All posts by medical

Why Isn’t Grey’s Anatomy on Tonight? – Heavy.com

Tonight, ABC will be airing a special, When We Rise, in place of Greys Anatomy. But dont worry, our favorite doctors will be back next week at their usual time for an all-new episode.

Next weeks episode is titled Civil War, and the synopsis reads: A grueling trauma case is complicated by hospital politics. Meanwhile, Amelia confronts her feelings regarding Owen; and Meredith finds herself stuck in the middle as Nathan and Alex butt heads over a patient.

So where did Greys leave off? Last week, Alex finally came back to Grey Sloan Memorial for work, and Meredith agreed to return to the hospital, too. Alexs first day back was, well, heavy. He was assigned to a mother-to-son kidney transplant, but things quickly turned dramatic when the boys father showed up to the hospital uninvited.

We learned that Cynthia (the mom) was a victim of domestic abuse at the hands of her husband, and after hearingthis, Jo toldOwen to ask the man to leave. But after that it all got worse. Cynthias second kidney failed and the doctors still needed to give her sona kidney to live. As it turns out, the husband never actually left the hospital, and he overheard the doctors conversation. He said he wanted to give up his kidney to save his son, putting the doctors in a moral dilemma. Should they save Chris with a kidney from his father, who abused his mother? Ultimately, they diduse the fathers kidney, but Jo secretly snuck into the OR to convince him to donate it anonymously and never admit to his wife or son that it was his kidney.

Another (maybe not-so-secret) secret that was revealed? Arizona and Eliza Minnick are togetherish. Theyve been meeting in the parking lot, hiding theirsteamy romance. Oh, and everyone seems to love to vocalize their disdain for Minnick in front of Arizona, which makes for an interesting juxtaposition.

Dont miss a new episode of Greys Anatomy, which will return to ABC on March 9 at 8 p.m. ET.

Why isn't How to Get Away with Murder on TV Tonight? When will HTGAWM be back for next season? Get the details here.

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Why Isn't Grey's Anatomy on Tonight? - Heavy.com

Recent Wildfire Study: 84% Are Caused By Humans – Kozi Radio

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A new study of wildfire data shows that humans are responsible for 84 percent of all wildfires started in the United States, but those fires burn only 44 percent of the acreage consumed by wildfires.

The study by the University of Colorado-Bolder also says that humans tripled the length of the wildfire season, noting that lightning-caused fires occur primarily in the Summer.

The researchers used the U.S. Forest Service Fire Program Analysis-Fire Occurrence Database to study records of all wildfires that required a response from a state or federal agency between 1992 and 2012, omitting intentionally set prescribed burns and managed agricultural fires.

The most common day for human-started fire by far, however, was July 4, with 7,762 total wildfires started on that day over the course of the 21-year period.

The new findings have wide-ranging implications for fire management policy and suggest that human behavior can have dramatic impact on wildfire totals, for good or for ill.

The findings were published yesterday (Mon) in the journal Proceedings of the National Academy of Sciences.

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Recent Wildfire Study: 84% Are Caused By Humans - Kozi Radio

DNA from taxidermy specimens explains genetic structure of British and Irish goats – Science Daily

Intensive selective breeding over the past 200 years and high extinction rates among feral populations has greatly reduced the genetic diversity present in domestic goat breeds. The effect these pressures have had on Irish and British goat populations has been explored in a landmark DNA study that compared modern-day domestic and feral goats with museum specimens from years gone by.

A collaborative team led by geneticists from Trinity College Dublin compared the mitochondrial DNA (mtDNA) of 15 historical taxidermy specimens from Britain and Ireland and nine modern samples taken from Irish dairy and feral populations.

The team has just published their results in the Royal Society journal Biology Letters. Their work provides the first example in which DNA from taxidermy specimens is used to answer questions about livestock genetics.

Lara Cassidy, a researcher from Trinity's School of Genetics and Microbiology, is the first author of the journal article. She said: "There is an amazing wealth of genetic information locked away in taxidermic collections of animals that were -- and still are -- important for agricultural reasons. As such these collections are invaluable in helping us study the population history of these domesticated animals."

"Studying these specimens and comparing them with modern-day animals also helps to pinpoint existing populations that have retained some of the past genetic diversity, much of which has been lost to industrialized breeding. Retaining this diversity as an option for future breeding is very important, but some of these populations are being pushed to extinction."

