Empirical Mode Decomposition and Wavelet Transform Based ECG Data Compression Scheme

ObjectiveIn health-care systems, compression is an essential tool to solve the storage and transmission problems. In this regard, this paper reports a new electrocardiogram (ECG) data compression scheme which employs sifting function based empirical mode decomposition (EMD) and discrete wavelet transform.MethodEMD based on sifting function is utilized to get the first intrinsic mode function (IMF). After EMD, the first IMF and four significant sifting functions are combined together. This combination is free from many irrelevant components of the signal. Discrete wavelet transform (DWT) with mother wavelet ‘bior4.4’ is applied to this combination. The transform coefficients obtained after DWT are passed through dead-zone quantization. It discards small transform coefficients lying around zero. Further, integer conversion of coefficients and run-length encoding are utilized to achieve a compressed form of ECG data.ResultsCompression performance of the proposed scheme is evaluated using 48 ECG records of the MIT-BIH arrhythmia database. In the comparison of compression results, it is observed that the proposed method exhibits better performance than many recent ECG compressors. A mean opinion score test is also conducted to evaluate the true quality of the reconstructed ECG signals.ConclusionThe proposed scheme offers better compression performance with preserving the key features of the signal very well.     

Association between the risk of coronary artery disease in South Asians and a deletion polymorphism in glutathione S-transferase M1

Background: The aim of the present study was to evaluate whether or not an elevated ischaemia-modified albumin (IMA) level provides any additional prognostic information to the validated Thrombolysis In Myocardial Infarction (TIMI) risk score in patients with ST-segment elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention (PCI). Methods: One hundred seven consecutive STEMI patients treated with primary PCI were included. The incidence of 30-day death was the prespecified primary end point. Serum IMA was measured immediately at hospital arrival. Results: The incidence of the primary end point was 6.5%. A significant predictive value of IMA in relation to the primary end point was indicated by an area under the ROC curve of 0.71 (p = 0.01). In the multivariate analysis, increased IMA remained a significant predictor of the primary end point after adjustment for TIMI risk predictors (p = 0.019). The area under the ROC curve for the TIMI risk score was 0.68 (p = 0.03). The addition of IMA to the TIMI risk score did not improve its prognostic value (area under the ROC curve 0.60, p = 0.25). Conclusion: IMA levels obtained at admission are a powerful indicator of short-term mortality in STEMI patients treated with primary PCI, but do not seem to be a marker that adds prognostic information to the validated STEMI TIMI risk score.     

Substrate specificity,plasma membrane localization,and lipid modification of the aldehyde dehydrogenase ALDH3B1

The accumulation of reactive aldehydes is implicated in the development of several disorders. Aldehyde dehydrogenases (ALDHs) detoxify aldehydes by oxidizing them to the corresponding carboxylic acids. Among the 19 human ALDHs, ALDH3A2 is the only known ALDH that catalyzes the oxidation of long-chain fatty aldehydes including C16 aldehydes (hexadecanal and trans-2-hexadecenal) generated through sphingolipid metabolism. In the present study, we have identified that ALDH3B1 is also active in vitro toward C16 aldehydes and demonstrated that overexpression of ALDH3B1 restores the sphingolipid metabolism in the ALDH3A2-deficient cells. In addition, we have determined that ALDH3B1 is localized in the plasma membrane through its C-terminal dual lipidation (palmitoylation and prenylation) and shown that the prenylation is required particularly for the activity toward hexadecanal. Since knockdown of ALDH3B1 does not cause further impairment of the sphingolipid metabolism in the ALDH3A2-deficient cells, the likely physiological function of ALDH3B1 is to oxidize lipid-derived aldehydes generated in the plasma membrane and not to be involved in the sphingolipid metabolism in the endoplasmic reticulum.     

