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Gene mutation in the fight against HIV
Research conducted at the laboratory of the University of Pennsylvania, provides data to the first change in the targeted gene, which leads to the creation of genetically modified immune cells impermeable to the HIV virus.
The study focuses on the use of a technique known as targeted gene editing.
The aim is to change conformation of the CC chemokine receptor type 5 (CCR5) delta32, which represents a protein on the surface of T - cells that HIV uses to connect to and infect healthy cells.
If the protein is changed even slightly, the virus is unable to continue its development. Although the modification of the protein is not able to kill the virus, its ability to proliferate is suppressed, generally used in drugs used for treatment of patients diagnosed with HIV.
Only a small portion of the world population carries an allele that cause this conformational change in CCR5 - delta32.
Basically everyone should copy inherited from both parents, which therefore does not allow inoculation with the virus. The fact is, however, that allele is owned by only 14% of the European population and carriage in African and Asian populations is even more rare.
It is this mutation serves as inspiration for the study.
There are involved only 20 subjects diagnosed as HIV positive by 2 persons they fell, due to the very low levels of T cells.
In the remaining 18 patients, the T cells are subjected to the modification, and then monitor their response to the match, and the virus.
In 6 th patient has seen a sharp rise in resistance to the virus, which even led to the discontinuation of drug therapy.
Although immune cell lives on average about six weeks, the modified cells can be detected several months later.
These changes have not eradicated the virus from the body, and although best results patients are not cured.
Yet to be made additional tests and studies, the researchers, however, have an optimistic attitude and better predict outcome.
Intestinal bacteria affect immune cells
According to a new study intestinal bacteria play an important role in the development of white blood cells (leukocytes) that are associated with the immune system and the basic unit to fight infections that affect the body.
The human body is home to thousands of species of microbes, which under certain conditions can cause disease, but also have a number of benefits to our health qualities.
The highest concentration and the greatest diversity of bacterial species these sows findeth in the gastrointestinal tract and in particular in the colon.
A team from the California Institute of Technology (Caltech) in Pasadena, led by Sarkis Mazmanian, a professor of biology and biological engineering, has conducted research on this area of the human body.
Their work with mice has led to many discoveries about the importance of intestinal bacteria for health.
For example, in 2013, the team reported the relationship between microbes and autism, as well as their impact on the development of multiple sclerosis.
In a recent study published in the journal Cell Host & microbe, researchers describe their discovery that the beneficial intestinal bacteria play a key role in the development of innate immune cells - macrophages, monocytes and neutrophils - special white blood cells that provide the first line of defense against invading pathogens.
When the team comparing the number of white blood cells in these areas in mice born without intestinal bacteria - known as " non -microbial " mice and normal mice with normal colonic fluorines, they found that non - microbial mice had fewer white blood cells.
The team tested the ability of mice to combat infections by exposing them to a mono-cytogenetic bacterium Listeria.
Significant discrepancies between FISH, IHC results for ALK testing
The findings of a recent study indicate that routine testing with both fluorescent in situ hybridization (FISH) and immunohistochemistry (IHC) may enhance the detection of ALK-positive non-small cell lung cancer (NSCLC). Accurate determination of ALK-positive tumors is necessary to identify patients with advanced NSCLC who are most likely to benefit from targeted therapy with an ALK inhibitor.
The discovery of ALK rearrangement in about 1% to 7% of NSCLCs led to the development of ALK inhibitors, such as crizotinib, which have significantly improved treatment response among people with ALK-positive NSCLC. FISH with break-apart probes is currently the only approved test for the detection of ALK positivity in NSCLC, but this technique may not be available or feasible in all institutions. IHC, which is more affordable and accessible than FISH, has been found to be reliable as a screening tool, but interpretation of its results have not been standardized. Researchers continue to explore the optimal testing process for identifying ALK-positive NSCLCs.
Parallel testing with both FISH and IHC on 3,234 NSCLCs led to the identification of 150 tumors that were ALK positive by either test. The results of FISH and IHC were discordant in 80 of these tumors. As such, the use of FISH or IHC alone would have missed approximately 25% of ALK-positive cases. The findings of the study are published in the March issue of the International Association for the Study of Lung Cancer's journal, the Journal of Thoracic Oncology (JTO).