The geneticists' study highlights an endangered feral herd living in Mulranny, Co. Mayo, as one such unique population in need of protection. Mulranny goats show a genetic similarity to extinct 'Old Goat' populations that lived on the Isle of Skye in the 1800s. They can therefore be considered among the last remaining 'Old Irish' goats.

The 'Old Goat' populations of Britain and Ireland were once ubiquitous throughout the islands but today have been replaced in agriculture by improved Swiss breeds. The native 'Old Goats' are now only found in small feral herds, whose existence is under constant threat from habitat loss, culling and the ongoing impact of Swiss introgression.

The geneticists sampled a number of different 'Old Goat' herds among the 15 taxidermy specimens. The results showed these goats formed two genetic groupings, distinct from other European breeds. Importantly, all of the modern-day Irish dairy goats fell into a genetic groupings outside these two.

Dr Valeria Mattiangeli, one of the study's lead researchers, said: "This highlights the impact that transportation and mass importation of continental breeds has had on Ireland's goat populations, and underlines how selective breeding for agricultural purposes can impact the genetic diversity of animals."

Sen Carolan of the Old Irish Goat Society, who is a co-author of the journal article, said: "We hope this study will play a key role in saving what was and still is a diminutive creature that is both resilient and charismatic and that represents our cultural and pastoral history."

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DNA from taxidermy specimens explains genetic structure of British and Irish goats - Science Daily

Why it might be time to reconsider the money spent on genetics research – The Conversation AU

Genetic testing has many touted future benefits - but are any of them coming to fruition?

Worldwide, at least US$3 billion is spent every year on genetics research, with half coming from governments. Yet less than 3% of this is spent on research addressing how to incorporate genetics into medical practice, and even less is spent applying genetics to the prevention of disease.

Right now, optimism about the potential of genetics is high. Breakthroughs in genetics are reported with enthusiasm, and genetics research continues to comprise a large proportion of all funded research. Funding is often awarded because researchers claim once we understand the genetic components of a disease like cancer, we will be able to better predict, prevent, and even cure disease. Future cures are often reported long before theyre available.

However, some scientists and medical specialists are starting to question whether the money invested in genetic research is well spent. Are we getting the promised benefits from this investment?

Heres an example in which genetic testing applies. Once a person is found to have a hereditary colorectal cancer syndrome, usually after a diagnosis of colorectal cancer, all members of the family can be offered genetic testing for the particular genetic mutation found in the person with cancer.

Family members found positive can then be screened more intensively to prevent future colorectal cancers. Those found not to carry the mutation will not need intensive screening, despite the family history. Research on how this works in practice has found that only about half (56%) of nearly 2,000 eligible family members underwent testing. Those untested were also less likely (compared to those tested) to undergo other forms of screening for colorectal cancer.

We know that for most people who have predictive genetic testing, the process is psychologically beneficial and improves their risk perception. But we know less about the attitudes of people in the community, outside of academic institutions and specialist clinics, who are not having testing. Along with colleagues at the University of Melbourne, I study how genetic testing is received in Australia.

We have previously found only 56% of 862 people offered predictive genetic testing for hereditary colorectal cancer as part of their participation in a research study actually went ahead with a test, and received their results. Earlier, we found similarly low rates of uptake for hereditary breast cancer.

We recently published the results of a study that explored the reasons these people declined genetic testing.

We interviewed 33 men and women who declined the offer of genetic testing and found they were at one of four stages in the process of declining genetic testing:

1) uninformed

2) weak intention

3) conditionally declining

4) unconditionally declining.

Four were considered uninformed because they had not understood the offer, so were not in a position to make a decision. Nine described a weak intention to have genetic testing. They knew there was a test available, and they understood some aspects of it, but they were putting off going ahead with the test because they were not convinced the benefits would outweigh the risks.

Another nine participants were conditionally declining testing, as they had decided not to pursue testing now, but felt they may change their minds in the future. Their reasons for not wanting testing were either that it wouldnt make much difference, or there would be negative side effects of testing. The latter includes increased worry from a positive result, or concerns it would impact access to life insurance products (premiums could rise or they could be declined cover).

The largest group of 11 participants were unconditional decliners who, unlike the other groups, could not imagine going ahead with genetic testing either now or in the future. While the reasons were similar to the previous groups, they were not open to changing their mind.

