bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of angiotensin II on primary cardiac fibroblast matrix metalloproteinase activities
Authors: Stacy Laura Buford , Yu Qianli , Horak Katherine , Larson Douglas F
Published: July 2007

Left ventricular dysfunction is associated with reperfusion injury occurring during open-heart surgery. There is an increased secretion of angiotensin II (Ang II) and increased matrix metalloproteinases (MMPs) activities associated with open-heart surgery that may affect the cardiac extracellular matrix (ECM). The goal of this study was to determine the effects of Ang II and selective angiotensin II receptor (AT1-R and AT2-R) blockers on the enzymatic activities of MMPs in primary adult murine cardiac fibroblasts (CF). Our hypothesis is that Ang II, with and without a selective receptor blocker, differentially affects CF MMPs activities. The CF were treated with Ang II (10-6M) and doses of AT1-R and AT2-R blockers (losartan and PD123319, respectively) at doses of 10-7to 10-5M for 48 hours. The Ang IIstimulated CF reduced collagenase activities by only 24% (p =0.004); however, the MMP-2 and MMP-9 gelatinase activities were reduced by 42% and 39%, respectively (p =0.022). The losartan dose dependently increased MMP-2 (p =0.02) and MMP-9 (ns). PD123319 at 10-5M significantly reduced MMP-2 and MMP-9 activities compared with the Ang II group (p =0.014 and p =0.02, respectively). The doses of PD123319 at 10-6and 10-7M increased the MMP-2 and MMP-9 enzymatic activities significantly above the Ang II only group. Thus, Ang II and AT1-R and AT2-R differentially affect the collagenase and gelatinase MMPs activities released by cardiac fibroblasts. Perfusion (2007) 22, 51-55.
The Structure and Function of Frail Male Veterans' Informal Networks
Authors: Abbott Katherine Harris , Stoller Eleanor Palo , Rose Julia Hannum
Published: July 2007

Objectives: This research focuses on the role of informal networks in providing emotional support, instrumental aid, and assistance with chronic disease management for frail male veterans. Methods: Telephone interviews were conducted with nursing home eligible veterans living in the community. Name-generating questions were used to illicit network members. Results: Data on 198 frail male veterans indicate that they have about three people they rely on for emotional support, instrumental aid, health appraisal, and health monitoring. Networks are composed primarily of family, and adult sons are mentioned almost as often as adult daughters. Discussion: Findings illustrate not only the role women play as providers of the majority of informal care to veterans but also the substantial role adult sons have in providing support to their fathers. Many veterans are at risk of institutionalization by having no one to provide instrumental support and health monitoring.
Dynamics of Acacia aneura—Triodia boundaries using carbon (14C and δ 13C) and nitrogen (δ15N) signatures in soil organic matter in central Australia
Authors: Bowman D.M.J.S. , Boggs Guy S. , Prior Lynda D. , Krull Evelyn S.
Published: July 2007

Soil organic matter (SOM) was sampled from soil profiles on a near level sandsheet at the southern limit of the Tanami Desert in central Australia to determine if boundaries of Triodia hummock grassland— Acacia aneura shrublands had changed in the Holocene. Accelerator Mass Spectrometry (AMS) 14C dating of 16 soil profiles showed that SOM that had accumulated at 100 to 140 cm depth, (near the base of most profiles) had ages between 1175 and 2630 14C years, averaging 1906 14C years. The stable carbon isotopic (δ13C) composition of SOM from the upper 50 cm soil profiles in the A. aneura shrubland (inhabited by plants with predominantly C3 photosynthetic pathway) was significantly more 13C-depleted than the comparable soil interval beneath a Triodia grassland (predominantly C4 photosynthetic pathway). Mean age of SOM at 50 cm depth was 830 14C years, suggesting the vegetation has been stable for about 1000 years. However, soil profiles in Triodia grassland adjacent to the shrubland boundary had slightly more depleted δ 13C relative to sites >0.5 km from the boundary. With respect to stable nitrogen isotopic values, only surface soils in the Acacia shrublands were found to be 15N-enriched relative to all other soil depths. Although there were no obvious environmental discontinuities, such as change in soil type or slope angle, associated with the ecosystem boundaries, the Acacia shrublands were found to occur on more clay-rich soils with higher concentrations of total phosphorus, nitrogen and potassium compared with the surrounding grasslands, and these trends became more pronounced with increasing distance from the ecotone: it is unclear if these differences are a cause or an effect of the vegetation mosaic. The concordance of the vegetation boundaries with the δ13C and δ15N and of soil nutrients are consistent with only minor attrition of the A. aneura shrublands in the late Holocene at this site.
Does Evaluation Build or Destroy Trust?
Authors: Schwarz Christine , Struhkamp Gerlinde
Published: July 2007

This article reflects on the relationship between evaluation and trust. Evaluation has become prominent in recent years as a way to control administrative action.The underlying assumption here is that administrative action, e.g. in the form of publicly funded programmes, requires control in order to gain or sustain its legitimacy.Two case studies of programmes of higher education reform in Germany, initiating so-called `virtual universities', are used to investigate how stakeholders experienced evaluation. Informants argued that there was too much evaluation, that confusion and competition arose about the roles of evaluation, and that little instrumental use occurred. This situation caused frustration and begs the question whether evaluation, intended to increase trust through systematic and transparent inquiry and rational decision-making, contradicted its own claims. It is argued that evaluation can be endangered by `inverse process use' or `process damage'.
Focus Groups as an Instrument to Define Evaluation Criteria
Authors: Moro Giuseppe , Cassibba Rosalinda , Costantini Alessandro
Published: July 2007

