Showing papers by "University of Alcalá published in 2001"
TL;DR: The results suggest that ecological networks are very robust against random removals but can be extremely fragile when selective attacks are used, and have important consequences for biodiversity dynamics and conservation issues, current estimations of extinction rates and the relevance and definition of keystone species.
Abstract: A detailed analysis of three species–rich ecosystem food webs has shown that they display skewed distributions of connections. Such graphs of interaction are, in fact, shared by a number of biological and technological networks, which have been shown to display a very high homeostasis against random removals of nodes. Here, we analyse the responses of these ecological graphs to both random and selective perturbations (directed against the most–connected species). Our results suggest that ecological networks are very robust against random removals but can be extremely fragile when selective attacks are used. These observations have important consequences for biodiversity dynamics and conservation issues, current estimations of extinction rates and the relevance and definition of keystone species.
728 citations
TL;DR: A growing body of evidence suggests that cisplatin-induced cell death does not always come from "classic" apoptosis, and some cells might die as a result of an unfinished apoptotic program.
Abstract: It is generally accepted that DNA damage and subsequent induction of apoptosis may be the primary cytotoxic mechanism of cisplatin and other DNA-binding antitumor drugs (Fisher,1994). Because the final step of apoptosis is characterized by morphological changes in the nucleus, the death signals of the execution phase must be transmitted from the cytoplasm to the nucleus. Thus, the recognition and processing of cisplatin-induced DNA damage through"classic" apoptosis, requires that a nuclear signal, generated at the initiation phase, be transmitted to the cytoplasm to be processed through the effector and execution phases. At the end of the execution phase, the apoptotic signal must come back to the nucleus to produce internucleosomal DNA degradation. Therefore, the induction of apoptosis from detection and subsequent processing of cisplatin-induced DNA damage seems to be a long and complex process of cell death. However, because cisplatin is a nonspecific drug and reacts not only with DNA but also with proteins,we cannot rule out the possibility that in some cases of cisplatin-induced apoptosis, an easier process of initiation, such as damage to cytoplasmic proteins, may take place (Perez, 1998). Thus, damage to proteins is worth considering as a factor contributing to cisplatin-induced apoptosis. Moreover, it is possible that cisplatin damage to proteins could induce apoptosis at the execution phase level. In fact, initiation of apoptosis at the execution phase (activation of caspases) has been previously reported for the cell killing produced by cytotoxic T lymphocytes (Golstein et al., 1991). Although apoptosis and necrosis are conceptually distinct forms of cell death with very different morphological and biochemical characteristics, these two types of demise may occur simultaneously in tissues or cell cultures exposed to the same insult (Eguchi et al., 1997, Zhan et al., 1999). In fact, both types of cell death have been found in the same population of cisplatin-treated cells (Pestell et al., 2000). Moreover, it has been hypothesized that in a tissue or cell population,apoptosis and necrosis might be two extremes of a continuum of possible types of cell demise. Individual cell death would be decided by factors such as the availability of energy and the metabolic condition of the cell (Leist et al., 1997). Thus, some cells might die as a result of an unfinished apoptotic program. In fact, in L1210 leukemic cells, cisplatin-induced cell death seems to be the result of a defective apoptotic program that lacks some morphological and biochemical characteristics attributed to apoptosis (Segal-Bendirdjian and Jacquemin-Sablon, 1995). In addition, at high doses, cisplatin could damage molecules involved in cellular energy supply (i.e., ATP) and also proteins directly or indirectly involved in the apoptotic process (i.e., p53, Bax, Bcl-2, and caspases), leading to necrotic cell death. In fact, in cisplatin-resistant keratinocytes transformed by H-ras oncogene, a high dose of cisplatin (312 microM) induces characteristic features of necrotic cell death(Perez et al., 1999). Thus, depending on the level of cellular damage induced by cisplatin, necrosis could take place either directly or as a consequence of an unfinished apoptotic program. In summary, a growing body of evidence suggests that cisplatin-induced cell death does not always come from "classic"apoptosis. Depending on both cisplatin dose and cellular status, cisplatin may also induced cell death by a defective apoptotic program or even by necrosis. Elucidation of the conditions under which the apoptotic program induced by cisplatin as well as other antitumor drugs is totally or partially executed may have important implications for the outcome of cancer chemotherapy.
552 citations
TL;DR: In this article, a study of the relationship between landscape structure and species diversity distribution (estimated in terms of richness of birds, amphibians, reptiles and butterflies) in the region of Madrid, Spain is presented.
