Glioblastoma is an aggressive brain cancer that has no cure.A recent chart study of patients with glioblastoma found that taking chemotherapy in the morning was associated with athree-to six-month increase in median survival.Now astudy from Washington University in St.Louis reports that glioblastoma cells have built-in circadian rhythms that create better times of day for treatment.Biologists and clinicians recorded daily rhythms in“clock gene”expression from avariety of cultured human and mouse glioblastoma cell lines and isolates.These rhythms aligned with daily activity of aDNA repair enzyme known as MGMT.The scientists then conducted tests and found that tumor cells were more likely to die when chemotherapy was administered at the time of day—the morning—when tumor cells had the least MGMT activity.Repeating their efforts in mice with glioblastoma,the scientists found that morning administration of chemotherapy decreased tumor size and increased body weight compared with evening drug delivery.The study was published in the Journal of Neuro-Oncology.“There might be an avenue for better treating this disease with adrug at the times of day when the cells are more susceptible,”said Maria F.Gonzalez-Aponte,a graduate student in biology in Arts&Sciences at Washington University,who is afirst author of the new study.“We found that delivering chemotherapy with temozolomide(TMZ)in the subjective morning can significantly decrease tumor growth and improve disease outcomes for human and mouse models of glioblastoma.”“Because TMZ is taken orally at home,translation of these findings to patients is relatively simple,”said Erik D.Herzog,PhD,the Viktor Hamburger Distinguished Professor and aprofessor of biology in Arts&Sciences,corresponding author of the new study.“We will need additional clinical trials to verify our laboratory findings,but evidence so far suggests that the standard-of-care treatment for glioblastoma could be improved simply by asking patients to take the approved drug in the morning,”Herzog said.While largely understudied for TMZ and glioblastoma,the practice of considering time of day in treating disease has been shown to improve outcomes in several cancers,including acute lymphoblastic leukemia,colorectal and ovarian and other gynecological cancers,study authors noted.Joshua B.Rubin,MD,PhD,a professor of pediatrics and of neuroscience at the School of Medicine,is alongtime collaborator with the Herzog laboratory and aco-author on the paper.Gary J.Patti,PhD,a professor of chemistry in Arts&Sciences and of medicine at the School of Medicine,and staff scientist Kevin Cho,PhD,in chemistry are also co-authors.Findings from this study have implications for both treatment and diagnosis of glioblastoma.In general,glioblastoma patients who are diagnosed with what is called MGMT methylated tumors tend to respond better to chemotherapy with TMZ.But this study found that MGMT methylation levels rise and fall based on the circadian time of the tumor.As aresult,doctors should control for the time of day when the biopsy of atumor is taken to properly compare results and improve diagnoses,study authors said.“Despite extensive research over the past 20 years,the median survival for glioblastoma patients post-treatment remains at about 15 months,a grim statistic,”Herzog said.“Incorporating chronotherapy,or timed delivery of drugs,could help improve things.”Herzog,Patti and Rubin are research members of Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine. 查看详细>>

Gas vesicles are hollow structures made of protein found in the cells of certain microorganisms,and researchers believe they can be programmed for use in biomedical applications.“Inside cells,gas vesicles are packed in abeautiful honeycomb pattern.How this pattern is formed has never been thoroughly understood.We are presenting the first identification of aprotein that is responsible for this pattern,and we believe it can be very useful,”said George Lu,an assistant professor of bioengineering and aCancer Prevention and Research Institute of Texas scholar at Rice University.Lu and colleagues from Washington University in St.Louis and Duke University have shared their findings in apaper published in Nature Microbiology.Co-author Yifan Dai,an assistant professor of biomedical engineering at WashU’s McKelvey School of Engineering,said they were drawn to the research with the question of why the vesicles can form in the honeycomb pattern.With help from WashU colleague Alex Holehouse along with Ashutosh Chilkoti and Lingchong You,of Duke University,the team found this pattern is the most efficient use of space,and the cluster form plays apart in how it functions.Notably,these protein clusters formed in subsaturated solution,a previously identified new form of biological structure,and that drives the organization of these vesicles.Bottom line,they found the function behind this mysterious new form. 查看详细>>

