Correlation of protein expression, Gleason score and DNA ploidy in prostate cancer

The prognosis of prostate cancer correlates with tumor differentiation. Gleason score and DNA ploidy are two prognostic factors that correlate with prognosis. We analyzed differences in protein expression in prostate cancer of high and low aggressiveness according to these measures. From 35 prostatectomy specimens, 29 cancer samples and 10 benign samples were harvested by scraping cells from cut surfaces. DNA ploidy was assessed by image cytometry. Protein preparations from cell suspensions were examined by 2-DE. Protein spots that differed quantitatively between sample groups were identified by MS fingerprinting of tryptic fragments and MS/MS sequence analysis. We found 39 protein spots with expression levels that were raised or lowered in correlation with Gleason score and/or DNA ploidy pattern (31 overexpressed in high-malignant cancer, 8 underexpressed). Of these, 30 were identified by MS. Among overexpressed proteins were heat-shock, structural and membrane proteins and enzymes involved in gene silencing, protein synthesis/degradation, mitochondrial protein import (metaxin 2), detoxification (GST-pi) and energy metabolism. Stroma-associated proteins were generally underexpressed. The protein expression of prostate cancer correlates with tumor differentiation. Potential prognostic markers may be found among proteins that are differentially expressed and the clinical value of these should be validated.     

Ozone exposure during growth affects the feeding value of rice shoots

Rising tropospheric ozone concentrations have been observed in many Asian countries in recent years. Ozone pollution reduces the yield of agricultural crops but may also affect crop quality. This study aimed at estimating the effect of ozone exposure on feeding quality of rice shoots for ruminant herbivores. Rice plants from two genotypes differing in ozone tolerance were exposed to ozone at a concentration of 120 nl/l for 18 days, and feeding value was determined by chemical analyses and in vitro incubation in rumen fluid. Rice biomass was reduced by an average of 24% in the ozone treatment as compared to the control. Moreover, ozone exposure affected various feed quality parameters. Crude protein content was lower in ozone treated plants (P<0.05). Potential gas production during the in vitro incubation for 96 h also dropped (P<0.01) due to ozone treatment, indicating reduced digestibility of the plant materials. This was explained with an increase in the antinutritive components lignin (P<0.05) and phenolics (P<0.001) due to ozone exposure. An ozone tolerant genotype exhibited a more pronounced increase in phenolics, suggesting that this may constitute a stress defense mechanism. Our results suggest that ozone may affect the feeding value of cereal straws and calls for further research in this direction.     

Comments on the rank product method for analyzing replicated experiments

Breitling et al. [1] introduced a statistical technique, the rank product method, for detecting differentially regulated genes in replicated microarray experiments. The technique has achieved widespread acceptance and is now used more broadly, in such diverse fields as RNAi analysis, proteomics, and machine learning. In this note, we relate the rank product method to linear rank statistics and provide an alternative derivation of distribution theory attending the rank product method.     

The natriuretic peptide time-course in end-stage heart failure patients supported by left ventricular assist device implant: focus on NT-proCNP

This study aimed to evaluate left ventricular assist device (LVAD) effects on natriuretic peptide (NP) prohormone plasma levels in end-stage heart failure (HF) patients, especially NT-proCNP, in order to better characterize the NP system during hemodynamic recovery by LVAD. HF patients (n=17, NYHA III-IV) undergoing LVAD were studied: 6 died of multi-organ failure syndrome (NS) and 11 survived (S). Total sequential organ failure assessment (t-SOFA) score and blood samples were obtained at admission (T1) and at 24, 72h and 1, 2, 4 weeks (T2-T6) after LVAD. In S, NT-proANP and NT-proCNP significantly increased at 24h after implantation, reaching a reduction to basal levels at 4 weeks following LVAD [NT-proANP: T1 vs. T2 p=0.017, NT-proCNP: T1 vs. T2 p=0.028, T1 vs. T3 p=0.043]. Elevated NT-proBNP plasma levels were observed at all times. In NS, NP plasma levels sustained higher with respect to S. No statistical variation was observed for NT-proCNP and NT-proANP in S and NS while NT-proBNP reached significant differences at T4 in NS. Considering S+NS, only NT-proCNP strongly correlated with t-SOFA score at T1 (rho=0.554, p=0.04) while subdividing patients NT-proCNP positively correlated in NS with t-SOFA score (rho=0.988, p=0.002) only at T4. In NS a correlation between NT-proCNP and NT-proBNP at T1 was observed (rho=-0.900, p=0.037). Both IL-6 and TNF-alpha sustained higher in NS patients than in S; in particular, statistical significance was observed for IL-6. The study of new peptides, such as NT-proCNP, would provide additional information for identifying patients who are more likely to recover.     

