Historical genomes reveal recent changes in genetic health of eastern gorillas

Press Releases   •   Dec 27, 2018 16:00 GMT

The critically endangered Grauer’s gorilla has recently lost genetic diversity and has experienced an increase in harmful mutations. These conclusions were reached by an international team of researchers who sequenced eleven genomes from eastern gorilla specimens collected up to 100 years ago, and compared these with genomes from present-day individuals. Results are published in Current Biology.

Our Universe: An expanding bubble in an extra dimension

Press Releases   •   Dec 27, 2018 16:00 GMT

Uppsala University researchers have devised a new model for the Universe – one that may solve the enigma of dark energy. Their new article, published in Physical Review Letters, proposes a new structural concept, including dark energy, for a universe that rides on an expanding bubble in an additional dimension.

Simple method rescues stressed liver cells

Press Releases   •   Dec 21, 2018 11:23 GMT

Isolated human hepatocytes are essential tools in preclinical and clinical liver research, but cell quality is highly variable. Now, researchers from Uppsala University have devised a simple protocol that improves hepatocyte quality and enables cells from a wider quality spectrum to be used in standard and advanced cell culture. The findings are published in Archives of Toxicology.

Hepatocytes are responsible for detoxification of the blood, and constitute around 80% of the liver volume. They are used extensively in laboratory experiments, such as studies of drug uptake, metabolism, and toxicity. Freshly isolated human hepatocytes are not regularly available, however, as they can only be prepared by highly specialized laboratories. Therefore, researchers rely on deep-frozen (cryopreserved) cells to ensure continuous access. Unfortunately, freezing and thawing mammalian cells is very stressful and frequently results in loss of function.

“The cellular stress associated with isolation and freezing takes its toll on the hepatocytes, and many cells are too damaged to recover completely after thawing. When too many cells are damaged, they become practically useless for most applications,” says Magnus Ölander, a PhD student in the Drug Delivery group headed by professor Per Artursson at Uppsala University.

The research group used state-of-the-art mass spectrometry to compare the expression of thousands of proteins in damaged and healthy hepatocytes, and found that the damage involved apoptosis, a controlled form of cell death.

“Through further analysis, we noticed that the damaged cells were mostly in the early stages of apoptosis. We reasoned that if we could figure out a way to temporarily decrease the stress, we could give the cells a chance to recover,” says Magnus Ölander.

The researchers therefore treated hepatocytes with different stress-reducing compounds, and discovered that the damage could indeed be reversed by using a specific apoptosis inhibitor. Based on these findings, they designed a simple restoration protocol that improves the quality of suboptimal human hepatocyte preparations to the point where they can be used for most applications, with restored functionality in terms of drug uptake, metabolism, and toxicity. This is the first time that human hepatocytes of suboptimal quality have been ‘rescued’ from the freeze state, which has previously been considered a futile endeavor.

“Another novel aspect is the transient nature of our approach. The inhibitor is only used for a short time after thawing, and does not need to be included in the cell culture medium. We predict that our protocol can dramatically increase the availability of human hepatocytes of high quality, as suboptimal human hepatocytes can be found in deep-freezers in laboratories all over the world. This will ultimately give the scientific community improved access to these important cells,” says Magnus Ölander.

Ölander et al., A simple approach for restoration of differentiation and function in cryopreserved human hepatocytes, Archives of Toxicology, DOI: 10.1007/s00204-018-2375-9

For more information, please contact:
Magnus Ölander, PhD student at the Department of Pharmacy at Uppsala University, tel: + 46 70 307 56 49, email: magnus.olander@farmaci.uu.se
Per Artursson, Professor at the Department of Pharmacy at Uppsala University, tel: + 46 70-425 08 88 email: per.artursson@farmaci.uu.se

Uppsala University -- quality, knowledge, and creativity since 1477
World-class research and outstanding education of global benefit to society, business, and culture.
Uppsala University is one of northern Europe's highest ranked academic institutions. www.uu.se

Isolated human hepatocytes are essential tools in preclinical and clinical liver research, but cell quality is highly variable. Now, researchers from Uppsala University have devised a simple protocol that improves hepatocyte quality and enables cells from a wider quality spectrum to be used in standard and advanced cell culture. The findings are published in Archives of Toxicology.

