espresso machines

An espresso machine brews coffee by forcing pressurized water near boiling point through a "puck" of ground coffee and a filter in order to produce a thick, concentrated coffee called espresso. The first machine for making espresso was built and patented in 1884 by Angelo Moriondo of Turin, Italy. An improved design was patented on April 28, 1903, by Luigi Bezzera. The founder of the La Pavoni company bought the patent and from 1905 produced espresso machines commercially on a small scale in Milan. Multiple machine designs have been created to produce espresso. Several machines share some common elements, such as a grouphead and a portafilter. An espresso machine may also have a steam wand which is used to steam and froth liquids (such as milk) for coffee drinks such as cappuccino and caffe latte. Espresso machines may be steam-driven, piston-driven, pump-driven, or air-pump-driven. Machines may also be manual or automatic.

Geologists determine early Earth was a 'water world' by studying exposed ocean crust

Ocean panorama (stock image).

The Earth of 3.2 billion years ago was a "water world" of submerged continents, geologists say after analyzing oxygen isotope data from ancient ocean crust that's now exposed on land in Australia.

And that could have major implications on the origin of life.

"An early Earth without emergent continents may have resembled a 'water world,' providing an important environmental constraint on the origin and evolution of life on Earth as well as its possible existence elsewhere," geologists Benjamin Johnson and Boswell Wing wrote in a paper just published online by the journal Nature Geoscience.

Johnson is an assistant professor of geological and atmospheric sciences at Iowa State University and a recent postdoctoral research associate at the University of Colorado Boulder. Wing is an associate professor of geological sciences at Colorado. Grants from the National Science Foundation supported their study and a Lewis and Clark Grant from the American Philosophical Society supported Johnson's fieldwork in Australia.

Johnson said his work on the project started when he talked with Wing at conferences and learned about the well-preserved, 3.2-billion-year-old ocean crust from the Archaean eon (4 billion to 2.5 billion years ago) in a remote part of the state of Western Australia. Previous studies meant there was already a big library of geochemical data from the site.

Johnson joined Wing's research group and went to see ocean crust for himself -- a 2018 trip involving a flight to Perth and a 17-hour drive north to the coastal region near Port Hedland.

After taking his own rock samples and digging into the library of existing data, Johnson created a cross-section grid of the oxygen isotope and temperature values found in the rock.

(Isotopes are atoms of a chemical element with the same number of protons within the nucleus, but differing numbers of neutrons. In this case, differences in oxygen isotopes preserved with the ancient rock provide clues about the interaction of rock and water billions of years ago.)

Once he had two-dimensional grids based on whole-rock data, Johnson created an inverse model to come up with estimates of the oxygen isotopes within the ancient oceans. The result: Ancient seawater was enriched with about 4 parts per thousand more of a heavy isotope of oxygen (oxygen with eight protons and 10 neutrons, written as 18O) than an ice-free ocean of today.

How to explain that decrease in heavy isotopes over time?

Johnson and Wing suggest two possible ways: Water cycling through the ancient ocean crust was different than today's seawater with a lot more high-temperature interactions that could have enriched the ocean with the heavy isotopes of oxygen. Or, water cycling from continental rock could have reduced the percentage of heavy isotopes in ocean water.

"Our preferred hypothesis -- and in some ways the simplest -- is that continental weathering from land began sometime after 3.2 billion years ago and began to draw down the amount of heavy isotopes in the ocean," Johnson said.

The idea that water cycling through ocean crust in a way distinct from how it happens today, causing the difference in isotope composition "is not supported by the rocks," Johnson said. "The 3.2-billion-year-old section of ocean crust we studied looks exactly like much, much younger ocean crust."

Johnson said the study demonstrates that geologists can build models and find new, quantitative ways to solve a problem -- even when that problem involves seawater from 3.2 billion years ago that they'll never see or sample.

And, Johnson said these models inform us about the environment where life originated and evolved: "Without continents and land above sea level, the only place for the very first ecosystems to evolve would have been in the ocean."

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Story Source:

Materials provided by Iowa State University. Note: Content may be edited for style and length.

Geologists determine early Earth was a 'water world' by studying exposed ocean crust

Ocean panorama (stock image).

The Earth of 3.2 billion years ago was a "water world" of submerged continents, geologists say after analyzing oxygen isotope data from ancient ocean crust that's now exposed on land in Australia.

And that could have major implications on the origin of life.

"An early Earth without emergent continents may have resembled a 'water world,' providing an important environmental constraint on the origin and evolution of life on Earth as well as its possible existence elsewhere," geologists Benjamin Johnson and Boswell Wing wrote in a paper just published online by the journal Nature Geoscience.

Johnson is an assistant professor of geological and atmospheric sciences at Iowa State University and a recent postdoctoral research associate at the University of Colorado Boulder. Wing is an associate professor of geological sciences at Colorado. Grants from the National Science Foundation supported their study and a Lewis and Clark Grant from the American Philosophical Society supported Johnson's fieldwork in Australia.

