Dynamic Interplay of Spectrosome and Centrosome Organelles in Asymmetric Stem Cell Divisions

<div><p>Stem cells have remarkable self-renewal ability and differentiation potency, which are critical for tissue repair and tissue homeostasis. Recently it has been found, in many systems (e.g. gut, neurons, and hematopoietic stem cells), that the self-renewal and differentiation balance is maintained when the stem cells divide asymmetrically. <i>Drosophila</i> male germline stem cells (GSCs), one of the best characterized model systems with well-defined stem cell niches, were reported to divide asymmetrically, where centrosome plays an important role. Utilizing time-lapse live cell imaging, customized tracking, and image processing programs, we found that most acentrosomal GSCs have the spectrosomes reposition from the basal end (wild type) to the apical end close to hub-GSC interface (acentrosomal GSCs). In addition, these apically positioned spectrosomes were mostly stationary while the basally positioned spectrosomes were mobile. For acentrosomal GSCs, their mitotic spindles were still highly oriented and divided asymmetrically with longer mitosis duration, resulting in asymmetric divisions. Moreover, when the spectrosome was knocked out, the centrosomes velocity decreased and centrosomes located closer to hub-GSC interface. We propose that in male GSCs, the spectrosome recruited to the apical end plays a complimentary role in ensuring proper spindle orientation when centrosome function is compromised.</p></div

Dynamic migration patterns of spectrosomes are quantified utilizing time-lapse live-imaging.

<p><b>(A)</b> Spectrosome localization in <i>DSas4-mut</i> becomes predominantly apical compared to wild type. #: p<0.05. <b>(B)</b> Live image sequences shows apically (to the hub cells) migrating spectrosome in a dividing <i>DSas4-mut</i> GSC. Arrowhead: spectrosome. *: hub cells. Yellow dash-line: GSC. <b>(C)</b> In wild type GSCs, large majority of spectrosomes were mobile and located basally (39%) during interphase. In <i>DSas4-mut</i> GSCs, majority of spectrosomes were stationary and located apically (54%). Wild type: n = 23, DSas4-mut: n = 24. <b>(D)</b><i>DSas4-mut</i> GSCs had higher percentage of spectrosomes migrating from apical to the basal side prior to mitosis. Spectrosome switches are categorized as such if they migrate within 30 mins prior to mitosis (identified by nuclear envelope breakdown).</p

Most spindle orientation at anaphase and stem cell number are maintained in GSCs without centrosomes.

<p><b>(A)</b> Live imaging reveals that most <i>DSas4-mut</i> GSCs maintain their spindle orientation compared to the wild type. <b>(B)</b> There is no significant difference of GSC number per testes in <i>DSas4-mut</i> and wild type flies. <b>(C)</b> The mitosis duration from pro-metaphase to anaphase in <i>DSas4-mut</i> GSCs is significantly longer than that in wild type.</p

Spectrosome Knockout minimally affects centrosome orientation, spindle orientation, mitosis duration, and stem cell numbers in male GSCs.

<p><b>(A)</b> Centrosome misorientation during interphase was analyzed from time lapse image sequences, and there is no significant difference between the <i>hts-mut</i> and the wild type. <b>(B)</b> There is minimal change in the spindle orientation between the <i>hts-mut</i> and the wild type. <b>(C)</b> Mitosis duration is not affected in <i>hts-mut</i> compared to the wild type when measured from nuclear envelope breakdown time to anaphase. <b>(D)</b> There is no significant difference for GSC number per testis in hts-mut and wild type flies.</p

Centrosome velocity and distance to hub-GSC interface change in <i>hts-mut</i> GSCs.

<p>Based on the centrosome tracking analysis of live-image sequences, the <b>A)</b> Interphase centrosome velocities are shown for both <i>hts-mut</i> GSCs and wild type GSCs (p<0.01 between <i>hts-mut</i> and wild type for both GSC-inherited and GB-inherited centrosomes), and the <b>B)</b> GSC-inherited centrosome distance to the hub-GSC interphase histograms are shown for both <i>hts-mut</i> and wild type GSCs (p<0.01).</p

Accelerating Computation of Acidity Constants and Redox Potentials for Aqueous Organic Redox Flow Batteries by Machine Learning Potential-Based Molecular Dynamics

Due to the increased concern about energy and environmental issues, significant attention has been paid to the development of large-scale energy storage devices to facilitate the utilization of clean energy sources. The redox flow battery (RFB) is one of the most promising systems. Recently, the high cost of transition-metal complex-based RFB has promoted the development of aqueous RFBs with redox-active organic molecules. To expand the working voltage, computational chemistry has been applied to search for organic molecules with lower or higher redox potentials. However, redox potential computation based on implicit solvation models would be challenging due to difficulty in parametrization when considering the complex solvation of supporting electrolytes. Besides, although ab initio molecular dynamics (AIMD) describes the supporting electrolytes with the same level of electronic structure theory as the redox couple, the application is impeded by the high computation costs. Recently, machine learning molecular dynamics (MLMD) has been illustrated to accelerate AIMD by several orders of magnitude without sacrificing the accuracy. It has been established that redox potentials can be computed by MLMD with two separated machine learning potentials (MLPs) for reactant and product states, which is redundant and inefficient. In this work, an automated workflow is developed to construct a universal MLP for both states, which can compute the redox potentials or acidity constants of redox-active organic molecules more efficiently. Furthermore, the predicted redox potentials can be evaluated at the hybrid functional level with much lower costs, which would facilitate the design of aqueous organic RFBs

