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UK Researchers Uncover 58 New Mutational Signatures of Cancer – BioSpace
Posted: April 25, 2022 at 5:20 pm
Scientists from the United Kingdom may have identified several more environmental causes for cancer after evaluating the genetic data of over 12,000 cancer patients from National Health Servicefiles.
In arguably thelargest studyof its kind, researchers at Cambridge University Hospitals and the University of Cambridgelooked into whole-genome sequencing data of 12,222 patients to detect possible patterns in the DNA of cancer patients and succeeded. They found 58 new "mutational signatures," or patterns that offer clues on whether a particular patient had been exposed to certain environmental elements which led to cancer. These included cellular malfunctions, smoking and exposure to UV light.
Data were taken from the NHS's 100,000 Genomes Project, Genomics England's massivegenome sequencing projectbased on data from more than 85,000 patients diagnosed with cancer or rare diseases.
The research,publishedinScience, featured a new method the Signature Fit Multi-Step (FitMS) algorithm to enhance discrimination of common mutational processes from the rare, lower-frequency mutagenic processes. FitMS looks at signatures from new samples and compares these with existing findings by monitoring commonalities and identifying additional rare signatures.
The set of reference signatures used was identified after comparing and contrasting independent tissue-specific signatures and clustering mutational signatures from various tissues that may be due to similar processes. Other mutation bases were also linked to past clinical and treatment histories, where applicable.
"Whole genome sequencing gives us a total picture of all the mutations that have contributed to each person's cancer. With thousands of mutations per cancer, we have unprecedented power to look for commonalities and differences across NHS patients, and in doing so we uncovered 58 new mutational signatures and broadened our knowledge of cancer," said Dr. Andrea Degasperi, the study's first author and a research associate at the University of Cambridge, in a statement.
"The reason it is important to identify mutational signatures is because they are like fingerprints at a crime scene - they help to pinpoint cancer culprits. Some mutational signatures have clinical or treatment implications - they can highlight abnormalities that may be targeted with specific drugs or may indicate a potential 'Achilles heel' in individual cancers," added Serena Nik-Zainal, leader of the study and a professor of genomic medicine and bioinformatics at the University of Cambridge.
Cancer is a complex beast and severalstudies on mutationsalso came to light at the American Association for Cancer Research's annual meeting in mid-April 2022. Aadi Biosciencegot the U.S. Food and Drug Administration's green light for Fyarro, a new drug designed to treat PEComa, a very rare type of sarcoma. Fyarro has demonstrated the ability to treat patients with TSC1 or TSC2 mutations.
Ikena Oncologyalso presented data on an ongoing trial for IK-930. This TEAD inhibitor targets the Hippo signaling pathway and binds to TEAD transcription factors with the goal of preventing the transcription of genes that drive the progression of cancer.
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Detecting skin cancer with a blood test – Cosmos
Posted: at 5:20 pm
A team of US researchers have found a way to diagnose skin cancer using blood tests.
The researchers have shown in a lab-based study that melanoma cells can be detected in blood and plasma. If the test makes it through clinical trials, the researchers hope that it could one day be used to sidestep the invasive biopsies that are currently required to diagnose melanoma.
The test uses melanoma-specific antibodies, and a device designed specifically to react them with blood. The device is called MelanoBean, and it works with microfluidics: manipulating tiny amounts of fluid to do interesting things that they wouldnt do in larger volumes.
The test is described in a paper in Advanced NanoBiomed Research.
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This is the first comprehensive study of circulating tumour cells or CTCs to evaluate the efficacy of surgery using microfluidic systems in melanoma, including changes in the number of CTCs, CTC cluster configuration, and gene expression profiling, says first author Dr Yoon-Tae Kang, a researcher at the University of Michigan, US.
Read more: New cancer detection technique using old oranges
The researchers found that with their test, melanoma cells (CTCs) could be found in the blood of cancer patients at all stages of the disease I through to IV.
It could also identify whether any CTCs were hanging around in the blood of patients whod had skin cancer surgery to get their cells removed.
CTCs have the potential to pinpoint treatment resistance and recurrence, and can be a valuable biomarker to non-invasively monitor for disease progression, says corresponding author Dr Sunitha Nagrath also from the University of Michican.
Theres never been a more important time to explain the facts, cherish evidence-based knowledge and to showcase the latest scientific, technological and engineering breakthroughs. Cosmos is published by The Royal Institution of Australia, a charity dedicated to connecting people with the world of science. Financial contributions, however big or small, help us provide access to trusted science information at a time when the world needs it most. Please support us by making a donation or purchasing a subscription today.
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HER2 negative Breast Cancer Pipeline Insights | Research Report 2022 by DelveInsight – GlobeNewswire
Posted: at 5:20 pm
Las Vegas, USA, April 25, 2022 (GLOBE NEWSWIRE) -- HER2 negative Breast Cancer Pipeline Insights | Research Report 2022 by DelveInsight
HER2 negative Breast Cancer Pipeline involves 85+ key companies continuously working towards developing 85+ HER2 negative Breast Cancer treatment therapies, as per DelveInsight
DelveInsights HER2 negative Breast Cancer Pipeline Insight 2021 report offers exhaustive global coverage of available, marketed, and pipeline therapies in different phases of clinical development, major pharmaceutical companies working to advance the pipeline space, and future growth potential of the HER2 negative Breast Cancer pipeline domain.
Some of the essential takeaways from theHER2 negative Breast Cancer Pipelinereport:
Request a sample and discover more about the report offerings @ HER2 negative Breast Cancer Emerging Therapies
The HER2 negative Breast Cancer pipeline report lays down detailed profiles of the pipeline assets, comparative analysis of clinical and non-clinical stage HER2 negative Breast Cancer products, inactive and dormant assets, comprehensive assessment of driving and restraining factors, as well as the opportunities and risks in the HER2 negative Breast Cancer pipeline landscape.
