Culture

The development of functional nanomaterials has been a major landmark in the history of materials science. Nanoparticles with diameters ranging from 5 to 500 nm have unprecedented properties, such as high catalytic activity, compared to their bulk material counterparts. Moreover, as particles become smaller, exotic quantum phenomena become more prominent. This has enabled scientists to produce materials and devices with characteristics that had been only dreamed of, especially in the fields of electronics, catalysis, and optics.

But what if we go smaller? Sub-nanoparticles (SNPs) with particle sizes of around 1 nm are now considered a new class of materials with distinct properties due to the predominance of quantum effects. The untapped potential of SNPs caught the attention of scientists from Tokyo Tech, who are currently undertaking the challenges arising in this mostly unexplored field. In a recent study published in the Journal of the American Chemical Society, a team of scientists from the Laboratory of Chemistry and Life Sciences, led by Dr Takamasa Tsukamoto, demonstrated a novel molecular screening approach to find promising SNPs.

As one would expect, the synthesis of SNPs is plagued by technical difficulties, even more so for those containing multiple elements. Dr Tsukamoto explains: "Even SNPs containing just two different elements have barely been investigated because producing a system of subnanometer scale requires fine control of the composition ratio and particle size with atomic precision." However, this team of scientists had already developed a novel method by which SNPs could be made from different metal salts with extreme control over the total number of atoms and the proportion of each element.

Their approach relies on dendrimers (see Figure 1), a type of symmetric molecule that branches radially outwards like trees sprouting form a common center. Dendrimers serve as a template on which metal salts can be accurately accumulated at the base of the desired branches. Subsequently, through chemical reduction and oxidation, SNPs are precisely synthesized on the dendrimer scaffold. The scientists used this method in their most recent study to produce SNPs with various proportions of indium and tin oxides and then explored their physicochemical properties.

One peculiar finding was that unusual electronic states and oxygen content occurred at an indium-to-tin ratio of 3:4 (see Figure 2). These results were unprecedented even in studies of nanoparticles with controlled size and composition, and the scientists ascribed them to physical phenomena exclusive to the sub-nanometer scale. Moreover, they found that the optical properties of SNPs with this elemental proportion were different not only from those of SNPs with other ratios, but also of nanoparticles with the same ratio. As shown in Figure 3, the SNPs with this ratio were yellow instead of white and exhibited green photoluminescence under ultraviolet irradiation.

Exploring material properties at the sub-nanometer scale will most likely lead to their practical application in next-generation electronics and catalysts. This study, however, is just the beginning in the field of sub-nanometer materials, as Dr Tsukamoto concludes: "Our study marks the first-ever discovery of unique functions in SNPs and their underlying principles through a sequential screening search. We believe our findings will serve as the initial step toward the development of as-yet-unknown quantum sized materials." The sub-nanometric world awaits!

An international long-term research collaboration aimed at creating high yielding and water use efficient rice varieties, has successfully installed part of the photosynthetic machinery from maize into rice.

"We assembled five genes from maize that code for five enzymes in the C4 photosynthetic pathway into a single gene construct and installed it into rice plants," said lead author Dr Maria Ermakova, who works at The Australian National University (ANU), as part of the international C4 Rice Project, led by Oxford University.

Rice, one of the main world food staples, uses the less efficient C3 photosynthetic pathway. Scientists predict that the introduction of the more efficient C4 photosynthesis traits into rice can potentially increase photosynthetic efficiency by fifty percent, improve nitrogen use efficiency and double water use efficiency.

"Although introducing all the genes required to make C4 rice still a long way off, this is the first paper where we assembled a functional C4 biochemistry in rice, which is very exciting," said Dr Ermakova, from the ARC Centre of Excellence for Translational Photosynthesis (CoETP).

Using synthetic biology, scientists can introduce several genes at the same time, get a plant in just a year and make prototypes to redesign their "constructs" very rapidly, just in a matter of months. In sharp contrast, using to the old approach, which inserts one single gene each time, can take several years.

"For me, the most important aspect of this paper is that we have mastered the technology that will help us in our journey towards C4 rice and now we can move forward to the next phase at a higher velocity than ever before," said CoETP's Deputy Director Professor Susanne von Caemmerer, one of the co-authors of this study.

Using the same kind of technique that Hal Hatch used in 1966 during the discovery of the C4 pathway, the team of researchers from the Max Planck Institute were able to follow the labeled CO2 on its way through the pathway.

