Category Archives: Molecular Genetics

Genetic analysis found no greater risk of miscarriage, stillbirth, or premature birth for women who drink coffee.

According to genetic tests conducted by academics at the University of Queensland, drinking a daily latte or long black does not raise the risk of pregnancy

A daily latte or long black does not raise the risk of pregnancy, according to a study from the University of Queensland.

Genetic analysis of coffee drinking behavior by Drs. Gunn-Helen Moen, Daniel Hwang, and Caroline Brito Nunes from the University of Queenslands Institute for Molecular Bioscience revealed that limited coffee consumption during pregnancy did not increase the risk of miscarriage, stillbirth, or premature birth.

Their findings have been published in the International Journal of Epidemiology.

Current World Health Organisation guidelines say pregnant women should drink less than 300mg of caffeine or two to three cups per day, Dr. Moen said.

But thats based on observational studies where its difficult to separate coffee drinking from other risk factors like smoking, alcohol, or poor diet. We wanted to find out if coffee alone really does increase the risk of adverse pregnancy outcomes, and the research shows this isnt the case.

Dr. Hwang said coffee-drinking behavior is partly due to genetics, with a specific set of genetic variants affecting how much coffee we drink.

We showed that these genetic variants not only affect coffee consumption in the general population but also in pregnant women, he said.

IMB researchers have used genetics to show that a daily coffee causes no increased risk to pregnancy. Credit: University of Queensland

The researchers used a method called Mendelian Randomisation which used eight genetic variants that predicted pregnant womens coffee-drinking behavior, and examined whether these variants were also associated with birth outcomes.

Because we cant ask women to drink prescribed amounts of coffee during their pregnancy, we used genetic analyses to mimic a randomized control trial, Dr. Hwang said.

The genetic analysis found there was no greater risk of miscarriage, stillbirth, or premature birth for women who drank coffee.

When it comes to diet during pregnancy women are often advised to cut things out, but this study shows they can still enjoy coffee without worrying about increasing the risk of these pregnancy outcomes, Dr. Hwang said.

The researchers emphasize the study only looked at certain adverse pregnancy outcomes, and it is possible caffeine consumption could affect other important aspects of fetal development.

For that reason, we dont recommend a high intake during pregnancy, but a low or moderate consumption of coffee, Dr. Moen said.

This research used genetic data from the Coffee and Caffeine Genetics Consortium, the UK BioBank, the Avon Longitudinal Study of Parents and Children, and 23andMe.

The study was funded by the Australian NHMRC and the Norwegian Research Council.

Reference: Mendelian randomization study of maternal coffee consumption and its influence on birthweight, stillbirth, miscarriage, gestational age and pre-term birth by Caroline Brito Nunes, Peiyuan Huang, Geng Wang, Mischa Lundberg, Shannon DUrso, Robyn E Wootton, Maria Carolina Borges, Deborah A Lawlor, Nicole M Warrington, David M Evans, Liang-Dar Hwang and Gunn-Helen Moen, 9 June 2022, International Journal of Epidemiology.DOI: 10.1093/ije/dyac121

Read more:
New Research Finally Proves That Coffee Is Safe During Pregnancy - SciTechDaily

Stephen Buranyi misses some key points in his article (Do we need a new theory of evolution?, 28 June). Darwin saw novel speciation as resulting from natural selection acting on anatomical variants, but that simple skeleton needed fleshing out. It took a century of research, for example, for us to understand the importance of inheritance in very small populations if novel variants were to become predominant.

The major problems in understanding evolutionary change today are as follows. First, working out how anatomical variants form and this is hard because we dont yet have a full understanding of how normal embryology works (evolution, it has been claimed, is development gone wrong) and can only rarely recognise a favourable mutation. Second, unpicking the generally opaque processes of selection (there are at least four independent reasons why zebra stripes would be favoured). Third, understanding why substantial evolutionary change seems so slow, albeit that this is what the fossil record demonstrates. This is the topic that excites the community that Buranyi discusses, even though modern molecular genetics and systems biology show that heritable novelties can form more rapidly than they realise.

The deeper problem is that evolutionary change involves the complete scale of nature, from DNA mutation to climate change, so of course there can be no unifying theory. The difficulty for scientists is that convincing experimentation is hard and slow.Prof Jonathan BardOxford

Those biologists who are critical of current Darwinian orthodoxy and who want to modify the theory in the direction of the extended Darwinian synthesis need to take things further. They need to recognise that all living things are purposive. They pursue goals without necessarily being aware of it the ultimate goal being survival and reproductive success.

Purposive action can, in a multitude of ways, influence what has survival value and thus influence the future course of evolution. Purposive action that results in living in a new environment, or pursuing new kinds of food, can change what has survival value for that creature and its offspring, and thus can influence the future course of evolution. Foxes hunting rabbits breed rabbits better able to escape; and rabbits escaping breed foxes better able to catch them.

Above all, when animals make discoveries and learn from one another, cultural evolution becomes possible, and that can have a massive impact on subsequent evolution, as the case of human evolution, and the evolution of language, show.

We need a new, unified version of Darwinian theory that recognises that the purposive actions of living things play a vital role in evolution. This is very definitely not Lamarckism, although too many biologists have denied the Darwinian role of purposive action in evolution for fear that that commits one to Lamarckism. For more about this, see chapter 6 of my 2020 book Our Fundamental Problem: A Revolutionary Approach to Philosophy.Nicholas MaxwellEmeritus reader, science and technology studies, University College London

Surely theres no problem with having several conflicting theories of evolution? Eventually the fittest will survive.Pete BibbySheffield

Have an opinion on anything youve read in the Guardian today? Please email us your letter and it will be considered for publication.

Here is the original post:
Scientists are still fleshing out Darwins theory of evolution - The Guardian

Advancements in cancer research and treatment have resulted in great improvements in survival rates today, there are almost 17 million people in the United States alone who have survived their diagnosis because of the physicians and scientists who have dedicated their careers to breakthrough approaches. June is Cancer Survivor Month, and as we celebrate the individuals living with, through and beyond their disease, the Michigan State University College of Osteopathic Medicine is spotlighting some of the researchers contributing to these advancements in science, including Yasser Aldhamen, Ph.D.

