#Tuberculosis bacteria hide in low oxygen niches of bone marrow stem cells A new study from the Forsyth Institute is helping to shed light on latent tuberculosis and the bacteria's ability to hide in stem cells.
Some bone marrow stem cells reside in low oxygen (hypoxia) zones. These specialized zones are secured as immune cells
and toxic chemicals cannot reach this zone. Hypoxia-activated cell signaling pathways may also protect the stem cells from dying or aging.
A new study led by Forsyth Scientist Dr. Bikul Das has found that Mycobacterium tuberculosis (Mtb) hijack this protective hypoxic zone to hide intracellular to a special stem cell type.
The study was published online on June 8th in the American Journal of Pathology. Mtb the causative organism of tuberculosis, infects nearly 2. 2 billion people worldwide
and causes 1. 7 million annual deaths. This is largely attributed to the bacteria's ability to stay dormant in the human body
and later resurface as active disease. Earlier research at Forsyth revealed that Mtb hides inside a specific stem cell population in bone marrow, the CD271+mesenchymal stem cells.
However, the exact location of the Mtb harboring stem cells was known not.""From our previous research, we learned that cancer stem cells reside in the hypoxic zones to maintain self-renewal property,
and escape from the immune system"said Bikul Das, MBBS, Phd, Associate Research Investigator at the Forsyth Institute,
like cancer, may also have figured out the advantage of hiding in the hypoxic area.""To test this hypothesis, Dr. Das and his collaborators at Jawarharlal Nehru Univeristy (JNU), New delhi,
and Kavikrishna Laboratory, Indian Institute of technology, Guwahati, utilized a well-known mouse model of Mtb infection, where months after drug treatment,
Using this mouse model of dormancy, scientists isolated the special bone marrow stem cell type, the CD271+mesenchymal stem cells, from the drug treated mice.
Experiments also confirmed that these stem cells express a hypoxia activated gene, the hypoxia inducible factor 1 alpha (HIF-1 alpha.
the team isolated the CD271+stem cell type from the bone marrow of TB infected human subjects who had undergone extensive treatment for the disease.
"These findings now explain why it is difficult to develop vaccines against tuberculosis, "said Dr. Das."
"The immune cells activated by the vaccine agent may not be able to reach the hypoxic site of bone marrow to target these"wolfs-in-stem-cell-clothing."
and its application to global health issues including TB, HIV and oral cancer, all critical problems in the area where Kavikrishna Laboratory is located d
#Discovery promises new treatments to thwart colon cancer Scientists at St jude Children's Research Hospital have discovered how an immune system protein,
called AIM2 (Absent in Melanoma 2), plays a role in determining the aggressiveness of colon cancer.
a member of the St jude Department of Immunology, published their findings in a recent issue of the journal Cell.
'Since reduced AIM2 activity in colorectal cancer patients is associated with poor survival, it might be useful to detect the level of AIM2 expression in polyps taken from colonoscopy and use this as one of the biomarkers for prognosis,
'Kanneganti said. Kanneganti and her team believe that it might be possible to prevent the disease
or reduce its risk by treating susceptible people to increase AIM2 activity and give them healthy donor bacteria.'
'In people who already have colorectal cancer, therapies that boost the expression of AIM2, such as interferons, might reduce tumor progression.
Also, transferring healthy microbiota or a group of'good'bacteria to patients with colorectal cancer at the early stage of disease may prolong survival,
'Kanneganti said. Cancer researchers had known that mutations in AIM2 were frequently found in patients with colorectal cancers.
And a study by other researchers had found that more than half of small bowel tumors had AIM2 mutations.
However, AIM2's established function in the cell was not in the machinery of cancer
said one of the paper's first authors Si Ming Man, Ph d.,a postdoctoral fellow in Kanneganti's laboratory.
'This was how we became interested in AIM2 and colorectal cancer.''In their experiments with mice, the scientists used chemicals to trigger the process mimicking the development of colorectal cancer.
They found that the mice showed drastically reduced AIM2 function, confirming the finding in humans with the cancer.
They also found that mice genetically altered to have reduced AIM2 function, when treated with the chemicals,
showed significantly more tumors than normal mice. The scientists'studies also showed that AIM2 played a role independent of its immune role,
'Many previous studies have indicated that AIM2 contributes to the immune system by acting as a pathogen sensor,
'However, our work is the first to identify AIM2's role in controlling proliferation of intestinal stem cells.