Johnson said his work on the project started when he talked with Wing at conferences and learned about the well-preserved, 3.2-billion-year-old ocean crust from the Archaean eon (4 billion to 2.5 billion years ago) in a remote part of the state of Western Australia. Previous studies meant there was already a big library of geochemical data from the site.

Johnson joined Wing's research group and went to see ocean crust for himself -- a 2018 trip involving a flight to Perth and a 17-hour drive north to the coastal region near Port Hedland.

After taking his own rock samples and digging into the library of existing data, Johnson created a cross-section grid of the oxygen isotope and temperature values found in the rock.

(Isotopes are atoms of a chemical element with the same number of protons within the nucleus, but differing numbers of neutrons. In this case, differences in oxygen isotopes preserved with the ancient rock provide clues about the interaction of rock and water billions of years ago.)

Once he had two-dimensional grids based on whole-rock data, Johnson created an inverse model to come up with estimates of the oxygen isotopes within the ancient oceans. The result: Ancient seawater was enriched with about 4 parts per thousand more of a heavy isotope of oxygen (oxygen with eight protons and 10 neutrons, written as 18O) than an ice-free ocean of today.

How to explain that decrease in heavy isotopes over time?

Johnson and Wing suggest two possible ways: Water cycling through the ancient ocean crust was different than today's seawater with a lot more high-temperature interactions that could have enriched the ocean with the heavy isotopes of oxygen. Or, water cycling from continental rock could have reduced the percentage of heavy isotopes in ocean water.

"Our preferred hypothesis -- and in some ways the simplest -- is that continental weathering from land began sometime after 3.2 billion years ago and began to draw down the amount of heavy isotopes in the ocean," Johnson said.

The idea that water cycling through ocean crust in a way distinct from how it happens today, causing the difference in isotope composition "is not supported by the rocks," Johnson said. "The 3.2-billion-year-old section of ocean crust we studied looks exactly like much, much younger ocean crust."

Johnson said the study demonstrates that geologists can build models and find new, quantitative ways to solve a problem -- even when that problem involves seawater from 3.2 billion years ago that they'll never see or sample.

And, Johnson said these models inform us about the environment where life originated and evolved: "Without continents and land above sea level, the only place for the very first ecosystems to evolve would have been in the ocean."

---

Story Source:

Materials provided by Iowa State University. Note: Content may be edited for style and length.

Cancer mortality continues steady decline, driven by progress against lung cancer

Medical report (stock image).

The cancer death rate declined by 29% from 1991 to 2017, including a 2.2% drop from 2016 to 2017, the largest single-year drop in cancer mortality ever reported. The news comes from Cancer Statistics, 2020, the latest edition of the American Cancer Society's annual report on cancer rates and trends.

The steady 26-year decline in overall cancer mortality is driven by long-term drops in death rates for the four major cancers -- lung, colorectal, breast, and prostate, although recent trends are mixed. The pace of mortality reductions for lung cancer -- the leading cause of cancer death -- accelerated in recent years (from 2% per year to 4% overall) spurring the record one-year drop in overall cancer mortality. In contrast, progress slowed for colorectal, breast, and prostate cancers. The article appears early online in CA: A Cancer Journal for Clinicians, and is accompanied by a consumer version, Cancer Facts & Figures 2020.

Overall cancer death rates dropped by an average of 1.5% per year during the most recent decade of data (2008-2017), continuing a trend that began in the early 1990s and resulting in the 29% drop in cancer mortality in that time. The drop translates to approximately 2.9 million fewer cancer deaths than would have occurred had mortality rates remained at their peak. Continuing declines in cancer mortality contrast with a stable trend for all other causes of death combined, reflecting a slowing decline for heart disease, stabilizing rates for cerebrovascular disease, and an increasing trend for accidents and Alzheimer disease.

Lung cancer death rates have dropped by 51% (since 1990) in men and by 26% (since 2002) in women, with the most rapid progress in recent years. For example, reductions in mortality accelerated from 3% per year during 2008-2013 to 5% per year during 2013-2017 in men and from 2% to almost 4% in women. However, lung cancer still accounts for almost one-quarter of all cancer deaths, more than breast, prostate, and colorectal cancers combined.

The most rapid declines in mortality occurred for melanoma of the skin, on the heels of breakthrough treatments approved in 2011 that pushed one-year survival for patients diagnosed with metastatic disease from 42% during 2008-2010 to 55% during 2013-2015. This progress is likewise reflected in the overall melanoma death rate, which dropped by 7% per year during 2013-2017 in people ages 20 to 64, compared to declines during 2006-2010 (prior to FDA approval of ipilimumab and vemurafenib) of 2%-3% per year in those ages 20 to 49 and 1% per year in those ages 50 to 64. Even more striking are the mortality declines of 5% to 6% in individuals 65 and older, among whom rates were previously increasing.

