Culture

CIA's misleading inoculation drive led to vaccine decline in Pakistan

A new paper in the Journal of the European Economic Association, published by Oxford University Press, indicates that distrust generated by a 2011 CIA-led vaccination campaign ruse designed to catch Osama Bin Laden resulted in a significant vaccination rate decline in Pakistan.

Using a local doctor, the US Central Intelligence Organization planned an immunization plan in Pakistan to obtain DNA samples of children living in a compound in Abbottabad where American authorities suspected Bin Laden was hiding in order to obtain proof of Bin Laden's location (because the presence of close relatives would be a likely indication of Bin Laden's presence). Without consent from the Pakistani health authorities, the doctor began to administer hepatitis B vaccines to children in Abbottabad. The Guardian published an article revealing the vaccine project shortly after a United States military special operations unit killed Bin Laden on May 2, 2011.

Even prior to this campaign extremist groups in Pakistan have worked to discredit formal medicine and vaccines. By discrediting such services (which are provided by the state) extremist groups may increase the credibility of non-state actors such as the Taliban.

The Taliban increased propaganda efforts against vaccines in the aftermath of the publication of the Guardian article. In particular, the Taliban issued several religious edicts linking vaccination campaigns to CIA espionage activities and later used violent action against vaccination workers.

Using data from the Pakistan Social and Living Standards Measurement on children born between January 2010 and July 2012, researchers have investigated the effects of the disclosure of this vaccination ruse on the extent to which children in Pakistan received doses of the polio, DPT, or measles vaccine. Their estimates indicate that the vaccination rate declined between 23% and 39% in districts with higher levels of electoral support for an alliance of parties espousing political extremism relative to districts with lower levels of electoral support for such groups. The researchers' investigation also revealed that the decline in girls' vaccination rates is larger than the decline in the vaccination rate of boys.

"The empirical evidence highlights that events which cast doubt on the integrity of health workers or vaccines can have severe consequences for the acceptance of health products such as vaccines," said Andreas Stegmann, one of the paper's authors. "This seems particularly relevant today as public acceptance of the new vaccines against Covid-19 is crucial to address the pandemic."

Credit: 
Oxford University Press USA

Rural school districts swifter to return to in-person instruction than urban districts

About 42% of rural school districts in the U.S. offered fully in-person instruction as of February, compared with only 17% for urban districts, according to a new RAND Corporation survey of school district leaders. The opposite pattern held for fully remote learning: 29% of urban districts offered fully remote instruction compared with 10% of rural districts and 18% of suburban districts.

The choice of in-person versus remote learning has important implications. Over a third of all U.S. school districts offering some form of remote instruction in early 2021 had shortened the school day, and a quarter had reduced instructional minutes.

"This survey shows how the choice of remote instruction has ramifications that extend beyond longstanding concerns about the lower quality of remote instruction.," said Heather Schwartz, lead author of the report and director of the Pre-K to 12 educational systems program at RAND, a nonprofit research organization. "Rural districts - which were primarily fully in-person or hybrid - did not decrease instructional minutes as often as urban districts, which means that urban students of color have likely lost more instructional time this school year than their white counterparts in rural districts."

To offset pandemic learning challenges, many districts added services. More than half of districts overall, and about seven in 10 urban districts, offered tutoring in 2020-2021 and increased social and emotional learning minutes or programming.

The survey found that about eight in 10 districts have not cut spending in 2020-2021, and most foresee spending the same or more next academic year. Similarly, many more districts have hired rather than fired school staff this academic year, and the prospect for next year looks the same.

Two-thirds of districts lost some enrollment this academic year from the year before, with an average decline of 5%. This is twice as many districts, and twice as large a decline, as the year before.

Looking forward, district leaders have great concern about a shortage of substitute teachers, bus drivers and teachers in several historically difficult-to-staff subject areas for 2021-2022.

RAND fielded the survey to the American School District Panel (ASDP) Jan. 21 through March 5. The report is based on responses from 434 district leaders from 48 states and the District of Columbia.

The ASDP is the first-of-its-kind nationally representative, longitudinal panel of school districts across the U.S., providing opportunities for district and charter management organization leaders to inform policy and practice.

The other authors of "Urban and Rural Districts Show a Strong Divide During the COVID-19 Pandemic: Results from the Second American School District Panel Survey" are Melissa Kay Diliberti, Lisa Berdie, David Grant, Gerald P. Hunter and Claude Messan Setodji.

RAND Education and Labor, a division of RAND, is dedicated to improving education and expanding economic opportunities for all through research and analysis. Its researchers address key policy issues in U.S. and international education systems and labor markets, from pre-kindergarten to retirement planning.

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RAND Corporation

High rates of childhood obesity alarming given anticipated impact of COVID-19 pandemic

In some countries of the WHO European Region, 1 in 3 children aged 6 to 9 years is living with overweight or obesity. Mediterranean countries have the highest rates of obesity, but the situation there is starting to improve.

These are some of the findings of a new WHO European Childhood Obesity Surveillance Initiative (COSI) report on the fourth round of data collection (2015-2017), presented at this week's European Congress on Obesity (held online this year). The report gives the latest data available on 6- to 9-year-olds in 36 countries in the region. A questionnaire collecting data from 2021 on the impact of the pandemic will follow from some countries.

"COVID-19 could potentially amplify one of the most worrying trends in the WHO European Region - growing childhood obesity," said Dr Hans Henri P. Kluge, WHO Regional Director for Europe.

