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Showing posts with label Biology. Show all posts
Showing posts with label Biology. Show all posts

Monday, 24 February 2020

Superresolution provides unexpected insights into the dynamic structure of mitochondria

Researchers have discovered an exciting property of mitochondria - the power plants of our cells. Their experiments show that the inner membranes of these cell power plants change their structure every few seconds. In this way, the team apparently can dynamically adapt to the energy requirements in the cell.

As power plants and energy stores, mitochondria are essential components of almost all cells in plants, fungi and animals. Until now, it has been assumed that these functions underlie a static structure of mitochondrial membranes. Researchers at the Heinrich Heine University Düsseldorf (HHU) and the University of California Los Angeles (UCLA) have now discovered that the inner membranes of mitochondria are by no means static, but rather constantly change their structure every few seconds in living cells.

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This dynamic adaptation process further increases the performance of our cellular power plants. "In our opinion, this finding fundamentally changes the way our cellular power plants work and will probably change the textbooks," says Prof. Dr. Andreas Reichert, Institute of Biochemistry and Molecular Biology I at the HHU. The results are described in a publication in EMBO Reports.

Mitochondria are extremely important components in cells performing vital functions including the regulated conversion of energy from food into chemical energy in the form of ATP. ATP is the energy currency of cells and an adult human being produces (and consumes) approximately 75 kilograms of ATP per day. One molecule of ATP is produced about 20,000 times a day and then consumed again for energy utilization.

This immense synthesis capacity takes place in the inner membrane of the mitochondria, which has numerous folds called cristae. It was previously assumed that a specific static structure of the cristae ensured the synthesis of ATP. Whether and to what extent cristae membranes are able to dynamically adapt or alter their structure in living cells and which proteins are required to do so, was unknown.

MIC13‐SNAP shows that CJs and cristae undergo remodelling at a timescale of seconds

The research team of Prof. Dr. Andreas Reichert with Dr. Arun Kondadi and Dr. Ruchika Anand from the Institute of Biochemistry and Molecular Biology I of the HHU in collaboration with the research team of Prof. Dr. Orian Shirihai and Prof. Dr. Marc Liesa from UCLA (USA), also supported by the Center for Advanced Imaging (CAi) of HHU, succeeded for the first time in showing that cristae membranes in living cells continuously change their structure dynamically within seconds within mitochondria.

This showed that the cristae membrane dynamics requires a recently identified protein complex, the MICOS complex. Malfunctions of the MICOS complex can lead to various serious diseases, such as Parkinson's disease and a form of mitochondrial encephalopathy with liver damage. After the identification of the first protein component of this complex (Fcj1/Mic60) about ten years ago by Prof. Andreas Reichert and his research group, this is another important step to elucidate the function of the MICOS complex.

"Our now published observations lead to the model that cristae, after membrane fission, can exist for a short time as isolated vesicles within mitochondria and then re-fuse with the inner membrane. This enables an optimal and extremely rapid adaptation to the energetic requirements in a cell," said Prof. Andreas Reichert.


Cristae undergo continuous cycles of membrane remodelling in a MICOS ‐dependent manner

Arun Kumar Kondadi, Ruchika Anand, Sebastian Hänsch, Jennifer Urbach, Thomas Zobel, Dane M Wolf, Mayuko Segawa, Marc Liesa, Orian S Shirihai, Stefanie Weidtkamp‐Peters, Andreas S Reichert.

EMBO reports, 2020;

DOI: 10.15252/embr.201949776

Monday, 17 February 2020

Unique recordings provide insight into the sexual activity of the arthropods

Millipedes during sex - the structures of their genitals are clearly visible in UV light. © Stephanie Ware, Field Museum

Researchers have observed millipedes during sex - and looked very closely. Her recordings of the sexual act reveal for the first time in detail how the genitals of males and females of the genus pseudopolydesmus interact with each other. It also turned out: After sex, the millipede lady apparently seals her vulva with a sticky secretion - maybe this way she protects the sperm, the team suspects.

