RACK1 modulates polyglutamine-induced neurodegeneration by promoting ERK degradation in Drosophila.

Polyglutamine diseases are neurodegenerative diseases caused by the expansion of polyglutamine (polyQ) tracts within different proteins. Although multiple pathways have been found to modulate aggregation of the expanded polyQ proteins, the mechanisms by which polyQ tracts induced neuronal cell death remain unknown. We conducted a genome-wide genetic screen to identify genes that suppress polyQ-induced neurodegeneration when mutated. Loss of the scaffold protein RACK1 alleviated cell death associated with the expression of polyQ tracts alone, as well as in models of Machado-Joseph disease (MJD) and Huntington's disease (HD), without affecting proteostasis of polyQ proteins. A genome-wide RNAi screen for modifiers of this rack1 suppression phenotype revealed that knockdown of the E3 ubiquitin ligase, POE (Purity of essence), further suppressed polyQ-induced cell death, resulting in nearly wild-type looking eyes. Biochemical analyses demonstrated that RACK1 interacts with POE and ERK to promote ERK degradation. These results suggest that RACK1 plays a key role in polyQ pathogenesis by promoting POE-dependent degradation of ERK, and implicate RACK1/POE/ERK as potent drug targets for treatment of polyQ diseases.

Clinical evaluation of deep learning-based automatic clinical target volume segmentation: a single-institution multi-site tumor experience.

PURPOSE: The large variability in tumor appearance and shape makes manual delineation of the clinical target volume (CTV) time-consuming, and the results depend on the oncologists' experience. Whereas deep learning techniques have allowed oncologists to automate the CTV delineation, multi-site tumor analysis is often lacking in the literature. This study aimed to evaluate the deep learning models that automatically contour CTVs of tumors at various sites on computed tomography (CT) images from objective and subjective perspectives. METHODS AND MATERIALS: 577 patients were selected for the present study, including nasopharyngeal (n = 34), esophageal (n = 40), breast-conserving surgery (BCS) (left-sided, n = 71; right-sided, n = 71), breast-radical mastectomy (BRM) (left-sided, n = 43; right-sided, n = 37), cervical (radical radiotherapy, n = 45; postoperative, n = 85), prostate (n = 42), and rectal (n = 109) carcinomas. Manually delineated CTV contours by radiation oncologists are served as ground truth. Four models were evaluated: Flexnet, Unet, Vnet, and Segresnet, which are commercially available in the medical product "AccuLearning AI model training platform". The data were divided into the training, validation, and testing set at a ratio of 5:1:4. The geometric metrics, including Dice Similarity Coefficient (DSC) and Hausdorff Distance (HD), were calculated for objective evaluation. For subjective assessment, oncologists rated the segmentation contours of the testing set visually. RESULTS: High correlations were observed between automatic and manual contours. Based on the results of the independent test group, most of the patients achieved satisfactory quantitative results (DSC > 0.8), except for patients with esophageal carcinoma (DSC: 0.62-0.64). The subjective review indicated that 82.65% of predicted CTVs scored either as clinically accepting (8.68%) or requiring minor revision (73.97%), and no patients were scored as rejected. CONCLUSION: This experimental work demonstrated that auto-generated contours could serve as an initial template to help oncologists save time in CTV delineation. The deep learning-based auto-segmentations achieve acceptable accuracy and show the potential to improve clinical efficiency for radiotherapy of a variety of cancer.

Impact of water deficiency on leaf cuticle lipids and gene expression networks in cotton (Gossypium hirsutum L.).