Abstract: The parameters referring to landscape structure are essential in any evaluation for conservation because of the relationship that exists between the landscape structure and the ecological processes. This paper presents a study of the relationships between landscape structure and species diversity distribution (estimated in terms of richness of birds, amphibians, reptiles and butterflies) in the region of Madrid, Spain. The results show that the response of species richness to landscape heterogeneity varies depending on the group of species considered. For birds and lepidopterans, the most important factor affecting the distribution of richness of species is landscape heterogeneity, while other factors, such as the specific composition of land use, play a secondary role at this scale. On the other hand, richness of amphibians and reptiles is more closely related to the abundance of certain land-use types. The study highlights the importance of heterogeneity in Mediterranean landscapes as a criterion for landscape planning and for definition of management directives in order to maintain biodiversity.
388 citations
TL;DR: In this article, a new approach to the error sources in the spectrophotometric determination of total phenols in foods has been performed and the choice of the suitable phenolic standard and the influence of sugars and proteins as interfering compounds were carefully studied.
358 citations
TL;DR: It is concluded that this model represents a useful tool both for phenotyping mutant mice and for classical pharmacology since information on visceral pain, referred hyperalgesia and colon inflammation can all obtained from the same animal.
Abstract: The generation of transgenic mice that lack or overexpress genes relevant to pain is becoming increasing common. However, only one visceral pain model, the writhing test, is widely used in mice. Here we describe a novel model, chemical stimulation of the colon, which we have developed in mice. Mice of either sex were injected i.v. with 30 mg/kg Evan's Blue for subsequent determination of plasma extravasation. For behavioural testing, they were placed on a raised grid and 50 microl of saline, mustard oil (0.25-2.5%) or capsaicin (0.03-0.3%) was administered by inserting a fine cannula into the colon via the anus. Visceral pain-related behaviours (licking abdomen, stretching, contractions of abdomen etc) were counted for 20 min. Before intracolonic administration, and 20 min after, the frequency of withdrawal responses to the application of von Frey probes to the abdomen was tested. The colon was removed post-mortem and the Evan's Blue content measured. Mustard oil and capsaicin administration evoked dose-dependent visceral pain behaviours, referred hyperalgesia (significant increase in responses to von Frey hairs) and colon plasma extravasation. The peak behavioural responses were evoked by 0.1% capsaicin and by 1% mustard oil respectively. The nociceptive behavioural responses were dose-dependently reversed by morphine (ED50 = 1.9 +/- 1 mg/kg s.c.). We conclude that this model represents a useful tool both for phenotyping mutant mice and for classical pharmacology since information on visceral pain, referred hyperalgesia and colon inflammation can all obtained from the same animal.
329 citations
TL;DR: The hypothesis that chemokines initiate leukocyte infiltration and precede proteinuria and renal damage in MRL/lpr mice is supported and chemokine generation is restricted to sites of subsequent inflammatory cell infiltration and the onset of proteinuria.
Abstract: Lupus nephritis is characterized by immune complex deposition and inflammatory cell infiltration. Therefore, the initiation and progression of lupus nephritis in MRL/MpJ Fas(lpr/lpr) (MRL/lpr) mice were investigated, with a focus on the expression of several chemokines and chemokine receptors. Mice were monitored for proteinuria from 6 to 20 wk of age, and kidneys were examined every 2 wk by light microscopy, electron microscopy, and immunohistologic analyses. Furthermore, the expression of chemokines, chemokine receptors, and proinflammatory cytokines was analyzed in ribonuclease protection assays. MRL/lpr mice demonstrated increased expression of monocyte chemoattractant protein-1, regulated upon activation, normal T cell-expressed and -secreted protein, inducible protein of 10 kD, and macrophage inflammatory protein-1beta at week 8. At that time point, levels of circulating and glomerular immune complexes were increased, and no proteinuria or histopathologic signs of renal damage could be observed. As assessed in immunohistochemical and in situ hybridization analyses, monocyte chemoattractant protein-1 and regulated upon activation, normal T cell-expressed and -secreted protein expression was preferentially located in the glomeruli and interstitium. Mononuclear cell infiltration of the kidney was observed by weeks 10 to 12. At week 12, the renal expression of chemokine receptor 1 (CCR1), CCR2, and CCR5 was increased, mice became proteinuric, and renal damage was histologically evident. Finally, the expression of proinflammatory cytokines was detected (weeks 12 to 14). In summary, (1) chemokines are upregulated before inflammatory cell infiltration, proteinuria, and kidney damage are observed; (2) chemokine generation is restricted to sites of subsequent inflammatory cell infiltration, i.e., glomeruli and interstitium; (3) chemokine receptor expression parallels mononuclear cell infiltration; and (4) proinflammatory cytokines are upregulated later, in parallel with inflammatory cell infiltration and the onset of proteinuria. These results support the hypothesis that chemokines initiate leukocyte infiltration and precede proteinuria and renal damage in MRL/lpr mice.
