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How to best build a cell

Inlägg av Tryggve » tor 08 maj 2014, 17:34

Även denna var intressant, det är en kommentar kring syntetisk biologi från några olika forskare.

Experts weigh in on the biggest obstacles in synthetic biology — from names to knowledge gaps — and what it will take to overcome them.
James J. Collins: Bring in the biologists

Professor of biomedical engineering,
Boston University

Synthetic biology is often described as bringing together engineers and biologists to build genetic circuits for some useful task. In fact, the field has engaged relatively few biologists. This is holding back its progress. We do not yet know enough biology to make synthetic biology a predictable engineering discipline.
Mary Maxon: Agree on a definition

Head of biosciences strategic planning and development, Lawrence Berkeley National Laboratory

Researchers, regulators, consumers and detractors in the United States cannot agree on whether synthetic biology is a new discipline of engineering or an extension of biotechnology. Debates abound over whether geneticist Craig Venter created artificial life using synthetic biology, and whether that term is just another name for genetic engineering. These ambiguities complicate discussions among scientists, hinder policy-makers, impede efforts to fund synthetic-biology research and thwart regulation that might build public confidence.
Andy Ellington: Build green 'bioalchemists'

Professor of biochemistry, University of Texas at Austin

The biggest challenge for synthetic biology is how to extend beyond projects that focus on single products, organisms and processes. Right now, most applications engineer bacteria that start a synthesis with glucose and turn out biofuels or fine chemicals, such as vanillin or artemesinin. A broader scope could help to build a 'greener' economy, in which more organisms make a greater range of chemicals.
Martin Fussenegger: Make tools for mammalian cells

Professor of biotechnology and bioengineering, Swiss Federal Institute of Technology, Zurich

For synthetic biology to be useful in medicine, more and better tools are needed for work with mammalian cells. The tools that are now standard for bacteria are missing or underdeveloped for mammalian cells. (Similar challenges exist for engineering plant cells.)
Ron Weiss: Automate efficient design

Professor of biological engineering, Massachusetts Institute of Technology

As synthetic biologists build ever more genetic parts, efficient design has become a major stumbling block. In a system with three components, many of the possible combinations can be explored experimentally, so a design does not need to be perfect. However, once the number of components exceeds five or so, it often becomes impractical to explore the relevant design space completely. Without a much greater effort, synthetic biology will be left with many clever parts, but only limited and inefficient ways to combine them.
Herbert Sauro: Capitalize on evolution

Associate professor of bioengineering, University of Washington

Engineering life is not like engineering concrete or silicon. Bioengineers painstakingly craft a design, and a day later it has crumbled in the face of evolutionary selection. Synthetic biologists must learn to address this.

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Re: Stamceller

Inlägg av Hexmaster » tor 08 maj 2014, 19:17

Tryggve skrev:Detta kanske inte är så känt, men det har stormat en del kring ett par artiklar angående stamceller publicerat av Nature i januari.. Nu ska metoden granskas än mer ingående.
Vad säger du om avslutningen?
Josh Brickman, of the Danish Stem Cell Center at the University of Copenhagen, says that although negative results should settle the issue, “a positive replication, or worse, a limited positive replication” would just lead to more questions. “I would not be surprised if stress-induced reprogramming ends up being partially reproducible — an extremely rare and fickle process,” he says. “If this is the case, it may become increasingly difficult to determine exactly what was right in the original papers.”
Skulle en lyckad upprepning vara mer problematisk än en helt misslyckad? Och vad kan "partially reproducible" innebära?
Detta skall jag visa dig medelst ett stort papper som jag har fyllt med faktiska upplysningar! - Strindberg