The whole idea is to treat patients from within, rather than with drugs to eradicate cancer, Aldhamen said.

Building on his past work, the lab devised a way to harness the naturally active immune system to control tumor growth by activating cytolytic cells, such as NK-cells, and innate immune cells, such as macrophages and dendritic cells, within tumors.

Our lab has experience with viral vectors as gene therapy and vaccines, Aldhamen explained. We developed a cancer-killing agent by using a virus (Ad-SLAMF7-Fc) to harness the activity of the immune system. We used a protein (SLAMF7-Fc fusion) that we know activates immune cells in the tumor microenvironment. Using colon cancer and melanoma cancer mouse models, we showed that we can control tumor growth and increase survival in mice with these tumors. We can induce tumor control by activating the innate immune system.

Dr. Patrick OConnell, Ph.D., an eighth-year D.O.-Ph.D. student who worked on the research project, described it as a multi-pronged approach to activate immune cells in a tumor to direct those cells to kill cancer cells. He further explained, Were trying to re-educate the immune system to teach it that, This is a cancer cell, now target it for destruction.

In short, the team proved that adapting the bodys own immunity to control tumors is possible allowing doctors to target this function as part of a patients cancer treatment in the future. Aldhamen envisions that this approach could be combined with another FDA-approved immunotherapy, such as anti-PD-1 checkpoint blockade, to create an additive effect and boost the efficacy of anti-PD-1 treatment.

Aldhamen said this approach is practical and cost-saving. Biologic therapeutics are expensive, Aldhamen said. We can get a more powerful response by putting the SLAMF7-Fc gene in a viral vector and producing it in the tumor microenvironment to attract the cytolytic immune cells to the tumor. It turns the tumors into mini factories that produce a lot of our immune modulatory SLAMF7-Fc protein, which gives us the immune response were looking for.

Aldhamen works in the colleges microbiology and molecular genetics department and oversaw the two-year research project, which started in 2019 and involved several other MSU faculty members, including College of Osteopathic Medicine Dean Andrea Amalfitano.

In addition to proving the feasibility of this new immunotherapy approach, the team also used machine learning to better understand the mechanism of how Ad-SF7-Fc-induces anti-tumor activity.

We tested this new immunotherapy approach in multiple mice models to show it works in different types of mice and with different cancers its broadly applicable, OConnell said.With further testing, A new cancer drug could target the SLAMF7 protein to help cancer patients with other types of resistant cancers, OConnell added.

The lab has seen some interest from the biotech field in licensing this technology. We can target the receptor within tumors with small molecules as drugs, Aldhamen said.

Aldhamen is already designing future experiments focused on studying plasmacytoid dendritic cells in tumors as another potential suitable target to harness the immune cells in the tumor microenvironment.

It is the colleges commitment to invest in innovative research, such as this, that will continue to advance the field of medicine and improve the lives of millions of patients with cancer.

This story has been adapted from an article originally published by the College of Osteopathic Medicine.

See the article here:
New immunotherapy research sees promising results in shrinking treatment-resistant cancer tumors - MSUToday

BOONE, N.C. Catching fish, salamanders and an occasional water snake is all in a days work for Appalachian State University biology students Nick Campany and Carson Scott interns this summer for nonprofit organization ACleanWilsonCreek.org (ACWC).

Our interns are gaining a valuable perspective of the various partnerships and cooperative efforts that take place in a (conservation) venture like this.

Dr. Shea Tuberty, professor and assistant chair of student affairs in App States Department of Biology and conservation biologist and freshwater stream specialist for ACleanWilsonCreek.org

In addition to collecting and evaluating wildlife, the interns are providing hands-on cleanup service and conservation education along a 15-mile stretch of Wilson Creek, which is part of the U.S. National Park Services National Wild and Scenic Rivers System.

Located in Caldwell County about a 45-minute drive from App States campus the river serves as a natural playground to a throng of hikers, mountain bikers, campers, anglers and other outdoor enthusiasts, said Dr. Shea Tuberty, professor and assistant chair of student affairs in App States Department of Biology. Tuberty serves as the conservation biologist and freshwater stream specialist for ACWC, acting as the liaison in recruiting biology interns from App State.

Dr. Shea Tuberty, professor in App States Department of Biology, center, leads a group of students and interns in collecting fish and macroinvertebrates to identify and catalog for conservation research on National Wild and Scenic River Wilson Creek in Caldwell County. Photo submitted

Campany, a senior from Harrisburg, and Scott, a junior from Lexington, are both biology majors with a concentration in ecology, evolution and environmental biology. Campany is also pursuing a minor in animal studies. As part of their internships, the two students:

Wilson Creek is in the Grandfather Mountain Ranger District of the Pisgah National Forest. At one time, the remote but heavily used section of the waterway next to Brown Mountain Beach Road lacked sufficient waste control infrastructure and had a high volume of litter and graffiti.

Cleanup work on Wilson Creek began as a grassroots effort in 2007 by a local store owner in Mortimer, with assistance from his employees and other occasional volunteers. Over a 10-year period, the local group removed approximately 144,000 pounds of trash, with daily trips along the riverside to gather loose litter and excess trash bags left vulnerable to raiding by wildlife.

App State alumna Katie Krogmeier 18 21, a conservation center assistant at ACleanWilsonCreek.org, examines a small northern water snake, captured in a survey of river wildlife at Wilson Creek. Photo submitted

In 2017, Wes Waugh became involved with the volunteer effort after hiking and fly-fishing in the Wilson Creek area for about 40 years. Waugh retired in 2020 after more than 30 years of service at App State, including his last position as the director of auxiliary services in the Student Learning Center.

I was acutely aware of the growing problems associated with recreational overuse and was concerned that the river and riparian zones were in great danger of being destroyed, he said. Working with the local store owner, Waugh filed the paperwork to establish the nonprofit ACWC and became executive director of the initiative.

