Culture

The structure and function of cortical brain cells modulated by attention

image: Figure 1 of the study: Behavioural task and recording setup

Image: 
Demetrio Ferro, Jochem van Kempen, Michael Boyd, Stefano Panzeri and Alexander Thielee

To effectively perform any daily task, the human brain needs to process information from the outside world using various cognitive functions. This cognitive processing passes through a dense interconnected network of cells whose physiology is specialized. The interconnected cell network needs to perform this processing of information efficiently and interact cooperatively to provide us, in real time, with useful instructions for living.

Research published on 23 March in the journal Proceedings of the National Academy of Sciences of the United States of America challenges recent scientific advances seeking to find out how cognitive control and sensory information relate to the cortical machinery consisting of specialized overlapping layers of cells.

"We have had the opportunity to investigate for the first time how between different depths signals propagate between the two cortical areas V1 and V4, and how they are modulated by attention"

A study by Demetrio Ferro, first author of the article and a researcher at the Center for Brain and Cognition (CBC) of the UPF Department of Information and Communication Technologies (DTIC), which he has carried out together with researchers from the Centre for Neuroscience and Cognitive Systems, the Italian Institute of Technology (IIT), the University of Trento (Italy) and Newcastle University (UK).

Previously, it has been argued that this operation of the cell network is not implemented in a step-by-step flow process, that would the conventional algorithmic calculation we generally apply to the tools of our technology of everyday use. There might be a need for another important instrument of cognitive control to enable selecting which objects of the visual world are important for processing, i.e., focal attention.

Focal attention is an important tool of cognitive control in information processing

Anatomical arrangement of cortical brain cells

The most recent scientific evidence suggests that cognitive control over the variables in our environment may be implemented in a parallel processing flow associated with various rhythmic oscillations of neural signals used for integrating inbound details (colour, shape, spatial orientation) of the sensory visual domain.

"Moreover, it is interesting to ask ourselves whether we can inspect the architecture of neural processing units by their structure, that is, by how they are physically implemented in the anatomy of the cerebral cortex", Demetrio Ferro asserts.

And the researcher adds: "the circuits associated with these calculations show a layered structure made of laminar plates of overlapping specialized types of cell at cortical depth, each possibly specialized to perform certain functions".

For this study, the researchers worked with primates and analysed cortical electrophysiological signals at multiple depths recorded simultaneously in V1 and V4 brain areas. "Our analyses provided new knowledge about how information spreads along the dimension of depth within and between the two cortical areas V1 and V4", they assert in their study.

The authors reveal that "we have had the opportunity to investigate for the first time how this signal propagation circuit is modulated by attention, that is, to identify what depths interact with more or less force when we have more or less attention involvement".

"This study opens the way to associating deficits in fundamental cognitive functions such as attention at specific depths of neural tissue, and even the possibility of clinical-pharmacological intervention on their interaction"

First, "our contribution shows how the previous vision of canonical circuits within visual cortical areas is not immediately linked to the idea of parallel processing flows divided in frequency for cognitive control and sensory processing. Rather, the combination of the two is a more complex and interesting scene", Ferro explains.

Credit: 
Universitat Pompeu Fabra - Barcelona

First images of cells exposed to COVID-19 vaccine reveal native-like Coronavirus spikes

image: Artist image of protein spikes

Image: 
University of Southampton

New research has for the first time compared images of the protein spikes that develop on the surface of cells exposed to the Oxford-AstraZeneca vaccine to the protein spike of the SARS-CoV-19 coronavirus. The images show that the spikes are highly similar to those of the virus and support the modified adenovirus used in the vaccine as a leading platform to combat COVID-19.

The SARS-CoV-2 virus, which causes COVID-19, has a large number of spikes sticking out of its surface that it uses to attach to, and enter, cells in the human body. These spikes are coated in sugars, known as glycans, which disguise parts of the viral proteins to the human immune system.

The vaccine developed by the University of Oxford and AstraZeneca is an adenovirus-vectored vaccine, which involves taking a safe version of a virus and adding in the information from part of a pathogen, in this case the SAR-CoV-2 spike, in order to generate neutralising antibodies against that target.

In this new study, published in the journal ACS Central Science, scientists from the University of Oxford and the University of Southampton, worked together to characterise the SARS-CoV-2 spikes manufactured by the cells presented with the Oxford-AstraZeneca vaccine. The Oxford work was led by Professors Teresa Lambe, Peijun Zhang and Sarah Gilbert and Professor Max Crispin led the work in Southampton.

The Scientists exposed a range of cells in vitro to the Oxford-AstraZeneca vaccine. Using an imaging technique known as cryo-electron microscopy (cryoEM) they took thousands of images which they then combined to build up a clear picture of the resulting protein spikes on the cells. Professor Peijun Zhang, of the University of Oxford and the Electron Bio-Imaging Centre (eBIC) at Diamond Light Source, who led the imaging work said, "CryoEM is an immensely powerful technique which enabled us to visualise the dense array of spikes that had been manufactured and presented on the surface of the cells".