Identifying Trapped Electronic Holes at the Aqueous TiO₂ Interface

Trapping of photogenerated holes near or at the surface is believed to be a crucial step in the photo-oxidation of water and organic pollutants by TiO₂. The detailed nature of these localized states is however still a matter of debate. Here, we investigate this question for the rutile TiO₂(110) water interface using ab initio molecular dynamics simulation methods based on a state-of-the-art hybrid density functional. We identify the reactive surface trapped holes as the OH^• on five-coordinated terminal Ti and its deprotonated O^•–. Our calculations show that the large reorganization energies hold the key to reconciling some of the conflicting interpretations of spectroscopic and thermodynamic measurements reported in the literature. We also observe an asymmetry in reorganization energies owing to the pinning of the valence band of TiO₂. This has important implications for the understanding of the heterogeneous electron transfer kinetics driving photo-oxidation

Aligning Electronic Energy Levels in Pyridine-Assisted CO₂ Activation at the GaP(110)/Water Interface Using Ab Initio Molecular Dynamics

Photoelectrochemical CO2 reduction has attracted considerable attention as a route to convert CO2 into value-added products. Pyridine (Py)-catalyzed CO2 reduction on a GaP photoelectrode has been shown to be a promising photoelectrochemical system to produce methanol under the underpotential condition. However, whether the dramatic decrease in overpotential can be attributed to the CO2 activation by the formation of the zwitterionic complex PyCO2 is currently under debate. Because the alignment between the band edge positions of photoelectrodes and the redox potentials of species determines the desired redox reactions, calculations have been performed to evaluate the band edge positions of GaP and the redox potentials of relevant reactions. In these works, the water effect has been either neglected or approximated by using the dielectric continuum or a few explicit water molecules, which may not be enough to determine the accurate energy level alignment in realistic chemical environments. Moreover, calculations performed in conventional implicit solvation models suggested that PyCO2 is unstable in homogeneous aqueous, while the bonding interactions between CO2 and N species have been experimentally detected. Thus, we performed ab initio molecular dynamics to investigate the band alignment of GaP, as well as the stability and the reducibility of PyCO2 in more realistic chemical environments. Our results showed that the solvation effect and the pyridine adsorption could shift up the band edge positions of GaP significantly, and neglecting such effects could result in a serious underestimation of the activity of the photocatalysts. More importantly, we found that the interaction between pyridine and CO2 at the GaP(110)/water interface is strong due to the synergetic stabilization effect, which leads to an about 0.6 V less negative redox potential of PyCO2/PyCO2– than that of CO2/CO2– in the homogeneous aqueous. Furthermore, we compared the redox potential of PyCO2/PyCO2– at the GaP(110)/water interface with the conduction band minimum of GaP, which showed that the reduction of the adsorbed PyCO2 is thermodynamically feasible. Our results suggested that the CO2 activation by the formation of PyCO2 at the GaP(110)/water interface could be responsible for the low overpotential. This work provides valuable insights into the mechanism of pyridine-catalyzed CO2 reduction on GaP and could pave the way for the development of efficient catalysts for CO2 reduction

Density Functional Theory Calculation of the Band Alignment of (101̅0) In_<i>x</i>Ga_1–<i>x</i>N/Water Interfaces

Conduction band edge (CBE) and valence band edge (VBE) positions of In_<i>x</i>Ga_1–<i>x</i>N photoelectrodes were computed using density functional theory methods. The band edges of fully solvated GaN and InN model systems were aligned with respect to the standard hydrogen electrode using a molecular dynamics hydrogen electrode scheme applied earlier to TiO₂/water interfaces. Similar to the findings for TiO₂, we found that the Purdew–Burke–Ernzerhof (PBE) functional gives a VBE potential which is too negative by 1 V. This cathodic bias is largely corrected by application of the Heyd–Scuseria–Ernzerhof (HSE06) hybrid functional containing a fraction of Hartree–Fock exchange. The effect of a change of composition was investigated using simplified model systems consisting of vacuum slabs covered on both sides by one monolayer of H₂O. The CBE was found to vary linearly with In content. The VBE, in comparison, is much less sensitive to composition. The data show that the band edges straddle the hydrogen and oxygen evolution potentials for In fractions less than 47%. The band gap was found to exceed 2 eV for an In fraction less than 54%

High-Oxidation-State 3d Metal (Ti–Cu) Complexes with <i>N</i>‑Heterocyclic Carbene Ligation

High-oxidation-state 3d metal species have found a wide range of applications in modern synthetic chemistry and materials science. They are also implicated as key reactive species in biological reactions. These applications have thus prompted explorations of their formation, structure, and properties. While the traditional wisdom regarding these species was gained mainly from complexes supported by nitrogen- and oxygen-donor ligands, recent studies with <i>N</i>-heterocyclic carbenes (NHCs), which are widely used for the preparation of low-oxidation-state transition metal complexes in organometallic chemistry, have led to the preparation of a large variety of isolable high-oxidation-state 3d metal complexes with NHC ligation. Since the first report in this area in the 1990s, isolable complexes of this type have been reported for titanium­(IV), vanadium­(IV,V), chromium­(IV,V), manganese­(IV,V), iron­(III,IV,V), cobalt­(III,IV,V), nickel­(IV), and copper­(II). With the aim of providing an overview of this intriguing field, this Review summarizes our current understanding of the synthetic methods, structure and spectroscopic features, reactivity, and catalytic applications of high-oxidation-state 3d metal NHC complexes of titanium to copper. In addition to this progress, factors affecting the stability and reactivity of high-oxidation-state 3d metal NHC species are also presented, as well as perspectives on future efforts