Toxin-Antidote Elements Across the Tree of Life.

In life's constant battle for survival, it takes one to kill but two to conquer. Toxin-antitoxin or toxin-antidote (TA) elements are genetic dyads that cheat the laws of inheritance to guarantee their transmission to the next generation. This seemingly simple genetic arrangement-a toxin linked to its antidote-is capable of quickly spreading and persisting in natural populations. TA elements were first discovered in bacterial plasmids in the 1980s and have recently been characterized in fungi, plants, and animals, where they underlie genetic incompatibilities and sterility in crosses between wild isolates. In this review, we provide a unified view of TA elements in both prokaryotic and eukaryotic organisms and highlight their similarities and differences at the evolutionary, genetic, and molecular levels. Finally, we propose several scenarios that could explain the paradox of the evolutionary origin of TA elements and argue that these elements may be key evolutionary players and that the full scope of their roles is only beginning to be uncovered.

Standard Deviations: The Biological Bases of Transmission Ratio Distortion.

The rule of Mendelian inheritance is remarkably robust, but deviations from the equal transmission of alternative alleles at a locus [a.k.a. transmission ratio distortion (TRD)] are also commonly observed in genetic mapping populations. Such TRD reveals locus-specific selection acting at some point between the diploid heterozygous parents and progeny genotyping and therefore can provide novel insight into otherwise-hidden genetic and evolutionary processes. Most of the classic selfish genetic elements were discovered through their biasing of transmission, but many unselfish evolutionary and developmental processes can also generate TRD. In this review, we describe methodologies for detecting TRD in mapping populations, detail the arenas and genetic interactions that shape TRD during plant and animal reproduction, and summarize patterns of TRD from across the genetic mapping literature. Finally, we point to new experimental approaches that can accelerate both detection of TRD and characterization of the underlying genetic mechanisms.

Minimizing the diffusivity difference between vacancies and interstitials in multi-principal element alloys.

Interstitial atoms usually diffuse much faster than vacancies, which is often the root cause for the ineffective recombination of point defects in metals under irradiation. Here, via ab initio modeling of single-defect diffusion behavior in the equiatomic NiCoCrFe(Pd) alloy, we demonstrate an alloy design strategy that can reduce the diffusivity difference between the two types of point defects. The two diffusivities become almost equal after substituting the NiCoCrFe base alloy with Pd. The underlying mechanism is that Pd, with a much larger atomic size (hence larger compressibility) than the rest of the constituents, not only heightens the activation energy barrier (Ea) for interstitial motion by narrowing the diffusion channels but simultaneously also reduces Ea for vacancies due to less energy penalty required for bond length change between the initial and the saddle states. Our findings have a broad implication that the dynamics of point defects can be manipulated by taking advantage of the atomic size disparity, to facilitate point-defect annihilation that suppresses void formation and swelling, thereby improving radiation tolerance.

Structures of RNA Polymerase Closed and Intermediate Complexes Reveal Mechanisms of DNA Opening and Transcription Initiation.

Gene transcription is carried out by RNA polymerases (RNAPs). For transcription to occur, the closed promoter complex (RPc), where DNA is double stranded, must isomerize into an open promoter complex (RPo), where the DNA is melted out into a transcription bubble and the single-stranded template DNA is delivered to the RNAP active site. Using a bacterial RNAP containing the alternative σ54 factor and cryoelectron microscopy, we determined structures of RPc and the activator-bound intermediate complex en route to RPo at 3.8 and 5.8 Å. Our structures show how RNAP-σ54 interacts with promoter DNA to initiate the DNA distortions required for transcription bubble formation, and how the activator interacts with RPc, leading to significant conformational changes in RNAP and σ54 that promote RPo formation. We propose that DNA melting is an active process initiated in RPc and that the RNAP conformations of intermediates are significantly different from that of RPc and RPo.

Lattice Distortion Promotes Incipient Plasticity in Multiprincipal Element Alloys.

