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Vol. 02 NO 16 April 17th, 2018.

NEWS - PAGE 3 NEWS - PAGE 4 NEWS - PAGE 6 NEWS - PAGE 10


TOP 30 UNIVERSITIES AS PER – ADHESION PROTEIN THAT HELPS BACTERIA CARDIOVASCULAR RISK
TOP 20 COLLEGES OF INDIA AS PER
MHRD, GOVT OF INDIA FOR 2018 STICK TO CELLS COULD HELP FIND NEW INCIDENCE PREDICTING BLOOD TEST
GOVT OF INDIA SURVEY – 2018
ANTIBIOTICS DEVELOPED

NEWS EDITION
THE DOWNFALL
OF BACTERIA?

The shape, elongation, division and


sporulation (SEDS) proteins are a large
family of ubiquitous and essential trans-
membrane enzymes with critical roles in
bacterial cell wall biology.

By Disha Padmanabha

microbiology and immunobiology at Harvard School. “You get to the most fundamental lev-

A CELL-WALL BUILDING Medical School. el of things that are found across all species,
and when something works in one of them,

PROTEIN COULD CAUSE THE


“A chemical compound—an inhibitor— chances are it will work across the board.”
that binds to this pocket would interfere with
the protein’s ability to synthesize and main- The success of this “roundabout” approach,

DOWNFALL OF BACTERIA tain the bacterial wall,” Rudner said. “That


would, in essence, crack the wall, weaken
researchers said, circumvents a significant
hurdle in field of structural biology and can
the cell and set off a cascade that eventually open the doors toward defining the structures
The exact function of SEDS proteins was The researchers mapped RodA’s molecular causes it to die.” of many more newly discovered proteins.
for a long time poorly understood, but now, structure and found that it included an unusu-
a recent research by a team at the Harvard al cavity on its outer edge. And where there’s Additionally, because the protein is highly “These insights underscore the importance
Medical School has revealed how it could a gap – in anything, really – sooner or later conserved across all bacterial species, the of creative crosspollination among scien-
make for an uncompromisable Achilles heel someone will find an object to fill it. discovery of an inhibiting compound means tists from multiple disciplines and depart-
of most bacteria. To test the limits of RodA’s apparent weak that, at least in theory, a drug could work ments,” said study first author Megan Sjodt,
The study has revealed that the prototypi- spot, the scientists set up experiments using against many kinds of harmful bacteria. a research fellow in biological chemistry and
cal SEDS family member RodA is a pepti- two species drawn from the two basic bacte- molecular pharmacology at Harvard Med-
doglycan polymerase—a role previously rial domains – gram-negative and gram-pos- “This highlights the beauty of super-basic ical School. “We believe our results set the
attributed exclusively to members of the pen- itive. scientific discovery,” said co-investigator stage for subsequent work toward the discov-
icillin-binding protein family. This discovery In both cases, they found that making Thomas Bernhardt, professor of microbiolo- ery and optimization of new classes of anti-
has thereby made RodA and other SEDS pro- even small changes to the shape of the cav- gy and immunobiology at Harvard Medical biotics.”
teins promising targets for the development ity caused the bacteria to distort, swell, and
of next-generation antibiotics. eventually burst. For drug developers, the re-
sult is potentially great news.
“Our latest findings reveal the molecular
structure of RodA and identify targetable “What makes us excited is that this protein
spots where new antibacterial drugs could has a fairly discrete pocket that looks like it
bind and subvert its work,” said study senior could be easily and effectively targeted with
investigator Andrew Kruse, associate profes- a drug that binds to it and interferes with
sor of biological chemistry and molecular the protein’s ability to do its job,” said study
pharmacology at Harvard Medical School. co-senior author David Rudner, professor of

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1
April 17th, 2018. Vol. 02 NO 16

TOP 30 UNIVERSITIES AS PER – MHRD,


GOVT OF INDIA FOR 2018

By Shekhar Suman

MHRD, Govt of India under National Insti- versities of India. For all PhD Admissions,
tutional Ranking Framework has released a Msc Admissions, B.tech Admissions, B.Sc
list of Top 100 Universities with rank. Listed Admissions, M.Tech Admissions.
below are names and scores of Top 30 Uni-

2
Vol. 02 NO 16 April 17th, 2018.

TOP 20 COLLEGES OF INDIA AS PER GOVT OF


INDIA SURVEY – 2018

As per survey done by NIRF, Government below. In the Top 5 list are 3 colleges from
of India for the year 2018, listed below are Delhi – Miranda House, St. Stephen`s Col-
top 20 colleges of India. List of top 20 colleg- lege & Hindu College each occupying 1st, LIVER REGENERATION THROUGH
es has been released with their score. Names
of Top Colleges all across India can be found
2nd & 4th position respectively. TELOMERASE REPOPULATION

Myriad genetic and epigenetic alterations and form clones throughout the liver,” said
are required to drive normal cells toward ma- Artandi, who holds the Jerome and Daisy
lignant transformation. These somatic events Low Gilbert Professorship in Biochemistry.
commandeer many signaling pathways that “As mature hepatocytes die off, these clones
cooperate to endow aspiring cancer cells with replace the liver mass. But they are working
a full range of biological capabilities needed in place; they are not being recruited away
to grow, disseminate and ultimately kill its to other places in the liver. This may explain
host. how the liver can quickly repair damage re-
Telomeres are nucleoprotein structures gardless of where it occurs in the organ.”
that protect the ends of eukaryotic chromo- In the course of their investigation, the team
somes and are particularly vulnerable due to found that, in mice, about 3-5 percent of all
progressive shortening during each round of liver cells express unusually high levels of
DNA replication and, thus, a lifetime of tis- telomerase. During regular cell turnover or
sue renewal places the organism at risk for after the liver was damaged, these cells pro-
increasing chromosomal instability. liferate in place to make clumps of new liver
Telomere dysfunction can produce the cells. The fact that these stem cells express
opposing pathophysiological states of de- fewer metabolic genes might be one way to
generative aging or cancer with the specific protect the cells from the daily grind faced
outcome dictated by the integrity of DNA by their peers, and to limit the production of
damage checkpoint responses. metabolic byproducts that can damage DNA.
Hepatocytes are replenished gradually dur-
ing homeostasis and robustly after liver inju- “This may be one way to shelter these
ry. In adults, new hepatocytes originate from important cells and allow them to pass on
the existing hepatocyte pool, but the cellular a more pristine genome to their daughter
source of renewing hepatocytes remains un- cells,” Artandi said. “They are not doing all
clear. the ‘worker bee’ functions of normal hepat-
Now, Stanford scientists have identified a ocytes.”
subset of hepatocytes that expresses high lev-
els of telomerase and show that this hepato- When Lin engineered the telomerase-ex-
cyte subset repopulates the liver during ho- pressing hepatocytes to die in response to
meostasis and injury. a chemical signal and gave the mice with a
liver-damaging chemical, he found that those
“The liver is a very important source of animals in which the telomerase cells had
human disease,” said professor of medicine been killed exhibited much more severe liver
Steven Artandi, MD, PhD. “It’s critical to scarring than those in which the cells were
understand the cellular mechanism by which functional.
the liver renews itself. We’ve found that these
rare, proliferating cells are spread through- “You could imagine developing drugs that
out the organ, and that they are necessary to protect these telomerase-expressing cells, or
enable the liver to replace damaged cells. We ways to use cell therapy approaches to renew
believe that it is also likely that these cells livers,” said Artandi. “On the cancer side, I
could give rise to liver cancers when their think that these cells are very strong candi-
regulation goes awry.” dates for cell of origin. We are finally begin-
ning to understand how this organ works.”
By Shekhar Suman
“These rare cells can be activated to divide By Disha Padmanabha