'This is another key result, as we were able to prove that carbon dioxide is fixed using the C4 pathway. In other words, we achieved gene expression, but we also got the enzymes involved to be active and functioning in the plant in the right cells," says Professor von Caemmerer.

"Even though the plants we produced are not yet working very efficiently as C4, we now know that part of their photosynthesis is moving through the C4 pathway," she says.

"The research team include scientists with diverse expertise from microscopy to physiology, plant breeding and modelling" says Dr Florence Danila, who was in charge of the enzyme localisation using molecular microscopy techniques at the ANU C4 Rice Project Node.

"We started the C4 rice project ten years ago, involving sixteen labs in eleven countries. This particular research has taken us five years to complete, and the coordinated effort of several researchers from multiple organisations around the world, including Washington State University, Oxford University, Cambridge University, ANU and the Max Planck Institute," says Professor Robert Furbank, Director of the ARC Centre of Excellence for Translational Photosynthesis and one of the authors of the study.

"Our next step is to assemble a construct using sixteen genes, so we have lots of work to do. These are the first wobbly steps towards achieving C4 rice. These results show that we can manipulate a whole metabolic pathway. These results show that creating a functional C4 rice is possible," Professor Furbank says.

The loss of oligodendrocytes (OLs) -highly specialized cells of the brain that produce myelin, an essential structure enabling an efficient transmission of electrical signals and the support of neural activity- is a frequent condition in patients suffering neurodegenerative diseases.

Researchers of the Department of Cellular Biology, Genetics and Physiology of the University of Malaga (UMA) have succeeded in generating human OLs from pluripotent stem cells derived from patients with nervous system diseases, specifically multiple sclerosis or ALS.

This is a new method that is faster and more efficient, because it enables the generation of OLs in just three weeks. This find is highlighted on the November cover of the scientific journal Nature Protocols.

"So far, no one has developed any treatment that reverts the loss of myelin and OLs in these patients, probably because there hasn't been an appropriate platform available to study these phenomena", says the researcher of the UMA Juan Antonio García-León, main author of this study.

According to this expert, the generated cells are equivalent of the OLs of a human brain, and they produced myelin around neurons when transplanted in the brain of an animal model.

Efficient drugs

García-León explains that these cells could be used to advance in searching efficient treatments that favor myelination. In fact, as he asserts, a biotechnology company already uses this new method to develop an efficient drug to revert myelin loss involved in multiple sclerosis, something crucial to counteract its symptoms and pathologies.

Neurological diseases

Although the studies on the alteration of OLs and myelin in patients with neurological diseases such as Alzheimer's disease or schizophrenia are still limited, some recent studies argue its fundamental role in these conditions.

The UMA is working in collaboration with other national and international R&D&I groups on the application of this new technology in those diseases in which its exact involvement is unknown.

This study has been conducted by the R&D&I group of the UMA "NeuroAD" -member of the Biomedical Research Institute of Malaga (IBIMA) and the Network Center for Biomedical Research in Neurodegenerative Diseases (CIBERNED)- led by Professor Antonia Gutiérrez. The researchers of the UMA José Carlos Dávila and Laura Cáceres have also participated in the study. Likewise, this research has been developed in collaboration with the KU Leuven University (Belgium) and the Sorbonne University (Paris).

Summary:

Using practical nano-DDS technology, a polymeric nanomicelle that effectively delivers the potent mitotic inhibitor desacetyl vinblastine hydrazide (DAVBNH) to glioblastoma (GBM) was developed. GBM, which grows rapidly under anaerobic conditions, causes acidosis due to enhanced glycolysis, and the developed nanomicelle accurately senses the pH lowering to release the contained anticancer drug. Vinca alkaloids, represented by vinblastine, are long-known anticancer agents that strongly inhibit mitosis of cells, but they are highly toxic to normal cells and poorly tolerated for treatment. This major issue was greatly improved by our nano-DDS technology. In the experiment using mice with GBM transplanted intracranial, the DAVBNH loaded nanomicelle treated group containing improved 100% survival rate by 2 times and 50% survival rate by 2.6 times in comparison with the free DAVBNH treated group. This result, published in "Biomaterials" (IF = 10.317, 2019) on October 23, suggests that it may be clinically applicable to cancers with rapid disease progression other than glioblastoma. https://doi.org/10.1016/j.biomaterials.2020.120463

Main Body:

November 12, 2020, Kawasaki in Japan: The Innovation Center of NanoMedicine (Director General: Prof. Kazunori Kataoka, Location: Kawasaki-City in Japan, Abbreviation: iCONM) announced in "Biomaterials" (Impact Factor: 10.317 in 2019) that polymeric nanomicelles that selectively releases anti-cancer drugs by utilizing the acidity in the cells of glioblastoma (GBM) has been developed focusing on the fact that the hydrogen ion concentration (pH) of GBM cells is lower than healthy tissues. GBM is a brain tumor with extremely fast disease progression and poor prognosis (5-year survival rate: 10.1%). Although some drug candidates are under clinical trials, there are currently no drug therapies that can significantly improve the overall survival. Besides, it is difficult to completely remove it by surgery keeping the brain function as much as possible while the boundary with normal tissues is unclear.