Further chemical analysis of the glycans that coat the newly developed protein spikes revealed that they bear a high resemblance to those surrounding the SARS-CoV-2 spikes. This is an essential feature of the vaccine as it means that it can deliver close mimics of the coronavirus that are important in triggering the immune response needed to protect against COVID-19.

Professor Crispin said, "In this study we set out to see how closely the vaccine induced spikes resembled those of the infectious virus. We were really pleased to see a large amount of native-like spikes."

"This study will hopefully provide further understanding for the public, helping them see how the Oxford-AstraZeneca vaccine works. Many people may not realise how their cells become little factories manufacturing viral spikes that then trigger the immune response needed to fight off the disease. This may also provide reassurance that the vaccine is doing its job and generating the material that we need to present to our immune systems."

Credit: 
University of Southampton

'Patchwork' tumors prevalent across multiple cancer types

Researchers at the Francis Crick Institute, as part of an international collaboration of scientists through the Pan-Cancer Analysis of Whole Genomes Consortium, have analysed the whole genomes of tumour samples from over 2,600 patients with different types of cancer. They identified a high prevalence of genetic diversity within individual tumours, which they further characterised. Their findings confirm that, even at late stages of development, tumour evolution is driven by changes that benefit the cancer.

When cancer cells divide, errors occur in the process of copying their DNA. These copying errors mean that different tumours can be made up of cells presenting a wide range of genetic diversity. This variation is a challenge for doctors as a treatment that works for one group of genetically related tumour cells, called a subclone, may not be effective against another. And certain subclones can initiate tumour spread or drug resistance.

Cancer researchers are working to understand what drives the evolution of these subclones, which arise at different points during the course of disease.

In their study, published in Cell today (7 April), researchers analysed the whole-genomes of 2,658 cancer samples, spanning 38 types of cancer. They found that 95% of samples contain at least one identifiable subclone.

They also showed that the levels of and types of genetic changes varied between cancer types. And even in the same tumour, the genetic makeup of different subclones varied widely.

Researchers think that these subclones arise due to particular evolutionary pressures present at different times during tumour development or affecting different areas of the tumour. For example, to resist a particular microenvironmental condition such as to evade the immune system.

In support of this theory, they found evidence that the evolution of subclones is affected by whether the genetic changes are helpful to the cancer subclones or not. Subclones with advantages are more likely to develop.

Peter Van Loo, author and group leader of the Cancer Genomics Laboratory at the Crick says: "Cancers are constantly changing over time, so it's important to recognise that a sample taken from a tumour reflects a single point in time and the cancer will continue to evolve after this. They can grow into a patchwork with sections driven by different mutations and evolutionary pressures.

"Understanding more about the evolution of subclones, why they develop in one direction over another, as well as how common they are, could help doctors better predict the levels of and types of variation likely to be present in a specific cancer type."

Research in this area has already shown that understanding this genetic diversity can be harnessed to predict survival or relapse, which could help doctors and patients make important treatment decisions.*

The researchers have created an open-access resource that documents the genetic variation they found in the subclones. Their computational methods are also available for others to analyse cancer genomes.

Maxime Tarabichi, author and postdoc in the Cancer Genomics Laboratory at the Crick says: "We combined a number of high-quality computational methods to analyse these complex genetic data. Reassuringly, when we put the methods together in different ways and put them through independent simulations, the results always gave findings that fit the same story."

Credit: 
The Francis Crick Institute

The opportunities and risks of digitalization for sustainable development

Digitalisation can support transitions towards a more sustainable society if technologies and processes are designed in line with suitable criteria. This requires a systemic focus on the risks and benefits of digital technologies across the three dimensions of sustainable development: the environment, society, and the economy. This is the conclusion of a study prepared by a team of researchers at the Institute for Advanced Sustainability Studies (IASS) in Potsdam. Applying this precautionary approach to digitalisation requires the active involvement of developers, users, and regulators.

Digitalisation is a complex and dynamic process often regarded as the fourth major innovation cycle in human history. The use of a systemic risk-benefit perspective could shed light on the links and interdependencies between digital technologies and the environmental, economic, and social dimensions of sustainability, emphasise the team of researchers at the IASS.

The flexibility of digital services creates important opportunities for efforts to achieve sustainability goals. However, this can also lead to path dependencies that are difficult to reverse or otherwise correct unless they are discovered at an early stage. These closely intertwined opportunities and risks call for informed and judicious decision-making in order to foster sustainable development.

Digital innovations will not deliver the 17 UN Sustainable Development Goals (SDGs) as a matter of course; instead, the development of digital innovations must be guided by:

a systemic perspective that acknowledges the connections and interdependencies between their environmental, economic and socio-cultural impacts,

a professional technology assessment informed by interdisciplinary insights, and

an inclusive decision-making style that facilitates broad participation in the development of digital services.