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Surgery unnecessary for many prostate cancer patients

Press Releases   •   Dec 12, 2018 22:00 GMT

Otherwise healthy men with advanced prostate cancer may benefit greatly from surgery, but many with this diagnosis have no need for it. These conclusions were reached by researchers after following a large group of Scandinavian men with prostate cancer for 29 years. The results are now published in The New England Journal of Medicine.

The research findings now presented are from the 29-year follow-up of the Scandinavian Prostate Cancer Group Study Number Four (SPCG-4), investigating the benefits of surgery for prostate cancer. The study comprised 695 men who were randomly assigned to two groups, one to get surgical treatment and the other to receive treatment of symptoms only (“watchful waiting”).

The men in this study were diagnosed between 1989 and 1999. Only a few (12 per cent) of them had their cancer detected early by having their blood tested for prostate-specific antigen (PSA). The study was carried out during the period before large-scale use of the PSA test began in Scandinavia.

After 29 years’ follow-up, 80 per cent of the men had died. For 32 per cent of these, death was due to prostate cancer. Seventy-one men in the surgery group died of prostate cancer, while 110 did so in the group receiving symptom treatment only. The study showed that 12 per cent of those who had prostatectomies had been saved from dying of prostate cancer; that 19 per cent had incurable cancer; but that the majority of the men had died of other causes. The results also showed that the men who had been operated on lived, on average, 2.9 years longer than the men who received treatment of symptoms only.

It is evident from the study that men who are otherwise healthy and whose advanced prostate cancer is confined to the prostate gland alone may benefit greatly from the surgery. Nevertheless, it was also found that, despite their diagnoses of prostate cancer, many men never suffered from a serious relapse during their lives, nor died from the disease. For the treatment to be optimally beneficial for men with prostate cancer, it is therefore crucially important to find the correct balance between the benefit from prostatectomy, on the one hand, and its side-effects on the other.

Through PSA, many men are now being diagnosed with prostate cancer who will never develop advanced or life-threatening symptoms. Compared with the 1990s, more men with prostate cancer should thus be actively followed up and treated only if signs of advanced cancer are present.

For more information, contact Anna Bill-Axelsson, email: anna.bill.axelson@surgsci.uu.se Mobile phone: +46 70-167 9747.

Radical Prostatectomy or Watchful Waiting in Prostate Cancer — 29-Year Follow-up, N Engl J Med 2018;379:2319-29. DOI: 10.1056/NEJMoa1807801.

Uppsala University -- quality, knowledge, and creativity since 1477
World-class research and outstanding education of global benefit to society, business, and culture.
Uppsala University is one of northern Europe's highest ranked academic institutions. www.uu.se

Otherwise healthy men with advanced prostate cancer may benefit greatly from surgery, but many with this diagnosis have no need for it. These conclusions were reached by researchers after following a large group of Scandinavian men with prostate cancer for 29 years. The results are now published in The New England Journal of Medicine.

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Biologists shed new light on an old question

Press Releases   •   Dec 12, 2018 17:00 GMT

For nearly 100 years biologists have argued about how exactly natural selection can possibly work. If nature selects the individuals with the best genes then why aren’t all organisms the same? What maintains the genetic variation that natural selection acts upon, the genetic variation that has ultimately led to the spectacular diversity of life on Earth today? Recent findings made at Uppsala University suggest that the answer could be sex.

Evolutionary genetic theory shows that genetic variation can be maintained when selection favors different versions of the same genes in males and females – an inevitable outcome of having separate sexes. That is, for many genes there may not be a universally ‘best’ version, but rather one is best for males and one is best for females. This is known as sexually antagonistic genetic variation, but it might only be maintained under a narrow set of conditions, limiting its prevalence in nature. However, Dr. Karl Grieshop and Professor Göran Arnqvist’s study, published in PLoS Biology, may change this view.