"The news this year is mixed," said Rebecca Siegel, MPH, lead author of the report. "The exciting gains in reducing mortality for melanoma and lung cancer are tempered by slowing progress for colorectal, breast, and prostate cancers, which are amenable to early detection. It's a reminder that increasing our investment in the equitable application of existing cancer control interventions, as well as basic and clinical research to further advance treatment, would undoubtedly accelerate progress against cancer."

Highlights from the report:

• The death rate for breast cancer dropped by 40% from 1989 to 2017.
• The death rate for prostate cancer dropped by 52% from 1993 to 2017.
• The death rate for colorectal cancer dropped by 53% from 1980 to 2017 among males and by 57% from 1969 to 2017 among females.
• Decades-long rapid increases in liver cancer mortality appear to be abating in both men and women.
• Cervical cancer, which is almost completely preventable, caused ten premature deaths per week in women ages 20-39 in 2017.

Other highlights:

• In 2020, 1,806,590 new cancer cases and 606,520 cancer deaths are projected to occur in the United States.*
• Progress for hematopoietic and lymphoid malignancies (leukemias and lymphomas) has been especially rapid due to improvements in treatment protocols, including the development of targeted therapies. The 5-year relative survival rate for chronic myeloid leukemia increased from 22% in the mid-1970s to 70% for those diagnosed during 2009 through 2015, and most patients treated with tyrosine kinase inhibitors now experience nearly normal life expectancy.
• The overall cancer incidence rate in men declined rapidly from 2007 to 2014, but stabilized through 2016, reflecting slowing declines for colorectal cancer and stabilizing rates for prostate cancer.
• The overall cancer incidence rate in women has remained generally stable over the past few decades because lung cancer declines have been offset by a tapering decline for colorectal cancer and increasing or stable rates for other common cancers in women.
• The slight rise in breast cancer incidence rates (by approximately 0.3% per year) since 2004 has been attributed at least in part to continued declines in the fertility rate and increased obesity, factors that may also contribute to increasing incidence for uterine cancer (1.3% per year from 2007-2016).
• Lung cancer incidence continues to decline twice as fast in men as in women, reflecting historical differences in tobacco uptake and cessation.
• In contrast, colorectal cancer incidence patterns are generally similar in men and women, with the rapid declines noted during the 2000s in the wake of widespread colonoscopy uptake appearing to taper in more recent years.
• Incidence continues to increase for cancers of the kidney, pancreas, liver, and oral cavity and pharynx (among non-Hispanic whites) and melanoma of the skin. Liver cancer is increasing most rapidly, by 2% to 3% annually during 2007 through 2016, although the pace has slowed from previous years.
• The 5-year relative survival rate for all cancers combined diagnosed during 2009 through 2015 was 67% overall, 68% in whites, and 62% in blacks.
• Cancer survival has improved since the mid-1970s for all of the most common cancers except cervical and uterine cancers. Stagnant survival rates for these cancers largely reflect a lack of major treatment advances for patients with recurrent and metastatic disease.

"The accelerated drops in lung cancer mortality as well as in melanoma that we're seeing are likely due at least in part to advances in cancer treatment over the past decade, such as immunotherapy," said William G. Cance, M.D., chief medical and scientific officer for the American Cancer Society. "They are a profound reminder of how rapidly this area of research is expanding, and now leading to real hope for cancer patients."

Note:

*Estimates should not be compared year-to year. They are based on computer models of cancer trends and population and may vary considerably. Cancer trends should be based on age-adjusted cancer incidence and death rates (expressed as the number of cancer deaths per 100,000 people).

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Story Source:

Materials provided by American Cancer Society. Note: Content may be edited for style and length.

Pathways that extend lifespan by 500 percent identified

Caenorhabditis elegans (stock image).

Scientists at the MDI Biological Laboratory, in collaboration with scientists from the Buck Institute for Research on Aging in Novato, Calif., and Nanjing University in China, have identified synergistic cellular pathways for longevity that amplify lifespan fivefold in C. elegans, a nematode worm used as a model in aging research.

The increase in lifespan would be the equivalent of a human living for 400 or 500 years, according to one of the scientists.

The research draws on the discovery of two major pathways governing aging in C. elegans, which is a popular model in aging research because it shares many of its genes with humans and because its short lifespan of only three to four weeks allows scientists to quickly assess the effects of genetic and environmental interventions to extend healthy lifespan.

Because these pathways are "conserved," meaning that they have been passed down to humans through evolution, they have been the subject of intensive research. A number of drugs that extend healthy lifespan by altering these pathways are now under development. The discovery of the synergistic effect opens the door to even more effective anti-aging therapies.