"Overweight and obesity are directly associated with life-threatening noncommunicable diseases such as cardiovascular diseases, diabetes and cancer. What we must do to brighten the future of coming generations is implement science- and data-based policies that can help reduce childhood obesity, while promoting healthier diets and physical activity," Dr Kluge added.

Effect of the COVID-19 pandemic on childhood obesity

COVID-19 is likely to negatively impact childhood obesity levels in the WHO European Region, and hence the results of the next rounds of the COSI survey. School closures and lockdowns can impact access to school meals and physical activity times for children, widening inequalities. Childhood obesity prevention strategies should therefore remain a priority during the pandemic.

Policies having a positive effect in hardest-hit countries

Overweight and obesity stabilized or declined in some of the 13 European countries where it was possible to examine trends over time. Greece, Italy, Portugal and Spain, which all have the highest rates of obesity, as well as Slovenia showed a decreasing trend for both overweight and obesity. The reduction of the overweight prevalence ranged from 4 to 12 percentage points for boys and from 3 to 7 for girls.

In the last years, some of these countries implemented WHO-recommended measures to help tackle obesity rates, such as imposing taxes on sweetened beverages, food marketing restrictions and physical education classes.

"The COSI data show a decreasing trend in childhood obesity in the countries which have the highest rates of obesity. They have heard the alarm from the previous studies and implemented the policies we know work. It is heartening to see that when countries act it has a measurable effect," said Dr Nino Berdzuli, Director of the Division of Country Health Programmes at the WHO Regional Office for Europe.

Comprehensive data

The latest COSI data come from 36 countries that participated in the survey during the 2015-2016 and 2016-2017 school years, measuring around 250 000 primary school-aged children. The COSI report holds the most comprehensive data for boys and girls on overweight, physical activity and dietary patterns.

Key findings

Overall, the prevalence of overweight (including obesity) was 29% in boys and 27% in girls aged 6 to 9 years; the prevalence of obesity was 13% in boys and 9% in girls. These figures hide wide variations between countries. For more data on overweight and obesity among boys and girls in 36 countries, please see the figure at the end of this press release.

The highest proportions of childhood overweight and obesity were observed in Mediterranean countries such as Cyprus, Greece, Italy and Spain, where over 40% of boys and girls were living with overweight, and 19% to 24% of boys and 14% to 19% of girls were living with obesity.

The lowest proportions of childhood overweight and obesity were observed in central Asian countries such as Kyrgyzstan, Tajikistan and Turkmenistan, where 5% to 12% of boys and girls were living with overweight and less than 5% were living with obesity.

Dietary habits

On average, almost 80% of children had breakfast every day, around 45% ate fruit daily, and around 25% consumed vegetables daily. However, country-level figures for these healthy habits varied widely: daily consumption ranged from 49% to 96% for breakfast, from 18% to 81% for fruit, and from 9% to 74% for vegetables.

Frequent consumption of sweet snacks (27% of children overall) was more widespread than consumption of savoury snacks (14%). The percentage of children eating these unhealthy foods more than 3 days a week also varied greatly between countries - from 5% to 62% for sweet snacks and from less than 1% to 35% for savoury snacks.

Physical activity

On average, 1 in 2 children used active transport (walking or cycling) to and from school. In all countries, most children spent at least 1 hour per day playing outside (ranging from 62% to 98% in different countries).

Children with more educated parents were more likely to engage in sports/dancing in most countries. The difference between children of parents with high and low levels of education exceeded 20 percentage points in 7 countries. On the contrary, children of less educated parents were more likely to walk or cycle to and from school.

Lack of data for children under 5 years

COSI provides the Region with a large dataset on the prevalence of overweight and obesity and the determinants of childhood obesity for primary school-aged children. Unfortunately, no such large dataset exists for children under 5. The need to strengthen surveillance initiatives for this younger age group with the support of all governments and other stakeholders is urgent.

Credit: 
European Association for the Study of Obesity

Study finds pretty plants hog research and conservation limelight

image: One of the plant species, Gentinana nivalis, found to attract more than its share of research attention.

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n/a

New Curtin University research has found a bias among scientists toward colourful and visually striking plants, means they are more likely to be chosen for scientific study and benefit from subsequent conservation efforts, regardless of their ecological importance.

Co-author John Curtin Distinguished Professor Kingsley Dixon from Curtin's School of Molecular and Life Sciences was part of an international team that looked for evidence of an aesthetic bias among scientists by analysing 113 plant species found in global biodiversity hotspot the Southwestern Alps and mentioned in 280 research papers published between 1975 and 2020.

Professor Dixon said the study tested whether there was a relationship between research focus on plant species and characteristics such as the colour, shape and prominence of species.

"We found flowers that were accessible and conspicuous were among those that were most studied, while colour also played a big role," Professor Dixon said.

"Blue plants, which are relatively rare, received the most research attention and white, red and pink flowers were more likely to feature in research literature than green and brown plants.

"Stem height, which determines a plant's ability to stand out among others, was also a contributing factor, while the rarity of a plant did not significantly influence research attention."

Professor Dixon said plant traits such as colour and prominence were not indicators of their ecological significance, and so the 'attractiveness bias' could divert important research attention away from more deserving species.

"This bias may have the negative consequence of steering conservation efforts away from plants that, while less visually pleasing, are more important to the health of overall ecosystems," Professor Dixon said.

"Our study shows the need to take aesthetic biases more explicitly into consideration in experimental design and choice of species studied, to ensure the best conservation and ecological outcomes."