Multiprincipal element alloys usually exhibit earlier pop-in events than pure metals and dilute solid solutions during nanoindentation experiments. To understand the origin of this phenomenon, large-scale atomic simulations of nanoindentation were performed on a series of metallic materials to investigate the underlying physics of incipient plasticity at the nanoscale. Statistical result shows that lattice distortion δ and normalized critical pressure pc/Es follow a power-law relationship. Via quantitative analysis on the relative positions of the atoms within the nearest neighbor shell, the physical origin of premature incipient plasticity is revealed as severe lattice distortion induces large relative atomic displacement, so only a small indentation strain is required to meet the critical displacement threshold that triggers incipient plasticity. Therefore, for perfect crystals, lattice distortion is an intrinsic and determinative factor that affects the first pop-in event.

Manipulative Single Electric Dipole with Spontaneous Translational Symmetry Breaking in a Two-Dimensional Crystal.

It is widely acknowledged that quantum entities with minimal mass cannot undergo spontaneous symmetry breaking due to strong quantum fluctuations. Here, we report the discovery of a positionally settled single electric dipole that can be manipulated and electrically polarized in a monolayer CoCl2-graphite heterostructure, which demonstrates an unprecedented example of spontaneous lattice-translational-symmetry breaking. Scanning tunneling microscopy and atomic force microscopy show that the solitons are intrinsic paraelectric dipoles driven by synchronous charge-lattice distortion around individual CoCl6 octahedrons. Both the dipole moment and lateral position of the soliton can be manipulated by the electric field exerted from the tip, which offers polarity-switchable and layout-designable electrostatic potential landscapes that determine the band bending configuration. This study exemplifies a brand-new type of local charge-lattice order, appealing for further research on the mechanism underlying the soliton robustness, and the electrically and positionally controllable single dipole supports the feasibility of band tailoring in device applications.

Direct Nanosecond Multiframe Imaging of Irreversible Dynamics in 4D Electron Microscopy.

Irreversible ultrafast events are prevalent in nature, yet their capture in real time poses significant challenges. Traditional single-shot imaging technologies, which utilize a single optical pump and single delayed electron probe, offer high spatiotemporal resolution but fail to capture the entire dynamic evolutions. Here, we introduce a novel imaging method employing a single optical pump and delayed multiple electron probes. This approach, facilitated by an innovative deflector in ultrafast electron microscopy, enables the acquisition of nine frames per exposure, paving the way for statistical and quantitative analyses. We have developed an algorithm that corrects frame-by-frame distortions, realizing a cross-correlation enhancement of ∼26%. Achieving ∼12 nm and 20 ns resolution, our method allows for the comprehensive visualization of laser-induced behaviors in Au nanoparticles, including merging, jumping, and collision processes. Our results demonstrate the capability of this multiframe imaging technique to document irreversible processes across materials science and biology with unprecedented nanometer-nanosecond precision.

Somatic Integration of Incoherent Dendritic Inputs in the Gerbil Medial Superior Olive.

The medial superior olive (MSO) is a binaural nucleus that is specialized in detecting the relative arrival times of sounds at both ears. Excitatory inputs to its neurons originating from either ear are segregated to different dendrites. To study the integration of synaptic inputs both within and between dendrites, we made juxtacellular and whole-cell recordings from the MSO in anesthetized female gerbils, while presenting a "double zwuis" stimulus, in which each ear received its own set of tones, which were chosen in a way that all second-order distortion products (DP2s) could be uniquely identified. MSO neurons phase-locked to multiple tones within the multitone stimulus, and vector strength, a measure for spike phase-locking, generally depended linearly on the size of the average subthreshold response to a tone. Subthreshold responses to tones in one ear depended little on the presence of sound in the other ear, suggesting that inputs from different ears sum linearly without a substantial role for somatic inhibition. The "double zwuis" stimulus also evoked response components in the MSO neuron that were phase-locked to DP2s. Bidendritic subthreshold DP2s were quite rare compared with bidendritic suprathreshold DP2s. We observed that in a small subset of cells, the ability to trigger spikes differed substantially between both ears, which might be explained by a dendritic axonal origin. Some neurons that were driven monaurally by only one of the two ears nevertheless showed decent binaural tuning. We conclude that MSO neurons are remarkably good in finding binaural coincidences even among uncorrelated inputs.SIGNIFICANCE STATEMENT Neurons in the medial superior olive are essential for precisely localizing low-frequency sounds in the horizontal plane. From their soma, only two dendrites emerge, which are innervated by inputs originating from different ears. Using a new sound stimulus, we studied the integration of inputs both within and between these dendrites in unprecedented detail. We found evidence that inputs from different dendrites add linearly at the soma, but that small increases in somatic potentials could lead to large increases in the probability of generating a spike. This basic scheme allowed the MSO neurons to detect the relative arrival time of inputs at both dendrites remarkably efficient, although the relative size of these inputs could differ considerably.