Recently, it has been noted that as a treatment method for GBM, a method using an electromagnetic pulse called Tumor Treatment Fields (TTF) improved the overall survival (10-14 months to 16-24 months). The mechanism is known to be mitotic inhibition based on the destruction of the mitotic spindle that occurs during cell division. Therefore, we focused on the vinca alkaloids represented by vinblastine, an anticancer drug, which has been used as a mitosis inhibitor for decades. This type of drug suppresses mitosis by inhibiting the polymerization of intracellular microtubules and shows strong cytotoxicity, but it also affects not only cancer cells but also normal cells, and results in various types of serious adverse events including myelosuppression. Therefore, we considered the selective delivery of vinblastine to tumor tissue using nano-DDS (drug delivery system) with polymeric micelles. In this system, the drug must be released after reaching the tumor tissue. Cancer cells are usually placed in an anaerobic environment, unable to successfully run the TCA cycle to sustain their lives, and obtain the life energy exclusively from glycolysis. This nature makes cancer tissues accumulate acidic molecules and result in acidosis. This is more pronounced in faster-growing cells and is more acidic in rapidly developing cancers such as GBM. We wanted to take advantage of this property for drug release from micelles.

Hydrazone bonding was chosen as a linker that causes acidic cleavage and prepared by selecting a block polymer with carbonyl group such as ketones or aldehydes and using desacetyl vinblastine hydrazide (DAVBNH) as a vinca alkaloid. It is known that DAVBNH is 6 times more potent than vinblastine in suppressing the growth of glioblastoma. Self-association of a PEG-PAA block copolymer with DAVBNH attached to an aliphatic ketone residue in water was able to produce nanomicelles with an average diameter of 31 nm, containing DAVBNH in its inner core. Examining the stability of these micelles in solutions at various acidities from pH 6.0 to pH 7.4, the amount of free DAVBNH was significantly different between pH 6.9 and pH 7.4. In other words, it was found that the drug can be released on the slightly acidic side by accurately capturing the subtle difference in pH. It was also found that when the ketone residue is changed to an aldehyde residue, the drug is not released until the pH drops below 5.0.

Using mice in which GL261-Luc cells, which are a type of GBM cells, were transplanted intracranially, a micelle preparation of DAVBNH or a free drug was injected through the tail vein and the antitumor effect was examined. Compared with the free drug administration group, the 100% survival rate was improved by 2 times, and the 50% survival rate was improved by 2.6 times.

New economic research from the University of Kent, University of Reading and IHS Markit, reveals the extent to which UK consumers dislike food produced using production methods such as hormones in beef and chlorine washed chicken.

The research also reveals that UK consumers highly value food production that adheres to food safety standards set by the EU as well as UK produced food. These findings are particularly relevant for post-Brexit trade deals and the ongoing debates about UK food standards.

The researchers conducted choice experiments for four food products examining UK consumer attitudes for food produced using several agricultural production methods currently prohibited in the UK, including chlorine washed chicken and beef from cattle grown using hormone implants.

These methods of food production are common in the USA but are prohibited under EU food safety regulations.

Results confirm that UK consumers dislike food produced using these production methods. In contrast, participants positively valued EU food safety standards as well as the UK as a country of origin for beef, chicken pork and corn production.

These findings are timely given the status of the UK's post-Brexit agricultural trade negotiations and the ongoing debate in Parliament about legislative basis of future food standards.

Professor Iain Fraser, Principle Investigator and Professor of Agri-Environmental Economics at the University of Kent said: 'Our findings are a strong indicator of the expectations placed on food production by UK consumers. Methods of food production that fall short in terms of animal welfare draw a negative response from UK consumers, whilst in contrast the presence of EU food safety standards on packaging results in a positive response from consumers. Data from the same project also suggests that consumers tend to strongly value EU food standards regardless of their attitudes towards Brexit.

'As the UK continues to consider post-Brexit agricultural trade arrangements, as well as how to capture industry and public views within the Agricultural Bill currently going through Parliament, these findings support the need to maintain high UK food standards.'