The new research uses a double mutant in which the insulin signaling (IIS) and TOR pathways have been genetically altered. Because alteration of the IIS pathways yields a 100 percent increase in lifespan and alteration of the TOR pathway yields a 30 percent increase, the double mutant would be expected to live 130 percent longer. But instead, its lifespan was amplified by 500 percent.

"Despite the discovery in C. elegans of cellular pathways that govern aging, it hasn't been clear how these pathways interact," said Hermann Haller, M.D., president of the MDI Biological Laboratory. "By helping to characterize these interactions, our scientists are paving the way for much-needed therapies to increase healthy lifespan for a rapidly aging population."

The elucidation of the cellular mechanisms controlling the synergistic response is the subject of a recent paper in the online journal Cell Reports entitled "Translational Regulation of Non-autonomous Mitochondrial Stress Response Promotes Longevity." The authors include Jarod A. Rollins, Ph.D., and Aric N. Rogers, Ph.D., of the MDI Biological Laboratory.

"The synergistic extension is really wild," said Rollins, who is the lead author with Jianfeng Lan, Ph.D., of Nanjing University. "The effect isn't one plus one equals two, it's one plus one equals five. Our findings demonstrate that nothing in nature exists in a vacuum; in order to develop the most effective anti-aging treatments we have to look at longevity networks rather than individual pathways."

The discovery of the synergistic interaction could lead to the use of combination therapies, each affecting a different pathway, to extend healthy human lifespan in the same way that combination therapies are used to treat cancer and HIV, Pankaj Kapahi, Ph.D., of the Buck Institute, has said. Kapahi is a corresponding author of the paper with Rogers and Di Chen, Ph.D., of Nanjing University.

The synergistic interaction may also may explain why scientists have been unable to identify a single gene responsible for the ability of some people to live to extraordinary old ages free of major age-related diseases until shortly before their deaths.

The paper focuses on how longevity is regulated in the mitochondria, which are the organelles in the cell responsible for energy homeostasis. Over the last decade, accumulating evidence has suggested a causative link between mitochondrial dysregulation and aging. Rollins' future research will focus on the further elucidation of the role of mitochondria in aging, he said.

The research was conducted at the MDI Biological Laboratory and Nanjing University using information from double mutants developed by Kapahi. Rollins' and Rogers' work was supported by the National Institutes of Health (AG056743), the Morris Scientific Discovery Fund and the National Institute of General Medical Sciences (P20GM103423 and P20GM104318).

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Story Source:

Materials provided by Mount Desert Island Biological Laboratory. Note: Content may be edited for style and length.

Pathways that extend lifespan by 500 percent identified

Caenorhabditis elegans (stock image).

Scientists at the MDI Biological Laboratory, in collaboration with scientists from the Buck Institute for Research on Aging in Novato, Calif., and Nanjing University in China, have identified synergistic cellular pathways for longevity that amplify lifespan fivefold in C. elegans, a nematode worm used as a model in aging research.

The increase in lifespan would be the equivalent of a human living for 400 or 500 years, according to one of the scientists.

The research draws on the discovery of two major pathways governing aging in C. elegans, which is a popular model in aging research because it shares many of its genes with humans and because its short lifespan of only three to four weeks allows scientists to quickly assess the effects of genetic and environmental interventions to extend healthy lifespan.

Because these pathways are "conserved," meaning that they have been passed down to humans through evolution, they have been the subject of intensive research. A number of drugs that extend healthy lifespan by altering these pathways are now under development. The discovery of the synergistic effect opens the door to even more effective anti-aging therapies.

The new research uses a double mutant in which the insulin signaling (IIS) and TOR pathways have been genetically altered. Because alteration of the IIS pathways yields a 100 percent increase in lifespan and alteration of the TOR pathway yields a 30 percent increase, the double mutant would be expected to live 130 percent longer. But instead, its lifespan was amplified by 500 percent.

"Despite the discovery in C. elegans of cellular pathways that govern aging, it hasn't been clear how these pathways interact," said Hermann Haller, M.D., president of the MDI Biological Laboratory. "By helping to characterize these interactions, our scientists are paving the way for much-needed therapies to increase healthy lifespan for a rapidly aging population."

The elucidation of the cellular mechanisms controlling the synergistic response is the subject of a recent paper in the online journal Cell Reports entitled "Translational Regulation of Non-autonomous Mitochondrial Stress Response Promotes Longevity." The authors include Jarod A. Rollins, Ph.D., and Aric N. Rogers, Ph.D., of the MDI Biological Laboratory.

"The synergistic extension is really wild," said Rollins, who is the lead author with Jianfeng Lan, Ph.D., of Nanjing University. "The effect isn't one plus one equals two, it's one plus one equals five. Our findings demonstrate that nothing in nature exists in a vacuum; in order to develop the most effective anti-aging treatments we have to look at longevity networks rather than individual pathways."