232 citations
TL;DR: In this article, the authors offer an overview on what is actually happening in the European Union in contrast to some generally accepted hypotheses and models predicting regional convergence, showing that after a period of relative regional convergence in GDP per capita as well in terms of labour productivity, this process has almost completely ended.
Abstract: Economic convergence or non-convergence between countries and regions continues to attract analytical attention in Europe. To converge in real terms and not only in terms of nominal variables is one of the basic aims of the European Union Treaty. A first objective of this paper is to offer an overview on what is actually happening in the European Union in contrast to some generally accepted hypotheses and models predicting regional convergence. Empirical evidence shows that after a period of (relative) regional convergence in GDP per capita as well in terms of labour productivity, this process has almost completely ended. Possible explanations go from the most pro-convergence theories (optimists) to those that outweigh real obstacles to theoretical assumptions (pessimists). As a second objective the paper examines two important facts that can contribute to explaining the actual trends. The first is named the `national effect', where regions of each country have economic behaviour strongly linked to the national economy as a whole. The second is the `differential' behaviour of many European regions in terms of economic outcomes.
196 citations
TL;DR: A Holocene palaeoecological sequence from Villaverde, south-central Spain, is presented in this paper, where the pollen stratigraphy is used to infer past vegetation changes within a catchment area that represents the boundary between semi-arid, plateau and mountain vegetation.
Abstract: A Holocene palaeoecological sequence from Villaverde, south-central Spain, is presented. The pollen stratigraphy is used to infer past vegetation changes within a catchment area that represents the boundary between semi-arid, plateau and mountain vegetation. From c. 9700-7530 cal. yr BP, Pinus is dominant, probably as a result of a combination of a relatively dry climate and natural fire disturbance. From c. 7530-5900 cal. yr BP, moderate invasion by Quercus appears to be a migrational response following increased moisture and temperature, but in part shaped by competitive adjustments. From c. 5900-5000 cal. yr BP, the pine forests are replaced by deciduous-Quercus forests with an important contribution from Corylus, Betula, Fraxinus and Alnus. Mediterranean-type forests spread from c. 5000 to 1920 cal. yr BP coincident with expansions of Artemisia, Juniperus and other xerophytes. From c. 1920-1160 cal. yr BP, Pinus becomes dominant after a disturbance- mediated invasion of the oak forests. Human impact u...
184 citations
TL;DR: In this article, it was shown that oxidation-mediated alterations in mitochondrial function regulate the selection between apoptosis and necrosis in alkylating drug-treated human promonocytic cells.
172 citations
TL;DR: The increased epithelial immunostaining for both ER-alpha and ER-beta in BPH and PC suggests that the involvement of estrogen receptors in hyperplasia and cancer concerns mainly the epithelium.
Abstract: Two different estrogen receptors (ER-alpha and ER-beta) have been described, which are differentially involved in regulating the normal function of reproductive tissues. ER-alpha was considered for a long time to be the only estrogen receptor, and it has been detected in the stromal cells of the human prostate but not in the epithelium. To obtain new information about the differential effects of both receptor types, we have investigated their localization in normal prostates, benign prostatic hyperplasia (BPH), and prostatic cancer (PC) by immunohistochemistry, ELISA and Western blot. Epithelial immunostaining was absent in normal prostates and was present in BPH (10% of cells) and PC (80% of cells), whereas about 15% of stromal cells were positively immunostained for ER-alpha in the three types of prostatic specimens studied. Epithelial immunostaining for ER-beta was detected in normal prostates (13% of cells), BPH (30% of cells) and PC (79% of cells), whereas stromal immunostaining for ER-beta was absent in normal and hyperplastic prostates and was present in PC (12% of cells). The complementary presence of both receptor types in the normal prostate (ER-beta in the epithelium and ER-alpha in the stroma) might explain the mechanism of estrogen action in the development of BPH. The increased epithelial immunostaining for both ER-alpha and ER-beta in BPH and PC suggests that the involvement of estrogen receptors in hyperplasia and cancer concerns mainly the epithelium.