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Re: Stamceller

Inlägg av Tryggve » tor 08 maj 2014, 19:28

Hexmaster skrev:
Tryggve skrev:Detta kanske inte är så känt, men det har stormat en del kring ett par artiklar angående stamceller publicerat av Nature i januari.. Nu ska metoden granskas än mer ingående.
Vad säger du om avslutningen?
Josh Brickman, of the Danish Stem Cell Center at the University of Copenhagen, says that although negative results should settle the issue, “a positive replication, or worse, a limited positive replication” would just lead to more questions. “I would not be surprised if stress-induced reprogramming ends up being partially reproducible — an extremely rare and fickle process,” he says. “If this is the case, it may become increasingly difficult to determine exactly what was right in the original papers.”
Skulle en lyckad upprepning vara mer problematisk än en helt misslyckad? Och vad kan "partially reproducible" innebära?
Jag förstår inte riktigt det där, måste jag säga. Går det inte att reproducera enligt den metod som beskrivs så finns det rimligen tvivel på hur det gått till. Det exempel som jag kommer på direkt är detta, där man drog tillbaka en Science-artikel efter att personen som tog över projektet inte kunde upprepa resultaten.

http://forum.vof.se/viewtopic.php?f=10&t=2972

"partilly repoducible" betyder nog att vissa steg fungerar. Att man kommer en bit på vägen, så att säga.

Sedan ska sägas att det kan vara förbaskat svårt att reproducera en del saker, speciellt sådana där man t ex hanterar prover genom pipettering, eller transformerar celler, eller liknande. Varför? Ingen som vet.

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HIV-behandling,.

Inlägg av Tryggve » mån 12 maj 2014, 12:35

Nature Biotechnology skrev förra veckan om en ny typ av behandling av HIV. En slags form av genterapi vill man kalla det i artikeln i alla fall.

http://www.nature.com/nbt/journal/v32/n ... NBT-201405
HIV immunity goes direct

The commencement of human trials of a gene therapy delivering HIV-neutralizing antibodies is a welcome addition to efforts to develop conventional vaccines against this scourge.

At the start of the year, the International Aids Vaccine Initiative, in collaboration with The Children's Hospital of Philadelphia and the US National Institute of Allergy and Infectious Diseases, initiated a phase 1 clinical trial at the UK's Surrey Clinical Research Centre to analyze the safety of an experimental HIV 'vaccine'. The trial is a landmark because the agent is not a conventional B-cell vaccine but a gene therapy that generates passive immunity via intramuscular injection with adeno-associated virus serotype 9 (AAV9) encoding the HIV broadly neutralizing antibody PG9. The approach, called vector-mediated gene transfer or vectored immunoprophylaxis, represents an intriguing alternative to efforts to create a conventional vaccine to HIV. Vectored immunoprophylaxis not only sidesteps some major drawbacks of traditional B-cell vaccines against HIV, but also could be a useful adjunct, particularly in some populations. No one should be in any doubt, however, that it still faces some stiff challenges to achieve successful translation.

The field of conventional HIV vaccines also remains a work in progress. The most successful vaccine trial to date—after more than three decades of effort—was of RV144, a recombinant canarypox vector vaccine plus two booster injections of a recombinant glycoprotein 120 subunit vaccine (N. Engl. J. Med. 361, 2209–2220, 2009). That vaccine, administered to 16,402 healthy men and women between the ages of 18 and 30 years in Thailand, was, at most, 31% effective.

The modest success of conventional HIV vaccines can be explained in part by numerous confounding challenges in vaccination trials, including variation in volunteer immune status, the co-occurrence of other sexually transmitted pathogenic agents and differences in the frequencies at which volunteers are exposed to virus. But the key limitation of RV144 and other conventional B-cell vaccines to date has been their inability to reliably elicit production of a broad spectrum of virus-neutralizing antibodies. Although new technologies for antibody repertoire sequencing have spurred progress in isolating broadly neutralizing antibodies from HIV-infected individuals and longitudinally tracking the natural B-cell response to HIV (a key prerequisite for development of an effective vaccine), we're not nearly there yet.

One reason is that HIV-neutralizing antibodies contain an unusually high number of somatic hypermutations and therefore diverge markedly from the unmutated ancestor germline antibodies expressed by naive B lymphocytes. The rare, unmutated ancestor antibody of HIV-neutralizing antibodies was recently identified in one individual, but whether humans of different genetic backgrounds and living in different geographical regions harbor similar, rare, unmutated ancestors is unclear. In other words, one vaccine may not cover everyone. In addition, it's likely that multiple rounds of immunization with precisely engineered immunogens will be needed to guide unmutated ancestor B cells down a relatively convoluted path of somatic hypermutation toward broadly neutralizing progeny.

