Generalizable Sample-Efficient Siamese Autoencoder for Tinnitus Diagnosis in Listeners With Subjective Tinnitus.

Electroencephalogram (EEG)-based neurofeedback has been widely studied for tinnitus therapy in recent years. Most existing research relies on experts' cognitive prediction, and studies based on machine learning and deep learning are either data-hungry or not well generalizable to new subjects. In this paper, we propose a robust, data-efficient model for distinguishing tinnitus from the healthy state based on EEG-based tinnitus neurofeedback. We propose trend descriptor, a feature extractor with lower fineness, to reduce the effect of electrode noises on EEG signals, and a siamese encoder-decoder network boosted in a supervised manner to learn accurate alignment and to acquire high-quality transferable mappings across subjects and EEG signal channels. Our experiments show the proposed method significantly outperforms state-of-the-art algorithms when analyzing subjects' EEG neurofeedback to 90dB and 100dB sound, achieving an accuracy of 91.67%-94.44% in predicting tinnitus and control subjects in a subject-independent setting. Our ablation studies on mixed subjects and parameters show the method's stability in performance.

CsSWEET1a and CsSWEET17 Mediate Growth and Freezing Tolerance by Promoting Sugar Transport across the Plasma Membrane.

Sugars Will Eventually be Exported Transporters (SWEETs) are important in plant biological processes. Expression levels of CsSWEET1a and CsSWEET17 are induced by cold acclimation (CA) and cold stress in Camellia sinensis. Here, we found that CsSWEET17 was alternatively spliced, and its exclusion (Ex) transcript was associated with the CA process. Both plasma membrane-localized CsSWEET1a and CsSWEET17 transport hexoses, but cytoplasm-localized CsSWEET17-Ex does not. These results indicate that alternative splicing may be involved in regulating the function of SWEET transporters in response to low temperature in plants. The extra C-terminal of CsSWEET17, which is not found in the tonoplast fructose transporter AtSWEET17, did not affect its plasma membrane localization but promoted its sugar transport activities. The overexpression (OE) of CsSWEET1a and CsSWEET17 genes resulted in an increased sugar uptake in Arabidopsis, affecting plant germination and growth. The leaf and seed sizes of the CsSWEET17-OE lines were significantly larger than those of the wild type. Moreover, the OE of CsSWEET1a and CsSWEET17 significantly reduced the relative electrolyte leakage levels under freezing stress. Compared with the wild type, the expression of AtCWINV genes was suppressed in both CsSWEET1a-OE and CsSWEET17-OE lines, indicating the alteration in sugar contents in the cell walls of the OE lines. Furthermore, the interaction between CsSWEET1a and CsSWEET17 was confirmed using yeast two-hybrid and bimolecular fluorescence complementation assays. We showed that CsSWEET1a and CsSWEET17 form homo-/heterodimers in the plasma membrane and mediate the partitioning of sugars between the cytoplasm and the apoplast, thereby regulating plant growth and freezing tolerance.

Characterization of CBL-CIPK signaling complexes and their involvement in cold response in tea plant.

Calcineurin B-like (CBL) proteins, a class of Ca2+-binding proteins, play vital roles in calcium signal transduction by interacting specifically with CBL-interacting protein kinases (CIPKs), and these two gene families and their interacting complexes are involved in regulating plant responses to various environmental stimuli. In the present study, eight CBL and 25 CIPK genes were identified in tea plant and divided into four and five subfamilies, respectively. Analysis of the expression of these genes in response to abiotic stresses (mature leaves treated with cold, salinity, and PEG and young shoots treated with cold) revealed that CsCBL1/3/5 and CsCIPK1/4/5/6a/7/8/10b/10c/12/14a/19/23a/24 could be induced by at least two stresses. Under cold stress, CsCBL9 and CsCIPK4/6a/6b/7/11/14b/19/20 were upregulated in both mature leaves and young shoots, CsCBL1/3/5 and CsCIPK1/8/10a/10b/10c/12/14a/23a/24 were induced only in mature leaves, and CsCIPK5/25 were induced only in young shoots. Yeast two-hybrid analysis showed that CsCBL1 could interact with CsCIPK1/10b/12 but not with CsCIPK6a/7/11/14b/20. CsCBL9 was found to interact with CsCIPK1/10b/12/14b but not with CsCIPK6a/7/11/20. These results suggest divergent responses to cold stress regulated by CBL-CIPK complexes between tea plant and Arabidopsis, as well as between mature leaves and young shoots in tea plant. A model of Ca2+-CsCBL-CsCIPK module-mediated abiotic stress signaling in tea plant is proposed.

