bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pneumococcal zinc metalloproteinase ZmpC cleaves human matrix metalloproteinase 9 and is a virulence factor in experimental pneumonia
Authors: Oggioni Marco R. , Memmi Guido , Maggi Tiziana , Chiavolini Damiana , Iannelli Francesco , Pozzi Gianni 
Published: July 2003

SummaryThe ZmpC zinc metalloproteinase of Streptococcus pneumoniae, annotated in the type 4 genome as SP0071, was found to cleave human matrix metalloproteinase 9 (MMP‐9). The previously described IgA protease activity was confirmed to be specifically linked to the IgA1‐protease/SP1154 zinc metalloproteinase. MMP‐9 is a protease cleaving extracellular matrix gelatin and collagen and is activated by proteolytic cleavage like most proteases. MMP‐9 is a human protease and is involved in a variety of physiological and pathological matrix degrading processes, including tissue invasion of metastases and opening of the blood–brain barrier. While TIGR4 (serotype 4) and G54 (serotype 19) pneumococcal genome strains have a highly conserved copy of zmpC, the genome of R6 (a derivative of serotype 2 D39 strain) lacks zmpC. Both the analysis for zmpC presence and MMP‐9 cleavage activity in various pneumococcal strains showed correlation of ZmpC with MMP‐9 cleavage activity. When assaying clinical isolates of S. pneumoniae, the zmpC gene was not found in any of the nasal and conjunctival swab isolates, but it was present in 1 out of 13 meningitis isolates and in 6 out of 11 pneumonia isolates. In a murine pneumonia model, infection with a zmpC‐mutant reduced mortality at 3–4 days post‐infection by 75%, when compared with infection with wild‐type strains. These data indicate that the ZmpC pneumococcal protease may play a role in pneumococcal virulence and pathogenicity in the lung.
Mapping of the Plasmodium falciparum multidrug resistance gene 5′‐upstream region, and evidence of induction of transcript levels by antimalarial drugs in chloroquine sensitive parasites
Authors: Myrick Alissa , Munasinghe Anusha , Patankar Swati , Wirth Dyann F. 
Published: July 2003

SummaryThe Plasmodium falciparum multidrug resistance gene, pfmdr1, has been shown to be involved in the mediation of the parasite's response to various antimalarial drugs. Previous studies of pfmdr1 expression have shown that transcript levels are increased in drug‐resistant isolates. However, a detailed examination of the transcriptional regulation of this gene has not been completed. The aim of this study was to map the 5′ UTR of pfmdr1, and to examine the transcriptional profile of the gene in sensitive parasites treated with four different antimalarial drugs. RT‐PCR and 5′‐RACE mapping showed that the 5′ UTR has a length of 1.94 kb. A putative promoter has been identified via transient transfection. Northern analysis revealed a 2.1‐ to 2.7‐fold increase in pfmdr1 expression in 3D7 parasites treated with 50 nM chloroquine for 6 h, confirming results from Serial Analysis of Gene Expression. 3D7 parasites were subsequently treated with experimentally derived IC50 concentrations of mefloquine, quinine and pyrimethamine. pfmdr1 transcript levels specifically increased 2.5‐fold at 6 h in mefloquine‐treated parasites and threefold in parasites treated with quinine for 30 min. There was no evidence of transcript induction in pyrimethamine‐treated parasites. This is the first evidence of induction of pfmdr1 expression in sensitive cells; and suggests a novel method of transcriptional control for this gene.
Two‐component system VraSR positively modulates the regulation of cell‐wall biosynthesis pathway in Staphylococcus aureus
Authors: Kuroda Makoto , Kuroda Hiroko , Oshima Taku , Takeuchi Fumihiko , Mori Hirotada , Hiramatsu Keiichi 
Published: July 2003

