1,721,117 research outputs found
Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Bile secretion of sulfated glycolithocholic acid is required for its cholestatic action in rats
No full text To test our hypothesis that the cholestatic action of sulfated glycolithocholic acid (SGLC) in the rat is related to its interaction with calcium in the biliary tree [R. van der Meer, R. J. Vonk, and F. Kuipers. Am. J. Physiol. 254 (Gastrointest. Liver Physiol. 17): G644-G649, 1988], we have now compared its effects on bile formation in control Wistar rats and mutant Groningen Yellow (GY) Wistar rats. Intravenous injection of 0.6 mumol/100 g body wt of [14C]SGLC in unanesthetized rats with permanent biliary drainage did not induce cholestasis in either of the strains; however, its biliary secretion was strongly impaired in GY rats (12% dose at 1 h after injection vs. 95% dose in controls). Injection of 6.0 and 12.0 mumol/100 g body wt of [14C]SGLC caused an almost complete cessation of bile flow in control rats within 3 and 1 h, respectively. In contrast, administration of the same doses did not cause cholestasis in GY rats. Cholestasis in control rats was preceded by coprecipitation of [14C]SGLC and calcium in bile and incomplete biliary recovery of radioactivity. The hepatic content 15 min after injection of [14C]SGLC (6.0 mumol/100 g body wt) was similar in control and GY rats, 51 and 49% of the dose, respectively. Administration of glycolithocholic acid, the unsulfated parent compound of SGLC (6.0 mumol/100 g body wt), induced a rapid but reversible cessation of bile flow in both controls and GY rats; in this case no precipitation was observed in bile. This study shows that rapid bile secretion of SGLC is required for the induction of cholestasis.(ABSTRACT TRUNCATED AT 250 WORDS) </jats:p
Amphiprion latezonatus microsatellite data
No full textmicrosatellite data for Amphiprion latezonatus. For information on primers, please see "Steinberg, R., van der Meer, M., Hobbs, J. P., Berumen, M. L., & van Herwerden, L. (2015). Characterization of 22 microsatellite loci for conservation genetic studies of an endemic anemonefish, Amphiprion latezonatus. Conservation Genetics Resources, 7(1), 95-97". for analysis and results, please see "Steinberg, R., van der Meer, M., Walker, E., Berumen, M. L., Hobbs, J. P. A., & van Herwerden, L. (2016). Genetic connectivity and self-replenishment of inshore and offshore populations of the endemic anemonefish, Amphiprion latezonatus. Coral Reefs, 35(3), 959-970"
Variations on the Author
Get PDF“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Get PDFWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Dietary calcium as a possible anti-promoter of colon carcinogenesis
No full textSUMMARYColon cancer is the second-most common malignancy in both males and females and is strongly related to environmental factors of which diet seems to be the most important one. Dietary fat is positively correlated with the incidence of colon cancer whereas dietary fibre and dietary calcium seem to be negatively associated with the risk of colon cancer. The development of colon cancer can genetically and histologically be characterized in different phases which may offer several oppertunities for dietary intervention. A high intake of dietary fat promotes colon cancer in tumor-induction models whereas dietary calcium counteracts this promotive effect of dietary fat. The promotive effect of dietary fat may be mediated by bile acids and fatty acids in colon which induce hyperproliferation of the colonic epithelium. Colonic hyperproliferation is generally considered as a biomarker of an increased susceptibility to colon cancer. The mechanism by which the surface-active bile acids and fatty acids induce hyperproliferation consists probably of damage of the cell-membrane resulting in cytolysis and cell-death. Luminal binding of these surfactants by insoluble calcium phosphate may decrease the solubility of these surfactants, their cytotoxic effects and the induction of hyperproliferation (Figure 1).The experimental studies described in this thesis investigated this hypothesized mechanism by which dietary calcium inhibits proliferation of the colonic epithelium and the risk of colon cancer using the following step-wise approach. First, in in vitro studies (chapter 3) it was shown that bile acids and fatty acids are toxic for erythrocytes and for colonic epithelial cells in vitro (CaCo-2 cells). Moreover, cytotoxicity of these surfactants was similar in both cell-types. Fatty acids were as cytotoxic as bile acids with a similar dependency on hydrophobicity, but in contrast to bile acids, cytotoxicity of fatty acids was apparently not associated with micelle-formation. Low submicellar, sublytic concentrations of bile acids synergistically stimulated fatty acid-induced cytotoxicity. Cytotoxicity of these mixtures of bile acids and fatty acids was, analogous to cytotoxicity of bile acids alone, dependent on micelle formation. The synergistic effect of bile acids on fatty acid-induced cytotoxicity was stimulated by an increasing hydrophobicity of the bile acids. Lowering of the fatty acid concentration