ABA-dependent bZIP transcription factor, CsbZIP18, from Camellia sinensis negatively regulates freezing tolerance in Arabidopsis.

KEY MESSAGE: Overexpression of the tea plant gene CsbZIP18 in Arabidopsis impaired freezing tolerance, and CsbZIP18 is a negative regulator of ABA signaling and cold stress. Basic region/leucine zipper (bZIP) transcription factors play important roles in the abscisic acid (ABA) signaling pathway and abiotic stress response in plants. However, few bZIP transcription factors have been functionally characterized in tea plants (Camellia sinensis). In this study, a bZIP transcription factor, CsbZIP18, was found to be strongly induced by natural cold acclimation, and the expression level of CsbZIP18 was lower in cold-resistant cultivars than in cold-susceptible cultivars. Compared with wild-type (WT) plants, Arabidopsis plants constitutively overexpressing CsbZIP18 exhibited decreased sensitivity to ABA, increased levels of relative electrolyte leakage (REL) and reduced values of maximal quantum efficiency of photosystem II (Fv/Fm) under freezing conditions. The expression of ABA homeostasis- and signal transduction-related genes and abiotic stress-inducible genes, such as RD22, RD26 and RAB18, was suppressed in overexpression lines under freezing conditions. However, there was no significant change in the expression of genes involved in the C-repeat binding factor (CBF)-mediated ABA-independent pathway between WT and CsbZIP18 overexpression plants. These results indicate that CsbZIP18 is a negative regulator of freezing tolerance via an ABA-dependent pathway.

The involvements of calcium-dependent protein kinases and catechins in tea plant [Camellia sinensis (L.) O. Kuntze] cold responses.

Temperature is one of the most important environmental factors limiting tea plant growth and tea production. Previously we reported that both Ca2+ and ROS signals play important roles in tea plant cold acclimation. Here, we identified 26 CsCPK transcripts, analyzed their phylogenetic and sequence characters, and detected their transcriptions to monitor Ca2+ signaling status. Tissue-specific expression profiles indicated that most CsCPK genes were constitutively expressed in tested tissues, suggesting their possible roles in development. Cold along with calcium inhibitor assays suggested that CsCPKs are important cold regulators and CsCPK30/5/4/9 maybe the key members. Moreover, LaCl3 or EGTA pre-treatment could result in impaired Ca2+ signaling and compromised cold-responding network, but higher catechins accumulation revealed their potential positive roles in cold responses. Those findings indicated that catechins and other secondary metabolites in tea plant may form an alternative cold-responding network that closely correlated with Ca2+ signaling status.

Tea plant SWEET transporters: expression profiling, sugar transport, and the involvement of CsSWEET16 in modifying cold tolerance in Arabidopsis.

