#Multiple neurodevelopmental disorders have a common molecular cause Neurodevelopmental disorders such as Down syndrome and autism-spectrum disorder can have profound lifelong effects on learning
and memory but relatively little is known about the molecular pathways affected by these diseases. A study published by Cell Press October 9th in the American Journal of Human genetics shows that neurodevelopmental disorders caused by distinct genetic mutations produce similar molecular effects in cells suggesting that a one-size-fits-all therapeutic approach could be effective
for conditions ranging from seizures to attention-deficit hyperactivity disorder. Neurodevelopmental disorders are rare meaning trying to treat them is not efficient says senior study author Carl Ernst of Mcgill University.
Once we fully define the major common pathways involved targeting these pathways for treatment becomes a viable option that can affect the largest number of people.
but the genetic factors responsible for these diseases are very complex. For example whereas common variants in the same gene have been associated with two
or more different disorders mutations in many different genes can lead to similar diseases. As a result it has not been clear
and his team used human fetal brain cells to study the molecular effects of reducing the activity of genes that are mutated in two distinct autism-spectrum disorders.
Changes in transcription factor 4 (TCF4) cause 18q21 deletion syndrome which is characterized by intellectual disability and psychiatric problems and mutations in euchromatic histone methyltransferase 1 (EHMT1) cause similar symptoms in a disease known as 9q34 deletion syndrome.
Interfering with the activity of TCF4 or EHMT1 produced similar molecular effects in the cells.
Our study suggests that one fundamental cause of disease is that neural stem cells choose to become full brain cells too early Ernst says.
This could affect how they incorporate into cellular networks for example leading to the clinical symptoms that we see in kids with these diseases s
#Gene that drives aggressive brain cancer found by new computational approach Using an innovative algorithm that analyzes gene regulatory and signaling networks,
Columbia University Medical center (CUMC) researchers have found that loss of a gene called KLHL9 is the driving force behind the most aggressive form of glioblastoma, the most common form of brain cancer.
The CUMC team demonstrated in mice transplants that these tumors can be suppressed by reintroducing KLHL9 protein,
offering a possible strategy for treating this lethal disease. The study was published today in the online issue of Cell.
and heritable variants that have been linked to breast cancer and Alzheimer's disease, suggesting that the algorithm, combined with the researchers'sophisticated computer models of cellular regulation, is a powerful method for identifying genetic drivers of a wide range of diseases."
"This algorithm adds a new dimension to our ability to identify the genetic causes of complex disease.
When combined with other tools that our lab has developed, it will help identify many more genes that hold potential as genetic biomarkers of disease progression
and targets for treatment,"said study leader Andrea Califano, Phd, the Clyde and Helen Wu Professor of Chemical Biology (in Biomedical Informatics and the Institute for Cancer Genetics), chair of the Department of Systems Biology,
and director of the JP Sulzberger Columbia Genome Center, at Columbia's College of Physicians and Surgeons.
In previous studies Dr. Califano and his colleagues used high-power computer models to demonstrate that certain types of cancer have conserved highly"master regulators"--genes
whose individual or synergistic activity is necessary for disease to develop and persist. However, these models provided no information on the key genetic mutations that presumably drive the abnormal activity of these master regulators.
In the current study, the team combined its existing computational tools with a new algorithm called DIGGIT (for Driver-Gene Inference by Genetical-Genomic Information theory),
which"walks"backward from the master regulators to find the genetic events that drive cancer."
"Conventional techniques, like genome-wide association studies, must test all possible genetic mutations and variants in a disease cell, compared with a normal cell,
"The new approach was tested on mesenchymal glioblastoma, the most aggressive subtype of the disease, by jointly analyzing the gene expression
and mutational profile data of more than 250 patients collected by the Cancer Genome Atlas consortium.