The National Science Foundation(NSF)has awarded aFaculty Early Career Development(CAREER)award to Nathaniel Huebsch,an assistant professor of biomedical engineering in the McKelvey School of Engineering at Washington University in St.Louis.With afive-year$695,746 CAREER award,Huebsch will grow heart muscle in the lab that is more representative of adult heart tissue and use that muscle to predict how drugs will affect patients’hearts.CAREER awards support junior faculty who model the role of teacher-scholar through outstanding research,excellence in education and the integration of education and research within the context of the mission of their organization. 查看详细>>

Many species experience little to no change over long periods of time.Biologists often fall back on the same explanation for why this is true:that natural selection favors individuals with more moderate characteristics.Individuals with more extreme features—longer limbs,for example—have adisadvantage,while more moderate or average individuals are more likely to survive and reproduce,passing on their common features.But new research from Washington University in St.Louis and the Georgia Institute of Technology provides amore complete explanation of how evolution plays out among species that live side-by-side.By directly measuring the long-term survival of lizards in the wild,the scientists showed that co-existing species each occupy adistinct“fitness peak”that is best understood as part of acommunitywide“fitness surface”or landscape.The study,led by James Stroud at Georgia Tech and publishing this week in the Proceedings of the National Academy of Sciences,offers anew way of thinking about how species relate to each other over time and how the differences between them reinforce their distinctness.Jonathan Losos,the William H.Danforth Distinguished University Professor and aprofessor of biology in Arts&Sciences at Washington University,said:“If species are adapted to their environment,and the environment doesn’t change,then you wouldn’t expect the species to change.However,when scientists have gone out and studied natural selection,they rarely find evidence of such stabilizing selection.“Given this disconnect,we set out to study natural selection on the organisms we know so well,Anolis lizards,to measure selection over several years and try to understand what’s going on,”Losos said.Stroud,who was working as apostdoctoral researcher in Losos’lab at WashU at the time,identified aplace where four different species of anoles were living together on asmall island in alake in the Fairchild Tropical Botanical Garden near Miami.He caught thousands of individual lizards on the island,tagged them and measured their body proportions.Stroud then re-caught all of the lizards on the island every six months for 2½years,a period of time representing two to three generations of lizards.New lizards that showed up were island babies,obviously.If alizard disappeared from his census rolls,it was safe for Stroud to assume it had died,because the surrounding lake,filled with predatory fish,didn’t let them leave.By determining which lizards survived from one year to the next,the researchers could evaluate whether survival was related to the body traits they had been measuring,like leg length.“What is special about this study is that we simultaneously measured natural selection on four co-existing species,something that has rarely been accomplished,”said Losos,who also serves as the director of the Living Earth Collaborative.“By coincidence,just as our paper was published,another group published asimilar study on Darwin’s famous finches of the Galapagos Islands.”In the Florida lizards,Losos and Stroud found that the stabilizing form of natural selection—that which maintains aspecies’same,average features—was extremely rare.In fact,natural selection varied massively through time.Some years,lizards with longer legs would survive better,and other years,lizards with shorter legs fared better.For other times,there was no clear pattern at all.“The most fascinating result is that natural selection was extremely variable through time,”Stroud said.“We often saw that selection would completely flip in direction from one year to the next.When combined into along-term pattern,however,all this variation effectively canceled itself out:species remained remarkably similar across the entire time period.”Scientists do not yet fully understand how evolution works on the community level.There are very few long-term studies like this one because of the great amount of work and time required.“Evolution can and does happen—it’s this ongoing process,but it doesn’t necessarily mean things are constantly changing in the long run,”Stroud said.“Now we know that even if animals appear to be staying the same,evolution is still happening.” 查看详细>>

