How Do Shipworms Eat Wood? (Biology)

New research reveals that we know less about the history-altering shipworm than we thought

Humans have known for over two thousand years that shipworms, a worm-like mollusk, are responsible for damage to wooden boats, docks, dikes and piers. Yet new research from the University of Massachusetts Amherst published in Frontiers in Microbiology reveals that we still don’t know the most basic thing about them: how they eat.

“It’s unbelievable,” says Reuben Shipway, adjunct assistant professor in microbiology at UMass Amherst, research fellow at the Centre for Enzyme Innovation at the University of Portsmouth, UK, and one of the paper’s authors. “The ancient Greeks wrote about them, Christopher Columbus lost his fleet due to what he called ‘the havoc which the worm had wrought,’ and, today, shipworms cause billions of dollars of damage a year.”

Shipworms also play a key role in mangrove forest ecosystems, found throughout the world’s tropical regions, and are responsible for cycling a huge amount of carbon through the web of life. “Yet,” says Shipway, “we still don’t know how they do what they do.”

Part of the problem is that the nutritious part of wood – cellulose – is encased in a thick and extremely difficult-to-digest layer of lignin. “Imagine a really thick, unbreakable eggshell,” says senior author and UMass professor of microbiology, Barry Goodell.

Certain fungi possess enzymes capable of digesting the lignin, and it has long been thought that symbiotic bacteria living in shipworms’ gills also had the enzymes. “We thought that the bacteria were doing the work,” says Goodell, “but we now know they are not.”

Researchers are still trying to figure out what within the shipworm could be responsible for breaking down the lignin. “I combed through the entire genomes of five different species of shipworm,” says Stefanos Stravoravdis, the paper’s lead author and a graduate student in microbiology at UMass, “looking for specific protein groups which create the enzymes that we know are capable of digesting lignin. My search turned up nothing.”

This, however, is not the end of the story, and the team will be publishing more research in the near future that will help unravel the mystery of how shipworms eat wood. “We need to understand this process” says Stravoravdis.

This research was supported by the National Science Foundation; National Institute of Food and Agriculture; U.S. Department of Agriculture; the Center for Agriculture, Food and the Environment; and the UMass Amherst microbiology department.

Featured image: Section of a piling attacked by shipworms in Belfast, Maine. Credit: Barry Goodell.


Reference: Stefanos Stravoravdis et al., “How Do Shipworms Eat Wood? Screening Shipworm Gill Symbiont Genomes for Lignin-Modifying Enzymes”,Front. Microbiol., 12 July 2021 | https://doi.org/10.3389/fmicb.2021.665001


Provided by University of Massachusetts Amherst

Bentonite-containing Nasal Spray Provide Protection Against SARS-CoV-2 (Medicine)

Fabio Fais and colleagues developed and tested a bentonite-containing nasal spray (AM-301) that could protect against SARS-CoV-2 and other airborne pathogens. They showed that it is not only safe but also it significantly decelerated viral titer growth in experimental models of prophylaxis and mitigation. Their study recently appeared in bioRxiv.

The coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Detection of the virus was first reported in Wuhan, China and has since spread worldwide, emerging as a global pandemic. During the first days of SARS-CoV-2 infection and other respiratory viruses, the nasal tract has a high viral load than throat swabs. The same distribution was observed in an asymptomatic patient, implicating the nasal epithelium as a portal for initial infection and transmission. Therefore, the nose is important target of prophylactic and therapeutic interventions against these viruses.

Bentonite is a clay mineral composed of thin aluminum silicate sheets with a net negative charge; these properties contribute to its ability to adsorb viral particles and molecules such as drugs. Thus, Fabio Fais and colleagues hypothesized that a bentonite-containing nasal spray could protect against SARS-CoV-2 and other airborne pathogens.

“Bentonite suspensions can have thixotropic properties, that is, they reversibly change from a gel when undisturbed to a fluid colloid when agitated. We envisioned a bentonite-containing nasal spray that could be applied as a liquid, but in the nasal cavity it would form a durable, protective gel barrier.”

They therefore devised a bentonite-containing nasal spray (AM-301, Bentrio) with the aim of providing a safe and effective means of self-protection against exposure to harmful airborne particles.

Figure 1: Schematics of experimental protocols. A Safety assays. CBF, cilia beating frequency; LDH, lactate dehydrogenase; TEER, transepithelial electric resistance. B Prophylaxis assay. C Mitigation assay. © Fabio Fais et al.