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Syrsor anpassar sig snabbt...

Inlägg av Tryggve » tis 03 jun 2014, 16:18

Det börjar bli tjatigt att säga att något är häftigt, men nog är detta häftigt? Syrsor anpassar sig snabbt till nytt hot.

http://www.nature.com/news/evolution-sp ... S-20140603
Evolution sparks silence of the crickets

Males on two Hawaiian islands simultaneously went mute in just a few years to avoid parasite.

Populations of a male cricket on different Hawaiian islands have lost their ability to chirp as a result of separate, but simultaneous, evolutionary adaptations to their wings. The changes, which allow the insects to avoid attracting a parasitic fly, occurred independently over just 20 generations and are visible to the human eye, a study reveals.

The findings could help to shed light on the earliest stages of convergent evolution — when separate groups or populations independently evolve similar adaptations in response to natural selection.

Male field crickets (Teleogryllus oceanicus) are known for their chirping sound, which is produced by scraping their wings across one another. The wings’ veins form special structures that make the vibrations that we hear as the crickets’ song. “The mechanism is like rubbing your fingernail on the file of a comb,” says study leader and evolutionary biologist Nathan Bailey of the University of St Andrews, UK.

The nightly serenades lure in females and facilitate reproduction — but unfortunately for the males in Hawaii, the chirping also attracts a deadly parasitic fly, Ormia ochracea. The fly larvae burrow into the cricket and grow inside, killing the host when they emerge a week or so later.

Both species are likely to have arrived in Hawaii at the end of the last century — the cricket from Oceania, and the fly from North America. To protect themselves from their new enemy, large numbers of male crickets on the Hawaiian island of Kauai quickly stopped chirping.

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Förfadern till borrelia hittad?

Inlägg av Tryggve » tis 10 jun 2014, 18:41

Här ser man vad ett souvenirköp kan ge. En forskare tog en närmare titt på en bärnsten som han införskaffade för 25 år sedan i Dominikanska Republiken. När han använde ett kraftigt mikroskop så upptäckte han fästingar i bärnstenen.


http://www.nature.com/news/lyme-bacteri ... S-20140610
Lyme bacterium's possible ancestor found in ancient tick

Parasite trapped in ancient amber carried the oldest documented ancestor of the Borrelia that causes Lyme disease.

An article by Scientific American.

Ancient evidence of a familiar foe has emerged in a fossil tick infested with what appears to be spirochetes, a group of rotini-shaped bacteria responsible for many human diseases. The spirochetes in question closely resemble those of modern-day Borrelia, the genus responsible for Lyme disease. The finding, recently described in Historical Biology1, could offer insight into the evolutionary history of the Lyme disease–causing pathogen that plagues people today, but is also notable for its novelty.

“This is the first evidence of spirochetes in a fossil tick prior to Homo,” says George Poinar, Jr., a palaeoentomologist and parasitologist at Oregon State University, and author of the new paper. Although Lyme disease did not exist back then, the spirochetes in the fossil tick probably contributed to the genetic diversity of the 12 or more species of Borrelia that cause Lyme and similar diseases today, he says.

Parasites represent at least half of all modern animal species, and that distribution probably held true millions of years ago, too. “In a sense, this [finding] is not surprising since virtually every species on the planet is parasitized,” says Armand Kuris, a parasitologist at the University of California, Santa Barbara, who was not involved in the study. Evidence of those ancient parasite–host associations is difficult to come by, however. “In terms of finding any kind of physical documentation in the fossil record, that’s really rare — especially for a microbial pathogen,” Kuris says. “That’s what makes this paper just plain interesting.”

