Energy-Efficient Visual Search by Eye Movement and Low-Latency Spiking Neural Network

Human vision incorporates non-uniform resolution retina, efficient eye movement strategy, and spiking neural network (SNN) to balance the requirements in visual field size, visual resolution, energy cost, and inference latency. These properties have inspired interest in developing human-like computer vision. However, existing models haven't fully incorporated the three features of human vision, and their learned eye movement strategies haven't been compared with human's strategy, making the models' behavior difficult to interpret. Here, we carry out experiments to examine human visual search behaviors and establish the first SNN-based visual search model. The model combines an artificial retina with spiking feature extraction, memory, and saccade decision modules, and it employs population coding for fast and efficient saccade decisions. The model can learn either a human-like or a near-optimal fixation strategy, outperform humans in search speed and accuracy, and achieve high energy efficiency through short saccade decision latency and sparse activation. It also suggests that the human search strategy is suboptimal in terms of search speed. Our work connects modeling of vision in neuroscience and machine learning and sheds light on developing more energy-efficient computer vision algorithms

The ecdysteroid receptor regulates salivary gland degeneration through apoptosis in Rhipicephalus haemaphysaloides

Background: It is well established that ecdysteroid hormones play an important role in arthropod development and reproduction, mediated by ecdysteroid receptors. Ticks are obligate hematophagous arthropods and vectors of pathogens. The salivary gland plays an essential role in tick growth and reproduction and in the transmission of pathogens to vertebrate hosts. During tick development, the salivary gland undergoes degeneration triggered by ecdysteroid hormones and activated by apoptosis. However, it is unknown how the ecdysteroid receptor and apoptosis regulate salivary gland degeneration. Here, we report the functional ecdysteroid receptor (a heterodimer of the ecdysone receptor [EcR] and ultraspiracle [USP]) isolated from the salivary gland of the tick Rhipicephalus haemaphysaloides and explore the molecular mechanism of ecdysteroid receptor regulation of salivary gland degeneration. Methods: The full length of RhEcR and RhUSP open reading frames (ORFs) was obtained from the transcriptome. The RhEcR and RhUSP proteins were expressed in a bacterial heterologous system, Escherichia coli. Polyclonal antibodies were produced against synthetic peptides and were able to recognize recombinant and native proteins. Quantitative real-time PCR and western blot were used to detect the distribution of RhEcR, RhUSP, and RhCaspases in the R. haemaphysaloides organs. A proteomics approach was used to analyze the expression profiles of the ecdysteroid receptors, RhCaspases, and other proteins. To analyze the function of the ecdysteroid receptor, RNA interference (RNAi) was used to silence the genes in adult female ticks. Finally, the interaction of RhEcR and RhUSP was identified by heterologous co-expression assays in HEK293T cells. Results: We identified the functional ecdysone receptor (RhEcR/RhUSP) of 20-hydroxyecdysone from the salivary gland of the tick R. haemaphysaloides. The RhEcR and RhUSP genes have three and two isoforms, respectively, and belong to a nuclear receptor family but with variable N-terminal A/B domains. The RhEcR gene silencing inhibited blood-feeding, blocked engorgement, and restrained salivary gland degeneration, showing the biological role of the RhEcR gene in ticks. In the ecdysteroid signaling pathway, RhEcR silencing inhibited salivary gland degeneration by suppressing caspase-dependent apoptosis. The heterologous expression in mammalian HEK293T cells showed that RhEcR1 interacts with RhUSP1 and induces caspase-dependent apoptosis

Structures of human gastrin-releasing peptide receptors bound to antagonist and agonist for cancer and itch therapy

Gastrin releasing peptide receptor (GRPR), a member of the bombesin (BBN) G protein-coupled receptors, is aberrantly overexpressed in several malignant tumors, including those of the breast, prostate, pancreas, lung, and central nervous system. Additionally, it also mediates non-histaminergic itch and pathological itch conditions in mice. Thus, GRPR could be an attractive target for cancer and itch therapy. Here, we report the inactive state crystal structure of human GRPR in complex with the non-peptide antagonist PD176252, as well as two active state cryo-electron microscopy (cryo-EM) structures of GRPR bound to the endogenous peptide agonist gastrin-releasing peptide and the synthetic BBN analog [D-Ph

Saikosaponin A Alleviates Symptoms of Attention Deficit Hyperactivity Disorder through Downregulation of DAT and Enhancing BDNF Expression in Spontaneous Hypertensive Rats

The disturbed dopamine availability and brain-derived neurotrophic factor (BDNF) expression are due in part to be associated with attention deficit hyperactivity disorder (ADHD). In this study, we investigated the therapeutical effect of saikosaponin a (SSa) isolated from Bupleurum Chinese DC, against spontaneously hypertensive rat (SHR) model of ADHD. Methylphenidate and SSa were orally administered for 3 weeks. Activity was assessed by open-field test and Morris water maze test. Dopamine (DA) and BDNF were determined in specific brain regions. The mRNA or protein expression of tyrosine hydroxylase (TH), dopamine transporter (DAT), and vesicles monoamine transporter (VMAT) was also studied. Both MPH and SSa reduced hyperactivity and improved the spatial learning memory deficit in SHRs. An increased DA concentration in the prefrontal cortex (PFC) and striatum was also observed after treating with the SSa. The increased DA concentration may partially be attributed to the decreased mRNA and protein expression of DAT in PFC while SSa exhibited no significant effects on the mRNA expression of TH and VMAT in PFC of SHRs. In addition, BDNF expression in SHRs was also increased after treating with SSa or MPH. The obtained result suggested that SSa may be a potential drug for treating ADHD

