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Scientists’ fears of racial bias surge amid US crackdown on China ties (2021)

Subbaraman, Nidhi

Springer Nature

In: Nature. 2021; Published 2021 Oct 29. doi: 10.1038/d41586-021-02976-8. [early online release]

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Publikationsdatum: 2021-10-29

Print ISSN: 0028-0836

Digitale ISSN: 1476-4687

Thema: Biologie , Chemie und Pharmazie , Medizin , Allgemeine Naturwissenschaft , Physik

Publiziert von Springer Nature

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Synthetic zwitterions as efficient non-permeable cryoprotectants (2021)

Kato, Yui ; Uto, Takuya ; Tanaka, Daisuke ; [weitere]

Springer Nature

In: Communications Chemistry. 2021; 4(1): 151. Published 2021 Oct 28. doi: 10.1038/s42004-021-00588-x.

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Publikationsdatum: 2021-10-28

Beschreibung: Cryopreservation of cells is necessary for long periods of storage. However, some cell lines cannot be efficiently cryopreserved, even when optimized commercial cryoprotectants are employed. Previously, we found that a low-toxic synthetic zwitterion aqueous solution enabled good cryopreservation. However, this zwitterion solution could not cryopreserve some cells, such as human kidney BOSC cells, with good efficiency. Therefore, details of the cryoprotective effect of the zwitterions and optimization based on its mechanisms are required. Herein, we synthesized 18 zwitterion species and assessed the effects of the physical properties of water/zwitterion mixtures. Non-cell-permeable zwitterions can inhibit ice crystal formation extracellularly via direct interaction with water and intracellularly via dehydration of cells. However, cells that could not be cryopreserved by zwitterions were insufficiently dehydrated in the zwitterion solution. Dimethyl sulfoxide (DMSO) was combined as a cell-permeable cryoprotectant to compensate for the shortcomings of non-cell-permeable zwitterions. The water/zwitterion/DMSO (90/10/15, v/w/w) could cryopreserve different cells, for example freezing-vulnerable K562 and OVMANA cells; yielding ~1.8-fold cell viability compared to the case using a commercial cryoprotectant. Furthermore, molecular dynamics simulation indicated that the zwitterions protected the cell membrane from the collapse induced by DMSO.

Digitale ISSN: 2399-3669

Thema: Chemie und Pharmazie

Publiziert von Springer Nature

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Improvement of a synthetic live bacterial therapeutic for phenylketonuria with biosensor-enabled enzyme engineering (2021)

Adolfsen, Kristin J. ; Callihan, Isolde ; Monahan, Catherine E. ; [weitere]

Springer Nature

In: Nature Communications. 2021; 12(1): 6215. Published 2021 Oct 28. doi: 10.1038/s41467-021-26524-0.

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Publikationsdatum: 2021-10-28

Beschreibung: In phenylketonuria (PKU) patients, a genetic defect in the enzyme phenylalanine hydroxylase (PAH) leads to elevated systemic phenylalanine (Phe), which can result in severe neurological impairment. As a treatment for PKU, Escherichia coli Nissle (EcN) strain SYNB1618 was developed under Synlogic’s Synthetic Biotic™ platform to degrade Phe from within the gastrointestinal (GI) tract. This clinical-stage engineered strain expresses the Phe-metabolizing enzyme phenylalanine ammonia lyase (PAL), catalyzing the deamination of Phe to the non-toxic product trans-cinnamate (TCA). In the present work, we generate a more potent EcN-based PKU strain through optimization of whole cell PAL activity, using biosensor-based high-throughput screening of mutant PAL libraries. A lead enzyme candidate from this screen is used in the construction of SYNB1934, a chromosomally integrated strain containing the additional Phe-metabolizing and biosafety features found in SYNB1618. Head-to-head, SYNB1934 demonstrates an approximate two-fold increase in in vivo PAL activity compared to SYNB1618.

Digitale ISSN: 2041-1723

Thema: Biologie , Chemie und Pharmazie , Allgemeine Naturwissenschaft , Physik

Publiziert von Springer Nature

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Effectiveness of ChAdOx1 vaccine in older adults during SARS-CoV-2 Gamma variant circulation in São Paulo (2021)

Hitchings, Matt D. T. ; Ranzani, Otavio T. ; Dorion, Murilo ; [weitere]

Springer Nature

In: Nature Communications. 2021; 12(1): 6220. Published 2021 Oct 28. doi: 10.1038/s41467-021-26459-6.

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Publikationsdatum: 2021-10-28

Beschreibung: A two-dose regimen of the Oxford-AstraZeneca (ChAdOx1) Covid-19 vaccine with an inter-dose interval of three months has been implemented in many countries with restricted vaccine supply. However, there is limited evidence for the effectiveness of ChAdOx1 by dose in elderly populations in countries with high prevalence of the Gamma variant of SARS-CoV-2. Here, we estimate ChAdOx1 effectiveness by dose against the primary endpoint of RT-PCR-confirmed Covid-19, and secondary endpoints of Covid-19 hospitalization and Covid-19-related death, in adults aged ≥60 years during an epidemic with high Gamma variant prevalence in São Paulo state, Brazil using a matched, test-negative case-control study. Starting 28 days after the first dose, effectiveness of a single dose of ChAdOx1 is 33.4% (95% CI, 26.4–39.7) against Covid-19, 55.1% (95% CI, 46.6–62.2) against hospitalization, and 61.8% (95% CI, 48.9–71.4) against death. Starting 14 days after the second dose, effectiveness of the two-dose schedule is 77.9% (95% CI, 69.2–84.2) against Covid-19, 87.6% (95% CI, 78.2–92.9) against hospitalization, and 93.6% (95% CI, 81.9–97.7) against death. Completion of the ChAdOx1 vaccine schedule affords significantly increased protection over a single dose against mild and severe Covid-19 outcomes in elderly individuals during widespread Gamma variant circulation.

