Study shows that smoking ‘stops’ cancer-fighting proteins, causing cancer and making it harder to treat

In-depth analysis links harmful DNA mutations to tobacco smoking and other causes of cancer

Peer-Reviewed Publication

ONTARIO INSTITUTE FOR CANCER RESEARCH

November 3, TORONTO — Scientists at the Ontario Institute for Cancer Research (OICR) have uncovered one way tobacco smoking causes cancer and makes it harder to treat by undermining the body’s anti-cancer safeguards.

Their new study, published today in Science Advances, links tobacco smoking to harmful changes in DNA called ‘stop-gain mutations’ that tell the body to stop making certain proteins before they are fully formed.

They found that these stop-gain mutations were especially prevalent in genes known as ‘tumour-suppressors’, which make proteins that would normally prevent abnormal cells from growing.

“Our study showed that smoking is associated with changes to DNA that disrupt the formation of tumour suppressors,” says Nina Adler, a University of Toronto PhD student who led the study during her postgraduate research in Dr. Jüri Reimand’s lab at OICR. “Without them, abnormal cells are allowed to keep growing unchecked by the cell’s defenses and cancer can develop more easily.”

Adler, Reimand and colleagues used powerful computational tools to analyze DNA from more than 12,000 tumour samples across 18 different types of cancer. Their analysis showed a strong link between stop-gain mutations in lung cancer and the telltale ‘footprint’ that smoking leaves in DNA.

The researchers then looked at whether how much someone smoked had an impact. Sure enough, their analysis showed that more smoking led to more of these harmful mutations, which can ultimately make cancer more complex and harder to treat.

“Tobacco does a lot of damage to our DNA, and that can have a major impact on the function of our cells,” says Reimand, an OICR Investigator and Associate Professor at the University of Toronto. “Our study highlights how tobacco smoking actually deactivates critical proteins, which are the building blocks of our cells, and the impact that can have on our long-term health.”

The study also identified other factors and processes responsible for creating large numbers of stop-gain mutations, which are also called ‘nonsense’ mutations. Some, like a group of enzymes called APOBEC that is strongly linked to stop-gain mutations in breast cancer and other cancer types, occur naturally in the body. Other factors like unhealthy diet and alcohol consumption are also likely to have similar damaging effects on DNA, but Reimand says more information is needed to fully understand how that works.

As for smoking, Adler says the findings from this study are an important piece of the puzzle behind a leading cause cancer in the world.

“Everyone knows that smoking can cause cancer, but being able to explain one of the ways this works at a molecular level is an important step in understanding how our lifestyle affects our risk of cancer,” Adler says.

OICR President and Scientific Director Dr. Laszlo Radvanyi says these new insights should reinforce that tobacco smoking is one of the biggest threats to our health.

“This is further proof of the immense damage smoking has on our bodies, and further evidence that stopping smoking is always the right choice,” Radvanyi says.

OICR is a collaborative, not-for-profit research institute funded by the Government of Ontario. We conduct and enable high-impact translational cancer research to accelerate the development of discoveries for patients around the world while maximizing the economic benefit of this research for the people of Ontario. For more information visit http://www.oicr.on.ca.

The views expressed are those of OICR and do not necessarily reflect the views of the Province of Ontario.

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JOURNAL

Science Advances

DOI

10.1126/sciadv.adh3083 

SUBJECT OF RESEARCH

Not applicable

ARTICLE TITLE

Mutational processes of tobacco smoking and APOBEC activity generate protein-truncating mutations in cancer genomes

ARTICLE PUBLICATION DATE

3-Nov-2023

 

How salt from the Caribbean affects our climate

Study explores link between salinity, ocean currents and climate

Peer-Reviewed Publication

HELMHOLTZ CENTRE FOR OCEAN RESEARCH KIEL (GEOMAR)

Joint press release by MARUM - Center for Marine Environmental Sciences at the University of Bremen and GEOMAR Helmholtz Centre for Ocean Research Kiel

The distribution of salt by ocean currents plays a crucial role in regulating the global climate. This is what researchers from Dalhousie University in Canada, GEOMAR Helmholtz Centre for Ocean Research Kiel, Alfred Wegener Institute, Helmholtz Centre for Polar and Marine Research (AWI) and MARUM – Center for Marine Environmental Sciences at the University of Bremen have found in a new study. They studied natural climate anomalies, including the so-called Little Ice Age. This cold period from the 15th to the mid-19th century led to poor harvests, famine and disease in Europe. Although the Little Ice Age is one of the most studied periods in recent history, the underlying climatic mechanisms remain controversial.