Under Waughs leadership, the organization was awarded a sponsorship from the USDA Forest Service resulting in infrastructure support, provision of necessary equipment and supplies and the ability to operate out of a workstation managed by the Forest Service. The North Carolina Wildlife Resources Commission also partnered with the ACWC, providing trash bags and cleanup supplies.

In 2021, Waugh reached out to Tuberty to initiate ACWCs summer internship program employing App State biology students.

The partnership is a perfect example of the university involving App State students in community partnerships and environmental sustainability efforts, Waugh said.

Prior to releasing the fish back into the waters of Wilson Creek, biology students evaluate, identify and record information about the specimens to add to a collection of data about the wildlife in the area. The information will serve as a baseline on the population sizes, types of species and health of the fish in Wilson Creek. Photo submitted

Scott, who plans to pursue a career in wildlife biology research after he graduates, said, Getting connected to people associated with Wilson Creek and taking care of such a beautiful place is an amazing privilege. I love understanding the interactions between the community, animals and their habitats.

Scott is conducting research on salamanders in Wilson Creek, establishing baseline data on the population and types of species. I feel like herpetology is my calling, and the work Im doing at Wilson Creek plays into what I want to do with my career, he said.

Campany hopes to become a fishery biologist and said his internship will help him gain valuable experience in research and in conducting his own surveying.

Dr. Tuberty has been a great mentor, teaching us the correct methods of sampling and collecting specimens, Campany said. However, the most valuable thing Campany said he has learned is the importance of establishing and maintaining connections with people.

Tuberty said, Our interns are gaining a valuable perspective of the various partnerships and cooperative efforts that take place in a venture like this. To support a sustainable relationship between sensitive plants and wildlife and the various human stakeholders, we have to consider cultural elements and social dynamics of the residents in the area, as well as the recreational users.

App State alumni Katie Krogmeier 18 21 is a conservation center assistant at ACleanWilsonCreek.org. She supervises interns, aids in the design and development of conservation and information centers, and organizes volunteer events for the organization. Photo submitted

Interns with ACleanWilsonCreek.org prepare to survey fish and macroinvertebrates living in Wilson Creek. Pictured, from left to right, are App States Nick Campany, a senior from Harrisburg, and Carson Scott, a junior from Lexington, both of whom are majoring in biology with a concentration in ecology, evolution and environmental biology, and Andie Waugh, an intern from North Carolina State University. Photo submitted

App State alumna Katie Krogmeier 18 21, who earned a Bachelor of Science and a Master of Science in biology at App State, served as an intern with ACWC in summer 2021. Now she is employed by the organization as a conservation center assistant.

Krogmeier is aiding in the design and development of two conservation centers, located on the upper and lower ends of Wilson Creek, which will serve as the headquarters for ACWC. Staff and volunteers will hold kiosk events at the centers, where they will educate visitors about the Leave No Trace principles and about the areas wildlife and flora.

Krogmeier also conducts volunteer events, supervises interns in their research and coordinates with faculty who want to utilize the area for their classes. Several App State departments including Recreation Management and Physical Education, Geological and Environmental Sciences and Biology use the Wilson Creek area as a training ground.

Interns and students who study this area are able to gain useful skills and practical experience to apply in their future careers, Krogmeier said. We hope to use their research to build more displays in our conservation centers to educate the public on why it is important to keep Wilson Creek healthy, so we can all continue to enjoy it.

Share your feedback on this story.

In this biology degree, students examine the characteristics of ecosystems, their evolution and the greater environment all in a geographic location known for its great biodiversity.

Sep. 10, 2019

Top-notch N.C. high schoolers take to the river for research, instructed by Appalachian State University faculty, staff and students. Its a learning experience for all.

Jan. 25, 2021

App States New River Light and Power has completed its grant-funded project to remove the historic Payne Branch dam from the New Rivers Middle Fork, helping to restore this river corridor to a more natural state which includes improved water quality and enhanced habitat for the areas aquatic wildlife. Dive in to learn more.

The Department of Biology is a community of teacher-scholars, with faculty representing the full breadth of biological specializations from molecular genetics to landscape/ecosystem ecology. The department seeks to produce graduates with sound scientific knowledge, the skills to create new knowledge, and the excitement and appreciation of scientific discovery. Learn more at https://biology.appstate.edu.

The College of Arts and Sciences (CAS) at Appalachian State University is home to 17 academic departments, two centers and one residential college. These units span the humanities and the social, mathematical and natural sciences. CAS aims to develop a distinctive identity built upon our university's strengths, traditions and unique location. The colleges values lie not only in service to the university and local community, but through inspiring, training, educating and sustaining the development of its students as global citizens. More than 6,400 student majors are enrolled in the college. As the college is also largely responsible for implementing App States general education curriculum, it is heavily involved in the education of all students at the university, including those pursuing majors in other colleges. Learn more at https://cas.appstate.edu.

As the premier public undergraduate institution in the Southeast, Appalachian State University prepares students to lead purposeful lives as global citizens who understand and engage their responsibilities in creating a sustainable future for all. The Appalachian Experience promotes a spirit of inclusion that brings people together in inspiring ways to acquire and create knowledge, to grow holistically, to act with passion and determination, and to embrace diversity and difference. Located in the Blue Ridge Mountains, Appalachian is one of 17 campuses in the University of North Carolina System. Appalachian enrolls nearly 21,000 students, has a low student-to-faculty ratio and offers more than 150 undergraduate and graduate majors.

View post:
App State biology interns spend summer in Wilson Creek's 'natural playground': Cleanup, conservation and outreach for a National Wild and Scenic River...

Singapore, 30 June 2022 A team of clinician-scientists and scientists, led by the National Cancer Centre Singapore (NCCS) and A*STARs Genome Institute of Singapore (GIS) together with collaborators in Europe and South Korea, used single cell techniques to uncover a central dichotomy for colorectal cancer cells, leading to a proposed update of the classification system for the disease. These findings, published in Nature Genetics on 30 June 2022, have implications for drug development and treatment approaches in colorectal cancer.

