SAN FRANCISCO — When making his free agency decision this summer, Warriors forward Glenn Robinson III wasn’t just looking for playing time. He made that mistake before. Instead, he prioritized a place that could utilize his talents. Disappointed after falling out of the rotation with the Detroit Pistons last season, Robinson asked his agent to reach out to the Warriors, who entertained signing him two years ago. Mutual interest led to a one-year, $1.9 million deal.In the wake of injuries to …
Ross Anderson (PhD biochemistry) is professor of biochemistry at The Master’s University in southern California. Dr Anderson’s expertise is in the area of biochemistry and molecular biology. He has taught Biochemistry and helped to direct research projects of graduate and medical students at Baylor College of Medicine, Houston, TX. Dr. Anderson was a post-doctoral researcher in the Molecular Genetics Division of the Department of Ophthalmology at the Houston Neurosensory Center.Dr Anderson was a member of both the undergraduate and graduate faculty at Lamar University, Beaumont, TX. There he taught and directed the research activities of undergraduates and Masters of Science degree candidates in Biology. Currently he is professor of biochemistry at The Master’s University in southern California.Dr Anderson’s research interests include structure-function studies of DNA polymerizing enzymes and the synthesis and expression of synthetic human genes in bacterial hosts. He has authored or co-authored several publications in major, peer-reviewed journals. He is a member of the American Chemical Society and Sigma Xi Research Society. by Ross Anderson, PhDMitochondria are very interesting and unique organelles. All eukaryotic cells possess them. They are indispensable in a number of cell activities beyond their well-known role of synthesizing the bulk of ATP used to power cells. Mitochondria reproduce at rates that are, for the most part, independent of the cell division cycle. However, they always manage to generate about twice the number just before the time of mitosis and cytokinesis so that each daughter cell receives approximately equal numbers of mitochondria. How this is regulated and coordinated is unknown.The Mitochondrial GenomeMitochondria have their own genomes separate from that in the nucleus. Each mitochondrion may have 5 to 10 copies of the genome organized into clusters called nucleoids, and a cell may have a thousand mitochondria. This means that each cell may have 5,000 to 10,000 copies of the mitochondrial genome! At conception it is estimated that mammals inherit 100,000 to 500,000 mitochondrial genomes via the egg!The Problem of Mutational DegradationDue to mutations, it is possible for a single mitochondrion to have “healthy” copies as well as defective/mutated copies. Such cells with two or more distinct varieties of mitochondrial DNA (mtDNA) are said to be heteroplasmic. Mitochondrial DNA encodes various protein subunits used for ATP production, their own transfer RNAs (tRNA), and ribosomal RNAs (rRNA). Most of the proteins used in the mitochondria, however, are encoded in nuclear genes.Like nuclear DNA, mtDNA mutates, but at a much greater rate; 5 to 10 times greater than the genes in the nucleus. This may possibly be due to lower fidelity in DNA replication, lower efficiency in DNA repair mechanisms, or both. There are a number of disease states that are the result of too many mutated mitochondrial genes.Mitochondrial InheritanceMitochondria of mammalian cells and fruit flies, indeed most eukaryotes, are inherited from the mother’s egg cells. These diseases then are inherited through the mother. Consequently, it is imperative that those mitochondria be as “healthy” genetically as possible. If a mitochondrion generates more mutated copies than can be tolerated, there must be a mechanism for recognizing these defective mitochondria and destroying them so that only “healthy” mitochondria are maintained in the egg and passed on to the next generation. The high rates of mutation would suggest that most cells would exhibit heteroplasmy, but this is not the case. Most cells are homoplastic; i.e., they have mitochondria with identical genomes. Thus, there must be a way that cells are able to identify mitochondria with defective DNA, keep them from reproducing and eliminate them. The cells, in effect, create a bottleneck through which only “healthy” mitochondria are permitted to