Recombinant inbred line panels inform the genetic architecture and interactions of adaptive traits in Drosophila melanogaster.

The distribution of allelic effects on traits, along with their gene-by-gene and gene-by-environment interactions, contributes to the phenotypes available for selection and the trajectories of adaptive variants. Nonetheless, uncertainty persists regarding the effect sizes underlying adaptations and the importance of genetic interactions. Herein, we aimed to investigate the genetic architecture and the epistatic and environmental interactions involving loci that contribute to multiple adaptive traits using two new panels of Drosophila melanogaster recombinant inbred lines (RILs). To better fit our data, we re-implemented functions from R/qtl (Broman et al. 2003) using additive genetic models. We found 14 quantitative trait loci (QTL) underlying melanism, wing size, song pattern, and ethanol resistance. By combining our mapping results with population genetic statistics, we identified potential new genes related to these traits. None of the detected QTLs showed clear evidence of epistasis, and our power analysis indicated that we should have seen at least one significant interaction if sign epistasis or strong positive epistasis played a pervasive role in trait evolution. In contrast, we did find roles for gene-by-environment interactions involving pigmentation traits. Overall, our data suggest that the genetic architecture of adaptive traits often involves alleles of detectable effect, that strong epistasis does not always play a role in adaptation, and that environmental interactions can modulate the effect size of adaptive alleles.

Causes and Consequences of Varying Transposable Element Activity: An Evolutionary Perspective.

Transposable elements (TEs) are genomic parasites found in nearly all eukaryotes, including humans. This evolutionary success of TEs is due to their replicative activity, involving insertion into new genomic locations. TE activity varies at multiple levels, from between taxa to within individuals. The rapidly accumulating evidence of the influence of TE activity on human health, as well as the rapid growth of new tools to study it, motivated an evaluation of what we know about TE activity thus far. Here, we discuss why TE activity varies, and the consequences of this variation, from an evolutionary perspective. By studying TE activity in nonhuman organisms in the context of evolutionary theories, we can shed light on the factors that affect TE activity. While the consequences of TE activity are usually deleterious, some have lasting evolutionary impacts by conferring benefits on the host or affecting other evolutionary processes.

Blessing or curse: how the epigenetic resolution of host-transposable element conflicts shapes their evolutionary dynamics.

Transposable elements (TEs) are selfish genetic elements whose antagonistic interactions with hosts represent a common genetic conflict in eukaryotes. To resolve this conflict, hosts have widely adopted epigenetic silencing that deposits repressive marks at TEs. However, this mechanism is imperfect and fails to fully halt TE replication. Furthermore, TE epigenetic silencing can inadvertently spread repressive marks to adjacent functional sequences, a phenomenon considered a 'curse' of this conflict resolution. Here, we used forward simulations to explore how TE epigenetic silencing and its harmful side effects shape the evolutionary dynamics of TEs and their hosts. Our findings reveal that epigenetic silencing allows TEs and their hosts to stably coexist under a wide range of conditions, because the underlying molecular mechanisms give rise to copy-number dependency of the strength of TE silencing. Interestingly, contrary to intuitive expectations that TE epigenetic silencing should evolve to be as strong as possible, we found a selective benefit for modifier alleles that weaken TE silencing under biologically feasible conditions. These results reveal that the dual nature of TE epigenetic silencing, with both positive and negative effects, complicates its evolutionary trajectory and makes it challenging to determine whether TE epigenetic silencing is a 'blessing' or a 'curse'.

Cotransport of aged biochar colloids and thallium(I) in water-saturated porous media: Impact of the ionic strength, pH and aging degree.

Biochar colloids entering the soil undergo aging over time and exhibit strong capabilities in adsorbing and transporting pollutants. Therefore, investigating the cotransport of aged biochar colloids and thallium (Tl(I)) in quartz sand media is crucial for understanding Tl(I) migration in underground environments. This study investigated the migration of biochar colloids with two different aging degrees and Tl(I) in quartz sand media at various pH and ionic strengths (ISs). The results revealed that under all ISs and pH, 30%AWB (biochar aged with 30 % (w/w) HNO3) inhibited Tl(I) migration in media. This inhibition primarily arose from the introduction of hydroxyl and carboxyl groups during aging, which significantly enhanced colloid adsorption onto Tl(I). At lower ISs, 30%AWB colloids exhibited greater inhibition of Tl(I) migration due to their increased adsorption capacity. Additionally, aging promoted the migration of biochar colloids in the media. Greater biochar aging notably enhanced this promotion, potentially owing to reduced colloidal particle size and the formation of biochar derivatives. Moreover, 50%AWB (biochar aged with 50 % (w/w) HNO3) inhibited Tl(I) migration under low ISs but had almost no impact under high ISs. Nonetheless, at high pH, 50%AWB colloids facilitated Tl(I) migration. This phenomenon might be attributed to the inhibitory effect of aged biochar colloids on Tl(I) adsorption onto media at a high pH, as well as the stable binding between Tl(I) and aged biochar colloids. This study discusses the cotransport of biochar with various degrees of aging and Tl(I) in media, providing insights into remediating soils contaminated with Tl.

