bluuebunny/crossref_metadata_2025_split huggingface dataset:
Frameshifting by transcriptional slippage is involved in production of MxiE, the transcription activator regulated by the activity of the type III secretion apparatus in Shigella flexneri
Authors: Penno Christophe , Sansonetti Philippe , Parsot Claude 
Published: March 2005

SummaryBacteria of Shigella spp. are responsible for shigellosis in humans. They use a type III secretion (TTS) system encoded by a 200 kb virulence plasmid to enter epithelial cells and trigger apoptosis in macrophages. This TTS system comprises a secretion apparatus, translocators and effectors that transit through this apparatus, cytoplasmic chaperones and specific transcription regulators. The TTS apparatus assembled during growth of Shigella flexneri in broth is activated upon contact with epithelial cells. Transcription of ≈ 15 genes encoding effectors, including IpaH proteins, is regulated by the TTS apparatus activity and controlled by MxiE, a transcription activator of the AraC family, and IpgC, the chaperone of the translocators IpaB and IpaC. We present evidence that MxiE is produced by a frameshift between a 59‐codon open reading frame (ORF) (mxiEa) containing the translation start site and a 214‐codon ORF (mxiEb) encoding the DNA binding domain of the protein. The mxiEa encoded N‐terminal part of MxiE is required for MxiE function. Frameshifting efficiency was ≈ 30% during growth in broth and was not modulated by the activity of secretion or the coactivator IpgC. Frameshifting involves slippage of RNA polymerase during transcription of mxiE, which results in the incorporation of one additional nucleotide in the mRNA and places mxiEa and mxiEb in the same reading frame. Frameshifting might represent an additional means of controlling gene expression under specific environmental conditions.
Human fibrinogen bound to Streptococcus pyogenes M protein inhibits complement deposition via the classical pathway
Authors: Carlsson Fredric , Sandin Charlotta , Lindahl Gunnar 
Published: March 2005

SummaryHuman fibrinogen (Fg) binds to surface proteins expressed by many pathogenic bacteria and has been implicated in different host–pathogen interactions, but the role of bound Fg remains unclear. Here, we analyse the role of Fg bound to Streptococcus pyogenes M protein, a major virulence factor that confers resistance to phagocytosis. Studies of the M5 system showed that a chromosomal mutant lacking the Fg‐binding region was completely unable to resist phagocytosis, indicating that bound Fg plays a key role in virulence. Deposition of complement on S. pyogenes occurred via the classical pathway even under non‐immune conditions, but was blocked by M5‐bound Fg, which reduced the amount of classical pathway C3 convertase on the bacterial surface. This property of M protein‐bound Fg may explain its role in phagocytosis resistance. Previous studies have shown that many M proteins do not bind Fg, but interfere with complement deposition and phagocytosis by recruiting human C4b‐binding protein (C4BP), an inhibitor of the classical pathway. Thus, all M proteins may share ability to recruit a human plasma protein, Fg or C4BP, which inhibits complement deposition via the classical pathway. Our data identify a novel function for surface‐bound Fg and allow us to propose a unifying mechanism by which M proteins interfere with innate immunity.
Characterization of a Type III secretion substrate specificity switch (T3S4) domain in YscP from Yersinia enterocolitica
Authors: Agrain Céline , Callebaut Isabelle , Journet Laure , Sorg Isabel , Paroz Cécile , Mota Luís Jaime , Cornelis Guy R. 
Published: March 2005

SummaryThe length of the needle ending the Yersinia Ysc injectisome is determined by YscP, a protein acting as a molecular ruler. In addition, YscP is required for Yop secretion. In the present paper, by a systematic deletion analysis, we localized accurately the region required for Yop secretion between residues 405 and 500. As this C‐terminal region of YscP has also been shown to control needle length it probably represents the substrate specificity switch of the machinery. By a bioinformatics analysis, we show that this region has a globular structure, an original α/β fold, a P‐x‐L‐G signature and presumably no catalytic activity. In spite of very limited sequence similarities, this structure is conserved among the proteins that are presumed to control the needle length in many different injectisomes and also among members of the FliK family, which control the flagellar hook length. This region thus represents a new protein domain that we called T3S4 for Type III secretion substrate specificity switch. The T3S4 domain of YscP can be replaced by the T3S4 domain of AscP (Aeromonas salmonicida) or PscP (Pseudomonas aeruginosa) but not by the one from FliK, indicating that in spite of a common global structure, these domains need to fit their partner proteins in the secretion apparatus.
The origin and evolution of human pathogens
Authors: Groisman Eduardo A. , Casadesús Josep 
Published: March 2005

