bluuebunny/crossref_metadata_2025_split huggingface dataset:
Long‐term motor cortex reorganization after facial nerve severing in newborn rats
Authors: Franchi Gianfranco , Veronesi Carlo 
Published: December 2004

AbstractUsing the model of facial nerve injury, we have compared the effect of injury in newborn and adult rats on the adult rat motor cortex (M1). To this end, the facial nerve was severed in 10 newborn rats 2 days after birth (Newborn group) and in 10 adult rats (Adult group). In both the Control (contralateral to untouched nerve) and the Experimental (contralateral to severed nerve) hemisphere of each rat, the M1 output organization was assessed by intracortical microstimulation. Our findings demonstrated that: (i) there is no statistical difference in the percentage of movement sites and in current thresholds required to evoke movement in Control hemispheres between the Adult and Newborn groups of rats; (ii) in Adult Experimental hemispheres, neck sites expand in the medial part of the vibrissae representation more extensively than shown in Newborn Experimental hemispheres; (iii) in Newborn Experimental hemispheres eye sites expand in the medial part of the vibrissae representation more extensively than in Adult Experimental hemispheres (these sites overlap the cortical region where electrical stimulation evokes neck movement in Adult Experimental hemispheres) and (iv) in both Newborn and Adult Experimental hemispheres, forelimb sites expand similarly thereby overlapping the same cortical region, corresponding to the lateral part of the vibrissae representation. We conclude that, when the facial nerve injury is performed in the newborn rat, the pattern of movement representation differs from that obtained with the same lesion in the mature brain only in the frontal cortex corresponding to the medial part of the normal vibrissae representation.
Death of dopaminergic neurones in the rat substantia nigra can be induced by damage to globus pallidus
Authors: Wright A. K. , Atherton J. F. , Norrie L. , Arbuthnott G. W. 
Published: December 2004

AbstractParkinson's disease is a debilitating disorder that results from the death of dopaminergic neurones in the substantia nigra. Subthalamic nucleus neurones use glutamate as their neurotransmitter and send excitatory projections to the substantia nigra. Changes in both the mean firing rate and firing pattern of neurones of the subthalamic nucleus have been found in patients with this disease. This has led to the suggestion that hyperactivity of the subthalamic nucleus may be involved in the pathology of the dopaminergic neurones. Subthalamic nucleus lesions or treatment with glutamatergic antagonists can be neuroprotective in animal models of Parkinson's disease but until now there has been no direct evidence that hyperactivity of subthalamic nucleus neurones can lead to downstream cell death. Here we show that lesions of the rat globus pallidus (a treatment that has been shown to increase subthalamic nucleus neuronal activity) result in a significant reduction of the number of dopaminergic neurones in the substantia nigra.
Topography of cortico‐striatal connections in man: anatomical evidence for parallel organization
Authors: Wiesendanger E. , Clarke S. , Kraftsik R. , Tardif E. 
Published: December 2004

AbstractTracing studies in non‐human primates support the existence of several parallel neuronal circuits involving cerebral cortex, basal ganglia and thalamus. Distinct functional loops were proposed to underlie multiple aspects of normal and pathological behaviour in man. We present here the first anatomical evidence for separate corticostriatal systems in humans. Neural connections of the sensorimotor and prefrontal cortex to the striatum were studied in one human brain using the Nauta method for anterogradely degenerating axons. Axons originating from a lesion in the left sensorimotor cortex, including the face area, were found to terminate in the superolateral part of the ipsilateral putamen, forming a narrow band in its posterior part. Inside the band, the distribution of degenerating axons was inhomogeneous; high‐density clusters of approximately 2.5 mm in diameter were separated by regions with less dense cortical projections. Axons originating from a small lesion in the fundus of the right superior frontal sulcus were found in the upper part of the ipsilateral caudate nucleus. The existence of discrete and anatomically segregated terminal patches originating from distinct cortical regions suggests parallel organization of cortico‐striatal connections in man.
Caspase‐1 and poly (ADP‐ribose) polymerase inhibitors may protect against peroxynitrite‐induced neurotoxicity independent of their enzyme inhibitor activity
Authors: Zhang Yumin , Rosenberg Paul A. 
Published: December 2004

