A2aAR protein resembles a chain, and it crisscrosses the cell membrane. An opening is present on the side that faces out of the cell. For signaling associate proteins inside the cell, a section of the GPCR structure emerges out of the membrane and gets associated with drugs.

During inactive and active-like states, an outline of the receptor’s shape was provided by the crystal structure. When A2aAR was combined with new candidate compounds of the pharmaceutical industry, they acted as binding partners; however, no motion and changes in cell structure was observed.

In this study, researchers realized that they need to establish the molecular mechanism through which A2aAR works in combating diseases. Nuclear magnetic resonance (NMR) spectroscopy was used by researchers for investigation. In this process, strong magnetic fields were used to probe the samples.

By using NMR technique, the structure of proteins was determined by scientists. Scientists also investigated the dynamic properties of the solutions at temperatures prevalent in the human body. The team of researchers visualized the internal structural changes in the A2aAR proteins.

In this study, researchers investigated the effects of binding drugs with extracellular surface. Changes were observed in the structure of proteins and in the dynamics of the protein surface at an intracellular level. Thus, scientists discovered the mechanism of signal transfer through intracellular pathways. Chemists modified drugs and manipulated the switch to control A2aAR signals.

 

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Researchers develop a remote-controlled cancer immunotherapy system

An innovative ultrasound system has been developed to control genetic processes in live T cells of the immune system. This team of researchers can destroy cancer cells. By developing non-invasive immunotherapeutic strategies, cancer cells can be manipulated and destroyed.

An innovative approach was used to improve practical applications of mechanogenetics: a field of science that improves the expression of genetics and activity of cells. T cells were mechanically destroyed by ultrasound. To genetically control cells, mechanical signals were used.

In this study, it was found that mechanogenetics system could be remote controlled and T cells can be manipulated by chimeric antigen receptor (CAR). Cancer cells can be targeted and killed with this innovative approach.

Researchers have engineered CAR-T cells with mechano-sensors, genetically transducing modules. This innovative approach was termed as CAR-T cell therapy, which provided a paradigm shift for the treatment of cancer.

Life-threatening complications develop when CAR-T cells are non-specifically targeted. Precision and accuracy of CAR-T cell immunotherapy was improved in an unprecedented manner. This innovative immunotherapy was used to target solid tumors. At the same time, off-tumor activities were minimized.

Microbubbles were conjugated to streptavidin and they were attached to cell surface. Mechanical vibration and stimulation of Piezo1 ion channels was performed by microbubbles when they were exposed to ultrasound waves. This led to the entry of calcium ions into the cell, triggering the following downstream pathways: calcineurin activation, NFAT dephoshorylation and translocation into the nucleus.

With recognition and destruction of targeted cancer cells, chimeric antigen receptor (CAR) was used to initiate the expression of genes.

 

 

 

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Possible Cure for Drug-resistant malaria: toothpaste ingredient

Researchers at the University of Cambridge have an innovative cure for drug-resistant malaria. This ingredient is commonly found in toothpastes.

A mosquito is the key carrier of malarial pathogens. Whenever such a mosquito bites a human being, these parasites are transferred into bloodstream of humans. Such parasites move through the liver for colonization and proliferation.

After proliferation and colonization in the liver, they attack red blood cells and multiply continuously. This further leads to potentially threatening illnesses.

In Africa and south-east Asia, more than a million people are affected by malaria. Although numerous medicines are commercially available in the market, it has been found that malarial parasites are mutating in recent times.

According to a recent study in the journal “Scientific Reports,” a team of researchers discovered that triclosan is the active ingredient that can fight “drug-resistant bacteria.” Triclosan obstructs the development of plaque bacteria with the help of the enzyme enoyl reductase (ENR). This enzyme was used for producing fatty acids.

To investigate therapeutic efficiency of triclosan, scientists attacked the culture of pathogens. They found that triclosan could target ENR, which is a virulent strain of pathogenic bacteria in the liver.

Triclosan suppresses the growth of parasites by completely inhibiting an enzyme, named DHFR. An anti-malarial drug named pyrimethamine targets DHFR; however, this target is also resisted by malarial parasites in Africa. Interestingly, triclosan could target even these parasites resistant to pyrimethamine.