BACKGROUND: Water deficit (WD) has serious effect on the productivity of crops. Formation of cuticular layer with increased content of wax and cutin on leaf surfaces is closely related to drought tolerance. Identification of drought tolerance associated wax components and cutin monomers and the genes responsible for their biosynthesis is essential for understanding the physiological and genetic mechanisms underlying drought tolerance and improving crop drought resistance. RESULT: In this study, we conducted comparative phenotypic and transcriptomic analyses of two Gossypium hirsutum varieties that are tolerant (XL22) or sensitive (XL17) to drought stress. XL17 consumed more water than XL22, particularly under the WD conditions. WD significantly induced accumulation of most major wax components (C29 and C31 alkanes) and cutin monomers (palmitic acid and stearic acid) in leaves of both XL22 and XL17, although accumulation of the major cutin monomers, i.e., polyunsaturated linolenic acid (C18:3n-3) and linoleic acid (C18:2n-6), were significantly repressed by WD in both XL22 and XL17. According to the results of transcriptome analysis, although many genes and their related pathways were commonly induced or repressed by WD in both XL22 and XL17, WD-induced differentially expressed genes specific to XL22 or XL17 were also evident. Among the genes that were commonly induced by WD were the GhCER1 genes involved in biosynthesis of alkanes, consistent with the observation of enhanced accumulation of alkanes in cotton leaves under the WD conditions. Interestingly, under the WD conditions, several GhCYP86 genes, which encode enzymes catalyzing the omega-hydroxylation of fatty acids and were identified to be the hub genes of one of the co-expression gene modules, showed a different expression pattern between XL22 and XL17 that was in agreement with the WD-induced changes of the content of hydroxyacids or fatty alcohols in these two varieties. CONCLUSION: The results contribute to our comprehending the physiological and genetic mechanisms underlying drought tolerance and provide possible solutions for the difference of drought resistance of different cotton varieties.

Parallel processing of radiation measurements and radiation video optimization.

In this study, we propose a parallel processing method for analyzing video-image radiation-response signals and suppressing radiation noise. We studied the linear-representation law of various image-information components on the radiation dose rate. Subsequently, the simulation images were used to examine the response-signal extract and radiation-noise suppression. The results indicate that the majority of response signals in the global image comprise forward superposition. The peak signal-to-noise ratio of the red channel was significantly improved when the noise signal-substitution algorithm and median filter were applied successively. Real-time radiation dose-rate measurements and clear images under irradiation can be obtained simultaneously.

Research on Calculation Method of Radiation Response Eigenvalue of a Single-Chip Active Pixel Sensor.

In this paper, we present a calculation method for the radiation response eigenvalue based on a monolithic active pixel sensor. By comparing the statistical eigenvalues of different regions of a pixel array in bright and dark environments, the linear relationship between the statistical eigenvalues obtained by different algorithms and the radiation dose rate was studied. Additionally, a dose rate characterization method based on the analysis of the eigenvalues of the MAPS response signal was proposed. The experimental results show that in the dark background environment, the eigenvalues had a good linear response in the region of any gray value in the range of 10-30. In the color images, due to the difference in the background gray values in adjacent color regions, the radiation response signal in dark regions was confused with the image information in bright regions, resulting in the loss of response signal and affecting the analysis results of the radiation response signal. For the low dose rate radiation field, as the radiation response signal was too weak and there was background dark noise, it was necessary to accumulate frame images to obtain a sufficient response signal. For the intense radiation field, the number of response events in a single image was very high, and only two consecutive frames of image data needed to be accumulated to meet the statistical requirements. The binarization method had a good characterization effect for the radiation at a low dose rate, and the binarization processing and the total gray value statistics of the response data at a high dose rate could better characterize the radiation dose rate. The calibration experiment results show that the binarization processing method can meet the requirements of using a MAPS for wide-range detection.

Real-Time Monitoring Method for Radioactive Substances Using Monolithic Active Pixel Sensors (MAPS).

This study presents a real-time monitoring technique for radioactive substances that meets safety management needs. We studied the accumulation characteristics of radiation response signals of monolithic active pixel sensors (MAPSs) based on their response and discrimination ability to gamma (γ) photon or neutron radiation. The radiation status of the radioactive substances was determined by monitoring the accumulation data of radiation responses. As per the results, Am-Be and 252Cf radiation response signals are primarily concentrated in the range of 0-70 pixels. Response signals of 60Co and 137Cs γ-ray were concentrated in two regions; there was a peak in the region with a pixel value of less than 50, and a plateau in the region with a pixel value of more than 75. Therefore, the results are able to discriminate between spectra. Furthermore, we designed a radioactivity monitoring system that is able to examine multiple radioactive materials. Its working principle is that a change in the accumulation of radioactivity monitoring data indicates a radiation change during the last accumulation cycle. This study provides vital technical support for the long-term supervision of radioactive substances.