This article reports the results of a research project that aimed to identify the criteria upon which a foster care intervention may be considered as having been successful. The aim was to confirm the existence of shared evaluation criteria among the different groups involved in foster care and, moreover, to investigate possible differences in the meaning given to the foster care experience by the different stakeholders. The data collected from six focus groups was analysed in two ways: first, the criteria necessary to evaluate foster care were derived; second, a textual analysis was undertaken to investigate the associations and the frequency of use of some significant terms.
The chloroplast genome sequence of the green alga Leptosira terrestris: multiple losses of the inverted repeat and extensive genome rearrangements within the Trebouxiophyceae
Authors: de Cambiaire Jean-Charles , Otis Christian , Turmel Monique , Lemieux Claude
Published: July 2007

Background

In the Chlorophyta – the green algal phylum comprising the classes Prasinophyceae, Ulvophyceae, Trebouxiophyceae and Chlorophyceae – the chloroplast genome displays a highly variable architecture. While chlorophycean chloroplast DNAs (cpDNAs) deviate considerably from the ancestral pattern described for the prasinophyte Nephroselmis olivacea, the degree of remodelling sustained by the two ulvophyte cpDNAs completely sequenced to date is intermediate relative to those observed for chlorophycean and trebouxiophyte cpDNAs. Chlorella vulgaris (Chlorellales) is currently the only photosynthetic trebouxiophyte whose complete cpDNA sequence has been reported. To gain insights into the evolutionary trends of the chloroplast genome in the Trebouxiophyceae, we sequenced cpDNA from the filamentous alga Leptosira terrestris (Ctenocladales).

Results

The 195,081-bp Leptosira chloroplast genome resembles the 150,613-bp Chlorella genome in lacking a large inverted repeat (IR) but differs greatly in gene order. Six of the conserved genes present in Chlorella cpDNA are missing from the Leptosira gene repertoire. The 106 conserved genes, four introns and 11 free standing open reading frames (ORFs) account for 48.3% of the genome sequence. This is the lowest gene density yet observed among chlorophyte cpDNAs. Contrary to the situation in Chlorella but similar to that in the chlorophycean Scenedesmus obliquus, the gene distribution is highly biased over the two DNA strands in Leptosira. Nine genes, compared to only three in Chlorella, have significantly expanded coding regions relative to their homologues in ancestral-type green algal cpDNAs. As observed in chlorophycean genomes, the rpoB gene is fragmented into two ORFs. Short repeats account for 5.1% of the Leptosira genome sequence and are present mainly in intergenic regions.

Conclusion

Our results highlight the great plasticity of the chloroplast genome in the Trebouxiophyceae and indicate that the IR was lost on at least two separate occasions. The intriguing similarities of the derived features exhibited by Leptosira cpDNA and its chlorophycean counterparts suggest that the same evolutionary forces shaped the IR-lacking chloroplast genomes in these two algal lineages.
TRPM5, a taste-signaling transient receptor potential ion-channel, is a ubiquitous signaling component in chemosensory cells
Authors: Kaske Silke , Krasteva Gabriele , König Peter , Kummer Wolfgang , Hofmann Thomas , Gudermann Thomas , Chubanov Vladimir
Published: July 2007

Background

A growing number of TRP channels have been identified as key players in the sensation of smell, temperature, mechanical forces and taste. TRPM5 is known to be abundantly expressed in taste receptor cells where it participates in sweet, amino acid and bitter perception. A role of TRPM5 in other sensory systems, however, has not been studied so far.

Results

Here, we systematically investigated the expression of TRPM5 in rat and mouse tissues. Apart from taste buds, where we found TRPM5 to be predominantly localized on the basolateral surface of taste receptor cells, TRPM5 immunoreactivity was seen in other chemosensory organs – the main olfactory epithelium and the vomeronasal organ. Most strikingly, we found solitary TRPM5-enriched epithelial cells in all parts of the respiratory and gastrointestinal tract. Based on their tissue distribution, the low cell density, morphological features and co-immunostaining with different epithelial markers, we identified these cells as brush cells (also known as tuft, fibrillovesicular, multivesicular or caveolated cells). In terms of morphological characteristics, brush cells resemble taste receptor cells, while their origin and biological role are still under intensive debate.

Conclusion

We consider TRPM5 to be an intrinsic signaling component of mammalian chemosensory organs, and provide evidence for brush cells being an important cellular correlate in the periphery.
Enhancement of intracellular γ-tocopherol levels in cytokine-stimulated C3H 10T1/2 fibroblasts: relation to NO synthesis, isoprostane formation, and tocopherol oxidation
Authors: Tanaka Yuichiro , Wood Leslie A Lesoon , Cooney Robert V
Published: July 2007

Background

Stimulation of C3H 10T1/2 murine fibroblasts with interferon-γ(IFN) and bacterial lipopolysaccharide (LPS) generates reactive oxygen and nitrogen species leading to DNA damage, lipid oxidation, and tocopherol oxidation. The tocopherols possess unique chemical and biological properties that suggest they have important roles related to intracellular defense against radical-mediated damage.