This research reveals several things first, that community understanding of predictive genetic testing is poor in some groups, and second, the value assigned to this testing is far lower than the hype around genetic discoveries would suggest.

Third, it reveals that significant structural barriers stand in the way of genetic testing, particularly the concern life insurance companies can use genetic test information to refuse cover or adjust premiums.

If genetic tests are going to fulfil their promise of contributing to cancer prevention, they need to be seen as something of value, and they need to reach everybody in the community, not just a select few. There needs to be more effort spent engaging with the intended recipients of new technology, and potential barriers, earlier in the process.

Its foolish to ignore the perceptions, assumptions, and concerns of the very people who are meant to use the technology. Predictive genetic testing for hereditary colorectal cancer is in some ways a straightforward test, with clear consequences for medical management. Yet this testing is far from mainstream or acceptable for the people we spoke to.

Its time to devote more than 3% of funding to translation, to ensure scientific advances in genetics result in improved human health and we get value for the whole society from the money spent on research.

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Why it might be time to reconsider the money spent on genetics research - The Conversation AU

Breeder focuses on genetics with goal of improving customers’ feeder calves – Farm Talk

When it comes to knowing what bull buyers want, the Aschermanns have made it their business to be ahead of the game.

At Aschermann Charolais in Carthage, Missouri, the goal is to help commercial cattlemen raise better feeder calves by raising bulls with a reputation for calving ease, good disposition, sound feet and legs, and fescue tolerance. Both Larry and his wife, Peggy, have worked to build that reputation by using their experiences in the cattle business.

Her history is really in cattle and wheat so she provides good insight into the cattle operation about things we need to be aware of for our customers, Larry said, explaining Peggys family raised Herefords and wheat for generations in Kansas. I was born on a grain farm in Illinois and we raised hogs.

During his 4-H years, his great uncle gave him two heifers on shares Larry fed them and they split the money when they were sold and he was hooked. At the age of 13, he began to borrow money and buy cattle.

Theres nothing I like better than watching a cow have a baby calf, he said with a smile.

After attending Kansas State University and showing cattle for people to put himself through school, Larry worked as a fieldman for the American Shorthorn Association and was the first executive secretary for the American Maine-Anjou Association. He went back to Illinois and farmed for a period but quickly learned grain farming was not where his heart was. He took a position at a Monsanto subsidiary called Farmers Hybrids and worked on a program, which was developing eight proprietary composite lines of cattle for a rotational crossbreeding system.

But during that time, I became infatuated with southwest Missouri, Larry said, adding they bought an existing livestock facility and moved to the area.

Under their direction, the Four State Stockyards in Diamond grew to be one of the top livestock markets in the state. It also provided Larry with the unique perspective of seeing what worked for commercial cattlemen and what didnt.

In 1980, the area had a mixed bag of genetically diverse cows, Larry said. Later, I saw my good producers go to Angus bulls to clean up their cowherds or make them more functional.

When it came time to sell the stockyards and reenter the purebred business, he narrowed his breed choices down to Charolais. He chose the breed because Charolais-Angus cross cattle were and still are desired by feedlots and packers, he explained.

I saw a chance to moderate Charolais to where they were functional in the commercial cattle business in this part of the world and, at the same time, provide more growth and hybrid vigor, he explained, adding his confidence in crossbreeding and hybrid vigor really cemented his decision to go with Charolais cattle.

I took the breed and started modernizing them for lack of a better term through moderation, he continued. In the process, the show ring started picking the kind of cattle we were raising so we had great success in the show ring.

During the 15 years they had the stockyards, they saw the difference genetics makes in the prices received for calves due to disposition, growth or hair color.

Larry spends a lot of time on genetics, Peggy said with obvious pride in her husband. I may not have a lot of experience with geneticists but its amazing to me how he can figure out today what the cattle market is going to want and need in the future. And, truthfully, sometimes hes a little ahead of everybody else. He really is. It takes them a few years to catch up with him. But Ive never known him to be wrong, and its amazing how good he is at genetics.

Larry added tweaking the breeding and genetics of their cattle has been a long-term project. Breeding decisions today have to be what customers need years in the future when the animals are actually sold.

They have two to three generations of calving ease built into their cowherd. At the same time, they take pelvic measurements into consideration as well as calving ease. This keeps cow size in check and keeps calving ease consistent in the herd, Larry explained.