“Looking at recent, natural climate anomalies helps to understand the processes and mechanisms that human-induced global warming may trigger,” says Dr Anastasia Zhuravleva, lead author of the study. She was a PhD student at GEOMAR and received the Annette Barthelt Prize for her dissertation in 2019. She then worked as a post-doctoral researcher at GEOMAR and Dalhousie University, where the study was completed.

“Researchers often consider an increase in sea ice extent and desalination in the subpolar North Atlantic as possible triggers for past cold periods, but processes in the tropical Atlantic appear to be equally important," says Dr Zhuravleva. “In fact, in contrast to the northern and mid-latitudes, there is little information on these recent climate events from the subtropical-tropical Atlantic and their impact on regions in the Northern Hemisphere,” adds Dr Henning Bauch, paleoclimatologist at AWI and GEOMAR, co-initiator and co-author of the study. “This is where our research comes in.”

So, what happened in the tropical Atlantic during historical climate anomalies, and how might potential changes there have affected ocean circulation and climate much further north? To answer these questions, the team worked on a sediment profile from the southern Caribbean and reconstructed the salinity and temperature of the surface water over the last 1700 years. Among other things, the researchers determined the isotopic and elemental composition of the calcareous shells of plankton.

The results show a cooling of about 1°C during the Little Ice Age. “It is a significant temperature change for this region,” says Dr Mahyar Mohtadi, co-author of the study and head of the Low Latitude Climate Variability group at MARUM. “Particularly noteworthy is the occurrence of another pronounced cooling for the 8th-9th centuries. Colder temperatures in the otherwise warm tropical ocean led to lower regional rainfall, which coincided with severe droughts in the Yucatan Peninsula and the decline of the Classic Maya culture.”

In addition, the researchers found that the cold climate anomalies in the subpolar North Atlantic and Europe were accompanied by weaker ocean circulation and increased salinity in the Caribbean. “Advection, or the movement of tropical salt to high northern latitudes, is essential for maintaining high surface densities in the subpolar North Atlantic. This is a prerequisite for the overall stability of the large-scale ocean circulation, including the transfer of warm Gulf Stream water, which is responsible for our mild temperatures in Europe,” says Dr Bauch.

The data on the historical past thus allow a reconstruction of the connection across the North Atlantic. Initial cooling can be caused by volcanic eruptions, low solar activity and feedbacks between sea ice and the ocean in the north. The new study provides evidence that a decrease in salt movement to high northern latitudes will amplify and prolong these climate events. Conversely, the slow movement of positive salinity anomalies from the tropics will eventually increase the density at the surface of the subpolar North Atlantic. This may favour the northward transport of heat by ocean currents, resulting in milder temperatures over Europe and North America.

“Such a salinity feedback is known from models and has been assumed for the Little Ice Age. However, in the absence of tropical ocean data, these assumptions have been based on less direct precipitation records,” says Dr Zhuravleva.

There is evidence that the Gulf Stream is weakening and that human-induced warming is a likely cause. What is certain is that the consequences of this change will be global. The extent to which the different climate mechanisms interact has been an open question. This study now confirms that the south-north transport of salt is a key factor in the processes involved.

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JOURNAL

Science Advances

DOI

10.1126/sciadv.adg2639 

ARTICLE TITLE

Caribbean salinity anomalies contributed to variable North Atlantic circulation and climate during the Common Era

ARTICLE PUBLICATION DATE

3-Nov-2023

 

Seeing the unseen: How butterflies can help scientists detect cancer

Peer-Reviewed Publication

UNIVERSITY OF ILLINOIS GRAINGER COLLEGE OF ENGINEERING

 

IMAGE: 

ARTISTIC DEPICTION OF A BUTTERFLY ABOVE THE BIOINSPIRED IMAGING SENSOR

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CREDIT: THE GRAINGER COLLEGE OF ENGINEERING AT UNIVERSITY OF ILLINOIS URBANA-CHAMPAIGN

There are many creatures on our planet with more advanced senses than humans. Turtles can sense Earth’s magnetic field. Mantis shrimp can detect polarized light. Elephants can hear much lower frequencies than humans can. Butterflies can perceive a broader range of colors, including ultraviolet (UV) light.

