Application of Proteomics in Pancreatic Ductal Adenocarcinoma Biomarker Investigations: A Review

Pancreatic ductal adenocarcinoma (PDAC), a highly aggressive malignancy with a poor prognosis is usually detected at the advanced stage of the disease. The only US Food and Drug Administration-approved biomarker that is available for PDAC, CA 19-9, is most useful in monitoring treatment response among PDAC patients rather than for early detection. Moreover, when CA 19-9 is solely used for diagnostic purposes, it has only a recorded sensitivity of 79% and specificity of 82% in symptomatic individuals. Therefore, there is an urgent need to identify reliable biomarkers for diagnosis (specifically for the early diagnosis), ascertain prognosis as well as to monitor treatment response and tumour recurrence of PDAC. In recent years, proteomic technologies are growing exponentially at an accelerated rate for a wide range of applications in cancer research. In this review, we discussed the current status of biomarker research for PDAC using various proteomic technologies. This review will explore the potential perspective for understanding and identifying the unique alterations in protein expressions that could prove beneficial in discovering new robust biomarkers to detect PDAC at an early stage, ascertain prognosis of patients with the disease in addition to monitoring treatment response and tumour recurrence of patients.     

Inter-organisational knowledge transfer in social networks: A definition of intermediate ties

A social network perspective helps identify and analyse informal knowledge transfer among people and organisations with the aim to recommend organisational interventions and improvements, for example in the form of Information and Communication Technology (ICT) support. This paper particularly focuses on a key concept of social network analysis (SNA), the concept of tie strength, in an inter-organisational knowledge transfer context. Tie strength describes the strength of a social relationship. In the past, SNA literature with a knowledge management context has often emphasized the importance of strong and/or weak ties rather than of intermediate (medium strong) ties in a social network. Nevertheless, in this study, intermediate ties are identified as the dominant links among key groups of organisation in a social network. Intermediate ties also help connect otherwise weakly linked organisations. Moreover, a definition of intermediate ties in the context of knowledge management is introduced. With the help of cluster analysis and an investigation into the levels of reciprocity, intermediate ties can be clearly defined in a social network. Due to their importance for knowledge transfer in a social network, intermediate ties should be primarily supported, for example by appropriate ICT.     

Membrane topology of the Rickettsia prowazekii ATP/ADP translocase revealed by novel dual pho-lac reporters

Here, we report the construction and characterization of dual reporters, consisting of both an Escherichia coli alkaline phosphatase (AP) gene and an alpha-fragment of the beta-galactosidase (BG) gene, for studying membrane protein topology by the gene fusion approach. Each of the reporters, when fused to periplasmic domains of polytopic proteins, produces fusions with high AP activity and, when fused to cytoplasmic domains, produces fusions with high BG activity in E. coli strains capable of alpha-complementation. The dual nature of these reporters simplifies interpretation of data obtained with poorly expressed fusions and allows one to evaluate the reliability of topological data. Deleterious effects resulting from the cell's attempt to export the full-length BG are eliminated in this approach. We describe dual indicator plates that allow for discrimination between colonies bearing cytoplasmic fusions, periplasmic fusions, and no fusions. We have generated a set of fusions to the topologically well-studied lactose permease of E. coli and demonstrated that topological information generated by these new reporters is in good agreement with the existing model. We used this new methodology for the determination of membrane topology of the Rickettsia prowazekii ATP/ADP translocase (Tlc). Our results were in agreement with the proposed in silico topological model in which Tlc traverses the cytoplasmic membrane of E. coli 12 times with its N and C termini facing the cytoplasm.     

