Hessellundclemmensen4288

To identify novel D3 dopamine receptor (D3R) agonists, we conducted a high-throughput screen using a β-arrestin recruitment assay. Counterscreening of the hit compounds provided an assessment of their selectivity, efficacy, and potency. The most promising scaffold was optimized through medicinal chemistry resulting in enhanced potency and selectivity. The optimized compound, ML417 (20), potently promotes D3R-mediated β-arrestin translocation, G protein activation, and ERK1/2 phosphorylation (pERK) while lacking activity at other dopamine receptors. Screening of ML417 against multiple G protein-coupled receptors revealed exceptional global selectivity. Molecular modeling suggests that ML417 interacts with the D3R in a unique manner, possibly explaining its remarkable selectivity. ML417 was also found to protect against neurodegeneration of dopaminergic neurons derived from iPSCs. Together with promising pharmacokinetics and toxicology profiles, these results suggest that ML417 is a novel and uniquely selective D3R agonist that may serve as both a research tool and a therapeutic lead for the treatment of neuropsychiatric disorders.To mimic the tactile sensing properties of the human skin, signals from tactile sensors need to be processed in an efficient manner. The integration of the tactile sensor with a neuromorphic device can potentially address this issue, as the neuromorphic device has both signal processing and memory capability through which parallel and efficient processing of information is possible. In this article, an intelligent haptic perception device (IHPD) is presented that combines pressure sensing with an organic electrochemical transistor-based synaptic device into a simple device architecture. More importantly, the IHPD is capable of rapid and reversible switching between short-term plasticity (STP) and long-term plasticity (LTP) operation through which accelerated learning, processing of new information, and distinctive operation of STP and LTP are possible. Various types of pressure information such as magnitude, rate, and duration were processed utilizing STP by which error-tolerant perception was demonstrated. Meanwhile, memorization and learning of pressure through a stepwise change in a conductive state was demonstrated using LTP. These demonstrations present unique approaches to process and learn tactile information, which can potentially be utilized in various electronic skin applications in the future.The novel sulfonate-carboxylate ligand of 5,7-disulfonate-1,4-naphthalenedicarboxylic acid (H4-DSNPDC) was synthesized, and its series of lanthanide compounds [Ln3(μ2-OH)(DSNPDC)2(H2O)x]·yH2On (JXNU-7; Ln = La3+, x = 10. y = 4; Ln = Nd3+, Sm3+ Eu3+, x = 9, y = 2) and [Ln4(μ3-OH)4(DSNPDC)2(H2O)11]·28H2On (JXNU-8; Ln = Eu3+, Gd3+) are presented. JXNU-7 is a three-dimensional structure based on linear trinuclear Ln3 building units, while JXNU-8 has a two-dimensional layer constructed from tetranuclear Ln4(μ3-OH)4 building units. The representative Eu compounds of JXNU-7 and -8 show good proton conductive properties under high humidity. The hydrophilic sulfonate groups pointing to the pores and the water molecules included in the pores mainly contribute to the high proton conductivity for the materials. The presence of one-dimensional infinite hydrogen-bonded networks in channels of JXNU-7(Eu) facilitates a fast and efficient proton transfer, resulting in higher proton conductivity in comparison to that of JXNU-8(Eu). Additionally, JXNU-7(Eu) with a characteristic red emission exhibits a promising potential for selective sensing of Fe3+ ions in aqueous solution. Our work demonstrates the integration of functional organic components (sulfonate groups) and inorganic components (lanthanide centers) in MOFs for the successful preparation of multifunctional MOF materials.Biofouling is a worldwide problem from healthcare to marine exploration. Aggressive biofouling, wear, and corrosion lead to severe deterioration in function and durability. Here, micro- and nanostructured hierarchical diamond films mimicking the morphology of plant leaves were developed to simultaneously achieve superhydrophobicity, antibacterial efficacy, and marine antibiofouling, combined with mechanical and chemical robustness. These coatings were designed and successfully constructed on various commercial substrates, such as titanium alloys, silicon, and quartz glass via a chemical vapor deposition process. The unique surface structure of diamond films reduced bacteria attachment by 90-99%. In the marine environment, these biomimetic diamond films significantly reduced more than 95% adhesion of green algae. The structured diamond films retained mechanical robustness, superhydrophobicity, and antibacterial efficacy under high abrasion and corrosive conditions, exhibiting at least 20 times enhanced wear resistance than the bare commercial substrates even after long-term immersion in seawater.Two species of the genus Pungentus, one new and one known, collected in natural vegetation and cultivated soils in northwest of Iran, are studied. Pungentus sufiyanensis n. sp. is characterized by its 1.22 to 1.57 mm long body, offset lip region by a constriction and 7 to 9 μm broad, 18 to 21 μm long odontostyle, 304 to 348 μm long neck, 133 to 161 μm long esophageal expansion, mono-opisthodelphic female genital system without anterior uterine sac, slightly backward directed vagina, absence of pars refringens vaginae, V = 47-54, rounded-conoid caudal region (17.5-23 μm, c = 65-84, c´ = 0.7-1) with saccate bodies, and the absence of male. Molecular analysis, based on D2-D3 expansion segments of the 28S rDNA (LSU), confirms the monophyly of the family Nordiidae and suggests the monophyly of the genus Pungentus, with the new species forming a clade with other Iranian species. New data are presented for six Iranian populations of P. engadinensis, and an updated key for the identification of Pungentus species is also provided.Two cultured populations of Acrobeloides saeedi are described from India. TTK21 cost Morphologically and morphometrically this material agrees with other species of the Maximus-group (A. bodenheimeri, A. longiuterus, and A. maximus), especially with A. longiuterus. However, molecular studies based on 18 S, 28 S and ITS rDNA confirmed the Indian material is well differentiated from all of these species. According to this, A. saeedi is considered a valid taxon distinguished mainly from A. bodenheimeri by having dextral female reproductive system (vs sinistral), from A. longiuterus by having larger females (1.03-1.57 vs 0.57-0.88 mm) and from A. maximus by having seta-like labial processes (vs absent) and males as frequent as females (vs males very infrequent). Molecular and phylogenetic studies revealed the present specimens to be conspecific to undescribed Acrobeloides sp. population from Iran, and hence, both regarded to be conspecific to each other. In addition, other similar species are revised Acrobeloides ishraqi is considered new junior synonym of A.