bluuebunny/crossref_metadata_2025 huggingface dataset:
Construction and Characterization of Bivalent
Shigella flexneri
2a Vaccine Strains SC608(pCFAI) and SC608(pCFAI/LTB) That Express Antigens from Enterotoxigenic
Escherichia coli
Authors: Ranallo Ryan T. , Fonseka C. Piyumi , Cassels Fred , Srinivasan Jay , Venkatesan Malabi M.
Published: December 2004

An invasive strain of
Shigella flexneri
2a (SC608) has been developed as a vector for the expression and delivery of heterologous antigens. SC608 is an aspartate semialdehyde dehydrogenase (
asd
) derivative of SC602 (
icsA iuc
), a well-characterized live attenuated vaccine strain which has undergone several clinical trials in human volunteers. When administered orally at a single 10
4
(CFU) dose, SC602 is both immunogenic and efficacious against shigellosis. Using
asd
-based plasmid vectors, we designed SC608 to express the enterotoxigenic
Escherichia coli
(ETEC) fimbrial subunit CfaB (CFA/I structural subunit) alone or in combination with the
E. coli
B subunit of heat-labile enterotoxin (LTB). The expression of each heterologous protein in SC608 was verified by immunoblot analysis. Each strain was comparable to the parent strain, SC602, in a HeLa cell invasion assay. After intranasal immunizations of guinea pigs, serum and mucosal immune responses were detected against both
Shigella
lipopolysaccharide and heterologous ETEC antigens by enzyme-linked immunosorbent assay and ELISPOT analysis. All immunized animals were subsequently protected against a challenge with wild-type
S. flexneri
2a in a keratoconjunctivitis Sereny test. Serum antibodies generated against LTB and CfaB demonstrated antitoxin and agglutination activities, respectively. These results suggest that CfaB and LTB expressed in SC608 retain important conformational epitopes that are required for the generation of antibodies that have functional activities. These initial experiments demonstrate that a fully invasive
Shigella
vaccine strain can be engineered to deliver antigens from other diarrheal pathogens.
The Clinical-Grade 42-Kilodalton Fragment of Merozoite Surface Protein 1 ofPlasmodium falciparumStrain FVO Expressed inEscherichia coliProtectsAotus nancymaiagainst Challenge with Homologous Erythrocytic-Stage Parasites
Authors: Darko Christian A. , Angov Evelina , Collins William E. , Bergmann-Leitner Elke S. , Girouard Autumn S. , Hitt Stacy L. , McBride Jana S. , Diggs Carter L. , Holder Anthony A. , Long Carole A. , Barnwell John W. , Lyon Jeffrey A.
Published: December 2004

A 42-kDa fragment from the C terminus of major merozoite surface protein 1 (MSP1) is among the leading malaria vaccine candidates that target infection by asexual erythrocytic-stage malaria parasites. The MSP142gene fragment from the Vietnam-Oak Knoll (FVO) strain ofPlasmodium falciparumwas expressed as a soluble protein inEscherichia coliand purified according to good manufacturing practices. This clinical-grade recombinant protein retained some important elements of correct structure, as it was reactive with several functional, conformation-dependent monoclonal antibodies raised againstP. falciparummalaria parasites, it induced antibodies (Abs) that were reactive to parasites in immunofluorescent Ab tests, and it induced strong growth and invasion inhibitory antisera in New Zealand White rabbits. The antigen quality was further evaluated by vaccinatingAotus nancymaimonkeys and challenging them with homologousP. falciparumFVO erythrocytic-stage malaria parasites. The trial included two control groups, one vaccinated with the sexual-stage-specific antigen ofPlasmodium vivax, Pvs25, as a negative control, and the other vaccinated with baculovirus-expressed MSP142(FVO) as a positive control. Enzyme-linked immunosorbent assay (ELISA) Ab titers induced byE. coliMSP142were significantly higher than those induced by the baculovirus-expressed antigen. None of the six monkeys that were vaccinated with theE. coliMSP142antigen required treatment for uncontrolled parasitemia, but two required treatment for anemia. Protective immunity in these monkeys correlated with the ELISA Ab titer against the p19 fragment and the epidermal growth factor (EGF)-like domain 2 fragment of MSP142, but not the MSP142protein itself or the EGF-like domain 1 fragment. Soluble MSP142(FVO) expressed inE. colioffers excellent promise as a component of a vaccine against erythrocytic-stage falciparum malaria.
A Peptide Mimotope of Type 8 Pneumococcal Capsular Polysaccharide Induces a Protective Immune Response in Mice
Authors: Buchwald Ulrike K. , Lees Andrew , Steinitz Michael , Pirofski Liise-anne
Published: December 2004

Increasing antibiotic resistance and a rising patient population at risk for infection due to impaired immunity underscore the importance of vaccination against pneumococci. However, available capsular polysaccharide vaccines are often poorly immunogenic in patients at risk for pneumococcal disease. The goal of this study was to explore the potential of peptide mimotopes to function as alternative vaccine antigens to elicit a type-specific antibody response to pneumococci. We used a human monoclonal immunoglobulin A (IgA) antibody (NAD) to type 8Streptococcus pneumoniaecapsular polysaccharide (type 8 PS) to screen a phage display library, and the phage PUB1 displaying the peptide FHLPYNHNWFAL was selected after three rounds of biopanning. Inhibition studies with phage-displayed peptide or the peptide PUB1 and type 8 PS showed that PUB1 is a mimetic of type 8 PS. PUB1 conjugated to tetanus toxoid (PUB1-TT) induced a type 8 PS-specific antibody response in BALB/c mice, further defining it as a mimotope of type 8 PS. The administration of immune sera obtained from PUB1-TT-immunized mice earlier (days 14 and 21) and later (days 87 and 100) after primary and reimmunization resulted in a highly significant prolongation of the survival of naive mice after pneumococcal challenge compared to controls. The survival of PUB1-TT-immunized mice was also prolonged after pneumococcal challenge nearly 4 months after primary immunization. The efficacy of PUB1-TT-induced immune sera provides proof of principle that a mimotope-induced antibody response can protect against pneumococci and suggests that peptide mimotopes selected by type-specific human antibodies could hold promise as immunogens for pneumococci.
Role of CD44 and Its v7 Isoform in Staphylococcal Enterotoxin B-Induced Toxic Shock: CD44 Deficiency on Hepatic Mononuclear Cells Leads to Reduced Activation-Induced Apoptosis That Results in Increased Liver Damage
Authors: McKallip Robert J. , Fisher Michael , Gunthert Ursula , Szakal Andras K. , Nagarkatti Prakash S. , Nagarkatti Mitzi
Published: December 2004

