Scientists Focus On Cone Targets to Enhance Temperature of Electron Beams (Physics)

Intense short-pulse laser-driven production of bright high-energy sources, such as X-rays, neutrons and protons, has been shown to be an invaluable tool in the study of high energy density science.

In an effort to address some of the most challenging applications, such as X-ray radiography of high areal density objects for industrial and national security applications, both the yield and energy of the sources must be increased beyond what has currently been achieved by state-of-the-art high-intensity laser systems.

A team of scientists from Lawrence Livermore National Laboratory (LLNL), University of Austin and General Atomics took on this challenge. Specifically, the team conducted experimental measurements of hot electron production using a short-pulse, high-contrast laser on cone and planar targets.

The cone geometry is a Compound Parabolic Concentrator (CPC) designed to focus the laser to the tip. The cone geometry shows higher hot electron temperatures than planar foils. Simulations identified that the primary source of this temperature enhancement is the intensity increase caused by the CPC.

Led by LLNL postdoctoral appointee Dean Rusby, the research findings are featured in Physical Review E.

“We were able enhance the temperature of the electron beam from our high-intensity laser interactions by shooting into a focusing cone target,” Rusby said. “It shows that we understand how the compound parabolic concentrator works under these laser conditions.”

Rusby said increasing the coupling into high-energy electrons in these interactions is crucial for developing applications from laser-plasma interactions.

“It is very encouraging to see significant enhancements are possible using the CPC target platform on a petawatt 100 fs class laser system, which is already capable of near diffraction limited operation,” said Andrew MacPhee, co-author of the paper. “Non-imaging optics applied to laser target interactions are redefining the parameter space accessible to the community.”

The team used the Texas petawatt laser system at the University of Austin during a six-week period, which has a short pulse and high contrast that allowed the experiment to work. The target is a compound CPC that is specifically designed to focus more laser energy toward the tip and increase the intensity.

“The increase in electron temperature strongly agreed with the increase we would expect when using the CPC,” Rusby said.

The Department of Energy’s Office of Science supported the LaserNetUS initiative at Texas Petawatt and LLNL’s Laboratory Directed Research and Development program funded the team and the crucially important target development from General Atomics.

cpc 062421
This image shows the experimental setup displaying the target, laser and electron spectrometer. A 3D drawing of the CPC, tantalum substrate and the incoming laser also is shown. © LLNL

The team has been awarded additional time through LaserNetUS at the Texas petawatt to continue research on CPCs targets. This time, the team will concentrate on the acceleration of the protons from the rear surface and the enhancement that the CPCs provide.

Andrew Mackinnon, a co-author of the paper and a principal investigator for a Strategic Initiative Laboratory Directed Research & Development, is using these CPC targets for the project. 

“These experiments showed that miniature plasma mirror targets do improve coupling of petawatt-class lasers to MeV (mega-electronvolt) electrons, which benefits potential applications such as laser-based MeV radiography,” he said.

In addition to Rusby, MacPhee and Mackinnon, co-authors include Paul King, Arthur Pak, N. Lemos, Shaun Kerr, Ginny Cochran, Anthony Link, Andreas Kemp, Scott Wilks, George Williams, Felicie Albert, Maurice Aufderheide, H. Chen, Craig Siders and Andrew Macphee from LLNL; I. Pagano, A. Hannasch, H. Quevedo, M. Spinks and M. Donovan from the University of Austin; and M. J.-E. Manuel, Z. Gavin and A. Haid from General Atomics.

Featured image: This image shows the intensification of the laser in simulations and the electrons being accelerated. © LLNL


Reference: D. R. Rusby, P. M. King, A. Pak, N. Lemos, S. Kerr, G. Cochran, I. Pagano, A. Hannasch, H. Quevedo, M. Spinks, M. Donovan, A. Link, A. Kemp, S. C. Wilks, G. J. Williams, M. J.-E. Manuel, Z. Gavin, A. Haid, F. Albert, M. Aufderheide, H. Chen, C. W. Siders, A. Macphee, and A. Mackinnon, “Enhancements in laser-generated hot-electron production via focusing cone targets at short pulse and high contrast”, Phys. Rev. E 103, 053207 – Published 14 May 2021. DOI: https://doi.org/10.1103/PhysRevE.103.053207


Provided by LLNL

Researchers Revealed Molecular Details of an Uncommon Form of Programmed Cell Death (Biology)

Revealing the details of an alternative cell death may lead to new therapies for a variety of diseases

Unlikely causes of death, like lightning, may strike out of the blue, but for our cells even an unusual form of death is not left to chance. That’s the conclusion drawn from a recent Weizmann Institute of Science study that revealed the molecular details of an uncommon form of programmed cell death, called parthanatos – a term derived from Thanatos, the personification of death in Greek mythology – in fruit fly embryos.