Most discordant results were FISH-positive/IHC-negative (36 cases); FISH-negative/IHC-positive results were found in 19 cases, and FISH-noncontributive/IHC-positive results were found in 15 cases. Preliminary data from 44 evaluable patients showed that treatment with an ALK inhibitor was associated with a high response rate, with response noted among patients who had tumors with discordant results (either FISH-positive/IHC-negative or FISH-negative/IHC-positive).
"Data on crizotinib response in patients who have been diagnosed differently by FISH and IHC are still preliminary. Thus, until large-scale studies in patients under therapy with crizotinib determine which testing is the most relevant to predict responses to ALK inhibition, our data support the need to routinely perform both analyses because of the difficulty in detecting the chimeric ALK protein in NSCLC and the presence of false-negative cases for each method," says lead author Florian Cabillic, PharMD, PhD, Université de Rennes, Rennes, France.
The study also demonstrated that systematic testing of NSCLC by both FISH and IHC is feasible in routine practice. In addition, the findings indicate that performing FISH routinely on all NSCLC specimens may require an automated process at various stages of the analysis.
In Tibet, Dogs Breathe Comfortably With Less Oxygen
See Spot run. See Lassie save Timmy from a well. See Tibetan Mastiffs climb 4,500 meters above sea level on the Tibetan Plateau. The ever-so-fluffy Tibetan Mastiff, which commonly serves as a guard dog for the plateau's residents, is able to breathe comfortably at high altitudes. Like the Tibetan people, Tibetan Mastiffs have adapted to air with less oxygen.
Ya-Ping Zhang and a team of scientists examined sets of genes from 32 Tibetan Mastiffs, 20 Chinese native dogs, and 14 wolves to investigate how the Mastiffs have adjusted. They looked for variations in the DNA sequence called single-nucleotide polymorphisms (SNPs, also pronounced simply as "snips"). The scientists genotyped the SNPs in the Mastiffs and compared them to the ones in the dogs and wolves.
After finding more than 120,000 SNPs, Zhang and the scientists identified 16 genes with signals of positive selection in the Tibetan Mastiff – 12 of these genes are connected to functions in the body that would help the canine adapt to high altitudes with low oxygen levels. Several of these genes are responsible for the building of hemoglobin, which helps transport oxygen through blood, and monitoring metabolism. Oxygen is required to process consumed food into energy, so efficient metabolizing means less oxygen is used. One of the genes, EPAS1, has also been linked to helping Tibetan humans adapt to high altitudes.
Potential new treatment for sepsis
Sepsis is the leading cause of in-hospital death and there is no specific treatment for it. Now, research led by Dr. Qingping Feng of Western University suggests a protein called recombinant human annexin A5 may have therapeutic potential for the treatment of this disease. The paper is published in advance, online in Critical Care Medicine.
Sepsis is caused by an overwhelming immune response to an existing infection. It's estimated there are 18 million cases annually worldwide. The mortality rate is 30 to 40 per cent for severe sepsis and 40 to 80 per cent for septic shock. Dr. Feng, a professor in the Departments of Physiology and Pharmacology, and Medicine at Western's Schulich School of Medicine & Dentistry and a scientist at Lawson Health Research Institute is particularly interested in how sepsis causes cardiac dysfunction.
Annexin A5 is a lipid-binding protein produced by cells. Using mice with induced sepsis, Dr. Feng, Dr. Xiangru Lu, and Paul Arnold, MSc, studied the effects of annexin A5 on cardiac function and animal survival.
"We treated the septic animals and to our surprise we found a dramatic, significant effect in improving cardiac function during sepsis and improved survival rates in the mice," says Dr. Feng. "We also found it helped even if administered hours after the septic infection. This is important because the delayed treatment simulates what usually happens in a clinical setting. The patient often has had sepsis for several hours, or a few days when they seek treatment."
Annexin A5 is not currently used as a therapeutic agent, but its safety has been tested in humans. It's currently used in imaging studies to identify cells undergoing apoptosis (cell death).