Exposure to bacterial superantigens such as staphylococcal enterotoxin B (SEB) leads to the induction of toxic shock syndrome which results in multiorgan failure, including liver damage. In the present study, we investigated the role of CD44 in SEB-induced liver injury. Injection of SEB intod-galactosamine-sensitized CD44 wild-type (WT) mice led to a significant increase in CD44 expression on liver T cells, NK cells, and NKT cells. Administration of SEB to CD44 knockout (KO) mice caused significantly enhanced liver damage which correlated with elevated numbers of T cells, NK cells, NKT cells, and macrophages in the liver and increased production of tumor necrosis factor alpha and gamma interferon compared to CD44 WT mice. Furthermore, liver mononuclear cells from CD44 KO mice were resistant to SEB-induced apoptosis, and cDNA microarray analysis revealed that SEB activation of such cells led to the induction of several antiapoptotic genes and repression of proapoptotic genes. Examination of CD44 isoforms revealed that SEB exposure altered CD44 variant 7 (v7) isoform expression. Interestingly, mice bearing a specific deletion of the CD44v7 exon exhibited increased susceptibility to SEB-induced hepatitis. Finally, treatment of CD44 WT mice with anti-CD44 monoclonal antibodies reduced expression of CD44 in liver mononuclear cells and caused increased susceptibility to SEB-induced liver injury. Together, these data demonstrate that the expression of CD44 and/or CD44v7 on SEB-activated liver mononuclear cells facilitates their rapid apoptosis, thereby preventing severe liver injury in wild-type mice, and suggest that CD44 plays an important role in the regulation and elimination of immune cells in the liver.
Central Role of Toll-Like Receptor 4 Signaling and Host Defense in Experimental Pneumonia Caused by Gram-Negative Bacteria
Authors: Schurr Jill R. , Young Erana , Byrne Pat , Steele Chad , Shellito Judd E. , Kolls Jay K.
Published: December 2004

Toll-like receptor 4 (TLR4) has been identified as a receptor for lipopolysaccharide. However, the precise role of TLR4 in regulating gene expression in response to an infection caused by gram-negative bacteria has not been fully elucidated. The role of TLR4 signaling in coordinating gene expression was assessed by gene expression profiling in lung tissue in a mouse model of experimental pneumonia with a low-dose infection ofKlebsiella pneumoniae. We analyzed four mouse strains: C57BL/6 mice, which are resistant to bacterial dissemination; 129/SvJ mice, which are susceptible; C3H/HeJ mice, which are susceptible and have defective TLR4 signaling; and their respective control strain, C3H/HeN (intermediate resistance). At 4 h after infection, C57BL/6 and C3H/HeN mice demonstrated the greatest number of genes, with 67 shared induced genes which were TLR4 dependent and highly associated with the resistance phenotype. These genes included cytokine and chemokine genes required for neutrophil activation or recruitment, growth factor receptors, MyD88 (a critical adaptor protein for TLR signaling), and adhesion molecules. TLR4 signaling accounted for over 74% of the gene expression in the C3H background. These data suggest that early TLR4 signaling controls the vast majority of gene expression in the lung in response to an infection caused by gram-negative bacteria and that this subsequent gene expression determines survival of the host.
Ground reaction forces associated with an effective elementary school based jumping intervention
Authors: McKay H , Tsang G , Heinonen A , MacKelvie K , Sanderson D , Khan K M
Published: December 2004

Background:Mechanical loading during childhood plays a critical role in normal growth and development of the skeleton. Ground reaction forces (GRFs) may provide a surrogate measure for the strain experienced by bone on landing and at take off. However, there appear to be no paediatric studies that assess GRFs across a variety of loading activities.

Objectives:To measure biomechanical variables in commonly performed childhood activities used in an elementary physical education intervention study which augmented bone health in boys and girls.

Methods:Maximal GFR, maximal rates of force, and time to maximum force were measured for 12 different jumping activities on a force platform. The jumps measured were drop jumps from 10, 30, and 50 cm, all followed by a plyometric jump, submaximal and maximal jumping jacks, alternating feet jump, counter movement jumps, and side to side jumps over 10 and 20 cm foam barriers. The subjects were 70 children (36 boys and 34 girls), 8.3–11.7 years old.

Results:Subjects ranged in height from 128.4 to 172.6 cm and had a mass of 25.0–57.0 kg. Mean (SD) for vertical jump was 24.2 (5.5) cm and 135.2 (16.6) cm for standing long jump. The children engaged in loaded physical activity 5.7 (5.3) hours a week, on average. The highest mean maximal GRFs, normalised for body weight (BW), were generated from the plyometric portion of the drop jumps and the counter movement jump (about 5 times BW) compared with 3.5 times BW for jumping jacks. Similarly, the highest rates of change in force were 514 times BW/s for the drop jump from 10 cm and 493 times BW/s for the counter movement jump.

Conclusions:Simple jumps requiring minimal equipment produce GRFs of 3.5–5 times BW and rates of force of around 500 times BW/s. As children appear to attenuate higher impact forces when jumping from increased heights, it cannot be assumed that merely increasing the height of the jump will necessarily “progress” the exercise intervention.
Developing learning outcomes for an ideal MSc course in sports and exercise medicine
Authors: Kordi R , Dennick R G , Scammell B E
Published: December 2004

Objective:To develop learning outcomes for an ideal MSc in sports and exercise medicine.

