Documentaries, videos and podcasts
June 22, 2021
Alchemab Therapeutics today announced the appointment of Douglas A. Treco, PhD as Chief Executive Officer.
June 4, 2021
The News Minute
The Anna Arignar Anna Zoological Park said that samples were sent after some lions showed loss of appetite and occasional coughing, and nine out of 11 returned positive.
Bryant, J. M., Brown, K. P., Burbaud, S., Everall, I., Belardinelli, J. M., Rodriguez-Rincon, D., Grogono, D. M., Peterson, C. M., Verma, D., Evans, I. E., Ruis, C., Weimann, A., Arora, D., Malhotra, S., Bannerman, B., Passemar, C., Templeton, K., MacGregor, G., Jiwa, K., Fisher, A. J., Blundell, T. L., Ordway, D. J., Jackson, M., Parkhill, J., Floto, R. A.
April 30, 2021
Mycobacteria are mostly environmental saprotrophs, but during human history, some have become our pathogens. In the past 50 years or so, intractable and virulent infections of Mycobacterium abscessus have emerged in people with cystic fibrosis. Bryant et al. investigated how these mycobacteria have evolved into human pathogens so quickly (see the Perspective by Brugha and Spencer). Chronic infections in the lung offer plenty of evolutionary scope for the emergence of virulent clones after horizontal gene transfer and hypermutation. Pathogens are acquired by environmental contamination, which leaves open a window for clinical control because the most virulent clones survive poorly outside the body. Therefore, immediate treatment and enhanced infection-control measures for M. abscessus cases could reduce opportunities for the evolution of direct person-to-person transmission. Science , this issue p. [eabb8699]; see also p.  ### INTRODUCTION Nearly all mycobacterial species are free-living environmental saprophytes. A few, such as Mycobacterium tuberculosis , have evolved to cause transmissible human infection and eventually to become obligate human pathogens. The recent emergence and global spread of virulent clones of the environmental nontuberculous mycobacterium M. abscessus has provided a unique opportunity to examine the pathogenic evolution of mycobacteria. ### RATIONALE M. abscessus , a multidrug-resistant species of nontuberculous mycobacteria, has recently emerged as a major threat to individuals with cystic fibrosis (CF) and other chronic lung conditions. Infection rates within the CF community are increasing globally, driven in part by indirect person-to-person transmission of M. abscessus. Currently more than 70% of infections in CF patients are caused by genetically clustered (and thus transmitted) isolates, of which the majority are from three dominant circulating clones (DCCs) that have emerged within the past 50 years and have spread globally. These clustered isolates are more virulent when tested in vitro and in vivo and result in worse clinical outcomes, which suggests that they are evolving from environmental saprophytes into obligate lung pathogens. We reasoned that functional genomic analysis of M. abscessus might identify important generalizable steps in this evolutionary trajectory and highlight potential interventions to mitigate this process for this and other emergent mycobacterial pathogens. ### RESULTS We initially sought to understand how the DCCs may have emerged. Using graphical pan-genome analysis, we found that horizontal gene transfer--particularly gene transfer of global transcriptional regulators--can provide an important mechanism for creating large phenotypic variance in environmental M. abscessus isolates, consequently enabling saltational evolution toward enhanced human infectivity. This process may be generalizable across mycobacterial species where gene gain or loss events have been associated with the pathogenic evolution of virulent clones in several species, including cluster 1a within M. avium , clone A within M. canettii , and the monophyletic M. tuberculosis complex from an M. canettii- like ancestor. We next examined whether ongoing adaptation of infecting M. abscessus clones could further promote pathogenicity. We reconstructed the evolutionary trajectories of individual M. abscessus subclones within chronically infected patients, identifying convergent allopatric evolution within and between individuals as a key driver for pathogenic adaptation. Specifically, recurrent mutations within a small set of genes from a single functional network are likely to drive enhanced macrophage survival and increased virulence in vivo. We observed reduced transmission fitness for many adaptive mutations. For two frequently mutated genes ( phoR and the GPL locus), knockouts showed impaired survival on fomites. These findings suggest that within-host evolution is constrained, while an environmental intermediary is required for transmission. ### CONCLUSION Our results point to a generalizable model for mycobacterial pathogenic evolution. Initially, horizontal gene acquisition by environmental clones (particularly of genes with global transcriptional effects) drives saltational evolution and increases virulence, giving rise to the ancestors of the dominant circulating clones of M. abscessus and driving the emergence of virulent clones in other mycobacterial species. Next, within-host adaptation during chronic infection drives increased intracellular survival within macrophages and inflammatory lung damage. However, pathogenic evolution is constrained while M. abscessus is transmitted through environmental intermediaries, because the most highly adapted strains lose transmission fitness through reduced fomite survival. Ultimately, we predict that opportunities for direct transmission of emergent mycobacteria (potentially through increases in population density and/or host susceptibility) will permit unconstrained, accelerated evolution into an obligate human pathogen (as occurred in M. tuberculosis several thousand years ago). Our findings indicate how key interventions, such as early treatment and cross-infection control, might restrict existing pathogens and prevent new, emergent ones. ![Figure] Steps involved in mycobacterial pathogenic evolution. (1) Horizontal gene acquisition by environmental clones drives saltational evolution and gives rise to the ancestors of the dominant circulating clones of M. abscessus (and virulent clones within other mycobacterial