In Africa and south-east Asia, a growing concern is the proliferation of drug-resistant malaria. The expression of ENR and DHFR was inhibited by triclosan. Triclosan is found to be effective on the parasite both in the liver and bloodstream. Thus, there is hope of a new drug against drug-resistant parasites.

This experimental research study was conducted in conjunction with robot scientist “Eve” in order to accelerate drug discovery process. With the help of artificial intelligence and machine learning, an innovative approach can be established for inventing new drugs.

 

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Innovative colitis treatment through precision editing of gut bacteria

Medical researchers at Southwestern Medical Center, Utah, performed precision editing on the bacterial colonies found in the gastrointestinal tract. This reduced the inflammation’s severity and colitis caused in experimental mice.

The primary strategy was to target cellular pathways associated with metabolic activities, which are associated with gastrointestinal inflammation. The main object was to prevent or reduce the inflammation caused in mice with colitis. At the same time, the control animals showed no signs of inflammation; the bacterial colonies in the gut were balanced and healthy.

This path-breaking discovery was published in latest issue of Nature magazine. A framework was developed from our results, and the bacterial species that line the gastrointestinal tract were precisely altered to reduce the inflammation caused by colitis and other forms of inflammatory bowel disease [IBD].

In this experimental study, we used a heavy metal called tungsten, which is dangerous when ingested in high doses. It should be noted that no heavy metal is safe for consumption. Our primary goal was to develop a novel therapy that induces a similar effect but within the acceptable limits of safety.

There is a diverse population of microbes, which form a thin line on the gastrointestinal tract. These microbes are essential for the maintenance of good health. They help in digestion, improve the immune system, and effectively combat all kinds of infections.

When there is an imbalance in microbial populations, these beneficial bacteria become a nuisance as they develop invasive qualities and drive out species that compete with them for space. It is difficult to understand the biology of gut microbiota because they are  highly diverse in nature.

In humans, several bacterial species are found in the gastrointestinal tract. The composition of species differs extensively for individuals. The composition of gut microbiota changes considerably, causing many chronically progressive diseases, such IBD, ulcerative colitis, and Crohn’s disease.

According to Centers for Disease Control and Prevention, at least 1 million adults are affected by IBD in the United States of America . Currently, there is no cure for such diseases. The gut microbiota also undergoes changes in patients with Type 2 diabetes, HIV-related intestinal disease, colon cancer, and necrotizing enterocolitis. These diseases are also observed in certain premature infants.

The bacteria found in the microbiota of the gastrointestinal tract belonged to enterobacteriaceae family, causing many inflammatory diseases.  In healthy gut, a small number of healthy bacteria are present. They belong to E.coli (Escherichia coli). These bacteria also protect pathogenic bacteria, such as Salmonella, which is responsible for food poisoning in humans. In mouse afflicted with colitis, there is an uncontrolled growth of enterobacteriaceae species.

In a paper published by Cell Host & Microbe, it was reported that cellular energy was produced by Enterobacteriaceae family. Gut bacteria uses this energy for improving growth and obtaining nutrients. Unique metabolic pathways were used to improve the growth and drive out beneficial bacteria at the time of illness.

These unique pathways are used to improve inflammation in gut. In current study, tungsten was used to inhibit the pathways obstructing metabolism. An inflammation develops due to incessant growth of pathogenic bacteria.

These researchers have reported that bacteria absorbed tungsten, and they developed an important cofactor of bacteria. Due to the inflammation, enterobacteriaceae lost its capacity to generate energy.

A soluble salt of tungsten was orally administered to patients. The useful bacteria were not affected in this innovative experiment. This is because a particular the cofactor could not govern the metabolism of beneficial bacteria.

The proliferation of enterobacteriaceae was stopped in our current experiment. When enterobacteriaceae  species were present in correct ratios, colonization would be resisted by bacterial pathogens.

By controlling the proliferation of bacteria, inflammatory episodes were prevented completely. With miniscule experimental evidence, it can be postulated that diseases of the gut worsen due to changes in the composition of microbiota.