SummaryWhat are the genetic origins of human pathogens? An international group of scientists discussed this topic at a workshop that took place in late October 2004 in Baeza (Spain). Focusing primarily on bacterial pathogens, they examined the role that pathogenicity islands and bacteriophages play on determining the virulence properties that distinguish closely related members of a given species, such as host range and tissue specificity. They also discussed an instance in which closely related bacterial species differ in the production of a cell surface modification mediating resistance to an antibiotic as a result of the disparate regulation of homologous genes. In certain pathogens, genes normally carrying out housekeeping functions may adopt new functions, whereas in other organisms, genes that respond to stresses associated with non‐host environments are silenced during infection to prevent the expression of products that interfere with the normal colonization process. The adaptive behaviour of certain pathogens relies on gene variation at certain loci that by virtue of containing polymeric repeats in regulatory or coding regions, can generate variants that may or may not express products that modify the cell surface of the organism. The meeting also addressed the properties of ORFan genes, which have no homologues in the sequence databases, as well as the creation of genes de novo by duplication and divergence.
Evaluation of clinical features of ischemic colitis: Comparison between young and elderly
Authors: Tohda Gen , Higashi Seiju , Sumiyoshi Ken‐Ichi , Sakumoto Hitoshi , Kato Chikako , Kane Teruyuki 
Published: March 2005

Background: It has been thought that ischemic colitis is caused by vascular and intestinal factors. Although elderly patients with arteriosclerosis are more susceptible to ischemic colitis, many young patients suffering ischemic colitis are also reported. The present study aimed to clarify the relationship between arteriosclerosis and ischemic colitis, and to evaluate various risk factors for ischemic colitis.Methods: We compared the clinical features of patients with ischemic colitis (54 cases) and control patients without ischemic colitis (86 cases), all diagnosed by colonoscopy. Subjects were classified into a young group (60 cases) under 60 years of age, and an elderly group (80 cases) of over 60 years. The degree of arteriosclerosis was measured by pulse wave velocity (PWV) level, and the effects of vascular and intestinal factors in the development of ischemic colitis were evaluated using multivariate analytical models.Results: In the elderly group, the PWV level was significantly higher in ischemic colitis patients than in the controls. By analyzing with multivariate analytical models, a high level of PWV and underlying diseases related to arteriosclerosis were thought to be risk factors for ischemic colitis in the elderly group. In the young group, intestinal factors such as irregular bowel movement, which is often seen in irritable bowel syndrome, habitual constipation, and prior history of an abdominal operation, were thought to be contributors to ischemic colitis.Conclusion: These findings suggest that intestinal factors in younger patients and vascular factors in more elderly patients are the primary contributors in the development of ischemic colitis.
Endoscopic variceal ligation of patients with liver cirrhosis and cirrhosis accompanied by hepatocellular carcinoma
Authors: Khien Vu Van , Bang Mai Hong , Lac Bui Van , Uemura Masayuki , Nouso Kazuhiro , Taketa Kazuhisa 
Published: March 2005