of these mixtures drastically decreased their cytotoxic effects. This in vitro study showed that physiologically relevant mixtures of bile acids and fatty acids are toxic to enterocytes as well as erythrocytes.Secondly, it was investigated in rats whether a diet-induced increase in colonic bile acids stimulated cytotoxicity of fecal water and colonic proliferation (chapter 4). Therefore, fecal water was isolated from feces. Fecal water is that fraction of feces which contains the soluble surfactants which are assumed to damage cells. A dietinduced increase in colonic bile acids drastically stimulated cytotoxicity of fecal water analogous to the increase in concentration of bile acids in fecal water. Also an increase in colonic proliferation measured as [ 3H]-incorporation into DNA was observed. Cytotoxicity of fecal water and colonic proliferation were highly correlated (r=0.85, n=24, P4 stimulated the intestinal formation of insoluble CaP i , decreased the concentrations of soluble surfactants and lowered cytotoxicity of fecal water, was investigated (chapter 5). Supplemental CaHPO 4 resulted in a dosedependent decrease in bile acid concentration of fecal water and an increased precipitated fraction of bile acids. Consequently a drastic, dose-dependent fall in cytotoxicity was observed. Correlations between precipitated bile acids and cytotoxicity with precipitated calcium and inorganic phosphate (r>0.90) showed that theseparameters were closely associated. Thus, dietary supplementation with CaHPO 4 decreased cytotoxicity of fecal water by intestinal precipitation of bile acids.Because bile acids and fatty acids are products of fat digestion, the type of dietary fat may influence the cytotoxic effects of the intestinal contents and the interaction with calcium phosphate. Therefore, three different purified types of dietary fat (milk fat, palm oil and corn oil) were used each at a low (25 μmol CaHPO 4 /g diet) and a high (225 μmol CaHPO 4 /g diet) level (chapter 6). Milk fat contains rather large amounts of short- and medium-chain triglycerides (C 4:0 -C 12:0 ), palm oil contains triglycerides rich in palmitate (Ca 16:0 ) and oleate (C 18:1 ) and corn oil contains linoleate (C 18:2 ) rich triglycerides. The excretion of fatty acids was dependent on the type of dietary fat and increased in the order corn oil 4 drastically stimulated fatty acid excretion with the same fat-type dependency. In contrast, concentrations of soluble fatty acids and bile acids were drastically decreased by supplemental CaHPO 4 . This effect was dependent on the type of dietary fat with palm oil resulting in the highest concentration of fatty acids. Cytotoxicity of fecal water decreased analogous to the decrease in concentrations of soluble surfactants with the same fat-type dependency. Multiple regression analysis showed that the concentrations of soluble bile acids and fatty acids are equally important determinants of cytotoxicity and explain 80% (R = 0.89) of the cytotoxicity of fecal water. Intestinal alkaline phosphatase activity in fecal water as a marker of intestinal epitheliolysis showed that the effects on cytotoxicity of fecal water were reflected in effects on intestinal epitheliolysis (r=0.92, PTo investigate whether the luminal effects of dietary calcium resulted in a change in response of the colonic epithelium, the anti-proliferative effect of calcium was studied in rats fed Western-type high risk diets containing low CaHPO 4 (25 μmol Ca/g), low fibre and high fat (40 en-%) levels (chapter 7). It should be noted that this low calcium diet mimicked a human diet with a calcium consumption of 500 mg/day (mean intake in The Netherlands is about 1000 mg/day). Types of fat used were commercially available fats: butter, mimicking a diet with a high saturated mediumchain triglycerides content, saturated margarine, reflecting a diet with a high long-chain saturated fat content, and polyunsaturated margarine, ressembling a diet with a high polyunsaturated fat content. Diets were also supplemented with CaHP0 4 to 225 μmol/g diet. Dietary calcium phosphate decreased soluble surfactant concentrations and cytotoxicity of fecal water. These luminal effects of dietary calcium resulted in a lower intestinal epitheliolysis. On the butter and saturated margarine diets, these protective effects of calcium resulted in a decreased colonic proliferation. On the polyunsaturated diet, proliferation was not decreased by supplemental calcium which may suggest an additional mechanism in the induction of hyperproliferation. Multiple regression analysis of soluble surfactants with cytotoxicity, epitheliolysis and colonic proliferation showed highly significant associations. Cytotoxicity and epitheliolysis as well as epitheliolysis and colonic proliferation were highly correlated (resp. r=0.97 and r=0.88) for control and Ca-supplemented groups. This is consistent with the proposed mechanism and may indicate cause-and-effect relationships. Thus the anti-proliferative effect of dietary calcium is mediated by luminal surfactants and dependent on the type of dietary fat.Finally, the luminal effects of supplemental dietary calcium were studied in