Indiana: A team of researchers developed a technology that may detect symptoms of Parkinson's disease in urine samples. The approach allows researchers to assess if LRRK2 (leucine-rich repeat kinase 2) proteins and their downstream pathways, which have been related to Parkinson's disease, are changed in Parkinson's patients' samples. The technology might potentially lead to widespread noninvasive testing for other neurological diseases, in addition to cancer. "We believe this is a logical and rational approach to move forward for diagnosing Parkinson's disease," said W. Andy Tao, professor of biochemistry at Purdue. "Diagnosis for this type of neurodegenerative disease is difficult." Cognitive and movement testing can take a year or more to confirm the diagnosis, so molecular tests for early diagnosis and intervention can help people with Parkinson's faster, he explained. Tao and eight co-authors from Purdue, Tymora, The Michael J. Fox Foundation for Parkinson's Research, and Columbia University published their findings in the Communications Medicine journal. "It's going to be a big new area in diagnostic development," predicted co-author Anton Iliuk, Tymora's president and chief technology officer, "especially for neurodegenerative diseases and cancer." Parkinson's disease alone affects an estimated 1% of the over-60 population. Up to a million Americans live with the disease, while 90,000 new cases are diagnosed each year. The paper's co-authors include Marco Hadisurya, a doctoral student in biochemistry; Kananart Kuwaranancharoen, a doctoral student in electrical and computer engineering; Xiaofeng Wu, who received his doctorate in chemistry at Purdue in 2022; Li Li, Tymora Analytical Operations; Zheng-Chi Lee, West Lafayette Junior/Senior High School; Roy Alcalay, MD, Columbia University; and Shalini Padmanabhan from The Michael J. Fox Foundation, which funded the work. The project began several years ago after Padmanabhan read some of Iliuk and Tao's work on the EVtrap (Extracellular Vesicles total recovery and purification) method for urinary analysis and proposed a collaboration. "When I reviewed the data from their previous publication," Padmanabhan said, "it was interesting to note the expression of an important Parkinson's disease-linked protein, LRRK2. This piqued my interest since this approach provided us with an opportunity to determine if LRRK2 proteins or the downstream pathways they impact are actually altered in urinary samples from Parkinson's patients who harbor a mutation in the gene."  In 2017, Tao led a team that developed a blood test that could feasibly detect breast cancer. In that work, Tao and his colleagues compared samples taken from breast cancer patients and a healthy control group. "We identified phosphorylated proteins, which are a typical hallmark of cancers," Tao said. And within those proteins, the team found extracellular vesicles, small packages that cells use as their molecular delivery system. The finding demonstrated that a blood sample yielding phosphoproteins could serve as a potential marker for early cancer diagnosis or for monitoring disease progression. The team was able to rapidly isolate the vesicles from urine samples, using the EVtrap method developed by Tymora. "We have used the method for a number of indications, primarily focusing on different cancers for biomarker discovery and validation," said Iliuk, who received his doctorate in biochemistry at Purdue in 2011. Iliuk and Tao co-founded Tymora Analytical, which specializes in technology and services for detecting disease biomarkers in biofluids. "This kind of analysis opens a new frontier in noninvasive diagnostics development. It's showing that biomarkers previously thought to be undetectable have become uncovered and do a really good job of differentiating disease from non-disease state," Iliuk said. "It's not obvious that urine would be a source of brain-based chemicals or signatures, but it is. These EVs can penetrate the blood-brain barrier quite easily." After export from the brain into the bloodstream, they become concentrated or filtered into urine. But sampling such biomarkers from the brain via spinal tap is a highly invasive procedure. "Especially for early diagnosis that is not the preferred sampling method," Tao said. Urine samples contain proteins that could be disease markers, but many perform housekeeping functions that are unrelated to disease. "Extracellular vesicles provide a way to focus on disease markers because they are released by certain types of cells," he said. Among the many ways to study the impact of LRRK2 is to track its biological pathway, which can be done by analyzing urine, blood and cerebrospinal fluid. The EVtrap method provided an easy way to track changes in urine, which is collected for many clinical studies. The LRRK2 Biobanking Study at Columbia University has a large bank of urine samples available for meaningful Parkinson's disease research. Columbia University co-author Alcalay, who provided many of the samples, also helped correlate EVtrap data with the clinical data. For the Communication Medicine study, the team studied samples from people with and without the LRRK2 gene mutation, and patients with and without the disease. Padmanabhan noted, "This study also highlighted that changes in urinary proteins could serve as a proxy for changes in protein signatures that occur in brain diseases like Parkinson's disease." (ANI)

A team of researchers developed a technology that may detect symptoms of Parkinson's disease in urine samples.