In this study, it was found that the inflammation of the gut was reduced and a normal state was achieved by using tungsten treatment. In most experiments, tungsten was used to rectify a molecular target. This treatment was therapeutic for patients. At the same time, tungsten is the heavy metal that provokes neurological and reproductive diseases.

Conventional approaches are focused on treating bacterial pathogens. However, this path-breaking research is quite useful to harness bacteria in the normal gut. The composition and the function of gut microbiota was controlled.

Most doctors prescribe broad spectrum antibiotics. The final objective is to tarnish numerous bacteria in the gut. Whenever a patient visits the clinic in a critical state, most doctors prescribe antibiotics and do not conduct tests to identify the specific pathogens in the human body. In such a scenario,  the prescribed antibiotics have broad-spectrum activity, killing most pathogens and beneficial bacteria.

Only one family of bacteria, enterobacteriaceae, was targeted in our study. Although results are promising, more studies must be conducted to identify potential therapies that cause human diseases.

 

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How Accessible Publishing has Revolutionized Academic Publishing

The world of scientific publishing has undergone a metamorphosis in recent times. The key ingredients here are “authentication” and “piracy” in scholarly communications. Many people have come up with “inclusiveness of scholarly communications,” for disabled people. There seems to be a lacuna in the world of scientific publications, given the “professional” and “educational” spheres of education. In a highly connected world, knowledge must be disseminated through “journals,” “books,” and “databases.”

At one end, most academicians are of the view that

knowledge must grow with highly authoritative communications being accessible to readers. At the other end, publishers argue about “copyright infringement” with new challenges towards tackling piracy and digital infringement. Accessibility is still an issue for scholarly communications.

According to the National Institute of Health, there are more than 285 million people with some form of physical, cognitive, and educational challenge in the USA. Nevertheless, the enrollment of disabled masses is just 10–20% across colleges in the USA. People with disabilities are a sizeable population if we take into consideration that they can be perennial customers of scholarly communications.

“Accessibility” is still an issue here for most publishers. Publishers are concerned about “return on investment” while catering to such people. Accessible publishing is not really avenue for making great revenues. However, people with disabilities are now being considered for inclusiveness and diversity. They are provided with “navigable, feature-rich content” through various innovative publishers: DAISY and ReadSpeaker.

Accessible publishing is far superior given the fact that it can improve the “quality” and “interoperability” of metadata. With proliferation of machine learning and search engine optimization (SEO), general discoverability of such innovative publications is improved significantly. Publishers and technological evangelists provide deciphering workflow with maximum accessibility to all stages of publications, right from manuscript selection, improvement, and publications. Right from increasing submissions to improving usage, measurable benefits can be availed through “accessible publishing.”

Accessible publishing is much easier today thanks to developments in technology although it does require some efforts out here. Technologies such as HTML, EPUB, etc., would be leveraged to provide the best practices in accessible publishing. Industry-standard workflow formats of publishing are now accessible to all readers. The mission of academic publishing would be to disseminate knowledge through “accessible publishing.” They can envision the horizon of many accessible publishers.

 

 

 

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In Mice with Alzheimer’s, memory loss is reversed with diabetic drug

According to a recently published paper in Brain Research, a diabetic drug could be used to reverse memory loss in mice with Alzheimer’s disease. This study was conducted at Lancaster University in the UK. Professor Christian Holscher was the lead researcher of this study. This is a promising line of treatment for Alzheimer’s disease, a common neurodegenerative disorder. The drug was conventionally used to treat patients with type 2 diabetes.

Memory loss and dementia are the most common signs of Alzheimer’s disease. According to Alzheimer’s Society, more than two million people would suffer from Alzheimer’s disease by 2051. This research study was partially funded by Alzheimer’s Society. It is alarming rate of increase and there has been no new treatment for Alzheimer’s disease in recent times.

Since the past 15 years, physicians have been prescribing the same medications for patients with Alzheimer’s disease. According to Dr Doug Brown at the Alzheimer’s Society, new drugs must be urgently developed to tackle the growing number of patients with Alzheimer’s disease. Patients with Alzheimer’s disease cannot lead normal lives as dementia progresses quickly, limiting their cognitive skills and memory.