Methods:Twenty nine learning outcomes were developed based on the learning outcomes, aims, and objectives of current sports medicine courses, occupational standards, and other related data. Using a Likert scale, the opinion of MSc/Dip course directors in the United Kingdom, Ireland, Australia, New Zealand, and South Africa as well as teachers, graduates, and students of the MSc/Dip course at the University of Nottingham were surveyed. An email questionnaire listing the 29 learning outcomes was sent to the subjects. A mixed reminder via email or mail was used. The results were treated as ordinal data, and reliability and internal consistency of the questionnaire was tested using Cronbach’s coefficient α.

Results:Response rates were high (75% course directors, 79%, 54%, and 78% University of Nottingham teachers, graduates, and students respectively). The questionnaire was highly reliable (α>0.8).The total scores of all but one of the responders were above the midpoint (>87, possible range 29–145). Most course directors (>80%) agreed or strongly agreed with each of the learning outcomes, except two. Most of the other subjects also agreed or strongly agreed with the learning outcomes, with few exceptions.

Conclusion:The results suggest that there is a consensus among subjects that the final listed learning outcomes should be included in an ideal MSc in sports and exercise medicine.
Effect of static stretching of quadriceps and hamstring muscles on knee joint position sense
Authors: Larsen R , Lund H , Christensen R , Røgind H , Danneskiold-Samsøe B , Bliddal H
Published: December 2004

Objectives:To evaluate if a stretch regimen consisting of three 30 second stretches would alter joint position sense (JPS).

Methods:A blinded, randomised, cross over design with a washout time of 24 hours was used with 20 healthy volunteers. JPS was estimated from the ability to reproduce the same position in one knee (target versus estimated angle) expressed as the difference between target and estimated angle (constant error, CE). Measurements were repeated three times in a sitting and a prone position on the dominant leg measured before and immediately after the static stretch. The static stretch consisted of a 30 second stretch followed by a 30 second pause, repeated three times.

Results:At baseline, the mean (SD) CE was −2.71 (3.57)° in the sitting position. No difference (p  =  0.99) in CE between stretching and control was observed (0.00; 95% confidence interval −0.98 to 0.99). At baseline, the CE was −3.28 (4.81)° in the prone position. No difference (p  =  0.89) in CE between stretching and control was observed (0.12; 95% confidence interval −1.52 to 1.76).

Conclusion:A static stretch regimen had no effect on JPS in healthy volunteers.
LONG VIRTUAL KNOTS AND THEIR INVARIANTS
Authors: MANTUROV VASSILY O.
Published: December 2004

There are some phenomena arising in the virtual knot theory which are not the case for classical knots. One of them deals with the "breaking" procedure of knots and obtaining long knots. Unlike the classical case, they might not be the same. The present work is devoted to construction of some invariants of long virtual links. Several explicit examples are given. For instance, we show how to prove the non-triviality of some knots obtained by breaking virtual unknot diagrams by very simple means.
IDENTIFIABLE PROJECTIONS OF SPATIAL GRAPHS
Authors: HUH YOUNGSIK , TANIYAMA KOUKI
Published: December 2004

A generic map from a finite graph to the 2-space is called identifiable if any two embeddings of the graph into the 3-space obtained by lifting the map with respect to the natural projection from the 3-space to the 2-space are ambient isotopic in the 3-space. We show that only planar graphs have identifiable maps. We characterize the identifiable maps for some planar graphs.
Unique modulation of L-type Ca2+channels by short auxiliary β1dsubunit present in cardiac muscle
Authors: Cohen Risa M. , Foell Jason D. , Balijepalli Ravi C. , Shah Vaibhavi , Hell Johannes W. , Kamp Timothy J.
Published: December 2004

Recent studies have identified a growing diversity of splice variants of auxiliary Ca2+channel Cavβ subunits. The Cavβ1disoform encodes a putative protein composed of the amino-terminal half of the full-length Cavβ1isoform and thus lacks the known high-affinity binding site that recognizes the Ca2+channel α1-subunit, the α-binding pocket. The present study investigated whether the Cavβ1dsubunit is expressed at the protein level in heart, and whether it exhibits any of the functional properties typical of full-length Cavβ subunits. On Western blots, an antibody directed against the unique carboxyl terminus of Cavβ1didentified a protein of the predicted molecular mass of 23 kDa from canine and human hearts. Immunocytochemistry and surface-membrane biotinylation experiments in transfected HEK-293 cells revealed that the full-length Cavβ1bsubunit promoted membrane trafficking of the pore-forming α1C(Cav1.2)-subunit to the surface membrane, whereas the Cavβ1dsubunit did not. Whole cell patch-clamp analysis of transfected HEK-293 cells demonstrated no effect of coexpression of the Cavβ1dwith the α1C-subunit compared with the 15-fold larger currents and leftward shift in voltage-dependent activation induced by full-length Cavβ1bcoexpression. In contrast, cell-attached patch single-channel studies demonstrated that coexpression of either Cavβ1bor Cavβ1dsignificantly increased mean open probability four- to fivefold relative to the α1C-channels alone, but only Cavβ1bcoexpression increased the number of channels observed per patch. In conclusion, the Cavβ1disoform is expressed in heart and can modulate the gating of L-type Ca2+channels, but it does not promote membrane trafficking of the channel complex.
Impact of altered substrate utilization on cardiac function in isolated hearts from Zucker diabetic fatty rats
Authors: Wang Peipei , Lloyd Steven G. , Zeng Huadong , Bonen Arend , Chatham John C.
Published: December 2004

