Selective Manipulation Research Articles

Pharmacological modulation of dopamine receptors reveals distinct brain-wide networks associated with learning and motivation in non-human primates.

D1 and D2 receptors are heavily implicated in cognitive and motivational processes, as well as in a number of psychiatric disorders. Despite this, little is known about how selective manipulation of these different receptors impacts cognition through changing activity across brain-wide intrinsic networks. Here, we examined the acute behavioral and brain-wide effects of D1 and D2 receptor-selective antagonists, SCH-23390 and haloperidol, in macaques performing a probabilistic learning task. SCH administration diminished, and haloperidol improved, animals' task performance. Mirroring these effects on behavior, SCH reduced, and haloperidol increased, the resting-state functional connectivity across brain-wide networks, most notably in the cortico-striatal areas. Thus, our results highlight the opposing effects of D1 and D2 receptor modulation on the brain and behavior.

Total Synthesis of Ryanodane Diterpenoids Garajonone and 3‐epi‐Garajonone

AbstractRyanodane diterpenes are structurally complex natural products that are well‐known for their high degree of oxidation and the challenges associated with synthesizing them within the terpene class. Herein, we present a two‐stage synthetic strategy that draws inspiration from the broad biosynthesis of terpenes, allowing us to achieve the first chemical synthesis of garajonone, a ryanodane diterpenoid that occurs naturally at low abundance, as well as its epimer, 3‐epi‐garajonone. The key to this success lies in the rapid construction of the carbon framework of the target molecule by employing an early‐stage palladium‐catalyzed Heck/carbonylative esterification cascade annulation, followed by successive late‐stage selective redox manipulation to establish the desired oxidation state of the molecule. This research not only showcases the synthesis of garajonone and its epimer but also provides a platform for the chemical synthesis of other members and analogs of this complex diterpenoid family.

Total Synthesis of Ryanodane Diterpenoids Garajonone and 3-epi-Garajonone.

Ryanodane diterpenes are structurally complex natural products that are well-known for their high degree of oxidation and the challenges associated with synthesizing them within the terpene class. Herein, we present a two-stage synthetic strategy that draws inspiration from the broad biosynthesis of terpenes, allowing us to achieve the first chemical synthesis of garajonone, a ryanodane diterpenoid that occurs naturally at low abundance, as well as its epimer, 3-epi-garajonone. The key to this success lies in the rapid construction of the carbon framework of the target molecule by employing an early-stage palladium-catalyzed Heck/carbonylative esterification cascade annulation, followed by successive late-stage selective redox manipulation to establish the desired oxidation state of the molecule. This research not only showcases the synthesis of garajonone and its epimer but also provides a platform for the chemical synthesis of other members and analogs of this complex diterpenoid family.

Movable surface acoustic wave tweezers: a versatile toolbox for micromanipulation

Surface acoustic wave (SAW) tweezers are a promising multifunctional micromanipulation method that controls microscale targets via patterned acoustic fields. Owing to their device structure and bonding process, most SAW tweezers have limitations in terms of controlling the position and motion of the acoustic traps, as they generate an acoustic field with a fixed region and adjust the manipulation effects via signal modulation. To address this challenge, we propose movable SAW tweezers with a multilayer structure, achieving dynamic control of their wave field and acoustic trap positions; we demonstrate their precise manipulation functions, such as translation, in-plane rotation, out-of-plane rotation, and cluster formation, on a wide spectrum of samples, including particles, bubbles, droplets, cells, and microorganisms. Our method not only improves the degree of freedom and working range of SAW tweezers but also allows for precise and selective manipulation of microtargets via microtools and localized wavefields. Owing to their flexibility, versatility, and biocompatibility, the movable SAW tweezers can be a practical platform for achieving arbitrary manipulation of microscale targets and have the potential to play significant roles in biomedical microrobotics.

Forging 1,1'-Bicyclopropenyls by Synergistic Au/Ag Dual-Catalyzed Cyclopropenyl Cross-Coupling.