C/EBPD, had already been identified by the labs of Dr. Califano and of Antonio Iavarone, MD, professor of neurology and of pathology & cell biology (in the Institute for Cancer Genetics),
as a master regulator of the disease, so the researchers focused on KLHL9, which had never been tied to this or any other form of cancer.
In subsequent laboratory studies, the researchers reactivated the defective KLHL9 gene in aggressive glioblastoma cells,
When KLHL9 protein was reintroduced into mice receiving direct transplants from patients with mesenchymal glioblastoma, their tumors regressed, providing further evidence that KLHL9 mutations
(which were found in 50 percent of the mesenchymal glioblastoma patients), are directly responsible for driving this cancer subtype.
DIGGIT may be applicable to other complex diseases. In further studies by the Califano team, the algorithm identified 35 genes as drivers of breast cancer.
Of the 25 genes previously identified in the literature 19 (76 percent) were identified by DIGGIT,
confirming that the algorithm is capable of capturing driver mutations in other types of cancer.
In a study of Alzheimer's disease, DIGGIT found 14 genetic variants that appear to drive the condition,
that had not been connected previously with the disease and that are currently being investigated.""It's important to stress that this constitutes an important improvement over traditional gene-association studies.
The latter can identify statistical associations between mutations and disease, but cannot explain how the mutation drives that effect,
"Because DIGGIT identifies disease-causing genes by tracing their aberrant activity through the regulatory network of the cell,
it provides direct information on the specific molecular interactions through which a genetic mutation causes disease--the'mechanism.'
""Even in our studies of breast cancer and Alzheimer's disease, where the goal was simply to show that DIGGIT could identify mutations
which these mutations likely work to drive disease, adding significant new knowledge that can be tested rapidly in the lab"Dr. Chen said a
whether defects in these mechanisms might even contribute to human disease. tory Source: The above story is provided based on materials by Whitehead Institute for Biomedical Research.
The original article was written by Nicole Giese Rura. Note: Materials may be edited for content and length.
what type of chemotherapy you attack a tumor with, many cancer cells resort to the same survival tactic:
"This gives us a therapeutic avenue to target autophagy in tumors, "said Josh Andersen, a BYU chemistry professor."
"The idea would be to make tumors more chemo-sensitive. You could target these proteins and the mechanism of this switch to block autophagy,
they forced tumor cells to undergo autophagy by depriving them of oxygen and glucose. A comparison with a control group let them see that the two proteins hook up only when under attack.
That's because stress makes Atg9 undergo a modification that enables 14-3-3 zeta to bind with it
Andersen notes that several medicines already exist that could block autophagy and make chemotherapy more effective.
#Minimally invasive surgery with hydraulic assistance Endoscopic surgery requires great manual dexterity on the part of the operating surgeon.
Their outstanding sensitivity simplifies the biopsy procedure. Minimally invasive techniques, also known as"keyhole surgery,"enable surgeons to operate on patients without requiring major incisions.
This method causes much less trauma for the patient, and is used commonly when performing lung, esophageal and joint biopsies,
and most especially when operating inside the abdominal cavity. An endoscope is inserted through one or two small incisions in the abdominal wall
allowing the internal organs to be visualized for surgery. Surgical techniques have advanced by leaps and bounds in recent years.
The same cannot be said for surgical instruments. In certain types of endoscope, the tip can be oriented at different angles."
and even physical strength on the part of the surgeon, has changed barely since the earliest days of endoscopy,"says Timo Cuntz, a member of the Project Group for Automation in Medicine and Biotechnology PAMB in Mannheim, a part of the Fraunhofer Institute for Manufacturing Engineering and Automation IPA.
The force required to deflect the tip is transmitted by a wire mechanism known as a Bowden cable (similar to a bicycle brake cable.
The cable mechanism transmits the surgeon's hand movements at one end to the tiny instruments at the other extremity of the endoscope.
making it difficult for the surgeon to manipulate the tissue precisely.""The surgeon's work would be made much easier
if it were possible to reduce the friction and increase the power density. Hydraulic instruments are one of the alternatives being considered as a substitute for mechanical transmission based on Bowden cable."
