Ma. Celna Icban 2PN2

Latest Updates of the Diseases

Immune System

• New discovery on early immune system development• Date: November 12, 2013• Source: Lund University• Summary:• Researchers have shed light on how and when the immune

system is formed, raising hope of better understanding various diseases in children, such as leukemia.

• The immune system is complex and a number of genetic diseases are attributed to defects in the cells that form its origins. The study from Lund and Oxford University presents unique findings on the formation of these cells.

• We know that the first blood stem cells are formed in the aorta region and then travel to the liver, which is the body's major blood-forming organ during the fetal stage. In the liver, the blood stem cells produce the more mature blood cells that form our blood system. At the same time, T- and B-cells are formed, which comprise the basis of our advanced immune system. From birth, this process takes place in the bone marrow and the liver ceases to form blood cells.

• Researchers have long believed that the first cells that lead to the development of our immune system, the immune-competent cells, are formed from blood stem cells in the liver while the fetus is developing. Blood stem cells can be found in the liver from day 11-12 in a mouse fetus, which is the equivalent of around 6-7 weeks' gestation in humans.

• In the current study, which was performed on mice, researchers showed that these cells linked to our immune system are formed even earlier than this, in the embryo's yolk sac, i.e. before the first blood stem cells are formed. In the human embryo, the yolk sac is one of the three fetal sacs and appears in around the fifth week of pregnancy.

• "The question we have posed is whether the immune system is formed in a different way in the fetus than in an adult and how early in the development of the fetus the cells that form our early immune system can be found. Knowledge of this is important because it helps us to understand how and when our immune system begins to form and what can go wrong in that process," explained Charlotta Böiers, a postdoctoral fellow at Lund University.

• Childhood leukemia is one example of how important it is to understand how the immune system is formed. The first mutation on the path to childhood leukemia has been shown to take place while the child is still in the womb.

• "It is still not known in which cell or cells this first step takes place and it is therefore important for us to continue our research on how the immune system starts in humans. The aim is now to continue our investigations in humans," said Charlotta Böiers.

• If it is possible to prove that the cells mutate at this very early stage of development, then this would increase our understanding of how childhood leukemia occurs.

• "These first cells seem to disappear in the late stages of development of the fetus. This may not happen when there is a mutation. Perhaps the defective cells instead remain alive, and further mutations occur that in turn could lead a child to develop cancer."

• Story Source:

• The above story is based on materials provided by Lund University. Note: Materials may be edited for content and length.

• Immune Biomarkers Help Predict Early Death, Complications in HIV Patients with TB

• Date:• February 9, 2015• Source:• Perelman School of Medicine at the University of Pennsylvania• Summary:• Medical researchers have identified immune biomarkers in HIV/TB patients

before they begin ART that could help distinguish who goes on to develop IRIS or die after treatment

•

Renal System

• Gene leads to malformation of the urinary tract• Researchers at the University of Bonn discover a new hereditary

factor associated with a rare disease• An interdisciplinary team of researchers under the direction of the

University of Bonn Hospital have discovered a gene which is associated with a rare congenital anomaly of the urinary tract called classic bladder exstrophy. It increases the likelihood that the urinary tract will not form properly during embryonic development. The finding is an important step for understanding the developmenta of urinary tract malformations in general and for developing prophylactic measures. The results are published in the current online edition of the journal "PloS Genetics".

The kidneys and urinary tract are the sites affected most frequently by congenital malformations. Approximately 1 out of every 200 children suffers from such a malformation. "These diseases make up about 20 to 30 percent of all congenital malformations," says Associate Professor Dr. Heiko Reutter from the Institute of Human Genetics and the Department of Neonatology and Pediatric Intensive care medicine of university of Bonn.

Care Medicine of the University of Bonn. 

• For many years, the pediatrician has investigated the genetic causes of classic bladder exstrophy comprising malformations ranging from the bladder to the entire urinary tract. These malformations frequently result in urinary tract infections, incontinence, renal damage and sexual dysfunction. Approximately one out of 20,000 newborns is affected by this rare disease which is considered to be one of the most severe forms of malformations on this spectrum. "Congenital classic bladder exstrophy thus represents an enormous challenge in the medical care of patients affected and their families," says Dr. Reutter.

• Focus at the Center for Rare Diseases

To date, the genetic causes of this rare disease have been basically unknown. In the past ten years, with the bladder extrophy/epispadias self-help group and leading pediatric urologists and pediatric surgeons in Germany - including from the Barmherzigen Brüder Pediatric Hospital in Regensburg as well as the universities of Mainz and Ulm - researchers at the University of Bonn hospital have been able to gather the largest group of patients in the world. The researchers in Bonn received additional support for the current study from researchers at the Max Planck Institute for Molecular Genetics in Berlin. Assistance was also provided by the Center for Rare Diseases at the University of Bonn Hospital (ZSEB). The researchers focus on rare uro-rectal malformations there. 