The full paper, 'Plant scientists research attention is skewed towards colorful, conspicuous, and broadly distributed flowers' was published in Nature Plants.

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Curtin University

Analysis of autopsy, toxicological and psychiatric reports of Portugal's first major forensic case

image: Recovered portrait of Vicente Urbino de Freitas in Brazil during his heyday.

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Forensic Sciences Research

Analysis of The Autopsy, Toxicological, and Psychiatric Reports of Portugal's First Major Forensic Case: Part III
https://doi.org/10.1080/20961790.2021.1898079

Announcing a new article publication for Forensic Sciences Research journal. In this review article the author Ricardo Jorge Dinis-Oliveira of the University Institute of Health Sciences (IUCS)-CESPU, Gandra, Portugal continues a three-part investigation of the "Crime of Flores Street" one of the most famous cases of poisoning which occurred in Portugal in the late 19th century. The case demonstrated the weaknesses of the Portuguese medicolegal system and attests to the importance of toxicological analysis. The first article retold the case which gave birth to forensic toxicology studies in Portugal and informed present day Portuguese medicolegal procedures. The second article analysed all the relevant and contradictory testimonial evidence of the prosecution and defence witnesses.

In this latest publication the author analyses the forensic evidence, particularly from the autopsy, toxicological, and psychiatric forensic reports. Today, it would be easy to perform irrefutable toxicological analysis, but in those times, the circumstantially produced evidence, together with the toxicological expert reports, allowed the court to produce a damning judgment. The author suggests, that with current knowledge, it is now possible to add further insights if the burial location of at least one victim could be identified. In late 2020 one of the victims was finally located. Permission for a new autopsy for samples collection was obtained and has been performed more than 130 years after the first major autopsy was executed in Portugal. Future research will include correlation of the identity of the victim by DNA analysis and comparison with relatives and toxicological analyses.

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Compuscript Ltd

Biomarker detects severe COVID-19 early on

Most people who are infected with SARS-CoV-2 develop no or only mild symptoms. However, some patients suffer severe life-threatening cases of COVID-19 and require intensive medical care and a ventilator to help them breathe. Many of these patients eventually succumb to the disease or suffer significant long-term health consequences. To identify and treat these patients at an early stage, a kind of "measuring stick" is needed - predictive biomarkers that can recognize those who are at risk of developing severe COVID-19.

First biomarker to predict severity of disease

A team led by Professor Burkhard Becher at the Institute of Experimental Immunology at the University of Zurich, working with researchers from Tübingen, Toulouse and Nantes, has now discovered such a biomarker - the number of natural killer T cells in the blood. These cells are a type of white blood cell and part of the early immune response. "The number of natural killer T cells in the blood can be used to predict severe cases of COVID-19 with a high degree of certainty - even on a patient's first day in hospital," says Burkhard Becher.

Targeted therapy thanks to precise immunopathogenesis

The new biomarker test helps clinicians decide which organizational and treatment measures need to be taken for patients with COVID-19, such as transfer to the ICU, frequency of oxygen measurements, type of therapy and treatment start. "Predictive biomarkers are very useful for making these decisions. They help clinicians provide patients suffering severe symptoms with the best care possible," says Stefanie Kreutmair, first author of the study. "Our findings also make it possible to investigate new therapies against COVID-19."

With the help of high-tech

The rapid deterioration in the health of COVID-19 patients is caused by an overreaction of the body's immune system. "The body produces small proteins called cytokines at a much higher rate, which leads to a 'cytokine storm' and triggers massive inflammation. Immune cells invade the lungs, where they disrupt gas exchange," explains Becher. To detect the immune cells and cytokines in patient samples, the UZH researchers used high-dimensional cytometry. This technology enables researchers to characterize many surface and intracellular proteins in millions of individual cells and process them using computer algorithms.

SARS-CoV-2-specific immune signature deciphered

Many other pathogens besides SARS-CoV-2 can cause pneumonia - and thus spark an immune response. The immune response triggered by COVID-19 has been studied extensively, but the exact nature of the immune response to SARS-CoV-2 has, to date, been unclear. To characterize this response, the researchers also analyzed blood samples of patients with severe pneumonia driven by a pathogen other than the novel coronavirus. By comparing the immune responses in COVID-19 patients with those of the control group, the researchers were able to determine the unique characteristics of the SARS-CoV-2 immune response.

"The immune responses to the various pneumonias are very similar and part of the body's general inflammatory response, as often observed in patients in intensive care. When it comes to COVID-19, however, T cells and natural killer cells display a unique behavior and describe a kind of pattern in the immune system - the immune signature specific to COVID-19," explains Becher.

Credit: 
University of Zurich

Identifying the rise of multi drug resistant E. coli

Antibiotic resistance in E. coli has been steadily increasing since the early 2000s despite attempts to control it, a new study suggests. In the biggest genomic survey of E. coli to date, that took more than 16 years in Norway, researchers have successfully tracked the spread of antibiotic resistant genes and have shown that these genes are being transferred between E. coli strains.

Researchers from the Wellcome Sanger Institute and University of Oslo have tracked multidrug resistance in Norway and compared this to a previous study from the UK. They found that resistant strains developed around the same time, but increased more rapidly in the UK population.

