Black Hole Pretenders Could Really Be Bizarre Quantum Stars

New research reveals a possible mechanism allowing “black stars” and “gravastars” to exist

When giant stars die, they don’t just fade away. Instead they collapse in on themselves, leaving behind a compressed stellar remnant, usually a city-size, superdense ball of neutrons appropriately called a neutron star. In extreme cases, however, most theorists believe an expiring giant star will form a black hole—a pointlike “singularity” with effectively infinite density and a gravitational field so powerful that not even light, the fastest thing in the universe, can escape once falling in. Now a new study is reinvigorating an alternate idea, that objects with names such as “black stars,” or “gravastars,” might exist midway between neutron stars and black holes. If real, these exotic stellar corpses should appear nearly identical to black holes save in one key way—they could not irretrievably swallow light.

There are good reasons to seek such alternatives, because black holes raise a host of theoretical problems. For instance, their singularities are supposedly hidden by invisible boundaries known as event horizons. Throw something into a black hole, and once it passes the event horizon it should be gone—forever—with no hope whatsoever of return. But such profound annihilation clashes with other long-cherished laws of physics that suggest the destruction of information is impossible, including information encoded within anything falling into black holes.

Conceived and developed across the past two decades, in part to sidestep such conundrums, models of black stars and gravastars postulate these objects would lack singularities and event horizons. But questions have lingered as to whether such objects could actually form—and remain stable after they did. New research from theoretical physicist Raúl Carballo-Rubio at the International School for Advanced Studies in Italy provides a novel mechanism that might allow black stars and gravastars to exist.

Carballo-Rubio investigated a strange phenomenon known as quantum vacuum polarization. Quantum physics, the best description yet of how all known subatomic particles behave, suggests reality is fuzzy, limiting how precisely one can know the properties of the most basic units of matter—for instance, one can never absolutely know a particle’s position and momentum at the same time. One strange consequence of this uncertainty is that a vacuum is never completely empty but instead foams with so-called “virtual particles” that continuously fluctuate into and out of existence.

In the presence of gigantic amounts of energyof the sort produced by the collapse of a giant starprevious research found these virtual particles can polarize, or arrange themselves depending on their properties, much as magnets are divided into north and south poles. Carballo-Rubio calculated the polarization of these particles can produce a surprising effect inside the powerful gravitational fields of dying giant stars—a field that repels instead of attracts.

Matter and energy curve the fabric of spacetime, resulting in gravitational fields, according to Einstein’s theory of general relativity. Planets and stars have a positive amount of energy on average, and the resulting gravitational fields are attractive in nature. When virtual particles polarize, however, the vacuum they occupy can on average possess negative energy, and “this curves spacetime in a way that the associated gravitational field is repulsive,” Carballo-Rubio says. Which, of course, could prevent the formation of a black hole. (A similar phenomenon causes relatively light stellar remnants to form neutron stars instead of black holes; their gravitational fields are not strong enough to crush neutrons into a singularity.)

Two prior models suggested repulsive gravity might keep stellar remnants from collapsing to form black holes. One proposed stellar remnants instead formed gravastars, objects filled with quantum vacuum overlaid by a thin shell of matter. The other model suggested the result of these collapses were black stars, where “matter and the quantum vacuum are interlaced throughout the structure in a meticulous balance,” Carballo-Rubio says. Both objects still have powerful gravitational fields that profoundly warp light, so they look dark, like black holes.

Carballo-Rubio says there was previously great uncertainty regarding the properties of black stars and gravastars. His new work tackled this issue by creating a mathematical framework that incorporated the effects of repulsive gravity into equations describing the expansion and contraction of stars, a problem “that was thought to be tractable only with the help of computers,” he notes. His new model suggests a hybrid of a black star and a gravastar could exist—one where matter and quantum vacuum are spread throughout the structure, but with matter in higher concentrations in the shell than in the core. Carballo-Rubio detailed his study online February 6 in Physical Review Letters.