Periselectivity and ambimodal transition states in cycloadditions of tetrachloro-o-benzoquinone with 6,6-dimethylfulvene.

The reaction mechanism of cycloadditions of tetrachloro-o-benzoquinone with 6,6-dimethylfulvene were systematically investigated with density functional theory calculations. It was found that conditional primary interactions stabilize the ambimodal transition states in the endo pathways. Ambimodal transition states lead to [6 + 4]/[4 + 2] adducts or [4 + 2]/[2 + 4] adducts, which interconvert through 3,3-sigmatropic shift reactions. The substituent effects on periselectivity were also investigated.

Efficient Tin Perovskite Solar Cells via Suppressing Autoxidation in Inert Atmosphere.

The unsatisfactory power conversion efficiency (PCE) and long-term stability of tin perovskite solar cells (TPSCs) restrict its further development as alternatives to lead perovskite solar cells (LPSCs). Considerable research has focused on the negative impacts of O2 and H2 O, while discussions about degradation mechanism in an inert atmosphere remains insufficient. Herein, the light-induced autoxidation of tin perovskite in nitrogen atmosphere is revealed for the first time and the elastic lattice distortion is demonstrated as the crucial role of rapid degradation. The continuous injection of photons induces energy transfer from excited A-site cations to vibrating Sn-I framework, leading to the elastic deformation of perovskite lattice. Consequently, the over distorted Sn-I framework releases free iodine and further oxidizes Sn2+ in the form of molecular iodine. Through an appropriately designed light-dark cyclic test, a remarkable PCE of 14.41% is achieved based on (Cs0.025 (MA0.25 FA0.75 )0.975 ) 0.98 EDA0.01 SnI3 solar cells, which is the record of hybrid triple TPSCs so far. The findings unveil autoxidation as the crux of TPSCs' degradation in an inert atmosphere and suggest the possibility of reinforcing the tin perovskite lattice towards highly efficient and stable TPSCs.

Unraveling Lattice-Distortion Hardening Mechanisms in High-Entropy Carbides.

Uncovering the hardening mechanisms is of great importance to accelerate the design of superhard high-entropy carbides (HECs). Herein, the hardening mechanisms of HECs by a combination of experiments and first-principles calculations are systematically explored. The equiatomic single-phase 4- to 8-cation HECs (4-8HECs) are successfully fabricated by the two-step approach involving ultrafast high-temperature synthesis and hot-press sintering techniques. The as-fabricated 4-8HEC samples possess fully dense microstructures (relative densities of up to ≈99%), similar grain sizes, clean grain boundaries, and uniform compositions. With the elimination of these morphological properties, the monotonic enhancement of Vickers hardness and nanohardness of the as-fabricated 4-8HEC samples is found to be driven by the aggravation of lattice distortion. Further studies show no evident association between the enhanced hardness of the as-fabricated 4-8HEC samples and other potential indicators, including bond strength, valence electron concentration, electronegativity mismatch, and metallic states. The work unveils the underlying hardening mechanisms of HECs and offers an effective strategy for designing superhard HECs.

Enhanced Spin-Polarized Electric Field Modulating p-Band Center on Ni-Doped CdS for Boosting Photocatalytic Hydrogen Evolution.

It is a challenge to regulate charge separation dynamics and redox reaction kinetics at the atomic level to synergistically boost photocatalytic hydrogen (H2) evolution. Herein, a robust Ni-doped CdS (Ni-CdS) photocatalyst is synthesized by incorporating highly dispersed Ni atoms into the CdS lattice in substitution for Cd atoms. Combined characterizations with theoretical analysis indicate that local lattice distortion and S-vacancy of Ni-CdS induced by Ni incorporation lead to an increased dipole moment and enhanced spin-polarized electric field, which promotes the separation and transfer of photoinduced carriers. In this contribution, charge redistribution caused by enhanced internal electric field results in the downshift of the S p-band center, which is conducive to the desorption of intermediate H* for boosting the H2 evolution reaction. Accordingly, the Ni-CdS photocatalyst shows a remarkably improved photocatalytic performance with an H2 evolution rate of 20.28 mmol g-1 h-1 under visible-light irradiation, which is 5.58 times higher than that of pristine CdS. This work supplied an insightful understanding that the enhanced polarization electric field governs the p-band center for efficient photocatalytic H2 evolution activity.