The discovery of the synergistic interaction could lead to the use of combination therapies, each affecting a different pathway, to extend healthy human lifespan in the same way that combination therapies are used to treat cancer and HIV, Pankaj Kapahi, Ph.D., of the Buck Institute, has said. Kapahi is a corresponding author of the paper with Rogers and Di Chen, Ph.D., of Nanjing University.

The synergistic interaction may also may explain why scientists have been unable to identify a single gene responsible for the ability of some people to live to extraordinary old ages free of major age-related diseases until shortly before their deaths.

The paper focuses on how longevity is regulated in the mitochondria, which are the organelles in the cell responsible for energy homeostasis. Over the last decade, accumulating evidence has suggested a causative link between mitochondrial dysregulation and aging. Rollins' future research will focus on the further elucidation of the role of mitochondria in aging, he said.

The research was conducted at the MDI Biological Laboratory and Nanjing University using information from double mutants developed by Kapahi. Rollins' and Rogers' work was supported by the National Institutes of Health (AG056743), the Morris Scientific Discovery Fund and the National Institute of General Medical Sciences (P20GM103423 and P20GM104318).

---

Story Source:

Materials provided by Mount Desert Island Biological Laboratory. Note: Content may be edited for style and length.

Deadly 'superbugs' destroyed by molecular drills

Klebsiella bacteria illustration (stock image).

Molecular drills have gained the ability to target and destroy deadly bacteria that have evolved resistance to nearly all antibiotics. In some cases, the drills make the antibiotics effective once again.

Researchers at Rice University, Texas A&M University, Biola University and Durham (U.K.) University showed that motorized molecules developed in the Rice lab of chemist James Tour are effective at killing antibiotic-resistant microbes within minutes.

"These superbugs could kill 10 million people a year by 2050, way overtaking cancer," Tour said. "These are nightmare bacteria; they don't respond to anything."

The motors target the bacteria and, once activated with light, burrow through their exteriors.

While bacteria can evolve to resist antibiotics by locking the antibiotics out, the bacteria have no defense against molecular drills. Antibiotics able to get through openings made by the drills are once again lethal to the bacteria.

The researchers reported their results in the American Chemical Society journal ACS Nano.

Tour and Robert Pal, a Royal Society University Research Fellow at Durham and co-author of the new paper, introduced the molecular drills for boring through cells in 2017. The drills are paddlelike molecules that can be prompted to spin at 3 million rotations per second when activated with light.

Tests by the Texas A&M lab of lead scientist Jeffrey Cirillo and former Rice researcher Richard Gunasekera, now at at Biola, effectively killed Klebsiella pneumoniae within minutes. Microscopic images of targeted bacteria showed where motors had drilled through cell walls.

"Bacteria don't just have a lipid bilayer," Tour said. "They have two bilayers and proteins with sugars that interlink them, so things don't normally get through these very robust cell walls. That's why these bacteria are so hard to kill. But they have no way to defend against a machine like these molecular drills, since this is a mechanical action and not a chemical effect."

The motors also increased the susceptibility of K. pneumonia to meropenem, an antibacterial drug to which the bacteria had developed resistance. "Sometimes, when the bacteria figures out a drug, it doesn't let it in," Tour said. "Other times, bacteria defeat the drug by letting it in and deactivating it."

He said meropenem is an example of the former. "Now we can get it through the cell wall," Tour said. "This can breathe new life into ineffective antibiotics by using them in combination with the molecular drills."

Gunasekera said bacterial colonies targeted with a small concentration of nanomachines alone killed up to 17% of cells, but that increased to 65% with the addition of meropenem. After further balancing motors and the antibiotic, the researchers were able to kill 94% of the pneumonia-causing pathogen.

Tour said the nanomachines may see their most immediate impact in treating skin, wound, catheter or implant infections caused by bacteria -- like staphylococcus aureus MRSA, klebsiella or pseudomonas -- and intestinal infections. "On the skin, in the lungs or in the GI tract, wherever we can introduce a light source, we can attack these bacteria," he said. "Or one could have the blood flow through a light-containing external box and then back into the body to kill blood-borne bacteria."

"We are very much interested in treating wound and implant infections initially," Cirillo said. "But we have ways to deliver these wavelengths of light to lung infections that cause numerous mortalities from pneumonia, cystic fibrosis and tuberculosis, so we will also be developing respiratory infection treatments."

Gunasekera noted bladder-borne bacteria that cause urinary tract infections may also be targeted.

The paper is one of two published by the Tour lab this week that advance the ability of microscopic nanomachines to treat disease. In the other, which appears in ACS Applied Materials Interfaces, researchers at Rice and the University of Texas MD Anderson Cancer Center targeted and attacked lab samples of pancreatic cancer cells with machines that respond to visible rather than the previously used ultraviolet light. "This is another big advance, since visible light will not cause as much damage to the surrounding cells," Tour said.

