The Worlds Sexiest Fragrance Unveiled, But Its Not For You – Revyuh

Pheromones are intricate chemical compounds that organisms produce and emit as a form of communication. They enable members of the same species to transmit messages, including signaling their search for a mate.

To mimic the signals of female insects, farmers can place pheromone dispersers among their crops, which either trap or distract male insects from finding a mate.

While some of these molecules can be produced by chemical methods, chemical synthesis often generates harmful byproducts and incurs high expenses.

Researchers at the Earlham Institute in Norwich have used precision gene engineering techniques to transform tobacco plants into solar-powered factories that produce moth sex pheromones.

The key feature is that the scientists have demonstrated how these molecules can be produced without hindering the normal growth of the plant.

The Synthetic Biology Group, headed by Dr Nicola Patron at the Earlham Institute, employs advanced techniques to enable plants to produce highly valuable natural products. Through the principles of synthetic biology, the team constructs genetic modules that provide instructions to produce new molecules, which ultimately transforms plants such as tobacco into highly efficient factories. These plants merely require access to sunlight and water to carry out the production process.

Synthetic biology, as explained by Dr. Tatron, can allow us to engineer plants to make a lot more of something they already produced, or we can provide the genetic instructions that allow them to build new biological molecules, such as medicines or these pheromones.

The research team collaborated with scientists at the Plant Molecular and Cell Biology Institute in Valencia to genetically engineer Nicotiana benthamiana, a species of tobacco, to produce moth sex pheromones. This plant has previously been modified to produce Ebola antibodies and even coronavirus-like particles for use in COVID-19 vaccines. The group created new DNA sequences in the laboratory to imitate the genes of moths and added a few molecular switches to regulate their expression precisely, turning the manufacturing process on and off as needed.

A crucial aspect of the recent study was the capacity to adjust the production of pheromones, as forcing plants to constantly produce these molecules can have negative consequences.

As we increase the efficiency, too much energy is diverted away from normal growth and development, adds Dr. Patron.

The plants are producing a lot of pheromone but theyre not able to grow very large, which essentially reduces the capacity of our production line.

This new study provides a way to regulate gene expression with much more subtlety.

The team conducted experiments in the laboratory to test and improve the regulation of genes responsible for generating a mixture of particular molecules that imitate the sexual pheromones of moth species, such as cotton bollworm and navel orangeworm moths.

Through their research, they demonstrated that copper sulfate could be utilized to precisely adjust the behavior of these genes, enabling them to manage both the extent and timing of gene expression.

This is especially significant since copper sulfate is a cost-effective and easily accessible substance that has already been approved for agricultural use. Moreover, they were able to meticulously regulate the production of diverse pheromone components, which enabled them to modify the combination to better match specific moth species.

Weve shown we can control the levels of expression of each gene relative to the others, points out Dr. Patron. This allows us to control the ratio of products that are made.

Getting that recipe right is particularly important for moth pheromones as theyre often a blend of two or three molecules in specific ratios. Our collaborators in Spain are now extracting the plant-made pheromones and testing them in dispensers to see how well they compare to female moths.

The team aims to establish a pathway for using plants as a standard method for producing an extensive variety of valuable natural products.

A major advantage of using plants is that it can be far more expensive to build complex molecules using chemical processes, adds Dr. Patron. Plants produce an array of useful molecules already so were able to use the latest techniques to adapt and refine the existing machinery.

In the future, we may see greenhouses full of plant factories providing a greener, cheaper and more sustainable way to manufacture complex molecules.

The findings were published in the journalPlant Biotechnology.

Image Credit: Getty

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The Worlds Sexiest Fragrance Unveiled, But Its Not For You - Revyuh

City of Hope appoints John D. Carpten, Ph.D., as director of its … – BioSpace

LOS ANGELES, April 6, 2023 /PRNewswire/ --City of Hope, one of the largest cancer research and treatment organizations in the United States, today announced the appointment of John D. Carpten, Ph.D., as director of the National Cancer Institute-designated comprehensive cancer center, director of Beckman Research Institute of City of Hope and chief scientific officer. Carpten will also hold the Irell & Manella Cancer Center Director's Distinguished Chair and the Morgan & Helen Chu Director's Chair of the Beckman Research Institute. Carpten will provide overall executive leadership and strategic direction for research at City of Hope. He joins City of Hope from the University of Southern California (USC), where he was professor and chair of the Department of Translational Genomics at the Keck School of Medicine of USC and associate director of the cancer center.

John Carpten to direct City of Hope Comprehensive Cancer Center and its Beckman Research Institute

"We are excited to welcome Dr. Carpten to City of Hope and look forward to his leadership in advancing the research mission of our growing national cancer research and care system," saidRobert Stone, City of Hope's CEO and Helen and Morgan Chu Chief Executive Officer Distinguished Chair. "Dr. Carpten's expertise and unwavering commitment to drive and accelerate cancer research and discovery will benefit our patients across the country."

