#Environment not genes dictates human immune variation study finds A study of twins conducted by Stanford university School of medicine investigators shows that our environment more than our heredity plays the starring role in determining the state of our immune system the body's primary defense against disease.
Stunning advances in gene-sequencing technologies in concert with their plummeting costs have turned many scientists'attention to minute variations in the genome--the entire toolbox of genes carried in virtually every cell in the body--in the hope of predicting people's future health.
if you sequence someone's genome you can tell what diseases they're going have 50 years later said Mark Davis Phd professor of microbiology and immunology and director of Stanford's Institute for Immunity Transplantation and Infection.
But while genomic variation clearly plays a key role in some diseases he said the immune system has to be tremendously adaptable
in order to cope with unpredictable episodes of infection injury and tumor formation. The immune system has to think on its feet said Davis senior author of the new study which will be published Jan 15 in Cell.
Lead authorship is shared by former Stanford postdoctoral scholars Petter Brodin MD Phd and Vladimir Jojic Phd.
Unlike inbred lab mice people have broadly divergent genetic heritages said Davis who is also the Burt and Marion Avery Family Professor.
But what we found was that in most cases including the reaction to a standard influenza vaccine
or no genetic influence at work and most likely the environment and your exposure to innumerable microbes is the major driver.
Monozygotic twins inherit the same genome. Despite inevitable copying errors when cells divide which cause tiny genetic divergences to accumulate between monozygotic twins over time they remain almost 100 percent genetically identical.
Because both types of twins share the same environment in utero and usually share the same environment in childhood they make excellent subjects for contrasting hereditary versus environmental influence.
About two decades ago study co-author Gary Swan Phd who was then at SRI Inc
. and is now a consulting professor of medicine at Stanford began curating a registry of twins for research purposes.
All samples were sent immediately to Stanford's Human Immune Monitoring Core which houses the latest immune-sleuthing technology under a single roof.
or toxic exposures vaccinations diet and dental hygiene--trumped heritable ones when it came to accounting for differences within a pair of twins.
This environmental dominance was pronounced more in older identical twins (age 60 and up) than in younger twins (under age 20.
Davis and his associates also observed considerable environmental influence over the quantities of antibodies produced in members of twin pairs who had been vaccinated for influenza in a separate Stanford investigation directed by study co-author Cornelia Dekker MD professor of pediatric infectious disease
and medical director of the Stanford-Lucile Packard Children's Hospital Vaccine Program. While many previous studies have suggested a powerful genetic component in vaccine responsiveness Davis noted that those studies typically were performed in very young children who had undergone not yet the decades of environmental exposure that appears to reshape the immune system over time.
In a striking example of the immune system's plasticity the Stanford scientists found that the presence
or absence of a single chronic viral infection could have a massive effect on the system's composition and responsiveness.
A healthy human immune system continually adapts to its encounters with hostile pathogens friendly gut microbes nutritional components
Other Stanford co-authors of the study are Atul Butte MD Phd associate professor of pediatrics (systems medicine) and of genetics;
Holden Maecker Phd associate professor of microbiology and immunology and director of Stanford's Human Immune Monitoring Center;
former postdoctoral scholar Shai Shen-Orr Phd; research associate David Furman Phd; software specialist Sanchita Bhattacharya;
and MD/Phd student Cesar Lopez Angel. The study was funded by the National institutes of health (grants U19ai057229 U19ai090019 DA011170 DA023063 AI057229 AI090019 ES022153 and UL1 RR025744) SRI the Howard hughes medical institute the Wenner-Gren Foundation and the Sweden-America Foundation.
Information about Stanford's Department of Microbiology and Immunology which also supported the work is available at http://microimmuno. stanford. edu
#Novel molecular mechanism involved in the formation of the skin Specifically researchers identify Fra-2 an AP-1 transcription factor as a key regulator for the differentiation of keratinocytes:
if Fra-2 is activated not epidermal differentiation fails and the skin does not properly form.
the study is directed by Erwin Wagner head of the BBVA Foundation-CNIO Cancer cell Biology Program.
