Looking Beyond DNA to See Cancer with New Clarity

Mapping How Mutated Proteins Interact Reveals Previously Unseen Cancer Targets

SAN FRANCISCO, Sept. 30, 2021 (GLOBE NEWSWIRE) — Researchers at UC San Francisco and UC San Diego have mapped out how hundreds of mutations involved in two types of cancer affect the activity of proteins that are the ultimate actors behind the disease. The work points the way to identifying new precision treatments that may skirt side effects common with much current chemotherapy.

The effort, dubbed Cancer Cell Mapping Initiative (CCMI), is led by Nevan Krogan, PhD, director of UCSF’s Quantitative Biosciences Institute and Trey Ideker, PhD, professor at University of California San Diego School of Medicine and Moores Cancer Center, who are also co-senior authors on a set of three related studies that describe the map. The papers appear September 30 in Science.

“This is an entirely new way to do cancer research,” said Nevan Krogan. Krogan noted that targeted treatments based simply on DNA sequencing of tumors haven’t been as effective as hoped. “We realized we need another way to look at cancer that takes it a step beyond DNA.”

“The bottom line is that we’re elevating the conversation about cancer from individual genes to whole protein complexes,” Ideker said. “For years different groups have been discovering more and more gene mutations that are involved in cancers. But now we’re able to explain these mutations at the next level — by looking at how the different gene mutations in different patients actually have the same downstream effects on the same protein machines. This is the first map of cancer from the protein complex lens.”

Looking Beyond Gene Mutations to the Protein Disruptions They Cause

The team looked at proteins, which carry out the vast majority of functions in the body—and which take on a collection of forms that far outnumber our genes, providing a much more expansive view of the activity underlying cancer.

DNA contains the instructions for building proteins, which then interact with other proteins, almost always in large groups called complexes. These protein complexes regulate an activity or turn a function on or off. If the underlying DNA has a mutation, the resulting protein complexes will as well.

These gene mutations can affect how well the resulting protein complexes do their jobs. For example, a particular interaction between two proteins might be crucial to repairing damaged DNA. If the mutated version of one of those proteins is shaped differently than normal, it may not interact correctly with the other protein, and the DNA might not get repaired, leading to cancer.

Mapping Protein Mutations

There is a subset of genes that are commonly mutated in cancer, Krogan said, and each of these genes can be mutated in hundreds of different ways. In addition, the function of a particular protein may be different in different types of cells, so a mutation in a breast cancer cell might have different effects on protein complexes than that same mutation’s effect in a cell in the throat.

CCMI’s goal was to map the constellation of protein complexes formed by approximately 60 proteins commonly involved in either breast cancer and cancers of the head and neck, and to see what each looked like in healthy cells. Alongside that effort, they created maps of how protein complexes are affected by hundreds of different gene mutations in two cancerous cell lines.

Doing so presented a formidable computational challenge. But the CCMI collaboration allowed the team to use advanced and novel data analyses to reveal not only whether the mutation affected interactions between proteins, but to what extent.

“That kind of detail shows us how well an existing drug might work, or explains why it doesn’t,” Ideker said.

The most powerful aspect of these extensive protein interaction maps is that they can shed the same light on many other conditions, Krogan said. For example, the team is also at work on similar studies of protein interactions in psychiatric and neurodegenerative disorders, as well as infectious disease.

Collaboration is Key

Krogan and Ideker see the CCMI collaboration as the real source of strength behind the approach.

“We’re not only making connections between different genes and proteins but between different people and different disciplines,” Krogan said. “Those collaborations have built up an infrastructure that allows them to integrate an array of types of information and push the boundaries of what’s possible in applying data science to complex diseases.”

“We’re in the perfect position to take advantage of this revolution on every level. I couldn’t be more excited than I am right now. We can do such damage to cancer.”

Funding: This research was supported by grants from the National Cancer Institute (U54 CA209891, U54 CA209988, 5F30CA236404-02) and the National institutes of Health (F32 CA239336, R50 CA243885, S10 OD026929) as well as other public and philanthropic sources.

About QBI: The Quantitative Biosciences Institute (QBI) fosters collaborations across the biomedical and the physical sciences, seeking quantitative methods to address pressing problems in biology and biomedicine. Motivated by problems of human disease, QBI is committed to investigating fundamental biological mechanisms, because ultimately solutions to many diseases have been revealed by unexpected discoveries in the basic sciences.