Network pharmacology combined with Mendelian randomization analysis to identify the key targets of renin-angiotensin-aldosterone system inhibitors in the treatment of diabetic nephropathy

BackgroundDiabetic Nephropathy (DN) is one of the microvascular complications of diabetes. The potential targets of renin-angiotensin-aldosterone system (RAAS) inhibitors for the treatment of DN need to be explored.MethodsThe GSE96804 and GSE1009 datasets, 729 RAAS inhibitors-related targets and 6,039 DN-related genes were derived from the public database and overlapped with the differentially expressed genes (DN vs. normal) in GSE96804 to obtain the candidate targets. Next, key targets were screened via the Mendelian randomization analysis and expression analysis. The diagnostic nomogram was constructed and assessed in GSE96804. Additionally, enrichment analysis was conducted and a ‘core active ingredient-key target-disease pathway’ network was established. Finally, molecular docking was performed.ResultsIn total, 60 candidate targets were derived, in which CTSC and PDE5A were screened as the key targets and had a causal association with DN as the protective factors (P < 0.05, OR < 1). Further, a nomogram exhibited pretty prediction efficiency. It is indicated that Benadryl hydrochloride might play a role in the DN by affecting the pathways of ‘cytokine cytokine receptor interaction’, etc. targeting the CTSC. Moreover, PDE5A might be involved in ‘ECM receptor interaction’, etc. for the effect of NSAID, captopril, chlordiazepoxide on DN. Molecular docking analysis showed a good binding ability of benadryl hydrochloride and CTSC, NSAID and PDE5A. PTGS2, ITGA4, and ANPEP are causally associated with acute kidney injury.ConclusionCTSC and PDE5A were identified as key targets for RAAS inhibitors in the treatment of DN, which might provide some clinical significance in helping to diagnose and treat DN. Among the targets of RAAS inhibitors, PTGS2, ITGA4 and ANPEP have a causal relationship with acute kidney injury, which is worthy of further clinical research

Unveiling the causal link between metabolic factors and ovarian cancer risk using Mendelian randomization analysis

BackgroundMetabolic abnormalities are closely tied to the development of ovarian cancer (OC), yet the relationship between anthropometric indicators as risk indicators for metabolic abnormalities and OC lacks consistency.MethodThe Mendelian randomization (MR) approach is a widely used methodology for determining causal relationships. Our study employed summary statistics from the genome-wide association studies (GWAS), and we used inverse variance weighting (IVW) together with MR-Egger and weighted median (WM) supplementary analyses to assess causal relationships between exposure and outcome. Furthermore, additional sensitivity studies, such as leave-one-out analyses and MR-PRESSO were used to assess the stability of the associations.ResultThe IVW findings demonstrated a causal associations between 10 metabolic factors and an increased risk of OC. Including “Basal metabolic rate” (OR= 1.24, P= 6.86×10-4); “Body fat percentage” (OR= 1.22, P= 8.20×10-3); “Hip circumference” (OR= 1.20, P= 5.92×10-4); “Trunk fat mass” (OR= 1.15, P= 1.03×10-2); “Trunk fat percentage” (OR= 1.25, P= 8.55×10-4); “Waist circumference” (OR= 1.23, P= 3.28×10-3); “Weight” (OR= 1.21, P= 9.82×10-4); “Whole body fat mass” (OR= 1.21, P= 4.90×10-4); “Whole body fat-free mass” (OR= 1.19, P= 4.11×10-3) and “Whole body water mass” (OR= 1.21, P= 1.85×10-3).ConclusionSeveral metabolic markers linked to altered fat accumulation and distribution are significantly associated with an increased risk of OC

Neutral top-pion and tγ(z)t\gamma(z) production at the HERA and THERA colliders

In the context of top-color assisted technicolor ($TC2$) models, we calculate the contributions of the neutral top-pion $\pi_{t}^{0}$ to $t\gamma$ and $tz$ production via the processes $ep\to \gamma c \to t\gamma$ and $ep\to \gamma c \to tz$ at the $HERA$ and $THERA$ colliders. Our results show that the cross sections $\sigma_{t\gamma}(s)$ and $\sigma_{tz}(s)$ are very small at the $HERA$ collider with $\sqrt{s}=320GeV$. However, in most of the parameter space, $\sigma_{t\gamma}(s)$ or $\sigma_{tz}(s)$ is in the range of about $0.1pb \sim 1 pb$ at the $THERA$ collider with $\sqrt{s}=1000GeV$.Comment: 10 pages, typos corrected, version accepted for publication in Phys. Lett.