The results, published today (10th May) in The Lancet Microbe show that tracking these resistant strains is important in the surveillance and control of drug resistant E. coli, which poses a significant issue in hospitals where it can cause severe infection and mortality. In addition, understanding how these genes are transferred between strains, and what has caused them to acquire drug resistance can help prevent the growth of antibiotic resistance strains.

The bacterium, Escherichia coli is a common cause of bloodstream infections world-wide*, which seem to be increasing over the last decade. E. coli is commonly found in the gut, where it does not cause harm, but if it gets into the bloodstream due to a weakened immune system it can cause severe and life threatening infections. As an added challenge for health care providers, multi-drug resistance (MDR) has become a frequent feature of such infections, and in a worrying number of cases the available treatment options are becoming limited.

In the largest study of its kind, and only the second systematic longitudinal genomic study of bacteremia E. coli, researchers from the Wellcome Sanger Institute and the University of Oslo processed a nation-wide catalogue of samples from more than 3,200 patients to track antibiotic resistance over 16 years. By harnessing the power of large-scale DNA sequencing, they tracked the emergence of drug resistance and compared this to a similar study conducted in the UK**.

The team found that MDR started to increase and show in more strains in the early 2000s due to antibiotic pressure, and now multiple MDR E. coli strains are present in Norway. However, MDR E. coli seems to be more widely present in the UK, despite similar policies in place around antibiotic use. The UK population however is considerably larger than Norway which could explain some of the differences. Further research is needed to allow for closer comparison and to identify the exact factors that cause rapid spread in some locations compared to others.

MDR is relatively rare in bacteria. However, this new study has identified that lineages that previously were not thought to have MDR have acquired drug-resistance genes, showing the increased ability of E. coli to share MDR genes that move horizontally between strains.

Professor Jukka Corander, co-author and Associate Faculty member at the Wellcome Sanger Institute, said: "The high number of samples from the Norwegian population and the level of genomic detail on the strains of bacteria enabled us to make much more far-reaching conclusions than were ever possible before. This study demonstrates the power arising from a systematic national surveillance of resistant organisms, which both collects and makes the data available for in-depth analyses. Without these in place, it would have been impossible to approach the central research questions formulated in the study and find answers to them."

The researchers hope to conduct similar research in the UK to build on previous studies and gain a full data set of 16 years in the UK in order to more closely track MDR resistant E. coli.

Dr Rebecca Gladstone, lead author of the study and Bioinformatician at the University of Oslo, Norway, said: "Being able to estimate the expansion timelines of the MDR clones of E. coli and to identify multiple occasions of novel acquisition of resistance genes is particularly exciting as this is the first time that this has been possible. Understanding and tracking the movement of these drug resistance genes and the strains that carry them are necessary for controlling the spread of drug-resistant bacteria, which is a huge issue in healthcare."

Professor Julian Parkhill, co-author and Professor in the Department of Veterinary Medicine at University of Cambridge, said: "Long-term studies such as this one provide in-depth understanding about the complex epidemiology underlying bloodstream infections. The next step would be further research to detail the factors determining the success of emerging pathogenic clones of these bacteria, to help find a way to control and possibly minimise the spread of multidrug resistance."

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Wellcome Trust Sanger Institute

Why Germany's coal compromise failed to end the debate

Can expert commissions develop solutions for controversial issues that will enjoy broad democratic support? A team of researchers from the Institute for Advanced Sustainability Studies (IASS) has analysed the work of Germany's "Coal Exit Commission" using a set of new criteria. While the authors view positively the Commission's success in reaching a compromise, they criticise its failure to deliver an outcome that promotes the common good, particularly with respect to the high cost of the coal exit and its unambitious contribution towards Germany's climate goals, as well as the lack of public participation.

On 29 April 2021, Germany's Federal Constitutional Court ruled that the provisions of the Climate Protection Act (2019) are incompatible with the constitution - a ruling that has put Germany's "coal compromise" back in the spotlight. The ruling has forced the government to amend its existing climate targets rather making effective climate action merely a matter for future generations.

Fierce debates accompanied the decision-making process around the coal phase-out. There were widespread concerns that the end of Germany's coal era would affect the economic performance of the coal regions, reducing quality of life and endangering social cohesion. In response to this, a special commission was established by the Federal Government on 6 June 2018. "The Commission on Growth, Structural Change and Employment - also known as the 'Coal Commission' for short - was the most important commission in this legislative period and was supposed to help resolve the conflict around the coal phase-out," says project leader David Loew Beer, who led the study at the IASS. "Today we can say that it has been at least partially successful in this respect. Our research aimed to evaluate whether the commission's work has benefited democracy and sustainability."

For the study, which has been published in the "Zeitschrift fuer Politikwissenschaft" (Journal of Political Science), the researchers evaluated the reports of the Commission and articles from various media outlets as well as statements and studies released by participating organisations. In addition, interviews were conducted with 14 of the 28 members or their deputies.

At the time, a range of stakeholder groups were included in the commission, including representatives from environmental organisations, private sector entities, trade unions, science, and the regions. In the end, 27 of the 28 members approved the compromise. "The federal government viewed this as confirmation that the commission had been able to strike a fair balance between the different interests," says scientist Loew Beer. Interviews with those involved in the negotiations, however, revealed that the final negotiations were largely conducted by a small and informal group of participants.

How widely accepted was the Coal Commission?