156 citations
TL;DR: If the inverse relationship between impulsivity and lethality is replicated in other large and representative samples, new studies will be needed to clarify the complex interactions between the clinical dimensions (lethality, impulsivity as a state, and impulsiveness as a personality trait) and the biological correlates (particularly serotonergic function) of suicidal behavior.
Abstract: Background: Biological studies suggest that lower serotonergic activity is associated with both greater suicide lethality and impulsive personality traits. These results may lead to the conclusion that impulsivity in the attempt should be associated with greater lethality. However, Klerman's review of epidemiologic suicide studies suggests an inverse relationship between impulsivity and lethality. This seemingly paradoxical relationship between impulsivity and lethality has not been explored in large representative clinical samples of suicide attempts. Method: During 1996 to 1998, 478 individuals who attempted suicide were studied in a general hospital in Madrid, Spain. Impulsivity was measured as described in the literature by combining 2 items of Beck's Suicidal Intent Scale (active preparation for attempt and degree of premeditation). Lethality of the attempt was assigned I of 4 levels according to the need for medical and/or psychiatric treatment. Results: More than half of the attempts were impulsive (55%; 95% confidence interval [CI], 51% to 59%), approximately one fourth of the attempts had an intermediate level of impulsivity (28%; 95% CI, 24% to 32%), and approximately one sixth of the attempts were not impulsive (17%, 95% CI, 13% to 21%). There was an inverse association between the impulsivity and lethality of the suicide attempt (X 2 = 62.639, df = 6, p <.0001). The most impulsive attempts tended to result in less morbidity, while the less impulsive attempts tended to be more lethal. Conclusion: If the inverse relationship between impulsivity and lethality is replicated in other large and representative samples, new studies will be needed to clarify the complex interactions between the clinical dimensions (lethality, impulsivity as a state, and impulsivity as a personality trait) and the biological correlates (particularly serotonergic function) of suicidal behavior.
TL;DR: In this paper, the authors deal with flood events in Mediterranean ephemeral streams typical of the Valencia region, using daily hydrological data from the Rambla de la Viuda basin and 5-min data from both the Barranc del Carraixet and the RamBLa de Poyo basins.
Abstract: This article deals with flood events in Mediterranean ephemeral streams typical of the Valencia region. The combination of the basin physical characteristics (steep slopes, sparse vegetation, thin soils and permeable rock) and intense, heavy and irregularly distributed rain, generates flash floods. Runoff generation is sudden, giving rise to flash floods with sharp, narrow hydrographs with short time lags. The high amount of runoff is, nevertheless, only a small fraction of the total rainfall, since the characteristics of the river basins are such that infiltration of large amounts of water occurs. Using daily hydrological data from the Rambla de la Viuda basin and 5-min data from both the Barranc del Carraixet and the Rambla de Poyo basins, the rainfall–runoff processes have been analysed during flood events in these ephemeral streams.
TL;DR: Three classes of exactly solvable models for fermion and boson systems, based on the pairing interaction, are presented, which are solvable in any dimension and show attractive pair correlations.
Abstract: We present three classes of exactly solvable models for fermion and boson systems, based on the pairing interaction. These models are solvable in any dimension. As an example we show the first results for fermions interacting with repulsive pairing forces in a two-dimensional square lattice. In spite of the repulsive pairing force the exact results show attractive pair correlations.
TL;DR: The contributions of recently identified symporter proteins to solute transfer are reviewed here, as is the role of apoplastic invertases in promoting solute assimilation.
TL;DR: Unlike propranolol, long-term losartan administration does not significantly reduce HVPG in patients with cirrhosis treated after a variceal bleeding episode, and it caused hypotension and reduced GFR in patientswith moderate liver failure.
TL;DR: The fossil pollen record of Canada de la Cruz in the Segura mountains of southern Spain yields insights into high-elevation vegetational dynamics over the last c. 8320 years as mentioned in this paper.
Abstract: Summary
1
The fossil pollen record of Canada de la Cruz in the Segura mountains of southern Spain yields insights into high-elevation vegetational dynamics over the last c. 8320 years. Phases of xerophytic grassland alternate with high-mountain open pine forests and expansion of deciduous forests and Mediterranean scrub at lower altitudes.
2
Longer-term stable vegetation patterns are interrupted by multidecadal to century-scale shifts at about 7770, 3370, 2630, 1525 and 790 years BP.
3
Some of the vegetation types have no modern analogues and represent high-altitude remnants of widespread last-glacial xerophytic communities. Other species patterns, characteristic of current scrub associations, appeared only within the last 800 years.