pass.Forcing Mitochondria Through a Bottleneck InspectionThe authors of a letter in Nature by Lieber et al. performed a series of ingenious experiments investigating factors that may be involved in identifying defective mitochondria; i.e., creating the bottleneck. They transplanted wild-type mitochondria from one species of fruit fly, D. yakuba, into another species of fruit fly, D. melanogaster, which already had mitochondrial genomes with a temperature-sensitive point mutation in the cytochrome c oxidase subunit I gene. Flies grown at the permissive temperature (18○C) exhibited little effect, while those grown at the restrictive temperature (29○C) exhibited reduced cytochrome c oxidase activity.When grown at the restrictive temperature, they found there was a marked increase in the proportion of wild-type mitochondrial DNA from D. yakuba relative to the defective mtDNA, but only in the germline cells—not somatic cells. This indicated that the defective mtDNA was somehow selectively detected and destroyed.Whether from an evolutionary or a design perspective, this makes perfect sense. Somatic cells can tolerate defective mitochondria more than germline cells because only that cell would be affected; it would not necessarily impact the next generation. Germline cells, though, would carry the defect into the next generation. Not surprisingly, it was also found that detection and destruction of defective mtDNA was limited to female germline cells, not male germline cells.Selection for destruction appeared to initiate in the very early stages of egg development; after the stem cell stage and during the cyst formation stage. Further experiments revealed that selection was at the level of whole mitochondria—not just defective DNA. Thus, it was the defective mitochondria that were being detected and destroyed.How Fragmentation Rescues Healthy mtDNAThe morphology of the mitochondrion changes from the stem cell stage to the cyst stage. The authors postulate that this change is due to fragmentation of the mitochondria, such that defective mitochondria are more easily detected. Additionally, from the 2-to-8-cell stage in the cyst, mtDNA is not replicated. This reduces the number of genomes per mitochondrion and decreases the possibility of both defective and wild-type genomes residing in the same mitochondrion. This strategy leads to improved selection. Mitochondria in the stem cell stage (which occurs prior to the cyst stage) were shown to share their contents easily. Fragmentation in the cyst cell stage, however, decreases the possibility of defective and wild-type mitochondria from sharing their contents.In this respect the stem cells are more like somatic cells. The reasoning is that in somatic cells mitochondria with defective DNA can fuse and share their contents, thus a “healthy” mitochondrion can complement and rescue a mitochondrion with defective DNA. Fusion cannot be permitted in germline cells, because the defective mtDNA would be masked by the “healthy” DNA, allowing mutations to accrue and to be passed on to each subsequent generation. The authors suggest that fragmentation, in some unknown way, aids in distinguishing defective from wild-type mitochondria.Intelligent SelectionThe authors were able to show that either overexpression of the protein Mitofusin (a protein involved in the fusion of mitochondria, and suppression of fragmentation), or the reduced expression of DrpI (a protein involved in mitochondrial fission; promotes fragmentation) led to loss of selection. This, again, suggested that a time of sustained fragmentation is necessary for selection. It was shown that mitochondrial fragmentation is not only necessary, but also sufficient for effective selection against defective mtDNA.Interestingly, experimentally reduced expression of Mitofusin in somatic cells also led to sustained fragmentation and subsequent selection against defective mtDNA. However, a reduction in Mitofusin expression (both the protein and its mRNA) is normally found only in the germline cells at the cyst cell stage; i.e., this reduction in Mitofusin is observed selectively in germline cells, not somatic cells.Design in the Timing, TooATP synthase is a rotary motor that generates 3 ATP per revolution.This observation strongly suggests a design feature for the purpose of generating a period of sustained fragmentation early in egg development so that selection against defective mtDNA can be more