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Hydra can modify its genetic program

Champion of regeneration, the freshwater polyp Hydra is capable of reforming a complete


individual from any fragment of its body. It is even able to remain alive when all its neurons have
disappeared. Researcher the University of Geneva (UNIGE), Switzerland, have discovered how:
cells of the epithelial type modify their genetic program by overexpressing a series of genes,
among which some are involved in diverse nervous functions. Studying Hydra cellular plasticity
may thus influence research in the context of neurodegenerative diseases. The results are
published in Philosophical Transactions of the Royal Society.

The freshwater Hydra is endowed with an extraordinary power of regeneration, discovered by the
Swiss naturalist Abraham Trembley more than 250 years ago. The group of Brigitte Galliot,
professor at the Department of Genetics and Evolution of the Faculty of Science of UNIGE, has
studied the stem cells functioning and cellular plasticity of the polyp: "its nervous system regulates in
particular contraction bursts, feeding behavior, moving or swimming. If the stem cells responsible for
its renewal are depleted, the Hydra can still develop, even when all its neurons have disappeared.
We wanted to understand how this is possible."

Enhancing other cells' sensing ability

The researchers compared gene expression at various positions along the body axis in polyps
devoid or not of their nervous stem cells. They observed a modification of the genetic program in
animals depleted of these cells: "we identified 25 overexpressed genes in epithelial cells, the cells
forming the Hydra's coating tissues. Some of these genes are involved in diverse nervous functions,
such as neurogenesis or neurotransmission," says Yvan Wenger, co-first author of the article.

"Epithelial cells do not possess typical neuronal functions. However, Hydra's loss of neurogenesis
induces epithelial cells to modify their genetic program accordingly, indicating that they are ready to
assume some of these functions. These "naturally" genetically modified epithelial cells are thus likely
to enhance their sensitivity and response to environmental signals, to partially compensate for the
lack of nervous system," explains Wanda Buzgariu, co-first author of the article. The detail of these
new functions remains to be discovered, as well as how epithelial cells proceed to overexpress
these genes and thus adapt their genetic program.

Cellular plasticity maintains youth

Studying Hydra's cellular plasticity may be relevant in the context of neurodegenerative diseases.
Indeed, some of the genes identified in this animal play an important role in cellular reprogramming
or in neurogenesis in mammals. The researchers therefore wonder: would it be possible to restore
sensing or secretion functions from other cell types, when some neurons degenerate?

This study also allows to go back to the origins of nervous systems. Epithelial cells most probably
preceded nerve cells, performing some of their functions, although in a much slower way. "The loss
of neurogenesis in Hydra may provide an opportunity to observe a reverse evolutive process,
because it sheds light on a repressed ancestral genetic toolkit. An atavism of epithelial cells, when
they most probably also possessed proto-neuronal functions," concludes Brigitte Galliot.
Sensory illusion causes cells to self-destruct
Magic tricks work because they take advantage of the brain's sensory assumptions, tricking
audiences into seeing phantoms or overlooking sleights of hand. Now a team of UC San
Francisco researchers has discovered that even brainless single-celled yeast have sensory
biases that can be hacked by a carefully engineered illusion, a finding that could be used to
develop new approaches to fighting diseases such as cancer.

"The ability to perceive and respond to the environment is a basic attribute of all living organisms,
from the greatest to the smallest," said Wendell Lim, PhD, the study's senior author. "And so is the
susceptibility to misperception. It doesn't matter if the illusion is based on molecular sensors within a
single cell or neurons in the brain."

In the new study, published online Nov. 19, 2015 in Science Express, Lim and his team discovered
that yeast cells falsely perceive a specifically timed pattern of stress -- caused by alternating
between low and mildly increased sodium levels -- as a massive, continuously increasing ramp of
stress. In response, the microbes end up over-responding and killing themselves. The results, Lim
says, suggest a whole new way of looking at the perceptual abilities of simple cells and could even
be used to develop new approaches to fighting diseases using the power of illusion.

Timing of stress response is yeast cells' 'Achilles heel'

"This discovery was a bit of an accident actually," said Lim, chair of the Department of Cellular and
Molecular Pharmacology at UCSF, director of the UCSF Center for Systems and Synthetic Biology,
and a Howard Hughes Medical Institute (HHMI) investigator. "We were interested in the general
issue of how cells interpret information over time. Frequency is a key aspect of all our
communications, whether it's hearing language or transmitting radio signals, but do cells themselves
use this kind of information? It's something we don't know much about."