They allow the surgeon to carry out much finer movements, "says the engineer. A plastic tube filled with a sterile,
biocompatible fluid based on medicinal white oil is used in place of the wire cable. To control the attached instruments and orient the tip of the endoscope,
the surgeon manipulates a hydraulic cylinder or robotic muscle that exerts the required pressure to compress the fluid and push it through the hydraulic tube onto a second, spring-mounted cylinder.
Such hydraulically actuated instruments are suited ideally for use in connection with a technique known as natural orifice transluminal endoscopic surgery (NOTES),
in which the surgeon operates through natural body orifices in order to access internal organs; going through the stomach, for instance,
#Mining big data yields Alzheimers discovery Scientists at The University of Manchester have used a new way of working to identify a new gene linked to neurodegenerative diseases such as Alzheimer's.
which is linked to a group of neurodegenerative diseases. The study has just been published in the journal BMC Genomics.
"Ultimately this could provide another biomarker in the toolkit for identifying those at greatest risk of developing diseases such as Alzheimer's."
but also the networks it uses to influence a disease like Alzheimer's. We believe this information will be incredibly useful for future studies looking at treatments and preventative measures."
advancing our knowledge of diseases and ultimately improving detection and treatment
#RNA molecules found in urine, tissue that detect prostate cancer Researchers at Sanford-Burnham Medical Research Institute have identified a set of RNA molecules that are detectable in tissue samples and urine of prostate cancer patients,
but not in normal healthy individuals. The study sets the stage for the development of more-sensitive and specific noninvasive tests for prostate cancer than those currently available,
which could result in fewer unnecessary prostate biopsies with less treatment-related morbidity, according to a new study in The Journal of Molecular Diagnostics.
According to the American Cancer Society, prostate cancer is the second most common type of cancer in American men (behind skin cancer
and the second-leading cause of cancer death in men (after lung cancer. In 2014, more than 230,000 new cases of prostate cancer will be diagnosed.
One in seven American men will get prostate cancer during his lifetime, and one in 36 will die from it.
Since most men with prostate cancer have indolent (nonaggressive) disease for which conservative therapy or surveillance would be appropriate treatment,
the clinical challenge is not only how to identify those with prostate cancer, but also how to distinguish those who would benefit from surgical
or other aggressive treatment from those who would not. Today, prostate cancer is detected primarily and monitored by testing for high concentrations of prostate specific-antigen antigen (PSA) in blood samples.
High PSA levels are followed often by a biopsy to confirm the presence of cancer, and whether it's slow growing or aggressive."
"While elevated PSA can be an alert to a lethal cancer, it can also detect less aggressive cancers that may never do said any harm
Vipul Patel, M d.,medical director of the Global Robotics Institute at Florida Hospital in Orlando."
"Moreover, only 25 percent of men with raised PSA levels that have a biopsy actually have prostate cancer.
Prostate cancer needs to be screened for; we just need to find a better marker.""The researchers believe that they have identified a group of RNA molecules--known as long noncoding RNAS (lncrnas)--that hold the potential for serving as better prognostic markers for prostate cancer. lncrnas are non-coding RNA
molecules that until recently were dismissed by scientists as nonfunctional noise in the genome. Now, lncrnas are thought to regulate normal cellular development
and are reported increasingly as contributing to a range of diseases, including cancer.""We have identified a set of lncrnas that appear to have an important role in prostate cancer diagnostics,
"said Ranjan J. Perera, Ph d.,associate professor and scientific director of Analytical Genomics and Bioinformatics at Sanford-Burnham's Lake Nona campus in Orlando."
"The findings advance our understanding of the role of lncrnas in cancer biology and, importantly, broaden the opportunity to use lncrnas as biomarkers to detect prostate cancer."