Carpten is an internationally recognized expert in genome science, with training in multiple disciplines, including germline genetics for disease risk and predisposition, somatic cancer genomics, health disparities research, cell biology, functional genomics and precision medicine. Prior to USC, he served as director of the Division of Integrated Cancer Genomics, and later, deputy director of Basic Research at Translational Genomics Research Institute, now a part of City of Hope. Earlier in his career, Carpten completed a postdoctoral fellowship at the National Human Genome Research Institute (part of the National Institutes of Health) in cancer genetics, where he was later promoted to the tenure track in 2000. Carpten earned his Ph.D. from The Ohio State University in 1994, with a focus on human genetics.

Nationally recognized as a leader in health disparities research, he has been a tireless advocate for reaching underserved populations. Carpten has been a pioneer in the understanding of the role biology plays in disparate cancer incidence and mortality rates experienced by underrepresented populations. As such, his work has impacted our understanding of a variety of cancer types, particularly those that disproportionately affect underrepresented minorities, including prostate cancer, breast cancer, colorectal cancer, multiple myeloma and pediatric cancers.

Carpten has also played a significant role in the national cancer research agenda and has won numerous awards. He has served as a member of the National Cancer Institute (NCI) Board of Scientific Counselors. In 2019, he served as Program Committee chair for the American Association of Cancer Research (AACR) Annual Scientific Conference in Atlanta, which included over 21,500 international participants. In 2021, he was inducted into the AACR Fellows of the Academy.Appropriately, in 2022, President Joe Biden appointed Carpten as the first African-American chair of the National Institutes of Health's National Cancer Advisory Board, a distinguished post that helps set the national cancer research policy agenda.

"Dr. Carpten will be a key catalyst in driving the democratization of cutting-edge cancer care across the City of Hope national network in order to ensure more patients and diverse communities have full access to the leading cancer research, treatment and care they need," said Michael A. Caligiuri, M.D., president of City of Hope National Medical Center and the Deana and Steve Campbell Physician-in-Chief Distinguished Chair. "He has been a leading national voice and expert in ending disparities in cancer outcomes and care, and the importance of building a more diverse workforce in cancer research."

"Along with tremendous honor and humility, I am both thrilled and eager to work with the exceptional leadership, faculty, staff and trainees to build upon the significant success of the research enterprise at City of Hope," said Carpten. "My goal is to create, execute and advance a transformative vision for cancer research that aligns with national priorities to significantly reduce cancer mortality rates and improve outcomes for patients from all walks of life through the unique national patient reach of City of Hope. To have the opportunity to help lead this world-class, translational cancer research platform is a dream come true."

As part of this transition, City of Hope's current provost, chief scientific officer, and Beckman Research Institute and cancer center director, Steven T. Rosen, M.D., will step into a new leadership role as executive vice president and director emeritus of Beckman Research Institute and City of Hope's cancer center, continuing to improve the lives of cancer patients through his research and patient care, and his dedication to building coalitions among like-minded organizations and individuals dedicated to preventing and curing cancer. During his decade-long tenure, Rosen has made countless contributions to faculty recruitment, research and treatment advances in the field, to the growth and reach of City of Hope, to the education, development and mentorship of faculty and staff, and to guiding City of Hope as one of only 53 NCI-designated comprehensive cancer centers, most recently earning an "exceptional" rating by the NCI in the 2023 renewal of this designation.

"City of Hope and the countless patients he has so positively impacted owe a tremendous debt of gratitude to Dr. Rosen for all he has done to advance science and research at City of Hope and save lives," said Caligiuri. "We will benefit tremendously from Dr. Rosen's continued leadership and expertise through this transition and into the future."

About City of Hope

City of Hope's mission is to deliver the cures of tomorrow to the people who need them today. Founded in 1913,City of Hopehas grown into one of the largest cancer research and treatment organizations in the U.S. and one of the leading research centers for diabetes and other life-threatening illnesses. City of Hope research has been the basis fornumerous breakthrough cancer medicines, as well as human synthetic insulin and monoclonal antibodies. With an independent, National Cancer Institute-designated comprehensive cancer center at its core,City of Hope brings a uniquely integrated model to patients spanning cancer care, research and development, academics and training, and innovation initiatives. City of Hope's growing national system includes its Los Angeles campus, a network of clinical care locations across Southern California, a new cancer center in Orange County, California, andtreatment facilities in Atlanta, Chicago and Phoenix. City of Hope's affiliated group of organizations includesTranslational Genomics Research InstituteandAccessHopeTM. For more information about City of Hope, follow us onFacebook,Twitter,YouTube,InstagramandLinkedIn.

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City of Hope appoints John D. Carpten, Ph.D., as director of its ... - BioSpace

Modernized Algorithm Predicts Drug Targets for SARS-CoV-2, Other … – GenomeWeb

NEW YORK Researchers in Germany have modernized an aging computational tool for metabolomics and built a new workflow for predicting drug targets to fight SARS-CoV-2. While the COVID-19 pandemic may be winding down, the developers believe the technology can help manage the disease as it becomes endemic and be applied to other RNA viruses.