Results

Despite increased levels of reactive oxidants and decreased media tocopherol, cellular levels of γ-tocopherol, but not α-tocopherol, were observed to increase significantly when cells were treated with IFN/LPS. Inhibition of nitric oxide (NO) synthesis by a specific inhibitor of inducible NO synthase (iNOS) increased both intracellular α-tocopherol and γ-tocopherol concentrations, but did not significantly alter the reduction in media tocopherol levels caused by IFN/LPS treatment. Both exposure to exogenous NO and cellular synthesis of NO in cell culture increased media levels of 8-epi-prostaglandin F2α, a marker of oxidative lipid damage, whereas inhibition of endogenous NO synthesis reduced media 8-epi-prostaglandin F2α formation to control levels.

Conclusion

Elevated intracellular levels of γ-tocopherol in response to the cellular inflammatory state may indicate that it serves a unique role in minimizing cellular damage resulting from endogenous NO synthesis. Results of the current study suggest that NO is an important mediator of damage within the cell, as well as in the oxidation of both α- and γ-tocopherols. The paradoxical increase in cellular tocopherol associated with the induction of NO synthesis may indicate either enhanced cellular transport/decreased export for tocopherols or recruitment of free tocopherol from tocopherol storage molecules.
Mating behaviour in the sea slug Elysia timida (Opisthobranchia, Sacoglossa): hypodermic injection, sperm transfer and balanced reciprocity
Authors: Schmitt Valerie , Anthes Nils , Michiels Nico K
Published: July 2007

Background

In simultaneous hermaphrodites with copulation and internal fertilization it is often unclear whether reciprocal sperm exchange results from the unconditional willingness of both partners to donate and receive sperm, or whether it follows from a more controlled process such as conditional reciprocal sperm exchange, i.e. sperm trading. While in some sea slugs mating is assumed to be based on sperm trading, it seems to be unconditional in others. Here, we describe the unusual mating behaviour of Elysia timida, a small sacoglossan, focussing on indications for conditional reciprocity.

Results

E. timida shows an as yet unique combination of a long series of hypodermic transfers followed by a short phase with standard insemination into a female genital aperture. Hypodermic transfer takes place in the form of repeated small injections into the dorsal surface of the partner, interrupted by synchronised circling movements. In the final mating phase sperm is transferred into the female genital aperture in a short period. In both phases the two mating individuals show a high degree of transfer symmetry and synchrony. While total duration and number of transfers were balanced within pairs, they varied significantly between pairs. Furthermore, looking at individual hypodermic transfers within pairs, reciprocal transfers lasted longer than unilateral transfers. Final sperm transfers were always reciprocal except for two cases which also diverted from the usual pattern in ways that were suggestive of a conflict over reciprocity.

Conclusion

Our results suggest that individual mating decisions in E. timida depend on what the partner does, indicating conditional reciprocity. If hypodermic transfers also involve the transfer of sperm (which remains to be confirmed), this system represents an up to now unique transition stage between hypodermic and standard insemination, both of which are widespread in this group of sea slugs, but never have been observed to co-occur within the same species.
Acute panuveitis with hypopyon in Crohn's disease secondary to medical therapy: a case report
Authors: Haider David , Dhawahir-Scala Felipe E , Strouthidis Nicholas G , Davies Nigel
Published: July 2007

Background

A case report to highlight the association between rifabutin and hypopyon

Methods

A 56 year old male presented with a one day history of blurred vision in his right eye. He had an established diagnosis of Crohn's disease which was in remission following treatment with rifabutin and clarithromycin. A brisk anterior uveitis with hypopyon and a mild vitritis was detected in the right eye. The acute inflammatory episode resolved following treatment with topical corticosteroids and withdrawal of rifabutin.

Results

The presence of hypopyon is atypical in uveitis associated with inflammatory bowel disease. The association between rifabutin treatment and hypopyon uveitis is well recognised in Mycobacterium avium paratuberculosis. However, use of rifabutin in the management of Crohn's disease is controversial and not widely known to an ophthalmic readership.

Conclusion

This report highlights the importance of keeping abreast of novel therapeutic developments in systemic conditions likely to be encountered in ophthalmology.
A Comparison of 1850 (50 mCi) and 3700 MBq (100 mCi) 131-Iodine Administered Doses for Recombinant Thyrotropin-Stimulated Postoperative Thyroid Remnant Ablation in Differentiated Thyroid Cancer
Authors: Pilli Tania , Brianzoni Ernesto , Capoccetti Francesca , Castagna Maria Grazia , Fattori Sara , Poggiu Angela , Rossi Gloria , Ferretti Francesca , Guarino Elisa , Burroni Luca , Vattimo Angelo , Cipri Claudia , Pacini Furio
Published: July 2007

Objective: Recently, a multicenter study in differentiated thyroid cancer (DTC) patients showed that 3700 MBq 131-iodine (131I) after recombinant human TSH (rhTSH) had a successful thyroid ablation rate similar to that obtained after thyroid hormone withdrawal. We investigated whether 1850 MBq 131I had a similar successful rate to 3700 MBq in patients prepared with rhTSH.