Understanding unusual, or what scientists call alternative, cell deaths may lead to a variety of new and improved therapies. Cancerous tumors, for example, commonly become resistant to the apoptosis – the major type of cell death – that is triggered by chemotherapy or irradiation therapy; inflicting an alternative death such as parthanatos upon them may offer a solution. On the other hand, recent research suggests that in Parkinson’s disease, neurons are not killed by apoptosis but rather by parthanatos, so understanding the mechanisms of this alternative cell death in a living organism is critical for learning how to block it. And this understanding may also one day help to treat a number of diseases such as ischemic stroke, heart disease and diabetes, in which parthanatos has also been implicated.

Inflicting an alternative death such as parthanatos on apoptosis-resistant tumor cells may offer a solution to this adverse phenomenon

Scientists have produced a dozen forms of alternative cell death in a laboratory dish, but it’s been hard to know which of these occur in the living organism and how exactly they unfold. Prof. Eli Arama of the Molecular Genetics Department and his team set out to fill this gap by studying the embryos of fruit flies – the Drosophila. About a third of the germ cells, which create the testes or ovaries, normally die as they migrate to either side of the embryo. Studies had long shown that apoptosis was not involved, so how these cells die remained a mystery for some two decades. Arama decided to check whether they are eliminated by any known form of alternative cell death.

Postdoctoral fellow Dr. Lama Tarayrah-Ibraheim in Arama’s lab led the experiments in which she first confirmed that the Drosophila germ cells don’t die by apoptosis: Even when she blocked all of the seven enzymes that result in apoptosis or perform related functions in fruit flies, a third of the cells continued to die. As Tarayrah-Ibraheim and other team members studied the genes involved, the resulting picture suggested that the germ cells die by mechanisms reminiscent of parthanatos, which until then had been investigated in cellular culture or in mouse models of human diseases, and had been found to result from massive DNA damage caused by stress or disease.

Germ cells of the fruit fly embryo visualized under a confocal microscope by means of anti-Vasa antibodies. In a living cell (top row), the DNA-cleaving enzyme DNase II (green) is contained within the lysosomes (red), whereas in a cell dying by parthanatos (bottom row), this enzyme (green; marked by white arrow) has spilled out of the lysosome and entered the nucleus © Weizmann Institute of Science

Tarayrah-Ibraheim and colleagues then experimented with mutant flies in order to clarify the roles of different genes. The scientists used antibodies to trace the locations of proteins manufactured by these genes, blocked some of the cellular signaling and conducted other experiments that ultimately enabled them to reveal the molecular details of the germ cells’ death. Not only did they confirm that the three critical components of the parthanatos pathway were required for the death of germ cells, they unraveled the entire biological pathway leading to this alternative cell death, completing the fragmented knowledge arising from tissue-culture studies. In particular, they determined that this pathway must necessarily include a DNA nuclease – a DNA-cleaving enzyme originating in the cellular organelle known as the lysosome – as well as the key parthanatos mediating proteins PARP-1 and AIF. This study is the first to identify and explore a developmental form of parthanatos – one that occurs in embryonic development, under normal conditions.

Evolution had favored parthanatos in developmental processes since it does not block cell migration

But why did parthanatos evolve in the first place? Why should the germ cells die this alternative death rather than by the ubiquitous apoptosis? Arama believes this has to do with caspases, the enzymes responsible for apoptosis. His lab had previously shown that low-level caspase activity performs vital functions that are unrelated to apoptosis – among them, blocking cell migration.