Researchers from the University of Seville and the University of Oxford have described how the presence of brain metastases causes acute cerebrovascular dysfunction from the early stages of the disease. The study, whose main author was Manuel Sarmiento Soto, Marie Curie researcher and member of the Group on Mechanisms of Cell Death in Neurodegenerative Diseases at the University of Seville, shows that this alteration is chiefly caused by the activation of cells called astrocytes.

By using a specific treatment to override this activation, the researchers were able to return cerebrovascular flow to healthy levels. This improvement in blood flow around the metastases can limit the neurological deterioration associated with the progression of this disease and improve the otherwise poor life expectancy of these patients. In addition, the same specific inhibitors used in this study were also used in several ongoing clinical trials, a fact that could significantly shorten the delay in transferring the results obtained by US researchers to use in the clinic.

Astrocytes are the most abundant sort of cell in the central nervous system. One of their critical functions is to protect the neurons, thus ensuring a proper supply of nutrients from the blood flow. As an organ, the brain consumes high levels of energy. Any failure in the blood supply to any region of the brain could cause irreversible damage leading to the onset of various pathologies such as Alzheimer's disease, Parkinson's or even death.

The key role played by the astrocytes in brain metastasis has been thoroughly proven. For example, in the specific case of brain metastases from breast cancer, when the tumour cells reach the brain they produce a significant activation of astrocytes causing a dysregulation of the afferent blood flow. This causes a decrease in brain perfusion in the areas adjacent to the brain metastases, with the consequent damage that this drop could cause to neurons and other brain cells.

Parkinson's disease (PD) is the second most common neurodegenerative disease, with patient numbers being expected to double worldwide in the next 20 years. The detailed molecular and cellular mechanisms underlying its pathogenesis remains unclear, although recent evidence has pointed towards the role of mitochondrial dysfunction in the onset of the disease. Mitochondria -- small cellular 'subunits' involved in cell metabolism and energy generation -- constantly and dynamically interact with each other, forming perpetually changing networks known as mitochondria interaction networks (MINs). The researchers therefore sought to understand the correlation between the mitochondrial impairments observed in PD and any specific network topological changes in MINs, with the aim of advancing the early diagnosis and classification of PD patients.

"Since conventional analysis focusing on individual mitochondria has not provided satisfying insights into PD pathogenesis, our pioneering work has gone a step forward by investigating the interaction networks between these organelles", explains Dr Feng He, Group Leader of the Immune Systems Biology Group of the LIH Department of Infection and Immunity and corresponding author of the publication.

Leveraging their strong expertise in network analysis and machine learning, the scientists analysed a large 700 Gigabyte dataset of three-dimensional mitochondrial images of colonic neurons, collected from PD patients and healthy controls, and dopaminergic neurons, derived from stem cells. They found that particular network structure features within MINs were altered in PD patients compared to controls. For instance, in PD patients, mitochondria formed connected subnetworks that were generally larger than in healthy individuals. In line with this result, the efficiency of the energy and information transmission and distribution among the different mitochondria in PD patient MINs was significantly lower than in controls, suggesting that the longer 'transmission delays' were associated with the larger diameter of the components of the MINs observed in PD subjects. "These different topological patterns in MINs may mean that energy and information are possibly produced, shared and distributed less competently in the neuronal mitochondria of PD patients relative to healthy controls, suggesting their connection to mitochondrial damage, deficiencies and fragmentation typical of neurodegenerative disorders", adds Dr He.

Moreover, the research team found these different MIN patterns to be highly correlated with the commonly-used PD clinical scores of individual patients, i.e. the Unified Parkinson's Disease Rating Scale (UPDRS). Indeed, when applying a machine learning approach to analyse these MIN characteristics, the researchers observed that the use of a combination of those network features alone allowed them to accurately distinguish between PD patients and healthy controls.

"Our findings bring forward the potential of using particular mitochondrial network features as novel biomarkers for the early diagnosis and classification of PD patients, which might help develop a new health index. As a next step, we will explore how our results may offer new perspectives for the understanding of various other neurodegenerative diseases characterised by mitochondrial dysregulation, such as Huntington disease and Alzheimer's, making our work a true instance of translational and transversal research", states Prof Rejko Krüger, Director of Transversal Translational Medicine at LIH and contributing author of the study.

"This publication also constitutes a major step forward in the application of advanced machine-learning techniques to unravel the complex network interactions of cellular organelles for disease stratification. Indeed, data analytics and innovative digital technologies are a core priority area for our department and for LIH as a whole", concludes Prof Markus Ollert, Director of the Department of Infection and Immunity and contributing author of the paper.

