The role of glyoxylic acid in the chemistry of the origin of life

I present detailed mechanistic analysis on the chemistry of glyoxylate as it pertains to forming biologically relevant molecules on the Hadean Earth. Chemistry covered includes: 1) the dimerization of glyoxylate to form dihydroxyfumarate(DHF), a heretofore unknown reaction, important to substantiating Eschenmoser's glyoxylate scenario. 2) Formation of sugars from polymerization of glyoxylate. 3) Formation of tartrate and sugar acids from high pH reactions of DHF. 4) Formation of glycine polypeptides from glyoxylate by transamination and coupling promoted by hexamethylenetetramine. 5) Formation of glyoxylate under conditions which could be plausibly found on the early earth.Ph.D

Extreme magnetic field-boosted superconductivity

Applied magnetic fields underlie exotic quantum states, such as the fractional quantum Hall effect and Bose-Einstein condensation of spin excitations. Superconductivity, on the other hand, is inherently antagonistic towards magnetic fields. Only in rare cases can these effects be mitigated over limited fields, leading to reentrant superconductivity. Here, we report the unprecedented coexistence of multiple high-field reentrant superconducting phases in the spin-triplet superconductor UTe2. Strikingly, we observe superconductivity in the highest magnetic field range identified for any reentrant superconductor, beyond 65 T. These extreme properties reflect a new kind of exotic superconductivity rooted in magnetic fluctuations and boosted by a quantum dimensional crossover

Detection of a Pair Density Wave State in UTe2_2

Although UTe$_2$ is a very promising candidate material to embody bulk topological superconductivity, its superconductive order-parameter $\Delta(\mathbf{k})$ remains unknown. Many diverse forms for $\Delta(\mathbf{k})$ are physically possible because, in uranium-based heavy fermion materials, strongly hybridized flat bands of composite fermions generate highly complex interactions. Moreover, in such materials intertwined density waves of spin (SDW), charge (CDW) and pairs (PDW) may interpose, with the latter state exhibiting spatially modulating superconductive order-parameter $\Delta(\mathbf{r})$, electron pair density and pairing energy-gap. Hence, the newly discovered CDW state in UTe$_2$ motivates the exciting prospect that a PDW state may exist in this material. To search for a PDW in UTe$_2$, we visualize the pairing energy-gap with $\mu$$V$-scale energy-resolution made possible by superconductive STM tips at subkelvin temperatures. We detect three PDWs, each with peak-peak gap modulations circa 10 $\mu$$eV$ and at incommensurate wavevectors $\mathbf{P}_{i=1,2,3}$ that are indistinguishable from the wavevectors $\mathbf{Q}_{i=1,2,3}$ of the prevenient CDW. Concurrent visualization of the UTe$_2$ superconductive PDWs and the non-superconductive CDWs reveals that every $\mathbf{P}_i$ : $\mathbf{Q}_i$ pair is registered to each other spatially, but with a relative phase $\delta\phi \approx \pi$. From these observations, and given UTe$_2$ as a spin-triplet superconductor, the PDW state detected here should be a spin-triplet pair density wave. While such states do exist in superfluid $^{3}$He, for superconductors they are unprecedented.Comment: 37 pages, 13 figure

A Strategy for Origins of Life Research

Aworkshop was held August 26–28, 2015, by the Earth- Life Science Institute (ELSI) Origins Network (EON, see Appendix I) at the Tokyo Institute of Technology. This meeting gathered a diverse group of around 40 scholars researching the origins of life (OoL) from various perspectives with the intent to find common ground, identify key questions and investigations for progress, and guide EON by suggesting a roadmap of activities. Specific challenges that the attendees were encouraged to address included the following: What key questions, ideas, and investigations should the OoL research community address in the near and long term? How can this community better organize itself and prioritize its efforts? What roles can particular subfields play, and what can ELSI and EON do to facilitate research progress? (See also Appendix II.) The present document is a product of that workshop; a white paper that serves as a record of the discussion that took place and a guide and stimulus to the solution of the most urgent and important issues in the study of the OoL. This paper is not intended to be comprehensive or a balanced representation of the opinions of the entire OoL research community. It is intended to present a number of important position statements that contain many aspirational goals and suggestions as to how progress can be made in understanding the OoL. The key role played in the field by current societies and recurring meetings over the past many decades is fully acknowledged, including the International Society for the Study of the Origin of Life (ISSOL) and its official journal Origins of Life and Evolution of Biospheres, as well as the International Society for Artificial Life (ISAL)

Computational Exploration of the Chemical Space of Nucleic Acid-Like Compounds

Biological information storage for life as we know it is carried out by the nucleic acids DNA and RNA. However, these may be optimized end-states for life on Earth, or there may be other types of molecules which are similarly capable of carrying out these functions, perhaps used in alien biochemistries or in earlier biochemical states. A number of these have already been synthesized in the lab, however the set of molecules compatible with this function may be far larger. Understanding this wider "chemical space" may give insights into what makes the biological isomers unique, as well as whether there are other isomers more easily accessed by abiotic chemistry

Open questions in understanding life's origins

The chemical space of prebiotic chemistry is extremely large, while extant biochemistry uses only a few thousand interconnected molecules. Here we discuss how the connection between these two regimes can be investigated, and explore major outstanding questions in the origin of life