a pilot intervention trial with young healthy volunteers. In this study supplemental calcium complexated with phosphate to insoluble calcium phosphate, but in contrast to the animal studies the (already low) concentration of soluble bile acids was not further decreased. The free fatty acid concentration in fecal water was lowered by supplemental calcium. Gaschromatographic analysis of fecal water showed that the composition of the bile acids in fecal water was altered from hydrophobic to hydrophilic. The overall effect of dietary calcium supplementation was a decrease in hydrophobicity of fecal water measured as a decrease in free fatty acid concentration, hydrophobic bile acids and neutral sterols. This resulted in a significant decrease in cytotoxicity of fecal water in these healthy volunteers. Thus, luminal effects of dietary calcium supplementation in humans are analogous to the effects in rats. These effects may offer a molecular explanation of the protective effects of dietary calcium supplementation on colonic epithelial proliferation in patients at risk for colon cancer.CONCLUDING REMARKSThe experimental studies described in this thesis lead to the following conclusions:1. Bile acids and fatty acids are cytotoxic surfactants which cause damage of cellular membranes resulting in cell-death. Lysis of erythrocytes is a convenient and relevant model system to determine cytotoxicity of these surfactants (chapter 3).2. Diet may modulate the proliferative behavior of the colonic epithelium by luminal effects. Cytotoxicity of fecal water measured as lysis of erythrocytes providesrelevant information about the luminal effects of diet (chapter 4 & 5).3. The type of dietary fat influences the concentrations of luminal surfactants, cytotoxicity, intestinal epitheliolysis (chapter 6 & 7) and colonic proliferation (chapter 7). Dietary calcium phosphate supplementation causes precipitation of luminal surfactants. As a consequence, concentrations of soluble cytotoxic surfactants are lowered, which results in a decreased cytotoxicity of fecal water (chapter 5-7). These luminal effects of dietary calcium phosphate decrease intestinal epitheliolysis (chapter 6 & 7) and lower colonic epithelial proliferation (chapter 7).4. In humans, supplemental calcium lowers the hydrophobicity of fecal water and consequently decreases cytotoxicity of fecal water.With regard to these conclusions some remarks have to be made concerning the protective effects of calcium. It should be stressed that cytotoxicity is not a measure of intestinal cell-damage. Luminal cytotoxicity only refers to the potency of the intestinal contents to damage cells. Cytotoxicity is therefore solely determined by the physicochemical characteristics of the luminal surfactants. Lysis of epithelial cells is dependent on this cytotoxicity, but also on the susceptibility of the plasmamembrane to the luminal surfactants. Determinants of this epithelial susceptibility are at present largely unknown. In rats consuming identical diets only differing in the amount of CaHPO 4 and type of dietary fat, the proposed sequence of effects (figure 1) has been demonstrated. However, in the experiment with human volunteers only the luminal effects of dietary calcium supplementation were studied (chapter 8). Whether the observed protective effects result, analogous to the effects in rats, in alower colonic proliferation is at present unknown. Therefore, the results of chapter 8 should only be interpreted as a first indication how dietary calcium in humans could decrease the risk of colon cancer.Further investigations regarding calcium and colon cancer should focuss on the effects of calcium supplementation on colonic epithelial proliferation using a combined biochemical and physiological design. Only these combined efforts may shed some light on the complex role of diet in colorectal carcinogenesis. Many questions have still to be answered. Dose-response and time-relationships need to be ascertained. Whether an optimal dose of calcium supplementation exists, is not clear. Whether dairy products, which are rich in calcium, have the same effects should also be ascertained. Possible interactions not only influenced by the the type of dietary fat, but also interactions between the protective agents fibre and calcium in the intestinal lumen may be important. It should be clear that luminal colonic effects of diet are very complex to study, because of intestinal interactions between the different dietary components. However, these interactions are important in the dietary prevention of colon cancer.In conclusion, the experiments described in this thesis show that dietary supplementation with CaHPO 4 decreases cytotoxicity of fecal water resulting in a decreased colonic epithelial proliferation. The relative importance of dietary calcium as an anti-promoter of colon carcinogenesis has to be established in the following years. Several multi-center intervention trials have started during the last few years studying the effects of calcium supplementation on proliferation-markers and recurrence of polyps. However, one should be cautious not to neglect biochemical and animal studies to investigate mechanisms how calcium could affect the risk of colon cancer. Dietary advice with regard to calcium-intake and the prevention of colon cancer has to await knowledge of relevant mechanisms combined with consistent results in in vitro studies, experiments with animals and human intervention trials