1,1'-Bicyclopropenyl is a constitutional isomer of benzene comprising two coupled cyclopropene units with the endocyclic double bonds in conjugation. Due to the intrinsic high strain energy, it remains a long-standing challenge to prepare 1,1'-bicyclopropenyl derivatives, particularly multisubstituted, nonsymmetrical ones, in an efficient and modular manner. Herein a straightforward Au/Ag bimetallic-catalyzed cyclopropenyl cross-coupling has been developed, providing a robust and versatile strategy for the rapid assembly of symmetrical and unsymmetrical 1,1'-bicyclopropenyl derivatives from cyclopropenyl benziodoxoles (CpBXs) and terminal cyclopropenes. Advantages of this strategy include tolerance to a wide range of synthetically useful functional groups, mild reaction conditions, and a simple catalytic system. The obtained 1,1'-bicyclopropenyl derivatives were shown to be valuable synthetic intermediates through selective downstream manipulations.

Physicochemical and Structural Validation of Myxovirus Resistance 1 (Mx1) Protein of Three Strains of the Nigerian Indigenous (<i>Gallus Gallus domesticus</i>) and Exotic Chickens

This research was conducted on three strains of Nigerian Indigenous (<i>gallus gallus domesticus</i>) and Noiler (exotic) chickens. It examined the physicochemical and structural validation of Myxovirus resistance 1 (Mx1) protein on the three strains of Nigerian indigenous (naked neck, frizzle feather, normal feather) and noiler (exotic) chickens and also the prediction of the Physicochemical Analysis of protein. Nucleotide sequence were retrieved from National Center for Bio-Technology Information (NCBI) database and subjected to multiple sequence alignment, prediction of the physicochemical analysis of protein was done in the ProtParam web server. Modeling of 3D structural validation, Swiss modeling and Statistical analysis were all carried out. Software was used to align the sequences to find any Single Nucleotide Polymorphism (SNPS). The result of physicochemical analysis showed that the properties of the Mx1 protein fell within accepted threshold and predicted that the proteins were generally related. To validate the structure obtained from modeling, the obtained PDB files were ran on the Pro-check validation server and obtained Errat and Ramachandran plots. The study elucidates the unique features and potential functional implications of Mx1 protein across different strains of Nigerian indigenous and exotic chickens. This knowledge can inform the development of strategies to improve disease resistance in local chicken populations through selective breeding or genetic manipulation. Comparing the Mx1 protein among different strains of Nigerian indigenous chickens can reveal evolutionary adaptations and provide valuable information for understanding the molecular basis of immune defense mechanisms in poultry. Understanding the physicochemical properties and structural dynamics of Mx1 protein contributes to the broader understanding of innate immune responses in indigenous chicken breeds, offering insights into their disease resistance and adaptation mechanisms.

Separate mechanisms regulating accumbal taurine levels during baseline conditions and following ethanol exposure in the rat

Ethanol-induced dopamine release in the nucleus accumbens (nAc) is associated with reward and reinforcement, and for ethanol to elevate nAc dopamine levels, a simultaneous increase in endogenous taurine is required within the same brain region. By employing in vivo microdialysis in male Wistar rats combined with pharmacological, chemogenetic and metabolic approaches, our aim with this study was to identify mechanisms underlying ethanol-induced taurine release. Our results demonstrate that the taurine elevation, elicited by either systemic or local ethanol administration, occurs both in presence and absence of action potential firing or NMDA receptor blockade. Inhibition of volume regulated anion channels did not alter the ethanol-induced taurine levels, while inhibition of the taurine transporter occluded the ethanol-induced taurine increase, putatively due to a ceiling effect. Selective manipulation of nAc astrocytes using Gq-coupled designer receptors exclusively activated by designer drugs (DREADDs) did not affect ethanol-induced taurine release. However, activation of Gi-coupled DREADDs, or metabolic inhibition using fluorocitrate, rather enhanced than depressed taurine elevation. Finally, ethanol-induced taurine increase was fully blocked in rats pre-treated with the L-type Ca2+-channel blocker nicardipine, suggesting that the release is Ca2+ dependent. In conclusion, while astrocytes appear to be important regulators of basal taurine levels in the nAc, they do not appear to be the main cells underlying ethanol-induced taurine release.