While this study looked at the heart, Dr. Feng believes annexin A5's beneficial properties could apply to multiple organs including liver, lungs and kidney, all which can all be affected by sepsis.
Cancer cells appear to change while moving throughout body
For the majority of cancer patients, it's not the primary tumor that is deadly, but the spread or "metastasis" of cancer cells from the primary tumor to secondary locations throughout the body that is the problem. That's why a major focus of contemporary cancer research is how to stop or fight metastasis.
Previous lab studies suggest that metastasizing cancer cells undergo a major molecular change when they leave the primary tumor -- a process called epithelial-to-mesenchymal transition (EMT). As the cells travel from one site to another, they pick up new characteristics. More importantly, they develop a resistance to chemotherapy that is effective on the primary tumor. But confirmation of the EMT process has only taken place in test tubes or in animals.
In a new study, published in the Journal of Ovarian Research, Georgia Tech scientists have direct evidence that EMT takes place in humans, at least in ovarian cancer patients. The findings suggest that doctors should treat patients with a combination of drugs: those that kill cancer cells in primary tumors and drugs that target the unique characteristics of cancer cells spreading through the body.
The researchers looked at matching ovarian and abdominal cancerous tissues in seven patients. Pathologically, the cells looked exactly the same, implying that they simply fell off the primary tumor and spread to the secondary site with no changes. But on the molecular level, the cells were very different. Those in the metastatic site displayed genetic signatures consistent with EMT. The scientists didn't see the process take place, but they know it happened.
"It's like noticing that a piece of cake has gone missing from your kitchen and you turn to see your daughter with chocolate on her face," said John McDonald, director of Georgia Tech's Integrated Cancer Research Center and lead investigator on the project. "You didn't see her eat the cake, but the evidence is overwhelming. The gene expression patterns of the metastatic cancers displayed gene expression profiles that unambiguously identified them as having gone through EMT."
The EMT process is an essential component of embryonic development and allows for reduced cell adhesiveness and increased cell movement.
According to Benedict Benigno, collaborating physician on the paper, CEO of the Ovarian Cancer Institute and director of gynecological oncology at Atlanta's Northside Hospital, "These results clearly indicate that metastasizing ovarian cancer cells are very different from those comprising the primary tumor and will likely require new types of chemotherapy if we are going to improve the outcome of these patients."
Ovarian cancer is the most malignant of all gynecological cancers and responsible for more than 14,000 deaths annually in the United States alone. It often reveals no early symptoms and isn't typically diagnosed until after it spreads.
"Our team is hopeful that, because of the new findings, the substantial body of knowledge that has already been acquired on how to block EMT and reduce metastasis in experimental models may now begin to be applied to humans," said Georgia Tech graduate student Loukia Lili, co-author of the study.
Microbes more likely to adhere to tube walls when water is moving
In a surprising new finding, researchers have discovered that bacterial movement is impeded in flowing water, enhancing the likelihood that the microbes will attach to surfaces. The new work could have implications for the study of marine ecosystems, and for our understanding of how infections take hold in medical devices.
The findings, the result of microscopic analysis of bacteria inside microfluidic devices, were made by MIT postdoc Roberto Rusconi, former MIT postdoc Jeffrey Guasto (now an assistant professor of mechanical engineering at Tufts University), and Roman Stocker, an associate professor of civil and environmental engineering at MIT. Their results are published in the journal Nature Physics.
The study, which combined experimental observations with mathematical modeling, showed that the flow of liquid can have two significant effects on microbes: "It quenches the ability of microbes to chase food," Stocker says, "and it helps microbes find surfaces."
That second finding could be particularly beneficial: Stocker says in some cases, that phenomenon could lead to new approaches to tuning flow rates to prevent fouling of surfaces by microbes—potentially averting everything from bacteria getting a toehold on medical equipment to biofilms causing drag on ship hulls.
The effect of flowing water on bacterial swimming was "a complete surprise," Stocker says. "My own earlier predictions of what would happen when microbes swim in flowing water had been: 'Nothing too interesting,'" he adds. "It was only when Roberto and Jeff did the experiments that we found this very strong and robust phenomenon."