The method, called pymCADRE, represents an update to a 2012 method called mCADRE, but it is written in the more widely used Python programming language. The researchers then paired it with an algorithm called PREDICATE for Prediction of Antiviral Targets which is based on a method developed by Sean Aller and colleagues at the University of Warwick and at the UK's Defence Science and Technology Laboratory.

The combined workflow enables the creation of metabolic models and analysis of viral biomass functions to predict antiviral targets for host organs using multiple genomes. Viruses, including SARS-CoV-2, have to draw on metabolic resources from host cells in order to replicate in the body.

"Our tool predicts exploitable cellular metabolic pathways that can be inhibited to suppress virus replication with minimal or no effect on the cell," computational biologists at Eberhard Karls University of Tbingen in Germany wrote in a recent paper in PLOS Computational Biology that described both updated algorithms and the combined workflow.

While scientists worldwide were able to develop messenger RNA and viral vector COVID-19 vaccines in record time, the Tbingen group noted that immunity to viral infections wanes over time and vaccines cannot keep up with later mutations. "Hence, effective pandemic preparedness requires discovering broadly acting antivirals with high resistance barriers," they wrote.

The Tbingen researchers chose to adapt mCADRE short for metabolic Context-specificity Assessed by Deterministic Reaction Evaluation because the transcriptomic data of host cells they had at the start of their work fit mCADRE, according to lead author Nantia Leonidou, a PhD student in bioinformatics at the university. Leonidou began the pymCADRE work as part of her thesis for a master's degree she received in 2020.

The group decided to update mCADRE by translating it to the open-source Python language to make it more accessible because Python is more widely used by bioinformaticians mCADRE was written in Matlab, a proprietary language that dates to the 1970s.

"It's nice to see it updated. It makes it more usable," said Nathan Price, one of the developers of mCADRE. "That will make the method more broadly used again."

The pymCADRE and PREDICATE combination workflow looks at metabolic networks and viral genome sequences to predict "robust druggable targets" to fight emerging RNA viruses, as SARS-CoV-2 was when the project started, according to the PLOS Computational Biology article.

With these algorithms, the University of Tbingen team was able to build a metabolic network of primary bronchial epithelial cells that had been infected with the then-novel coronavirus. They subsequently identified "promising" targets in purine metabolism and uncovered evidence of viral inhibition in pyrimidine and carbohydrate metabolism.

"We put everything together to be able to create multiple viral biomass reactions at the time," such as for multiple sequences and multiple variants, Leonidou said. "We try to see what metabolic changes happen" after infection, she said.

The PREDICATE software also provided in silico verification of the targets for all five SARS-CoV-2 variants of concern that the World Health Organization had designated by the time the paper was submitted for publication in July 2022.

Price, who was affiliated with the Institute for Systems Biology in Seattle and with the University of Illinois at the time he worked on mCADRE, said that it was "interesting" that the German team is looking at viral replication because he and his colleagues were not involved in target discovery in the early 2010s.

"The more that we can understand the processes behind viral replication, [the more we can] understand the weaknesses that might be able to be exploited as a drug target for their specific needs to achieve this replication," said Price, who is now CSO of Thorne HealthTech, a data-driven wellness and nutritional supplements company.

Leonidou said that pymCADRE is "fully transferable and applicable to any RNA virus," and PREDICATE can be used to create multiple viral biomass reactions. This makes the technology useful for the next viral epidemic, or even for investigating coronaviruses linked to the common cold. A preprint manuscript by some of Leonidou's colleagues, for instance, tests the pipeline on theinfluenzaAanddengueviruses.

As it stands now, though, pymCADRE is not suitable for bacterial diseases because bacteria have their own metabolic systems and are not dependent on a host.

But Leonidou noted that her team is building models to simulate bacterial metabolism because the epidemiologic world "kind of forgot antibacterial resistance" during the COVID-19 pandemic, which could be a recipe for disaster in the future. "Maybe the next pandemic is not viral [but] bacterial," she said.

Leonidou said that it is too soon to think about commercializing the pymCADRE and PREDICATE technology, though her team at Tbingen has some academic and pharmaceutical industry partners who are working on medicinal chemistry, pharmacokinetics, and pharmacogenomics applications of the workflow in silico and with mouse models. She declined to name any of those partners because their work has not been published.

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BU researcher wins $3.9 million NIH grant to develop novel therapeutic modalities for Alzheimer’s – News-Medical.Net

Julia TCW, PhD, assistant professor of pharmacology & experimental therapeutics at Boston University Chobanian & Avedisian School of Medicine, has received a five-year, $3.9 million grant from the National Institutes of Health's (NIH) National Institute on Aging. The award will fund her research project, "Elucidating endolysosomal trafficking dysregulation induced by APOE4 in human astrocytes."