Strong Radiation Field Online Detection and Monitoring System with Camera.

Herein, we report the γ-ray ionizing radiation response of a commercial monolithic active-pixel sensor (MAPS) camera under strong-dose-rate irradiation with an online detection and monitoring system for strong radiation conditions. We present the first results of the distribution of three types of MAPS camera and establish a linear relationship between the average response signal and radiation dose rate in the strong-dose-rate range. There is an obvious response signal in the video frames when the camera module parameters are set to automatic, but the linear response is very poor. However, the fixed image parameters are not good at adapting to the changes of the environment and affect the quality of the video frames. A dual module online radiation detection and monitoring probe was made to carry out effective video monitoring and radiation detection at the same time. The measurement results show that the dose rate detection error is less than 5% with a dose rate in the range of 60 to 425 Gy/h, and the visible light image does not have obvious distortion, deformation, or color shift due to the interference of the radiation response event and radiation damage. Hence, the system test results show that it can be used for online detection and monitoring in a strong radiation environment.

Low dose rate γ-ray detection using a MAPS camera under a neutron radiation environment.

We present γ-ray radiation detection in a neutron radiation environment using a monolithic active pixel sensor (MAPS) camera without conversion or shielding layers. The measured output signal is the sum of the pedestal value, noise, and real radiation response signal. The sensor response shows that the MAPS camera is sensitive to neutrons and can capture a single photon. The number of pixels with a signal exceeding 100 exhibits a strong dependence on the dose rate and is the best indicator of this value. Therefore, a MAPS camera can be efficiently used as a radiation detection sensor in a robotic system, further limiting human errors in performing radiation detection in complex nuclear radiation environments.

Video Monitoring Application of CMOS 4T-PPD-APS Under γ-ray Radiation.

In this paper, we discuss the potential use of four transistor active pixel sensor (4T-APS) as a video monitor at a nuclear accident site with a high level of γ radiation. The resistance and radiation responses to γ radiation were investigated by radiation experiments using 137Cs and 60Co γ-ray sources. The radiation resistance of 4T-APS was studied by testing the mean and the maximum dark current of the sensors after irradiation. A random spatial distribution of radiation response events was observed upon analyzing these events on the video images in a given time during irradiation. The background dependence of the 4T-APS was also studied by comparing the grayscale incremental value of the images with different color and grayscale backgrounds: the radiation response events were obvious on the images with a background having a smaller grayscale value or a deeper color. Finally, the color saturation and resolution of the images were tested using a vector oscilloscope and a test card. When the total ionizing dose was less than or equal to the damage threshold, no significant performance deterioration of 4T-APS was observed in an environment with sufficient light.

Effect of Commercial Off-The-Shelf MAPS on γ-Ray Ionizing Radiation Response to Different Integration Times and Gains.

We report the γ-ray ionizing radiation response of commercial off-the-shelf (COTS) monolithic active-pixel sensors (MAPS) with different integration times and gains. The distribution of the eight-bit two-dimensional matrix of MAPS output frame images was studied for different parameter settings and dose rates. We present the first results of the effects of these parameters on the response of the sensor and establish a linear relationship between the average response signal and radiation dose rate in the high-dose rate range. The results show that the distribution curves can be separated into three ranges. The first range is from 0 to 24, which generates the first significant low signal peak. The second range is from 25 to 250, which shows a smooth gradient change with different integration times, gains, and dose rates. The third range is from 251 to 255, where a final peak appears, which has a relationship with integral time, gain, and dose rate. The mean pixel value shows a linear dependence on the radiation dose rate, albeit with different calibration constants depending on the integration time and gain. Hence, MAPS can be used as a radiation monitoring device with good precision.

Hypervalent-Iodine-Mediated Formation of Epoxides from Carbon(sp2)-Carbon(sp3) Single Bonds.