Researchers develop new technique to reveal signs of Parkinson's disease

New York: According to a recent study headed by Columbia researchers and including hundreds of ageing specialists from across the world, taurine deficiency--a vitamin generated in the body and available in many foods--is a cause of ageing in animals. The same study also found that taurine supplements can slow down the aging process in worms, mice, and monkeys and can even extend the healthy lifespans of middle-aged mice by up to 12%. The study was published June 8 in Science. "For the last 25 years, scientists have been trying to find factors that not only let us live longer, but also increase healthspan, the time we remain healthy in our old age," says the study's leader, Vijay Yadav, PhD, assistant professor of genetics &amp; development at Columbia University Vagelos College of Physicians and Surgeons. "This study suggests that taurine could be an elixir of life within us that helps us live longer and healthier lives." Anti-aging molecules within us Over the past two decades, efforts to identify interventions that improve health in old age have intensified as people are living longer and scientists have learned that the aging process can be manipulated. Many studies have found that various molecules carried through the bloodstream are associated with aging. Less certain is whether these molecules actively direct the aging process or are just passengers going along for the ride. If a molecule is a driver of aging, then restoring its youthful levels would delay aging and increase healthspan, the years we spend in good health. Taurine first came into Yadav's view during his previous research into osteoporosis that uncovered taurine's role in building bone. Around the same time, other researchers were finding that taurine levels correlated with immune function, obesity, and nervous system functions. "We realized that if taurine is regulating all these processes that decline with age, maybe taurine levels in the bloodstream affect overall health and lifespan," Yadav says. Taurine declines with age, supplementation increases lifespan in mice First, Yadav's team looked at levels of taurine in the bloodstream of mice, monkeys, and people and found that the taurine abundance decreases substantially with age. In people, taurine levels in 60-year-old individuals were only about one-third of those found in 5-year-olds. "That's when we started to ask if taurine deficiency is a driver of the aging process, and we set up a large experiment with mice," Yadav says. The researchers started with close to 250 14-month-old female and male mice (about 45 years old in people terms). Every day, the researcher fed half of them a bolus of taurine or a control solution. At the end of the experiment, Yadav and his team found that taurine increased average lifespan by 12% in female mice and 10% in males. For the mice, that meant three to four extra months, equivalent to about seven or eight human years. To learn how taurine impacted health, Yadav brought in other aging researchers who investigated the effect of taurine supplementation on the health and lifespan in several species. These experts measured various health parameters in mice and found that at age 2 (60 in human years), animals supplemented with taurine for one year were healthier in almost every way than their untreated counterparts. The researchers found that taurine suppressed age-associated weight gain in female mice (even in "menopausal" mice), increased energy expenditure, increased bone mass, improved muscle endurance and strength, reduced depression-like and anxious behaviors, reduced insulin resistance, and promoted a younger-looking immune system, among other benefits. "Not only did we find that the animals lived longer, we also found that they're living healthier lives," Yadav says. At a cellular level, taurine improved many functions that usually decline with age: The supplement decreased the number of "zombie cells" (old cells that should die but instead linger and release harmful substances), increased survival after telomerase deficiency, increased the number of stem cells present in some tissues (which can help tissues heal after injury), improved the performance of mitochondria, reduced DNA damage, and improved the cells' ability to sense nutrients. Similar health effects of taurine supplements were seen in middle-aged rhesus monkeys, which were given daily taurine supplements for six months. Taurine prevented weight gain, reduced fasting blood glucose and markers of liver damage, increased bone density in the spine and legs, and improved the health of their immune systems. Randomized clinical trial needed The researchers do not know yet if taurine supplements will improve health or increase longevity in humans, but two experiments they conducted suggest taurine has potential. In the first, Yadav and his team looked at the relationship between taurine levels and approximately 50 health parameters in 12,000 European adults aged 60 and over. Overall, people with higher taurine levels were healthier, with fewer cases of type 2 diabetes, lower obesity levels, reduced hypertension, and lower levels of inflammation. "These are associations, which do not establish causation," Yadav says, "but the results are consistent with the possibility that taurine deficiency contributes to human aging." The second study tested if taurine levels would respond to an intervention known to improve health: exercise. The researchers measured taurine levels before and after a variety of male athletes and sedentary individuals finished a strenuous cycling workout and found a significant increase in taurine among all groups of athletes (sprinters, endurance runners, and natural bodybuilders) and sedentary individuals. "No matter the individual, all had increased taurine levels after exercise, which suggests that some of the health benefits of exercise may come from an increase in taurine," Yadav says. Only a randomized clinical trial in people will determine if taurine truly has health benefits, Yadav adds. Taurine trials are currently underway for obesity, but none are designed to measure a wide range of health parameters. Other potential anti-aging drugs--including metformin, rapamycin, and NAD analogs--are being considered for testing in clinical trials. "I think taurine should also be considered," Yadav says. "And it has some advantages: Taurine is naturally produced in our bodies, it can be obtained naturally in the diet, it has no known toxic effects (although it's rarely used in concentrations used ), and it can be boosted by exercise. "Taurine abundance goes down with age, so restoring taurine to a youthful level in old age may be a promising anti-aging strategy." —ANI