“One of the simplest ways for sexually antagonistic selection to maintain genetic variation in fitness is via sex-specific dominance reversal, where neither version of a gene is always dominant or recessive, but rather the version that benefits a given sex is also dominant in that sex. So, whether a given version of a gene is dominant or recessive to the other will depend upon which sex it is in,” says Dr. Karl Grieshop.

This mechanism was met with early skepticism, but has seen recent theoretical and empirical support.

Grieshop and Arnqvist have now provided the first evidence of sex-specific dominance reversal for fitness. Using a panel of genetic strains of a seed beetle population that Grieshop studied throughout his PhD, and analyzing crosses among these strains, they could determine which strains harbored genetic variation that was dominant to the others’. Further, they could do this with regard to male fitness and female fitness separately. When they ranked the strains according to their relative dominance over one another they found that strains tending to be dominant over other strains with regard to male fitness also tended to be recessive to other strains with regard to female fitness, and vice versa. Thus, whether the genetic variation for fitness in each of their strains was dominant or recessive to that of other strains depended, oppositely, on whether it was in a male or a female.

The pattern suggests that sex-specific dominance reversal for fitness is a strong and common phenomenon throughout the genome in their study population.

For more information, please contact:
Dr. Karl Grieshop
karlgrieshop@gmail.com
+1 647 230 5077

Grieshop, K., & Arnqvist, G. (accepted for PLoS Biology). Sex-specific dominance reversal of genetic variation for fitness. DOI: 10.1371/journal.pbio.2006810

Related articles:
Connallon T. & Chenoweth SF. (upcoming PLoS Biology Primer). Dominance reversals and the maintenance of genetic variation for fitness.

Dr. Grieshop defended his PhD at Uppsala University’s Institute for Ecology and Genetics (IEG) in September of 2017. He is now at the University of Toronto’s Department of Ecology and Evolutionary Biology as a Faculty of Arts and Science Postdoctoral Fellow, and he is a recent recipient of an International Postdoctoral Fellowship from the Swedish Research Council (VR), which will extend his stay in Toronto before returning him to Sweden. Professor Göran Arnqvist – Grieshop’s PhD supervisor – is the chair of the Animal Ecology program at IEG, and the study was funded by his research grants from the European Research Council and VR.

Uppsala University -- quality, knowledge, and creativity since 1477
World-class research and outstanding education of global benefit to society, business, and culture.
Uppsala University is one of northern Europe's highest ranked academic institutions. www.uu.se

For nearly 100 years biologists have argued about how exactly natural selection can possibly work. If nature selects the individuals with the best genes then why aren’t all organisms the same? Recent findings made at Uppsala University suggest that the answer could be sex.

Read more »

​White-browed Shortwing is not 1 but 4 species

Press Releases   •   Nov 26, 2018 09:00 GMT

The White-browed Shortwing has been considered to be a single species. But now the mainland and Taiwan Island populations have been studied by an international team of researchers, led by Uppsala University. They analysed DNA, plumages, structure, songs and geographical distributions, and concluded that the continental and Taiwanese populations are actually three rather than one species.

​Hundreds of babblers’ DNA analysed

Press Releases   •   Nov 23, 2018 15:58 GMT

Using DNA sequences for 402 of the 452 species of the world’s “babblers”, an international team from China, Sweden, Denmark, Switzerland and the USA have analysed the evolutionary relationships among these species. Many of these species have not previously been studied using genetic methods, and this is by far the most comprehensive analysis of this group of birds to date.

Gigantic mammal “cousin” discovered

Press Releases   •   Nov 22, 2018 19:00 GMT

During the Triassic period mammal-like reptiles called therapsids co-existed with ancestors to dinosaurs, crocodiles, mammals, pterosaurs, turtles, frogs, and lizards. Researchers at Uppsala University in Sweden, together with colleagues in Poland, have discovered fossils from a new genus of gigantic dicynodont. The new species Lisowicia bojani is described in the journal Science.

