CRISPR-Cas9 mediated RALA knockout and reconstitution: insights into the detection and role of RALA S194 phosphorylation in Ras-dependent and Ras-independent cancers.

Downstream of oncogenic RAS, RALA is critical for cancer tumorigenesis, possibly regulated by phosphorylation of its Serine194 residue. We made CRISPR-Cas9 RALA knockout (RALA KO) in three RAS-dependent and two RAS-independent cancer cells. Detection of RALA S194 phosphorylation using the commercial anti-phospho-RALA antibody lacks specificity in all three RAS-dependent cancers.

Introductory notes before zebra finch song have unique timing properties while sharing acoustic properties with song.

Preparatory neural activity precedes the initiation of simple movements and a key feature of this preparatory activity is its trial-by-trial correlation with features of the upcoming movement. Recent studies in the zebra finch, a songbird with a complex, naturally learned, movement sequence (song), have suggested that the repeats of short introductory notes (INs) at the start of each song bout, reflect motor preparation. However, whether IN properties correlate with upcoming song features remains poorly understood.

Tweaking Unimolecular Micellar Nanoarchitecture for Drug Delivery in Tumor Xenograft Mice Models.

Uncontrolled rapture of prodrug nano-formulation under physiological concentration gradient is a bottleneck in the effective delivery of anticancer drugs to solid tumors in vivo. The present investigation reports macromolecular nano-compartmentalization in single polymer chain micellar nanoparticle (or unimolecular micelle nanoparticle, UMNp) and demonstrates its therapeutic efficacies in pancreatic cancer xenograft mouse model. The UMNp is engineered in a six-arm enzymatic-biodegradable polycaprolactone star-polymer by employing a divergent approach using identical chemical constituents but varying the arms-lengths.

Synthetic Strategy to Build High-Molecular-Weight Poly(L-tyrosine) and Its Unexplored β-Sheet Block Copolymer Nanoarchitectures.

Synthesis of high-molecular-weight polypeptides and their block copolymer macromolecular architectures from β-sheet-promoting L-amino acids is still an unresolved problem. Here, an elegant steric hindrance-assisted ring-opening polymerization (SHAROP) strategy is introduced to access β-sheet poly(L-tyrosine) having more than 250 units. The scope of the synthetic methodology is expanded to access unexplored poly(L-tyrosine)-based higher-order β-sheet block copolymer nanoassemblies.

Palladium Catalyzed C3-(sp)-H Alkenylation of Pyrroles via a Benzothiazole Directing Group: A Direct Access to Organic Thermally Activated Delayed Fluorescence Materials.

A Pd (II)-catalyzed direct C3-(sp)-H alkenylation of heteroarenes using benzothiazole as a directing group was successfully achieved. A wide range of 2--alkylpyrroles undergo an oxidative coupling with a variety of acrylates to furnish highly regio- and chemoselective E-alkenylation products at the C3 position. An important intermediate complex has been isolated and characterized so as to have an insight into the mechanism.

Visible-Light-Induced Copper-Catalyzed Radical Reactions of Diazo Arylidene Succinimides to Access the Pyromellitic Diimide (PMDI) Core.

The synthesis of pyromellitic diimides (PMDIs) through visible-light-promoted copper-catalyzed reaction of diazo arylidene succinimides has been accomplished without the use of external oxidants. This transformation involves a carbon radical from diazo arylidene succinimides with a copper catalyst or photocatalyst via the proton-coupled electron transfer (PCET) process. This approach successfully challenges a long-standing paradigm in the synthesis of PMDIs.

Star-polymer unimolecular micelle nanoparticles to deliver a payload across the blood-brain barrier.

Nanocarrier-mediated therapeutic delivery to brain tissue is impeded by tightly controlled transportation across the blood-brain barrier (BBB). Herein, we report a well-defined core-shell star-shaped unimolecular micelle (star-UMM; a single polymer entity) as an efficient BBB-breaching nanoparticle for brain-specific administration of the fluorescent anticancer drug doxorubicin and mapping of brain tissues by the near-infrared biomarker IR780 in mice. The star-UMM was engineered by precisely programming the polymer topology having hydrophobic and hydrophilic polycaprolactone blocks and in-built with lysosomal enzyme-biodegradation stimuli to deliver the payloads at intracellular compartments.

The Reactivity of Acceptor-Acceptor Diazo Pyrazolones with Allyl Thioethers under Visible Light: Access to Homoallyl Sulfides, Spiropyrazolones - Pesticide Analogues and Photoflow Synthesis.