Digital products help reduce demand for energy and raw materials

What else will it take to foster more sustainable outcomes? Co-author and research group leader at the IASS, Pia-Johanna Schweizer, explains: "Ensuring that all sectors of society have access to digital media and possess the digital literacy needed to use them is vital to delivering an inclusive digital transformation. We also need fast and reliable Internet access nationwide - including in rural areas." Similarly, targeted support is needed for small and medium-sized enterprises as they modernize their processes.

The development of digital products and production processes that reduce energy and material demand are also important building blocks for a sustainable digital future, says co-author Grischa Beier. As Pia-Johanna Schweizer explains "Above all, it is crucial to establish clear rules for data security and data sovereignty. If these challenges are not adequately addressed, acceptance of digital innovations is likely to erode and efforts towards a sustainable digitalisation process may be jeopardized."

Finally, new societal initiatives are needed to help shape an enabling environment for the development of sustainable digital technologies and services. The three authors recommend a participatory process in which stakeholders co-design the objectives, rules and regulations for a governance structure that engages with the Sustainable Development Goals of the United Nations.

Credit: 
Research Institute for Sustainability (RIFS) – Helmholtz Centre Potsdam

Manual workers face twice the risk of developing ALS

image: Construction workers in Malta

Image: 
Source: Mark Zammit Cordina, Times of Malta

ALS is a progressive neurological disease that attacks the nerves that interact with the body's muscles. The disease typically leads to complete paralysis of the body, robbing patients of their ability to walk, speak, eat and breathe.

Researchers studied ALS patients and healthy elderly volunteers living in Malta who took part in an ongoing study aiming at identifying genetic and environmental risk factors. Malta is a sovereign microstate in the middle of the Mediterranean Sea, and is home to a geographically and culturally isolated population. Recently, Maltese ALS patients were found to have a unique genetic makeup compared to their European counterparts.

In this study, based on demographic data collected over a four-year period, the researchers found that manual workers were twice as likely to develop ALS. Indeed, close to two thirds of ALS patients reported a blue-collar job as their main occupation during their entire career.

"We have long known that Italian football players, American National Football League players and military serviceman have an increased risk of ALS compared to the general population. A common thread running through these professions is sustained or strenuous physical exertion. Our study supports this notion," said the study's lead researcher Dr Ruben J. Cauchi, PhD, a senior lecturer at the University of Malta's School of Medicine and lead investigator at the University of Malta's Centre for Molecular Medicine and Biobanking.

Despite the fact that Malta does not have professional football players nor an elite military service, the study found that sweat-inducing jobs including those in construction and carpentry were associated with a higher ALS risk. Patients in these occupations were more prone to develop bulbar-onset ALS, a form of the disease in which speech or swallowing problems appear before muscle weakness in the limbs. Patients with bulbar-onset ALS fare worse than those with limb-onset.

The setting up of a national ALS Registry and Biobank at the University of Malta in 2017, with the aim of identifying and tracking ALS patients and healthy volunteers, was key for this discovery. Right now, the research team is studying the interplay between genetics and environmental exposures in causing ALS in patients.

Credit: 
University of Malta

Foetus in bishop's coffin was probably his grandson

image: The bundle found at the feet of Peder Winstrup

Image: 
Gunnar Menander

Bishop Peder Winstrup died in 1679, and is one of the most well-preserved human bodies from the 1600s. Researchers at Lund University in Sweden may now have solved the mystery of why a foetus was hidden in his coffin in Lund Cathedral. DNA from the bishop and the foetus, along with kinship analyses, has shown that the child was probably the bishop's own grandson.

Something is protruding between Bishop Peder Winstrup's two calves. The X-ray reveals small bones. Could it be an animal? When the image is studied more closely, the osteologists from Lund University can see faint signs of what is to become the collarbones - it is a human foetus.

Inside the coffin they find the bundle, wrapped in a piece of linen cloth. Judging by the length of the femur, it was 5-6 months old and stillborn. The discovery raised a number of questions - one of them was why it was in the bishop's coffin.

"It was not uncommon for small children to be placed in coffins with adults. The foetus may have been placed in the coffin after the funeral, when it was in a vaulted tomb in Lund Cathedral and therefore accessible", says Torbjörn Ahlström, professor of historical osteology at Lund University, and one of the leading researchers behind the study.

The burial book from Lund Cathedral confirms that coffins of children were placed here, without them being related to the family.

"Placing a coffin in a vault is one thing, but placing the foetus in the bishop's coffin is quite another. It made us wonder if there was any relationship between the child and the bishop", says Torbjörn Ahlström.

Therefore, researchers at Stockholm University analyzed samples from Peder Winstrup and the foetus. The results show that it was a boy, and that they had a second-degree kinship, that is, they shared roughly 25% of the same genes. Since they had different mitochondrial lineages, but there was a Y-chromosome match, the relationship was determined to be on the father's side.

"Archaeogenetics can contribute to the understanding of kinship relations between buried individuals, and in this case more specifically between Winstrup and the foetus", says Maja Krzewinska at the Center for Paleogenetics at Stockholm University, who was involved in the analysis.