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Re: Nature News

Inlägg av Hexmaster » ons 11 jun 2014, 07:13

Utöver att vara en intressant nyhet i sig (visste inte att man kan hitta sådana mikroorganismer i fossiler) så finns det visst en konspirationsteori om att borrelia är en modern laboratorieprodukt.
Detta skall jag visa dig medelst ett stort papper som jag har fyllt med faktiska upplysningar! - Strindberg

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Re: Nature News

Inlägg av Tryggve » ons 11 jun 2014, 08:34

Hexmaster skrev:Utöver att vara en intressant nyhet i sig (visste inte att man kan hitta sådana mikroorganismer i fossiler) så finns det visst en konspirationsteori om att borrelia är en modern laboratorieprodukt.
Oj, det hade jag missat. Men det kanske i sig inte är förvånande.

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Re: Nature News

Inlägg av Blafsen » ons 11 jun 2014, 11:27

Och hur kan man vara säker på att fossiler inte är moderna laboratorieprodukter? :roll: :lol:
......men jag är inte smartare än en femteklassare.

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ISS

Inlägg av Tryggve » fre 13 jun 2014, 00:35

Lite mer info, nu om det där med att krisen i Ukraina också får en del följer i rymden. NASA anser att det kanske är dags att skynda på lite med forskningen på ISS.
http://www.nature.com/news/space-statio ... up-1.15388


Space-station science ramps up

NASA pushes research agenda in face of Russian resistance.

n January, when the United States proposed extending International Space Station (ISS) operations until 2024, the world was a very different place. That was before Russian military intervention in Ukraine, before US–Russian relations foundered and before Russian deputy prime minister Dmitry Rogozin suggested that US astronauts use a trampoline to get themselves to orbit (see Nature http://doi.org/s4f; 2014).

Rogozin also suggested last month that Russia would stop participating in the space-station programme after its scheduled end date of 2020. That statement did not set official government policy, but given Russia’s key role in the orbiting outpost it cast a shadow over hopes for the four-year extension.

With the clock ticking, the race is on to conduct as much science as possible in whatever time the space station has left. At a conference next week in Chicago, Illinois, NASA scientists will try to lure researchers who have not worked with near-zero-gravity conditions before. The goal is to get them to propose anything from the usual research agenda — such as protein crystallization and human physiology experiments — to basic biomedical research and Earth-science observations that can take advantage of the high-flying platform before its mission ends (see ‘Research push’). “There’s never been anything like it,” says Julie Robinson, NASA’s space-station research chief at the Johnson Space Center in Houston, Texas. “It’s like a university, all together with all the disciplines — I don’t know if we’ll see that again.”

Det där med proteinkristallisering i rymden är alltså något man fortfarande vill pusha för. Undrar hur mycket det har gett egentligen. Jag hade en föreläsare en gång i forntiden som berättade att hon hade varit med i en grupp som skickat upp en set med proteiner för kristallisering med en rymdfärja någon gång runt 1997 eller så. Gick sådär... Men det vore väl kanske en annan sak om det rör sig om mer än 10 dagars tyngdlöshet.
Fast då måste man väl ha utrustning för analysen av kristallerna på stationen. För det är väl ofta nedfärden som är problemet för proteinkristaller.

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Fotosyntes

Inlägg av Tryggve » fre 11 jul 2014, 13:24

Den här var så pass häftig att jag bara måste lägga in den. Artikeln är nog dock bakom betalvägg. Detta är den som bland annat DN har skrivit om det. Man har filmat (typ) fotosyntesen för första gången på nivån att man ser vad som händer på proteinnivå i stegen.

http://www.dn.se/nyheter/sverige/forska ... osyntesen/


Artikeln i Nature
http://www.nature.com/nature/journal/va ... 13453.html

Serial time-resolved crystallography of photosystem II using a femtosecond X-ray laser