SummaryDNA microarray covering the whole genome of Staphylococcus aureus strain N315 was prepared to investigate transcription profiles. The microarray analyses revealed that vancomycin induces transcription of 139 genes. Forty‐six genes among them failed to be induced in the vraSR null mutant KVR. Part of the genes regulated by VraSR system is associated with cell‐wall biosynthesis, such as PBP2, SgtB and MurZ. Other cell‐wall synthesis inhibitors also induced VraSR, suggesting that the sensor kinase VraS responds to the damage of cell‐wall structure or inhibition of cell‐wall biosynthesis. Additionally, the vraSR null mutants derived from hetero‐ and homo‐methicillin‐resistant S. aureus showed significant decrease of resistance against teicoplanin, β‐lactam, bacitracin and fosfomycin but not of d‐cycloserine and levofloxacin. The observation strongly indicates that VraSR constitutes a positive regulator of cell‐wall peptidoglycan synthesis, and that is deeply involved in the expression of β‐lactam and glycopeptide resistance in S. aureus.
Genetic characterization of pilin glycosylation and phase variation in Neisseria meningitidis
Authors: Power P. M. , Roddam L. F. , Rutter K. , Fitzpatrick S. Z. , Srikhanta Y. N. , Jennings M. P. 
Published: July 2003

SummaryPili of Neisseria meningitidis are a key virulence factor, being the major adhesin of this capsulate organism and contributing to specificity for the human host. Pili are post‐translationally modified by addition of either an O‐linked trisaccharide, Gal (β1‐4) Gal (α1‐3) 2,4‐diacetamido‐2,4,6‐trideoxyhexose or an O‐linked disaccharide Gal (α1,3) GlcNAc. The role of these structures in meningococcal pathogenesis has not been resolved. In previous studies we identified two separate genetic loci, pglA and pglBCD, involved in pilin glycosylation. Putative functions have been allocated to these genes; however, there are not enough genes to account for the complete biosynthesis of the described structures, suggesting additional genes remain to be identified. In addition, it is not known why some strains express the trisaccharide structure and some the disaccharide structure. In order to find additional genes involved in the biosynthesis of these structures, we used the recently published group A strain Z2491 and group B strain MC58 Neisseria meningitidis genomes and the unfinished Neisseria meningitidis group C strain FAM18 and Neisseria gonorrhoeae strain FA1090 genomes to identify novel genes involved in pilin glycosylation, based on homology to known oligosaccharide biosynthetic genes. We identified a new gene involved in pilin glycosylation designated pglE and examined four additional genes pglB/B2, pglF, pglG and pglH. A strain survey revealed that pglE and pglF were present in each strain examined. The pglG, pglH and pglB2 polymorphisms were not found in strain C311♯3 but were present in a large number of clinical isolates. Insertional mutations were constructed in pglE and pglF in N. meningitidis strain C311♯3, a strain with well‐defined lipopolysaccharide (LPS) and pilin‐linked glycan structures. Increased gel migration of the pilin subunit molecules of pglE and pglF mutants was observed by Western analysis, indicating truncation of the trisaccharide structure. Antisera specific for the C311♯3 trisaccharide failed to react with pilin from these pglE and pglF mutants. GC‐MS analysis of the sugar composition of the pglE mutant showed a reduction in galactose compared with C311♯3 wild type. Analysis of amino acid sequence homologies has suggested specific roles for pglE and pglF in the biosynthesis of the trisaccharide structure. Further, we present evidence that pglE, which contains heptanucleotide repeats, is responsible for the phase variation between trisaccharide and disaccharide structures in strain C311♯3 and other strains. We also present evidence that pglG, pglH and pglB2 are potentially phase variable.
Experimental evidence for alternative stable equilibria in a benthic pond food web
Authors: Chase Jonathan M. 
Published: July 2003

AbstractBoth local and initial conditions have been implicated in causing variation in the strengths of predator effects among natural communities. In this study, I performed a controlled mesocosm experiment using two common snails, Physella gyrina and Helisoma trivolvis, and their insect predator, Belostoma flumineum, to explicitly quantify and understand the causes of previously observed variation in food web interactions in natural ecosystems. The results from a controlled mesocosm experiment showed that: (1) at low productivity, snails were dominated by small‐vulnerable species (P. gyrina), predator effects were strong and predator effects caused a trophic cascade extending to producers; (2) at high productivity, snails were dominated by large‐invulnerable species (H. trivolvis), predator effects were weak and there was no trophic cascade to producers; (3) at intermediate productivity, alternative stable equilibria were implicated, such that depending on initial conditions, snails were dominated by either small‐vulnerable or large‐invulnerable species and predator effects were either strong or weak. Thus, this study represents one of the first to quantify how variation in food web structure can result from the local environment, initial conditions and their interaction.
Reciprocal phenotypic plasticity in a predator–prey system: inducible offences against inducible defences?
Authors: Kopp Michael , Tollrian Ralph 
Published: July 2003