Reliable Off-Resonance Correction in High-Field Cardiac MRI Using Autonomous Cardiac B0 Segmentation with Dual-Modality Deep Neural Networks.

B0 field inhomogeneity is a long-lasting issue for Cardiac MRI (CMR) in high-field (3T and above) scanners. The inhomogeneous B0 fields can lead to corrupted image quality, prolonged scan time, and false diagnosis. B0 shimming is the most straightforward way to improve the B0 homogeneity. However, today's standard cardiac shimming protocol requires manual selection of a shim volume, which often falsely includes regions with large B0 deviation (e.g., liver, fat, and chest wall). The flawed shim field compromises the reliability of high-field CMR protocols, which significantly reduces the scan efficiency and hinders its wider clinical adoption. This study aims to develop a dual-channel deep learning model that can reliably contour the cardiac region for B0 shim without human interaction and under variable imaging protocols. By utilizing both the magnitude and phase information, the model achieved a high segmentation accuracy in the B0 field maps compared to the conventional single-channel methods (Dice score: 2D-mag = 0.866, 3D-mag = 0.907, and 3D-mag-phase = 0.938, all p < 0.05). Furthermore, it shows better generalizability against the common variations in MRI imaging parameters and enables significantly improved B0 shim compared to the standard method (SD(B0Shim): Proposed = 15 ± 11% vs. Standard = 6 ± 12%, p < 0.05). The proposed autonomous model can boost the reliability of cardiac shimming at 3T and serve as the foundation for more reliable and efficient high-field CMR imaging in clinical routines.

Enhancing Whole-Brain Magnetic Field Homogeneity for 3D-Magnetic Resonance Spectroscopic Imaging with a Novel Unified Coil: A Preliminary Study.

The spectral quality of magnetic resonance spectroscopic imaging (MRSI) can be affected by strong magnetic field inhomogeneities, posing a challenge for 3D-MRSI's widespread clinical use with standard scanner-equipped 2nd-order shim coils. To overcome this, we designed an empirical unified shim-RF head coil (32-ch RF receive and 51-ch shim) for 3D-MRSI improvement. We compared its shimming performance and 3D-MRSI brain coverages against the standard scanner shim (2nd-order spherical harmonic (SH) shim coils) and integrated parallel reception, excitation, and shimming (iPRES) 32-ch AC/DC head coil. We also simulated a theoretical 3rd-, 4th-, and 5th-order SH shim as a benchmark to assess the UNIfied shim-RF coil (UNIC) improvements. In this preliminary study, the whole-brain coverage was simulated by using B0 field maps of twenty-four healthy human subjects (n = 24). Our results demonstrated that UNIC substantially improves brain field homogeneity, reducing whole-brain frequency standard deviations by 27% compared to the standard 2nd-order scanner shim and 17% compared to the iPRES shim. Moreover, UNIC enhances whole-brain coverage of 3D-MRSI by up to 34% compared to the standard 2nd-order scanner shim and up to 13% compared to the iPRES shim. UNIC markedly increases coverage in the prefrontal cortex by 147% and 47% and in the medial temporal lobe and temporal pole by 29% and 13%, respectively, at voxel resolutions of 1.4 cc and 0.09 cc for 3D-MRSI. Furthermore, UNIC effectively reduces variations in shim quality and brain coverage among different subjects compared to scanner shim and iPRES shim. Anticipated advancements in higher-order shimming (beyond 6th order) are expected via optimized designs using dimensionality reduction methods.

Prevalent fast evolution of genes involved in heterochromatin functions.