species). (2) Allopatric within-host adaptation during chronic infection drives increased intracellular survival within macrophages and inflammatory lung damage. (3) Evolution is constrained while M. abscessus is transmitted through environmental intermediaries because the most highly adapted strains lose transmission fitness through reduced fomite survival. (4) Opportunities for direct transmission of emergent mycobacteria (potentially through increases in population density and/or host susceptibility) permit unconstrained, accelerated evolution (as occurred in M. tuberculosis ). Although almost all mycobacterial species are saprophytic environmental organisms, a few, such as Mycobacterium tuberculosis , have evolved to cause transmissible human infection. By analyzing the recent emergence and spread of the environmental organism M. abscessus through the global cystic fibrosis population, we have defined key, generalizable steps involved in the pathogenic evolution of mycobacteria. We show that epigenetic modifiers, acquired through horizontal gene transfer, cause saltational increases in the pathogenic potential of specific environmental clones. Allopatric parallel evolution during chronic lung infection then promotes rapid increases in virulence through mutations in a discrete gene network; these mutations enhance growth within macrophages but impair fomite survival. As a consequence, we observe constrained pathogenic evolution while person-to-person transmission remains indirect, but postulate accelerated pathogenic adaptation once direct transmission is possible, as observed for M. tuberculosis . Our findings indicate how key interventions, such as early treatment and cross-infection control, might restrict the spread of existing mycobacterial pathogens and prevent new, emergent ones. : /lookup/doi/10.1126/science.abb8699 : /lookup/doi/10.1126/science.abi5695 : pending:yes
Science X staff
April 29, 2021
A research group working at Uppsala University has succeeded in studying 'translation factors' - important components of a cell's protein synthesis machinery--that are several billion years old. By studying these ancient 'resurrected' factors, the researchers were able to establish that they had much broader specificities than their present-day, more specialized counterparts.
Science X staff
April 12, 2021
Jaakko Patrakka and his research group at the Department of Laboratory Medicine have together with Professor Rickard Sandberg's group at the Department of Cell and Molecular Biology got a publication accepted in Nature Communications about single cell sequencing unravels molecular identity of rare renal cell types.
Liu, C., Shen, L., Xiao, Y., Vyshedsky, D., Peng, C., Sun, X., Liu, Z., Cheng, L., Zhang, H., Han, Z., Chai, J., Wu, H.-M., Cheung, A. Y., Li, C.
April 9, 2021
When a pollen grain lands on a receptive flower's pistil, a complex dance leading to sexual reproduction begins. Liu et al. show some of the early steps that help to distinguish a compatible pollen grain from a random piece of dust. Normally, a stigmatic gatekeeper, the ANJEA-FERONIA receptor kinase complex, perceives signaling peptides produced by the stigma that drive the production of reactive oxygen species at the stigma papillae. Upon pollination, POLLEN COAT PROTEIN B-class peptides compete with those stigmatic peptides for binding to the stigmatic receptor kinase complex. The subsequent decline of stigmatic reactive oxygen species production allows hydration and opens the gates to pollen germination. Science , this issue p.  Sexual reproduction in angiosperms relies on precise communications between the pollen and pistil. The molecular mechanisms underlying these communications remain elusive. We established that in Arabidopsis , a stigmatic gatekeeper, the ANJEA-FERONIA (ANJ-FER) receptor kinase complex, perceives the RAPID ALKALINIZATION FACTOR peptides RALF23 and RALF33 to induce reactive oxygen species (ROS) production in the stigma papillae, whereas pollination reduces stigmatic ROS, allowing pollen hydration. Upon pollination, the POLLEN COAT PROTEIN B-class peptides (PCP-Bs) compete with RALF23/33 for binding to the ANJ-FER complex, leading to a decline of stigmatic ROS that facilitates pollen hydration. Our results elucidate a molecular gating mechanism in which distinct peptide classes from pollen compete with stigma peptides for interaction with a stigmatic receptor kinase complex, allowing the pollen to hydrate and germinate. : /lookup/doi/10.1126/science.abc6107
March 4, 2021
The Economic Times
The study was carried out by the Centre for Cellular and Molecular Biology, the National Institute of Nutrition (NIN) and vaccine innovator Bharat Biotech International (BBIL) on seroprevalence of antibodies to SARS-COV-2 in around 9,000 persons in Hyderabad.
New York Genome Center
December 9, 2020
/PRNewswire/ -- The New York Genome Center (NYGC) announced today that it has created a Scientific Advisory Board (SAB) to provide counsel and support for the...
Science X staff
November 30, 2020
A research group from the Department of Biochemistry and Molecular Biology of the University of Valencia (UV), in coordination with the National Center for Biotechnology (CNB) of the CSIC, has studied the role of the interactions within the membrane of proteins of viral families Herpesviridae and Poxviridae in the control of programmed cell death. The work, published in Nature Communications, could have implications for the development of treatments for viral infection, as well as the prevention of cancers associated with them.
June 9, 2020
AXIM® Biotechnologies, Inc. (OTCQB: AXIM) ("AXIM® Biotech," "AXIM" or "the Company"), an international healthcare solutions company targeting oncological research, announced today it has appointed Dr. Alim Seit-Nebi as the Chief Technology Officer ("CTO") of its subsidiary Sapphire Biotech, Inc. ("Sapphire").
Science X staff
October 2, 2019
Parasitic flukes have been a leading source of food-borne infections, sparking fear and wreaking havoc on human public health, and contributed to more than 3 billion in animal agricultural losses per year in the U.S. alone.
November 30, 2018
Born in Lithuania, raised in South Africa and working in Britain, he made large strides in understanding the structure of proteins, DNA and more.