“Had caspases been involved in killing some of the germ cells, they might have prevented the rest of these cells from properly migrating – which would create a major conflict in the embryo’s development,” Arama says. “Evolution has apparently resolved this conflict by killing the germ cells in an alternative, non-caspase-dependent way, by parthanatos.” Apparently, cell death is so important to the life of multicellular organisms that their cells may carry a range of plans for suicide, adapted to fit different needs.

The details of parthanatos, as revealed in fruit flies, can now provide the basis for studying this cell death in mammalian development and the role it plays in human diseases. Such studies may ultimately help prevent parthanatos if it leads to disease or do the opposite – trigger it on demand – for example, in order to kill cancer cells.

The nuclear DNA (blue) of living germ cells in the fruit fly embryo is gradually destroyed by DNase II (green), a DNA-cleaving enzyme, in germ cells dying by parthanatos © Weizmann Institute of Science

Tarayrah-Ibraheim: “We’ve shown that parthanatos is a naturally occurring programmed cell death, which means that the molecular machinery for this alternative cell death can be normally activated in the cell. Such activation may make it possible to kill cells much more selectively and efficiently than by general-purpose chemical drugs.”

Study participants included Elital Chass Maurice, Guy Hadary, Sharon Ben-Hur, Dr. Alina Kolpakova, Tslil Braun and Dr. Keren Yacobi-Sharon of the Molecular Genetics Department and Dr. Yoav Peleg of the Life Sciences Core Facilities Department.

Prof. Eli Arama is the incumbent of the Harry Kay Professorial Chair of Cancer Research.

Prof. Arama’s research is supported by the Kekst Family Institute for Medical Genetics; the M. Judith Ruth Institute for Preclinical Brain Research; and the Y. Leon Benoziyo Institute for Molecular Medicine.

Science Numbers

Scientists have successfully identified 12 different cell death pathways in lab cultures; if and how they apply to living organisms remains a mystery.

Featured image: (l-r) Dr. Lama Tarayrah Ibraheim and Prof. Eli Arama. This study is the first to identify and explore a developmental form of parthanatos © Weizmann Institute of Science


Reference: Tarayrah-Ibraheim, L., Maurice, E.C., Hadary, G. et al. DNase II mediates a parthanatos-like developmental cell death pathway in Drosophila primordial germ cells. Nat Commun 12, 2285 (2021). https://doi.org/10.1038/s41467-021-22622-1


Provided by Weizmann Institute of Science

Researchers Reveal Mechanism of Arenavirus Replication Machinery (Biology)

Arenaviruses encode their own RNA-dependent RNA polymerase (RdRp), namely the L protein, for replication and transcription of the viral genome, and this molecule is quite conserved among different viral species, which indicates a very important antiviral therapeutic target.

Z protein has been revealed to interact with the polymerase to inhibit RNA synthesis at the late stage of viral replication, initiating the assembly of progeny virions. Therefore, elucidating the working mechanism of arenavirus polymerase and the regulatory mechanism of Z protein for the polymerase activity is of great significance for developing specific and broad-spectrum antiviral drugs.

In a study published in Nature Microbiology, SHI Yi’s lab at the Institute of Microbiology of the Chinese Academy of Sciences investigated the mechanism of arenavirus matrix protein Z regulating the polymerase activity.

In 2020, SHI’s lab reported the first near-atomic resolution structure of arenavirus polymerase, as well as its complex with viral RNA (vRNA) promoter. The findings constitute a basic framework for understanding the mechanism of arenavirus replication, but yet many further questions remain.

In this new study, the researchers determined the structures of Lassa virus (LASV) and Machupo mammarenavirus (MACV) L proteins in complex with their cognate Z proteins, and the ternary complexes of L-Z-vRNA.

These structures revealed that the Z protein binds to the periphery of palm domain of RdRp, far away from the binding site of vRNA. Therefore, the binding of Z protein does not prevent vRNA recruitment by the L polymerase. Despite no catalytic residues being directly engaged by Z protein, the distal ends of two catalytic motifs are involved in interactions with Z protein outside the catalytic center. These binding motifs are located at the interface between multiple domains. The binding of Z protein would restrict the conformational changes of key catalytic motifs required for catalysis, resulting in inactivation of the polymerase.