Alzheimer's disease (AD) is a progressive neurodegenerative disorder and the most common cause of dementia, affecting more than 5.8 million individuals in the U.S. Scientists have discovered some genetic variants that increase the risk for developing Alzheimer's; the most well-known of these, for people over the age of 65, is APOE4.

"APOE4 is the major genetic risk factor for Alzheimer's disease, however we do not fully understand how APOE4-driven endolysosomal trafficking defects influence disease risk in human AD brain cells. The goal of this project is to understand the molecular mechanisms of APOE4 and identify targets that can reverse the phenotype," says TCW, who also is a director of the Laboratory of Human Induced Pluripotent Stem Cell Therapeutics.

One of the important questions is whether these endolysosomal pathway genes reveal novel mechanistic defects that can be targeted for therapeutics.

Human induced pluripotent stem cells (iPSC) model application, and the knowledge gained from this proposal, will be essential to the development of novel AD therapeutic modalities."

Julia TCW, PhD, assistant professor of pharmacology & experimental therapeutics at Boston University Chobanian & Avedisian School of Medicine

TCW received her PhD and AM in molecular and cellular biology from Harvard University. She then pursued her postdoctoral research in the department of neuroscience at the Ronald M. Loeb Center for Alzheimer's Disease at Icahn School of Medicine at Mount Sinai, New York. Subsequently she served there as research faculty in the department of genetics and genomic sciences and neuroscience where her research focus was on the development of iPSC models and AD genetics.

In addition to this grant, TCW has been awarded the Druckenmiller Fellowship award from New York Stem Cell Foundation, a K award from the National Institutes of Health-National Institute of Aging, a BrightFocus Foundation grant, and was named a 2022 Toffler Scholar by the Karen Toffler Charitable Trust.

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BU researcher wins $3.9 million NIH grant to develop novel therapeutic modalities for Alzheimer's - News-Medical.Net

Providing critical insights for animal development – HKU biologists … – EurekAlert

A research team led by Dr Chaogu ZHENG from the School of Biological Sciences at the University of Hong Kong (HKU) has made a significant discovery about the evolutionary age of different type of cells in a small animal calledCaenorhabditis elegans (C. elegans). By using single-cell transcriptomic data and refined phylostratigraphy, the team determines the transcriptomic age of individual cells, which means they are able to estimate the evolutionary origin of different cells based on the age of the genes expressed in the cells.

Their findings shed light on the cellular basis of the hourglass pattern of animal development, revealing significant variation in the transcriptome age of different cell types. These results also provide insights into the varying contribution of different cells and tissues to adaptation, and the evolutionary relationship among cell types. These findings offer new perspectives on the genetic mechanisms that drive the evolution of species and have been published in the leading multidisciplinary journalPNAS.

Insights from Molecular Studies on Hourglass ModelThe embryos of all animals share similar morphology at the middle stage of embryonic development while having larger morphological divergence at earlier and later stages. This pattern is often referred to as the hourglass pattern of development, meaning that all animal development experiences an evolutionarily conserved phase during mid-embryogenesis.

Recent molecular studies have shown that embryos at the middle stage of embryogenesis express the oldest transcriptome, which means that the oldest and most conserved genes are used at this stage during gene expression. In contrast, younger genes are expressed in the earlier and later stages of embryonic development. This was discovered by analysing gene expression of the embryos in different developmental stages using a technique called phylostratigraphy, a method used to determine gene ages by comparing their sequences across different species.

However, these studies are limited in that they could only determine the transcriptome age of the entire organism throughout development but not in individual cells or tissue. This limitation is significant because obtaining information about the age of genes expressed in specific cells and tissue is crucial for gaining a more detailed understanding of the evolution of developmental patterns among species, as well as the genetic mechanismsdriving it. Additionally, it can shed light on how individual tissue and cells contribute to the hourglass pattern, which is a crucial aspect of understanding how different organs and tissues contribute to the evolution and adaptation of the overall developmental process in animals.

From Whole-Organism to Single-Cell AnalysisTo fill this knowledge gap, the research team studies the transcriptome age of the nematodeC. elegansat the single cell level using RNA sequencing. They look at RNA expression from both whole embryos (or organism) and individual cells to gain a comprehensive understanding of how different genes are used during embryonic and larval development.

The team first identifies a period of the oldest transcriptome duringC. elegansmid-embryogenesis, which starts after gastrulation, a process that forms different germ layers in the embryo and continues into the early development of an organ. More importantly, the research team finds that in early embryos, certain cells used older genes than other cells. For example, cells that would later become the germline (which is responsible for passing on genetic information to offspring) use older genes than somatic tissues in the body. Similarly, cells that would later become the endoderm (which gives rise to the digestive tract) use older genes compared to other cell types during early development. Among differentiated cells, muscles appear to have the oldest transcriptome than other cell types.

It is also observed that the variation in transcriptome ages among the cell and tissue types remain small in early embryonic stages and grow bigger at late embryonic and larval stages as cells differentiate. Tracking the dynamics of transcriptome age along lineages identifies certain tissues, such as the skin, that contribute to the rise of the transcriptome age in late embryos.

