Long-range Molecules Research Articles

MiREx: mRNA levels prediction from gene sequence and miRNA target knowledge

Messenger RNA (mRNA) has an essential role in the protein production process. Predicting mRNA expression levels accurately is crucial for understanding gene regulation, and various models (statistical and neural network-based) have been developed for this purpose. A few models predict mRNA expression levels from the DNA sequence, exploiting the DNA sequence and gene features (e.g., number of exons/introns, gene length). Other models include information about long-range interaction molecules (i.e., enhancers/silencers) and transcriptional regulators as predictive features, such as transcription factors (TFs) and small RNAs (e.g., microRNAs - miRNAs). Recently, a convolutional neural network (CNN) model, called Xpresso, has been proposed for mRNA expression level prediction leveraging the promoter sequence and mRNAs’ half-life features (gene features). To push forward the mRNA level prediction, we present miREx, a CNN-based tool that includes information about miRNA targets and expression levels in the model. Indeed, each miRNA can target specific genes, and the model exploits this information to guide the learning process. In detail, not all miRNAs are included, only a selected subset with the highest impact on the model. MiREx has been evaluated on four cancer primary sites from the genomics data commons (GDC) database: lung, kidney, breast, and corpus uteri. Results show that mRNA level prediction benefits from selected miRNA targets and expression information. Future model developments could include other transcriptional regulators or be trained with proteomics data to infer protein levels.

Study on physicochemical, structural, and functional properties of Zhengdan958 and Xianyu335 cornstarch from newly harvested corn under postharvest ripening conditions at ambient temperature

The importance of starch in nutrition and industry is unquestionable. This study investigated the changes in physicochemical, structural, and functional properties of cornstarch from newly harvested Zhengdan958 (Zd958) and Xianyu335 (Xy335) corn during for 0, 20, 40, and 60 d at ambient temperature. The results showed no significant changes in the proximate components and apparent structure of Zd958 and Xy335 cornstarch under postharvest ripening conditions. Compared with 0 d, the molecular weight distribution and mass fraction of Zd958 and Xy335 cornstarch have changed significantly, the relative crystallinity (RC) has significantly increased from 26.4% to 26.5%–28.8% and 28.4%, and R1045/1022 has significantly increased from 0.828 to 0.826 to 0.843 and 0.883, respectively. The changes in structure indicated that the synthesis and rearrangement of cornstarch molecules formed highly ordered crystalline structures, and the ordered structures of long-range and short-range molecules increased. Moreover, the changes in structure affected the pasting characteristics and texture profiles of cornstarch, therefore, affecting the final food quality.

Charged ultralong-range Rydberg trimers

We show that the recently observed class of long-range ion-Rydberg molecules can be divided into two families of states, which are characterised by their unique electronic structures resulting from the ion-induced admixture of quantum defect-split Rydberg $n$P states with different low-field seeking high-$l$ states. We predict that in both cases these diatomic molecular states can bind additional ground state atoms lying within the orbit of the Rydberg electron, thereby forming charged ultralong-range Rydberg molecules (ULRM) with binding energies similar to that of conventional non-polar ULRM. To demonstrate this, we consider a Rydberg atom interacting with a single ground state atom and an ion. The additional atom breaks the system's cylindrical symmetry, which leads to mixing between states that would otherwise be decoupled. The electronic structure is obtained using exact diagonalisation over a finite basis and the vibrational structure is determined using the Multi-Configuration Time-Dependent Hartree method. Due to the lobe-like structure of the electronic density, bound trimers with both linear and nonlinear geometrical configurations of the three nuclei are possible. The predicted trimer binding energies and excitation series are distinct enough from those of the ion-Rydberg dimer to be observed using current experimental techniques.

Phase Transformations from Nanocrystalline to Amorphous (Zr70Ni25Al5)100-xWx (x; 0, 2, 10, 20, 35 at. %) and Subsequent Consolidation.