Weve worked on calving ease from the sire side but weve also done it from the cow side, he added, emphasizing they have worked diligently to develop cattle that will perform consistently for their customers.

EPDs such as calving ease and birth weight are only one of the tools they use to make breeding decisions.

A lot of the things we select for there are no EPDs, Larry said, emphasizing their focus on foot and leg soundness, fescue tolerance and eye appeal. When youre producing feeder calves that go into the sale ring and the order buyer has a minute to decide breed composition, body condition, whether they look like theyre going to feed good or not, they have to make snap decisions. So, you provide them with cattle that look the part, act the part, have the color, and have the growth.

Peggy added, Disposition is big. If Im out there by myself, I dont want to get run over by a bull.

At Aschermann Charolais, they do not spend much time trying to improve their fescue pastures but instead focus on animals that can handle the often-unimproved fescue pastures where they are expected to perform.

We dont shy away from fescue hay or pasture, Larry said. We almost insist that we grow our bulls on fescue so they are ready to go.

In addition to developing reputable lines of Charolais bulls, they have also branched out and experimented with Charolais-hybrid bulls.

Purebred breeders are, in general, innovators and tinkerers to try and make the product better, he said. We added Red Angus-Charolais crosses to our breeding program and, about five or six years ago, we started experimenting with a breed of cattle from Japan.

The introduction of purebred red Charolais, Red Angus-Charolais crosses and Akaushi crosses have allowed them to expand their offerings to commercial cattlemen who may want black calves, calves with the potential to grade Prime, or just composite bulls.

You have to have years of experience, know what your customers want, and provide what theyll pay for and what will improve their feeder calf production, he emphasized.

We try to respond to what our customers want but, right now, we think we have what they need, the cattleman continued. We try to be a one-stop shop. If you do not want a purebred Charolais, weve got some composites.

For cattlemen wanting to improve their operations, he recommended looking at their bulls.

A bulls half your herd, he said. You can have about any cow but youve got to have good bulls if youre serious about making money.

And the Aschermanns are doing their best to help those producers.

Our main business is Charolais, but we continue to try to achieve our goals of easy calving, good-footed bulls that thrive in the Four State area on the grasses that we have.

Weve bred trait leaders for the breed, he continued. Weve owned and bred cattle that win purple ribbons but our main focus is just on folks that want to raise better feeder calves.

The Aschermanns are believers in the auction system and sell bulls twice a year in sales at the ranch. Occasionally, they have their herd built up enough for a female sale but that typically doesnt take place on a regular basis.

We dont sell any bulls private treaty, he said. If youre going to come to our bull sale and buy a bull, you really dont want to buy something thats been picked over. Youd like to have the opportunity to buy the best one weve got. You may decide not to buy it but I feel like were obliged to give you the opportunity to buy the very best one.

With no private treaty sales, the semi-annual sales help them cater to customers who may have bull needs more than once a year. Bulls average 18 months in age at the sales.

The Aschermann Charolais 24th Edition Bull Sale is scheduled for March 18 at the ranch at 3852 County Road 110, Carthage, Missouri. To view the catalog or for more information, visit http://www.AschermannCharolais.com.

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Breeder focuses on genetics with goal of improving customers' feeder calves - Farm Talk

Graham joins Crestview extension office staff – Crestview News Bulletin

By Veronica Graham | Okaloosa County Extension Office

Hello, my name is Veronica Graham and I am the new 4H Program Assistant for Okaloosa County.

Istarted working at the extension office as a volunteer for the Master Gardener Program in 2016, butjoined the 4-H team just before Christmas of 2016. I grew up in Livingston, Montana, where I enjoyedoutdoor activities such as bike riding, hiking and spending time with my three horses and two dogs.

After high school I joined the Air Force, where I served four years as an EOD technician.

During that time,I had two beautiful children and decided that they needed me more than the military did. I put down myboots and picked up the books. By 2014, I had my bachelors degree in Project Management with afocus in Training and Development.

Currently, I am leading the Embryology School Enrichment Programin 8 schools that include 54 classes. I really enjoy the fact that these students are learning thedevelopmental stages of life.

I have also been working with the Family Nutrition Program to developnew raised bed gardens for local schools.

Contact me at vgraham@co.okaloosa.fl.us or call 689-5850to find out more about 4-H in our county.

