Time doesn’t heal all wounds: how DNA damage as we age causes cancer


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Our risk of cancer is determined by a complex mix of genes, environment and lifestyle factors.
Claudia van Zyl

Ian Majewski, Walter and Eliza Hall Institute and Edward Chew, Walter and Eliza Hall Institute

As we age, our bodies inevitably deteriorate. Some changes, like grey hair and wrinkles, are easily visible. Others, like high blood pressure, often go unnoticed, but can be deadly.

Just as our body shows signs of ageing, so does our genome. Damage comes from chemical reactions that alter our DNA, and from errors introduced when it is copied. Our cells protect against these ravages, but these mechanisms are not foolproof and cells gradually accumulate DNA damage over a lifetime.

As a consequence of this damage, your genome is not the same in every cell; you are a patchwork of cells with subtle differences in their DNA. When a cell divides it will pass on these changes, and as they accumulate there is more and more likelihood that there will be consequences.

If these changes – we call them mutations – chip away at the systems that govern cell proliferation and survival, this can lead to cancer.

Our latest research, published today in the journal Blood, provides new clues about how our cells protect their genome and guard against cancer.

Guarding the genome

Nearly 10% of cancers have a familial component. Genes like BRCA1 and TP53 are among the best known cancer susceptibility genes, and both are involved in coordinating the cell’s response to DNA damage.

BRCA1 helps to repair a specific type of DNA damage, in which both strands of DNA are broken. Inheriting a defective BRCA1 gene elevates the lifetime risk of both breast and ovarian cancer.




Read more:
Angelina Jolie has had a double mastectomy, so what is BRCA1?


When DNA repair mechanisms break down, cells can accumulate staggering numbers of mutations, and cancer becomes almost inevitable.

Beyond genetics, a complex mix of environmental and lifestyle factors modify cancer risk.

When we read the genome of a cancer it is possible to attribute mutations to certain types of stress. UV radiation, for example, will fuse certain DNA bases. The UV damage signature is writ large in melanoma, a cancer linked to sun exposure.

Lung cancers from smokers and non-smokers have different mutation patterns because of the action of chemicals in cigarette smoke that attack the DNA.

We can also use this approach to diagnose defective DNA repair, as each defect triggers a characteristic pattern of mutations. In this way, mutation signatures can help us understand why a cancer has developed.

A ticking genetic clock

Smoking, UV radiation and X-rays all damage your DNA, but damage also comes from reactive molecules present within the cell. These molecules are fundamental to the chemistry of life – take water, for example.




Read more:
Chemistry Nobel DNA research lays foundation for new ways to fight cancer


Water is a very reactive molecule and can do damage to our DNA. One of the most common mutations, either in cancer or in normal cells, results from water molecules reacting with methylated DNA.

DNA methylation is a small chemical modification that acts as a signpost on top of our genetic code. It helps to control which genes are switched on or off. This fine-tuning is essential for normal development, but methylation also makes DNA more susceptible to damage. Most of these events are quickly repaired, but the damage is unrelenting and some sneak through.

Cells accumulate mutations when DNA repair mechanisms break down.
K.D.P/Shutterstock

Methylation damage is the most prominent feature of an ageing genome. It’s so pervasive and reliable it has been proposed as a molecular clock that marks ageing. But our new research shows this process occurs more rapidly in some people.

We found and studied three people whose pathways to repair methylation damage had broken down. They all lacked a DNA repair protein called MBD4, which led to a marked accumulation of methylation damage – as though their cells were ageing prematurely.

All three developed an aggressive form of leukaemia in their early 30s, a cancer which usually wouldn’t be seen until the person is in their 60s or 70s.

Methylation damage plays a role in most cancers, but in these cases it was the primary driver of the disease.

While complete inactivation of MDB4 – as occurred in the three participants – is extremely rare, our findings raise the question of how more subtle differences in DNA repair shape cancer risk, particularly in the context of ageing.

Turning back the clock

Ageing contributes to cancer risk in myriad ways. While we’ve focused here on the buildup of DNA damage, our immune system also plays an important role and tends to fade as we get older.

Lifestyle factors – such as obesity, stress and diet – also provide a cumulative risk that builds over a lifetime.




Read more:
What does DNA sound like? Using music to unlock the secrets of genetic code


Understanding the interplay between these factors is key to finding strategies that will effectively diffuse the health consequences associated with ageing.