To explore this question, two postdoctoral fellows in Lim's lab, Ping Wei, PhD, now at Peking
University School of Life Sciences, and Amir Mitchell, PhD, set up a system that allowed them to
expose yeast to a mild stressor -- a small increase in salt in the yeast's environment -- and to
oscillate between the increased salt level and the baseline level at different frequencies.

Normally, sensor molecules in a yeast cell detect changes in salt concentration and instruct the cell
to respond by producing a protective chemical. After this transient response, the cell can resume
growing happily as if conditions had not changed. The researchers found that the cells were
perfectly capable of adapting when they flipped the salt stress on and off every minute or every 32
minutes. But to their surprise, when they tried an eight-minute oscillation of precisely the same salt
level the cells quickly stopped growing and began to die off.

"That was just a jaw-dropping moment," said Mitchell. "These cells should be able to handle this
level of osmotic stress, but at one particular frequency they just go haywire. We'd never seen
anything like this before."

Could sensory illusions be used to fight cancer?


Mitchell, who was first author on the new study, went on to inspect the cellular mechanism
underlying this unexpected, frequency-dependent toxicity. Using mathematical modeling and
experiments in which he tweaked the molecular wiring of the mitogen activated protein kinase
(MAPK) pathway that mediates the cells' salt-sensing system, he revealed a sensory misperception:
Because of the way the MAPK pathway is set up, the cells interpret an eight-minute oscillation as an
ever-increasing staircase of salt concentration. This leads to excessive activation of the cells'
protective response, and ultimately to their death (see Movie).

"Why would these cells have evolved this bizarre sensitivity to salt oscillations?" Mitchell asked.
"Well, we don't think that they did. It's just a side effect of the fact that the molecular signaling
network yeast cells use to mediate this stress response was optimized for their natural environment,
in which salt stress normally occurs in a gradually increasing ramp -- like if the yeast is sitting on a
grape as morning dew slowly evaporates. It's this assumption on the part of the yeast -- their
anticipation that the stress will keep getting more severe -- that creates their Achilles heel."

The study suggests that many cell types, including human cells, may be predisposed to
misperceptions and could be fooled by carefully engineered illusions. For instance, Mitchell said, the
signaling pathway by which human cancer cells respond to chemical growth factors is closely related
to the stress-sensing MAPK pathway in yeast. Thus, identification of cell-specific misperceptions
might ultimately be exploited to induce cancer cells to kill themselves, he suggested, while minimally
harming healthy, neighboring cells.

"On its own, this is a humble finding," Lim said, but he believes it has broader implications for
biomedical research. "Like us, cells have biased perceptions based on what environmental patterns
they've evolved with. By understanding these biases, we can modulate their behavior," he said. "In
particular, it's striking to realize how important the time domain is for cells. The temporal pattern with
which we present any stimulus, whether it's salt concentrations, drugs or beams of light, may make
all the difference."

Treatment for sickle cell disease may help protect patients'


kidney function
A drug used to treat sickle cell disease may provide an added benefit of protecting patients'
kidney function, according to a study appearing in an upcoming issue of the Journal of the
American Society of Nephrology (JASN).

Sickle cell disease, a blood disorder, can impact the function of the kidneys, and the earliest sign of
kidney damage in affected patients is albuminuria, or the presence of albumin in the urine.

Hydroxyurea (HU), which makes red blood cells more flexible, is one of the cornerstones of sickle
cell disease treatment, but its effects on kidney function are unclear. To investigate, Pablo
Bartolucci, MD, PhD, Vincent Audard, MD, PhD (Université Paris-Est Créteil, in France), and their
colleagues studied 58 adults with sickle cell disease who were starting HU therapy. After 6 months
of treatment, patients' kidney function, as measured by the urinary albumin/creatine ratio, improved
significantly.

"The findings offer further evidence, albeit not yet definitive, of a potential renal benefit of HU, and
should strengthen arguments favoring its use in sickle cell disease for other indications and
encouraging patient adherence to this drug," said Dr. Bartolucci. "Our preliminary results require
additional larger, prospective, randomized, controlled trials to clearly demonstrate the positive effect
of HU to reduce albuminuria levels and delay chronic kidney disease progression," added Dr.
Audard.