We have developed an efficient method for direct formation of epoxide groups from carbon(sp2)-carbon(sp3) single bonds of ß-keto esters; the reaction is mediated by the water-soluble hypervalent iodine(V) reagent AIBX (5-trimethylammonio-1,3-dioxo-1,3-dihydro-1λ5-benzo[d][1,2]iodoxol-1-ol anion). On the basis of the results of density functional theory calculations and experimental studies, we propose that the reaction proceeds by a two-stage mechanism involving dehydrogenation of the ß-keto ester substrates and epoxidation of the resulting enone intermediates. The rate-limiting step is abstraction of the ß'-C-H (calculated free energy of activation, 24.5 kcal/mol).

CmpacC regulates mycoparasitism, oxalate degradation and antifungal activity in the mycoparasitic fungus Coniothyrium minitans.

The PacC/Rim101 pH-responsive transcription factor is an important pathogenicity element for many plant-pathogenic fungi. In this study, we investigated the roles of a PacC homologue, CmpacC, in the mycoparasitic fungus Coniothyrium minitans. CmpacC was confirmed to have the transcriptional activation activity by the transcriptional activation test in Saccharomyces cerevisiae. Disruption of CmpacC resulted in impaired fungal responses to ambient pH. Compared to the wild-type, the CmpacC-disruption mutant ΔCmpacC-29 was significantly suppressed for activities of chitinase and ß-1,3-glucanase at pH 5 and 7, consistent with reduced expression levels of Cmch1 and Cmg1 coding for the two enzymes respectively. However, the mutant displayed acidity-mimicking phenotypes such as improved oxalate degradation and increased antifungal activity at pH 6 or higher. Improved efficacy in oxalate degradation by ΔCmpacC-29 was consistent with the enhanced expression level of Cmoxdc1 coding for oxalate decarboxylase. CmpacC transcriptional activation of Cmch1 and Cmg1 and repression of Cmoxdc1 were verified by the presence of the PacC/Rim101 consensus binding-motifs in gene promoter regions and by the promoter DNA-binding assays. This study suggests that CmpacC plays an activator role in regulation of C. minitans mycoparasitism, whereas plays a repressor role in regulation of oxalate degradation and possibly antifungal activity of C. minitans.

Degradation of oxalic acid by the mycoparasite Coniothyrium minitans plays an important role in interacting with Sclerotinia sclerotiorum.

Coniothyrium minitans (Cm) is a mycoparasite of the phytopathogenic fungus Sclerotinia sclerotiorum (Ss). Ss produces a virulence factor oxalic acid (OA) which is toxic to plants and also to Cm, and Cm detoxifies OA by degradation. In this study, two oxalate decarboxylase genes, Cmoxdc1 and Cmoxdc2, were cloned from Cm strain Chy-1. OA and low pH induced expression of Cmoxdc1, but not Cmoxdc2. Cmoxdc1 was partially responsible for OA degradation, whereas Cmoxdc2 had no effect on OA degradation. Disruption of Cmoxdc1 in Cm reduced its ability to infect Ss in dual cultures where OA accumulated. Compared with Chy-1, the Cmoxdc1-disrupted mutants had reduced expression levels of two mycoparasitism-related genes chitinase (Cmch1) and ß-1,3-glucanase (Cmg1), and had no detectable activity of extracellular proteases in the presence of OA. On the other hand, the cultural filtrates of the Cmoxdc1-disrupted mutants in OA-amended media showed enhanced antifungal activity, possibly because of increased production of antifungal substances under acidic pH condition resulted from reduced Cmoxdc1-mediated OA degradation. This study provides direct genetic evidence of OA degradation regulating mycoparasitism and antibiosis of Cm against Ss, and sheds light on the sophisticated strategies of Cm in interacting with metabolically active mycelia and dormant sclerotia of Ss.

A deep learning model for translating CT to ventilation imaging: analysis of accuracy and impact on functional avoidance radiotherapy planning.