In Singapore and worldwide, colorectal cancer is one of the most common cancers and the second-leading cause of cancer death. As it is a heterogeneous disease with substantial biological and clinical differences amongst patients, treating colorectal cancer and prescribing individualised treatment for patients directed by the biology of their disease is a challenge. In 2015, clinicians and scientists classified colorectal cancer based on genes expressed by the tumour (transcriptomics) leading to the 2015 international consensus molecular subtype (CMS1-4) classification, that is to date, the most robust and widely used transcriptomic system. However, the CMS classification relied on transcriptomic analysis of the entire tumour which meant that the individual differences from cancer cells and other stromal cells (e.g. immune, fibroblast & blood vessel cells) were obscured and could not be distinguished.

The current classification systems for colorectal cancer do not adequately highlight the molecular underpinnings of the disease, said co-senior author Professor Shyam Prabhakar, Associate Director of Spatial and Single Cell Systems at GIS. Our team examined the malignant (epithelial) cell subtypes and defined their properties to understand their interactions with other cells using single cell profiling, so that we could accurately describe the heterogeneity of colorectal cancer.

The NCCS and GIS-led research team analysed 373,000 single cells from 141 tumour samples collected from 63 colorectal cancer patients in Singapore, Belgium and South Korea. Using single-cell and bulk transcriptomics, the team found that the malignant cells belong to two major epithelial subtypes, that they have termed intrinsic-consensus molecular subtypes (iCMS), consisting of iCMS2 and iCMS3, uncovering a central dichotomy that cut across previous classifications of colorectal cancer. Each subtype is characterised by distinct molecular signalling cascades and patterns of DNA duplications or deletions, mutations in key genes, RNA abundance patterns and gene regulatory networks.

Colorectal cancer is widely classified by two systems, microsatellite instable (MSI-H) and microsatellite stable (MSS) colorectal cancer. Colorectal cancer with MSI-H is considered to be very responsive to immunotherapy while MSS cancers are refractory to immunotherapy. Drug development and clinical trials are ongoing to address this pressing unmet need of finding immunotherapies that can work to treat MSS colorectal cancers. However, these trials currently classify MSS colorectal cancer as one group.

The research team found that one-third of MSS tumours were iCMS3 subtype and had cancer cells much more similar to MSI cancers rather than other MSS cancers. Understanding the similarities between MSI-H cancers and iCMS3 MSS cancers could lead to an identification of components that can be exploited to adapt and modify immunotherapy regimens, that might work best in these patients with biology similar to MSI-H cancers. Conversely, understanding the distinct biology of iCMS2 MSS cancers could allow targeted drug development focused on this group of colorectal cancer. Furthermore, the CMS4 group of colorectal cancers, known to have the highest tendency to metastasise, was evenly divided into the iCMS2 and iCMS3 subtypes. Between these two groups, CMS4 cancers with iCMS3 epithelial cells were found to have the worst prognosis.

Based on their findings the research team proposed a refinement of the CMS classification known as IMF, which groups colorectal cancer into five groups based on their epithelial status, microsatellite status and the presence of fibrosis. The proposed IMF classification provides new insight into colorectal cancer and its origin, evolution and response to therapies. Further pre-clinical and clinical studies into the biology of the five groups could inform prevention, diagnosis and therapy.

Currently, clinical trials focus on using immunotherapy combinations to treat microsatellite stable colorectal cancers as one group, not accounting for differences amongst microsatellite stable colorectal cancers. Our study changes the understanding of the diversity of colorectal cancer by showing that there are fundamentally different biological subsets with distinct epithelial characteristics, microsatellite status and interactions with fibrosis. This could help purposefully strategise drug development efforts to effectively target these different subsets of colorectal cancer, said co-senior author Associate Professor Iain Tan, Senior Consultant and Director of Research, Division of Medical Oncology, NCCS.

The research team plans to perform further analyses to characterise the biological properties, interactions and drug response of iCMS2 and iCMS3 cells, and also re-analyse data from clinical trials to identify differences in treatment response between these two cancer types.

This research is supported by the Singapore Ministry of Healths National Medical Research Council under its Clinician Scientist Award (MOH-000012) and Clinician Scientist - Individual Research Grant (MOH-000969), and the Agency of Science, Technology and Research (A*STAR).

***

Study citation: Joanito, I.et al.Single-cell and bulk transcriptome sequencing identifies two epithelial tumor cell states and refines the consensus molecular classification of colorectal cancer.Nature Genetics(2022). doi:10.1038/s41588-022-01100-4

- - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - -

For media queries and clarifications, please contact:

National Cancer Centre Singapore

Dharshini Subbiah

Assistant Manager, Corporate Communications

HP: +65 9616 7532

Email: dharshini.subbiah@nccs.com.sg

Lo Sok Wan

Manager, Corporate Communications

HP: +65 9689 8791

Email: lo.sok.wan@nccs.com.sg

Genome Institute of Singapore, A*STAR

Lyn Lai

Officer, Office of Corporate Communications

Tel: +65 6808 8258

HP: +65 8755 8759

Email: laiy@gis.a-star.edu.sg

About the National Cancer Centre Singapore

The National Cancer Centre Singapore (NCCS) is a leading national and regional tertiary cancer centre with specialists who are experts in treating cancer. NCCS attends to the majority of cancer cases in Singapore's public healthcare sector. In addition to offering holistic and multidisciplinary oncology care, our clinicians and scientists collaborate with local and international partners to conduct robust, cutting-edge clinical and translational research. To achieve the vision of being a global leading cancer centre, NCCS offers world-class care and shares its depth of experience and expertise by training local and overseas medical professionals.

To meet growing needs, the new NCCS building will be completed in 2022 with increased capacity and expanded facilities dedicated to cancer care, rehabilitation, research and education. To give patients the best treatment outcomes, NCCS will offer access to advanced and innovative treatment such as proton therapy at the new Goh Cheng Liang Proton Therapy Centre.