A fascination with tailless mice: a scientific historical review of studies of the T/t complex.

The T/t complex of the mouse attracted many of the major figures of mouse genetics to perform genetic, cytogenetic, physiological, biochemical and molecular biological studies of it. These studies started with the discovery of short tailed mutants (Ts) and recessive lethal developmental mutations (ts) which mapped to the same "locus" in the early 1920s in France. However, due to the non-receptivity of French scientists to genetics, they continued to be studied in mostly Anglophone countries to be joined by a wider international community in the 1970s. These discoveries led to developmental studies of the lethal mutants which provided the origin of mammalian developmental genetics. The fascinating property of transmission ratio distortion (non-50/50 segregation of alleles in offspring of males) elicited tremendous interest. There were false leads (that the region consisted of unusual DNA, that the alleles controlled cell surface antigens on embryonic cells and spermatozoa) and exciting discoveries. This historical review provides a review of this extensive area of research and some of the individuals involved in it.

Spatiotemporal encoding MRI in a portable low-field system.

PURPOSE: Demonstrate the potential of spatiotemporal encoding (SPEN) MRI to deliver largely undistorted 2D, 3D, and diffusion weighted images on a 110 mT portable system. METHODS: SPEN's quadratic phase modulation was used to subsample the low-bandwidth dimension of echo planar acquisitions, delivering alias-free images with an enhanced immunity to image distortions in a laboratory-built, low-field, portable MRI system lacking multiple receivers. RESULTS: Healthy brain images with different SPEN time-bandwidth products and subsampling factors were collected. These compared favorably to EPI acquisitions including topup corrections. Robust 3D and diffusion weighted SPEN images of diagnostic value were demonstrated, with 2.5 mm isotropic resolutions achieved in 3 min scans. This performance took advantage of the low specific absorption rate and relative long TEs associated with low-field MRI. CONCLUSION: SPEN MRI provides a robust and advantageous fast acquisition approach to obtain faithful 3D images and DWI data in low-cost, portable, low-field systems without parallel acceleration.

Dynamic field mapping and distortion correction using single-shot blip-rewound EPI and joint multi-echo reconstruction.

PURPOSE: To develop a method for dynamic ∆ B 0 $$ \Delta {B}_0 $$ mapping and distortion correction. METHODS: A blip-rewound EPI trajectory was developed to acquire multiple 2D EPI images in a single readout with an interleaved order, which allows a short TE difference. A joint multi-echo reconstruction was utilized to exploit the shared information between EPI images. The reconstructed images from each readout are combined to produce a final magnitude image. A ∆ B 0 $$ \Delta {B}_0 $$ map is calculated from the phase of these images for distortion correction. The efficacy of the proposed method is assessed with phantom and in vivo experiments. The performance of the proposed method in the presence of subject motion is also investigated. RESULTS: Compared to conventional multi-echo EPI, the proposed method allows dynamic ∆ B 0 $$ \Delta {B}_0 $$ mapping at matched resolution with a much shorter TR. Phantom and in vivo results show that the proposed method can provide a comparable magnitude image as conventional single-shot EPI. The ∆ B 0 $$ \Delta {B}_0 $$ maps calculated from the proposed method are consistent with conventional multi-echo EPI in the phantom experiment. For in vivo experiments, the proposed method provides a more accurate estimation of ∆ B 0 $$ \Delta {B}_0 $$ than conventional multi-echo EPI, which is prone to phase wrapping problems due to the long TE difference. In-vivo scan with subject motion shows the proposed dynamic field mapping method can improve the temporal stability of EPI time series compared to gradient echo (GRE) based static field mapping. CONCLUSION: The proposed method allows accurate dynamic ∆ B 0 $$ \Delta {B}_0 $$ mapping for robust distortion correction without compromising spatial or temporal resolution.

3D distortion-free, reduced FOV diffusion-prepared gradient echo at 3 T.