Heterochromatin is a gene-poor and repeat-rich genomic compartment ubiquitously found in eukaryotes. Despite its low transcriptional activity, heterochromatin plays important roles in maintaining genome stability, organizing chromosomes, and suppressing transposable elements (TEs). Given the importance of these functions, it is expected that the genes involved in heterochromatin regulation would be highly conserved. Yet, a handful of these genes have been found to evolve rapidly. To investigate whether these previous findings are anecdotal or general to genes modulating heterochromatin, we compiled an exhaustive list of 106 candidate genes involved in heterochromatin functions and investigated their evolution over both short and long evolutionary time scales in Drosophila. Our analyses found that these genes exhibit significantly more frequent evolutionary changes, both in the forms of amino acid substitutions and gene copy number variation, when compared to genes involved in Polycomb-based repressive chromatin. While positive selection drives amino acid changes within both structured domains with diverse functions and irregular disordered regions (IDRs), purifying selection may have maintained the proportions of IDRs. Together with the observed negative associations between rates of protein evolution of these genes and genomic TE abundance, we propose an evolutionary model where the fast evolution of genes involved in heterochromatin functions is an inevitable outcome of the unique molecular features of the heterochromatin environment, while the rapid evolution of TEs may be an effect rather than cause. Our study provides an important global view of the evolution of genes involved in this critical cellular domain and provides insights into the factors driving the distinctive evolution of heterochromatin.

Microelectromechanical system for in situ quantitative testing of tension-compression asymmetry in nanostructures.

Tension-compression asymmetry is a topic of current interest in nanostructures, especially in strain engineering. Herein, we report a novel on-chip microelectromechanical system (MEMS) that can realize in situ quantitative mechanical testing of nanostructures under tension-compression functions. The mechanical properties of three kinds of nanostructures fabricated by focused ion beam (FIB) techniques were systematically investigated with the presented on-chip testing system. The results declare that both Pt nanopillars and C nanowires exhibit plastic deformation behavior under tension testing, with average Young's moduli of 70.06 GPa and 58.32 GPa, respectively. However, the mechanical deformation mechanisms of the two nanostructures changed in compression tests. The Pt nanopillar exhibited in-plane buckling behavior, while the C nanowire displayed 3D twisting behavior with a maximum strain of 25.47%, which is far greater than the tensile strain. Moreover, asymmetric behavior was also observed in the C nanospring during five loading-unloading tension-compression deformation tests. This work provides a novel insight into the asymmetric mechanical properties of nanostructures, with potential applications in nanotechnology research.

Removal of thallium by MnOx coated limestone sand filter through regeneration of KMnO4: Combination of physiochemical and biochemical actions.

Treatment of industrial thallium(Tl)-containing wastewater is crucial for mitigating environmental risks and health threats associated with this toxic metal. The incorporation of Mn oxides (MnOx) into the filtration system is a promising solution for efficient Tl(I) removal. However, further research is needed to elucidate the underlying mechanism behind MnOx-enhanced filtration and the rules of its stable operation. In this study, limestone, a cost-effective material, was selected as the filter media. Raw water with Mn(II), Tl(I), and other pollutants was prepared after a thorough investigation of actual industrial wastewater conditions. KMnO4 was added to induce the formation of MnO2 on limestone surfaces, while long-term operation led to enrichment of manganese oxidizing microorganisms (MnOM). Results revealed a dual mechanism. Firstly, most Mn(II) were oxidized by KMnO4 to form MnO2 attaching to limestone sands, and both Tl(I) and residual Mn(II) were adsorbed onto the newly formed MnO2. Subsequently, enzymes secreted by MnOM facilitated oxidation of remaining Mn(II), resulting in the generation of biogenic manganese oxides (BioMnOx) with numerous vacancies during long-term operation. The generated BioMnOx not only adsorbed Mn(II) and Tl(I) but also promoted their oxidation process. This approach offers an effective and sustainable method for removing both Mn(II) and Tl(I) from industrial wastewater, thereby addressing the challenges posed by thallium-contaminated effluents.

Changes of the gut microbiota composition and short chain fatty acid in patients with atrial fibrillation.