The goal of this study was to determine whether changes in cardiac metabolism in Type 2 diabetes are associated with contractile dysfunction or impaired response to ischemia. Hearts from Zucker diabetic fatty (ZDF) and lean control rats were isolated and perfused with glucose, lactate, pyruvate, and palmitate. The rates of glucose, lactate, pyruvate, and palmitate oxidation rates and glycolysis were determined during baseline perfusion and low-flow ischemia (LFI; 0.3 ml/min for 30 min) and after LFI and reperfusion. Under all conditions, ATP synthesis from palmitate was increased and synthesis from lactate was decreased in the ZDF group, whereas the contribution from glucose was unchanged. During baseline perfusion, the rate of glycolysis was lower in the ZDF group; however, during LFI and reperfusion, there were no differences between groups. Despite these metabolic shifts, there were no differences in oxygen consumption or ATP production rates between the groups under any perfusion conditions. Cardiac function was slightly depressed before LFI in the ZDF group, but during reperfusion, function was improved relative to the control group despite the increased dependence on fatty acids for energy production. These data suggest that in this model of diabetes, the shift from carbohydrates to fatty acids for oxidative energy production did not increase myocardial oxygen consumption and was not associated with impaired response to ischemia and reperfusion.
Cholinergic Control of Firing Pattern and Neurotransmission in Rat Neostriatal Projection Neurons: Role of CaV2.1 and CaV2.2 Ca2+Channels
Authors: Perez-Rosello Tamara , Figueroa Alejandra , Salgado Humberto , Vilchis Carmen , Tecuapetla Fatuel , Guzman Jaime N. , Galarraga Elvira , Bargas Jose
Published: December 2004

Besides a reduction of L-type Ca2+-currents (CaV1), muscarine and the peptidic M1-selective agonist, MT-1, reduced currents through CaV2.1 (P/Q) and CaV2.2 (N) Ca2+channel types. This modulation was strongly blocked by the peptide MT-7, a specific muscarinic M1-type receptor antagonist but not significantly reduced by the peptide MT-3, a specific muscarinic M4-type receptor antagonist. Accordingly, MT-7, but not MT-3, blocked a muscarinic reduction of the afterhyperpolarizing potential (AHP) and decreased the GABAergic inhibitory postsynaptic currents (IPSCs) produced by axon collaterals that interconnect spiny neurons. Both these functions are known to be dependent on P/Q and N types Ca2+channels. The action on the AHP had an important effect in increasing firing frequency. The action on the IPSCs was shown to be caused presynaptically as it coursed with an increase in the paired-pulse ratio. These results show: first, that muscarinic M1-type receptor activation is the main cholinergic mechanism that modulates Ca2+entry through voltage-dependent Ca2+channels in spiny neurons. Second, this muscarinic modulation produces a postsynaptic facilitation of discharge together with a presynaptic inhibition of the GABAergic control mediated by axon collaterals. Together, both effects would tend to recruit more spiny neurons for the same task.
Two Intra-Amygdaloid Pathways to the Central Amygdala Exhibit Different Mechanisms of Long-Term Potentiation
Authors: Fu Yu , Shinnick-Gallagher Patricia
Published: December 2004

Synaptic plasticity in the amygdala is thought to underlie aversive or rewarding learning and emotional memories. In this study, different mechanisms were found to underlie synaptic plasticity in lateral (LA) and basolateral (BLA) amygdala pathways to the primary output nucleus of the amygdala, the central amygdala (CeA). Specifically, 1) long-term potentiation (LTP) at the BLA-CeA synapses was independent of inhibition and mediated through N-methyl-d-aspartate receptors (NMDARs) and L-type voltage-gated calcium channels (VGCCs), and 2) LTP in the LA-CeA pathway was gated by inhibition and mediated through VGCCs but not NMDARs.
Neuromuscular Reflexes Contribute to Knee Stiffness During Valgus Loading
Authors: Dhaher Y. Y. , Tsoumanis A. D. , Houle T. T. , Rymer W. Z.
Published: December 2004

We have previously shown that abduction angular perturbations applied to the knee consistently elicit reflex responses in knee joint musculature. Although a stabilizing role for such reflexes is widely proposed, there are as of yet no studies quantifying the contribution of these reflex responses to joint stiffness. In this study, we estimate the mechanical contributions of muscle contractions elicited by mechanical excitation of periarticular tissue receptors to medial-lateral knee joint stiffness. We hypothesize that these reflex muscle contractions will significantly increase knee joint stiffness in the adduction/abduction direction and enhance the overall stability of the knee. To assess medial-lateral joint stiffness, we applied an abducting positional deflection to the fully extended knee using a servomotor and recorded the torque response using a six degree-of-freedom load-cell. EMG activity was also recorded in both relaxed and preactivated quadriceps and hamstrings muscles with surface electrodes. A simple, linear, second-order, delayed model was used to describe the knee joint dynamics in the medial/lateral direction. Our data indicate that excitation of reflexes from periarticular tissue afferents results in a significant increase of the joint’s adduction-abduction stiffness. Similar to muscle stretch reflex action, which is modulated with background activation, these reflexes also show dependence on muscle activation. The potential significance of this reflex stiffness during functional tasks was also discussed. We conclude that reflex activation of knee muscles is sufficient to enhance joint stabilization in the adduction/abduction direction, where knee medial-lateral loading arises frequently during many activities.
Discharge Rate Variability Influences the Variation in Force Fluctuations Across the Working Range of a Hand Muscle
Authors: Moritz Chet T. , Barry Benjamin K. , Pascoe Michael A. , Enoka Roger M.
Published: December 2004