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Whether foreplay-loving tardigrade, the underwater act of the dolphins or snow monkeys with extraordinary erotic preferences: The diverse genital organs and sex practices in the animal kingdom always amaze researchers. Even males who mutilate their partner's genitals after mating and species in which the female sex has the penis have already discovered biologists.

At the same time, there are many animals that have not yet been observed during lovemaking. How they do it is therefore largely a mystery - this also applies to the millipedes. These multi-legged arthropods have produced thousands of species in the course of evolution, and each of them is likely to reproduce in its own way, as Xavier Zahnle from the University of California at Davis and his colleagues explain.

Love game in the petri dish

In order to find out more about the genitals and sex practices of the millipedes, the team of scientists has now devoted itself to representatives from the genus Pseudopolydesmus. “The problem with millipedes is that they do many things underground. If you take them out, you disturb them and then they stop,” says co-author Petra Sierwald of the Field Museum in Chicago. Not so pseudopolydesmus millipedes: "These animals have sex even in bright light in the petri dish."

This exhibitionistic disposition was just right for the researchers: they observed the arthropods during reproduction and took a large number of photos of the act. They used UV light, among other things, because the genital organs of the arthropods shine under the influence of this radiation and the individual tissues can be better distinguished. Computed tomography (CT) studies provided additional insights into the structure of the genitals.

View of the female genital organs on the second pair of legs © Stephanie Ware, Field Museum

Ejaculation and mating members separated

The recordings of the millipede genitals - both individually and combined in the sexual act - now reveal for the first time how sex works in the genus pseudopolydesmus. Specifically, it turned out that, as already known from other millipedes, the testicles of the males are not directly connected to the mating extremities. "The male must therefore ejaculate and immerse his so-called gonopods in the bluish ejaculate," reports Sierwald.

For the actual sexual act, the female then turns her vulva outwards, as the scientists found. "She has two openings between her second pair of legs," says the researcher. When the male penetrates, tiny pliers hook it into the end of his gonopods in the female genitals. Gonopods and vulva fit together like a key to the lock - this is the only way the mating act works, as the team suspects.

Sealing of Vulva after sex

Also interesting: After sex, the vulva is sealed with a sticky secretion and the sperm is enclosed in the female's body. If the millipede later lays eggs, they come into contact with the stored sperm on the way out. But who actually closes the external female genital organs?

"Before the study, I thought that the secretion came from the male, who wants to use this method to prevent the female from mating again," reports Sierwald. “But our CT images revealed glands inside the vulva. This suggests that much of the secretion could come from the female. Whether it wants to protect his genitals or the sperm, it is an exciting question for further research."

In addition to giving us a better understanding of the mechanics of millipede sex, Sierwald hopes the project will enable scientists to better understand the relationships between different millipede species, which could shed light on how they evolved.

"This study will be important for understanding how millipedes in this genus are related and how they're distributed," says Sierwald. "They can tell us about the geologic history of North America. As mountain ranges and rivers formed, groups of millipedes would get cut off from each other and develop into new species." And, she notes, Pseuopolydesmus is just the tip of the iceberg.

"There are 16 orders of millipedes in the world, and for most of them, we have only faint ideas what the vulvae look like."


Genital morphology and the mechanics of copulation in the millipede genus Pseudopolydesmus (Diplopoda: Polydesmida: Polydesmidae).

Xavier J. Zahnle, Petra Sierwald, Stephanie Ware, Jason E. Bond

Arthropod Structure & Development, 2020; 54: 100913

DOI: 10.1016/j.asd.2020.100913

Research: Prenatal exposure to cosmetic ingredients promote childhood overweight

If unborn babies in the womb increasingly come into contact with butylparaben, their risk of later being overweight obviously increases. © Janulla / thinkstock

Consequential stress in the womb: If pregnant women use paraben-containing cosmetics, this could harm their offspring. As a study shows, prenatal exposure to butyl paraben increases the risk of being overweight in childhood. This could be due to epigenetic changes triggered by the environmental hormone. Butyl paraben is often used in skin creams, make-up and the like as a preservative.