One special feature of the study is that it applies a comprehensive system of criteria that was developed to examine the legitimacy of the Coal Commission and that enables researchers to derive generalisable findings which can be applied to other commissions. "Our analysis also examines the third area of legitimacy, so-called throughput legitimacy," explains Loew Beer. "This offers insights into the democratic quality of the Commission's work and considers issues such as: were members able to contribute equally? What was the quality of the debate? How were the individual members of the Commission equipped? There is very little empirical research on this - and our approach has enabled us to gain new insights."

Recommendations for future commissions

The Commission's work resulted in:

1) the Coal Phase-out Act

2) the Structural Strengthening Act for Coal Regions, which provides for extensive financial aid for the affected regions.

According to the study's conclusion, in its various legislative initiatives the federal government frequently refers to the agreement reached by the Commission, even where these deviate from the Commission's recommendations in practice. From the perspective of democratic theory, it is problematic that the federal government failed to assume political responsibility for its decisions. According to the authors, this explains why the "coal policies" pursued by the federal and state governments continued to meet with public resistance.

Other critical aspects: It was difficult for the public to understand how exactly the decisions were made. Was a solution found to compensate for the differences in expertise, experience, and access to resources among the Coal Commission's members? Not at all. The federal government's desire to limit its financial exposure, coupled with its unambitious approach to climate policy, diminished the Commission's ability to pursue the common good, resulting in an outcome that the Federal Constitutional Court has rightly criticised as unsustainable.

The researchers also note that it is somewhat paradoxical that while government has allocated substantial funding for the affected regions, the compromise has met with little approval in the regions. Loew Beer speculates that this could be due to the lack of involvement of citizens in the Commission's work and the legislative process.

The researchers recommend the following for future commissions:

- binding criteria for the composition and support of future commissions, as well as transparency guidelines

- mandates that reflect the diverse interests of the affected parties

- a broadening and strengthening of parliamentary debates and decision-making processes. Such far-reaching issues as this should be debated and decided by parliament

- professional and inclusive moderation

- the creation of citizen participation processes to accompany the work of future commissions

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

Errors at the start of life

image: A bovine egg after fertilization: The parental genomes are still located in two separate pronuclei. Before unification, the chromosomes (magenta) cluster at the pronuclear interface. Part of the cytoskeleton is colored blue. Super resolution microscopy image.

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MPI for Biophysical Chemistry/ Tommaso Cavazza and Melina Schuh

Only one in three fertilizations leads to a successful pregnancy. Many embryos fail to progress beyond early development. Cell biologists at the Max Planck Institute (MPI) for Biophysical Chemistry in Göttingen (Germany), together with researchers at the Institute of Farm Animal Genetics in Mariensee and other international colleagues, have now developed a new model system for studying early embryonic development. With the help of this system, they discovered that errors often occur when the genetic material from each parent combines immediately after fertilization. This is due to a remarkably inefficient process.

Human somatic cells typically have 46 chromosomes, which together carry the genetic information. These chromosomes are first brought together at fertilization, 23 from the father's sperm, and 23 from the mother's egg. After fertilization, the parental chromosomes initially exist in two separate compartments, known as pronuclei. These pronuclei slowly move towards each other until they come into contact. The pronuclear envelopes then dissolve, and the parental chromosomes unite.

The majority of human embryos, however, end up with an incorrect number of chromosomes. These embryos are often not viable, making erroneous genome unification a leading cause of miscarriage and infertility.

"About 10 to 20 percent of embryos that have an incorrect number of chromosomes result from the egg already containing too few or too many chromosomes prior to fertilization. This we already knew," explains Melina Schuh, director at the MPI for Biophysical Chemistry. "But how does this problem arise in so many more embryos? The time immediately after the sperm and egg unite - the so-called zygote stage - seemed to be an extremely critical phase for the embryo's development. We wanted to find out why this is the case."

Insights from a new model system

For their investigations, the scientists analyzed microscopy videos of human zygotes that had been recorded by a laboratory in England. They additionally set out to find a new model organism suitable for studying early embryonic development in detail. "Together with our collaboration partners at the Institute of Farm Animal Genetics, we developed methods for studying live bovine embryos, which closely resemble human embryos," explains Tommaso Cavazza, a scientist in Schuh's department. "The timing of the first cell divisions is comparable in human and bovine embryos. Furthermore, the frequency of chromosomes distributing incorrectly is about the same in both systems." Another advantage of this model system is: The scientists obtained the eggs from which the bovine embryos developed from slaughterhouse waste, so no additional animals had to be sacrificed.

Schuh's team fertilized the bovine eggs in vitro and then used live-cell microscopy to track how the parental genetic material unites. They found that the parental chromosomes cluster at the interface between the two pronuclei. In some zygotes, however, the researchers noticed that individual chromosomes failed to do so. As a result, these chromosomes were 'lost' when the parental genomes united, leaving the resulting nuclei with too few chromosomes. These zygotes soon showed developmental defects.

"The clustering of chromosomes at the pronuclear interface seems to be an extremely important step," Cavazza explains. "If clustering fails, the zygotes often make errors that are incompatible with healthy embryo development."

Dependent on an inefficient process

But why do parental chromosomes often fail to cluster correctly? The Max Planck researchers were able to uncover that as well, as Cavazza reports: "Components of the cytoskeleton and the nuclear envelope control chromosome movement within the pronuclei. Intriguingly, these elements also steer the two pronuclei towards each other. So we are dealing with two closely linked processes that are essential, but often go wrong. Thus, whether an embryo will develop healthily or not depends on a remarkably inefficient process."