Besides, looking into the L-Z contacting interface, the researchers found that Z protein binds to the L protein through its central domain, in which a highly conserved hydrophobic loop dominates the interaction with the L polymerase. Because of the conservation of the dominant binding motif, they observed that LASV and MACV Z proteins could cross-inhibit the activity of heterologous L polymerases. This observation is quite remarkable. This indicated the regulatory effect of Z protein on polymerase might be a universal mechanism among all arenaviruses, and suggested the possibility of cross-inhibition between different viruses.

These findings provide a new strategy for developing broad-spectrum antiviral drugs against different arenaviruses.

Arenaviruses are a group of enveloped and segmented negative-sense RNA viruses (sNSVs), comprising the family Arenaviridae. All human-infecting arenaviruses belong to the genus mammarenavirus, exemplified by LASV. Unfortunately, there are no specific drugs or vaccines available for most arenavirus infections, posing great challenges for the treatments of related diseases.


Reference: Xu, X., Peng, R., Peng, Q. et al. Cryo-EM structures of Lassa and Machupo virus polymerases complexed with cognate regulatory Z proteins identify targets for antivirals. Nat Microbiol (2021). https://doi.org/10.1038/s41564-021-00916-w


Provided by Chinese Academy of Sciences

Deeply Mining a Universe of Peptides Encoded by Long Noncoding RNAs (Biology)

Long noncoding RNAs (lncRNAs), a family of non-coding RNAs (ncRNAs) that are greater than 200 nucleotides in length, were formerly regarded as “junk RNAs” due to the lack of long or conserved open reading frames (ORFs).

Growing amount of evidence has demonstrated that many short or small open reading frames (smORFs) embedded in lncRNA transcripts are able to encode functional polypeptides (smORFs-encoded polypeptides, SEPs).  Thousands of additional lncRNA transcripts with smORFs have been discovered, suggesting that SEPs may represent a large albeit neglected portion of non-annotated peptides involved in diverse physiological process. Therefore, large-scale discovery and functional characterization of unknown SEPs might provide new clues for the annotation and functional analysis of noncoding elements in the genome and their effects on biological evolution.

In a study published in Molecular and Cellular Proteomics, Prof. YANG Fuquan’s group and Prof. CHEN Runsheng’s group from the Institute of Biophysics of the Chinese Academy of Sciences implemented a novel strategy for SEP discovery and characterization, which enabled the discovery of 762 novel SEPs from different human and murine cell lines and tissues, representing the largest number of MS-detected SEPs ever to be reported.

The improved SEP discovery rate can be attributed to an optimized MS-based workflow by combining a de novo construction of a high-quality putative SEP database with two effective and complementary polypeptide enrichment methods.

The researchers take advantage of NONCODE, a repository containing the most complete collection and annotation of lncRNA transcripts from different species, to build a novel database that maximize a collection of SEPs from human and mouse lncRNA transcripts. The combination of 30 kD MWCO membrane filtration and C8 SPE for SEP enrichment also promote the discovery and identification of novel SEPs from different cell cultures and tissues.

The increased number of discovered SEPs in this study provides new opportunities to gain deeper insights into their physical and chemical properties.

For instance, bioinformatic analysis revealed that the physical and chemical properties of these novel SEPs were varied from canonical proteins. More than 60% of the identified SEPs from both human or mouse are initiated by unknown start codons (i.e. non-AUG), which typically have reduced efficiency when compared with AUG codons. Moreover, SEPs are commonly shorter in amino acid length and enriched with more basic residues, which are typical features of known coding genes lacking mass spectrometry evidence.

This study can not only provide new clues for the annotation of noncoding elements in the genome, but also serve as a valuable resource for the functional characterization of individual SEPs and the exploration of the possible mechanism of lncRNA translation.

Featured image: Graphical abstract by Qing Zhang et al.


Provided by Chinese Academy of Sciences

Scientists Discover Novel Oncogenic Driver Gene in Human Lung Cancer (Biology)

A research team led by Prof. WANG Yuexiang from the Shanghai Institute of Nutrition and Health (SINH) of the Chinese Academy of Sciences discovered a novel oncogenic driver gene in human lung cancer, the leading cause of cancer-related mortality worldwide.  

Their findings were published in Journal of Experimental Medicine on June 18.     