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Meet ‘Oumuamua, the first observed interstellar visitor to our solar system

On October 19, the Pan-STARRS 1 telescope in Hawaii spotted something strange zooming through our solar system. It turned out to be a visitor from beyond our solar system, and it’s unlike anything astronomers have seen before.

It is the first observed object from outside our solar system, according to a study published Monday in the journal Nature — and, as the researchers call it, an “oddball.”
Journal retracts study linking “gut makeover” to weight loss, improved health

Over the objections of the authors, PLOS ONE has retracted a paper linking a diet designed to restore healthy gut bacteria to weight loss and other benefits.

The study, published in June 2017, claimed to show that a “Microbiome restoration diet improves digestion, cognition and physical and emotional wellbeing.” The diet was one championed by The Gut Makeover, whose author, Jeannette Hyde, is also a co-author on the paper (which the paper clearly disclosed). The diet is “designed to improve the health and diversity of the microbiome,” the microbiota that live within us.

The paper apparently prompted some criticisms, and even led one academic editor at PLOS ONE to resign. The journal  now says “the conclusions of this study are not supported by the data presented,” and have retracted it. But the case may reveal more about the limitations of peer review at the journal than it does about any weaknesses of the study.

That’s because many of the reasons given for the retraction are limitations authors included in the paper. For example, retraction notice notes that there was no control group, and the participants weren’t blinded to the diet. But readers — and peer reviewers — would have known all that. From the Discussion section of the paper, which repeats some of what also appears in the Materials and Methods section:

There was no control group in the study and the participants were not blind to the treatment protocol.

If we may: It’s one thing to reject a paper because the study it’s based on is too flawed to be published — or “not even wrong,” as some might put it. It’s another to retract it because peer reviewers apparently missed the fact that it was too flawed to be published. That’s not among the Committee on Publication Ethics (COPE) criteria for retraction.

Authors object

Not surprisingly, the two authors of the study objected to the retraction. Asked for comment, corresponding author Kate Lawrencereferred us to a statement by Philip Booth, the director of research at her university, St. Mary’s, in Twickenham, UK. Lawrence told Retraction Watch that she agrees with the statement, in which Booth said he has “huge concerns regarding this decision,” calling it “bizarre and unusual,” and likely unprecedented. He adds:

A study was produced and went through the peer-review process. It was published and led to substantial discussion. The limitations of the study were clearly laid out in the article and were there for any reader and, of course, the editors and reviewers to see. Indeed, I believe that these facts are not in dispute.

There seems to be a serious problem here in that the journal’s editors do not understand how science is carried out and certainly have not followed normal guidelines for the retraction of papers. Empirical science is never definitive (or academic work would one day come to an end). There are greater doubts about some studies than others depending on the nature of the problem and the methodology used in a study. Science progresses through the production of work and then others use better methods, larger samples, different methodologies or different circumstances to produce different results. Debates then ensue and, as a result of this, the nature of problems and the answers to questions becomes clearer. This process of thesis, anti-thesis, synthesis is probably at least 800 years old and applies not just to sciences but to other disciplines.  In this case, of course, a pioneering study was necessary in order to help start the debate – which it has done. The study had its limitations which were clear to the reader and, of course, any journal is free to reject such a study: PLOS ONE chose not to reject it.

Articles should only be retracted if there are problems that have been in some sense concealed or for other reasons of malpractice or where error is discovered. There is no suggestion of any of these issues arising here. Error is not the same as uncertainty due to the limitations of a study and the limitations were expressed in the article itself. For a journal to effectively retrospectively change its peer review decisions is bizarre and it reflects extremely badly on all the editorial processes connected to the journal. No academic could possibly be advised to submit an article to this journal. After all, they could never know if the article really had been accepted. How many years afterwards might it be “unpublished”?