PURPOSE: Radiotherapy planning incorporating functional lung images has the potential to reduce pulmonary toxicity. Free-breathing 4DCT-derived ventilation image (CTVI) may help quantify lung function. This study introduces a novel deep-learning model directly translating planning CT images into CTVI. We investigated the accuracy of generated images and the impact on functional avoidance planning. MATERIALS AND METHODS: Paired planning CT and 4DCT scans from 48 patients with NSCLC were randomized to training (n = 41) and testing (n = 7) data sets. The ventilation maps were generated from 4DCT using a Jacobian-based algorithm to provide ground truth labels (CTVI4DCT). A 3D U-Net-based model was trained to map CT to synthetic CTVI (CTVISyn) and validated using fivefold cross-validation. The highest-performing model was applied to the testing set. Spearman's correlation (rs) and Dice similarity coefficient (DSC) determined voxel-wise and functional-wise concordance between CTVI4DCT and CTVISyn. Three plans were designed per patient in the testing set: one clinical plan without CTVI and two functional avoidance plans combined with CTVI4DCT or CTVISyn, aimed at sparing high-functional lungs defined as the top 50% of the percentile ventilation ranges. Dose-volume (DVH) parameters regarding the planning target volume (PTV) and organs at risk (OARs) were recorded. Radiation pneumonitis (RP) risk was estimated using a dose-function (DFH)-based normal tissue complication probability (NTCP) model. RESULTS: CTVISyn showed a mean rs value of 0.65 ± 0.04 compared to CTVI4DCT. Mean DSC values over the top 50% and 60% of ventilation ranges were 0.41 ± 0.07 and 0.52 ± 0.10, respectively. In the test set (n = 7), all patients' RP-risk benefited from CTVI4DCT-guided plans (Riskmean_4DCT_vs_Clinical: 29.24% vs. 49.12%, P = 0.016), and six patients benefited from CTVISyn-guided plans (Riskmean_Syn_vs_Clinical: 31.13% vs. 49.12%, P = 0.022). There were no significant differences in DVH and DFH metrics between CTVISyn and CTVI4DCT-guided plan (P > 0.05). CONCLUSION: Using deep-learning techniques, CTVISyn generated from planning CT exhibited a moderate-to-high correlation with CTVI4DCT. The CTVISyn-guided plans were comparable to the CTVI4DCT-guided plans, effectively reducing pulmonary toxicity in patients while maintaining acceptable plan quality. Further prospective trials are needed to validate these findings.

CT ventilation image-guided helical Tomotherapy at sparing functional lungs for locally advanced lung cancer: analysis of dose-function metrics and the impact on pulmonary toxicity.

PURPOSE: CT ventilation image (CTVI)-guided radiotherapy that selectively avoids irradiating highly-functional lung regions has potential to reduce pulmonary toxicity. Considering Helical TomoTherapy (HT) has higher modulation capabilities, we investigated the capability and characteristic of HT at sparing functional lungs for locally advanced lung cancer. METHODS AND MATERIALS: Pretreatment 4DCT scans were carried out for 17 patients. Local lung volume expansion (or contraction) during inspiration is related to the volume change at a given lung voxel and is used as a surrogate for ventilation. The ventilation maps were generated from two sets of CT images (peak-exhale and peak-inhale) by deformable registration and a Jacobian-based algorithm. Each ventilation map was normalized to percentile images. Six plans were designed for each patient: one anatomical plan without ventilation map and five functional plans incorporating ventilation map which designed to spare varying degrees of high-functional lungs that were defined as the top 10%, 20%, 30%, 40%, and 50% of the percentile ventilation ranges, respectively. The dosimetric and evaluation factors were recorded regarding planning target volume (PTV) and other organs at risk (OARs), with particular attention to the dose delivered to total lung and functional lungs. An established dose-function-based normal tissue complication probability (NTCP) model was used to estimate risk of radiation pneumonitis (RP) for each scenario. RESULTS: Patients were divided into a benefit group (8 patients) and a non-benefit group (9 patients) based on whether the RP-risk of functional plan was lower than that of anatomical plan. The distance between high-ventilated region and PTV, as well as tumor volume had significant differences between the two groups (P < 0.05). For patients in the benefit group, the mean value of fV5, fV10, fV20, and fMLD (functional V5, V10, V20, and mean lung dose, respectively) were significantly lower starting from top 30% functional plan than in anatomical plan (P < 0.05). With expand of avoidance region in functional plans, the dose coverage of PTV is not sacrificed (P > 0.05) but at the cost of increased dose received by OARs. CONCLUSION: Ventilation image-guided HT plans can reduce the dose received by highly-functional lung regions with a range up to top 50% ventilated area. The spatial distribution of ventilation and tumor size were critical factors to better select patients who could benefit from the functional plan.

