#Scientists discover key to what causes immune cell migration to wounds Immune cells play an important role in the upkeep
and repair of our bodies, helping us to defend against infection and disease. Until now, how these cells detect a wounded
or damaged site has remained largely a mystery. New research, led by University of Bristol academics in collaboration with a team from the University of Sheffield,
has identified the triggers which lead these cells to react and respond in cell repair. It is hoped the findings,
published in Current Biology, could help scientists design therapies to manipulate the cell repair process
and direct immune cells away from sites where they are doing damage, such as tumours, and send them to places where they are needed.
Previous studies had found that the earliest signal produced at a wound site responsible for attracting immune cells to the damaged site is hydrogen peroxide (H2o2.
However, it was still unclear how these cells detect this chemical, and what signaling occurs in these cells downstream of H2o2 detection to power their rapid migration.
Using the common fruitfly (Drosophila melanogaster) and timelapse microscopy, the team led by Professor Will Wood at the University of Bristol were able to study the process in situ
and identify what causes the cells to migrate to sites of damage where they then detect,
ingest and degrade debris, dying cells and invading pathogens. After dissecting the signaling occurring in immune cells responding to wound induced (H2o2),
the team found that it involved a well-established immune signalling pathway used in vertebrate adaptive immune responses.
The results suggest that adaptive immune signalling pathways important in distinguishing self from non-self in vertebrates appear to have evolved from a more ancient response designed to distinguished amaged selffrom ealthy Self will Wood, Professor of Developmental biology
, in Bristol School for Cellular and Molecular Medicine, and the study lead author, said: hile inflammation is critical to prevent infection,
too much of a response by immune cells can cause or worsen a wide range of human diseases
and conditions including autoimmunity, atherosclerosis, cancer and chronic inflammation. his research is therefore critical for improving human health as it enables us to discover novel points of intervention to manipulate immune cell behaviour
and allow us to design therapies to direct immune cells away from sites where they are doing damage
and send them into places where they are needed. y
#First successful study of virus attack on cancer It a new weapon in the arsenal of cancer fighting treatments:
utilizing genetically modified viruses to invade cancer cells and destroy them from the inside. University of Louisville researcher Jason Chesney, M d.,Ph d.,deputy director of the James Graham Brown Cancer Center (JGBCC),
and a team of international scientists found that stage IIIB to IV melanoma patients treated with a modified cold sore (herpes virus had improved survival.
The results of the findings were published recently in the Journal of Clinical Oncology. Uofl was one of the major sites for the phase III clinical trial involving 436 patients who received the viral immunotherapy, talimogene laherparepvec (T-VEC.
Scientists genetically engineered the herpes simplex I virus to be non-pathogenic, cancer-killing and immune-stimulating.
The modified herpes virus does not harm healthy cells, but replicates when injected into lesions or tumors,
and then stimulates the body immune system to fight the cancer. he results from this study are said amazing,
Chesney. atients given T-VEC at an early stage survived about 20 months longer than patients given a different type of treatment.
For some, the therapy has lengthened their survival by years. hari Wells from Ashland, Kentucky is one of those patients.
She entered the trial in 2010 with stage IV or metastatic, melanoma. Before entering the T-VEC trial,
she had been through numerous procedures and major surgeries. According to Wells, nothing worked and she was facing a death sentence. hen you hear that you may only have three to six months to live,
it is very scary, Wells said. would not be alive today if I had not been accepted into the T-VEC trial.
Dr. Chesney and the James Graham Brown Cancer Center saved my life. ells drove to Louisville every two weeks for about two
and a half years to receive injections in each of the more than 60 lesions on her leg.
The lesions eventually began to fade and finally disappeared. She has been in remission for almost three years. want everyone to know they should never give up hope.
With research there will always be something new tomorrow that wasn here today, she said.
The U s. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) are considering findings from the trial to make the treatments available to more patients with advanced melanoma.
More Researchthe Journal of Clinical Oncology report comes on the heels of Chesney findings from another study published this month in the New england Journal of Medicine.
The article describes an immunotherapy for melanoma utilizing the checkpoint inhibitors, ipilimumab and nivolumab. In cell biology
their role is to reduce the effectiveness of two immune checkpoint proteins responsible for telling the immune system to turn off
and not kill the cancer cells. The study found that injection of the two inhibitors shrunk tumors in the majority of patients with advanced melanoma.