KEY MESSAGE: Thirteen SWEET transporters were identified in Camellia sinensis and the cold-suppression gene CsSWEET16 contributed to sugar compartmentation across the vacuole and function in modifying cold tolerance in Arabidopsis. The sugars will eventually be exported transporters (SWEET) family of sugar transporters in plants is a recently identified protein family of sugar uniporters that contain seven transmembrane helices harbouring two MtN3 motifs. SWEETs play important roles in various biological processes, including plant responses to environmental stimuli. In this study, 13 SWEET transporters were identified in Camellia sinensis and were divided into four clades. Transcript abundances of CsSWEET genes were detected in various tissues. CsSWEET1a/1b/2a/2b/2c/3/9b/16/17 were expressed in all of the selected tissues, whereas the expression of CsSWEET5/7/9a/15 was not detected in some tissues, including those of mature leaves. Expression analysis of nine CsSWEET genes in leaves in response to abiotic stresses, natural cold acclimation and Colletotrichum camelliae infection revealed that eight CsSWEET genes responded to abiotic stress, while CsSWEET3 responded to C. camelliae infection. Functional analysis of 13 CsSWEET activities in yeast revealed that CsSWEET1a/1b/7/17 exhibit transport activity for glucose analogues and other types of hexose molecules. Further characterization of the cold-suppression gene CsSWEET16 revealed that this gene is localized in the vacuolar membrane. CsSWEET16 contributed to sugar compartmentation across the vacuole and function in modifying cold tolerance in Arabidopsis. Together, these findings demonstrate that CsSWEET genes play important roles in the response to abiotic and biotic stresses in tea plants and provide insights into the characteristics of SWEET genes in tea plants, which could serve as the basis for further functional identification of such genes.

A sensor-based wrist pulse signal processing and lung cancer recognition.

Pulse diagnosis is an efficient method in traditional Chinese medicine for detecting the health status of a person in a non-invasive and convenient way. Jin's pulse diagnosis (JPD) is a very efficient recent development that is gradually recognized and well validated by the medical community in recent years. However, no acceptable results have been achieved for lung cancer recognition in the field of biomedical signal processing using JPD. More so, there is no standard JPD pulse feature defined with respect to pulse signals. Our work is designed mainly for care giving service conveniently at home to the people having lung cancer by proposing a novel wrist pulse signal processing method, having an insight from JPD. We developed an iterative slide window (ISW) algorithm to segment the de-noised signal into single periods. We analyzed the characteristics of the segmented pulse waveform and for the first time summarized 26 features to classify the pulse waveforms of healthy individuals and lung cancer patients using a cubic support vector machine (CSVM). The result achieved by the proposed method is found to be 78.13% accurate.

Identification of a novel bZIP transcription factor in Camellia sinensis as a negative regulator of freezing tolerance in transgenic arabidopsis.

Background and Aims: Basic region/leucine zipper (bZIP) transcription factors play vital roles in the abiotic stress response of plants. However, little is known about the function of bZIP genes in Camellia sinensis . Methods: CsbZIP6 was overexpressed in Arabidopsis thaliana . Effects of CsbZIP6 overexpression on abscisic acid (ABA) sensitivity, freezing tolerance and the expression of cold-responsive genes in arabidopsis were studied. Key Results: CsbZIP6 was induced during cold acclimation in tea plant. Constitutive overexpression of CsbZIP6 in arabidopsis lowered the plants' tolerance to freezing stress and ABA exposure during seedling growth. Compared with wild-type (WT) plants, CsbZIP6 overexpression (OE) lines exhibited increased levels of electrolyte leakage (EL) and malondialdehyde (MDA) contents, and reduced levels of total soluble sugars (TSS) under cold stress conditions. Microarray analysis of transgenic arabidopsis revealed that many differentially expressed genes (DEGs) between OE lines and WT plants could be mapped to 'response to cold' and 'response to water deprivation' terms based on Gene Ontology analysis. Interestingly, CsbZIP6 overexpression repressed most of the cold- and drought-responsive genes as well as starch metabolism under cold stress conditions. Conclusions: The data suggest that CsbZIP6 functions as a negative regulator of the cold stress response in A. thaliana , potentially by down-regulating cold-responsive genes.

[Analysis of allergens characteristic in 1172 patients with allergic rhinitis in Changzhou area].

OBJECTIVE: To determine the distribution of allergens in patients with allergic rhinitis during from 2008 to 2015 in Changzhou area. METHOD: Allergy Screen method was used to detect the specifical-allergen IgE levels of 1172 patients with allergic rhinitis. Among the patients, the distribution of all allergens was analyzed. The positive rate was compared with age, gender, season and so on. RESULT: The most common allergens in allergic rhinitis patients in Changzhou were dust mite, fungus, house dust, milk, dander of dog, weed mixture, farina and dander of cat. The more higher positive rates of dust mite, fungus, house dust, milk, dander of dog, dander of cat, eggs were found in teenager group than adult group (P < 0.05). There were more higer positive rates of weed mixture, farina, cashew, cockroaches and crab in teenager group than adult group (P < 0.05). There was no significant difference of positive rate between female group and male group. There was significant difference of variation with seasons. CONCLUSION: Dust mite, fungus and house dust were the most common allergens among patiens with allergic rhinitis in Changzhou area. The positive rates of allergens varied with ages and seasons.