Approximately 85% of all lung cancer cases are non-small cell lung cancers (NSCLCs). Although tyrosine kinase inhibitors and immunotherapy have contributed to survival benefits in some patients, the overall survival rates for NSCLCs remain low.  

Patients with NSCLC that are driven by KRAS mutations are often unresponsive to tyrosine kinase inhibitors and have a poor prognosis. Although inhibitors for the KRASG12C mutant have been approved to treat NSCLC patients, a general strategy that targets all KRASmutants remains elusive. 

Central precocious puberty (CPP) is largely caused by germline mutations inthe MKRN3 gene. Interestingly, CPP has been epidemiologically linked to various diseases in adulthood, including cancers. Cohorts of individuals with CPP show an increased risk of malignancies such as lung cancers.  

To investigate whether central precocious puberty-associated MKRN3 gene is mutated in human cancers, the research team led by Prof. WANG Yuexiang queried The Cancer Genome Atlas (TCGA) Pan-Cancer genomic data sets. Strikingly, MKRN3 is frequently mutated in NSCLCs. MKRN3 aberrations are significantly enriched in human NSCLC samples harboring oncogenic KRAS mutations.   

The researchers further presented genetic, functional, mouse models and mechanistic data that identify the central precocious puberty-associated gene MKRN3 gene as a bona fide tumor suppressor in NSCLC. They uncovered its tumor suppressing mechanism and highlighted MKRN3-PABPC1 axis deregulation as a key pathway in lung cancer oncogenesis.  

MKRN3 inactivation led to lung cancer proliferation and progression through PABPC1 ubiquitination mediated global protein synthesis. MKRN3 restoration in MKRN3-inactivated NSCLC suppressed tumor growth in nude mice. Therefore, molecular interventions targeting MKRN3 deficiency may have therapeutic potential for KRAS-mutant NSCLC treatment.     

These findings showed that biological mechanisms of central precocious puberty are relevant in tumorigenesis, which may help in developing anticancer drugs.     

This project was supported by the National Natural Science Foundation of China, Ministry of Science and Technology of China, Science and Technology Commission of Shanghai Municipality, and Chinese Academy of Sciences.  

Featured image: A model depicting how the MKRN3-PABPC1 axis controls cell proliferation and progression in lung cancer. (Image by WANG Yuexiang’s group)  


Reference: Ke Li, Xufen Zheng, Hua Tang, Yuan-Sheng Zang, Chunling Zeng, Xiaoxiao Liu, Yanying Shen, Yuzhi Pang, Simin Wang, Feifei Xie, Xiaojing Lu, Yuxiang Luo, Zhang Li, Wenbo Bi, Xiaona Jia, Tao Huang, Rongqiang Wei, Kenan Huang, Zihao Chen, Qingchen Zhu, Yi He, Miaoying Zhang, Zhizhan Gu, Yichuan Xiao, Xiaoyang Zhang, Jonathan A. Fletcher, Yuexiang Wang; E3 ligase MKRN3 is a tumor suppressor regulating PABPC1 ubiquitination in non–small cell lung cancer. J Exp Med 2 August 2021; 218 (8): e20210151. doi: https://doi.org/10.1084/jem.20210151


Provided by Chinese Academy of Sciences

Tiny Ancient Bird from China Shares Skull Features with Tyrannosaurus rex (Paleontology)

Researchers from the Institute of Vertebrate Paleontology and Paleoanthropology (IVPP) of the Chinese Academy of Sciences have discovered a 120-million-year-old partial fossil skeleton of a tiny extinct bird that fits in the palm of the hand and preserves a unique skull with a mix of dinosaurian and bird features.

The two-centimeter-long (0.75 inch) skull of the fossil shares many structural and functional features with the gigantic Tyrannosaurus rex, indicating that early birds kept many features of their dinosaurian ancestors and their skulls functioned much like those of dinosaurs rather than living birds.

Their findings were published in Nature Communications on June 23.

The bird was deposited 120 million years ago in a shallow lake in what is today Liaoning Province in northeastern China.

Through detailed reconstruction of the bird family tree, the researchers demonstrated that the new fossil bird species belongs to an extinct group of birds called enantiornithines, or “opposite birds.” They are the most diverse group of birds from the time of the dinosaurs in the Cretaceous and have been found all over the world.

