Deficiency of FRMD5 results in neurodevelopmental dysfunction and autistic-like behavior in mice.

The pathophysiology of autism spectrum disorders (ASDs) is causally linked to postsynaptic scaffolding proteins, as evidenced by numerous large-scale genomic studies [1, 2] and in vitro and in vivo neurobiological studies of mutations in animal models [3, 4]. However, due to the distinct phenotypic and genetic heterogeneity observed in ASD patients, individual mutation genes account for only a small proportion (<2%) of cases [1, 5]. Recently, a human genetic study revealed a correlation between de novo variants in FERM domain-containing-5 (FRMD5) and neurodevelopmental abnormalities [6]. In this study, we demonstrate that deficiency of the scaffolding protein FRMD5 leads to neurodevelopmental dysfunction and ASD-like behavior in mice. FRMD5 deficiency results in morphological abnormalities in neurons and synaptic dysfunction in mice. Frmd5-deficient mice display learning and memory dysfunction, impaired social function, and increased repetitive stereotyped behavior. Mechanistically, tandem mass tag (TMT)-labeled quantitative proteomics revealed that FRMD5 deletion affects the distribution of synaptic proteins involved in the pathological process of ASD. Collectively, our findings delineate the critical role of FRMD5 in neurodevelopment and ASD pathophysiology, suggesting potential therapeutic implications for the treatment of ASD.

Room-Temperature Ferromagnetism in Epitaxial Bilayer FeSb/SrTiO3(001) Terminated with a Kagome Lattice.

Two-dimensional (2D) magnets exhibit unique physical properties for potential applications in spintronics. To date, most 2D ferromagnets are obtained by mechanical exfoliation of bulk materials with van der Waals interlayer interactions, and the synthesis of single- or few-layer 2D ferromagnets with strong interlayer coupling remains experimentally challenging. Here, we report the epitaxial growth of 2D non-van der Waals ferromagnetic bilayer FeSb on SrTiO3(001) substrates stabilized by strong coupling to the substrate, which exhibits in-plane magnetic anisotropy and a Curie temperature above 390 K. In situ low-temperature scanning tunneling microscopy/spectroscopy and density-functional theory calculations further reveal that an Fe Kagome layer terminates the bilayer FeSb. Our results open a new avenue for further exploring emergent quantum phenomena from the interplay of ferromagnetism and topology for application in spintronics.

Excitatory neurons in the lateral parabrachial nucleus mediate the interruptive effect of inflammatory pain on a sustained attention task.

BACKGROUND: Attentional deficits are among the most common pain-induced cognitive disorders. Pain disrupts attention and may excessively occupy attentional resources in pathological states, leading to daily function impairment and increased disability. However, the neural circuit mechanisms by which pain disrupts attention are incompletely understood. METHODS: We used a three-choice serial reaction time task (3CSRTT) to construct a sustained-attention task model in male C57BL/6J mice. Formalin or complete Freund's adjuvant was injected into a paw to establish an inflammatory pain model. We measured changes in 3CSRTT performance in the two inflammatory pain models, and investigated the neural circuit mechanisms of pain-induced attentional deficits. RESULTS: Acute inflammatory pain impaired 3CSRTT performance, while chronic inflammatory pain had no effect. Either inhibition of the ascending pain pathway by blockade of the conduction of nociceptive signals in the sciatic nerve using the local anesthetic lidocaine or chemogenetic inhibition of Ca2+/calmodulin-dependent protein kinase IIα (CaMKIIα) neurons in the lateral parabrachial nucleus (LPBN) attenuated the acute inflammatory pain-induced impairment of 3CSRTT performance, while chemogenetic activation of CaMKIIα neurons in the LPBN disrupted the 3CSRTT. Furthermore, the activity of CaMKIIα neurons in the LPBN was significantly lower on Day 2 after complete Freund's adjuvant injection than on the day of injection, which correlated with the recovery of 3CSRTT performance during chronic inflammatory pain. CONCLUSIONS: Activation of excitatory neurons in the LPBN is a mechanism by which acute inflammatory pain disrupts sustained attention. This finding has implications for the treatment of pain and its cognitive comorbidities.

Pilot investigation on biostability of drinking water distribution systems under water source switching.