4
The sequence fits within the regional context of a generally wet mid-Holocene (c. 7700–3300 years BP) characterized by spread of mesophilous vegetation, between drier conditions characterized by greater abundance of xerophytes.
5
The pollen record and current ecological studies on high-elevation vegetation of Mediterranean Spain suggest that control of vegetation is primarily climatic although grazing pressure, which would have pushed vegetation over a threshold for change, cannot be discounted.
TL;DR: Somatostatin is highly effective in controlling variceal bleeding and patients with active bleeding at emergency endoscopy may benefit from higher doses of somatostAT infusion.
TL;DR: The specific localization of CLA-1/SR-BI and CD36 along the human gastrointestinal tract and their ability to interact with a large variety of lipids strongly support a physiological role for them in absorption of dietary lipids.
Abstract: The scavenger receptors CLA-1/SR-BI and CD36 interact with native and modified lipoproteins and with some anionic phospholipids. In addition, CD36 binds/transports long-chain free fatty acids. Recent biochemical evidences indicates that the rabbit CLA-1/SR-BI receptor can be detected in enterocytes, and previous studies showed the presence of mRNA for both CLA-1/SR-BI and CD36 in some segments of the intestinal tract. These findings prompted us to study their respective localization and distribution from the human stomach to the colorectal segments, using immunohistochemical methods. Their expression in the colorectal carcinoma-derived cell line Caco-2 was analyzed by Northern blotting. In the human intestinal tract, CLA-1/SR-BI was found in the brush-border membrane of enterocytes from the duodenum to the rectum. However, CD36 was found only in the duodenal and jejunal epithelium, whereas enterocytes from other intestinal segments were not stained. In the duodenum and jejunum, CD36 co-localized with CLA-1/SR-BI in the apical membrane of enterocytes. The gastric epithelium was immunonegative for both glycoproteins. We also found that CLA-1/SR-BI mRNA was expressed in Caco-2 cells and that its expression levels increased concomitantly with their differentiation. In contrast, the CD36 transcript was not found in this colon cell line, in agreement with the absence of this protein in colon epithelium. The specific localization of CLA-1/SR-BI and CD36 along the human gastrointestinal tract and their ability to interact with a large variety of lipids strongly support a physiological role for them in absorption of dietary lipids.
TL;DR: Is-MN does not reduce the incidence of FVB in patients with cirrhosis and esophageal varices who cannot be treated with beta-blockers because contraindications or intolerance to these drugs, suggesting that Is-MN has no place in the primary prophylaxis of variceal bleeding.
TL;DR: It is concluded that peripheral blood cells of patients with COPD show clear defects in natural immunity that are partially rescued by glycophosphopeptical.
Abstract: We have investigated both modifications in natural (innate) immunity caused by chronic obstructive pulmonary disease (COPD) and the effects of a glycophosphopeptical immunomodulator (Inmunoferon) treatment on COPD-associated immunoalterations. In a double-blinded clinical trial, 60 patients with COPD received glycophosphopeptical or placebo during 90 consecutive days at oral doses of 3 g/d. Fifty-six sex- and age-matched healthy control subjects were included as a reference group for immunologic parameters. Peripheral blood natural killer (PBNK) cell cytotoxic activity and phagocytic activity of peripheral monocytes/macrophages (Mo/Ma) and polymorphonuclear (PMN) cells were assessed at baseline and then again at the end of treatments. We found both PBNK activity and phagocytic activity to be significantly decreased in patients with COPD compared with levels in healthy volunteers. The treatment with glycophosphopeptical provoked significant stimulatory effects on PBNK cytotoxic activity. This stimulation w...
TL;DR: It is proposed that the induction of chloroplastic ndh genes under photooxidative stress is mediated by H2O2 through mechanisms that involve a rapid translation of pre-existing transcripts and the increase of the ndh transcript levels.