"The study profiled the lncrnas in three distinct groups:(1) human prostate cancer cell lines and normal prostate epithelial cells,(2) prostate adenocarcinoma tissue samples and matched normal tissue samples,(3) urine samples
from patients with prostate cancer or benign prostate hypoplasia, and normal healthy individuals. In each case, the lncrnas were elevated in prostate cancer patient samples,
but not in patients with benign prostate hypoplasia or normal healthy individuals. One advantage of lncrnas is that the molecules can be detected in urine samples,
which are more easily available than blood tests. One lncrna, PCA3, was commercialized recently as a urine test to identify which men suspected of having prostate cancer should undergo repeat prostate biopsy.
However discrepancies have been found to exist between PCA3 levels and clinicopathologic features, said Dr. Perera.
In the current study, PCA3 was detected in some, but not all of the study samples, suggesting that reliance on a single biomarker may be insufficient for prostate cancer detection,
while combining additional markers may increase the specificity and sensitivity of the test.""There is a tremendous unmet clinical need for better noninvasive screening tools for early detection of prostate cancer to reduce the overtreatment and morbidity of this disease,"added Dr. Patel."
"Our findings represent a promising approach to meet this demand.""Technical Details of the Study The goal of the first experiment was to see
whether lncrnas are expressed differentially in prostate cancer by measuring total RNA from prostate cancer cell lines
and normal epithelial prostatic cells using NCODE human ncrna array and Sureprint G3 human lncrna microarrays.
Hierarchical clustering revealed distinguishable lncrna expression profiles. Thirty lncrnas were regulated up and the expression levels of three top-ranking candidates XLOC 007697, LOC100287482,
and AK024556 (also known as SPRY4-IT1) were confirmed in prostate cancer cell lines by quantitative real-time polymerase chain reaction (qpcr) analysis. The SPRY4-IT1 was found to be regulated up more than 100-fold in PC3 cells compared with prostatic epithelial cells.
In a second experiment lncrna expression was compared in pooled prostate cancer tissue samples and matched normal tissues from 10 frozen biopsy specimens.
Hierarchical clustering of the differentially expressed lncrnas was observed and 10 up-regulated lncrnas were detected using microarrays.
An additional set of 18 prostate cancer tissue samples was analyzed by qpcr and five lncrnas were found to be significantly higher in prostate tumor tissues compared with matched normal tissues.
Researchers used qpcr to analyze total RNA isolated from urine in another experiment. Urine was collected from 13 prostate cancer patients and 14 healthy controls.
All six lncrnas were found to be regulated significantly up in the urine samples from the prostate cancer patients compared with normal patient controls
while there were no differences between normal and benign prostatic hyperplasia patient samples. In other studies focused particularly on SPRY4-IT1.
Using both qpcr and highly sensitive droplet digital PCR, expression of SPRY-IT1 was found to be increased in 16 of 18 (89 percent) tissue samples from patients with prostatic adenocarcinoma,
compared to normal tissue samples. The researchers developed chromogenic in situ hybridization (CISH) techniques to visualize SPRY4-IT1 expression in cancerous and matched normal tissue.
Intense staining was seen in all adenocarcinoma samples, but not in normal prostatic tissue. Finally, the investigators showed that reduction of SPRY4-IT1 in prostate cancer cells through the use of small interfering RNA (sirna) leads to decreased cell viability and cellular invasion as well as increased apoptosis similar to
what is seen in melanoma cells s
#Experimental rapid test could tell sinusitis sufferers if they need antibiotics...or just patience It's that time of the year where a perfect storm of fall allergies
and cold and flu season will send hordes of sniffling sneezing sufferers to the doctor's office.
Currently, physicians don't have a quick way to tell if sinus problems are allergic, viral or bacterial.