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About UCSF: The University of California, San Francisco (UCSF) is exclusively focused on the health sciences and is dedicated to promoting health worldwide through advanced biomedical research, graduate-level education in the life sciences and health professions, and excellence in patient care. UCSF Health, which serves as UCSF’s primary academic medical center, includes top-ranked specialty hospitals and other clinical programs, and has affiliations throughout the Bay Area. UCSF School of Medicine also has a regional campus in Fresno. Learn more at ucsf.edu or see our Fact Sheet.

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Yemen’s Humanitarian Situation ‘Fragile’

The United Nations’ top humanitarian official in Yemen says that while widespread famine was averted in the country earlier this year with a surge in donor support, the situation is fragile and many essential programs remain at risk of further cuts.
“It’s not enough that we just got that one push, we need a continuous stream of support coming in over the next weeks into 2022,” David Gressly told VOA. “And until this crisis is solved politically, this situation on the ground will persist.”
Seven years of war between the Saudi-backed government of President Abdu Rabu Mansour Hadi and Iranian-supported Houthi rebels has pushed the Middle East’s poorest country to the brink.
Ongoing U.N. efforts to broker a nationwide cease-fire, reopen Sana’a airport, ease restrictions on the flow of fuel and other imports through Hodeidah port, and get direct talks going again have been unsuccessful.
More than 20 million Yemenis – in a population of around 30 million – need humanitarian assistance. The World Food Program says 16 million of them are “marching towards starvation,” due to a combination of conflict and a crippling economic crisis.
The situation of children is especially critical: the U.N. says one child dies every 10 minutes from preventable causes, including malnutrition and vaccine-preventable diseases.
The United Nations has appealed for nearly $4 billion to meet needs through December. Gressly said they have received about $2.6 billion in cash and pledges, casting uncertainty over the future of some assistance.
In March, there was a severe shortage of humanitarian funding for Yemen, which caused WFP to halve rations to people already in dire need. An injection of cash from major donors, including the United States, Germany, the United Arab Emirates and Saudi Arabia, helped restore them to full rations, but Gressly said without sustained funding, his “greatest fear” is this could happen again.
WFP’s executive director, David Beasley, warned last week that without more money, his agency may have to cut rations to 3.2 million people by October, and by December that number could grow to 5 million people.
While funding to food and nutrition programs is up, Gressly said other essential sectors including health, water and sanitation are 80-85% underfunded.
Affordability crisis
Gressly, who took up his post in March, says food and other items are available in most of Yemen’s urban markets, but with rampant inflation driving up prices, unemployment, exhausted savings, and civil servants not being paid, people simply do not have the money to buy things.
“It’s an affordability crisis,” he said.
“That’s why we need to find a complementary strategy, one that addresses not only humanitarian assistance directly to those in need, but also an economic one that takes a look at what can — even in the context of a conflict — what can be done to help revive at least, in part, the economy,” he added.
Pandemic
Yemen’s already overstretched health care system is also coping with a third wave of the coronavirus pandemic.
While confirmed cases have been low compared to other countries – just over 9,000 according to the Johns Hopkins University Coronavirus Resource Center – there has been a high proportion of deaths – more than 1,700.
Gressly said vaccinations have also been very slow to roll out and it will take years to vaccinate the entire country.
“The bigger issue is probably twofold: one is getting enough vaccine in the country — we’re not getting anywhere near enough for the population, maybe between 1 and 2 percent,” he said. “So that’s not going to make a major difference on its own.”
The vaccine alliance, COVAX, has allocated nearly 3 million doses for Yemen. Only 868,000 have been shipped so far.
“Secondly, there’s a lot of hesitation in the south and denial by authorities in the north on the reality of COVID and the necessity for vaccination,” he noted of the different factions in control of Yemen’s territory.
Earlier this week, Gressly met with USAID officials in Washington, where he pressed for continued humanitarian funding into next year and support for economic initiatives.
The United States pledged an additional $290 million to humanitarian efforts in Yemen at a donors conference on the sidelines of last week’s U.N. General Assembly. It has provided nearly $806 million in humanitarian assistance since last October.