In recent years a number of biochemical processes involved in the differentiation of keratinocytes have been identified.
The work now published shows that Fra-2 one of these transcription factors plays a key regulatory role.
With the help of specific mouse models we demonstrate that the expression of Fra-2 in keratinocytes induces the expression of genes in the EDC the authors write.
The authors also found a possible link to cancer. In mice prone to develop benign skin tumors-papillomas-the activation of Fra-2 reduced skin tumor burden.
The authors demonstrate that Fra-2 induces premature differentiation of keratinocytes. An additional novelty is related to the regulation of the transcriptional activity of Fra-2. The work reveals that the activation of this transcription factor depends on chemical protein modifications
and the interaction with two important enzymes Ezh2 and ERK1/2. This mode of activation was known not
whether inhibition of Ezh2 may be a valuable therapeutic strategy for skin diseases related to keratinocyte differentiation defects s
X-rays have very short wavelengths of only about 1 to 0. 01 nanometres (nm), compared to 400 to 800 nm for visible light.
A nanometre is a millionth of a millimetre. The high penetration of X-rays is favoured for three-dimensional tomographic imaging of objects such as biological cells
computer chips, and the nanomaterials involved in energy conversion or storage. But this also means that the X-rays pass straight through conventional lenses without being bent or focussed.
One possible method to focus X-rays is to merely graze them from the surface of a mirror to nudge them towards a new direction.
But such X-ray mirrors are limited in their convergence power and must be polished mechanically to high precision,
An alternative means to bend X-rays is to use crystals. A crystal lattice diffracts X-rays, as the German physicist Max von Laue discovered a century ago.
artificial crystals can be tailor-made to sharply focus X-rays by depositing different materials layer by layer.
From this building block comes the multilayer Laue lens or MLL, made by coating a substrate with thin layers of the chosen substances."
where a mask partially shields the substrate from the depositing material. In the half-shade of the mask a wedged structure builds up,
The researchers manufactured a wedged lens from 5500 alternating layers of silicon carbide (Sic) and tungsten (W), varying in thickness.
"It appears that the long-sought goal of focusing X-rays to a nanometre is in reach."
"This will put X-ray imaging on par with the quality achieved with scanning electron microscopes, that typically have a resolution of 4 nm.
Specifically diode lasers bars in the wavelength range 930 to 970 nm are the fundamental building blocks for pump sources for Ytterbium-doped crystals in large laser facilities,
where optical pulses are generated with petawatt class peak energies and picosecond pulse widths. The individual laser bars in these pump sources have a typical output power between 300 and 500 Watts.
Building on advances in epitaxial design and packaging technology, FBH bars around 940 nm at temperatures of-70°C (203 K) delivered a worldwide best result of 2 kw peak power per bar at a current of 2 ka, a pulse width of 200 s
corresponding to a pulse energy of 0. 4 J. Peak power was limited by the available current.
Such bars have the potential to play an important role in future high-energy-class laser facilities.
The final pump sources are being evaluated for potential use in high-energy-class diode-pumped solid-state laser systems together with the world-leading groups in the field
major disease implications"Instead of asking,'How do we study the immune response of the brain?''''Why do multiple sclerosis patients have the immune attacks?'
'now we can approach this mechanistically. Because the brain is like every other tissue connected to the peripheral immune system through meningeal lymphatic vessels,
"said Jonathan Kipnis, Phd, professor in the UVA Department of Neuroscience and director of UVA's Center for Brain Immunology and Glia (BIG)."
"Arraythe discovery was made possible by the work of Antoine Louveau, Phd, a postdoctoral fellow in Kipnis'lab. The vessels were detected after Louveau developed a method to mount a mouse's meninges--the membranes covering the brain--on a single slide
so that they could be examined as a whole.""It was fairly easy, actually, "he said.""There was one trick:
Harris, a Phd, is an assistant professor of neuroscience and a member of the BIG center.
Kipnis also saluted the"phenomenal"surgical skills of Igor Smirnov, a research associate in the Kipnis lab whose work was critical to the imaging success of the study.