However, many patients will end up with a diagnosis of bacterial sinusitis and a prescription for antibiotics--despite evidence showing that in most cases,
the medication won't help. Now, researchers from The Ohio State university Wexner Medical center and Nationwide Children's Hospital have developed a new rapid screening test that could help physicians know exactly what type of sinusitis they are dealing with
--and help get patients the right treatment.""A quick in-office nose swab, and less than 5 minutes later, physicians will be able to more confidently prescribe antibiotics for the estimated 10 percent of sinusitis sufferers who actually need them,
versus the 53 percent that currently get them, "said Subinoy Das, MD, an adjunct professor of otolaryngology at Ohio State's College of Medicine,
who spent nearly a decade working with a team of researchers to develop the diagnostic."
"The use of the test could translate into 18 million fewer people getting antibiotics that they don't need,
and a positive step towards addressing the major public health issue of antibiotic overuse.""Investors seem to agree.
A presentation given by Das about the science behind the diagnostic caught the attention of two Texas-based entrepreneurs.
The executives recently formed a start-up called ENTVANTAGE, with Das as Chief Medical officer, and are actively seeking funding to help push the screening tool closer to market.
Bacteria behaving badly Das first became interested in diagnostics as an otolaryngology resident during research to find potential biomarkers of sinusitis in the blood.
The project wasn't successful, but it got Das thinking about a more specific target--bacteria in the nasal passages."
"Nasal bacteria seem like an obvious place to start, but at any given time there are hundreds of different types of bacteria in your nose.
"Research has shown that people with chronic sinusitis often have bacteria in their sinuses that have created biofilms--communities of bacteria with sticky protective covers that help them evade antibiotics and flourish unchecked.
Bakaletz, who is director of the Center for Microbial Pathogenesis at Nationwide Children's Hospital
In the process, they developed a novel chinchilla model of bacterial sinusitis following a viral infection.
who is also a professor of Pediatrics and Otolaryngology at Ohio State's College of Medicine."
not only help dramatically reduce the overuse of antibiotics in sinusitis, but could also be used to identify other types of pathogenic respiratory bacteria
so that patients can get the best medicine for the specific type of infection that they have.""Das says the research also helps explain why viral infections appear to promote bacterial infections--a primary reason physicians will often"preemptively"prescribe antibiotics."
"Viruses don't have great mechanisms for spreading on their own, so they hijack bacteria to help them.
but some doctors make the mistake of trying to prevent an infection that isn't likely to develop anyway."
An accomplished sinus surgeon, Das is working with his nurses and staff to engineer and test hundreds of nasal swab collection devices to make sure that they are simple
#Skin exposure may contribute to early risk for food allergies Many children may become allergic to peanuts before they first eat them
Early in the process of developing an allergy skin exposure to food allergens contributes to sensitization which means the skin is reactive to an antigen such as peanuts especially by repeated exposure.
The question of how peanut allergies start is an important one given the extremity of some reactions the prevalence (1 to 2 percent of the population)
and because such allergies tend to be lifelong. Past studies have shown that children may first become allergic
when exposed to peanut proteins through breast milk or in house dust but this current study adds skin exposure to the list of culprits that make a child allergic by the first time they taste a peanut.
The results also make elements of the human immune system in the skin targets for future treatments or preventive efforts.
The peanut protein responsible for most allergic reactions in humans is seen as foreign or dangerous by the immune system of the skin said Cecilia Berin Phd Associate professor of Pediatrics at the Icahn School of medicine at Mount sinai.
Blocking those immune pathways activated in the skin prevented the development of peanut allergy in the mice
and our next step will be to confirm this in humans. In a collaboration among the Jaffe Food Allergy Institute The Mindich Child Health and Development Institute Immunology Institute and Tisch Cancer Institute at The Mount sinai Hospital researchers exposed mice
to peanut protein extract on the skin and observed that repeated topical exposure to peanut allergens led to sensitization and a severe whole-body allergic reaction upon a second exposure.
The data found that peanuts are allergenic due to inherent components the lead to a more robust immune response.