According to a recent study headed by Columbia researchers and including hundreds of ageing specialists from across the world

Taurine Might Be A Key To Longer, Healthier Life: Research

Washington: Researchers found a novel solid-phase alkylation (SPA)-based sample preparation method for low-loss, anti-interference processing of sub-microgram proteomic samples. The study was published in Journal, URINE.' Because urine can accumulate and reflect changes in the human body while being collected non-invasively, it is one of the most appealing sources for early and sensitive biomarker discovery. The analysis of the urine proteome, on the other hand, presents difficulties due to its wide dynamic range, which spans approximately 10 orders of magnitude in protein concentrations. High-abundance proteins in urine can obscure potential disease biomarkers, making identification difficult. To improve the detection and identification of these elusive biomarkers, fractionation and depletion strategies are commonly used prior to performing mass spectrometry (MS) analysis. As a promising alternative, urine fractionation through ultracentrifugation (UC) can be employed to deplete high-abundance proteins, allowing for the isolation of exosomes with high purity while retaining most of the high-abundance proteins in the supernatant. Nonetheless, the strong centrifugal shearing force during UC can unavoidably disrupt the intact structure of exosomes, resulting in the isolation of only trace amounts from a small urine volume. With all the existing limitations in mind, a team of researchers in China proposed a novel solid-phase alkylation (SPA)-based sample preparation method for low-loss, anti-interference processing of sub-microgram proteomic samples. "Our method combines UC fractionation, solid-phase extraction (SPA) sample preparation, and liquid chromatography-mass spectrometry (LC-MS) to enable comprehensive proteome profiling of urine, known as CPU, or comprehensive proteome profiling of urine," explained corresponding author Huiming Yuan, a professor at the Dalian Institute of Chemical Physics, Chinese Academy of Sciences. "This facile strategy resulted in the identification of a total of 1,659 proteins using a short LC gradient of approximately 1 hour, which is 2.3 times more than the 730 proteins identified from raw urine without fractionation." Notably, in comparison to existing urine sample preparation methods, CPU offers significant advantages. Not only does it drastically reduce the analysis time by 3-4 times, but it also enhances the identification coverage of the urine proteome by 130%-160%. "The method was further employed in combination with label-free quantification to conduct comparative proteome analysis of urine from both IgA nephropathy (IgAN) patients and healthy donors," shared lead author Xinxin Liu, a technician at Dalian Institute of Chemical Physics, Chinese Academy of Sciences. "As a result, 227 differentially expressed proteins were identified, shedding light on potential biomarkers associated with IgAN." Several members of the solute carrier family 22 (SLC22) were found to be up-regulated in IgAN patients, suggesting a potential link to the disruption of renal metabolic function in these individuals. The team reported their study in the KeAi journal Urine. "Our results demonstrated that our developed method holds promise as a valuable tool for the discovery of disease-related biomarkers in urine" Liu concluded. —ANI

Researchers found a novel solid-phase alkylation (SPA)-based sample preparation method for low-loss

New Method For Comprehensive Urine Proteome Analysis: Study

Tel Aviv: A 74-year-old woman strolling on Israel's Palmahim beach south of Tel Aviv found a 3,000-year-old figurine of an Egyptian goddess which she turned over to grateful archaeologists at the Israel Antiquities Authority. Lydia Marner, a resident of Lod and an Azerbaijani immigrant, said she and her husband noticed an object emerge from the sea one stormy day "about a month ago". Understanding she had found something significant, Marner contacted friends who were knowledgeable in archaeology, then reached out to the Antiquities Authority via its Facebook page. Inspectors Dror Citron and Idan Horn were dispatched to examine the ancient figurine. After reading and cleaning the statuette, the Authority announced the find on Tuesday. "I can't believe I won this. At first, my husband laughed at me, but today the whole family already knows the amazing story that happened to me. I'm very happy that the right to find it fell to me," Marner said. The Authority confirmed that the figurine represented Hathor, an Egyptian goddess associated with fertility, strength, protection, and wisdom. According to Dr Amir Golani, an expert on the Bronze Age at the Antiquities Authority, "The Canaanites used to adopt ritual and religious customs of the Egyptians, who ruled our region at the time. Just like homes today, where you install a mezuzah or hang a picture of a saint on the wall, then, they used to place ritual figurines in a central place in the house, for good luck and protection from bad things." He explained that the statuette was made of clay which was embedded into a stone pattern, a process allowing people to quickly produce numerous such figurines. "It can be recognized that this is Ella Hathor by her hairstyle, which simulates the horns of a bull, and by the prominent eyes and ears that were designed for her," Golani said. Marner's discovery coincides with the launch of the Antiquities Authority's "Return Them With a Click" campaign to encourage Israelis with artefacts in their homes to turn them over to the state. There is a legal obligation to report to the Antiquities Authority about any accidental finding of antiquities. —ANI