Source: Voice of America

Breastmilk is the source for healthy nations

Ms Ien is Phunoi and 21 years old. She lives in Ngapoung village, Phongsaly district, with her husband’s family composed of five people including her two children. Their main activity is tea leaves collection and selling. “Because collecting the tea leaves takes a lot of time, I gave my first child rice and powdered milk when he was three months old. But the facilitator from the EU-funded SCALING project explained what to do for pregnant women and their babies. Now I’ve got a second child and he is nine months old. I will continue to breastfeed and give him some other food. I see he is growing very well and has good health”. The Sustainable Change Achieved through Linking Improved Nutrition and Governance (SCALING) project aims to improve food and nutrition security in 420 villages in 14 districts in Huaphan, Luang Namtha, Luang Prabang and Phongsaly provinces in Northern Laos with a special focus on adolescent girls, pregnant and lactating women, and children under 5 years old.
Did you know that breastfeeding within the first hour of birth (colostrum) protects new-born babies from infections and saves lives?
The means or the ends. In other words, infant formula manufacturers have a duty to elevate the sales of baby formula and convince new mothers of the benefits of their nutritional product compared to breastfeeding. Their for-profit agenda leads to adverse health impacts through misleading and faulty advertising activities.
The Government of the Lao PDR has reached an important milestone to control the damage by adopting the International Code of Marketing Breast-milk Substitutes in December 2019, locally named as “Decree on Food Products and Feeding Equipment for Infants and Toddlers”.
The decree aims to protect and promote breastfeeding by prohibiting unethical marketing activities aiming to promote breast milk substitutes. By applying international and national regulations, the detrimental effects on breastfeeding success caused by baby formula promotions could be limited, preventing the increase in misperceptions among mothers about the benefits of using infant formula.
However, despite the presence of multiple laws and international legislation safeguarding the importance of breastfeeding, poor enforcement of these regulations still exists. Therefore, the nationwide implementation and support of breastfeeding can significantly contribute to the improvement of maternal health and child health, and thus reduce the burden of morbidities and mortalities occurring within these two population groups.
The Lao PDR has shown significant improvements in the nutritional status of children under 5 over the past 10 years. Nevertheless, breastfeeding rates are still low; 45% of infants under six months are exclusively breastfed (Lao Statistics Bureau & Ministry of Health, 2016).
The European Union cooperation with the Lao PDR is very much attached to the Nutrition cause with special attention to the 1,000 days. By applying a multi-dimensional approach, EU-funded projects in the Lao PDR support the implementation of the National Nutrition Strategy (2016-2025) from national to village levels, and address nutrition through behaviour change, health systems strengthening, gender equality, water, sanitation and hygiene, nutrition-sensitive agriculture and coordination across different line ministries.
Budget support is central to European Union’s international cooperation; it involves direct financial transfers to the national treasury engaging in sustainable development reforms. In the Lao PDR, the EU cooperation supports directly the State budget to accomplish specific targets in the nutrition agenda up to 2022, including the national decree on ‘infant and young child product control’, among others (BMS decree).
The EU cooperation continues to support the nutrition community in dissemination and monitoring of the BMS Decree across the country at different levels to protect breastfeeding and promote good nutrition and wellbeing for all Lao people.

Source: Lao News Agency

WHO: Most of Africa Has Missed 10 Percent COVID-19 Vaccination Goal

Fifteen African countries have succeeded in fully vaccinating at least 10 percent of their populations against COVID-19 by September 30, a goal set by the World Health Organization in May. However, that leaves two-thirds of the continent’s 54 nations extremely vulnerable to the deadly disease.
Several countries have performed extremely well. Seychelles and Mauritius have fully vaccinated more than 60 percent of their populations and Morocco has inoculated 48 percent against the coronavirus.
Richard Mihigo is coordinator of the Vaccine-preventable Diseases Department in the WHO’s regional office for Africa. He said those countries were able to achieve and even excede the 10 percent target because they had a steady vaccine supply available.
He said most had the money to strike bilateral deals to procure vaccine in addition to the supplies delivered through the COVAX facility.
“Unfortunately, 70 percent of African countries have missed this important milestone to protect their most vulnerable, with half of the 52 countries with COVID-19 vaccination programs in Africa having inoculated less than two percent of their populations,” said Mihigo.
That compares to an inoculation rate of 50 percent or higher in wealthier countries.
The WHO reports monthly vaccine deliveries to Africa have increased 10-fold since June. However, it notes more than double that amount is needed to reach the 40 percent immunization target of Africa’s 1.3 billion people by the end of the year.
Mihigo said COVAX is identifying countries that do not have the means to procure vaccines and put them in the front of the line to get enough doses to cover their most at-risk populations. However, he said pledges of doses by wealthier countries need to materialize soon.
“Starting next week, we are sending multi-disciplinary teams of international experts to countries that are struggling to scale up their operations so that we can drill down and identify the bottlenecks so that the local authorities and their partners can remedy them as they continue to rollout the vaccines,” said Mihigo.
On a more positive note, the World Health Organization says COVID-19 infections in Africa dropped by 35 percent to just over 74,000 last week, with more than 1,700 deaths reported in 34 countries.
Despite the declining numbers, the WHO warns people must remain vigilant and continue to adhere to proven public health measures to save lives. Those include the wearing of masks, regular hand washing, and physical distancing.