Inspired by the enhanced visual system of the Papilio xuthus butterfly, a team of researchers have developed an imaging sensor capable of “seeing” into the UV range inaccessible to human eyes. The design of the sensor uses stacked photodiodes and perovskite nanocrystals (PNCs) capable of imaging different wavelengths in the UV range. Using the spectral signatures of biomedical markers, such as amino acids, this new imaging technology is even capable of differentiating between cancer cells and normal cells with 99% confidence.

This new research, led by University of Illinois Urbana-Champaign electrical and computer engineering professor Viktor Gruev and bioengineering professor Shuming Nie, was recently published in the journal Science Advances.

Small Variations

“We've taken inspiration from the visual system of butterflies, who are able to perceive multiple regions in the UV spectrum, and designed a camera that replicates that functionality,” Gruev says. “We did this by using novel perovskite nanocrystals, combined with silicon imaging technology, and this new camera technology can detect multiple UV regions.”

UV light is electromagnetic radiation with wavelengths shorter than that of visible light (but longer than x-rays). We are most familiar with UV radiation from the sun and the dangers it poses to human health. UV light is categorized into three different regions—UVA, UVB and UVC— based on different wavelength ranges. Because humans cannot see UV light, it is challenging to capture UV information, especially discerning the small differences between each region.

Butterflies, however, can see these small variations in the UV spectrum, like humans can see shades of blue and green. Gruev notes, “It is intriguing to me how they are able to see those small variations. UV light is incredibly difficult to capture, it just gets absorbed by everything, and butterflies have managed to do it extremely well.”

The Imitation Game

Humans have trichromatic vision with three photoreceptors, where every color perceived can be made from a combination of red, green and blue. Butterflies, however, have compound eyes, with six (or more) photoreceptor classes with distinct spectral sensitivities. In particular, the Papilio xuthus, a yellow, Asian swallowtail butterfly, has not only blue, green and red, but also violet, ultraviolet and broadband receptors. Further, butterflies have fluorescent pigments that allow them to convert UV light into visible light which can then be easily sensed by their photoreceptors. This allows them to perceive a broader range of colors and details in their environment.

Beyond the increased number of photoreceptors, butterflies also exhibit a unique tiered structure in their photoreceptors. To replicate the UV sensing mechanism of the Papilio xuthus butterfly, the UIUC team has emulated the process by combining a thin layer of PNCs with a tiered array of silicon photodiodes.

PNCs are a class of semiconductor nanocrystals that display unique properties similar to that of quantum dots—changing the size and composition of the particle changes the absorption and emission properties of the material. In the last few years, PNCs have emerged as an interesting material for different sensing applications, such as solar cells and LEDs. PNCs are extremely good at detecting UV (and even lower) wavelengths that traditional silicon detectors are not. In the new imaging sensor, the PNC layer is able to absorb UV photons and re-emit light in the visible (green) spectrum which is then detected by the tiered silicon photodiodes. Processing of these signals allows for mapping and identification of UV signatures.

Healthcare and Beyond

There are various biomedical markers present in cancerous tissues at higher concentrations than in healthy tissues—amino acids (building blocks of proteins), proteins, and enzymes. When excited with UV light, these markers light up and fluoresce in the UV and part of the visible spectrum, in a process called autofluorescence. “Imaging in the UV region has been limited and I would say that has been the biggest roadblock for making scientific progress,” explains Nie. “Now we have come up with this technology where we can image UV light with high sensitivity and can also distinguish small wavelength differences.”

Because cancer and healthy cells have different concentrations of markers and therefore different spectral signatures, the two classes of cells can be differentiated based on their fluorescence in the UV spectrum. The team evaluated their imaging device on its ability to discriminate cancer-related markers and found that is capable of differentiating between cancer and healthy cells with 99% confidence.