effective. Further investigation is needed to ascertain just how defective mtDNA is identified. However, the authors were able to determine that reduction in ATP production is sufficient to induce selection. This makes sense considering that most of the protein-coding genes of mitochondria are for subunits of the ATP synthase rotary engines or for the other complex machinery of the electron transport chain.Another protein, BNIP3, was also found to be selectively upregulated in cyst cells. This protein is located in the mitochondrial outer membrane. It plays an important role in mitophagy [mitochondrial recycling] in somatic cells as when maturing red blood cells need to rid themselves of all their organelles including mitochondria.Design ThroughoutSo, the selective reduction of Mitofusin expression and increased expression of DrpI and BNIP3 at the same time and in the same select group of cells (cyst cells) smacks of design! We must also keep in mind that these proteins do not work alone, but rather in coordinated complexes with a number of other proteins designed to carry out a specific function at a specific time and place. If that’s not enough, these authors also mention reports that another protein, Pink1, may recognize and inhibit replication of the defective mtDNA, which in some unknown way stimulates replication of the wild-type DNA so that the “healthy” DNA can dominate.Design in the CleanupOnce mitochondria carrying defective DNA have been selected, they are destroyed by a process known as mitophagy, a type of autophagy whereby certain organelles are selectively destroyed, and their contents recycled by the cell. Pink1 in conjunction with another protein, Parkin, initiate mitophagy. In healthy mitochondria, Pink1 is imported into the matrix of the mitochondrion, but is not imported by defective mitochondria. Instead it accumulates on the outer surface of the outer membrane, recruits Parkin which, in turn, adds ubiquitin tags to outer membrane proteins targeting them for destruction.SummaryIt appears that the ability of a developing egg cell to create the genetic bottleneck leading to homoplastic cells is its ability to initiate sustained fragmentation whereby mitochondria containing defective DNA are selectively eliminated. Taken in toto with other information not in the article, it seems to me that the design inference is strong.This article, like virtually all others of its kind, addresses the scientific questions of ‘What is it? What does it do?’ And ‘How does it do it?’ While we slowly learn more and more answers to these questions, and someday may be able to describe in intimate detail the inner workings of cells, we will never be able to accurately answer the question of ‘How it came to be?’ short of invoking the genius of an all-powerful, creative designer.The authors, unfortunately, felt the need to attribute the process of selective identification and destruction of aberrant mtDNA to the all-powerful deity, Evolution, and thus gave their token bow. I find it simply amazing how so many intelligent researchers can report many of the detailed features of living creatures yet still attribute it to chance and state that any inference to design is only an illusion. All researchers need to take a few steps back and look at the forest, and not be so focused on the trees. (Visited 304 times, 1 visits today)FacebookTwitterPinterestSave分享0
About the authorPaul VegasShare the loveHave your say Neville: Solskjaer personality just what Man Utd needby Paul Vegas10 months agoSend to a friendShare the loveManchester United legend Gary Neville says the personality of Ole Gunnar Solskjaer is just what Old Trafford needs.The Norwegian took over a United’s interim manager on Wednesday following the sacking of Jose Mourinho and faces his first match at another former club, Cardiff City, on Saturday evening.Neville told Sky Sports, “He is so popular, he is one of the most popular players that exists at Manchester United in terms of what he achieved at the club and that goal in 1999.”He is a gentleman, he really is. He is a good person and has immersed himself in coaching. When he finished as a player he obviously became the reserve team coach at Manchester United. He wanted to learn the ropes.”He will be better for that experience at Cardiff. We have a stigma in this country of managers that have been sacked.”What it means is he is more mature and more experienced after having that experience.”
