Preface by Prof. Titia de Lange, Laboratory for Cell Biology and Genetics, The Rockefeller University, New York, NY 10065, USA The 19th Annual Wiley Prize in Biomedical Sciences celebrated a breakthrough in cell biology: how membrane-less cellular compartments are formed. The existence of membrane-less organelles, often called bodies or puncta, have been known for a long time, but what exactly they represented and how they were formed was not known. This problem was solved by a physicist, Clifford Brangwynne, a cell biologist, Anthony Hyman and a chemist, Michael Rosen. Each, synergistically, made groundbreaking contributions to the discovery that membrane-less organelles are liquid-liquid phase-separated entities. The two independent discoveries leading to the principle that multivalent low-affinity interactions between selected sets of macromolecules, some containing intrinsically disordered regions, formed a molecular condensate with unique dynamic properties, gave birth to the large, blossoming field of biomolecular condensates. The implications of those findings have influenced almost all further research of intracellular processes, including RAS signaling, immune synapses, DNA repair, transcriptional activation, and the functions of nuclear pores, the nucleolus and centrosomes. In this Perspective article, the laureates of the award take us on their personal and professional trip that led to their scientific discoveries. Their stories are a celebration of the interdisciplinary essence of Natural Sciences and the potential unlocked when scientists from different fields work together to solve mysteries.
Since a polyvalent strategy has recently been assumed to be adopted by Deinococcus radiodurans that can generate various resistance against many different detrimental sources of oxidative damage (e.g. reactive oxygen species, heavy metal ions and ionising radiation), investigating more than one restorative metabolic activities and their interrelation of the very same entities of Deinococcus radiodurans is of great significance for exploring its polyextremophile nature, which will be insightful for obtaining fundamental generic insights into life sustainability. Herein, we apply mainly fluorescence microscopy and back reflection microscopy to visibly assess the respective activities of superoxide radical generation and silver ion metabolism for individual Deinococcus radiodurans. Strikingly, only a minority (<20%) of the bacteria which show low superoxide radical levels is revealed to exhibit considerable formation of silver nanoparticles whilst those containing more superoxide radicals all show minimum silver ion metabolism. The discovery of the strong negative correlation for the small subpopulation between the two visualised different metabolic activities not only provides direct experimental evidence in terms of bacterial functionality for the inferred survival regime of the extreme microbe, but also suggests a new way of chemically examining biology from the perspective of inter-functional relationship.
Mitochondria continuously undergo morphologically dynamic processes of fusion and fission to maintain their size, shape, amount, and function; yet the precise molecular mechanisms by which mitochondrial dynamics is regulated remain to be fully elucidated. Here, we report a previous unappreciated but critical role of eukaryotic elongation factor 2 (eEF2) in regulating mitochondrial fission. eEF2, a G-protein superfamily member encoded by EEF2 gene in human, has long been appreciated as a promoter of the GTP-dependent translocation of the ribosome during protein synthesis. We found unexpectedly in several types of cells that eEF2 was not only present in the cytosol but also in the mitochondria. Furthermore, we showed that mitochondrial length was significantly increased when the cells were subjected to silencing of eEF2 expression, suggesting a promotive role for eEF2 in the mitochondrial fission. Inversely, overexpression of eEF2 decreased mitochondrial length, suggesting an increase of mitochondrial fission. Inhibition of mitochondrial fission caused by eEF2 depletion was accompanied by alterations of cellular metabolism, as evidenced by a reduction of oxygen consumption and an increase of oxidative stress in the mitochondria. We further demonstrated that eEF2 and Drp1, a key driver of mitochondrial fission, co-localized at the mitochondria, as evidenced by microscopic observation, co-immunoprecipitation, and GST pulldown assay. Deletion of the GTP binding motif of eEF2 decreased its association with Drp1 and abrogated its effect on mitochondria fission. Moreover, we showed that wild-type eEF2 stimulated GTPase activity of Drp1, whereas deletion of the GTP binding site of eEF2 diminished its stimulatory effect on GTPase activity. This work not only reveals a previously unrecognized function of eEF2 (i.e., promoting mitochondrial fission), but also uncovers the interaction of eEF2 with Drp1 as a novel regulatory mechanism of the mitochondrial dynamics. Therefore, eEF2 warrants further exploration for its potential as a therapeutic target for the mitochondria-related diseases.
This Research Highlight showcases the two Research Papers entitled, A precise photometric ratio via laser excitation of the sodium layer – I. One-photon excitation using 342.78 nm light, https://doi.org/10.1093/mnras/stab1621 and A precise photometric ratio via laser excitation of the sodium layer – II. Two-photon excitation using lasers detuned from 589.16 nm and 819.71 nm resonances, https://doi.org/10.1093/mnras/stab1619.