Conductive MOF on ZIF-Derived Carbon Fibers as Superior Anode in Sodium-Ion Battery.

Superior specific capacity, high-rate capability, and long-term cycling stability are essential to anode materials in sodium-ion batteries, and conductive metal-organic frameworks (cMOF) with good electronic and ionic conductivity may satisfy these requirements. Herein, conductive neodymium cMOF (Nd-cMOF) produced in situ on the zeolitic imidazolate framework (ZIF)-derived carbon fiber (ZIF-CFs) platform is used to synthesize the Nd-cMOF/ZIF-CFs hierarchical structure. Four types of ZIFs with different pore diameters are prepared by electrospinning. In this novel structure, ZIF-CFs provide the electroconductivity, flexible porous structure, and mechanical stability, while Nd-cMOF provides the interfacial kinetic activity, electroconductivity, ample space, and volume buffer, consequently giving rise to robust structural integrity and excellent conductivity. The sodium-ion battery composed of the Nd-cMOF/ZIF-10-CFs anode has outstanding stability and electrochemical properties, such as a specific capacity of 480.5 mAh g-1 at 0.05 A g-1 as well as capacity retention of 84% after 500 cycles.

A Case-Control Study on Factors of HPV Vaccination for Mother and Daughter in China.

(1) Background: To explore the influencing factors of human papillomavirus (HPV) vaccination among mothers and daughters so as to provide evidence and strategies for improving the HPV vaccination rate of 9-18-years-old girls. (2) A questionnaire survey was conducted among the mothers of 9-18-year-old girls from June to August 2022. The participants were divided into the mother and daughter vaccinated group (M1D1), the mother-only vaccinated group (M1D0), and the unvaccinated group (M0D0). Univariate tests, the logistic regression model, and the Health Belief Model (HBM) were employed to explore the influencing factors. (3) Results: A total of 3004 valid questionnaires were collected. According to the regions, Totally 102, 204, and 408 mothers and daughters were selected from the M1D1, M1D0, and M0D0 groups, respectively. The mother having given her daughter sex education (OR = 3.64; 95%CI 1.70, 7.80), the mother's high perception of disease severity (OR = 1.79; 95%CI 1.02, 3.17), and the mother's high level of trust in formal information (OR = 2.18; 95%CI 1.26, 3.78) were all protective factors for both the mother and her daughter's vaccination. The mother's rural residence (OR = 0.51; 95%CI 0.28, 0.92) was a risk factor for vaccination of both mother and daughter. The mother's education of high school or above (OR = 2.12; 95%CI 1.06, 4.22), the mother's high level of HPV and HPV vaccine knowledge (OR = 1.72; 95%CI 1.14, 2.58), and the mother's high level of trust in formal information (OR = 1.72; 95%CI 1.15, 2.57) were protective factors of mother-only vaccination. The older the mother (OR = 0.95; 95%CI 0.91, 0.99) was classed as a risk factor for mother-only vaccination. "Waiting until the daughters are older to receive the 9-valent vaccine" is the main reason why the daughters of M1D0 and M0D0 are not vaccinated". (4) Chinese mothers had a high willingness to vaccinate their daughters with the HPV vaccine. The higher education level of the mother, giving sex education to the daughter, the older ages of mothers and daughters, the mother's high level of HPV and HPV vaccine knowledge, a high level of perception of the disease severity, and a high level of trust in formal information were promoting factors of HPV vaccination for mother and daughter, and rural residence was a risk factor to vaccination. To promote HPV vaccination in girls from 9-18 years old, communities could provide health education to rural mothers with low education levels; the government could advocate for HPV vaccination through issuing policy documents; and doctors and the CDC could popularize the optimal age for HPV vaccination to encourage mothers to vaccinate their daughters at the age of 9-14 years old.