Colon tumour secretopeptidome: Insights into endogenous proteolytic cleavage events in the colon tumour microenvironment

The secretopeptidome comprises endogenous peptides derived from proteins secreted into the tumour microenvironment through classical and non-classical secretion. This study characterised the low-M_r (< 3 kDa) component of the human colon tumour (LIM1215, LIM1863) secretopeptidome, as a first step towards gaining insights into extracellular proteolytic cleavage events in the tumour microenvironment. Based on two biological replicates, this secretopeptidome isolation strategy utilised differential centrifugal ultrafiltration in combination with analytical RP-HPLC and nanoLC-MS/MS. Secreted peptides were identified using a combination of Mascot and post-processing analyses including MSPro re-scoring, extended feature sets and Percolator, resulting in 474 protein identifications from 1228 peptides (≤ 1% q-value, ≤ 5% PEP) — a 36% increase in peptide identifications when compared with conventional Mascot (homology ionscore thresholding). In both colon tumour models, 122 identified peptides were derived from 41 cell surface protein ectodomains, 23 peptides (12 proteins) from regulated intramembrane proteolysis (RIP), and 12 peptides (9 proteins) generated from intracellular domain proteolysis. Further analyses using the protease/substrate database MEROPS, (http://merops.sanger.ac.uk/), revealed 335 (71%) proteins classified as originating from classical/non-classical secretion, or the cell membrane. Of these, peptides were identified from 42 substrates in MEROPS with defined protease cleavage sites, while peptides generated from a further 205 substrates were fragmented by hitherto unknown proteases. A salient finding was the identification of peptides from 88 classical/non-classical secreted substrates in MEROPS, implicated in tumour progression and angiogenesis (FGFBP1, PLXDC2), cell–cell recognition and signalling (DDR1, GPA33), and tumour invasiveness and metastasis (MACC1, SMAGP); the nature of the proteases responsible for these proteolytic events is unknown. To confirm reproducibility of peptide fragment abundance in this study, we report the identification of a specific cleaved peptide fragment in the secretopeptidome from the colon-specific GPA33 antigen in 4/14 human CRC models. This improved secretopeptidome isolation and characterisation strategy has extended our understanding of endogenous peptides generated through proteolysis of classical/non-classical secreted proteins, extracellular proteolytic processing of cell surface membrane proteins, and peptides generated through RIP. The novel peptide cleavage site information in this study provides a useful first step in detailing proteolytic cleavage associated with tumourigenesis and the extracellular environment. This article is part of a Special Issue entitled: An Updated Secretome.     

恶性滋养细胞肿瘤治疗、预后的评价-附169例临床分析

目的:对恶性滋养细胞肿瘤按2000年国际妇产科联盟(FIGO)预后评分标准评分并选择治疗方案的疗效进行评价.方法:恶性滋养细胞肿瘤患者169例,治疗前按2000年FIGO预后评分标准进行分期及评分,以此选择治疗方案.结果:169例患者中,绒毛膜癌49例,30例为高危,19例为低危;侵蚀性葡萄胎120例,8例为高危,112例为低危.治疗原则:低危患者以单药化疗为主,高危患者采用多药联合化疗.本组患者的1年、3年、5年生存率分别为98.8％、97.6％及96.9％.无一例因毒副反应或并发症而死亡.结论:治疗前应用2000年FIGO顸后评分系统选择恶性滋养细胞肿瘤治疗方案取得较好的临床效果,新分期系统对指导临床治疗有重大意义.     

Type 3 IP3 receptors driving oncogenesis

Type 3 Inositol 1,4,5-trisphosphate (IP₃) receptors (IP₃R3s) have been identified as anti-oncogenic channels by propelling pro-apoptotic Ca²⁺ signals to mitochondria. Yet, recent studies (Rezuchova et al, Cell Death Dis, 2019; Ueasilamongkol et al, Hepathology, 2019; Guerra et al, Gut, 2019) revealed that IP₃R3 upregulation drives oncogenesis via ER-mitochondrial Ca²⁺ crosstalk, adding complexity to IP₃R3’s role in cancer.     