HER2 negative Breast Cancer Overview
Most Breast Cancers express the Estrogen Receptor (ER) receptor and are negative for the human epidermal growth factor receptor 2 (HER2) receptor. ER+/ HER2 ve Breast Cancer includes tumors that are ER-positive and PR positive, but negative for HER2. ER+/ HER2 ve Breast Cancer is heterogeneous and accounts for about 70% of all breast cancers. HER2 stands for human epidermal growth factor receptor 2. There are various types of breast cancer, some have hormone receptors like estrogen or progesterone (some have both) and are called ER+ or PR+ breast cancer respectively.
Find out more about the disease and recent developments @ HER2 negative Breast Cancer Pipeline Assessment
HER2 negative Breast Cancer Pipeline Drugs
Learn more about the novel and emerging HER2 negative Breast Cancer pipeline therapies @ HER2 negative Breast Cancer Pipeline Analysis
HER2 negative Breast Cancer Therapeutics Assessment
TheHER2 negative Breast Cancer Pipelinereport proffers an integral view of the HER2 negative Breast Cancer emerging novel therapies segmented by Stage, Product Type, Molecule Type, Mechanism of Action, and Route of Administration.
Scope of the HER2 negative Breast Cancer Pipeline Report
Dive deep into rich insights for emerging therapies and assessment, visit @ HER2 negative Breast Cancer Emerging Therapies
Table of Contents
For further information on the HER2 negative Breast Cancer current pipeline therapeutics, reach out @ HER2 negative Breast Cancer Ongoing Clinical Trials
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Xalud Therapeutics Adds Amy Chappell, MD, as a Strategic Advisor – BioSpace
Posted: at 5:20 pm
NEW YORK, April 25, 2022 (GLOBE NEWSWIRE) -- Xalud Therapeutics, a clinical-stage biotechnology company developing DNA-delivered therapeutics, today announced the appointment of Amy Chappell, M.D., as an independent strategic advisor. Dr. Chappell will work with Xalud senior management and other advisors to provide strategic input and direction for Xaluds R&D programs, including XT-150, a nonviral DNA-based delivery platform with potential for a broad number of indications.
Amys experience as a physician-scientist, especially with respect to her expertise in pain, will be invaluable to Xalud as we continue to develop XT-150 and advance our novel therapeutic platform for the treatment of chronic inflammatory disorders, which are often accompanied by pain, said Diem Nguyen, Ph.D., MBA, chief executive officer of Xalud.
Dr. Chappell has more than 30 years of experience planning, designing and implementing all stages of clinical trials in neurosciences with expertise in pain, migraine and epilepsy. Dr. Chappell serves on the scientific advisory board of Pinteon Therapeutics, is an adjunct clinical associate professor at the Indiana University School of Medicine and is a fellow of the American Academy of Neurology (FAAN). She spent over 25 years at Eli Lilly and Company, where she started as an associated clinical research physician and took on roles of increasing responsibility until her retirement in 2014 as a senior medical fellow. Dr. Chappell earned her B.S. in biology from Antioch College and her M.D. from Indiana University School of Medicine.
I believe that Xaluds DNA-delivered therapeutic approach holds significant promise for treating a range of inflammatory disorders, Dr. Chappell noted. Im grateful for the opportunity to influence the clinical development of the companys innovative therapies.
About Xalud TherapeuticsXalud Therapeutics is a biotechnology company developing a DNA-delivered therapy platform to treat pathologic inflammation through immune modulation. The company is harnessing the power of interleukin-10 (IL-10), a potent cytokine that acts as a master regulator for multiple inflammatory pathways, to address the root cause of inflammation and subsequently restore homeostasis in the immune system. Xaluds lead product candidate, XT-150, is a locally injectable plasmid DNA gene therapy expressing IL-10v, a proprietary modified variant of IL-10, that addresses pathologic inflammation and pain.
Media Contact
Kara Stephens-WeaverLifeSci CommunicationsKstephens-weaver@lifescicomms.com407-765-1185
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Scientists use machine learning to identify antibiotic resistant bacteria that can spread between animals, humans and the environment – Newswise
Posted: at 5:20 pm
Newswise Experts from the University of Nottingham have developed a ground-breaking software, which combines DNA sequencing and machine learning to help them find where, and to what extent, antibiotic resistant bacteria is being transmitted between humans, animals and the environment.
The study, which is published inPLOS Computational Biology, was led by Dr Tania Dottorini from the School of Veterinary Medicine and Science at the University.
Anthropogenic environments (spaces created by humans), such as areas of intensive livestock farming, are seen as ideal breeding grounds for antimicrobial-resistant bacteria and antimicrobial resistant genes, which are capable of infecting humans and carrying resistance to drugs used in human medicine. This can have huge implications for how certain illnesses and infections can be treated effectively.
China has a large intensive livestock farming industry, poultry being the second most important source of meat in the country, and is the largest user of antibiotics for food production in the world.
In this new study, a team of experts looked at a large scale commercial poultry farm in China, and collected 154 samples from animals, carcasses, workers and their households and environments. From the samples, they isolated a specific bacteria calledEscherichia coli (E. coli).These bacteria can live quite harmlessly in a persons gut, but can also be pathogenic, and genome carry resistance genes against certain drugs, which can result in illness including severe stomach cramps, diarrhoea and vomiting.
Researchers used a computational approach that integrates machine learning, whole genome sequencing, gene sharing networks and mobile genetic elements, to characterise the different types of pathogens found in the farm. They found that antimicrobial genes (genes conferring resistance to the antibiotics) were present in both pathogenic and non-pathogenic bacteria.
The new approach, using machine learning, enabled the team to uncover an entire network of genes associated with antimicrobial resistance, shared across animals, farm workers and the environment around them. Notably, this network included genes known to cause antibiotic resistance as well as yet unknown genes associated to antibiotic resistance.
Dr Dottorini said: We cannot say at this stage where the bacteria originated from, we can only say we found it and it has been shared between animals and humans. As we already know there has been sharing, this is worrying, because people can acquire resistances to drugs from two different ways - from direct contact with an animal, or indirectly by eating contaminated meat. This could be a particular problem in poultry farming, as it is the most widely used meat in the world.
The computational tools that we have developed will enable us to analyse large complex data from different sources, at the same time as identifying where hotspots for certain bacteria may be. They are fast, they are precise and they can be applied on large environments for instance multiple farms at the same time.