Diabetic drug liraglutide was tested on mice with Alzheimer’s disease; however, its efficacy must be further tested on human patients with Alzheimer’s disease. Randomized clinical trial need to be carried out with this objective. “Triple agonist drugs” have also shown promising results on mice with Alzheimer’s disease. Nevertheless, much needs to be done in the area of research and development.

Liraglutide is a “triple receptor drug” that has been tested for the first time. Researchers found that this drug could offer protection against degeneration of brain cells. Growth factors GLP-1, GIP, and Glucagon are combined in the formulation of the diabetic drug liraglutide. Previous studies have reported that growth signaling factors get impaired in the brain of patients with Alzheimer’s disease.

In this research study, scientists used transgenic mice APP/PSI. In these mice, they observed the expression of mutated genes, which cause Alzheimer’s disease. The same genes also undergo mutation in humans with Alzheimer’s disease. This form of Alzheimer’s is inherited through genetic mutation.

Researchers found that even in the advanced stage of neurodegeneration, memory loss could be significantly reversed in transgenic mice. By administering liraglutide drug to these aged mice, they could not improve memory but also cognitive ability. By performing maze test, they found that growth factors were enhanced in the brain of aged transgenic mice.

These growth factors in the brain would ensure normally functioning of nerve cells, preventing them from undergoing degeneration. Moreover, the drug decreased the formation of amyloid plaques in the brain of patients with Alzheimer’s disease. Furthermore, oxidative stress and chronic inflammation were reduced with the administration of this drug. Finally, the rate of nerve cell loss decreased following the action of this drug.

According to Professor Holscher, clinical trials have been successfully conducted with an older version of this drug. The promising results suggested that this drug was suitable for treating patients with Alzheimer’s disease. Although this drug was originally developed to manage type 2 diabetes, many studies have reported about its neuro-protective effects.

Our study is unique in the fact that a novel triple drug shows promising results when used as a line of treatment for Alzheimer’s disease. However, further clinical trials must be conducted in a dose-dependent manner on humans, and its efficacy must be compared with existing drugs to know whether if the novel drug is superior to existing ones.

The risk of Alzheimer’s disease is high in patients with type 2 diabetes. Quite often, Alzheimer’s disease develops with the progression of type 2 diabetes. Owing to impaired insulin levels, cerebral degeneration occurs in patients with type 2 diabetes. This leads to the development of Alzheimer’s disease.

In the brain of patients with Alzheimer’s disease, scientists have found that there is no sensitivity to insulin. They believe that neurodegenerative disorders occur due to insulin desensistization in the brain. This is because insulin exhibits neuroprotective effects as it is a growth factor in human brain.

 

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A new recyclable treatment for destroying cancer cells selectively

Researchers at the University of Warwick have developed a new recyclable treatment for destroying cancer cells. This research study was led by Professor Peter J. Sadler, who works at the Department of Chemistry at the University of Warwick. They have synthesized an organic-osmium compound, which can selectively attack cancer cells. The compound was synthesized using sodium formate in non-toxic dosages. Sodium formate is found in many organisms as a natural product. Ants and nettles also synthesize this natural product.

The novel organic-osmium compound was named JPC11 by researchers. They found that this compound can target metabolic process that governs the survival and proliferation of cancer cells. Cancer cells derive energy for rapid division and proliferation from a key substance, which belongs to the class of pyruvates. This key substance is converted into unnatural lactate by JPC11. The resultant lactate destroys cancer cells.

The significance of this treatment lies in the fact that the chemo-catalyst JPC11 is recyclable; therefore, it can be reused to repeatedly attack a particular cancer cell line. This is a path-breaking innovation in cancer treatment as JPC11 is a novel compound that paves the way for recyclable treatment of cancer. In future, side-effects and toxicity of chemotherapy can be minimized by administering such recyclable drugs in smaller dosages. The functional capacity of JPC11 is unprecedented given the recyclable ability of the compound. Researchers have been now focusing on how this compound can be effectively used to treat ovarian cancer.