2 months and counting: Pastillas Girl, Chard


mark monthsary
MANILA -- Angelica Yap, known to many as "Pastillas Girl," and Richard Parojinog recently
celebrated their second month of courtship.

A lot has happened since Yap chose Parojinog on the "It's Showtime" segment "Nasaan Ka, Mr.
Pastillas."

(LOOK: How is Pastillas Girl after 'Showtime')

A few weeks ago, Parojinog brought Yap to Ozamiz City to formally introduce her to his family.

During their stay in Ozamiz, Yap also had an opportunity to meet Parojinog's father, Misamis
Occidental Second District Board Member Ricardo Parojinog.

In an interview with Boy Abunda, the two admitted that they are now "exclusively dating" but are
not yet a couple.

As they celebrate another milestone, here are some photos showing the developing friendship
between Yap and Parojinog. And judging through their smiles in this video, will there be forever for
#ChardGel?

Paulo Avelino has message for JaDine,


OTWOL fans
MANILA -- Actor Paulo Avelino is honored to be part of hit primetime series "On The Wings of
Love" starring the popular love team of James Reid and Nadine Lustre.
"Medyo late na ako papasok. It's an honor to be part of the cast and to be considered na
masama sa teleseryeng ito lalo na at alam nating hit ang 'On The Wings of Love," Avelino told
reporters in a press conference on Tuesday.

In the series, Avelino will portray Simon, the newest boss of Lea (Lustre) in the advertising firm
she is working for.

"Working with a love team, I'm really excited and nae-excite ako sa maibibigay kong bago sa
show," he said. "Hindi totally manggulo pero mayanig at palakasin lalo 'yung 'On The Wings of
Love.'"

"The challenge dito is 'yung mystery ni Leah (Lustre) na parang brilliant pero at the same time
ay hindi ako maka-connect dahil busy siyang minamahal na si Clark," the actor said.

Avelino revealed that his character will definitely "affect" the love story of Clark and Leah.

"These are two very young people na ikinasal kaagad, nagkarelasyon at engaged. Kumbaga sa
mga ganitong relasyon sa tingin ko ay parang kulang lagi 'yung maturity. So siguro 'yung
maturity ni Simon, not just as a boss but bilang mas matanda siya kay Leah, baka 'yun ang ma-
present or makita ni Leah na pwedeng ma-attract siya," the actor said.

Avelino said he's really thankful to all the fans of Reid and Lustre, adding that he also don't mind
being bashed for his newest role.

"Hindi naman maiiwasan 'yon, minsan nadadala tayo sa mga characters on TV. Kahit naman
ako kapag may napapanood akong show, kapag may sumisingit or kapag sa tingin mong threat
ang isa," he said.

The actor, however, assured fans that he will not be a threat to Reid and Lustre's love team.

"Well alam natin na they are good friends at hindi naman ako doon para sirain 'yung
pagkakaibigan nila. Pero regarding sa show siyempre I will be coming in as a threat," Avelino
explained.

Avelino is expected to appear in the hit soap starting next week.

"On The Wings of Love" airs weeknights after "Pangako Sa 'Yo."

LOOK: Karla Estrada turns 41 in fairy tale-


themed party
Actress Karla Estrada had a fairy tale-themed party at the Celebrity Sports Plaza over the weekend
to mark her 41st birthday.

The event was attended by Estrada’s family and friends within and outside showbiz.
Among the celebrities who were at the party were her son Daniel Padilla, Kathryn Bernardo, Jolina
Magdangal, Nyoy Volante, Tutti Caringal, Edgar Allan Guzman, Wenn De Ramas, Sunshine Cruz
and Bayani Agbayani.

Former “Pinoy Big Brother” housemates Ylona Garcia, Bailey May, Zeus Collins, Jameson Blake
and Richard Juan were also there.

Also spotted at Estrada’s party were broadcast journalist Korina Sanchez, comedian Vice Ganda
and designer Paul Cabral.

As seen in the pictures, Estrada donned a blue ball gown and a crown for her party

Aquino holds meeting


with Lumad in
Malacañang
MANILA, Philippines – President Benigno Aquino III met with several Lumad,
the indigenous peoples in Mindanao, on Tuesday, November 24, in
Malacañang, months after a spate of killings that have pitted the indigenous
community against the military.