As is the case for second-degree relationships, the following constellations involving Winstrup and the foetus are possible: uncles, nephews, grandparents, grandchildren, half-siblings and double cousins. What is the most probable relationship in this scenario can be deduced from the knowledge that exists about the Winstrup family.

By studying this, the researchers were able to rule out a number of possible relationships, however, one remained a distinct possibility.

"It is possible that the stillborn baby boy was Peder Pedersen Winstrup's son, and therefore the bishop was his grandfather", says Maja Krzewinska.

Perhaps it is a family drama we see the contours of here. Peder Pedersen Winstrup did not follow in his father's and grandfather's footsteps and study theology, instead he became interested in the art of fortification. He lost his father's property in the Great Reduction in 1680, and probably lived on alms from relatives during the latter part of his life. With Peder Pedersen Winstrup's death, the male lineage came to an end for the noble family Winstrup. Placing the deceased foetus in the bishop's coffin must have been a heavily symbolic act: he had given birth to a son, albeit stillborn.

Credit: 
Lund University

New method advances single-cell transcriptomic technologies

Single-cell transcriptomic methods allow scientists to study thousands of individual cells from living organisms, one-by-one, and sequence each cell's genetic material. Genes are activated differently in each cell type, giving rise to cell types such as neurons, skin cells and muscle cells.

Single-cell transcriptomics allows scientists to identify the genes that are active in each individual cell type, and discover how these genetic differences change cellular identity and function. Careful study of this data can allow new cell types to be discovered, including previously unobserved stem cells, and help scientists trace complex developmental processes.

"Single-cell transcriptomics have revolutionised biology but are still an area in active development," explains Helena Garcia Castro, a PhD student in the Department of Biological and Medical Science at Oxford Brookes University and co-author of the paper.

"Current methods use cell dissociation protocols with 'live' tissues, which put cells under stress, causing them to change, and limiting accurate investigations."

To solve this problem, the research team used historical research and revived a process from the 19th and 20th centuries to create the ACME (ACetic acid MEthanol dissociation) method.

Scientists realised that with this method, cells did not suffer from the dissociation as it stops their biological activity and 'fixes' them from the very beginning of the investigation.

The ACME method then allows cells to be cryopreserved, one or several times throughout the process, either immediately after the dissociation process, in the field or when doing multi-step protocols.

Dr Jordi Solana, Research Fellow at Oxford Brookes University adds: "This means scientists can now exchange samples between labs, preserve the cell material and large sample sets can be frozen in order to be analysed simultaneously, without destroying the integrity of the genetic material in the cell.

"We took the method from the old papers and repurposed it to make it work with current single-cell transcriptomic techniques. With our new method, we will now set out to characterise cell types in many animals."

Scientists are now able to collaborate with other laboratories and research a wider variety of animal cells, thanks to the ACME method. This would not have been possible without the technology to dissociate and freeze live cell tissues.

Credit: 
Oxford Brookes University

Gender inequality study shows women under-represented on marketing academic journal boards

Women are significantly underrepresented in the editorial boards of marketing academic journals, and awards and recognition favour men, new research from the University of Bath School of Management has found.

In their study 'It's hard to be what you can't see - gender representation in marketing's academic journals', Professor Andrea Prothero of Business and Society at University College Dublin and co-researcher Professor Pierre McDonagh examined gender representation in 20 marketing academic journals through three areas - the gender composition of editorial boards, special issue celebrations and the awards process.

The research found that since 2017 the number of women in editorial board roles had grown by 4.5% and that the number of female editors-in-chief had risen to 39 percent from 18 percent over the same period. But men still held 68% of all editorial board roles and the discrepancy was even greater at the advisory board level.

"The results are stark, disappointing and somewhat shocking. I think many people might expect both marketing and academia to be progressive areas but in 2021 it is simply not acceptable for example, that 88% of advisory board members within our journals are men, or that some journals in our field have never had a female editor-in-chief," McDonagh said.

Prothero said she and McDonagh were moved to study this issue as they believed many scholars were not aware of the scale of the gender discrimination problem in marketing academic journals or of the particular challenges around awards and celebrations of academic achievement.

"Our research also highlighted how journal celebrations also favour men. Special issues for example include reflections from previous editors (who are mostly men), and invited commentaries (who are mostly men). And, where journals and/or their related associations celebrate outstanding research through awards processes, those awards which are named after leading figures in the field are all named after men!" she said.

McDonagh said he and Prothero were not arguing that women are deliberately excluded from awards and recognition, but that structural, systemic and institutional biases meant male colleagues were privileged over women.

"And this of course, also means that injustice and inequality for female academics are perpetuated. Our goal is to get scholars in the marketing academy to think differently about things that are hidden in plain sight. We also want them to join us in asking for meaningful change with respect to existing gender discrimination in the marketing journals," he said.

McDonagh said publishing houses and editors should take four steps towards tackling gender representation issues.

Firstly, build diversity into existing journal review boards, and second, introduce a quota system to ensure diversity of people across advisory boards, manuscript review boards, and in roles such as associate editors, co-editors, and editors-in-chief. Publishing houses in particular, have been discussing more inclusive and diverse editorial boards across academia, but Prothero said it was important to move beyond talk and implement new policies. And, while this study focused on gender representation, other dimensions such as race were equally as important.