The novel reactivity of a less selective and more reactive acceptor-acceptor kind of diazo pyrazolone (DIPOL) has been explored under visible light for the first time. We have successfully demonstrated the reaction of DIPOL and different allyl thioethers under blue light to construct a wide variety of products including a pesticidal analogue exclusively in excellent chemoselectivity in good to excellent yields. Moreover, possible side products emanating from ketene were not observed.

Melt Polycondensation Strategy to Access Unexplored l-Amino Acid and Sugar Copolymers.

Biodegradable polymers from bioresources are highly in demand for the development of sustainable polymer platforms for commodity plastics and in the biomedical field. Here, an elegant one-pot synthetic strategy is developed, for the first time, to access unexplored hybrid polymers from two naturally abundant resources: carbohydrates (sugars) and l-amino acids. A bottleneck in the synthetic strategy is overcome by tailor-making d-mannitol-based six- and five-membered bicyclic acetalized diols, and their structures are confirmed by single-crystal X-ray diffraction and 2D NMR spectroscopy.

Rational Monomer Design for the Synthesis of Conjugated Polymers by Direct Heteroarylation Polymerization.

This study focuses on the design concepts that contribute to the C-H activation in bithiophene-flanked monomers incorporating naphthalene diimide (NDI), perylene diimide (PDI), and fluorene (FLU) and their polymerization by direct heteroarylation. Density functional theory (DFT) calculations reveal distinct energy requirements for C-H bond abstraction, which is dictated by the electron-withdrawing strength of the central aromatic core flanked by bithiophene. These provide insights into the reactivity of each monomer for C-H bond activation.

Structural Engineering of l-Aspartic Amphiphilic Polyesters for Enzyme-Responsive Drug Delivery and Bioimaging in Cancer Cells.

Design and development of amphiphilic polyesters based on bioresources are very important to cater to the ever-growing need for biodegradable polymers in biomedical applications. Here, we report structural engineering of enzyme-responsive amphiphilic polyesters based on l-amino acid bioresources and study their drug delivery aspects in the cancer cell line. For this purpose, an l-aspartic acid-based polyester platform is chosen, and two noncovalent forces such as hydrogen bonding and side-chain hydrophobic interactions are introduced to study their effect on the aqueous self-assembly of nanoparticles.

Visible Light-Induced Organophotoredox-Catalyzed β-Hydroxytrifluoromethylation of Unactivated Alkenes.

Herein, we report a mild transition metal-free organophotoredox-catalyzed approach for β-hydroxytrifluoromethylation of unactivated alkenes using CFSONa and acridinium salt. The protocol is compatible with various mono-, di-, and trisubstituted aliphatic unactivated alkenes containing numerous functional groups and natural product derivatives. Further, the postsynthetic modifications of the synthesized trifluoromethylated products have been demonstrated through cross-coupling and functional group interconversion reactions.

Photosensitizer-Free Photoinduced Ground-State Triplet Carbene-Assisted Persistent Aryloxy Radical Generation via Hydrogen Atom Transfer.

The traditional intermolecular O-H insertion strategy is typically associated with the reactivity exhibited by the singlet spin state, or it can alter the spin state from triplet to singlet by hydrogen bonding. Herein, we report diazoarylidene succinimide that generates a persistent ground-state triplet carbene under visible light (Blue LED, 456 nm) without a photosensitizer. This triplet carbene undergoes an intramolecular O-H insertion via hydrogen atom transfer, forming a persistent aryloxy radical without altering its spin state and leading to biologically relevant 2-chromenes.

KnotResolver: tracking self-intersecting filaments in microscopy using directed graphs.

Motivation: Quantification of microscopy time series of in vitro reconstituted motor-driven microtubule transport in "gliding assays" is typically performed using computational object tracking tools. However, these are limited to non-intersecting and rod-like filaments.

Results: Here, we describe a novel computational image-analysis pipeline, KnotResolver, to track image time series of highly curved self-intersecting looped filaments (knots) by resolving cross-overs.

Switchable molecular electrocatalysis.

We demonstrate a switchable electrocatalysis mechanism modulated by hydrogen bonding interactions in ligand geometries. By manipulating these geometries, specific electrochemical processes at a single catalytic site can be selectively and precisely activated or deactivated. The α geometry enhances dioxygen electroreduction (ORR) while inhibiting protium redox processes, with the opposite effect seen in the β geometry.

Size- and Shape-controlled Biodegradable Polymer Brushes Based on l-Amino Acid for Intracellular Drug Delivery and Deep-Tissue Penetration.