Later, they tested the safety and efficacy of nasal spray against SARS-CoV-2 infection on an in vitro 3D model of primary human nasal airway epithelium.

“Safety was assessed in assays for tight junction integrity, cytotoxicity and cilia beating frequency. Efficacy against SARS-CoV-2 infection was evaluated in prophylaxis and infection mitigation assays.”

They showed that, product (nasal spray) didn’t have any adverse effects on the nasal epithelium. In addition, prophylactic treatment with product reduced viral titer significantly vs. controls over 4 days, reaching a maximum reduction of 99%. Moreover, when treatment with product was started 24 or 30 h after infection, epithelia that received the formulation had a 12- or 14-fold lower titer than controls.

All these results suggested that the product is safe in vitro and it significantly decelerated viral titer growth in experimental models of prophylaxis and mitigation.


Reference: Fabio Fais, Reda Juskeviciene, Veronica Francardo, Stéphanie Mateos, Samuel Constant, Massimo Borelli, Ilja P. Hohenfeld, Thomas Meyer, “Drug-free nasal spray as a barrier against SARS-CoV-2 infection: safety and efficacy in human nasal airway epithelia”, bioRxiv 2021.07.12.452021; doi: https://doi.org/10.1101/2021.07.12.452021


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One Shot of the Sputnik V Vaccine Triggers Strong Antibody Responses (Medicine)

A single dose of the Sputnik V vaccine may elicit significant antibody responses against SARS-CoV-2, finds a study published July 13 in the journal Cell Reports Medicine.

“Due to limited vaccine supply and uneven vaccine distribution in many regions of the world, health authorities urgently need data on the immune response to vaccines to optimize vaccination strategies,” says senior author Andrea Gamarnik (@GamarnikLab) of the Fundación Instituto Leloir-CONICET in Buenos Aires, Argentina. “The peer-reviewed data we present provide information for guiding public health decisions in light of the current global health emergency.”

Past research has shown that two doses of Sputnik V results in 92% efficacy against coronavirus disease 2019 (COVID-19), which is caused by SARS-CoV-2. An important question is whether a single dose would achieve greater public health benefit than two doses by allowing protection of a larger population more quickly.

Evidence from other vaccines offers support for the one-shot approach. The AstraZeneca vaccine shows 76% efficacy after a single dose, and the Moderna and Pfizer vaccines may induce sufficient immunity in previously infected individuals after one dose, with no apparent benefit of an additional dose.

In the Cell Reports Medicine study, Gamarnik and her colleagues compared the effects of one and two shots of Sputnik V on SARS-CoV-2-specific antibody responses in 289 healthcare workers in Argentina. Three weeks after the second dose, all volunteers with no prior infection generated virus-specific immunoglobulin G (IgG) antibodies – the most common type of antibody found in blood.

But even within three weeks of receiving the first dose, 94% of these participants developed IgG antibodies against the virus, and 90% showed evidence of neutralizing antibodies, which interfere with the ability of viruses to infect cells.

Additional results showed that IgG and neutralizing antibody levels in previously infected participants were significantly higher after one dose than those in fully vaccinated volunteers with no history of infection. A second dose did not increase the production of neutralizing antibodies in previously infected volunteers.

“This highlights the robust response to vaccination of previously infected individuals, suggesting that naturally acquired immunity might be enhanced sufficiently by a single dose, in agreement with recent studies using mRNA vaccines,” Gamarnik says.

Further studies are needed to evaluate the duration of the immune response and to assess how antibody levels relate to vaccine protection against COVID-19. “Evidence based on quantitative information will guide vaccine deployment strategies in the face of worldwide vaccine supply restriction,” Gamarnik says.

This work was supported by the National Institutes of Health (NIAID) and by the National Ministry of Science Technology and Innovation of Argentina.