Background: With the establishment of the cardiac-gut axis concept, increasing evidence has suggested the involvement and important regulatory role of the gut microbiota (GM) and short chain fatty acid (SCFA) in cardiovascular diseases. However, the relationship between GM and atrial fibrillation (AF) is still poorly understood. Objectives: The aim of this study was to investigate whether there were differences in GM and SCFA between AF patients and healthy controls. Methods: In this study, we enrolled 30 hospitalized patients with AF and 30 matched patients with sinus rhythm (SR). GM species in fecal samples were evaluated through amplicon sequencing targeting the 16Sribosomal RNA gene. The feces SCFAs were describe step by step the quantitative analysis using gas chromatography-mass spectrometry (GC-MS). GM species richness, diversity, differential abundance of individual taxa between AF and SR were analyzed. Results: AF patients showed decreased species richness and α-diversity compared to SR patients, but there was no statistical difference. The phylogenetic diversity was significant decreased in AF group. The ß-diversity indexes revealed significant differences in GM community structure between the AF group and the SR group. After investigated the individual taxa, AF group showed altered relative abundance in several taxa compared to the SR group. linear discriminant analysis (LDA) effect size (LEfSe) analysis revealed, a significant decrease in Bifidobacterium and a greater abundance of Lactobacillus, Fusobacterium, Haemophilus in AF group compared with the SR group. The abundance of haemophilus was negative correlated with isovaleric acid and isobutyric acid. Conclusions: In AF patients, the GM phylogenetic diversity and ß-diversity decreased, the relative abundance altered in several taxa and the bacterial community structure changed as well as the SCFA level. GM and SCFA dysbiosis might play a crucial part in the occurrence and development of AF.

Harvesting electrons and holes from photodriven symmetry-breaking charge separation within a perylenediimide photosynthetic model dimer.

Understanding how to utilize symmetry-breaking charge separation (SB-CS) offers a path toward increasingly efficient light-harvesting technologies. This process plays a central role in the first step of photosynthesis, in which the dimeric "special pair" of the photosynthetic reaction center enters a coherent SB-CS state after photoexcitation. Previous research on SB-CS in both biological and synthetic chromophore dimers has focused on increasing the efficiency of light-driven processes. In a chromophore dimer undergoing SB-CS, the energy of the radical ion pair product is nearly isoenergetic with that of the lowest excited singlet (S1) state of the dimer. This means that very little energy is lost from the absorbed photon. In principle, the relatively high energy electron and hole generated by SB-CS within the chromophore dimer can each be transferred to adjacent charge acceptors to extend the lifetime of the electron-hole pair, which can increase the efficiency of solar energy conversion. To investigate this possibility, we have designed a bis-perylenediimide cyclophane (mPDI2) covalently linked to a secondary electron donor, peri-xanthenoxanthene (PXX) and a secondary electron acceptor, partially fluorinated naphthalenediimide (FNDI). Upon selective photoexcitation of mPDI2, transient absorption spectroscopy shows that mPDI2 undergoes SB-CS, followed by two secondary charge transfer reactions to generate a PXX•+-mPDI2-FNDI•- radical ion pair having a nearly 3 µs lifetime. This strategy has the potential to increase the efficiency of molecular systems for artificial photosynthesis and photovoltaics.

Spin-Frustrated Trisradical Trication of PrismCage.

Organic trisradicals featuring threefold symmetry have attracted significant interest because of their unique magnetic properties associated with spin frustration. Herein, we describe the synthesis and characterization of a triangular prism-shaped organic cage for which we have coined the name PrismCage6+ and its trisradical trication─TR3(•+). PrismCage6+ is composed of three 4,4'-bipyridinium dications and two 1,3,5-phenylene units bridged by six methylene groups. In the solid state, PrismCage6+ adopts a highly twisted conformation with close to C3 symmetry as a result of encapsulating one PF6- anion as a guest. PrismCage6+ undergoes stepwise reduction to its mono-, di-, and trisradical cations in MeCN on account of strong electronic communication between its 4,4'-bipyridinium units. TR3(•+), which is obtained by the reduction of PrismCage6+ employing CoCp2, adopts a triangular prism-shaped conformation with close to C2v symmetry in the solid state. Temperature-dependent continuous-wave and nutation-frequency-selective electron paramagnetic resonance spectra of TR3(•+) in frozen N,N-dimethylformamide indicate its doublet ground state. The doublet-quartet energy gap of TR3(•+) is estimated to be -0.08 kcal mol-1, and the critical temperature of spin-state conversion is found to be ca. 50 K, suggesting that it displays pronounced spin frustration at the molecular level. To the best of our knowledge, this example is the first organic radical cage to exhibit spin frustration. The trisradical trication of PrismCage6+ opens up new possibilities for fundamental investigations and potential applications in the fields of both organic cages and spin chemistry.