Photosynthesis, a process catalysed by plants, algae and cyanobacteria converts sunlight to energy thus sustaining all higher life on Earth. Two large membrane protein complexes, photosystem I and II (PSI and PSII), act in series to catalyse the light-driven reactions in photosynthesis. PSII catalyses the light-driven water splitting process, which maintains the Earth’s oxygenic atmosphere1. In this process, the oxygen-evolving complex (OEC) of PSII cycles through five states, S0 to S4, in which four electrons are sequentially extracted from the OEC in four light-driven charge-separation events. Here we describe time resolved experiments on PSII nano/microcrystals from Thermosynechococcus elongatus performed with the recently developed2 technique of serial femtosecond crystallography. Structures have been determined from PSII in the dark S1 state and after double laser excitation (putative S3 state) at 5 and 5.5 Å resolution, respectively. The results provide evidence that PSII undergoes significant conformational changes at the electron acceptor side and at the Mn4CaO5 core of the OEC. These include an elongation of the metal cluster, accompanied by changes in the protein environment, which could allow for binding of the second substrate water molecule between the more distant protruding Mn (referred to as the ‘dangler’ Mn) and the Mn3CaOx cubane in the S2 to S3 transition, as predicted by spectroscopic and computational studies3, 4. This work shows the great potential for time-resolved serial femtosecond crystallography for investigation of catalytic processes in biomolecules.

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Tråkliga nyheter

Inlägg av Tryggve » tis 15 jul 2014, 15:31

Vet inte hur mycket det har uppmärksammats. Jag såg en notis om det i någon svensk tidning, tror jag. Det har ju rapporterats om ett fall där man var försiktigt positiv till att ett barn som hade behandlats 30 timmar efter födseln möjligen hade blivit botad.
http://www.nature.com/news/infant-s-van ... ed-1.12531

Nu har man 27 månader efter det att behandlingen avbröts (när hon var 18 månader, tydligen stoppade familjen behandlingen) hittat spår av virus.


http://www.nature.com/news/hiv-rebound- ... S-20140715

“It felt very much like a punch to the gut,” says Hannah Gay, a paediatric HIV specialist at the University of Mississippi Medical Center in Jackson who had treated the girl. The young patient will now face years, if not a lifetime, of antiretroviral therapy. And researchers are now scrambling to determine how this will affect clinical trials aiming to repeat the child's apparent cure.

The ‘Mississippi baby’ was born to an HIV-positive mother who had not received any treatment during pregnancy. Doctors began treating the child by the time she was 30 hours old, but the family stopped antiretroviral therapy at 18 months. She remained off the drugs for the next 27 months with no signs of the virus in her blood1.

The finding encouraged scientists hoping to find a way to save children from a lifetime of antiretroviral treatment. The trial inspired researchers to plan a federally funded clinical trial to find out whether the results can be repeated in other children.

The trial, which has yet to accrue any patients, is now being re-evaluated, says Anthony Fauci, director of the US National Institute of Allergy and Infectious Diseases in Bethesda, Maryland. “The study is still in play,” he says. Researchers will take a close look at the design, which calls for treatment to be suspended after two years, in some cases. They may also adjust the forms used to tell patients about the possible risks of participating in the study, Fauci adds.

Doctors do not know what caused the virus to rebound in the young girl, who was monitored and tested for HIV every 6–8 weeks. There were no signs of trouble until lab results last week showed that levels of her CD4+ immune cells had dropped. Gay's fears that the virus had rebounded were confirmed a few days later, when tests for HIV came back positive. The sequence of the virus matched that taken from the girl’s mother two years earlier.

Doctors immediately started the girl on antiretroviral medication and her immune cells are recovering, says Gay. She has shown no other signs of infection, such as enlarged lymph nodes.

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Tänk om det går...

Inlägg av Tryggve » tor 17 jul 2014, 15:54

.... att faktiskt utrota polio nu? Den här ledarartikeln i Nature diskuterar det.


http://www.nature.com/news/within-reach ... E-20140717
Within reach

A redoubling of efforts should swiftly eradicate polio from its last strongholds

The global effort to eradicate poliomyelitis has been spectacularly successful, eliminating 99% of cases in its 26-year history. But that progress has begun to unravel in the past 18 months, with outbreaks in east and west Africa and in the Middle East. The lesson is clear: as long as the virus is allowed to persist in the three countries in which it remains endemic — Pakistan, Afghanistan and Nigeria — exports of the disease will continue to affect other countries. A determined effort is needed to eradicate the virus from these endemic countries, and fast.