The goal of this study was to improve the ability of a motor unit model to predict experimentally measured force variability across a wide range of forces. Motor unit discharge characteristics were obtained from 38 motor units of the first dorsal interosseus muscle. Motor unit discharges were recorded in separate isometric contractions that ranged from 4 to 85% of the maximal voluntary contraction (MVC) force above recruitment threshold. High-threshold motor units exhibited both greater minimal and peak discharge rates compared with low-threshold units ( P < 0.01). Minimal discharge rate increased from 7 to 23 pps, and peak discharge rate increased from 14 to 38 pps with an increase in recruitment threshold. Relative discharge rate variability (CV) decreased exponentially for each motor unit from an average of 30 to 13% as index finger force increased above recruitment threshold. In separate experiments, force variability was assessed at eight force levels from 2 to 95% MVC. The CV for force decreased from 4.9 to 1.4% as force increased from 2 to 15% MVC ( P < 0.01) and remained constant at higher forces (1.2–1.9%; P = 0.14). When the motor unit model was revised using these experimental findings, discharge rate variability was the critical factor that resulted in no significant difference between simulated and experimental force variability ( P = 0.22) at all force levels. These results support the hypothesis that discharge rate variability is a major determinant of the trends in isometric force variability across the working range of a muscle.
Renewal of the Neurophysiology of Language: Functional Neuroimaging
Authors: Démonet Jean-François , Thierry Guillaume , Cardebat Dominique
Published: December 2004

Functional neuroimaging methods have reached maturity. It is now possible to start to build the foundations of a physiology of language. The remarkable number of neuroimaging studies performed so far illustrates the potential of this approach, which complements the classical knowledge accumulated on aphasia. Here we attempt to characterize the impact of the functional neuroimaging revolution on our understanding of language. Although today considered as neuroimaging techniques, we refer less to electroencephalography and magnetoencephalography studies than to positron emission tomography and functional magnetic resonance imaging studies, which deal more directly with the question of localization and functional neuroanatomy. This review is structured in three parts. 1) Because of their rapid evolution, we address technical and methodological issues to provide an overview of current procedures and sketch out future perspectives. 2) We review a set of significant results acquired in normal adults (the core of functional imaging studies) to provide an overview of language mechanisms in the “standard” brain. Single-word processing is considered in relation to input modalities (visual and auditory input), output modalities (speech and written output), and the involvement of “central” semantic processes before sentence processing and nonstandard language (illiteracy, multilingualism, and sensory deficits) are addressed. 3) We address the influence of plasticity on physiological functions in relation to its main contexts of appearance, i.e., development and brain lesions, to show how functional imaging can allow fine-grained approaches to adaptation, the fundamental property of the brain. In closing, we consider future developments for language research using functional imaging.
The Multifunctional Fish Gill: Dominant Site of Gas Exchange, Osmoregulation, Acid-Base Regulation, and Excretion of Nitrogenous Waste
Authors: Evans David H. , Piermarini Peter M. , Choe Keith P.
Published: December 2004

The fish gill is a multipurpose organ that, in addition to providing for aquatic gas exchange, plays dominant roles in osmotic and ionic regulation, acid-base regulation, and excretion of nitrogenous wastes. Thus, despite the fact that all fish groups have functional kidneys, the gill epithelium is the site of many processes that are mediated by renal epithelia in terrestrial vertebrates. Indeed, many of the pathways that mediate these processes in mammalian renal epithelial are expressed in the gill, and many of the extrinsic and intrinsic modulators of these processes are also found in fish endocrine tissues and the gill itself. The basic patterns of gill physiology were outlined over a half century ago, but modern immunological and molecular techniques are bringing new insights into this complicated system. Nevertheless, substantial questions about the evolution of these mechanisms and control remain.
Information society revisited: from vision to reality
Authors: Martin Bill
Published: December 2004

In this article a range of national and international policies, many tied to electronic business and electronic government initiatives, are reviewed from the much older perspective of the Information Society. As a concept, the Information Society has retained a form of residual currency but while not quite dormant, it has been overshadowed by what are essentially techno-economic New Economy perspectives. Although these techno-economic priorities can be viewed as contributing to the ultimate development of an Information Society, this contribution continues to fall somewhat short of what would be deemed sufficient. The shortfalls are particularly evident in the case of socially disadvantaged members of the community. In reviewing such developments mainly in Europe but with examples drawn from elsewhere, progress towards Information Society status is assessed in a social context that illustrates the gap that exists between aspiration and achievement in this regard.
Executive functions in children with communication impairments, in relation to autistic symptomatology
Authors: Bishop Dorothy V. M. , Norbury Courtenay Frazier
Published: December 2004

Although impairment in executive functions has been described in autism, there has been debate as to whether response inhibition is specifically affected. We compared four groups: highfunctioning autism; pragmatic language impairment; specific language impairment; and control. Inhibition was assessed using two subtests from the Test of Everyday Attention for Children, one requiring a verbal response and the other a non-verbal response. Although we found evidence of inhibitory deficits, these were neither specific to autism, nor linked to particular aspects of autistic symptomatology. Rather, they appeared to be associated with poor verbal skills and inattention. It is suggested that future studies need to control for structural language skills and attention deficit when evaluating cognitive deficits in autism. Reliance on control groups matched solely on vocabulary level or nonverbal mental age may obscure the important role played by language skills in executive functions.
Sleep disturbances in adolescents and young adults with autism and Asperger syndrome
Authors: Øyane Nicolas M.F. , Bjorvatn Bjørn
Published: December 2004

Sleep problems are commonly reported in children with autistic disorders. Most studies are based on sleep questionnaires and sleep diaries, but polysomnographic and actigraphic data have also been used. In this study we investigated sleep in older individuals (aged 15-25 years) with autism and Asperger syndrome, using sleep questionnaires, sleep diaries and actigraphy. Although the sleep questionnaires completed by parents and caretakers revealed only a moderate degree of sleep problems, greater sleep disturbance was recorded with actigraphy. Using the latter method, low sleep efficiency (below 85 percent) or long sleep latency (more than 30 minutes) were found in 80 percent of the individuals. There was no early morning awakening, contrary to some earlier reports. This study suggests that even though subjective complaints of sleep disturbances are less common in adolescents and young adults with autism, this may be due to an adaptation process rather than an actual reduction in sleep disturbances.
Do adolescents with autistic spectrum disorders adhere to social conventions in virtual environments?
Authors: Parsons Sarah , Mitchell Peter , Leonard Anne
Published: December 2004