Parabens are mainly used as preservatives in numerous everyday products. Recently, however, these connections have come under increasing criticism. Because studies suggest that certain parabens act as so-called endocrine disruptors. This means that they behave like hormones and can therefore intervene in the hormonal balance of humans and animals . As a result, developmental and reproductive disorders or other health problems may occur.

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The butyl paraben often found in cosmetic products such as skin creams, make-up and sun milk was considered to be comparatively harmless for a long time. But then studies indicated that this paraben variant also acts more like a hormone than assumed.

Stress in pregnancy

For this reason, Beate Leppert from the Helmholtz Center for Environmental Research in Leipzig and her colleagues have now devoted more attention to this paraben. You wanted to know: Does prenatal exposure to butyl paraben affect the later risk of being overweight? After all, environmental hormones like bisphenol A are already known to be able to set the course for extra pounds in the womb.

For their study, the scientists first evaluated data from 629 mother-child pairs. The mothers were asked about their cosmetic use during pregnancy and their urine was checked for parabens. After the birth, the focus was on the children: How would their body weight develop over the years?

From the skin to the body

The evaluations showed that many women used at least one cosmetic product that contained parabens during pregnancy. This was also evident in her urine: compared to subjects who only used paraben-free cosmetics, they had increased concentrations of these chemicals in their urine. As the research team explains, parabens can enter the body through the skin and can then also be detected in blood and excretions.

But this also means that if substances such as butyl paraben penetrate the organism, they may strain the unborn child in the event of pregnancy. But with what consequences? In their investigations, Leppert and her colleagues actually found a connection between the concentration of butyl paraben in the mother's urine and the later body weight of the children.

Increased risk of being overweight

Specifically, it became clear that the greater the exposure to butyl paraben during pregnancy, the more the offspring tended to be overweight in the first eight years of life. This relationship was more pronounced in girls than in boys, as the scientists found.

Looking for a possible explanation, the researchers then carried out experiments with mice. It also became apparent in the rodents: exposure to butyl paraben during pregnancy and lactation, especially in the offspring of female mice, led to the animals eating more and getting fatter. However, increased contact with this paraben in adulthood did not appear to affect weight gain.

Changes in appetite regulators

The exciting thing: paraben exposure in the young mice was not only associated with an increased risk of being overweight, but also with a striking epigenetic change in the hypothalamus. For example, the genes for the leptin receptor and prohormone proopiomelanocortin (POMC) were less active than normal, as studies revealed. Leptin is known as a satiety hormone and POMC also plays an important role in regulating appetite - this regulation could therefore be disrupted by paraben exposure.

“Childhood obesity has now reached epidemic-like dimensions worldwide. Endocrine disruptors are an example of environmental factors that can contribute to programming for overweight and obesity - especially in the sensitive phase around childbirth,” stated Leppert and her colleagues. "Our results suggest that prenatal exposure to butyl paraben also promotes the development of obesity in children."

Gender differences in view

As the scientists emphasize, other influencing factors such as nutrition or physical activity are of course also decisive for body weight in childhood. In her view, however, prenatal stress and its consequences play a significant role in the susceptibility to excess pounds. In the future, Leppert and her colleagues want to get to the bottom of the effects of butyl paraben. They also want to find out why girls are apparently more sensitive to this environmental hormone than boys - a possible explanation could be, for example, the different concentrations of sex hormones such as estrogen.

In view of their results to date, the researchers are already making a clear recommendation: "Expectant mothers should definitely use paraben-free products during the sensitive phases of pregnancy and lactation with a view to future health," says co-author Irina Lehmann. "Many cosmetics have already been declared paraben-free, otherwise take a look at the list of ingredients or, for example, using the ToxFox app helps," she concluded.


