#Researchers Find New Target for Anti-Malaria Drugs A new target for drug development in the fight against the deadly disease malaria has been discovered by researchers at MIT.
which causes toxoplasmosis, and Plasmodium, which causes malaria, access vital nutrients from their host cells.
Around one-third of the world deadly infectious diseases, including malaria and tuberculosis, are caused by pathogens that spend a large portion of their life inside specially built compartments within their host cells.
These compartments known as arasitophorous vacuoles, separate the host cytoplasm and the parasite by a membrane,
and thereby protect the parasites from the host cell defenses. They also provide an environment tailored to their needs, according to Dan Gold,
This makes it more difficult for the parasite to release proteins involved in the transformation of the host cell beyond the membrane in order to spread the disease
and for the pathogen to gain access to vital nutrients, Gold said. ltimately what defines a parasite is that they require certain key nutrients from their host,
Similar research into how the related Plasmodium pathogen performs this trick had identified a so-called rotein export complexthat transports encoded proteins from the parasite into its host red blood cell,
which transforms these red blood cells in a way that is vital to the spread of malaria. he clinical symptoms of malaria are dependent on this process
they could be used as a drug target against the diseases they cause, including malaria, he said. his very strongly suggests that you could find small-molecule drugs to target these pores,
which would be very damaging to these parasites, but likely wouldn have any interaction with any human molecules,
In addition to malaria the technique could also be used to target the parasite Eimeria, which affects cattle and poultry, among other animals,
a professor of immunology and infectious diseases at Harvard School of Public health who was involved not in the research. trikingly,
#Diagnosing Sepsis through Genetic Signature Investigators at the Stanford university School of medicine have identified a pattern of gene activity that could help scientists create a blood test for quickly
Sepsis is a whole-body inflammation syndrome set off when the immune system wildly overreacts to the presence of infectious pathogens.
The great majority of sepsis cases are caused by bacterial rather than viral infections and are treated best with antibiotics.
when a patient has an outwardly similar but infection-free syndrome called sterile inflammation, an intense, systemic inflammatory response to traumatic injuries, surgery,
blood clots or other noninfectious causes. t critical for clinicians to diagnose sepsis accurately and quickly,
said Purvesh Khatri, Ph d.,assistant professor of biomedical informatics research. Sepsis or sterile inflammation? In practice, distinguishing sepsis from sterile inflammation is a toss-up.
Right now, the only diagnostics that can help do this are too slow or too inaccurate,
or both, Khatri said. As a result, hospital clinicians are pressured to treat anybody showing signs of systemic inflammation with antibiotics.
The inability to easily distinguish sepsis from sterile inflammation makes it tough for pharmaceutical companies to conduct clinical trials of drugs aimed at treating sepsis;
patients may be assumed mistakenly to have sepsis when they in fact have sterile inflammation, and vice versa, Khatri said. e think wee got the makings of a diagnostic blood test that will allow clinicians to distinguish between these two types of inflammation,
Khatri is the senior author of the new study, published May 13 in Science Translational Medicine, in
and his associates to tease out a gene-activation pattern that distinguishes septic from sterile systemic inflammation. e thought there might be some genes that the body turns on specifically in response to infection,
. a postdoctoral scholar now doing a residency in general surgery at Stanford. Numerous studies have been conducted to find differences in the activation levels of immune-response genes between infection-related inflammation and sterile inflammation.
But these studies have yielded conflicting or murky results. One big reason is that both infection
and noninfectious tissue trauma activate many of the same immune-system components and pathways. At the gene-activation level, the overlap is staggering:
whether due to sepsis or sterile causes. That overlap obscures any easily detectable changes attributable solely to infection.
Needle in a haystack Further confounding attempts to identify patterns of increases or decreases in gene activity is that fact that some patients are already experiencing sepsis
when theye admitted to the hospital, while others become infected during their hospital stay. So two different sepsis patients admitted at the same time may be at very different stages of a complex inflammation process. ow do you figure out which tiny fraction of those changes was caused by infection?
Youe looking for a needle in a haystack, Khatri said. The needle, it turns out,
consists of a signature formed by consistent changes in the activity levels of a mere 11 genes amid the chaotic background of the other 20,000-plus genes
The Stanford sleuths analyzed a number of publicly available data sets containing results of studies that had assessed activity levels for the entire human genome in sepsis cases,
600 patients in 27 different data sets containing medical information on diverse patient groups men and women, young and old,
suffering from sterile inflammation or sepsis, including patients who already had sepsis when first admitted to the hospital as well as patients who were diagnosed with it later in addition to healthy control subjects.