Gruev, Nie and their collaborative research team envision being able to use this sensor during surgery. One of the biggest challenges is knowing how much tissue to remove to ensure clear margins and such a sensor can help facilitate the decision-making process when a surgeon is removing a cancerous tumor.

“This new imaging technology is enabling us to differentiate cancerous versus healthy cells and is opening up new and exciting applications beyond just health,” Nie says. There are many other species besides butterflies capable of seeing in the UV, and having a way to detect that light will provide interesting opportunities for biologists to learn more about these species, such as their hunting and mating habits. Bringing the sensor underwater can help bring a greater understanding of that environment as well. While a lot of UV is absorbed by water, there is still enough that makes it through to have an impact and there are many animals underwater that also see and use UV light.  

***

Viktor Gruev is also an affiliate of Beckman Institute for Advanced Science and Technology, the department of bioengineering and the Carle Illinois College of Medicine at UIUC.

Shuming Nie is also an affiliate of Beckman Institute for Advanced Science and Technology, and the department of electrical and computer engineering.

Other contributors to this work include Cheng Chen (department of electrical and computer engineering at UIUC), Ziwen Wang (department of bioengineering at UIUC), Jiajing Wu (College of Engineering and Applied Sciences at Nanjing University, China and School of Chemistry and Chemical Engineering at Yangzhou University, China), Zhengtao Deng (College of Engineering and Applied Sciences at Nanjing University, China), Tao Zhang (College of Engineering and Applied Sciences at Nanjing University, China), Zhongmin Zhu (department of electrical and computer engineering at UIUC), Yifei Jin (department of electrical and computer engineering at UIUC), Benjamin Lew (department of electrical and computer engineering at UIUC), Indrajit Srivastava (department of electrical and computer engineering at UIUC) and Zuodong Liang (department of electrical and computer engineering at UIUC).

This research was funded by the U.S. Air Force Office of Scientific Research, Office of Naval Research, the National Science Foundation, the National Institute of Health, and the University of Illinois Institutional Funds.

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JOURNAL

Science Advances

DOI

10.1126/sciadv.adk3860 

ARTICLE PUBLICATION DATE

3-Nov-2023

 

Transforming the food system to serve all

Grant of $2.8M from Novo Nordisk Inc. to American University to address food security in D.C.’s Wards 7 and 8

Grant and Award Announcement

AMERICAN UNIVERSITY

Health happens where people work, live, play and worship, says Prof. Stacey Snelling, chair of the Department of Health Studies in American University’s College of Arts and Sciences. And that’s where the Healthy Schools, Healthy Communities Lab engages children, adults and older adults to tackle health inequities. Snelling received a three-year grant of $2.8 million from Novo Nordisk Inc. for health education and to grow the number of Black farmers producing locally grown fruit and vegetables. The goal is to improve local food supply chains and healthy foods options for residents in Wards 7 and 8.  

“Obesity, high blood pressure and other chronic ailments that disproportionately affect residents in Wards 7 and 8 show how the food system is not serving all residents in Washington, D.C.,” Snelling said. “Transforming the food system is needed to improve health for all.” 

In the United States, 40 million people are food insecure, according to Feeding America. Chronic conditions including obesity, diabetes, hypertension, heart disease and several types of cancer are associated with poor nutrition. According to Community Health Administration at DC Health, Wards 7 and 8 experience the starkest health disparities in the District, and 72 percent of residents are considered obese. 

“Novo Nordisk is strongly committed to reducing the burden of chronic disease – and that includes partnering with community-based organizations in underserved communities to improve access to drivers of health and wellness, such as food security,” said Jennifer Duck, vice president of public affairs at Novo Nordisk Inc. “Dynamic programs such as this one have the potential to build a holistically healthier future for the next generation. We couldn’t be more excited to join American University in taking on these challenges in the District of Columbia.” 

To expand agriculture and the supply chain, agricultural partners to the grant will create an apprentice and scholarship program for five urban youth every year to advance interest, knowledge and job training for Black and brown farmers. Training on regenerative agriculture practices and the establishment of hydroponic farms and smart greenhouses will take place, as well as a “Food Ambassadors” program of five mobile markets to serve residents and expand the distribution of locally grown produce. 