This work is truly exciting to us because we have found a new role for AIM2 in regulating colorectal cancer,
and it does so by inhibiting excessive proliferation of stem cells in the large intestine.''The researchers also pinpointed the specific cellular machinery regulated by AIM2.
based on studies from Kanneganti's lab and others indicating that microbial sensors similar to AIM2 contributed to healthy gut microbiota.
The scientists found a striking reduction in colon tumors in the AIM2-deficient mice and an increase in tumors in the normal mice.'
'What this might suggest is that transfer of some of the'good'microbiota from wild-type mice to replace the'bad'microbiota from mice lacking AIM2 offers increased protection against colorectal cancer,
or decelerate the progression of colorectal cancer in humans, especially in those who have mutations in the AIM2 gene,
by simply giving them'good'microbiota.''''We have scratched only the surface of the role of AIM2 in controlling stem cell proliferation and the maintenance of a healthy gut microbiota,
#Supercomputers surprisingly link DNA crosses to cancer Supercomputers have helped scientists find a surprising link between cross-shaped (or cruciform) pieces of DNA and human cancer, according to a study at The University of Texas at Austin (UT Austin.
scientists estimate as many as 500,000 cruciform-forming sequences may exist on average in a normal human genome.
Small cruciforms enable DNA replication and gene expression, essential for human life. But scientists have suspected also these small cruciforms--a structure of DNA itself--to be linked to mutations that can elevate cancer risk.
DNA cruciforms are created by short inverted repeats of the nucleotides Adenine-Thymine-Cytosine-Guanine that form the bases of DNA structure.
altering DNA in a way that can increase risk of cancer in yeast, monkeys, and in humans.
High performance computing at UT Austin's Texas Advanced Computing Center (TACC) with the Stampede and Lonestar supercomputers helped the researchers find short inverted repeats of 30 base pairs
and under in a reference database of mutations in human cancer that are somatic, meaning not inherited.
or translocations'can lead to cancer development.''We found that short inverted repeats are enriched indeed at translocation breakpoints in human cancer genomes,
'lead author Karen Vazquez said. Vasquez is the James T. Delucio Regents Professor in the Division of Pharmacology and Toxicology at The University of Texas at Austin.'
'In many cases, translocations are what turn a normal cell into a cancer cell,'co-author Albino Bacolla said.
Bacolla is a research associate in the Vasquez Lab.'What we found in our study was that the sites of chromosome breaks are not random along the DNA double helix;
built by the short inverted repeats, mark the spots for chromosome breaks, mutations, and potentially initiate cancer development.'
'Vasquez said, 'We have studied also the potential mechanisms that are involved in the interplays among alternative DNA structures and cancer development.
Our team has discovered at least two different mechanistic pathways: one involving DNA replication, where these unusual structures cause a roadblock to DNA replication;
'DNA double-strand breaks can increase the risk of cancer because they can result in translocations, deletions,
'These modifications of the DNA can lead to cancer, 'Vasquez said. According to Paul Okano, program director at the Division of Cancer Biology of the National Cancer Institute,
'The focus of Dr. Vasquez'research on the mechanisms of alternate DNA structure-induced mutations, DNA breaks,
and chromosome translocations is a novel and significant aspect of NCI grant supported studies on mechanisms of genomic instability.
Dr. Vasquez'studies on the role of non-B DNA sequences in these mechanisms can contribute to our knowledge of the etiology of human cancer.'
'Several studies went into the report Vasquez and her lab electronically published ahead of print in March 2015 in the journal Cell Reports.
We used the TACC supercomputers for that aspect of the work.''''We have used both the Stampede and the Lonestar Linux clusters.
We usually back up our data on Corral, 'Bacolla said. The challenge and need for using HPC,
said Bacolla, is that the time required to find all combinations of inverted repeats, given a DNA sequence is enormous.
The Vasquez team designed their algorithm to take a string of letters corresponding to the DNA bases A-t-C-G
Then the number of these iterations needs to be multiplied by the length of the DNA, then by the number of the translocations in our cancer patients,
'We needed to compare the frequencies of inverted repeats found in the COSMIC data set with those that we would find in control, by chance.'
'COSMIC is maintained a database by the Sanger Institute in the U k. of mutations found in human somatic, or noninheritable cancer.'
'We had 20,000 translocations from human cancers from the COSMIC database; 200 bases of DNA for each translocation;
We certainly cannot do this kind of work on our laptop or anything like a normal system in our laboratories;
when he tried to scale up to 100 or more sequences on one processor.''To solve this, we had to get in touch with TACC support staff,
'Bacolla said.''They checked our script and analyzed the error log that we got. Finally, we ended up with a solution by giving to each processor fewer sequences.'