The JGBCC was one of the top centers worldwide to enroll patients and find that ipilimumab combined with nivolumab resulted in the highest anticancer efficacy ever observed after treatment with a cancer immunotherapy.
Chesney and his team, working with the pharmaceutical company Amgen, are taking the success of their trials a step further combining T-VEC with the immune checkpoint inhibitor ipilimumab into a treatment regimen.
The clinical trial is underway at the JGBCC and other sites in hopes of accelerating cancer immunity and curing patients. e finally understand how to activate the human immune system to clear cancer cells,
having developed new classes of immunotherapies that dramatically improve the survival of cancer patients, Chesney said. believe T-VEC combined with immune checkpoint inhibitors will not only reduce cancer-related mortality in melanoma but in all cancer types,
and we are moving quickly to develop these methods. ource: Uof e
#Researchers retrieve ostmemories Retrograde amnesia is the inability to recall established memories. In humans, amnesia is associated with traumatic brain injury, Alzheimer disease,
and other neurological conditions. Whether memories lost to amnesia are erased completely or merely unable to be recalled remains an open question.
Now, in a finding that casts new light on the nature of memory, published in Science,
researchers from the RIKEN-MIT Center for Neural Circuit Genetics demonstrated in mice that traces of old memories do remain in the amnestic brain,
and that the cellular pathways underlying them can be reactivated, allowing lost memories to be found.
The research team led by Susumu Tonegawa, Director of the RIKEN Brain science Institute in Saitama, Japan, was interested in how stable memories are formed in the brain and whether memories
whose storage was disrupted by chemically inducing retrograde amnesia, could still be recalled. rain researchers have been divided for decades on
whether amnesia is caused by an impairment in the storage of a memory, or in its recall, said Tonegawa.
To make mice amnestic, they were trained first to associate a mild foot shock with a specific environment,
chamber A, eliciting a typical reezingbehavior. Eventually, trained mice would freeze in chamber A even without the shock.
Neurons activated during memory formation were labeled genetically to allow their visualization and reactivation. Then some mice were given a chemical, anisomycin,
which inhibits new protein synthesis and prevents increases in synaptic strength important for memory encoding,
thus inducing retrograde amnesia. Other mice received saline as a control. As expected, amnestic mice returned to chamber A did not freeze,
indicating that they could not recall the memory for the specific association of the chamber and the mild foot shock.
Next, to investigate whether the stored memory from the foot shock training in chamber A was absent from the amnestic mice
or remained present but was not retrievable, the researchers used optogenetic technology to selectively activate neurons that were labeled genetically during their training in chamber A with a blue light-sensitive protein,
channelrhodopsin, but this time while the mice were in a novel, neutral environment, chamber B. Surprisingly,
during activation of the cells involved in the foot shock memory, collectively called a emory engram with blue light pulses,
despite the induction of retrograde amnesia, the authors suggest that different processes may control memory encoding and recall.
during the training period, brain connections between unique memory engrams in neighboring brain structures may be strengthened
says Tonegawa, s that in retrograde amnesia, past memories may not be erased, but could simply be lost and inaccessible for recall.
and will stimulate future research on the biology of memory and its clinical restoration. d
and save thousands of dollars per transplant. UCLA researchers measured liver function in 53 potential organ donors using the fingertip probe.
In the study, it successfully predicted every time which livers would function properly in transplant patients,
the study first author and an assistant professor of surgery in UCLA division of liver and pancreas transplantation. his device is best single predictor of organ survival in our patients,
Larger scale gene function studies A relatively new method of targeting specific DNA sequences in zebrafish could dramatically accelerate the discovery of gene function and the identification of disease genes in humans, according to scientists at the National Human genome Research
. a senior investigator with NHGRI Translational and Functional genomics Branch and head of the Developmental Genomics Section. hat we have done is to establish an entire pipeline for knocking out many genes and testing their function quickly in a vertebrate
or have been identified as possible disease genes, but the functions of those genes have not been confirmed by knocking them out in animal models and seeing
Dr. Burgess said. he study of zebrafish has led already to advances in our understanding of cancer
and other human diseases, said NHGRI Director Eric Green, M d, . Ph d. e anticipate that the techniques developed by NHGRI researchers will accelerate understanding the biological function of specific genes
and the role they play in human genetic diseases. The CRISPR/Cas9 method of gene editing is one of the two essential components in the NHGRI team high-throughput method.
