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Snippets of RNA that accumulate in brain cells could interfere with normal function — ScienceDaily

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Snippets of RNA that accumulate in brain cells could interfere with normal function -- ScienceDaily

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As we age, neurons in our brains can become damaged by free radicals. MIT biologists have now discovered that this type of damage, known as oxidative stress, produces an unusual pileup of short snippets of RNA in some neurons.

This RNA buildup, which the researchers believe may be a marker of neurodegenerative diseases, can reduce protein production. The researchers observed this phenomenon in both mouse and human brains, especially in a part of the brain called the striatum — a site involved in diseases such as Parkinson’s and Huntington’s.

“The brain is very metabolically active, and over time, that causes oxidative damage, but it affects some neurons more than others,” says Christopher Burge, an MIT professor of biology. “This phenomenon appears to be a previously unrecognized consequence of oxidative stress, which impacts hundreds of genes and may influence translation and RNA regulation globally.”

Burge and Myriam Heiman, the Latham Family Career Development Associate Professor of Brain and Cognitive Sciences, are the senior authors of the paper, which appears in the Nov. 27 issue of Cell Reports. Peter Sudmant, a former MIT postdoc, is the lead author of the paper, and postdoc Hyeseung Lee and former postdoc Daniel Dominguez are also authors.

A mysterious finding

For this study, the researchers used a technique developed by Heiman that allows them to isolate and sequence messenger RNA from specific types of cells. Messenger RNA carries protein-building instructions to cell organelles called ribosomes, which read the mRNA and translate the instructions into proteins by stringing together amino acids in the correct sequence.

Heiman’s technique involves tagging ribosomes from a specific type of cells with green fluorescent protein, so that when a tissue sample is analyzed, researchers can use the fluorescent tag to isolate and sequence RNA from only those cells. This allows them to determine which proteins are being produced by different types of cells.

“This is particularly useful in the nervous system where you’ve got different types of neurons and glia closely intertwined together, if you want to isolate the mRNAs from one particular cell type,” Burge says.

In separate groups of mice, the researchers tagged ribosomes from either D1 or D2 spiny projection neurons, which make up 95 percent of the neurons found in the striatum. They labeled these cells in younger mice (6 weeks old) and 2-year-old mice, which are roughly equivalent to humans in their 70s or 80s.

The researchers had planned to look for gene expression differences between those two cell types, and to explore how they were affected by age. “These two types of neurons are implicated in several neurodegenerative diseases that are aging-related, so it is important to understand how normal aging changes their cellular and molecular properties,” Heiman says.

To the researchers’ surprise, a mysterious result emerged — in D1 neurons from aged mice (but not neurons from young mice or D2 neurons from aged mice), they found hundreds of genes that expressed only a short fragment of the original mRNA sequence. These snippets, known as 3′ untranslated regions (UTRs), were stuck to ribosomes, preventing the ribosomes from assembling normal proteins. “While these RNAs have been observed before, the magnitude and age-associated cell-type specificity was really unprecedented,” says Sudmant.

The 3′ UTR snippets appeared to originate from about 400 genes with a wide variety of functions. Meanwhile, many other genes were totally unaffected.

“There are some genes that are completely normal, even in aged D1 neurons. There’s a gene-specific aspect to this phenomenon that is quite interesting and mysterious,” Burge says.

The findings led the researchers to explore a possible role for oxidative stress in this 3′ UTR accumulation. Neurons burn a great deal of energy, which can produce free radicals as byproducts. Unlike many other cell types, neurons do not get replaced, so they are believed to be susceptible to accumulated damage from these radicals over time.

The MIT team found that the activation of oxidative stress response pathways was higher in D1 neurons compared to D2 neurons, suggesting that they are indeed undergoing more oxidative damage. The researchers propose a model for the production of isolated 3′ UTRs involving an enzyme called ABCE1, which normally separates ribosomes from mRNA after translation is finished. This enzyme contains iron-sulfur clusters that can be damaged by free radicals, making it less effective at removing ribosomes, which then get stuck on the mRNA. This leads to cleavage of the RNA by a mechanism that operates upstream of stalled ribosomes.