Normal thyroid stimulating hormone is associated with all-cause mortality in patients with acute myocardial infarction after percutaneous coronary intervention.

BACKGROUND: Circulating thyroid-stimulating hormone (TSH) levels within the normal reference range can affect the cardiovascular system. The present study investigated the prognostic value of normal TSH levels in patients presenting with acute myocardial infarction (AMI) following percutaneous coronary intervention (PCI). METHODS: Between January 2013 and July 2019, 1240 patients with AMI and normal thyroid function were enrolled and classified according to TSH tertile. The trial endpoint was all-cause mortality. The integrated discrimination index (IDI) and the net reclassification index (NRI) were used to assess the combined predictive values of the TSH levels and the Global Registry of Acute Coronary Events (GRACE) scores. RESULTS: After a median 44.25-month follow-up, 195 individuals died. Even after covariate adjustment by multivariate Cox regression (HR: 1.56; 95% CI 1.08-2.25; P = 0.017), the patients in the third TSH tertile were at the highest risk of all-cause mortality. A subgroup analysis revealed significant interactions between the TSH levels and the GRACE scores (high risk vs. low/medium risk) (P = 0.019). The addition of the TSH levels to the GRACE scores substantially improved the prediction of all-cause mortality, especially for high-risk patients (NRI = 0.239; IDI = 0.044; C-statistic value range 0.649-0.691; all significant). CONCLUSIONS: The third TSH tertile is associated with a higher incidence of all-cause mortality than the first TSH tertile in high-risk patients presenting with AMI after PCI.

Association of the Systemic Immune-Inflammation Index with Outcomes in Acute Coronary Syndrome Patients with Chronic Kidney Disease.

Background: The systemic immune-inflammation index (SII; neutrophil × platelet/lymphocyte) is a novel marker for immune and inflammatory status and is associated with adverse prognosis in cardiovascular disease. Methods: In total, 744 patients diagnosed with acute coronary syndrome (ACS) and chronic kidney disease (CKD) were included in our study, received standard therapies, and were followed up. Patients were divided into high and low SII groups according to the baseline SII. The primary endpoint was major cardiovascular events (MACEs), defined as cardiovascular death, nonfatal myocardial infarction, and nonfatal stroke. Results: During a median follow-up of 2.5 years, a total of 185 (24.9%) MACEs were recorded. Analysis of the ROC curve revealed that the best cutoff value of SII was 1159.84×109/L for predicting MACEs. The Kaplan-Meier analysis showed that those patients in the low SII group had higher survival rates than those in the high SII group (p < 0.001). Compared to those in the low SII group, patients in the high SII group were at significantly higher risk of MACEs (134 (38.8%) vs 51 (12.8%), p < 0.001). Univariate and multivariable Cox regression analyses revealed that a high SII level was independently associated with MACEs in ACS patients with CKD (adjusted hazard ratio [HR]: 1.865, 95% confidence interval [CI]: 1.197-2.907, p = 0.006). Conclusion: The present study showed that an elevated SII is associated with adverse cardiovascular outcomes in ACS with CKD patients, suggesting that SII may be a valuable predictor of poor prognosis in ACS with CKD patients. Further studies are needed to confirm our findings.

Sequestration and oxidation of heavy metals mediated by Mn(II) oxidizing microorganisms in the aquatic environment.

Microorganisms can oxidize Mn(II) to biogenic Mn oxides (BioMnOx), through enzyme-mediated processes and non-enzyme-mediated processes, which are generally considered as the source and sink of heavy metals due to highly reactive to sequestrate and oxidize heavy metals. Hence, the summary of interactions between Mn(II) oxidizing microorganisms (MnOM) and heavy metals is benefit for further work on microbial-mediated self-purification of water bodies. This review comprehensively summarizes the interactions between MnOM and heavy metals. The processes of BioMnOx production by MnOM has been firstly discussed. Moreover, the interactions between BioMnOx and various heavy metals are critically discussed. On the one hand, modes for heavy metals adsorbed on BioMnOx are summarized, such as electrostatic attraction, oxidative precipitation, ion exchange, surface complexation, and autocatalytic oxidation. On the other hand, adsorption and oxidation of representative heavy metals based on BioMnOx/Mn(II) are also discussed. Thirdly, the interactions between MnOM and heavy metals are also focused on. Finally, several perspectives which will contribute to future research are proposed. This review provides insight into the sequestration and oxidation of heavy metals mediated by Mn(II) oxidizing microorganisms. It might be helpful to understand the geochemical fate of heavy metals in the aquatic environment and the process of microbial-mediated water self-purification.