In living birds, the quadrate is one of the most movable bones in the skull and allows for the unique feature of living birds known as “kinetic skull,” which allows the upper jaw to move independently of the brain and the lower jaw.

In contrast with living birds, however, the skull of this new “opposite bird”, as well as those of dinosaurs like Tyrannosaurus rex and the close dinosaurian relatives of birds (e.g., troodontids and dromaeosaurs), is not kinetic. Instead, its bones are “locked up” and unable to move.

The temporal regions (sides) of the skull of this bird fossil are very different from living birds. This new species has two bony arches for jaw muscle attachment like those found in reptiles such as lizards, alligators, and dinosaurs, making the rear of the skull rigid and resistant to movement among the bones.

Fig. Digital reconstruction of the new Mesozoic bird skull with expanded detail of the dinosaur-like palatal bones, i.e., the basisphenoid (red), pterygoid (pink), and quadrate (purple). The stars indicate the two parts of the pterygoid prong that extend behind the eye. (Image by WANG Min)

“When reconstructing all parts of the skull three-dimensionally from the high resolution CT scans of the fossil, I had a problem figuring out one bone in particular,” said Dr. WANG Min, the lead and corresponding author of the study. He said his colleague Dr. Thomas Stidham proposed that the bone was the pterygoid and looked “exactly like that of the dromaeosaur Linheraptor.” The fossil has the first well-preserved pterygoid bone found in an early bird.

The researchers compared CT scans of the bird skull to scans of the skull of the well-known dromaeosaur Linheraptor from Inner Mongolia, China. The results showed that many other features of the rear portion of the skull, including the shape of the basisphenoid bone and its connections with other skull bones, also resemble dromaeosaurs rather than living birds.

“The fossil bird and dinosaurs also lack the discrete contact between the pterygoid and quadrate near the palate that is used in skull kinesis in living birds. In combination with the ‘locked up’ temporal bones, the difference in the palate structure also points to the absence of kinesis among early birds,” said Dr. Stidham, co-author of the study.

Furthermore, the team’s discovery and meticulous anatomical research help to reinforce the already well-supported contention, based on many different lines of evidence, that birds are not only living dinosaurs, but evolved from the branch of dinosaurs that includes troodontids and dromaeosaurs like the “four-winged” Microraptor and swift Velociraptor.

“Having a ‘dinosaur’ skull on a bird body certainly did not stop the enantiornithines, or other early birds, from being highly successful in places all around the world for tens of millions of years during the Cretaceous,” said Dr. WANG.

Featured image: Digital reconstruction of the new Mesozoic bird fossil skeleton (scale bar: 10 mm) (Image by WANG Min)


Reference: Wang, M., Stidham, T.A., Li, Z. et al. Cretaceous bird with dinosaur skull sheds light on avian cranial evolution. Nat Commun 12, 3890 (2021). https://doi.org/10.1038/s41467-021-24147-z


Provided by Chinese Academy of Sciences

New Findings Unveil a Missing Piece of Human Prehistory (Paleontology)

A joint research team led by Prof. FU Qiaomei from the Institute of Vertebrate Paleontology and Paleoanthropology (IVPP) of the Chinese Academy of Sciences sequenced the ancient genomes of 31 individuals from southern East Asia, thus unveiling a missing piece of human prehistory. 

The study was published in Cell on June 24. 

Prof. FU’s team used DNA capture techniques to retrieve ancient DNA from Guangxi and Fujian, two provincial-level regions in southern China. They sequenced genome-wide DNA from 31 individuals dating back 11,747 to 194 years ago. Of these, two date back to more than 10,000 years ago, making them the oldest genomes sampled from southern East Asia and Southeast Asia to date. 

Previous ancient DNA studies showed that ~8,000–4,000-year-old Southeast Asian Hòabìnhian hunter-gatherers possessed deeply divergent Asian ancestry, whereas the first Southeast Asian farmers beginning ~4,000 years ago show a mixture of ancestry associated with Hòabìnhian hunter-gatherers and present-day southern Chinese populations. In coastal southern China, ~9,000–4,000-year-old individuals from Fujian province show ancestry not as deeply divergent as the Hòabìnhian. 

