Ru(II)-Catalyzed C-H Activation/[4+2] Annulation of Sulfoxonium Ylide with Maleimide: Access to Fused Benzo[]isoindole-1,3,5-trione.

A ruthenium-catalyzed C-H activation and a concomitant [4+2] annulation of sulfoxonium ylide with maleimide have been demonstrated. This tandem reaction results in the formation of fused benzo[]isoindole-1,3,5-trione. The method employs mild conditions and is free of metal oxidants.

Distinct Bin/Amphiphysin/Rvs (BAR) family proteins may assemble on the same tubule to regulate membrane organization .

Intracellular membrane tubules play a crucial role in diverse cellular processes, and their regulation is facilitated by Bin-Amphiphysin-Rvs (BAR) domain-containing proteins. This study investigates the roles of ICA69 (dICA69) (an N-BAR protein) and CIP4 (dCIP4) (an F-BAR protein), focusing on their impact on membrane tubule organization. In contrast to the prevailing models of BAR-domain protein function, we observed colocalization of endogenous dICA69 with dCIP4-induced tubules, indicating their potential recruitment for tubule formation and maintenance.

Ru(II)-Catalyzed C-H Alkylation of N-Benzyltriflamide with Maleimides: Synthesis of o-Succinimide Substituted Benzaldehydes.

A ruthenium-catalyzed N-benzyltriflamide assisted C-H alkylation with maleimide followed by hydrolysis of in situ generated imine has been developed for the first time. This synthetic method results in the efficient synthesis of o-succinimide derivatives of benzaldehydes. This reaction involves less expensive and mild reaction conditions and shows excellent site selectivity and good functional group compatibility.

dAsap regulates cellular protrusions via an Arf6-dependent actin regulatory pathway in S2R+ cells.

Membrane protrusions are fundamental to cellular functions like migration, adhesion, and communication and depend upon dynamic reorganization of the cytoskeleton. GAP-dependent GTP hydrolysis of Arf proteins regulates actin-dependent membrane remodeling. Here, we show that dAsap regulates membrane protrusions in S2R+ cells by a mechanism that critically relies on its ArfGAP domain and relocalization of actin regulators, SCAR, and Ena.

Beadex, the LIM only protein, is required for the growth of the larval neuromuscular junction.

The appropriate growth of the neurons, accurate organization of their synapses, and successful neurotransmission are indispensable for sensorimotor activities. These processes are highly dynamic and tightly regulated. Extensive genetic, molecular, physiological, and behavioral studies have identified many molecular candidates and investigated their roles in various neuromuscular processes.

Total synthesis of diplofuranone A and diapolic acid A.

The first and concise syntheses of the anticancer agent diplofuranone A and the fatty acid-derived metabolite diapolic acid A have been demonstrated using easily accessible and commercially available starting materials. The key feature of these syntheses is the efficient diversification of highly stereo- and chemoselectively constructed (,)-1,6-dioxo-2,4-dienes using ruthenium catalytic conditions, which enabled straightforward access to diversely substituted bioactive molecules.

A palladium catalyzed asymmetric desymmetrization approach to enantioenriched 1,3-disubstituted isoindolines.

Herein, we report the first palladium/MPAA catalyzed enantioselective C-H activation/[4 + 1] annulation of diarylmethyltriflamide and olefins to construct chiral -1,3-disubstituted isoindoline derivatives. The use of a readily accessible mono-N-protected amino acid as a chiral ligand improves the efficiency and enantioselectivity of the catalytic transformation. The developed method provides access to both enantiomers of a product using either d or l-phenylalanine derivative as a chiral ligand facilitating the synthesis of both optically active 1,3-disubstituted isoindoline derivatives.

AP2 Regulates Thickveins Trafficking to Attenuate NMJ Growth Signaling in .

Compromised endocytosis in neurons leads to synapse overgrowth and altered organization of synaptic proteins. However, the molecular players and the signaling pathways which regulate the process remain poorly understood. Here, we show that σ2-adaptin, one of the subunits of the AP2-complex, genetically interacts with Mad, Medea and Dad (components of BMP signaling) to control neuromuscular junction (NMJ) growth in Ultrastructural analysis of mutants show an accumulation of large vesicles and membranous structures akin to endosomes at the synapse.

Diversification of ()-1,6-Dioxo-2,4-Dienes for the Synthesis of (+)-Aspicillin, Isolaurepan, and β-Parinaric Acid.