One Among Millions: The Chemical Space of Nucleic Acid-Like Molecules

Biology encodes hereditary information in DNA and RNA, which are finely tuned to their biological functions and modes of biological production. The central role of nucleic acids in biological information flow makes them key targets of pharmaceutical research. Indeed, other nucleic acid-like polymers can play similar roles to natural nucleic acids both in vivo and in vitro; yet despite remarkable advances over the last few decades, much remains unknown regarding which structures are compatible with molecular information storage. Chemical space describes the structures and properties of molecules that could exist within a given molecular formula or other classification system. Using structure generation methods, we explore nucleic acid analogues within the formula ranges BC3-7H5-15O2-4 and BC3-6H5-15N1-2O0-4, where B is a recognition element (e.g., a nucleobase). Other restrictions included two obligatory points of attachment for inclusion into a linear polymer and substructures predicting chemical stability. These sets contain 86,007 (CHO) and 75,309 (CHNO) compositionally isomeric structures, representing 706,568 CHO and 454,422 CHNO stereoisomers, that diversely and densely occupy this space. These libraries point toward there being large spaces of unexplored chemistry relevant to pharmacology and biochemistry and efforts to understand the origins of life

Computational Investigations of Traditional Chinese Medicinal Compounds against the Omicron Variant of SARS-CoV-2 to Rescue the Host Immune System

Macrodomain-I of the NSP3 (non-structural protein 3) is responsible for immune response hijacking in the SARS-CoV-2 infection known as COVID-19. In the omicron variant (B.1.1.529), this domain harbors a new mutation, V1069I, which may increase the binding of ADPr and consequently the infection severity. This macrodomain-I, due to its significant role in infection, is deemed to be an important drug target. Hence, using structural bioinformatics and molecular simulation approaches, we performed a virtual screening of the traditional Chinese medicines (TCM) database for potential anti-viral drugs. The screening of 57,000 compounds yielded the 10 best compounds with docking scores better than the control ADPr. Among the top ten, the best three hits—TCM42798, with a docking score of −13.70 kcal/mol, TCM47007 of −13.25 kcal/mol, and TCM30675 of −12.49 kcal/mol—were chosen as the best hits. Structural dynamic features were explored including stability, compactness, flexibility, and hydrogen bonding, further demonstrating the anti-viral potential of these hits. Using the MM/GBSA approach, the total binding free energy for each complex was reported to be −69.78 kcal/mol, −50.11 kcal/mol, and −47.64 kcal/mol, respectively, which consequently reflect the stronger binding and inhibitory potential of these compounds. These agents might suppress NSP3 directly, allowing the host immune system to recuperate. The current study lays the groundwork for the development of new drugs to combat SARS-CoV-2 and its variants

A novel near-infrared EGFR targeting probe for metastatic lymph node imaging in preclinical mouse models

Abstract For the treatment of patients with oral squamous cell carcinoma (OSCC), the imaging of cervical lymph nodes and the evaluation of metastastic progression are of great significance. In recent years, the development of new non-radioactive lymph node tracers has been an area of intense research. Here, we report the synthesis, good biocompatibility, and in vivo evaluation of a new small molecule near-infrared (NIR) fluorescence probe by the conjugation of Lapatinib to S0456 (LP-S). We show that like Lapatinib, LP-S binds to the epidermal growth factor receptor (EGFR) resulting in high quality fluorescence imaging of metastatic lymph nodes in OSCC mouse models. After local injection of LP-S into the tumor, the lymphatic drainage pathway and lymph nodes can be clearly identified by NIR fluorescence imaging. Further, the LP-S probe shows higher contrast and longer retention in metastatic lymph nodes, allowing them to be differentiated from normal lymph nodes, and affording a new choice for fluorescence-guided surgery. Graphical abstract Scheme. Chemical synthesis and application of EGFR targeting probe LP-S for imaging of metastatic lymph nodes (mLNs) in OSC

Asymmetric Schottky Contacts in van der Waals Metal-Semiconductor-Metal Structures Based on Two-Dimensional Janus Materials

Physical and electronic asymmetry plays a crucial role in rectifiers and other devices with a directionally variant current-voltage (I-V) ratio. Several strategies for practically creating asymmetry in nanoscale components have been demonstrated, but complex fabrication procedures, high cost, and incomplete mechanistic understanding have significantly limited large-scale applications of these components. In this work, we present density functional theory calculations which demonstrate asymmetric electronic properties in a metal-semiconductor-metal (MSM) interface composed of stacked van der Waals (vdW) heterostructures. Janus MoSSe has an intrinsic dipole due to its asymmetric structure and, consequently, can act as either an n-type or p-type diode depending on the face at the interior of the stacked structure (SeMoS-SMoS vs. SMoSe-SMoS). In each configuration, vdW forces dominate the interfacial interactions, and thus, Fermi level pinning is largely suppressed. Our transport calculations show that not only does the intrinsic dipole cause asymmetric I-V characteristics in the MSM structure but also that different transmission mechanisms are involved across the S-S (direct tunneling) and S-Se interface (thermionic excitation). This work illustrates a simple and practical method to introduce asymmetric Schottky barriers into an MSM structure and provides a conceptual framework which can be extended to other 2D Janus semiconductors