Human eggs remain healthy for decades by putting 'batteries on standby mode'

Immature human egg cells skip a fundamental metabolic reaction thought to be essential for generating energy, according to the findings of a study by researchers at the Centre for Genomic Regulation (CRG) published today in the journal Nature.
By altering their metabolic activity, the cells avoid creating reactive oxygen species, harmful molecules that can accumulate, damage DNA and cause cell death. The findings explain how human egg cells remain dormant in ovaries for up to 50 years without losing their reproductive capacity.
“Humans are born with all the supply of egg cells they have in life. As humans are also the longest-lived terrestrial mammal, egg cells have to maintain pristine conditions while avoiding decades of wear-and-tear. We show this problem is solved by skipping a fundamental metabolic reaction that is also the main source of damage for the cell. As a long-term maintenance strategy, its like putting batteries on standby mode. This represents a brand new paradigm never before seen in animal cells,” says Dr. Aida Rodriguez, postdoctoral researcher at the CRG and first author of the study.
Human eggs are first formed in the ovaries during fetal development, undergoing different stages of maturation. During the early stages of this process, immature egg cells known as oocytes are put into cellular arrest, remaining dormant for up to 50 years in the ovaries. Like all other eukaryotic cells, oocytes have mitochondria — the batteries of the cell — which they use to generate energy for their needs during this period of dormancy.
Using a combination of live imaging, proteomic and biochemistry techniques, the authors of the study found that mitochondria in both human and Xenopus oocytes use alternative metabolic pathways to generate energy never before seen in other animal cell types.
A complex protein and enzyme known as complex I is the usual ‘gatekeeper’ that initiates the reactions required to generate energy in mitochondria. This protein is fundamental, working in the cells that constitute living organisms ranging from yeast to blue whales. However, the researchers found that complex I is virtually absent in oocytes. The only other type of cell known to survive with depleted complex I levels are all the cells that make up the parasitic plant mistletoe.
According to the authors of the study, the research explains why some women with mitochondrial conditions linked to complex I, such as Leber’s Hereditary Optic Neuropathy, do not experience reduced fertility compared to women with conditions affecting other mitochondrial respiratory complexes.
The findings could also lead to new strategies that help preserve the ovarian reserves of patients undergoing cancer treatment. “Complex I inhibitors have previously been proposed as a cancer treatment. If these inhibitors show promise in future studies, they could potentially target cancerous cells while sparing oocytes,” explains Dr. Elvan Böke, senior author of the study and Group Leader in the Cell & Developmental Biology programme at the CRG.
Oocytes are vastly different to other types of cells because they have to balance longevity with function. The researchers plan to continue this line of research and uncover the energy source oocytes use during their long dormancy in the absence of complex I, with one of the aims being to understand the effect of nutrition on female fertility.
“One in four cases of female infertility are unexplained — pointing to a huge gap of knowledge in our understanding of female reproduction. Our ambition is to discover the strategies (such as the lack of complex I ) oocytes employ to stay healthy for many years in order to find out why these strategies eventually fail with advanced age” concludes Dr. Böke.
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Surgery risks go up depending upon the anesthesiologist's workload, study suggests

Most major surgeries would not be possible without anesthesia to render a patient unconscious and pain free and to ensure that their vital functions — including blood pressure, breathing, and heart rate and rhythm — remain stable throughout the procedure.
As the demand for such surgical care grows, many clinicians, including anesthesia care teams, are being asked to take care of more patients, all while maintaining patient safety.
An anesthesia clinician — a certified registered nurse anesthetist, certified anesthesia assistant, anesthesiology resident or anesthesiologist — is continuously present in the operating room and delivering important care during every surgery requiring anesthesia. However, it is not uncommon to have one anesthesiologist directing the anesthesia care delivered by other anesthesia clinicians for multiple surgical cases at a time, according to Sachin Kheterpal, M.D. M.B.A., associate dean for Research Information Technology and professor of Anesthesiology at Michigan Medicine.
A new study appearing in JAMA Surgery from a team at the University of Michigan examines whether the number of overlapping procedures managed by the anesthesiologist increases the risk of death or complications after surgery.
Using data from the Multicenter Perioperative Outcomes Group electronic health record registry, the team investigated surgical procedures that involved an anesthesiologist directing a CRNA or an anesthesiology resident. This anesthesia care team model is the most common model used to deliver anesthesia in the United States.
Focusing their analysis on cases with CRNA involvement and minimal anesthesiology resident involvement, the authors looked at data from more than 570,000 surgical cases at 23 hospitals in the United States between 2010 and 2017.