Featured image: This graphical abstract shows antibody responses to Sputnik V vaccine in Argentina. On the top, schematic representation of the two-component adenovirus based vaccine (rAD26 and rAD5) Sputnik V. Bottom, IgG antibody levels measured by International Units and SARS CoV-2 Neutralizing Titers in vaccinated naïve (seronegative, blue) and previously infected (seropositive, red) volunteers. There is a high seroconversion rate following the first dose in naïve individuals. In previously infected participants, a single dose of Sputnik V elicits a fast and robust antibody response without apparent benefit from a second dose. © Rossi and Ojeda et al./Cell Reports Medicine


Reference: Rossi and Ojeda et al.: “Sputnik V Vaccine Elicits Seroconversion and Neutralizing Capacity to SARS-CoV-2 after a Single Dose”, Cell Reports Medicine, 2021. https://www.cell.com/cell-reports-medicine/fulltext/S2666-3791(21)00208-1


Provided by Cell Press

Mosquito-Resistant Clothing Prevents Bites in Trials (Material Science)

North Carolina State University researchers have created insecticide-free, mosquito-resistant clothing using textile materials they confirmed to be bite-proof in experiments with live mosquitoes. They developed the materials using a computational model of their own design, which describes the biting behavior of Aedes aegypti, the mosquito that carries viruses that cause human diseases like Zika, Dengue fever and yellow fever.

Ultimately, the researchers reported in the journal Insects that they were able to prevent 100 percent of bites when a volunteer wore their clothing – a base layer undergarment and a combat shirt initially designed for the military – in a cage with 200 live, disease-free mosquitoes. Vector Textiles, an NC State startup company, has licensed the related patent rights and intends to make clothing for commercial sale in the United States.

The researchers think their computational model could be used more widely to develop clothing to reduce transmission of diseases.

“The fabric is proven to work – that’s the great thing we discovered,” said study co-author Andre West, associate professor of fashion and textile design at NC State and director of Zeis Textiles Extension for Economic Development. “To me, that’s revolutionary. We found we can prevent the mosquito from pushing through the fabric, while others were thick enough to prevent it from reaching the skin.”

To develop the computational model to design textile materials that could prevent A. aegypti bites, researchers investigated the dimensions of the head, antenna and mouth of A. aegypti, and the mechanics of how it bites. Then, they used the model to predict textile materials that would prevent bites, depending on their thickness and pore size. Researchers said they believe the materials could be effective against other mosquito species in addition to A. aegypti because of similarities in biology and biting behavior.

“There are different uses for clothing,” said the study’s first author Kun Luan, postdoctoral research scholar of forest biomaterials at NC State. “The idea is to have a model that will cover all possible garments that a person would ever want.”

To test the accuracy of their model, the researchers tested the materials predicted to be bite-proof. In experiments with live, disease-free mosquitoes, the researchers surrounded a blood reservoir with plastic materials made according to parameters predicted by the model. They then counted how many mosquitoes became engorged with blood.

One material they initially tested was very thin – less than one millimeter thick – but had a very small pore size to prevent the mosquito from sticking its mouth parts, or proboscis, through the material. Another material had a medium pore size to prevent the mosquito from inserting its head through the textile far enough to reach the skin; and a third material had larger pores, but was sufficiently thick that the mosquito’s mouth still couldn’t reach the skin.

In a subsequent test, the researchers chose a series of knitted and woven fabrics that met the bite-proof parameters determined by the model, and validated they worked in experiments using both the blood reservoir and human volunteers. The researchers tested the number of bites received by volunteers when study participants inserted an arm covered by a protective sleeve into a mosquito cage. The researchers also compared the fabrics’ ability to prevent bites and repel mosquitoes to fabrics treated with an insecticide.

From what they learned in early experiments, researchers developed the bite-resistant, form-fitting undergarment made with a thin material, as well as a long-sleeved shirt, which was initially envisioned as a combat shirt for the military.

When a volunteer wore the garments sitting for 10 minutes and standing for 10 minutes in a walk-in cage with 200 hungry mosquitos, the volunteer found the combat shirt was 100 percent effective at preventing bites. In the first trial testing the base layer, the volunteer received bites on the back and shoulders – seven bites for 200 mosquitoes. The researchers attributed the bites to the fabric stretching and deforming, so they doubled the material layer around the shoulders, and were ultimately able to prevent 100 percent of bites. They also tested the clothing for comfort, and to see how well it trapped heat and released moisture.

“The final garments that were produced were 100 percent bite-resistant,” said Michael Roe, William Neal Reynolds Distinguished Professor of Entomology at NC State. “Everyday clothing you wear in the summer is not bite-resistant to mosquitoes. Our work has shown that it doesn’t have to be that way. Clothes that you wear every day can be made bite-resistant. Ultimately, the idea is to have a model that will cover all possible garments that person would ever want – both for the military as well as for private use.”