Water quality deterioration of drinking water distribution systems (DWDSs) caused by water source switching has been reported previously. However, systematic investigation of the biostability of DWDS under water source switching is limited. Aged pipes, including three commonly used pipe materials dug out from a practical DWDS, were used to systematically investigate the biofilm stability mechanism of DWDS under water source switching to quality-improved water. An increase in adenosine triphosphate (ATP) concentration in the bulk water during the initial stage of the switching period was observed, indicating the risk of biofilm release through aged pipe surfaces after water source switching. Sloughing of biofilms might contribute to temporary instability. From day 35, the ATP concentration in the polyethylene (PE) and plastic stainless steel composite (PS) pipes were maintained at approximately 2.40 and 2.56 ng/L, respectively. In contrast, the ATP concentration in the ductile iron (DI) pipes was higher, at approximately 3.43 ng/L from day 42. The water quality variation could cause areas of the biofilm to slough and reduce the biomass of biofilm, causing partial alteration of the microbial community. 16S rRNA gene amplicon sequencing-based functional prediction revealed that the biofilm could increase the abundance of chlorine-resistant bacteria attributed to the increase in Pseudomonas and Methylobacterium after switching to quality-improved water. Moreover, the profiles of specific pathways linked to human diseases, antibiotic resistance, and antibiotic biosynthesis revealed that the safety of the biofilm could improve after switching to quality-improved water. KEY POINTS: • The PE and PS biofilm showed improved resistance to water quality perturbation. • Greater number of Methylobacterium was found in the biofilm after water source switching. • 3.16S gene-based metagenomics prediction revealed that the safety of the biofilm under water source switching.

Giant Third-Harmonic Optical Generation from Topological Insulator Heterostructures.

The downscaling of nonlinear optical devices is significantly hindered by the inherently weak nonlinearity in regular materials. Here, we report a giant third-harmonic generation discovered in epitaxial thin films of V-VI chalcogenide topological insulators. Using a tailored substrate and capping layer, a single reflection from a 13 nm film can produce a nonlinear conversion efficiency of nearly 0.01%, a performance that rivals micron-scale waveguides made from conventional materials or metasurfaces with far more complex structures. Such strong nonlinear optical emission, absent from the topologically trivial member in the same compound family, is found to be generated by the same bulk band characteristics that are responsible for producing the band inversion and the nontrivial topological ordering. This finding reveals the possibility of obtaining superior optical nonlinearity by examining the large pool of newly discovered topological materials with similar band characteristics.

Human-Robot Perception in Industrial Environments: A Survey.

Perception capability assumes significant importance for human-robot interaction. The forthcoming industrial environments will require a high level of automation to be flexible and adaptive enough to comply with the increasingly faster and low-cost market demands. Autonomous and collaborative robots able to adapt to varying and dynamic conditions of the environment, including the presence of human beings, will have an ever-greater role in this context. However, if the robot is not aware of the human position and intention, a shared workspace between robots and humans may decrease productivity and lead to human safety issues. This paper presents a survey on sensory equipment useful for human detection and action recognition in industrial environments. An overview of different sensors and perception techniques is presented. Various types of robotic systems commonly used in industry, such as fixed-base manipulators, collaborative robots, mobile robots and mobile manipulators, are considered, analyzing the most useful sensors and methods to perceive and react to the presence of human operators in industrial cooperative and collaborative applications. The paper also introduces two proofs of concept, developed by the authors for future collaborative robotic applications that benefit from enhanced capabilities of human perception and interaction. The first one concerns fixed-base collaborative robots, and proposes a solution for human safety in tasks requiring human collision avoidance or moving obstacles detection. The second one proposes a collaborative behavior implementable upon autonomous mobile robots, pursuing assigned tasks within an industrial space shared with human operators.

Rewritable Nanoplasmonics through Room-Temperature Phase Manipulations of Vanadium Dioxide.