3
April 17th, 2018. Vol. 02 NO 16

Scientists Coax Scientists Grow First


Oil-Gulping Bacteria into Adult-like Cardiac Tissue
Cleaning Spills from Patient-Specific Stem
Bioremediation for degradation of hydro-
carbons is a widely used alternative for the
recovery of contaminated sites. Now, re-
soils, purified enzymes from A. borkumensis
effectively degraded over 80 percent of some
hydrocarbon compounds. The degradation
Cells
searchers at the INRS in Canada have isolat- efficiency for different concentrations of pe- Cardiac tissues generated from human in- tures characteristic of adult heart tissue, the
ed the key enzymes that a oil-hungry bacteri- troleum hydrocarbon substrates was signifi- duced pluripotent stem cells (iPSCs) can team states. Such features included the phys-
um, Alcanivorax borkumensis, uses in order cant, reaching 73.75 percent for 5000 ppm of serve as platforms for patient-specific stud- iological length of the sarcomeres, density
to clean oil samples in lab. These enzymes hexadecane, 82.80 percent for 1000 ppm of ies of physiology and disease. But then, the of mitochondria, the presence of transverse
give it the special ability to use hydrocarbons motor oil, 64.70 percent for 70 ppm of ben- predictive power of these models is presently tubules, and the switch to oxidative metab-
as a source of energy. zene-toluene-xylene and 88.52 percent for limited by the immature state of the cells. olism. “The increasing contractile demands
This microorganism exists in every ocean 6000 ppm of contaminated soil. Now however, Columbia University re- induced the adult-like cardiac morphology
and multiplies quickly where there are high searchers have developed a radically new that is necessary for high force generation
concentrations of oil. In fact, this bacteria “The degradation of hydrocarbons using approach to growing in the lab adult-like hu- in early-stage intensity-trained tissues,” the
is likely responsible for some of the natural the crude enzyme extract is really encourag- man heart muscle from blood-derived human team writes. “The cell size increased (an indi-
degradation of ocean spills, but researchers ing and reached over 80 percent for various induced pluripotent stem cells (iPSCs), over cator of physiological hypertrophy) and both
want to amplify this effect to speed up the compounds,” says Satinder Kaur Brar, lead only four weeks of bioreactor cultivation. cells and nuclei were elongated (an indicator
clean up process. The enzymes in the bacteria researcher on the study. “The process is ef- of maturation). The sarcomere length reached
do the work and in particular the hydroxylas- fective in removing benzene, toluene, and xy- “Many of the ongoing efforts—including 2.2 μm, a similar value to that of adult human
es are very effective and resistant to chemical lene, and has been tested under a number of those from our lab—have been biomimetic ventricular myocytes.”
conditions. different conditions to show that it is a pow- in nature, trying to recapitulate the known
Since its remedial potential had not been erful way to clean up polluted land and ma- events present during native development,” The team is now extending their study into
assessed, the team characterized the enzymes rine environments.” says the study’s senior author Gordana Vun- broader aspects of disease modeling to get a
produced and revealed thr presence of hy- jak-Novakovic, University Professor, The better understanding of the mechanistic basis
droxylases that are resistant to chemical con- The researchers plan to continue studying Mikati Foundation Professor at Columbia of cardiac disease and cardiotoxicity induced
ditions and far more effective in promoting how A. borkumensis metabolizes these hy- Engineering, and professor of medicine at by drugs used to treat other organ systems.
hydrocarbon degradation than those found in drocarbons, and figure out how they might Columbia University Vagelos College of Phy- Their work could facilitate discovery of new
other species. be put to work cleaning up real-life oil spills. sicians and Surgeons. “Because these efforts therapeutic targets and lead to new cardio-
When applied to samples of contaminated have been limited in how much maturation protective or curative treatment modalities.
can be achieved, we decided to try something This ongoing research is part of the “organs
totally new: to explore the concept of accel- on a chip” project funded by the National
erated development. It took a lot of creative Institutes of Health, which uses multi-tissue
thinking and clever engineering by the whole platforms that include the adult heart muscle
team across both campuses of Columbia Uni- referenced in this paper as well as bone, liver,
versity to develop the model we now have, a vasculature, skin, and solid tumors.
highly matured, patient-specific heart muscle
that can be used for studies of heart develop- “The resulting engineered tissue is truly
ment, physiology, disease, and responses to unprecedented in its similarity to function-
drugs.” ing human tissue,” said Seila Selimovic,
director of the NIBIB (National Institute of
Stem cells are an especially awesome type Biomedical Imaging and Bioengineering)
of undifferentiated cells that are able to Tissue Chips program, within the National
change into specialized cells. The team got Institutes of Health that funded this research.
their hands on some by simply taking a blood “The ability to develop mature cardiac tissue
sample. From this, they derived early-stage in such a short time is an important step in
cardiac muscle cells, also known as cardio- moving us closer to having reliable human
myocytes and then cultured them using their tissue models for drug testing.” The better
new revolutionary method. This approach al- the engineered tissues emulate the human
lowed the researchers to nurture the cells to heart, the better they can predict the effects
maturity in just four weeks, compared to the that drugs or environmental factors have on
usual nine months. the actual heart tissue of a patient. Having a
The results showed that intensity-trained reliable human tissue model would help make
tissues grown from early-stage hiPS-CMs drug development significantly faster, safer,
matured quickly to display “remarkably or- and cheaper.”
By Disha Padmanabha
ganized ultrastructure,” and structural fea-
By Disha Padmanabha

Ben Waldau says. a single organoid and transplanted it into a


tiny cavity carefully carved into a mouse’s
STEM CELL DERIVED MINI BRAIN THAT The breakthrough could allow the brains to brain. Two weeks later the organoid was
ENGENDERS BLOOD VESSELS survive for longer, thanks to the vital oxygen alive, well—and, critically, had grown cap-
and nutrients supplied by the vessels, and illaries that penetrated all the way to its inner
could encourage them to keep growing. layers.
The human cerebral cortex defines us as the head of a pin. Using brain membrane cells taken from one These so-called brain balls are the first to
who we are. Its development and function With induced pluripotent stem cells (iPSCs) of his patients during a routine surgery, the become vascularised (meaning they’re the
underlie complex human cognitive behavior, derived from a readily-accessible skin sam- team coaxed them first into stem cells, then first to sprout vessels), with previous experi-
while its malfunction or degeneration causes ple from patients, it’s possible to generate some of them into the endothelial cells that ments resulting in mouse blood cells infiltrat-
countless neurological and psychiatric dis- three-dimensional balls of cells that mimic line blood vessels’ insides. The stem cells ing the small cerebrums.
eases. Additionally, shielded by by our thick particular parts of the brain’s anatomy. But they grew into brain balls, which they incu- However, scientists still aren’t certain if the
skulls and swaddled in layers of protective then, as with any new tech, there is always bated in a gel matrix coated with those en- blood this network of vessels carries is hu-
tissue, the human brain is extremely difficult room for improvement. One thing that most dothelial cells. man or rodent.
to observe in action. mini-brains lack is their own system of blood After incubating for three weeks, they took By Disha Padmanabha
And in both these cases- emerges a sav- vessels, or vasculature.
iour- the mini brain. Lab-grown miniature
brains are poised to shake up drug testing for “The whole idea with these organoids is to
everything from Alzheimer’s disease to Zika. one day be able to develop a brain structure
Reported early last year, each bundle of hu- the patient has lost made with the patient’s
man brain cells is so tiny that it could fit on own cells,” UC Davis vascular neurosurgeon