Glasses, which date back to about 2500 BC, originated in Mesopotamia and were later brought to Egypt in approximately 1450 BC. In contrast to the long-range order materials (crystalline materials), the atoms and molecules of glasses, which are noncrystalline materials (short-range order) are not organized in a definite lattice pattern. Metallic glassy materials with amorphous structure, which are rather new members of the advanced materials family, were discovered in 1960. Due to their amorphous structure, metallic glassy alloys, particularly in the supercooled liquid region, behave differently when compared with crystalline alloys. They reveal unique and unusual mechanical, physical, and chemical characteristics that make them desirable materials for many advanced applications. Although metallic glasses can be produced using different techniques, many of these methods cannot be utilized to produce amorphous alloys when the system has high-melting temperature alloys (above 1500 °C) and/or is immiscible. As a result, such constraints may limit the ability to fabricate high-thermal stable metallic glassy families. The purpose of this research is to fabricate metallic glassy (Zr70Ni25Al5)100-xWx (x; 0, 2, 10, 20, and 35 at. %) by cold rolling the constituent powders and then mechanically alloying them in a high-energy ball mill. The as-prepared metallic glassy powders demonstrated high-thermal stability and glass forming ability, as evidenced by a broad supercooled liquid region and a high crystallization temperature. The glassy powders were then consolidated into full-dense bulk metallic glasses using a spark plasma sintering technique. This consolidation method did not result in the crystallization of the materials, as the consolidated buttons retained their short-range order fashion. Additionally, the current work demonstrated the capability of fabricating very large bulk metallic glassy buttons with diameters ranging from 20 to 50 mm. The results indicated that the microhardness of the synthesized metallic glassy alloys increased as the W concentration increased. As far as the authors are aware, this is the first time this metallic glassy system has been reported.

Differential compartmentalization of BMP4/NOGGIN requires NOGGIN trans-epithelial transport.

Using self-organizing human models of gastrulation, we previously showed that (1) BMP4 initiates the cascade of events leading to gastrulation, (2) BMP4 signal reception is restricted to the basolateral domain, and (3) in a human-specific manner, BMP4 directly induces the expression of NOGGIN. Here, we report the surprising discovery that in human epiblasts, NOGGIN and BMP4 were secreted into opposite extracellular spaces. Interestingly, apically presented NOGGIN could inhibit basally delivered BMP4. Apically imposed microfluidic flow demonstrated that NOGGIN traveled in the apical extracellular space. Our co-localization analysis detailed the endocytotic route that trafficked NOGGIN from the apical space to the basolateral intercellular space where BMP4 receptors were located. This apical-basal transcytosis was indispensable for NOGGIN inhibition. Taken together, the segregation of activator/inhibitor into distinct extracellular spaces challenges classical views of morphogen movement. We propose that the transport of morphogen inhibitors regulates the spatial availability of morphogens during embryogenesis.

Ultra-cold long-range Rydberg-ground molecules

<sec> Ultra-cold long-range Rydberg-ground molecule consisting of a Rydberg atom and one or more ground-state atoms is formed by low-energy scattering between the Rydberg electron and ground-state atoms located inside the Rydberg electron’s wave function. The low-energy scattering interaction, initially investigated by Fermi and Omont, has been predicted to lead to molecular binding in a novel type of Rydberg molecules, including the trilobite and butterfly molecules. Their unconventional binding mechanism, which is unlike covalent, or ionic, or van der Waals bonds, results in loosely bound molecules with bond lengths on the order of thousands of Bohr radius. This kind of molecule with large size and huge permanent electric dipole moment is a good candidate for realizing the certain strongly correlated many-body gases and for quantum information processing, as well as for dipolar quantum gases and spin systems with long-range interactions. Consequently, these molecules have received considerable attention in recent years.</sec><sec>In this paper, we review the recent theoretical and experimental investigations of ultra-cold long-range Rydberg-ground molecules, including the scattering interaction between the Rydberg electron and ground-state atom and the resulting adiabatic potential curves, experimental observations of photo-associated Rydberg-ground molecules spectra, as well as the measurements of permanent electric dipole moment. Ultra-cold long-range Rydberg-ground molecules are prepared by photoassociation in a high-density cold atom sample. Therefore, the Rydberg electron can bind several ground-state atoms to form a polyatomic Rydberg-ground molecule. The permanent molecular electric-dipole moments are revealed by spectral line broadening in the electric fields. The latest research pointed out that the permanent electric dipole moments of the Cs <i>n</i>D<sub><i>J</i></sub> -type Rydberg-ground molecules are negative, which is different from the previous reports (the electric dipole moments are positive). The negative sign reflects a deficiency of Rydberg-electron density near the ground-state perturber, which is caused by electronic configuration mixing. </sec>