Design: A total of 72 patients with DTC were randomly assigned to receive 1850 (group A, n = 36) or 3700 MBq (group B, n = 36) 131I after rhTSH. One injection of 0.9 mg rhTSH was administered for 2 consecutive days; 131I therapy was delivered 24 h after the last injection, followed by a posttherapy whole-body scan. Successful ablation was assessed 6–8 months later.

Results: Successful ablation (no visible uptake in the diagnostic whole-body scan after rhTSH stimulation) was achieved in 88.9% of group A and B patients. Basal and rhTSH-stimulated serum thyroglobulin was undetectable (<1 ng/ml) in 78.9% of group A and 66.6% of group B patients (P = 0.46). Similar rates of ablation were obtained in both groups also in patients with node metastases.

Conclusion: Therapeutic 131I activities of 1850 MBq are equally effective as 3700 MBq for thyroid ablation in DTC patients prepared with rhTSH, even in the presence of node metastases.
Regulation of Suppressor of Cytokine Signaling 3 (SOC3) by Growth Hormone in Pro-B Cells
Authors: Barclay Johanna L. , Anderson Stephen T. , Waters Michael J. , Curlewis Jon D.
Published: July 2007

Suppressor of cytokine signaling 3 (SOCS3) is expressed by lymphoid cells and can modulate the sensitivity of these cells to cytokine stimulation through inhibition of Janus kinase (JAK)/signal transducers and activators of transcription (STAT) signaling pathways. This study employed a mouse pro-B cell line expressing the human GH receptor (BaF/3-GHR), to elucidate the signal transduction pathways used by GH to elicit SOCS3 expression. GH treatment of these cells caused a rapid, dose-dependent increase in SOCS3 mRNA expression, which was independent of de novo protein synthesis. As expected, GH treatment increased JAK-dependent STAT5 tyrosine phosphorylation, which bound to the proximal STAT response element (pSRE) on the SOCS3 promoter. This process appeared to involve STAT5b, rather than STAT5a. In addition, GH activation of the SOCS3 promoter required a nearby activator protein (AP) 1/cAMP response element (CRE), which bound cAMP response element binding protein, c-Fos, and c-Jun. Moreover, inhibitors of p38 MAPK and c-Jun N-terminal kinase prevented GH-stimulation of SOCS3 mRNA expression in these cells, suggesting a role for these kinases in SOCS3 transcription. Importantly, GH stimulation increased binding of FOXO3a to the SOCS3 promoter at a site overlapping the AP1/CRE response element, and overexpression of FOXO3a in these cells augmented SOCS3 promoter activation. In addition, we show a direct interaction between FOXO3a and STAT5 in these cells, which may provide a link between STAT5 and the AP1 transcription factors on the SOCS3 promoter. We conclude that regulation of SOCS3 expression by GH in a pro-B cell involves not only the pSRE, but also a transcriptionally active complex involving cAMP response element binding protein/c-Fos/c-Jun and FOXO3a. This study has implications for cytokine regulation of SOCS gene expression in lymphoid cells.
Cyclosporine Monitoring
Authors: Taylor William J. , Robinson J. Daniel , Burckart Gilbert J. , Canafax Daniel M. , Yee Gary C.
Published: July 2007

Cyclosporine is an important immunosuppressive agent in organ and bone marrow transplantation. The pharmacokinetics of cyclosporine are quite complex and are complicated by the availability of two assay systems that yield differing results. This article summarizes the views from two major solid organ transplant centers and one bone marrow transplant center on important cyclosporine monitoring questions. A general consensus exists in the four areas discussed that: (1) cyclosporine concentrations must be monitored due in part to the extreme variability in kinetics, (2) either blood or plasma can be used in monitoring programs, (3) the radioimmunoassay or high pressure liquid chromatography can be used in routine monitoring, and (4) the interpretation of cyclosporine concentrations must be performed in relation to patient variables that affect drug response and toxicity.
Pharmacoeconomic Analysis of Angiotensin-Converting Enzyme Inhibitors in Type 2 Diabetes: A Markov Model
Authors: Campbell Heather M , Boardman Kathy D , Dodd Melanie A , Raisch Dennis W
Published: July 2007

Background:

Prevention of cardiovascular disease (CVD) events by initiating an angiotensin-converting enzyme (ACE) inhibitor on diagnosis of type 2 diabetes may increase survival and decrease costs.

Objective:

To determine the incremental cost-effectiveness ratios of ACE inhibitor initiation in normoaIbuminuric, microalbuminuruc, and macroaIbuminuric patients with newly diagnosed type 2 diabetes.

Methods:

A cohort of patients with newly diagnosed type 2 diabetes was followed for 8 years in a Markov model. Clinical outcomes included CVD events, dialysis, all-cause mortality, and the composite endpoints of the 3 events. Probabilities and costs were obtained from the literature. One-way and two-way sensitivity analyses were conducted to test the robustness of the model.