It is difficult to treat patients with ovarian cancer because they are usually resistant to conventional chemotherapeutic drugs. In particular, they are highly resistant to the platinum drug cisplatin. This new drug broadens the scope of anticancer treatment given the fact that it is recyclable and reusable. The new drug is promising as it destroys cancer cells through a completely novel mechanism, so ovarian cancer patients may not be resistant to this novel drug.

One of the major attractions of this compound is the fact that it selectively destroys cancer cells. Researchers found that JPC11 compound primarily targeted the expression of cancer cells. The compound did not attack healthy living cells, so they were mostly unaffected by exposure to JPC11 compound. Compared to conventional platinum drugs, the selectivity of JPC11 compound is far more superior and effective. In fact, the conventional platinum drugs would also destroy healthy living cells which were in the vicinity of cancer cells. Thus, the selective activity of JPC11 compound seems to be a major breakthrough in cancer treatment.

According to Dr. James Coverdale, this is a path-breaking discovery in the treatment of cancer. Dr. James Coverdale is a research scholar at the Department of Chemistry, University of Warwick. He worked with his colleagues to develop this innovative compound, which holds promising results in cancer treatment. By synthesizing this compound, they broadened the applications of chemistry in medical science. With this compound, they have come up with a novel strategy for killing cancer cells selectively. The compound JPC11 is a chemo-catalyst with a unique mechanism of action, which seems to be more selective and effective in destroying cancer cells. Given its high selectivity, it paves the way for new treatments that are much safer and effective than conventional treatments.

Peter Sadler is a medicinal chemist who also worked with this research group at the University of Warwick. According to Professor Peter Sadler, cancer chemotherapy mainly involves the use of platinum compounds. However, these drugs have poor selectivity and less safety, so new drugs must be invented to overcome the problem of side-effects and drug-resistance. In this research study, a truly novel drug was discovered for cancer treatment. Professor Peter Sadler believes that chemo-catalysts are promising in cancer treatment since they have immunogenic properties. However, the efficacy of this drug must be further established by conducting clinical trials.

 

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Twenty-six articles are retracted from Elsevier following fake peer review

Fake peer review has traumatized the business of scholarly communications in 2017. Springer announced that it would retract 107 papers in April 2017 after unearthing the scam of fake peer review. Closely following the steps of its competitor, Elsevier announced in December 2017 that it would retract 26 papers as they suspected they were approved by fake peer review racket. In a remarkable blow to scholarly publishers, peer review was systematically manipulated by digging into the loopholes of authorship. These papers were published in six journals of Elsevier from 2014 to 2017. Interestingly, all papers were written by Iranian research scholars. Moreover, A Salar Elahi is a common author in 24 out of 26 retracted papers. A Salar Elahi is a research scholar at Islamic Azad University in Tehran, Iran.

According to a statement released by Elsevier on 21st December 2017, 26 papers were found to be published due to academic misconduct. They had already retracted 13 out of 26 papers from their prestigious journals. It is important to note that the International Journal of Hydrogen Energy contained 10 out of these 13 retracted papers. The remaining three retracted papers had been published in the journal Results in Physics.

Elsevier declared that the remaining 13 papers would also be retracted soon from their esteemed journals following charges of fake peer review. Out of these 13 papers, four were published in the journal Results in Physics. Moreover, the Journal of Crystal Growth had also published 4 papers, which are in the process of retraction. Three papers will soon be retracted from the Journal of Alloys and Compounds. One paper would be retracted from each of the following journals: i) Fusion Engineering and Design and ii) International Journal of Thermal Sciences. These papers were submitted and published by Iranian researchers from 2014 to 2017.

Elsevier has found that peer review process was faked for publishing these 26 papers in journals. Interestingly, names of problematic reviewers were suggested by authors themselves.  The fraud of these authors was caught by editors of two Elsevier journals. These editors immediately informed Elsevier authorities of academic fraud. The email addresses of these recommended reviewers could not be validated by Elsevier editors. While submitting their manuscripts to Elsevier journals, the authors had provided these suspicious email addresses.

To tackle this menace, Elsevier decided to take strong punitive action against this group of authors. They investigated all papers submitted by this group of authors to Elsevier journals and they found that those papers were also published by following fake peer review process. To tackle this academic scam, Elsevier retracted all the 26 papers written by this group of authors.  Fake peer review was not the only issue for retracting these papers. Elsevier authorities found that the list of authors was also changed in these papers without informing journal editors prior to publication.