Arraythe unexpected presence of the lymphatic vessels raises a tremendous number of questions that now need answers, both about the workings of the brain and the diseases that plague it.
take Alzheimer's disease.""In Alzheimer's, there are accumulations of big protein chunks in the brain, "Kipnis said."
"We think they may be accumulating in the brain because they're not being removed efficiently by these vessels."
so the role they play in aging is another avenue to explore. And there's an enormous array of other neurological diseases, from autism to multiple sclerosis,
that must be reconsidered in light of the presence of something science insisted did not exist t
remove contraceptive implants To address a global health challenge, a team of biomedical engineering undergraduates has developed a kit to teach front-line health care workers in developing countries how to implant contraceptives.
In developing regions where the economy is weak and medical services are limited, global health experts say as many as 200 million women want access to long-term,
reversible contraceptives to avoid unintended pregnancies and to help space out the births of their children.
One of the most convenient and effective options--a tiny implant that can delay conception for three to five years--is inserted into a woman's arm
and can later be removed at any time to restore fertility. In developing nations, however, these simple procedures often must be done by frontline providers who have minimal training.
Sometimes, the cylindrical toothpick-shaped implant may be inserted inadvertently into the woman's fat tissue instead of just under the outer skin layer.
This causes the contraceptive to become ineffective and makes removal of the implant far more difficult.
To help prevent such problems, a team of Johns hopkins university biomedical engineering undergraduates has developed a teaching set called the Contraceptive Implant Training Tool kit or CITT Kit, for short.
The medical simulator includes two training models: a stand-alone replica arm and a layered band that can be worn by health workers who act as"patients"during practice sessions."
"We've produced a kit that's designed to effectively teach lower-level health-care providers the proper way to insert
and remove these subdermal contraceptive implants, "said team leader Taylor Lam from Thousand Oaks, Calif,
. who graduated in May. The student inventors say their new system better mimics anatomical textures,
resulting in a more realistic representation than current training tools that use materials such as Styrofoam and latex.
The Johns Hopkins students instead used silicone layers of different densities to more closely represent the physiology of skin,
fat and muscle in a human arm. The CITT Kit's components also feature landmarks that can help the students identify the correct placement site for a cylindrical implant
which is a little less than 2 inches long. It needs to be inserted just under the outermost skin layer, about 4 inches above the elbow,
the students say their kit provides more advanced training in how to safely and easily remove an implant,
a procedure that's considered to be more challenging than insertion of the contraceptive. With this kit, the students say,
health workers will be able to make practice incisions through replaceable silicones layers that respond more like human skin."
"In designing these teaching tools, every choice we made was to pursue biofidelity, trying to prepare the health workers as closely as possible for the conditions they'll face
when they actually perform these procedures in a clinic, "said rising junior Miguel Sobral, a team member from Lisbon, Portugal.
The other team members were rising senior Christopher Coughlan; Chloé Quinlan and Nick Bello, who both graduated in May:
While working on their training kit, the student inventors were advised by physician Ricky Lu, technical director for reproductive health and family planning at Jhpiego,
a nonprofit Johns hopkins university affiliate that focuses on global health issues involving women and families.""The student inventors came up with a novel and exciting idea of using replaceable training pods,
"Lu said.""These pods have embedded placebo implants to simulate a range of removal challenges, from easy pop outs to deeply located and adherent implants requiring additional skills to extract them.
This is critical to have in clinical training where removal cases for practice may be limited during a short training course."
"The student inventors showcased their device recently at the annual Johns Hopkins Biomedical engineering Design Day event, organized by the university's Center for Bioengineering Innovation and Design.
The CITT Kit was developed within the yearlong undergraduate design team program, directed by Robert H. Allen, a lecturer in the Department of Biomedical engineering,
which is shared by the university's Whiting School of engineering and its School of medicine. Allen also is a lecturer in the School of medicine's Department of Gynecology and Obstetrics.