As faith organizations are an important part of African American life in Wards 7 and 8, tapping their social support networks for health promotion and education has shown success. Partnerships with faith organizations will help residents with food assistance, nutrition counseling, and in addressing isolation among older adults through socialization over food.  

In Ward 7, for example, Pastor Wil Stroman’s Urban Outreach Ministries is in a food desert of few grocery stores and fresh foods. Stroman, a partner to the Healthy Schools, Healthy Communities Lab, has been working to change this in his community by partnering with the lab to expand his ministry’s offerings. The new grant makes funds available to continue Stroman’s work and engage other faith-based groups.

“Working with new partners and accelerating the work of our existing ones will grow urban agriculture, the distribution of healthy foods, and increase education on healthy eating and disease prevention,” Snelling said.

 

Neighborhood stressors dangerously elevate pregnancy hormones

Peer-Reviewed Publication

RUTGERS UNIVERSITY

Pregnant women living in blighted neighborhoods with high levels of known stressors have higher levels of testosterone – the primary sex hormone in males -- which disrupt hormone regulation and may lead to life-threatening complications during and after childbirth, according to Rutgers research. 

“Previous research has shown that exposure to neighborhood stressors is associated with preterm birth, low birth weight and other complications such as preeclampsia, gestational diabetes and stillbirth,” said Zorimar Rivera Núñez, an assistant professor of epidemiology at the Rutgers School of Public Health and a senior author of the study published in BMC Pregnancy and Childbirth.

“The purpose of this study was to look at possible mechanisms between neighborhood stressors and pregnancy health, and we looked at sex steroid hormones because they’re critically important for both fetal development and maternal health,” Rivera-Núñez said.

Researchers analyzed data from 262 pregnant women who completed a questionnaire about their neighborhoods and underwent blood tests that measured sex hormones such as testosterone in each trimester.

The researchers found that women living in neighborhoods with stressors such as vacant lots, derelict buildings and other signs of disorder had significantly higher levels of testosterone – nearly 40 percent higher by the third trimester of pregnancy – than women living in well-ordered neighborhoods.

Testosterone is known to play a role in a variety of pregnancy-related processes, including sexual differentiation of the brain during early development.

Megan Hansel, first author and doctoral student at the Rutgers School of Public Health, said their findings suggest interventions to reduce neighborhood stress, such as improving access to green spaces and community resources, could help to improve pregnancy outcomes for all pregnant people.

In addition to the potential physical health risks for pregnant people and their babies, neighborhood stress also can harm maternal mental health, previous studies show. Pregnant people living in stressful neighborhoods are more likely to experience anxiety, depression and other mental health problems. These mental health problems also can hurt pregnancy outcomes.

Data for the study come from the Understanding Pregnancy Signals and Infant Development (UPSIDE) cohort, which collected biospecimens, questionnaires and medical record data from 262 women living in and around Rochester, N.Y. Researchers measured the sex hormones maternal serum total testosterone, free testosterone, estrone, estradiol and estriol in each trimester and surveyed participants about neighborhood stressors. UPSIDE is part of the NIH program Environmental Influences on Child Health Outcomes (ECHO), the largest study on child health in the U.S.

The new analysis of UPSIDE data found that 73 percent of women in the cohort reported exposure to one or more types of neighborhood disorder, while 22 percent reported any exposure to violence.

In adjusted models, neighborhood disorder was associated with higher testosterone across pregnancy, with the strongest associations observed in the third trimester, where neighborhood disorder was associated with an average testosterone elevation of 38 percent. The effect was more pronounced in women carrying male rather than female fetuses.

Exposure to violence wasn’t associated with any hormones.

“The findings suggest that stress may alter prenatal testosterone levels, which could explain some of the adverse outcomes we find when pregnant people live with neighborhood stressors,” Rivera Núñez said. “But more research is needed to prove a causal link.”