AbstractWe describe one of the first examples of reciprocal phenotypic plasticity in a predator–prey system: the interaction between an inducible defence and an inducible offence. When confronted with the predatory ciliate Lembadion bullinum, the hypotrichous ciliate Euplotes octocarinatus develops protective lateral wings, which inhibit ingestion by the predator. We show that L. bullinum reacts to this inducible defence by expressing an inducible offence – a plastic increase in cell size and gape size. This counteraction reduced the effect of the defence, but did not completely neutralize it. Therefore, the defence remained beneficial for E. octocarinatus. From L. bullinum's point of view, the increase in feeding rate because of the offence was not larger than the increase in mean cell volume and apparently, did not increase the predator's fitness. Therefore, the inducible offence of L. bullinum does not seem to be an effective counter‐adaptation to the inducible defence of E. octocarinatus.
Ecological and evolutionary significance of dispersal by freshwater invertebrates
Authors: Bohonak Andrew J. , Jenkins David G. 
Published: July 2003

AbstractTraditional expectations for how widely and how often freshwater invertebrates disperse differ from empirical data. Freshwater invertebrates have been characterized as frequent, widespread dispersers, particularly those that are transported passively. Our review finds that this characterization may describe thepotentialfor dispersal in some taxa, but it is not an accurate generalization foractualdispersal rates. High variance among habitats and taxonomic groups is a consistent theme. Advances in population genetics may help resolve these issues, but underlying assumptions should be carefully tested. Further, even unbiased estimates of gene flow may not equate with individual movement, because not all dispersers survive and reproduce. Some freshwater invertebrates may exist in classic Levins metapopulations. However, other species fit into a broader metapopulation definition, where temporal dispersal via diapause is functionally equivalent to spatial dispersal. In the latter case, local extinctions and rescue effects may be rare or absent. Finally, limited dispersal rates in many taxa suggest that theories of freshwater community assembly and structure can be made more robust by integrating dispersal and local processes as joint, contingent regulators. Recent research on freshwater invertebrate dispersal has substantially advanced our basic and applied understanding of freshwaters, as well as evolutionary ecology in general.
Does Mother Nature really prefer rare species or are log‐left‐skewed SADs a sampling artefact?
Authors: McGill Brian J. 
Published: July 2003

AbstractIntensively sampled species abundance distributions (SADs) show left‐skew on a log scale. That is, there are too many rare species to fit a lognormal distribution. I propose that this log‐left‐skew might be a sampling artefact. Monte Carlo simulations show that taking progressively larger samples from a log‐unskewed distribution (such as the lognormal) causes log‐skew to decrease asymptotically (move towards −∞) until it reaches the level of the underlying distribution (zero in this case). In contrast, accumulating certain types of repeated small samples results in a log‐skew that becomes progressively more log‐left‐skewed to a level well beyond the underlying distribution. These repeated samples correspond to samples from the same site over many years or from many sites in 1 year. Data from empirical datasets show that log‐skew generally goes from positive (right‐skewed) to negative (left‐skewed) as the number of temporally or spatially replicated samples increases. This suggests caution when interpreting log‐left‐skew as a pattern that needs biological interpretation.
Biological vs. social, economic and political priority‐setting in conservation
Authors: O'Connor Casey , Marvier Michelle , Kareiva Peter 
Published: July 2003