There are many antimicrobial resistant genes we already know about, but how do we go beyond these and unravel new targets to design new drugs?
Our approach, using machine learning, opens up new possibilities for the development of fast, affordable and effective computational methods that can provide new insights into the epidemiology of antimicrobial resistance in livestock farming.
The research was done in collaboration with Professor Junshi Chen, Professor Fengqin Li and Professor Zixin Peng from China National Center for Food Safety Risk Assessment (CFSA).
The full study can be foundhere.
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Health Canada Grants Marketing Authorization for TRIKAFTA (elexacaftor/tezacaftor/ivacaftor and ivacaftor) in Children With Cystic Fibrosis Ages 6…
Posted: at 5:20 pm
-Approximately 500 Canadians ages 6-11 are now eligible for PrTRIKAFTA-
-Vertex has submitted this indication to CADTH & INESSS for Health Technology Assessments-
TORONTO, April 20, 2022 /CNW/ - Vertex Pharmaceuticals Incorporated (Nasdaq: VRTX) today announced that Health Canada has granted Marketing Authorization for the expanded use of PrTRIKAFTA (elexacaftor/tezacaftor/ivacaftor and ivacaftor) to include children with cystic fibrosis (CF) ages 6 through 11 years who have at least one F508del mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. With this announcement, approximately 500 Canadians with CF ages 6-11 are now eligible for TRIKAFTA. As a result of this approval, an additional dosage strength of TRIKAFTA tablets is now available (elexacaftor 50 mg/tezacaftor 25 mg/ivacaftor 37.5 mg and ivacaftor 75 mg).
Vertex Pharmaceuticals (Canada) Inc. Logo (CNW Group/Vertex Pharmaceuticals (Canada) Inc.)
"We are delighted that TRIKAFTA is now available for these young patients in Canada. It provides a new treatment option for those with CF ages 6-11 with at least one F508del mutation and a first-in-class treatment option for the approximately 500 6-11-year-olds who are newly eligible for a medicine that treats the underlying cause of their disease," said Reshma Kewalramani, M.D., Chief Executive Officer and President at Vertex. "This important milestone brings us one step closer to our ultimate goal of developing treatments for all patients living with CF. We will now work closely with all provinces and territories to secure access for eligible patients as quickly as possible."
Vertex completed a 24-week Phase 3 open-label, multicenter study which enrolled 66 children ages 6 through 11 years old with CF who have either two copies of the F508del mutation or one copy of the F508del mutation and one minimal function mutation to evaluate the safety, pharmacokinetics and efficacy of TRIKAFTA. The regimen was generally well tolerated, and safety data were consistent with those observed in previous studies in patients ages 12 years and older.
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"As a trial investigator, I have seen firsthand the demonstrated efficacy of TRIKAFTA in people ages 6-11 living with cystic fibrosis," said Larry C. Lands, M.D., Ph.D., Director, Pediatric Respiratory Medicine, Pediatric Cystic Fibrosis Clinic, and Pediatric Pulmonary Function Laboratory, Montreal Children's Hospital, McGill University Health Center, and Professor, Department of Pediatrics, Faculty of Medicine, McGill University. "This is an exciting next step that will allow eligible patients to begin treatment earlier."
Vertex has also submitted this indication to both the Canadian Agency for Drugs and Technologies in Health (CADTH) and the Institut national d'excellence en sant et en services sociaux (INESSS) in Qubec for Health Technology Assessments.
About Cystic Fibrosis
Cystic fibrosis (CF) is a rare, life-shortening genetic disease affecting more than 83,000 people globally. CF is a progressive, multi-organ disease that affects the lungs, liver, pancreas, GI tract, sinuses, sweat glands and reproductive tract. CF is caused by a defective and/or missing CFTR protein resulting from certain mutations in the CFTR gene. Children must inherit two defective CFTR genes one from each parent to have CF, and these mutations can be identified by a genetic test. While there are many different types of CFTR mutations that can cause the disease, the vast majority of people with CF have at least one F508del mutation. CFTR mutations lead to CF by causing CFTR protein to be defective or by leading to a shortage or absence of CFTR protein at the cell surface. The defective function and/or absence of CFTR protein results in poor flow of salt and water into and out of the cells in a number of organs. In the lungs, this leads to the buildup of abnormally thick, sticky mucus, chronic lung infections and progressive lung damage that eventually leads to death for many patients. The median age of death is in the early 30s.
About PrTRIKAFTA (elexacaftor/tezacaftor/ivacaftor and ivacaftor)
In people with certain types of mutations in the CFTR gene, the CFTR protein is not processed or folded normally within the cell, and this can prevent the CFTR protein from reaching the cell surface and functioning properly. PrTRIKAFTA (elexacaftor/tezacaftor/ivacaftor and ivacaftor) is an oral medicine designed to increase the quantity and function of the CFTR protein at the cell surface. Elexacaftor and tezacaftor work together to increase the amount of mature protein at the cell surface by binding to different sites on the CFTR protein. Ivacaftor, which is known as a CFTR potentiator, is designed to facilitate the ability of CFTR proteins to transport salt and water across the cell membrane. The combined actions of elexacaftor, tezacaftor and ivacaftor help hydrate and clear mucus from the airways. TRIKAFTA is a prescription medicine used for the treatment of cystic fibrosis (CF) in patients ages 6 years and older who have at least one copy of the F508del mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene.
About Vertex
Vertex is a global biotechnology company that invests in scientific innovation to create transformative medicines for people with serious diseases. The company has multiple approved medicines that treat the underlying cause of cystic fibrosis (CF) a rare, life-threatening genetic disease and has several ongoing clinical and research programs in CF. Beyond CF, Vertex has a robust pipeline of investigational small molecule, cell and genetic therapies in other serious diseases where it has deep insight into causal human biology, including sickle cell disease, beta thalassemia, APOL1-mediated kidney disease, pain, type 1 diabetes, alpha-1 antitrypsin deficiency and Duchenne muscular dystrophy.