Stimulation of σ1-receptor restores abnormal mitochondrial Ca mobilization and ATP production following cardiac hypertrophy

Background

We previously reported that the σ₁-receptor (σ₁R) is down-regulated following cardiac hypertrophy and dysfunction in transverse aortic constriction (TAC) mice. Here we address how σ₁R stimulation with the selective σ₁R agonist SA4503 restores hypertrophy-induced cardiac dysfunction through σ₁R localized in the sarcoplasmic reticulum (SR).

Methods

We first confirmed anti-hypertrophic effects of SA4503 (0.1–1 μM) in cultured cardiomyocytes exposed to angiotensin II (Ang II). Then, to confirm the ameliorative effects of σ₁R stimulation in vivo, we administered SA4503 (1.0 mg/kg) and the σ₁R antagonist NE-100 (1.0 mg/kg) orally to TAC mice for 4 weeks (once daily).

Results

σ₁R stimulation with SA4503 significantly inhibited Ang II-induced cardiomyocyte hypertrophy. Ang II exposure for 72 h impaired phenylephrine (PE)-induced Ca^2 + mobilization from the SR into both the cytosol and mitochondria. Treatment of cardiomyocytes with SA4503 largely restored PE-induced Ca^2 + mobilization into mitochondria. Exposure of cardiomyocytes to Ang II for 72 h decreased basal ATP content and PE-induced ATP production concomitant with reduced mitochondrial size, while SA4503 treatment completely restored ATP production and mitochondrial size. Pretreatment with NE-100 or siRNA abolished these effects. Chronic SA4503 administration also significantly attenuated myocardial hypertrophy and restored ATP production in TAC mice. SA4503 administration also decreased hypertrophy-induced impairments in LV contractile function.

Conclusions

σ₁R stimulation with the specific agonist SA4503 ameliorates cardiac hypertrophy and dysfunction by restoring both mitochondrial Ca^2 + mobilization and ATP production via σ₁R stimulation.

General significance

Our observations suggest that σ₁R stimulation represents a new therapeutic strategy to rescue the heart from hypertrophic dysfunction.     

The extrapituitary prolactin promoter polymorphism is associated with rheumatoid arthritis and anti-CCP antibodies in Mexican population

Prolactin (PRL) is a hormone–cytokine that has been involved in autoimmunity due to its immunoregulatory and lymphoproliferative effects. It is produced by various extrapituitary sites including immune cells, under control of a superdistal promoter that contains a single nucleotide polymorphism − 1149 G/T previously associated with rheumatoid arthritis (RA) susceptibility in European population. The aim of this study was to investigate the association of the extrapituitary PRL − 1149 G/T promoter polymorphism with clinical parameters, clinical activity and disability indices in RA patients from Western Mexico and to analyze the PRL mRNA expression according to the PRL − 1149 G/T promoter polymorphism in total leucocytes from RA patients and controls. We conducted a case–control study that included 258 RA patients and 333 control subjects (CS). The DNA samples were genotyped using the PCR–RFLP method and the PRL mRNA expression was determined by quantitative real time PCR. PRL serum levels and antibodies to cyclic citrullinated peptides (anti-CCP) were measured with ELISA. We found significant differences in the genotype (p = 0.022) and allelic (p = 0.046) distribution of the polymorphism between RA patients and control subjects. According to the dominant genetic model, there is an association between the T allele (GT + TT genotypes) and decreased RA susceptibility in comparison to the G allele carriers (GG genotype) (OR 0.64, 95% CI 0.45–0.92; p = 0.011). The T allele carriers (GT + TT genotypes) had lower titers of anti-CCP antibodies in comparison to the G allele carriers (GG genotype) (median, 66 U/mL vs. 125 U/mL; p = 0.03). Furthermore, the GG homozygotes had higher PRL mRNA expression in comparison to the GT heterozygotes, and this latter with respect to the TT homozygotes, in both groups (RA: 1 > 0.72 > 0.19; CS: 1 > 0.54 > 0.28). However, PRL serum levels were similar in both groups. Our results suggest that the PRL − 1149 T allele is a genetic marker for decreased RA susceptibility and is associated with lower titers of anti-CCP antibodies in Mexican population. We also suggest influence of genotype upon PRL mRNA expression.