The journal should be aware of how a retraction affects an individual academic. If the journal has come to the conclusion that its review processes were not handled competently, I am sure that I don’t have to point out the ethical flaws in an approach that leads to the consequences of the journal deciding that its processes were inadequate being borne by the author in the form of the kind of public humiliation that a retraction involves – this humiliation arising because retractions imply some kind of malpractice or author failure which has not happened in this case.

This article has, apparently, led to a great deal of discussion. If I were editor of a journal I would be pleased by that and would be welcoming further articles that contributed to the debate and led to the science being furthered.

PLOS told Retraction Watch:

PLOS ONE editors became aware of the concerns about this article when readers posted critical comments on social media and contacted the editorial office. Investigating this case, it became apparent that some of the issues were raised during peer review but were not adequately addressed. We are therefore taking steps to strengthen our editorial processes for manuscripts involving health-related interventions.

Duane Mellor, a nutrition lecturer at Coventry University in the UK, resigned from his position as an academic editor at PLOS ONE after reading the paper. We asked him if the retraction was likely to change his mind.

The reason I resigned was that it was not handled as an intervention study which it clearly is and would have prevented this happening potentially.

It would change my mind, about my resignation, although I have other journal roles now and as such may not have adequate time to do this role.


Tiny implants for cells are functional in vivo

For the first time, researchers have succeeded in integrating artificial organelles into the cells of living zebrafish embryos.

For the first time, an interdisciplinary team from the University of Basel has succeeded in integrating artificial organelles into the cells of living zebrafish embryos. This innovative approach using artificial organelles as cellular implants offers new potential in treating a range of diseases, as the authors report in an article published in Nature Communications.

In the cells of higher organisms, organelles such as the nucleus or mitochondria perform a range of complex functions necessary for life. In the networks of the Swiss Nanoscience Institute and the NCCR “Molecular Systems Engineering”, the group led by Professor Cornelia Palivan from the Department of Chemistry at the University of Basel is working to produce organelles of this kind in the laboratory, to introduce them into cells, and to control their activity in response to the presence of external factors (e.g. change in pH values or reductive conditions).

These cellular implants could, for example, carry enzymes able to convert a pharmaceutical ingredient into the active substance and release it “on demand” under specific conditions. Administering drugs in this way could considerably reduce both the amounts used and the side effects. It would allow treatment to be delivered only when required by changes associated with pathological conditions (e.g., a tumor).

Tiny capsules with an enzymatic cargo

The artificial organelles are based on tiny capsules that form spontaneously in solution from polymers and can enclose various macromolecules such as enzymes. The artificial organelles presented here contained a peroxidase enzyme that only begins to act when specific molecules penetrate the wall of the capsules and support the enzymatic reaction.

To control the passage of substances, the researchers incorporated chemically modified natural membrane proteins into the wall of the capsules. These act as gates that open according to the glutathione concentration in the cell.

At a low glutathione value, the pore of the membrane proteins are “closed” – that is, no substances can pass. If the glutathione concentration rises above a certain threshold, the protein gate opens and substances from outside can pass through the pore into the cavity of the capsule. There, they are converted by the enzyme inside and the product of the reaction can leave the capsule through the open gate.

Also effective in living organisms

In collaboration with the group led by Professor Jörg Huwyler of the Department of Pharmaceutical Sciences at the University of Basel, the artificial organelles have also been studied in vivo. “We’ve now been able to integrate these controllable artificial organelles into the cells of a living organism for the first time,” says Cornelia Palivan.

The researchers chose zebrafish embryos because their transparent bodies allow excellent tracking of the cellular implants under a microscope when they are marked with a fluorescent dye.

After the artificial organelles were injected, they were “eaten” by macrophages and therefore made their way into the organism. The researchers were then able to show that the peroxidase enzyme trapped inside the artificial organelle was activated when hydrogen peroxide produced by the macrophages entered through the protein gates.