The inter-disciplinary study relied on the close cooperation between clinicians, neuroscientists, network biologists, big data and machine learning experts from the Luxembourg Institute of Health (LIH), the Luxembourg Centre for Systems Biology (LCSB) and the Central Hospital of Luxembourg (CHL), particularly via clinical neurologist Dr Nico Diederich, as well as on the collaboration with other international partners such as the Instituto de Fi?sica Interdisciplinar y Sistemas Complejos IFISC (Spain).

To close the substantial gaps in our knowledge, scientists at the German Federal Institute for Risk Assessment (BfR) are investigating which particles are released into the environment and what their properties are. Different substances are released into the air depending on the material used for printing. For example, BfR experts were able to detect particles of the widely-used plastic polylactic acid and copper crystals, among other substances.

The size of the particles was 50 nanometres (polylactic acid) and 120 to 150 nanometres (copper). This means that they are so small that they can get into the alveoli, the smallest branches of the lungs. The higher the temperature during "printing", the more particles were released. The BfR is now exploring whether "3D printer dust" poses a health risk.

Consumer safety regarding 3D printers was also the focus of an expert meeting (partly held online) that took place at the BfR on 28 August 2020. In addition to the BfR, the participating institutions were the German Federal Institute for Materials Research and Testing (BAM), the German Environment Agency (UBA), the Institute for Occupational Safety and Health of the German Social Accident Insurance (IFA) and the US Consumer Products Safety Commission (CPSC). Research institutes from Technische Universität Berlin, interest groups and mem-bers of the 3D printing association "3DDruck e.V.", in which users and manufacturers are or-ganised, were also represented.

The event focused on fused deposition modelling (FDM, also known as fused filament fabri-cation, FFF). In this additive production process, a thermoplastic, the filament, is heated and then applied layer by layer to create the desired object.

The BfR, BAM and CPSC presented their initial results at the meeting. These showed that volatile components and particles are released during printing. Release is influenced by the materials used (plastic, dyes, additives) and the printing temperature. Investigations con-ducted by BAM and CPSC were carried out with 3D printers, while the BfR also tested 3D printing pens. There is little information available on possible health effects so far, so the BfR sees this as a core research area.

Different measures were discussed to reduce the release and ensure consumer protection. Other issues included possible risks in the subsequent treatment of 3D printed objects (e.g. through smoothing down) as well as the use of other 3D printing methods, such as stereo-lithography (SLA) or selective laser sintering (SLS). Better ways to distribute the information regarding possible health risks to the consumers were also discussed.

A group of researchers from Charité - Universitätsmedizin Berlin have confirmed Germany's first-ever case of animal-to-human transmission involving a specific species of virus known as the 'Seoul virus'. Working alongside colleagues from Friedrich-Loeffer-Institut (FLI), the researchers were able to confirm the presence of the virus in a young female patient and her pet rat. Their findings, which have been published in Emerging Infectious Diseases*, may influence the way in which we deal with both wild and domesticated rats.

Following multiple outbreaks earlier in the 21st century, hantavirus disease syndromes have gained increasing levels of public attention and were made notifiable in Germany in 2001. The Puumala and Dobrava-Belgrade viruses, for instance, which are common across central Europe and can be spread by numerous types of mice, usually cause acute fever. Occasionally, infection may result in HFRS (hemorrhagic fever with renal syndrome), an illness characterized by fever, low blood pressure and acute kidney failure. The Seoul virus, in contrast, which is mainly found in Asia and transmitted exclusively by rats, is far more likely to cause severe disease. Even outside Asia, however, there have been numerous reports of rat-to-human transmission of this highly virulent virus.

For the first time, a team of researchers led by Prof. Dr. Jörg Hofmann, Head of the National Consultant Laboratory for Hantaviruses at Charité's Institute of Virology, has been able to describe an autochthonous (i.e. acquired in Germany) case of Seoul virus infection transmitted by a rat. Working in close collaboration with a team of researchers led by Prof. Dr. Rainer G. Ulrich at the Friedrich-Loeffler-Institut (FLI) in Greifswald and colleagues at both local and regional health authorities, the researchers were able to identify the virus in samples from a young female patient from Lower Saxony and her pet rat. "The virus originally comes from Asia and was probably carried to Europe by wild rats on ships. However, it had not previously been observed in Germany," says the study's first author, Prof. Hofmann. The infected rat, which had been bred for domestic life, is likely to have been imported from a different country.