Abstract: Chloroplast-encoded NDH polypeptides (components of the plastid Ndh complex) and the NADH dehydrogenase activity of the Ndh complex (NADH-DH) increased under photooxidative stress. The possible involvement of H2O2-mediated signaling in the photooxidative induction of chloroplastic ndh genes was thoroughly studied. We have analyzed the changes in the NADH-DH and steady-state levels of NDH-F polypeptide and ndhB and ndhF transcripts in barley (Hordeum vulgare cv Hassan) leaves. Subapical leaf segments were incubated in growing light (GL), photooxidative light (PhL), GL and H2O2 (GL + H2O2), or PhL and 50 nM paraquat in the incubation medium. Treatments with H2O2 under GL mimicked the photooxidative stimulus, causing a dose-dependent increase of NADH-DH and NDH-F polypeptide. The kinetic of Ndh complex induction was further studied in leaves pre-incubated with or without the H2O2-scavenger dimethyltiourea. NADH-DH and NDH-F polypeptide rapidly increased up to 16 h in PhL, GL+ H2O2, and, at higher rate, in PhL and paraquat. The observed increases of NADH-DH and NDH-F after 4 h in PhL and GL + H2O2 were not accompanied by significant changes in ndhB and ndhF transcripts. However, at 16-h incubations NADH-DH and NDH-F changes closely correlated with higher ndhB and ndhF transcript levels. All these effects were prevented by dimethylthiourea. It is proposed that the induction of chloroplastic ndh genes under photooxidative stress is mediated by H2O2 through mechanisms that involve a rapid translation of pre-existing transcripts and the increase of the ndh transcript levels.
TL;DR: Results indicate that MMP-2 may be involved in the TF matrix degradative process in patients with direct hernia, suggesting a genetic defect or irreversible change as the origin of this pathology rather than environmental factors, which may later participate in the development of the hernial process.
Abstract: Inguinal hernias are among the disorders that most frequently require surgery: their repair accounts for 10% to 15% of all general surgical procedures. 1 Although the cause remains unknown, it has been established that the integrity of the abdominal wall in the groin area is dependent on the transversalis fascia (TF), the oblique orientation of the inguinal canal, and a sphincterlike structure of the internal ring. 2
Despite numerous predisposing factors, including anatomical features (persistence of the peritoneal-vaginal conduit, high insertion point of the transverse arch) and those associated with other diseases (obesity, chronic obstructive pulmonary disease, constipation), the underlying cause of the development of the different types of hernias is of a biologic nature. Research aimed at evaluating the role played by biologic factors has centered on possible alterations in connective tissue metabolism. This idea is also supported by the fact that diseases such as Marfan and Ehlers-Danlos syndromes, cutis laxa, osteogenesis imperfecta, 3 and congenital hip dislocation 4 have been associated with hernial processes.
Tissue specimens from patients with hernias for this type of experimental study include the abdominal anterior rectus muscle sheath, 5 cremaster, hernial sac, 6 and even skin tissue. 7 The expression pattern of certain types of collagen 8 and certain enzyme dysfunctions 9 have also been the subject of several of these studies.
Concerned about the cause of hernias, we have conducted several investigations on TF biopsy specimens from patients with hernias. We correlated the ultrastructural features of the TF with collagen activity and degradation through the study of certain metalloproteinases (MMPs) and observed an increase in MMP-2 expression in TF specimens from patients with direct hernias. 10 This enzyme degrades and participates in the turnover of the extracellular matrix, acting on certain types of collagen and elastin. Its expression is enhanced in processes such as genitourinary prolapse 11 and aortic aneurysm. 12,13 Further, it has been reported that patients with this last pathology have an increased incidence of hernias. 14,15 These findings prompted us to propose a hypothesis for the behavior of MMP-2 in TF specimens of patients with hernias, based on the possibility of a similar mechanism that might explain why in some patients the posterior wall of the inguinal canal of the TF remains unaltered, and in others it presents defects that lead to hernial processes.
To this end, we designed an in vitro model using cultured fibroblasts from the TF to determine whether the modifications in MMP expression found in tissue are maintained in culture. If this were the case, it could point to a genetic predisposing factor for this pathology, and thus hernia types showing some alteration at the level of the TF could be candidates for primary repair with a prosthetic material in a effort to prevent future relapses.
TL;DR: These findings are consistent with a potential role for eif4E, 4E-BP1 and eIF4G in the down-regulation of translation during ischaemia, and suggest eIF 4F complex formation is likely to contribute to the persistent inhibition of translation observed at longer reperfusion times.