The interactions between light and plasmonic charge oscillations in conducting materials are important venues for realizing nanoscale light manipulations. Conventional metal-based plasmonic devices lack tunability due to the fixed material permittivities. Here, we show that reconfigurable plasmonic functionalities can be achieved using the spatially controlled phase transitions in strongly correlated oxide films. The experimental results discussed here are enabled by a recently developed scanning probe-based technique that allows a nonvolatile, monoclinic-metal VO2 phase to be reversibly patterned at the nanoscale in ambient conditions. Using this technique, rewritable waveguides, spatially modulated plasmonic resonators, and reconfigurable wire-grid polarizers are successfully demonstrated. These structures, effectively controlling infrared lights through spatially confined mobile carriers, showcase a great potential for building programmable nanoplasmonic devices on correlated oxide platforms.

Algae-induced taste and odour problems at low temperatures and the cold stress response hypothesis.

The existence of taste and odour (T&O) in drinking water is one of the principal causes of consumer complaints and is commonly related to algae growth. Numerous studies have confirmed the existence of algal blooms emerging specifically in low-temperature periods, herein referred to as "cold algae"; these include chrysophytes, cryptophytes, dinoflagellates and diatoms. In addition, the adaption mechanisms of these "cold algae" involve high flexibility in their nutrient intake and to the hydrological characteristics of the waters and their high contents of intracellular polyunsaturated fatty acids (PUFAs). Like algae proliferating in higher temperature waters, cold algae can also produce offensive odours. The potential dominant T&O compounds of low-temperature algae probably include saturated/unsaturated aldehydes and even some terpenoids. Among these, the polyunsaturated aldehydes (PUAs), the derivatives of polyunsaturated fatty acids, are the dominant T&O compounds and are probably synthesized during cell rupture. It was found that, for cold algae, low temperature may have a favourable effect on the generation of algae-induced T&O compounds. Furthermore, to better understand the internal mechanisms of algal T&O production, the stress response theory is introduced, which provides ideas for T&O control in raw water and in water treatment. Finally, implications for T&O management are given based on this review. KEY POINTS: • Like algae proliferating in higher temperature waters, cold algae can produce offensive odours. • Low temperatures may have a favourable effect on the generation of algae-induced T&O compounds. • The stress response theory can help to better understand the internal mechanisms of algal T&O production.

PLD1 promotes dendritic spine morphogenesis via activating PKD1.

Dendritic spines on the dendrites of pyramidal neurons are one of the most important components for excitatory synapses, where excitatory information exchanges and integrates. The defects of dendritic spine development have been closely connected with many nervous system diseases including autism, intellectual disability and so forth. Based on our previous studies, we here report a new functional signaling link between phospholipase D1 (PLD1) and protein kinase D1 (PKD1) in dendritic spine morphogenesis. Coimmunoprecipitation assays showed that PLD1 associates with PKD1. A series of knocking down and rescuing experiments demonstrated that PLD1 acts upstream of PKD1 in positively regulating dendritic spine morphogenesis. Using PLD1 inhibitor, we found that PLD1 activates PKD1 to promote dendritic spine morphogenesis. Thus, we further reveal the roles of the two different enzymes in neuronal development.

Large and Reconfigurable Infrared Photothermoelectric Effect at Oxide Interfaces.

To maximize the photovoltaic efficiency, it is highly desirable to enable the electricity conversion from low energy photons and to extract the excessive energy from hot carriers. Here we report a large photovoltage generation at the LaAlO3/SrTiO3 interfaces from infrared photons with energies far below the oxide bandgaps. This effect is a result of the photoexcitation of hot carriers in metasurface electrical contacts and the subsequent thermoelectric charge separations by the interfacial two-dimensional electron gas (2DEG). Reaching a room-temperature responsivity of 4.4 V/W, such light-to-charge conversion can be spatially controlled and reconfigured through the patterning of 2DEG using conducting atomic force microscope. Compatible for broadband applications, our results demonstrate a new path toward efficient and programmable light sensing using oxide-based low-dimensional electron systems.

PKD1 Promotes Functional Synapse Formation Coordinated with N-Cadherin in Hippocampus.