In Guangxi, FU and her team’s sampling showed that the ancestry present was unlike that sampled previously in Fujian and Southeast Asia. Instead, they found a unique East Asian ancestral population (represented by the 11,000-year-old Longlin individual from Guangxi). Their findings highlight that 11,000 years ago, at least three genetically distinct ancestries composed the human landscape in southern East Asia and Southeast Asia: Fujian ancestry, Hòabìnhian ancestry, and Guangxi ancestry. 

In addition to sharing Longlin ancestry, the Dushan and Baojianshan individuals in Guangxi also show strong evidence for admixture in southern China ~9,000 to 6,000 years ago. Dushan and Baojianshan were a mixture of local Guangxi ancestry, southern ancestry previously sampled in Fujian, and Deep Asian ancestry related to Southeast Asian Hòabìnhian hunter-gatherers. 

Previously, it was shown that southern Chinese populations expanded to Southeast Asia, mixing with and eventually replacing Hòabìnhians in Southeast Asia. FU’s team showed that the dynamics were more complex, since populations carrying Hòabìnhian ancestry either co-existed with populations carrying Guangxi ancestry in southern China or gene flow upwards from Southeast Asia to southern China also occurred as early as ~8,000–6,000 years ago. 

The study fills a research gap in the region connecting East and Southeast Asia, revealing a new genetic ancestry different from that found in coastal areas of southern China and in Southeast Asia. 

Furthermore, it shows the impact of migration and admixture of populations at the crossroads of East and Southeast Asia in the last 11,000 years, revealing a long history of intermingling between these two regions. 

“While we now have a better understanding of the population history in the last 11,000 years at the crossroads of East and Southeast Asia, future sampling in regions near the Yangtze River and southwest China are needed for a comprehensive understanding of the genetic history of humans in southern China,” said Prof. FU. 

Genetic samples from ancient humans in these regions will likely further clarify the remarkably diverse genetic prehistory of humans in southeastern Asia, and inform the genetic shifts that occurred between 6,000 and 1,500 years ago and contributed to the genetic composition observed today in southern China. 

Fig.1 Geographical and temporal distribution of newly sampled individuals (Image by IVPP)
Fig. 2 Phylogenetic tree of early Asian populations (Image by IVPP)

Featured image: Overview of population dynamical history at the crossroads of East and Southeast Asia since 11,000 years ago (Image by IVPP)


Reference: Tianyi Wang, Wei Wang, Guangmao Xie, Zhen Li, Xuechun Fan, Qingping Yang, Xichao Wu, Peng Cao, Yichen Liu, Ruowei Yang, Feng Liu, Qingyan Dai, Xiaotian Feng, Xiaohong Wu, Ling Qin, Fajun Li, Wanjing Ping, Lizhao Zhang, Ming Zhang, Yalin Liu, Xiaoshan Chen, Dongju Zhang, Zhenyu Zhou, Yun Wu, Hassan Shafiey, Xing Gao, Darren Curnoe, Xiaowei Mao, E. Andrew Bennett, Xueping Ji, Melinda A. Yang, Qiaomei Fu, Human population history at the crossroads of East and Southeast Asia since 11,000 years ago, Cell, 2021, , ISSN 0092-8674, https://doi.org/10.1016/j.cell.2021.05.018. (https://www.sciencedirect.com/science/article/pii/S0092867421006358)


Provided by Chinese Academy of Sciences

Researchers Reveal New Mechanism Underlying Pyroptosis Induced by Yersinia Infection (Biology)

Multiple strategies have been employed by pathogenic bacteria to sabotage host innate immune signaling to facilitate their infection.  

Previous studies revealed that the Yersinia effector protein YopJ targets and inhibits transforming growth factor-β–activated kinase 1 (TAK1) to block pro-inflammatory cytokine production. To counteract, host cells undergo pyroptosis via initiating receptor-interacting serine/threonine-protein kinase 1 (RIPK1)–dependent caspase-8–directed gasdermin D (GSDMD) cleavage. However, how RIPK1-caspase-8-GSDMD axis is instructed during Yersinia infection remains unknown. 

In a study published online in Science, Prof. LIU Xing’s group at the Institut Pasteur of Shanghai of the Chinese Academy of Sciences, and Prof. Judy LIEBERMAN’s group at Harvard Medical School, discovered via an unbiased CRISPR screen a critical and unexpected role of the lysosomal membrane-resident Rag-Ragulator complex in Yersinia infection-triggered pyroptosis.  