Purely long-range polar molecules composed of identical lanthanide atoms

Doubly polar molecules, possessing an electric dipole moment and a magnetic dipole moment, can strongly couple to both an external electric field and a magnetic field, providing unique opportunities to exert full control of the system quantum state at ultracold temperatures. We propose a method for creating a purely long-range doubly polar homonuclear molecule from a pair of strongly magnetic lanthanide atoms, one atom being in its ground level and the other in a superposition of quasi-degenerate opposite-parity excited levels [Phys.~Rev.~Lett.~\textbf{121}, 063201 (2018)]. The electric dipole moment is induced by coupling the excited levels with an external electric field. We derive the general expression of the long-range, Stark, and Zeeman interaction energies in the properly symmetrized and fully-coupled basis describing the diatomic complex. Taking the example of holmium, our calculations predict shallow long-range wells in the potential energy curves that may support vibrational levels accessible by direct photoassociation from pairs of ground-level atoms.

Long-range Rydberg molecules, Rydberg macrodimers and Rydberg aggregates in an ultracold Cs gas

We present an overview of our recent investigations of long-range interactions in an ultracold Cs Rydberg gas. These interactions are studied by high-resolution photoassociation spectroscopy, using excitation close to one-photon transitions into np3/2 Rydberg states with pulsed and continuous-wave ultraviolet laser radiation, and lead to the formation of long-range Cs2 molecules. We observe two types of molecular resonances. The first type originates from the correlated excitation of two atoms into Rydberg-atom-pair states interacting at long range via multipole-multipole interactions. The second type results from the interaction of one atom excited to a Rydberg state with one atom in the electronic ground state. Which type of resonances is observed in the experiments depends on the laser intensity and frequency and on the pulse sequences used to prepare the Rydberg states. We obtain insights into both types of molecular resonances by modelling the interaction potentials, using a multipole expansion of the long-range interaction for the first type of resonances and a Fermi-contact pseudo-potential for the second type of resonances. We analyse the relation of these long-range molecular resonances to molecular Rydberg states and ion-pair states, and discuss their decay channels into atomic and molecular ions. In experiments carried out with a two-colour two-photon excitation scheme, we observe a large enhancement of Rydberg-excitation probability, which we interpret as a saturable autocatalytic antiblockade phenomenon.

Observation of Rydberg-Atom Macrodimers: Micrometer-Sized Diatomic Molecules.

Long-range metastable molecules consisting of two cesium atoms in high Rydberg states have been observed in an ultracold gas. A sequential three-photon two-color photoassociation scheme is employed to form these molecules in states, which correlate to np(n+1)s dissociation asymptotes. Spectral signatures of bound molecular states are clearly resolved at the positions of avoided crossings between long-range van der Waals potential curves. The experimental results are in agreement with simulations based on a detailed model of the long-range multipole-multipole interactions of Rydberg-atom pair states. We show that a full model is required to accurately predict the occurrence of bound Rydberg macrodimers. The macrodimers are distinguished from repulsive molecular states by their behavior with respect to spontaneous ionization and possible decay channels are discussed.

Exotic Chemistry with Ultracold Rydberg Atoms.