A derivative of the CRMP2 binding compound lanthionine ketimine provides neuroprotection in a mouse model of cerebral ischemia

Lanthionines are novel neurotrophic and neuroprotective small molecules that show promise for the treatment of neurodegenerative diseases. In particular, a recently developed, cell permeable lanthionine derivative known as LKE (lanthionine ketimine 5-ethyl ester) promotes neurite growth at low nanomolar concentrations. LKE also has neuroprotective, anti-apoptotic, and anti-inflammatory properties. Its therapeutic potential in cerebral ischemia and its mechanisms of neurotrophic action remain to be fully elucidated. Here, we hypothesize that the neuroprotective actions of LKE could result from induction or modulation of CRMP2. We found that treating primary cultured mouse neurons with LKE provided significant protection against t-butyl hydroperoxide-induced neuronal death possibly through CRMP2 upregulation. Similarly, in vivo studies showed that LKE pre and/or post-treatment protects mice against permanent distal middle cerebral artery occlusion (p-MCAO) as evidenced by lower stroke lesions and improved functional outcomes in terms of rotarod, grip strength and neurologic deficit scores in treated groups. Protein expression levels of CRMP2 were higher in brain cortices of LKE pretreated mice, suggesting that LKE’s neuroprotective activity may be CRMP2 dependent. Lower activity of cleaved PARP-1 and higher activity of SIRT-1 was also observed in LKE treated group suggesting its anti-apoptotic properties. Our results suggest that LKE has potential as a therapeutic intervention in cerebral ischemia and that part of its protective mechanism may be attributed to CRMP2 mediated action and PARP-1/SIRT-1 modulation.     

Correlation analysis of clinical parameters with epigenetic modifications in the DUX4 promoter in FSHD

The aim of our study was to identify relationships between epigenetic parameters correlating with a relaxed chromatin state of the DUX4 promoter region and clinical severity as measured by a clinical severity score or muscle pathologic changes in D4Z4 contraction-dependent (FSHD1) and –independent (FSHD2) facioscapulohumeral muscular dystrophy patients. Twenty primary fibroblast (5 control, 10 FSHD1 and 5 FSHD2) and 26 primary myoblast (9 control, 12 FSHD1 and 5 FSHD2) cultures originating from patients with FSHD and controls were analyzed. Histone modification levels were determined by chromatin immunoprecipitation. We examined correlations between the chromatin compaction score (ChCS) defined by the H3K9me3:H3K4me2 ratio and an age corrected clinical severity score (CSS) or muscle pathology score (MPS). Possible relationships were investigated using linear regression analysis and significance was tested by Pearson’s product-moment coefficient.   We found a significant difference of the ChCS between controls and patients with FSHD1 and between controls and patients with FSHD2. Tissue specific differences in ChCS were also observed. We also found a near-significant relationship between ChCS and the age corrected CSS in fibroblasts but not in myoblasts. Surprisingly, we found a strong correlation between the MPS of the vastus lateralis and the CSS. Our results confirm the D4Z4 chromatin relaxation previously shown to be associated with FSHD in a small number of samples. A possible relationship between clinical and epigenetic parameters could be established in patient fibroblasts, but not in myoblasts. The strong correlation between the MPS of the vastus lateralis and the CSS suggests that this muscle can be used to study for surrogate markers of overall disease severity.     