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Engineers develop new tool that will allow for more personalized cell therapies

A University of Minnesota Twin Cities team has, for the first time, developed a new tool to predict and customize the rate of a specific kind of DNA editing called “site-specific recombination.” The research paves the way for more personalized, efficient genetic and cell therapies for diseases such as diabetes and cancer.
The study is published in Nature Communications.
The process of site-specific recombination involves using enzymes that recognize and modify specific sequences of DNA in living cells. It has important applications for treating myriad diseases using cellular therapies.
Immunotherapy, for example, entails extracting immune cells from a patient and genetically modifying them to fight back against a disease like cancer. In these applications, it is important to precisely control the timing of gene expression to maximize the effects of the treatment while minimizing adverse reactions in the body.
University of Minnesota engineers have developed a method that combines high-throughput experiments with a machine learning model to make the site-specific recombination process more efficient and predictable. The model allows researchers to program the rate at which the DNA is edited. This means they can control the speed at which a therapeutic cell responds to its environment, thereby controlling how quickly or slowly it produces a drug or therapeutic protein.
“To our knowledge, this is the first example of using a model to predict how modifying a DNA sequence can control the rate of site-specific recombination,” said Casim Sarkar, senior author on the paper and an associate professor in the University of Minnesota Twin Cities Department of Biomedical Engineering. “By applying engineering principles to this problem, we can dial in the rate at which DNA editing happens and use this form of control to tailor therapeutic cellular responses. Our study also identified novel DNA sequences that are much more efficiently recombined than those found in nature, which can accelerate cellular response times.”
Sarkar and his team first developed an experimental method to calculate the rate of site-specific recombination, then used that information to train a machine learning algorithm. Ultimately, this allows the researchers to simply type in a DNA sequence, and the model predicts the rate at which that DNA sequence will be recombined.
They also found that they could use modeling to predict and control the simultaneous production of multiple proteins within a cell. This could be used to program stem cells to produce new tissues or organs for regenerative medicine applications or to endow therapeutic cells with the ability to produce multiple drugs in pre-defined proportions.
“Different patients may require different doses or a faster or slower cell response — not everyone is the same,” Sarkar explained. “By building genetic circuits inside cells that utilize multiple DNA sequences with different and defined recombination rates, we can now achieve things that were difficult to do previously, like program ratios of protein production in therapeutic cells. Our rational approach enables personalized treatment for the patient.”
This research was funded by the National Institutes of Health.
In addition to Sarkar, the research team included University of Minnesota Department of Chemical Engineering and Materials Science researchers Qiuge Zhang, a recently graduated doctoral student, and Samira Azarin, an associate professor.
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Grab a coffee before shopping? You may want to think twice