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Story Source:

Materials provided by Rice University. Original written by Mike Williams. Note: Content may be edited for style and length.

Deadly 'superbugs' destroyed by molecular drills

Klebsiella bacteria illustration (stock image).

Credit: © Kateryna_Kon / Adobe Stock

Molecular drills have gained the ability to target and destroy deadly bacteria that have evolved resistance to nearly all antibiotics. In some cases, the drills make the antibiotics effective once again.

Researchers at Rice University, Texas A&M University, Biola University and Durham (U.K.) University showed that motorized molecules developed in the Rice lab of chemist James Tour are effective at killing antibiotic-resistant microbes within minutes.

"These superbugs could kill 10 million people a year by 2050, way overtaking cancer," Tour said. "These are nightmare bacteria; they don't respond to anything."

The motors target the bacteria and, once activated with light, burrow through their exteriors.

While bacteria can evolve to resist antibiotics by locking the antibiotics out, the bacteria have no defense against molecular drills. Antibiotics able to get through openings made by the drills are once again lethal to the bacteria.

The researchers reported their results in the American Chemical Society journal ACS Nano.

Tour and Robert Pal, a Royal Society University Research Fellow at Durham and co-author of the new paper, introduced the molecular drills for boring through cells in 2017. The drills are paddlelike molecules that can be prompted to spin at 3 million rotations per second when activated with light.

Tests by the Texas A&M lab of lead scientist Jeffrey Cirillo and former Rice researcher Richard Gunasekera, now at at Biola, effectively killed Klebsiella pneumoniae within minutes. Microscopic images of targeted bacteria showed where motors had drilled through cell walls.

"Bacteria don't just have a lipid bilayer," Tour said. "They have two bilayers and proteins with sugars that interlink them, so things don't normally get through these very robust cell walls. That's why these bacteria are so hard to kill. But they have no way to defend against a machine like these molecular drills, since this is a mechanical action and not a chemical effect."

The motors also increased the susceptibility of K. pneumonia to meropenem, an antibacterial drug to which the bacteria had developed resistance. "Sometimes, when the bacteria figures out a drug, it doesn't let it in," Tour said. "Other times, bacteria defeat the drug by letting it in and deactivating it."

He said meropenem is an example of the former. "Now we can get it through the cell wall," Tour said. "This can breathe new life into ineffective antibiotics by using them in combination with the molecular drills."

Gunasekera said bacterial colonies targeted with a small concentration of nanomachines alone killed up to 17% of cells, but that increased to 65% with the addition of meropenem. After further balancing motors and the antibiotic, the researchers were able to kill 94% of the pneumonia-causing pathogen.

Tour said the nanomachines may see their most immediate impact in treating skin, wound, catheter or implant infections caused by bacteria -- like staphylococcus aureus MRSA, klebsiella or pseudomonas -- and intestinal infections. "On the skin, in the lungs or in the GI tract, wherever we can introduce a light source, we can attack these bacteria," he said. "Or one could have the blood flow through a light-containing external box and then back into the body to kill blood-borne bacteria."

"We are very much interested in treating wound and implant infections initially," Cirillo said. "But we have ways to deliver these wavelengths of light to lung infections that cause numerous mortalities from pneumonia, cystic fibrosis and tuberculosis, so we will also be developing respiratory infection treatments."

Gunasekera noted bladder-borne bacteria that cause urinary tract infections may also be targeted.

The paper is one of two published by the Tour lab this week that advance the ability of microscopic nanomachines to treat disease. In the other, which appears in ACS Applied Materials Interfaces, researchers at Rice and the University of Texas MD Anderson Cancer Center targeted and attacked lab samples of pancreatic cancer cells with machines that respond to visible rather than the previously used ultraviolet light. "This is another big advance, since visible light will not cause as much damage to the surrounding cells," Tour said.

---

Story Source:

Materials provided by Rice University. Original written by Mike Williams. Note: Content may be edited for style and length.

Researchers determine age for last known settlement by a direct ancestor to modern humans

Homo erectus skull (stock image).

Credit: © stockdevil / Adobe Stock

Homo erectus, one of modern humans' direct ancestors, was a wandering bunch. After the species dispersed from Africa about two million years ago, it colonized the ancient world, which included Asia and possibly Europe.

But about 400,000 years ago, Homo erectus essentially vanished. The lone exception was a spot called Ngandong, on the Indonesian island of Java. But scientists were unable to agree on a precise time period for the site -- until now.

In a new study published in the journal Nature, an international team of researchers led by the University of Iowa; Macquarie University; and the Institute of Technology Bandung, Indonesia, dates the last existence of Homo erectus at Ngandong between 108,000 and 117,000 years ago.

The researchers time-stamped the site by dating animal fossils from the same bonebed where 12 Homo erectus skull caps and two tibia had been found, and then dated the surrounding land forms -- mostly terraces below and above Ngandong -- to establish an accurate record for the primeval humans' possible last stand on Earth.