AbstractWe investigated the mechanism of 3‐morpholinosyndnomine (SIN‐1) neurotoxicity in nearly pure neuronal cultures. In a simple saline solution, SIN‐1 neurotoxicity was found to be mediated by peroxynitrite and independent of glutamate receptor activation [Y. Zhang & P.A. Rosenberg (2002) Eur. J. Neurosci, 16, 1015–1024]. To further study the mechanism of peroxynitrite toxicity to neurons we investigated the role of caspases and poly (ADP‐ribose) polymerase (PARP) in this model system. Ac‐Tyr‐Val‐Ala‐Asp‐chloromethyl ketone (Ac‐YVAD‐cmk), a specific caspase‐1 inhibitor, completely blocked neurotoxicity as well as ATP depletion induced by SIN‐1. However, a caspase‐3 inhibitor and a pan‐caspase inhibitor were both without effect. These results suggested that the protection of Ac‐YVAD‐cmk might not be due to its inhibition of caspase‐1. Indeed, Western blot analysis and assay of caspase activity indicated that caspase activation was not involved in SIN‐1 toxicity. Ac‐YVAD‐cmk also completely blocked in vitro protein nitration induced by SIN‐1 or peroxynitrite, suggesting that Ac‐YVAD‐cmk may interact with peroxynitrite directly. Similarly, although activation of PARP is thought to be a major cause of peroxynitrite‐induced ATP depletion, and two PARP inhibitors, 1,5‐dihydroxyisoquinoline (DHQ) and 3‐aminobenzamide (3‐AB), completely prevented ATP depletion and neurotoxicity induced by SIN‐1, SIN‐1 did not increase poly (ADP‐ribosyl)ation and PARP activity. Furthermore, DHQ and 3‐AB completely prevented in vitro protein nitration induced by peroxynitrite, indicating that DHQ and 3‐AB directly interact with peroxynitrite. Taken together, these results suggest that in the model system used here peroxynitrite neurotoxicity is independent of caspase and PARP activation, and therefore implicate a novel mechanism.
Posttranscriptional regulation of the immediate‐early gene EGR1 by light in the mouse retina
Authors: Simon Perikles , Schott Klaus , Williams Robert W. , Schaeffel Frank 
Published: December 2004

AbstractSynaptic plasticity is modulated by differential regulation of transcription factors such as EGR1 which binds to DNA via a zinc finger binding domain. Inactivation of EGR1 has implicated this gene as a key regulator of memory formation and learning. However, it remains puzzling how synaptic input can lead to an up‐regulation of the EGR‐1 protein within only a few minutes. Here, we show by immunohistochemical staining that the EGR‐1 protein is localized in synapses throughout the mouse retina. We demonstrate for the first time that two variants of Egr‐1 mRNA are produced in the retina by alternative polyadenylation, with the longer version having an additional 293 base pairs at the end of the 3′UTR. Remarkably, the use of the alternative polyadenylation site is controlled by light. The additional 3′UTR sequence of the longer variant displays an even higher level of phylogenetic conservation than the coding region of this highly conserved gene. Additionally, it harbours a cytoplasmic polyadenylation element which is known to respond to NMDA receptor activation. The longer version of the Egr‐1 mRNA could therefore rapidly respond to excitatory stimuli such as light or glutamate release whereas the short variant, which is predominantly expressed and contains the full coding sequence, lacks the regulatory elements for cytoplasmic polyadenylation in its 3′UTR.
Relevance of ammonium oxidation within biological soil crust communities
Authors: Johnson Shannon L. , Budinoff Charles R. , Belnap Jayne , Garcia‐Pichel Ferran 
Published: December 2004