For more information, please visit: http://www.nccs.com.sg

About A*STARs Genome Institute of Singapore (GIS)

The Genome Institute of Singapore (GIS) is an institute of the Agency for Science, Technology and Research (A*STAR). It has a global vision that seeks to use genomic sciences to achieve extraordinary improvements in human health and public prosperity. Established in 2000 as a centre for genomic discovery, the GIS pursues the integration of technology, genetics and biology towards academic, economic and societal impact, with a mission to "read, reveal and write DNA for a better Singapore and world".

Key research areas at the GIS include Precision Medicine & Population Genomics, Genome Informatics, Spatial & Single Cell Systems, Epigenetic & Epitranscriptomic Regulation, Genome Architecture & Design, and Sequencing Platforms. The genomics infrastructure at the GIS is also utilised to train new scientific talent, to function as a bridge for academic and industrial research, and to explore scientific questions of high impact.

For more information about GIS, please visit http://www.a-star.edu.sg/gis.

About the Agency for Science, Technology and Research (A*STAR)

A*STAR is Singapore's lead public sector R&D agency. Through open innovation, we collaborate with our partners in both the public and private sectors to benefit the economy and society. As a Science and Technology Organisation, A*STAR bridges the gap between academia and industry. Our research creates economic growth and jobs for Singapore, and enhances lives by improving societal outcomes in healthcare, urban living, and sustainability. A*STAR plays a key role in nurturing scientific talent and leaders for the wider research community and industry. A*STARs R&D activities span biomedical sciences to physical sciences and engineering, with research entities primarily located in Biopolis and Fusionopolis. For ongoing news, visit http://www.a-star.edu.sg.

Follow us on

Facebook | LinkedIn | Instagram | YouTube

Randomized controlled/clinical trial

Single-cell and bulk transcriptome sequencing identifies two epithelial tumor cell states and refines the consensus molecular classification of colorectal cancer.

30-Jun-2022

Read this article:
New classification system proposed for colorectal cancer to guide treatment and clinical trials - EurekAlert

On a summer hike into the High Country, you may notice patches of red or pink watermelon snow on melting snowfields. The color represents millions of tiny dormant cysts of a cold-tolerant algal species, Chlamydomonas nivalis, becoming concentrated as the snow decreases.Walking on the snow compresses and concentrates the red algae in your footprints.Take a moment to marvel at how these little organisms are uniquely adapted to their inhospitable habitat: high elevation, cold, intense sunlight, UV radiation and few nutrients.

These single-celled C. nivalis algae were once called psychrophiles (meaning cold-loving), but more recent research suggests they are cold-tolerant mesophiles,growing best at temperatures ranging from 41-59degrees Fahrenheit, but not above 86 degrees. They can persist in their cyst form when temperatures are below freezing (32 degrees).

A relative of C. nivalis, C. reinhardtii, is a true mesophile, growing best at moderate temperatures between 68-86 degrees in fresh water.C. reinhardtii has been highly studied as a model organism for research on major questions in cell and molecular biology, such as genetics and mechanisms of photosynthesis, flagellar movement and cell response to light.

Like all green plants, these algae have chloroplasts that contain the green pigment chlorophyll.Their photosynthesis uses the energy of the sun to convert carbon dioxide and water to sugars and other essential organic compounds and releases oxygen.In the dark, they can also take in organic material from the environment as a source of energy and food.

The red color of C. nivalis reflects that they contain an accessory pigment,astaxanthin,in addition to the green chlorophyll.The red carotenoid pigment functions like sunscreen to protect the DNA and other cell components from intense solar UV radiation. However, in absorbing the radiation, this red pigmentalso leads to melting of the snow,which causes concern that these algae, and even dust blown onto the snow, may accelerate glacial melting.

C. nivalis spends much of its year as a thick-walled, dormant cyst. As conditions warm, the cyst forms four motile green vegetative cells, each containing two flagella (cellular tails) to propel it in the liquid melting snow. Each has an eyespot to orient it for optimal photosynthesis. Sensitive to temperature and drought stress, these cells swim in the snow to reach optimal conditions, dividing to form more cells during the brief summer. Later, two vegetative cells fuse to form a zygote: it loses the flagella, makes more red pigment to pack around cell components, and forms a thick cell wall to protect the cyst from dehydration.While vegetative cells diameters measure about 10 micrometers larger than bacteria, similarly sized to yeast cells the cysts are much larger, 35-50 micrometers.

Is it safe to eat watermelon snow? Its not a snow cone. Some reports say it acts as laxative. But consider that C. nivalis isnt the only thing living in this inhospitable ecosystem. There are also diverse fungi, bacteria, viruses and some worms, along with dust, pollen and other debris carried by winds and deposited on the snow.

C. nivalis is the most common of the snow algae, although there are some 60 other species identified in the West alone.The snow algae Chloromonas brevispina makes green cysts deeper in the snow, or in areas with less UV light. Sometimes orange and purple patches appear on snow, which could be different varieties of C. nivalis, or other species. For now, enjoy the lovely colors on the snow as you hike in the High Country, and appreciate these tiny organisms that can thrive in such an environment.

Joan Betz is a retired Biology professor from Regis University, and a Board member ofEagle Summit Wilderness Alliance, an all-volunteer nonprofit that helps the U.S. Forest Service protect and preserve the wilderness areas in Eagle and Summit counties. For more information, visitEagleSummitWilderness.org.

Visit link:
Get Wild: Watermelon snow in the High Country - Summit Daily

CAMBRIDGE, Mass.--(BUSINESS WIRE)--GV20 Therapeutics, a biopharmaceutical company using cutting-edge genomics and artificial intelligence approaches to discover next-generation cancer therapeutics, announced three key executive appointments to accelerate its growth and transition into a clinical-stage company. Pioneering cancer researcher and co-founder Shirley Liu, Ph.D. was named the Chief Executive Officer; former executive at Shape Pharmaceuticals and Tensha Therapeutics, Steven Landau, M.D., became the Chief Medical Officer; and Genentech veteran Ying Gong, Ph.D. was appointed Chief Business Officer.