The potential for using virtual environments (VEs) in educational contexts for people with autistic spectrum disorders (ASDs) has been recognized. However, very little is known about how people with ASDs interpret and understand VEs. This study aimed to investigate this directly with a group of 12 adolescents with ASDs, each individually matched with comparison participants. Participants were presented with VEs to assess whether they adhered to particular social conventions, such as not walking across grass and flowerbeds en route to a cafÈ, or not walking between two people (ostensibly involved in conversation) en route to the bar. Whilst a significant minority of the ASD group adhered to the social conventions, others displayed substantial ‘off-task’ behaviour and a limited understanding of the VE. It is suggested that some individuals with an ASD, low verbal IQ and weak executive ability require the most support to complete tasks successfully in the VE.
2-Ethylhydracrylic Aciduria in Short/Branched-Chain Acyl-CoA Dehydrogenase Deficiency: Application to Diagnosis and Implications for the R-Pathway of Isoleucine Oxidation
Authors: Korman Stanley H , Andresen Brage S , Zeharia Avraham , Gutman Alisa , Boneh Avihu , Pitt James J
Published: December 2004

Background: Isolated excretion of 2-methylbutyrylglycine (2-MBG) is the hallmark of short/branched-chain acyl-CoA dehydrogenase deficiency (SBCADD), a recently identified defect in the proximal pathway of l-isoleucine oxidation. SBCADD might be underdiagnosed because detection and recognition of urine acylglycines is problematic. Excretion of 2-ethylhydracrylic acid (2-EHA), an intermediate formed in the normally minor R-pathway of l-isoleucine oxidation, has not previously been described in SBCADD.

Methods: Samples from four patients with 2-MBG excretion were analyzed by gas chromatography–mass spectrometry for urine organic acids, quantification of 2-MBG, and chiral determination of 2-methylbutyric acid. Blood-spot acylcarnitines were measured by electrospray–tandem mass spectrometry. Mutations in the ACADSB gene encoding SBCAD were identified by direct sequencing.

Results: SBCADD was confirmed in each patient by demonstration of different ACADSB gene mutations. In multiple urine samples, organic acid analysis revealed a prominent 2-EHA peak usually exceeding the size of the 2-MBG peak. Approximately 40–46% of total 2-methylbutyric acid conjugates were in the form of the R-isomer, indicating significant metabolism via the R-pathway.

Conclusions: If, as generally believed, SBCAD is responsible for R-2-MBG dehydrogenation in the R-pathway, 2-EHA would not be produced in SBCADD. Our observation of 2-ethylhydracrylic aciduria in SBCADD implies that a different or alternative enzyme serves this function. Increased flux through the R-pathway may act as a safety valve for overflow of accumulating S-pathway metabolites and thereby mitigate the severity of SBCADD. Awareness of 2-ethylhydracrylic aciduria as a diagnostic marker could lead to increased detection of SBCADD and improved definition of its clinical phenotype.
Das Experiment: Kosmetika — Do it yourself
Authors: Vogel Friedrich
Published: December 2004

In den letzten Jahren nimmt das Interesse an den Hintergründen, am Aufbau und an der Zusammensetzung von kosmetischen Präparaten zu. Schließlich möchte manch einer hinter die Geheimnisse der phantasievollen Cremes und Lotionen der Großen Kosmetikhäuser kommen. Um es vorwegzunehmen: Anders als bei Lebensmitteln, die zuhause zubereitet oft besser schmecken als fertig gekauft, ist die Zubereitung einer ausgezeichneten Creme immer noch ein wohlgehütetes Geheimnis und erfordert ein beträchtliches Wissen über die optimale Mischung der Bestandteile. Für den Spaß am Ausprobieren, das Experiment in der Schule oder im Labor oder einen ersten Kontakt zur Grundlagen aus. Mit geringen Mitteln lassen sich durchaus befriedigende Kosmetikprodukte herstellen.
Hochauflösende Durchstrahlungs‐Elektronenmikroskopie
Authors: Gruehn Reginald , Roß Ronald
Published: December 2004

Der Nobelpreis für Physik wurde 1986 je zur Hälfte dem Berliner Physiker Ernst Ruska für seinen bedeutenden Beitrag zur Entwicklung des Durchstrahlungs‐Elektronenmikroskops und den Physikern Gerd Binnig und Heinrich Rohrer in Zürich für die Erfindung des Raster‐Tunnelmikroskops zuerkannt. Die Auswahl der Preisträger verdeutlicht, welche Bedeutung Methoden der „Übermikroskopie”︁, mit denen eine weit höhere Auflösung [1] als mit der Licht‐mikroskopie erreicht werden kann, inzwischen zukommt. Besonders mit Hilfe der Durchstrahlungs‐Elektronenmikroskopie gelang es der Biologie und Medizin, den feineren Aufbau der Zelle kennenzulernen. Darüber hinaus stößt diese leistungsfähige Untersuchungsmethode bis in atomare Dimensionen vor und ist deshalb aus der Werkstoffkunde, der Mineralogie, der Physik und der Festkörperchemie nicht mehr wegzudenken.
100 Jahre Metallcarbonyle. Eine Zufallsentdeckung macht Geschichte
Authors: Herrmann Wolfgang A.
Published: December 2004

In den meisten Bereichen der chemischen Forschung dürfen metallorganische Verbindungen unterschiedlichster Prägung heutzutage eine Schlüsselfunktion beanspruchen, zumindest aber wertvolle Hilfsdienste anbieten. Ob man sich für Grundfragen der chemischen Bindung interessiert oder für den gezielten Aufbau organischer Moleküle, komplizierte Naturstoffe eingeschlossen, ob über stöchiometrische Bindungsknüpfungen hinaus katalytisch verlaufende Prozesse gefragt sind, ob Oberflächeneffekte von Metallen und Metalloxiden auf kohlenstoffhaltige Verbindungen studiert und modellhaft verstanden werden sollen, ob endlich auch die differenzierten Wirkungen von Metallen, leichten wie schweren, auf körpereigene Stoffe zu erforschen sind – für alles das muß man eine Menge metallorganische Chemie verstehen. Gerade das hochbrisante Thema der Lebensbedrohung durch Schwermetalle sollte uns daran erinnern, daß wir den Inhalt der „Büchse der Pandora”︁ nur begreifen, wenn wir sie öffnen, den gefährlichen Stoff mit Umsicht charakterisieren und daraus unsere Schlüsse ziehen. 100 Jahre Metallcarbonyle [1] sind dazu angetan, auch darüber nachzudenken.
Berliner Blau
Authors: Ludi Andreas
Published: December 2004