Our research is helping to tease apart the contribution of DNA damage in different disease processes. Our findings suggest that some people accumulate more DNA damage than others – their clocks are ticking a little faster – and measuring these differences may help to spot people at risk of developing cancer, or help match them with more effective treatments.The Conversation

Ian Majewski, Laboratory Head & Victorian Cancer Agency Fellow, Cancer & Haematology Division, Walter and Eliza Hall Institute and Edward Chew, PhD candidate, Cancer and Haematology Division, Walter and Eliza Hall Institute

This article is republished from The Conversation under a Creative Commons license. Read the original article.

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Lombok earthquakes: different building designs could lessen future damage



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A 6.9 magnitude earthquake led to the collapse of thousands of houses in the northern parts of the Indonesian island of Lombok.
Adi Weda / AAP, CC BY-SA

Graeme MacRae, Massey University

The series of earthquakes in North Lombok and others further east goes on. But hopefully the worst is over and the intensity will recede from now.

Hundreds of people have been killed and a lot more injured, many of them seriously. Nearly all this human suffering was caused by collapsing buildings. The subsequent homelessness will go on for many months for hundreds of thousands of people.

But a lot of this suffering need not have happened.




Read more:
After devastating earthquakes, Indonesia must embrace radical change


Changing building standards

The strongest quake on August 5, 6.9 in magnitude and at a relatively shallow depth, is large by any standard. But, as photos and video footage show, not all buildings collapsed. Among the landscape of devastation are many buildings that appear to have suffered little if any damage.

According to one estimate, 70% of buildings suffered serious damage, which means 30% did not. In many parts of the world, such as Japan, New Zealand and Chile, buildings are designed to withstand earthquakes of this scale and many of them do, repeatedly.




Read more:
Two types of tectonic plate activity create earthquake and tsunami risk on Lombok


About 70% of buildings suffered serious damage in the Lombok earthquakes, but some stood up to the shaking.
AAP, CC BY

Traditional buildings in most of Indonesia, including northern Lombok, were built of timber framing with thatched roofs. In an earthquake they flex and sway but rarely collapse. If they do, it is likely to happen slowly and incompletely and any falling roofing is relatively light and soft.

But over recent decades, building materials and methods have changed. Timber and thatch have become scarce and expensive and popular tastes have shifted towards houses that look, at least superficially, like those of the global modern middle class – little villas with plastered walls, glass windows and tiled roofs.

But underneath the (often picturesque) facades, the construction is of brick or concrete blocks, held together only with weak mortar and supported by little or no framing. The better ones may have some concrete framing, but the quality of the concrete is usually poor and the steel reinforcing, especially at joints, is minimal. These facades do not reliably support infill materials and they are heavy when they fall.

Roof tiles are only loosely secured and ceilings below them are too light to catch them. If one had to design a system of construction for easy collapse and maximum injuries, this would be the perfect model.

Learning from past earthquakes

In Yogyakarta, in central Java, in May 2006, at least 150,000 houses of exactly this kind collapsed in less than a minute of shaking caused by a lesser earthquake than the largest in Lombok. Nearly 6,000 people were killed and thousands more injured. Farm animals housed in traditional buildings mostly survived.

A massive international humanitarian aid response and significant government programmes followed and within a year Yogyakarta was largely rebuilt – an astonishing result in the circumstances. Both government and international agencies went to considerable lengths to design safer methods, educate people about them and offer support, materials and incentives to “build back better”.

An expert report ten years later (unfortunately not yet published) concluded that:

The overall poor quality of construction however has almost certainly placed more people at increased risk of larger, heavier building elements collapsing upon them.

Northern Lombok has not had this kind of experience in recent decades and, because it is a relatively poor part of Indonesia, until 20 years ago, many people outside the urban areas lived in traditional houses. However, over recent years, partly as a result of tourism revenues, many houses have been built or extended in the new style and construction.

Here too, construction standards tend to be low, and even lower for poorer households. The video evidence shows exactly the kind of failures as in Yogyakarta 12 years ago, because of exactly the same basic weaknesses of design. The next earthquake, wherever it may be in Indonesia, will almost certainly have the same effects.

Houses in Lombok collapsed because of design failures similar to those in Yogyakarta 12 years ago.
AAP, CC BY

No easy solutions

A recent article makes similar points and blames inadequate enforcement of building codes and lack of government commitment. Unfortunately the reality is not so simple.

The Yogyakarta experience shows that even with a massive campaign by government and international agencies, and with the fear of earthquakes still fresh in people’s minds, the rebuilding was little better than what it replaced. Building codes do exist in Indonesia, but they are rarely followed, easily evaded, and rarely enforced, least of all at the level of owner-built local housing.

Even if there were a serious effort to implement codes, it would be undermined by well-known levels of bureaucratic inefficiency and corruption, as well as public resistance and evasion. It would also have unintended consequences, including making decent housing even less affordable, especially for poorer people.