'This allowed Bacolla to scale his code up and use over 1, 000 processors at once.'
'It would not have been possible to do this job without the TACC resources, 'Bacolla said.''The center is an incredible resource in terms of its capacity and support.
and staff support for some time now. It's a wonderful opportunity for researchers at UT Austin.''
''With TACC's support, we were able to see that this is at least one plausible explanation in human cancer etiology,
'Our overarching interest is to understand how DNA structure can influence cancer development. With access to TACC, we are more confident that DNA sequences capable of forming particular unusual structures present a plausible explanation for how DNA breaks can lead to translocations in cancer,
'Vasquez said.''Our next steps are to go forward with a mouse model that can detect mutations
and translocations in the mouse genome using human sequences from these cancer breakpoints, 'Vasquez said.
Does this really occur now in the context of chromosomes in living organisms? Is it tissue specific?
Does aging make a difference? These are the types of questions that the researchers will ask.'
'The long term goal for these studies is to develop better prevention or treatment strategies for cancer patients,
They facilitate replication origin firing, initiating human DNA replication.''They have both positive and negative functions,
''If we can help clinical scientists apply mechanistic information such as we hope will be gained from our research to better cancer treatment and a cancer prevention strategies,
'Vasquez sees a bright future in the intertwining of computation and the life sciences.''I think the potential of the computational analysis is mind-blowing.
Bioinformatics and computational centers like TACC are critical for the next steps in science. It's an exciting time,
#Miniscule mirrored cavities connect quantum memories The enhanced interactions between light and atoms and the extended spin-coherence times are essential steps toward realizing real-world quantum memories and, hence, quantum computing systems,
which could solve some problems faster than conventional systems. Additionally, these advances could significantly impact the development of high-security, long-distance, cryptographic fiber optic communication networks.
Nanoscale mirrored cavities that trap light around atoms in diamond crystals increase the quantum mechanical interactions between light and electrons in atoms.
Such interactions are essential to the creation and the connection of memory for quantum computers. Recent research
and the Center for Functional Nanomaterials at the U s. Department of energy's Brookhaven National Laboratory, has demonstrated a new process to construct such diamond nanocavities in
This improvement in the coherence time is more than two orders of magnitude better than previously reported times for cavity-coupled single quantum memories in solid state systems.
The fabrication of the optical cavities relied on a new silicon hard-mask fabrication process that applies mature semiconductor fabrication methods for patterning high-quality photonic devices into unconventional substrates.
Fabrication and experiments were supported in part by the Air force Office of Scientific research (AFOSR Grant No.
Research was carried out in part at the Center for Functional Nanomaterials, Brookhaven National Laboratory, which is supported by the U s. Department of energy, Office of Science, Office of Basic energy Sciences, under Contract No.
DE-AC02-98ch10886. Support is acknowledged also from the Alexander Von humboldt Foundation, the NASA Office of the Chief Technologist's Space technology Research Fellowship, the AFOSR Quantum memories Multidisciplinary University Research Initiative,
and the National Science Foundation Integrative Graduate education and Research Traineeship Program, Interdisciplinary Quantum Information science and Engineering (iquise
#Cell that replenishes heart muscle found by researchers Regenerative medicine researchers at UT Southwestern Medical center have identified a cell that replenishes adult heart muscle by using a new cell lineage-tracing technique they devised.
Adult heart muscle is comprised of cells called cardiomyocytes. Most cardiomyocytes don't replenish themselves after a heart attack or other significant heart muscle damage.
The UT Southwestern researchers were able to devise a new cell-tracing technique, allowing them to detect cells that do replenish themselves after being damaged."
Dr. Hesham Sadek, Assistant professor of Internal medicine and with the Hamon Center for Regenerative Science and Medicine.
Previous research by UT Southwestern scientists revealed that it is oxygenated the highly environment of the heart that prevents most heart muscle cells from dividing.
"This is exciting work from both scientific and methodological standpoints, "said Dr. Joseph Hill, Chief of the Division of Cardiology and Professor of Internal medicine at UT Southwestern,
who holds the James T. Willerson, M d. Distinguished Chair in Cardiovascular diseases and the Frank M. Ryburn, Jr.
Chair in Heart Research.""Dr. Sadek's discovery points to a novel mechanism of cell-cycle control in cardiac myocytes
as well as in cancers, the researchers said. Traditional fate mapping, which is somewhat like developing a family tree for cells, labels cells based on the expression of a certain gene.
which are regulated mainly at the protein level rather than the gene expression level. Instead, the researchers developed a sophisticated protein-tracking technique based on the presence of a hypoxia-responsive protein called Hif-1alpha.