Das komplexe Eisencyanid Berliner Blau ist die älteste synthetisch hergestellte Koordinationsverbindung und fand wegen seiner charakteristischen Farbe recht vielseitige Anwendungen. Das wissenschaftliche Interesse konzentrierte sich auf die Koexistenz der Oxidationsstufen II und III des Eisens. Experimentelle Untersuchungen und theoretische Überlegungen beschäftigten sich mit den Koordinationsverhältnissen der beiden verschiedenartigen Eisenzentren, einer Reihe von spektroskopischen Eigenschaften und der Struktur dieser polymeren Verbindung. Die Herstellung im Laboratorium entspricht der Idealformel Fe4[Fe(CN)6]3 · 15H2O, bei der Anwendung als Pigment spielen Alkali‐Ionen für die Erzeugung bestimmter Farbtöne eine Rolle.
Martin Heinrich Klaproth als Archäometer
Authors: Schütt Hans‐Werner
Published: December 2004

Der Mann, der hier als einer der ersten auf dem Gebiet der Archäometrie forschenden Chemiker vorgestellt werden soll, nämlich Martin Heinrich Klaproth, hat eine für das Ende des 18. Jahrhunderts ganz ungewöhnliche Karriere durchlaufen, die ihn aus dem Tal kleinstädtischer Enge auf die Höhe internationaler Anerkennung führen sollte: Geboren wurde er 1743 in Wernigerode am Harz als Sohn eines armen Scheiders; 1817 starb er in Berlin als einer der einflußreichsten Gelehrten Europas [1]. Auch um öffentliche Anerkennung brauchte er, der übrigens zeitlebens persönlich sehr bescheiden war, sich nicht zu beklagen: Seit 1788 war er Mitglied der Köngl. Preußischen Akademie der Wissenschaften und außerdem promovierte ihn, der nie an einer Universität immatrikuliert war, die Universität Erlangen 1806 zum Ehrendoktor. 1810 wurde er erster Ordinarius für Chemie an der eben gegründeten Berliner Universität.
Chemie unter Hochdruck Die Steuerung organisch‐chemischer Reaktionen mit hohem Druck
Authors: Klärner Frank‐Gerrit
Published: December 2004

Hoher Druck im Bereich von 5 bis 20 kbar beeinflußt Geschwindigkeit und Gleichgewichtslage vieler Reaktionen stark. Bei Reaktionen (z. B. Additionen, Heteriktse usw.), die mit einer Volumenabname verbunden sind, führt hoher Druck zu einer Reaktionbeschleunigung und einer Gleichgewichtsverschiebung zugunsten der Produkte, bei anderen Reaktionen (z. B. Homolyse, Ionenrekombinationusw.), die mit einer Volumenzunahme verbunden sind, dagegen zu einer Reajtuibsverzogerung und Gleichgewichtsverschiebung zugunsten der Ausgangssverbindungen. Bei Gleichgewichts‐, Konkurrenz‐ und Folgereaktionen lassen sich diese unterschiedlichen Druckeffekte zur Reaktionssteuerung ausnutzen. Beispielsweise kann man bei Konkurrenzreaktionen durch Druck das Produktverhältnis verschieben und damit die Selektivität erhöhen. Bei Folgereaktionen ist es in günstigen Fällen moglich, mit Hilfe von Druck reaktive Zwischenprodukte zu isolieren, die sonst nicht isolierbar sind. In dieser Übersicht werden Beispiele diskutiert, die hauptsächlich zu den Diels‐Alder‐ und anderen Cycloadditions‐Reaktionen gehören.
Struktur und Dynamik von Modell‐Biomembranen
Authors: Winter Roland
Published: December 2004

Biomembranen können als sehr komplexe zweidimensionale “Lösungen” bestehend aus Lipiden, Proteinen und Steroiden aufgefaßt werden. Das Interesse an der Struktur, Dynamik und damit der Funktion biologischer Membranen hat intensive physikalisch‐chemische Untersuchungen an einfacheren Systemen, sogenannten Modell‐Biomembranen, initiiert. Die am besten untersuchten Modellsysteme sind die reinen Lipid‐Doppelschichten, z. B. die der Phosphatidylcholine. Sie bilden die Grundstruktur biologischer Membranen und liefern bereits wichtige Informationen über die Eigenschaften natürlicher Membranen. Hier sollen vor allem der Einfluß der Konfiguration der Lipide und der Einfluß des Einbaus von Cholesterin in die Membran auf das temperatur‐ und druckabhängige Phasenverhalten der Phosphatidylcholine erörtert und die biologisch relevanten Aspekte der Untersuchungen diskutiert werden.
Das Experiment: Der Eisentest im Waldboden
Authors: Bartels Ulrich , Knabe Wilhelm
Published: December 2004