Maternal paraben exposure triggers childhood overweight development.

Beate Leppert, Sandra Strunz, Bettina Seiwert, Linda Schlittenbauer, Rita Schlichting, Christiane Pfeiffer, Stefan Röder, Mario Bauer, Michael Borte, Gabriele I. Stangl, Torsten Schöneberg, Angela Schulz, Isabell Karkossa, Ulrike E. Rolle-Kampczyk, Loreen Thürmann, Martin von Bergen, Beate I. Escher, Kristin M. Junge, Thorsten Reemtsma, Irina Lehmann, Tobias Polte.

Nature Communications, 2020;

DOI: 10.1038/s41467-019-14202-1

Saturday, 15 February 2020

Researchers make human organs transparent to enable 3D mapping down at cellular level

This image shows details of a human kidney that has been made transparent. © Helmholtz Zentrum München / Ertürk Lab

A look inside the organ: For the first time, researchers have succeeded in making human organs completely transparent. Thanks to their process, the complex structure of these tissues can be visualized and analyzed down to the cellular level. This enables accurate mapping of the organs - and could one day help create functional artificial replicas.

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Whether brain , heart or kidney: human organs are incredibly complex. Doctors now know the basic structure and function of these tissues. Deciphering its structure in every detail has always been a challenge. Because technologies to make organ structures visible down to the cellular level were missing.

That should change with so-called tissue clearing. This process makes organs transparent and thus enables complex 3D images of them to be generated. So far, however, this was only possible with tissues from mice. The problem: In the course of time, insoluble molecules such as collagen accumulate in human organ tissue and make it stiff. Common cleaning agents can therefore make mouse organs transparent - but they fail to work on human organs, especially to human tissue in adults.

A look into the brain, kidney and co

Shan Zhao from Helmholtz Zentrum München and her colleagues have now succeeded in making the apparently impossible: They have made intact human organs transparent. "We had to take a completely new path and start all over again to find a chemical that could also make human organs transparent," reports the researcher.

After a series of experiments, the scientists came up with the solution: They found that a detergent called CHAPS can create small holes in the stiff organs. This makes them more permeable to other solutions, which then penetrate the fabric a centimeter deep and convert it into transparent structures. In this way, Zhao's team managed, among other things, a unique look into a human brain and kidney.

For example, SHANEL provides insight into the cellular structures of an intact human eye.© Helmholtz Zentrum München / Ertürk Lab

"Key for mapping"

In order to be able to examine the transparent organs in detail, the researchers developed a new laser scanning microscope with a particularly large recording capacity and a self-learning algorithm. As they report, the microscope can take pictures of entire human organs up to the size of a kidney. The algorithm is then used to analyze the millions of cells imaged.

Zhao and her colleagues summarize their entire method under the name SHANEL (Small-micelle-mediated human organ efficient clearing and labeling). “SHANEL could become a key technology for mapping intact human organs in the near future. This would enable us to quickly understand much better how organs such as our brain develop and how they function in a healthy and diseased state,” explains Zhao's colleague Ali Ertürk.

Alternative to donor organs?

According to the scientists, this will result in exciting new possibilities for 3D printing of organs. Because cellular three-dimensional maps of human organs could in future serve as templates for such artificially produced tissues. To achieve this goal, the team is already working on mapping the most important human organs, starting with the pancreas, heart and kidney.

If one day the detailed replication of human organs succeeds, patients who depend on a donor organ in particular could benefit. "There is a huge shortage of organ donors for hundreds of thousands of people," says Ertürk. "The waiting time for patients and the transplantation costs are a real burden. Detailed knowledge about the cellular structure of human organs brings us an important step closer to creating functional organs artificially on demand." emphasizes the researcher.


