Down-Regulated E-Cadherin Expression Is Associated with Poor Five-Year Overall Survival in Bone and Soft Tissue Sarcoma: Results of a Meta-Analysis

Purpose

To conduct a meta-analysis to evaluate the prognostic role of E-cadherin expression in bone and soft tissue sarcomas.

Methods

The PubMed, EMBASE, and Web of Science databases were searched using terms related to E-cadherin, sarcoma, and prognosis for all articles published in English before March 2014. Pooled effect was calculated from the available data to evaluate the association between negative E-cadherin expression and 5-year overall survival and tumor clinicopathological features in sarcoma patients. Pooled odds ratios (OR) and risk ratios (RR) with 95% confidence intervals (CI) were calculated using a fixed-effects model.

Result

Eight studies met the selection criteria and reported on 812 subjects. A total of 496 subjects showed positive E-cadherin expression (59.9%). Negative E-cadherin expression in bone and soft tissue sarcomas was correlated with lower 5-year overall survival (OR = 3.831; 95% CI: 2.246–6.534), and was associated with higher clinical stage (RR = 1.446; 95% CI: 1.030–2.028) and with male sex (RR = 0.678; 95% CI: 0.493–0.933).

Conclusion

In the E-cadherin negative group, 5-year overall survival was significantly worse than in the E-cadherin positive group. However, further studies are required to confirm these results.     

Spectrophotometric Studies on Intact Muscle : I. Components of the respiratory chain

The concentrations of the components of the respiratory chain were determined in a variety of intact skeletal muscles by a method of spectrophotometric observation of the transmitted light. In the case of the toad sartorius, these measurements were checked against isolated mitochondrial suspensions prepared from toad skeletal muscles. The relative concentrations of the respiratory components were found to be in reasonable agreement with those of various mitochondrial preparations of mammalian tissues and of the ones from toad skeletal muscle. The rather low cytochrome b and pyridine nucleotide levels in the anoxic minus oxygenated difference spectra were shown to be caused to a certain degree by a partial reduction during the resting steady state. Upon treatment with a strong, reducing agent or after long anoxia some absorption bands appeared with maxima at 591, 562 to 564, and 432 to 434 mµ both in the intact and in the mitochondrial fractions of muscle tissue; they do not appear to be associated with the respiratory chain.     

Calcium Transport in Sealed Vesicles from Red Beet (Beta vulgaris L.) Storage Tissue : I. Characterization of a Ca-Pumping ATPase Associated with the Endoplasmic Reticulum

Calcium transport was examined in microsomal membrane vesicles from red beet (Beta vulgaris L.) storage tissue using chlorotetracycline as a fluorescent probe. This probe demonstrates an increase in fluorescence corresponding to calcium accumulation within the vesicles which can be collapsed by the addition of the calcium ionophore A23187. Calcium uptake in the microsomal vesicles was ATP dependent and completely inhibited by orthovanadate. Centrifugation of the microsomal membrane fraction on a linear 15 to 45% (w/w) sucrose density gradient revealed the presence of a single peak of calcium uptake which comigrated with the marker for endoplasmic reticulum. The calcium transport system associated with endoplasmic reticulum vesicles was then further characterized in fractions produced by centrifugation on discontinous sucrose density gradients. Calcium transport was insensitive to carbonylcyanide m-chlorophenylhydrazone indicating the presence of a primary transport system directly linked to ATP utilization. The endoplasmic reticulum vesicles contained an ATPase activity that was calcium dependent and further stimulated by A23187 (Ca(2+), A23187 stimulated-ATPase). Both calcium uptake and Ca(2+), A23187 stimulated ATPase demonstrated similar properties with respect to pH optimum, inhibitor sensitivity, substrate specificity, and substrate kinetics. Treatment of the red beet endoplasmic reticulum vesicles with [gamma-(32)P]-ATP over short time intervals revealed the presence of a rapidly turning over 96 kilodalton radioactive peptide possibly representing a phosphorylated intermediate of this endoplasmic reticulum associated ATPase. It is proposed that this ATPase activity may represent the enzymic machinery responsible for mediating primary calcium transport in the endoplasmic reticulum linked to ATP utilization.     