Researchers from University of South Florida, European University Viadrina, Louisiana State University, SKEMA Business School, and Neoma Business School published a new Journal of Marketing article that examines how caffeine affects consumer spending.
The forthcoming study is titled “Caffeine’s Effects on Consumer Spending” and is authored by Dipayan Biswas, Patrick Hartmann, Martin Eisend, Courtney Szocs, Bruna Jochims, Vanessa Apaolaza, Erik Hermann, Cristina M. López, and Adilson Borge.
How does drinking a caffeinated beverage influence shopping behavior? Are customers prone to impulsive purchases after consuming coffee, tea, or soda at retail stores or car dealerships?
These researchers say that “Understanding how and why caffeine consumption influences spending is important since caffeine is one of the most powerful stimulants that is both legal and widely available.” About 85% of Americans consume at least one caffeinated beverage every day with coffee being the primary source of caffeine, followed by tea and soda. Caffeine is also found in energy drinks, chocolate, and in many over the counter and prescription medications.
The study finds that drinking a caffeinated beverage before shopping leads to more items purchased at the store and increased spending. Their studies also show that the effect of caffeine is stronger for “high hedonic” products such as scented candles, fragrances, décor items, and massagers and weaker for “low hedonic” products such as notebooks, kitchen utensils, and storage baskets.
Several studies have demonstrated that caffeine intake enhances arousal, which is experienced as a state of activation and alertness that can range from extreme drowsiness to extreme excitement. Arousal can be a positive hedonic state — referred to as excitement or energetic arousal — such as when one feels active, energized, and excited or a negative hedonic state — referred to as “tense arousal” — such as when one experiences tension and nervousness. Energetic arousal enhances the perception of product features and, in turn, increases purchase intentions for hedonic products such as buttery, salty popcorn, chocolate candy, and luxury vacations.
Prior research has shown that consuming caffeine in the range of 25 mg to 200 mg enhances energetic arousal with practically no effects on tense arousal. This study examines effects of caffeine intake in the range of about 30 mg to 100 mg since most caffeinated beverage servings have caffeine content in this range. As part of the study, the research team set up an espresso station near the entrance of two different retail stores in two major cities in France and outside a department store in Spain. Upon entry, half of the 300 shoppers were handed a complementary cup of coffee containing caffeine and the other half offered decaf or water. “We found that the caffeine group spent significantly more money and bought a higher number of items than those who drank decaf or water,” says the researchers.
Caffeine also impacted the types of items bought at the stores. The group that took in caffeine bought more hedonic (enjoyable/fun) items such as scented candles and fragrances. However, there was very little difference between the two groups with regard to utilitarian purchases such as utensils and storage baskets. Also, the effects of caffeine on spending hold for those who drink a little over two cups of coffee (or less) daily and is weakened for heavy coffee drinkers.
“Overall, retailers can benefit financially if shoppers consume caffeine before or during shopping and that the effects are stronger for high hedonic products. This is important for retailers to factor in to determine the proportion of hedonic products in their stores. Policy makers may also want to inform consumers about the potential effects of caffeine on spending,” concludes the researchers.
This research can be extended in several directions. Can arousing elements such as loud music influence the effects of caffeine on shopping behavior? It is possible that high levels of arousal induced by a combination of caffeine and ambient elements can alter shopping behavior. What if shoppers consume coffee along with some food like chocolate cake? Several interesting findings could emerge from research involving caffeine and these variables.
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Materials provided by American Marketing Association. Original written by Marilyn Stone. Note: Content may be edited for style and length.

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Wearable activity trackers encourage us to walk up to 40 minutes more each day

New findings from Australian researchers have endorsed what millions of people around the world believe: fitness trackers, pedometers and smart watches motivate us to exercise more and lose weight.
Wearable activity trackers encourage us to walk up to 40 minutes more each day (approximately 1800 more steps), resulting in an average 1kg weight loss over five months.
Researchers from the University of South Australia reviewed almost 400 studies involving 164,000 people across the world using wearable activity trackers (WATs) to monitor their physical activity.
Their findings, published in Lancet Digital Health today, underline the value of low-cost interventions to tackle a growing epidemic of health conditions partially caused by a lack of exercise, including cardiovascular disease, stroke, type 2 diabetes, cancers, and mental illness.
Lead researcher UniSA PhD candidate Ty Ferguson says despite the popularity of WATs, there is widespread scepticism about their effectiveness, accuracy, and whether they fuel obsessive behaviours and eating disorders, but the evidence is overwhelmingly positive.
“The overall results from the studies we reviewed shows that wearable activity trackers are effective across all age groups and for long periods of time,” Ferguson says. “They encourage people to exercise on a regular basis, to make it part of their routine and to set goals to lose weight.”
The 1kg weight loss may not seem a lot, but researchers say from a public health perspective it is meaningful.
“Bearing in mind these were not weight loss studies, but lifestyle physical activity studies, so we wouldn’t expect dramatic weight loss,” says UniSA Professor Carol Maher, co-author of the review.
“The average person gains about 0.5 kg a year in weight creep so losing 1kg over five months is significant, especially when you consider that two thirds of Australians are overweight or obese.”
Between 2014 and 2020, the number of wearable activity trackers shipped worldwide increased by almost 1500 per cent, translating to a global spend of $2.8 billion in 2020.
Apart from the extra physical activity and weight loss attributed to WATs, there is some evidence that fitness trackers also help lower blood pressure and cholesterol in people with type 2 diabetes and other health conditions.
“The other reported benefit is that WATs improved depression and anxiety through an increase in physical activity,” Ferguson says.
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Melanoma thickness equally hard for algorithms and dermatologists to judge