AbstractThe most influential conservation priority‐setting approaches emphasize biodiversity and threats when deciding where to focus investment. However, socio‐economic and political attributes of nations influence the effectiveness of conservation actions. A combination of biological and sociological variables in the context of a ‘return on investment’ framework for establishing conservation priorities was explored. While there was some overlap between megadiversity nations and return on investment priorities, only a few countries emerged as high priorities irrespective of which factors were included in the analysis. Conversely, some countries that ranked highly as priorities for conservation when focusing solely on biological metrics, did not rank highly when governance, population pressure, economic costs and conservation needs were considered (e.g. Colombia, Ecuador, Indonesia and Venezuela). No priority‐setting scheme is a priori superior to alternative approaches. However, the analyses suggest that attention to governance and return on investment may alter biocentric assessments of ideal conservation investments.
Strontium isotopic characterization of the Palmottu hydrosystem (Finland): water–rock interaction and geochemistry of groundwaters
Authors: Negrel Philippe , Casanova Joël , Blomqvist Runar , Kaija Juha , Frape Shaun 
Published: July 2003

AbstractThe Palmottu hydrosystem is located in a granitic host rock in southern Finland. Along well‐defined pathways in the fractured crystalline rock, strontium isotopes are used to trace the degree of water–rock interaction (WRI) and mixing processes in groundwaters.The87Sr/86Sr ratios range between 0.716910 and 0.735606 in the surface waters and between 0.719991 and 0.750787 in the groundwaters, but are between 0.720 and 0.735 in most of the samples. Moreover, the results show a lack of correlation between the water chemistries determining the classification into different water‐types (Na–Cl, Na–SO4, etc.) and the results of the strontium (Sr) contents and Sr isotopic ratios. From a WRI standpoint, this implies that the Sr behaviour is independent of the water chemistry; the occurrence of large87Sr/86Sr variations is site specific and mainly dependent on the lithology. A model to determine the87Sr/86Sr ratio of water after interaction with granite was developed. This model is based on the assumption that Sr was derived from three minerals: plagioclase, K‐feldspar and biotite. The results of the calculation indicate that around half of the water analysed within the Palmottu hydrosystem can be explained by the weathering of the granites. However, clearly lower87Sr/86Sr are observed in waters when compared to the calculated87Sr/86Sr and other sources of Sr, with low87Sr/86Sr, rather than the calculated granite–water interaction, which may be suspected.When comparing the87Sr/86Sr and ion ratios (Ca/Na, Mg/Na, Sr/Na, Cl/Na), the scattering of the data can be explained by the presence of four end‐members: a brine component (low87Sr/86Sr and Ca/Na ratios…), a deep granitic component (high87Sr/86Sr ratios and low Ca/Na ratios…), a subsurface component (intermediate87Sr/86Sr ratios associated with high Ca/Na ratios…) and a surface end‐member:snow and river drainage (low87Sr/86Sr and low Ca/Na ratios…). These extreme end‐members define a series of WRI‐mixing line within a rather complex hydrosystem.
Impaired fast axonal transport in neurons of the sciatic nerves from dystonia musculorum mice
Authors: De Repentigny Yves , Deschênes‐Furry Julie , Jasmin Bernard J. , Kothary Rashmi 
Published: July 2003

Abstract Dystonia musculorum (dt) mice suffer from a severe sensory neuropathy caused by mutations in the gene encoding the cytoskeletal cross‐linker protein dystonin/bullous pemphigoid antigen 1 (Bpag1). Loss of function of dystonin/Bpag1 within neurons leads to a loss in the maintenance of cytoskeletal organization and to the development of focal axonal swellings prior to death of the neuron. In the present study, we demonstrate that neurons within the sciatic nerves of dt27J mice undergo axonal degeneration as has been previously reported for the dorsal roots. Furthermore, ultrastructural studies reveal a perturbed organization of the neurofilament and microtubule networks within the axons of sciatic nerves in dt27J mice. The disrupted cytoskeletal organization suggested that axonal transport is affected in dt mice. To address this, we assessed fast axonal transport by measuring the rate of accumulation of acetylcholinesterase (AChE) proximal and distal to a surgically introduced ligature on the sciatic nerves of normal and dt27J mice. Our findings demonstrate that axonal transport of AChE in both orthograde and retrograde directions is markedly affected, and allow us to conclude that axonal transport defects do exist in the sciatic nerves of dt27J mice.
Perspectives on the metabolic management of epilepsy through dietary reduction of glucose and elevation of ketone bodies
Authors: Greene Amanda E. , Todorova Mariana T. , Seyfried Thomas N. 
Published: July 2003