Nickel‐Catalyzed α‐selective Hydroalkylation of Vinylarenes

AbstractC(sp3) centers adjacent to (hetero) aryl groups are widely present in physiologically active molecules. Metal‐hydride‐catalyzed hydroalkylation of alkenes represents an efficient means of forging C(sp3)−C(sp3) bonds, boasting advantages as a wide source of substrates, mild reaction conditions, and facile selectivity manipulation. Nevertheless, the hydroalkylation of vinylarenes encounters constraints in terms of substrate scope, necessitating the employment of activated alkyl halides or alkenes containing chelating groups, remains a challenge. In this context, we report a general nickel‐hydride‐catalyzed hydroalkylation protocol for vinylarenes. Remarkably, this system enables α‐selective hydroalkylation of both aryl and heteroaryl alkenes under an extra ligand‐free condition, demonstrating excellent coupling efficiency and selectivity. Furthermore, through the incorporation of chiral bisoxazoline ligands, we have achieved regio‐ and enantioselective hydroalkylation of vinylpyrroles, thereby facilitating the synthesis of α‐branched alkylated pyrrole derivatives.

Nickel-Catalyzed α-selective Hydroalkylation of Vinylarenes.

C(sp3) centers adjacent to (hetero) aryl groups are widely present in physiologically active molecules. Metal-hydride-catalyzed hydroalkylation of alkenes represents an efficient means of forging C(sp3)-C(sp3) bonds, boasting advantages as a wide source of substrates, mild reaction conditions, and facile selectivity manipulation. Nevertheless, the hydroalkylation of vinylarenes encounters constraints in terms of substrate scope, necessitating the employment of activated alkyl halides or alkenes containing chelating groups, remains a challenge. In this context, we report a general nickel-hydride-catalyzed hydroalkylation protocol for vinylarenes. Remarkably, this system enables α-selective hydroalkylation of both aryl and heteroaryl alkenes under an extra ligand-free condition, demonstrating excellent coupling efficiency and selectivity. Furthermore, through the incorporation of chiral bisoxazoline ligands, we have achieved regio- and enantioselective hydroalkylation of vinylpyrroles, thereby facilitating the synthesis of α-branched alkylated pyrrole derivatives.

The Moderating Effect of Monitoring on The Relationship Between Adverse Selection and Decision-Making Involving Escalation Situations: An Experimental Study

The streams of research on adverse selection and escalation of commitment are still inconclusive and limited by only manipulating adverse selection in 2 conditions, namely the presence and absence of adverse selection. Meanwhile, the literature shows that adverse selection will always exist in agency contracts even though the information asymmetry mechanism has been modified. This study considers adverse selection manipulation into two levels: high and low. This research investigates the moderating effect of supervision on the impact of adverse selection and commitment escalation. This research used an experimental method with a 2 x 2 factorial design between subjects. This study involved undergraduate accounting students as extension practitioners. The test results show that different levels of adverse selection impact levels of commitment escalation. The research also indicates that supervision is quite effective in filtering the impact of adverse selection on commitment escalation behavior

Genome-wide re-sequencing reveals regulatory genes and variants involved in the regulation of intermittent fertilization intensity in Wenchang chickens.

Intermittent fertilization intensity (IFI) is closely related to higher fertilization in chickens, but the genetic basis of IFI is not clearly understood. Here, we sampled a total of 939 Wenchang chickens with IFI. The IFI traits had negative correlation with the fertilization rate and exhibited huge phenotypic variations among individuals of the same strain. Based on SNPs derived from a subset of 499 whole genome data, a genome-wide association study with mixed linear model and further linkage disequilibrium analysis were performed to test potential associations between IFI traits and genomic variants. We identified 35 SNP variants and a 19.82 kb linkage disequilibrium block on chr8 significantly associated with IFI. This block is in the intron of LOC101750715, which shows significant homology with the human LMO4. Therefore, LOC101750715 and LMO4 may regulate IFI. The oviduct's immune regulation is crucial for fertilization. LMO4, activated by IL-6 and IL-23, promotes inflammation in epithelial cells. Thus, LOC101750715 and LMO4 may affect fertilization by regulating oviductal inflammation, impacting IFI. Our findings will provide targets for molecular-marker selection and genetic manipulation for lines of chickens with lower IFI.

Chemogenetic Tools and their Use in Studies of Neuropsychiatric Disorders.