Shirley Liu is an innovative and prolific computational cancer biologist. Having been on the faculty at the Dana-Farber Cancer Institute and Harvard T.H. Chan School of Public Health for almost 20 years, she has made significant contributions to the understanding of gene regulation and drug response in cancer. Dr. Liu and Ted Xiao, Ph.D., a former postdoctoral fellow at Dana-Farber Cancer Institute and Harvard Medical School, co-founded GV20 Therapeutics in 2016 with the goal of applying high-throughput genomics and computational approaches to the discovery and development of novel cancer drugs. The companys efforts have led to the identification of novel targets and drug candidates including its first candidate, XBH25, a novel NK checkpoint inhibitor targeting solid tumors. GV20 expects to file an IND for XBH25 in the second half of 2022.

We are excited to welcome Steve and Ying and their expertise to the GV20 team, said CEO Shirley Liu. Ying and Steve both bring a wealth of experience advancing innovative oncology pipelines and building high-performing teams. That Ying and Steve have chosen to help lead GV20 at this crucial inflection point speaks to the power of our drug discovery capabilities and the potential of our pipeline. With their leadership, we are excited to advance XBH25 toward the clinic, and to discover more promising candidates at speed and scale with our integrated STEAD genomics and AI platform. We are well-positioned to bring next-generation immunotherapies to cancer patients.

ABOUT SHIRLEY LIU, PH.D.

Shirley Liu, Ph.D., co-founded GV20 Therapeutics in 2016 and joined the company full-time as the CEO in 2022. A highly cited cancer researcher, Dr. Liu was previously a Professor of Biostatistics and Computational Biology at Dana-Farber Cancer Institute and Harvard T.H. Chan School of Public Health, and the co-director of the Center for Functional Cancer Epigenetics at Dana-Farber. With more than 250 peer-reviewed publications, her research has refined the understanding of hormone receptor therapies, epigenetic inhibitors, gamma-secretase inhibitors, receptor tyrosine kinase inhibitors, and immune checkpoint inhibitors in different cancers. She is a fellow of the International Society of Computational Biology (ISCB), American Institute for Medical and Biological Engineering (AIMBE), and was a Breast Cancer Research Foundation Investigator (2017-2021). Liu is a recipient of the Sloan Research Fellowship (2008), Weitzman Outstanding Early Career Investigator Award from the Endocrine Society (2016), ISCB Innovator Award (2020), and the Benjamin Franklin Award for Open Access in the Life Sciences (2020). Dr. Liu received her Ph.D. in Biomedical Informatics and Ph.D. minor in Computer Science from Stanford.

ABOUT STEVEN LANDAU, M.D.

Steven Landau, M.D., has more than 25 years of experience developing products for the treatment of cancers and inflammatory diseases, including the FDA-approved monoclonal antibody Entyvio. He has previously served as Chief Medical Officer at oncology-focused companies including Shape Pharmaceuticals and Tensha Therapeutics. Dr. Landau has also supported product development at OraVax, LeukoSite, Millennium Pharmaceuticals, and Praecis Pharmaceuticals. Dr. Landau earned his M.D. from Case Western Reserve University, and completed his post-graduate training at the Beth Israel Hospital and the Brigham and Women's Hospital in Boston.

ABOUT YING GONG, PH.D.

Ying Gong, Ph.D., is an experienced strategist, drug developer and team leader. Most recently, she served as Project Team Leader for oncology at Genentech, where she led drug development programs and business development projects from late-stage research to clinical proof-of-concept. Dr. Gong also served as Senior Director of Portfolio Strategy and Planning, shaping Genentech's industry-leading R&D strategy. Prior to that, she held roles in medical affairs, market access, global product strategy, and market planning at Genentech and Roche, and worked on a broad range of projects including new indication launches of Perjeta and Avastin. She began her career as a management consultant at Bain & Company. Dr. Gong earned a Ph.D. in Biochemistry and Molecular Biophysics from the California Institute of Technology, and an M.A. in Molecular Genetics from Smith College.

ABOUT GV20 THERAPEUTICS

GV20 Therapeutics is a biopharmaceutical company with 50 employees and sites in Cambridge, Massachusetts and Shanghai, China. The company closed a series B financing led by Coatue Management in October 2021. GV20 uses high-throughput functional genomics and artificial intelligence to identify novel cancer immunology drug targets and antibody therapeutics. The companys pipeline includes XBH25, a novel NK checkpoint inhibitor targeting solid tumors, which is currently progressing toward the clinic. GV20 references one of the most important acupoints for the human body, symbolizing the companys mission to find and exploit vulnerabilities in cancer biology.

To learn more about GV20, please visit https://gv20tx.com/ and follow the company on LinkedIn and Twitter.

More:
GV20 Therapeutics Builds Experienced Leadership Team with Appointments of Three Key Executives - Business Wire

Work type: Full-timeDepartment: Department of Surgery, School of Clinical Medicine (21700)Categories: Academic-related Staff

Applications are invited for appointment asResearch Assistant Professor (RAP)/Scientific Officer (SO) in the Department of Surgery, School of Clinical Medicine(Ref.:515452),to commence as soon as possible on a two-year fixed-term basis.

Applicants should possess a Ph.D. degree with proven experience in molecular genetics, next generation sequencing and cancer biology.They should have an excellent command of written and spoken English and Chinese (including Cantonese and Putonghua) and excellent communication skills. They should be outstanding and self-motivated researchers with a strong track record in molecular and cancer biology indicated by an excellent publication record. Post-doctoral experience in clinical studies and grant applications is essential.

The appointee will work independently and be involved in various projects related to breast cancer biology. He/She is expected to take up a leading role to oversee the team. Enquiries about the duties of the post should be directed to Professor Ava Kwong at avakwong@hku.hk.

A highly competitive salary commensurate with qualifications and experience will be offered, in addition to annual leave and medical benefits. At current rates, salaries tax does not exceed 15% of gross income. The appointment will attract a contract-end gratuity and University contribution to a retirement benefits scheme, totalling up to 15% of basic salary. For SO, housing benefits will also be provided as applicable.