Tadr is an axonal histidine transporter required for visual neurotransmission in Drosophila.

Neurotransmitters are generated by de novo synthesis and are essential for sustained, high-frequency synaptic transmission. Histamine, a monoamine neurotransmitter, is synthesized through decarboxylation of histidine by histidine decarboxylase (Hdc). However, little is known about how histidine is presented to Hdc as a precursor. Here, we identified a specific histidine transporter, TADR (torn and diminished rhabdomeres), which is required for visual transmission in Drosophila. Both TADR and Hdc localized to neuronal terminals, and mutations in tadr reduced levels of histamine, thus disrupting visual synaptic transmission and phototaxis behavior. These results demonstrate that a specific amino acid transporter provides precursors for monoamine neurotransmitters, providing the first genetic evidence that a histidine amino acid transporter plays a critical role in synaptic transmission. These results suggest that TADR-dependent local de novo synthesis of histamine is required for synaptic transmission.

Drosophila HisT is a specific histamine transporter that contributes to histamine recycling in glia.

Histamine is an important monoamine neurotransmitter that regulates multiple physiological activities in both vertebrates and invertebrates. Clearance and recycling of histamine are critical for sustaining histaminergic transmission. However, unlike other monoamine neurotransmitters, a histamine-specific transporter capable of clearing histamine from the synaptic cleft has not been identified. Here, through an in vitro histamine uptake screening, we identified an epithelial glia-expressing transporter, HisT (Histamine Transporter), that specifically transports histamine into cells. HisT misexpression in both pre- and postsynaptic neurons revealed a critical in vivo role for HisT in histamine transport and synaptic transmission. Last, we generated null hist alleles and demonstrated key physiological roles of HisT in maintaining histamine pools and sustaining visual transmission when the de novo synthesis of histamine synthesis was reduced. Our work identifies the first transporter that specifically recycles histamine and further indicates that the histamine clearance pathway may involve both the uptake-1 and uptake-2 transport systems.

Deciphering the Molecular Signatures Associated With Resistance to Botrytis cinerea in Strawberry Flower by Comparative and Dynamic Transcriptome Analysis.

Gray mold caused by Botrytis cinerea, which is considered to be the second most destructive necrotrophic fungus, leads to major economic losses in strawberry (Fragaria × ananassa) production. B. cinerea preferentially infects strawberry flowers and fruits, leading to flower blight and fruit rot. Compared with those of the fruit, the mechanisms of flower defense against B. cinerea remain largely unexplored. Therefore, in this study, we aimed to unveil the resistance mechanisms of strawberry flower through dynamic and comparative transcriptome analysis with resistant and susceptible strawberry cultivars. Our experimental data suggest that resistance to B. cinerea in the strawberry flower is probably regulated at the transcriptome level during the early stages of infection and strawberry flower has highly complex and dynamic regulatory networks controlling a multi-layered defense response to B. cinerea. First of all, the higher expression of disease-resistance genes but lower expression of cell wall degrading enzymes and peroxidases leads to higher resistance to B. cinerea in the resistant cultivar. Interestingly, CPKs, RBOHDs, CNGCs, and CMLs comprised a calcium signaling pathway especially play a crucial role in enhancing resistance by increasing their expression. Besides, six types of phytohormones forming a complex regulatory network mediated flower resistance, especially JA and auxin. Finally, the genes involved in the phenylpropanoid and amino acids biosynthesis pathways were gene sets specially expressed or different expression genes, both of them contribute to the flower resistance to B. cinerea. These data provide the foundation for a better understanding of strawberry gray mold, along with detailed genetic information and resistant materials to enable genetic improvement of strawberry plant resistance to gray mold.