"This site is the last known appearance of Homo erectus found anywhere in the world," says Russell Ciochon, professor in the Department of Anthropology at Iowa and co-corresponding author on the study. "We can't say we dated the extinction, but we dated the last occurrence of it. We have no evidence Homo erectus lived later than that anywhere else."

The research team presents 52 new age estimates for the Ngandong evidence. They include animal fossil fragments and sediment from the rediscovered fossil bed where the original Homo erectus remains were found by Dutch surveyors in the 1930s, and a sequence of dates for the river terraces below and above the fossil site.

In addition, the researchers determined when mountains south of Ngandong first rose by dating stalagmites from caves in the Southern Mountains. This allowed them to determine when the Solo River began coursing through the Ngandong site, and the river terrace sequence was created.

"You have this incredible array of dates that are all consistent," Ciochon says. "This has to be the right range. That's why it's such a nice, tight paper. The dating is very consistent."

"The issues with the dating of Ngandong could only ever be resolved by an appreciation of the wider landscape," says Kira Westaway, associate professor at Macquarie University and a joint-lead author on the paper. "Fossils are the byproducts of complex landscape processes. We were able to nail the age of the site because we constrained the fossils within the river deposit, the river terrace, the sequence of terraces, and the volcanically active landscape."

Previous research by Ciochon and others shows Homo erectus hopscotched its way across the Indonesian archipelago, and arrived on the island of Java about 1.6 million years ago. The timing was good: The area around Ngandong was mostly grassland, the same environment that cradled the species in Africa. Plants and animals were abundant. While the species continued to venture to other islands, Java, it appears, likely remained home -- or least a way station -- to some bands of the species.

However, around 130,000 years ago, the environment at Ngandong changed, and so did Homo erectus's fortunes.

"There was a change in climate," Ciochon explains. "We know the fauna changed from open country, grassland, to a tropical rainforest (extending southward from today's Malaysia). Those were not the plants and animals that Homo erectus was used to, and the species just could not adapt."

Ciochon co-led a 12-member, international team that dug at Ngandong in 2008 and in 2010, accompanied by Yan Rizal and Yahdi Zaim, the lead researchers from the Institute of Technology, Bandung, on the excavation. Using notes from the Dutch surveyors' excavation in the 1930s, the team found the original Homo erectus bone bed at Ngandong and re-exposed it, collecting and dating 867 animal fossil fragments. Meanwhile, Westaway's team had been dating the surrounding landscapes, such as the terraces, during that time.

"It was coincidental" the teams were working in the same place -- one group at the fossil bed, the other group dating the surrounding area, Ciochon says.

"With the data we had, we couldn't really date the Ngandong fossils," Ciochon continues. "We had dates on them, but they were minimum ages. So, we couldn't really say how old, although we knew we were in the ballpark. By working with Kira, who had vast amount of dating data for the terraces, mountains, and other landscape features, we were able to provide precise regional chronological and geomorphic contexts for the Ngandong site."

Researchers from multiple institutions contributed to the manuscript, including those from the Institute of Technology in Bandung, Indonesia; the University of Wollongong, Australia; the University of Texas-Austin; Griffith University in Nathan, Australia; Southern Cross University in Lismore, Australia; the University of Oxford, United Kingdom; the Geological Agency in Bandung; the University of Queensland in Brisbane Australia; the University of New England in Armidale, Australia; the University of Copenhagen in Denmark; Minnesota State University-Mankato; Bluestone Heights in Cleveland, Ohio; the University of Alberta in Edmonton, Canada; Rutgers University; Indiana University; and Illinois State University.

Rizal is a joint-lead author on the paper. E. Arthur Bettis III, emeritus professor in the Department of Earth and Environmental Sciences at Iowa, is a contributing author.

Funders include the University of Iowa, the Australian Research Council, the Wenner-Gren Foundation for Anthropological Research, the Geological Survey Institute in Bandung, and the Villum Foundation.

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Materials provided by University of Iowa. Original written by Richard C. Lewis. Note: Content may be edited for style and length.

By targeting flu-enabling protein, antibody may protect against wide-ranging strains

Influenza virus illustration

A nationwide team of researchers has found an antibody that protects mice against a wide range of potentially lethal influenza viruses, advancing efforts to design of a universal vaccine that could either treat or protect people against all strains of the virus.

The study, which Scripps Research conducted jointly with Washington University School of Medicine in St. Louis and Icahn School of Medicine at Mount Sinai in New York, points to a new approach to tackle severe cases of the flu, including pandemics. The research is published in the Oct. 25 issue of Science.

Scripps Research's Ian Wilson, DPhil, one of three senior co-authors, says the antibody at the center of the study binds to a protein called neuraminidase, which is essential for the flu virus to replicate in the body.

