Loss of transient receptor potential channel 5 causes obesity and postpartum depression.

Hypothalamic neural circuits regulate instinctive behaviors such as food seeking, the fight/flight response, socialization, and maternal care. Here, we identified microdeletions on chromosome Xq23 disrupting the brain-expressed transient receptor potential (TRP) channel 5 (TRPC5). This family of channels detects sensory stimuli and converts them into electrical signals interpretable by the brain. Male TRPC5 deletion carriers exhibited food seeking, obesity, anxiety, and autism, which were recapitulated in knockin male mice harboring a human loss-of-function TRPC5 mutation. Women carrying TRPC5 deletions had severe postpartum depression. As mothers, female knockin mice exhibited anhedonia and depression-like behavior with impaired care of offspring. Deletion of Trpc5 from oxytocin neurons in the hypothalamic paraventricular nucleus caused obesity in both sexes and postpartum depressive behavior in females, while Trpc5 overexpression in oxytocin neurons in knock-in mice reversed these phenotypes. We demonstrate that TRPC5 plays a pivotal role in mediating innate human behaviors fundamental to survival, including food seeking and maternal care.

5-HT Neurons Integrate GABA and Dopamine Inputs to Regulate Meal Initiation.

Obesity is a growing global health epidemic with limited effective therapeutics. Serotonin (5-HT) is one major neurotransmitter which remains an excellent target for new weight-loss therapies, but there remains a gap in knowledge on the mechanisms involved in 5-HT produced in the dorsal Raphe nucleus (DRN) and its involvement in meal initiation. Using a closed-loop optogenetic feeding paradigm, we showed that the 5-HTDRN→arcuate nucleus (ARH) circuit plays an important role in regulating meal initiation. Incorporating electrophysiology and ChannelRhodopsin-2-Assisted Circuit Mapping, we demonstrated that 5-HTDRN neurons receive inhibitory input partially from GABAergic neurons in the DRN, and the 5-HT response to GABAergic inputs can be enhanced by hunger. Additionally, deletion of the GABAA receptor subunit in 5-HT neurons inhibits meal initiation with no effect on the satiation process. Finally, we identified the instrumental role of dopaminergic inputs via dopamine receptor D2 in 5-HTDRN neurons in enhancing the response to GABA-induced feeding. Thus, our results indicate that 5-HTDRN neurons are inhibited by synergistic inhibitory actions of GABA and dopamine, which allows for the initiation of a meal.

Genome-based reclassification of Salipiger manganoxidans (Rajasabapathy et al. 2016) Wirth et al. 2018 as a later heterotypic synonym of Salipiger marinus (Lai et al. 2011) Wirth et al. 2018.

Salipiger manganoxidans VSW210T was compared with Salipiger marinus CK-I3-6T to examine the taxonomic relationship between the two type strains. In phylogenetic trees drawn using whole genome sequences and 16S rRNA gene sequences, S. manganoxidans VSW210T and S. marinus CK-I3-6T clade together and showed a 99.6 % 16S rRNA sequence similarity. The average amino acid identity (AAI), average nucleotide identity (ANIb and ANIm) and digital DNA-DNA hybridization (dDDH) values between S. manganoxidans VSW210T and S. marinus CK-I3-6T were below 97.5, 97.4, 98.4 and 85.1±2.5 %, respectively, all of which were greater than the species delineation threshold AAI value (95.5 %), ANI value (95-96 %) and dDDH value (70 %). Most phenotypic features between both species were almost identical, although there were some differences. The present results show that Salipiger manganoxidans is a later heterotypic synonym of Salipiger marinus.

Reliance on Episodic vs. Procedural Systems in Decision-Making Depends on Individual Differences in Their Relative Neural Efficiency.

Experiential decision-making can be explained as a result of either memory-based or reinforcement-based processes. Here, for the first time, we show that individual preferences between a memory-based and a reinforcement-based strategy, even when the two are functionally equivalent in terms of expected payoff, are adaptively shaped by individual differences in resting-state brain connectivity between the corresponding brain regions. Using computational cognitive models to identify which mechanism was most likely used by each participant, we found that individuals with comparatively stronger connectivity between memory regions prefer a memory-based strategy, while individuals with comparatively stronger connectivity between sensorimotor and habit-formation regions preferentially rely on a reinforcement-based strategy. These results suggest that human decision-making is adaptive and sensitive to the neural costs associated with different strategies.

Allocating Mental Effort in Cognitive Tasks: A Model of Motivation in the ACT-R Cognitive Architecture.