A divergent formal synthesis of polyhydroxylated macrocyclic lactone (+)-aspicillin and polyene bioactive natural product β-parinaric acid and the total synthesis of non-terpenoid metabolite isolaurepan have been achieved using a ruthenium-catalyzed stereo- and chemoselective oxidative coupling reaction of easily accessible vinyl ketones and acrylates. The crucial transformation involves the efficient synthesis and functionalization of stereodefined ()-1,6-dioxo-2,4-dienes using simple reaction protocols, which enabled straightforward access to a diverse range of bioactive natural products.

Role of Bin-Amphiphysin-Rvs (BAR) domain proteins in mediating neuronal signaling and disease.

Several proteins contain signaling domains that can regulate the cell membrane dynamics as well as the underlying cytoskeleton. Among these, Bin-Amphiphysin-Rvs (BAR) domain-containing proteins, with their membrane deforming properties, have emerged as the key players in regulating neuronal morphology and inducing neuronal signaling that can modulate synaptic architecture. While the biochemical and structural basis of membrane deformation by the BAR-domain proteins has been extensively studied, the in vivo contexts in which these proteins function remain to be elucidated.

Synthesis of Polyene Bioactive Natural Products: FR252921 and Vitamin A.

A formal synthesis of FR252921, a potent macrocyclic immunosuppressive agent, and a six-step synthesis of vitamin A have been demonstrated. The application of a ruthenium-catalyzed step-economic and environmentally benign strategy for the highly stereo- and chemoselective construction of valuable polyene motifs of FR252921 and vitamin A highlights the syntheses. The key features for the synthesis FR252921 include preparation of the triene moiety followed by two consecutive peptide couplings of the three fragments.

Ruthenium-catalyzed stereo- and chemoselective oxidative coupling of vinyl ketones: efficient access to (,)-1,6-dioxo-2,4-dienes.

A Ru-catalyzed direct oxidative coupling reaction of vinyl ketones was developed. It offers a straightforward and atom-economical protocol for the synthesis of functionalized (,)-1,6-dioxo-2,4-diene derivatives in moderate to good yields with excellent stereo- and chemoselectivities. In addition, the synthetic utility of this method was further demonstrated by its application to the synthesis of bioactive natural products such as (7,9)-henicosa-7,9-diene-6,11-dione (sex pheromone), ostopanic acid (plant anticancer agent), JA (anti-tumor agent) and the southern part (C1-C13) of the antibiotic macrolactin-T.

Weakly Coordinating, Hydroxyl Directed Ruthenium Catalyzed C-H Alkylation of Ubiquitous Benzyl Alcohols with Maleimides.

Benzyl alcohols have been employed as effective coupling partners in Ru-catalyzed C-H functionalization reactions, and their annulation with maleimides then offers efficient synthesis of useful ortho substituted succinimide aromatic aldehydes and ketones. Detailed mechanistic studies have been demonstrated by performing preliminary reactions, deuterium studies, and competitive experiments.

Modulation of fungal virulence through CRZ1 regulated F-BAR-dependent actin remodeling and endocytosis in chickpea infecting phytopathogen Ascochyta rabiei.

Polarized hyphal growth of filamentous pathogenic fungi is an essential event for host penetration and colonization. The long-range early endosomal trafficking during hyphal growth is crucial for nutrient uptake, sensing of host-specific cues, and regulation of effector production. Bin1/Amphiphysin/Rvs167 (BAR) domain-containing proteins mediate fundamental cellular processes, including membrane remodeling and endocytosis.

Fragile X premutation rCGG repeats impair synaptic growth and synaptic transmission at Drosophila larval neuromuscular junction.

Fragile X-associated tremor/ataxia syndrome (FXTAS) is a late-onset neurodegenerative disease that develops in some premutation (PM) carriers of the FMR1 gene with alleles bearing 55-200 CGG repeats. The discovery of a broad spectrum of clinical and cell-developmental abnormalities among PM carriers with or without FXTAS and in model systems suggests that neurodegeneration seen in FXTAS could be the inevitable end-result of pathophysiological processes set during early development. Hence, it is imperative to trace early PM-induced pathological abnormalities.

Spermatozoa produced during winter are superior in terms of phenotypic characteristics and oviduct explants binding ability in the water buffalo (Bubalus bubalis).

Although reduced reproductive efficiency during summer has been well documented in buffaloes, the reason for the same is yet to be understood. The present study was conducted to identify the subtle differences in sperm phenotypic characteristics (motility, membrane integrity, acrosome reaction and lipid peroxidation status), oviduct binding ability and expression of fertility-associated genes (AK 1, ATP5D, CatSper 1, Cytochrome P450 aromatase, SPP1 and PEBP1) between winter and summer seasons in buffaloes. Cryopreserved spermatozoa from 6 Murrah buffalo bulls (3 ejaculates/bull/season) were utilized for the study.

Drosophila Mon1 and Rab7 interact to regulate glutamate receptor levels at the neuromuscular junction.