The protein, located on the surface of the virus, enables infected host cells to release the virus so it can spread to other cells. Tamiflu, the most widely used drug for severe flu infection, works by inactivating neuraminidase. However, many forms of neuraminidase exist, depending on the flu strain, and such drugs aren't always effective -- particularly as resistance to the drugs is developing.

"There are many strains of influenza virus that circulate so every year we have to design and produce a new vaccine to match the most common strains of that year," says co-senior author Ali Ellebedy, PhD, an assistant professor of pathology and immunology at Washington University. "Now imagine if we could have one vaccine that protected against all influenza strains, including human, swine and other highly lethal avian influenza viruses. This antibody could be the key to design of a truly universal vaccine."

Ellebedy discovered the antibody -- an immune molecule that recognizes and attaches to a foreign molecule -- in blood taken from a patient hospitalized with flu at Barnes-Jewish Hospital in St. Louis in the winter of 2017.

Ellebedy was working on a study analyzing the immune response to flu infection in humans in collaboration with the Washington University Emergency Care and Research Core, which was sending him blood samples from consenting flu patients. He quickly noticed that a particular blood sample was unusual: In addition to containing antibodies against hemagglutinin, the major protein on the surface of the virus, it contained other antibodies that were clearly targeting something else.

"At the time we were just starting, and I was setting up my lab so we didn't have the tools to look at what else the antibodies could be targeting," says Ellebedy, an assistant professor of medicine and of molecular microbiology.

He sent three of the antibodies to co-senior author Florian Krammer, PhD, a microbiology professor at the Icahn School of Medicine at Mount Sinai. An expert on neuraminidase, Krammer tested the antibodies against his extensive library of neuraminidase proteins. At least one of the three antibodies blocked neuraminidase activity in all known types of neuraminidase in flu viruses, representing a variety of human and nonhuman strains.

"The breadth of the antibodies really came as a surprise to us," says Krammer. "Typically, anti-neuraminidase antibodies can be broad within a subtype, like H1N1, but an antibody with potent activity across subtypes was unheard of. At first, we did not believe our results. Especially the ability of the antibodies to cross between influenza A and influenza B viruses is just mind-boggling. It is amazing what the human immune system is capable of if presented with the right antigens."

To find out whether the antibodies could be used to treat severe cases of flu, Krammer and colleagues tested them in mice that were given a lethal dose of influenza virus. All three antibodies were effective against many strains, and one antibody, called "1G01," protected against all 12 strains tested, which included all three groups of human flu virus as well as avian and other nonhuman strains.

"All the mice survived, even if they were given the antibody 72 hours after infection," Ellebedy says. "They definitely got sick and lost weight, but we still saved them. It was remarkable. It made us think that you might be able to use this antibody in an intensive care scenario when you have someone sick with flu and it's too late to use Tamiflu."

Tamiflu must be administered within 24 hours of symptoms. A drug that could be used later would help many people diagnosed after the Tamiflu window has closed. But before the researchers could even think of designing such a drug based on the antibody, they needed to understand how it was interfering with neuraminidase.

They turned to Scripps Research's Wilson, known globally for his work as a structural biologist. Wilson is Chair of the Institute's Department of Integrative Structural and Computational Biology, and has made numerous seminal findings that have shaped efforts to develop universal vaccines for flu and other complex viruses such as HIV.

Wilson and Xueyong Zhu, PhD, a staff scientist in Wilson's lab, mapped the structures of the antibodies while they were bound to neuraminidase. They found that the antibodies each had a loop that slid inside the active site of neuraminidase like a stick between gears. The loops prevented neuraminidase from releasing new virus particles from the surface of cells, thereby breaking the cycle of viral production in host cells.

"We were surprised at how these antibodies managed to insert a single loop into the conserved active site without contacting the surrounding hypervariable regions, thereby achieving much greater breadth against the neuraminidase of different influenza viruses than we have seen before," Wilson says.

The structures showed that the antibodies provide such broad protection because they target the conserved residues in the active site of the neuraminidase protein. That site stays much the same across distantly related flu strains because even minor changes could abolish the protein's ability to do its job, thereby preventing the virus from replicating.

The researchers are working on developing new and improved treatments and vaccines for influenza based on antibody 1G01.

"Neuraminidase has been ignored as a vaccine candidate for a long time," Ellebedy says. "These antibodies tell us that it should not have been overlooked. Now that we know what a broadly protective antibody to the neuraminidase looks like, we have an alternative approach to start designing novel vaccines that induce antibodies like this. And that could be really important if we are going to figure out how to design a truly universal vaccine."

The study was supported by the grants from the National Institute of Allergy and Infectious Diseases (R01 AI117287, R21 AI139813, U01 AI141990) and the National Institutes of Health (R56 AI117675).

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Materials provided by Scripps Research Institute. Note: Content may be edited for style and length.