4
Vol. 02 NO 16 April 17th, 2018.

Scientists Unveil New


Bioengineering Tech to
Manufacture Complex
Medicines
Microbial biosynthesis of plant natural prod- Stanford University bioengineering profes-
ucts from simple building blocks is a prom- sor Christina Smolke said: “This is a tech-
ising approach toward scalable production nology that’s going to change the way we
and modification of high-value compounds. manufacture essential medicines.” By Disha Padmanabha
Now, researchers describe a bioengineering
process in which brewer’s yeast, along with Noscapine’s cough-suppressing capability soldiers from different units, deploying them can spew out substantial amounts of noscap-
engineered genes from opium poppies and was discovered in 1930. The drug was also on Mars, and telling each of them, ‘Now, I ine in three or four days. The investigators
rats, is used to produce a non-narcotic cough found to be a potential oncology therapy dur- want you to get some serious work done achieved this result by stitching three sepa-
suppressant with potential anticancer proper- ing preclinical trials, where it exhibited less here, and I want you to work with these other rate sections of the noscapine biosynthesis
ties. impact on healthy cells than currently availa- soldiers you haven’t worked with before,’” pathway into a single yeast strain. They used
Stanford researchers inserted 25 foreign ble chemotherapy. Smolke continued. “Good luck with that. We CRISPR, a gene-editing tool, to alter insert-
genes, which came from the opium pop- modified them so they’d get along with one ed genes so that the enzymes for which they
py, other plants and even rats, into the one- “Traditionally, we’ve gotten our medi- another better on this new planet.” coded would work most efficiently amid the
celled fungus. All those genes were recipes cines from the natural world, mainly from exotic acidity, osmotic character and chemi-
for enzymes: protein machines that, working plants,” Smolke told me when I interviewed The only viable source of noscapine is opi- cal composition of their new home.
together, can build complex substances from her about the study. “But the plants’ molec- um poppies. Many tons of noscapine are ex- They also souped up the yeast’s production
simple starting materials. ular assembly lines have evolved to optimize tracted annually from the plant, which takes a of a chemical whose levels would have other-
The researchers also modified some of the the plants’ survival, not to churn out buckets full year to mature. wise been too low to sustain robust noscapine
plant, rat and yeast genes, as well as the me- of one substance we humans want to get our While noscapine itself is harmless, the pop- production.
dium in which the yeast proliferates, to help hands on. Plus, we’re putting them into our pies’ illicit potential requires costly controls
everything work better together. yeast strain, which is foreign turf. A yeast cell and restrictive regulations. Additionally, nat- “We’re no longer limited to what nature
The result was an 18,000-fold improvement and a poppy cell have a lot in common, but urally occurring noscapine must be thorough- can make,” Smolke said. “We’re moving to
in noscapine output, compared with what in some respects they’re as different as Earth ly separated from numerous molecular com- an age where we can borrow nature’s med-
could be obtained by just inserting the plant and Mars.” panions, narcotic and otherwise, that don’t icine-manufacturing processes and, using
and rat genes into yeast. occur in yeast. genetic engineering, build miniature living
“It’s as if we’re grabbing a couple dozen The yeast Smolke’s group bioengineered factories that make what we want.”

Abundant Giant Virus in


Sea Captured
and Characterized
Viruses are the most abundant biological oplankton. It is found to possess an arsenal
entities on the planet and there are typically of toxins and DNA cutting enzymes, which
millions of virus particles in each milliliter likely interfere with other viruses trying to
of marine or fresh waters that are estimated replicate inside the host.
to kill about 20% of the living biomass each During an infection, BsV maneuvers in di-
day in surface marine waters. Most of these rection of the rear of the host cell and releases
viruses are tiny, often 10 or 100 times smaller its viral genome. It seems on observation that
than bacteria. However, a few reach a similar as BsV advanced it stole genetic equipment By Disha Padmanabha
size and complexity to bacteria, and so stand from the host to assist in the an infection
out as relative giants. course of. BsV would not carry switch RNA Christoph Deeg and Curtis Suttle isolated Bodo saltans virus in samples from UBC’s Nitobe Memorial Garden.

Relative to other viruses, Giant Viruses have (tRNA), half of the replication equipment
much more DNA in their genome, which in all different big viruses carry. It does, nev-
turn provides the genetic template to produce ertheless, carry tRNA restore genes, making
the proteins that allow viruses to reproduce it doubtless that the virus makes use of the
largely independently of its host. host’s personal tRNA throughout an infec-
Typically, more than half of the genes en- tion.
coded by Giant Viruses have no evident sim- Again, these genes seem to have been
ilarity to genes from other viruses or cellu- coopted by the virus straight from the host.
lar life. Sequencing DNA from ocean water More than 10 per cent of BsV’s genome en-
suggests that Giant Viruses are abundant and codes the identical group of proteins which
ecologically important; yet, few have been are doubtless concerned in combating the
isolated from the microbes that they infect. host’s antiviral system.
Without being able to study Giant Viruses in This suggests that the virus is engaged in
the laboratory, little can be known about their an evolutionary arms race with its host, and
biology, the way they infect their hosts, and could offer on explanation of how the ge-
their broader influence on aquatic life. nomes of giant viruses could reach their im-
Motivated by the lack of ecologically rele- pressive complexity.
vant giant-virus isolates- Bodo saltans virus,
the first isolated representative of the most
abundant giant viruses in the sea, has now
been unveiled by researchers at the Universi-
ty of British Columbia.
The Bodo saltans virus (BsV), whose ge-
nome weighs in at 1.39 million bases of
DNA, is one of the largest giant viruses ever
isolated, and the largest known to infect zo-

5
April 17th, 2018. Vol. 02 NO 16

Double Attack Antibody


Picks on Viruses from Two
Sides
Immunoglobulin A (IgA) plays an important The team studied different kinds of anti-
role in protecting our mucosal surfaces from bodies in cell cultures to find out which ones
viral infection, in maintaining a balance with were most potent against the flu virus. They
the commensal bacterial flora, and in extend- found that a subtype called IgA1, which has
ing maternal immunity via breast feeding. a special tail at one end that contains sialic
Working together with scientists from the acids, was the most effective.
US, researchers at the University of Zurich It was found through investigation that this
have now discovered a new aspect of how the tail blocks the part of the virus that allows it to
flu virus interacts with antibodies in the lungs. attach to the cells it wants to infect. This sug-
“This was a completely unexpected and un- gests that the IgA1 antibody works through
foreseen finding,” says Lars Hangartner, two different types of immune activity.
former professor at the Institute of Medical Firstly, through acquired immunity, which
Virology of UZH. “We found that antibod- is traditionally associated with antibodies
ies called IgAs, which are commonly found that specifically recognize pathogens. And
on mucosal surfaces, can actually protect us secondly, through innate immunity via the
from infections in two different ways,” adds sialic acids at the other end of the molecule,
the head of the study, who now works at The which is more of a non-specific, broad-rang-
Scripps Research Institute in the USA. ing attack. IgA antibodies thus attach them-
The University of Zurich (UZH) team has selves to flu viruses in two places at once.
discovered a new mechanism that could po- The team believes that this study could help
tentially be used to develop better flu vac- improve the effectiveness of flu vaccinations
cines and more effective drugs. and drugs. Since IgAs are notoriously hard
Antigens provide the immune system with to work with, Hangartner believes future re- By Disha Padmanabha
a kind of blueprint that allows it to recognize search should focus on developing antibodies
flu viruses and start the production of anti- that are easier to produce and can be tested Immune cells produce certain antibodies that attack influenza viruses from two sides. (Image: iStock/selvanegra)

bodies as soon as it encounters them again. in mice.


