High chondroitin sulfate proteoglycan 4 expression correlates with poor outcome in patients with breast cancer

Chondroitin sulfate proteoglycan 4 (CSPG4), a transmembrane proteoglycan originally identified in melanoma cells, has been reported to be expressed in breast cancer cells. This study was performed to examine the expression and significance of CSPG4 in a cohort of breast cancer patients. Immunohistochemical analysis of CSPG4 was performed on tissue microarrays constructed from tissue specimens from 240 breast cancer patients. CSPG4 staining was correlated with clinical and pathological characteristics, overall survival (OS), and disease recurrence. Contradicting to a previous report, our results showed that high CSPG4 expression was not related to triple-negative status of breast cancer patients. The Kaplan–Meier method showed that high CSPG4 expression was significantly associated with shorter time to recurrence (TTR). Patients with high CSPG4 expression had poorer OS and shorter TTR in a multivariate survival analysis after adjustment for stage, tumor grade, expression of estrogen receptor and progesterone receptor, and HER2 overexpression. This study showed that high CSPG4 expression correlates with disease recurrence and OS in breast cancers.     

Inducible nitric oxide synthase mediates cytokine release: the time course in conscious and septic rats

Nitric oxide (NO), tumor necrosis factor-alpha (TNF-alpha), and interleukin 1-beta (IL-1beta) are postulated to play a key pathophysiologic role during sepsis. In this study, we examined the time course of inducible NO synthase (iNOS) mRNA expression and the plasma TNF-alpha and IL-1beta in lipopolysaccharide (LPS)-treated conscious rats. The hemodynamic pattern in septic shock is more similar to clinical conditions without anesthesia. The data showed that a significant increase in iNOS mRNA levels was found in the spleen, lung, liver, with slight elevation in the heart and kidney at 3 h after LPS administration. However, iNOS mRNA levels were not elevated significantly in all tissues examined at 24 h. In the plasma, TNF-alpha and IL-1beta culminated within 1 h, and reduced gradually to baseline levels in a relatively short period (within 9 h). The results suggest that local NO production by activation of iNOS mRNA expression and cytokine release may contribute to LPS-induced organ dysfunction at various time points.     

Implication of life history strategies for prenatal investment in cetaceans

Prenatal investment directly determines the size at birth and fetus growth rate, which affects neonatal survival and growth and potentially affects maternal fitness. This study explored the associated prenatal life history traits of cetaceans. Using multivariate analysis and ANCOVA, baleen whales and toothed cetaceans had distinct energy patterns, with two exceptions including beaked whales and eusocial cetaceans. Baleen whales are characterized by fast prenatal growth, which suggests high prenatal energetics, and utilize the capital breeder tactic. Toothed cetaceans, except for beaked whales, utilize income breeder energetics, which yields relatively slow prenatal growth. However, eusocial cetaceans have especially slow prenatal growth, suggesting very low prenatal energetic effort with social compensation. Although beaked whales are behaviorally income breeders, both discriminant analysis and ANCOVA showed that they are energetically similar to baleen whales, utilizing capital energetics. ANCOVA further revealed that beaked whales have comparatively large calf size, suggesting high prenatal investment. Because all cetaceans wean their calves at comparable size, high prenatal investment may further suggest reduced cost of lactation, which may be behaviorally and energetically adaptive to their specific deep‐dive‐feeding niche.     

Power overshoot in two-chambered microbial fuel cell (MFC)

A two-chamber microbial fuel cell was started using iron-reducing strains as inoculum and acetate as carbon sources. The tested microbial fuel cell had an open-circuit voltage of 0.67 V, and reached 1045 mA m⁻² and a power density of 486 mW m⁻² at 0.46 V before power overshoot occurred. Anodic reactions were identified as the rate-determining steps. Stirring the anolyte insignificantly increased cell performance, suggesting a minimal external mass transfer resistance from the anolyte to the anodic biofilm. Data regression analysis indicates that charge transfer resistance at the biofilm-anode junction was negligible. The order of magnitude estimation of electrical conductance indicates that electron transfer resistance had an insignificant effect on microbial fuel cell performance. Resistance in electrogens for substrate utilization is proposed to induce microbial fuel cell power overshoot.     

TRADD contributes to tumour suppression by regulating ULF-dependent p19Arf ubiquitylation

Tumour necrosis factor receptor (TNFR)-associated death domain (TRADD) protein is a central adaptor in the TNFR1 signalling complex that mediates both cell death and inflammatory signals. Here, we report that Tradd deficiency in mice accelerated tumour formation in a chemical-induced carcinogenesis model independently of TNFR1 signalling. In vitro, primary cells lacking TRADD were less susceptible to HRas-induced senescence and showed a reduced level of accumulation of the p19(Arf) tumour suppressor protein. Our data indicate that TRADD shuttles dynamically from the cytoplasm into the nucleus to modulate the interaction between p19(Arf) and its E3 ubiquitin ligase ULF, thereby promoting p19(Arf) protein stability and tumour suppression. These results reveal a previously unknown tumour-suppressive role for nuclear TRADD, augmenting its long-established cytoplasmic functions in inflammatory and immune signalling cascades. Our findings also make an important contribution to the rapidly expanding field of p19(Arf) post-translational regulation.     