After developing symptoms of acute kidney failure, the young patient required intensive care treatment and was hospitalized for several days. Serology testing quickly confirmed a suspected diagnosis of hantavirus infection. The species of hantavirus responsible, however, remained unclear.

Working at Charité's specialist hantavirus laboratory, Prof. Hofmann and his team of researchers developed a special molecular diagnostic technique capable of identifying the Seoul virus in samples collected from the patient. Using the same technique, experts at the Friedrich-Loeffler-Institut were able to confirm that the patient's pet rat had been infected by the same virus. Explaining the results, Prof. Hofmann says: "Both viral sequences - the patient's and the rat's - were identical. This confirms that the disease was transmitted by an animal to a person - which means it is a zoonotic disease."

"Until now, only contact with mice would result in a suspected diagnosis of hantavirus infection. It will now be necessary to consider the possibility of infection after contact with either wild or domesticated rats as well," caution the study's authors. "The fact that this pathogen has been confirmed in a pet rat also means that the virus is capable of being exported, via the trade in these animals, practically anywhere in the world." Those keeping rats are therefore advised to exercise caution.

A new analysis of the United States government's response to COVID-19 highlights myriad problems with an approach that relied, in large part, on international supply chains and the Strategic National Stockpile (SNS). A panel of academic and military experts is instead calling for a more dynamic, flexible approach to emergency preparedness at the national level.

"When COVID-19 hit, the U.S. was unable to provide adequate testing supplies and equipment, unable to provide adequate personal protective equipment (PPE), and didn't have a functioning plan," says Rob Handfield, first author of the study and Bank of America University Distinguished Professor of Operations and Supply Chain Management at North Carolina State University.

"The SNS hadn't replenished some of its supplies since the H1N1 pandemic in 2009-10. Many of its supplies were expired. And there was no clear leadership. Federal authorities punted problems to the states, leaving states to fight each other for limited resources. And the result was chaos.

"We need to be talking about this now, because the nation needs to be better prepared next time. And there is always a next time."

To that end, Handfield and collaborators from NC State, Arizona State University, the Naval Postgraduate School and the Air Force's Contracting Career Field Management Team came together to outline the components that are necessary to ensure that there is an adequate federal response to future health crises. They determined that an effective federal program needs to address five criteria:

More Flexibility: In order to respond to unanticipated threats, any government system needs to have sufficient market intelligence to insure that it has lots of options, relationships and suppliers across the private sector for securing basic needs.

"You can't stockpile supplies for every possible contingency," Handfield says.

Inventory Visibility: The government would need to know what supplies it has, where those supplies are, and when those supplies expire. Ideally, it would also know which supplies are available in what amounts in the private sector, as well as how quickly it could purchase those supplies.

"The same is true on the demand side," Handfield says. "What do people need? Where? When?"

Responsiveness: The governmental institution overseeing emergency preparation needs to have leadership that can review information as it becomes available and work with experts to secure and distribute supplies efficiently. This would be an ongoing process, rather than a system that is put in place only in the event of crises.

Global Independence: The COVID-19 pandemic has highlighted the fact that the U.S. has outsourced manufacturing of critical biomedical materiel, because it was cheaper. Authorities need to consider investing in domestic manufacturing of PPE, testing supplies and equipment, pharmaceutical chemicals, syringes, and other biomedical supplies.

"The past year has really driven home the consequences of being dependent on other nations to meet basic needs during a pandemic," Handfield says. "Relying largely on the least expensive suppliers for a given product has consequences."

Equitable: The government needs to ensure that supplies get to where they are most needed in order to reduce the infighting and hoarding that we've seen in the COVID-19 pandemic.

"A first step here is to settle on a way of determining how to prioritize needs and how we would define an equitable allocation and distribution of supplies," Handfield says.

The last ingredient is bureaucratic: Coordinating all five of these components should be done by a permanent team that is focused solely on national preparation and ensuring that the relevant federal agencies are all on the same page.

"This is a fundamental shift away from the static approach of the SNS," Handfield says. "We need to begin exploring each of these components in more detail - and defining what a governing structure would look like. We don't know how long we'll have until we face another crisis."

COLUMBUS, Ohio - A new national survey by The Ohio State University Wexner Medical Center finds that although a majority of Americans plan to take precautions at holiday gatherings, such as social distancing and asking those with COVID symptoms not to attend, many will also put themselves at risk. Nearly two in five report they will likely attend a gathering with more than 10 people and a third will not ask guests to wear masks.

