#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.
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.
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.
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,
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.
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
#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,
lncrna expression was compared in pooled prostate cancer tissue samples and matched normal tissues from 10 frozen biopsy specimens.
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,
Bacteria behaving badly Das first became interested in diagnostics as an otolaryngology resident during research to find potential biomarkers of sinusitis in the blood.
"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.
In the process, they developed a novel chinchilla model of bacterial sinusitis following a viral infection.
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."
#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
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
and observed that repeated topical exposure to peanut allergens led to sensitization and a severe whole-body allergic reaction upon a second exposure.
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.
#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.
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,
however for communicating with deaf people; they are for controlling your smartphone. By mimicking the firing of a pistol for example a user can switch to another browser tab change the map's view from satellite to standard
The new technology platform opens new possibilities for devising an approach to prevent HIV infection,
"We desperately need solutions to prevent HIV infection, which, to date, has infected or killed more than 70 million people worldwide,
it could potentially be used to decode infection processes for other viruses, he says. Using Light to Watch HIV Dance In the Science study,
exposing the gp41 subunit that is essential for subsequent aspects of the mechanism that causes infection."
when they introduced a small molecule now under development to prevent HIV infection.""The practical outcome from this technology is that we can begin to understand how the biological system moves.
Technologies Work Hand in hand The Nature study, led by researchers at the National Institute of Allergy and Infectious diseases,
#Slime-producing molecules help spread disease from cats to endangered sea otters The spread of diseases from land animals to sea otters
These large complex molecules form slimy biofilms and bind waterborne organic matter into larger particles in which disease-causing microorganisms can become embedded
Using the parasite Toxoplasma gondii as a model they showed how these sticky polymers increase the chance that disease-causing organisms would be picked up by marine snails
Findings from the new study will be published Oct 8 in the journal Proceedings of the Royal Society B. Discovering the role that these invisible polymers play in disease transmission in the ocean is a tremendous step forward in helping us better understand
Contamination of coastal waters with disease-causing microorganisms is known to pose a threat to the health of both humans
and animals but the mechanisms by which diseases are transmitted in marine ecosystems has remained until now a mystery.
Puzzled by the high rate of T. gondii infection in sea otters and other marine mammals the researchers set out to track the route of transmission.
Noting that T. gondii infections were 10 times more common among sea otters that fed heavily on kelp-grazing marine snails than among otters that fed on abalone
In laboratory tests the researchers discovered that the gelatinous polymers excreted by seaweed act in two ways to provide an environment conducive to transmission of infectious diseases.
when the snails are eaten by otters completing the intricate chain of disease transmission from land-based cats to the endangered coastal sea otters Other researchers on the study were Colin Krusor Patricia A. Conrad John L. Largier
and Ecology of Infectious disease program provided funding for the study y
#Colorectal cancer: New clues for early detection Researchers at the University of Luxembourg have identified potential new ways to test for the first signs of one of the most deadly types of cancer:
colorectal cancer. They have found new biomarkers: molecules whose increased presence or absence in tissue suggests the development of tumorous cells.
These indicators could help detect colorectal cancer at an early stage predict its severity or even offer new treatments.
Colorectal cancer is still one of the most frequent and deadliest cancers worldwide. But diagnosed in time it can be cured in 9 out of 10 cases said Professor Serge Haan from the Life science Research Unit at the University of Luxembourg.
Thus it is highly important to identify more sensitive and specific markers to improve early diagnosis as well as therapeutic strategies.
The research team around Prof. Serge Haan and Dr. Elisabeth Letellier studied over 800 detailed results of tissue-analysis of both patients with various stages of colorectal cancer and healthy individuals.
They completed this study with original analysis of patient material from the Ontario Tumor Bank in Canada and the Integrated Biobank of Luxembourg.
The Luxembourg-based team were the first to see a significant reduction in certain proteins (specifically SOCS2 and SOCS6) in pre-cancerous and cancerous colorectal cells.
Further analysis also revealed that this protein could even give an early prediction of the cancer's severity.
There is increasing evidence that the loss of SOCS proteins plays a role in many cancers as this induce uncontrolled cell growth and tumour development.
These findings have been published in The british Journal of Cancer. The research team included several Luxembourg biomedical research institutions:
This study was financed by the Luxembourg Cancer Foundation. Further work is needed now to expand on these findings before they can be used clinically l
and select the best population of stem cells that we can use for treating different diseases such as brittle-bone disease
and found that these cells could repair both muscle and bone injuries, while marrow-derived cells identified as osteogenic stromal cells were able to repair bone but not muscle.
#Double blast to ward off pneumonia: Dry powder inhaler formulation Despite advances in vaccination and antimicrobial therapy, community-acquired pneumonia remains a leading cause of morbidity and mortality, even in highly developed countries.
Desmond Heng, Reginald Tan and co-workers at the A*STAR Institute of Chemical and Engineering sciences have developed now a dry powder inhalation formulation to treat bacterial infections associated with this disease1.
Community-acquired pneumonia, a type of lung inflammation contracted outside of a hospital or nursing-home setting, is caused most often by infections with bacteria, such as Klebsiella pneumoniae, Pseudomonas aeruginosa and Staphylococcus aureus.
The condition affects people of all ages but is particularly prevalent among infants, the elderly and patients with chronic obstructive pulmonary disease.
The formulation developed by the team contains two important ingredients: ciprofloxacin hydrochloride (CIP), an antibiotic commonly used to eliminate pathogenic bacteria,
"Our follow-up microbial assays show that a concentration as low as one microgram per milliliter is enough to inhibit three of the bacteria known to cause this type of pneumonia.""
""We found that it is feasible to package the CIP-BP dry powder in an inhaler that can treat bacterial infections associated with community-acquired pneumonia,
The delivery of CIP and BP via dry powder inhalers may become a novel and useful strategy for treating patients with community-acquired pneumonia a
and to aid our understanding of a range of diseases, "explained Evans. Aside from biological applications,
or to create artificial noses for the early detection of disease or simply to advise you that the milk in your fridge has gone off."
Key contributions to this work were provided by Dr. John Dye's laboratory at the U s army Medical Research Institute of Infectious diseases (USAMRIID), the lab of Christopher P. Hill, D. Phil.
initiating infection. Importantly, the researchers were able to demonstrate this peptide target is suitable for use in high-throughput drug screens.
Current experimental drugs generally target only one of Ebola's five species."The current growing epidemic demonstrates the need for effective broad-range Ebola virus therapies,
"Importantly, viral sequence information from the epidemic reveals rapid changes in the viral genome, while our target sequence remains the same.
Therefore, our target will enable the discovery of drugs with the potential to treat any future epidemic,
"Ebola is a lethal virus that causes severe hemorrhagic fever with a 50 percent to 90 percent mortality rate.
"Although the current push of clinical trials will hopefully lead to an effective treatment for the Zaire species causing the present epidemic,
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