Identification of a Gene (GPR30) with Homology to the G-Protein-Coupled Receptor Superfamily Associated with Estrogen Receptor Expression in Breast Cancer

Using the technique of differential cDNA library screening, a cDNA clone was isolated from an estrogen receptor (ER)-positive breast carcinoma cell line (MCF7) cDNA library based upon the overexpression of this gene compared to an ER-negative cell line (MDA-MB-231). Sequence analysis of this clone determined that it shared significant homology to G-protein-coupled receptors. This receptor, GPCR-Br, was abundantly expressed in the ER-positive breast carcinoma cell lines MCF7, T-47D, and MDA-MB-361. Expression was absent or minimal in the ER-negative breast carcinoma cell lines BT-20, MDA-MB-231, and HBL-100. GPCR-Br was ubiquitously expressed in human tissues examined but was most abundant in placenta. GPCR-Br expression was examined in 11 primary breast carcinomas. GPCR-Br was detected in all 4 ER-positive tumors and only 1 of 7 ER-negative tumors. Based upon PCR analysis in hybrid cell lines, the gene for GPCR-Br (HGMW-approved symbol GPR30) was mapped to chromosome 7p22. The pattern of expression of GPCR-Br indicates that this receptor may be involved in physiologic responses specific to hormonally responsive tissues.     

The Respiratory Chain of Plant Mitochondria: V. Reaction of Reduced Cytochromes a and a3 in Mung Bean Mitochondria with Oxygen in the Presence of Cyanide

The half-times of oxidation by oxygen pulses of reduced cytochromes a and a(3) in mung bean mitochondria made anaerobic with succinate have been measured by means of a rapid mixing flow apparatus coupled to a dual wave length spectrophotometer in the presence and absence of cyanide. The absorbance changes at 438 to 455 millimicrons and 603 to 620 millimicrons are suitable for recording the time course of cytochrome a oxidation; the half-time is 2.0 milliseconds at 24 Celsius. This half-time does not change over the range 0 to 300 mum KCN, but the fraction of cytochrome a oxidized falls to a limiting value of 0.3 at the higher cyanide concentrations. The absorbance changes at 445 to 455 millimicrons record the time course of both cytochrome a and cytochrome a(3) oxidation; the former contributes 60% of the absorbance change and the latter 40%. The half-time for a(3) oxidation is calculated as 0.9 milliseconds at 24 Celsius. This half-time increases slightly to 1.3 milliseconds at 300 mum KCN. Reduced cytochrome a(3), whether uncomplexed or complexed with cyanide, becomes fully oxidized. The dissociation constant for the reduced cytochrome a(3)-cyanide complex is estimated to be 30 mum, whereas that for the oxidized a(3)-cyanide complex which inhibits electron transport is estimated to be 2 mum. This suggests two different binding sites for cyanide on the reduced and oxidized forms of cytochrome a(3). The fact that a limiting fraction of reduced cytochrome a can be oxidized at high cyanide concentrations implies that there is no interference by cyanide with electron transport from a to a(3), if cyanide remains bound to the site it occupies on reduced a(3) after this carrier becomes oxidized on reaction with molecular oxygen. Rearrangement of cyanide from this noninhibitory site to the inhibitory site occurs rapidly enough to compete with cytochrome a oxidation. The half-time for the rearrangement is calculated to be 0.9 milliseconds.     

Abnormal Vacuolization of the Tapetum During the Tetrad Stage is Associated with Male Sterility in the Recessive Genic Male Sterile <Emphasis Type="Italic">Brassica napus</Emphasis> L. Line 9012A

In the recessive genic male sterile line 9012A of Brassica napus, pollen development is affected during the tetrad stage. According to the light and electron microscopy analysis of tapetal cells and tetrads, the sterile tapetal cells swelled with expanded vacuoles at the early tetrad stage and finally filled the center of the locules where a majority of tetrads encased with the thick callose wall collapsed and degraded. We suggested that an absence of callase, which is a wall-degrading enzyme stored in the vacuoles of tapetal cells before secretion, resulted in the failure of tetrad separation. Moreover, transmission electron microscopy analysis showed that the secretory tapetal cells were not observed in sterile anthers, which indicated that the transition of the tapetum from the parietal type to the secretory type was probably aberrant. In plants, degeneration of the tapetum is thought to be the result of programmed cell death (PCD). PCD of tapetal cells was investigated by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling assay and signals indicative of deoxyribonucleic acid fragmentation were detected much earlier in sterile anther than in fertile anther. This suggests that tapetal breakdown does not occur by the normal procession of PCD and might be following an alternative mechanism of unscheduled apoptosis in line 9012A. This research supports the hypothesis that premature PCD is associated with male sterility in B. napus.     