Effects of hepatocyte CD14 upregulation during cholestasis on endotoxin sensitivity

Cholestasis is frequently related to endotoxemia and inflammatory response. Our previous investigation revealed a significant increase in plasma endotoxin and CD14 levels during biliary atresia. We therefore propose that lipopolysacharides (LPS) may stimulate CD14 production in liver cells and promote the removal of endotoxins. The aims of this study are to test the hypothesis that CD14 is upregulated by LPS and investigate the pathophysiological role of CD14 production during cholestasis. Using Western blotting, qRT-PCR, and promoter activity assay, we demonstrated that LPS was associated with a significant increase in CD14 and MD2 protein and mRNA expression and CD14 promoter activity in C9 rat hepatocytes but not in the HSC-T6 hepatic stellate cell line in vitro. To correlate CD14 expression and endotoxin sensitivity, in vivo biliary LPS administration was performed on rats two weeks after they were subjected to bile duct ligation (BDL) or a sham operation. CD14 expression and endotoxin levels were found to significantly increase after LPS administration in BDL rats. These returned to basal levels after 24 h. In contrast, although endotoxin levels were increased in sham-operated rats given LPS, no increase in CD14 expression was observed. However, mortality within 24 h was more frequent in the BDL animals than in the sham-operated group. In conclusion, cholestasis and LPS stimulation were here found to upregulate hepatic CD14 expression, which may have led to increased endotoxin sensitivity and host proinflammatory reactions, causing organ failure and death in BDL rats.     

Arabidopsis thaliana CENTRORADIALIS homologue (ATC) acts systemically to inhibit floral initiation in Arabidopsis

Floral initiation is orchestrated by systemic floral activators and inhibitors. This remote‐control system may integrate environmental cues to modulate floral initiation. Recently, FLOWERING LOCUS T (FT) was found to be a florigen. However, the identity of systemic floral inhibitor or anti‐florigen remains to be elucidated. Here we show that Arabidopsis thaliana CENTRORADIALIS homologue (ATC), an Arabidopsis FT homologue, may act in a non‐cell autonomous manner to inhibit floral initiation. Analysis of the ATC null mutant revealed that ATC is a short‐day‐induced floral inhibitor. Cell type‐specific expression showed that companion cells and apex that express ATC are sufficient to inhibit floral initiation. Histochemical analysis showed that the promoter activity of ATC was mainly found in vasculature but under the detection limit in apex, a finding that suggests that ATC may move from the vasculature to the apex to influence flowering. Consistent with this notion, Arabidopsis seedling grafting experiments demonstrated that ATC moved over a long distance and that floral inhibition by ATC is graft transmissible. ATC probably antagonizes FT activity, because both ATC and FT interact with FD and affect the same downstream meristem identity genes APETALA1, in an opposite manner. Thus, photoperiodic variations may trigger functionally opposite FT homologues to systemically influence floral initiation.     

Enhancing dopamine detection using a glassy carbon electrode modified with MWCNTs, quercetin, and Nafion

Glassy carbon (GC) electrode was modified using multi-wall carbon nanotubes (MWCNTs), quercetin (Q) and Nafion^® in this sequence. The thus modified electrode was used for the detection of dopamine (DA) in the presence of equimolar ascorbic acid (AA). It is demonstrated in this study that MWCNTs can increase the current response of DA by five-fold and Q can reduce the oxidation overpotential of DA by about 60 mV, compared to these parameters obtained with a bare GC electrode. It is also shown that a layer of Nafion^® can virtually eliminate the interference of AA for the detection of DA. The GC/MWCNTs/Q/Nafion^® electrode (hereafter also called composite electrode) shows a current density of about 900 μA cm⁻² for DA, compared to the value of 80 μA cm⁻² of the GC electrode and to the value of 390 μA cm⁻² of the GC/MWCNTs electrode. The 11-fold enhancement in the sensitivity of the GC electrode for DA determination is attributed to the composite modification of the electrode, and is substantiated through various cyclic voltammetric experiments. Cyclic voltammetry (CV) and linear sweep voltammetry were used to characterize the electrodes. Calibration curves of batch and flow systems were obtained by amperometry for the detection of DA. Additionally, the composite modified electrode was tested with a human serum sample for the determination of DA and was found to be promising at our preliminary experiments.