Results:

Implementation of ACE inhibitor therapy on diagnosis of type 2 diabetes in normoalbuminuric and microalbuminuric patients is a dominant strategy (ie, more effective and less costly) across all outcomes. In macro-albuminuric patients, an additional $4,10 and $4.58 saves one life and avoids one composite endpoint, respectively; however, in these patients, not giving an ACE inhibitor is dominant for prevention of CVD events and dialysis. This is due to a 28.62% higher mortality rate in patients not receiving an ACE inhibitor. Thus, analysts of the composite endpoint shows that not giving an ACE inhibitor does not remain dominant. A limitation of our study is the inability to determine causality.

Conclusions:

If every newly diagnosed patient with type 2 diabetes in the US was prescribed an ACE inhibitor, our model shows that 68 314 CVD events would be averted, 46410 lives would be saved, and 48 people would be prevented from needing dialysis over 8 years. These findings suggest that ACE inhibitors prevent numerous events in patients with type 2 diabetes who are normoalbuminuric at diagnosis, in addition to those already identified as being at risk for CVD events.
Interaction Between Valproate and Meropenem: A Retrospective Study
Authors: Spriet Isabel , Goyens Jo , Meersseman Wouter , Wilmer Alexander , Willems Ludo , Paesschen Wim Van
Published: July 2007

Background:

Valproate and meropenem are frequently used in the intensive care unit to treat seizures and serious infections, respectively. Several case reports have described a remarkable interaction between the drugs when administered concurrently. The interaction leads to a significant drop in plasma concentrations of valproate within 24 hours and relapse of seizures in some patients.

Objective:

To evaluate a consecutive population of hospitalized patients who were simultaneously treated with meropenem and valproate and assess the effect on epileptic activity.

Methods:

A retrospective study of an 18 month period was performed to assess the extent and clinical impact of this interaction. To assess the relevance of the interaction, the time-relationship between the drop in plasma concentrations and relapse in seizure activity and/or deterioration of electroencephalogram recordings was determined. We investigated other contributing preconvulsive cofactors and concomitant antiepileptic treatment. Drug interaction probability scale (DIPS) scores were calculated.

Results:

Thirty-nine patients were treated simultaneously with valproate and meropenem. The pharmacokinetic interaction was observed in all 39 patients, with an average drop in valproate plasma concentrations of 66%, The decrease occurred within 24 hours, as shown in 19 patients who had daily plasma concentration monitoring, The clinical impact of the interaction could not be assessed in 19 (49%) patients due to death (n = 13) or incomplete charts (n = 6). In the remaining 20 (51%) patients, DIPS scores were calculated and clinical relevance was assessed. The interaction was considered to be probable in 16 patients and possible in 4, as calculated by the DIPS. The interaction contributed to electroclinical deterioration in 11 patients.

Conclusions:

The pharmacokinetic interaction between valproate and meropenem was present in all patients and led to a drop of valproate concentrations with an average of 66% within 24 hours. This interaction was clinically relevant with electroclinical deterioration in 55% of patients. To avoid patients’ possible neurologic deterioration, meropenem and valproate should not be administered together.
Construct validity, reliability and predictive validity of the dynamic risk assessment and management system (DRAMS) in offenders with intellectual disability
Authors: Steptoe Lesley R. , Lindsay William R. , Murphy Lesley , Young Steven J.
Published: July 2007

Background. There have been a number of developments in the assessment of dynamic risk in the criminological literature. The dynamic risk assessment and management system (DRAMS) has been developed to facilitate the measurement of dynamic factors of risk for offenders with intellectual disability.

Method. The study was designed to assess the construct validity, reliability and predictive utility of the DRAMS in 23 male forensic patients in a high secure setting. Predictions were made against independently collected incident data. Concurrent validity was assessed against the Ward Anger Rating Scale (WARS).

Results. A reformulation of the individual section variables according to convergent and discriminant correlational analysis revealed Cronbach's alpha levels of >.8 for all sections apart from mood (alpha .750) and items retained to facilitate clinical information (alpha −.017). Two hundred pairs of WARS and DRAMS assessments revealed orderly sectional correlations. The sections of mood, antisocial behaviour, and intolerance/agreeableness predicted incidents with a medium effect size as did total DRAMS score. There were highly significant differences between assessments taken 1 or 2 days prior to an incident and control assessments conducted at least 7 days from an incident.

Conclusions. The reformulated DRAMS has good construct and concurrent validity. It appears to be a reliable assessment tool and informs on risk levels relating to stable and acute proximal factors. It appears as an important addition to the utility of risk assessments for this population.
Spare Respiratory Capacity Rather Than Oxidative Stress Regulates Glutamate Excitotoxicity after Partial Respiratory Inhibition of Mitochondrial Complex I with Rotenone
Authors: Yadava Nagendra , Nicholls David G.
Published: July 2007