Chemogenetics is a newly developed set of tools that allow for selective manipulation of cell activity. They consist of a receptor mutated irresponsive to endogenous ligands and a synthetic ligand that does not interact with the wild-type receptors. Many different types of these receptors and their respective ligands for inhibiting or excitating neuronal subpopulations were designed in the past few decades. It has been mainly the G-protein coupled receptors (GPCRs) selectively responding to clozapine-N-oxide (CNO), namely Designer Receptors Exclusively Activated by Designer Drugs (DREADDs), that have been employed in research. Chemogenetics offers great possibilities since the activity of the receptors is reversible, inducible on demand by the ligand, and non-invasive. Also, specific groups or types of neurons can be selectively manipulated thanks to the delivery by viral vectors. The effect of the chemogenetic receptors on neurons lasts longer, and even chronic activation can be achieved. That can be useful for behavioral testing. The great advantage of chemogenetic tools is especially apparent in research on brain diseases since they can manipulate whole neuronal circuits and connections between different brain areas. Many psychiatric or other brain diseases revolve around the dysfunction of specific brain networks. Therefore, chemogenetics presents a powerful tool for investigating the underlying mechanisms causing the disease and revealing the link between the circuit dysfunction and the behavioral or cognitive symptoms observed in patients. It could also contribute to the development of more effective treatments.

Neural circuit-selective, multiplexed pharmacological targeting of prefrontal cortex-projecting locus coeruleus neurons drives antinociception.

Selective manipulation of neural circuits using optogenetics and chemogenetics holds great translational potential but requires genetic access to neurons. Here, we demonstrate a general framework for identifying genetic tool-independent, pharmacological strategies for neural circuit-selective modulation. We developed an economically accessible calcium imaging-based approach for large-scale pharmacological scans of endogenous receptor-mediated neural activity. As a testbed for this approach, we used the mouse locus coeruleus due to the combination of its widespread, modular efferent neural circuitry and its wide variety of endogenously expressed GPCRs. Using machine learning-based action potential deconvolution and retrograde tracing, we identified an agonist cocktail that selectively inhibits medial prefrontal cortex-projecting locus coeruleus neurons. In vivo , this cocktail produces synergistic antinociception, consistent with selective pharmacological blunting of this neural circuit. This framework has broad utility for selective targeting of other neural circuits under different physiological and pathological states, facilitating non-genetic translational applications arising from cell type-selective discoveries.

Recent Advances in Dielectrophoretic Manipulation and Separation of Microparticles and Biological Cells.

Dielectrophoresis (DEP) is an advanced microfluidic manipulation technique that is based on the interaction of polarized particles with the spatial gradient of a non-uniform electric field to achieve non-contact and highly selective manipulation of particles. In recent years, DEP has made remarkable progress in the field of microfluidics, and it has gradually transitioned from laboratory-scale research to high-throughput manipulation in practical applications. This paper reviews the recent advances in dielectric manipulation and separation of microparticles and biological cells and discusses in detail the design of chip structures for the two main methods, direct current dielectrophoresis (DC-DEP) and alternating current dielectrophoresis (AC-DEP). The working principles, technical implementation details, and other improved designs of electrode-based and insulator-based chips are summarized. Functional customization of DEP systems with specific capabilities, including separation, capture, purification, aggregation, and assembly of particles and cells, is then performed. The aim of this paper is to provide new ideas for the design of novel DEP micro/nano platforms with the desired high throughput for further development in practical applications.

Lying to Speak the Truth: Selective Manipulation and Improved Information Transmission

ABSTRACTWe analyze a principal‐agent model in which an effort‐averse agent can manipulate a publicly observable performance report. The principal cannot observe the agent's cost of effort, her effort choice, and whether she manipulated the report. An optimal contract links compensation to the realized output and the (possibly manipulated) report. Manipulation can be beneficial to the principal because it can make the report more informative about the agent's effort choice, thereby reducing the agent's information rent. This is achieved through a contract that incentivizes the agent to selectively engage in manipulation based on her effort choice.

Tuning optical excitations of graphene quantum dots through selective nitrogen doping

Our research has revealed that the nitrogen doping configuration has a significant impact on the absorption properties and band gap of nitrogen doped graphene quantum dots (NGQDs). By analyzing the composition and character of optical transitions, we have observed that nitrogen doping causes a redistribution of oscillator strength between significant peaks and the emergence of new optical features. These changes lead to broken molecular orbital degeneracies, optical peak splitting, and activation of dark states in the visible to near-infrared (NIR) region. These findings shed light on the mechanisms that govern alterations in the spectral properties of NGQDs within the visible and near-infra red (NIR) absorption bands. Furthermore, selective manipulation of optoelectronic properties via distinct N-doping patterns could pave the way for the development of novel optoelectronic nanodevices and functional materials.

