A transition-constrained discrete hidden Markov model for automatic sleep staging

Background

Principal component analysis (PCA) has been widely employed for automatic neuronal spike sorting. Calculating principal components (PCs) is computationally expensive, and requires complex numerical operations and large memory resources. Substantial hardware resources are therefore needed for hardware implementations of PCA. General Hebbian algorithm (GHA) has been proposed for calculating PCs of neuronal spikes in our previous work, which eliminates the needs of computationally expensive covariance analysis and eigenvalue decomposition in conventional PCA algorithms. However, large memory resources are still inherently required for storing a large volume of aligned spikes for training PCs. The large size memory will consume large hardware resources and contribute significant power dissipation, which make GHA difficult to be implemented in portable or implantable multi-channel recording micro-systems.

Method

In this paper, we present a new algorithm for PCA-based spike sorting based on GHA, namely stream-based Hebbian eigenfilter, which eliminates the inherent memory requirements of GHA while keeping the accuracy of spike sorting by utilizing the pseudo-stationarity of neuronal spikes. Because of the reduction of large hardware storage requirements, the proposed algorithm can lead to ultra-low hardware resources and power consumption of hardware implementations, which is critical for the future multi-channel micro-systems. Both clinical and synthetic neural recording data sets were employed for evaluating the accuracy of the stream-based Hebbian eigenfilter. The performance of spike sorting using stream-based eigenfilter and the computational complexity of the eigenfilter were rigorously evaluated and compared with conventional PCA algorithms. Field programmable logic arrays (FPGAs) were employed to implement the proposed algorithm, evaluate the hardware implementations and demonstrate the reduction in both power consumption and hardware memories achieved by the streaming computing

Results and discussion

Results demonstrate that the stream-based eigenfilter can achieve the same accuracy and is 10 times more computationally efficient when compared with conventional PCA algorithms. Hardware evaluations show that 90.3% logic resources, 95.1% power consumption and 86.8% computing latency can be reduced by the stream-based eigenfilter when compared with PCA hardware. By utilizing the streaming method, 92% memory resources and 67% power consumption can be saved when compared with the direct implementation of GHA.

Conclusion

Stream-based Hebbian eigenfilter presents a novel approach to enable real-time spike sorting with reduced computational complexity and hardware costs. This new design can be further utilized for multi-channel neuro-physiological experiments or chronic implants.     

Type III polyketide synthases in natural product biosynthesis

Polyketides represent an important class of biologically active and structurally diverse compounds in nature. They are synthesized from acyl-coenzyme A substrates by polyketide synthases (PKSs). PKSs are classified into three groups: types I, II, and III. This article introduces recent studies on type III PKSs identified from plants, bacteria, and fungi, and describes the catalytic functions of these enzymes in detail. Plant type III PKSs have been widely studied, as exemplified by chalcone synthase, which plays an important role in the synthesis of plant metabolites. Bacterial type III PKSs fall into five groups, many of which were identified from Streptomyces, a genus that has been well known for its production of bioactive molecules and genetic alterability. Although it was believed that type III PKSs exist exclusively in plants and bacteria, recent fungal genome sequencing projects and biochemical studies revealed the presence of type III PKSs in filamentous fungi, which provides a new chance to study fungal secondary metabolism and synthesize "unnatural" natural products. Type III PKSs have been used for the biosynthesis of novel molecules through precursor-directed and structure-based mutagenesis approaches.     

The effects of starvation on digestive tract function and structure in juvenile southern catfish (Silurus meridionalis Chen)