Abstract: The striking correlation between neuronal vulnerability and down-regulation of translation suggests that this cellular process plays a critical part in the cascade of pathogenetic events leading to ischaemic cell death. There is compelling evidence supporting the idea that inhibition of translation is exerted at the polypeptide chain initiation step, and the present study explores the possible mechanism/s implicated. Incomplete forebrain ischaemia (30 min) was induced in rats by using the four-vessel occlusion model. Eukaryotic initiation factor (eIF)2, eIF4E and eIF4E-binding protein (4E-BP1) phosphorylation levels, eIF4F complex formation, as well as eIF2B and ribosomal protein S6 kinase (p70(S6K)) activities, were determined in different subcellular fractions from the cortex and the hippocampus [the CA1-subfield and the remaining hippocampus (RH)], at several post-ischaemic times. Increased phosphorylation of the alpha subunit of eIF2 (eIF2 alpha) and eIF2B inhibition paralleled the inhibition of translation in the hippocampus, but they normalized to control values, including the CA1-subfield, after 4--6 h of reperfusion. eIF4E and 4E-BP1 were significantly dephosphorylated during ischaemia and total eIF4E levels decreased during reperfusion both in the cortex and hippocampus, with values normalizing after 4 h of reperfusion only in the cortex. Conversely, p70(S6K) activity, which was inhibited in both regions during ischaemia, recovered to control values earlier in the hippocampus than in the cortex. eIF4F complex formation diminished both in the cortex and the hippocampus during ischaemia and reperfusion, and it was lower in the CA1-subfield than in the RH, roughly paralleling the observed decrease in eIF4E and eIF4G levels. Our findings are consistent with a potential role for eIF4E, 4E-BP1 and eIF4G in the down-regulation of translation during ischaemia. eIF2 alpha, eIF2B, eIF4G and p70(S6K) are positively implicated in the translational inhibition induced at early reperfusion, whereas eIF4F complex formation is likely to contribute to the persistent inhibition of translation observed at longer reperfusion times.
TL;DR: Like some other compounds found in medicinal herbs, these molecules possess an array of potentially beneficial anti-eicosanoid properties which may, alongside other constituents, contribute to the claimed therapeutic properties of the plant from which they are derived.
Abstract: Three phenylpropanoid glycosides (salidroside, syringin and coniferin) and one lignan (phillyrin) isolated from the leaves of Phillyrea latifolia L. (Oleaceae) were tested for interactions with the cyclo-oxygenase and 5-lipoxygenase pathways of arachidonate metabolism in calcium-stimulated mouse peritoneal macrophages and human platelets, and for their effects on cell viability. These compounds are capable of exerting inhibitory actions on enzymes of the arachidonate cascade. Phillyrin, salidroside and syringin exert a preferential effect on the cyclo-oxygenase pathway, inhibiting release of the cyclo-oxygenase metabolites prostaglandin E2 (IC50 values 45.6 microM, 72.1 microM and 35.5 microM, respectively) and to a lesser extent reducing thromboxane B2 levels (IC50 values 168 microM, 154 microM and 29.3 microM, respectively). In contrast, coniferin can be classified as a "dual inhibitor", since it produces reduction in generation of both cyclo-oxygenase (IC50 values 75.2 microM for prostaglandin E2 and 619 microM for thromboxane B2) and 5-lipoxygenase metabolites, but the effects are greater against leukotriene C4 (IC50 value 63.6 microM). Structure-activity relationships of the three phenylpropanoid glycosides are discussed. Thus, like some other compounds found in medicinal herbs, our molecules possess an array of potentially beneficial anti-eicosanoid properties which may, alongside other constituents, contribute to the claimed therapeutic properties of the plant from which they are derived.
TL;DR: In this paper, a diagnostic framework for evaluating landscapes is presented, which is based on quantifiable land cover and landscape structure characteristics, and the process of landscape evaluation is an iterative improvement and refinement of indicators and reference data.
TL;DR: An overview of MC phenotypes in health and disease is given, and explanations for the phenotypic variability of MC are attempted to provide.
Abstract: Mast cells (MC) are multipotent effector cells of the immune system. They contain an array of biologically active mediator substances in their granules. MC also express a number of functionally important cell surface antigens, including stem cell factor receptor (SCFR=kit=CD117), high affinity IgER (FcepsilonRI), or CSaR (CD88). Respective ligands can induce or promote degranulation, migration, or cytokine production. Other integral surface molecules can mediate adhesion or cell aggregation. Recent data suggest that a number of critical molecules are variably expressed on the surface of human MC. In fact, depending on the environment (organ), stage of cell maturation, type of disease, and other factors, MC express variable amounts of activation-linked antigens (CD25, CD63, CD69, CD88), cell recognition molecules (CD2, CD11, CD18, CD50, CD54), or cytokine receptors. At present, however, little is known about the mechanisms and regulation of expression of such antigens. The present article gives an overview of MC phenotypes in health and disease, and attempts to provide explanations for the phenotypic variability of MC.