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JOURNAL

BMC Pregnancy and Childbirth

DOI

10.1186/s12884-023-06043-0 

METHOD OF RESEARCH

Observational study

SUBJECT OF RESEARCH

People

ARTICLE TITLE

Associations between neighborhood stress and maternal sex steroid hormones in pregnancy

U$A

County-level structural racism may affect mortality rates in people with kidney failure

Reports and Proceedings

AMERICAN SOCIETY OF NEPHROLOGY

Highlights

• In a recent analysis of US data, Black patients with kidney failure experienced survival advantages compared with White patients when county-level structural racism was low, but they experienced survival disadvantages compared with White patients at higher levels of structural racism.
• Results from the study will be presented at ASN Kidney Week 2023 November 1–November 5.

Philadelphia, PA (November 3, 2023) — A new analysis indicates that county-level structural racism is a significant determinant of death among individuals with kidney failure. The research will be presented at ASN Kidney Week 2023 November 1–November 5.

For the analysis, investigators examined data from United States Renal Data System, the American Community Survey 2006–10, and the Vera Institute, linked by county. They determined county-level structural racism from Black-White disparities in imprisonment, homeownership, college graduation, median income, unemployment, poverty, and segregation.

The researchers found that Black race interacted with structural racism to predict monthly mortality risk among individuals with kidney failure. Black patients experienced survival advantages compared with White patients at lower levels of structural racism, but they experienced survival disadvantages compared with White patients at higher levels of structural racism. These associations were also apparent when patients were divided into groups based on treatment (hemodialysis, peritoneal dialysis, deceased donor kidney transplant, and living donor kidney transplant).

“This study contributes to a rapidly-growing empirical consensus that structural factors driving racial disparities in non-health life circumstances also drive racial disparities in health and mortality outcomes. The implication is that to eliminate or ameliorate racial disparities in health, systematic social factors driving those disparities must be addressed,” said corresponding author Jonathan Daw, PhD, of Penn State. “Our hope is that our quantitative research studies will eventually, with continued study and committed engagement with affected communities, lead to promising targeted interventions to blunt the worst effects of structural racism on marginalized racial/ethnic groups' health. However, these efforts (even if successful) should not obscure the need for more foundational changes.”

Study: “County-Level Structural Racism Predicts Black-White ESKD Patient Mortality Disparities”

The world's premier nephrology meeting, ASN Kidney Week, brings together approximately 12,000 kidney professionals from across the world. The largest nephrology meeting provides participants with exciting and challenging opportunities to exchange knowledge, learn the latest scientific and medical advances, and listen to engaging and provocative discussions with leading experts in the field.

About ASN

Since 1966, ASN has been leading the fight to prevent, treat, and cure kidney diseases throughout the world by educating health professionals and scientists, advancing research and innovation, communicating new knowledge and advocating for the highest quality care for patients. ASN has nearly 21,000 members representing 140 countries. For more information, visit www.asn-online.org and follow us on Facebook, X, LinkedIn, and Instagram.

 

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The first semi-wild-type melon T2T genome assembled by Zhengzhou Fruit Research Institute, Chinese Academy of Agricultural Sciences, and China Agricultural University

Peer-Reviewed Publication

NANJING AGRICULTURAL UNIVERSITY THE ACADEMY OF SCIENCE

 

IMAGE: 

PHENOTYPE, HI-C MAP AND GENOMIC LANDSCAPE OF 821

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CREDIT: HORTICULTURAL RESEARCH

Melon (Cucumis melo L.) is an important vegetable crop that has an extensive history of cultivation, and has been classified into two subspecies, C. melo ssp. agrestis and C. melo ssp. melo. Previous study suggested that the two subspecies were domesticated independently [1], which may have generated different genetic mechanisms for the same trait between the two subspecies. Furthermore, the difference in their geographical distribution resulted in diverse characteristics between the two subspecies, shaping genomic imprinting in their genomes. Wild germplasm is an important genetic resource in crop breeding because of its high genetic diversity and resistance against diseases. However, all of the previous reported genomes were assembled based on the cultivated melon[2-7], the genome of wild and semi-wild melon types is not yet available. Therefore, assembling high-quality wild/semi-wild melon genome will provide an unprecedented opportunity for gene discovery and resistance breeding in melon.