The size and functional capacity of the gastrointestinal (GI) tract and associated organs vary in response to environmental cues. The GI tract and associated organs are also very metabolically active in animals. Hence, animals may reduce the size and function of their GI tract to conserve energy when deprived of food. The main aims of this study were to investigate how Silurus meridionalis regulates the function and structure of its GI tract and associated organs during starvation. Starvation induced a decrease in both maintenance metabolism (MO(2rest), decreased by approximately 50%) and respiratory frequency (indicated by double side gill activity and notated as f(R), decreased by 29%). Lipase, trypsin and aminopeptidase-A showed a similar reduction in mass-specific activities during starvation, but pepsin and α-amylase did not. The starvation of experimental fish resulted in a significant reduction in body weight, the wet mass of the liver and the digestive-somatic system, the hepato-somatic index and the condition factor whereas the wet masses of the GI tract, pancreas, gall bladder and the relative intestinal length did not vary significantly during starvation. The reduction in liver wet mass was the main reason for the decrease in the wet mass of digestive-somatic system in this species. Only the mucosal area of the PI was affected significantly by starvation, decreasing by 34% at the end of the experiment. S. meridionalis displayed a decreasing intestinal mucosal area towards the distal intestine, and this gradient was not affected by starvation. The morphology and structure of both the GI tract and the liver were greatly down-regulated, as indicated by decreases in liver cell size, the mucosal thickness of the stomach and intestine, the density of goblet cells and microvilli surface area (MVSA), implying that food deprivation greatly impaired the digestive and absorptive functions of the GI tract in S. meridionalis. When deprived of food, S. meridionalis can endure harsh periods of starvation and adaptively down-regulate the function and structure of the digestive tract with physiological and biochemical strategies.     

Delicate analysis of post-translational modifications on Dishevelled 3

The Wnt/β-catenin signaling pathway plays a critical role in multiple developmental events during embryogenesis and adult tissue homeostasis. Dishevelled (Dvl) is an important component of Wnt/β-catenin signaling pathway, although the modification, especially phosphorylation, seems closely related to the activity and stability of Dvl, the overall modification status of Dvl is still poorly understood. In this study, we focused on low abundant Dvl3, one of the three Dvl isoforms. Using affinity purification of different sources of Dvl3, followed by digestion with both trypsin and chymotrypsin, we systematically analyzed the overall modification status of Dvl3 with liquid chromatography coupled LTQ-Orbitrap. Altogether, we confidently identified Dvl3 with more than 50% sequence coverage, including 6 phosphorylation, 4 methylation, and 1 dimethylation sites. Most of the identified modification sites were novel and located in the linker region between different motifs. Subsequently, the validity of modified peptides was confirmed by synthetic modified peptides. Finally, SRM analysis was performed to verify and quantify the successive change of one dimethylation site on Dvl3 in vivo during Wnt signaling. Taken together, our study elucidated the existence of a novel post-translational modification on Dvl3 and provided a delicate experimental procedure for analysis of modification on low abundant proteins.     

Identification of new autoantigens for primary biliary cirrhosis using human proteome microarrays

Primary biliary cirrhosis (PBC) is a chronic cholestatic liver disease of unknown etiology and is considered to be an autoimmune disease. Autoantibodies are important tools for accurate diagnosis of PBC. Here, we employed serum profiling analysis using a human proteome microarray composed of about 17,000 full-length unique proteins and identified 23 proteins that correlated with PBC. To validate these results, we fabricated a PBC-focused microarray with 21 of these newly identified candidates and nine additional known PBC antigens. By screening the PBC microarrays with additional cohorts of 191 PBC patients and 321 controls (43 autoimmune hepatitis, 55 hepatitis B virus, 31 hepatitis C virus, 48 rheumatoid arthritis, 45 systematic lupus erythematosus, 49 systemic sclerosis, and 50 healthy), six proteins were confirmed as novel PBC autoantigens with high sensitivities and specificities, including hexokinase-1 (isoforms I and II), Kelch-like protein 7, Kelch-like protein 12, zinc finger and BTB domain-containing protein 2, and eukaryotic translation initiation factor 2C, subunit 1. To facilitate clinical diagnosis, we developed ELISA for Kelch-like protein 12 and zinc finger and BTB domain-containing protein 2 and tested large cohorts (297 PBC and 637 control sera) to confirm the sensitivities and specificities observed in the microarray-based assays. In conclusion, our research showed that a strategy using high content protein microarray combined with a smaller but more focused protein microarray can effectively identify and validate novel PBC-specific autoantigens and has the capacity to be translated to clinical diagnosis by means of an ELISA-based method.     