• Using blood samples from a total of 210 patients, the scientists isolated the genetic information and compared it with a control group of healthy persons. The researchers used automated analysis methods to record more than 700,000 genetic markers in each case which are evenly distributed throughout the DNA. The evaluation using biostatistical methods revealed a clear connection with an altered gene: ISL1, which is located on chromosome five. "In this way, a gene in connection with this disease was identified for the very first time," says Prof. Dr. Michael Ludwig from the Institute of Clinical Chemistry and Clinical Pharmacology of the University of Bonn Hospital.  The search for other genes

This has been a breakthrough for science. "With the discovery of this gene, it now becomes possible to clarify the biological foundations of this disease," says Prof. Dr. Markus Nöthen from the Institute of Human Genetics from the University of Bonn. Beyond the genetic causes of classic exstrophy, the objective is to now identify risk factors during pregnancy and to develop preventive approaches from this for the unborn child. Further investigations are intended to demonstrate which yet undiscovered genes play an additional role in the development of the disease. The scientists are still looking for affected to continue the studies. Anyone interested may email Dr. Reutter directly: reutter@uni-bonn.de. 

• Publication: Genome-wide association study and meta-analysis identify ISL1 as genome-wide significant susceptibility gene for bladder exstrophy, "PLOS Genetics", DOI: 10.1371/journal.pgen.1005024.

Media contact information:

PD Dr. Heiko ReutterInstitute of Human Genetics/Department of Neonatology and Pediatric Intensive Care Medicineof the University of Bonn HospitalTel. ++49-(0)228-28751000

Sensorineural System

• Brain: Striatum acts as hub for multisensory integration• Date:• August 22, 2014• Source:• Karolinska Institutet• Summary:• A new study provides insight on how the brain processes

external input such as touch, vision or sound from different sources and sides of the body, in order to select and generate adequate movements. The findings show that the striatum acts as a sensory ‘hub’ integrating various types of sensory information, with specialized functional roles for the different neuron types.

• new study from Karolinska Institutet in Sweden provides insight on how the brain processes external input such as touch, vision or sound from different sources and sides of the body, in order to select and generate adequate movements. The findings, which are presented in the journalNeuron, show that the striatum acts as a sensory 'hub' integrating various types of sensory information, with specialised functional roles for the different neuron types.

• "The striatum is the main input structure in the basal ganglia, and is typically associated with motor function," says Principal Investigator Gilad Silberberg at the Department of Neuroscience. "Our study focuses on its role in processing sensory input. This is important knowledge, since the striatum is implicated in numerous diseases and disorders, including Parkinson's disease, Huntington's disease, ADHD and Tourette syndrome."

• The striatum is the largest structure in a collection of brain nuclei called the basal ganglia, which are located at the base of the forebrain. It is involved in motor learning, planning and execution as well as selecting our actions out of all possible choices, based on the expected reward by the dopamine system. Most research performed in the striatum is focused on the motor aspects of its function, largely due to the devastating motor symptoms of the related diseases.

• However, in order to select the correct actions, and generate proper motor activity it is essential to continuously process sensory information, often arriving from different sources, different sides of the body and from different sensory modalities, such as tactile (touch), visual, auditory, and olfactory. This integration of sensory information is in fact a fundamental function of our nervous system.

• In the current study, researchers Gilad Silberberg and Ramon Reig show that individual striatal neurons integrate sensory input from both sides of the body, and that a subpopulation of these neurons process sensory input from different modalities; touch, light and vision. The team used intracellular patch-clamp recordings from single neurons in the mouse striatum to show their responses to whisker stimulation from both sides as well as responses to visual stimulation. Neurons responding to both visual and tactile stimuli were located in a specific medial region of the striatum.

• "We also showed that neurons of different types integrate sensory inputs in a different manner, suggesting that they have specific roles in the processing of such sensory information in the striatal network," says Gilad Silberberg

Story Source:The above story is based

on materials provided by Karolinska Institutet. Note: Materials may be

edited for content and length.

Integumentary System

• Benefits of immunotherapy, cancer-targeted treatment in triple combo drug for melanoma

• Date:• March 18, 2015• Source:• University of California, Los Angeles (UCLA),

Health Sciences• Summary:• A groundbreaking new triple combination therapy

shows promising signs of more effectively controlling advanced melanoma than previous BRAF + MEK inhibitor or BRAF inhibitor + immunotherapy combos alone, and with increased immune response and fewer side effects.