“In this study, we showed that the artificial organelles, which are inspired by nature, continue to work as intended in the living organism, and that the protein gate we incorporated not only works in cell cultures but also in vivo,” comments Toma Einfalt, the first author of the article and graduate of the PhD School of the Swiss Nanoscience Institute. The idea of using artificial organelles as cell implants with the potential to produce active pharmaceutical compounds, for example, opens up new perspectives for patient-oriented protein therapy.


Greenland Is Literally Cracking Apart and Flooding the World

Visit Greenland on the right summer day, and you could see a 12-billion-gallon lake disappear before your very eyes.

Glaciologists saw this happen for the first time in 2006, when a 2.2-square-mile (5.6 square kilometers) lake of melted ice drained away into nothing in less than 2 hours. Researchers now see such events as a regular part of Greenland’s increasingly hot summer routine; every year, thousands of temporary lakes pop up on Greenland’s surface as the surrounding ice melts, sit around for a few weeks or months, and then suddenly drain away through cracks in the ice sheet underneath. [Images of Melt: Earth’s Vanishing Ice]

On a recent expedition, however, researchers saw an alarming new pattern behind Greenland’s mysterious disappearing lakes: They’re starting to drain farther and farther inland. According to a new paper published today (March 14) in the journal Nature Communications, that’s because the summer lakes of Greenland drain in a “cascading” chain reaction enabled by a vast, interconnected web of cracks below the ice — and as temperatures climb, the web is getting wider.

Scientists abseil into a fracture in the ice left behind when one of Greenland’s summer lakes rapidly drained.

Credit: Samuel Doyle

“Lakes that drain in one area produce fractures that cause more lakes to drain somewhere elsewhere,” co-author Marion Bougamont, a glaciologist at the University of Cambridge’s Scott Polar Research Institute, said in a statement. “It all adds up when you look at the pathways of water underneath the ice.”

In the new paper, Bougamont and her colleagues used 3D ice-flow models and satellite images of the Greenland Ice Sheet to study this chain reaction. The authors found that when warming weather causes a single lake to drain into the underlying ice sheet, the ice flow below that lake can accelerate dramatically — up to 400 percent faster than in winter months.

As the draining water surges away from the original lake, it can destabilize other nearby ice beds. Fresh cracks form, new lakes drain and the reaction intensifies day by day. In one incident, the researchers observed 124 lakes drain in just five days. Even lakes that formed hundreds of kilometers inland, which were previously thought to be too far removed from the ice bed to drain into it, proved vulnerable to the chain-drain-reaction as new fissures in the ice formed.

This all amounts to billions of gallons of melted ice plunging below Greenland’s surface every few days. Some of this water remains trapped in the ice sheet; much of it pours into the surrounding ocean.

“This ice sheet, which covers 1.7 million square kilometers [650,000 square miles], was relatively stable 25 years ago, but now loses one billion tons [900 million metric tons] of ice every day,” lead author Poul Christoffersen, also from Cambridge’s Scott Polar Research Institute, said in the statement. “This causes one millimeter of global sea level rise per year, a rate which is much faster than what was predicted only a few years ago.”

According to a 2017 report, ice loss in Greenland was responsible for about 25 percent of global sea level rise in 2014 — up from just 5 percent in 1993.

If Greenland melts completely, it could result in a global sea-level rise of about 20 feet (6 meters). According to the Cambridge researchers, a total loss of Greenland’s ice is “extremely unlikely in this century” — but even minor increases in sea level could have severe consequences around the world, the authors noted. According to a recent report from the National Oceanic and Atmospheric Administration (NOAA), if sea levels rise half a meter (1.6 feet) by 2100, many American coastal cities will experience high-tide flooding “every other day” or more.

Source: Live Science.