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The Conversation

There will be no easy solutions, but national education in basic structural design principles, subsidised design, production and distribution of cheap and simple hardware for mitigating the most common failures of design and financial incentives for appropriate construction might be worthwhile places to start.

Graeme MacRae, Senior Lecturer in Social Anthropology, Massey University

This article was originally published on The Conversation. Read the original article.

New Zealand Escapes Major Damage from Massive Earthquake


The links below are to articles reporting on a major earthquake that hit New Zealand today, measuring 6.9 and located between the two islands in Cook Strait.

For more visit:
http://www.stuff.co.nz/national/8945358/Big-quake-shakes-central-New-Zealand
New Zealand hit by quake of magnitude 6.9, minor damage | Reuters
http://www.theaustralian.com.au/news/world/strong-69-magnitude-earthquake-hits-wellington-new-zealand/story-e6frg6so-1226682714587
http://worldnews.nbcnews.com/_news/2013/07/21/19590327-65-earthquake-strikes-near-wellington-new-zealand

A large number of earthquakes have hit the New Zealand area in recent days.

For more visit:
http://www.stuff.co.nz/dominion-post/news/8945362/Quakes-shake-central-New-Zealand


Australia: South Australia – Earthquake


A reasonably strong earthquake (5.6) has just struck South Australia’s outback – basically in the desert. From what I understand there is a small town located 10 minutes from the suspected epicentre of the earthquake. There is potential for significant damage within that sort of radius of the earthquake, but thankfully it has struck a fairly remote region. It is of a similar magnitude to the earthquake that struck Newcastle in 1989.

For more visit:
http://earthquake-report.com/2012/03/23/strong-earthquake-in-australia/

USA: Tornado Season Update


The following article includes a number of ‘very good’ photos of damage caused by the tornadoes in the USA. These photos show very graphically the amount of damage and heartache caused by these destructive storms.

For more visit:
http://www.boston.com/bigpicture/2012/03/tornadoes_rip_through_the_midw.html

 

New Zealand: Christchuch Reeling Again


A major aftershock/earthquake has struck Christchurch, causing more damage to the devastated city.

More at:
http://www.nzherald.co.nz/nz/news/article.cfm?c_id=1&objectid=10775043

 

Persecution News: What was Missed While on My Break – Part 1


The following are articles from Compass Direct News from the period I was on my break:

 

Detained Pakistani Christian Released – But Two Others Held


Christian falsely accused of ‘blasphemy’ taken into custody, released – and detained again.

LAHORE, Pakistan, April 18 (CDN) — A Christian illegally detained in Faisalabad on false blasphemy charges was freed last night, while two other Christians in Gujranwala arrested on similar charges on Friday (April 15) were also released – until pressure from irate mullahs led police to detain them anew, sources said.

Masih and his family have relocated to a safe area, but just 10 days after he was falsely accused of desecrating the Quran in Faisalabad district of Punjab Province on April 5, in Gujranwala Mushtaq Gill and his son Farrukh Mushtaq were taken into “protective custody” on charges that the younger man had desecrated Islam’s holy book and blasphemed the religion’s prophet, Muhammad. A police official told Compass the charges were false.

Gill, an administrative employee of the Christian Technical Training Centre (CTTC) in Gujranwala in his late 60s, was resting when a Muslim mob gathered outside his home in Aziz Colony, Jinnah Road, Gujranwala, and began shouting slogans against the family. They accused his son, a business graduate working in the National Bank of Pakistan as a welfare officer and father of a little girl, of desecrating the Quran and blaspheming Muhammad.

The purported evidence against Farrukh were some burnt pages of the Quran and a handwritten note, allegedly in Farrukh’s handwriting, claiming that he had desecrated Islam’s holy book and used derogatory language against Muhammad. A Muslim youth allegedly found the pages and note outside the Gills’ residence.

Inspector Muhammad Nadeem Maalik, station house officer of the Jinnah Road police station, admitted that the charges against the accused were baseless.

“The initial investigation of the incident shows Mr. Gill and his son Farrukh are innocent,” he told Compass.

The two were kept at a safe-house, instead of the police station, out of fear that Islamist extremists might attack them; their subsequent release led to Islamic protests that compelled police to detain them anew today, sources said.

Despite police admitting that the two Christians were not guilty, a First Information Report (No. 171/2011) was registered against them under Sections 295-B and C in Jinnah Road Police Station early on Saturday (April 16).

“Yes, we have registered an FIR of the incident, yet we have sealed it until the completion of the investigation,” Inspector Maalik said, adding that the police had yet to formally arrest Gill and his son. “We registered the FIR for their own safety, otherwise the mob would have become extremely violent and things could have gone out of control.”