The National Institutes of Health(NIH)is channeling$50.3 million over the next five years into anew consortium dedicated to advancing the generation and analysis of multi-omics data for human health research.As part of this team,Washington University in St.Louis is establishing and will lead acentral production center that functions as ahub for multi-omics analyses for materials from consortium members at each of six disease study sites identified by the NIH.Gary Patti,the Michael and Tana Powell Professor of Chemistry in Arts&Sciences and aprofessor of medicine and of genetics at the School of Medicine,and Ting Wang,head of the Department of Genetics at the School of Medicine and the Sanford C.and Karen P.Loewentheil Distinguished Professor of Medicine,are principal investigators with the new consortium.Patti,who recently founded amulti-omics company called Panome Bio,is an innovator in multi-omics research,and Wang is involved in multiple other NIH consortia,such as the Human Pangenome Reference Consortium.Collaborators will take advantage of cutting-edge resources at Washington University,such as the Center for Proteomics,Metabolomics,and Isotope Tracing on the Danforth Campus.The university estimates the value of its portion of the new grant at$19.2 million.“Most human diseases have complex origins that are influenced by acombination of genetic and environmental components such as diet,physical activity,exposure to pollutants and social determinants,”Patti said.“We are working to understand how disease develops in aperson by studying the flow of molecular information at multiple levels of‘omics’in parallel.“This consortium model eliminates one important barrier to progress by making it easier to collect multi-omics data from the same sets of samples and developing collaborative teams with the appropriate expertise to harmonize and integrate the results,”he said.A more holistic view Multi-omics incorporates several“omics”data types,including genomics,epigenomics,transcriptomics,proteomics and metabolomics.Each of these data types reveals distinct information about different aspects of abiological system,and leveraging all these data types at once is becoming increasingly possible with advances in high-throughput technologies and data science.The integration of multiple types of data from an individual participant’s biological sample can provide amore holistic view of the molecular factors and cellular processes involved in human health and disease,including untangling genetic and non-genetic factors in health and disease.This approach offers great promise in areas such as defining disease subtypes,identifying biomarkers and discovering drug targets.“With each additional layer of omics information comes more clues about biology,”Wang said.“I’m really excited about the work we will do in this consortium to integrate genomics,proteomics and metabolomics data.This is the future of systems biology.”“Beyond gaining insights into individual diseases,the primary goal of this consortium is to develop scalable and generalizable multi-omics research strategies as well as methods to analyze these large and complex datasets,”said Joannella Morales,a National Human Genome Research Institute(NHGRI)program director involved in leading the consortium.“We expect these strategies will ultimately be adopted by other research groups,ensuring the consortium’s work will have broad and long-lasting impacts for clinical research.”Funding for the consortium will support work at six disease study sites,which will examine conditions such as fatty liver diseases,hepatocellular carcinoma,asthma,chronic kidney disease and preeclampsia,among others.The sites will enroll research participants,at least 75%of whom will be from ancestral backgrounds underrepresented in genomics research.The sites also will collect data on participants’environments and social determinants of health to be used in conjunction with the multi-omics data.Combining the multi-omic and environmental data can offer an even more comprehensive view of the factors that contribute to disease risk and outcomes. 查看详细>>

A multi-institutional research project led by Todd Braver,a professor of psychological and brain sciences in Arts&Sciences at Washington University in St.Louis,received aMultidisciplinary University Research Initiative(MURI)award from the U.S.Department of Defense to study attention control and strategies to improve it.The project—“A computational cognitive neuroscience framework for attentional control traits and states(CCN-FACTS)”—is expected to span five years with atotal budget of about$8.8 million,of which WashU will receive up to$2.5 million.In addition to Braver,the U.S.research team includes as core members Julie Bugg and Wouter Kool from WashU’s Department of Psychological and Brain Sciences;David Badre and Michael Frank from Brown University;Mark Steyvers and Jeffrey Rouder from the University of California,Irvine;and Susanne Jaeggi and Aaron Seitz from Northeastern University.The project also features aclose collaborative partnership with aparallel team of researchers from Australia,led by Andrew Heathcote at Newcastle University.Over the next five years,the research team will develop neurocomputational models of both individual differences and state-related fluctuations in attention control due to factors such as motivation,stress and mind-wandering.They will test the models using multi-modal neuroimaging methods,including functional MRI and EEG.They will also develop novel tasks to investigate attention control in both laboratory and real-world complex environments.“A major goal of the project will be to harness the modeling and task development efforts to implement and evaluate new training strategies for enhancement of attention control,”Braver said.“Such strategies will be useful in enabling individuals to maintain high levels of focus and concentration even in high-pressure situations,such as those faced by military personnel.”The MURI program supports research in areas of critical importance to national defense and brings together researchers from multiple universities to collaborate on projects that are expected to bring significant advances in science and technology.Altogether,31 projects received$220 million in awards this year. 查看详细>>