Impact of HIV-1 Envelope Conformation on ADCC Responses

HIV-1 envelope glycoproteins (Env) represent the only virus-specific antigen exposed at the surface of infected cells. In its unliganded form, Env from primary viruses samples a ‘closed’ conformation (State 1), which is preferentially recognized by broadly neutralizing antibodies (bNAbs). CD4 engagement drives Env into an intermediate ‘partially open’ (State 2) and then into the ‘open’ CD4-bound conformation (State 3). Emerging evidence suggests a link between Env conformation and Ab-dependent cellular cytotoxicity (ADCC). HIV-1-infected cells exposing Env in the CD4-bound conformation are susceptible to ADCC mediated by CD4-induced Abs and HIV + sera. Cells exposing State 1 Env are susceptible to ADCC mediated by bNAbs. Here, we discuss how Env conformation affects ADCC responses and in vitro measurements.


bNAbs preferentially recognize Env in its ‘closed’ conformation, while non-neutralizing CD4-induced Abs target the ‘open’ CD4-bound conformation.

Env tightly controls its transition from the unbound to the CD4-bound conformation to avoid recognition by host CD4-induced Abs.

Nef and Vpu accessory proteins protect HIV-1-infected cells from ADCC by preventing Env–CD4 interactions and by reducing the expression levels of cell surface NKG2D ligands.

Gp120 shed from infected cells binds CD4 on uninfected bystander CD4+ T cells, sensitizing them to ADCC and influencing in vitro ADCC measurements.

Targeting the Env ‘closed’ conformation with bispecific Abs and/or proteins or exposing vulnerable ADCC-mediating epitopes using CD4 mimetics are emerging approaches to eliminate HIV-1-infected cells.

Impact of Antibody-Dependent Cellular Cytotoxicity on HIV-1 Replication and Transmission

HIV-1 continues to infect more than 1,8 million individuals annually, with an estimated total of 36,7 million people living with this virus in 2016i. Enormous effort has been made to improve the clinical management of HIV/AIDS through highly active antiretroviral therapy (HAART). Accordingly, HIV-1 infection can be controlled with HAART and, in most cases, allows for a significant increase in the life expectancy of infected individuals [1. However, viral rebounds can occur upon HAART interruption due to the presence of latent viral reservoirs [23], persisting mainly in long-lived memory CD4+ T cells [4. Efforts to design efficient preventive or curative strategies have yet to produce results in the clinic. Identifying and characterizing the immune functions needed to establish a protective immunity and understanding how the virus responds and protects itself from these immune functions represent a highly complex, multifaceted problem.

At the time of writing, only one anti-HIV-1 vaccine trial, the RV144 Thai trial (see Glossary), has presented a modest (31.2%) efficacy in preventing infection by HIV-1 [5. Interestingly, correlates of protection in this trial suggested that increased ADCCcould be linked with decreased HIV-1 acquisition [6 and Abs with potent ADCC activity were isolated from some RV144 vaccinees [7. ADCC is thought to represent an important immune effector function in the protection and control of different viral infections and could be mediated by natural killer (NK) cells, monocytes/macrophages, or neutrophils [891011]. Decreased viral load, rate of disease progression, and decreased mother–child transmission correlated with Fc-mediated effector functions in HIV-1 and simian immunodeficiency virus (SIV) infections in some [1213141516171819202122], but not in all studies [232425]. Of note, Fc-mediated effector functions appear to be important against not only infected cells, but also free virus [26. While some studies failed to show that passive administration of non-neutralizing Abs (nnAbs) presenting ADCC activity could confer protection against SIV or simian-HIV (SHIV) challenges in macaque models [27282930], a recent study clearly indicated that nnAbs could alter the course of HIV-1 infection in humanized mice [31. Supporting an important role of ADCC in preventing viral transmission, a recent pentavalent HIV-1 vaccine was shown to protect 55% of pentavalent vaccine-immunized rhesus macaques from SHIV challenge. Systems serology of the Ab responses in this study identified ADCC activity as one of the four main immunological parameters able to predict decreased infection risk [32.