"As a third step, we should ask awkward questions of the leaders in our field - why do the majority of named awards in our field honour white men? We request awards which also honour the leading people of colour and females in our field, he said.

Finally, Prothero and McDonagh urged editors-in-chief to celebrate those less visible to others.

"We have female role models for younger scholars to inspire them to greatness, but they are not celebrated or included either in editorial boards or in special issue celebrations to the same extent as men. Let's rectify this. Quite simply the current status quo is an injustice - not everyone is a white male academic, so why do they dominate everything?" he asked.

Credit: 
University of Bath

Genomes of the earliest Europeans

image: The Niche 1 sector (left) and the Main sector (right) during the excavations of Bacho Kiro Cave, Bulgaria, in 2016. The cement area in the foreground was previously excavated in the 1970s. New excavations picked up where these excavations left off.

Image: 
MPI-EVA/ Nikolay Zaheriev

An international research team has sequenced the genomes of the oldest securely dated modern humans in Europe who lived around 45,000 years ago in Bacho Kiro Cave, Bulgaria. By comparing their genomes to the genomes of people who lived later in Europe and in Asia the researchers from the Max Planck Institute for Evolutionary Anthropology in Leipzig, Germany, show that this early human group in Europe contributed genes to later people, particularly present-day East Asians. The researchers also identified large stretches of Neandertal DNA in the genomes of the Bacho Kiro Cave people, showing that they had Neandertal ancestors about five to seven generations back in their family histories. This suggests that mixture with Neandertals was the rule rather than the exception when the first modern humans arrived in Europe.

Last year, a research team led by researchers from the National Institute of Archaeology with Museum at the Bulgarian Academy of Sciences and the Max Planck Institute for Evolutionary Anthropology, Germany, reported the discovery of modern human remains found in direct association with the Initial Upper Palaeolithic stone tools at the site of Bacho Kiro Cave in Bulgaria. The oldest individuals found in the cave were directly radiocarbon dated to between 43,000 and 46,000 years ago. They are thus the earliest known dispersal of modern humans across the mid-latitudes of Eurasia.

Mateja Hajdinjak and colleagues have now sequenced the genomes of five individuals found at the Bacho Kiro Cave. Four individuals are between 43,000 to 46,000-years-old and were found together with stone tools belonging to the Initial Upper Palaeolithic, the earliest culture associated with modern humans in Eurasia. An additional individual found in the cave is around 35,000-years-old and found with stone tools of a later type. It was previously thought that bearers of the Initial Upper Palaeolithic died out without contributing genetically to modern humans arriving later. However, the researchers now show that the oldest Bacho Kiro Cave individuals, or groups closely related to them, contributed genes to present-day people. Surprisingly, this contribution is found particularly in East Asia and the Americas rather than in Europe where the Bacho Kiro Cave people lived. These genetic links to Asia mirror the links seen between the Initial Upper Palaeolithic stone tools and personal ornaments found in Bacho Kiro Cave and tools and ancient jewelry found across Eurasia to Mongolia.

Genetic differences between individuals

Importantly, the later 35,000-year-old individual found in Bacho Kiro Cave belonged to a group that was genetically distinct from the earlier inhabitants of the cave. This shows that the earliest history of modern humans in Europe may have been tumultuous and involved population replacements.

The earliest people at Bacho Kiro Cave lived at a time when Neandertals were still around. The researchers therefore scanned their genomes for fragments of Neandertal DNA. "We found that the Bacho Kiro Cave individuals had higher levels of Neandertal ancestry than nearly all other early humans, with the exception of a 40,000-year-old individual from Romania. Crucially, most of this Neandertal DNA comes in extremely long stretches. This shows that these individuals had Neandertal ancestors some five to seven generations back in their family trees" says Mateja Hajdinjak.

Although only a handful of genomes from modern humans who lived at the same time in Eurasia as some of the last Neandertals have been recovered, nearly all of them have recent Neandertal ancestors. "The results suggest that the first modern humans that arrived in Eurasia mixed frequently with Neandertals. They may even have become absorbed into resident Neandertal populations. Only later on did larger modern human groups arrive and replace the Neandertals" says Svante Pääbo, who coordinated the genetic research.

Credit: 
Max-Planck-Gesellschaft

Fewer breast cancer cases between screening rounds with 3D-mammography

3D-mammography reduces the number of breast cancer cases diagnosed in the period between routine screenings, when compared with traditional mammography, according to a large study from Lund University in Sweden. The results are published in the journal Radiology.

"Our results indicate that 3D-mammography, or digital breast tomosynthesis, possibly detects cancers that would otherwise have been diagnosed later at a more advanced stage", says Kristin Johnson, doctoral student at Lund University and radiology resident at Skåne University Hospital.