The analysis consisted of two separate steps. First, the researchers scoured nine data sets containing more than 650 patient samples.
in patients within 24 hours of a sepsis diagnosis compared with genes from those not diagnosed with sepsis.
following a surgery or injury, in inflammation-related gene activity over time, independent of the presence or absence of infection.
therefore time according to how soon a blood sample was drawn after the initial injury or surgery.
11 genes jumped out of the haystack as likely sepsis markers. The researchers confirmed this 11-gene signature in an additional 18 cohorts comprising more than 1,
800 patient samples. e were able to identify a slight bump in activity of these 11 genes in patients two to five days prior to their clinical diagnosis,
That could mean getting an earlier diagnosis than can be achieved with current approaches, which is key considering the rapid rate at which sepsis mortality rises once it gets a foothold.
The gene-activation signature showed a sepsis-detecting accuracy surpassing that of methods now in use
Sweeney said. Combining the new technique with other current diagnostic methods is likely to be more accurate than using any one alone,
The study was funded by the Stanford Department of Surgery and by the National Library of Medicine and the National Institute of Allergy and Infectious diseases.
Daniel Moran, Ph d.,professor of biomedical engineering in the School of engineering & Applied science and of neurobiology, of physical therapy and of neurological surgery at Washington University School of medicine in St louis
Moran team includes Harold Burton, Ph d.,professor of neurobiology and Wilson (Zach) Ray, M d.,assistant professor of neurological surgery, both at the School of medicine;
#Uncovering Genetic Factors in Leukemia Northwestern Medicine scientists have discovered how a gene linked to leukemia functions,
a finding that may have important implications for children with Down syndrome who have a higher risk of developing the blood cancer.
Patients with Down syndrome have three copies of chromosome 21 in their cells. Theye also 20 times more likely to contract childhood B-cell acute lymphoblastic leukemia than the general population,
making that chromosome an important avenue for researching the genetic basis of the cancer. major goal of my laboratory is to identify the specific gene or genes on chromosome 21 responsible for the increased incidence of leukemia in this population,
. and Lora S. Lurie Professor in Medicine-Hematology/Oncology and Biochemistry and Molecular genetics, and a member of the Robert H. Lurie Comprehensive Cancer Center of Northwestern University.
In previous work, Crispino and colleagues found that a gene on chromosome 21 called DYRK1A contributes to the development of leukemia.
Now, in a paper published in the Journal of Experimental Medicine, they expanded on that research by studying the gene in depth.
Specifically, they wanted to understand how DYRK1A plays a role in blood cell production. Over-production of immature lymphocytes is a hallmark of acute lymphoblastic leukemia.
children with Down syndrome have more DYRK1A than usual. his finding is exciting to us because human B-cell acute lymphoblastic leukemia cases show increased levels of DYRK1A, said Crispino. he results suggest that DYRK1A may be a novel target for therapy in this form of leukemia.
This work was supported by a National institutes of health grant, the Samuel Waxman Cancer Research Foundation, the Leukemia and Lymphoma Society, the Rally Foundation and the Bear Necessities Foundation e
#Sleep Position May Impact Brain Ability to Clear Waste How you sleep on your side, on your back,
The findings could have implications for the prevention of neurodegenerative diseases that are characterized by plaque buildup.
and professor in the department of Anesthesiology and Radiology at Stony Brook University School of medicine in New york told Bioscience Technology that it is too early to comment on humans,
or cause brain diseases. o why is the glymphatic system more effective when sleeping in the lateral position?
and therefore overall waste clearance is diminished. his could have implications for prevention of certain neurodegenerative diseases. e speculate that
or postpone onset of neurodegenerative diseases such as Alzheimer, Benveniste told Bioscience Technology. Imaging testing in humans is needed still.
and to prevent neurodegenerative diseases
#Capturing Cell Growth in 3d Replicating how cancer and other cells interact in the body is somewhat difficult in the lab. Biologists generally culture one cell type in plastic plates,
which doesn represent the dynamic cell interactions within living organisms. Now MIT spinout AIM Biotech has developed a microfluidics device based on years of research that lets researchers co-culture multiple cell types in a 3d hydrogel environment that mimics natural tissue.
Among other things, the device can help researchers better study biological processes, such as cancer metastasis, and more accurately capture how cancer cells react to chemotherapy agents,
Cancer drugs or other therapeutics can then be added to better monitor how cells respond in a patient.
including studies of cancer and stem cell research, neuroscience, and the circulatory system. This month AIM Biotech will begin deploying the commercial devices to 47 research groups in 13 countries for user feedback.