However, current vaccines stimulate the pro- to handle. “It would combine the best of both very useful when it comes to fighting the flu,”
duction of another type of antibodies: Immu- His idea is to graft the tail of the IgA1 onto worlds and give us a molecule that’s more ef- adds the immunologist.
noglobulin G (IgG). an IgG-type antibody, which is much easier fective and hardy, and that ultimately may be

Adhesion Protein that


Helps Bacteria Stick to
Cells Could Help Find
New Antibiotics
Many pathogenic bacteria, including Strep- icated molecular supply chains were doing.
tococcus gordonii, possess a pathway for the
cellular export of a single serine-rich-repeat “I was intrigued by the fact that there is a
protein that mediates the adhesion of bacteria second secretion system in some bacteria that
to host cells and the extracellular matrix. is separate from the canonical secretion sys-
Now, researchers at Harvard Medical tem and is just dedicated to the secretion of
School, the University of California–San one protein,” he said. “There is a whole ma-
Francisco, and the University of Georgia chinery, and it’s only doing one thing.”
have described how the protein that allows
strep and staph bacteria to stick to human The researchers found that in order to be
cells is prepared and packaged. transported, the adhesin protein needed to be
An important class of extracellular mole- modified with specific sugars by three en-
cules produced by pathogenic bacteria are zymes acting in a specific sequence. These
adhesins, proteins that enable bacteria to ad- sugar modifications stabilize the protein and
here to host cells. For unknown reasons, the enhance its stickiness to target cells.
SRR (serine-rich-repeat) adhesins of Staph- The experiments the team carried out indi-
ylococcus and Streptococcus bacteria- path- cated that two proteins in the adhesin-specif-
ogens that can be involved in serious infec- ic pathway, whose function had previously
tions such as bacterial meningitis, bacterial been mysterious, seemed to be able to bind
pneumonia and pericarditis- are transported to these sugars, presumably enabling them to By Disha Padmanabha
through a secretion pathway that is similar to carry the adhesin to the cell membrane where
tered a lot of challenges,” said Yu Chen who to strep and staph bacteria, the new under-
the standard system, but dedicated solely to adhesin’s dedicated exit channel is located.
led the investigation. standing of its components could help re-
adhesin.
searchers develop highly targeted antibiotics
Tom Rapoport, a professor at Harvard “It’s a complicated system because it in-
The reason that these bacteria use this sep- to treat infections caused by these bacteria in
Medical School who oversaw the new study, volves protein modification, chaperone activ-
arate export pathway for adhesins remains the future.
wanted to understand what exactly these ded- ity and membrane targeting, so we encoun-
elusive. But because this pathway is unique

6
Vol. 02 NO 16 April 17th, 2018.

Space Salad: Scientists


Grow Plants in Space-like
Conditions at Antarctica LED system allows for each light to be indi-
By Disha Padmanabha
NASA estimates that a trip to Mars and back
Gardening in microgravity will lettuce go supplied with fresh food in the future. vidually controlled by a computer. Plants are would require thousands of pounds of food;
into space- probably even make it to Mars This mission worked to test just how astro- illuminated for 16 hours and get a standard just four crew members on a three-year mis-
without a worry. nauts will be able to sustain themselves while eight hours of beauty rest without light. sion would need more than 24,000 pounds
The ability to grow plants in limited condi- in space. There will be manned missions to For researchers living in Antarctica, the (10,886 kilograms) of food to eat three meals
tions is aessential for the future of deep-space Mars and the moon that will seek to colonize prospect of fresh vegetables will be an excit- per day. If those voyages could start an aero-
exploration. A critical component of future, both worlds. EDEN ISS is a consortium of ing change from stations’ usual dependency ponic garden when they landed, and synthe-
human exploration to worlds unknown, will European, American, and Canadian experts on planes to deliver fresh food, and reliance size other supplies (like nutrients and water)
be the supply of edible food for crewmem- in human spaceflight and CEA. on frozen or dried food otherwise. For inter- from the soil of their new home, they could
bers. To develop innovations in cultivating planetary explorers, the ability to grow food extend that food supply for weeks, months,
food in closed-loop systems becomes integral “It was special to have the first fresh salad on others worlds could mean the difference and even years without bringing the weight
to future missions. of the Antarctic,” said station manager Bern- between life and death. of extra food aboard.
Scientists at Germany’s Neumayer Station hard Gropp in a statement. “It tasted as if we
III in Antarctica have just harvested a crop had harvested it fresh in the garden.” A DNA PROBE PATCH TO TEST FOR FOOD
of vegetables grown in the unlikely location
of their Antarctic lab. The haul consisted of Located at the Neumeyer-Station III, the CONTAMINATION
3.6 kg of salad greens, 18 cucumbers, and 70 greenhouse defies the Arctic winter with its
radishes. state-of-the-art technology; pipes supply suf- Scientists at the McMaster University have a graduate student and research assistant in
Cucumbers, radishes and lettuce are just ficient water, lamps provide the right light, now reported a a transparent, durable, and McMaster’s Faculty of Engineering.
some of the green delights that have been and filters and nozzles provide the right mix- flexible sensing surface that generates a flu-
thriving in the experimental EDEN-ISS ture of air to promote growth. orescence signal in the presence of a specific The signaling technology for the food test
greenhouse in Antarctica. The project follows Large water tanks installed in the floor are target bacterium. And this new tech has the was developed in the McMaster labs of bio-
in the footsteps of successful US operations filled with melted, filtered, and purified ice potential to replace the traditional “best be- chemist Yingfu Li.
cultivating crops in the harsh climate. from the station. Water is then added to a fore” date on food and drinks alike with a de-
In addition to the veggies they just harvest- “special nutrient solution” that is automati- finitive indication that it’s time to chuck that “He created the key, and we have built a
ed, the scientists also planted strawberries, cally sprayed on the plants every five to 10 roast or pour out that milk. lock and a door to go with it,” says Filipe,
bell peppers, and a number of herbs. By May, minutes, a process called aeroponics. Bottles The patch can be incorporated directly into who is Chair of McMaster’s Department of
DLR says they expect to be able to get about of carbon dioxide were shipped along with food packaging, and signal E coli and Salmo- Chemical Engineering.
10 pounds of produce per week. the container to provide the plants with ideal nella contamination as it happens. Dubbed
Despite temperatures in Antarctica falling air. The air is then filtered by a UV radiation “Sentinel Wrap,” the patch triggers a molec- Mass producing such a patch would be fair-
below -20 degrees Celsius (-4 F) and the sun system similar to the closed-circuit system ular signal that a disease-causing agent has ly cheap and simple, the researchers say, as
barely coming above the horizon, the first onboard the ISS. contaminated products like meat, bottled wa- the DNA molecules that detect food patho-
harvest from the project led by the German In a land of extreme light cycles, the crew ter or milk. The triggered signal could be read gens can be printed onto the test material.
Aerospace Center (DLR) demonstrates how needed to make sure plants got a “blue and red by a smartphone or other devices. The patch The researchers are naming the new material
astronauts on the moon and Mars could be light cocktail”. A customized water-cooled does not affect the contents of the package. “Sentinel Wrap” in tribute to the McMas-
ter-based Sentinel Bioactive Paper Network,
“Right now, if you want to know if there’s an interdisciplinary research network that
any contamination in a food sample, you worked on paper-based detection systems.
NOVEL RNA VACCINE COULD FREE PLANTS need to bring it into a lab … and it takes at That network’s research ultimately gave rise
FROM PESTICIDE USE least a day or two to find out if there’s any to the new food-testing technology.
pathogen present in that food sample,” said Getting the invention to market would need
mechanical-biomedical engineer Tohid Di- a commercial partner and regulatory approv-
Pesticides are the only toxic substances re- the production of RNA molecules. Dou- dar, one of the product’s developers. als, the researchers say. They point out that
leased intentionally into our environment to ble-stranded RNA molecules have been pro- the same technology could also be used in
kill living things. This includes substances duced through chemical synthesis, both as “In the future, if you go to a store and you other applications, such as bandages to indi-
that kill weeds (herbicides), insects (insecti- drug molecules and for research purposes, want to be sure the meat you’re buying is safe cate if wounds are infected, or for wrapping
cides), fungus (fungicides), rodents (rodenti- but such production methods are inefficient at any point before you use it, you’ll have surgical instruments to assure they are sterile.
cides), and others. and expensive for plant protection,” Poranen a much more reliable way than the expira-
The use of toxic pesticides to manage pest states. tion date,” says lead author Hanie Yousefi,
problems has become a common practice Emerging technologies for crop protection
around the world. It is difficult to find some- include the external treatment of plants with
where where pesticides aren’t used- from the double-stranded (ds) RNA to trigger RNA
can of bug spray under the kitchen sink to the interference. However, using this method in
airplane crop dusting acres of farmland, our greenhouses and fields depends on the dsR-
world is filled with pesticides. In addition, NA quality, stability and efficient large-scale
pesticides can be found in the air we breathe, production.
the food we eat, and the water we drink. In this particular study, scientists designed a
Now, an international team led by research- vaccine that uses RNA interference, which is
ers from the University of Helsinki and the an innate defence mechanism of plants, ani-
French National Centre for Scientific Re- mals and other eukaryotic organisms against
search has created a new method to produce pathogens.
a vaccine that triggers RNA interference—an This vaccine can be targeted to the chosen
innate defense mechanism of plants, animals pathogen by using RNA molecules which
and other eukaryotic organisms against path- share sequence identity with the pest’s genes
ogens. and prevents their expression; thereby not in-
“A new approach to plant protection in- fluencing the expression of genes in the pro-
volves vaccinating plants against pathogens tected plant in anyway.
with double-stranded RNA molecules that Together with researchers at the CNRS, the
can be sprayed directly on the leaves,” ex- group has demonstrated the efficacy of RNA-
plains Dr Minna Poranen of the Molecular based vaccines produced using the new meth-
and Integrative Biosciences Research Pro- od against plant virus infections.
gramme at the University of Helsinki’s Fac-
ulty of Biological and Environmental Scienc- This new method will enable the effective
es. production of RNA-based vaccines and pro- By Disha Padmanabha
“The challenge in developing RNA-based mote the development and adoption of RNA-
vaccines to protect plants has involved based plant protection methods. Immune cells produce certain antibodies that attack influenza viruses from two sides. (Image: iStock/selvanegra)