Modeled on a defense mechanism evolved by bacteria against viruses, CRISPR/Cas9 activity was described first in 2012.
The zebrafish and the mouse are the most commonly studied vertebrate laboratory animals whose genomes have been sequenced completely.
The zebrafish is suited better to larger scale gene editing because about 70 percent of zebrafish genes appear to have human counterparts
of which are similar to human genes involved in deafness. Hearing is one of the other interests of Dr. Burgess lab.)This produced mutations in 82 of the 83 genes.
In screening embryos by fluorescent polymerase chain reaction (a technology that allows researchers to produce millions of copies of a specific DNA sequence)
and high-throughput DNA sequencing, the researchers determined that overall, mutations were passed on to the next generation in 28 percent of cases.
The transmission rate was higher for some genes than for others, but in most cases, screening offspring from parent fish should be enough to spot most mutations, the researchers reported.
The results demonstrated that using the CRISPR/Cas9 technique in zebrafish will make it possible to both generate mutants for all genes in the zebrafish genome
and carry out arge-scale phenotyping, they noted in the Genome Research paper. The CRISPR/Cas9 methodology works in mice, too,
but it is more costly and takes far longer. Although mice actually reach sexual maturity earlier than zebrafish,
they produce far fewer offspring. Ultimately, Dr. Burgess hopes that his lab will use the new method to knock out about 10 percent of the zebrafish roughly 25,000 genes,
you could target every gene in the genome with what would be a relatively modest scientific investment in the low tens of millions of dollars. e
#Researchers Discover Electron Pairing without Superconductivity A team of physicists from the University of Pittsburgh, the University of Wisconsin-Madison,
and the U s. Naval Research Laboratory (NRL) has discovered electron pairing in strontium titanate far above the superconducting transition temperature.
Superconductors are used for many applications including in magnetic resonance imaging devices and for magnetic energy storage. The basis for all superconductors is the formation of electron pairs.
In the normal non-superconducting phase, the electrons in most metals move independentlyhe scattering of electrons causes electrical resistance.
In a superconductor, the paired electrons move in a highly coordinated fashion that has zero electrical resistance.
The new research identified an intermediate phase in which electrons form pairs, but the pairs move independently.
The researchers used quantum dots in strontium titanate to observe the electron pairs. Quantum dots are small regions of a material in
which the number of electrons can be controlled precisely, in this case using an electrostatic gate. The quantum dots were large enough to support a superconducting phase at low temperatures
but the researchers observed that the dots always preferred an even number of electrons in the new phase at higher temperatures.
When the researchers applied a magnetic field, they observed breaking of the electron pairs one at a time. A theory of electron pairing without formation of a superconducting state was published first by David M. Eagles in 1969.
C. Stephen Hellberg, a physicist in NRL Material Science and Technology Division and the team theorist, observed he results are described well by a simple model with attractive interactions between electrons.
and measured 58 quantum dots with varying dimensions and barriers between the quantum dots and the leads.
The discovery provides clues about the mechanisms causing superconductivity in strontium titanate, which may eventually help researchers to the discovery of a material that superconducts at room temperature.
These images show differential conductance through the quantum dot as a function of the gate voltage that controls the number of electrons in the dot (x-axis) and the applied magnetic field (y-axis).
The top panel shows the measured differential conductance; the bottom panel shows the theoretical calculation (which has no disorder.
Both experiment and theory show splitting of the electron pairs with increasing field and reentrant pairing at higher fields (the merging of pairs of boundaries into vertical boundaries) l
#Injectable electronics New system holds promise for basic neuroscience, treatment of neurodegenerative diseasesit a notion that might be pulled from the pages of science-fiction novel electronic devices that can be injected directly into the brain,
and treat everything from neurodegenerative disorders to paralysis. It sounds unlikely, until you visit Charles Lieber lab. A team of international researchers, led by Lieber, the Mark Hyman, Jr.
Professor of Chemistry, an international team of researchers developed a method for fabricating nanoscale electronic scaffolds that can be injected via syringe.
Once connected to electronic devices the scaffolds can be used to monitor neural activity, stimulate tissues and even promote regenerations of neurons.