Cellular and Molecular Probing of Intact Human Organs

Shan Zhao, Mihail Ivilinov Todorov, Ruiyao Cai, Hanno Steinke, Elisabeth Kemter, Eckhard Wolf, Jan Lipfert, Ingo Bechmann, Ali Ertürk

Published:February 13, 2020


Wednesday, 12 February 2020

Discovery of a mysterious virus in Brazil whose genome is almost completely unknown

Paulo VM Boratto et al. 2020

With almost 5000 species currently described, viruses are ubiquitous on Earth. From the bottom of the oceans to the human blood via the atmosphere, these acaryotic infectious agents can adopt extremely simple as well as extremely complex structures; as such, virologists have been studying them for many years, focusing more and more on viral genomes. And recently, a team of researchers discovered a virus whose genome is unlike any other known viral genome.

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The Yaravirus , named after Yara - or Iara, a figure of water queen in Brazilian mythology -, was recovered from Lake Pampulha, an artificial lake in the Brazilian city of Belo Horizonte. The Yaravirus ( Yaravirus brasiliensis ) constitutes a new line of amoebic viruses with a confusing origin and phylogeny, according to the research team.

Virologists Bernard La Scola from the University of Aix-Marseille in France and Jônatas S. Abrahão from the Federal University of Brazil Minas Gerais, however, are not beginners. Two years ago, the duo helped discover another aquatic viral novelty: the Tupanvirus, a potentially giant virus found in extreme aquatic habitats.

Giant viruses: that can perform complex biological tasks

Giant viruses, unlike the regular variety, are so called because of their huge capsids (protein shells that encapsulate virions). These much larger viral forms were only discovered this century, but they are not only remarkable for their size. They also have more complex genomes, giving them the ability to synthesize proteins, and therefore to perform complex tasks such as DNA repair, as well as DNA replication, transcription and translation.

Before their discovery, it was thought that viruses could not do such things, being considered as relatively inert and non-living entities, only capable of infecting their hosts. We now know that viruses are much more complex than previously believed, and in recent years scientists have discovered other types of viral forms that also challenge our thinking about how viruses can spread. and operate. The new discovery, the Yaravirus, does not appear to be a giant virus, made up of small 80 nm particles.

Transmission electron microscopy images of the Yaravirus (A) and its infection cycle (B, C, D, E). Credits: Paulo VM Boratto et al. 2020

Yaravirus: an almost completely new genome virus

But what is remarkable is how unique its genome is. “Most of the known amoeba viruses have been seen to share many features that ultimately prompted the authors to classify them into common evolving groups. Contrary to what is observed in other viruses isolated from the amoeba, the Yaravirus is not represented by a giant size and a complex genome, but at the same time carries a significant number of genes not previously described", write the authors.

Circular representation of the Yaravirus genome. Only six genes (red arrows) in total are identical to known viral genes. Credits: Paulo VM Boratto et al. 2020

In their investigations, the researchers discovered that more than 90% of the genes of Yaravirus had never been described before, constituting what are called orphan genes (ORFans). Only six genes found by far resembled known viral genes documented in public scientific databases, and a search among more than 8,500 metagenomes available to the public gave no clue as to what the Yaravirus could be closely linked to.

Giant viruses with more reduced viral forms?

“Using standard protocols, our very first genetic analysis could not find any recognizable capsid or other conventional viral genes sequences in the Yaravirus. According to current metagenomic protocols for viral detection, the Yaravirus would not even be recognized as a viral agent”.

As for what Yaravirus really is , the researchers can only speculate for the moment, but suggest that it could be the first isolated case of an unknown group of amoebic viruses, or potentially of a distant type giant virus that could have evolved into a reduced form.


A mysterious 80 nm amoeba virus with a near-complete “ORFan genome” challenges the classification of DNA viruses

Paulo V. M. Boratto, Graziele P. Oliveira, Talita B. Machado, Ana Cláudia S. P. Andrade, Jean-Pierre Baudoin, Thomas Klose, Frederik Schulz, Saïd Azza, Philippe Decloquement, Eric Chabrière, Philippe Colson, Anthony Levasseur, Bernard La Scola, Jônatas S. Abrahão


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