Tough childhood damages life prospects

Press releases   •   Jan 21, 2021 10:17 GMT

An adverse upbringing often impairs people’s circumstances and health in their adult years, especially for couples who have both had similar experiences. This is shown by a new study, carried out by Uppsala University researchers, in which 818 mothers and their partners filled in a questionnaire one year after having a child together. The study is now published in the scientific journal PLOS ONE.

Natural hazard events and national risk reduction measures unconnected

Press releases   •   Jan 20, 2021 12:13 GMT

Countries where massive natural hazard events occur frequently are not more likely than others to make changes to reduce risks from future disasters. This is shown in an interdisciplinary Uppsala University study now published in Nature Communications.

European eels – one gene pool fits all

Press releases   •   Jan 20, 2021 10:02 GMT

European eels spend most of their adult life in a range of fresh- and brackish waters, across Europe and Northern Africa. Using whole-genome analysis, a new study finds that all European eels belong to a single panmictic population, an extraordinary finding for a species living under such variable environmental conditions. The study is published in PNAS.

​Disrupted immune cell navigation in lymph nodes of breast cancer patients

Press releases   •   Jan 13, 2021 12:30 GMT

In breast cancer, tumours of different types have divergent effects on the functioning of the lymph nodes. In patients with invasive breast cancer, the blood vessels and supporting tissue of the lymph nodes change, but this does not occur in patients with a non-invasive form of breast cancer (ductal carcinoma in situ). This is shown in a new study from Uppsala University, now published online in the scientific journal Cancers.

In invasive breast cancer, i.e. breast cancer that spreads beyond the original tissue where it arose, cancer cells commonly spread to the lymph nodes (metastasis). Lymph node metastasis indicates an unfavourable prognosis for the patient. The study now shows that in patients with invasive breast cancer, changes are seen both in the specialised blood vessels of the lymph nodes (high endothelial venules, HEVs) and in the supporting cells that surround these vessels (fibroblastic reticular cells, FRCs). These changes occur even before the cancer cells spread to the lymph nodes (pre-metastatic).

To enable the body to defend itself against the cancer, the T cells – white blood cells that fight diseases – must be able to reach the lymph nodes. They do so through the HEVs assisted by the supporting FRCs. In simple terms, the HEVs may be said to form the roads while the FRCs, surrounding them, serve as road signs, showing the T cells the right way.

“We can identify changes of the T cells indicating that, in invasive breast cancer, their ability to navigate is impaired. But we still want to learn more about the immunological consequences of the changes we see in the HEVs and surrounding FRCs,” says Tove Bekkhus, a PhD student at Uppsala University’s Department of Immunology, Genetics and Pathology, and the first author of the study.

Previous studies have indicated that tumour diseases can affect the functionsing of the lymph node vessels, and also their surrounding supporting cells. However, in the present study the two changes were found to be connected, for the first time.

The study is also the first to show that patients who have the non-invasive form of breast cancer lack or have very limited changes of the HEVs in the lymph nodes.

In patients with invasive breast cancer, on the other hand, such changes are evident even before cancer cells spread to the lymph nodes. This is a new piece of knowledge for understanding why metastasis to the lymph nodes is so common in this type of breast cancer.

“This is a step on the way to understanding better how invasive cancer affects our immune system at several different levels. The lymph nodes are small organs that serve as our body’s defence headquarters. In the lymph nodes, the immune cells get instructions on how to combat the cancer. The fact that cancer cells can spread to the lymph nodes suggests that they must be able to inhibit the immune system there. We now have new opportunities to understand why. Our work also paves the way for evaluating these and other changes in lymph nodes as biomarkers in breast cancer and other tumour types”, says Maria Ulvmar, group leader at the Department of Immunology, Genetics and Pathology at Uppsala University.

Bekkhus et al., Remodeling of the lymph node high endothelial venules reflects tumor invasiveness in breast cancer and is associated with dysregulation of perivascular stromal cells, Cancers 2021, 13(2), 211; https://doi.org/10.3390/cancers13020211

Further information:

Maria Ulvmar, Researcher at Department of Immunology, Genetics and Pathology, Uppsala University, Sweden, email: maria.ulvmar@igp.uu.se, phone: 073-783 42 97 

Uppsala University
The first University in Sweden. Quality, knowledge, and creativity since 1477. Education and research of the highest quality and relevance to society, business, and culture. Uppsala University is ranked among the world’s top higher education institutions. www.uu.se

In breast cancer, tumours of different types have divergent effects on the functioning of the lymph nodes. In patients with invasive breast cancer, the blood vessels and supporting tissue of the lymph nodes change, but this does not occur in patients with a non-invasive form of breast cancer. This is shown in a new study from Uppsala University, published online in the scientific journal Cancers.