Silicon-based anodes with lithium ions as charge carriers have the highest predicted theoretical specific capacity of 3579 mA h g-1 (for Li15Si4). Contemporary electrodes do not achieve this theoretical value largely because conventional production paradigms rely on the mixing of weakly coordinated components. In this paper, a semi-conductive triazine-based graphdiyne polymer network is grown around silicon nanoparticles directly on the current collector, a copper sheet. The porous, semi-conducting organic framework (i) adheres to the current collector on which it grows via cooperative van der Waals interactions, (ii) acts effectively as conductor for electrical charges and binder of silicon nanoparticles via conjugated, covalent bonds, and (iii) enables selective transport of electrolyte and Li-ions through pores of defined size. The resulting anode shows extraordinarily high capacity at the theoretical limit of fully lithiated silicon. Finally, we combine our anodes in proof-of-concept battery assemblies using a conventional layered Ni-rich oxide cathode.
￼￼￼￼￼￼￼The free propagation in time of a normalisable wave packet is the oldest problem of continuum quantum mechanics. Its motion from microscopic to macroscopic distance is the way in which most quantum systems are detected experimentally. Although much studied and analysed since 1927 and presented in many text books, here the problem is re-appraised from the standpoint of semi-classical mechanics. Particular aspects are the emergence of deterministic trajectories of particles emanating from a region of atomic dimensions and the interpretation of the wave function as describing a single particle or an ensemble of identical particles. Of possible wave packets, that of gaussian form is most studied due to the simple exact form of the time-dependent solution in real and in momentum space. Furthermore, this form is important in laser optics. Here the equivalence of the time-dependent Schroedinger equation to the paraxial equation for the propagation of light is demonstrated explicitly. This parallel helps to understand the relevance of trajectory concepts and the conditions necessary for the perception of motion as classical.
This Research Highlight provides context for the report of Gope et al. on experimental and computational probes of the decay of doubly-ionized methanol to H3+ and HCO+/COH+. The formation of the H3+ ionic product is shown to occur through the agency of a roaming H2 molecule generated from the carboxyl moiety that undergoes prompt proton transfer from the carbon atom, or, delayed proton transfer from the oxygen atom. This novel method for H3+ formation is contrasted with the conventional ion-molecule pathway, known for over a century, that forms the basis for interstellar molecule formation.
Background: Oral squamous cell carcinoma (OSCC) accounts for 90 % of oral cancers. If a necessary intervention before tumorigenesis could be conducted, the current 60% 5-year survival rate would be expected to be majorly improved. This fact motivates the search for developing a highly sensitive and specific in vitro diagnostic method to conduct rapid OSCC screening. Method: Serum samples from 819 volunteers, consisted of 241 healthy contrast (HC) and 578 OSCC patients, were collected, and their metabolic profiles were acquired using conductive polymer spray ionization mass spectrometry (CPSI-MS). Univariate analysis was used to select significantly changed metabolite ions in the OSCC group compared to the HC group. Identities of these metabolite ions were determined by MS/MS experiments and reconfirmed at the tissue level by desorption electrospray ionization mass spectrometry (DESI-MS). The supporting vector machine (SVM) algorithm was employed as the machine learning model to implement the automatic prediction of OSCC. Results: Through statistical analysis, 65 metabolites were selected as potential characteristic marker candidates for serum OSCC screening. In situ validation by DESI-MSI revealed that 8 out of top 10 metabolites showed the same trends of change in tissue and serum. With the aid of machine learning, OSCC can be distinguished from HC with an accuracy of 98.0 % by cross-validation in the discovery cohort and 89.2% accuracy in the validation cohort. Furthermore, orthogonal partial least square-discriminant analysis (OPLS-DA) also showed the potential for recognizing OSCC stages. Conclusion: Using CPSI-MS combined with SVM, it is possible to distinguish OSCC from HC in a few minutes with high specificity and sensitivity, making this rapid diagnostic procedure a promising approach for high-risk population screening.
Molecular motors change conformation under the influence of light and when attached to host molecules they may find applications as sensors and switchable catalysts. Here we present a porphyrin macrocyclic host functionalized with two motor appendages for future catalytic applications. The compound is formed as a mixture of six stereoisomers (three sets of enantiomers), which have been separated by (chiral) chromatography. 1H NMR and chiral spectroscopy revealed that in one set of diastereomers the two motors interact with the cavity of the host (bound-bound), whereas in a second set one interacts and the other one does not (bound-loose). In the third set both motors do not interact with the host compound (loose-loose). The motorized hosts bind guest molecules in the order: (loose-loose) > (bound-loose) > (bound-bound). They can be switched with light to pseudo-identical diastereomers, leading to orthogonal behavior in the light-gated binding of guest molecules. Whereas the photo-isomerization of the diastereomer set loose-loose significantly lowers the binding affinity for viologen guests, the opposite is true for the diastereomer set bound-bound, i.e. the binding affinity increases. For the diastereomer set bound-loose no influence on guest binding is observed as the effect of photoisomerization on the motors is cancelled out.