“Sending neural signals takes a lot of energy,” Burge says. “Over time, that causes oxidative damage, and in our model one of the proteins that eventually gets damaged is ABCE1, and that triggers the production of 3′ UTRs.”

RNA buildup

The researchers also found the same accumulation in most parts of the human brain, including the frontal cortex, which is very metabolically active. They did not see it in most other types of human tissue, with the exception of liver tissue, which is exposed to high levels of potentially toxic molecules.

In human brain tissue, the researchers found that the amount of 3′ UTRs gradually increased with age, which fits their proposed model of gradual damage by oxidative stress. The researchers’ findings and model suggest that the production of these 3′ UTRs involves the destruction of normal mRNAs, reducing the amount of protein produced from the affected genes. This buildup of 3′ UTRs with ribosomes stuck to them can also block ribosomes from producing other proteins.

It remains to be seen exactly what effect this would have on those neurons, Burge says, but it is possible that this kind of cellular damage could combine with genetic and environmental factors to produce a general decline in cognitive ability or even neurodegenerative conditions such as Parkinson’s disease. In future studies, the researchers hope to further explore the causes and consequences of the accumulation of 3′ UTRs.

The research was funded by the National Institutes of Health and the JPB Foundation.

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Imo Governor’s aide visits Oziza FM Staff, Ogechi Iwu in hospital

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Imo Governor’s aide visits Oziza FM  Staff, Ogechi Iwu in hospital

The Chief Press Secretary and Media Adviser to Governor Hope Uzodimma of Imo State, Mr. Oguwike Nwachuku has visited Mr. Ogechi Iwu, a journalist with Osiza FM.

The media man is hospitalized at the Federal Medical Centre (FMC), Owerri over complications from diabetes that led to his right leg being amputated.

Mr. Nwachuku said the visit was to show solidarity on behalf of Governor Uzodimma to his professional colleague, assuring him of their prayers, particularly that of his principal, and the prayers of Mr. Iwu’s numerous friends and well wishers who are touched by his plight.

“I am here on behalf of my principal to associate with him in this time of health challenge and to encourage him not to see the sickness as a death sentence.”

Oge Iwu at fmc

L-R: Chief Akaraonye, Mr. Oguwike Nwachuku with Ogechi Iwu during the visit

Mr. Nwachuku urged Mr. Iwu to continue in the high spirit he saw him and trust God for his total recovery “because healing is a thing of mind and when a sick person is in high spirit the patient gets recovered quickly.”

The spokesman of the Governor promised to bring the plight of the journalist to the attention of his principal, and assured that the Governor will, in his usual manner of one with milk of human sympathy, show concern over Iwu’s plight.

Earlier, Mr. Iwu thanked the CPS/Media Adviser, the State Chairman of NUJ, Imo State, Chief Christopher Akaraonye and other journalists who were on the entourage, for coming to identify with him on his sick bed, and assured that God in his infinite mercy will quicken his recovery.

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Lessons from the Melee in Mali

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Lessons from the Melee in Mali

Just a couple of days ago, former president of Nigeria, Dr. Goodluck Jonathan, penned an assuring message on his successful mediation trips – leading the ECOWAS fact-finding and resolution team to Mali. The ink is still wet on that page when we however, woke up to the news of a coup in Mali. Whether it is Gambia, Guinea, Sudan, name them, Africa seems to be on the back foot when it comes to democratic gains. Is this a recurring narrative?

Mali should be another stark reminder to other African governments especially Nigeria that when an ineffective, out of touch and repressive government is about to come to an end, it always happens suddenly, not gradually. The tempo always builds up but from the inside, presenting a false calm exterior. Then like a landslide, it unexpectedly gives; the whole mountain comes crumbling as can be seen happening right now in Mali.

Seething resentments towards kleptocratic African governments always showcase themselves at the fall. African governments are miles behind, regarding the yearnings of their people and just like it happened in the ’60’s and ’70’s during our independence and subsequent coups and counter coups, Africa – led by its yearning youths connected globally through technology and the internet –is again bursting at the seams for legitimacy, effective leadership, direction and global integration.