The study, “Mosquito-textile physics: A mathematical roadmap to insecticide-free, bite-proof clothing for everyday life,” was published online July 13, 2021, in the journal Insects. It was authored by Luan, Roe, West, Charles Apperson, Marian McCord, Emiel DenHartog, Quan Shi, Nicholas Travanty, Robert Mitchell, Grayson Cave, John Strider and Youngxin Wang from NC State University and Isa Bettermann, Florian Neumann and Tobias Beck from Aachen University, Germany. The study was supported by the National Science Foundation, the Department of Defense Deployed War Fighter Program, Natick Contracting Division of the U.S. Department of Defense, the Chancellor’s Innovation Fund at NC State, the Southeast Center for Agricultural Health and Injury Prevention, PILOTS and the NC Agriculture Research Experiment Station.

Featured image: Mosquitoes landing on bite-resistant fabric during an in vivo bioassay in which they fail to probe through the fabric due to its small pore size. The proboscis bends when mosquitoes try to push through the fabric. Credit: Matt Bertone


Reference:

  • “Mosquito-textile physics: A mathematical roadmap to insecticide-free, bite-proof clothing for everyday life”
  • Authors: Kun Luan, Andre J. West, Marian G. McCord, Emiel DenHartog, Quan Shi, Isa Bettermann, Jiayin Li, Nicholas V. Travanty, Robert D. Mitchell III, Grayson L. Cave, John B. Strider, Yongxin Wang, Florian Neumann, Tobias Beck, Charles S. Apperson and R. Michael Roe.
  • Published online in Insects on July 13, 2021.
  • DOI: 10.3390/insects12070636 

Provided by NC State

High Performance Polarization Sensitive Photodetectors On 2D β-InSe (Physics)

To extract the polarization information of incident light, polarization-sensitive photodetectors (PSPDs) exhibit significant practical application in both military and civil areas, like bio-imaging, remote sensing, night vision, and helmet-mounted sight for fighter plane. Optical filters combined with polarizers are usually needed for traditional photodetectors to realize polarized light detection. But it will increase the size and complexity of devices. To obtain a small-size PSPD, one-dimensional (1D) nanomaterials with geometrical anisotropy, such as nanowires, nanoribbons, and nanotubes, have been used as the sensitive materials for PSPDs, which can directly identify the polarization information of incident light without any optical filters and polarizers. However, it is not an easy task for patterning and integrating these 1D nanochannels for mass production of PSPDs.

Atomically layered two-dimensional (2D) semiconductors with low crystal symmetry show great potential in micro-nano PSPDs recently due to their intrinsically in-plane anisotropic properties. For example, SnS, ReS2, GeS2, GeAs2, AsP and black phosphorus (BP) exhibit an obvious in-plane anisotropy behavior in carrier transport, thermal conductivity, electrical conductivity, thermoelectric transport and optical absorption processes. They have potential applications in polarization sensitive photodetectors, polarization ultrafast lasers, polarization field effect transistors and polarization sensors. Among them, BP-based PSPDs have the highest photocurrent anisotropy ratio of 0.59, benefitting from its high carrier mobility and the strong in-plane anisotropy coming from the low-symmetry puckered honeycomb crystal structure. But BP-based optoelectronic devices are hard to get rid of the ambient degradation problem. 2D layered indium selenide (InSe), which also has high carrier mobility and is more stable than BP in atmospheric environment, exhibit huge potential application in high performance optoelectronic and electronic devices. In addition, the anisotropic optical and electronic properties of 2D layered InSe have already been demonstrated in 2019. Worth noting that InSe crystal has three specific polytypes, which are in β, γ, and ε phases, respectively. Among them, InSe in γ-phase and ε-phase belong to symmetry groups. Only the InSe in β-phase (β-InSe) belongs to the nonsymmetry point group, indicating that β-InSe exhibits better anisotropic optoelectronic properties than the other two polytypes.

In order to achieve high performance PSPDs with good stability, the advanced optoelectronic devices research team led by Professor Han Zhang from the Shenzhen University prepare the stable p-type 2D layered β-InSe via temperature gradient method. The anisotropic nature of the β-InSe has been revealed by angle-resolved Raman. The intensity of the out-of-plane and in-plane vibrational modes exhibit pronounced periodic variations with the polarization angle of the excitations. Besides, a good stability of β-InSe flakes and their FET devices has been proved by long-time AFM measurement and multi-repeat electrical performance test. The experimental results (a-b) are in good agreement with the theoretical calculations (c-d) that there are strong anisotropic transport and polarization-sensitive photoresponse in 2D layered β-InSe flakes. The photocurrent anisotropic ratio of the β-InSe photodetector reaches 0.70, which is ranking high among the single 2D material based PSPDs. The strong anisotropic Raman, transport and photoresponse properties of the β-InSe enable its great application potential in filter-free polarization sensitive photodetectors.