As Canadian wildfire smoke continues to impact large swaths of the United States,resulting in poor air quality and negative health outcomes for millions of Americans,more people than ever are feeling the effects of longer fire seasons and achanging climate.Now,researchers at Washington University in St.Louis have discovered that wildfires may have even bigger climate impacts than previously thought.In anew study published Aug.7 in Nature Geoscience,researchers led by Rajan Chakrabarty,the Harold D.Jolley Career Development Associate Professor in the Department of Energy,Environmental&Chemical Engineering at the McKelvey School of Engineering,found that wildfires are causing amuch greater warming effect than has been accounted for by climate scientists.The work,which focuses on the role of“dark brown carbon”—an abundant but previously unknown class of particles emitted as part of wildfire smoke—highlights an urgent need to revise climate models and update approaches for the changing environment.To conduct acomprehensive analysis of what makes up wildfire smoke plumes,Chakrabarty’s team spent 45 days traveling to different wildfire locations in the western United States,where they sampled gaseous smoke and aerosol species and analyzed their chemical and optical properties.This research was conducted as part of the Fire Influence on Regional to Global Environments and Air Quality(FIREX-AQ)field campaign,a joint venture led by the National Aeronatics and Space Administration and the National Oceanic and Atmospheric Administration.“The conventional understanding has been that dark plumes of wildfire smoke contain black carbon soot,which absorbs solar radiation,while lighter plumes contain mostly organic carbon that scatters sunlight,meaning it offsets the absorption or warming effect of soot,”Chakrabarty said.“Typically,climate models ignore or dismiss organic carbon as insignificant compared to black carbon when it comes to warming,but that is not what field observations reveal.“This is not abinary picture.Instead,we are looking at an entire continuum where there is strong light absorption by organic carbon,or dark brown carbon,similar to black carbon,”he said.During their sampling of ground and airborne smoke from largescale wildfires,Chakrabarty’s team encountered an abnormally strong light absorber in plumes that wasn’t black carbon,yet it accounted for more than half of observed total absorption. 查看详细>>

Researchers in the Department of Physics in Arts&Sciences at Washington University in St.Louis received$1.5 million from NASA to fund anew flight of XL-Calibur,a balloon-borne telescope built to examine the most extreme objects in the universe.XL-Calibur will be launched from Esrange Space Center in Sweden,north of the Arctic Circle,in May 2024.Henric Krawczynski,professor and chair of physics,is leading acollaboration of more than 50 scientists from three countries—the United States,Japan and Sweden—on the project.Krawczynski and his group at Washington University developed XL-Calibur and its successful predecessor X-Calibur to unlock the secrets of astrophysical black holes and neutron stars.The telescope last flew in 2022.The XL-Calibur instrument measures polarized X-ray light as it is lofted under ascientific balloon flown at 125,000 feet in the air.The data that it gathers can be used on its own or together with data from aspace-based polarization detector called IXPE.Krawczynski and his collaborators participate in IXPE as members of the science team.During their upcoming flight,the XL-Calibur scientists plan to study how the black hole Cygnus X-1 accretes matter and to test models of particle acceleration by pulsars and blazars.XL-Calibur scientists also seek to validate certain findings suggested by IXPE,including anew theory about the nature of the X-ray source known as Cygnus X-3,which may be aneutron star in disguise and not ablack hole.XL-Calibur scientists will be able to take aclose look at the Cygnus X-3 accretion disk and determine how matter and magnetic fields are organized in the extreme environment close to this compact object.Krawczynski is teaming up with Alex Chen and Yayie Yuan,both assistant professors of physics in Arts&Sciences;graduate students Nicole Rodriguez Cavero and Ephraim Gau;and postdoctoral fellow Kun Hu to work on anew theory to explain the recent IXPE observations of stellar mass black holes.“Most of the recent IXPE black hole observations have given us really surprising results,”said Krawczynski,who is afaculty fellow of the McDonnell Center for the Space Sciences.“We are getting the first information about the magnetization of black hole accretion disk atmospheres.” 查看详细>>