Further analysis of the variation in transcriptome ages among the 128 different types of neurons inC. elegansnervous system reveals that a specific group of chemosensory neurons and their downstream interneurons express very young transcriptomes, which may have contributed to adaptation in recent evolution, as many newly evolved young genes are associated with sensing environmental factors. Finally, by analysing the variation in transcriptome age among the different neuron types, as well as the age of the genes that regulate their development (fate regulators), the research team is able to hypothesize about the evolutionary history of some of these 128 neuron types.

UsingC. elegansas an example, we showcase how the transcriptome age at the single-cell level can provide insight into the cellular basis of developmental innovation and help understand the functional diversity and evolutionary origin of cell types, said Dr Fuqiang MA, a Postdoctoral Fellow of HKU School of Biological Sciences and the first author of the paper.

Dr Zheng, the supervisor of the research project, highlighted that this study serves as an example of using the cutting-edge single-cell transcriptomics to study old problems in evolutionary biology. Dr Zheng envisions that the possibility of determining the evolutionary age of individual cell types at the transcriptome level can open up new research directions and advance our understanding of the genetic mechanisms that drive the evolution of species.

About the research paper:Ma F, Zheng C. Transcriptome age of individual cell types in Caenorhabditis elegans.Proc Natl Acad Sci U S A.2023 Feb 28;120(9):e2216351120. doi: 10.1073/pnas.2216351120.

The journal paper can be accessed from here:www.pnas.org/doi/10.1073/pnas.2216351120

This work is supported by funding from the National Science Foundation of China, the Research Grant Council of Hong Kong, and The University of Hong Kong.

Images download and captions:https://www.scifac.hku.hk/press

For media enquiries, please contact Ms Casey To, External Relations Officer (Tel: 3917-4948; email:caseyto@hku.hk) and Ms Cindy Chan, Assistant Communications Director of Faculty of Science (Tel: 3917-5286; email:cindycst@hku.hk).

Proceedings of the National Academy of Sciences

Meta-analysis

Cells

Transcriptome age of individual cell types in Caenorhabditis elegans

22-Feb-2023

Disclaimer: AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert system.

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Providing critical insights for animal development - HKU biologists ... - EurekAlert

Students Express Frustrations About the Middle Class Scholarship – The Triton

On the UC San Diego subreddit, multiple UCSD students have made posts asking if others had delays receiving their Middle Class Scholarship (MSC), with commenters saying that they were also either experiencing delays, the amount they received was lowered, or their scholarships were applied in a way that they did not expect.

The Middle Class Scholarship is for University of California (UC) or California State University (CSU) students who are California residents and have a family income of $201,000 or less.

The delay with the Middle Class Scholarship is not specific to UCSD all CSU campuses have also experienced delays in awarding the MCS for the 2022-23 school year.

Iris Chen, a second-year Clinical Psychology major, shared some of her experience with the scholarship. Chen received an email from the UCSD Financial Aid and Scholarships Office in October 2022 that said the scholarship would be sent out by late November 2022.

I did not receive my amounts for Fall and Winter until mid-January after Winter [tuition] fees were due, Chen said.

In addition to the delay, Chen had to have a Zoom meeting with a UCSD financial aid advisor and then wait a week for the scholarship amount to be added to her financial aid because it was not done automatically. The amount she received was also $2,000 less than what was expected because of institutional aid. Institutional aid is money that comes from the university, and is usually given in the form of grants or scholarships.

Despite the inconvenience of these issues, Chen stated, I am grateful that the MCS exists because the extra $3,000 helps me cover textbooks, online homework access codes, and gas.

Arlene Nagtalon, a second-year Molecular and Cell Biology major, is another student who qualified for the scholarship. She stated that she had very mixed feelings about it this year and that the waiting period was nerve-wracking.

As a way to try to relieve her concerns, Nagtalon continued to apply to other scholarships. After looking through Reddit and seeing that other people were also experiencing the same issues as she was, Nagtalon thought it was reassuring to know she was not the only one who had to wait.

The amount of scholarship money Nagtalon received this year in January was lower than the amount she received last year, which she did not expect.

Its really frustrating to know that the amount I was offered last year was decreased now considering that, you know, my family is still considered middle class and we havent done anything to either increase or decrease [the amount]; our family income has stayed pretty much the same, Nagtalon stated.

Nagtalon continued to convey the concerns she had, not only for herself, but for other students who would hope to benefit from this scholarship.

Im lucky to still be living at home, and this is my second year commuting as well, but I do know friends who rely on these types of scholarships for rent, and you know, groceries and other things basic needs essentially, Nagtalon said.

For Nagtalon, receiving an email or other form of communication to let her know that the scholarship amount she was receiving this year would be less compared to last year would have been preferred to the unpleasant surprise of the decrease. She still does not know the reason for the change in the amount she was given.

Silvia Marquez, Executive Director of the Financial Aid and Scholarships Office, explained that the amount of scholarship funds that were awarded had changed for some students due to adjustments made to the MCS program.