A large prospective screening study conducted at Skåne University Hospital in Malmö (Malmö Breast Tomosynthesis Screening Trial) between 2010 and 2015 included almost 15,000 women who received both 3D-mammography and traditional mammography. In 2018, the researchers published results from the trial showing that 3D-mammography detects just over 30 percent more cases of breast cancer compared to traditional mammography.

This time, the researchers compared cancers detected in between screenings, so called interval cancers. The women who received 3D-mammography were matched by age and screening date with women in a control group who were screened using regular mammography. A total of 13,369 women were included in the study and 26,738 women in the control population.

The number of interval cancer cases can be used to assess a screening method's effectiveness in detecting cancer and potential to reduce breast cancer mortality in the long run, and is one of the most important outcome measures to take into account in discussions about possibly switching to 3D-mammography as a screening method. The researchers also compared the types of breast cancer involved as well as the extent of the spread of cancer in the patients.

"Among the study participants who received 3D-mammography, we found that it was less likely, 40 percent lower odds, to get interval cancer compared to the control group that was screened with regular mammography. Interval cancer cases generally have a relatively aggressive biological profile with faster growing tumors than in screening-detected breast cancer. However, the study did not show any major differences between the groups regarding the biological profile, says Kristin Johnson.

Kristin Johnson clarifies that the women who were screened with both 3D-mammography and 2D-mammography thus received two radiological assessments, in contrast to the control group. This may have had some effect on the fewer number of cases of interval cancer in the study group.

Several European studies have shown that 3D-mammography detects more cases of breast cancer, although the scientific basis for using 3D-mammography in screening is considered weak due to lack of information on effects on interval cancer rates. Therefore, today's overall European guidelines are still vague. In addition, the guidelines for screening programs differ between countries within as well as outside Europe.

The researchers believe that their results, which so far are the only ones published that show a reduced interval cancer rate, further support that 3D-mammography can supplement or replace mammography in screening. In the long run, they can also help strengthen the European recommendations.

"Screening with 3D-mammography shows potential in reducing interval cancers. However, we need to see more studies pointing in the same direction", concludes Kristin Johnson.

Credit: 
Lund University

Researchers validate new technique for rapidly diagnosing herbicide-resistant weeds

WESTMINSTER, Colorado - April 07, 2021 - As the number of weed populations resistant to multiple herbicides continues to soar, it is clear that better tools are needed to help growers rapidly diagnose resistance issues. With more timely access to information, they can take earlier, proactive steps to keep resistant weeds from spreading.

A recent article in the journal Weed Science describes a new rapid "leaf-disk assay" that uses chlorophyll fluorescence emissions to determine whether a weed is resistant to various systemic and contact herbicides. In contrast to time-consuming and labor-intensive greenhouse screenings and population studies, leaf-disk assay results are available in about 48 hours.

In a recent research study, scientists were able to use the fluorescence technique to rapidly detect resistance to glyphosate, dicamba and fomesafen in broadleaf and grass weeds, including Palmer amaranth, waterhemp, kochia and goosegrass.

The assay clearly separated populations susceptible to herbicides from those that are highly resistant. It exhibited less sensitivity, though, in identifying populations with lower levels of resistance.

Though further work is needed to fine-tune the new test for greater precision, researchers say it holds great promise.

"In addition to the speed, the leaf-disk assay requires fewer technical skills," says Chenxi Wu, research scientist at Bayer CropScience. "That means more weed science labs will be able to use the technique to identify multiple resistances efficiently - helping growers take more immediate and informed actions."

Credit: 
Cambridge University Press

Red deer have personality and it is related to their dominance behavior

image: Two male red deers fighting

Image: 
University of Turku

An international team of researchers has studied individual differences in the behaviour of red deer. They found that several observed behaviours form a personality component, which they labelled "Confidence/Aggressiveness".

As is commonly known, individual people behave consistently different from each other and these kinds of consistent differences in behaviour are called personality. Studies on species other than humans, from insects to elephants, have found that personalities are widespread in nature.

The team consists of researchers from the Czech University of Life Sciences Prague, the University of South Bohemia, Czech Republic, the University of Vienna, Austria, and the University of Turku, Finland and is led by Bruno Esattore from the Department of Ethology at the Institute of Animal Science in Prague. The team of researchers studied personality of red deer with a newly developed questionnaire, as well as observed their behaviours.

The researchers identified a single personality component related to Confidence/Aggressiveness. Interestingly, some of the behaviours making up this component were linked with dominance behaviour in red deer. The study has just been published in Behavioural Processes.

- Many personality studies have focused on primates, rodents, birds, field crickets or fish. Despite of their well-studied biology and increasing popularity in the farming sector, the personality structure of one of Europe's most iconic mammals, the red deer, has until now been unknown, says the lead author of the study Bruno Esattore.

The personality data were collected by using a novel questionnaire for which experienced observers rated 15 behaviours on a scale from 1 to 5, with 1 meaning the deer shows this behaviour "Almost never" and 5 meaning "Most of the time".