Functional synapse formation is critical for the wiring of neural circuits in the developing brain. The cell adhesion molecule N-cadherin plays important roles in target recognition and synaptogenesis. However, the molecular mechanisms that regulate the localization of N-cadherin and the subsequent effects remain poorly understood. Here, we show that protein kinase D1 (PKD1) directly binds to N-cadherin at amino acid residues 836-871 and phosphorylates it at Ser 869, 871, and 872, thereby increasing the surface localization of N-cadherin and promoting functional synapse formation in primary cultured hippocampal neurons obtained from embryonic day 18 rat embryos of either sex. Intriguingly, neuronal activity enhances the interactions between N-cadherin and PKD1, which are critical for the activity-dependent growth of dendritic spines. Accordingly, either disruption the binding between N-cadherin and PKD1 or preventing the phosphorylation of N-cadherin by PKD1 in the hippocampal CA1 region of male rat leads to the reduction in synapse number and impairment of LTP. Together, this study demonstrates a novel mechanism of PKD1 regulating the surface localization of N-cadherin and suggests that the PKD1-N-cadherin interaction is critical for synapse formation and function.SIGNIFICANCE STATEMENT Defects in synapse formation and function lead to various neurological diseases, although the mechanisms underlying the regulation of synapse development are far from clear. Our results suggest that protein kinase D1 (PKD1) functions upstream of N-cadherin, a classical synaptic adhesion molecule, to promote functional synapse formation. Notably, we identified a crucial binding fragment to PKD1 at C terminus of N-cadherin, and this fragment also contains PKD1 phosphorylation sites. Through this interaction, PKD1 enhances the stability of N-cadherin on cell membrane and promotes synapse morphogenesis and synaptic plasticity in an activity-dependent manner. Our study reveals the role of PKD1 and the potential downstream mechanism in synapse development, and contributes to the research for neurodevelopment and the therapy for neurological diseases.

Tailoring the Doping Mechanisms at Oxide Interfaces in Nanoscale.

Here, we demonstrate the nanoscale manipulations of two types of charge transfer to the LaAlO3/SrTiO3 interfaces: one from surface adsorbates and another from oxygen vacancies inside LaAlO3 films. This method can be used to produce multiple insulating and metallic interface states with distinct carrier properties that are highly stable in air. By reconfiguring the patterning and comparing interface structures formed from different doping sources, effects of extrinsic and intrinsic material characters on the transport properties can be distinguished. In particular, a multisubband to single-subband transition controlled by the structural phases in SrTiO3 was revealed. In addition, the transient behaviors of nanostructures also provided a unique opportunity to study the nanoscale diffusions of adsorbates and oxygen vacancies in oxide heterostructures. Knowledge of such dynamic processes is important for nanodevice implementations.

Tailoring LaAlO3/SrTiO3 Interface Metallicity by Oxygen Surface Adsorbates.

We report an oxygen surface adsorbates induced metal-insulator transition at the LaAlO3/SrTiO3 interfaces. The observed effects were attributed to the terminations of surface Al sites and the resultant electron-accepting surface states. By controlling the local oxygen adsorptions, we successfully demonstrated the nondestructive patterning of the interface two-dimensional electron gas (2DEG). The obtained 2DEG structures are stable in air and also robust against general solvent treatments. This study provides new insights into the metal-insulator transition mechanism at the complex oxide interfaces and also a highly efficient technique for tailoring the interface properties.

Oxide-based platform for reconfigurable superconducting nanoelectronics.

We report quasi-1D superconductivity at the interface of LaAlO3 and SrTiO3. The material system and nanostructure fabrication method supply a new platform for superconducting nanoelectronics. Nanostructures having line widths w ~ 10 nm are formed from the parent two-dimensional electron liquid using conductive atomic force microscope lithography. Nanowire cross-sections are small compared to the superconducting coherence length in LaAlO3/SrTiO3, placing them in the quasi-1D regime. Broad superconducting transitions versus temperature and finite resistances in the superconducting state well below Tc ≈ 200 mK are observed, suggesting the presence of fluctuation- and heating-induced resistance. The superconducting resistances and V-I characteristics are tunable through the use of a back gate. Four-terminal resistances in the superconducting state show an unusual dependence on the current path, varying by as much as an order of magnitude. This new technology, i.e., the ability to 'write' gate-tunable superconducting nanostructures on an insulating LaAlO3/SrTiO3 'canvas', opens possibilities for the development of new families of reconfigurable superconducting nanoelectronics.

Decoding algae under abnormal temperature variability with odorant as a responsive indicator.