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Antibiotic resistance from random DNA sequences

Press releases   •   Jan 08, 2021 09:38 GMT

An important and still unanswered question is how new genes that cause antibiotic resistance arise. In a new study, Swedish and American researchers have shown how new genes that produce resistance can arise from completely random DNA sequences. The results have been published in the journal PLOS Genetics.

Antibiotic resistance is a major global problem and the spread of resistant bacteria causes disease and death, and constitutes a major cost to society. The most common way for bacteria to develop resistance is by taking up various types of resistance genes from other bacteria. These genes encode proteins (peptides) that can lead to resistance by: (i) deactivating the antibiotic, (ii) reducing its concentration, or (iii) altering the antibiotic’s target so that the antibiotic can no longer bind to that target and hence halt the growth of the bacterium. Once resistance genes have arisen, they can quickly spread between different pathogenic bacteria and reduce the effectiveness of our antibiotics. It is therefore important to detect and characterise new resistance genes as quickly as possible – in order to monitor the spread of resistance and also to facilitate treatment and the development of new antibiotics.

To study the emergence of resistance genes, the researchers used laboratory experiments to investigate whether it was possible to generate a gene from random DNA sequences that would give rise to antibiotic resistance. This was done by first designing nearly one billion random DNA sequences that were then placed on a plasmid in the intestinal bacterium Escherichia coli. (Plasmids are DNA molecules that replicate independently and can be transferred from one organism to another.)

These random DNA sequences were then expressed in the bacterium as short peptides. While most of these peptides had no effect on the bacterium at all, six different peptides did, causing the bacterium to become resistant to the antibiotic Colistin, an important antibiotic medication of last resort that is used in severe infections to kill the bacteria by binding to and destroying the bacterium’s cell membrane. These peptides caused resistance by increasing the expression of genes that are involved in the modification of the bacterium’s cell membrane. This modification of the cell membrane resulted in the antibiotic not being able to bind to cell membrane, and thus not being able to reduce the survival of the bacterium.

“We have now shown in two different studies that random sequences of amino acids can give rise to new functions that are beneficial to the bacterium such as antibiotic resistance. This suggests that the evolution of new functions from random DNA sequences is not as unusual as previously thought,” says Dan I. Andersson, Professor in Medical Bacteriology and responsible for the study.

“An important question that remains unanswered and requires further study is whether these new genes are naturally present in bacteria or can only be observed in laboratory experiments,” says Michael Knopp, post-doctoral researcher at the Department of Medical Biochemistry and Microbiology and the study’s first author.

For more information about this research at Uppsala University, please contact Dan I. Andersson, phone: +46 18 471 4175, email: Dan.Andersson@imbim.uu

A novel type of colistin resistance genes selected from random sequence space (2021) PLOS Genetics, DOI: 10.1371/journal.pgen.1009227

This research was funded by the Wallenberg Foundation and the Swedish Research Council.

Uppsala University
The first University in Sweden. Quality, knowledge, and creativity since 1477. Education and research of the highest quality and relevance to society, business, and culture. Uppsala University is ranked among the world’s top higher education institutions. www.uu.se

An important and still unanswered question is how new genes that cause antibiotic resistance arise. In a new study, Swedish and American researchers have shown how new genes that produce resistance can arise from completely random DNA sequences. The results have been published in the journal PLOS Genetics.

Read more »

Faulty metabolism of Parkinson’s medication in the brain linked to severe side effects

Press releases   •   Jan 07, 2021 12:41 GMT

Until now, the reason why the drug levodopa (L-Dopa), which reduces the motor symptoms of Parkinson’s disease, declines in efficacy after a few years’ use has been unknown. A side effect that then often occur is involuntary movements. A Swedish–French collaboration, led from Uppsala University, has now been able to connect the problems with defective metabolism of L-Dopa in the brain. The study is published in Science Advances.

“The findings may lead to new strategies for treating advanced Parkinson’s,” says Professor Per Andrén of the Department of Pharmaceutical Biosciences at Uppsala University. He and Dr Erwan Bézard of the University of Bordeaux, France, headed the study jointly.