The scientists' findings are also relevant for in vitro fertilization in humans. It has been discussed for some time whether the accumulation of the so-called nucleoli at the pronuclear interface in human zygotes could be used as an indicator for the chance of successful fertilization. Zygotes in which these pronuclear components all cluster at the interface have a better chance of developing successfully, and could therefore be preferentially used for fertility treatment. "Our observation that chromosomes need to cluster at the interface to guarantee healthy embryo development supports this selection criterion," Schuh says.

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Max-Planck-Gesellschaft

Conservationists concerned about illegal hunting and exploitation of porcupines in Indonesia

image: Porcupines are being illegally hunted and exploited throughout their range in Indonesia for local subsistence and commercial trade. They are reportedly in decline, yet there seems to be little control or monitoring on uptake and trade. A new study examining seizure data of porcupines in Indonesia found a total of 39 incidents from January 2013 to June 2020 involving an estimated 452 porcupines. The research was published in the open-access, peer-reviewed journal Nature Conservation.

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James Eaton

Porcupines are frequently traded across Asia, and Indonesia, home to five species, is no exception. They are targeted for a number of reasons: their meat as an alternative source of protein, their bezoars consumed as traditional medicine, and their quills used as talismans and for decorative purposes.

A new study examining seizure data of porcupines, their parts and derivatives in Indonesia found a total of 39 incidents from January 2013 to June 2020 involving an estimated 452 porcupines. The research was published in the open-access, peer-reviewed journal Nature Conservation.

There are no harvest quotas for any porcupine species in Indonesia, which makes all hunting and trade in porcupines illegal. Of the five species found in the country, only the Sunda porcupine (Hystrix javanica) is currently protected, with its protected status only introduced in 2018. Interestingly, prior to 2018, the Malayan porcupine (H. brachyura) was the only protected porcupine species in Indonesia, but then it was removed from the updated species protection list and replaced with the Sunda porcupine.

"The reasons for this are unclear, but certainly unwarranted, considering that the Malayan porcupine is the species most frequently identified as confiscated, and one can only assume the reason for its removal is due to its commercial value," says Lalita Gomez, author of the study and Programme Officer of Monitor Conservation Research Society.

What clearly emerges from this study is that porcupines are being illegally hunted and exploited throughout their range in Indonesia for local subsistence and commercial trade. Porcupines are reportedly in decline in Indonesia, yet there seems to be little control or monitoring on uptake and trade. This is particularly concerning because four of the five porcupine species in Indonesia have a restricted range, and three of them are island endemics - the Sumatran porcupine (H. sumatrae), Sunda porcupine, and Thick-spined porcupine (H. crassispinis).

Illegal hunting and trade of porcupines in Indonesia is facilitated by poor enforcement and legislative weakness, and it is imperative that effective conservation measures are taken sooner rather than later to prevent further depletion of these species.

Gomez recommends that all porcupines be categorised as protected species under Indonesian wildlife laws and listed in Appendix II of the Convention on International Trade in Endangered Species of Wild Fauna and Flora (CITES). This would require any international trade to take place through a supervisory system, which would allow for regulation and make it easier to track and analyse trends, thus providing an early warning system in case wild populations begin to decline.

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Pensoft Publishers

Prenatal exposure to famine heightens risk for later being overweight

An analysis of historical medical records found that men who were prenatally exposed during early gestation to the Dutch famine of 1944-1945 were 30 percent more likely to be overweight with a Body Mass Index of 25 or over at age 19, compared to a similar group not exposed to the famine. Professor L. H. Lumey at Columbia University Mailman School of Public Health led the study, which is published in the International Journal of Obesity. The study confirms evidence on the health risks of prenatal famine exposure, which also includes diabetes and schizophrenia.

The mechanism by which famine exposure raises the risk for later excess weight is still unknown. The researchers speculate that famine exposure could lead to changes in DNA methylation that stimulate being overweight. Or that surviving babies might have genetic profiles enabling them to thrive on fewer calories. "If so, it is tragic and ironic that surviving the famine would increase one's risk for obesity," says first author L. H. "Bertie" Lumey, MD, PhD, professor of epidemiology at Columbia Mailman School. "A slower metabolism that would have helped them survive the pandemic, in times of plenty could also contribute to weight problems and related health issues."

The researchers studied heights and weights of 371,100 men in the Netherlands born between 1943 and 1947 and examined for military service at age 19, including men with and without prenatal exposure to the Dutch famine. They found that a heightened overweight risk was present in men with famine exposure starting at the very beginning of gestation, not with exposure starting in the middle or at the end of gestation--a finding they say points to the start of pregnancy as a sensitive period of fetal development.

The study shows that the heightened overweight risk was limited to sons of manual workers born in the large cities of Western Netherlands, consistent with historical evidence on the socioeconomic and geographic populations known to be most affected by the famine.

Not surprisingly, excess weight presented its own risks. Those who were overweight at age 19 had a 30 percent greater mortality risk through age 63 relative to those with a BMI in the normal range. This was independent of famine exposure.

Further development of a 1976 Paper

The new paper extends and refines a 1976 study by Columbia researchers using current definitions of overweight. Contrary to the earlier paper, current analytic approaches show no weight changes in sons of non-manual workers exposed in early gestation in the famine cities. The researchers note that the military examinations did not include waist or hip circumference or other measures of body mass distribution which could be even better indicators of chronic disease risk.

The new study also looked at whether or not a decline in birthrates among manual workers during the famine explained the relationship between prenatal famine exposure and risk for excess weight. It didn't.