Founded in 1989 in Cambridge, Mass., Vertex's global headquarters is now located in Boston's Innovation District and its international headquarters is in London. Additionally, the company has research and development sites and commercial offices in North America, Europe, Australia and Latin America. Vertex is consistently recognized as one of the industry's top places to work, including 12 consecutive years on Science magazine's Top Employers list and one of the 2021 Seramount (formerly Working Mother Media) 100 Best Companies. For company updates and to learn more about Vertex's history of innovation, visit http://www.vrtx.com or follow us on Facebook, Twitter, LinkedIn, YouTube and Instagram.
Special Note Regarding Forward-Looking Statements
This press release contains forward-looking statements as defined in the Private Securities Litigation Reform Act of 1995, as amended, including, without limitation, statements made by Dr. Kewalramani and Dr. Lands in this press release, and statements regarding the estimated number of children eligible for TRIKAFTA for the first time, our beliefs regarding the benefits of our medicines, and anticipated patient access to TRIKAFTA. While Vertex believes the forward-looking statements contained in this press release are accurate, these forward-looking statements represent the company's beliefs only as of the date of this press release and there are a number of risks and uncertainties that could cause actual events or results to differ materially from those expressed or implied by such forward-looking statements. Those risks and uncertainties include, among other things, that data from the company's development programs may not support registration or further development of its compounds due to safety, efficacy, or other reasons, and other risks listed under the heading "Risk Factors" in Vertex's most recent annual report and subsequent quarterly reports filed with the Securities and Exchange Commission at http://www.sec.gov and available through the company's website at http://www.vrtx.com. You should not place undue reliance on these statements or the scientific data presented. Vertex disclaims any obligation to update the information contained in this press release as new information becomes available.
(VRTX-GEN)
SOURCE Vertex Pharmaceuticals (Canada) Inc.
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Health Canada Grants Marketing Authorization for TRIKAFTA (elexacaftor/tezacaftor/ivacaftor and ivacaftor) in Children With Cystic Fibrosis Ages 6...
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Characterization of host factors associated with the internal ribosomal entry sites of foot-and-mouth disease and classical swine fever viruses |…
Posted: at 5:20 pm
Cell culture, virus, and plasmids
The human kidney cell line (HEK293) used in this study was obtained and cultured as previously described14,15. The swine kidney line L (SK-L) cells were propagated in Eagles Minimum Essential Medium (Nissui Pharmaceutical, Tokyo, Japan) supplemented with 0.3mg/mL l-glutamine (Nacalai Tesque, Kyoto, Japan), 100 U/mg penicillin G (Meiji Seika Pharma, Tokyo, Japan), 8mg/mL gentamycin (TAKATA Pharmaceutical, Saitama, Japan), sodium bicarbonate (Nacalai Tesque), 0.1mg/mL streptomycin (Meiji Seika Pharma), 0.295% tryptose phosphate broth (Becton Dickinson and Company, Franklin Lakes, NJ, USA), 10mMN,N-bis-(2-hydroxyethyl)-2-aminoethanesulfonic acid (BSE; MilliporeSigma, St. Louis, MO, USA), and 10% horse serum (Thermo Fisher Scientific, Waltham, MA, USA).
The vCSFV GPE-/HiBiT recombinant classical swine fever virus encoding the HiBit luciferase gene16 was derived from the recombinant full-length cDNA of the CSFV GPE-strain17. SK-L cells were infected with tenfold serially diluted vCSFV GPE-HiBiT in 96-well plates and incubated at 37C for 3 days. Virus growth was analyzed using luciferase activity as an indicator. Viral titers were calculated and expressed as the tissue culture infectious dose (TCID50) per mL. The luciferase assay was performed according to a previously described protocol18. The luciferase activity of the culture supernatants was measured using a Nano-Glo HiBiT lytic detection system (Promega, Madison, WI, USA) according to the manufacturers protocol. Twenty L of culture medium was mixed with an equal volume of Nano-Glo HiBiT lytic buffer. Luciferase activity was measured in a 96-well LumiNunc plate (Thermo Fisher Scientific) using the microtiter plate reader POWERSCAN 4 (DS Pharma Biomedical, Osaka, Japan). The average number of mock-infected 96-well plates plus five times the standard deviation of this population (i.e., luciferase activity=70) was set as the cutoff value.
The pRF vector containing an FMDV-IRES (serotype C; 5-UTR sequence: nucleotides (nt) 5691038 in FMDV serotype C, AF274010.1)19 was kindly donated by Dr. Hirasawa of the Memorial University of Newfoundland, and those containing a CSFV-IRES20 were gifts from Professor Graham J. Belsham of the University of Copenhagen. The pCAGGS-Neo vector was constructed using the pCAG Neo (Fujifilm Wako, Tokyo, Japan) and pCAGGS vectors (Cat. No. RDB08938; Riken Bank, Ibaraki, Japan). The CSFV-IRES cDNA (nt. 124401) was excised from a reporter plasmid20 using the EcoRI and NcoI restriction sites, and the excised DNA was inserted between the Renilla and firefly luciferase genes. Reporter genes were cut using the restriction endonucleases EcoRV (Toyobo, Osaka, Japan) and BamHI (New England Biolabs, Ipswich, MA, USA). A pCAGGS-Neo/CSFV-IRES vector was generated by inserting a reporter gene into pCAGGS-Neo, which was subsequently treated with EcoRV (Toyobo), BamHI (New England Biolabs), and rAPid alkaline phosphatase (Roche, Basel, Switzerland) using a ligation mixture (Mighty Mix, Takara, Shiga, Japan).
Cells expressing pCAGGS-Neo-CSFV-IRES (clones pCI5 and pCI5-1) and pCAGGS-Neo-FMDV-IRES (clones B5 and B10) were established as described previously15.
DNA sequencing was performed by FASMAC Co. (Kanagawa, Japan), and DNA sequence characterization was performed using the GENETYX-Mac software (GENETYX Co., Tokyo, Japan) and GENBANK.
Cell viability was evaluated using WST assays (Dojindo, Kumamoto, Japan) by determining the optical density at 450nm (OD450) according to the manufacturers instructions. Luciferase assays were performed using a dual-luciferase reporter assay system (Promega, Madison, WI, USA). Luminescence was measured using a GloMax 96 Microplate Luminometer (Promega) for 10s, as described previously14.