Parkinson’s disease (PD) is caused by the slow death of nerve cells that produce the key neurotransmitter dopamine. This results in the typical symptoms, such as rigidity and tremor. Treatment with L-Dopa, a precursor to dopamine, initially works very well as a rule; but after a few years, the effect of each dose becomes progressively more short-lived. Adverse side effects, such as rapid alternation between rigidity and uncontrolled movements that become increasingly severe over time, are very common. Finally, the benefits of L-Dopa treatment are jeopardised and the symptoms can become debilitating. Which neurochemical mechanisms cause these side effects is unknown. The involuntary movements are collectively known as “L-Dopa-induced dyskinesia”.

Using a new method, “matrix-assisted laser desorption/ionisation mass spectrometry imaging” (MALDI-MSI), the researchers were able to map numerous neurotransmitters and other biomolecules directly in non-human primate brain tissue, which had not been possible before. The samples came from a French biobank.

Thus, they were able to compare in detail, and identify the differences between, the brains of two groups of parkinsonian animals. One group was suffering from motor complications caused by long-term L-Dopa treatment. In the second group were individuals who had PD symptoms to the same degree, and were receiving identical L-Dopa treatment, but in whom the medication had not caused the motor side effects.

In the group with motor disorders, abnormally elevated levels of both L-Dopa and 3-O-methyldopa were detected. The latter, a metabolite, is a product formed when L-Dopa is converted to dopamine. This was seen in all the brain regions examined, except – to the researchers’ surprise – the particular part of the brain known as the striatum, which is thought to be involved in L-Dopa-induced movement disorders.

This suggests that brain mechanisms other than those that were previously recognised may underlie the motor disorders. Instead of originating in the striatum, these problems are most likely triggered by a direct effect of L-Dopa or dopamine, or a combination of the two, in some other part of the brain.

“Although there seems to be a direct connection between L-Dopa and motor complications, the mechanism that brings about the involuntary movements is still unclear and subject to further research. On the other hand, the new results show a direct role for L-Dopa in this motor disorder – independently from dopamine. And this indicates that L-Dopa may also act on its own in the brain,” Andrén says.


Elva Fridjonsdottir et al., Mass spectrometry imaging identifies abnormally elevated brain L-DOPA levels and extrastriatal monoaminergic dysregulation in L-DOPA–induced dyskinesia, Science Advances. DOI: 10.1126/sciadv.abe5948


For more information, please contact:
Per Andrén, Professor at the Department of Pharmaceutical Biosciences, Uppsala University Tel: +46 70 167 93 34, email: per.andren@farmbio.uu.se

Uppsala University
The first University in Sweden. Quality, knowledge, and creativity since 1477. Education and research of the highest quality and relevance to society, business, and culture. Uppsala University is ranked among the world’s top higher education institutions. www.uu.se

Until now, the reason why the drug levodopa (L-Dopa), which reduces the motor symptoms of Parkinson’s disease, declines in efficacy after a few years’ use has been unknown. A side effect that then often occur is involuntary movements. A Swedish–French collaboration, led from Uppsala University, has now been able to connect the problems with defective metabolism of L-Dopa in the brain.

Read more »

Parents’ finances differently affected by having a child diagnosed with cancer

Press releases   •   Jan 04, 2021 11:51 GMT

Mothers and fathers of children diagnosed with cancer are affected financially in different ways. While mothers’ incomes fall in the short term and then rise, the adverse financial repercussions on fathers occur later. Researchers at Uppsala University have investigated the socioeconomic impact on parents of having a child diagnosed with cancer.

New Centre for Nuclear Disarmament for Uppsala University

Press releases   •   Dec 22, 2020 14:45 GMT

Today, the Swedish Government decided to assign to Uppsala University the task of setting up a new national knowledge centre for research on nuclear disarmament. With an interdisciplinary approach and researchers in fields including peace and conflict research and nuclear physics, the incipient Alva Myrdal Centre will conduct research with the goal of contributing to a safer world for humankind.

​Archives crucial for Freemasons’ identity

Press releases   •   Dec 22, 2020 10:42 GMT

The Order of Freemasons’ meticulous archives are fundamental to their identity. The unique structure of the masonic archives reinforces the secrecy and mystique of the self-image that has been fashioned by the Order — and characterises it in the eyes of others. This is shown in a recent thesis from Uppsala University, which focuses on the Masons’ archives in the 18th and 19th centuries.

Parlour games 400 years ago – almost like today

Press releases   •   Dec 17, 2020 13:34 GMT

In a new thesis from Uppsala University, art historian Greger Sundin studied 16th and 17th century games that have been preserved in princely collections for example. Right at the end of his work on the thesis, he and a colleague were able to solve an over 300 year old riddle about a game in the Augsburg Art Cabinet.

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