The study is described in a June 8 paper in Nature Nanotechnology. Contributing to the work were Jia Liu, Tian-Ming Fu, Zengguang Cheng, Guosong Hong, Tao Zhou, Lihua Jin, Madhavi Duvvuri, Zhe Jiang, Peter
Kruskal, Chong Xie, Zhigang Suo, Ying Fang do feel that this has the potential to be said revolutionary,
Lieber. his opens up a completely new frontier where we can explore the interface between electronic structures and biology.
but no one has addressed this issue the electronics/cellular interface at the level at which biology works. he idea of merging the biological with the electronic is not a new one for Lieber.
In an earlier study, scientists in Lieber lab demonstrated that the scaffolds could be used to create yborgtissue
When releasing the electronics scaffold completely from the fabrication substrate, we noticed that it was almost invisible and very flexible like a polymer
and could literally be sucked into a glass needle or pipette. From there, we simply asked, would it be possible to deliver the mesh electronics by syringe needle injection,
a process common to delivery of many species in biology and medicine you could go to the doctor
and you inject this and youe wired up.''hough not the first attempts at implanting electronics into the brain deep brain stimulation has been used to treat a variety of disorders for decades the nano-fabricated scaffolds operate on a completely different scale. xisting techniques are crude relative
to the way the brain is wired, Lieber explained. hether it a silicon probe or flexible polymershey cause inflammation in the tissue that requires periodically changing the position or the stimulation.
But with our injectable electronics, it as if it not there at all. They are one million times more flexible than any state-of-the-art flexible electronics
and have subcellular feature sizes. Theye what I call euro-philicthey actually like to interact with neurons..
espite their enormous potential, the fabrication of the injectable scaffolds is surprisingly easy. hat the beauty of this it compatible with conventional manufacturing techniques,
The process is used similar to that to etch microchips, and begins with a dissolvable layer deposited on a substrate.
researchers lay out a mesh of nanowires sandwiched in layers of organic polymer. The first layer is dissolved then, leaving the flexible mesh,
which can be drawn into a syringe needle and administered like any other injection. After injection, the input/output of the mesh can be connected to standard measurement electronics
so that the integrated devices can be addressed and used to stimulate or record neural activity. hese type of things have never been done before, from both a fundamental neuroscience and medical perspective,
Lieber said. t really exciting there are a lot of potential applications. oing forward, Lieber said, researchers hope to better understand how the brain
and other tissues react to the injectable electronics over longer periods. Harvard Office of Technology Development has filed for a provisional patent on the technology
and is actively seeking commercialization opportunities. aving those results can prove that this is really a viable technology,
Lieber said. he idea of being able to precisely position and record from very specific areas,
#Nanomaterial Self-Assembly Imaged In real time A team of researchers from UC San diego, Florida State university and Pacific Northwest National Laboratories has visualized for the first time the growth of anoscalechemical complexes in real time,
which will make possible many future advances in nanotechnology, is detailed in a paper published online in the Journal of the American Chemical Society.
for example, to better understand the stepwise formation of nanostructures. Previously, scientists could examine changes in nanostructures only by looking at the large-scale alterations of a bulk population of particles
or by taking creen shotsin a static fashion of individual nanostructures with electron microscopy. hat process is like taking photos every 10 minutes of a football game
and then trying to piece these photos together to tell the story of what is really a highly dynamic process,
an associate professor of chemistry and biochemistry at UC San diego who headed the research effort with Seth Cohen,
chair of UC San diego Department of chemistry and Biochemistry. ntil now, this was the state of the art in terms of how we could document how nanostructures formed.
by literally videoing these processes on the nanoscale level using an electron microscope. The development employed a recently developed process called Liquid Cell Transmission Electron microscopy.
or TEM, has long been used by scientists to image nanoscale materials and understand nanoscale structure.
While advances in Liquid Cell TEM or LCTEM, had permitted scientists to visualize the motion of nanoscale objects in liquids,
researchers had figured not yet out a way to use it to visualize the growth of complex self-assembled,
chemical nanostructures. e showed for the first time that this technique can be used to observe the growth of complex organic-inorganic hybrid materials,
providing an unprecedented understanding of their formation, said Gianneschi. his demonstration marks a significant step forward in LCTEM becoming essential for our understanding of nanoscale processes for all materials in liquids.
who is an expert in the technique, while Park was responsible for the video analysis. To make things simple,
if these nanostructures would survive the experiment. This is necessary because materials are susceptible to being destroyed by the high energy electron beam that is used to image them.