This research received funding from the National Key Research and Development Project, the National Natural Science Foundation of China, the Natural Science Foundation of Guangdong Province for Distinguished Young Scholars, the Innovation Team Project of Department of Education of Guangdong Province, the Science and Technology Innovation Commission of Shenzhen, and the Scientific Research Fund of Jilin Provincial Education Department.

Featured image: (a) The configuration for angle-dependent transport behavior determination. (b) Angular dependence of the photocurrent of the device at Vds = 0.5 V and Vds = 1 V, respectively. (c) Top-view and side-view of the contributing orbital to the photocurrent. Red arrow indicates the light polarization angle θ. (d) The quantum transport calculation of photocurrent with different polarized angle θ for ± 0.5 V and ±1.0 V bias voltages, when the light of the wavelength of 800 nm is irradiated. © Science China Press


See the article: Zhinan Guo, Rui Cao, Huide Wang, Xi Zhang, Fanxu Meng, Xue Chen, Siyan Gao, David K Sang, Thi Huong Nguyen, Anh Tuan Duong, Jinlai Zhao, Yu-Jia Zeng, Sunglae Cho, Bing Zhao, Ping-Heng Tan, Han Zhang, Dianyuan Fan, “High performance polarization sensitive photodetectors on two-dimensional β-InSe”, Natl Sci Rev, 2021. nwab098, https://doi.org/10.1093/nsr/nwab098


Provided by Science China Press

Higher-order Topological Superconductivity In Monolayer Fe(Te,Se) (Material Science)

In particle physics, a Majorana Fermion is charge neutral and its antiparticle is just itself. In condensed matter physics, a Majorana zero mode (MZM) is a quasi-particle excitation, which appears in the surfaces or edges of topological superconductors. Unlike the ordinary particles or quasi-particles that obey boson or fermion statistics, MZM obeys non-abelian statistics, a key property that makes MZM the building block for realizing topological quantum computation. Currently major experimental efforts focus on heterostructures made of superconductors and spin-orbit coupled systems (such as semiconducting nano-wires and topological insulators), where evidences of MZMs have been found. Unambiguous detection and manipulation of MZMs in these heterostructures, however, heavily rely on the superconducting proximity effect that suffers from the complexity of the interface. Furthermore, the low operation temperature of conventional superconducting materials complicates further manipulation of MZMs.

Iron-based superconductor was discovered in 2008 by the Japanese scientist Hideo Hosono as the second class of high-Tc materials. In the past decade, intensive studies focused on their unconventional superconductivity and strong correlation effect. Recently, the discovery of topological surface states on the surfaces of iron based superconductor Fe(Te,Se) renders it a unique system integrating both high-Tc superconductivity and topology. Therefore, it provides an exciting opportunity to realize MZM at comparably high critical temperature Tc. Moreover, the monolayer Fe(Te,Se) has a maximum Tc of 40 K and good tenability with a large in-plane upper critical field.

In a study published in Beijing-based National Science Review, a research team led by Chaoxing Liu, an associate professor from Pennsylvania State University, proposed to realize MZMs in monolayer Fe(Te,Se) by applying an in-plane magnetic field and electric gating.

The researchers found that applying an in-plane magnetic field can drive monolayer Fe(Te,Se) into the higher-order topological superconducting phase, in which the MZMs can appear at the corners. Furthermore, through electric gating, MZM can also occur at the domain wall of chemical potentials at one edge and certain type of tri-junction in the two-dimensional bulk (see Figure). According to their estimation, the needed magnetic field is well below the in-plane upper critical magnetic field of monolayer Fe(Te,Se) superconductor. In addition, rotating the magnetic field may provide an efficient approach to perform the braiding operation for the corner MZMs. Therefore, their study demonstrates that monolayer Fe(Te,Se) is a promising Majorana platform with scalability and electrical tunability and within reach of contemporary experimental capability.

This research received funding from the Office of Naval Research 330 (Grant No.N00014-18-1-2793), the Kaufman New Initiative research grant of the Pittsburgh Foundation, the German Research Foundation (DFG) through DFG-SFB 1170, project B04 and the Wuerzburg-Dresden Cluster of Excellence on Complexity and Topology in Quantum Matter – ct.qmat (EXC 2147, project-id 39085490).