From Ancient Chinese Medicine to a Novel Approach to Treat Cocaine Addiction.

Pharmacologic agents for CNS disorders are often inhibitors that occupy receptors, with frequent unavoidable side effects likely due to continuous binding. This review summarizes development of a novel aldehyde dehydrogenase 2 (ALDH2) inhibitor that specifically targets unique drug related episodic surges in dopamine (DA), a pathophysiologic mechanism that appears to underlie much of drug-seeking behavior. We have synthesized highly selective novel ALDH2 inhibitors (ALDH2i) that block alcohol- and cocaine cue-induced surges in nucleus accumbens (NAc) DA and prevent reinstatement of alcohol heavy drinking, cocaine self-administration and reinstatement of cocaine relapse-like behavior. The mechanism of action of ALDH2i depends on inhibiting dopamine aldehyde (DOPAL) clearance by ALDH2, enabling unmetabolized DOPAL to condense with DA to generate tetrahydropapaveroline (THP). THP selectively inhibits the activated (phosphorylated) tyrosine hydroxylase (TH) to suppress DA synthesis. Selective inhibition of ALDH2 appears to have therapeutic potential for treating cue-induced drug relapse, a major unmet need for treating addicted subjects.

PECTATE LYASE-LIKE 9 from Brassica campestris is associated with intine formation.

Brassica campestris pectate lyase-like 9 (BcPLL9) was previously identified as a differentially expressed gene both in buds during late pollen developmental stage and in pistils during fertilization in Chinese cabbage. To characterize the gene's function, antisense-RNA lines of BcPLL9 (bcpll9) were constructed in Chinese cabbage. Self- and cross-fertilization experiments harvested half seed yields when bcpll9 lines were used as pollen donors. In vivo and in vitro pollen germination assays showed that nearly half of the pollen tubes in bcpll9 were irregular with shorter length and uneven surface. Aniline blue staining identified abnormal accumulation of a specific bright blue unknown material in the bcpll9 pollen portion. Scanning electron microscopy observation verified the abnormal outthrust material to be near the pollen germinal furrows. Transmission electron microscopy observation revealed the internal endintine layer was overdeveloped and predominantly occupied the intine. This abnormally formed intine likely induced the wavy structure and growth arrest of the pollen tube in half of the bcpll9 pollen grains, which resulted in less seed yields. Collectively, this study presented a novel PLL gene that has an important function in B. campestris intine formation.

PECTATE LYASE-LIKE10 is associated with pollen wall development in Brassica campestris.

PECTATE LYASE-LIKE10 (PLL10) was previously identified as one of the differentially expressed genes both in microspores during the late pollen developmental stages and in pistils during the fertilization process in Chinese cabbage (Brassica campestris ssp. chinensis). Here, antisense-RNA was used to study the functions of BcPLL10 in Chinese cabbage. Abnormal pollen was identified in the transgenic lines (bcpll10-4, -5, and -6). In fertilization experiments, fewer seeds were harvested when the antisense-RNA lines were used as pollen donor. In vivo and in vitro pollen germination assays less germinated pollen tubes were observed in bcpll10 lines. Scanning electron microscopy observation verified that the tryphine materials were over accumulated around the pollen surface and sticked them together in bcpll10. Moreover, transmission electron microscopy observation revealed that the internal endintine was overdeveloped and predominantly occupied the intine, and disturbed the normal proportional distribution of the two layers in the non-germinal furrow region; and no obvious demarcation existed between them in the germinal furrow region in the bcpll10 pollen. Collectively, this study presented a novel PLL gene that played an important role during the pollen wall development in B. campestris, which may also possess potential importance for male sterility usage in agriculture.