Motivation is the driving force that influences people's behaviors and interacts with many cognitive functions. Computationally, motivation is represented as a cost-benefit analysis that weighs efforts and rewards in order to choose the optimal actions. Shenhav and colleagues proposed an elegant theory, the Expected Value of Control (EVC), which describes the relationship between cognitive efforts, costs, and rewards. In this paper, we propose a more fine-grained and detailed motivation framework that incorporates the principles of EVC into the ACT-R cognitive architecture. Specifically, motivation is represented as a specific slot in the Goal buffer with a corresponding scalar value, M, that is translated into the reward value Rt that is delivered when the goal is reached. This implementation is tested in two models. The first model is a high-level model that reproduces the EVC predictions with abstract actions. The second model is an augmented version of an existing ACT-R model of the Simon task. The motivation mechanism is shown to permit optimal effort allocation and reproduce known phenomena. Finally, the broader implications of our mechanism are discussed.

Estradiol-mediated small GTP-binding protein GDP dissociation stimulator induction contributes to sex differences in resilience to ferroptosis in takotsubo syndrome.

BACKGROUND: Declining beneficial cardiovascular actions of estradiol (E2) have been associated with disproportionate susceptibility to takotsubo syndrome (TTS) in postmenopausal women. However, the underlying mechanisms between E2 and this marked disproportion remain unclear. SmgGDS (small GTP-binding protein GDP dissociation stimulator), as a key modulator of cardiovascular disease, plays protective roles in reducing oxidative stress and exerts pleiotropic effects of statins. Whether SmgGDS levels are influenced by E2 status and the effect of SmgGDS on sex differences in TTS are poorly understood. METHODS: Clinical data were reviewed from TTS inpatients. Echocardiography, immunofluorescence, and immunohistochemistry were performed together with expression analysis to uncover phenotypic and mechanism changes in sex differences in TTS-like wild-type (WT) and SmgGDS± mice. HL-1 cardiomyocytes were used to further examine and validate molecular mechanisms. RESULTS: In 14 TTS inpatients, TTS had a higher incidence in postmenopausal women as compared to premenopausal women and men. In murine TTS, female WT mice exhibited higher cardiac SmgGDS levels than male WT mice. Ovariectomy reduced SmgGDS expression in female WT mice similar to that observed in male mice, whereas E2 replacement in these ovariectomized (OVX) female mice reversed this effect. The physiological importance of this sex-specific E2-mediated SmgGDS response is underscored by the disparity in cardiac adaptation to isoproterenol (ISO) stimulation between both sexes of WT mice. E2-mediated SmgGDS induction conferred female protection against TTS-like acute cardiac injury involving ferritinophagy-mediated ferroptosis. No such cardioprotection was observed in male WT mice and OVX female. A causal role for SmgGDS in this sex-specific cardioprotective adaptation was indicated, inasmuch as SmgGDS deficiency abolished E2-modulated cardioprotection against ferritinophagy and aggravates TTS progression in both sexes. Consistently, knockdown of SmgGDS in HL-1 cardiomyocytes exacerbated ferroptosis in a ferritinophagy-dependent manner and abrogated the protective role of E2 against ferritinophagy. Mechanistically, our findings revealed that SmgGDS regulated E2-dependent cardioprotective effects via AMPK/mTOR signaling pathway. SmgGDS deficiency abolished E2-conferred protection against ferritinophagy through activating AMPK/mTOR pathway, while treatment with recombinant SmgGDS in HL-1 cells significantly mitigated this pathway-associated ferritinophagy activity. CONCLUSIONS: These results demonstrate that SmgGDS is a central mediator of E2-conferred female cardioprotection against ferritinophagy-mediated ferroptosis in TTS.

Genome-based reclassification of Deinococcus saudiensis Hussain et al. 2016 as a later heterotypic synonym of Deinococcus soli Cha et al. 2014.

Deinococcus saudiensis YIM F302T was compared with Deinococcus soli N5T to examine the taxonomic relationship between the two type strains. The 16S rRNA gene sequence of D. saudiensis YIM F302T showed high similarity (99.9 %) to that of D. soli N5T. The results of phylogenetic analyses based on 16S rRNA gene sequences indicated that the two strains formed a tight cluster within the genus Deinococcus. A draft genomic comparison between the two strains revealed average nucleotide identity values of 96.8-97.9 % and a digital DNA-DNA hybridization estimate of 80.7±1.9 %, strongly indicating that the two strains represented a single species. Based on the combined phylogenetic, genomic and phenotypic characterization presented here, we propose D. saudiensis as a later heterotypic synonym of D. soli N5T.

Super Sparse 3D Object Detection.