Fine particulate matter comes from wood burning,power generation,motor vehicles and other combustion sources that emit tiny particles into the air.At only 2.5 micrometers or smaller,these particles are small enough to be inhaled and cause lasting damage to the heart and lungs.Known as PM2.5,exposure to these particles is aleading mortality risk factor in India and the surrounding region of South Asia.A new study by researchers in Randall Martin’s lab in the McKelvey School of Engineering at Washington University in St.Louis evaluated the contribution of various emission sectors and fuels to PM2.5 mass for 29 states in India and six surrounding countries:Pakistan,Bangladesh,Nepal,Bhutan,Sri Lanka and Myanmar.The results,published July 7in Environmental Science&Technology,identify primary organics—organic particles emitted directly into the atmosphere from various sources—as the main drivers of high concentrations of PM2.5 over South Asia.The paper also illuminates potential pathways to reduce PM2.5 mass and improve population health across South Asia.“Countries in South Asia have substantial emissions and associated air pollution and mortality burden,”said first author Deepangsu Chatterjee,a doctoral student in energy,environmental&chemical engineering in the McKelvey School of Engineering.“Our study shows that over 1million deaths in South Asia attributable to ambient PM2.5 in 2019 were primarily from residential combustion,industry and power generation.Solid biofuel is the leading combustible fuel contributing to the PM2.5-attributable mortality,followed by coal and oil and gas.”“Air pollution,both indoors and outdoors,is the leading risk factor for death in South Asia,”said co-author Michael Brauer,professor at the Institute for Health Metrics and Evaluation at the University of Washington and the University of British Columbia.“Understanding the major contributing sources is acritical first step towards management of this serious problem.”A major challenge in evaluating the impacts of PM2.5 is understanding how it is produced and distributed over time.Chatterjee and Martin,the Raymond R.Tucker Distinguished Professor in McKelvey Engineering,combined global emission inventories,satellite-derived fine surface particulate matter estimates and state-of-the-art global scale modeling capabilities to develop regional simulations.They also accounted for long-range transport to understand how different emission sectors and fuels contributed to PM2.5 and associated mortality rates.“Advances in modeling atmospheric composition with constraints from satellite remote sensing enabled our assessment of the sources of PM2.5 across South Asia,”Martin said.“That helped draw our attention to large contributions from burning biofuel and coal.”Chatterjee also noted that PM2.5 mass composition in South Asia is driven by primary organics across major contributing sectors.The team’s PM2.5 composition analysis can be particularly useful to develop mitigation strategies associated with particular species.A few other notable features include high contribution from coal in central and eastern India,higher household air pollution in north-east and central India,biofuel contributions in Bangladesh and open fires in Myanmar.“This study shows that the air pollution problem in South Asia is not just an urban scale problem,so policies targeted at urban scale development will not be enough to mitigate the national level PM2.5 exposure,”Chatterjee said.Chatterjee,Martin and their co-authors suggest several strategies for future interventions throughout South Asia,including policies encouraging the replacement of traditional fuel sources with sustainable sources of energy.“Policies in India in the past five to 10 years have worked toward identifying and improving air pollution concerns and associated health burden and mortality risks.Seeing these policies be effective is motivating for the South Asian population to keep moving the needle and develop strategic policies to curb the growth of air pollution,”Chatterjee said.“Our paper provides detailed sector-,fuel-and composition-based information for different states in India along with surrounding countries,which could be useful for local policymakers to eliminate PM2.5 sources associated with their specific region.” 查看详细>>

Atmospheric chemistry can have profound impacts on daily life,influencing air quality,UV radiation levels,pollution,climate and weather patterns.Researchers at Washington University in St.Louis will study the advanced modeling techniques used to understand the behavior of chemicals in the atmosphere to improve the models’accuracy and resolution.Randall Martin,the Raymond R.Tucker Distinguished Professor at the McKelvey School of Engineering at Washington University in St.Louis,and Chi Li,a postdoctoral fellow in Martin’s lab,will study the errors that arise in model simulations due to coarse spatial resolution with athree-year$500,000 grant from the National Science Foundation. 查看详细>>