Recently, the study of ‘The haplotype resolved T2T reference genome highlights structural variation underlying agronomic traits of melon’ was published on Horticulture Research by Yongyang Xu, from Melon Genetic Breeding Team of Zhengzhou Fruit Research Institute, Chinese Academy of Agricultural Sciences, cooperated with professor Tao Lin from China Agricultural University.

PI 313970 is an accession derived from C. melo ssp. agrestis var. acidulus native to India, which possess high resistance to powdery mildew and a variety of viral diseases (ToLCNDV, CYSDV, CABYV, WmCSV and CuLCrV). The ‘821’ accession was self-fertilized from PI 313970 for several generations. Here we reported a chromosome-level T2T genome assembly for 821 (C. melo ssp. agrestis var. acidulus), a semi-wild melon with two haplotypes of ~373 Mb and ~364 Mb, respectively (Fig.1).

Comparative genome analysis discovered a significant number of structural variants (SVs) between melo and agrestis genomes, including a copy number variation located in the ToLCNDV resistance locus on chromosome 11, of which a candidate gene was identified for ToLCNDV resistance (Fig. 2). Additionally, melon is a unique model species for studying fruit ripening because of presenting both climacteric and non-climacteric types. Genome-wide association studies detected a significant signal associated with climacteric ripening and identified one candidate gene CM_ac12g14720.1 (CmABA2), encoding a cytoplasmic short chain dehydrogenase/reductase, which controls the biosynthesis of abscisic acid. This study provides valuable genetic resources for future research on resistance breeding in melon.

References

1. Zhao, G. et al. (2019) A comprehensive genome variation map of melon identifies multiple domestication events and loci influencing agronomic traits. Nat Genet 51, 1607-1615.
2. Garcia-Mas J et al. (2012) The genome of melon (Cucumis melo L.). PNAS 109, 11872-11877.
3. Yang, J.H. et al. (2020) The chromosome-scale genome of melon dissects genetic architecture of important agronomic traits. iScience 23, 101422.
4. Zhang, H. et al. (2019) A high-quality melon genome assembly provides insights into genetic basis of fruit trait improvement. iScience 22, 16-27.
5. Pichot, C. et al. (2022) Cantaloupe melon genome reveals 3D chromatin features and structural relationship with the ancestral cucurbitaceae karyotype. iScience 25, 103696.
6. Ling, J. et al. (2021) High-quality chromosome-level genomes of Cucumis metuliferus and Cucumis melo provide insight into Cucumis genome evolution. Plant J 107, 136-148.  
7. Castanera, R. et al. (2019) An improved melon reference genome with Single-Molecule Sequencing Uncovers a recent burst of transposable elements with potential impact on genes. Front Plant Sci 10, 1815.

###

Authors

Guoli Li1,2#, Lingli Tang1,3,4#, Yuhua He1,3, Yongyang Xu1,3, Abdelhafid Bendahmane5, Jordi Garcia-Mas6,7, Tao Lin2*, Guangwei Zhao1,3,4*

Affiliations

1. National Key Laboratory for Germplasm Innovation & Utilization of Horticultural Crops, Zhengzhou Fruit Research Institute, Chinese Academy of Agricultural Sciences, Zhengzhou, Henan, 450009, China.

2. China Agricultural University, College of Horticulture, Beijing 100193, China.

3. National Nanfan Research Institute (Sanya), Chinese Academy of Agricultural Sciences, Sanya Hainan, 572024, China

4. Zhongyuan Research Center, Chinese Academy of Agricultural Sciences, Xinxiang 453400, China.

5. Institute of Plant Sciences Paris-Saclay (IPS2), INRAE, CNRS, University of Paris-Saclay, University of Evry, University of Paris-Diderot, Gif sur Yvette 91192, France.

6. Centre for Research in Agricultural Genomics (CRAG) CSIC-IRTA-UAB-UB, Edifici CRAG, Campus UAB, 08193 Bellaterra, Barcelona, Spain.

7. Institut de Recerca i Tecnologia Agroalimentàries (IRTA), Edifici CRAG, Campus UAB, 08193 Bellaterra, Barcelona, Spain.