A liposomal model that mimics the cutaneous production of vitamin D3. Studies of the mechanism of the membrane-enhanced thermal isomerization of previtamin D3 to vitamin D3

We reported previously that the rate of previtamin D3 (preD3) <==> vitamin D3 isomerization was enhanced by about 10 times in the skin compared with that in organic solvents. To elucidate the mechanism by which the rate of this reaction is enhanced in the skin, we developed a liposomal model that mimicked the enhanced isomerization of preD3 to vitamin D3 that was described in human skin. Using this model we studied the effect of changing the polarity of preD3 as well as changing the chain length and the degree of saturation of liposomal phospholipids on the kinetics of preD3 <==> vitamin D3 isomerization. We found that a decrease in the hydrophilic interaction of the preD3 with liposomal phospholipids by an esterification of the 3beta-hydroxy of preD3 (previtamin D3-3beta-acetate) reduced the rate of the isomerization by 67%. The addition of a hydroxyl on C-25 of the hydrophobic side chain (25-hydroxyprevitamin D3), which decreased the hydrophobic interaction of preD3 with the phospholipids, reduced the rate by 87%. In contrast, in an isotropic n-hexane solution, there was little difference among the rates of the conversion of preD3, its 3beta-acetate, and 25-hydroxy derivatives to their corresponding vitamin D3 compounds. We also determined rate constants (k) of preD3 <==> vitamin D3 isomerization in liposomes containing phosphatidylcholines with different carbon chain lengths. The rates of the reaction were found to be enhanced as the number of carbons (Cn) in the hydrocarbon chain of the phospholipids increased from 10 to 18. In conclusion, these results support our hypothesis that amphipathic interactions between preD3 and membrane phospholipids stabilize preD3 in its "cholesterol like" cZc-conformer, the only conformer of preD3 that can convert to vitamin D3. The stronger these interactions were, the more preD3 was likely in its cZc conformation at any moment and the faster was the rate of its conversion to vitamin D3.     

Marie-Fran?oise Collière--nurse and ethnohistorian: a conversation about nursing and the invisibility of care. Interview by Jocalyn Lawler

The purpose of this study was to describe an episode of increased mortality, whose cause was initially unknown. This retrospective cohort investigation was conducted on a dementia special care unit of a Department of Veterans Affairs facility, with more than 75% of residents clinically diagnosed with dementia of the Alzheimer type. One hundred five residents residing in the facility during February 1995 were included as subjects. A cluster of deaths occurred, triggering the investigation. Ultimately, 21 deaths (three times greater than any previous month in the past 5 years) occurred during the 1-month period. Measures included the presence of clinical influenza-like illness based on signs, serology, and autopsy results. Of the 105 residents, 45 (42.8%) met the clinical definition for influenza-like illness. Eight autopsies were performed, and the causes of death consisting of bronchopneumonia in seven and aspiration pneumonia in one were compatible with influenza. There were no differences among those who died from those who lived with regards to age, race, gender, clinical influenza-like illness, vaccination status, diagnosis of Alzheimer disease, or duration of dementia (all p > or = 0.2). However, those who died were at a higher risk of dying due to a greater number of coexisting conditions (p < 0.01). Also, overall the groups differed in Mini-Mental State Examination and Bedford Alzheimer Nursing Scale scores with those who died being more impaired (p < 0.01). Thus, the presentation of influenza-like illness can be subtle in onset, underappreciated in this population, and not recognized until excess mortality, which affects the most frail, is noted. Care providers need to be vigilant during the winter months for the presence of influenza.     

Cerebral emboli and serum S100beta during cardiac operations

BACKGROUND: The glial protein S100beta has been used to estimate cerebral damage in a number of clinical settings. The purpose of this investigation was to determine the correlation between cerebral microemboli and S100beta levels during cardiac operations. METHODS: Transcranial Doppler ultrasonography was used to measure emboli in the right middle cerebral artery. Emboli counts (n = 111) were divided into five time periods: (1) incision to aortic cannulation; (2) aortic cannulation to cross-clamp onset; (3) cross-clamp onset to cross-clamp release; (4) cross-clamp release to decannulation; and (5) decannulation to chest closure. The level of S100beta (n = 156) was measured at baseline, at the end of cardiopulmonary bypass, then 150 and 270 minutes after cross-clamp release. RESULTS: The level of S100beta correlated with age, cardiopulmonary bypass time, cross-clamp time, and number of emboli at time period 2. Although cardiopulmonary bypass time was univariately associated with S100beta level, it became nonsignificant in a multivariable model that included age and cross-clamp time. CONCLUSIONS: The correlation of S100beta level with emboli measured during cannulation (time period 2) supports the hypothesis that cannulation is a high-risk time period for cerebral injury.     