The University only accepts online applications for the above post. Applicants should apply online and upload an up-to-date C.V.Review of applications will start on July 12, 2022 and continue untilJuly 31, 2022, or until the post is filled, whichever is earlier.

Read more:
Research Assistant Professor / Scientific Officer, Department of Surgery job with THE UNIVERSITY OF HONG KONG | 299022 - Times Higher Education

When I found out I was pregnant with my fifth child, my first words were, Oh my god, NO! I was alone in the bathroom while my husband was on a conference call, and all I could think of was how my life was ruined.

I texted my brother, asking him not to tell our mother yet because I was debating on whether or not to keep it. He texted back a wrap it up meme and I laughed, but inside, I was panicking.

More from SheKnows

I texted a friend, then multiple friends.

I waited impatiently by the door for my husbands call to end, and when he opened it, I practically threw the test at him. I cant quite recall exactly what happened except that there were lots of tears and he held me as I sobbed in his arms.

Click here to read the full article.

Im sorry I was selfish, he said.

You see, Ive been trying to get him to get a vasectomy for years. I was sick of hormonal birth control, sick of being the one in charge of birth control, sick of being the one tracking my ovulation, sick of the burden of me not getting pregnant being solely on my shoulders when he is an equal partner in the relationship. I had been on hormonal birth control for a decade prior to having children, and it wasnt until I was off it that I realized the hormones had wreaked havoc on my emotional state.

There was no way I was going back to that.

I know how babies are made, I replied.

And its true. I do.

Ive had 4 pregnancies and live births. Ive written countless articles about pregnancy, fertility, and womens health. I was a microbiology and molecular genetics major in college. I religiously track my ovulation and know its signs in my body, too.

I have always known I was pregnant either prior to a missed period or days after. Always.

This pregnancy was not a surprise. We both knew the risks of having unprotected sex particularly after I remembered I was ovulating. However, after more than five years of this same scare (look, you can know all the things and also be stupid and lazy) and having false alarms, we got complacent.

Story continues

So imagine my chagrin when about a week after having unprotected sex, my nipples were sore and Id been so exhausted that Id fallen asleep twice before 8:30 pm.

I took a pregnancy test two days before my expected period and it was negative. The sigh of immediate relief (albeit, accompanied with a slight twinge of disappointment) coursed through my entire body.

Of course, Id had thoughts of having a fifth child.

I love babies children not as much but I recognize that kids are the natural consequence of babies. My husband adores our children and considers them the best thing weve ever done (or will ever do). Were financially and emotionally able to have another child. And yes, the thought of having another fat, chubby baby to snuggle and nurse and hold was tempting.

But, I have also only recently reclaimed my life from 4 back-to-back pregnancies. Prior to this pregnancy, I have been pregnant for 3 years and nursed for over 9. I will be 44 years old in two months and already have four other kids aged 12, 10, 8, and 5.

My body is tired. I am tired.

So when I had a positive pregnancy test 4 days after my period was supposed to start, I was severely dismayed. More than that, I was terrified.

I mourned.

I would be restarting the clock on when I would have bodily autonomy without being tethered to a tiny human who needs so much. I realize its my job and function as a parent to provide that and also, my freedom will be severely restricted and I mourn that inevitability. They can both be true at the same time.

I will forever love and appreciate my husband for what he said to me after I finished crying. He said he was okay if I did not want to keep it that he would support me.

We discussed it at length and decided wed most likely choose to proceed with the pregnancy.

What if my husband hadnt been so supportive?

What if I didnt live in California, where it is legal up to 10 weeks pregnant to have a medical abortion (abortion via drugs) and 24 weeks for a surgical abortion?

What if I wasnt regularly having conversations about abortion with both my husband and our kids? (Yes, weve discussed the topic many times with my kids and in fact, when we told them about my pregnancy, I told them we might not keep it in order to normalize abortion.)

What if I still felt the effects of my Christian and sex-negative upbringing in regards to pregnancy and sex? What if I felt shame for even contemplating an abortion?

What if I could not afford to have this baby, did not have adequate healthcare, or did not have a vast network of people to help me?

I know that once this article publishes, I will receive hate emails and death threats because thats what happens every time I, a woman of color, publish an article that the establishment doesnt like. People will call me all sorts of vile names and threaten to report me to Child Protective Services (CPS).

But I also know that I have a lot of privilege in where I live, in being financially able to support this baby along with my other children, in having excellent healthcare, and in the fact that our livelihood is not dependent on me staying in the good graces of public opinion.

I tell you my story because I am confident that I am not the only person who is tired. I am not the only one who has children and has contemplated abortion despite being financially and emotionally capable of carrying a baby to term.

I tell you my story because Im sick of people dying.

Ultimately, the consequence of overturning Roe v. Wade is that people who did not need to die for want of a medical procedure, will.

According to the Guttmacher Institute, 930,000 abortions were performed in the U.S. in 2020, of which more than 1 in 3 were obtained in the 26 states that will, or are likely to, ban abortion. 13 of these states have trigger laws in place so that within days or hours of Roe v. Wade being overturned, bans were automatically enacted.

Evidence also shows the disproportionate and unequal impact abortion restrictions have on people who are already marginalized and oppressed, said Dr. Herminia Palacio, Guttmacher Institute President and CEO, in a recent statement. Including Black and Brown communities, other people of color, people with low incomes, young people, LGBTQ communities, immigrants and people with disabilities.

The overturning of Roe v. Wade isnt about states rights. Its about terrorizing our communities with the threat of maternal death, lost wages, disability due to complications in pregnancy, and shame.

And lets be real. The overturning of Roe v. Wade doesnt stop abortions for the privileged. Those who have access to money and networks will always have options with unwanted or life-threatening pregnancies; it is unacceptable that someone with fewer privileges and less access will not.

Ill be honest.

I did not want to tell people that I considered aborting this pregnancy, except I refuse to live in shame or hiding. I refuse to contribute to the further stigmatization of a perfectly reasonable option for a pregnant person, no matter what that reason may be.