Dietary modulation of the resistance to intestinal infections
No full textGastrointestinal infections are still a major health problem, not only in developing countries. Even in Europe and the United States about 10-15 % of the population contracts an intestinal infection each year, mostly of foodborne origin. The growing resistance of pathogens to antibiotics stresses the importance to prevent and treat intestinal infections by other means. Modulation of the diet to improve host resistance to foodborne infections might be an attractive, alternative approach.The diet determines the composition of intestinal contents, which in turn affects the gastrointestinal survival of pathogens, the protective endogenous microflora and the epithelial barrier function. These parameters ultimately determine the susceptibility of the host to intestinal infectious disease. Scientific interest in dietary modulation of the resistance to intestinal infections is just emerging. Notwithstanding the results of numerous in-vitro studies, strictly controlled infection studies showing the importance of the diet (supplemented with pre- or probiotics) to inhibit or ameliorate intestinal infections in-vivo are scarce. Even less is known about the potential protective effect of dietary calcium on the resistance to intestinal infections. At the same time, evidence accumulates showing that calcium is likely an antipromoter of colon carcinogenesis.In the intestine, calcium forms an insoluble complex with phosphate which strongly binds bile acids and fatty acids. In soluble form, these surfactants are highly irritating to the intestinal epithelium. Therefore, precipitation of bile acids and fatty acids by calcium phosphate decreases luminal cytotoxicity, resulting in diminished epithelial cell damage and reduced epithelial proliferation. This may also be relevant for host resistance to intestinal infections. A reduced epithelial cell damage may strengthen the mucosal barrier function. In addition, it can be speculated that the decreased cytotoxicity of intestinal contents by calcium phosphate may stimulate growth of the protective endogenous microflora and improve its antagonistic activity towards invading pathogens. Figure 1 summarizes the hypothetical mechanism by which dietary calcium phosphate may decrease the severity of an intestinal infection, for instance caused by salmonella.The strictly-controlled experimental studies described in this thesis mainly focused on the proposed protective effect of dietary calcium phosphate on the resistance to intestinal infections. The rat was chosen as animal model and the invasive pathogen Salmonella enteritidis as infective agent. Salmonellosis is one of the most common foodborne, bacterial infections in the world and its pathology in humans and rodents is quite similar. The first study of this thesis investigated the application of urinary nitrate excretion as a marker of intestinal bacterial translocation (chapter 2).To study dietary modulation of host resistance to translocation of pathogens a non-invasive, sensitive and quantifiable marker is needed. Classical organ cultures do not meet those criteria. Nitric oxide (NO) is produced by inducible nitric oxide synthase of phagocytes upon contact with bacteria or cell wall components of bacteria, like lipopolysaccharides. To prevent damage to host cells, NO is rapidly oxidized to nitrite and nitrate (summed as NO x ) and these are quantitatively excreted in urine. It was shown that intraperitoneally injected S. enteritidis lipopolysaccharides transiently increased the urinary NO x output within a certain dose-range. Concomitant administration of a competitive inhibitor of nitric oxide synthase (N G-nitro-L-arginine methyl ester) almost completely abolished the rise in NO x excretion. Importantly, increasing the oral dose of viable S. enteritidis resulted in a time- and dose-dependent exponential increase in urinary NO x excretion. Translocation was a prerequisite for provoking a NO x response, because neither orally administered, heat-killed S. enteritidis nor non-invasive, enterotoxigenic Escherichia coli (data not shown) induced an increase in NO x excretion above base-line level. Total urinary NO x excretion after infection of the rats with viable S. enteritidis and weight of the mesenteric lymph nodes were highly correlated.After validation of this new translocation marker, the effect of different milk products (low-calcium milk, milk, milk acidified with hydrochloric acid, and pasteurized yogurt) on the resistance of rats to S. enteritidis was studied (chapter 3). Compared with the low-calcium milk group, all high-calcium groups had an increased colonization resistance, as judged by the strongly reduced fecal salmonella excretion in time. The yogurt-fed rats had the best colonization resistance. Before infection, the bile acid