7
April 17th, 2018. Vol. 02 NO 16

Atomically Thin Synthetic


Eardrum Offers Cat-Like
“Hearing” Capability
Case Western Reserve University research- Dynamic range is the ratio between the sig-
ers are now reportedly designing a wearable nal ceiling over the noise floor and is typically
device that can send and receive signals at measured in decibels (dB). Human eardrums
radio frequencies even greater than those we typically have a dynamic range of about 60
can hear with our natural ear. to 100 dB in the range of 10 Hz to 10 kHz,
Nicknamed the “drumhead”, it is and human hearing rapidly drops outside this
10,000,000,000,000 times smaller in volume frequency range. Other animals, such as the
and 100,000 times thinner than the human beluga whale or common house cat can have
eardrum and can detect a much wider range comparable or even broader dynamic ranges
of signal than other similar devices. in higher frequency bands.
Their work will likely contribute to making The vibrating nanoscale drumheads built by
the next generation of ultralow-power com- Feng and his team are composed of atomic
munications and sensory devices smaller and layers of semiconductor crystals (single-, bi-,
with greater detection and tuning ranges. tri-, and four-layer MoS2 flakes, with a thick-
ness of 0.7, 1.4, 2.1, and 2.8 nm), with diam-
“Sensing and communication are key to a eters only around 1 µm.
connected world,” said Philip Feng, an asso- In order to duplicate this effect, the re-
ciate Professor of electrical engineering and searchers needed to construct the ‘eardrums’
computer science and corresponding author on an atomic level. They used a combination
on the paper. “In recent decades, we have of nanofabrication and micromanipulation to
been connected with highly miniaturized de- suspend atomic layers over a silicon wafer.
vices and systems, and we have been pursu- The team then made electrical contacts to
ing ever-shrinking sizes for those devices.” the devices. Even for all its tiny size, the
resonators show frequency “tunability,” ac-
The challenge with miniaturization: Also cording to the researchers, which means that
achieving a broader dynamic range of detec- tones can be manipulated by stretching the
tion, for small signals, such as sound, vibra- drumhead membranes through electrostatic
tion, and radio waves. forces. It would be similar to tuning a kettle
drum in an orchestra, Feng noted.
“In the end, we need transducers that can
handle signals without losing or compromis- “Not only having surprisingly large dynam-
ing information at both the ‘signal ceiling’ ic range with such tiny volume and mass,
(the highest level of an undistorted signal) they are also energy-efficient and very ‘quiet’
and the ‘noise floor’ (the lowest detectable devices,” Feng said, “We ‘listen’ to them very
level),” Feng said. carefully and ‘talk’ to them very gently.” By Disha Padmanabha

PANCANCER ATLAS REVEALS UTTERLY FIRST RAPID DIAGNOSTIC PLATFORM FOR


COMPLEX NATURE OF CANCER RESPIRATORY INFECTIONS GETS FDA NOD

Ever since the first draft of the human ge- sidered heterogeneous as they contained up Dutch molecular diagnostics company, Cu- der five hours. It covers more than 90% of
nome was published, there has been an ex- to 25 different histological tumor types that, retis, has now received the FDA approval for infection cases of hospitalized patients with
pectation that this genetic code would reveal traditionally, would all be treated differently. its multiplex assay to detect lower respirato- pneumonia and provides clinicians with a
the secrets of life, ultimately leading to novel The PanCancer Atlas, published as a col- ry tract infections, as well as for the firm’s comprehensive overview on genetic antibiot-
therapeutic strategies for a multitude of dis- lection of 27 papers across a suite of Cell molecular diagnostic platform, Unyvero. The ic resistance markers detected.
eases. To effectively identify disease genes, journals, sums up the work accomplished assay is the first multiplex lower respiratory Data from a clinical trial, which included
DNA sequencing has been frequently applied by The Cancer Genome Atlas (TCGA) – a tract infection test to be cleared by the FDA. more than 2,200 patient samples at nine par-
to study cohorts of individuals afflicted with multi-institution collaboration initiated and ticipating U.S. hospitals, were submitted to
the same disease so that important variants supported by the National Human Genome “The launch of our Unyvero System and the FDA in early 2017. Curetis’ clinical trial
associated with disease risk can be uncov- Research Institute (NHGRI) and the Nation- LRT Application Cartridge in the United operations team has worked in close collab-
ered when compared to healthy individuals. al Cancer Institute (NCI), both part of NIH. States will address a pressing unmet med- oration with the FDA’s review team to eval-
However, it remains unclear which are the The program, with over $300 million in total ical need as it delivers results much faster uate the study data set and develop relevant
key driver mutations or dependencies in a funding, involved upwards of 150 research- than current standard of care microbiology statistics and reports, as well as a benefit-risk
given cancer and how these influence patho- ers at more than two dozen institutions across culture“, said Curetis’ co-founder and Chief analysis which was compiled with input and
genesis and response to therapy. Although tu- North America. Operating Officer Johannes Bacher. support from several renowned U.S. clinical
mors of similar types and clinical outcomes “Insights about how one type of cancer re- experts.
can have patterns of mutations that are strik- lates to another form of the disease can have “We expect that the LRT panel will trans- Curetis further plans to submit an appli-
ingly different, it is becoming apparent that real clinical implications,” said Josh Stuart, form our approach to the diagnosis of lower cation to the FDA for an expanded label on
these mutations recurrently hijack the same Baskin Professor of Biomolecular Engineer- respiratory tract infections“, said Dr. Don- its diagnostic system, which would include
hallmark molecular pathways and networks. ing at UC Santa Cruz and an organizer of na Mildvan, Infectious Diseases Physician clearance for bronchial lavage sample types
The Pan-Cancer Initiative launched as part the Pan-Cancer Initiative. “In some cases, and Clinical Professor of Medicine at Icahn and additional diagnostic targets.
of an international collaboration has now we can borrow clinical practices from bet- School of Medicine at Mount Sinai, New
completed its comprehensive analysis of the ter-known diseases and apply them to can- York, NY. “Having the opportunity to char- “We have assembled a team of high-caliber
complete set of tumors in The Cancer Ge- cers for which treatment options are less well acterize pneumonia by knowing the causative talent here at Curetis USA, and we will con-
nome Atlas (TCGA), consisting of approx- defined.” organism as well as relevant antibiotic resist- tinue to expand our commercial organization
imately 10,000 specimens and representing The PanCancer Atlas is divided into three ance markers in 4 to 5 hours has great clin- in support of the Unyvero product launch in
33 types of cancer. main categories, each anchored by a summa- ical implications – it is game changing and Q2/2018. We are truly excited to bring the
The new analysis shows that all 33 cancer ry paper that recaps the core findings for the exciting.” innovative Unyvero Solution to clinicians,
types, based on their cellular and genetic topic. The main topics include cell of origin, microbiologists in clinical laboratories, and
makeup and independent of their anatom- oncogenic processes, and oncogenic path- The sample-to-answer Unyvero System above all to patients in the Unites States,”
ic site of origin, could be reclassified into ways. Multiple companion papers report in- together with the Unyvero LRT Application Chris Bernard, president & CEO of Curetis
28 different molecular types, or “clusters”. depth explorations of individual topics within Cartridge provides rapid infectious disease USA Inc. and EVP of global sales, said.
Nearly two-thirds of these clusters were con- these categories. testing directly from aspirate samples in un-