• An estimated 70,000 new cases of metastatic melanoma are diagnosed each year in the United States, and of those 8,000 will die of the disease. About 50 percent of these men and women (or 35,000 a year) have a mutated protein called a BRAF mutation, which in most cases allows melanoma to eventually build up a resistance to many drug therapies.

• In the new study led by UCLA Jonsson Comprehensive Cancer Center member Dr. Antoni Ribas and colleague Dr. Siwen Hu-Lieskovan, UCLA scientists combined targeted therapies utilizing a BRAF inhibitor (dabrafenib) and MEK inhibitor (trametinib) with immunotherapy. The three together are shown to be more effective treatments by sensitizing the patients' own immune system to enhance immunotherapy, and reduce the probability of the melanoma eventually developing resistance.

• This is a significant advance compared to previous drug combination findings, in which a combined BRAF inhibitor (vemurafenib) with immunotherapy (ipilimumab) caused serious liver toxicity in some patients, and the targeted therapies (BRAF and/or MEK inhibitors) became less effective and reactivated cancer cell growth.

• "The two drug combination of BRAF and MEK inhibitors works synergistically and decreases the side effects of the BRAF inhibitor or normal cells. We reasoned that this combo would allow us to synergize with immunotherapy without increasing toxicities," said Ribas, a professor of hematology and oncology. "We have made incredible progress in the last three years of treating advanced melanoma, with six new drug therapies approved by the FDA. Half are immunotherapies and the other half are BRAF or MEK inhibitors. The next step is to figure out how to rationally combine them and merge their benefits in the clinic."

• "The triple combination of targeted therapies BRAF (dabrafinib) and MEK (trametinib) inhibitors with immunotherapy (tumor antigen-specific adoptive cell transfer or anti-PD1 antibody) makes immune therapy more effective at killing cancerous tumors and causes less toxicity " said Hu-Lieskovan, a UCLA clinical instructor of hematology and oncology. "We're trying to take advantage of the high response rate of the targeted therapy and durability of the immune therapy to induce a response that lasts in the majority of patients."

• Ribas and Hu-Lieskovan have opened two clinical trials to test the effectiveness of the triple combination therapy in advanced melanoma patients. The first reported findings will be presented at the American Society of Clinical Oncology (ASCO) annual meeting in May 2015.

• Story Source:

• The above story is based on materials provided by University of California, Los Angeles (UCLA), Health Sciences. Note: Materials may be edited for content and length.

Reproductive System

• November 8, 2011 106

• A team of New York University biologists has uncovered a previously unknown role for a set cells within the female reproductive tract of insects. Their discovery, which appears in the journal PloS Biology, could lead into a range of innovations pertaining to insect life, from curbing the growth of mosquitos to bolstering the population of honey bees.

• The researchers, part of NYU’s Center for Genomics and Systems Biology, studied spermathecal secretory cells (SSCs), a set of cells in the female reproductive tract whose existence had previously been determined but whose function was unknown.

• To explore the role of SSCs, the NYU researchers studied female Drosophila melanogaster, a fruit fly. Fruit flies have rapid developmental time, allowing biologists to examine genetic and physical changes over a relatively short period. In addition, many of the genetic processes identified in flies are conserved in humans.

• In order to isolate the role SSCs play, the researchers used a genetic technique to eliminate SSCs in a sample of flies and monitored how their reproductive process was affected. This method did not alter the function of these flies’ other cells.

• Their results indicated that SSCs have two fundamental roles in the reproductive process: they are necessary for moving fertlized eggs through the reproductive tract and they assist in storing sperm.

• Normal female fruit flies store sperm in two different organs--the seminal receptacle and two mushroom-shaped spermathecae. However, in flies missing SSCs, sperm never reached the spermathecae, and those that reached the seminal receptacle subsequently lost their motility—i.e., they stopped swimming. Lacking SSCs, D. melanogaster loses its ability to move fertilized eggs through the reproductive tract and, as a result, will hatch eggs internally—in utero—rather than outside the body.

• “We are excited to see whether our findings apply to insects that are important to human health or agriculture,” said Mark Siegal, the study’s senior author and a professor of biology at NYU. “For instance, future work could explore boosting the reproduction of honeybees or, conversely, curbing this same process in disease-transmitting insects such as mosquitoes.”

• The study’s other authors were Sandra Schnakenberg, an NYU doctoral candidate who led the study, and Wilfredo Matias, an NYU undergraduate at the time of the study and now a student at Harvard Medical School.