TL;DR: The results presented herein are consistent with the interpretation that the intensity of AR staining in Sertoli cells diminishes as a function of the severity to which the cells are afflicted within a cryptorchid testis and that focal absence of AR expression in SERToli cells correlates with a lack of local spermatogenesis in the tubules.
Abstract: Androgen receptor (AR) immunohistochemistry was performed in an archival collection of adult human cryptorchid testes to determine whether AR cellular distribution and intensity of immunostaining were functions of the severity of cellular dysgenesis. The seminiferous tubule histology of cryptorchid testes collected from adults is marked by three specific patterns. 1) Seminiferous tubules are characterized as maintaining focal areas of germinal cell differentiation (albeit incomplete) that are interspersed with 2) tubules composed of Sertoli cells only, these latter cells being principally of the adult type, although dysgenetic and immature Sertoli cells may also be detected. 3) In contrast, there is a class of tubule that is characterized as being composed exclusively of Sertoli cells that are extremely dysgenetic in appearance. The majority of adult-type Sertoli cells found in the first types of tubules exhibited either robust or moderate AR staining intensity. Peritubular cells of these tubules also expressed a similar AR staining intensity. In contrast, in the more dysgenetic and immature type Sertoli cells found in the second type of tubules, the intensity of AR staining was significantly less, if not missing altogether. Finally, in the most dysgenetic tubules, Sertoli cell AR staining was never detected. To our knowledge, this is the first report in the literature that addresses the intensity of AR immunostaining in Sertoli cells of cryptorchid testes. The results presented herein are consistent with the interpretation that the intensity of AR staining in Sertoli cells diminishes as a function of the severity to which the cells are afflicted within a cryptorchid testis and that focal absence of AR expression in Sertoli cells correlates with a lack of local spermatogenesis in the tubules.
TL;DR: In this article, the authors take stock of the available Spanish evidence regarding the consequences of a dual labor market, in which one-third of employees are under very flexible employment contracts with low severance payments, and two-thirds are under permanent employment contract with very high employment protection.
Abstract: During the last two decades many EU countries have reformed the set of legal rules that regulate dismissals. And, in contrast with other institutional reforms of the labor market, there seems to be a common strategy of maintaining strict employment protection legislation for workers under the typical "full time" permanent employment contract, but liberalizing "atypical" temporary/part-time employment contracts for new entrants in the labor market. As a result, the incidence of temporary employment has noticeably increased across the EU, being Spain the paramount case in this regard. In this paper we aim at two goals. First, we take stock of the available Spanish evidence regarding the consequences of a dual labor market - in which one-third of employees are under very flexible employment contracts with low severance payments, and two-thirds are under permanent employment contracts with very high employment protection - and the lessons which can be drawn for other countries. Secondly, we address the puzzle of why temporary employment in Spain, despite recent labor market reforms which have reduced firing costs under the permanent contract and restricted the use of temporary contracts, remains so high.
TL;DR: Assessment of aspects of pathological processes such as fibrosis, frequency of centralized nuclei, presence of degenerative or regenerative fibres, expression of utrophin and associated protein complexes, and myosin heavy chain isoforms in three muscles from old male mdx mice provided evidence that the MAS mdx muscle presents a slight deterioration pattern in comparison to that of DIA and GTC muscles.
Abstract: X chromosome-linked muscular dystrophic mdx mouse lacks the sarcolemmal protein dystrophin and represents a genetic homologue of human Duchenne muscular dystrophy (DMD). The present study analysed some aspects of pathological processes such as fibrosis, frequency of centralized nuclei, presence of degenerative or regenerative fibres, expression of utrophin and associated protein complexes, and myosin heavy chain isoforms in three muscles [diaphragm (DIA), gastrocnemius (GTC) and masseter (MAS)] from old male mdx mice. All parameters investigated comparatively in these pathological muscles provided evidence that the MAS mdx muscle presents a slight deterioration pattern in comparison to that of DIA and GTC muscles. Utrophin and associated proteins are present in many cell clusters with continuous membrane labelling in MAS muscle. Respective proportions of myosin heavy chain isoforms, measured by electrophoresis/densitometry, showed only slight change in GTC muscle, significant evolution in DIA muscle but drastic isoform conversions in MAS muscle. These results highlighted the difference in deterioration susceptibility of various muscles to muscular dystrophy. The reason why this occurs in MAS muscles is still obscure and discussed in terms of the comparative developmental origins of these muscles.
TL;DR: The main topics concerning the epidemiology, clinical presentation and therapy of AIDS-related VL are reviewed.