Former Chelsea defender Chivers: Kids fighting tooth and nail for Lampardby Paul Vegasa month agoSend to a friendShare the loveFormer Chelsea defender Gary Chivers believes the club will give manager Frank Lampard time in charge of his young players.Chivers feels the Blues legend will be cut plenty of slack due to his cult-hero status in west London.He told brightonandhovealbion.com: “They’re definitely in a transitional stage, but they will be fighting tooth and nail for Frank Lampard. The kids that have come in, the likes of Mason Mount and Tammy Abraham, who have played at the likes of Derby and Aston Villa, have done brilliantly.“The fans will give Frank a lot of time because he was such a fantastic player and is a fantastic person. Appointing him is the best move Chelsea could’ve made because he loves the club, and knows the ins and outs of the club.“You can see that these players are playing for him. They’re a young side that are going to make mistakes, and Frank will too because this is only his second season as a manager, but the fans adore him and they will give him time.” About the authorPaul VegasShare the loveHave your say
Arsenal fullback Tierney admits PSG striker Mbappe toughest he’s facedby Paul Vegas20 days agoSend to a friendShare the loveArsenal fullback Kieran Tierney admits PSG striker Kylian Mbappe is the toughest opponent he’s faced.Tierney came up against Mbappe in the Champions League with Celtic.He told Arsenal’s YouTube channel: “The one who posed the most difficulties? Kylian Mbappé. He was so fast, like his entire team. It’s the toughest game I’ve played in my career, there was Daniel Alves and Mbappé on my side. “If I learned from this meeting? Yes, great, we suffered 7-1. But when you face the best players in the world, you learn anyway whatever the outcome. But yes, it was hard, my most difficult evening.” About the authorPaul VegasShare the loveHave your say
About the authorPaul VegasShare the loveHave your say Chelsea boss Lampard still has confidence in Pulisicby Paul Vegas7 days agoSend to a friendShare the loveChelsea boss Frank Lampard has assured Christian Pulisic he’s in his plans.The Sun says he has been impressed with the former Borussia Dortmund winger’s natural ability – but frustrated with his matchday performances.Insiders revealed how Lampard and his staff have seen plenty of potential and are quite excited by his raw ability, but they have been slightly frustrated by the fact he has not yet showcased that in the Premier League.USA international Pulisic, 21, – who was signed in January but stayed in the Bundesliga until the summer – has featured in just seven matches for the Blues so far this term.And in another blow, he was hauled off in USA’s embarrassing 2-0 defeat to Canada during the international break – and started crying on the bench.In training, Pulisic has looked top notch.But he has not been able to transfer that on to the pitch, which has forced Lamps to leave him on the sidelines quite often.
Martha TroianAPTN InvestigatesThe provincial government is moving forward with a plan in northwestern Alberta that has First Nations and Métis hunters and trappers worried about how it will effect them.The “caribou range plan” covers millions of hectares of land. One hectare equals 2.47 acres.Alberta says the plan is meant to address the declining number of caribou.But Graham Courtoreille, 69, from the Beaver Ranch Indian Reserve, near Fort Vermilion, believes the plan has nothing to do with protecting the herds but more to do with the government’s plan to turn his traditional territory into parkland and wash away Indigenous land rights.“Sure it could be good for the Native people but you know yourself the federal government has been trying to take away our treaty rights,” says Courtoreille.“I don’t trust Trudeau, I never trusted his dad, and I don’t trust him.”The woodland caribou are considered threatened under both the federal Species at Risk Act and Alberta’s Wildlife Act.The provinces caribou range plan is home to several First Nation communities and Métis settlements, along with six municipalities. In Alberta there is provincial legislation governing Metis settlements that is similar in many ways to the Indian Act.There are 15 caribou ranges in total in the province. In northwestern Alberta, the area could be affected by four caribou range plans; the Bistcho, Yates, Chinchaga and Caribou Mountains range.The largest range is the Caribou Mountains Range, measuring 2,065,873 hectares in size.Parkland status is one tool government could useA working document at the moment, referred as “Alberta’s Draft Provincial Woodland Caribou Range Plan,” proposes to restore the declining caribou population while meeting Canada’s requirements under the Species at Risk Act.According to one of the province’s primary guiding documents to deal with woodland caribou recovery efforts, herds in Alberta are declining at high rates.But for Courtoreille and for other trappers in the region, the caribou are not threatened.“There’s more caribou than elk and moose in this country,” says Courtoreille.Owen Sabiston, a retired fish and wildlife game warden who worked with the province for 30 years, echoes Courtoreille’s concerns.