Deciding not to resuscitate: nurses’ and physicians’ perspectives

Press Releases   •   Nov 15, 2018 10:37 GMT

When deciding not to resuscitate patients in cardiac arrest, ethical issues arise. Nurses and physicians conflicting perspectives often cause frustration. In a new doctoral thesis from Uppsala University, Mona Pettersson examines clinical and ethical perspectives on “DNR orders” in cancer care.

Sometimes, when a patient is so ill that performing cardiopulmonary rescue (CPR) would do more harm than good, a DNR order is issued. Sometimes they are issued very late, perhaps even after CPR has been initiated. Sometimes they are unclear, and sometimes contradictory. Performing CPR on a patient at the end of their cancer can also be experienced by caregivers as the opposite of good caregiving. This can cause stress among the medical staff.

From a physician’s perspective, there is often hope for the patient’s survival even when the cancer has progressed very far. The physicians sometimes choose not to inform the patient that a DNR order has been issued. Often with the patient’s best interest in mind. They do not want them to lose hope. If the decision is made close to the cardiac arrest, this can make it harder to inform the patient.

Nurses have close and daily contact with their patients. If the patient, and perhaps also their family, is informed about the DNR order, nurses can support them and answer their questions. Some nurses wish physicians would make DNR decisions sooner, for them to be able to do so.

According to the Swedish Patient’s Act, patients have the right to take part and be informed in their treatment. But both the Patient’s Act and the National Board of Health and Welfare’s recommendations underline the importance of adapting the information to the individual. Physicians and nurses have a responsibility to handle decisions and information with the patient’s best interest in mind. This could mean not to inform, if it could do more harm than good. Guidelines from the Swedish Society of Medicine, the Swedish Society of Nursing and the Swedish Resuscitation Council support this. 

The difficulty lies in assessing whether the information does more harm than good for patients and their families. This is where nurses and physicians have different perspectives.

At many haematology and oncology wards, there are experiences of DNR orders and the frustration they can cause. A majority of the nurses and physicians who took part in Mona Pettersson’s research express that it is important for patients and their next-of-kin to be involved in or informed about decisions made. But few of them think this can become the reality of their workplace.

Mona Pettersson’s thesis shows that it is important for nurses and physicians to understand each other’s perspectives. To avoid conflicts between them, communication and ethical competence is crucial.

“Nurses and physicians share the responsibility of communicating with one another. For a common understanding they need insight into each other’s perspectives on DNR orders”, says Mona Pettersson.

She hopes her research will lead to such an understanding between nurses and physicians, to patients receiving the same information from all parties and to safer end-of-life care.

For more information, contact Mona Pettersson, Department of Public Health and Caring Sciences, Centre for Research Ethics and Bioethics, phone: +4670-95324446, e-mail: mona.pettersson@pubcare.uu.se

COMPETENCE AND COMMUNICATION: Do Not Resuscitate Decisions in Cancer Care, Uppsala: Acta Universitatis Upsaliensis, 2018

Uppsala University -- quality, knowledge, and creativity since 1477
World-class research and outstanding education of global benefit to society, business, and culture.
Uppsala University is one of northern Europe's highest ranked academic institutions. www.uu.se

When deciding not to resuscitate patients in cardiac arrest, ethical issues arise. Nurses and physicians conflicting perspectives often cause frustration. In a new doctoral thesis from Uppsala University, Mona Pettersson examines clinical and ethical perspectives on “DNR orders” in cancer care.

Read more »

The unintended consequences of dams and reservoirs

Press Releases   •   Nov 13, 2018 16:54 GMT

An international team of drought scientists show that while many dams and reservoirs are built, or expanded, to alleviate droughts and water shortages, they can paradoxically contribute to make them worse. The study is published in Nature Sustainability.

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