BcMF21 is important for pollen development and germination in Brassica campestris ssp. chinensis.

Brassica campestris Male Fertility 21 (BcMF21) was previously isolated from the flower buds of Chinese cabbage (Brassica campestris L. ssp. chinensis Makino, syn. B. rapa ssp. chinensis) and expressed specifically in tapetum and microspores during the meiosis stage and the uninucleate stage of microspore development. Here, we used antisense RNA technology to knock down the expression level of BcMF21 in B. campestris and analyzed the phenotype of the transgenic plants. Alexander staining and scanning electron microscope revealed sterility and exine deformities in the mature pollen grains of BcMF21 antisense RNA transgenic plants. The germination furrow of the BcMF21 antisense RNA transgenic pollen was covered by lipid like materials. The pollen tubes burst and could not grow normally in vitro. Therefore, we presented here BcMF21 might be an important gene for pollen development and germination.

Sequence characterization and expression pattern of BcMF21, a novel gene related to pollen development in Brassica campestris ssp. chinensis.

In this report a full length cDNA, Brassica campestris Male Fertile 21 (BcMF21) was successfully isolated from one of the cDNA-amplified fragment length polymorphism (cDNA-AFLP) transcript-derived fragments (TDFs), BBP10, that was found down-regulated in the flower buds of sterile plants in Brassica campestris L. ssp. chinensis Makino genic male sterile (GMS) AB line system (Bcajh 97-01A/B). BcMF21 protein structure analysis showed a signal peptide at the N-terminus; two protein kinase C phosphorylation sites, five N-myristoylation sites and one casein kinase II phosphorylation site. The promoter region of BcMF21, a 779 bp upstream of ATG was isolated by thermal asymmetric interlaced-PCR (TAIL-PCR). Bioinformatics analysis revealed that the promoter of BcMF21 contained several classical cis-acting elements and three pollen specific elements. Transient expression analysis showed that the promoter could drive green fluorescence protein (GFP) expression. Quantitative reverse transcript-PCR analysis revealed that BcMF21 was specifically expressed in flower buds. The transcript level of BcMF21 was much lower in the sterile flower buds than in the fertile flower buds in 'Bcajh 97-01A/B' system. In situ hybridization further showed that BcMF21 was only expressed in the tetrads and the microspores at the tetrad stage and the uninucleate stage. In addition, phylogenetic analysis demonstrated that the BcMF21 was relative conserved within family Crucifereae and might be originated from the ancestor diploid B. campestris within genus Brassica according to the Triangle of U theory.

Inhibition of aldehyde dehydrogenase-2 suppresses cocaine seeking by generating THP, a cocaine use-dependent inhibitor of dopamine synthesis.

There is no effective treatment for cocaine addiction despite extensive knowledge of the neurobiology of drug addiction. Here we show that a selective aldehyde dehydrogenase-2 (ALDH-2) inhibitor, ALDH2i, suppresses cocaine self-administration in rats and prevents cocaine- or cue-induced reinstatement in a rat model of cocaine relapse-like behavior. We also identify a molecular mechanism by which ALDH-2 inhibition reduces cocaine-seeking behavior: increases in tetrahydropapaveroline (THP) formation due to inhibition of ALDH-2 decrease cocaine-stimulated dopamine production and release in vitro and in vivo. Cocaine increases extracellular dopamine concentration, which activates dopamine D2 autoreceptors to stimulate cAMP-dependent protein kinase A (PKA) and protein kinase C (PKC) in primary ventral tegmental area (VTA) neurons. PKA and PKC phosphorylate and activate tyrosine hydroxylase, further increasing dopamine synthesis in a positive-feedback loop. Monoamine oxidase converts dopamine to 3,4-dihydroxyphenylacetaldehyde (DOPAL), a substrate for ALDH-2. Inhibition of ALDH-2 enables DOPAL to condense with dopamine to form THP in VTA neurons. THP selectively inhibits phosphorylated (activated) tyrosine hydroxylase to reduce dopamine production via negative-feedback signaling. Reducing cocaine- and craving-associated increases in dopamine release seems to account for the effectiveness of ALDH2i in suppressing cocaine-seeking behavior. Selective inhibition of ALDH-2 may have therapeutic potential for treating human cocaine addiction and preventing relapse.