Ion Selectivity of the Cytoplasmic Binding Sites of the Na,K-ATPase: I. Sodium Binding is Associated with a Conformational Rearrangement

To investigate Na⁺ binding to the ion-binding sites presented on the cytoplasmic side of the Na,K-ATPase, equilibrium Na⁺-titration experiments were performed using two fluorescent dyes, RH421 and FITC, to detect protein-specific actions. Fluorescence changes upon addition of Na⁺ in the presence of various Mg²⁺ concentrations were similar and could be fitted with a Hill function. The half-saturating concentrations and Hill coefficients determined were almost identical. As RH421 responds to binding of a Na⁺ ion to the third neutral site whereas FITC monitors conformational changes in the ATP-binding site or its environment, this result implies that electrogenic binding of the third Na⁺ ion is the trigger for a structural rearrangement of the ATP-binding moiety. This enables enzyme phosphorylation, which is accompanied by a fast occlusion of the Na⁺ ions and followed by the conformational transition E₁/E₂ of the protein. The coordinated action both at the ion and the nucleotide binding sites allows for the first time a detailed formulation of the mechanism of enzyme phosphorylation that occurs only when three Na⁺ ions are bound. Received: 8 October 1998/Revised: 29 December 1998     

Structure of the Primary Cell Walls of Suspension-Cultured Rosa glauca Cells: I. Polysaccharides Associated with Cellulose

Cell walls of suspension-cultured cells of Rosa glauca were fractionated by two different extraction procedures. The first involved a stepwise fractionation scheme based on alkaline extraction. The second took advantage of the powerful cellulose solvent system N-methylmorpholine N-oxide/dimethyl sulfoxide which is capable of solubilizing whole cell walls. From the analytical composition of each solubilized fraction and of the corresponding residues, the fate of each type of cell wall polysaccharide constituent was followed at each step of the extraction scheme and the mode of action of the extractant was interpreted. Although the two fractionation procedures were very different, they yielded very similar cellulosic complex residues and extracts, thus delimiting two blocks of polysaccharides in the cell wall. The cellulose residues still comprised uronic acid-containing polysaccharides and hemicelluloses in association with cellulose. Graded acid hydrolysis provided evidence for the central role of a homogalacturonan core interconnecting xyloglucans and arabinogalactans. A tentative model showing the possible interaction existing between the constituent polysaccharides still associated to cellulose after alkaline extraction is presented. Hydrogen bonding between xyloglucan and cellulose is confirmed, and glycosidic linkages between xyloglucans and pectic polymers are suggested.     

Tissue interaction in chick liver development: a reevaluation. I. Epithelial morphogenesis: the role of vascularity in mesenchymal specificity.

Undifferentiated hepatic diverticula of the 60-hour chick embryo (26–32 somites) were cultivated either separately or in combination with various mesodermal derivatives, in vitro or on the chorioallantoic membrane (CAM). Cultures were examined histologically at the light-microscope level.Hepatic parenchymal morphology is shown to be a composite of two levels of histological organization, whose corresponding morphogenetic processes are experimentally separable from one another and differ in their interaction requirements. The formation of bile canaliculi is a process intrinsic to the cytologically mature epithelium; it appears to be inhibited by unfavorable mesenchymes, but requires no positive influence of mesenchymal origin. Formation of hepatic cords, on the other hand, depends upon the presence of both mesenchymal cells and sinusoidal endothelium. Epithelial-endothelial contiguity appears to be most directly responsible for this process, while mesenchyme determines the extent of endothelial invasion.These findings are discussed in terms of the correlation, established by previous investigators, between mesenchymal origin and morphogenetic influence. It is suggested (1) that embryonic derivation determines both mesenchymal efficacy for stimulation of vasculogenesis and the extent of epithelial dependence upon that mesenchymal property and (2) that it is the resulting distribution of these properties which determines (the differing degrees of) specificity among a wide variety of epithelial-mesenchymal relationships.     

