3. • 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.
4. • 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.
5. • 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."
6. • Story Source:
• The above story is based on materials provided
by Lund University. Note: Materials may be
edited for content and length.
7. • 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
•
9. • 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.
10. • 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.
11. • 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.
12. • 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.
13. • 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 Reutter
Institute of Human Genetics/Department
of Neonatology and Pediatric Intensive Care Medicine
of the University of Bonn Hospital
Tel. ++49-(0)228-28751000
15. • 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.
16. • 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.
17. • "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.
18. • 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
19. Story Source:
The above story is based
on materials provided by Karolinska
Institutet. Note: Materials may be
edited for content and length.
21. • 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.
22. • 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.
23. • "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.
24. • 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.
27. • 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.
28. • 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.