- We think it is extremely interesting that inter-individual differences which have been so far overlooked or even regarded as distracting are those that eventually make the difference when trying to identify the personality of these animals, states Doctoral Candidate Laura Saggiomo from the Faculty of Forestry and Wood Sciences of the Czech University of Life Sciences Prague.

- These findings are exciting, but of course, they are not the final picture of how personality manifests in red deer, says Postdoctoral Researcher Vedrana Šlipogor from the Department of Zoology of the University of South Bohemia in Budweiss, Czech Republic.

The team put lots of care into the making of the questionnaire, however, for a majority of the 15 behaviours the observers did not agree very well on their ratings of the deer.

- This was an unexpected result and shows that we have to be careful with our behavioural descriptions and to consider observer perceptions when using questionnaire ratings of animal behaviour for scientific studies, Šlipogor further states.

The team then linked these findings with observations of the dominance interactions of the male deer in their bachelor groups.

- We found no relationship between deer's dominance and personality, but dominance was related to some of the rated behaviours, showing our personality questionnaire captured some biologically meaningful variation, says Bruno Esattore.

Studies on animals kept in zoos or different facilities or farms have shown that knowing the individual characteristics or personalities of animals can help to implement the best strategy in guaranteeing their welfare.

- Personality has not been largely considered in welfare management decisions, but lately it is receiving more and more attention. We believe that studies like ours can help to add to the improvement of animal management and welfare, concludes Martin Seltmann from the Department of Biology at the University of Turku.

Credit: 
University of Turku

New Lyme disease test distinguishes between early and late-stage disease

For those who live in an area blighted by ticks, the threat of Lyme disease can cast a shadow over the joy of spring and summer. These blood-sucking arachnids can transmit bacteria into the bloodstream of their unsuspecting host, causing the disease. Early treatment is essential, but current tests are not usually sensitive enough to detect the disease in early-stage patients. A recent study in open-access journal Frontiers in Microbiology reveals a new test for Lyme disease, which is the first to reliably distinguish between early- and late-stage patients. The test detects a genetic sequence left by a virus that resides in Lyme-causing bacteria, and can detect just one bacterial cell in a small blood sample.

As the most common tick-borne infection, Lyme disease affects nearly 500,000 people in the U.S. every year. Symptoms include fever, fatigue, joint pain, and a distinctive 'bullseye' rash, but if left untreated, the disease can cause paralysis and even death. As such, early diagnosis is important, but difficult.

"Early diagnosis of Lyme disease is absolutely vital in reducing suffering, because early Lyme can be treated, but late Lyme is very difficult to treat," explained Dr Jinyu Shan of the University of Leicester, lead author on the study. "Current tests cannot typically detect the low numbers of bacteria in early-stage patient blood samples. Our goal was to design a highly sensitive test to help doctors to identify Lyme disease as early as possible."

Shan's test is based on polymerase chain reaction, or PCR, which works by amplifying small amounts of specific genetic material so that it can be detected. To date, this technique has not been particularly useful in detecting Lyme-causing bacteria in the blood. Such bacteria often lurk in tissues, and may not be present in the blood in large numbers. Additionally, many of the genetic sequences targeted by PCR have only a single copy within each cell, making it difficult to find and amplify enough for detection.

Shan and his colleagues realized that there is another potential PCR target in Lyme-causing bacteria. These targets are called prophages, and are a genetic sequence that was inserted into the bacteria by a virus. Happily, such genetic material can escape the bacteria and is therefore more likely to be detectable in the blood, and multiple copies are present in individual bacterial cells.

The researchers assessed their new prophage-targeted test by adding small amounts of Lyme-causing bacteria to blood samples. They found that the test was very sensitive, detecting just one bacterial cell in 0.3 mL of blood. This suggests that the test is sensitive enough for use with human samples, as people infected with Lyme-causing bacteria typically have between 1 and 100 bacterial cells per mL of blood.

Based on these promising results, the researchers used their PCR test to analyze blood samples from healthy volunteers and patients with either early-stage or late-stage Lyme disease. Strikingly, the test could successfully distinguish healthy, early-stage and late-stage Lyme disease samples, and is the first technology to successfully achieve this. "The test could also be very useful in rapidly ruling out someone with suspected Lyme disease," said Shan.

The technique may also be applicable to diagnostic tests for other bacterial infections, if researchers can identify suitable prophage sequences for such bacteria. The technology will need further development before it is suitable for clinical use, but the researchers have already begun the groundwork for this. "We are currently working with a commercial partner, and investigating regulatory issues and the potential for a clinical trial for this technology," said Shan.

Credit: 
Frontiers

Urolithin A shows effective against muscular dystrophy

image: Regenerating muscle cells thanks to Urolithin A

Image: 
© Amazentis / EPFL Auwerx Lab

Progression of Duchenne Muscle Dystrophy (DMD) can be delayed in mice by supplementing their diets with Urolithin A, according to new results reported today. The findings, published in Science Translational Medicine, raise hopes that new treatment options could one-day be developed for DMD, an uncurable genetic condition characterized by progressive muscle degeneration. About 1 in 3,500 boys are born with DMD, which usually develops in childhood and significantly reduces life expectancy.