Assessing the thickness of melanoma is difficult, whether done by an experienced dermatologist or a well-trained machine-learning algorithm. A study from the University of Gothenburg shows that the algorithm and the dermatologists had an equal success rate in interpreting dermoscopic images.
In diagnosing melanoma, dermatologists evaluate whether it is an aggressive form (“invasive melanoma”), where the cancer cells grow down into the dermis and there is a risk of spreading to other parts of the body, or a milder form (“melanoma in situ,” MIS) that develops in the outer skin layer, the epidermis, only. Invasive melanomas that grow deeper than one millimeter into the skin are considered thick and, as such, more aggressive.
Importance of thickness
Melanomas are assessed by investigation with a dermatoscope — a type of magnifying glass fitted with a bright light. Diagnosing melanoma is often relatively simple, but estimating its thickness is a much greater challenge.
“As well as providing valuable prognostic information, the thickness may affect the choice of surgical margins for the first operation and how promptly it needs to be performed,” says Sam Polesie, associate professor (docent) of dermatology and venereology at Sahlgrenska Academy, University of Gothenburg, Polesie is also a dermatologist at Sahlgrenska University Hospital and the study’s first author.
Tie between man and machine
Using a web platform, 438 international dermatologists assessed nearly 1,500 melanoma images captured with a dermatoscope. The dermatologists’ results were then compared with those from a machine-learning algorithm trained in classifying melanoma depth.

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New fast test discriminates between cellular immunity to SARS-CoV-2 after vaccination or infection

A MedUni Vienna research team has developed a new blood test that indicates a person’s status of cellular immunity to SARS-CoV-2 within just 48 hours. This test is particularly relevant for vulnerable patient groups, whose own antibody response is not meaningful. The test can even indicate whether immunity is the result of vaccination against SARS-CoV-2 or of survived infection. The study data were recently published in the journal Allergy.
The new test, developed by Bernhard Kratzer in a study conducted at MedUni Vienna’s Center for Pathophysiology, Infectiology and Immunology under the leadership of Winfried Pickl and Rudolf Valenta, is based on the memory response of T cells to three different SARS-CoV-2 peptide mixtures. T cells are an important part of the specific cellular immune defense: they eliminate cells infected with SARS-CoV-2 and support antibody production by B cells. “Currently, it takes at least a week to perform and evaluate such T-cell tests, and the tests can only be performed in specialised laboratories. In contrast, our newly developed test is performed directly with a whole blood sample and can be evaluated after only 48 hours,” explains study leader Winfried Pickl.
From September, the new test will be available at the Institute of Immunology at MedUni Vienna’s Center for Pathophysiology, Infectiology and Immunology and is particularly useful for those who are unable to produce antibodies against SARS-CoV-2.
Discriminating between vaccinated and recovered
Analyses of blood samples from COVID-19-recovered patients, based on peptide mixtures of S-, M- and NC-proteins, enabled the research team to not only detect the two antiviral cytokines interleukin (IL)-2 and interferon-gamma in large quantities but also to identify the cytokine IL-13 as a marker for the highly specific T-cell immune response against SARS-CoV-2. IL-13 was previously known as a marker for allergic immune responses, but it apparently also plays a key role in establishing a long-lasting antibody response.
By using the three different peptide mixtures, it is also possible to discriminate between those who have been vaccinated against SARS-CoV-2 and those who have had COVID-19. Samples from recovered volunteers responded with significant cytokine production to all three peptide mixtures, whereas samples from vaccinated volunteers only responded to the specific peptide mixture in which the protein was induced by vaccination (S protein), and to which the vaccinated subjects then went on to build up cellular immunity. The novel test therefore allows a specific cellular immune response to SARS-CoV-2 to be identified even in individuals who, for various reasons, are unable to develop meaningful antibody responses.
T-cell immunity post infection is detectable longer than antibody responses
In the study, the T-cell response was also analysed ten months after infection. It was found that the T-cell response was still as strong as that measured ten weeks after an infection. This is remarkable in that antibody levels in the blood have already dropped significantly ten months after infection. This long-lasting T-cell response may protect against severe disease in the event of re-infection with SARS-CoV-2.
The results of this study make a significant contribution to our understanding of the immune response to SARS-CoV-2 and will enable us to quickly establish whether specific individuals have built up cellular immunity to SARS-CoV-2.
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Scientists develop a new non-opioid pain killer with fewer side effects