Featured image: MZMs can be found at three different locations: (b) the corner between two perpendicular edges; (c) the CPDW along the 1D edge; (d) the tri-junction in the 2D bulk. The gray circles in (b), (c) and (d) represent the MZMs, and the magnetic field is in-plane. (e) The crystal structure for the Fe(Te,Se) monolayer. © Science China Press


See the article:

Xianxin Wu, Xin Liu, Ronny Thomale and Chao-Xing Liu, “High-Tc superconductor Fe(Se,Te) monolayer: an intrinsic, scalable and electrically tunable Majorana platform”, Natl. Sci. Rev. (2021)
https://doi.org/10.1093/nsr/nwab087


Provided by Science China Press

CHOP Researchers Use Base Editing in Preclinical Model to Correct Lethal Lysosomal Storage Disease Before Birth (Medicine)

Adding to the growing body of literature demonstrating the feasibility of correcting lethal genetic diseases before birth, researchers at Children’s Hospital of Philadelphia (CHOP) have used DNA base editing in a prenatal mouse model to correct a lysosomal storage disease known as Hurler syndrome. Using an adenine base editor delivered in an adeno-associated viral vector, the researchers corrected the single base mutation responsible for the condition, which begins before birth and affects multiple organs, with the potential to cause death in childhood if untreated.

Bill Peranteau, MD
William H. Peranteau, MD © CHOP

The findings were published today in Nature Communications.

“This study shows that prenatal base editing for Hurler syndrome is feasible in a preclinical mouse model,” said senior author William H. Peranteau, MD, an attending surgeon in the Division of General, Thoracic and Fetal Surgery at CHOP and Adzick-McCausland Distinguished Chair in Fetal and Pediatric Surgery. “In addition to showing the benefit of treating the disease before birth, we also showed some correction of the disease with base editing after birth, highlighting the promise of both pre- and postnatal base editing for Hurler syndrome.”

Hurler syndrome as a candidate for prenatal treatment

Hurler syndrome, also known as Mucopolysaccharidosis Type I (MPS-IH), is a lysosomal storage disease that affects approximately 1in 100,000 babies in the Western world and is commonly caused by a single DNA base mutation, where an adenine is present instead of a guanine. By 6 months of age, children can present with swelling of the liver and spleen, abdominal wall hernias, musculoskeletal abnormalities, retinal and neurocognitive degeneration, and cardiac disease. Untreated, patients can die of cardiorespiratory complications by 5 to 10 years of age. Even with treatment, patients experience complications, as current therapies have limited effectiveness, especially with delayed initiation.

Because the pathology of the disease begins before birth, the research team saw the syndrome as a candidate for prenatal treatment. With this goal, the researchers used CRISPR base editing, which requires only a single stranded DNA break and is thought to be more efficient and safer than other editing approaches, to convert the mutated adenine to guanine in the mouse model of MPS-IH.

The researchers used an adeno-associated virus serotype 9 (AAV9) viral vector to deliver the base editor to a fetal mouse model. They showed that prenatally treated mice demonstrated increased survival and improvement of metabolic, skeletal, and cardiac disease. Of note, the researchers observed corrected cells not only in the liver, but also in the heart, demonstrating the treatment was effective in multiple organs.

To assess the feasibility of the treatment after birth, the researchers tested the approach in 10-week-old MPS-IH mice and observed efficient on-target editing in the heart and liver, which was also associated with cardiac improvement. Whereas control models with the disease experienced cardiac decline between 4 and 6 months, sometimes resulting in death, postnatally treated mice demonstrated cardiac disease at 4 months, but the progression slowed between 4 and 6 months of age. Similar to prenatal treated mice, none of the mice treated after birth died by the study endpoint.

“Given the prenatal onset of disease, the potential for non-invasive prenatal diagnosis, and the progressive and morbid nature of the disease, Hurler syndrome and other lysosomal storage diseases represent attractive targets for treatment before birth,” Peranteau said. “Although the safety of these approaches for mothers and fetuses still needs to be rigorously characterized prior to clinical translation, this proof-of-concept study offers hope for genetic diseases with limited postnatal treatments.”