If you are pregnant or can become pregnant, you deserve the option of easily ending a pregnancy. I know my story isnt terribly dramatic or exciting except thats exactly why its important. Abortion does not need to be dramatic or exciting. It just is. If my story can can be one tiny pebble joining all the other pebbles rippling across the world to make abortion legal, safe, and normal, it will have been worth all my discomfort.

Launch Gallery: Celebrities Who Opened Up About Having Abortions

Best of SheKnows

Sign up for SheKnows' Newsletter.For the latest news, follow us on Facebook, Twitter, and Instagram.

Excerpt from:
I'm Pregnant with My 5th Child & I'm Not Ashamed to Say Abortion is an Option - Yahoo Life

Of all the fungi that live in the human body, the most infamous is probably the yeast Candida. This distant cousin of bakers yeast is notorious for causing various types of thrush that can be a major nuisance, but it can also lead to an invasive infection that may, on occasion, prove fatal. In a study published today in Nature Immunology, a Weizmann Institute of Science research team headed by Prof. Jakub Abramson uncovered a previously unknown defense mechanism employed by the immune system in fighting Candida infections.

Candida is present at low levels in the bodies of most healthy people, forming part of the microbiome a diverse spectrum of microbes that reside peacefully in our gut and on our skin. Under normal circumstances, Candida is held in check by the immune system, but it can occasionally grow excessively, invading the lining of the mouth, the vagina, the skin or other parts of the body. In severe cases, it can spread to the bloodstream and from there to the kidneys. Such life-threating infections may occur when a persons immune system has been weakened, for example, by AIDS or by immunosuppressive drugs such as cancer chemotherapy or steroids. Antibiotics, which wipe out many of the beneficial bacteria within our microbiome, can also unleash local or invasive Candida eruptions by providing this yeast with an unfair advantage vis--vis other microorganisms. Thats why, for instance, women sometimes develop a vaginal yeast infection after taking antibiotics.

Until now, the immune cells that got most of the credit for defending the body against Candida were the small, round lymphocytes of the T cell type, called TH17. These cells were also the ones to take the blame when this defense failed.

In the new study, postdoctoral fellow Dr. Jan Dobe, working together with colleagues in Abramsons lab in Weizmanns Immunology and Regenerative Biology Department, discovered that a powerful commando unit of TH17 cells capable of fighting Candida cannot be generated without crucial early support from an entirely different contingent: a subset of rare lymphoid cells known as type-3 innate lymphoid cells, or ILC3, that express a gene called the autoimmune regulator, or Aire

The two groups of cells belong to the two different arms of the immune system, which, like foot patrols and specialized units, join forces against a common enemy. The Aire-ILC3s part of the more ancient, innate arm spring into action almost immediately upon encountering a threat in this case, a Candida infection. The TH17s belong to the immune systems more recent, adaptive arm, which takes several days or even weeks to respond, but which launches a much more targeted and potent attack than the innate one.

The scientists found that as soon as Candida starts infecting tissues, the Aire-ILC3s engulf the yeast whole, chop them up and display some of the yeast pieces on their surfaces. Thats how these bits are presented to the TH17s, a few of which are generally on call in the lymph nodes, ready for an infection alert. This kind of presentation instructs the specialized T cells to start dividing rapidly, soaring in number from a few lone commandos to several hundred or even thousands of Candida-specific fighters, capable of destroying the yeast at the sites of infection.

We have identified a previously unrecognized immune system weapon that is indispensable for orchestrating an effective response against the fungal infection, Abramson says.

Abramson became intrigued by Candida because it commonly leads to severe, chronic infections in people with a rare autoimmune syndrome caused by defects in the Aire gene. Abramsons lab had conducted extensive studies of this gene, helping to clarify its role in preventing autoimmune disorders. That research, as well as studies by other scientists, had shown that Aire-expressing cells in the thymus instruct developing T cells to refrain from attacking the bodys own tissues. When Aire is defective, T cells fail to receive proper instructions, consequently causing widespread autoimmunity that wreaks havoc in multiple body organs. But one puzzle remained: Why would Aire-deficient patients suffering from a devastating autoimmune syndrome also develop chronic Candida infections?

While trying to complete the Aire puzzle, Dobe and colleagues found that outside the thymus, Aire is also expressed in a small subset of ILC3s in the lymph nodes. The researchers then genetically engineered two groups of mice: One lacked Aire in the thymus, and the other group lacked it in the ILC3s in the lymph nodes. The first group developed autoimmunity but was able to successfully fight off Candida. In contrast, those in the second group, the ones lacking Aire in ILC3s, did not suffer from autoimmunity, but were unable to generate numerous Candida-specific TH17s. Consequently, they failed to effectively eliminate Candida infections. In other words, without Aire-expressing ILC3s, the specialized T cells needed for fighting Candida were not produced in sufficient numbers.

We found an entirely new role for Aire, one that it plays in the lymph nodes turning on a mechanism that increases the numbers of Candida-fighting T cells, Dobe explains.

These findings open up new directions of research that in the future may help develop new treatments for severe Candida, and possibly for other fungal infections. The newly discovered mechanism might, for example, help produce large numbers of Candida-fighting T cells to be used in cell therapy. And if scientists one day identify the signals by which Aire-ILC3s boost T cell proliferation, these signals themselves might provide the basis for new therapies.

Study participants also included Osher Ben-Nun, Amit Binyamin, Dr. Yael Goldfarb, Dr. Noam Kadouri, Yael Gruper, Tal Givony and Itay Zalayat of Weizmanns Immunology and Regenerative Biology Department; Dr. Liat Stoler-Barak and Prof. Ziv Shulman of the Systems Immunology Department; Katarna Kovov, Helena Bhmov and Evgeny Valter of Charles University, Prague; Bergithe E. Oftedal and Prof. Eystein S. Husebye of the University of Bergen, Norway; and Dr. Dominik Filipp of the Institute of Molecular Genetics of the Czech Academy of Sciences, Prague.

Link:
Curbing Candida: The Cells That Keep Fungal Infections at Bay - Weizmann Wonder Wander - News, Features and Discoveries - Weizmann Institute of...