8
Vol. 02 NO 16 April 17th, 2018.

Non-Invasive Portable
Device Allows WBC Levels
Estimation in
Chemotherapy Patients
White-blood-cell (WBC) status is used as cell levels are below the threshold that doc-
one indicator of immunological status in the tors consider dangerous.
diagnosis and treatment of multiple medical
conditions, including cancer, infectious dis- “Our vision is that patients will have this
eases, sepsis, autoimmune disorders, and in portable device that they can take home,
the use of immunosuppressant drugs. and they can monitor daily how they are re-
However, all current methods require a acting to the treatment. If they go below the
blood sample which involves a visit to a threshold, then preventive treatment can be
healthcare center and trained clinical person- deployed,” says Carlos Castro-Gonzalez,
nel, even with finger-prick technologies. This a postdoc in MIT’s Research Laboratory of
limitation inherently restricts how frequently Electronics (RLE) and the leader of the re- By Disha Padmanabha
and quickly monitoring can be performed. search team.
MIT Bioengineers have now developed a “Based on the feature-set that our human tional cancer patients. They are also investi-
noninvasive, portable device that could be The technology does not provide a precise raters identified, we are now developing an gating whether they can get accurate results
used to monitor patients’ white blood cell count of white blood cells, but reveals wheth- AI and machine-vision algorithm, with pre- with shorter lengths of video.
levels at home, without taking blood samples. er patients are above or below the threshold liminary results that indicate the same accu-
The idea is to create a device that can be considered dangerous — defined as 500 racy as the raters,” says paper’s first author “There is a balancing act that oncologists
used to continuously monitor immunosup- neutrophils (the most common type of white is Aurélien Bourquard, an RLE postdoc. must do,” says Sanchez-Ferro. “Normally
pressed patients, such as those on chemother- blood cell) per microliter of blood. The ap- doctors want to make chemotherapy as in-
apy, and to detect serious infections. proach proved 95 percent accurate for deter- The research team has applied for patents tensive as possible but without getting peo-
Their tabletop prototype records video of mining whether a patient’s white cell levels on the technology and has launched a com- ple too immunosuppressed. Current 21-day
blood cells flowing through capillaries just were above or below the threshold when test- pany called Leuko. To help move the tech- cycles are based on statistics of what most
below the surface of the skin at the base of ed with 11 subjects at different points during nology further toward commercialization, patients can take, but if you are ready ear-
the fingernail. A computer algorithm can ana- their chemotherapy treatment. the researchers are building a new automated ly, then they can potentially bring you back
lyze the images to determine if white blood prototype. Using this new prototype, the re- early and that can translate into better sur-
searchers plan to test the device with addi- vival.”

Scientists Use CRISPR


Gene Editing System to
Perform Parallel Edits
The first use of CRISPR to edit human cells However, it is a tedious process- painstak-
in a dish was reported in 2013. It’s since been ingly introducing a variant, monitoring the
touted as an easy way to alter people’s DNA, effect gene by gene. Researchers currently
promising to banish what are currently lethal analyze each edit one at a time, a process that
or lifelong maladies with a single treatment can take weeks.
that fixes them at the genetic root. The UCLA team has now tweaked the
CRISPR tech so as to allow researchers to
And in a piece Bill Gates wrote for the For- monitor the outcome of tens of thousands
eign Affairs this week, he put further empha- of gene edits in the time it currently takes to
sis on how unique this technology is and how analyze a few. The UCLA investigators in-
our researches should be taken up a notch vented a method that physically connected
higher to meet growing demand for food and thousands of guides to their partner patches,
to improve disease prevention, particularly allowing a perfectly matched set to be deliv-
for malaria. “It would be a tragedy to pass ered to each cell.
up the opportunity,” he writes. In their study, the team physically connect-
ed thousands of guides to their partner patch- By Disha Padmanabha
Now, in another exciting advance, research- es, forming a perfectly matched set for each
ers at the University of California have suc- cell. In a test of a class of genetic mutations that died or survived after four days. damaging genetic edits from the harmless.
cessfully tested speeding up this process of suspected to be harmful to cells, they used
gene editing. yeast because cellular changes in response to “We were surprised to find that some genes “We can now edit the genome in thousands
In terms of understanding the function- gene alterations happen quickly and are easy believed to be essential for cell function ac- of different ways, while observing positive
al effects of DNA sequence variants, one to observe. tually aren’t,” said first author Meru Sadhu, or negative effects on cells,” said said lead
promising avenue is precise editing with the Researchers grew millions of cells inside a a postdoctoral researcher in Kruglyak’s lab. author Leonid Kruglyak, chair of human ge-
CRISPR–Cas9 system. Recent studies have flask of fluid. CRISPR delivered a custom- “In other genes, only a part of the protein is netics at the David Geffen School of Medi-
used CRISPR libraries to generate many ized set of paired guides and patches to each essential, while the rest can be chopped off cine at UCLA. “Our ultimate goal is to help
frameshift mutations genome wide through cell- about 10,000 distinct mutations simul- and the cell will still survive.” scientists zero in on the genetic culprit for a
faulty repair of CRISPR-directed breaks by taneously. The guide and patches instructed disease, leading doctors to a firm diagnosis
nonhomologous end joining (NHEJ). CRISPR where to snip the gene and what edit The UCLA team hopes their technique will and allowing patients to obtain the most ef-
to introduce. This process distinguished cells help scientists to rapidly distinguish the most fective treatment.“