Tunable Photonic Hook Design Based on Anisotropic Cutting Liquid Crystal Microcylinder

The selective control and manipulation of nanoparticles require developing and researching new methods for designing optical tweeters, mainly based on a photonic hooks (PHs) effect. This paper first proposes a tunable PH in which a structured beam illuminates an anisotropic cutting liquid crystal microcylinder based on the Finite-DifferenceTime-Domain (FDTD) method. The PHs generated by plane wave, Gaussian, and Bessel beam are analyzed and compared. The impact of beams and LC particle parameters on the PHs are discussed. Where the influence of the extraordinary refractive index (ne) on PHs is emphasized. Our results reveal that introducing birefringence can change the bending direction of PH. Besides, the maximum intensity of the PHs increases as ne increases regardless of the beam type. The PH generated by a plane wave has a higher maximum intensity and smaller FWHM than that generated by the Gaussian and Bessel beams. The smallest FWHM and maximum intensity of the PHs generated by the Gaussian falls between that generated by the plane wave and the Bessel beam. The PH generated by a Bessel beam has the minor maximum intensity and the largest FWHM. Still, it exceeds the diffraction limit and exhibits bending twice due to its self-recovery property. This paper provides a new way to modulate PH. This work offers novel theoretical models and the degree of freedom for the design of PHs, which is beneficial for the selective manipulation of nanoparticles. It has promising applications in Mesotronics and biomedicine.

Maternal manipulation of offspring size can trigger the evolution of eusociality in promiscuous species

Eusocial organisms typically live in colonies with one reproductive queen supported by thousands of sterile workers. It is widely believed that monogamous mating is a precondition for the evolution of eusociality. Here, we present a theoretical model that simulates a realistic scenario for the evolution of eusociality. In the model, mothers can evolve control over resource allocation to offspring, affecting offspring's body size. The offspring can evolve body-size-dependent dispersal, by which they disperse to breed or stay at the nest as helpers. We demonstrate that eusociality can evolve even if mothers are not strictly monogamous, provided that they can constrain their offspring's reproduction through manipulation. We also observe the evolution of social polymorphism with small individuals that help and larger individuals that disperse to breed. Our model unifies the traditional kin selection and maternal manipulation explanations for the evolution of eusociality and demonstrates that-contrary to current consensus belief-eusociality can evolve despite highly promiscuous mating.

Numerical and experimental demonstrations of optical trapping and manipulation of a selective red blood cell using a photonic hook based on broken symmetry tapered fiber probe

Optical tweezers and trapping technologies have a crucial impact on scientific research by precisely manipulating mesoscale objects at wavelength scales. The development of simple fiber-based optical tweezers foreseeing sorting and manipulation of a single cell has been firstly encouraged by biomedical requirements. The ability to manipulate mesoscale objects with high flexibility and precision is essential for a wide class of different fields. The ability to precisely arrange cells into desired structures is important for numerous biomedical and physical applications. This study experimentally reports for the first time a simple and low-cost strategy to produce an optical fiber-based photonic hook for achieving new unprecedented functionalities to selective particle manipulation in a lab-on-tip platform. We show perspectives opened by combining the fields of structured light in the form of the photonic hook and optical manipulation method. This enables new applications for optical trapping setups based on structured fields in the form of the photonic hook produced by an optical fiber tip with broken symmetry, where it becomes possible to manipulate and sort cells selectively.

Multi-organ transcriptomic profiles and gene-regulation network underlying vibriosis resistance in tongue sole

Vibrio spp. are major pathogens responsible for mortality and disease in various marine aquaculture organisms. Effective disease control and genetic breeding strategies rely heavily on understanding host vibriosis resistance mechanisms. The Chinese tongue sole (Cynoglossus semilaevis) is economically vital but suffers from substantial mortalities due to vibriosis. Through continuous selective breeding, we have successfully obtained vibriosis-resistant families of this species. In this study, we conducted RNA-seq analysis on three organs, including liver, spleen and intestine from selected resistant and susceptible tongue soles. Additionally, we integrated these data with our previously published RNA-seq datasets of skin and gill, enabling the construction of organ-specific transcriptional profiles and a comprehensive gene co-expression network elucidating the differences in vibriosis resistance. Furthermore, we identified 12 modules with organ-specific functional implications. Overall, our findings provide a valuable resource for investigating the molecular basis of vibriosis resistance in fish, offering insights into target genes and pathways essential for molecular selection and genetic manipulation to enhance vibriosis resistance in fish breeding programs.