Working with Johns Hopkins Technology Ventures, the students have obtained a provisional patent covering their invention.
They say their invention aligns with voluntary contraception programs supported by philanthropic global health organizations such the Bill and Melinda Gates Foundation.
The students say support from one of these groups could help move their prototype out of the lab and into the field-testing and eventual clinical use s
#X-ray scanning to guarantee meat tenderness Arraypackaged meat products can be found today on fresh food counters with labels declaring their level of tenderness and tenderization process.
However, the consumer has no guarantee of the veracity of these labels. The food sector has launched an initiative to make sure that the meat it supplies is up to scratch.
It wanted a project to measure tenderness.""SINTEF has been involved for several years in projects involving x-ray methods and x-ray detectors,
and has obtained know-how about their uses for a variety of purposes, "explain Marion O'Farell and Gregory Bouquet at SINTEF."
"This time we've been using low energy x-rays to measure tenderness and water bonding in meat,
"they say. In order to screen the structure of the meat, the new approach uses x-rays at energies that are lower than normal,
and at different levels.""This provides us with invaluable information about the tenderness of the meat,
Moreover, many large-scale experiments have been carried out at Liverpool John Moores University in collaboration with the rest of the project group.
Arraythe company Tomra AS is known best for plastic recycling and bottle recognition, but it also has extensive experience with x-ray applications in the mining industry.
Based on the results from a project called'Informed''Tomra has designed and built a prototype low energy x-ray device for the foodstuffs industry with the aim of measuring the tenderness of meat and detecting the presence of unwanted plastic objects in meat products.
The device is currently undergoing tests. Array"Consumers will soon be getting guarantees about the level of tenderness in the meat they buy,
and probably increase prices where quality can be guaranteed d
#Noncoding RNA CCDC26 regulates KIT expression An long noncoding RNA (lncrna), which might give an impact on tyrosine kinase-targeted leukemia therapy,
was found to be expressed in a leukemia cell line. The function of the lncrna CCDC26 is understood not fully;
however, researchers at Hiroshima University revealed the mechanisms by which CCDC26 controls the receptor tyrosine kinase KIT expression.
The results provide new insights into leukemia recurrence and may help to develop new leukemia therapies.
Recent transcriptomic studies have revealed the existence of numerous RNAS that are relatively long but not translated into proteins.
Some of such lncrnas are suggested to regulate the expression of other genes. Mutations or imbalances in the noncoding RNA repertoire within the body can
therefore cause a variety of diseases such as cancer. However, the molecular functions of lncrnas remain to be elucidated fully.
Dr. Tetsuo Hirano from the Graduate school of Integrated Arts and Science at Hiroshima University found that knockdown of the CCDC26 gene in cells results in significant upregulation of the KIT gene,
hyperactive mutations of which are often found in acute myeloid leukemia. Dr. Hirano and his collaborators at the School of medicine in Juntendo University showed that CCDC26 transcript levels are high in the nuclear fraction of human myeloid leukemia cell lines.
They also found that CCDC26 knockdown induces suppression of CCDC26 intron-containing transcripts, indicating transcriptional gene suppression.
Leukemia cells in which CCDC26 was knocked down showed enhanced survival periods after serum withdrawal. A KIT-specific inhibitor reversed this increased survival of the cells.
These results are published in a Molecular Cancer article titled""Long noncoding RNA, CCDC26, controls myeloid leukemia cell growth through regulation of KIT expression.""
""We suggested that CCDC26 controls growth of myeloid leukemia cells through regulation of KIT expression. Abnormal CCDC26 RNA structure could modulate the regulation of KIT to induce undesired overexpression.
Leukemia characterized by a mutated copy number of CCDC26 might be treated by KIT-targeted therapy"quoted Dr. Hirano o
#Two new groups of viruses discovered Two new groups of viruses have been discovered within the Bunyavirus family in the tropical forest of Ivory coast.
Researchers at the University of Bonn and the German Center for Infection Research (DZIF) have discovered two new groups of viruses within the Bunyavirus family in the tropical forest of Ivory coast.