Researchers developed a genetically modified mouse in which the Hif-1alpha protein is fused to another protein,
called Cre recombinase, which could then be used for cellular labeling.""This fate-mapping approach, based on protein stabilization rather than gene expression, is an important tool for studying hypoxia in the whole organism.
It can identify any hypoxic cell, not just cardiomyocytes, so this has broad implications for cellular turnover in any organ,
and even in cancer,"said Dr. Sadek, whose lab focuses on cardiac regeneration and stem cell metabolism m
#New material with superfast electrons: 300 kilometers per second Scientists at the Max Planck Institute for Chemical Physics of Solids have discovered that the electrical resistance of a compound of niobium
when the material is exposed to a magnetic field. This giant magnetoresistance, which is responsible for the large storage capacity of modern hard discs,
The Max Planck researchers, together with colleagues from the High-Field magnet Laboratories at the Helmholtz-Zentrum Dresden-Rossendorf and at the Radboud University in The netherlands
Electronic systems are expected to process and store a steadily increasing amount of data, faster and faster,
and in less space. Luckily, physicists discover effects that help engineers to develop better electronic components with surprising regularity, for instance a phenomenon known as giant magnetoresistance.
Modern hard discs utilize this phenomenon to significantly alter the resistance of a material by exposing it to a magnetic field.
Until now, the computer industry has used various materials stacked on top of each other in a filigree structure to achieve this effect.
Now Max Planck scientists in Dresden have observed a rapid increase in resistance by a factor of 10,000 in a non-complex material, namely niobium phosphide (Nbp.
The resistance of niobium phosphide changes so dramatically in a magnetic field, because the charge carriers are deflected by a phenomenon known as the Lorentz force.
This force causes an increasing percentage of electrons to start flowing in the"wrong"direction as the magnetic field is ramped up,
the greater the Lorentz force and thus the effect of a magnetic field,"explains Binghai Yan, a researcher at the Max Planck Institute for Chemical Physics of Solids in Dresden.
He and his colleagues therefore came up with the idea of investigating a compound consisting of the transition metal niobium (Nb
For their investigations, the scientists used the Dresden High Magnetic field Laboratory, as well as the High-Field magnet Laboratory at Radboud University in Nijmegen, Netherlands,
and the Diamond Light source in Oxfordshire, England. In the process, they discovered why the electrons are so fast and mobile.
The material owes its exotic properties to unusual electronic states in niobium phosphide. Some electrons in this material, known as a Weyl metal
This material class therefore has enormous potential for future applications in information technology
#Expanding the DNA alphabet:''Extra'DNA base found to be stable in mammals Array'This modification to DNA is found in very specific positions in the genome--the places which regulate genes,
'said the paper's lead author Dr. Martin Bachman, who conducted the research while at Cambridge's Department of chemistry.'
'said Professor Shankar Balasubramanian of the Department of chemistry and the Cancer Research UK Cambridge Institute, who led the research.'
but the fact that we've demonstrated it can be stable in living tissue shows that it could regulate gene expression and potentially signal other events in cells.'
The way these bases are ordered determines the makeup of the genome. In addition to G, C a and T, there are also small chemical modifications,
or epigenetic marks, which affect how the DNA sequence is interpreted and control how certain genes are switched on or off.
The study of these marks and how they affect gene activity is known as epigenetics. 5fc is one of these marks,
making it likely that it plays a key role in the genome. Using high-resolution mass spectrometry,
the researchers examined levels of 5fc in living adult and embryonic mouse tissues, as well as in mouse embryonic stem cells--the body's master cells which can become almost any cell type in the body.
They found that 5fc is present in all tissues but is very rare, making it difficult to detect.
and the role that these modifications may play in the development of certain diseases, 'said Balasubramanian.'
'While work is continuing in determining the exact function of this'extra'base, its position in the genome suggests that it has a key role in the regulation of gene expression.'
'The research was supported by Cancer Research UK, the Wellcome Trust and the Biotechnology and Biological sciences Research Council UK K
#New formula expected to spur advances in clean energy generation Researchers from the University of Houston have devised a new formula for calculating the maximum efficiency of thermoelectric materials, the first new formula in more than a half-century,
designed to speed up the development of new materials suitable for practical use. By using the new formula,
whether devices based on a material would generate energy efficiently enough to be worth pursuing, said Zhifeng Ren, principal investigator at the Texas Center for Superconductivity at UH (Tcsuh."
"This is a form for the quick screening of materials, "said Ren, who is also M d. Anderson Chair professor of physics at UH."