Interestingly, Elahi is the mastermind of this scam as he is corresponding author in 24 out of 26 papers that have been now retracted by Elsevier. He has successfully published 162 papers, which have been indexed by Web of Science (Thomson Reuter’s tool for SCI Journal list). Iran researchers have also defrauded Springer Nature earlier. In 2016, Springer Nature retracted 58 articles published by research scholars from Iran. These authors had also faked the peer review process to publish their papers.

Fake peer review was possible because the names of reviewers were suggested by authors themselves. Therefore, publishers should stop the practice of asking authors to suggest reviewers for their work, prior to publication in journals. However, publishers seem helpless here as they face scarcity of reviewers quite often. Elsevier spokesperson confirmed that journals have to cope with scarcity of reviewers in a highly competitive world of scholarly communications. Therefore, some journals had relented to the idea of receiving reviews from scholars recommended by authors themselves.

 

 

 

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Advanced skin cancer can now be treated with Arthritis drug

According to a latest research study, patients with advanced skin cancer can now be treated more effectively if they are administered a well-known drug, which is normally used to treat rheumatoid arthritis. This drug should be dispensed in combination with conventional drug therapy used to treat skin cancer. This study was conducted on mice by researchers at the University of East Anglia (UEA). Melanoma tumor growth stopped almost completely in mice with advanced skin cancer when they were treated with both conventional medications and arthritis drug. Melanoma tumor occurs only in five percent of patients with skin cancer; however, it is the deadliest form of tumor with high mortality rate. If melanoma growth is diagnosed at an early stage, then it can be completely treated with this combinatorial therapy. However, it is difficult to treat melanoma in metastasis stage.

In recent times, novel treatments have targeted genetic mutations that cause metastatic melanoma in patients. However, metastatic melanoma becomes resistant to drugs very quickly, so researchers are focusing on developing a combination of treatments that can effectively destroy the proliferation of metastatic melanoma. Dr Grant Wheeler was the lead researcher at the School of Biological Sciences, UEA. According to Dr. Wheeler, metastatic melanoma can be attacked from several angles, if researchers provide combinatorial therapies to patients with skin cancer. Melanoma tumors would then find it difficult to develop drug resistance. In their research study, they could further establish the benefits of combinatorial therapies: since they administered arthritis drug along with conventional therapy to mice with skin cancer, the benefits of both therapies were enhanced; therefore, the effects of combinatorial therapies were more than the sum total of all benefits.

In this research study, Dr Wheeler worked with colleagues at the School of Pharmacy in UEA. This study was conducted in collaboration with researchers at the Norwich Medical School. Leflunomide is an immunosuppressive drug that is normally prescribed to patients with rheumatoid arthritis. They investigated how effective was Lelunomide drug in treating skin cancer patients, which were also treated with skin cancer therapy simultaneously.

In a previous study, these researchers had found that Leflunomide was effective when used with drugs that target a certain genetic mutation of melanoma tumor, namely, BRAFV600E. In current research study, they tested the efficacy of leflunomide in combination with seflumetinib, which is a conventional drug used to treat melanoma. They found that this combination of drugs was more effective in treating melanoma. Melanoma depends on a protein called MEK for its survival. The activity of MEK protein is targeted by the drug Selumetinib. Many drugs act as inhibitor of MEK activity. These drugs are used along with BRAF inhibitors to tackle resistance. In current study conducted by Dr Wheeler, it was found that this combination of drugs was more effective when leflunomide was also included in it.

These researchers tested leflunomide on melanoma cells in the laboratory. They found that leflunomide was effective in combating melanoma growth, irrespective of its genetic mutation. This was a path-breaking discovery as leflunomide could now be used to treat all kinds of melanomas, and not just the tumors caused by BRAF mutation. The team of researchers investigated the activity of leflunomide on melanoma cells. They found that leflunomide could arrest of growth of melanoma cells when they were in their early stage of development. Then, leflunomide would initiate controlled cell death, known as apoptosis. It would force melanoma cells to kill themselves.