Harmful algal blooms impair the aesthetic quality and healthy performance of in-situ water. Worse yet, dramatic temperature variability arises additional difficulty in algal-induced risk assessment, which is so far poorly explored. Microcystis aeruginosa (FACHB 905), was selected to explore the odor-producing pattern (ß-cyclocitral, the major odorant of the test alga) under several temperature-varying scenarios. Significant differences were observed in total ß-cyclocitral yield between these scenarios, e.g., a rapid yield response as a result of acute temperature variation. Yield response was not only dependent on absolute temperature, but influenced by temperature variability stress. Acute increase (AI) or sequential increase (SI) in temperature caused extra production response, while the opposite was observed in groups with acute decrease (AD) and sequential decrease (SD) in temperature. Cell growth in AD group showed severe inhibition, with the specific growth rates fluctuating around half of that in 16-control. Whereas, SD could relieve such detrimental growth effects. Cell quota of ß-cyclocitral yield was sensitive to temperature variation, with notable increase in AI and SI. Further, peaks in cell quota for SI group (79.3 %) were higher than for AI group (57.9 %). Cell quota variations in temperature-varying conditions contributed to the total yield response (R2 = 0.566-0.980) more than cell intensity variations (R2 = 0.0397-0.548). Further, it was also found that the internal mechanism by reactive oxygen species and pigments varied in various thermal scenarios. Overall, it was demonstrated that more than absolute value differences, temperature varying patterns across time influence algal behavior and related hazards, which should be noted in resource water quality management.

Exploring the ignored role of escaped algae in a pilot-scale DWDS: Disinfectant consumption, DBP yield and risk formation.

Insufficient treatments during bloom-forming seasons allow algae to enter the subsequent drinking water distribution system (DWDS). Yet, scarce information is available regarding the role escaped algae to play in the DWDS, and how they interact with the system. Thus, three scenarios were conducted: a pilot DWDS with algae (a), pipe water (b), and pipe water with algae (c). Experimental results showed that, compared to biofilm and bulk water, escaped algae required fewer disinfectants. Competition for disinfectants varied with algal strains (Microcystis aeruginosa, MA; Pseudanabaena sp., PS) and disinfectant types (chlorine, Cl2; chloriamine, NH2Cl). Algae in the MA-Cl2 group showed the highest demand (6.25%-36.02%). However, the low-concentration disinfectants distributed to algae could trigger distinct algal status alternations. Cl2 diffused into intact MA cells and reacted with intracellular compositions. Damaged PS cells reached 100% within 2 h. Typical disinfection byproducts (DBPs), including trihalomethanes (THMs), haloacetic acids and halogenated acetonitriles were examined. Disinfectant types and algal strains affected DBP yield and distribution. Although disinfectants consumed by algae might not promote dissolved DBP formation, especially for THMs. DBP formation of the other components was affected by escaped algae via changing disinfectant assignment (reduced by 45.45% for MA-Cl2) and transformation efficiency (by 34.52%). The cytotoxicity risks were estimated. Dissolved DBP-induced risks were not added when escaped algae occurred, whereas disruption and release of intracellular substances increased risks; the maximum cytotoxicity did not occur at 12 h rather than at the end (24 h). Overall, this study provided an innovative perspective on algal-related water quality issues in water systems.

Phosphorylation-dependent positive feedback on the oxytocin receptor through the kinase PKD1 contributes to long-term social memory.

Social memory enables one to recognize and distinguish specific individuals. It is fundamental to social behaviors that can be mediated by the oxytocin receptor (OXTR), such as forming relationships. We investigated the molecular regulation and function of OXTR in animal behavior involving social memory. We found that Ser261 in OXTR was phosphorylated by protein kinase D1 (PKD1). Neuronal Ca2+ signaling and behavior analyses revealed that rats expressing a mutated form of OXTR that cannot be phosphorylated at this residue (OXTR S261A) in the medial amygdala (MeA) exhibited impaired long-term social memory (LTSM). Blocking the phosphorylation of wild-type OXTR in the MeA using an interfering peptide in rats or through conditional knockout of Pkd1 in mice reduced social memory retention, whereas expression of a phosphomimetic mutant of OXTR rescued it. In HEK293A cells, the PKD1-mediated phosphorylation of OXTR promoted its binding to Gq protein and, in turn, OXTR-mediated phosphorylation of PKD1, indicating a positive feedback loop. In addition, OXTR with a single-nucleotide polymorphism found in humans (rs200362197), which has a mutation in the conserved recognition region in the PKD1 phosphorylation site, showed impaired activation and signaling in vitro and in HEK293A cells similar to that of the S216A mutant. Our findings describe a phosphoregulatory loop for OXTR and its critical role in social behavior that might be further explored in associated disorders.