This holiday season comes with a lot of worry and stress as families try to find ways to balance their desire to celebrate together with the risk of spreading COVID-19. While cases of the virus remain high, colder weather across the country is forcing gatherings indoors, where the virus can more easily spread.

"We're going to look back at what happened during this holiday season and ask ourselves, 'Were we part of the solution or were we part of the problem?'" said Dr. Iahn Gonsenhauser, chief quality and patient safety officer at The Ohio State University Wexner Medical Center. "When you're gathered together around the table, engaged in conversation, sitting less than six feet apart with your masks down, even in a small group, that's when the spread of this virus can really happen."

Gonsenhauser says the safest solution is the one that people don't want to hear: find ways to communicate virtually and cancel in-person plans. However, if you do decide to have guests, it's important to have a plan in place and to communicate that plan to everyone attending. Consider wearing masks at all times, separating seating arrangements by household and assigning one or two people to serve the food. If you're moving your holiday plans outdoors, make sure to follow the same precautions you would indoors. And if you plan to travel or welcome out-of-town guests, stay informed about the COVID-19 rates and restrictions in both locations.

"If you have someone in your household who's high risk and you're in a low incidence area, you're going to want to think twice about having a celebration where people are coming from an area where there's a lot of virus in the community," Gonsenhauser said.

While celebrations will certainly look different this year, Gonsenhauser says it can also be an opportunity to make treasured memories with loved ones and experiment with new traditions. Try a virtual dinner or gift exchange or drop off surprise treats on friends' and family members' door steps.

The Bird 10,000 Genome Project (B10K) is a large international project co-led by University of Copenhagen, China National Genebank at BGI-Shenzhen, the Smithsonian National Museum of Natural History, Rockefeller University and the Chinese Academy of Sciences. In a study published today in Nature, the B10K achieved its family phase milestone releasing genomic resources for 363 bird species including 267 new genomes, and illustrating how these resources give improved resolution on genomic evolution analyses.

The paper also established a new pipeline to analyze the unprecedented scale of genomic data, which revealed a detailed landscape of genomic sequence gains and losses across bird lineages. The study showed that the passerine birds, the largest extant order of bird species, possessed genomic features that differed from other bird groups. Passerine genomes also contain an additional copy of the growth hormone gene. The songbirds, a group of Passeriformes, have lost a gene called cornulin, which might have contributed to the evolution of their diverse pure-tone vocalizations. Dense genomic sampling also facilitated the detection of signals of natural selection down to the single-base level, which may not be possible with few genomes.

- "Such detection power was only possible when the species were densely represented in the comparative genomic analyses," said Guojie Zhang, a principal investigator on the B10K and head of the Villum Centre for Biodiversity Genomics at Department of Biology, University of Copenhagen. "These genomes allow us to explore the genomic variations among different bird groups and help to understand their diversification processes".

The large collaborative effort involved over 150 researchers from 125 institutions in 24 countries. To sequence the bird genomes, the project heavily relies on tissue samples stored in museums around the globe. The Smithsonian National Museum of Natural History, the Natural History Museum of Denmark, and the Louisiana State University Museum of Natural Science contributed the majority of the samples for the project. This allowed them to sequence genomes from rare and endangered birds, which will be important resources for conservation actions.

Thirty years ago, the cloning of the green fluorescent protein GFP, together with genetic engineering tools, revolutionized biology by enabling researchers to fuse a fluorescent 'beacon' to any protein of interest so that it can be directly observed in living cells using fluorescence microscopy. Today's microscopes achieve live imaging, at nanometer resolution, in multicolor, allowing researchers to resolve even the smallest subcellular structures. Fluorescent proteins however have a limitation: the size of the fluorescent tag is often equivalent to the size of a typical folded protein, thus adding a considerable molecular 'cargo' to the protein under study and potentially impacting its function. This can become a particular obstacle for the study of microproteins, a newly appreciated class of proteins that are much smaller than average. Such tiny proteins have often been overlooked in the past but seminal discoveries of microproteins with important biological functions have sparked growing interest by the research community.

A study led by postdoctoral researcher Lorenzo Lafranchi from Simon Elsässer’s laboratory at Karolinska Institutet and SciLifeLab, now reports a method, which allows fluorescent tagging of proteins with minimal perturbation - a single amino acid - added genetically on either end of a (micro)protein of interest. The method is termed Single-residue Terminal Labeling, STELLA. It is based on a synthetic building block (a non-canonical "designer" amino acid, rather than one of the 21 canonical ones) that is incorporated together with a larger tag using a technique termed genetic code expansion. The tag is then swiftly removed by the cell, leaving a single terminal designer amino acid on the protein of interest. The designer amino acid introduces a chemical group into the protein that subsequently allows conjugation with a small organic fluorescent dye, lighting up the protein of interest inside of the living cell. As an advantage over existing labeling techniques relying on genetic code expansion, STELLA can be used to conveniently and universally label the termini of any proteins.