Partial inhibition of mitochondrial respiratory complex I by rotenone reproduces aspects of Parkinson's disease in rodents. The hypothesis that rotenone enhancement of neuronal cell death is attributable to oxidative stress was tested in an acute glutamate excitotoxicity model using primary cultures of rat cerebellar granule neurons. As little as 5 nmrotenone increased mitochondrial superoxide (O2·−) levels and potentiated glutamate-induced cytoplasmic Ca2+deregulation, the first irreversible stage of necrotic cell death. However, the potent cell-permeant O2·−trap manganese tetrakis (N-ethylpyridinium-2yl) porphyrin failed to prevent the effects of the inhibitor. The bioenergetic consequences of rotenone addition were quantified by monitoring cell respiration. Glutamate activation of NMDA receptors used the full respiratory capacity of thein situmitochondria, and >80% of the glutamate-stimulated respiration was attributable to increased cellular ATP demand. Rotenone at 20 nminhibited basal and carbonyl cyanidep-trifluoromethoxyphenylhydrazone-stimulated cell respiration and caused respiratory failure in the presence of glutamate. ATP synthase inhibition by oligomycin was also toxic in the presence of glutamate. We conclude that the cell vulnerability in the rotenone model of partial complex I deficiency under these specific conditions is primarily determined by spare respiratory capacity rather than oxidative stress.
Glial Scar Expression of CHL1, the Close Homolog of the Adhesion Molecule L1, Limits Recovery after Spinal Cord Injury
Authors: Jakovcevski Igor , Wu Junfang , Karl Nicole , Leshchyns'ka Iryna , Sytnyk Vladimir , Chen Jian , Irintchev Andrey , Schachner Melitta
Published: July 2007

The Ig superfamily adhesion molecule CHL1, the close homolog of the adhesion molecule L1, promotes neurite outgrowth, neuronal migration, and survivalin vitro. We tested whether CHL1, similar to its close homolog L1, has a beneficial impact on recovery from spinal cord injury using adult CHL1-deficient (CHL1−/−) mice and wild-type (CHL1+/+) littermates. In contrast to our hypothesis, we found that functional recovery, assessed by locomotor rating and video-based motion analyses, was improved inCHL1−/−mice compared with wild-type mice at 3–6 weeks after compression of the thoracic spinal cord. Better function was associated with enhanced monoaminergic reinnervation of the lumbar spinal cord and altered pattern of posttraumatic synaptic rearrangements around motoneurons. Restricted recovery of wild-type mice was likely related to early and persistent (3–56 d after lesion) upregulation of CHL1 in GFAP-positive astrocytes at the lesion core. In both the intact spinal cord and cultured astrocytes, enhanced expression of CHL1 and GFAP was induced by application of basic fibroblast growth factor, a cytokine involved in the pathophysiology of spinal cord injury. This upregulation was abolished by inhibitors of FGF receptor-dependent extracellular signal-regulated kinase, calcium/calmodulin-dependent kinase, and phosphoinositide-3 kinase signaling pathways. In homogenotypic and heterogenotypic cocultures of neurons and astrocytes, reduced neurite outgrowth was observed only if CHL1 was simultaneously present on both cell types. These findings and novelin vitroevidence for a homophilic CHL1–CHL1 interaction indicate that CHL1 is a glial scar component that restricts posttraumatic axonal growth and remodeling of spinal circuits by homophilic binding mechanisms.
Vesicular Glutamate Transporter 1 Is Required for Photoreceptor Synaptic Signaling But Not For Intrinsic Visual Functions
Authors: Johnson Juliette , Fremeau Robert T. , Duncan Jacque L. , Rentería René C. , Yang Haidong , Hua Zhaolin , Liu Xiaorong , LaVail Matthew M. , Edwards Robert H. , Copenhagen David R.
Published: July 2007

Glutamatergic neurotransmission requires vesicular glutamate transporters (VGLUTs) to sequester glutamate into synaptic vesicles. Generally, VGLUT1 and VGLUT2 isoforms show complementary expression in the CNS and retina. However, little is known about whether isoform-specific expression serves distinct pathways and physiological functions. Here, by examining visual functions in VGLUT1-null mice, we demonstrate that visual signaling from photoreceptors to retinal output neurons requires VGLUT1. However, photoentrainment and pupillary light responses are preserved. We provide evidence that melanopsin-containing, intrinsically photosensitive retinal ganglion cells (RGCs), signaling via VGLUT2 pathways, support these non-image-forming functions. We conclude that VGLUT1 is essential for transmitting visual signals from photoreceptors to second- and third-order neurons, but VGLUT1 is not necessary for intrinsic visual functions. Furthermore, melanopsin and VGLUT2 expression in a subset of RGCs immediately after birth strongly supports the idea that intrinsic vision can function well before rod- and cone-mediated signaling has matured.
The Nogo-66 Receptor NgR1 Is Required Only for the Acute Growth Cone-Collapsing But Not the Chronic Growth-Inhibitory Actions of Myelin Inhibitors
Authors: Chivatakarn Onanong , Kaneko Shinjiro , He Zhigang , Tessier-Lavigne Marc , Giger Roman J.
Published: July 2007