Total RNA was extracted from PYC-treated (10g/mL, 72h) and untreated B10 cells using ISOGEN (Nippon Gene Co. Tokyo, Japan) from cells growing in the linear phase of PYC treatment. RNA quality was measured using an Agilent 2100 bioanalyzer and showed an RNA integrity number (RIN) of 9.8 (7.0 The amounts of PKD1L3 and USP31 mRNA in cells were quantified using the SYBR Green real-time PCR master mix (Thermo Fisher, Waltham, MA, USA) and the primers pKD1L3-544S: 5-CATCTTCCAACCACATGTCACTATCC-3, pKD1L3-903AS: 5-CTGTAGTTTGTTAAGAGCTTGCAAACC-3; USP31-700S: 5- TGTGGCTTTTGGACCGAGTTGC-3, and USP31-900AS: 5- TGCAGTGAGAACATTTGCCTGC-3. The data was evaluated using the 2Ct method. The siRNAs targeting host factors (summarized in Table 2) were designed using the BLOCK-iT RNAi Designer (Thermo Fisher Scientific, Waltham, MA, USA). For the control siRNA, an ON-target plus siRNA control (Horizon/Dharmacon, Lafayette, CO, USA) was used. Then, siRNA (5nM) reverse transfection was performed using the Lipofectamine RNAiMAX reagent (Invitrogen) according to the manufacturers specifications. The effect of siRNA was evaluated by immunoblot analysis as described previously14 using anti-polycystic kidney disease 1-like 3 (PKD1L3) (OSP00014W, Invitrogen) and anti-ubiquitin-specific peptidase 31 (USP31) (Santa Cruz Biotechnology Co.) antibodies. Original blots presented in the supplementary original gel image_Fig. 5 which shows fuller-length of both sides and bottom, but top stacking part gel was removed. All data are presented as meanstandard deviation (S.D.) from three independent experiments, and figures were generated using GraphPad Prism (version 9) software. Statistical analysis was performed using Students t-test to evaluate significant differences. Statistical significance was set at P<0.05. This study was performed in accordance with institutional committee protocols of Kagoshima University. See the rest here:
Characterization of host factors associated with the internal ribosomal entry sites of foot-and-mouth disease and classical swine fever viruses |...
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Venice Biennale 2022: Man’s relationship with the planet gets surreal – Euronews
Posted: at 5:17 pm
At the 59th edition of the Venice Biennale art exhibition, the earth and its uncertain future are taking center stage.
Director Cecilia Alemani wants this years edition of the world's oldest international exhibition to ask some fundamental questions: "How is the definition of human changing? What constitutes life, and what differentiates plant and animal, human and non-human? What are our responsibilities towards the planet, other people, and other life forms? And what would life look like without us?"
The questions are inspired by "The Milk of Dreams," a book by British-born Mexican surrealist Leonora Carrington that is also the title of this years Biennale.
It is a world where everyone can change, be transformed, become something or someone else, says Alemani. The exhibition takes Leonora Carringtons otherworldly creatures, along with other figures of transformation, as companions on an imaginary journey through the metamorphoses of bodies and definitions of the human.
Visitors to the 80 national pavilions and dozens of collateral events will confront probing questions about how humans interact with technology, the possibility of a posthuman world and the ecological crisis facing the planet.
As the world begins to return to a fragile sense of normality amid the ongoing pandemic, the Biennale asks what that is going to look like.
Visitors to Denmark's national pavilion enter into a space that is both hauntingly beautiful and unsettling. It is a world inhabited by a family of centaurs set in an undefined moment of the future. These hyperrealistic transhuman creatures of Uffe Isolottos We Walked the Earth seem to represent the result of a biotechnological experiment. As Isolotto explains, They are attempting to survive in a world where it is no longer enough to be human as we know it.
In one room, the male centaur has taken his own life, his half-man half-horse body hanging limply from the ceiling. In the second room, the female centaur is giving birth.
"I think we are in a moment where the world is changing amid the pandemic and the ecological crisis," Isolotto says, "and this artwork suggests something has to die for something to be born."
Beneath the male centaur are small sculptures of mutated farm crops oozing a bright blue liquid. "These could be the nutrition of their future world, or perhaps a drug," says the artist, who deliberately avoids giving concrete explanations in order for the installation to represent the deep ambiguities of current times.
Instead, Isolotto wants visitors to meditate on this liminal world that includes elements from traditional Danish farm life merging with sci-fi-like forms. It is up to the viewer to decide if this is a tragic or a hopeful view of the future.
Italy's national pavilion is being taken over by a single artist for the first time this year. Gian Maria Tosatti's site-specific installation fills the vast nearly 2,000 sq.m Tese delle Vergini space with replicas of industrial warehouses. They represent Italys history of industrial boom followed by decline. Tosatti travelled the length of the country gathering scraps from abandoned factories to create the exhibition.
The thought-provoking work, entitled History of Night and Destiny of Comets, is separated into two sections. In the first, representing the historic part, rusty warehouse interiors are illuminated by harsh LED lights. The Destiny of Comets section instead looks towards the future and ends with a message of hope.
Together, the two sections ask powerful questions about the relationships between man and nature, industry and sustainability, and the exploitation and protection of the planet.
Latifa Echakhch is representing Switzerland this year with an eerie, immersive installation. On entering the pavilion, burnt sculptures and scattered ash on the ground suggest a catastrophic event that has ravaged the area. As Echakhch describes, You are walking in the ashes of what was played in that space.
With forms recalling giant heads and hands, the burnt wooden sculptures were inspired by the ritual fires lit in Switzerland to mark the end of the winter season. Fire is always both the end and the beginning on a constantly turning wheel of time, says Echakhch. The wooden sculptures themselves reuse materials from previous Biennials, continuing the idea of life cycles.
In collaboration with musician and composer Alexandre Babel and curator Francesco Stocchi, Echakhchs The Concert then takes visitors backwards through time as light and darkness alternatively illuminate and veil the monumental sculptures.