Prompted by the centenary of Alfred Landé’s g-factor, we reconstruct Landé’s path to his discovery of half-integer angular momentum quantum numbers and of vector coupling of atomic angular momenta - both encapsulated in the g-factor - as well as point to reverberations of Landé’s breakthroughs in the work of other pioneers of quantum physics.
Light pollution modelling and monitoring has traditionally used zenith sky brightness as its main indicator. Several other indicators (e.g. average sky radiance, horizontal irradiance, average sky radiance at given interval of zenith distances) may be more useful, both for general and for specific purposes of ecology studies, night sky and environmental monitoring. These indicators can be calculated after the whole sky radiance is known with sufficient angular detail. This means, for each site, to integrate the contribution in each direction of the sky of each light source in the radius of hundreds of km. This approach is extremely high time consuming if the mapping is desired for a large territory. Here we present a way to obtain maps of large territories for a large subset of useful indicators, bypassing the need to calculate first the radiance map of the whole sky in each site to obtain from it the desired indicator in that site. For each indicator, a point spread function (PSF) is calculated from the whole sky radiance maps generated by a single source at sufficiently dense number of distances from the observing site. If the PSF is transversally shift-invariant, i.e. if it depends only on the relative position of source and observer, then we can further speed up the map calculation via the use of fast Fourier-transform (FFT). We present here examples of maps for different indicators. Precise results can be calculated for any single site, taking into account the site and light sources altitudes, by means of specific inhomogeneous (spatially-variant) and anisotropic (non rotationally symmetric) PSFs.
The efficient construction of γ-chirogenic amines has been realized via asymmetric hydrogenation of γ-branched N-phthaloyl allylamines by using a bisphosphine-Rh catalyst bearing a large bite angle. The desired products possessing different types of γ-substituents were obtained in quantitative yields and with excellent enantioselectivities (up to >99.9% ee). This protocol provided a practical method for the preparation of γ-chirogenic amine derivatives such as the famous antidepressant drug Fluoxetine (up to 50000 S/C). The mechanism calculation shows a weak interaction-promoted activation mode which is completely different from the traditional coordination-promoted activation mode in the Rh-catalyzed hydrogenation.
Editorial: Natural Sciences is debuting“There’s a way to do it better – find it.” –Thomas A. EdisonWelcome to Wiley’s new flagship journal, Natural Sciences. Our aim is to meet the challenge of publishing top-tier papers in an open-science environment and thereby contribute to innovating the ways scientists communicate with one another and with society at large. We encourage you to partake in this transformative endeavor.Natural Sciences is an inter- and multidisciplinary journal that publishes outstanding research from the global community spanning biology, chemistry, and physics and their interfaces, as well as seminal works from related fields such as engineering and biomedical research. The journal’s aspiration is to promote the sharing and hybridization of disciplinary perspectives and thereby to foster crossing of the traditional boundaries that have previously separated disciplines. The journal will feature Research Articles of all lengths and formats, Commentaries, and Reviews, as well as Editorials, Highlights, Book Reviews, and News items.In contrast to many other high-ranking “elite” journals, Natural Sciences is run by practicing academic scientists who will treat submitted papers just like they wish their own papers would be treated – fairly, quickly, and without bias. That’s why our tagline readsA Journal of, by, and for scientists .By embracing open science, Natural Sciences will promote the global scientific community’s shared goal of enriching society with freely accessible prime scientific research. With open-science in general and open-access publishing in particular, the cost of scientific publishing will be carried by funding agencies or research institutions, and not the reader. Subscription-model-based academic publishing will be relegated to the sidelines, and scientific publications made freely accessible and re-usable for all.Moreover, Natural Sciences supports the cultural changes in the research community that call for increased transparency and openness in communicating and sharing the results of scientific research. Open science encompasses not only open-access publishing but also open peer review and sharing of primary scientific data. These, along with reviewer recognition, are key innovations effecting such a transformation and will be espoused by Natural Sciences .In developing the concept of Natural Sciences , we worked closely with Wiley to ensure efficient editorial practices. Wiley’s international network of experienced professionals steeped in scientific publishing are there for us 24/7. Together, we are committed to open-science publishing that is timely and rigorous – and to embracing open-science innovations in the process.The ideas and values that led us to envision Natural Sciences are summarized in our Manifesto [link to https://onlinelibrary.wiley.com/page/journal/26986248/homepage/manifesto].Natural Sciences is now open for submissions [link to https://mc.manuscriptcentral.com/naturalsciences]. The Article Processing Charge (APC) will be waived during the first two years.Looking forward to your submissions,Bretislav Friedrich, Executive EditorMarianne Bronner, Chief Biology EditorVivian Yam, Chief Chemistry EditorGerard Meijer, Chief Physics Editor [link all the names to https://onlinelibrary.wiley.com/page/journal/26986248/homepage/editorial-board]