“Earlier today, the President, along with key members of the Cabinet, met with
leaders from the Indigenous Peoples sector,” Presidential Spokesperson
Edwin Lacierda said in a statement on Tuesday.

While Lacierda only mentioned "Indigenous Peoples," a Rappler source privy


to the meeting confirmed they are indeed Lumad.

“[Aquino] heard the totality of their concerns and issued directives to come up
with concrete action plans to address these, both in immediate and long-
term,” Lacierda added.

Malacañang and Cabinet secretaries, however, were mum on the details.


Present were Education Secretary Armin Luistro, Budget Secretary Florencio
“Butch” Abad, Health Secretary Janette Garin, Secretary to the Cabinet Rene
Almendras, and Presidential Management Staff Chief Julia Abad.

The meeting came after hundreds of Lumad arrived in Manila to protest the
killings.

Several local and international groups have called on the Aquino


administration to look into the spate of killings of activists and Lumad in
Mindanao. (READ:Timeline: Attacks on the Lumad)

The Philippine military is accused of killing Lumad leaders on suspicion they're


guerrillas. The communities are in provinces influenced by the communist
New People's Army.

Auction houses ready


Philippines' Marcos
jewels for possible sale
MANILA, Philippines – Philippine authorities on Tuesday, November 24
showcased necklaces with diamonds the size of marbles and other jewels
seized from the family of late dictator Ferdinand Marcos in preparation for a
possible multi-million-dollar auction.

White-gloved appraisers from Christie's auction house examined about 600


pieces of jewelry, including gold chains covered with sparkling gems, a huge
circlet of rubies, and a necklace dripping with pink and yellow diamonds at a
special vault at the Philippine central bank (Bangko Sentral ng Pilipinas).

The Presidential Commission on Good Government (PCGG), a body created


to recover the millions stolen by Marcos and his allies, said that "due to the
vast quantity of jewelry to be appraised, it will take at least 5 days," for teams
to go over it.
After the appraisal by Christie's, a team from Sotheby's will have their turn.
Previous appraisals of the jewels in 1988 and 1991 estimated their worth at
between $5 and $7 million, but the PCGC said this is no longer current.

"This (appraisal) will significantly open the way to determining a final


resolution on the said assets, including the possible auction of the same," the
PCGG said in a statement, but added it was also open to putting the jewels on
display.

It said a final decision required the approval of other agencies, and that
Marcos's widow, flamboyant former first lady Imelda Marcos, and her children,
were still disputing the ownership of part of the collection before the Supreme
Court.

In January 2014, the Sandiganbayan forfeited in favor of the Philippine


government the third jewelry collection of the former first lady that was seized
from her in 1986.

In a 33-page ruling penned by Associate Justice Efren de la Cruz, the court's


special first division forfeited what is known as the "Malacañang Jewelry
Collection," the last of Mrs Marcos' 3 sets of collection covered by a court
case and which have sat in a bank vault for decades.

Two of these – known as Roumeliotes and Hawaii Collections – had already


been forfeited in favor of the government. (READ: Imelda's jewelry collection
belongs to gov't - court)

Political stunt

Imelda Marcos's lawyer Robert Sison said in a statement that ownership of


the jewels was still subject to litigation.

He described the appraisal as a "very obvious political stunt."

The long-hidden collection, seized in 3 batches after Marcos was overthrown


in 1986, has been cited by critics as proof of how his family enriched itself
while the nation sank deeper into poverty during his 20 years in power.

Imelda Marcos amassed a huge collection of jewels, valuable art works, and
shoes even as other Marcos relatives and allies gained fortunes during the
Marcos years, critics have said.

The PCGG has been charged with recovering this wealth which it dubs "ill-
gotten."

But since the late dictator died in exile in 1989, the family has made a political
comeback with many members elected to prestigious positions.

The son of the late dictator, Ferdinand Marcos Jr, is running for vice-president
in next year's elections, raising fears the family will regain its influence

Philadelphia nears record as 76ers crash


again
LOS ANGELES -- The Philadelphia 76ers edged closer to another chapter of NBA infamy on
Monday, crashing 100-95 to the Minnesota Timberwolves to leave them just one defeat away
from the worst losing streak in history.

The 76ers are now 0-15 for the season, and combined with a run of 10 straight defeats last year
have lost 25 games in a row.

One more defeat will see them match the all-time record of 26 straight losses, which the 76ers
2013-14 team currently shares with the Cleveland Cavaliers side of 2010-11.