Charts of the probability that a bacterium will have a given orientation, at three different positions in the moving stream of water, are plotted based on experimental data (solid lines) and mathematical models (dashed lines), showing how well the two agree.
Even though most microorganisms live in flowing liquid, most studies of their behavior ignore flow, Stocker explains. The new findings show, he says, that "any study of microbes suspended in a liquid should not ignore that the motion of that liquid could have important repercussions on the microbes."
The novelty of this result owes partly to the divisions of academic specialties, and partly to advances in technology, Stocker says. "Microbiologists have rarely taken into account fluid flow as an ecological parameter, whereas physicists have just recently started to pay attention to microbes," he says, adding: "The ability to directly watch microbes under the controlled flow conditions afforded by microfluidic technology—which is only about 15 years old—has made all the difference in allowing us to discover and understand this effect of flow on microbes."
The team found that swimming bacteria cluster in the "high shear zones" in a flow—the regions where the speed of the fluid changes most abruptly. Such high shear zones occur in most types of flows, and in many bacterial habitats. One prominent location is near the walls of tubes, where the result is a strong enhancement of the bacteria's tendency to adhere to those walls and form biofilms.
But this effect varies greatly depending on the speed of the flow, opening the possibility that the rate of biofilm formation can be tweaked by increasing or decreasing flow rates.
Guasto says the new understanding could help in the design of medical equipment to reduce such infections: Since the phenomenon peaks at particular rates of shear, he says, "Our results might suggest additional design criteria for biomedical devices, which should operate outside this range of shear rates, when possible—either faster or slower."
"Biofilms are found everywhere," Rusconi says, adding that the majority of bacteria spend significant fractions of their lives adhering to surfaces. "They cause major problems in industrial settings," such as by clogging pipes or reducing the efficiency of heat exchangers. Their adherence is also a major health issue: Bacteria concentrated in biofilms are up to 1,000 times more resistant to antibiotics than those suspended in liquid.
The concentration of microbes in the shear zones is an effect that only happens with those that can control their movements. Nonliving particles of similar size and shape show no such effect, the team found, nor do nonmotile bacteria that are swept along passively by the water. "Without motility, bacteria are distributed everywhere and there is no preferential accumulation," Rusconi says.
The new findings could also be important for studies of microbial marine ecosystems, by affecting how bacteria move in search of nutrients when one accounts for the ubiquitous currents and turbulence, Stocker says. Though they only studied two types of bacteria, the researchers predict in their paper that "this phenomenon should apply very broadly to many different motile microbes."
In fact, the phenomenon has no inherent size limit, and could apply to a wide range of organisms, Guasto says. "There's really nothing special about bacteria compared to many other swimming cells in this respect," he says. "This phenomenon could easily apply to a wide range of plankton and sperm cells as well."
Howard A. Stone, a professor of mechanical and aerospace engineering at Princeton University, who was not involved in this research, calls this a "very interesting paper" and says "the observation of shear-induced trapping, which can impact the propensity for bacterial attachment on surfaces, is an important observation and idea, owing to the major importance of bacterial biofilms."
Breast Milk Custom Formulated For Baby’s Gender
Milk straight from the source contains a variation of vitamins, minerals, fats, sugars, and other factors that promote optimal growth, development, and behavior in babies. Not only does the nutrient content of the milk change over time as the baby grows, but the milk’s composition will actually differ based on the gender of the child.
In a variety of mammals, including humans, gender also plays an important part in milk composition. Males, who tend to be more muscular, require additional fat and protein. While the fat content in the milk females drink isn’t as high, they tend to consume more milk per meal and will nurse longer. A 2012 study led by Masako Fujita from Michigan State University published in the American Journal of Physical Anthropology showed that human mothers produce milk with 2.8% fat for sons and 1.74% for daughters. In extremely impoverished locations where infant mortality is high, the fat content is higher for girls.
A new study has shown that these differences may very well begin during fetal development. The study was led by evolutionary biologist Katie Hinde from Harvard University and was published in PLOS One. She presented her results this past Saturday at the AAAS 2014 Annual Meeting. The differences appear to begin during fetal development, according to Hinde’s study. Hinde analyzed 2.39 million lactation records from 1.49 million dairy cows and determined that those who had birthed females produced an average of about 445 kg (980 lbs) more milk than those who birthed males, over a two year lactation span. Even if the mother and calf were separated shortly after birth, the volume differences persisted. For cows, however, gender does not impact nutrient content.