This group of scientists then tested the efficacy of combining leflunomide with selumetinib. They found that this combination of drugs was more effective in killing melanoma cells. This finding was confirmed by administering leflunomide and selumetinib to mice with melanoma tumors. Over a period of 12 days, this combination of drugs was administered to mice with melanoma tumors. It was found that the combinatorial therapy worked wonders in completing stopping the growth of melanoma tumors. The efficacy of combinatorial therapy was far superior to those of individual drugs. However, further clinical trials need to be carried out to ascertain if melanoma tumors show drug resistance to this combinatorial treatment.

According to Dr. Wheeler, death rate is quite high in patients with melanoma tumors because these tumors usually develop resistance to drugs. Therefore, most patients respond poorly to melanoma treatments. To tackle this problem, doctors are now propagating immunotherapeutic treatments to boost defence mechanisms within the human body. However, researchers are still hopeful that novel combinatorial therapies would work wonders in association with immunotherapy, which is now being provided to most patients with melanoma tumors. According to Dr. Wheeler, the combination of leflunomide and selumetinib can destroy melanoma tumors effectively.

 

 

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Elsevier and American Chemical Society sue Sci-Hub for copyright infringement

Sci-Hub was a popular website that provided access to academic papers free of cost. Elsevier pressed charges of copyright infringement against Sci-Hub at a U.S federal court in New York. In a historic judgment, the court convicted Sci-Hub for violating copyright laws.

As penalty, U.S court has ordered Sci-Hub to pay 15 million dollars as damages to Elsevier, world’s leading publisher of scientific, technical, and medical research. Sci-hub was penalized severely for copyright infringement, as more than 100 academic papers of Elsevier were pirated and downloaded free of cost. This website also contacted pirated copies of academic papers published in subscription journals of Springer Nature, Academic Chemical Society, and Wiley-Blackwell.

 

Elsevier had sued Sci-Hub in 2015 for copyright infringement as it unlawfully accessed and distributed more than 100 academic papers of Elsevier. The New York district judge convicted Sci-Hub for violating copyright laws severely and ordered to discontinue the website; however, the makers of Sci-Hub did not relent to the court and continued their website under different domain names and IP addresses.

Elsevier requested permanent ban on Sci-Hub in court and 15 million dollars as damages. Alexandra Elbakyan, the founder of Sci-Hub, did not hire any lawyer to represent her in the court. Thus, Elsevier easily won the lawsuit; however, it is not yet clear if Alexandra would relent to court orders.

Alexandra Elbakyan wanted to break the barriers in science and technology by providing free access to scholarly papers. Although several academics concede that the website violated copyright laws, they feel that this was the right step in letting knowledge grow. Most subscription journals of Elsevier are very expensive, so this limits access to published scientific literature. Libraries and academic institutions have been pressing for fairer pricing of subscription journals.

 

As per latest updates, American Chemical Society (ACS) has also filed a lawsuit against Sci-Hub in US court. The director of communications at ACS has alleged that Sci-Hub has managed to make many spoofed versions of ACS website. With these spoofed websites, Sci-Hub has managed to pirate and distribute many copyrighted journal articles of ACS. ACS also won copyright infringement case against Sci-Hub in November 2017.

According to the latest ruling of US court, Sci-Hub founder has to pay 4.8 million dollars as damages to ACS. Moreover, Sci-Hub and its domains have been asked to discontinue their operation with immediate effect. Search engines, hosting sites, internet service providers, and registries of domain names have been asked to ban Sci-Hub website and its related domains.

After receiving these landmark judgments against copyright infringement, speculations were rife about similar lawsuits against Google and other search engines, because they actively facilitated the operation of pirated academic content from Sci-Hub website. However, directors of ACS have clarified that they have no immediate plans of suing internet service providers and search engines.

Sci-Hub is operated and managed by Alexandra Elbakyan in Russia, which is outside the jurisdiction of US courts. She also does not hold any assets in USA, so it is not yet clear if she would comply with U.S court orders. In other words, this ruling may not really compel Sci-Hub to shut shop, though it is a brave step in deterring piracy of scholarly communications.

 

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