9
April 17th, 2018. Vol. 02 NO 16

Biomarkers Could Help


Predict Recurrence of
Malignant Brain Tumor
Glioblastoma (GBM) is a highly aggressive current gliomas from the identical sufferers
brain cancer and accounts for 46.6% of pri- to date. Comparing samples from the suf-
mary malignant brain tumors with a 5-year ferers’ preliminary analysis with these from
overall survival estimate post-diagnosis of their illness recurrence, researchers targeted,
5.5%. The WHO histomorphology and grad- particularly, on a definite epigenetic modifi-
ing classification of diffuse gliomas does cation occurring alongside the DNA phase, a
not have predictive clinical outcomes after course of referred to as DNA methylation.
GBMs have developed. Previously, their analysis confirmed that
Treating initially lower-grade glioma (LGG) when there was no change within the DNA
that relapses and undergoes malignant trans- methylation, sufferers had an excellent med-
formation to GBM is one of the greatest chal- ical consequence. When the DNA methyla-
lenges in neuro-oncology. To date, despite tion was misplaced, sufferers had a poor end
the efforts of the neuro-oncology community, result.
By Disha Padmanabha
no treatment regimens or bona fide biomark- In this newest research, the authors have
ers that significantly translate into a survival been in a position to determine a set of epi- molecular abnormalities, we can begin to DNA-methylation biomarkers that may help
benefit to GBM patients have been identified. genetic biomarkers that may predict, at a af- predict how aggressive a patient’s recurrence clinicians predict if someone’s brain tumor
Now, scientists led by the Henry Ford fected person’s preliminary analysis, which will be and that can better inform the treat- is heading in a more or less aggressive di-
Health System’s Department of Neuro- tumors are probably to recur with a extra ag- ment path we recommend from the very be- rection, essentially illustrating the behavior
surgery and Department of Public Health gressive tumor sort. ginning.” of a patient’s disease,” says James Snyder,
Sciences in Michigan, found that 9.5 percent Houtan Noushmehr, Ph.D., Henry Ford De- D.O., study co-author and neuro-oncologist,
had a distinct epigenetic alteration at genom- partment of Neurosurgery, Hermelin Brain Of the 200 tissue samples, 10% were found Henry Ford Department of Neurosurgery
ic sites that are active in regulating genes as- Tumor Center, and senior author of the study, to have a distinct epigenetic alteration at and Hermelin Brain Tumor Center. “If we
sociated with aggressive tumors that include says this discovery could make a huge differ- genomic sites known to be functionally ac- can identify which brain tumors will have a
glioblastoma. ence when a patient is first diagnosed. tive in regulating genes that are known to be more aggressive course at the point of initial
The group carried out an evaluation of 200 associated with aggressive tumors such as diagnosis then hopefully we can change the
brain tumor samples from 77 patients with “To date, we really don’t have any predic- glioblastoma. disease trajectory and improve care for our
diffuse glioma harboring IDH mutation, the tive clinical outcomes once a patient is di- patients.”
most important assortment of main and re- agnosed with glioma. By pinpointing these “This research presents a set of testable

Cardiovascular Risk STUDY DISPUTES NEUROGENESIS, FINDS

Incidence Predicting Blood ADULT BRAIN PRODUCING NEW CELLS

Test Developed
Columbia University researchers have now growth in this structure occurs in adulthood,
identified thousands of immature neurons in many scientists have argued that this repre-
the brain region, countering the popular no- sents existing neurons growing larger, or an
tion of stagnant brain growth as we age. expansion of blood vessels or other internal
Circulating branched-chain amino acids the more than 27,000 women studied, 2,207 There’s been considerable debate about support structures, rather than the addition of
(BCAAs; isoleucine, leucine, and valine) are experienced a cardiovascular event over the whether the human brain has the capacity to new neurons.
strong predictors of type 2 diabetes mellitus 18 year follow up period. make new neurons into adulthood. This re- For their analysis, the research team spent
(T2D), but their association with cardiovas- They noticed an association between BCAA cently published study offers some compel- 5 years collecting brain tissue from 59 peo-
cular disease (CVD) is uncertain. Now, in a levels and incident of CVD events. This asso- ling new evidence that’s the case. These find- ple who had died or had such tissue removed
new study, researchers of the Brigham and ciation was much more pronounced in wom- ings suggest that a healthy person in his or during surgery for epilepsy at different ages,
Women’s Hospital hypothesized that plasma en who developed diabetes before experienc- her seventies may have about as many young ranging from before birth to 77 years of age.
BCAAs are positively associated with CVD ing a cardiovascular event. neurons in a portion of the brain essential for They used fluorescent antibodies to label
risk and evaluated whether this was depend- learning and memory as a teenager does. proteins specific to cells at different states of
ent on an intermediate diagnosis of T2D. The researchers then adjusted for other To come to this conclusion, lead author Dr. maturity. With an electron microscope, they
biomarkers related to diabetes – including Maura Boldrini, a research scientist at Co- also looked for the characteristic long, slen-
“We examined more than 27,000 women hbA1c – finding evidence that BCAAs may lumbia University’s department of psychia- der, simple shapes of young neurons.
in the Women’s Health Study and found that be tied to downstream biomarkers of type 2 try, and her colleagues looked at the brains They found that people have large numbers
a one-time measurement of branched chain diabetes metabolism. of 28 deceased people aged 14 to 79. Their of neural stem cells and progenitors early in
amino acids in the blood stream – a test that goal was to see whether aging affects neuron life—an average of 1618 young neurons per
now can be easily done – predicted future “Impaired BCAA metabolism may rep- production. square millimeter of brain tissue at birth. But
risk of cardiovascular events to the same ex- resent a shared pathway of the metabolic Previous research had shown that neuro- these cells did not go on to form a proliferat-
tent and independent of LDL cholesterol and pathophysiology that links the risks of T2D genesis slows down in aging mice and non- ing layer of neural stem cells, and production
other risk factors,” said corresponding author and CVD,” the authors conclude. human primates. Boldrini’s group wanted of new neurons dropped 23-fold between 1
Samia Mora, MD, of the Center for Lipid to see whether a similar pattern occurred in and 7 years of age, the team reports. By
Metabolomics at BWH. “This was particu- “There is little known at this time as to what humans. adulthood the supply of young neurons had
larly so for women who developed type 2 di- leads to elevated levels of BCAAs or what petered out entirely.
abetes prior to their cardiovascular disease.” can be done clinically to reduce them, and if “The exciting part is that the neurons are
In the course of their investigation, the team this leads to a reduction in risk, but further re- there throughout a lifetime,” said Dr Maura “It is possible that ongoing hippocampal
of researchers measured BCAA levels in search will target these important questions,” Boldrini. “It seems that indeed humans are neurogenesis sustains human-specific cog-
blood samples using NMR spectrometry. Of said Tobias. different from mice – where [neuron produc- nitive function throughout life and that de-
tion] goes down with age really fast – and clines may be linked to compromised cog-
this could mean that we need these neurons nitive-emotional resilience,” said Boldrini,
for our complex learning abilities and cogni- who hopes her research will contribute to
tive behavioural responses to emotions.” further investigation of age-related condi-
tions such as Alzheimer’s.
The brain’s hippocampus, which is respon-
sible for memory and learning, has been a
major focus of studies on neurogenesis and
stem cell biology. Although neuroimag-
By Disha Padmanabha
ing studies of humans show that continued By Disha Padmanabha