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Venice Biennale 2022: the worst art on show in the city – Art Newspaper
Posted: at 5:17 pm
Leaping into the Metaverse, Ai-Da
Concilio Europeo dellArte (Giardini)
Where do you start with art produced by a machine rather than a human? The AI robot Ai-Da is almost as ubiquitous as Hans Ulrich Obrist on the art scene, popping up in prime art hotspots such as the Venice Biennale this week. Ai-Da has been given a new painting arm, resulting in an astonishing new painting ability, a press statement says. But her clunky self-portraits andImmortal Riddle sculpture still look like they were made by, well, a robot. The statement adds that Ai-Da has no life or sightthat is glaringly obvious from the art on display.
Sterling Ruby's HEX on the faade of Palazzo Diedo, the home of Berggruen Arts & Culture Photo: Andrea Avezz
Palazzo Diedo
In a Biennale dominated by women artists in the Giardini and Arsenale, the presence of male artists screaming from Palazzos (seemingly from a bygone era) provides a jarring counterpoint. Sterling Rubys giant relief sculpture HEX, splayed across the historic faade of the Palazzo Diedo in Venice s Canareggio district is just a representative example. We are told that it interrupts the classical architecture with a sense of precarity. The title "Hex refers to the geometric star emblems hex signs appearing on the sides of Pennsylvanian Dutch barns. Who knew? The Palazzo will be the new permanent home of the Beggruen Arts & Culture centre, following the palaces recent restoration, with Hex announcing Rubys inaugural residency. Will these male outliers in Venice still cast their spell on visitors?
Ignasi Aball's Correccin for the Spanish Pavilion Photo: Claudio Franzini; Courtesy of AECID
Correccin, Ignasi Aball
The Spanish Pavilion closed without giving a reason this morningthe dour gatekeeper staring out behind metal bars, informing hopeful art goers shivering under umbrellas they shalt not pass. Yet a crowd remained, dutifully waiting for entry to Ignasi Aball's representation of the joyous Spanish nation at the 2022 Biennale.
Once inside, they will find Correccin, an installation that attempts to fix the historical architectural "errors" found in the pavilion, rotating its walls by ten degrees. The artist demands we reconsider the space.
The error, perhaps, was the idea itself, which, to put it mildly, is indulgent, boring and pretentious. Once the wet hoards have shuffled through the show, they will likely wish on Aball a stay in a correctional facilityfor crimes committed in the name of conceptual art.
Marc Quinn's Historynow Photo: The Art Newspaper
Museo Archeologico
The British artist Marc Quinn has attempted to sum up viral moments from the past couple of years in the exhibition HISTORYNOW, which lines the walls and ceilings of the Museo Archeologico. Screenshots from social mediashowing images such as Donald Trump, the storming of the Capitol, a scantily clad Rihanna and a Ukrainian woman with her newbornhave been replicated on giant phone-shaped canvases measuring more than 2m, which have then been daubed and splashed with paint.
It would be kind to call these works kitsch, but kitsch can have layers, humour and depth of meaningthese seem to compress historical moments into decorative wallpaper for a Miami mansion. And despite the images being in the public domain and often of people who crave publicity, there is a sense that they are being exploited for someone elses spectacle. Not even Trump deserves this treatment.
Wallace Chan TOTEM exhibition at Fondaco Marcello Massimo Pistore, courtesy Wallace Chan
Fondaco Marcello
TOTEM, the new exhibition by Hong-Kong artist Wallace Chan, should workat least for those into shiny things. The setting is Fondaco Marcello, a 15th-century warehouse by the Grand Canal which houses Chans massive titanium sculptures of Buddhist iconography. The warehouse, was chosen, Chan said in an interview with TL magazine, for its "poetic beauty".
But Chan, for some abstract reason, has decided not to install his exhibition as he initially intendedsomethingabout wanting to reflect his curiosity about life, nature and the mysteries of the universe. Instead, he decided to "just leave it unassembled, so as to address the idea of fragmented reality and uncertainty." The result is collection of works strewn around the warehouse floor in a mess of blasphemous bling that looks like giant trinkets stolen from Venice street hawkers.
Correction: This article originally misinterpreted a quote from Wallace Chan referring to the exhibition's lighting. This has since been amdended.
Uffe Isolotto's We Walked the Earth for the Danish Pavilion Ugo Carmeni
We Walked the Earth, Uffe Isolotto
Uffe Isolottos transhuman installation for the Danish pavilion presents a spectacle that is disturbing and yet ultimately mystifying, failing to deliver any ideas to match the high-spec visuals. There is no denying the cinematic quality of the pavilions larger than life protagonists, a pair of hyperreal centaurs realised by a team of taxidermists, zoological model makers and prosthetic makeup specialists. But why are they here?
A trigger warning outside the pavilion advises visitors of sensitive content, including scenes of life and death. Sure enough, the male centaur hangs from the ceiling by a noose in a dingy chamber. His female partner lies in a farmhouse stall across the way, impassive in the act of giving birth. Mysterious glassy pods litter the floor and one room is inexplicably devoted to a hanging mutant leg of ham. No one seems any the wiser, with the most common reaction being a quick gawp and a photo opportunity, before hurrying out through the exit.
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Is this the technology to win Kiwis over to genetic engineering? – Stuff
Posted: at 5:09 pm
Youve heard of fermenting yeast to make beer, but what about brewing GM microbes to make bioplastic? Using designer microbes to make stuff in fermentation vats has been described as the next manufacturing revolution, with potential to produce everything from cow-free cheese to sustainable fossil fuel replacements. But is GE-free New Zealand ready for it?
Veronica Stevenson bet her house deposit on a bee.
Before using GM microbes to make stuff was all the talk (Impossible Burger, mRNA vaccines), Stevenson set out to find the genetic recipe for the plastic-like film that lines the nest of a solitary Aussie bee.
All she had to do was work out which bit of the bees DNA linked to the nest material and put that code into a micro-organism, which then makes it in a fermentation vat, or bioreactor.