AbstractBrain cells are metabolically flexible because they can derive energy from both glucose and ketone bodies (acetoacetate and β‐hydroxybutyrate). Metabolic control theory applies principles of bioenergetics and genome flexibility to the management of complex phenotypic traits. Epilepsy is a complex brain disorder involving excessive, synchronous, abnormal electrical firing patterns of neurons. We propose that many epilepsies with varied etiologies may ultimately involve disruptions of brain energy homeostasis and are potentially manageable through principles of metabolic control theory. This control involves moderate shifts in the availability of brain energy metabolites (glucose and ketone bodies) that alter energy metabolism through glycolysis and the tricarboxylic acid cycle, respectively. These shifts produce adjustments in gene‐linked metabolic networks that manage or control the seizure disorder despite the continued presence of the inherited or acquired factors responsible for the epilepsy. This hypothesis is supported by information on the management of seizures with diets including fasting, the ketogenic diet and caloric restriction. A better understanding of the compensatory genetic and neurochemical networks of brain energy metabolism may produce novel antiepileptic therapies that are more effective and biologically friendly than those currently available.
Brain levels of CDK5 activator p25 are not increased in Alzheimer's or other neurodegenerative diseases with neurofibrillary tangles
Authors: Tandon Anurag , Yu Haung , Wang Linda , Rogaeva Ekaterina , Sato Christine , Chishti M. Azhar , Kawarai Toshitaka , Hasegawa Hiroshi , Chen Fusheng , Davies Peter , Fraser Paul E. , Westaway David , St George‐Hyslop Peter H. 
Published: July 2003

AbstractElevated levels of p25 and constitutive activation of CDK5 have been observed in AD brains. This has led to the hypothesis that increased p25 levels could promote neurofibrillary tangles (NFT) through CDK5‐mediated hyperphosphorylation of tau, the principal component of NFTs. We examined p25 immunoreactivity in brains from sporadic and familial AD cases, as well as other neurologic diseases that exhibit NFT, such as Down's syndrome (DS), Pick's disease (Pick), corticobasal degeneration (CBD), progressive supranuclear palsy (PSP), frontotemporal dementia (FTD). Neither the p25 immunoreactivity nor the p25/p35 ratio was elevated in the AD brains or in the other tauopathies (n = 34) compared with controls (n = 11). Although Aβ peptides have been suggested to activate calpain‐mediated cleavage of p35 to p25 in cultured neurons, p25 levels in brains of TgCRND8 mice, which express high levels of brain Aβ peptides, were similar to those of non‐Tg littermates. Our data suggest that high Aβ levels in brain do not activate p35 proteolysis, and p25 is unlikely to be a causative agent for NFT formation in AD or other tauopathies.
Cytosolic and mitochondrial isoforms of NADP+‐dependent isocitrate dehydrogenases are expressed in cultured rat neurons, astrocytes, oligodendrocytes and microglial cells
Authors: Minich Tobias , Yokota Sadaki , Dringen Ralf 
Published: July 2003

AbstractNADP+‐dependent isocitrate dehydrogenases (ICDHs) are enzymes that reduce NADP+ to NADPH using isocitrate as electron donor. Cytosolic and mitochondrial isoforms of ICDH have been described. Little is known on the expression of ICDHs in brain cells. We have cloned the rat mitochondrial ICDH (mICDH) in order to obtain the sequence information necessary to study the expression of ICDHs in brain cells by RT‐PCR. The cDNA sequence of rat mICDH was highly homologous to that of mICDH cDNAs from other species. By RT‐PCR the presence of mRNAs for both the cytosolic and the mitochondrial ICDHs was demonstrated for cultured rat neurons, astrocytes, oligodendrocytes and microglia. The expression of both ICDH isoenzymes was confirmed by western blot analysis using ICDH‐isoenzyme specific antibodies as well as by determination of ICDH activities in cytosolic and mitochondrial fractions of the neural cell cultures. In astroglial and microglial cultures, the total ICDH activity was almost equally distributed between cytosolic and mitochondrial fractions. In contrast, in cultures of neurons and oligodendrocytes about 75% of total ICDH activity was present in the cytosolic fractions. Putative functions of ICDHs in cytosol and mitochondria of brain cells are discussed.