"If the engineering ZT is not high enough, don't waste your time trying to build a device."
Thermoelectric materials produce electricity by exploiting the flow of heat current from a warmer area to a cooler area,
In thermoelectric materials, efficiency is calculated as the measure of how well it converts heat--often waste heat generated by power plants or other industrial processes--into power.
and produces 10 watts of electricity has an efficiency rate of 10 percent. Top efficiency for current thermoelectric materials is about 12 percent
"For this reason, it is desirable to establish a new model to predict the energy conversion efficiency based on the temperature-dependent individual TE (thermoelectric) properties for devices operating under a large temperature difference."
including a magnesium-silver-antimony (Mgagsb) compound, bismuth tellurides, half-Heuslers and skutterudites. The tested values matched those determined by computational analysis using the new formulas,
gastric cancer Researchers have devised a breath test that can help doctors diagnose the early signs of esophageal and gastric cancer in minutes.
and will now be tested in a larger trial involving three hospitals in London. Researchers analysed breath samples of 210 patients using the test.
They found that the test can discriminate between malignant and benign esophageal cancer in patients for the first time.
The test can also be applied to detect gastric (stomach) cancer tumours. According to the researchers, economic modelling showed that the test could save the NHS £145 million a year
Esophageal and gastric malignancies account for 15 per cent of cancer-related deaths globally. Both cancers are diagnosed usually in the advanced stages
because they rarely cause any noticeable symptoms when they first develop. As a result, the long-term survival rate is 13 per cent for esophageal cancer and 15 per cent for gastric cancer in the UK.
However diagnosis of these cancers at an early stage can improve survival rates. Doctors diagnose esophageal and gastric cancers by carrying out an endoscopy.
This is a procedure where the inside of the body is examined using a probe with a light source and video camera at the end via the mouth and down the gullet.
However, the procedure is invasive and costs the NHS around £400-£600 per endoscopy. Only two per cent of patients who are referred for an endoscopy by GPS are diagnosed with esophageal or gastric cancer.
The first study, published in the Annals of Surgery was carried out by an international team led by scientists at Imperial College London and clinicians at Imperial College Healthcare NHS Trust.
Researchers from UCL (University college London), Keele University Medical school, Heyrovsky Institute of Physical chemistry and Academy of Sciences of the Czech republic were involved also in the study.
Now, 400 patients at UCLH (University college London Hospitals NHS Foundation Trust), The Royal Marsden NHS Foundation Trust,
and Guy's and St thomas'NHS Foundation Trust will take part in a further trial. The researchers hope to use the findings from the clinical trial to create a sensor device that can signal to clinicians
if a patient has a malignant tumour. Professor George Hanna lead author of the study
and Director of NIHR-Diagnostic Evidence Cooperatives at Imperial College London, said:""Esophageal and gastric cancers are on the rise in the UK with more than 16,000 new cases diagnosed each year.
The current method for detecting these cancers is expensive, invasive and a diagnosis is made usually at a late stage
and often the cancer has spread to other parts of the body. This makes it harder to treat and results in poor long-term survival rates.
Our breath test could address these problems because it can help diagnose patients with early nonspecific symptoms as well as reduce the number of invasive endoscopies carried out on patients,
which often lead to negative results. Diagnosis at an early stage could give patients more treatment options and ultimately save more lives."
"The test looks for chemical compounds in exhaled breath that are unique to patients with esophageal and gastric cancer.
The cancers produce a distinctive smell of volatile organic compounds (VOC), chemicals that contain carbon and are found in all living things,
which can help doctors detect early signs of the disease. Researchers were able to identify for the first time the number of VOCS in breath samples by using a selected ion flow tube mass spectrometer,
an analytical instrument used to identify what chemicals are present in a sample. This quantitative technology identified VOCS that were present at significantly higher concentrations in patients with esophageal and gastric cancer than in non-cancerous patients.
The researchers say that the results could be used to set a biomarker, a biological feature used to measure the presence or progress of a disease.
To take the test, patients breathe into a device similar to a breathalyser which is connected to a bag.
The compounds in their exhaled breath are analysed by a selected ion flow tube mass spectrometer. The researchers used breath samples of patients with esophageal and gastric cancer at Imperial College Healthcare NHS Trust from 2011 to 2013.
Patients who are at risk of developing these cancers and those who had benign tumours were tested also.
Similar breath tests to discriminate between benign and malignant tumours exist but researchers say they have lengthy processing times
and are unable to quantify the amounts of VOCS present in exhaled breath e
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