PURPOSE: To develop a 3D distortion-free reduced-FOV diffusion-prepared gradient-echo sequence and demonstrate its application in vivo for diffusion imaging of the spinal cord in healthy volunteers. METHODS: A 3D multi-shot reduced-FOV diffusion-prepared gradient-echo acquisition is achieved using a slice-selective tip-down pulse in the phase-encoding direction in the diffusion preparation, combined with magnitude stabilizers, centric k-space encoding, and 2D phase navigators to correct for intershot phase errors. The accuracy of the ADC values obtained using the proposed approach was evaluated in a diffusion phantom and compared to the tabulated reference ADC values and to the ADC values obtained using a standard spin echo diffusion-weighted single-shot EPI sequence (DW-SS-EPI). Five healthy volunteers were scanned at 3 T using the proposed sequence, DW-SS-EPI, and a clinical diffusion-weighted multi-shot readout-segmented EPI sequence (RESOLVE) for cervical spinal cord imaging. Image quality, perceived SNR, and image distortion were assessed by two expert radiologists. ADC maps were calculated, and ADC values obtained with the proposed sequence were compared to those obtained using DW-SS-EPI and RESOLVE. RESULTS: Consistent ADC estimates were measured in the diffusion phantom with the proposed sequence and the conventional DW-SS-EPI sequence, and the ADC values were in close agreement with the reference values provided by the manufacturer of the phantom. In vivo, the proposed sequence demonstrated improved image quality, improved perceived SNR, and reduced perceived distortion compared to DW-SS-EPI, whereas all measures were comparable against RESOLVE. There were no significant differences in ADC values estimated in vivo for each of the sequences. CONCLUSION: 3D distortion-free diffusion-prepared imaging can be achieved using the proposed sequence.

Single-shot echo planar time-resolved imaging for multi-echo functional MRI and distortion-free diffusion imaging.

PURPOSE: To develop a single-shot SNR-efficient distortion-free multi-echo imaging technique for dynamic imaging applications. METHODS: Echo planar time-resolved imaging (EPTI) was first introduced as a multi-shot technique for distortion-free multi-echo imaging. This work aims to develop single-shot EPTI (ss-EPTI) to achieve improved robustness to motion/physiological noise, increased temporal resolution, and higher SNR efficiency. A new spatiotemporal encoding that enables reduced phase-encoding blips and minimized echo spacing under the single-shot regime was developed, which improves sampling efficiency and enhances spatiotemporal correlation in the k-TE space for improved reconstruction. A continuous readout with minimized deadtime was employed to optimize SNR efficiency. Moreover, k-TE partial Fourier and simultaneous multi-slice acquisition were integrated for further acceleration. RESULTS: ss-EPTI provided distortion-free imaging with densely sampled multi-echo images at standard resolutions (e.g., ˜1.25 to 3 mm) in a single-shot. Improved SNR efficiency was observed in ss-EPTI due to improved motion/physiological-noise robustness and efficient continuous readout. Its ability to eliminate dynamic distortions-geometric changes across dynamics due to field changes induced by physiological variations or eddy currents-further improved the data's temporal stability. For multi-echo fMRI, ss-EPTI's multi-echo images recovered signal dropout in short- T 2 * $$ {\mathrm{T}}_2^{\ast } $$ regions and provided TE-dependent functional information to distinguish non-BOLD noise for further tSNR improvement. For diffusion MRI, it achieved shortened TEs for improved SNR and provided images free from both B0-induced and diffusion-encoding-dependent eddy-current-induced distortions with multi-TE diffusion metrics. CONCLUSION: ss-EPTI provides SNR-efficient distortion-free multi-echo imaging with comparable temporal resolutions to ss-EPI, offering a new acquisition tool for dynamic imaging.

Cardiac DTI using short-axis PROPELLER: A feasibility study.