Neuronal Nogo-66 receptor 1 (NgR1) has been proposed to function as an obligatory coreceptor for the myelin-derived ligands Nogo-A, oligodendrocyte myelin glycoprotein (OMgp), and myelin-associated glycoprotein (MAG) to mediate neurite outgrowth inhibition by these ligands. To examine the contribution of neuronal NgR1 to outgrowth inhibition, we used two different strategies, genetic ablation ofNgR1through the germline and transient short hairpin RNA interference (shRNAi)-mediated knock-down. To monitor growth inhibition, two different paradigms were used, chronic presentation of substrate-bound inhibitor to measure neurite extension and acute application of soluble inhibitor to assay growth cone collapse. We find that regardless of theNgR1genotype, membrane-bound MAG strongly inhibits neurite outgrowth of primary cerebellar, sensory, and cortical neurons. Similarly, substrate-bound OMgp strongly inhibits neurite outgrowth ofNgR1wild-type and mutant sensory neurons. Consistent with these results, shRNAi-mediated knock-down of neuronal NgR1 does not result in a substantial release of L-MAG (large MAG) inhibition. When applied acutely, however, MAG-Fc and OMgp-Fc induce a modest degree of growth cone collapse that is significantly attenuated inNgR1-null neurons compared with wild-type controls. Based on our findings and previous studies with Nogo-66, we propose that neuronal NgR1 has a circumscribed role in regulating cytoskeletal dynamics after acute exposure to soluble MAG, OMgp, or Nogo-66, but is not required for these ligands to mediate their growth-inhibitory properties in chronic outgrowth experiments. Our results thus provide unexpected evidence that the growth cone-collapsing activities and substrate growth-inhibitory activities of inhibitory ligands can be dissociated. We also conclude that chronic axon growth inhibition by myelin is mediated by NgR1-independent mechanisms.
Characterization of Neurons in the CA2 Subfield of the Adult Rat Hippocampus
Authors: Mercer Audrey , Trigg Hayley L. , Thomson Alex M.
Published: July 2007

The hippocampal cornu ammonis 2 (CA2) region is unique in being the only CA region receiving inputs from the hypothalamic supramammillary nucleus, of importance in modulating hippocampal theta rhythm, and is seizure resistant in temporal lobe epilepsy. CA2 has, however, been little studied, possibly because of its small size and difficulty encountered in defining its borders. To investigate the properties of CA2 interneurons, intracellular recordings with biocytin filling were made in adult hippocampal slices. Two types of basket cells were identified. A minority resembled those in CA1, with fast spiking behavior, vertically oriented dendrites, and axons confined to the region of origin. In contrast, the majority of parvalbumin-immunopositive CA2 basket and bistratified cells had long, horizontally oriented, sparsely spiny dendrites extending into all CA subfields in stratum oriens, adapting firing patterns and a pronounced “sag” in voltage responses to hyperpolarizing current, indicative ofIh. Broad CA2 basket cells innervated all three CA subfields and could thus provide CA1 and CA2 with feedforward and CA3 with feedback inhibition. In contrast, CA2 bistratified cell axons displayed striking subfield preference, innervating stratum oriens and stratum radiatum of CA2 and CA1 but stopping abruptly at the CA2/CA3 border, implying feedforward inhibition of CA2 and CA1. These unique features suggest that CA2 is more than a transitional region between CA1 and CA3. The pronounced slow sag current of many CA2 interneurons may contribute to coordination of pyramidal cell firing during theta, whereas the fast spiking behavior of a smaller population of interneurons supports more localized gamma.
Virtual Communities of Enquiry: An Argument for Their Necessity and Advice for Their Creation
Authors: Parsell Mitch , Duke-Yonge Jennifer
Published: July 2007

In this article it is argued that communities of enquiry can and should be developed in courses delivered online. These communities make the most of the available technological resources and overcome some otherwise daunting challenges faced in online course delivery. Indeed, asynchronous tools like discussion boards offer a range of benefits for the creation of such communities that are unobtainable in the traditional classroom. Further, the authors also point to some simple measures that have been found to be successful in helping to create net-based communities. Finally, they draw on recent empirical evidence to demonstrate that online communication tools can, if appropriately employed, offer unique benefits for the creation of learning communities.
Gait Training Combining Partial Body-Weight Support, a Treadmill, and Functional Electrical Stimulation: Effects on Poststroke Gait
Authors: Lindquist Ana RR , Prado Christiane L , Barros Ricardo ML , Mattioli Rosana , da Costa Paula H Lobo , Salvini Tania F
Published: July 2007

Background and Purpose: Treadmill training with harness support is a promising, task-oriented approach to restoring locomotor function in people with poststroke hemiparesis. Although the combined use of functional electrical stimulation (FES) and treadmill training with body-weight support (BWS) has been studied before, this combined intervention was compared with the Bobath approach as opposed to BWS alone. The purpose of this study was to evaluate the effects of the combined use of FES and treadmill training with BWS on walking functions and voluntary limb control in people with chronic hemiparesis.

Subjects: Eight people who were ambulatory after chronic stroke were evaluated.

Methods: An A1-B-A2 single-case study design was applied. Phases A1 and A2 included 3 weeks of gait training on a treadmill with BWS, and phase B included 3 weeks of treadmill training plus FES applied to the peroneal nerve. The Stroke Rehabilitation Assessment of Movement was used to assess motor recovery, and a videography analysis was used to assess gait parameters.

Results: An improvement (from 54.9% to 71.0%) in motor function was found during phase B. The spatial and temporal variables cycle duration, stance duration, and cadence as well as cycle length symmetry showed improvements when phase B was compared with phases A1 and A2.