length scales can be observed that are relevant to nanoscale materials and processes. In terms of imaging dynamics like this, we believe it will impact how nanotechnology is developed in the future. o
#UCLA researchers discover molecular rules that govern autoimmune disorders An international team led by researchers at UCLA Henry Samueli School of engineering
and Applied science and California Nanosystems Institute has identified an unexpectedly general set of rules that determine which molecules can cause the immune system to become vulnerable to the autoimmune disorders lupus and psoriasis.
a UCLA professor of bioengineering and chemistry who is affiliated with CNSI, the multidisciplinary team also included Michel Gilliet of Switzerland Lausanne University Hospital,
and Jure Dobnikar and Daan Frenkel of the University of Cambridge. Autoimmune diseases strike when the body attacks itself
because it fails to distinguish between host tissue and disease-causing agents, or pathogens. Two such disorders are lupus,
which can damage the skin, joints and organs, causing rashes, hair loss and fatigue; and psoriasis,
which causes rashes, lesions and arthritis, and creates an increased risk for cancer and diabetes.
When a healthy person is infected by a virus, VIRAL DNA can activate immune cells via a receptor called TLR9.
The receptor triggers the cells to send signaling molecules called interferons to initiate a powerful defensive response.
In people with lupus or psoriasis, these cells are activated by their own DNA, or self-DNA.
Using synchrotron X-ray scattering and other techniques, researchers determined that a broad range of molecules,
both organic and inorganic, can organize self-DNA into a liquid crystalline structure that binds strongly to the TLR9 receptors like the teeth on either side of a zipper.
This structure protects the DNA from becoming degraded and greatly amplifies the body immune response. Synchrotron X-ray scattering utilizes a particle accelerator to generate X-ray beams that allow researchers to determine how atoms
Wong said. his new knowledge will make it easier to design new therapeutic strategies to control immune responses.
and triggering responses in disorders such as lupus and psoriasis. We were able to elucidate something that was understood poorly a key to triggering the immune response is that the molecules must arrange the DNA
#Single Atom Building blocks For Future Electronics The material is called a silicene, a layer of silicon single atoms arranged in a honeycomb pattern that was fabricated first by researchers at UOW Institute for Superconducting and Electronic Materials (ISEM) and their partners in Europe and China.
An ISEM team led by Professor Shi Xue Dou and Dr Yi Du have published breakthrough research into a new material call silicene.
An ISEM team led by Professor Shi Xue Dou and Dr Yi Du have published breakthrough research into a new material call silicene.
Silicene great promise is related to how electrons can streak across it at incredible speed close to the speed of light.
Propelling the electrons in silicene requires minimal energy input, which means reducing power and cooling requirements for electronic devices. f silicene could be used to build electronic devices,
it could enable the semiconductor industry to achieve the ultimate in miniaturization, Dr Yi Du,
a research fellow at the ISEM, said. The difficulty for researchers, according to Dr Du, is that up until a couple of years ago,
the material existed only in theory. Its fundamental properties, or atomic fingerprint, were unreported in scientific literature.
ISEM, led by Professor Shi Xue Dou was the first research group in Australia to make silicene
and recently, using state-of-the-art equipment, they have identified more of its structural information, its stability when exposed to air as well as developed methods to precisely manipulate its reactivity.
This work paves the way to identifying and modifying silicene so it can be integrated it into ultra-small renewable energy devices, such as solar cells,
data storage hardware and advancing quantum computing. uow195685 o one in the scientific community believed silicene paper could be made
because silicon always adopt diamond-like structure but not honeycomb structures, he said. t also very unstable when exposed to oxygen.
To overcome these challenges, Dr Du team had to reak the laws of chemistryand create an artificial environment using an ultra-high vacuum. hen we vibrate the silicon atoms it causes heat
and the atoms disassemble, Dr Du said. hen we use two small robotic arms that we move with a hand-held video game controller to catch the atoms in the vacuum chamber
and place them one at a time on a plate to form the silicene paper. he process is like laying bricks,
only these are bricks are the size of a single atom. A 1 centimetre-long chain contains 10 million silicon atoms.
Studying the fundamental physics is helping the researchers build a more complete picture of the material,
its properties and how to make it. The next step will be to integrate it into electronic devices and test its usefulness for specific applications. he challenge is to make large-scale
and high-quality silicene layers that are large enough for integrated circuits, Dr Du said. here is also work to be done in developing ways to peel
and transfer the silicene layers from the base it has been assembled on, as well as embed electrodes in it. s
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