Background:  Rupture of esophageal varices with severe gastrointestinal hemorrhage is one of the most serious complications of liver cirrhosis (LC) and hepatocellular carcinoma (HCC) complicating LC. The present study looks at the success of hemostasis in LC and LC accompanied by HCC, the success of breaking the varices cluster and the rate of rebleeding in patients of LC subject to emergency ligation and prophylactic ligation.Methods: Seventy‐five patients were divided into three groups. Group 1: 30 patients with LC accompanied by HCC with digestive bleeding; group 2: 30 patients with LC with digestive bleeding; and group 3: 15 patients with LC with high risk of digestive bleeding from esophageal varices (with no medical history of digestive bleeding). Success of hemostasis 72 h after endoscopic variceal ligation (EVL) was that patients did not vomit blood nor produce black feces. The effectiveness of EVL for iradication of the variceal cluster was classified into three levels: good, fairly good and poor.Results: The hemostasis success in group 1 (LC accompanied by HCC) and group 2 (LC with digestive bleeding due to esophageal varices) was 73.3% and 93.4%, respectively. The success of breaking the varix cluster in group 2 (LC) and group 3 (LC with high risk of digestive bleeding and treated by prophylactic ligation) was 73.3% and 80%, respectively. The rate of rebleeding in group 2 and group 3 after 1 year was 20% and 13.3%, respectively.Conclusion: Endoscopic variceal ligation is a good technique for variceal hemostasis and eradication of the esophageal varices cluster.
Relationship between histopathological features and type V pit pattern determined by magnifying videocolonoscopy in early colorectal carcinoma
Authors: Oka Shiro , Tanaka Shinji , Nagata Shinji , Ito Masanori , Kitadai Yasuhiko , Shimamoto Fumio , Yosihara Masaharu , Chayama Kazuaki 
Published: March 2005

Background: The aim of the present study was to clarify the relationship between the histopathological features and type V pit pattern of early colorectal carcinoma.Methods: We examined the relationship between the type V pit pattern subtypes, the depth of submucosal invasion and the degrees of desmoplastic reaction, residual pit density and destruction of the intervening membrane between pits on the tumor surface in 135 cases of early colorectal carcinoma. The examinations involved magnifying videoendoscopy with indigo carmine dye spraying and crystal violet staining. The pit patterns were classified as one of two grades (VI, VN), and VN was further divided into three subtypes (A, B and C). The data obtained were evaluated by χ2 test, with significance accepted at < 0.05% for each analysis.Results: There were 64 VI, 24 VN‐A, 28 VN‐B and 19 VN‐C lesions. The incidence of massive submucosal invasion (sm2, sm3) was significantly higher in VN‐B and VN‐C lesions than in VI and VN‐A lesions (P < 0.05). Among VN pit pattern lesions, depth of submucosal invasion of VN‐B and VN‐C lesions was significantly greater than that of VN‐A lesions (P < 0.01). The incidence of severe desmoplastic reaction in VN‐B and VN‐C lesions was significantly greater than that in VI lesions (P < 0.01). The incidence of severe desmoplastic reaction in VN‐C lesions was significantly greater than that in VN‐A lesions (P < 0.05). The incidence of low residual pit density in VN‐C lesions was significantly greater than that in all other type V lesions. The incidence of mild to moderate and severe destruction of the intervening membrane between pits in VN lesions was significantly higher than that in VI lesions.Conclusions: Type V pit pattern subclassification is useful for predicting the depth of submucosal invasion in early colorectal carcinomas. The type V pit pattern subtypes are related to the degrees of desmoplastic reaction, the residual pit density and destruction of the intervening membrane between pits on the tumor surface.
Distinct properties of functional KCC2 expression in immature mouse hippocampal neurons in culture and in acute slices
Authors: Khirug Stanislav , Huttu Kristiina , Ludwig Anastasia , Smirnov Sergei , Voipio Juha , Rivera Claudio , Kaila Kai , Khiroug Leonard 
Published: March 2005

AbstractA hallmark in the development of GABAergic neurotransmission is the switch in GABAA‐mediated responses from depolarizing to hyperpolarizing. This occurs due to a gradual decrease in the intracellular concentration of chloride caused by the functional expression of the neuron‐specific K‐Cl cotransporter KCC2. Whether a mere increase in the amount of KCC2 protein is the rate‐limiting step in vivo, or a further activation of the otherwise nonfunctional cotransporter is required, is not clear. Imposing a fixed Cl– load via patch pipette we measured the resultant somato‐dendritic gradients in reversal potential of GABAergic currents to determine the time course of functional maturation of KCC2‐mediated Cl– extrusion in two preparations: cultured mouse hippocampal neurons plated at embryonic day 17 and CA1 pyramidal cells in acute slices. We found that in immature neurons in both preparations the gradient is initially small or not detectable. It undergoes an abrupt increase at around days 13–14 in culture, while a more gradual increase occurs between postnatal days 5–14 in slices. Consistent with the presence of a nonfunctional form of KCC2 in immature hippocampal neurons grown in culture, application of the broad‐spectrum kinase inhibitor staurosporine produces a rapid and potent up‐regulation of KCC2 function in these cultured neurons, but not in neonatal slices. Taken together with our previously published data, these results indicate that the functional activity of KCC2 in vivo parallels the developmental expression of the protein, whereas cultured neurons require an additional activation step (mimicked by staurosporine) for KCC2 to become functional.
A combination drug therapy improves cognition and reverses gene expression changes in a mouse model of Huntington's disease
Authors: Morton A. Jennifer , Hunt Mark J. , Hodges Angela K. , Lewis Paul D. , Redfern Amanda J. , Dunnett Stephen B. , Jones Lesley 
Published: March 2005