As the perception range of LiDAR expands, LiDAR-based 3D object detection contributes ever-increasingly to the long-range perception in autonomous driving. Mainstream 3D object detectors often build dense feature maps, where the cost is quadratic to the perception range, making them hardly scale up to the long-range settings. To enable efficient long-range detection, we first propose a fully sparse object detector termed FSD. FSD is built upon the general sparse voxel encoder and a novel sparse instance recognition (SIR) module. SIR groups the points into instances and applies highly-efficient instance-wise feature extraction. The instance-wise grouping sidesteps the issue of the center feature missing, which hinders the design of the fully sparse architecture. To further enjoy the benefit of fully sparse characteristic, we leverage temporal information to remove data redundancy and propose a super sparse detector named FSD++. FSD++ first generates residual points, which indicate the point changes between consecutive frames. The residual points, along with a few previous foreground points, form the super sparse input data, greatly reducing data redundancy and computational overhead. We comprehensively analyze our method on the large-scale Waymo Open Dataset, and state-of-the-art performance is reported. To showcase the superiority of our method in long-range detection, we also conduct experiments on Argoverse 2 Dataset, where the perception range ([Formula: see text] m) is much larger than Waymo Open Dataset ([Formula: see text] m).

What are the core concerns of policy analysis? A multidisciplinary investigation based on in-depth bibliometric analysis.

Policy analysis provides multiple methods and tools for generating and transforming policy-relevant information and supporting policy evolution to address emerging social problems. In this study, a bibliometric analysis of a large number of studies on historical policy analysis was performed to provide a comprehensive understanding of the distribution and evolution of policy problems in different fields among countries. The analysis indicates that policy analysis has been a great concern for scholars in recent two decades, and is involved in multiple disciplines, among which the dominant ones are medicine, environment, energy and economy. The major concerns of policy analysts and scholars are human health needs, environmental pressures, energy consumption caused by economic growth and urbanization, and the resulting demand for sustainable development. The multidisciplinary dialog implies the complicated real-world social problems that calls for more endeavors to develop a harmonious society. A global profiling for policy analysis demonstrates that the central policy problems and the corresponding options align with national development, for example, developing countries represented by China are faced with greater environmental pressures after experiencing extensive economic growth, while developed countries such as the USA and the UK pay more attention to the social issues of health and economic transformation. Exploring the differences in policy priorities among countries can provide a new inspiration for further dialog and cooperation on the development of the international community in the future.

Recognition of dipole-induced electric field in 2D materials for surface-enhanced Raman scattering.

The application of two-dimensional (2D) materials, including metallic graphene, semiconducting transition metal dichalcogenides, and insulating hexagonal boron nitride (h-BN) for surface-enhancement Raman spectroscopy has attracted extensive research interest. This article provides a critical overview of the recent developments in surface-enhanced Raman spectroscopy using 2D materials. By re-examining the relationship between the lattice structure and Raman enhancement characteristics, including vibration selectivity and thickness dependence, we highlight the important role of dipoles in the chemical enhancement of 2D materials.

NpPP2-B10, an F-Box-Nictaba Gene, Promotes Plant Growth and Resistance to Black Shank Disease Incited by Phytophthora nicotianae in Nicotiana tabacum.

Black shank, a devastating disease affecting tobacco production worldwide, is caused by Phytophthora nicotianae. However, few genes related to Phytophthora resistance have been reported in tobacco. Here, we identified NpPP2-B10, a gene strongly induced by P. nicotianae race 0, with a conserved F-box motif and Nictaba (tobacco lectin) domain, in the highly resistant tobacco species Nicotiana plumbaginifolia. NpPP2-B10 is a typical F-box-Nictaba gene. When it was transferred into the black shank-susceptible tobacco cultivar 'Honghua Dajinyuan', it was found to promote resistance to black shank disease. NpPP2-B10 was induced by salicylic acid, and some resistance-related genes (NtPR1, NtPR2, NtCHN50, and NtPAL) and resistance-related enzymes (catalase and peroxidase) were significantly upregulated in the overexpression lines after infection with P. nicotianae. Furthermore, we showed that NpPP2-B10 actively regulated the tobacco seed germination rate, growth rate, and plant height. The erythrocyte coagulation test of purified NpPP2-B10 protein showed that NpPP2-B10 had plant lectin activity, and the lectin content in the overexpression lines was significantly higher than that in the WT, which could lead to accelerated growth and improved resistance of tobacco. SKP1 is an adaptor protein of the E3 ubiquitin ligase SKP1, Cullin, F-box (SCF) complex. We demonstrated that NpPP2-B10 could interact with the NpSKP1-1A gene in vivo and in vitro through yeast two-hybrid (Y2H) and bimolecular fluorescence complementation (BiFC), indicating that NpPP2-B10 likely participates in the plant immune response by mediating the ubiquitin protease pathway. In conclusion, our study provides some important insights concerning NpPP2-B10-mediated regulation of tobacco growth and resistance.