Suppression of heavy drinking and alcohol seeking by a selective ALDH-2 inhibitor.

BACKGROUND: Inherited human aldehyde dehydrogenase 2 (ALDH-2) deficiency reduces the risk for alcoholism. Kudzu plants and extracts have been used for 1,000 years in traditional Chinese medicine to treat alcoholism. Kudzu contains daidzin, which inhibits ALDH-2 and suppresses heavy drinking in rodents. Decreased drinking due to ALDH-2 inhibition is attributed to aversive properties of acetaldehyde accumulated during alcohol consumption. However, daidzin can reduce drinking in some rodents without necessarily increasing acetaldehyde. Therefore, a selective ALDH-2 inhibitor might affect other metabolic factors involved in regulating drinking. METHODS: Aldehyde dehydrogenase 2 inhibitors were synthesized based on the co-crystal structure of ALDH-2 and daidzin. We tested the efficacy of a highly selective reversible ALDH-2 inhibitor, CVT-10216, in models of moderate and high alcohol drinking rats. We studied 2-bottle choice and deprivation-induced drinking paradigms in Fawn Hooded (FH) rats, operant self-administration in Long Evans (LE), FH, and inbred P (iP) rats and in cue-induced reinstatement in iP rats. We also assayed blood acetaldehyde levels as well as dopamine (DA) release in the nucleus accumbens (NAc) and tested possible rewarding/aversive effects of the inhibitor in a conditioned place preference (CPP) paradigm. RESULTS: CVT-10216 increases acetaldehyde after alcohol gavage and inhibits 2-bottle choice alcohol intake in heavy drinking rodents, including deprivation-induced drinking. Moreover, CVT-10216 also prevents operant self-administration and eliminates cue-induced reinstatement of alcohol seeking even when alcohol is not available (i.e., no acetaldehyde). Alcohol stimulates DA release in the NAc, which is thought to contribute to increased drinking and relapse in alcoholism. CVT-10216 prevents alcohol-induced increases in NAc DA without changing basal levels. CVT-10216 does not show rewarding or aversive properties in the CPP paradigm at therapeutic doses. CONCLUSION: Our findings suggest that selective reversible ALDH-2 inhibitors may have therapeutic potential to reduce excessive drinking and to suppress relapse in abstinent alcoholics.

[Concentration of airborne pollen in Beijing city with burkard sampler].

OBJECTIVE: To investigate the airborne pollen concentration in Beijing city during autumn and to grade the Artemisia pollen concentration. METHOD: Burkard volumetric trap was used to sample the airborne pollen in Beijing city from August 1st 2007 to October 10th 2007. Patients only allergic to mugwort pollen were followed up, and their symptom scores and the mugwort pollen concentration were analyzed statistically. RESULT: 1) Mugwort and Humulus (including Cannabis Sativa L) were the main airborne pollen during August and September in Beijing city, accounting for 31% and 51%, respectively; 2) Mugwort pollen season was from 8th August to 8th October; 3) The daily peak concentration of Mugwort pollen was 267 g/m3, with an average of 71 g/m3, the daily peak concentration of Humulus pollen was 672 g/m3, with an average of 124 g/m3; 4) 88.5% out-patients suffering from hay fever or asthma during Autumn were allergic to mugwort, 28.2% allergic to Humulus; 5) the grading of airborne Mugwort pollen concentration: 0-14 g/m3 as grade 0, 15-40 g/m3 as grade I, 41-116 g/m3 as grade II, more than 117 g/m3 as grade III. CONCLUSION: It was the first time that Burkard volumetric sampler was employed in monitoring Mugwort and Humulus concentration in Beijing city. Average concentration of mugwort pollen was about 100 g/m3, and concentration grade III of mugwort pollen was distributed during the last ten days of August and the beginning of September.