About Guangwei Zhao

Guangwei Zhao, Doctor, doctoral supervisor, engaged in melon genetic breeding, E-mail: zhaoguangwei@caas.cn

Structural variations between melo and agrestis

CREDIT

Horticultural Research

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JOURNAL

Horticulture Research

DOI

10.1093/hr/uhad182 

METHOD OF RESEARCH

Experimental study

SUBJECT OF RESEARCH

Not applicable

ARTICLE TITLE

The haplotype-resolved T2T reference genome highlights structural variation underlying agronomic traits of melon

 

Human insulin less temperature-sensitive than previously thought

A new Cochrane review has found that insulin can be kept at room temperature for months without losing potency, offering hope to people living with diabetes in regions with limited access to healthcare or stable powered refrigeration

Peer-Reviewed Publication

COCHRANE

A new Cochrane review has found that insulin can be kept at room temperature for months without losing potency, offering hope to people living with diabetes in regions with limited access to healthcare or stable powered refrigeration. This affects millions of people living in low- and middle-income countries, particularly in rural areas, as well as people whose lives have been disrupted by conflict or natural disasters.

Human insulin is a hormone produced by the body that helps turn food into energy and controls blood sugar levels. People with diabetes cannot make enough insulin and those with type 1 diabetes have to inject insulin several times a day, typically before every meal. Insulin is an essential medicine for people with diabetes and current guidance states that before use it must be kept refrigerated to preserve its effectiveness.

For millions of people with diabetes living in low- and middle-income countries, however, the harsh reality is that electricity and refrigeration are luxuries that are unavailable to them. Vulnerable populations in war-torn areas, disaster-prone regions, and climate crisis-affected areas, including those enduring extreme heat, also need solutions that don’t rely on powered fridges.

The new Cochrane review summarizes results of different studies investigating what happens to insulin when stored outside of fridges, including previously unpublished data from manufacturers. The review found that it is possible to store unopened vials and cartridges of specific types of human insulin at temperatures of up to 25°C for a maximum of six months, and up to 37°C for a maximum of two months, without any clinically relevant loss of insulin activity. Data from one study showed no loss of insulin activity for specific insulin types when stored in oscillating ambient temperatures of between 25°C and 37°C for up to three months. This fluctuation resembles the day-night temperature cycles experienced in tropical countries.

The research team, led by Bernd Richter from the Institute of General Practice, Medical Faculty of the Heinrich-Heine-University in Düsseldorf, Germany, conducted comprehensive research to investigate insulin stability under various storage conditions. The review analyzed a total of seventeen studies, including laboratory investigations of insulin vials, cartridges/pens, and prefilled syringes, demonstrating consistent insulin potency at temperatures ranging from 4°C to 37°C, with no clinically relevant loss of insulin activity.

Bernd stressed the significance of this research, particularly for people living with type 1 diabetes, where "insulin is a lifeline, as their very lives depend on it. While type 2 diabetes presents its challenges, type 1 diabetes necessitates insulin for survival. This underscores the critical need for clear guidance for people with diabetes in critical life situations, which many individuals lack from official sources.

"Our study opens up new possibilities for individuals living in challenging environments, where access to refrigeration is limited. By understanding the thermal stability of insulin and exploring innovative storage solutions, we can make a significant impact on the lives of those who depend on insulin for their well-being."

These findings can help communities facing challenges in securing constant cold storage of insulin. They provide reassurance that alternatives to powered refrigeration of insulin are possible without compromising the stability of this essential medicine. It suggests that if reliable refrigeration is not possible, room temperature can be lowered using simple cooling devices such as clay pots for insulin storage.

The researchers have also identified uncertainties for future research to address. There remains a need to better understand insulin effectiveness following storage under varying conditions. Further research is also needed on mixed insulin, influence of motion for example when insulin pumps are used, contamination in opened vials and cartridges, and studies on cold environmental conditions.

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JOURNAL

Cochrane Database of Systematic Reviews

DOI

10.1002/14651858.CD015385.pub2 

METHOD OF RESEARCH

Systematic review

SUBJECT OF RESEARCH

People

ARTICLE TITLE

Thermal stability and storage of human insulin

ARTICLE PUBLICATION DATE

2-Nov-2023

COI STATEMENT

All authors report no relevant interests