Metabolic remodeling in takotsubo syndrome.

The heart requires a large and constant supply of energy that is mainly the result of an efficient metabolic machinery that converges on mitochondrial oxidative metabolism to maintain its continuous mechanical work. Perturbations in these metabolic processes may therefore affect energy generation and contractile function directly. Metabolism characteristics in takotsubo syndrome (TTS) reveals several metabolic alterations called metabolic remodeling, including the hyperactivity of sympathetic metabolism, derangements of substrate utilization, effector subcellular dysfunction and systemic metabolic disorders, ultimately contributing to the progression of the disease and the development of a persistent and long-term heart failure (HF) phenotype. In this review, we explore the current literature investigating the pathological metabolic alterations in TTS. Although the metabolic dysfunction in takotsubo hearts is initially recognized as a myocardial metabolic inflexibility, we suggest that the widespread alterations of systemic metabolism with complex interplay between the heart and peripheral tissues rather than just cardiometabolic disorders per se account for long-term maladaptive metabolic, functional and structural impairment under this condition. Therapeutic strategies with the recent evidence from small clinical and animal researches, especially for targeting substrate utilization and/or oxidative stress, might be promising tools to improve the outcome of patients with TTS beyond that achieved with traditional sympathetic inhibition and symptomatic therapies.

Pseudomonas marianensis sp. nov., a marine bacterium isolated from deep-sea sediments of the Mariana Trench.

A novel marine Gram-stain-negative, aerobic, rod-shaped bacterium, designated as strain PS1T, was isolated from the deep-sea sediments of the Mariana Trench and characterized phylogenetically and phenotypically. Bacterial optimal growth occurred at 35 °C (ranging 10-45 °C), pH 6 (ranging pH 5-10) and with 11% (w/v) NaCl (ranging 0-17%). The 16S rRNA gene sequence similarity results revealed that strain PS1T was most closely related to Pseudomonas stutzeri ATCC 17588T, Pseudomonas nitrititolerans GL14T, Pseudomonas zhaodongensis NEAU-ST5-21T, Pseudomonas xanthomarina DSM 18231T and Pseudomonas kunmingensis HL22-2T with 98.3-98.7%. The digital DNA-DNA hybridization values and the average nucleotide identity between strain PS1T and the reference strains were 20.4-40.1% and 78.7-79.4%, respectively. The major respiratory quinone is ubiquinone Q-9. The major polar lipids were phosphatidylethanolamine, diphosphatidyglycerol, phosphatidylglycerol, phosphatidylcholine, aminoglycolipid, two unidentified glycolipids and one unidentified lipid. The predominant cellular fatty acids of strain PS1T were summed feature 8 (C18:1ω7c and/or C18:1ω6c), summed feature 3 (C16:1ω7c and/or C16:1ω6c), C16:0 and cyclo-C19:0 ω8c. The G + C content of the genomic DNA was 63.0%. The combined genotypic and phenotypic data indicated that strain PS1T represents a novel species of the genus Pseudomonas, for which the name Pseudomonas marianensis sp. nov. is proposed, with the type strain PS1T (= DSM 112238T = MCCC 1K05112T).

Can green finance promote green innovation? The moderating effect of environmental regulation.

Green finance has emerged as a main driving force for green development in which green innovation has served as the key approach. However, little is known about how green finance impacts green innovation performance. In this research, we empirically examined the hypotheses by fixed effect model with data of 30 provinces in China during 2008-2019. The result turns out that green finance has significantly positive effect on green innovation in all regions in China, and the effect is stronger in western and central regions than eastern region. Furthermore, we verified the effect of environmental regulations on green innovation, and the results show the effect is larger in eastern region than western and central regions. Additionally, with intense environmental regulations, the effect of green finance in promoting green innovation is enhanced in all regions. Our results thus contribute to unveil the mixed relationships among green finance, environmental regulations, and green innovation. Three policy recommendations for policymakers were also discussed, i.e., improving green finance system, staging green finance policies and regulations, and strengthening environmental regulations design to support green innovation.

Muricauda abyssi sp. nov., a marine bacterium isolated from deep seawater of the Mariana Trench.