10
Vol. 02 NO 16 April 17th, 2018.

New Framework for


Future Alzheimer’s
Research Proposed
Owing to a 15-year record of clinical fail- the continuum of the disease–from a stage
ures and pulled by an FDA searching for a preceding overt symptomatology (the “pre-
practical new path forward for Alzheimer’s clinical state”) to the progressively more im-
drug research, a joint committee organized by paired symptomatic states of mild cognitive
the NIH’s National Institute of Aging and the impairment (MCI) and dementia. The same By Disha Padmanabha
Alzheimer’s Association is suggesting a bio- biomarkers have also shown in greater res-
biologically, with clinical symptoms being populations. Innovative trial approaches that
marker-based approach to defining the illness olution how dementia may occur in people
a … consequence.” They say, “the goal of have been tested in other disease areas such
that can guide new development efforts. with both AD and non-AD pathology.
much of medicine is to identify and treat dis- as oncology- platform trials, umbrella and
This proposed “biological construct” is With this construct, researchers can study
eases prior to overt symptoms. The [NIA-AA basket designs- could be used with stratifica-
based on measurable changes in the brain and Alzheimer’s, from its earliest biological un-
Research] Framework is intended to pro- tion of patients by ATN profiling.
is expected to facilitate better understanding derpinnings to outward signs of memory loss
vide a path forward to … prevention trials of In an accompanying editorial, members of
of the disease process and the sequence of and other clinical symptoms, which could re-
Alzheimer’s disease among persons who are the NIH who worked on the report empha-
events that lead to cognitive impairment and sult in a more precise and faster approach to
clinically asymptomatic.” sized that the framework is still a work in
dementia. testing drug and other interventions.
progress. As science advances, even more bi-
The identification of Alzheimer’s disease
The biomarker-based definition relies on omarkers might need to be considered, they
(AD) biomarkers and their ability to measure “With the aging of the global population,
three neuropathological measures of beta-am- admit.
pathology antemortem has led to a funda- and the ever-escalating cost of care for peo-
yloid deposition, abnormal microtubule-as- And though the NIH expects and hopes
mental reconsideration of the pathogenesis of ple with dementia, new methods are desper-
sociated protein tau (tau; MAPT; FTDP-17) scientists use the framework in designing
AD. The importance of biomarkers was al- ately needed to improve the process of ther-
and neurodegeneration, collectively called their studies when submitting for grants, they
ready reflected in revised diagnostic criteria apy development and increase the likelihood
the “ATN system” that can be measured with won’t shut out those who don’t use these spe-
proposed by the National Institute on Aging of success,” said Maria Carrillo, Ph.D.,
imaging technology and analysis of cerebral cific biomarkers in their research.
and the Alzheimer’s Association in 2011. Alzheimer’s Association chief science officer
fluid samples.
Beginning in 2016, the NIA and AA con- and a co-author of the new article. “This new
“The NIH will consider research applica-
vened a new workgroup to develop a re- Research Framework is an enormous step in
The authors suggest the ATN framework tions using the Framework as well as propos-
search framework for AD that embodied the the right direction for Alzheimer’s research.”
can help in the design and execution of ob- als using alternative schemes when design-
paradigm shift occurring in the field. Rath-
servational studies and clinical trials, and can ing experimental approaches,” they wrote.
er than conceptualizing AD primarily as a According to the authors, “This evolution
enable trials to use biologically defined target “The NIH continues to welcome applications
clinicopathological entity, biomarkers have of the previous diagnostic criteria is in line
populations in addition to clinically defined where biomarkers may not be appropriate.”
demonstrated that AD pathology exists over with most chronic diseases that are defined

See No More of those


Pricks! Non-Invasive
Glucose Monitoring Patch
is Here
Finally, an end to all the pricking and pes- es inter- and intra-skin variability in glucose
tering. extraction and increases the accuracy of the
It is estimated that around 30.3 million peo- measurements taken such that calibration via
ple in the United States are living with dia- a blood sample is not required.
betes, and there are around 1.5 million new Further, the test can be taken as often as
By Disha Padmanabha
cases diagnosed every year. And currently, once every 10 to 15 minutes over a period of
there is no available needle-free approach for several hours. It is hoped that once commer- “The monitor developed at Bath promises a sign can be implemented using high-through-
diabetics to monitor glucose levels in the in- cialized, the inexpensive disposable device truly calibration-free approach, an essential put fabrication techniques like screen print-
terstitial fluid. could wirelessly transmit those readings to contribution in the fight to combat the ev- ing, which we hope will ultimately support a
Now however, scientists at the Bath Uni- an app on the user’s smartphone, providing er-increasing global incidence of diabetes,” disposable, widely affordable device.”
versity have designed an electronic patch alerts when necessary. he continued.
that non-invasively measure glucose levels In lab tests, the patch has been successful-
through the skin. It works by drawing out “A non-invasive – that is, needle-less – “The specific architecture of our array per- ly used to monitor fluctuating blood glucose
glucose from fluid between cells across hair method to monitor blood sugar has proven mits calibration-free operation, and it has the levels both in healthy human volunteers, and
follicles, which are individually accessed via a difficult goal to attain,” said professor of further benefit of allowing realization with a on pig skin with glucose levels representing
an array of miniature sensors using a small the university’s department of pharmacy and variety of materials in combination,” said Dr. the range seen in human diabetics. The sci-
electric current. The glucose collects in tiny pharmacology Richard Guy. “The closest Adelina Ilie, from the University’s Depart- entists are now planning on optimizing the
reservoirs and is measured. that has been achieved has required either ment of Physics. “We utilized graphene as number of sensors in the patch, demonstrat-
An important advantage of this device over at least a single-point calibration with a one of the components as it brings important ing its functionality over a 24-hour wear pe-
others is that each miniature sensor of the ar- classic ‘finger-stick’, or the implantation of advantages: specifically, it is strong, conduc- riod, and performing clinical trials.
ray can operate on a small area over an indi- a pre-calibrated sensor via a single needle tive, flexible, and potentially low-cost and
vidual hair follicle – this significantly reduc- insertion.” environmentally friendly. In addition, our de-

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April 17th, 2018. Vol. 02 NO 16

STAYING FIT COULD HELP STEER CLEAR OF


GENETIC HEART DISEASES

By Disha Padmanabha

It takes a special person to enjoy every sin- “The main message of this study is that ge- In one of the largest observational studies ipants who had the same genetic risk and the
gle workout every single time. You’re only netic risk isn’t deterministic,” says Erik In- on fitness and heart disease, researchers ex- weakest grips. Researchers determined vari-
human, right? So getting frustrated, angry, gelsson, M.D., Ph.D., professor of medicine amined data collected from nearly a half-mil- ous levels of genetic risk according to meas-
sleepy, teary, competitive and exhausted is at Stanford University School of Medicine lion people in the UK Biobank database. The urements based on discoveries from genome-
all part of the process. That said, so is feeling and lead author of the study published in the investigators found that people with higher wide association studies, the most common
happy, accomplished and proud when you American Heart Association journal, Circu- levels of grip strength, physical activity, and study design to discover genetic variation
make it to the end of your workout. lation. “Even if your parents died early of cardiorespiratory fitness had reduced risks of associated with disease.
And if you’re the kind that hates exercis- heart disease, you can reduce your risk to the heart attacks and stroke, even if they had a The study authors explained that the results
ing with the fiery passion of a thousand suns, level of someone with no family history of the genetic predisposition for heart disease. of this research could have important impli-
this piece.. erm, well I hope gets you right on disease by increasing your fitness.” For participants deemed at intermediate ge- cations for public health, especially consid-
back track (no pun intended). netic risk for cardiovascular diseases, those ering the fact that little is known about the
A new study indicates exercise may be the “This study further buoys what I’ve always with the strongest grips were 36 percent less effects of exercise in individuals who have
best way to keep off heart disease- even for said—that exercise is good for everyone and likely to develop coronary heart disease and genetically inherited a risk of cardiovascular
those with a genetic pre-disposition. everything,” says Consumer Reports’ chief had a 46 percent reduction in their risk for disease.
medical advisor Marvin M. Lipman, M.D. atrial fibrillation compared with study partic-

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