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Graham joins Crestview extension office staff - Crestview News Bulletin

Molecular structure of the cell nucleoskeleton revealed for the first time – Science Daily

Compared to bacteria, in eukaryotes the genetic material is located in the cell nucleus. Its outer shell consists of the nuclear membrane with numerous nuclear pores. Molecules are transported into or out of the cell nucleus via these pores. Beneath the membrane lies the nuclear lamina, a threadlike meshwork merely a few millionths of a millimeter thick. This stabilizes the cell nucleus and protects the DNA underneath from external influences. Moreover, the lamina plays a key role in essential processes in the cell nucleus -- such as the organization of the chromosomes, gene activity and the duplication of genetic material before cell division.

Detailed 3D image of the nuclear lamina in its native environment

Now, for the first time, a team of researchers headed by cell biology professor Ohad Medalia from the Department of Biochemistry at UZH has succeeded in elucidating the molecular architecture of the nuclear lamina in mammalian cells in detail. The scientists studied fibroblast cells of mice using cryo-electron tomography. "This technique combines electron microscopy and tomography, and enables cell structures to be displayed in 3D in a quasi-natural state," explains Yagmur Turgay, the first author of the study. The cells are shock-frozen in liquid ethane at minus 190 degrees without being pretreated with harmful chemicals, thereby preserving the cell structures in their original state.

"The lamin meshwork is a layer that's around 14 nanometers thick, located directly beneath the pore complexes of the nuclear membrane and consists of regions that are packed more or less densely," says Yagmur Turgay, describing the architecture of the nucleoskeleton. The scaffold is made of thin, threadlike structures that differ in length -- the lamin filaments. Only 3.5 nanometers thick, the lamin filaments are much thinner and more delicate than the structures forming the cytoskeleton outside the cell nucleus in higher organisms.

New approach for research on progeria and muscular dystrophy

The building blocks of the filaments are two proteins -- type A and B lamin proteins -- which assemble into polymers. They consist of a long stem and a globular domain, much like a pin with a head. Individual mutations in the lamin gene elicit severe diseases with symptoms such as premature aging (progeria), muscle wasting (muscular dystrophy), lipodystrophy and damage of the nervous system (neuropathies). "Cryo-electron tomography will enable us to study the structural differences in the nuclear lamina in healthy people and in patients with mutations in the lamin gene in detail in the future," concludes Ohad Medalia. According to the structural biologist, this method permits the development of new disease models at molecular level, which paves the way for new therapeutic interventions.

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Molecular structure of the cell nucleoskeleton revealed for the first time - Science Daily

SelectScience Interview: Live Cell Analysis in Chronic Inflammation Research at the University of Oxford – SelectScience.net (blog)

Professor David R. Greaves, University of Oxford, UK, discusses the technology that is enabling him to research tissue repair and chronic inflammation in real time

David R. Greaves,University of Oxford, UK

Professor David R. Greaves is using the latest live cell imaging technology to carry out ground-breaking research into inflammation biology. Sonia Nicholas, Associate Editor for SelectScience, spoke to Professor Greaves to find out more.

SN: Please could you confirm your name, full job title and place of work.

DRG: Im Professor David R. Greaves, I am a University Lecturer in Cellular Pathology at the Sir William Dunn School of Pathology, University of Oxford, UK.

SN: Could you tell us about your job, what you do and what your responsibilities are?

DRG: I run a research laboratory working on macrophage biology and inflammation. I am very interested in macrophage chemotaxis as well as other aspects of macrophage cell biology such as phagocytosis and cytokine secretion.

In addition to doing biomedical research I run the BM Principles of Pathology course for second year medical students at the University of Oxford, I run a final year lecture course in Inflammation Biology, I run the British Heart Foundation 4-year Cardiovascular Sciences PhD program and I am a Tutorial Fellow in Medicine at Hertford College where I give tutorials in Biochemistry, Cell Biology, Endocrinology, Medical Genetics and Pathology.

Inflammation and disease

SN: Can you tell us more about your research into inflammation?

DRG: Inflammation is the normal physiological response to tissue injury and infection. Most of the time our inflammatory responses are of an appropriate magnitude, they are quickly resolved and any damage to our tissues is successfully repaired. Inflammation is important because it drives the development of many important human diseases including rheumatoid arthritis, cardiovascular disease, inflammatory bowel disease and many others. Recent research suggests chronic inflammation may be an important driver of major mood disorders including depression.