Reference: Bose et al. “In utero split AAV9 adenine base editing corrects the multi-organ pathology in a lethal lysosomal storage disease,” Nature Communications, online July 13, 2021, DOI: 10.1038/s41467-021-24443-8


Provided by CHOP

CNIO Researchers Discover A New Pathway To Tackle Follicular Lymphoma (Medicine)

Alejo Efeyan’s team at the CNIO has shown in animal models that blocking signals controlled by the RagC protein delays the onset of follicular lymphoma without side effects. This strategy may also be effective in the treatment of autoimmune diseases

For their own benefit and to grow beyond control, tumours manipulate cell signals to make it appear as if the cells have the nutrients they need. That is the case in follicular lymphoma, a type of tumour that affects the B lymphocytes of the immune system. One in six follicular lymphoma patients has mutations in RagC, a gene involved in the mTOR nutrient signalling pathway.

The team led by Alejo Efeyan, head of the Metabolism and Cell Signalling Group at the Spanish National Cancer Research Centre (CNIO), has discovered that genetic inhibition of the RagC protein blocks the activation of B lymphocytes and delays the onset of follicular lymphomas without side effects. The study, which was carried out in animal models, was published this week in the journal Cell Reports.

One of the most common lymphomas

Follicular lymphoma is the second most common type of non-Hodgkin lymphoma. It affects the B cells of the immune system, and its incidence is increasing with 5-7 cases per 100,000 population. It is a cancer with a slow progression, but there is no cure for it: patients eventually stop responding to the few treatments available.

Efeyan’s team had observed that one in six follicular lymphoma patients had mutations in RagC. The RagC protein is part of the large complex of proteins involved in the mTOR pathway, identified decades ago to be essential for metabolic activity and cell growth.

In 2019, Efeyan’s team described in an article published in the prestigious journal Nature Metabolism that mutations in this gene cause these tumours. “We observed that the mutation we introduced into the RagC gene resulted in the gene being permanently in the ‘on’ mode,” Efeyan said, adding: “That study confirmed that mutations in RagC cause the disease and provided the first evidence of the tumour-promoting activity of RagC and of the whole set of genes that inform mTOR of the presence of nutrients for growth.”

Cells addicted to food

In the paper now published by the group, they did just the opposite: they studied a decreased activity of the gene and its effects on the development of follicular lymphomas.

Efeyan and his team reasoned that, if this pathway is important for the growth of these tumours – they become addicted to food through RagC and the mTOR pathway – perhaps inhibiting it would affect their development by removing their metabolic ability to use nutrients at will.

But this system is vitally important to the proper functioning of the body, and RagC cannot be forced to remain constantly in ‘off’ mode, as this is incompatible with life. Instead, the researchers introduced a specific mutation into the RagC gene that partially decreases its activity but does not compromise viability, mimicking the effect that a drug against RagC might have.

“Surprisingly, this decrease in RagC activity in mice caused a significant delay in the progression of follicular lymphomas, which was accompanied by a block in the activation of B lymphocytes,” says Ana Ortega-Molina, first author of the study. “Moreover, this decrease had no harmful side effects or a negative impact on longevity and life expectancy, which has been linked for years to the mTOR pathway. Mice show weights, glucose levels, neuromuscular coordination, skin thickness and liver damage normal for their age.”

These results support “the efficacy and safety of moderate inhibition of this signalling pathway against pathological B cells,” the authors write in the paper. In 2007, not a single protein of this pathway was known, and since then, the search for strategies to modulate these nutrient-mediated signals to combat diseases such as cancer has been unceasing.

Possible implications for the treatment of autoimmune diseases

The findings of the study can also have important implications for other diseases in which B cells are altered, such as autoimmune diseases.

“Now that we know that there is a possible therapeutic window for blocking the RagC pathway, the next step is to develop selective inhibitors that can block these signals in patients,” Efeyan explains.

This work was supported by the Spanish Ministry of Science and Innovation, the Carlos III Health Institute, the European Research Council, the European Regional Development Fund, the Association of Volunteers for Citizenship and Solidarity of the British Council School through the Spanish Association against Cancer, the FERO Foundation and the EMBO Young Investigator Programme.