A promising new non-opioid painkiller (analgesic) with potentially fewer side effects compared to other potent painkillers, has been discovered.
A team of scientists, co-led by researchers from the School of Life Sciences, University of Warwick, has investigated a compound called BnOCPA (benzyloxy-cyclopentyladenosine), found to be a potent and selective analgesic which is non-addictive in test model systems. BnOCPA also has a unique mode of action and potentially opens a new pipeline for the development of new analgesic drugs.
The research by the team at Warwick, together with colleagues at the University of Cambridge, University of Bern, Monash University, Coventry University and industrial collaborators, is published in Nature Communications in a paper entitled “Selective activation of G?ob by an adenosine A1 receptor agonist elicits analgesia without cardiorespiratory depression.”
In the UK between one third and one half of the population report moderately to severely disabling chronic pain. Such pain has a negative impact on quality of life and many of the commonly used pain killers produce side effects. Opioid drugs, such as morphine and oxycodone, can lead to addiction and are dangerous in overdose. There is therefore an unmet need for new and potent pain killing drugs.
Many drugs act via proteins on the surface of cell surfaces that activate adapter molecules called G proteins. The activation of G proteins can lead to many cellular effects. BnOCPA is unique in that it only activates one type of G protein, leading to very selective effects and thus reducing potential side effects.
Dr Mark Wall, from the School of Life Sciences at the University of Warwick, who led the research said: “The selectivity and potency of BnOCPA make it truly unique and we hope that with further research it will be possible to generate potent painkillers to help patients cope with chronic pain.”
Professor Bruno Frenguelli, principal investigator on the project, from the University of Warwick’s School of Life Sciences, said: “This is a fantastic example of serendipity in science. We had no expectations that BnOCPA would behave any differently from other molecules in its class, but the more we looked into BnOCPA we discovered properties that had never been seen before, and which may open up new areas of medicinal chemistry.”
Professor Graham Ladds, co-principal investigator on the project, from the University of Cambridge, said: “This is an amazing story looking at agonist bias for a GPCR. Not only does BnOCPA have the potential to be a new type of painkiller, but it has shown us a new method for targeting other GPCRs in drug discovery.”
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Biochemistry: Peptide 'fingerprint' enables earlier diagnosis of Alzheimer's disease