Potentially Infectious Agents Associated with Shearling Bedpads: I. Effect of Laundering with Detergent-Disinfectant Combinations on Polio and Vaccinia Viruses

Glutaraldehyde-tanned woolskin pads which are used for the prevention of decubitus ulcers in bed patients were experimentally contaminated with polio or vaccinia viruses. Two methods of exposure, direct contact and aerosol, were used in separate experiments. Attempts were made to remove or inactivate these virus contaminants by laundering the woolskins in a quaternary ammonium disinfectant, a phenolic disinfectant, or alkalinized glutaraldehyde, in combination with an anionic detergent or a nonionic detergent. The effect of a commercial detergent-sanitizer was also studied. The virus titers were significantly reduced in all experiments, but only laundering in glutaraldehyde in combination with either detergent lowered the vaccinia virus titers to below detectable limits. High concentrations of glutaraldehyde altered the texture of the wool and leather apparently by precipitating a component of the detergent onto the fibers. In all the poliovirus experiments, the virus was still detectable on either or both the wool and the leather of the pads after laundering. The rinse water from each experiment was tested for the presence of virus. No vaccinia virus was recovered, but poliovirus was demonstrated in titers up to 10(3) cell culture 50% infectious doses.     

Blood Microbiota Dysbiosis Is Associated with the Onset of Cardiovascular Events in a Large General Population: The D.E.S.I.R. Study

Aim

We recently described a human blood microbiome and a connection between this microbiome and the onset of diabetes. The aim of the current study was to assess the association between blood microbiota and incident cardiovascular disease.

Methods and Results

D.E.S.I.R. is a longitudinal study with the primary aim of describing the natural history of the metabolic syndrome and its complications. Participants were evaluated at inclusion and at 3-, 6-, and 9-yearly follow-up visits. The 16S ribosomal DNA bacterial gene sequence, that is common to the vast majority of bacteria (Eubac) and a sequence that mostly represents Proteobacteria (Pbac), were measured in blood collected at baseline from 3936 participants. 73 incident cases of acute cardiovascular events, including 30 myocardial infarctions were recorded. Eubac was positively correlated with Pbac (r = 0.59; P<0.0001). In those destined to have cardiovascular complications, Eubac was lower (0.14±0.26 vs 0.12±0.29 ng/µl; P = 0.02) whereas a non significant increase in Pbac was observed. In multivariate Cox analysis, Eubac was inversely correlated with the onset of cardiovascular complications, (hazards ratio 0.50 95% CI 0.35–0.70) whereas Pbac (1.56, 95%CI 1.12–2.15) was directly correlated.

Conclusion

Pbac and Eubac were shown to be independent markers of the risk of cardiovascular disease. This finding is evidence for the new concept of the role played by blood microbiota dysbiosis on atherothrombotic disease. This concept may help to elucidate the relation between bacteria and cardiovascular disease.     

A Common Polymorphism near the ESR1 Gene Is Associated with Risk of Breast Cancer: Evidence from a Case-Control Study and a Meta-Analysis

Background

Genome-wide association studies have reported that a polymorphism near the estrogen receptor gene (ESR1) (rs2046210) is associated with a risk of breast cancer, with the A allele conferring an increased risk. However, considering the controversial results from more recent replicated studies, we conducted a case-control study in an independent Chinese Han population and a meta-analysis to clarify the association of this polymorphism with breast cancer risk.

Method and Findings

A hospital-based case-control study including 461 cases and 537 controls from a Chinese Han population was conducted initially, and this study showed that the rs2046210 A allele was significantly associated with breast cancer risk, with an OR of 1.32 (95% CI  = 1.10–1.59). Subsequently, a meta-analysis integrating the current study and previous publications with a total of 53,379 cases and 55,493 controls was performed to further confirm our findings. Similarly, a significant association between this polymorphism and breast cancer risk was also observed in the overall population especially among Asians, with ORs for per A allele of 1.14 (95% CI  = 1.10–1.18) in the overall population and 1.27 (95% CI  = 1.23–1.31) in the Asian population.

Conclusion

Our results provide strong evidence to support that the common polymorphism near the ESR1 gene, rs2046210, is associated with an increased risk of breast cancer in Asian and European populations but not in Africans, although the biological mechanisms need to be further investigated.     