"The most well-known bunyaviruses include, for example, the Rift valley fever virus, which can cause febrile illnesses with severe bleeding in humans,
"says Dr. Sandra Junglen from the Bonn Institute of Virology, also affiliated with the German Center for Infection Research.
In 2011, the"Schmallenberg virus"gained much attention: also a part of the Bunyavirus family and transmitted by gnats,
it caused severe fetal malformations in ruminant animals including sheep in the German Sauerland region.
Not in Schmallenberg but instead in the African tropical forest of the Ivory coast, where the virologist has been conducting research for more than ten years,
Sorted according to species and sites of capture, the scientists combined the captured mosquitoes into 432 mixed samples.
Agents of human disease have developed from insect viruses"These were two groups of as yet-unknown viruses
The scientists obtained fragments of the viral genetic material from the insect samples and joined these fragments together like a puzzle,
thus reconstructing the entire genome sequence.""That alone took four years,"reported lead authors Marco Marklewitz and Florian Zirkel.
During the comparison of the genetic information with other viruses, it was found that Jonchet and Ferak viruses are two phylogenetically independent bunyavirus lineages.
They performed infection trials in a large number of cell cultures at different temperature levels. While pathogenic bunyaviruses can multiply at temperatures that include the human body temperature,
"says the researcher from the University of Bonn Hospital. Simplified test to test novel viruses for risk of human infection Triggered by epidemics such as SARS and Ebola,
virologists are now reaching out to discover the plethora of unknown viruses lurking in natural reservoirs such as insects, in an attempt to forecast pandemic risks."
"We hope our temperature test for estimating the risk of vertebrate infection can be useful for assessing other viruses that keep being discovered,
#Intelligent bacteria for detecting disease Another step forward has just been taken in the area of synthetic biology.
in association with Montpellier Regional University Hospital and Stanford university, have transformed bacteria into"secret agents"that can give warning of a disease based solely on the presence of characteristic molecules in the urine or blood.
the researchers inserted the equivalent of a computer programme into the DNA of the bacterial cells.
The bacteria thus programmed detect the abnormal presence of glucose in the urine of diabetic patients.
This work published in the journal Science Translational Medicine, is the first step in the use of programmable cells for medical diagnosis.
Bacteria have a bad reputation, and are considered often to be our enemies, causing many diseases such as tuberculosis or cholera.
However, they can also be witnessed allies, as by the growing numbers of research studies on our bacterial flora,
Since the advent of biotechnology, researchers have modified bacteria to produce therapeutic drugs or antibiotics. In this novel study, they have actually become a diagnostic tool.
Medical diagnosis is a major challenge for the early detection and subsequent monitoring of diseases.""In vitro"diagnosis is based on the presence in physiological fluids (blood and urine, for example) of molecules characteristic for a particular disease.
Because of its noninvasiveness and ease of use, in vitro diagnosis is of great interest. However, in vitro tests are sometimes complex,
and require sophisticated technologies that are often available only in hospitals. This is where biological systems come into play.
Living cells are real nanomachines that can detect and process many signals and respond to them.
They are therefore obvious candidates for the development of powerful new diagnostic tests. However, they have to be provided with the appropriate"programme"for them to successfully accomplish the required tasks.
To do this Jérôme Bonnet's team in Montpellier's Centre for Structural Biochemistry (CBS) had the idea of using concepts from synthetic biology derived from electronics to construct genetic systems making it possible to"programme"living cells like a computer.
The transcriptor: the cornerstone of genetic programming The transistor is the central component of modern electronic systems.
It acts both as a switch and as a signal amplifier. In informatics, by combining several transistors, it is possible to construct"logic gates,
"i e. systems that respond to different signal combinations according to a predetermined logic. For example, a dual input"AND"logic gate will produce a signal
only if two input signals are present. All calculations completed by the electronic instruments we use every day, such as smartphones, rely on the use of transistors and logic gates.
During his postdoctoral fellowship at Stanford university in the United states Jérôme Bonnet invented a genetic transistor, the transcriptor.