The new research carried out at the laboratory of Professor Johan Auwerx, MD, PhD at the Swiss Federal Institute of Technology EPFL and the University of Lausanne in collaboration with scientists at the Swiss life science company Amazentis, highlights the important role that defective mitochondria can play in DMD. The powerhouses of cells, mitochondria produce the energy necessary for normal muscle function. But muscle cells taken from both human DMD patients and from mice bred to mimic the condition show significant defects in mitochondrial activity, the study finds. Specifically, patterns of gene expression show the development of DMD is associated with a marked decrease in mitophagy - the process cells rely on to remove and recycle defective mitochondria and maintain energy levels high.

"Duchenne Muscle Dystrophy is the most common fatal genetic disease diagnosed in childhood with still no cure available," says Johan Auwerx, MD, PhD, lead-author and Professor at the EPFL. "Our work represents a significant breakthrough in the search for new therapeutic approaches for muscular dystrophies."

The natural compound Urolithin A is known to activate mitophagy and improve mitochondrial health in both mice and humans. When the study scientists and lead authors, Peiling Luan and Davide D'Amico, fed the compound to DMD mice for just ten weeks, they saw mitophagy levels rise effectively restoring them to normal. This led to a significant reduction of muscle damage and improvement in muscle health and performance. The DMD mice administered Urolithin A saw grip strength increase by 31% and running performance increase by 45% compared with control untreated animals. And they lived longer - survival increased by 40%.

Importantly for the human disease, Urolithin A reduced a damaging condition called fibrosis in muscles of the DMD mouse heart and diaphragm by 36% and 39%, respectively. Similar damage seen in DMD patients typically leads to fatal cardiac or respiratory failure. Urolithin A was also able to enhance the regeneration of mouse muscle stem cells. This is particularly relevant to the disease in humans as the onset of DMD is linked with the exhaustion of functional stem cells.

Davide D'Amico, PhD, Project Leader at Amazentis and a first author of the paper, said: "Prior to this study, it was understood that the dramatic loss of muscle function in DMD patients was associated with mitochondrial dysfunctions. Here we discovered that defective mitophagy, the removal and recycling of dysfunctional mitochondria, plays a key role in the progression of DMD."

Chris Rinsch, PhD, Co-founder and CEO of Amazentis, said, "The rigorous science being published in Science Translational Medicine strengthens the scientific evidence of Urolithin A as a potent enhancer of muscle function. It's exciting to see this natural metabolite can support not only healthy muscle, but also shows promise for progressive muscle diseases in pre-clinical research."

Credit: 
Ecole Polytechnique Fédérale de Lausanne

Fungi are present in your lungs

The lungs were for a long time considered to be sterile in health, while in diseases like chronic obstructive pulmonary disease (COPD) failure in immune mechanisms were thought to allow microorganisms to proliferate and persist. New sequencing techniques have shown that several microorganisms reside in the lungs of healthy individuals, as well. Few studies have examined the fungal community in COPD and compared it to healthy controls using such techniques. According to the study findings, the compositions of these environments seem to be unaffected by the use of inhaled steroids.

Lungs have a unique fungal environment

The Bergen COPD Microbiome study (short name "MicroCOPD") is the world's largest single-centre study on the fungal community in lungs of persons with COPD. The Bergen Respiratory Research Group collected samples from the lungs of 233 individuals with and without COPD using bronchoscopy. Lung and mouth samples from 193 of these individuals were subsequently sequenced to detect residing fungi.

"Results showed that both healthy and diseased lungs had a different fungal composition than the mouth, suggesting that lungs have a unique fungal environment", says PhD candidate Einar Marius Hjellestad Martinsen.

The lungs were dominated by the fungus Candida. Interestingly, there were no differences in compositions between lungs from healthy individuals and patients with COPD. Furthermore, patients with COPD using inhaled steroids did not have any differences in the fungal community of their lungs compared to those not using inhaled steroids.

Disease-causing fungus

The prevalence and severity of fungal infections have increased in recent years. The finding that Candida is frequently found in healthy lungs could thus be of special importance. Candida is found as part of the normal flora on several mucous membranes, and is capable of causing disease, for instance thrush in the mouth or vagina.

"It would be of great interest to further examine if fungal lung infections are caused by fungi that are already present in the lungs", says Hjellestad Martinsen.

"If so, emphasis should be placed on these fungi to reveal what triggers are responsible for converting them from being "friendly residents" of our lungs to disease-causing intruders."

We know that use of inhaled steroids can have immunosuppressive effects, which can predispose to fungal outgrowth. The observation that inhaled steroids did not seem to affect the composition of the fungal environments in the lungs is interesting in this regard. Inhaled steroids are frequently used by patients with COPD and asthma, hence it would be of importance to know more about their influence on fungi found in the lungs.

The research group consists of several researchers working on the bacterial and fungal microbiota in the lungs, and the group is currently examining whether fungi is present also in other lung diseases.

Credit: 
The University of Bergen