Development of AMPA-selective glutamate receptors in the auditory brainstem of the barn owl

AMPA receptor specific antibodies were used to study the distribution and development of glutamate receptor subtypes (GluR1-4) in nucleus magnocellularis, angularis, laminaris, and the superior olive of the barn owl. Each nucleus in the adult barn owl expresses characteristic levels of AMPA receptor subtypes, and all are enriched in the subunits associated with rapid desensitization (GluR2 and 4). In the auditory hindbrain of the barn owl, the levels of expression of all AMPA receptors were very low at the time of hatching. In all nuclei, the level of GluR1 immunoreactivity was low to undetectable at all ages studied. In the cochlear nuclei, angularis and magnocellularis, levels of GluR2/3 and GluR4 immunoreactivity increased over the first 2 weeks after hatching, coinciding with the morphological maturation of auditory nerve terminals in NM. In the nucleus laminaris and in the superior olive, GluR2/3 and GluR4 immunoreactivity reached adult-like patterns by 3 weeks after hatching. Thus, adult-like patterns of immunoreactivity appeared at least 1 month before the end of the sensitive period in all nuclei studied.     

Vitamin E supplementation attenuates myointimal proliferation of the abdominal aorta after balloon injury in diet-induced hypercholesterolemic rabbits

The effects of vitamin E supplementation in a dose of 450 mg/1000 g chow on the myointimal proliferation of the abdominal aorta after balloon injury were studied in 4 groups of rabbits (24 each). The animals were fed regular diet, regular diet plus vitamin E, 1% cholesterol-enriched diet, and 1% cholesterol-enriched diet plus vitamin E. Each animal underwent a balloon injury of the abdominal aorta and left common iliac artery after 2 weeks of feeding. The animals remained on their respective diets thereafter. In 8 balloon-injured and 8 sham-operated animals of each group, the abdominal aortas were harvested 3 days after the procedure for the analysis of prostacyclin and thromboxane A2 synthesis, thiobarbituric acid reactive substances (TBARS) levels, enzyme activities of glutathione reductase (GR) and glutathione peroxidase (GP) as well as reduced (GSH) and oxidized (GSSG) glutathione levels, 3H-thymidine uptake, cholesterol as well as vitamin E contents. In the other 8 balloon-injured rabbits of each group, the tissue was harvested 3 weeks later for the morphometric study. In dependent of high cholesterol feeding, the vitamin E-treated rabbits had lower aortic production of thromboxane B2, higher 6-keto-PGF1 alpha and higher 6-keto-PGF1 alpha/thromboxane B2 ratios in both procedures. The aortic TBARS levels of the rabbits treated high cholesterol alone were significantly higher than the other three groups in both procedures. Balloon injury had a trend to increase TBARS levels and had significantly higher 3H-thymidine uptake (each p < 0.001) than sham operation in each group. Vitamin E supplement to high cholesterol diet or regular chow reduced aortic TBARS levels (p < 0.005 and 0.01, respectively) and 3H-thymidine uptake (p < 0.05 and 0.01, respectively), as well as attenuated myointimal proliferation of the abdominal aorta and left common iliac artery after balloon injury; but only supplement to high cholesterol diet reached statistical significances (both p < 0.05 compared to rabbits fed high cholesterol alone). These results suggest that vitamin E supplement changes prostanoid metabolism to a favorable pattern and reduces lipid peroxidation of the abdominal aortic wall, thus attenuates myointimal proliferation after balloon injury; these presentations are particularly obvious in diet-induced hypercholesterolemic rabbits.     

Laser-induced chorioretinal venous anastomosis for nonischemic central or branch retinal vein occlusion

Sea urchin embryos have provided excellent material for experimental and molecular analyses of the processes of cell and axis specification during embryogenesis. These studies revealed the tremendous developmental plasticity of cells in early embryos and the roles that cell-cell interactions play in determining cell fates. Details concerning sea urchin development can be found in a number of excellent reviews. This review summarizes experimental and molecular studies relating to axis determination and cell fate specification in echinoid embryos. Correlations are drawn from research carried out on the development of axial systems in other organisms.