Env Conformation

The HIV-1 Env trimer mediates viral entry. HIV-1 Env is formed by three exterior gp120 and three transmembrane gp41 subunits, which are noncovalently associated [333435]. Interaction of gp120 with the CD4 receptor triggers major conformational changes in Env, including movement of the V1/V2 and V3 loops, and formation of the co-receptor binding site (CoRBS) and the bridging sheet [3637383940414243]. CD4 interaction also leads to the exposure of the gp41 helical heptad repeat (HR1) [44. CCR5 or CXCR4 co-receptor interaction with gp120 promotes additional conformational changes in gp41, resulting in the formation of a six-helix bundle formed by HR1 and HR2 heptad repeats and in the fusion of viral and cellular membranes.

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Atacama mummy’s deformities were unduly sensationalized

By analyzing the genome of a tiny fetal mummy known as Ata, researchers have learned more about what led to its strange-looking deformities — and that Ata was not an it, but a she.

The 6-inch human mummy, found in 2003 in Chile’s Atacama Desert, contains genetic mutations associated with skeletal abnormalities and joint problems, researchers report online March 22 in Genome Research. Those mutations help explain how Ata developed her elongated skull, large eye sockets and missing ribs — features that previously sparked suppositions the she was an extraterrestrial.

But Ata’s origins are not out of this world. She is probably of Chilean descent, says geneticist Garry Nolan of Stanford University, who has been the driving force behind examining Ata scientifically.

“I wanted to understand what could make something look like that,” he says. Nolan never claimed Ata was an alien, but he admits to playing a role in the hype surrounding Ata by participating in a documentary that advanced claims about her supposed otherworldly origins. He now says she should be buried as human remains.

Paolo Viscardi, a zoologist at the National Museum of Ireland in Dublin who was not involved with the research, says the new study helps debunk Ata’s origin myths. “Ata highlighted the fact that people are quick to dehumanize and sensationalize anything unusual,” he says.


Exploring the mysteries of Cuba’s coral reefs

Lessons that scientists learn here could help them safeguard other such ‘animal forests’

PLAYA LARGA, Cuba — The Bay of Pigs is surprisingly clear and vividly blue — nothing like its name might suggest. Cuba’s famous bay looks like an artist’s palette — one that stretches toward the horizon. There’s a streak of robin’s-egg blue by the rocky shore. Further out, the water turns turquoise, then navy blue where the seafloor drops down to meet the deeper ocean.

Beneath the surface, bright bursts of other colors come into view. Even in 10 meters (about 33 feet) of water, you can see hills on the sandy bottom. Look closer and you can see that each hill is a clump of fanciful structures in greens, browns, oranges and purples. They resemble piles of boulders topped by tubes, antlers, bushes and fans. They’re coral reefs, or stony ridges made from the external skeletons of millions of tiny marine creatures living together. Fittingly, some scientists call them “animal forests.”

Many of these animal forests around the world are in big trouble. People have harmed some by carelessly climbing on the corals or by catching too many of the fish that keep reefs healthy. Diseases, global warming and fierce storms have battered other reefs. Scientists are especially worried about Australia’s Great Barrier Reef. Unusually warm water there in 2016 killed large sections of the connected corals.

Bay of Pigs
The Bay of Pigs is like an artist’s palette of blues. The darker shapes visible in the water are patch reefs.
Bryn Nelson

Recent research suggests that pollution and warmer waters have raised the risk of mass die-offs in other tropical reefs. Such threats can leave huge dead zones in the water and turn corals a ghostly white. One recent study found that corals off the coast of Panama had been badly damaged within the past decade.

Other researchers have been noting more gradual changes that have taken place over centuries. To do this, they pored over old sailing charts. These charts had warned sailors about the locations of reefs to help prevent shipwrecks.

Looking at those charts now  suggests that the island chain making up the Florida Keys has lost more than half of its corals during the past 240 years. Reefs closest to shore have suffered most.

Most Cuban corals have avoided the same fate. Scientists now want to know why.