SummaryThin, vertically structured topsoil communities that become ecologically important in arid regions (biological soil crusts or BSCs) are responsible for much of the nitrogen inputs into pristine arid lands. We studied N2 fixation and ammonium oxidation (AO) at subcentimetre resolution within BSCs from the Colorado Plateau. Pools of dissolved porewater nitrate/nitrite, ammonium and organic nitrogen in wetted BSCs were high in comparison with those typical of aridosoils. They remained stable during incubations, indicating that input and output processes were of similar magnitude. Areal N2 fixation rates (6.5–48 µmol C2H2 m−2 h−1) were high, the vertical distribution of N2 fixation peaking close to the surface if populations of heterocystous cyanobacteria were present, but in the subsurface if they were absent. Areal AO rates (19–46 µmol N m−2 h−1) were commensurate with N2 fixation inputs. When considering oxygen availability, AO activity invariably peaked 2–3 mm deep and was limited by oxygen (not ammonium) supply. Most probable number (MPN)‐enumerated ammonia‐oxidizing bacteria (6.7–7.9 × 103 cells g−1 on average) clearly peaked at 2–3 mm depth. Thus, AO (hence nitrification) is a spatially restricted but important process in the nitrogen cycling of BSC, turning much of the biologically fixed nitrogen into oxidized forms, the fate of which remains to be determined.
An intelligent logistics support system for enhancing the airfreight forwarding business
Authors: Lau H.C.W. , Choy K.L. , Lau Peter K.H. , Tsui W.T. , Choy L.C. 
Published: December 2004

Abstract: Recent research related to the aircraft container loading and scheduling problem for airfreight forwarding business has seen significant advances in terms of load plan optimization, taking into account the cost and volume of packed boxes. In today's competitive industrial environment, it is essential that freight forwarders are able to collaborate with carriers (airline companies) to achieve the best possible selection of logistics workflow. However, study of contemporary research publications indicates that there is a dearth of articles related to the design and implementation of an intelligent logistics system to support decision‐making on carrier selection, aircraft container loading plans as well as carrier benchmarking.This paper presents an intelligent logistics support system (ILSS) which is able to provide expert advice related to the airfreight forwarding business, enhancing the logistics operations in relevant activities within the value chain of tasks. ILSS comprises a heuristics‐based intelligent expert system which supports carrier searching and cargo trading planning as well as load plan generation. The proposed approach is meant to enhance various operations in the airfreight forwarding business, adopting computational intelligence technologies such as rule‐based reasoning to provide domain advice and heuristics to support the generation of load plans. After potential outcomes are generated by the heuristics‐based intelligent expert system, a neural network engine is applied to support prediction of unexpected events. To validate the viability of this approach, a production system using the ILSS has been developed and subsequently applied in an emulated airfreight forwarding environment. The application results indicate that the operation time from searching for potential carriers to the execution of the order is greatly reduced. In this paper, details related to the structure, design and implementation of the ILSS are also covered with the inclusion of the actual program codes for building the prototype.
Removal of Group B Streptococci Colonizing the Vagina and Oropharynx of Mice with a Bacteriophage Lytic Enzyme
Authors: Cheng Qi , Nelson Daniel , Zhu Shiwei , Fischetti Vincent A. 
Published: December 2004

ABSTRACT

Group B streptococci (GBS) are the leading cause of neonatal meningitis and sepsis worldwide. The current treatment strategy is limited to intrapartum antibiotic prophylaxis in pregnant women to prevent early-onset neonatal diseases, but considering the potential for antibiotic resistance, the risk of losing control over the disease is high. To approach this problem, we have developed a bacteriophage (phage) lytic enzyme to remove colonizing GBS. Bacteriophage muralytic enzymes, termed lysins, are highly evolved molecules designed to degrade the cell wall of host bacteria to release phage particles from the bacterial cytoplasm. Several different lysins have been developed to specifically kill bacterial pathogens both on mucosal surfaces and in blood and represent a novel approach to control infection. A lysin cloned from a phage infecting GBS was found to contain two putative catalytic domains and one putative binding domain, which is similar to the domain organization of some staphylococcal phage lysins. The lysin (named PlyGBS) was recombinantly expressed in
Escherichia coli
, and purified PlyGBS efficiently killed all tested GBS serotypes in vitro. In a mouse model, a single dose of PlyGBS significantly reduced bacterial colonization in both the vagina and oropharynx. As an alternative strategy for intrapartum antibiotic prophylaxis, this approach may be used to reduce vaginal GBS colonization in pregnant women before delivery or to decontaminate newborns, thus reducing the incidence of GBS-associated neonatal meningitis and sepsis.
Emergence and Spread of
Neisseria gonorrhoeae
Clinical Isolates Harboring Mosaic-Like Structure of Penicillin-Binding Protein 2 in Central Japan
Authors: Ito Masayasu , Deguchi Takashi , Mizutani Koh-Suke , Yasuda Mitsuru , Yokoi Shigeaki , Ito Shin-Ichi , Takahashi Yoshito , Ishihara Satoshi , Kawamura Yoshiaki , Ezaki Takayuki 
Published: December 2004