Die schweren Stürme des Februars 1990, als zahlreiche Bäume nicht nur umgeknickt, sondern in einem bis dahin nicht gekannten Ausmaß mit ihren gesamten Wurzeltellern aus dem Boden herausgerissen wurden haben an vielen Stellen offenbart, was besorgte Forstwissenschaftler bereits seit einigen Jahren aufgrund bodenkundlicher Untersuchungen prognostiziert haben: Die Versauerung der Waldböden ist durch die seit jahrzehnten anhaltende Deposition saurer Luftverunreinigunngen derart fortgeschritten, daß die Pflanzen häufig kaum noch ein tiefreichendes Wurzelwerk entwickeln können. Dabei ist es weniger der pH‐Wert allein, der die Gefährdung kennzeichnet. Für das Ökosystem maßgebend ist, daß unter sauren Verhältnissen eine Reihe von Stoffen in eine für Pflanzenwurzeln verfügbare, toxische Form gebracht wird. An erster Stelle sind hier Aluminium und die Schwermetalle zu nennen, daneben auch Eisen. In jüngster Zeit werden zunehmend Nährstoff‐Ungleichgewichte diskutiert, wenn z. B. dem Mangel an Kalium‐, Magnesium‐ und Calcium‐Ionen in sauren Böden ein Überangebot an atmosphärischem, aus der Landwirtschaft stammenden Ammonium‐Stickstoff gegenübersteht (vgl. den Beitrag auf Seite 117).
Organische Pigmente für Photokopierer und Laserdrucker. Ein Kapitel angewandte Forschung
Authors: Macholdt Hans‐Tobias
Published: December 2004

Photokopierer und Laserdrucker haben sich weltweit durchgesetzt. Bis vor kurzem waren Photokopien üblicherweise schwarzweiß, neuerdings aber wird es in zunehmendem Maße möglich, farbig zu kopieren. Die Qualität dieser farbigen Kopien ist oft so gut, daß sich Original und Kopie kaum noch unterscheiden lassen (was bei kopierten Dokumenten z. B. durchaus problematisch ist). Die “elektronische Tinte” für die Photokopierer und Laserdrucker wird Toner genannt. Organische Buntpigmente geben dem Toner die Farbe. Sie beeinflussen darüber hinaus aber auch die elektrische Aufladbarkeit der Toner. Die richtige elektrostatische Aufladbarkeit des Toners ist jedoch eine grundlegende Voraussetzung für seine Verwendbarkeit. Vor diesem Hintergrund befaßt sich der vorliegende Beitrag mit dem Einfluß von organischen Pigmenten auf die elektrostatische Aufladung von Pulvertonern.
Ausbildungsintegrierter Umweltschutz durch Chemie. Wege zur Sonderabfallreduktion in einem Chemieanfängerpraktikum
Authors: Fischer Hanns
Published: December 2004

Kürzlich wurde berichtet [1], daß die jährlich zur Entsorgung abgeführten Sonderabfälle des Chemieanfängerpraktikums für Naturwissenschaftler an der Universität Zürich auf weniger als ein Hundertstel der früher üblichen Menge gesenkt wurden, ohne dadurch die Lehrinhalte und die Belastung der Teilnehmer merklich zu verändern. Zahlreiche Anfragen zu diesem „Zürcher Modell”︁ [2], in dem „Studenten Chemiemüll verringern”︁, veranlassen uns, die bei der Umgestaltung des Praktikums beschrittenen Wege hier etwas ausführlicher zu beschreiben. Dabei wird das allgemeine Konzept hervorgehoben, und seine wesentlichen Elemente werden in die Form von Empfehlungen gekleidet, die auch andere Praktika nutzen könnten und andernorts bereits teilweise genutzt werden. Sie werden durch Beispiele ergänzt.
Der Gütezustand des Rheins
Authors: Malle Karl‐Geert
Published: December 2004

Vor 13 Jahren haben wir schon einmal gefragt: „Wie schmutzig ist der Rhein?”︁ [vgl. diese Zeitschr. 12, 111 (1978)]. Damals wurde über den Gütezustand bis zum Jahre 1976 berichtet. Seither ist einiges Wasser den Rhein hinabgeflossen (von 1977 bis 1989 ca. eine Billion Kubikmeter), in allen Rheinanliegerstaaten sind viele Milliarden in den Bau weiterer Kläranlagen investiert worden. Es haben sich aber auch Umfang und Genauigkeit der Überwachung außerordentlich erhöht. Gründe genug, erneut über den Rhein zu berichten, genauer: über die Herkunft der Belastung, ihre zeitliche Entwicklung und ihren heutigen Umfang, aber auch über die natürlichen Mechanismen und die Maßnahmen des Menschen, die der Belastung entgegengewirkt haben.
Physikalische Methoden in der Chemie: Massenspektrometrie. Vorstoß zu Makromolekülen II:. Electrospray/Ion Spray und UV‐Laser‐Desorption/Ionisation
Authors: Lehmann Wolf‐Dieter
Published: December 2004

Nachdem im ersten Teil dieses Beitrags das Ionisierungsprinzip bei der Plasmadesorption (PD) und beim Fast Atom Bombardment (FAB) erläutert und einige Anwendungsbeispiele dieser Techniken vorgestellt wurden, geht es im folgenden zweiten Teil um das Ionisierungsprinzip bei Electrospray/‐Ionisation und UV‐Laser‐Desorption. Auch für diese schonenden Ionisierungstechniken werden Anwendungsbeispiele aus dem Proteinbereich gegeben.
Struktur und Biosynthese der Bakteriochlorophylle
Authors: Senge Mathias O.
Published: December 2004

Bakteriochlorophylle gehören zu der großen Gruppe der Metallotetrapyrrole. Als photosynthetische Pigmente sammeln sie Licht und überführen die Lichtenergie in biochemisch nutzbare Form. Damit stehen Bakteriochlorophylle an zentraler Stelle in einem Elementarprozeß der Natur.
Moderne Waschmittel
Authors: Hauthal Hermann G.
Published: December 2004

Waschmittel stehen heute in aller Öffentlichkeit im Spannungsfeld zwischen nicht nachlassendem Wohlstandsanspruch und wachsendem Umweltbewußtsein der Bevölkerung: Nach bestimmungsgemäßem Gebrauch gelangen die Inhaltsstoffe der Waschmittel vollständig in den Abwasserpfad und müssen in den Kläranlagen biologisch abgebaut oder durch Adsorption und Fällung aus dem Abwasser eliminiert werden. Da niemand auf Reinigung, Pflege und vor allem auch Hygiene verzichten will und soll, bieten die Umweltprobleme also eine ständige Herausforderung zur Innovation.