These findings suggest that skin exposure to food allergens contributes to sensitization to foods in early life.
This research helps us to understand why peanut out of the many foods in our diet is such a common cause of food allergy said Berin..
and prevent the food allergy altogether. Story Source: The above story is provided based on materials by The Mount sinai Hospital/Mount sinai School of medicine.
Note: Materials may be edited for content and length. Journal Reference e
#Community justice court associated with lower rearrest rates The opening of a community court in a high-crime area of San francisco was associated with a lower chance that offenders would be arrested for another crime within a year, according to a new RAND Corporation study.
like substance use disorders, mental health issues and unemployment. At community courts, the criminal case management process itself involves providing access to treatment and social services.
#Women who eat fried food regularly before conceiving at increased risk of developing gestational diabetes during pregnancy Women who eat fried food regularly before conceiving are increased at risk of developing gestational diabetes during pregnancy,
Gestational diabetes (GDM) is a complication that can arise during pregnancy, and is characterised by abnormally high blood glucose during the pregnancy (especially in the final 3 months).
It can lead to increased birthweight of the child, as well jaundice and other complications. When left untreated, it can cause complications or stillbirth.
New research published in Diabetologia (the journal of the European Association for the Study of Diabetes) shows that women who eat fried food regularly before conceiving are increased at risk of developing gestational diabetes during pregnancy.
Gestational diabetes (GDM) is a complication that can arise during pregnancy and is characterised by abnormally high blood glucose during the pregnancy (especially in the final 3 months.
It can lead to increased birthweight of the child, as well jaundice and other complications. When left untreated, it can cause complications or stillbirth.
Women who have GDM are more likely to later develop full blown type 2 diabetes.
However, there are few prospective epidemiological studies examining the association of fried food consumption with other health outcomes,
The authors included 21,079 singleton pregnancies from 15,027 women in the Nurses'Health Study II (NHS II) cohort.
NHS II is an ongoing prospective cohort study of 116,671 female nurses in the USA aged 25-44 years at the start of study in 1989.
The participants received a questionnaire every two years regarding disease outcomes and lifestyle behaviours, such as smoking status and medication use.
and diabetes, partly because they promote oxidative stress and inflammation. Moreover, intervention studies with a diet low in AGES have shown significantly improved insulin sensitivity, reduced oxidant stress, and alleviated inflammation."
"When analysed separately, the authors found that there was a statistically significant association of GDM with fried food consumption away from home,
Igor Spetic had family open his medicine bottles. Cotton balls give him goose bumps. Now, blindfolded during an experiment,
That's one of several types of sensation Spetic, of Madison, Ohio, can feel with the prosthetic system being developed by Case Western Reserve University and the Louis Stokes Cleveland Veterans Affairs Medical center.
"How the system works and the results will be published online in the journal Science Translational Medicine Oct 8."
Surgeons Michael W Keith, MD and J. Robert Anderson, MD, from Case Western Reserve School of medicine and Cleveland VA, implanted three electrode cuffs in Spetic
A novel osseointegrated (bone-anchored) implant system gives patients new opportunities in their daily life and professional activities.
An article about this achievement and its long-term stability will now be published in the Science Translational Medicine journal."
a technology in limb prostheses pioneered by associate professor Rickard Brånemark and his colleagues at Sahlgrenska University Hospital.
Rickard Brånemark led the surgical implantation and collaborated closely with Max Ortiz Catalan and Professor Bo Håkansson at Chalmers University of Technology on this project.
Before the surgery, his prosthesis was controlled via electrodes placed over the skin. Robotic prostheses can be advanced very,
and since the surgery he has experienced that he can cope with all the situations he faces; everything from clamping his trailer load and operating machinery,
Because the implant is a bidirectional interface, it can also be used to send signals in the opposite direction--from the prosthetic arm to the brain.
A percutaneous component (abutment) is attached then to the titanium implant to serve as a metallic bone extension,
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