READ MORE:* The secret to the perfect dairy free cheese could lie in lab grown milk protein* Snail farming, cricket flour, algae and lab-grown fish; Welcome to the brave new world of alternative protein* Fermentation might lead to a dairy protein to make fake milk* US testing begins on genetically modified ryegrass developed in NZ
Finding the bees was a nightmare. Sequencing the genome was tricky. Gathering funding was challenging (hence investing her house deposit).
Still, she overcame every obstacle.
Weve sequenced the genome. Weve expressed the genome in two microbial systems. So weve proven that we can make it. Which is a massive thing.
But when it came to the trial and error stage of perfecting the process, Stevenson ran into the legacy of New Zealands famously strict genetic engineering rules, which the Productivity Commission this month concluded failed to take into account tech advances, and should be reviewed.
Because the regulatory environment is what it is, theres just no infrastructure, Stevenson says. Just the ability to move through the product from concept to commercial viability.
The Australian native bee, Hylaeus Nubilosis, which lines its nest hole with a natural bioplastic.
In December, Stevensons company Humble Bee announced a six-month partnership with United States biotech company Gingko Bioworks.
Their automated system can test 3000-5000 gene variants, different microbial hosts and processes to devise the perfect formulation. Its the genetic equivalent of a sophisticated recipe tester, trying out thousands of tweaks to ingredients, quantities, or temperatures.
While New Zealand may never be able to justify a research facility on Gingkos scale, Stevenson is frustrated the country is not doing more to embrace the multibillion-dollar potential of synthetic biology.
In Australia, three or four years ago, they realised this was huge ... and they threw hundreds of millions of dollars at it. They have a centre for research excellence on it. They have a venture capital fund specifically for this space.
And New Zealand is like, its just not on the radar. Which is a real shame. I just feel like were missing out.
LAWRENCE SMITH/Stuff
Nikki Freed and Irina Miller, co-founders of Daisy Lab, aim to create a milk protein in the lab.
While most Kiwis probably eat GM wheat, corn and soy in imported foods, the idea of releasing genetically engineered organisms is likely to remain a hard sell in New Zealand. Stevenson and many scientists argue we should at least have the conversation.
But the beauty of the technology behind Humble Bee is that the end product is not genetically modified.
Known as precision fermentation, the process is a hot topic because it can be used to make anything from fossil-free biofuels to the animal-free milk products that some predict will bring down the dairy industry.
Basically, you isolate the DNA sequence that encodes for something you want to make, insert it into a microbial host, which then produces it in a fermentation vat.
The product is then extracted and purified from the fermentation soup, or from the microbe itself.
The stuff were doing is not scary, says Stevenson. What were going to produce is not going to be released into the wild. Its not going to have an impact, interacting or sharing genes with other things. Its not going to cross-pollinate with something. Its an inert substance.
Its a big vat. You pull out whats expressed from the microbes and you give it to your biofabricators and they can make it into a film or turn it into a yarn. And then that gets incorporated into clothes. Its like synthetic spider silk.
It's not a new process its been used for 40 years to make insulin, as an alternative to extracting it from pig pancreases.
But the field is burgeoning now, because the comparative ease of genome sequencing and DNA synthesis means its suddenly accessible. Pfizer used it to make its Covid vaccines, and Impossible Foods ferments genetically engineered yeast to make the heme that gives its plant-based burger its meaty taste.
As Scions biotechnology research group leader Gareth Lloyd-Jones explains, 20-30 years ago you might get a PhD for cloning one gene.
Whereas now, you could probably in a month design an experiment to clone any gene, and order it, get somebody to synthesise the DNA for you, and deliver that in a form which you can put into the host, and the DNA vector you want to use to produce it.
All the technology around how you make it is cheaper. The amount of options as to what you can produce it in is broader. So everything has become so much bigger in terms of what you could think of doing.
So how is New Zealand placed to get its slice of the pie?
John Selkirk/Stuff
LanzaTech co-founder Sean Simpson says New Zealands restrictive GM regulations are technical masochism, preventing commercialisation of bright ideas.(File photo)
Remember LanzaTech, New Zealands biotech poster child, which in 2014 moved to the United States?
Founder Sean Simpson started out using a microbe that naturally converts carbon dioxide into ethanol in a process called gas fermentation. The idea was to capture carbon from industrial waste and transform it into a fossil fuel replacement a climate change double whammy.
But that was just the beginning. The real prize was to genetically engineer that microbe to make other things acetone or the starting materials for rubber or plastics.
But Simpson knew New Zealands regulations would prevent him doing that at scale. It wasnt the only factor that pushed him offshore, but it was a factor.
If we're going to use agricultural waste, societal waste, industrial waste to deliver sustainable fuels and chemicals, and replace oil, then biology has a significant part to play ... And New Zealand is basically saying, we don't want any part of that. Which is fascinating to me.
Contrary to popular belief, there is no ban on genetic modification here. You can apply under the Hazardous Substances and New Organisms Act (HSNO) to do genetic engineering, but it has to be done in containment. That means inside an approved and regularly audited facility.
That was never going to work for LanzaTechs industrial-scale bioreactors, and scientists say the approval process for GM development outside containment is so difficult it creates an effective moratorium. That closes off opportunities to turn great ideas into businesses, Simpson says.
Its not like we cannot undertake genetic manipulation in New Zealand. We can, and we do. We don't want to do it at a certain scale.
And I can't understand the justification for that. It's technical masochism. We're going to build a little bit of it, but when it gets really exciting, we're going to stop. If this could turn into something, we're not going to do it.
What Veronica has done is remarkable. But imagine the number of people who never even bothered to try and get that far, because of the hurdle that they knew was ahead of them.
Supplied
Kiwi Matt Gibson took his company making animal-free dairy mozzarella to San Francisco, after struggling to get it off the ground in New Zealand.
In Matt Gibsons profile pic, hes proudly sporting a vintage All Blacks jersey. But the New Culture founder is beaming in from San Francisco, where hes developing animal-free dairy mozzarella.
Dairy cheese has a terrible environmental footprint, making it a prime target for sustainability advocates, Gibson says. But the plant-based alternatives are pretty awful.
But what if you could cut out the middle gal the cow and make dairy cheese without the climate guilt?
Milk protein casein gives cheese its character the melt, the stretch, the flavour.