冠心病合并代谢综合征患者的冠状动脉病变特点及与 代谢综合征组分的相关性研究

目的:探讨冠心病合并代谢综合征(metabolic syndrome,MS)患者的冠脉病变特点及冠心病与MS各组分的相关性。方法:选取540例冠心病患者为研究对象,其中合并MS患者164例,非合并MS患者376例,并将所有患者根据MS的组分个数进行分组,比较冠心病合并MS的病变特点、MS组分个数对冠状动脉病变程度的影响及冠状动脉病变程度与代谢综合症各组分的相关性;结果:①冠心病合并MS组BMI、FBG、TG、LDL-C、TC、UA、FIB、高血压分级等指标较非MS组高,差异有统计学意义(P<0.01),HDL-C、LVEF较非MS组低,差异有显著性(P<0.01);②MS组冠脉Gensini积分较高,三支病变、主干病变发生率高,差异有显著性(P<0.01);③随着合并MS组分个数的增加,冠脉Gensini积分也逐渐增加,各组间比较有显著性差异(P<0.01);④冠脉Gensini积分与MS组分BMI、高血压分级、TG、TC、LDL-C、UA等指标存在正相关(P<0.05),与性别、HDL-C存在负相关(p<0.01);调整传统危险因素后,Gensini积分与MS的组分数显著相关(r=0.739、P<0.01)。结论:冠心病患者有较高的MS患病率,冠心病合并MS患者冠脉病变程度更重,且以多支病变、主干病变为主;随着合并MS组分个数的增加,冠脉病变程度也呈加重趋势;MS的各个组分均与冠状动脉病变程度显著相关,可以作为冠心病严重程度的预测指标。     

Risk factors and milk yield losses associated with lameness in Holstein-Friesian dairy cattle

Weekly locomotion scores on a scale of 1 to 5 were used to investigate the relationship between cattle lameness, management systems and the impact of lameness on milk production. The data were 14026 locomotion scores from 248 Holstein-Friesian cows. Cows were managed in two groups, XE (high-concentrate feed and housed indoors all year) and XM (low-concentrate feed and outdoors in summer). Analysis was performed using residual maximum likelihood. Results indicated that the most significant variables affecting locomotion were time of year when the animal was locomotion scored and management group. Cows scored during February and August had increased locomotion problems. Cows in the more intensively managed group had significantly poorer locomotion compared with those in the more extensive group. Older animals were more susceptible to lameness than heifers. Body weight, body condition score and days in milk (DIM) also accounted for significant variation in locomotion score. Poor locomotion was associated with a significant reduction in the milk yield of later lactation cows. There was a significant difference in the shape of the lactation curve depending on whether or not the cow was lame during lactation. Average persistency was greater for the group of cows never lame throughout lactation compared with those lame before 60 DIM.     

The value of muscular and skeletal scores in the live animal and carcass classification scores as indicators of carcass composition in cattle

The objective was to determine the relationship of muscular and skeletal scores taken on the live animal and carcass conformation and fat scores with carcass composition and value. Bulls (n = 48) and heifers (n = 37) of 0.75 to 1.0 late-maturing breed genotypes slaughtered at 16 and 20 months of age, respectively, were used. At 8 months of age (weaning) and immediately pre-slaughter, visual muscular scores were recorded for each animal and additionally skeletal scores were recorded pre-slaughter. Carcass weight, kidney and channel fat weight, carcass conformation and fat scores, fat depth over the longissimus dorsi muscle at the 12th (bulls) or 10th (heifers) rib and carcass length were recorded post-slaughter. Each carcass was subsequently dissected into meat, fat and bone using a commercial dissection procedure. Muscular scores taken pre-slaughter showed positive correlations with killing-out rate (r ≈ 0.65), carcass meat proportion (r ≈ 0.60), value (r ≈ 0.55) and conformation score (r ≈ 0.70), and negative correlations with carcass bone (r ≈ -0.60) and fat (r ≈ -0.4) proportions. Corresponding correlations with muscular scores at weaning were lower. Correlations of skeletal scores taken pre-slaughter, carcass length and carcass weight with killing-out rate and the various carcass traits were mainly not significant. Carcass fat depth and kidney and channel fat weight were negatively correlated with carcass meat proportion and value, and positively correlated with fat proportion. Correlations of carcass conformation score were positive (r = 0.50 to 0.68) with killing-out rate, carcass meat proportion and carcass value and negative with bone (r ≈ -0.56) and fat (r ≈ -0.40) proportions. Corresponding correlations with carcass fat score were mainly negative except for carcass fat proportion (r ≈ 0.79). A one-unit (scale 1 to 15) increase in carcass conformation score increased carcass meat proportion by 8.9 and 8.1 g/kg, decreased fat proportion by 4.0 and 2.9 g/kg and decreased bone proportion by 4.9 and 5.2 g/kg in bulls and heifers, respectively. Corresponding values per unit increase in carcass fat score were -11.9 and -9.7 g/kg, 12.4 and 9.9 g/kg, and -0.5 and -0.2 g/kg. Carcass conformation and fat scores explained 0.70 and 0.55 of the total variation in meat yield for bulls and heifers, respectively. It is concluded that live animal muscular scores, and carcass conformation and fat scores, are useful indicators of carcass meat proportion and value.