My research is aimed at identifying endogenous pathways that are involved in regulating the magnitude and duration of inflammatory responses. Recently, we have been looking at the role of two independent cell signaling pathways in regulating the inflammatory response. One is centered on endocannabinoids a class of lipids that signals via a G protein coupled receptor (GPCR) called CB2 and the other pathway is centered on an unusual cytokine called Chemerin (TIG-2) whose effects are mediated by three different GPCRs ChemR23, CCRL2 and GPR1.

Macrophages in healthy and inflamed tissues play an essential role in the initiation and resolution of inflammation. One important aspect of macrophage biology in the context of inflammation resolution is phagocytosis of cellular debris and phagocytosis of neutrophils that have undergone apoptosis. Macrophage phagocytosis of apoptotic cells (efferocytosis) has a profound effect on inflammation resolution. Macrophage efferocytosis changes the profile of macrophage cytokine secretion towards a more anti-inflammatory / pro-resolution phenotype, which in turn will enhance inflammation resolution. Failure to clear apoptotic neutrophils from a site of inflammation can lead to failure of resolution and a substantially worse outcome caused by secondary necrosis.

The IncuCyte Live-Cell Analysis System enables detailed analysis of immune cell biology monitor changes in morphology and measure cell health, chemotactic migration and phagocytosis in real time. Automatically visualize the differentiation of immortalized THP-1 cells into M0 macrophages and qualitatively analyze the differentiation of primary monocytes into M1 and M2 macrophage populations

A powerful research tool

SN: How does the IncuCyte technology help you to achieve your research goals?

DRG: We have now been using the IncuCyte Live-Cell Analysis Systemto study several different aspects of macrophage cell biology in a wide range of different applications. We have found this real time live cell imaging system to be easy to use and the associated image analysis software makes this a very powerful research tool.

SN: How did you monitor cell behavior before you installed the IncuCyte? What does this technology enable you to do that you couldnt do before?

DRG: All the macrophage biology experiments that we have published using the IncuCyte platform could have been performed using other imaging modalities but I think that the big advantage of the IncuCyte live cell imaging platform lies in the ease of use and ease of analysis compared to other cell imaging methods (confocal microscopy, flow cytometry and Imagestream). What we particularly like about the IncuCyte system is the ability to develop protocols to study both generalized and cell type specific behavior. For instance we can follow proliferation or apoptosis of macrophages, and we can study macrophage specific cell behavior such as apoptosis or chemotaxis. Data analysis is greatly facilitated by user friendly software.

SN: What is next for your research?

DRG: I want to start using the IncuCyte system to do scratch wound migration assays where we look for macrophage secreted factors that play a role in wound repair processes. Hopefully we can scale up this cell-based assay to look for novel chemicals, peptides and proteins that will enhance tissue repair in the context of inflammation resolution.

The long-term goal of research in my laboratory is to turn high quality basic science into new treatments that enhance wound repair and help resolve chronic inflammation. Our ability to study both murine and human macrophages on the IncuCyte platform will be important in future translational research programs.

SN: Do you have any advice for other researchers who are considering using IncuCyte technology?

DRG: Take your time in setting up the assays before you pile in to testing lots of different mediators, drugs etc. Every cell type is different so one size fits all protocols are unlikely to work first time!

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SelectScience Interview: Live Cell Analysis in Chronic Inflammation Research at the University of Oxford - SelectScience.net (blog)

In cleaning up misfolded proteins, cell powerhouses can break down – Science Daily

Working with yeast and human cells, researchers at Johns Hopkins say they have discovered an unexpected route for cells to eliminate protein clumps that may sometimes be the molecular equivalent of throwing too much or the wrong trash into the garbage disposal. Their finding, they say, could help explain part of what goes awry in the progression of such neurodegenerative diseases as Parkinson's and Alzheimer's.

Proteins in the cell that are damaged or folded incorrectly tend to form clumps or aggregates, which have been thought to dissolve gradually in a cell's cytoplasm or nucleus thanks to an enzyme complex called the proteasome, or in a digestive organelle called the lysosome.

But in experiments on yeast, which has many structures similar to those in human cells, the Johns Hopkins scientists unexpectedly found that many of those protein clumps break down in the cell's energy-producing powerhouses, called mitochondria. They also found that too many misfolded proteins can clog up and damage this vital structure.

The team's findings, described March 1 in Nature, could help explain why protein clumping and mitochondrial deterioration are both hallmarks of neurodegenerative diseases.