In a 2011 study, researchers in his group discovered that breast cancer cells can break free from tumors
in a 2012 study, they found that macrophages a type of white blood cells were key in helping tumor cells break through blood vessels.
or something that is useful in the clinic, Kamm said. ne of the i-Teamsrecommendations was to develop systems for researchers.
is studying cancer metastasis as demonstrated with his own work to develop better treatments. In the body, cells break loose from a tumor
and migrate through tissue into the blood system, where they get stuck in the small blood vessels of a distant organ
Then they can escape from inside the vessel to form another tumor. AIM Biotech microfluidics device produces a similar microenvironment:
Tumor cells can be introduced, flowing naturally or getting stuck in the vessels. Kamm said this environment could be useful in testing cancer drugs,
as well as anti-angiogenesis compounds that prevent the development of blood vessels, effectively killing tumors by cutting off their blood supply.
AIM Biotech recently discovered that its devices revealed discrepancies in some clinically tested therapeutics. In a study published in Integrative biology,
MIT researchers used Kamm's microfluidics technology to screen several drugs that aim to prevent tumors from breaking up
#Researchers Uncover New Pathways for Diabetes Research A new Florida State university study is changing how scientists look at diabetes research
and the drugs used to treat the disease. In the Proceedings of the National Academy of Sciences, Associate professor of Chemistry Brian Miller and postdoctoral researcher Carl Whittington report that a key enzyme involved in the body response to glucose can essentially be corrupted by a new mechanism that scientists
This discovery shifts the current understanding of how this enzyme participates in certain diseases, including hyperinsulinemia and diabetes. n principle,
our findings could open the door for a new approach to treat diseases of glucose homeostasis, such as diabetes,
Miller said. The enzyme is called glucokinase and serves as the body primary glucose sensor as it relays signals in the pancreas
a person often suffers from diabetes, or other glucose-related illnesses. Because of its role in the cell, glucokinase has received considerable attention by pharmaceutical companies as a potential therapeutic target.
More than a decade ago researchers uncovered drugs that activate the enzyme, which offered hope for treating type 2 diabetes.
The focus, however, was on only one way that the enzyme was activated. Miller and Whittington research showed there is actually another avenue for activation. glucokinase The work showed that this new activation mechanism is operational in clinically characterized disease forms of the enzyme.
Activation of glucokinase is known a cause of hyperinsulinemia, a disease characterized by over secretion of insulin even in the absence of glucose,
often leading to insulin resistance. lucokinase-associated hyperinsulinemia varies in severity depending upon the level of activation of the enzyme,
because it sheds new light onto how the functional properties of the enzyme can manifest in disease.
In addition to the direct medical implications, the new study also shifts a fundamental principle of biochemistry known as allostery.
and disease-variant forms of glucokinase. e can see which parts of the enzyme move at what rate and speed,
According to the American Diabetes Association, 29.1 million Americans have diabetes and case numbers are expected to rise.
There have been some complications with diabetes drugs that activate glucokinase. As a result, some companies have started looking at other options to treat the disease,
and the new findings might aid this process. This research was funded by the National institutes of health, the National Science Foundation and the American Heart Association m
#Degenerating Neurons Respond to Gene therapy Treatment for Alzheimer Disease Degenerating neurons in patients with Alzheimer disease (AD) measurably responded to an experimental gene therapy in
report researchers at University of California, San diego School of medicine in the current issue of JAMA Neurology.
Institute and a neurologist at VA Medical center, San diego. The findings are derived from postmortem analyses of 10 patients who participated in phase
Administering NGF directly into the brain a first for treating of an adult neurodegenerative disorder was done for two reasons.
The published findings come from AD patients who participated in safety trials from March 2001 to October 2012 at UC San diego Medical center.
The participants lived one to 10 years after treatment. ll of the Alzheimer disease brains showed anatomical evidence of a growth response to the growth factor,
who has been principal investigator for the trials from the beginning. his means that growth factors as a class consistently result in activation of dying cells in human neurodegenerative disorders. uszynski said the findings indicate NGF is extended safe over periods and that it merits continued
Currently, there is no effective treatment or cure for AD..Funding support for this research came, in part, from the National institutes of health, the Veterans Health Administration, the Alzheimer Association, the Donald and Darlene Shiley Family Trusts and Ceregene, Inc. Disclosure:
To test the nanoclew CRISPR-Cas delivery system, the researchers treated cancer cell cultures and tumors in mice.