ABSTRACT

Of 150 clinical isolates of
Neisseria gonorrhoeae
recovered in 2001, we examined 55 clinical isolates of
N. gonorrhoeae
for which cefixime MICs were ≥0.125 μg/ml and randomly selected 15 isolates for which cefixime MICs were ≤0.06 μg/ml for analysis of alterations in the penicillin-binding protein 2 (PBP 2) gene. We found insertion of an extra codon (Asp-345a) in the transpeptidase domain of PBP 2, and this insertion occurred alone or in conjunction with other amino acid substitutions. We also found a mosaic PBP 2 that was composed of fragments of the PBP 2 proteins from
Neisseria cinera
and
Neisseria perflava
. This mosaic PBP 2 was significantly associated with decreased susceptibilities to penicillin and cephalosporins, especially oral cephalosporins. For most of the isolates with a mosaic PBP 2, the cefixime MICs were ≥0.5 μg/ml and the cefdinir MICs were ≥1 μg/ml. Analysis of chromosomal DNA restriction patterns by pulsed-field gel electrophoresis revealed that most isolates with the mosaic PBP 2 were genetically similar. The recombination events that generated the mosaic PBP 2 would likely have contributed to the decreased sensitivities to cephalosporins. Isolates with the mosaic PBP 2 appear to threaten the efficacy of the currently recommended regimen with cefixime. The emergence of such strains may be the result of the in vivo generation of clones in which interspecies recombination occurred between the
penA
genes of
N. gonorrhoeae
and commensal
Neisseria
species.
Efficacy and Safety of Pharmacokinetically Enhanced Amoxicillin-Clavulanate at 2,000/125 Milligrams Twice Daily for 5 Days versus Amoxicillin-Clavulanate at 875/125 Milligrams Twice Daily for 7 Days in the Treatment of Acute Exacerbations of Chronic Bronchitis
Authors: Sethi Sanjay , Breton John , Wynne Brian 
Published: December 2004

ABSTRACTThis randomized, controlled trial was designed to show that a short, 5-day course of pharmacokinetically enhanced amoxicillin-clavulanate at 2,000/125 mg (Augmentin XR) is as effective clinically as a longer, 7-day course of conventional amoxicillin-clavulanate at 875/125 mg (both given twice daily) in the treatment of acute exacerbations of chronic bronchitis (AECB). Amoxicillin-clavulanate at 2,000/125 mg was designed to extend the therapeutic levels of amoxicillin in serum over the 12-h dosing interval, compared with conventional formulations, to eradicate bacterial strains for which amoxicillin MICs were ≤4 μg/ml while retaining efficacy against β-lactamase-producing pathogens. A total of 893 patients were randomized and received study medication (amoxicillin-clavulanate at 2,000/125 mg for 443 patients and 875/125 mg for 450 patients). Overall, 141 patients receiving amoxicillin-clavulanate at 2,000/125 mg and 135 receiving the comparator formulation had at least one pathogen identified at screening. Amoxicillin-clavulanate at 2,000/125 mg was as effective clinically in the per-protocol (PP) population at the test of cure (days 14 to 21, primary efficacy endpoint) as amoxicillin-clavulanate at 875/125 mg (clinical success rates of 93.0 and 91.2%, respectively; treatment difference, 1.8; 95% confidence interval [CI], −2.2, 5.7). Bacteriological success in the bacteriology PP population was high for both formulations (amoxicillin-clavulanate at 2,000/125 mg, 76.7%; amoxicillin-clavulanate at 875/125 mg, 73.0%; treatment difference, 3.8; 95% CI, −7.5, 15.0). Both therapies were well tolerated, with a similar incidence of adverse events. Fewer than 5% of patients in each group withdrew from the study due to adverse events. The shorter, 5-day course of amoxicillin-clavulanate at 2,000/125 mg was shown to be as effective clinically as a longer, 7-day course of amoxicillin-clavulanate at 875/125 mg, with high bacteriological efficacy and no difference in tolerability.
Induction of β-Defensin Resistance in the Oral AnaerobePorphyromonas gingivalis
Authors: Shelburne Charles E. , Coulter Wilson A. , Olguin De'Avlin , Lantz Marilyn S. , Lopatin Dennis E. 
Published: December 2004