The study, published in the Journal of the American Chemical Society, demonstrates the utility of STELLA in fluorescent labeling a variety of human proteins and microproteins, localized to different subcellular compartments and organelles. Beyond cellular proteins, the team was also able to label and localize a number of elusive polypeptides produced by the SARS-CoV2 coronavirus causing Covid-19.

Men perceive themselves as having less power in their private than in their public lives, a new study from Lund University has suggested. Furthermore, both men and women agree: power in your private life matters more than that in public life.

Power is often associated with men who possess visible status and money. But it can also be exercised in one's private life to initiate and relationships with a partner, children and friends.

Researchers from Lund University, Stockholm University and Gävle University asked 808 Americans which areas they believe are important in life, and where they felt they had the most power.

"The debate on gender equality tends to focus on topics in the public domain such as salaries, leadership in companies and politics, where women are underrepresented. However, our results influence how we should view power today", says Sverker Sikström, professor of psychology at Lund University in Sweden.

The study showed that men perceive themselves as having more power in public life, while women view themselves as having more power in their private life. Notably, the participants valued private life over public life.

When power in the various areas was weighted by the importance participants assigned to each area, perceived gender differences in power disappeared.

"It is difficult to maintain the position that men have more power than women, when women are perceived as having more power in the areas that are viewed as the most important. The case for equality also needs to be made in the private life, where men often lose custody cases, are more negatively affected by separations, and have weaker networks of friends. Thus, equality needs to be improved both for men and women, in both private and public life", says Sverker Sikström.

It is important to note that the study primarily measured perceptions of power, rather than any objective measure of the concept, the researchers stress.

PLYMOUTH MEETING, PA [November 12, 2020] -- Studies have shown that utilizing a PARP inhibitor in the management of patients with metastatic pancreatic cancer who harbor BRCA 1/2 mutations is clinically beneficial [1]. New research in the November 2020 issue of JNCCN--Journal of the National Comprehensive Cancer Network sheds further light on this subject through cost-effectiveness analysis. The investigators seek to identify patient subgroups with the highest relative cost-effectiveness, through models based on efficacy and toxicity data from the Pancreas Cancer Olaparib Ongoing (POLO) trial, and measuring it against cost per quality-adjusted life year (QALY).

"With the present clinical evidence, olaparib should be prescribed for patients with metastatic pancreatic cancer harboring a germline BRCA 1/2 mutation, especially after the first-line platinum-based chemotherapy has been successfully completed," said researcher Lizheng Shi, PhD, School of Public Health and Tropical Medicine, Tulane University. "Our economic analysis found that olaparib might be a cost-effective option for patients, particularly if we select for optimal sub-groups, such as those who completed at least 16 weeks of continuous first-line platinum-based chemotherapy."

Bin Wu, PhD, of Shanghai Jiaotong University in China, who co-authored this study also pointed out: "The cost-effectiveness of olaparib as measured by cost-per-QALY is reasonably close to the commonly used willingness-to-pay thresholds. The value of olaparib maintenance would be even more attractive if the price were lower."

The researchers calculated incremental cost-utility ratios (ICUR) for patients taking maintenance olaparib versus those taking a placebo. Medical costs included drug acquisition, costs attributed to health states, costs for managing adverse effects, and costs for end-of-life care. All were calculated and considered based on 2018 U.S. dollar values. Modeling suggested that maintenance olaparib would be cost-effective in certain scenarios, using a threshold of $200,000 per QALY gained.

"While there is emerging evidence that precision medicine is relevant to subsets of patients with advanced pancreatic cancer, definitive results to support the cost-effectiveness of maintenance olaparib is lacking," commented Robert A. Wolff, MD, The University of Texas MD Anderson Cancer Center. Dr. Wolff is a member of the NCCN Guidelines® Panel for Pancreatic Adenocarcinoma and was not involved in this study. "Cost-effectiveness analyses of PARP inhibitors used in similar patient populations with recurrent ovarian cancer have been negative [2]. Thus, either improved patient selection for maintenance olaparib or reduced drug costs are likely necessary to establish olaparib as a cost-effective therapy in metastatic pancreatic cancer."