Neurodegenerative diseases like Alzheimer’s disease or Parkinson’s disease are caused by folding errors (misfolding) in proteins or peptides, i.e. by changes in their spatial structure. This is the result of minute deviations in the chemical composition of the biomolecules. Researchers at the Karlsruhe Institute of Technology (KIT) have developed a simple and effective method for detecting such misfolding at an early stage of the disease. Misfolding is revealed by the structure of dried residue from protein and peptide solutions. The method involves analyzing micrographs with neural networks and has a predictive accuracy of over 99 percent. The results have been published in Advanced Materials.
The biochemical structure of proteins and peptides determines their biological functions. There are many indications that even minute structural or spatial changes can promote the development of diseases. Many neurodegenerative diseases have been attributed to misfolding of proteins and peptides that is caused by such changes. Amyloid beta (Aβ42) peptides play a key role in Alzheimer’s disease; they differ in a single amino acid residue and represent hereditary mutants of Alzheimer’s disease.
Until now there has not been a simple and accurate method for predicting mutations in proteins. At KIT’s Institute of Functional Interfaces (IFG), a research group led by Professor Jörg Lahann has developed a method for detecting misfolding via the structure of dried protein and peptide solutions. “The stain patterns were not only characteristic and reproducible but also result in a classification of eight mutations with a predictive accuracy of more than 99 percent,” said Lahann, author of the study, in describing the results. The group showed that crucial information about the primary and secondary structures of peptides can be gleaned from the stains left behind by drying droplets of peptide solution on a solid surface.
Stain Patterns as Exact Peptide Fingerprints
The protein and peptide solutions are precisely placed on glass slides by an automated pipetting system to ensure controlled and reproducible results. The surfaces of the slides were prepared in advance with a hydrophobic polymer coating. To analyze the complex stain patterns from the dried droplets, the researchers acquired images using polarization microscopy. The images were then analyzed with deep-learning neural networks.
“Since the structures are very similar and difficult to distinguish with the naked eye, it was definitely a surprise that the neural networks were so effective,” says Lahann about the results. “The stain patterns of amyloid beta peptides serve as exact fingerprints that reflect the structural and spatial identity of a peptide.” This technology enables the identification of Alzheimer variants with maximum resolution within a few minutes, according to Lahann.
Simple Sample Preparation Delivers Fast Diagnoses
The results suggest that a method as simple as drying a droplet of peptide solution on a solid surface can serve as an indicator for minute differences in the primary and secondary structures of peptides. “Scalable and accurate detection methods for the stratification of conformational and structural protein alterations are urgently needed in order to decode the pathological signatures of diseases like Alzheimer’s and Parkinson’s,” says Lahann. It is also a relatively simple method that requires no elaborate preparation of samples and thus enables simple and patient-friendly diagnosis. Furthermore, the method has great potential for other applications in medical diagnostics and in the molecular detection of diseases. (sfo)
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Shift workers 'can't all adjust to a night shift'

Scientists at the University of Warwick, jointly with those at Université Paris-Saclay, Inserm and Assistance Publique-Hôpitaux de Paris (France), have challenged the widespread belief that shift workers adjust to the night shift, using data drawn from wearable tech.
By monitoring groups of French hospital workers working day or night shifts during their working and free time, the researchers have not only shown that night work significantly disrupts both their sleep quality and their circadian rhythms, but also that workers can experience such disruption even after years of night shift work.
Their findings, reported in a study in the Lancet group journal eBioMedicine, are the most detailed analysis of the sleep and circadian rhythm profiles of shift workers yet attempted, and the first to also monitor body temperature. This key circadian rhythm is driven by the brain pacemaker clock, and coordinates the peripheral clocks in all organs.
The research demonstrates the value of telemonitoring technology for identifying early warning signs of disease risks associated with night-shift work opening up intervention opportunities to improve the health of workers.
The study compared 63 night-shift workers, working three or more nights of 10 hours each per week, and 77 day-shifters alternating morning and afternoon shifts at a single university hospital (Paul Brousse Hospital in Villejuif, near Paris). Both groups wore accelerometers with chest surface temperature sensors throughout the day and night for a full week, with the data collected by the research team at Université Paris-Saclay and Inserm.
The accelerometer measured movement intensity and allowed the researchers to estimate how much sleep the participants had, how regular were their circadian rhythms, and whether that sleep was disrupted by movement. Patterns in the chest surface temperature gave a further indication of the participants’ circadian rhythm, the internal body clock that coordinates rest-activity phases, varying core body temperature, and an array of other bodily rhythms.

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