ABSTRACTInduction of resistance of oral anaerobes to the effects of human β-defensin 1 (hβD-1) to hβD-4 was investigated by pretreating cells with either sublethal levels of defensins or environmental factors, followed by a challenge with lethal levels of defensins. Cultures ofPorphyromonas gingivaliswere (i) pretreated with defensins at 1 ng/ml, (ii) heated to 42°C (heat stress), (iii) exposed to normal atmosphere (oxidative stress), or (iv) exposed to 1 mM hydrogen peroxide (peroxide stress). Samples (10 μl) were distributed among the wells of sterile 384-well plates containing hβD-1 to -4 (100 μg/ml). Plates were incubated at 37°C for 36 h in an anaerobe chamber. Growth inhibition was determined by a system that measures the total nucleic acid of a sample with a DNA binding dye. The MICs of the four defensins forP. gingivaliswere 3 to 12 μg/ml. We found that sublethal levels of the defensins and heat and peroxide stress, but not oxidative stress, induced resistance to 100 μg of defensin per ml inP. gingivalis. Resistance induced by sublethal levels of hβD-2 lasted 90 min, and the resistance induced by each defensin was effective against the other three. Multiple strains exposed to hβD-2 all evidenced resistance induction. Defensin resistance is vital to the pathogenic potential of several human pathogens. This is the first report describing the induction of defensin resistance in the oral periodontal pathogenP. gingivalis. Such resistance may have an effect on the ability of oral pathogens to persist in the mouth and to withstand innate human immunity.
Pharmacokinetics of Tigecycline after Single and Multiple Doses in Healthy Subjects
Authors: Muralidharan Gopal , Micalizzi Marlynne , Speth John , Raible Donald , Troy Steven 
Published: December 2004

ABSTRACT

Tigecycline, a novel glycylcycline antibiotic, exhibits strong activity against gram-positive, gram-negative, aerobic, anaerobic, and atypical bacterial species, including many resistant pathogens, i.e., vancomycin-resistant enterococci, methicillin-resistant
Staphylococcus aureus
and penicillin-resistant
Streptococcus pneumoniae
. The safety and tolerability of tigecycline administered as single or multiple doses or at various infusion rates were explored in three phase 1, randomized, double-blind, placebo-controlled studies in healthy subjects. Full pharmacokinetic profiles of tigecycline were determined in two of these studies. Subjects in the single-dose study received 12.5 to 300 mg of tigecycline, which differed with respect to the duration of infusion, subjects' feeding status, and ondansetron pretreatment. Subjects in the ascending multiple-dose study received 25 to 100-mg doses of tigecycline as a 1-h infusion every 12 h. The variable volume and infusion rate study consisted of administration of 100-mg loading dose of tigecycline, followed by 50 mg every 12 h for 5 days. Serum samples were analyzed for tigecycline by validated high-pressure liquid chromatography or liquid chromatography/tandem mass spectrometry methods. Systemic clearance ranged from 0.2 to 0.3 liters/h/kg, and the tigecycline half-life ranged from 37 to 67 h. Tigecycline had a large volume of distribution (7 to 10 liters/kg), indicating extensive distribution into the tissues. Food increased the maximum tolerated single-dose from 100 to 200 mg, but the duration of infusion did not affect tolerability. Side effects, mainly nausea and vomiting, which are common to the tetracycline class of antimicrobial agents, were seen in these studies. Tigecycline exhibits linear pharmacokinetics and is safe and well tolerated in the dose ranges examined.