(READ: Monroe helps Bucks beat Pistons)

Three more defeats will take them to 0-18, equalling the worst ever start to an NBA season, set
by the New Jersey Nets in 2009-2010. On current form, few would bet against them reaching
that landmark.

The 76ers next travel to Boston on Wednesday before heading to Houston on Friday. A further
road trip match against Memphis awaits on Sunday, before they return home to face the Los
Angeles Lakers next week.

Andrew Wiggins was the 76ers nemesis on Monday, pouring on 32 points as the Timberwolves
rallied to secure their first home win of the season.

Gorgui Dieng and Zach LaVine added 12 points each for Minnesota, who fought back from a
double-digit deficit in the first half and six in the fourth quarter to close out victory.

Rookie Jahlil Okafor was a rare beacon amid the gloom for the 76ers, adding 25 points in vain.
Spurs beat Suns, stay perfect at home
Christmas might still be a month away but the San Antonio Spurs and Phoenix Suns are already
in a giving mood, or so it seems from the two teams' combined 49 turnovers in the Spurs' 98-84
win versus the Suns Monday.

Forward Kawhi Leonard led the Spurs with 24 points and 13 rebounds as one of four San
Antonio players in double-figure scoring.

The Spurs remained unbeaten at home despite setting a season-high with 21 turnovers that
resulted in 18 points for the Suns.

But Phoenix were even more careless with the ball, recording a season-high 28 turnovers -- 18
of them steals by the Spurs, also a season-high -- that led to 27 San Antonio points.

"In the first half, we couldn't get it going because we were turning it over, too," said Spurs guard
Manu Ginobili, who had eight points in 19 minutes.

"We were not as sharp today (as we have been). We let them get away with a lot of open looks.
It's a win, but we've had better ones."

Phoenix played without leading scorer guard Eric Bledsoe, who was ruled out of the game just
before tipoff with a knee injury.

Guard Tony Parker added 20 points and guard Danny Green scored a season-high 18 points for
San Antonio (11-3), who are 7-0 at the AT&T Center this season. Reserve guard Patty Mills
scored for 10 points for the Spurs, who shot 51.2 percent from the floor but converted just five of
10 free throws.

Phoenix (7-7) were led by forward Markieff Morris' game-high 28 points, just two of which came
in the fourth quarter, on 12-of-15 shooting from the field.

Guard Brandon Knight scored 18 points for the Suns, including 12 in the fourth quarter, and
reserve forward T.J. Warren added 16 points.

"There's no way we can win when if we turn the ball over as much as we did tonight," Morris
said. "Some of that had to do with (Bledsoe) being out, and some of it had to do with the Spurs'
defense. We just have to take better care of the ball."

The Spurs led 20-17 at the end of the first quarter as Leonard poured in 11 points, including the
first seven, for San Antonio. Morris had eight points in the quarter for the Suns, who stayed
close even though they had had nine turnovers in the first 12 minutes.

San Antonio expanded their advantage to 44-34 at halftime despite missing five of their nine
free throws in the first two quarters and committing 10 turnovers.
Phoenix shot just 39.4 percent in the first 24 minutes and allowed San Antonio 10 points off of
their 15 turnovers, 10 of which were Spurs steals.

(READ: Wiggins scores 32 as Wolves drop Sixers to 0-15)

"You're not going to beat anybody with 28 turnovers," Suns coach Jeff Hornacek said. "At one
point, when I think we had 15, I counted 11 of them that were unforced.

"When they make a good play and you get a turnover, then so be it," Hornacek added. "I don't
know what we were doing -- just throwing soft passes. Even when we tried to lob it over, the
passes were like five feet short of where they were supposed to go. That's hard to overcome."

After the Suns cut the Spurs' lead to 44-38 on a Morris jumper with 10:22 left in the third
quarter, the Spurs reasserted themselves with a 10-3 run in which Leonard scored seven
straight points.

But Morris kept shooting -- he had 14 points in the quarter -- and Phoenix got within 67-60
heading into the fourth quarter.

Hornacek tried to steal a few extra minutes of rest for Morris at the start of the fourth quarter, but
the move backfired on the Suns.

By the time Morris came back in the game with 7:45 to play, San Antonio had built its lead back
to 78-64 and Phoenix never again got closer than nine points.

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