Optical Spin Polarization of a Narrow-Linewidth Electron-Spin Qubit in a Chromophore/Stable-Radical System.

Photoexcited organic chromophores appended to stable radicals can serve as qubit and/or qudit candidates for quantum information applications. 1,6,7,12-Tetra-(4-tert-butylphenoxy)-perylene-3,4 : 9,10-bis(dicarboximide) (tpPDI) linked to a partially deuterated α,γ-bisdiphenylene-ß-phenylallyl radical (BDPA-d16 ) was synthesized and characterized by time-resolved optical and electron paramagnetic resonance (EPR) spectroscopies. Photoexcitation of tpPDI-BDPA-d16 results in ultrafast radical-enhanced intersystem crossing to produce a quartet state (Q) followed by formation of a spin-polarized doublet ground state (D0 ). Pulse-EPR experiments confirmed the spin multiplicity of Q and yielded coherence times of Tm =2.1±0.1 µs and 2.8±0.2 µs for Q and D0 , respectively. BDPA-d16 eliminates the dominant 1 H hyperfine couplings, resulting in a single narrow line for both the Q and D0 states, which enhances the spectral resolution needed for good qubit addressability.

Comprehensive Analysis of Glutamate Receptor-like Genes in Rice (Oryza sativa L.): Genome-Wide Identification, Characteristics, Evolution, Chromatin Accessibility, gcHap Diversity, Population Variation and Expression Analysis.

Glutamate receptors (GLR) are widely present in animals and plants, playing essential roles in regulating plant growth, development and stress response. At present, most studies of GLRs in plants are focused on Arabidopsis thaliana, while there have been few studies on rice. In this study, we identified 26 OsGLR genes in rice (Oryza sativa L.). Then, we analyzed the chromosomal location, physical and chemical properties, subcellular location, transmembrane (TM) helices, signal peptides, three-dimensional (3D) structure, cis-acting elements, evolution, chromatin accessibility, population variation, gene-coding sequence haplotype (gcHap) and gene expression under multiple abiotic stress and hormone treatments. The results showed that out of the 26 OsGLR genes, ten genes had the TM domain, signal peptides and similar 3D structures. Most OsGLRs exhibited high tissue specificity in expression under drought stress. In addition, several OsGLR genes were specifically responsive to certain hormones. The favorable gcHap of many OsGLR genes in modern varieties showed obvious differentiation between Xian/indica and Geng/japonica subspecies. This study, for the first time, comprehensively analyzes the OsGLR genes in rice, and provides an important reference for further research on their molecular function.

Optimization of Spinal Reconstructions for Thoracolumbar Burst Fractures to Prevent Proximal Junctional Complications: A Finite Element Study.

The management strategies of thoracolumbar (TL) burst fractures include posterior, anterior, and combined approaches. However, the rigid constructs pose a risk of proximal junctional failure. In this study, we aim to systemically evaluate the biomechanical performance of different TL reconstruction constructs using finite element analysis. Furthermore, we investigate the motion and the stress on the proximal junctional level adjacent to the constructs. We used a T10-L3 finite element model and simulated L1 burst fracture. Reconstruction with posterior instrumentation (PI) alone (U2L2 and U1L1+(intermediate screw) and three-column spinal reconstruction (TCSR) constructs (U1L1+PMMA and U1L1+Cage) were compared. Long-segment PI resulted in greater global motion reduction compared to constructs with short-segment PI. TCSR constructs provided better stabilization in L1 compared to PI alone. Decreased intradiscal and intravertebral pressure in the proximal level were observed in U1L1+IS, U1L1+PMMA, and U1L1+Cage compared to U2L2. The stress and strain energy of the pedicle screws decreased when anterior reconstruction was performed in addition to PI. We showed that TCSR with anterior reconstruction and SSPI provided sufficient immobilization while offering additional advantages in the preservation of physiological motion, the decreased burden on the proximal junctional level, and lower risk of implant failure.

Tunable Toxicity of Bufadienolides is Regulated through a Configuration Inversion Catalyzed by a Short-Chain Dehydrogenase/Reductase.