We report size- and shape-controlled polymer brushes based on l-amino acid bioresource and study the role of polymer topology on the enzymatic biodegradation and deep-tissue penetration under in vitro and in vivo. For this purpose, l-tyrosine-based propargyl-functionalized monomer is tailor-made and polymerized via solvent-free melt polycondensation strategy to yield hydrophobic and clickable biodegradable poly(ester-urethane)s. Postpolymerization click chemistry strategy is applied to make well-defined amphiphilic one-dimensional rodlike and three-dimensional spherical polymer brushes by merely varying the lengths of PEG-azides in the reaction.

Zwitterionic Strategy to Stabilize Self-Immolative Polymer Nanoarchitecture under Physiological pH for Drug Delivery In Vitro and In Vivo.

The major bottleneck in using polymer nanovectors for biomedical application, particularly those based on self-immolative poly(amino ester) (PAE), lies in their uncontrolled autodegradation at physiological pH before they can reach the intended target. Here, an elegant triblock-copolymer strategy is designed to stabilize the unstable PAE chains via zwitterionic interactions under physiological pH (pH 7.4) and precisely program their enzyme-responsive biodegradation specifically within the intracellular compartments, ensuring targeted delivery of the cargoes.

Directional molecular transport in iron redox flow batteries by interfacial electrostatic forces.

The mounting global energy demand urges surplus electricity generation. Due to dwindling fossil resources and environmental concerns, shifting from carbon-based fuels to renewables is vital. Though renewables are affordable, their intermittent nature poses supply challenges.

PpSCARECROW1 (PpSCR1) regulates leaf blade and mid-vein development in Physcomitrium patens.

In plants, asymmetric cell divisions result in distinct cell fates forming large and small daughter cells, adding to the cellular diversity in an organ. SCARECROW (SCR), a GRAS domain-containing transcription factor controls asymmetric periclinal cell divisions in flowering plants by governing radial patterning of ground tissue in roots and cell proliferation in leaves. Though SCR homologs are present across land plant lineages, the current understanding of their role in cellular patterning and leaf development is mostly limited to flowering plants.

Variability of echo state network prediction horizon for partially observed dynamical systems.

Study of dynamical systems using partial state observation is an important problem due to its applicability to many real-world systems. We address the problem by studying an echo state network (ESN) framework with partial state input with partial or full state output. Application to the Lorenz system and Chua's oscillator (both numerically simulated and experimental systems) demonstrate the effectiveness of our method.

Peptides from conserved tandem direct repeats of SHORT-LEAF regulate gametophore development in moss P. patens.

Tandem direct repeat (TDR)-containing proteins, present across all domains of life, play crucial roles in plant development and defense mechanisms. Previously, we identified that disruption of a bryophyte-specific protein family, SHORT-LEAF (SHLF), possessing the longest reported TDRs, is the cause of the shlf mutant phenotype in Physcomitrium patens. shlf exhibits reduced apical dominance, altered auxin distribution, and 2-fold shorter leaves.

The phased short-interfering RNA siRD29(-) regulates GIBBERELLIN 3-OXIDASE 3 during stolon-to-tuber transitions in potato.

Phased short-interfering RNAs (phasiRNAs) fine tune various stages of growth, development, and stress responses in plants. Potato (Solanum tuberosum) tuberization is a complex process, wherein a belowground modified stem (stolon) passes through developmental stages like swollen stolon and minituber before it matures to a potato. Previously, we identified several phasiRNA-producing loci (PHAS) from stolon-to-tuber transition stages.

Electrostatically driven unidirectional molecular flux for high performance alkaline flow batteries.

To mitigate the mismatch between energy availability and energy demand due to day/night shifts and seasonal variations, intensive efforts have been dedicated to storing renewable energy in various energy storage modules. Redox flow batteries have an upper hand over conventional batteries as energy storage modules due to their capability of decoupling energy and power. However, interfacial events, such as mass transport and electron transfer, play pivotal roles in flow batteries' energy storage and conversion mechanisms.

Direct Access to Strained Fused Dihalo-Aziridino Quinoxalinones via C3-Alkylation Followed by Tandem Cyclization.

Quinoxalinones are a privileged class of compounds, and their structural framework is found in many bioactive compounds, natural compounds, and pharmaceuticals. Quinoxalinone is a promising scaffold for different types of functionalization, and the slight modification of the quinoxalinone skeleton is known to offer a wide range of compounds for drug discovery. Owing to the importance of the quinoxalinone scaffold, we have developed a base-mediated protocol for the C3-alkylation of quinoxalinone followed by tandem cyclization to access novel types of strenuous and fused dihalo-aziridino-quinoxalinone heterocycles via the construction of C-C and C-N bonds.