PURPOSE: We aimed to develop a free-breathing (FB) cardiac DTI (cDTI) method based on short-axis PROPELLER (SAP) and M2 motion compensated spin-echo EPI (SAP-M2-EPI) to mitigate geometric distortion and eliminate aliasing in acquired diffusion-weighted (DW) images, particularly in patients with a higher body mass index (BMI). THEORY AND METHODS: The study involved 10 healthy volunteers whose BMI values fell into specific categories: BMI <25 (4 volunteers), 25< BMI <28 (5 volunteers), and BMI >30 (1 volunteer). We compared DTI parameters, including fractional anisotropy (FA), mean diffusivity (MD), and helix angle transmurality (HAT), between SAP-M2-EPI and M2-ssEPI. To evaluate the performance of SAP-M2-EPI in reducing geometric distortions in the left ventricle (LV) compared to CINE and M2-ssEPI, we utilized the DICE similarity coefficient (DSC) and assessed misregistration area. RESULTS: In all volunteers, SAP-M2-EPI yielded high-quality LV DWIs without aliasing, demonstrating significantly reduced geometric distortion (with an average DSC of 0.92 and average misregistration area of 90 mm2) and diminished signal loss due to bulk motion when compared to M2-ssEPI. DTI parameter maps exhibited consistent patterns across slices without motion related artifacts. CONCLUSION: SAP-M2-EPI facilitates free-breathing cDTI of the entire LV, effectively eliminating aliasing and minimizing geometric distortion compared to M2-ssEPI. Furthermore, it preserves accurate quantification of myocardial microstructure.

Human prostate MRI at ultrahigh-performance gradient: A feasibility study.

PURPOSE: To demonstrate the technical feasibility and the value of ultrahigh-performance gradient in imaging the prostate in a 3T MRI system. METHODS: In this local institutional review board-approved study, prostate MRI was performed on 4 healthy men. Each subject was scanned in a prototype 3T MRI system with a 42-cm inner-diameter gradient coil that achieves a maximum gradient amplitude of 200 mT/m and slew rate of 500 T/m/s. PI-RADS V2.1-compliant axial T2 -weighted anatomical imaging and single-shot echo planar DWI at standard gradient of 70 mT/m and 150 T/m/s were obtained, followed by DWI at maximum performance (i.e., 200 mT/m and 500 T/m/s). In comparison to state-of-the-art clinical whole-body MRI systems, the high slew rate improved echo spacing from 1020 to 596 µs and, together with a high gradient amplitude for diffusion encoding, TE was reduced from 55 to 36 ms. RESULTS: In all 4 subjects (waist circumference = 81-91 cm, age = 45-65 years), no peripheral nerve stimulation sensation was reported during DWI. Reduced image distortion in the posterior peripheral zone prostate gland and higher signal intensity, such as in the surrounding muscle of high-gradient DWI, were noted. CONCLUSION: Human prostate MRI at simultaneously high gradient amplitude of 200 mT/m and slew rate of 500 T/m/s is feasible, demonstrating that improved gradient performance can address image distortion and T2 decay-induced SNR issues for in vivo prostate imaging.

Comparison of distortion correction preprocessing pipelines for DTI in the upper limb.

PURPOSE: DTI characterizes tissue microstructure and provides proxy measures of nerve health. Echo-planar imaging is a popular method of acquiring DTI but is susceptible to various artifacts (e.g., susceptibility, motion, and eddy currents), which may be ameliorated via preprocessing. There are many pipelines available but limited data comparing their performance, which provides the rationale for this study. METHODS: DTI was acquired from the upper limb of heathy volunteers at 3T in blip-up and blip-down directions. Data were independently corrected using (i) FSL's TOPUP & eddy, (ii) FSL's TOPUP, (iii) DSI Studio, and (iv) TORTOISE. DTI metrics were extracted from the median, radial, and ulnar nerves and compared (between pipelines) using mixed-effects linear regression. The geometric similarity of corrected b = 0 images and the slice matched T1-weighted (T1w) images were computed using the Sörenson-Dice coefficient. RESULTS: Without preprocessing, the similarity coefficient of the blip-up and blip-down datasets to the T1w was 0·80 and 0·79, respectively. Preprocessing improved the geometric similarity by 1% with no difference between pipelines. Compared to TOPUP & eddy, DSI Studio and TORTOISE generated 2% and 6% lower estimates of fractional anisotropy, and 6% and 13% higher estimates of radial diffusivity, respectively. Estimates of anisotropy from TOPUP & eddy versus TOPUP were not different but TOPUP reduced radial diffusivity by 3%. The agreement of DTI metrics between pipelines was poor. CONCLUSIONS: Preprocessing DTI from the upper limb improves geometric similarity but the choice of the pipeline introduces clinically important variability in diffusion parameter estimates from peripheral nerves.