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Enabled by long-read sequencing technologies, particularly Single Molecule, Real-Time sequencing, N6-methyladenine (6mA) footprinting is a transformative methodology for revealing the heterogenous and dynamic distribution of nucleosomes and other DNA-binding proteins. Here, we present ipdTrimming, a novel 6mA-calling pipeline that outperforms existing tools in both computational efficiency and accuracy. Utilizing this optimized experimental and computational framework, we are able to map nucleosome positioning and transcription factor occupancy in nuclear DNA and establish high-resolution, long-range binding events in mitochondrial DNA. Our study highlights the potential of 6mA footprinting to capture coordinated nucleoprotein binding and to unravel epigenetic heterogeneity. 

Light’sinteraction with objectsurfacesthrough anisotropic reflection– where reflected light varies with viewing angles–offers significant potential for enhancing visual capabilities and assisting informed decision-making. Such ubiquitous light transfer phenomenon supports directional information encoding in sensing and dynamic display applications. We present LumosX, a set of techniques for encoding and decoding information through light intensity changes using 3D-printed optical anisotropic properties. By optimizing directional reflection and brightness contrasts through off-the-shelf materials and precise control over processing parameters (e.g., extrusion volume, raster angles, layer height, nozzle positioning), we enable cost-effective fabrication of visually enhanced objects. Our method supports modular assembly for highly curved regular surfaces and direct printing on top of relatively flat curved surfaces, enabling flexible information encoding for diverse applications. We showcase LumosX’s effectiveness through various indoor and smart urban sensing scenarios, demonstrating significant improvements in both human interaction and autonomous machine perception. 

Attention-based models have achieved many remarkable breakthroughs in numerous applications. However, the quadratic complexity of Attention makes the vanilla Attentionbased models hard to apply to long sequence tasks. Various improved Attention structures are proposed to reduce the computation cost by inducing low rankness and approximating the whole sequence by sub-sequences. The most challenging part of those approaches is maintaining the proper balance between information preservation and computation reduction: the longer sub-sequences used, the better information is preserved, but at the price of introducing more noise and computational costs. In this paper, we propose a smoothed skeleton sketching based Attention structure, coined S3Attention, which significantly improves upon the previous attempts to negotiate this trade-off. S3Attention has two mechanisms to effectively minimize the impact of noise while keeping the linear complexity to the sequence length: a smoothing block to mix information over long sequences and a matrix sketching method that simultaneously selects columns and rows from the input matrix. We verify the effectiveness of S3Attention both theoretically and empirically. Extensive studies over Long Range Arena (LRA) datasets and six time-series forecasting show that S3Attention significantly outperforms both vanilla Attention and other state-of-the-art variants of Attention structures. 

Although DNAN⁶-adenine methylation (6mA) is best known in prokaryotes, its presence in eukaryotes has recently generated great interest. Biochemical and genetic evidence supports that AMT1, an MT-A70 family methyltransferase (MTase), is crucial for 6mA deposition in unicellular eukaryotes. Nonetheless, the 6mA transmission mechanism remains to be elucidated. Taking advantage of single-molecule real-time circular consensus sequencing (SMRT CCS), here we provide definitive evidence for semiconservative transmission of 6mA inTetrahymena thermophila. In wild-type (WT) cells, 6mA occurs at the self-complementary ApT dinucleotide, mostly in full methylation (full-6mApT); after DNA replication, hemi-methylation (hemi-6mApT) is transiently present on the parental strand, opposite to the daughter strand readily labeled by 5-bromo-2′-deoxyuridine (BrdU). In ΔAMT1cells, 6mA predominantly occurs as hemi-6mApT. Hemi-to-full conversion in WT cells is fast, robust, and processive, whereas de novo methylation in ΔAMT1cells is slow and sporadic. InTetrahymena, regularly spaced 6mA clusters coincide with the linker DNA of nucleosomes arrayed in the gene body. Importantly, in vitro methylation of human chromatin by the reconstituted AMT1 complex recapitulates preferential targeting of hemi-6mApT sites in linker DNA, supporting AMT1's intrinsic and autonomous role in maintenance methylation. We conclude that 6mA is transmitted by a semiconservative mechanism: full-6mApT is split by DNA replication into hemi-6mApT, which is restored to full-6mApT by AMT1-dependent maintenance methylation. Our study dissects AMT1-dependent maintenance methylation and AMT1-independent de novo methylation, reveals a 6mA transmission pathway with a striking similarity to 5-methylcytosine (5mC) transmission at the CpG dinucleotide, and establishes 6mA as a bona fide eukaryotic epigenetic mark. 

We report a joint negative ion photoelectron spectroscopy (NIPES) and quantum chemical computational study on glycine-chloride/bromide complexes (denoted Gly·X−, X = Cl/Br) in close comparison to the previously studied Gly·I− cluster ion. Combining experimental NIPE spectra and theoretical calculations, various Gly·X− complexes were found to adopt the same types of low-lying isomers, albeit with different relative energies. Despite more congested spectral profiles for Gly·Cl− and Gly·Br−, spectral assignments were accomplished with the guidance of the knowledge learned from Gly·I−, where a larger spin–orbit splitting of iodine afforded well-resolved, recognizable spectral peaks. Three canonical plus one zwitterionic isomer for Gly·Cl− and four canonical conformers for Gly·Br− were experimentally identified and characterized in contrast to the five canonical ones observed for Gly·I− under similar experimental conditions. Taken together, this study investigates both genericity and variations in binding patterns for the complexes composed of glycine and various halides, demonstrating that iodide-tagging is an effective spectroscopic means to unravel diverse ion-molecule binding motifs for cluster anions with congested spectral bands by substituting the respective ion with iodide. 

Beyond glycemic control, SGLT2 inhibitors (SGLT2i) have protective effects on cardiorenal function. Renoprotection has been suggested to involve inhibition of NHE3 leading to reduced ATP-dependent tubular workload and mitochondrial oxygen consumption. NHE3 activity is also important for regulation of endosomal pH, but the effects of SGLT2i on endocytosis are unknown. We used a highly differentiated cell culture model of proximal tubule (PT) cells to determine the direct effects of SGLT2i on Na⁺-dependent fluid transport and endocytic uptake in this nephron segment. Strikingly, canagliflozin but not empagliflozin reduced fluid transport across cell monolayers, and dramatically inhibited endocytic uptake of albumin. These effects were independent of glucose and occurred at clinically relevant concentrations of drug. Canagliflozin acutely inhibited surface NHE3 activity, consistent with a direct effect, but did not affect endosomal pH or NHE3 phosphorylation. Additionally, canagliflozin rapidly and selectively inhibited mitochondrial complex I activity. Inhibition of mitochondrial complex I by metformin recapitulated the effects of canagliflozin on endocytosis and fluid transport, whereas modulation of downstream effectors AMPK and mTOR did not. Mice given a single dose of canagliflozin excreted twice as much urine over 24 h compared with empagliflozin-treated mice despite similar water intake. We conclude that canagliflozin selectively suppresses Na⁺-dependent fluid transport and albumin uptake in PT cells via direct inhibition of NHE3 and of mitochondrial function upstream of the AMPK/mTOR axis. These additional targets of canagliflozin contribute significantly to reduced PT Na⁺-dependent fluid transport in vivo.