A Gram-stain-negative, non-motile and rod-shaped bacterium, designated as strain W52T, was isolated from deep seawater of the Mariana Trench and characterized phylogenetically and phenotypically. The strain could grow at 10-47 °C (optimum 32 °C), at pH 5.0-8.0 (optimum 6.0) and with 0-9% NaCl (optimum 3 %, w/v). The results of phylogenetic analysis based on 16S rRNA gene sequences indicated that W52T was related to members of the genus Muricauda and shared the highest identity with Muricauda oceani 501str8T (99.0 %), followed by Muricauda aquimarina JCM 11811T, Muricauda ruestringensis DSM 13258T, Muricauda oceanensis 40DY170T, Muricauda beolgyonensis KCTC 23501T and Muricauda zhangzhouensis 12C25T with 97.0-98.8 % sequence similarity. 16S rRNA gene sequence identities between W52T and other members of the genus Muricauda were below 97.0 %. The major respiratory quinone was MK-6. The polar lipids were phosphatidylethanolamine (PE), one unidentified aminolipid and three unidentified lipids. The strain had iso-C15 : 0, iso-C17 : 0 3-OH and iso-C15 : 1G as the major fatty acids. The G+C content of the genomic DNA was 41.7 %. The combined genotypic and phenotypic data indicated that strain W52T represents a novel species of the genus Muricauda, for which the name Muricauda abyssi sp. nov. is proposed, with the type strain W52T (=MCCC 1K05111T= KCTC 82315T).

Core Cognitive Mechanisms Underlying Syntactic Priming: A Comparison of Three Alternative Models.

Syntactic priming (SP) is the effect by which, in a dialogue, the current speaker tends to re-use the syntactic constructs of the previous speakers. SP has been used as a window into the nature of syntactic representations within and across languages. Because of its importance, it is crucial to understand the mechanisms behind it. Currently, two competing theories exist. According to the transient activation account, SP is driven by the re-activation of declarative memory structures that encode structures. According to the error-based implicit learning account, SP is driven by prediction errors while processing sentences. By integrating both transient activation and associative learning, Reitter et al.'s hybrid model 2011 assumes that SP is achieved by both mechanisms, and predicts a priming enhancement for rare or unusual constructions. Finally, a recently proposed account, the reinforcement learning account, claims that SP driven by the successful application of procedural knowledge will be reversed when the prime sentence includes grammatical errors. These theories make different assumptions about the representation of syntactic rules (declarative vs. procedural) and the nature of the mechanism that drives priming (frequency and repetition, attention, and feedback signals, respectively). To distinguish between these theories, they were all implemented as computational models in the ACT-R cognitive architecture, and their specific predictions were examined through grid-search computer simulations. Two experiments were then carried out to empirically test the central prediction of each theory as well as the individual fits of each participant's responses to different parameterizations of each model. The first experiment produced results that were best explained by the associative account, but could also be accounted for by a modified reinforcement model with a different parsing algorithm. The second experiment, whose stimuli were designed to avoid the parsing ambiguity of the first, produced somewhat weaker effects. Its results, however, were also best predicted by the model implementing the associative account. We conclude that the data overall points to SP being due to prediction violations that direct attentional resources, in turn suggesting a declarative rather than a RL based procedural representation of syntactic rules.

DRD4 (Dopamine D4 Receptor) Mitigate Abdominal Aortic Aneurysm via Decreasing P38 MAPK (mitogen-activated protein kinase)/NOX4 (NADPH Oxidase 4) Axis-Associated Oxidative Stress.

[Figure: see text].

When Fear Shrinks the Brain: A Computational Model of the Effects of Posttraumatic Stress on Hippocampal Volume.

Post-traumatic stress disorder (PTSD) is a psychiatric disorder often characterized by the unwanted re-experiencing of a traumatic event through nightmares, flashbacks, and/or intrusive memories. This paper presents a neurocomputational model using the ACT-R cognitive architecture that simulates intrusive memory retrieval following a potentially traumatic event (PTE) and predicts hippocampal volume changes observed in PTSD. Memory intrusions were captured in the ACT-R rational analysis framework by weighting the posterior probability of re-encoding traumatic events into memory with an emotional intensity term I to capture the degree to which an event was perceived as dangerous or traumatic. It is hypothesized that (1) increasing the intensity I of a PTE will increase the odds of memory intrusions, and (2) increased frequency of intrusions will result in a concurrent decrease in hippocampal size. A series of simulations were run and it was found that I had a significant effect on the probability of experiencing traumatic memory intrusions following a PTE. The model also found that I was a significant predictor of hippocampal volume reduction, where the mean and range of simulated volume loss match results of existing meta-analyses. The authors believe that this is the first model to both describe traumatic memory retrieval and provide a mechanistic account of changes in hippocampal volume, capturing one plausible link between PTSD and hippocampal volume.