The worsening situation meant that in May, the World Health Organization (WHO) declared polio a public-health emergency of international concern. This allowed it to impose a requirement that all travellers entering or leaving Pakistan, Cameroon, Syria and Equatorial Guinea — the countries currently exporting polio — must have up-to-date polio vaccinations. And it strongly recommended the same for other nations with ongoing polio outbreaks. The WHO also requires the governments of affected countries to declare that polio constitutes a national public-health emergency.

It is too soon to tell how well countries will enforce the travel restrictions or how effective they will be (see page 285). But the WHO’s declaration has another, and arguably more important, potential impact. It has greatly heightened public and political awareness of the global polio threat. The move could yet shame those nations with weak control efforts into doing better. Ultimately, political will, through every level of government right down to the local level, is crucial if eradication efforts are to succeed.

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ZMapp

Inlägg av Tryggve » fre 03 okt 2014, 13:20

Så, efter ett långt uppehåll så kanske det är dags att göra lite nytt i den här tråden. Den senaste uppdateringen från Nature News hade denna om ZMapp. Detta är alltså en primatstudie på ZMapp. Inte i människoapor, utan i rhesusapor.

Reversion of advanced Ebola virus disease in nonhuman primates with ZMapp
Without an approved vaccine or treatments, Ebola outbreak management has been limited to palliative care and barrier methods to prevent transmission. These approaches, however, have yet to end the 2014 outbreak of Ebola after its prolonged presence in West Africa. Here we show that a combination of monoclonal antibodies (ZMapp), optimized from two previous antibody cocktails, is able to rescue 100% of rhesus macaques when treatment is initiated up to 5 days post-challenge. High fever, viraemia and abnormalities in blood count and blood chemistry were evident in many animals before ZMapp intervention. Advanced disease, as indicated by elevated liver enzymes, mucosal haemorrhages and generalized petechia could be reversed, leading to full recovery. ELISA and neutralizing antibody assays indicate that ZMapp is cross-reactive with the Guinean variant of Ebola. ZMapp exceeds the efficacy of any other therapeutics described so far, and results warrant further development of this cocktail for clinical use.

http://www.nature.com/nature/journal/v5 ... E-20141002

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Ebola och malaria

Inlägg av Tryggve » fre 03 okt 2014, 16:52

En artikel tar upp problemet att det pågående utbrottet av ebola gör att de åtgärder som man har vidtagit för att försöka bekämpa malaria stoppas. Vilket väl kanske inte är så konstigt, men som väl sagt tål att belysas.

http://www.nature.com/news/ebola-outbre ... ts-1.16029

Ebola outbreak shuts down malaria-control efforts


Public-health experts fear that one epidemic may fuel another in West Africa.

As the Ebola death toll spirals into the thousands in West Africa, the outbreak could have a spillover effect on the region’s deadliest disease. The outbreak has virtually shut down malaria control efforts in Liberia, Guinea and Sierra Leone, raising fears that cases of the mosquito-borne illness may start rising — if they haven’t already.

So far, at least 3,000 people are estimated to have died of Ebola in Guinea, Sierra Leone and Liberia in the current outbreak, although World Health Organization (WHO) staff acknowledge that official figures vastly underestimate the total. By contrast, malaria killed more than 6,300 people in those countries in 2012, most of them young children. Overall, malaria deaths have fallen by about 30% in Africa since 2000 thanks to national programmes supported by international funding agencies such as the Global Fund to Fight AIDS, Tuberculosis and Malaria, the US Agency for International Development and the WHO’s Roll Back Malaria initiative. The schemes distribute free bed nets to protect sleeping children from mosquitoes, train health workers to find malaria cases and offer tests and treatment at no charge to patients.

But the Ebola outbreak has brought those efforts to a standstill in the three affected countries. “Nobody is doing a thing,” says Thomas Teuscher, acting executive director of the Roll Back Malaria Partnership, based in Geneva, Switzerland.

He says that malaria drugs are sitting in govern-ment warehouses, especially in Liberia and in Guinea, where medical supply trucks have been attacked by people angry with the government’s handling of the Ebola outbreak. Liberia had planned a national campaign to distribute bed nets this year, but Teuscher says that it may be difficult to launch that now.

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