Joint majorization of waterworks and secondary chlorination points considering the chloric odor and economic investment in the DWDS using machine learning and optimization algorithms.

The traditional methods of increasing the chlorine disinfectant dosage in the drinking water distribution system (DWDS) to control microorganisms and improve the safety of drinking water quality are subjected to several challenges. One noticeable problem is the unpleasant odor generated by chlorine and chloramines. However, the generally proposed chlorine dosage optimization model ignores the chloric odor distribution in the DWDS. This study proposes a comprehensive multi-parameter water quality model and aims to balance the trade-offs between: (i) minimize the flavor profile analysis (FPA) degree of the chloric odor produced by chlorine and chloramines in the DWDS, and (ii) minimize the economic investment (chlorine dosage and operation cost). EPANET and back propagation (BP) network integrated with the Borg algorithm were employed as innovative approaches to simulate the chlorine, chloramines, and chloric odor intensity in the DWDS. Moreover, the application of the multi-parameter model was demonstrated in a real-world DWDS case study. 0.5 mg-Cl2/L (mg/L) chlorine at 8 secondary chlorination points was added to the DWDS as an optimized chlorine dosing scheme considering the olfactory and financial objective functions simultaneously. When switching to a superior water source, the FPA of the chloric odor in DWDS increased by a maximum of 1.4 at most if the initial chlorine dosage remained as before. To avoid the occurrence of chloric odor and also control the residual free chlorine (residual chlorine) at a suitable value, the initial and secondary chlorine dosages were optimized to 0.4 mg/L and 0.3 mg/L, respectively. Under this condition, the initial chlorine dosage was reduced by 50% compared to the original operation scheme in City J, China, the qualification rate of the residual chlorine reached 97.2%, basically consistent with that before water source switching, and the chloric odor intensity of the DWDS was controlled below FPA 3.4.

Odor-producing response pattern by four typical freshwater algae under stress: Acute microplastic exposure as an example.

Algae-induced odor problems in water have been repeatedly occurred concerns for drinking water quality. However, present researches mostly focus on the odor-producing pattern of algae in normal growth, and there is scarce discussion on those under stress. Microplastics (MPs) pollution have been global concern for their negative ecological impacts and frequently co-occurs with odor-producing algal bloom in freshwaters. Thus, this study aimed to elucidate the effects and mechanisms of MPs as an environmental stress on algal odorant production for good illustration of odor-producing response pattern under stress. Variation in MP size (polystyrene microspheres; 100 nm, 1000 nm and 10 µm) had significant effects on odorant formation (ß-cycloidal, 2-methylisopropanol, 2,4-heptandienal and 2,4-decadienal) by four freshwater algae (Microcystis aeruginosa, Pseudanabaena sp., Cyclotella meneghiniana and Melosira varians). The size ratio of MPs over cells (SRMC) was proposed to categorize the size-ratio dependent effects on the algal odorant production. Interestingly, when SRMC was in the range of 0.1-1, there were always promoting effects; when SRMC < 0.1 or SRMC > 1, there exhibited inhibiting effects, and the inhibiting effects of SRMC < 0.1 were far more severe than those of SRMC > 1. The promotion on odorant production in the SRMC range of 0.1-1 was mainly attributed to the increase in cellular yield, which was related to the increased odorant precursors derived from the oxidation products of reactive oxygen species (ROS). Alternatively, the inhibition of odorant production caused by MPs with SRMC < 0.1 was the results of simultaneously inhibiting cellular density and cellular yield, which might be attributed to the cellular internalization of MPs, inducing the extensive toxic effects. This study illustrated the possibilities of MPs in impairing the esthetics of the source water and provided guidance for the future algal odor issues under stress.