Some reefs near Cuba’s coast, like those in the Bay of Pigs, have lost large predators, such as sharks and sea turtles. Even so, they still support communities teeming with colorful medium-sized and smaller fish. Coral hills, called patch reefs, grow closer together. They can rise up to become low mountains. Then they disappear into deepest blue down the ledge.

The United States and Cuba have a troubled past that can be traced in part to this very bay on the island’s southern coast. And their prickly relationship has often made it hard for the two countries’ scientists to work together.

In 1961, about 1,400 exiled Cuban soldiers returned to the Bay of Pigs and tried to invade the country. With support from the United States, they tried to overthrow a new ruler named Fidel Castro. He was a rebel who had seized power and was setting up a form of government known as communism.

The invasion failed. Castro stayed in power. And the United States and Cuba have been at odds ever since.

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Chemists develop new method to identify proteins

Proteins are the worker bees of the cell, mainly ganging up to form macromolecular, multicomponent complexes to perform intricate cellular tasks.

Trying to characterize such  complexes and all of their functions within organisms is a discipline called “proteomics.” Historically, scientists have studied the form and function of proteins by dissolving them with enzymes and sequencing the resulting tiny broken pieces, called peptides. But studying proteins this way causes the loss of a lot of essential information, says Brandon Ruotolo, an associate professor of chemistry at the University of Michigan.

Ruotolo and his team, including researchers from UCLA, University of Leeds and University of Antwerp, have developed a new way to study protein complexes that doesn’t involve destroying the intact assemblies in the process. Their method has been published in the journal Analytical Chemistry.

“Proteins are the main drivers of pretty much every critical cellular process—everything from cell division to cell death,” Ruotolo said. “They also dominate drug targets because of their central importance in the context of life as we know it. Understanding how these proteins work, compositionally, at a very basic level, is very important for understanding how diseases work.”

Both the traditional approach and Ruotolo’s method use a device called a , which measures the weight, or mass, of ionized molecules by drawing the molecules into a vacuum. In the traditional approach, after scientists have broken protein complexes down into peptides, they use a technology called electrospray ionization to give those peptides an electric charge. The mass spectrometer then measures the mass of these charged peptides, and breaks them down further using a background gas.

But using enzymes to digest proteins makes it difficult to understand the role of smaller chemical entities that accumulate on proteins, called post-translational modifications. Each time your cell expresses a protein, it can also produce hundreds of these individual post-translational modification states, collectively termed proteoforms, Ruotolo says.

It is the arrangement of these proteoforms within protein complexes that often determines their function. In traditional approaches to study protein complexes, these proteoforms are lost.

“The main movers and shakers in the cell are not individual proteins running around doing jobs—it’s actually dozens of proteins that come together to form super-molecular complexes that do very complicated jobs in the cell,” Ruotolo said. “Now, the real task is to understand how these big machines work.”

Ruotolo’s team uses electrospray ionization to ionize intact protein complexes. Like the peptides typically analyzed in proteomics studies, these multiprotein complexes can be sequenced by a mass spectrometer, but it is often not possible to sequence anything more than a small fraction of the assembly’s structure. Ruotolo’s team has developed a chemical modification strategy that significantly improves the ability to sequence large, multiprotein complexes directly by mass spectrometry.

“This is important because in the mass spectrometer, you have connectivity between the starting proteoform and the sequence ions,” Ruotolo said. “In the enzymatic digestion, that connectivity is broken.”

In his study, Ruotolo’s team developed their method using three different protein complexes. They hope to adapt their method to be able to study larger protein complexes, many times the size of those in their study.

“I think we’re learning every day that even a class of cancers, like leukemia, is actually composed of many different diseases,” Ruotolo said. “The types of measurements we’re developing will only increase our ability to observe that granularity and provide information that could hopefully inform the ability to discover new therapies.”