"Our study builds on the rigorous science behind the original research in the 1970s led by Columbia epidemiologists Mervyn Susser and Zena Stein," says Lumey.

About the Dutch Famine

The Dutch famine (Hunger Winter) of 1944-45 was a period of civilian famine under German occupation at the end of World War II. Contemporary reports show that the famine was concentrated in the large cities of the Western Netherlands. It was limited to the last months of the war in the period between November 1944 and the surrender of the German forces to the Allies in May 1945. After Liberation, food supplies were rapidly distributed across the country. The food crisis provides an opportunity to study the relationship between maternal nutrition in pregnancy and offspring health.

Previous research, beginning shortly after the end of the war found a link between famine-exposed mothers and birth weight. Subsequent research established links between famine exposure and risk for obesity, diabetes, and schizophrenia, as well as the specific genomic pathways involved. Importantly, the research also ruled out a link between famine exposure and mental retardation.

Credit: 
Columbia University's Mailman School of Public Health

Agents that target viral RNA could be the basis for next generation anti-viral drugs

A new approach to tackling viruses by targeting the 'control centre' in viral RNA could lead to broad spectrum anti-viral drugs and provide a first line of defence against future pandemics, according to new research at the University of Birmingham.

In a new study, published in Angewandte Chemie, researchers have shown how this approach could be effective against the SARS-CoV-2 virus responsible for the COVID-19 pandemic. Earlier modelling and in vitro analysis by the team and published in Chemical Science has also shown effectiveness against the HIV virus.

Professor Mike Hannon, from the University of Birmingham's School of Chemistry, is co-lead author of the study. He said: "Although SARS-CoV-2 vaccines have been developed with unprecedented speed, there has still been a 12-month wait for development and approval. Viral pandemics remain a big threat and so broad-spectrum anti-virals are urgently needed to keep diseases like coronaviruses at bay while effective drugs are developed."

The technique proposed by the team uses cylindrically-shaped molecules which can block the function of a particular section at one end of the RNA strand. These RNA sections, known as untranslated RNA, are essential for regulating the replication of the virus.

Untranslated RNA contain junction points and bulges - essentially small holes in the structure- which are normally recognised by proteins or other pieces of RNA - events that are critical for viral replication to occur. The cylindrical molecules are attracted to these holes, and once they slide into them, the RNA closes around them, forming a precise fit, which consequently will interfere with the virus's ability to replicate.

"Our approach offers a very promising new route for anti-viral drug design," says Professor Hannon. "While most drugs in development target the virus's proteins, we have identified molecules capable of tackling the most fundamental part of the virus - its RNA. Experiments backed up by computer modelling have already shown this to be effective against SARS-CoV-2 and the HIV viruses and we anticipate it will also be effective against a wide range of other viruses, offering an important first step towards a broad spectrum anti-viral drug."

Co-lead author Dr Pawel Grzechnik, of the University of Birmingham's School of Biosciences, said: "The ongoing COVID-19 pandemic has revealed how important is RNA biology to understand molecular processes taking place in our cells, to find ways to suppress pathogens and to make efficient and safe vaccines. RNA only now emerges in the general consciousness of society as the major tool in therapies. We hope to continue our research and further investigate antiviral properties of the cylinders at the University of Birmingham."

Dr Zania Stamataki, of the University of Birmingham's Institute of Immunology and Immunotherapy and also co-lead author, said: "The SARS-CoV-2 pandemic has stressed the pressing need for the development on new antiviral treatments, particularly for RNA viruses. In Birmingham we have state-of-the-art containment level 3 facilities that allow us to study the full virus life cycle. We have developed models to test the effects of new antiviral therapies, and the supramolecular cylinders show promising results against replicating SARS-CoV-2. The ambition is that these new categories of compounds can be refined and targeted to extend their function against many other viruses that infect humans and animals."

The team will continue to develop the design of the cylindrical molecule to improve its effectiveness and control, and also to fully understand how it works within the virus before testing it in a model organism.

The research was funded by the Engineering and Physical Sciences Research Council, the Biotechnology and Biological Sciences Research Council (both part of UK Research and Innovation), the Wellcome Trust, the Royal Society, the Medical Research Foundation and the EU Marie Curie Fellowship scheme.

The cylindrical molecules have been the subject of previous research, led by Professor Hannon, which focussed on finding a way to control the way the cylinder interacts with DNA and RNA. This research resulted in novel compounds that have the potential to be developed into targeted treatments for cancers, viruses and other diseases, and is the subject of a patent application filed by University of Birmingham Enterprise.

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University of Birmingham

SARS-CoV-2 research: Second possible effective mechanism of remdesivir discovered

FRANKFURT. The virostatic agent remdesivir was developed to disrupt an important step in the propagation of RNA viruses, to which SARS-CoV-2 also belongs: the reproduction of the virus's own genetic material. This is present as RNA matrices with which the host cell directly produces virus proteins. To accelerate the production of its own proteins, however, RNA viruses cause the RNA matrices to be copied. To do so, they use a specific protein of their own (an RNA polymerase), which is blocked by remdesivir. Strictly speaking, remdesivir does not do this itself, but rather a substance that is synthesized from remdesivir in five steps when remdesivir penetrates a cell.