The elitist old folks at the helm, unable to catch up and belligerent towards inclusive prosperity and development, are using their incumbent powers and minions to thwart the wishes of the people but for how long?

After the World War II, the world is again witnessing an unprecedented degree of untold suffering and death at peacetime, as a result of human disaster, but in Africa. It seems like the world rebuilt itself and moved on without us. How did we get here? How did we get left behind? First we started the blame game with the effect of slave trade, then the shackles of colonialism, yet Eastern countries have come out of both and are prosperous regardless.

China and the rest of the block are another testament that most of our arguments though with their merits, don’t hold water in their entirety. We are the makers of our destinies.
The origin of Mali’s problems, like every other Africa country, is government sectarianism – where a people in power skew electoral outcomes to favor themselves and their minions. This always led to widespread corruption, mismanagement of the economy, worsening security situations and exacerbating communal violence consequently.

For Mali, it started on June 5 when thousands of people went on street protest against the hijacked outcome of the parliamentary elections which took place on March 25. It turned deadly and 11 people were killed. As it is, regional security is threatened, at a time when COVID-19 and economic positions of these countries, indeed the whole world, are in tatters.

Whether it is Nigeria, Congo, Somalia, Kenya, name it, the problem is the same. When responsibility is alienated from governance, it breeds impunity which leads to corruption.

Like cancer, this corruption feeds and sustains itself by permeating all democratic institutions in its bid to replicate, validate and perpetuate itself, thus adulterating the electoral process which ultimately leads to political disintegration with the people seen as the enemy.

Our present crop of leaders has worked constitutions and political structures to such an extent that they sit home and predict electoral and judicial outcomes to the last digit.

This begs the question, is democracy working for Africa and if it doesn’t, what works? At times like this, we as Africans, should look inwards and take stock of how far we have come with the advent of constitutional democracy, where we have lost it and what should be done. The Chinese have found their formula, the Russians too. We too must find our path to an all inclusive, sustainable and prosperous future.

By Iboro Otu

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BAN ON THE CANAANLAND ADORATION (ALIAS E-DEY WORK) MINISTRY AND WITHDRAWAL OF FACULTY FROM REV. FR. MAGNUS EBERE SDV

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BAN ON THE CANAANLAND ADORATION (ALIAS E-DEY WORK) MINISTRY AND WITHDRAWAL OF FACULTY FROM REV. FR. MAGNUS EBERE SDV

To the Clergy, Religious and Laity of
Ahiara Diocese.

Dear people of God!

Compliments of the season: peace and joy!

As bishop, it is my duty to uphold authentic gospel values, sound Catholic traditions in worship and defend the teaching of the Catholic Church on faith and morals. It is also my responsibility to ensure that it is transmitted to the faithful in its purity and integrity in my area of pastoral jurisdiction.

Having established that there are serious abuses in the administration of the sacraments and sacramentals in the Canaanland Adoration Ministry a.k.a E-Dey Work as well as many other practices in the Adoration Ministry which are contrary to the teachings and traditions of the Catholic Church, I withdrew the Faculties of the Diocese of Ahiara from Fr. Magnus Ebere a priest of the Society of Divine Vocation (SDV), who started the Adoration Ministry without the required permission from an ecclesiastical authority. Consequently, he can no longer legitimately carry out priestly ministry such as preaching, celebration of the Mass, hearing confessions and administration of the other Sacraments and Sacramentals in the Diocese of Ahiara.

Nevertheless, Fr. Magnus has continued his private Ministry at his Centre in Onicha Ezinihitte in the Diocese of Ahiara in gross disobedience to me the bishop and also his Superior General in Rome who has also directed him to stop his Adoration Ministry. I hereby state that the Catholic Church has nothing to do with his Ministry. Accordingly, the faithful of Ahiara Catholic Diocese and other Dioceses are hereby warned to desist from attending the Ministry of a defiant priest, who has no respect for Church authority and Church law. Those who attend his private Ministry do so at their own spiritual peril.

God bless you!

Sincerely yours

Lucius Iwejuru Ugorji
Apostolic Administrator of Ahiara Diocese

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