The group has also published a paper in Analytical Chemistry detailing software, which was developed in collaboration with researchers in the Department of Computational Medicine and Bioinformatics at U-M. The software is capable of rapidly capturing sequence information from protein complexes.

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U.S. Tuberculosis Cases Are The Lowest In Years, But It’s Still A Threat

The treatable and curable disease is on the rise in New York City, and an alarming number of latent cases are lurking.

The number of tuberculosis cases is at its lowest point since the Centers for Disease Control and Prevention began reporting it in 1953. But the decline is far from enough to eliminate the treatable and curable disease in the U.S. during this century, the agency stressed.

A further dramatic drop in cases will be needed to accelerate efforts to wipe out the disease, and that won’t be possible without marked investment in programs to control TB and tackle latent infections, experts said.
“With better diagnostic tests, shorter treatments, and new guidelines to assist physicians in testing, the United States has a greater opportunity than ever before to eliminate TB in this country,” Dr. Philip LoBue, director of CDC’s Division of Tuberculosis Elimination, told HuffPost in an email. “Though we’ve come a long way, these data are a reminder that we must intensify our efforts and expand a dual approach to put an end to this disease.”

The CDC on Thursday reported that the number of TB cases dropped to 9,093 in 2017, a 1.8 percent decrease from the year before.

However, Donna Wegener, executive director of the National TB Controllers Association, a group of public health officials, said she worries the surveillance data doesn’t tell the full story of TB in the U.S.

“Despite the lower cases reported for 2017, we still have a lot of work to do as any significant number of cases in the U.S. of a disease that is totally preventable and curable should not be tolerated,” Wegener said.

She pointed to the rising number of cases in New York City as particularly alarming, considering the city is recognized for expertise and best practices for fighting TB.

Erica Lessem, deputy executive director of the TB project at advocacy organization Treatment Action Group, said last time cases jumped in New York was the horrific TB outbreak of ’80s and early ’90s that cost the city over $1 billion to control.

Data collected by the group shows that overall federal, state and local funding for New York’s TB efforts has dropped by more than half in inflation-adjusted numbers, to $14.7 million, from $34.3 million in 2007.

“We’re seeing a similar pattern of TB cuts at the federal, state and local levels, and we’re very concerned this is a harbinger of what’s to come,” Lessem said.

Treatment of one case of tuberculosis can cost from $18,000, to over $500,000 for drug-resistant forms of the disease.

The federal omnibus spending deal expected to pass this week contains an added $20 million for U.S. Agency for International Development efforts against TB. It also includes language from Congress asking the Department of Health and Human Services to prioritize the 2016 national action plan for combatting multidrug-resistant TB. However, it fails to include extra funding for CDC efforts against TB.

That flat funding sends a mixed message on fighting TB, Wegener said.

We’ve really exhausted what we can do given the current resources.Donna Wegener, executive director of the National TB Controllers Association

While half of all reported TB cases are in New York, California, Florida and Texas, 19 states saw an uptick in the latest data. Connecticut, Tennessee and Colorado show significant rises.

According to the CDC’s LoBue, reactivation of latent TB infection is the “primary driver of TB cases in the United States.”

About 13 million people in the U.S. have latent tuberculosis, the nonactive form of the disease. The CDC has called the number of infectious TB cases in the U.S. the “tip of the iceberg,” as some 5 percent to 10 percent of people with latent TB will progress to active tuberculosis. That means as many as 1.3 million cases of infectious tuberculosis could become activate in the U.S. over the lifetimes of people with latent TB.

Wegener warned that without more proactive treatment of TB ― screening through local health care providers, increased education and other outreach ― that reservoir of lurking TB could cause future case numbers to increase.

“We have the ability to be one of the first countries to eliminate TB,” Wegener said. “But we’ve really exhausted what we can do given the current resources.”

CORRECTIONS: This article previously misstated the percentage decrease in TB cases last year, due to an error on the CDC’s fact sheet, and misspelled Erica Lessem’s last name.