Digitale ISSN: 2041-1723

Thema: Biologie , Chemie und Pharmazie , Allgemeine Naturwissenschaft , Physik

Publiziert von Springer Nature

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Impact of intensifying nitrogen limitation on ocean net primary production is fingerprinted by nitrogen isotopes (2021)

Buchanan, Pearse J. ; Aumont, Olivier ; Bopp, Laurent ; [weitere]

Springer Nature

In: Nature Communications. 2021; 12(1): 6214. Published 2021 Oct 28. doi: 10.1038/s41467-021-26552-w.

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Publikationsdatum: 2021-10-28

Beschreibung: The open ocean nitrogen cycle is being altered by increases in anthropogenic atmospheric nitrogen deposition and climate change. How the nitrogen cycle responds will determine long-term trends in net primary production (NPP) in the nitrogen-limited low latitude ocean, but is poorly constrained by uncertainty in how the source-sink balance will evolve. Here we show that intensifying nitrogen limitation of phytoplankton, associated with near-term reductions in NPP, causes detectable declines in nitrogen isotopes (δ15N) and constitutes the primary perturbation of the 21st century nitrogen cycle. Model experiments show that ~75% of the low latitude twilight zone develops anomalously low δ15N by 2060, predominantly due to the effects of climate change that alter ocean circulation, with implications for the nitrogen source-sink balance. Our results highlight that δ15N changes in the low latitude twilight zone may provide a useful constraint on emerging changes to nitrogen limitation and NPP over the 21st century.

Digitale ISSN: 2041-1723

Thema: Biologie , Chemie und Pharmazie , Allgemeine Naturwissenschaft , Physik

Publiziert von Springer Nature

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Increasing the efficiency and precision of prime editing with guide RNA pairs (2021)

Zhuang, Yuan ; Liu, Jiangle ; Wu, Hao ; [weitere]

Springer Nature

In: Nature Chemical Biology. 2021; Published 2021 Oct 28. doi: 10.1038/s41589-021-00889-1. [early online release]

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Publikationsdatum: 2021-10-28

Print ISSN: 1552-4450

Digitale ISSN: 1552-4469

Thema: Biologie , Chemie und Pharmazie

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Microenvironmental IL-6 inhibits anti-cancer immune responses generated by cytotoxic chemotherapy (2021)

Bent, Eric H. ; Millán-Barea, Luis R. ; Zhuang, Iris ; [weitere]

Springer Nature

In: Nature Communications. 2021; 12(1): 6218. Published 2021 Oct 28. doi: 10.1038/s41467-021-26407-4.

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Publikationsdatum: 2021-10-28

Beschreibung: Cytotoxic chemotherapeutics primarily function through DNA damage-induced tumor cell apoptosis, although the inflammation provoked by these agents can stimulate anti-cancer immune responses. The mechanisms that control these distinct effects and limit immunogenic responses to DNA-damage mediated cell death in vivo are currently unclear. Using a mouse model of BCR-ABL+ B-cell acute lymphoblastic leukemia, we show that chemotherapy-induced anti-cancer immunity is suppressed by the tumor microenvironment through production of the cytokine IL-6. The chemotherapeutic doxorubicin is curative in IL-6-deficient mice through the induction of CD8+ T-cell-mediated anti-cancer responses, while moderately extending lifespan in wild type tumor-bearing mice. We also show that IL-6 suppresses the effectiveness of immune-checkpoint inhibition with anti-PD-L1 blockade. Our results suggest that IL-6 is a key regulator of anti-cancer immune responses induced by genotoxic stress and that its inhibition can switch cancer cell clearance from primarily apoptotic to immunogenic, promoting and maintaining durable anti-tumor immune responses.

Digitale ISSN: 2041-1723

Thema: Biologie , Chemie und Pharmazie , Allgemeine Naturwissenschaft , Physik

Publiziert von Springer Nature

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Mechanics-driven nuclear localization of YAP can be reversed by N-cadherin ligation in mesenchymal stem cells (2021)

Zhang, Cheng ; Zhu, Hongyuan ; Ren, Xinru ; [weitere]

Springer Nature

In: Nature Communications. 2021; 12(1): 6229. Published 2021 Oct 28. doi: 10.1038/s41467-021-26454-x.

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Publikationsdatum: 2021-10-28

Beschreibung: Mesenchymal stem cells adopt differentiation pathways based upon cumulative effects of mechanosensing. A cell’s mechanical microenvironment changes substantially over the course of development, beginning from the early stages in which cells are typically surrounded by other cells and continuing through later stages in which cells are typically surrounded by extracellular matrix. How cells erase the memory of some of these mechanical microenvironments while locking in memory of others is unknown. Here, we develop a material and culture system for modifying and measuring the degree to which cells retain cumulative effects of mechanosensing. Using this system, we discover that effects of the RGD adhesive motif of fibronectin (representative of extracellular matrix), known to impart what is often termed “mechanical memory” in mesenchymal stem cells via nuclear YAP localization, are erased by the HAVDI adhesive motif of the N-cadherin (representative of cell-cell contacts). These effects can be explained by a motor clutch model that relates cellular traction force, nuclear deformation, and resulting nuclear YAP re-localization. Results demonstrate that controlled storage and removal of proteins associated with mechanical memory in mesenchymal stem cells is possible through defined and programmable material systems.

Digitale ISSN: 2041-1723

Thema: Biologie , Chemie und Pharmazie , Allgemeine Naturwissenschaft , Physik

Publiziert von Springer Nature

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