Regulation of post-synaptic receptors plays an important role in determining synaptic strength and plasticity. The Drosophila larval neuromuscular junction (nmj) has been used extensively as a model to understand some of these processes. In this context, we are interested in the role of Drosophila Monensin sensitivity protein 1 (DMon1) in regulating glutamate receptor (GluRIIA) levels at the nmj.

ELYS regulates Dorsal dynamics during development.

Embryonic large molecule derived from yolk sac (ELYS) is a constituent protein of nuclear pores. It initiates assembly of nuclear pore complexes into functional nuclear pores toward the end of mitosis. Using cellular, molecular, and genetic tools, including fluorescence and Electron microscopy, quantitative PCR, and RNAi-mediated depletion, we report here that the ELYS ortholog (Elys) plays critical roles during development.

A cell-permeant small molecule for the super-resolution imaging of the endoplasmic reticulum in live cells.

The endoplasmic reticulum (ER) constitutes about half of the total membrane of a eukaryotic cell, and defects in the ER have been shown to be linked with a variety of diseases. To investigate these underlying mechanisms in detail, the specific labelling of the ER for high-resolution long-term live-imaging can serve as an important tool. Here, we report the identification of a stimulated emission depletion (STED) microscopy-compatible BODIPY derivative (NH2-BODIPY) to selectively image the ER.

Drosophila Choline transporter non-canonically regulates pupal eclosion and NMJ integrity through a neuronal subset of mushroom body.

Insect mushroom bodies (MB) have an ensemble of synaptic connections well-studied for their role in experience-dependent learning and several higher cognitive functions. MB requires neurotransmission for an efficient flow of information across synapses with different flexibility to meet the demand of the dynamically changing environment of an insect. Neurotransmitter transporters coordinate appropriate changes for an efficient neurotransmission at the synapse.

Transcriptional abundance of type-1 endocannabinoid receptor (CB1) and fatty acid amide hydrolase (FAAH) in bull spermatozoa: Relationship with field fertility.

A highly sophisticated endogenous cannabinoid system (ECS) has been shown to play a crucial role in controlling sperm functions and fertility in men. In the present study, we report the differences in the expression level of components of ECS [type-1 endocannabinoid receptor (CB1) and fatty acid amide hydrolase (FAAH)] in spermatozoa from bulls with different field fertility ratings. Cryopreserved spermatozoa from crossbred cattle bulls (n = 40) were utilized for the study.

Selective Imaging of Lipids in Adipocytes by Using an Imidazolyl Derivative of Perylene Bisimide.

A small molecule, perylene bisimide imidazolyl derivative (PBI-ID), has been identified and developed as a specific marker for labelling multifunctional fat bodies in various organisms, including Drosophila and mammalian adipocytes. Interestingly, PBI-ID neither labels the plasma membranes nor cell nuclei by trapping into it. A remarkable feature of unbound PBI-ID is diminished fluorescence, which reduces the background emission noise, while contrasting the bound state effectively.

Incubation of spermatozoa with Anandamide prior to cryopreservation reduces cryocapacitation and improves post-thaw sperm quality in the water buffalo (Bubalus bubalis).

Anandamide (AEA), an endocannabinoid, has been shown to reduce capacitation and acrosomal exocytosis in human spermatozoa. Because buffalo spermatozoa are highly susceptible to cryopreservation induced damage, AEA was assessed as to whether it could protect spermatozoa from cryo-damage. Six ejaculates from six Murrah buffalo bulls (total 36 ejaculates) were utilized for the study.

Anandamide exerts a suppressive effect on sperm binding to oviduct explants through CB1 receptors in the water buffalo (Bubalus bubalis).

An endocannabinoid system comprising of Anandamide (AEA) and its receptor has been shown to play a role in sperm acquisition of fertilizing potential and sperm-oviduct interaction. In the present study, we assessed the effect of sperm pre-treatment with AEA or co-incubation of sperm-oviduct explants with AEA in the presence or absence of CB1 receptor antagonist (SR141716A) on sperm-oviduct binding in the water buffalo. Cryopreserved spermatozoa from 3 Murrah buffalo bulls (3 ejaculates from each bull) were utilized for the study.

RNAi-Mediated Reverse Genetic Screen Identified Chaperones Regulating Eye and Neuromuscular Junction Morphology.

Accumulation of toxic proteins in neurons has been linked with the onset of neurodegenerative diseases, which in many cases are characterized by altered neuronal function and synapse loss. Molecular chaperones help protein folding and the resolubilization of unfolded proteins, thereby reducing the protein aggregation stress. While most of the chaperones are expressed in neurons, their functional relevance remains largely unknown.