Rong Li, Ph.D., professor of cell biology, biomedical engineering and oncology at the Johns Hopkins University School of Medicine and a member of the Johns Hopkins Kimmel Cancer Center, who led the study, likens the disposal system to the interplay between a household's trash and a garbage disposal in the kitchen sink. The disposal is handy and helps keep the house free of food scraps, but the danger is that with too much trash, especially tough-to-grind garbage, the system could get clogged up or break down.

In a previous study, Li and her team found protein aggregates, which form abundantly under stressful conditions, such as intense heat, stuck to the outer surface of mitochondria. In this study, they found the aggregates bind to proteins that form the pores mitochondria normally use to import proteins needed to build this organelle. If these pores are damaged by mutations, then aggregates cannot be dissolved, the researchers report. These observations led the team to hypothesize that misfolded proteins in the aggregates are pulled into mitochondria for disposal, much like food scraps dropped into the garbage disposal. Testing this hypothesis was tricky, Li says, because most of the misfolded proteins started out in the cytoplasm, and most of those that enter mitochondria quickly get ground up.

As a consequence, Li and her team used a technique in which a fluorescent protein was split into two parts. Then, they put one part inside the mitochondria and linked the other part with a misfolded and clumping protein in the cytoplasm. If the misfolded protein entered the mitochondria, the two parts of the fluorescent protein could come together and light up the mitochondria. This was indeed what happened.

"With any experiment," Li says, "you have a hypothesis, but in your head, you may be skeptical, so seeing the bright mitochondria was an enlightening moment."

To see what might happen in a diseased system, the team then put into yeast cells a protein implicated in the neurodegenerative disease known as amyotrophic lateral sclerosis (ALS), or Lou Gehrig's disease. After a heat treatment that caused the ALS protein to misfold, it also wound up in the mitochondria. The researchers then did an experiment in which a lot of proteins in the cytoplasm were made to misfold and found that when too much of these proteins entered mitochondria, they started to break down.

The team wanted to make sure that the phenomenon it had observed in the yeast cells could also happen in human cells, so the scientists used the same split-fluorescent protein method to observe misfolded proteins to enter the mitochondria of lab-grown human retinal pigmented epithelial cells. As observed in yeast, misfolded proteins, but not those that were properly folded, entered and lit up mitochondria.

Biological systems are in general quite robust, but there are also some Achilles' heels that may be disease prone, Li says, and relying on the mitochondrial system to help with cleanup may be one such example. While young and healthy mitochondria may be fully up to the task, aged mitochondria or those overwhelmed by too much cleanup in troubled cells may suffer damage, which could then impair many of their other vital functions.

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In cleaning up misfolded proteins, cell powerhouses can break down - Science Daily

‘Dairy farmers should check out their cows’ anatomy’ – Agriland

If farmers have a better understanding of the cows reproductive anatomy, then it becomes easier for them to understand the factors that come into play when it comes to getting her pregnant, according to UK veterinarian Roger Blowey.

For example, at a very practical level, the tip of an insemination gun should always be placed at the entrance to the cervix during the AI process. If it is pushed up beyond this point, damage to the uterus can result, which will diminish the cows chance of becoming pregnant.

Blowey confirmed that 90% of eggs will be fertilised if the cow is inseminated at the right time.

But problems can follow, when it comes to the new embryo implanting itself onto the wall of the uterus, he said.

This is because the cow does not pick up the signals coming from the fertilised egg and, as a result, does not respond in the ways required to allow implantation.

Blowey said that both external and internal factors can come into play, when determining whether or not implantation can take place.

Extraneous stimuli include lameness, mastitis, over-crowding, poor handling and other management related issues, he added.

Internal factors include endometritis and the physical condition of the uterus. For example, if full involution has not taken place, then the cow will not become pregnant.

This issue raises its head if a cow is inseminated too soon after having her previous calf.

Blowey also highlighted the implications of twin calves a heifer and a bull being born while attached to the same placenta during pregnancy.

Invariably the heifer will be a freemartin.This is because male hormones from the growing bull will be circulating prior to the heifer producing her own compliment of female hormones. As a consequence, the heifer will be born with both male and female sex organs.

Sometimes, the bull calf will be re-absorbed by the mother. However, the resulting single heifer calf will still be a freemartin.

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'Dairy farmers should check out their cows' anatomy' - Agriland