In the second of these five steps, an intermediate is formed from remdesivir, a substance with the somewhat unwieldy name GS-441524 (in scientific terms: a remdesivir metabolite). GS-441524 is a virostatic agent as well. As the scientists in the group headed by Professor Stefan Knapp from the Institute for Pharmaceutical Chemistry at Goethe University Frankfurt have discovered, GS-441524 targets a SARS-CoV-2 protein called nsP3. nsP3 is a multifunctional protein, whose tasks include suppressing the host cell's defence response. The host cell is not helpless in the face of a virus attack, but activates inflammatory mechanisms, among other things, to summon the aid of the cell's endogenous immune system. nsP3 helps the viruses suppress the cell's calls for help.

Professor Stefan Knapp explains: "GS-441525 inhibits the activities of an nsP3 domain which is important for the reproduction of viruses, and which communicates with human cellular defence systems. Our structural analysis shows how this inhibition functions, allowing us to lay an important foundation for the development of new and more potent antiviral drugs - effective not only against SARS-CoV-2. The target structure of GS-441524 is very similar in other coronaviruses, for example SARS-CoV and MERS-CoV, as well in a series of alphaviruses, such as the chikungunya virus. For this reason, the development of such medicines could also help prepare for future virus pandemics."

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Goethe University Frankfurt

Dartmouth-led study finds overemphasis on toy giveaways in TV ads unfairly promotes fast-food to children

video: Dartmouth College student Hannah Utter, Class of 2021, collaborated with researchers at the Koop Institute and Geisel School of Medicine at Dartmouth to analyze fast-food TV-ads directed at children. The team's research was published on May 10, 2021, in the journal Pediatrics. They found that ads often overemphasize premiums such as toy giveaways and games relative to the primary product being sold, the fast food itself. This marketing practice violates the industry's own guidelines--put in place to ensure that the use of premiums in ads is not deceptive or unfair--as young children lack the cognitive ability to understand advertising.

Image: 
C. Everett Koop Institute at Dartmouth

A new Dartmouth-led study, published this week in the journal Pediatrics, has found that the disproportionate use of premiums within child-targeted TV advertising for children's fast-food meals is deceptive. The researchers examined thousands of advertisements from 11 fast-food restaurants, but one company--McDonald's--accounted for nearly all the airtime and, as a result, the findings.

The researchers report that these ads often overemphasize premiums such as toy giveaways and games relative to the primary product being sold, the fast food itself. This marketing practice violates the industry's own guidelines--put in place to ensure that the use of premiums in ads is not deceptive or unfair--as young children lack the cognitive ability to understand advertising.

The practice also works against childhood obesity prevention efforts. Previous studies have shown that childhood obesity is common in the U.S. About 26 percent of children ages 2-5 are overweight or obese, putting them at risk for major health consequences as they get older. Still, fast food is heavily promoted and regularly consumed by kids--nearly one-third of U.S. children eat fast-food on any given day.

"In the past, we've looked at the prevalence of child-directed food marketing and how it negatively impacts kids' diets, behaviors, and even weight status, but this is the first time we've examined if these companies are adhering to their own guidelines, in relationship to the content they can present to children," explains first author Jennifer Emond, PhD, MS, an assistant professor of biomedical data science and of pediatrics at Dartmouth's Geisel School of Medicine.

In the study, the investigators analyzed content of all child-directed fast-food TV advertisements on four popular national networks--Disney XD, Nickelodeon, Nicktoons, and Cartoon Network--aired from February 1, 2019 through January 31, 2020.

The team quantified the percent of the audio transcript (word count) and visual airtime (seconds) that included premiums or food, as well as the onscreen size of the toys or giveaways. During the study period, which included 142 hours of total airtime, more than 20,000 child-directed ads from 11 fast-food restaurants were aired on the four TV networks.

Of the 28 unique child-directed advertisements for children's fast-food meals during the study year, 27 were for McDonald's Happy Meals, accounting for nearly all (99.8 percent) of the total airtime. On average, premiums (vs. food) accounted for 53 percent (vs. 16 percent) of words in the audio transcript and 59.2 percent (vs. 54.3 percent) of the visual airtime.

Industry guidelines, which are managed through the Children's Advertising Review Unit and are administered by the BBB National Programs (formerly the Better Business Bureau), clearly state that premiums within child-directed advertising must be secondary to the advertised product to avoid undue influence.

"I find it very interesting that these are self-regulatory guidelines or pledges that the companies have signed on to as part of an industry initiative," says Emond. "But they're not even adhering to their own pledges. We need to hold them accountable--through stronger oversight of child-directed marketing in the U.S., from an independent review body or regulatory agency."

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The Geisel School of Medicine at Dartmouth

Synergistic effects of acoustics-based therapy and immunotherapy in cancer treatment

Announcing a new article publication for BIO Integration journal. In this review the authors Yuheng Bao, Jifan Chen, Pintong Huang and Weijun Tong from Zhejiang University, Hangzhou, China discuss the synergistic effects of acoustics-based therapy and immunotherapy in cancer treatment.

Cancer immunotherapy to enhance the autogenous immune response to cancer tissue is reported to be a promising method for cancer treatment. After the release of damage-associated molecular patterns, dendritic cells mature and recruit activated T cells to induce immune response.

To trigger the release of cancer associated antigens, cancer acoustics-based therapy has various prominent advantages and has been reported in various research. In this article, the authors classify acoustics-based therapy into sonopyrolysis-, sonoporation-, and sonoluminescence-based therapy.

Detailed mechanisms of each therapy are discussed to demonstrate the status of cancer immunotherapy induced by acoustics-based therapy and to posit future research directions.

Credit: 
Compuscript Ltd