#Study in Mice Suggests How Anesthesia May Fight Lung Infections In use for more than a century,
inhaled anesthetics like nitrous oxide and halothane have made modern surgery possible. Now, in experiments in mice, researchers at Johns Hopkins and elsewhere have added to evidence that certain so-called"volatile"anesthetics--commonly used during surgeries--may also possess powerful effects on the immune system that can combat viral and bacterial infections in the lung,
including influenza and pneumonia. A report on the experiments is published in the September 1 issue of the journal Anesthesiology.
The Johns Hopkins and University of Buffalo research team built its experiments on previous research showing that children with upper viral respiratory tract infections who were exposed to the anesthetic halothane during minor surgical procedures had significantly less respiratory symptoms
and a shorter duration of symptoms compared with children who did not receive halothane during surgeries.
To examine just how some inhaled anesthetic drugs affect viral and bacterial infections, Krishnan Chakravarthy, M d.,Ph d.,a faculty member at the Johns Hopkins Institute of Nanobiotechnology and a resident physician in the department of anesthesiology and critical
care medicine at Johns hopkins university School of medicine and Paul Knight, M d.,Ph d.,a professor of anesthesiology at the University of Buffalo School of medicine and Biomedical sciences, along with others
exposed mice to both influenza virus and Streptococcus pneumoniae bacteria. The team discovered that giving the animals volatile anesthetics, such as halothane,
led to decreased bacterial burden and lung injury following infection. The researchers report that the anesthetics augmented the antibacterial immune response after influenza viral infection by blocking chemical signaling that involves type I interferon,
a group of proteins that help regulate the activity of the immune system. Using a combination of genetic, molecular,
and knockout animal techniques, the researchers found that animals that were exposed to halothane had 450-fold less viable bacteria compared with non-halothane exposed animals with respect to the initial inoculum dose,
and astoundingly, treatment made it as if the animals were infected never with a prior influenza virus. The investigators report that symptoms of piloerection (involuntary bristling of hairs of the skin), hunched posture, impaired gait, labored breathing, lethargy,
and weight loss (equal to or greater than 10 percent of body weight at the time of infection) were significantly less in mice exposed to halothane
and then infected with flu and S. pneumoniae. Similar results, they say, were seen in mice bred to lack the receptor for type
I interferon and not exposed to halothane before infection.""Our study is giving us more information about how volatile anesthetics work with respect to the immune system,
suggest that volatile anesthetics may someday be helpful for combatting seasonal and pandemic influenza, particularly when there are flu vaccine shortages or limitations."
"A therapy based on these inhaled drugs may help deal with new viral and bacterial strains that are resistant to conventional vaccines
and treatments and could be a game changer in terms of our preparedness for future pandemics and seasonal flu outbreaks because it's focusing on host immunity,
"said Chakravarthy.""We hope our study opens the door to the development of new drugs
and therapies that could change the infectious disease landscape.""The investigators say they are currently testing an oral small molecule immune modulator in phase 2 clinical trials that acts like volatile anesthetics to help reduce secondary infections after someone becomes sick with the flu.
This study was supported by the following National institutes of health grants: National Heart, Lung, and Blood Institute, National Institute of Allergy and Infectious diseases Extramural Activities and the National Institute on Deafness and other Communication Disorders s
#Study Reveals the Genetic Start-up of a Human Embryo An international team of scientists led from Sweden's Karolinska Institutet has mapped for the first time all the genes that are activated in the first few days of a fertilized human egg.
The study, which is being published in the journal Nature Communications, provides an in depth understanding of early embryonic development in human
-and scientists now hope that the results will help finding for example new therapies against infertility.
We identified novel factors that might be used in reprogramming cells into so-called pluripotent stem cells for possible treatment of a range of diseases,
the Swedish Research Council, the Strategic Research Program for Diabetes funding at Karolinska Institutet, Stockholm County, the Jane & Aatos Erkko Foundation, the Instrumentarium Science Foundation,
#Bacterial Study Points to Possible New MRSA Vaccine New research led by NYU Langone has uncovered why a particular strain of Staphylococcus aureusnown as HA-MRSAECOMES more deadly than other variations.
These new findings open up possible new pathways to vaccine development against this bacterium, which the Centers for Disease Control and Prevention said accounts for over 10,000 deaths annually, mostly among hospital patients.