Identification of candidate biomarkers for early detection of human lung squamous cell cancer by quantitative proteomics

To discover novel biomarkers for early detection of human lung squamous cell cancer (LSCC) and explore possible mechanisms of LSCC carcinogenesis, iTRAQ-tagging combined with two dimensional liquid chromatography tandem MS analysis was used to identify differentially expressed proteins in human bronchial epithelial carcinogenic process using laser capture microdissection-purified normal bronchial epithelium (NBE), squamous metaplasia (SM), atypical hyperplasia (AH), carcinoma in situ (CIS) and invasive LSCC. As a result, 102 differentially expressed proteins were identified, and three differential proteins (GSTP1, HSPB1 and CKB) showing progressively expressional changes in the carcinogenic process were selectively validated by Western blotting. Immunohistochemistry was performed to detect the expression of the three proteins in an independent set of paraffin-embedded archival specimens including various stage tissues of bronchial epithelial carcinogenesis, and their ability for early detection of LSCC was evaluated by receiver operating characteristic analysis. The results showed that the combination of the three proteins could perfectly discriminate NBE from preneoplastic lesions (SM, AH and CIS) from invasive LSCC, achieving a sensitivity of 96% and a specificity of 92% in discriminating NBE from preneoplatic lesions, a sensitivity of 100% and a specificity of 98% in discriminating NBE from invasive LSCC, and a sensitivity of 92% and a specificity of 91% in discriminating preneoplastic lesions from invasive LSCC, respectively. Furthermore, we knocked down GSTP1 in immortalized human bronchial epithelial cell line 16HBE cells, and then measured their susceptibility to carcinogen benzo(a)pyrene-induced cell transformation. The results showed that GSTP1 knockdown significantly increased the efficiency of benzo(a)pyrene-induced 16HBE cell transformation. The present data first time show that GSTP1, HSPB1 and CKB are novel potential biomarkers for early detection of LSCC, and GSTP1 down-regulation is involved in human bronchial epithelial carcinogenesis.     

Secretome-derived isotope tags (SDIT) reveal adipocyte-derived apolipoprotein C-I as a predictive marker for cardiovascular disease

We developed a quantitative strategy, named secretome-derived isotopic tag (SDIT), to concurrently identify and quantify the adipocyte-secreted plasma proteins from normal and high-fat-diet (HFD) induced obese mice, based on the application of isotope-labeled secreted proteins from cultured mouse adipocytes as internal standards. We detected 197 proteins with significant changes between normal and obese mice plasma. Importantly, a novel adipocyte-secreted plasma protein, apolipoprotein C-I (apoC-I), significantly increased in the obese mice plasma. The expression and secretion of adipocyte apoC-I was detected in differentiated 3T3-L1 and primary rat adipocytes. Our in vitro experiments proved that functional Golgi apparatus was required for apoC-I secretion. Additionally, obese mice had increased apoC-I production in adipose tissue. Population survey of 367 participants showed that the plasma level of apoC-I was significantly increased in obese individuals compared with healthy individuals. After multiple adjustments for age and sex, the odds ratios for risk factors of cardiovascular disease including high LDL cholesterol, hypercholesterolemia, and hypertriglyceridemia, respectively, were used to compare the highest with the lowest apoC-I quartile. Taken together, our studies provide a novel strategy to concurrently identify and quantify tissue-specific secreted proteins. This strategy can be used to identify the largest global characterization of adipocyte-derived plasma proteome and provides a potential disease-related biomarker for clinical diagnoses. By selectively analyzing adipocyte-secreted proteins in plasma from obese vs lean murine and/or human subjects, we discovered that apoC-I is an adipocyte-secreted plasma protein and a predictive marker for cardiovascular disease.     

Draft Genome Sequence of Aspergillus oryzae Strain 3.042

Aspergillus oryzae is the most important fungus for the traditional fermentation in China and is particularly important in soy sauce fermentation. We report the 36,547,279-bp draft genome sequence of A. oryzae 3.042 and compared it to the published genome sequence of A. oryzae RIB40.