“I have a problem with them calling it a recovery plan because they don’t have baseline numbers of the caribou in the wild, they don’t know how many caribou there were 50 years ago,” said Sabiston about the province’s Environment and Parks reports.He believes the province lacks scientific proof and does not have any data on the caribou prior to the 1990s.A spokesperson with the Alberta Environment and Parks stated that although one conservation method may include converting some land into parkland, it is only one tool at their disposal. They can also utilize restoration, land-use planning and habitat protection. The province’s goal is to work with each individual community to see what tools are most appropriate.Courtoreille says he just found out about the government’s plan recently.“Nobody knew about it, the trappers didn’t know, [and] there are still people who don’t know nothing about it.”However, the department said it met with First Nations and Métis groups in Alberta in early 2017, along with other stakeholders in the forestry and energy sector and with environmental organizations during their Phase 1 process, which informed the draft plan. Information sessions and workshops were also held in various municipalities and meetings with individual communities upon request.Graham Courtoreille, a trapper from the Beaver Ranch Indian ReserveTrappers scared, caribou fine, say advocatesCourtoreille says there are hundreds of trappers and mill workers scared of what’s to come.Calvin Bulldog, 49, from Beaver First Nation is another concerned trapper.Bulldog’s trapline is near Caribou Mountains, neighbouring Wood Buffalo National Park. It’s a trapline that has been passed down for generations. Bulldog said if he loses his trapline, he will have nothing. He said it was only recently he learned about the province’s caribou range plan. Until APTN Investigates informed Bulldog how much land could be affected in his region, he said he had no idea.The Northwest Species at Risk Committee (NSWAR), a grassroots organization made up of six northwestern municipalities, formed as a means to give local residents a voice to do with caribou recovery, released a news release asserting how the government’s plan could sterilize the region’s resources and devastate its economy.According to the NSWAR, 650 forestry jobs could be at risk, $1 billion of annual revenue in timber harvest, gas and oil fields would be greatly impacted, as well as other industries such as trapping, outfitting and agriculture.“We cannot understand why the provincial government wants to add more park space in our area,” wrote NSWAR chair Lisa Wardley. In northwest Alberta, the province is already home to Wood Buffalo National Park and Caribou Mountains Wildland Park.NSWAR is currently circulating a petition, asking concerned citizens to submit a statement declaring their opposition about the government’s plan and mail it to their provincial and/or federal environment ministers.Chief Trevor Mercredi of Beaver First Nation says his community will be meeting with the province to address their concerns.“From what I’m being told, the province cannot enact any sort of legislation that will impact our rights. But in saying that, we do have our eyes and ears open,” says Mercredi.Province said Indigenous rights will not be affectedThe spokesperson with Environment and Parks said they want to hear all concerns including those from Indigenous and Métis communities and from the Northwest Species at Risk Committee.The province also said they acknowledge the significance of Indigenous and Métis hunting and fishing rights, knowing it is part of their cultural heritage.When asked specifically what will become of fishing and hunting rights for Indigenous and Métis people, the spokesperson said their rights will not be affected“The traditional Indigenous hunting rights are not impacted by any of our range planning. They have that as part of their treaty rights and that’s protected by the constitution. We have no jurisdiction over Indigenous hunting.”The spokesperson also said no decisions have been made as to which conservations tools will apply in the region.The last information session for Phase 2 wrapped up this week, and now the province will move into Phase 3, which will lead to the province’s final caribou management plan.
The North Carolina Industrial Commission says a firefighter’s death from cancer was a “line of duty death.”The ruling on Asheville Fire Department Engineer Will Willis is only the second such in state history for a firefighter’s cancer death. Willis died Feb. 27, on his 34th birthday, from a rare form of kidney cancer.Chief State Fire Marshal Brian Taylor says the ruling sets a precedent, and helps Willis’ family. The family will receive disability benefits and his children will get a free college education at a state public university. Willis’ name will be added to a state memorial in Raleigh.According to the Asheville Citizen-Times, a 2013 Centers for Disease Control study said firefighters were more likely than the general U.S. population to die of cancer.Recent research studies show that synthetic materials used in buildings today produce carcinogens when they burn. A rise in the percentage of firefighters diagnosed with cancer has led to sweeping changes in firehouse procedures.