concentration and cytotoxicity of fecal water of the low-calcium milk group were significantly higher than those of the high-calcium groups. The reduced resistance of the low-calcium milk group corresponded with strong infection-induced disturbances of normal intestinal physiology. For instance, the apparent iron absorption was reduced and considerable increases in cytotoxicity of fecal water, fecal mucin and alkaline phosphatase excretion were observed in this group. The least infection-induced changes in luminal parameters were noticed in the yogurt-fed rats. Surprisingly, no infection-induced increase in urinary NO x excretion was observed in this study (data not shown).As the milk-based diets differed in several respects, another strictly controlled infection study was performed with rats on purified diets differing only in calcium phosphate (20, 60 and 180 mmol/kg) content (chapter 4). Compared with the low-calcium group, the medium- and high-calcium group shedded 10-1000 times less salmonella in their feces and thus had a substantially improved colonization resistance. Calcium supplementation also reduced translocation of salmonella, considering the diminished urinary NO x excretion and decreased viable salmonella counts in the ileal Peyer's patches and spleen. As shown earlier, the bile acid concentration and cytotoxicity of fecal water were decreased by dietary calcium phosphate. This resulted in an increased fecal output of several bacterial mass markers, indicating a stimulation of the endogenous microflora. Besides an enhanced fecal dry weight excretion, dietary calcium phosphate also increased fecal nitrogen, phospholipid and organic phosphate output.The non-digestible disaccharide lactulose is well-fermented by the intestinal microflora and has been used successfully in the treatment of certain intestinal infections. The organic acids (e.g. lactic acid) formed during bacterial lactulose fermentation probably play an important role in this protection. Nevertheless, excess acid production may damage the intestinal epithelium and even impair the mucosal barrier function. Considering the above-mentioned resistance-enhancing effects of dietary calcium phosphate and its ability to increase the intestinal buffering capacity, the possible superiority of a combination of dietary lactulose and calcium phosphate to improve host resistance was studied (chapter 5).S. enteritidis appeared to be very sensitive to lactic acid in-vitro, whereas Lactobacillus acidophilus (as a representative of the protective endogenous microflora) was unaffected. The infection experiment showed that dietary lactulose decreased fecal shedding of salmonella, thus increased the colonization resistance. The protective effects of lactulose were limited to the cecum and colon because this disaccharide did not decrease translocation of salmonella, as measured by urinary NO x excretion. In agreement with the study described above, calcium phosphate significantly inhibited translocation of salmonella. It is known that mucosal invasion of salmonella mainly takes place in the ileum, a region of the intestinal tract with a relatively less dense bacterial population. Obviously, the fermentation of lactulose in the ileum is limited and not sufficient to prevent translocation of salmonella. Supplementation of a lactulose diet with calcium phosphate reversed the unfavorable increased cytotoxicity of fecal water. In addition, calcium phosphate stimulated lactulose fermentation, as judged by the reduced lactulose excretion in feces and increased fecal lactic acid, ammonia, and nitrogen excretion.Finally, it was investigated whether the calcium phosphate-induced protection against colonization and translocation of salmonella was mediated by a stimulation of the intestinal lactobacilli (chapter 6). In-vitro, L. acidophilus was rapidly killed by physiologically relevant concentrations of fatty acids and (un)conjugated bile acids. In contrast, even high concentrations of these surfactants did not affect the viability of S. enteritidis . Calcium phosphate-supplementation reduced the cytotoxicity and the concentration of bile acids and fatty acids in ileal contents and fecal water of rats. Moreover, calcium phosphate notably changed the composition of ileal bile acids into a less cell-damaging direction. Consequently, significantly increased numbers of lactobacilli were detected in ileal contents, on the ileal mucosa and in feces of non-infected, calcium phosphate-supplemented animals. At the same time, the calcium phosphate group had less viable salmonella in ileal contents, on the ileal mucosa and in feces. In accordance, the infection-induced urinary NO x excretion was diminished by calcium phosphate supplementation.</p
Dispelling the Myths Behind First-author Citation Counts
Get PDFWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
BIOWEPRO. Biomolekulare Wechselwirkung von Proteinen
No full textSchomburg D, Jakob U, Meyer M, et al. BIOWEPRO. Biomolekulare Wechselwirkung von Proteinen. In: Wolf G, Schmidt R, van der Meer M, eds. Statusseminar des BMBF. Bioinformatik. 1995: 125-153
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