We review recent experiments carried out with dense (10(12) cm(-3)) ultracold (T = 40 μK) samples of Cs atoms which have the goal to characterize, by high-resolution spectroscopy, the interactions between Cs atoms, Cs(+) ions and electrons that lead to the formation of metastable long-range molecules. The types of molecules observed in these experiments and the mechanisms leading to the aggregation of atoms in weakly bound molecules are very different from those encountered in warmer samples. In particular, we present results on molecules with binding energies of less than 0.05 J/mol and discuss their properties in the context of a new category of molecular states arising from slow-electron-atom scattering and their relation to atomic and molecular Rydberg states. One of the astonishing aspects of these types of molecules is that they can still be treated in good approximation in the realm of the Born-Oppenheimer approximation despite a huge electronic-state density. Non-Born-Oppenheimer effects are revealed by the decay of the molecules into neutral and charged fragments.

A comprehensive survey of wnt and frizzled expression in the sea urchin Paracentrotuslividus

WNT signaling is, in all multicellular animals, an essential intercellular communication pathway that is critical for shaping the embryo. At the molecular level, WNT signals can be transmitted by several transduction cascades, all activated chiefly by the binding of WNT ligands to receptors of the FRIZZLED family. The first step in assessing the biological functions of WNT signaling during embryogenesis is thus the establishment of the spatiotemporal expression profiles of wnt and frizzled genes in the course of embryonic development. To this end, using quantitative polymerase chain reaction, Northern blot, and in situ hybridization assays, we report here the comprehensive expression patterns of all 11 wnt and 4 frizzled genes present in the genome of the sea urchin Paracentrotus lividus during its embryogenesis. Our findings indicate that the expression of these wnt ligands and frizzled receptors is highly dynamic in both time and space. We further establish that all wnt genes are chiefly transcribed in the vegetal hemisphere of the embryo, whereas expression of the frizzled genes is distributed more widely across the embryonic territories. Thus, in P. lividus, WNT ligands might act both as short- and long-range signaling molecules that may operate in all cell lineages and tissues to control various developmental processes during embryogenesis.

Accurate determination of the rotational constants of ultracold molecules using double photoassociation spectroscopy

We report on an accurate determination of the rotational constants of the ultracold long-range Cesium molecules in near dissociation domain. The scheme relies on a precise reference of the frequency difference in a double photoassociation spectroscopy induced by two laser beams based on an acoustic-optical modulator. The rotational constants are obtained by fitting a non-rigid rotor model into the frequency intervals of the neighboring rotational levels deduced from the reference.

Experimental Determination of the Rotational Constants of High-Lying Vibrational Levels of Ultracold Cs2 in the 0g– Purely Long-Range State

We report on a quantitative experimental determination of the rotational constants for the high-lying vibrational levels of the ultracold pure long-range Cesium molecules formed via photoassociation. The scheme relies on a precise reference of frequency difference in a double photoassociation spectroscopy, which is induced by two laser beams based on an acoustic-optical modulator. The rotational constants are obtained by fitting a nonrigid rotor model into the frequency intervals of the neighboring rotational levels deduced from the reference.

Approach to form long-range ion-pair molecules in an ultracold Rb gas

We propose a realizable and efficient approach for exciting long-range ion-pair molecules, known as heavy Rydberg states, in an ultracold ${}^{85}$Rb gas via Feshbach resonances. Heavy Rydberg states, the molecular analogs of electronic Rydberg states, with the electron replaced by an atomic anion, offer opportunities for novel physics, including the formation of ultracold anions and strongly coupled plasmas. We map the positions, lifetimes, and Franck-Condon factors of heavy Rydberg resonances across a wide range of excitation energies, and we calculate the rates of formation for the most promising transitions through long-lived intermediate interferometric resonances.

Bantam miRNA Promotes Systemic Growth by Connecting Insulin Signaling and Ecdysone Production

During the development of multicellular organisms, body growth is controlled at the scale of the organism by the activity of long-range signaling molecules, mostly hormones. These systemic factors coordinate growth between developing tissues and act as relays to adjust body growth in response to environmental changes [1]. In target organs, long-range signals act in concert with tissue-autonomous ones to regulate the final size of a given tissue. In Drosophila, the steroid hormone ecdysone plays a dual role: peaks of secretion promote developmental transitions and maturation, while basal production negatively controls the speed of growth. The antagonistic action of ecdysone and the conserved insulin/insulin growth factor (IGF) signaling pathway regulate systemic growth and modulate final body size [2, 3]. Here we unravel an unexpected role of bantam microRNA in controlling body size in Drosophila. Our data unveil that, in addition to its well-characterized function in autonomously inducing tissue growth [4-9], bantam activity in ecdysone-producing cells promotes systemic growth by repressing ecdysone release. We also provide evidence that the regulation of ecdysone production by insulin signaling relies on the repression of bantam activity. These results identify a molecular mechanism that underlies the crosstalk between these two hormones and add a new layer of complexity to the well-characterized role of bantam in growth control.