The MCS program was expanded beginning in the 2022-23 academic year as part of the state budget agreement, which included a $515 million ongoing augmentation to increase the number of eligible students in California, Marquez said. Overall, students saw an increase in the amount of gift aid awarded.

As a result of this expansion, the formula that determines the award amount a student receives was updated to take into account a students total cost of attendance instead of just tuition costs.

Marquez said that as a result of this new formula, At UC San Diego, the number of eligible students grew by approximately 800%, from just over 1,200 eligible students in 2021-22 to over 11,000 in 2022-23.

According to Marquez, MCS funds are still being awarded weekly, and the Financial Aid and Scholarships Office is in communication with colleagues across the UC system to give feedback on the updated MCS program.

Alorah Atondo is a Copy editor and News writer for The Triton.

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Mendus redeems the outstanding convertible bonds from Negma … – GlobeNewswire

Mendus AB (Mendus publ; IMMU.ST), a biopharmaceutical company focused on immunotherapies addressing tumor recurrence, today announced that the Company has agreed with Negma Group Ltd (Negma) to redeem the remainder of the first tranche of convertible bonds issued to Negma on 3 January 2023 for an amount of SEK 3.9M, corresponding to the nominal amount for the outstanding convertible bonds, plus paying an 8% premium in accordance with the provisions in the agreement with Negma.

The decision by Mendus to redeem the convertible bonds was triggered by the Mendus share price reaching the floor conversion price set for the first tranche of convertible bonds. Conversions below the floor conversion price result in higher conversion costs for Mendus.

The Negma financing is part of a total SEK 250M financing commitment by Van Herk Investments and Negma, which Mendus announced in August 2022. The use of the Negma facility is at the discretion of the Company. Following this redemption, there will be no remaining outstanding convertible bonds.

For further information regarding the financing arrangements in place with Negma and VHI, please refer to the press releases published on 26 August 2022, 26 October 2022, 5 January 2023 and 7 March 2023.

Please refer to the section Convertible Bonds of the Investors page at Mendus website for a summary of previously issued shares upon conversion in regard to the financing arrangement with Negma.

This information is such information that Mendus AB (publ) is obliged to make public pursuant to the EU Market Abuse Regulation (No. 596/2014). The information was submitted for publication through the agency of the contact persons set out below on April 6, 2023, at 17:15 CEST.

FOR MORE INFORMATION, PLEASE CONTACT:Erik Manting

Chief Executive Officer

E-mail: ir@mendus.com

INVESTOR RELATIONSCorey Davis

LifeSci Advisors, LLC

Telephone: + 1 212-915-2577

E-mail: cdavis@lifesciadvisors.com

MEDIA RELATIONSMario Brkulj

Valency Communications

Telephone: +49 160 9352 9951

E-mail: mbrkulj@valencycomms.eu

ABOUT MENDUS AB (PUBL)

Mendus is dedicated to changing the course of cancer treatment by addressing tumor recurrence and improving survival outcomes for cancer patients, while preserving quality of life. We are leveraging our unparalleled expertise in allogeneic dendritic cell biology to develop an advanced clinical pipeline of novel, off-the-shelf, cell-based immunotherapies which combine clinical efficacy with a benign safety profile. Based in Sweden and The Netherlands, Mendus is publicly traded on the Nasdaq Stockholm under the ticker IMMU.ST. http://www.mendus.com/

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Mendus redeems the outstanding convertible bonds from Negma ... - GlobeNewswire

Sustainability in research: If you want to green your lab, start with the … – McGill Reporter

Members of the Reinhardt lab use ultra-low temperature freezers to store reagents and other biological samples. Siddhi Aubeeluck

If you spend time in the Reinhardt Laboratory, you will likely see members of the lab reach into the ultra-low freezers to access biomedical samples needed for their work. What you wouldnt notice is that the freezer is several degrees warmer than it was in the past. In an effort to reduce the environmental impact of their research as well as the strain on their equipment, Dieter Reinhardts team raised the temperature of their freezers from the standard -80 degrees Celsius.

While ultra-low temperature freezers are crucial to preserving tissues, enzymes, antibodies, and other biological research samples, often the temperature is chosen based on convention rather than necessity.

Despite these machines being dubbed -80 freezers, there is no scientific reason behind that number when it comes to maintaining the quality and safety of samples. Whats more, increasing a freezers temperature from -80 C to -70 C or even -65 C can cut energy use by up to 30 per cent. With hundreds of ultra-low temperature freezers at McGill, this would be no small change in terms of the Universitys total energy consumption and the associated financial savings.

Compressors have to work very hard to maintain these ultra-low temperatures, said Reinhardt, PhD, and Canada Research Chair Tier 1 Laureate in Cell-Matrix Biology. This requires a lot of electricity, but its also hard on the compressors and will shorten the lifespan of your equipment, which is expensive to repair and replace. Increasing the temperature by just a few degrees can add years to this equipment and decrease how often you have to defrost it.