The researchers found that loss of components of Rag-Ragulator complex resulted in the failure of pyroptotic cell death in response to Yersinia infection, suggesting an essential role of Rag-Ragulator complex in caspase-8–mediated pyroptosis.  

Furthermore, they showed that upon infection with pathogenic Yersinia or its mimic (lipopolysaccharide plus TAK1 inhibitor), a FADD-RIPK1-caspase-8–containing complex was recruited via Rag-Ragulator complex to lysosomal membrane, and this process depended on Rag GTPase activity and Rag-Ragulator lysosomal binding but not Ragulator-activated mechanistic target of rapamycin complex 1 (mTORC1). 

This study uncovered a critical role of Rag-Ragulator in TAK1 inhibition-induced pyroptosis during Yersinia infection. The new role of Rag-Ragulator in caspase-8-mediated pyroptosis confirms its key function as a central hub for monitoring environmental cues to decide not only whether a cell proliferates, but also whether it survives.  

Also, this study shed new light on lysosome’s role in pyroptosis and in innate immune responses. Future studies will explore mechanistic details of pyroptosis to manipulate this process for therapeutic benefits.


Provided by Chinese Academy of Sciences

New Album Creates A Sonic Journey Through Our Cosmos (Astronomy)

A new free online album takes listeners on a cosmic and sonic journey through space, including past the two giant planets of our solar system, a galactic pulsar and colliding black holes.
 
Celestial Incantations combines the mysterious “sounds of space” with a massive musical palette, including orchestral and traditional instruments and electronics.

The new album is from the international Sounds of Space group, bringing together Associate Professor Kim Cunio from The Australian National University, UK artist Diana Scarborough and Dr Nigel Meredith from the British Antarctic Survey. It follows their first release, Aurora Musicalis.

Associate Professor Cunio said the new album charted a journey through some of the most mysterious and incredible examples of cosmic space and time across our Universe.
 
“Space is vast and with this album we have the opportunity to really think about what this vastness means for us as we listen,” Associate Professor Cunio said.  “We hope that this album allows people to imagine time and space in the grandest sense.”
 
Like the team’s first album, tracks on Celestial Incantations use the eerie and normally silent sounds of space to create music depicting interstellar travel, the slow dance of celestial bodies, the orbits of lonely comets and escaping air bubbles from ancient ice cores.    
 
“We even take listeners to the violent scene of super massive black holes colliding,” Dr Meredith said.
 
“The merger of two black holes was only captured several years ago through the first ever observation of gravitational waves, an almost unbelievable ripple through space and time. This was something Albert Einstein theorised but doubted we could ever capture.”
 
Dr Meredith said the team used electromagnetic and gravitational waves that travel vast distances across the Universe.

“Space is a vacuum and utterly silent, with no capacity for the transmission of sound waves,” he said.

“In this album we primarily hear the ‘sounds’ of space through the conversion of electromagnetic waves and gravitational waves to sound waves.”
 
Ms Scarborough said Celestial Incantations came at a time when humans were being inspired by a new era of space exploration and discovery.
 
“Scientists are proposing new theories on space time, dark matter and our expanding universe based on gravitational wave data and satellite data.
 
“Our Celestial Incantations album is a musical cocoon transporting us from Earth into this new wilderness, giving listeners time for reflection to ponder on the wonder and mystery of the Universe.”
 
Associate Professor Cunio said the album also explored how humanity has “imagined” the sounds of space over time.
 
“As a composer I can almost hear Pythagoras laughing,” he said.
 
“Pythagoras believed that he could hear the ‘Music of the Spheres’, a series of resonances and possibly even sounds that related to the major celestial bodies.

“Now we can join Pythagoras in a great imagining thanks to the ability of computers to speed up and transpose these phenomena into our perceptual ranges.”
 
Celestial Incantations is available for free online. It is based on the work of scientists from a number of institutions, including the British Antarctic Survey, the University of Iowa, the European Space Agency, Jodrell Bank Observatory, and the LIGO consortium.

Featured image credit: NASA


Provided by ANU