So thats what Gibson makes, using precision fermentation. He genetically engineers microbes to produce casein in fermentation tanks.
The extracted and purified casein is the same as casein from milk, and its not GM. The genetic manipulation occurs only in the process, not the product. Its then combined with plant-based fats and transformed into mozzarella through traditional cheesemaking.
Hes hoping to start selling commercially next year.
We are making animal-free dairy cheese today. Were making a lot of it. It melts, it stretches, it browns. It does everything youd expect dairy mozzarella to do.
But it wont be doing any of those things in New Zealand.
Supplied
New Cultures animal-free mozzarella melts, stretches and browns the same as the cow-made version.
Gibson started New Culture in Auckland in 2018.
He needed a lab for initial experimentation, but universities werent interested (he didnt want to sponsor a PhD student and lose control of the intellectual property). Commercial labs were keen to help, but their GM approvals were too narrow.
I just realised there was no way I could do any work, without having to get my own certification and set up my own lab, and that would cost a lot of money, compared to the United States, where nothing like that is required.
After six months of trying, I realised it was a fruitless endeavour.
So he moved to San Francisco, where he joined the IndieBio accelerator programme.
And now hes making cheese and New York Times headlines far from home.
Ultimately, if New Zealand doesnt embrace this, they are going to be left behind, and the future of dairy is going to be elsewhere, and it will be a shame.
Mike Scott/Stuff
Some predict animal-free dairy made using precision fermentation could spell the death of the dairy industry.
Reports of the dairy industrys imminent death have been greatly exaggerated.
Non-dairy products make up 15 per cent of the US dairy market, and a think tank report suggested animal-free dairy could kill off the cow milk industry by 2035.
That, says Gibson, is fantasy. His back-of-an-envelope calculation estimates just replacing New Zealands dairy output would require pretty much every existing fermentation tank in the world.
Its not going to happen in 10 years.
But its still a major risk for a country that relies so heavily on white gold, Gibson says.
The risk is that the economys biggest or second-biggest industry is going to become obsolete. Theres still going to be some demand for animal-derived dairy, but ultimately its going to become a niche product, and youre going to put a lot of people out of work.
Auckland Universitys 2020 Future of Food report notes international calls to swap from ruminant-based foods to plant-based ones could significantly affect the acceptability of New Zealands pastoral products in some markets.
The Ministry for Primary Industries, however, does not see novel methods for producing protein as a replacement for traditional forms. Any food produced with genetic modification also needs special Food Standards approval in New Zealand.
But the opportunities are much broader than just food. Australias Synthetic Biology Road Map estimates the technology of which precision fermentation is one part could be worth $27 billion a year and 44,000 jobs in Australia by 2040.
Whangarei Leader
Is precision fermentation the technology to win Kiwis over to GM?
But are GE-Free flag-waving Kiwi consumers ready to embrace genetic modification as a process rather than a product?
Humble Bees bioplastic is just one example of the technologys potential environmental wins providing more sustainable alternatives to fossil fuel-based products.
That means it has potential to win over the greenies who have traditionally opposed genetic modification.
Theres also a new generation of Kiwis who did not grow up in the shadow of GE-free placards. In 2019, 150 scientists aged under 30 signed an open letter to the Green Party asking them to reconsider their anti-GE stance.
Greenpeace does not oppose laboratory fermentation that does not result in environmental release of viable GM organisms. But they dont want to wait for lab-based food to reduce climate emissions.
Strong anti-GM voice The Sustainability Council would not say whether it opposes precision fermentation in principle, or its use to make casein, saying it has to assess every case separately. Executive director, Simon Terry, says using genetically modified organisms to aid fermentation is less risky for the environment than GM crops.
However, it should not be exempt from regulation, and the benefits should still have to outweigh the risks.
LAWRENCE SMITH/Stuff
It would be cheaper and easier to make animal-free dairy products almost anywhere else in the world, but Daisy Lab co-founder Nikki Freed is confident they can do it within New Zealands tough regulations.
One of the first questions potential investors ask about casein-culturing Kiwi startup Daisy Lab is Why would you be doing this in New Zealand? says co-founder Irina Miller.
Our response has always been well, yes, it is challenging. But its not impossible.
Both Miller and co-founder Nikki Freed are foreigners. They know it would be cheaper and easier to build their company just about anywhere else. But they want to do it here.
Im very interested in sustainability, says Freed, who is also the lead technologist at Auckland Universitys genomics facility. We want to see New Zealand succeed and become a great, green place for our kids to live.
Miller toyed with the idea of making animal-free dairy in 2016/17, while working for Fonterra. She figured someone else would do it. But when no-one did, she started Daisy Lab, in 2020.
LAWRENCE SMITH
Freed and Daisy Lab co-founder Irina Miller have been surprised at the lack of anti-GM feedback to their plans. (File photo)
The environmental gains from switching from cow udders to fermentation tanks could be huge, with one estimate finding it reduces greenhouse gas emissions by 91 to 97 per cent. There are no accurate estimates for New Zealands pasture-based farming.
Microbes still need to eat. Still researching at tiny scale, Daisy Lab is feeding its microbes pretty much pure sugar. But ultimately they hope to use food waste. If precision fermentation took off, farmers could grow sugar beets to feed the countrys army of micro-organisms.
Daisy Labs long-term vision is to tap into the dairy industrys supply chain for powdered milk, which is 80 per cent casein and makes up 95 per cent of all our milk exports. Farmers could be like micro-brewers, growing fermentation feed and making milk protein without the cow.
Freed and Miller have been surprised at the lack of backlash to their plans. Thats partly because people understand they wont actually be eating GMOs. But Freed thinks its also about their motivations.
At the heart of what were trying to do, is make a better planet. Were trying to improve sustainability. Were trying to improve animal welfare...Traditionally, other GMO have gotten a bad rap, because its more about making those seeds farmers have to buy each year. Its profit-driven.
Sarah Brook/Stuff
Synthase Biotech managing director Andy West says New Zealand could be making more high-value enzymes using precision fermentation. (File photo)
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Is this the technology to win Kiwis over to genetic engineering? - Stuff
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