In a series of experiments in mice and in human immune cells in the lab, recently published in the journal Nature Communications online September 2,
and its less virulent and more common, community-based cousin, CA-MRSA, the two main types of MRSA infection.
and poison immune system white blood cells meant to fight the bacterial infection, but LUK-PV is secreted only by community-acquired MRSA,
Torres also said that these study results challenge the current mindset for finding a vaccine against staphylococcal infections,
an associate professor at NYU Langone. e have to take a broader view of the pathogen
in order to develop an effective vaccine. n a separate set of laboratory experiments previously described in the journal Cell Host & Microbe online August 27, researchers at Torreslaboratory and colleagues in The netherlands, France,
and Australia showed how LUK-ED attacked red blood cells to obtain nutrients, most notably iron, essential for its rapid growth and infection.
The international team found that the toxin split apart the red blood cells by attaching itself first to their so-called Duffy antigen protein receptor
and red blood cells, making their host more vulnerable to infection. Other experiments are set to determine how widespread bacteremia from staphylococcal infections actually shuts down the mammalian body
causing death. Torres also has plans to study groups of Africans known to be genetically deficient in Duffy antigens and, hence, more resistant to malaria,
to see if they are resistant to staphylococcal infection, as well y
#Researchers Find New Clue to Halting Leukemia Relapse A protein domain once considered of little importance may be key to helping patients who are fighting acute myeloid leukemia (AML) avoid a relapse.
Researchers at Rice university, working with colleagues at Baylor College of Medicine and the University of Texas MD Anderson Cancer Center, have made a small molecule that could deliver a one-two punch to proteins that resist chemotherapy
in patients with AML. The protein, called STAT3, interferes with chemotherapy by halting the death of cancerous cells
and allowing them to proliferate. The molecule discovered at Rice locates and then attacks a previously unknown binding site on STAT3,
disrupting its disease-promoting effects. The new work led by Rice chemist Zachary Ball, Baylor pediatrician Michele Redell and MD Anderson oncologist David Tweardy appears this week in the journal Angewandte Chemie.
The discovery and exploitation of this new drug target was made possible by an earlier discovery by Ball lab. That finding enabled researchers to identify, on a molecular level,
and other cancers helps the cancer cells survive chemotherapy, so any new strategy we can develop to stop that process could mean real benefit for our patients,
who is also part of the leukemia and lymphoma teams at Texas Children Hospital. Ball said STAT3 has been a target for scientists trying to shut down cancer cells.
TAT fits in the broad category of what are called ndruggable protein-protein interactions. There a large surface area with weak interactions for which we have failed typically to find good drugs,
from a medicinal perspective, is that this compound also works in a mouse model, he said. ll the other compounds worked in cells,
and points the way to future anticancer approaches, including combination therapies of coiled-coil STAT3 inhibitors in tandem with other agents,
Such knowledge could pave the way for new drugs for a myriad of diseases, including cancer.
The human body has a nifty way of turning its proteins on and off to alter their function and activity in cells:
and structure of phosphoproteins and identify which ones are involved in disease. his innovation will help advance the understanding of human biochemistry and physiology,
Trouble in the phosphorylation process can be a hallmark of disease, such as cancer, inflammation and Alzheimer disease.
and their role in disease a daunting task. ur technology begins to make this a tractable problem,
As a synthetic biologist, Jewett uses cell-free systems to create new therapies, chemicals and novel materials to impact public health
and the environment. his work addresses the broader question of how can we repurpose the protein synthesis machinery of the cell for synthetic biology,
the researchers produced a human kinase that is involved in tumor cell proliferation and showed that it was functional and active.
Kinases are implicated in many diseases and therefore, of particular interest. he ability to produce kinases for study should be useful in learning how these proteins function and in developing new types of drugs,
impacting normal growth as well as cancer and disease. Dysregulation of histone methylation patterns is observed in a variety of human cancers, inflammation,
and neurodegenerative diseases, validating histone methyltransferases (HMTS) as an important class of drug targets among biomedical researchers.
The newly issued patent US No. 9, 120,820, claims detection analyte probes based on a natural product mimic of the methyltransferase cofactor S-adenosylmethionine (SAM.
An estimated 10 to 30 percent of global medicines sold in developing countries like Afghanistan
and parts of Africa are counterfeit, according to The Centers for Disease Control and Prevention (CDC).
Medical professionals would then be able to check these small notches with a scanner before they give the medication to a patient.
The new device uses microfluidics technology and could significantly reduce the cost of sophisticated tests for diseases such as HIV, Lyme disease and syphilis, according to the study authors.
The ability to analyze miniscule amounts of fluid could also promote more research on autoimmune joint diseases,
Overtext Web Module V3.0 Alpha
Copyright Semantic-Knowledge, 1994-2011