A 74-year-old woman strolling on Israel's Palmahim beach south of Tel Aviv found a 3,000-year-old figurine

Woman Walking On Israeli Beach Finds 3,000 Year-Old Figurine

Washington DC: An international team of scientists led by University of Vienna microbiologist Alexander Loy discovered new gut bacteria that just consume taurine and produce the noxious chemical hydrogen sulphide. As a result, the researchers have improved our understanding of the microbial pathways that have intriguing health implications. This is also true for Taurinivorans muris: the bacterium protects against the illnesses Klebsiella and Salmonella. The results are currently published in Nature Communications. The gut microbiome mediates our health in a myriad of ways. One of those ways is by contributing to the levels of hydrogen sulfide – the toxic gas responsible for foul smelling farts. Having small amounts of hydrogen sulfide in the gut is a good thing; in fact, it’s essential for a number of physiological processes, and can even protect against pathogens. Hydrogen sulfide-producing microbes in the gut may help "choke out" oxygen-dependent pathogens such as Klebsiella, making it harder for them to colonize. However, excessive levels can have negative consequences and have been associated with gut inflammation and damage to the intestinal lining. Discovering the key players and processes that produce this noxious gas in our gut is a fundamental first step on the road to developing therapeutic interventions, for example, for inflammatory bowel disease. The bacterium Bilophila wadsworthia is one of the most important taurine utilizers in humans. In the current study, researchers led by Alexander Loy at CeMESS, the Centre for Microbiology and Environmental Systems Science of the University of Vienna, have discovered a new genus of hydrogen sulfide-producing bacteria in the mouse intestine. "The bacterium we described has a rather unbalanced diet," explains Loy, "it specializes in consuming taurine." Taurine is a semi-essential amino acid, which we synthesize in small amounts in our liver. However, we get most of our taurine from our diets – especially meat, dairy and seafood. Like hydrogen sulfide, taurine is implicated in a smorgasbord of physiological processes. Recent studies have found a link between taurine and healthy ageing – it seems this nutrient may stave away age-related disease. In light of these findings, the discovery of a new gut microbe that feeds exclusively on taurine (aptly named Taurinivorans muris) is another piece of an exciting puzzle. "By isolating the first taurine degrader in the mouse gut, we’re one step closer to understanding how these gut microbes mediate animal and human health" explains Huimin Ye, lead author of the study. To access sufficient taurine in the gut, however, Taurinivorans muris needs the help of other gut microbes to release it from bile acids. Taurine-containing bile acids are produced in the liver and are increasingly released into the intestine during a high-fat diet to help our body digest fats. The activities of the bacteria in the intestine in turn influence the bile acid metabolism in the liver. The results of the Viennese researchers therefore also contribute to a better understanding of these complex interactions in bile acid metabolism, which has an impact on processes and diseases throughout the body. Taurine degrading microbes protect against pathogens One of the most important functions of the symbiotic microbes in the gut is to defend against pathogens. The microbiome has a versatile arsenal of protective mechanisms – and utilizing taurine to create hydrogen sulfide is one of them. "Hydrogen sulfide may suppress the oxygen-dependent metabolism of some pathogens," explains Ye. In the present study, the researchers found that Taurinivorans muris has a protective role against Klebsiella and Salmonella, two important gut pathogens. "The protective mechanism of Taurinivorans muris against pathogens may be via hydrogen sulfide but is essentially not yet fully understood" adds Alexander Loy. Taurine is one of the most important sources of hydrogen sulfide production in the gut. The study thus generates basic knowledge on the physiological interactions between the different gut microbes and their hosts, which is necessary to develop new microbiome-based therapies. —ANI

An international team of scientists led by University of Vienna microbiologist Alexander Loy discovered new gut bacteria

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Researchers develop new technique to reveal signs of Parkinson's disease

Inam Ansari

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Tag : Urine

Researchers develop new technique to reveal signs of Parkinson's disease

Inam Ansari

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