The insertion of one or more transcriptors into bacteria transforms them into microscopic calculators. The electrical signals used in electronics are replaced by molecular signals that control gene expression.
It is thus now possible to implant simple genetic"programmes"into living cells in response to different combinations of molecules.
In this new work, the teams led by Jérôme Bonnet (CBS, Inserm U1054, CNRS UMR5048, Montpellier University), Franck Molina (Sysdiag, CNRS FRE 3690),
in association with Professor Eric Renard (Montpellier Regional University Hospital) and Drew Endy (Stanford university), applied this new technology to the detection of disease signals in clinical samples.
Clinical samples are complex environments in which it is difficult to detect signals. The authors used the transcriptor's amplification abilities to detect disease markers,
even if present in very small amounts. They also succeeded in storing the results of the test in the BACTERIAL DNA for several months.
The cells thus acquire the ability to perform different functions based on the presence of several markers,
opening the way to more accurate diagnostic tests that rely on detection of molecular"signatures"using different markers."
"says Alexis Courbet, a postgraduate student and first author of the article. As a proof of concept, the authors connected the genetic transistor to a bacterial system that responds to glucose,
and detected the abnormal presence of glucose in the urine of diabetic patients.""We have deposited the genetic components used in this work in the public domain to allow their unrestricted reuse by other public
or private researchers,"says Jérôme Bonnet.""Our work is focused presently on the engineering of artificial genetic systems that can be modified on demand to detect different molecular disease markers,
"he adds. In future, this work might also be applied to engineering the microbial flora in order to treat various diseases, especially intestinal diseases
#Getting rid of pinholes in solar cells The pinholes, identified by OIST's Energy Materials and Surface Sciences Unit led by Prof.
Yabing Qi, were described in the Chemistry of Materials earlier this year. The pinholes in the top layer of the solar cell, known as the hole transport layer, were identified as a key cause for the quick degradation of perovskite solar cells.
Researchers around the world are investigating the potential of perovskite, a humanmade organic-inorganic hybrid material, as an alternative to silicon-based solar cells."
"Pinholes are a very critical problem because it's a pathway for moisture and oxygen to attack the perovskite material,
which is the active layer converting sunlight to energy, "said Min-Cherl Jung, a staff scientist at OIST and first author of this work."
"Without pinholes in the hole transport layer, the perovskite is protected and the lifetime improves.""The researchers eliminated the pinholes by using a different method to create the top layer of the solar cell,
which is made of a material called spiro-OMETAD. Instead of dissolving spiro-OMETAD powder in a solution
and then spin-coating it onto perovskite, they evaporated the powder in a vacuum chamber and the spiro-OMETAD molecules deposited onto the solar cell.
To create this layer, a solar cell is positioned upside down on the ceiling of a vacuum chamber. As the spiro-OMETAD is heated up,
it evaporates and the gas molecules that stick to the perovskite, creating an even layer--much like
when snow blankets the ground. Essentially, the spiro-OMETAD molecules are snowing, but up rather than down."
"Vacuum evaporation enables us to much more precisely control the deposition rate and thus the thickness of this layer,
"Jung said.""We were able to reduce the thickness of the solar cell from over 200 nanometers to 70 nanometers."
"This method also enabled the team to precisely control how and when they added other ingredients to the mix to make it more conductive.
The result again was a significant improvement--they could finely tune the energy level of that layer to closely match the layer beneath it,
which makes the movement of"holes"carrying positive charges around the solar cell circuit much easier.""A very small difference between the top layer and perovskite material means maybe we get greater energy efficiency,
"Jung said. The evaporation method also resulted in a much longer-lasting solar cell. Before, the cells would lose the ability to efficiently convert sunlight into electricity after a couple of days.
Now, their efficiency remains high for more than 35 days. While cheaper than conventional silicon-based solar cells, evaporation-based perovskite solar cells are more expensive than spin-coated cells.
The team is now working to determine how to strike a balance between cost and efficiency
and hopefully find a way to use solution processing without creating pinholes s
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