The answer isnt quite as simple as one-temperature-fits-all. Experience has taught me that for my reagents, theres not too much difference between -80 C and -65 C, which is what were using now, Reinhardt said. But if youre storing lots of messenger RNA, for example, your freezer might need to be colder because these reagents are the most sensitive to degradation.

For researchers working with samples that are difficult to acquire or take years to cultivate, the hesitation to change the temperature of their cold storage is understandable. This is why lab users around the world are working together to address this uncertainty by sharing their findings on how well specific reagents keep when stored in less cold but still very, very cold temperatures. Campaigns such as the Just Call Me Ultra-Low initiative, led by longtime independent sustainable research consultant Allen Doyle, are also encouraging scientists not to associate a specific temperature with their freezers.

This movement isnt novel on McGill campuses either. In 2011, researchers in the Faculty of Medicine received support from the Sustainability Projects Fund (SPF) for a Green Biobanking project, which helped labs implement a safe and effective technique for storing DNA samples at room temperature as an alternative to long-term freezer storage.

The reality is probably 80 to 90 per cent of the typical items stored in an ultra-low freezer are not being actively used and may never be, Reinhardt said. Since it takes so long to generate sophisticated reagents, you dont just get rid of the unused materials. You store them because they could very well be used in future experiments. As well as minimizing the energy used to keep research leftovers, its very important to have an accurate inventory of what is in the freezer and periodically review it, he added, to avoid losing track of samples due to high user turnover in the lab.

These sustainable lab practices and others are all steps that lab users can take as part of the International Freezer Challenge. This year, McGill is even offering its own prizes for labs that participate in the free competition, which has helped save more than 24 million kWh of energy worldwide since its creation six years ago.

Sign your lab up for the International Freezer Challenge and find McGill-specific resources and tips for how to take action on the Office of Sustainability website.

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Sustainability in research: If you want to green your lab, start with the ... - McGill Reporter

Two-organ chip to answer fatty liver questions – EurekAlert

image:The interaction between the small intestine and the liver of patients with non-alcoholic fatty liver disease (NAFLD) has been reproduced on a small chip view more

Credit: Mindy Takamiya/Kyoto University iCeMS

A new chip that holds different cell types in tiny, interconnected chambers could allow scientists to better understand the physiological and disease interactions between organs. The integrated-gut-liver-on-a-chip (iGLC) platform was designed by scientists at Kyoto Universitys Institute for Integrated Cell-Material Sciences (iCeMS), to improve understanding of non-alcoholic fatty liver disease (NAFLD). The researchers, together with colleagues in Japan, published their findings in the journal Communications Biology.

NAFLD affects a significant percentage of the population, but no effective treatments have been established, explains iCeMS bioengineer Ken-ichiro Kamei, who led the study. This is because NAFLD is a complex condition, involving a wide range of interactions inside and between the gut and the liver, known as the gut-liver-axis. It is very difficult to model these interactions using animals, such as mice, due to the many differences between species.

NAFLD involves the build-up of fat inside the liver, which can become severe. Currently, the only way to treat severe cases is with liver transplantation. Scientists need better approaches to study the condition to be able to discover improved options for treatment.

This isnt the first time scientists have developed organ-on-a-chip platforms, nor is it the first gut-liver platform, but previous devices have been imperfect. The platform developed by Kamei and his colleagues overcomes some but not all the issues with previous attempts.

The scientists tested their iGLC platform by placing cells from a liver cancer cell line and from a gut cancer cell line into separate chambers. The chambers are connected by tiny fluidic channels with strategically positioned valves that can be opened and closed. The platform also includes a pump for pushing fluid between the chambers. They allow a fluid medium to pass through both chambers while keeping the cells separate, mimicking the circulation moving between the gut and liver in the human body. It also allows the scientists to introduce new substances into the platform for example free fatty acids to test their impacts on the two interacting organs.

Importantly, the platform is made of a silicone material, called polydimethylsiloxane (PDMS), that is coated with two other substances: one that prevents the chip from absorbing fatty molecules that could affect experiments, and another that increases cell growth.

Significant changes in gene expression were seen in gut and liver cells cultured in the iGLC platform when compared to the same cells cultured on their own. The scientists also documented the specific changes that happened in the cells when free fatty acids were introduced for one or seven days. One day of free fatty acids led to the initiation of DNA damage inside the cells. Seven days of circulating free fatty acids led to their accumulation in the cells to the point that the DNA damage led to cell death, similar to severe cases of NAFLD.

The platform does not take into account the impacts of gut microbes or other factors on the gut-liver-axis. The experiments also used cancer cell lines, which dont represent the full diversity or functionality of cells in living human tissue, but the platform is a significant step forward.

We next plan to use liver and gut organoids derived from human stem cells so we can investigate NAFLD under precisely controlled conditions that more closely mimic patients physiological contexts, says iCeMS mechanical engineering researcher, Yoshikazu Hirai, the studys corresponding author.