For some animals, such as rhesus macaques, social status within the group is passed down from generation to generation. Previous research from Hinde has found that young female rhesus macaques get higher levels of calcium than their brothers, giving them stronger bones and potentially allowing them to reach sexual maturity more quickly. Because females cannot reproduce throughout their entire lives, starting early is an advantage. However, the males receive more cortisol, which helps to regulate metabolism and temperament, allowing them to grow up strong and sire more offspring.
Breast milk is hardly the static, homogenous liquid we are most familiar with from the store. Though the ability to nurse our young is one of the defining features that makes mammals distinct from every other class of animal, there is still an incredible amount about it that we are just discovering. Learning more about how the breast milk is formulated inside the mother’s body will allow us to better understand the ever-changing nutritional needs of babies and could even allow commercial formulas to be reconfigured to better nourish infants when breastfeeding is not an option.
Researchers have created embryonic stem cells for 30 minutes
Scientists from the U.S. and Japan have made a breakthrough in stem cell research, finding a cheap and easy way to reprogram adult cells from mice and return them in a state resembling embryonic when cells are able to differentiate into various cell types and tissues.
In other words - the specialists were able to obtain embryonic stem cells without embryos, Reuters, ending up publication in the journal "Nature." The discovery of embryonic stem cells, scientists have high hopes for their use in the treatment of many diseases because of their pluripotency - the ability to develop into different cells and tissues.
The problem with embryonic stem cells is that retrieval means the destruction of the embryo , which raises ethical issues. With the new method, these concerns fall. In 2006, scientists offer an alternative to embryonic cells - ie. induced pluripotent cells. These are normal adult cells back into an undifferentiated pluripotent state through the introduction of foreign genetic material. The problem of induced pluripotent cells , however, is that they can be differentiated only in certain cell types, in contrast to embryonic, which are able to develop into any cell type.
Now the authors of this study - specialists from Japan Institute for physico-chemical studies and their colleagues from the hospital "Brigham end uimins" in Boston and Harvard Medical School in the U.S. have demonstrated that any mature adult cell (somatic cell) has the potential to become equivalent of embryonic stem cells.
Scientists have demonstrated in preclinical models of innovative and unique way to reprogram adult cells that does not require the introduction of foreign DNA - a process used in induced pluripotent stem cells.
In the experiments specialists left mature adult cells to multiply , then they are stressed to near the limit, exposing them to different stress factors - trauma, limited oxygen, acidic environment. Scientists have found that within days the cells survived and recovered from stressful stimuls, returning naturally to a state similar to that of embryonic stem cells.
Thus obtained cells called STAP (Stimulus-triggered acquisition of pluripotency - acquired under the influence of incentives pluripotency) cells were able to differentiate and develop into different cell types and tissues depending on the conditions in which placed.
Scientists find groovy way to influence specialization of stem cells
The primary cilia were grown on micro-grooves 10 micrometres in size
Stem cells are capable of becoming any cell type within the body through the process of differentiation.
The discovery has the potential for application in the development of new therapies for a range of medical treatments where scientists aim to replace or regenerate tissues that have become diseased or dysfunctional.
Publishing in the journal Scientific Reports, the researchers found that growing adult stem cells on micro-grooved surfaces disrupts the biochemical pathway that determines the length of the primary cilia. This change in length of the structure ultimately controls the subsequent behaviour of the stem cells.
"Primary cilia are a thousand times smaller than the width of a human hair and are a ubiquitous feature of most cell types but were once thought to be irrelevant. However, our research shows that they play a key role in stem cell differentiation," explains co-author Professor Martin Knight from Queen Mary's School of Engineering and Materials Science and the Institute of Bioengineering.
"We found it's possible to control stem cell specialization by manipulating primary cilia elongation, and that this occurs when stem cells are grown on these special grooved surfaces."
Stem cells are being considered to treat a number of degenerative conditions such as arthritis, Alzheimer's disease and Parkinson's disease.