Featured image: Alejo Efeyan and Ana Ortega- Molina. /CNIO


Reference: Ana Ortega-Molina, “Inhibition of Rag GTPase signaling in mice suppresses B cell responses and lymphomagenesis with minimal detrimental trade-offs”, Cell Reports, 36(2), 2021. DOI: https://doi.org/10.1016/j.celrep.2021.109372


Provided by CNIO

This Device Harvests Power From Your Sweaty Fingertips While You Sleep (Science and Technology)

Feeling extra sweaty from a summer heat wave? Don’t worry–not all your perspiration has to go to waste. In a paper publishing July 13 in the journal Joule, researchers have developed a new device that harvests energy from the sweat on–of all places–your fingertips. To date, the device is the most efficient on-body energy harvester ever invented, producing 300 millijoules (mJ) of energy per square centimeter without any mechanical energy input during a 10-hour sleep and an additional 30 mJ of energy with a single press of a finger. The authors say the device represents a significant step forward for self-sustainable wearable electronics.

“Normally, you want maximum return on investment in energy. You don’t want to expend a lot of energy through exercise to get only a little energy back,” says senior author Joseph Wang (@JWangnano), a nanoengineering professor at the University of California San Diego. “But here, we wanted to create a device adapted to daily activity that requires almost no energy investment–you can completely forget about the device and go to sleep or do desk work like typing, yet still continue to generate energy. You can call it ‘power from doing nothing.'”

Previous sweat-based energy devices required intense exercise, such as a great deal of running or biking, before the user sweated enough to activate power generation. But the large amount of energy consumed during exercise can easily cancel out the energy produced, often resulting in energy return on investment of less than 1%.

In contrast, this device falls into what the authors call the “holy grail” category of energy harvesters. Instead of relying on external, irregular sources like sunlight or movement, all it needs is finger contact to collect more than 300 mJ of energy during sleep–which the authors say is enough to power some small wearable electronics. Since no movement is needed, the ratio between harvested energy and invested energy is essentially infinite.

This video shows the process of wrapping the BFC onto the fingertip using a stretchable, water-proof film. © Lu Yin

It may seem odd to choose fingertips as the source of this sweat over, say, the underarms, but in fact, fingertips have the highest concentration of sweat glands compared to anywhere else on the body.

“Generating more sweat at the fingers probably evolved to help us better grip things,” says first co-author Lu Yin (@YinLu_CLT), a nanoengineering PhD student working in Wang’s lab. “Sweat rates on the finger can reach as high as a few microliters per square centimeter per minute. This is significant compared to other locations on the body, where sweat rates are maybe two or three orders of magnitude smaller.”

The device the researchers developed in this study is a type of energy harvester called a biofuel cell (BFC) and is powered by lactate, a dissolved compound in sweat. From the outside, it looks like a simple piece of foam connected to a circuit with electrodes, all of which is attached to the pad of a finger. The foam is made out of carbon nanotube material, and the device also contains a hydrogel that helps maximize sweat absorption.

“The size of the device is about 1 centimeter squared. Its material is flexible as well, so you don’t need to worry about it being too rigid or feeling weird. You can comfortably wear it for an extended period of time,” says Yin.

Within the device, a series of electrochemical reactions occur. The cells are equipped with a bioenzyme on the anode that oxidizes, or removes electrons from, the lactate; the cathode is deposited with a small amount of platinum to catalyze a reduction reaction that takes the electron to turn oxygen into water. Once this happens, electrons flow from the lactate through the circuit, creating a current of electricity. This process occurs spontaneously: as long as there is lactate, no additional energy is needed to kickstart the process.

Separate from but complementary to the BFC, piezoelectric generators–which convert mechanical energy into electricity–are also attached to the device to harvest up to 20% additional energy. Relying on the natural pinching motion of fingers or everyday motions like typing, these generators helped produce additional energy from barely any work: a single press of a finger once per hour required only 0.5 mJ of energy but produced over 30 mJ of energy, a 6,000% return in investment.

The researchers were able to use the device to power effective vitamin C- and sodium-sensing systems, and they are optimistic about improving the device to have even greater abilities in the future, which might make it suitable for health and wellness applications such as glucose meters for people with diabetes. “We want to make this device more tightly integrated in wearable forms, like gloves. We’re also exploring the possibility of enabling wireless connection to mobile devices for extended continuous sensing,” Yin says.

“There’s a lot of exciting potential,” says Wang. “We have ten fingers to play with.”

This work was supported by the UCSD Center for Wearable Sensors.

Featured image: This image shows a small hydrogel (right) collecting sweat from the fingertip for the vitamin-C sensor (left), then displaying the result on the electrochromic display. © Lu Yin


Reference: Yin et al.: “A passive perspiration biofuel cell: High energy return on investment”, Joule, 2021. https://www.cell.com/joule/fulltext/S2542-4351(21)00292-0


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