Comparative Photosynthetic Properties of Palisade Tissue Chloroplasts and Spongy Tissue Chloroplasts of Camellia japonica L.: Functional Adjustment of the Photosynthetic Apparatus to Light Environment within a Leaf

The photochemical properties of chloroplasts isolated separatelyfrom palisade and spongy tissues of Camellia leaves, were compared,and the following results were obtained: (1) The content ofthe light-harvesting Chi a/b-protein complex was higher in spongytissue chloroplasts (S-Chlts) than in palisade tissue chloroplasts(P-Chlts), while the contents of P700 and PS IT polypeptideswere higher in P-Chlts. (2) Fluorescence induction was slowerin P-Chlts, indicating that they had a larger plastoquinonepool than S-Chlts. (3) The quantum yield of PS II electron transportin S-Chlts was appreciably higher, while that of PS I electrontransport was higher in P-Chlts. (4) The maximal rates of bothPS I and PS IT electron transport under saturating light werehigher in P-Chlts than in S-Chlts. From these results, we concluded that the photochemical propertiesin P-Chlts are adjusted to high light intensity and those ofS-Chlts to low intensity enriched in green and far-red; bothare adjusted to their respective in situ light environments. (Received December 24, 1983; Accepted March 6, 1984)     

piRNAs Are Associated with Diverse Transgenerational Effects on Gene and Transposon Expression in a Hybrid Dysgenic Syndrome of D. virilis

Sexual reproduction allows transposable elements (TEs) to proliferate, leading to rapid divergence between populations and species. A significant outcome of divergence in the TE landscape is evident in hybrid dysgenic syndromes, a strong form of genomic incompatibility that can arise when (TE) family abundance differs between two parents. When TEs inherited from the father are absent in the mother''s genome, TEs can become activated in the progeny, causing germline damage and sterility. Studies in Drosophila indicate that dysgenesis can occur when TEs inherited paternally are not matched with a pool of corresponding TE silencing PIWI-interacting RNAs (piRNAs) provisioned by the female germline. Using the D. virilis syndrome of hybrid dysgenesis as a model, we characterize the effects that divergence in TE profile between parents has on offspring. Overall, we show that divergence in the TE landscape is associated with persisting differences in germline TE expression when comparing genetically identical females of reciprocal crosses and these differences are transmitted to the next generation. Moreover, chronic and persisting TE expression coincides with increased levels of genic piRNAs associated with reduced gene expression. Combined with these effects, we further demonstrate that gene expression is idiosyncratically influenced by differences in the genic piRNA profile of the parents that arise though polymorphic TE insertions. Overall, these results support a model in which early germline events in dysgenesis establish a chronic, stable state of both TE and gene expression in the germline that is maintained through adulthood and transmitted to the next generation. This work demonstrates that divergence in the TE profile is associated with diverse piRNA-mediated transgenerational effects on gene expression within populations.     

The effect of transient temperatures on the growth of Salmonella typhimurium LT2. I: cycling within the growth region

The effect of fluctuating temperatures on microbial growth is important in the passage of foods through the food chain. Suspensions of Salmonella typhimurium were subjected to sinusoidally time-varying temperatures of periods from 40 to 480 min within their growth temperature range. The change in the numbers of viable bacteria was measured with time and the experimental growth curves and average generation times compared with predictions based on isothermal growth data. The experimental average generation times exceeded the predictions by less than 30%, although the discrepancy increased with cycle frequency. Instantaneous growth rates obtained for the 480 min cycles were in agreement with those predicted from isothermal behaviour.     

Graded and All-or-None Electrogenesis in Arthropod Muscle : I. The effects of alkali-earth cations on the neuromuscular system of Romalea microptera

Graded electrically excited responsiveness of Romalea muscle fibers is converted to all-or-none activity by Ba⁺⁺, Sr⁺⁺, or Ca⁺⁺, the two former being much the more effective in this action. The change occurs with as little as 7 to 10 per cent of Na⁺ substituted by Ba⁺⁺. The spikes now produced have overshoots and may be extremely prolonged, lasting many seconds. During the spike the membrane resistance is lower than in the resting fiber, but the resting resistance and time constant are considerably increased by the alkali-earth ions. The excitability is also increased, spikes arising neurogenically from spontaneous repetitive discharges in the axon as well as myogenically from spontaneous activity in the muscle fibers. Repetitive responses frequently occur on intracellular stimulation with a brief pulse. The data indicate that the alkali-earth ions exert a complex of effects on the different action components of electrically excitable membrane. They may be described in terms of the ionic theory as follows: The resting K⁺ conductance is diminished. The sodium inactivation process is also diminished, and sodium activation may be increased. Together these changes can act to convert graded responsiveness to the all-or-none variety. The alkali-earth ions can also to some degree carry inward positive charge during activity, since spikes are produced when Na⁺ is fully replaced with the divalent ions.