Bufadienolides are toxic components widely found in amphibious toads that exhibit a wide range of biological activities. Guided by UPLC-QTOF-MS analysis, several 3-epi-bufadienolides with unique structures were isolated from the bile of the Asiatic toad, Bufo gargarizans. However, the enzymatic machinery of this epimerization in toads and its significance in chemical ecology remains poorly understood. Herein, we firstly compared the toxicities of two typical bufadienolides, bufalin (featuring a 14ß-hydroxyl) and resibufogenin (containing a 14, 15-epoxy group), with their corresponding 3-epi isomers in a zebrafish model. The results of the toxicology assays showed that the ratio of maximum non-toxic concentrations of these two pairs of compounds are 256 and 96 times, respectively, thereby indicating that 3-hydroxyl epimerization leads to a significant decrease in toxicity. Aiming to investigate the biotransformation of 3-epi bufadienolides in toads, we applied liver lysate to transform bufalin and found that it could stereoselectively catalyze the conversion of bufalin into its 3α-hydroxyl epimer. Following this, we cloned and characterized a short-chain dehydrogenase/reductase, HSE-1, from the toad liver cDNA library and verified its 3(ß→α)-hydroxysteroid epimerization activity. To the best of our knowledge, this is the first hydroxyl epimerase identified from amphibians that regulates the toxicity of animal-derived natural products.

Species-specific chromatin landscape determines how transposable elements shape genome evolution.

Transposable elements (TEs) are selfish genetic parasites that increase their copy number at the expense of host fitness. The 'success', or genome-wide abundance, of TEs differs widely between species. Deciphering the causes for this large variety in TE abundance has remained a central question in evolutionary genomics. We previously proposed that species-specific TE abundance could be driven by the inadvertent consequences of host-direct epigenetic silencing of TEs-the spreading of repressive epigenetic marks from silenced TEs into adjacent sequences. Here, we compared this TE-mediated local enrichment of repressive marks, or 'the epigenetic effect of TEs', in six species in the Drosophila melanogaster subgroup to dissect step-by-step the role of such effect in determining genomic TE abundance. We found that TE-mediated local enrichment of repressive marks is prevalent and substantially varies across and even within species. While this TE-mediated effect alters the epigenetic states of adjacent genes, we surprisingly discovered that the transcription of neighboring genes could reciprocally impact this spreading. Importantly, our multi-species analysis provides the power and appropriate phylogenetic resolution to connect species-specific host chromatin regulation, TE-mediated epigenetic effects, the strength of natural selection against TEs, and genomic TE abundance unique to individual species. Our findings point toward the importance of host chromatin landscapes in shaping genome evolution through the epigenetic effects of a selfish genetic parasite.

All the instructions required for life are encoded in the set of DNA present in a cell. It therefore seems natural to think that every bit of this genetic information should serve the organism. And yet most species carry parasitic 'transposable' sequences, or transposons, whose only purpose is to multiply and insert themselves at other positions in the genome. It is possible for cells to suppress these selfish elements. Chemical marks can be deposited onto the DNA to temporarily 'silence' transposons and prevent them from being able to move and replicate. However, this sometimes comes at a cost: the repressive chemical modifications can spread to nearby genes that are essential for the organism and perturb their function. Strangely, the prevalence of transposons varies widely across the tree of life. These sequences form the majority of the genome of certain species ­ in fact, they represent about half of the human genetic information. But their abundance is much lower in other organisms, forming a measly 6% of the genome of puffer fish for instance. Even amongst fruit fly species, the prevalence of transposable elements can range between 2% and 25%. What explains such differences? Huang et al. set out to examine this question through the lens of transposon silencing, systematically comparing how this process impacts nearby regions in six species of fruit flies. This revealed variations in the strength of the side effects associated with transposon silencing, resulting in different levels of perturbation on neighbouring genes. A stronger impact was associated with the species having fewer transposons in its genome, suggesting that an evolutionary pressure is at work to keep the abundance of transposons at a low level in these species. Further analyses showed that the genes which determine how silencing marks are distributed may also be responsible for the variations in the impact of transposon silencing. They could therefore be the ones driving differences in the abundance of transposons between species. Overall, this work sheds light on the complex mechanisms shaping the evolution of genomes, and it may help to better understand how transposons are linked to processes such as aging and cancer.