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https://doi.org/10.1038/s42003-023-04710-8

About Kyoto Universitys Institute for Integrated Cell-Material Sciences (iCeMS):

At iCeMS, our mission is to explore the secrets of life by creating compounds to control cells, and further down the road to create life-inspired materials.

トップページ

For more information, contact:

I. Mindy Takamiya/Christopher Monahan

cd@mail2.adm.kyoto-u.ac.jp

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Please download the images and related files:

https://drive.google.com/drive/folders/17tsHLUg6Pd4BMlNsJPUaDYSmElurM3ou?usp=sharing

Communications Biology

Experimental study

Human tissue samples

Integrated-gut-liver-on-a-chip platform as an in vitro human model of non-alcoholic fatty liver disease

23-Mar-2023

Disclaimer: AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert system.

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Two-organ chip to answer fatty liver questions - EurekAlert

Blind dating in bacteria evolution – Newswise

Newswise Proteins are the key players for virtually all molecular processes within the cell. To fulfil their diverse functions, they have to interact with other proteins. Such protein-protein interactions are mediated by highly complementary surfaces, which typically involve many amino acids that are positioned precisely to produce a tight, specific fit between two proteins. However, comparatively little is known about how such interactions are created during evolution.

Classical evolutionary theory suggests that any new biological feature involving many components (like the amino acids that enable an interaction between proteins) evolves in a stepwise manner. According to this concept, each tiny functional improvement is driven by the power of natural selection because there is some benefit associated with the feature. However, whether protein-protein interactions also always follow this trajectory was not entirely known.

Using a highly interdisciplinary approach, an international team led by Max Planck researcher Georg Hochberg from the Terrestrial Microbiology in Marburg have now shed new light on this question. Their study provides definitive evidence that highly complementary and biologically relevant protein-protein interactions can evolve entirely by chance.

Proteins cooperate in a photoprotection system

The research team made their discovery in a biochemical system that microbes use to adapt to stressful light conditions. Cyanobacteria use sunlight to produce their own food through photosynthesis. Since much light damages the cell, cyanobacteria have evolved a mechanism known as photoprotection: if light intensities become dangerously high, a light intensity sensor named Orange Carotenoid Protein (OCP) changes its shape. In this activated form, OCP protects the cell by converting excess light energy into harmless heat. In order to return into its original state, some OCPs depend on a second protein: The Fluorescence Recovery Protein (FRP) binds to activated OCP1 and strongly accelerates its recovery.

Our question was: Is it possible that the surfaces that allow these two proteins to form a complex evolved entirely by accident, rather than through direct natural selection? says Georg Hochberg. The difficulty is that the end result of both processes looks the same, so we usually cannot tell why the amino acids required for some interaction evolved through natural selection for the interaction or by chance. To tell them apart, we would need a time machine to witness the exact moment in history these mutations occurred, Georg Hochberg explains.

Luckily, recent breakthroughs in molecular and computational biology has equipped Georg Hochberg and his team with a laboratory kind of time machine: ancestral sequence reconstruction. In addition, the light protection system of cyanobacteria, which is under study in the group of Thomas Friedrich from Technische Universitt Berlin since many years, is ideal for studying the evolutionary encounter of two protein components. Early cyanobacteria acquired the FRP proteins from a proteobacterium by horizontal gene transfer. The latter had no photosynthetic capacity itself and did not possess the OCP protein.

To work out how the interaction between OCP1 and FRP evolved, graduate student Niklas Steube inferred the sequences of ancient OCPs and FRPs that existed billions of years ago in the past, and then resurrected these in the laboratory. After translation of the amino acid sequences into DNA he produced them usingE. colibacterial cells in order to be able to study their molecular properties.

A fortunate coincidence

The Berlin team then tested whether ancient molecules could form an interaction. This way the scientists could retrace how both protein partners got to know each other. Surprisingly, the FRP from the proteobacteria already matched the ancestral OCP of the cyanobacteria, before gene transfer had even taken place. The mutual compatibility of FRP and OCP has thus evolved completely independently of each other in different species, says Thomas Friedrich. This allowed the team to prove that their ability to interact must have been a happy accident: selection could not plausibly have shaped the two proteins surfaces to enable an interaction if they had never met each other. This finally proved that such interactions can evolve entirely without direct selective pressure.

This may seem like an extraordinary coincidence, Niklas Steube says. Imagine an alien spaceship landed on earth and we found that it contained plug-shaped objects that perfectly fit into human-made sockets. But despite the perceived improbability, such coincidences could be relatively common. But in fact, proteins often encounter a large number of new potential interaction partners when localisation or expression patterns change within the cell, or when new proteins enter the cell through horizontal gene transfer. Georg Hochberg adds, Even if only a small fraction of such encounters ends up being productive, fortuitous compatibility may be the basis of a significant fraction of all interactions we see inside cells today. Thus, as in human partnerships, a good evolutionary match could be the result of a chance meeting of two already compatible partners.

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Blind dating in bacteria evolution - Newswise