Diffusion- and convection-based activation of Wnt/β-catenin signaling in a gradient generating microfluidic chip

Stem cells and developing tissues respond to long-range signaling molecules (morphogens), by starting different nuclear programs that decide about the cell fate. Cells sense the local morphogen concentration and the shape of the gradient. We developed a two-chambered microfluidic chip to reproduce the in vivo situation under shear stress free conditions. The gradient is generated in the lower part of our device and recognized by cells grown in the upper part in the microchamber. We tested our device by activating the Wnt/β-catenin signaling pathway in HeLa cells as proven by nuclear β-catenin accumulation in response to the Wnt pathway activator 6-bromoindirubin-3'-oxime (BIO). Applying the same readout system to a recombinant Wnt3a and Dkk-1 bipolar gradient we demonstrate that our microfluidic chip is suitable for morphogens as well as small molecules. More interestingly, our microfluidic device is highly flexible. While the generated gradients are stable for several hours and reproducible, we can change the kind and the shape of the gradient actively on demand. We also can switch from diffusion- to convection-based transport, thus applying the morphogen gradient either in a polarized or non-polarized manner.

Atom–molecule coherence for ultralong-range Rydberg dimers

Rydberg molecules—which involve atoms in highly excited electronic states and can be as large as 100 nanometres—have been created recently in cold gases of rubidium atoms. New work demonstrates that the inter-atomic interactions in these long-range molecules can be manipulated coherently, enabling controlled ‘making and breaking’ of the bond using laser light.

Wnt Trafficking: New Insights into Wnt Maturation, Secretion and Spreading

Proteins of the Wnt family are secreted signaling molecules that regulate multiple processes in animal development and control tissue homeostasis in the adult. Wnts spread over considerable distances to regulate gene expression in cells located at distant sites. Paradoxically, Wnts are poorly mobile because of their posttranslational modification with lipids. Recent evidence suggests that several pathways exist that are capable of transforming hydrophobic, insoluble Wnts into long-range signaling molecules. Furthermore, the discovery of Wntless as a protein specifically required for the secretion of Wnt suggests that Wnt trafficking through the secretory pathway is already under special scrutiny. Here, we review recent data on the molecular machinery that controls Wnt secretion and discuss how Wnts can be mobilized for long-range signaling.

Photoassociation spectroscopy of purely long-range krypton molecules

Photoassociation spectra for purely long-range (PLR) krypton molecules are both computed and measured. The photoassociation laser is tuned just red of the 5s[3/2]2-5p[5/2]2 transition at 810.6 nm, over a frequency range in which fourteen different PLR potential wells support hundreds of vibrational bound states. In the experiment, laser light is directed into a cloud of magneto-optically trapped 84Kr atoms, and the emission of both ultraviolet photons and ions is monitored. Peaks in these signals are observed for laser frequencies within 200 MHz of the atomic resonance. Ongoing work is aimed at improving the experimental signal and understanding the degree of agreement between empirical data and computed molecular spectra.

The radiative properties of long-range molecules

$^{1}$See e.g., W. C. Stwalley, ``Atom-Atom Interactions from Spectroscopy, in D. W. Smith and W. B. McRae, Editors, Energy, Structure, and Reactivity (Wiley, New York, 1973), p. 259. Acknowledgment is made to the Donors of the Petroleum Research Fund, administered by the American Chemical Society, and to the National Science Foundation for support of this work. Temporary address of William C. Stwalley: Chemistry Division, National Science Foundation, Washington, D. C., 2055 (8/1/75 - 7/31/76).