The police official said that after the Muslim youth made the accusation, he gathered area Muslims together.

“It seems to be a well thought-out scheme, because the perpetrators chose the time of the Friday prayers for carrying out their plan,” Maalik said. “They were sure that this news would spread quickly, and within no time people would come out of the mosques and react to the situation.”

He added that police were now inquiring of the Gills why they might suspect anyone of wanting to harm them.

“We are also looking for any signs of jealousy or old enmity,” Maalik said.

Soon after the Muslim youth found the alleged pages, announcements blared from the area’s mosques informing Muslims about the incident and asking them to gather at the “crime scene,” sources said.

There are about 300 Christian families residing in Aziz Colony, and news of the alleged desecration spread like jungle fire. Announcements from mosques sparked fear in the already shaken Christian families, and they started packing their things to leave the area, fearing the kind of carnage that ravaged Gojra on Aug. 1, 2009, killing at least seven Christians.

“It’s true…the news of the accusations against Gill and his son and the announcements being made from the mosque calling on Muslims to avenge the desecration sent shivers down our spines,” said Pastor Philip Dutt, who has known the Gill family for several years and lives in the same neighborhood. “The charges are completely baseless. I’m sure no person in his right frame of mind would even think of committing such a vile act. Someone has clearly conspired against the Gill family.”

He added that most of the area’s Christians had left their homes overnight, fearing an attack by Muslims.

Dutt said that a large police contingent arrived in time and took Gill and his son into custody after assuring the enraged mob that a case under the blasphemy laws would be registered against the two men. Police remained stationed in the area to provide protection to area Christians, but the atmosphere was tense.

According to some reports, a group of angry Muslims wanted to torch Gill’s house, but timely police intervention thwarted their plan.

At the same time, a group of Muslim extremists stormed into the house of Anwar Masih, a Christian factory owner in Aziz Colony, and started beating him and his son, sources said. The family managed to save themselves by calling the police and now they too are in “protective custody.”

The Rev. Arif Siraj, moderator of the Presbyterian Church of Pakistan, which also oversees the functioning of the Christian Technical Training Centre in Gujranwala, said the accusations against Farrukh were yet another example of how the country’s blasphemy laws are misused against innocent people.

“We have been engaged with the police and local Muslim leaders throughout the day to resolve this issue amicably,” Siraj said. “An eight-member committee comprising six Muslims and two Christian pastors has been formed to probe the incident, and they will make a report on Friday.”

The names of the Christians of the eight-member committee are Pastor Sharif Alam of Presbyterian Church Ghakarmandi and the Rev. Joseph Julius.

A large number of Muslims, including members of religious parties and banned outfits, came out to the roads of Gujranwala on Saturday (April 16) to protest the alleged desecration of the Quran and pressure police to take action against Gill and his son. The protestors reportedly gelled into one large demonstration on Church Road and headed towards the CTTC. Siraj said that some participants threw stones at a church on the road, but that Muslim elders immediately halted the stone-throwing.

“The district administration and Muslim leaders have now assured us that no one will target Christian churches and institutions,” he said, adding that both communities were now waiting for the committee’s report.

Sohail Johnson of Sharing Life Ministry expressed concern over the accusations.

“This case is a classic example of how Christians and Muslims continue to be charged with blasphemy on false accusations,” he said. “Isn’t it ridiculous that the accuser is claiming that Farrukh has confessed to burning the Quran in his note and thrown the burnt pages in front of his house – what sane person would even think of saying anything against prophet Muhammad in a country where passions run so deep?”

Arif Masih, the falsely accused Christian released last night, has reportedly been relocated along with this family to a safe location.

The original blasphemy law, introduced in British India in 1860, imposed a prison term of up to two years for any damage to a place of worship or sacred object carried out “with the intention of thereby insulting the religion of any class of persons or with the knowledge that any class of persons is likely to consider such destruction, damage or defilement as an insult to their religion…”

The current provision in the Pakistan Penal Code, as amended in 1986, introduces both the death penalty for insulting Muhammad and drops the concept of intent. According to Section 295-C of the Penal Code, “Whoever by words, either spoken or written, or by visible representation, or by any imputation, innuendo, or insinuation, directly or indirectly defiles the sacred name of the Holy Prophet Muhammad (peace be upon him) shall be punished with death, or imprisonment for life and shall also
be liable to fine.”

The laws have drawn condemnation across the world, and two senior government officials – Punjab Gov. Salman Taseer, a liberal Muslim, and Federal Minister for Minorities Shahbaz Bhatti, a Christian, have been assassinated this year for demanding a review of the legislation.

Report from Compass Direct News
http://www.compassdirect.org