AbstractHuntington's disease is a genetic disease caused by a single mutation. It is characterized by progressive movement, emotional and cognitive deficits. R6/2 mice transgenic for exon 1 of the HD gene with 150+ CAG repeats have a progressive neurological phenotype, including deterioration in cognitive function. The mechanism underlying the cognitive deficits in R6/2 mice is unknown, but dysregulated gene expression, reduced neurotransmitter levels and abnormal synaptic function are present before the cognitive decline becomes pronounced. Our goal here was to ameliorate the cognitive phenotype in R6/2 mice using a combination drug therapy (tacrine, moclobemide and creatine) aimed at boosting neurotransmitter levels in the brain. Treatment from 5 weeks of age prevented deterioration in two different cognitive tasks until at least 12 weeks. However, motor deterioration continued unabated. Microarray analysis of global gene expression revealed that many genes significantly up‐ or down‐regulated in untreated R6/2 mice had returned towards normal levels after treatment, though a minority were further dysregulated. Thus dysregulated gene expression was reversed by the combination treatment in the R6/2 mice and probably underlies the observed improvements in cognitive function. Our study shows that cognitive decline caused by a genetic mutation can be slowed by a combination drug treatment, and gives hope that cognitive symptoms in HD can be treated.
The relationship between V6 and PO in macaque extrastriate cortex
Authors: Galletti Claudio , Gamberini Michela , Kutz Dieter F. , Baldinotti Ivan , Fattori Patrizia 
Published: March 2005

AbstractThe cerebral cortex of three macaque monkeys, electrophysiologically studied in chronic preparations in order to recognize functionally the medial parieto‐occipital area V6, was reconstructed using the software CARET. Locations of cells recorded from area V6 (n = 553) and from neighbouring cortical areas V2/V3 and V6A (n = 1341) were displayed on surface‐based reconstructions of individual brains, and on a surface‐based atlas of the macaque cerebral cortex. Results show that area V6 occupies the ventral part and fundus of the parieto‐occipital sulcus, as well as the ventral part of the precuneate cortex. V6 borders areas V2/V3 posteriorly and laterally, and area V6A anteriorly. The visualization of individual cases on a common template (atlas), and the use of atlas datasets, allowed us to compare data coming from different individuals and different laboratories. In particular, a comparison of the location and extent of the medial parieto‐occipital areas V6 and PO indicates that area PO occupies different locations according to different authors but in general includes parts of both areas V6 and V6A. We therefore suggest that the term V6 is a more appropriate designation of the visuotopically‐organized area located on the anterior wall of the parieto‐occipital sulcus.
A modified MPTP treatment regime produces reproducible partial nigrostriatal lesions in common marmosets
Authors: Iravani Mahmoud M. , Syed Emilie , Jackson Michael J. , Johnston Louisa C. , Smith Lance A. , Jenner Peter 
Published: March 2005