Source: Voice of America

Laos logs 358 new Covid-19 cases

Some 358 new cases of Covid-19 have been recorded nationwide over the past 24 hours, bringing the total to 23,846 including 5,441 active cases and 19 deaths, according to Director General of the Department of Communicable Disease Control, Ministry of Health, Dr Rattanaxay Phetsouvanh.
Some 296 patients were discharged from hospital today.
“Of the new confirmed cases, 337 were classified as local infections and 21 as imported cases,” Dr Rattanaxay told a press conference today. “They were detected among 6,337 people tested for Covid-19 yesterday.”
The local infections were detected in Vientiane 128, Luang Prabang 71, Savannakhet 35, Vientiane (Province) 24, Champassak 20, Xaysomboun 16, Borikhamxay 15, Bokeo 14, Khammuan 11 and Attapeu 3.
The imported cases included 15 in Saravan, three each in Savannakhet and Borikhamxay.

Source: Lao News Agency

SafeAI Welcomes Automotive Veteran Roger Nielsen to Board of Directors

Former Daimler Trucks CEO and autonomy pioneer brings nearly 40 years of experience in the commercial vehicle industry to SafeAI

MILPITAS, Calif., Sept. 30, 2021 (GLOBE NEWSWIRE) — SafeAI, a global leader in autonomous heavy equipment, today announced that Roger Nielsen has joined its Board of Directors. Nielsen, the former President and CEO of Daimler Trucks North America and member of the Board of Management of Daimler Truck AG, brings nearly forty years of experience in the commercial vehicle industry to SafeAI’s growing company.

Nielsen spent 35 years at Daimler, the world’s leading commercial vehicle manufacturer, including four years as President and CEO of Daimler Trucks North America. During his tenure, he was involved in 40 acquisitions, mergers and divestitures across the automotive industry, including companies developing buses, telematics, electric vehicles and autonomous driving systems.

During Nielsen’s time at Daimler, electric and autonomous vehicles began rapidly gaining steam. As CEO, he spearheaded significant advancements in Daimler’s autonomous technology to meet rising demand across the trucking industry, including through the acquisition of vehicle automation company Torc Robotics. Under his leadership, Daimler’s Advanced Driver Assistance Systems (ADAS) won Best Transportation Technology at the 2019 Consumer Electronics Show (CES) for its Level 2 automated driving system. The company went on to become the first to deliver SAE level 2 (partially automated driving features) into series production and today, continues to forge a safer, more efficient standard for logistics.

“Roger was at the helm of one of the world’s top automotive companies as the tides began turning toward autonomous vehicles. He quickly recognized the opportunity and dove in headfirst to unlock the benefits of autonomy for the trucking industry,” said Bibhrajit Halder, founder and CEO of SafeAI. “His experience as a trailblazer in autonomous development and deployment is an invaluable asset to our board as we reimagine heavy industry through increased adoption of self-driving heavy equipment.”

“At Daimler, I had the opportunity to lead a team rethinking a more traditional industry, logistics, through autonomous technology. As a member of SafeAI’s board, I’m fortunate to have that opportunity again,” said Nielsen. “I firmly believe autonomy is the future, and SafeAI will be the company to deliver this future to heavy industry. I’m honored to be part of this team as they chart a new path forward for industries like construction and mining, powered by autonomy.”

Nielsen received his BS in Industrial Engineering from Oregon State University. He is also on the board of NODAR, a company that develops 3D vision for autonomous vehicles.

For more news from SafeAI, visit www.safeai.ai.

About SafeAI
SafeAI is a global autonomous heavy equipment leader focused on advancing modern industry. SafeAI retrofits heavy equipment for autonomous applications in mining and construction to serve a massive ecosystem of industry players with complex needs. By building a software platform with the most advanced, industry-specific AI, SafeAI enables equipment owners to transform existing machines, including skid steers, F-150s and articulated dump trucks, into self-operating robotic assets. SafeAI is based in Milpitas, CA.

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