AbstractStandard MPTP treatment regimens in primates result in > 85% destruction of nigral dopaminergic neurons and the onset of marked motor deficits that respond to known symptomatic treatments for Parkinson's disease (PD). The extent of nigral degeneration reflects the late stages of PD rather than events occurring at its onset. We report on a modified MPTP treatment regimen that causes nigral dopaminergic degeneration in common marmosets equivalent to that occurring at the time of initiation of motor symptoms in man. Subcutaneous administration of MPTP 1 mg/kg for 3 consecutive days caused a reproducible 60% loss of nigral tyrosine hydroxylase (TH)‐positive cells, which occurred mainly in the calbindin‐D28k‐poor nigrosomes with a similar loss of TH‐immunoreactivity (TH‐ir) in the caudate nucleus and the putamen. The animals showed obvious motor abnormalities with reduced bursts of activity and the onset of motor disability. However, the loss of striatal terminals did not reflect early PD because a greater loss of TH‐ir occurred in the caudate nucleus than in the putamen and a marked reduction in TH‐ir occurred in striatal patches compared to the matrix. Examination of striatal fibres following a partial MPTP lesion showed a conspicuous increase in the number and the diameter of large branching fibres in the putaminal and to some extent caudatal matrix, pointing to a possible compensatory sprouting of dopaminergic terminals. In addition, these partially lesioned animals did not respond to acute treatment with L‐DOPA. This primate partial lesions model may be useful for examining potential neuroprotective or neurorestorative agents for PD.
Inhibition of restraint stress‐induced neural and behavioural activation by endogenous cannabinoid signalling
Authors: Patel Sachin , Roelke Craig T. , Rademacher David J. , Hillard Cecilia J. 
Published: March 2005

AbstractThe role of endocannabinoid (eCB) signalling in restraint stress‐induced neuronal activation was studied. Male mice exposed to 30 min of restraint exhibit increased Fos protein within prefrontal cortex (PFC), lateral septum (LS), nucleus accumbens (Acb) and medial amygdala. SR141716 (2 mg/kg) itself had no effect on Fos but pretreatment with SR141716 significantly potentiated restraint‐induced Fos expression in cingulate, LS and Acb. SR141716 also significantly increased the time spent in active escape behaviours during the restraint. In restraint‐habituated mice (mice exposed to four previous restraint episodes), the fifth restraint exposure resulted in decreased expression of active escape behaviours compared to the first exposure and only induced Fos protein in the central and medial amygdala. Administration of SR141716 prior to the fifth restraint episode resulted in greater potentiation of restraint‐induced Fos induction than the first; significant increases occurred within all regions of PFC examined, LS and Acb. Brain regional eCB content was measured immediately after restraint. N‐arachidonylethanolamine content within the amygdala was significantly decreased after both restraint episodes. 2‐Arachidonylglycerol content was significantly increased in both the limbic forebrain and amygdala after the fifth restraint but not the first. Restraint had no effect on cerebellar eCB content. These data suggest that eCB activation of CB1 receptors opposes the behavioural and neuronal responses to aversive stimuli. Because repeated homotypic stress increased both limbic 2‐AG and resulted in a greater effect of SR141716 on limbic Fos expression, we hypothesize that increased CB1 receptor activity contributes to the expression of habituation to homotypic stress.
Neurons in monkey visual cortex detect lines defined by coherent motion of dots
Authors: Peterhans E. , Heider B. , Baumann R. 
Published: March 2005

AbstractForm perception from coherent motion is an important aspect of vision. Representations of one‐, two‐ and three‐dimensional forms have been found at various stages of cortical processing using random‐dot stimuli, whereas representations of biological objects like a walking human being concentrate at higher stages of processing. The perception of biological objects can be induced by sparse dot stimuli that consist of a few dots that mark the joints of the human body [G. Johansson (1973) Percept. Psychophys., 14, 201–211]. In the present study, we aimed to investigate whether neurons in early visual areas that respond to bars and edges defined by luminance contrast also signal bar‐like objects from sparse dot stimuli. We studied single neurons with rows of 3–24 dots that were either collinear or scattered within a rectangular form. These dots were moved coherently on a uniform or dotted background, and human observers perceived them as rigid rods or other bar‐like objects. We found neurons in the visual cortex of the awake, behaving monkey that responded to these stimuli and were sensitive to the orientation of these objects as for conventional bars or edges. Stimulus conditions that failed to induce these percepts in human observers also evoked weaker responses or none in these neurons. We found these neurons with increasing frequency in areas V1, V2 and V3/V3A. The results suggest that the visual cortex not only detects biological objects, but also lines and other bar‐like objects from sparse dot stimuli, and that this function evolves at an early stage of processing.