Discussion and Conclusions: The combined use of FES and treadmill training with BWS led to an improvement in motor recovery and seemed to improve the gait pattern of subjects with hemiparesis, indicating the utility of this combination method during gait rehabilitation. In addition, this single-case series showed that this alternative method of gait training—treadmill training with BWS and FES—may decrease the number of people required to carry out the training.
Transport characteristics of some carboxylic acids in the polymeric anion‐exchange membrane Neosepta‐AMH: Batch experiments
Authors: Palatý Zdeněk , Stoček Pavel , Žáková Alena , Bendová Helena
Published: July 2007

This article reports the transport of selected carboxylic acids—citric acid, oxalic acid, and tartaric acid—through an anion‐exchange membrane (Neosepta‐AMH) in a two‐compartment dialysis cell. These basic data have been completed by measurements of the sorption isotherms. The mass‐transfer rate has been quantified by the following transport characteristics: the overall dialysis coefficient, the permeability of the membrane, and the membrane mass‐transfer coefficient. The sorption experiments have revealed that the Neosepta‐AMH membrane exhibits the highest affinity to tartaric acid, whereas the lowest affinity has been found for citric acid. The analysis of the mass‐transfer data has shown that the membrane is relatively permeable for oxalic acid: all three transport characteristics for oxalic acid are approximately 1 order of magnitude higher than those for citric or tartaric acid. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci 106: 909–916, 2007
Synthesis, Crystal Structure, Cytotoxic and Superoxide Dismutase Activities of Copper(II) Complexes of N‐(4,5‐Dihydroimidazol‐2‐yl)azoles
Authors: Saczewski Franciszek , Dziemidowicz‐Borys Ewa , Bednarski Patrick J. , Gdaniec Maria
Published: July 2007

A series of four Cu(II) dichlorides with N‐(4,5‐dihydro‐1H‐imidazol‐2‐yl)azoles as chelating ligands has been prepared and characterized by IR, UV‐vis spectroscopy, and X‐ray crystallography. The complex [2‐(4,5‐dihydro‐1H‐imidazol‐2‐yl)‐1H‐benzotriazole]‐dichlorocopper(II) showed very potent SOD activity in vitro with a superoxide scavenging IC50 of 0.06 μM, comparable to those described in the literature for best low molecular weight SOD mimics. Cytotoxicity studies with seven human tumor cell lines in vitro showed that the most active complexes inhibited the growth of cancer cells with IC50 between 13–28 μM. No obvious correlation was found between cytotoxic potency and superoxide scavenging activity of the complexes in any of the cell lines.
Spectrofluorimetric determination of 5‐hydroxytryptamine using chlorosulphonylthenoyltrifluoroacetone–europium probe
Authors: Zhu Xiaojing , Wang Xiaolei , Jiang Chongqiu
Published: July 2007

A new spectrofluorimetric method was developed for the determination of trace amounts of 5‐hydroxytryptamine (5‐HT). Using chlorosulphonylthenoyltrifluoroacetone (CTTA)–europium (Eu3+) ion as a fluorescent probe in a buffer solution at pH 11.0, 5‐HT can remarkably enhance the fluorescence intensity of the CTTA–Eu3+ complex at λ = 612 nm; the enhanced fluorescence intensity of Eu3+ is proportional to the concentration of 5‐HT. Optimum conditions for the determination of 5‐HT were also investigated. The linear range and detection limit for the determination of 5‐HT were 1.0 × 10−7–1.2 × 10−5 mol/L and 8.5 × 10−8 mol/L, respectively. This method is simple, practical and relatively free of interference from coexisting substances, and can be applied to assess 5‐HT in urine samples. Copyright © 2007 John Wiley & Sons, Ltd.
From egg to crystal
Authors: Olieric Vincent , Schreiber Angélique , Lorber Bernard , Pütz Joern
Published: July 2007

A practical hands‐on course encompassing enzyme purification, biochemical characterization, and crystallization that completed the course work of 350 second‐year bachelor students enrolled in molecular biology/biochemistry was given at the Université Louis Pasteur of Strasbourg (France). The experimental part of the practical dealt entirely with the model protein lysozyme isolated from hen egg‐white. It was designed as a research project to give students the possibility to practice biochemical methods such as chromatography, electrophoresis, and spectrophotometry. It also included enzyme activity assay and protein crystal growth that are usually taught in master‐level courses. The organization of the practical work and the related experimental procedures are described and discussed.
Molecular modeling of estrogen receptor using molecular operating environment
Authors: Roy Urmi , Luck Linda A.
Published: July 2007

Molecular modeling is pervasive in the pharmaceutical industry that employs many of our students from Biology, Chemistry and the interdisciplinary majors. To expose our students to this important aspect of their education we have incorporated a set of tutorials in our Biochemistry class. The present article describes one of our tutorials where undergraduates use modeling experiments to explore the structure of an estrogen receptor. We have employed the Molecular Operating Environment, a powerful molecular visualization software, which can be implemented on a variety of operating platforms. This tutorial reinforces the concepts of ligand binding, hydrophobicity, hydrogen bonding, and the properties of side chains and secondary structure taught in a general biochemistry class utilizing a protein that has importance in human biology.
Tris(dimethylamino)phosphane as a New Ligand in Gold(I) Chemistry: Synthesis and Crystal Structures of [(Me2N)3P]AuCl, {[(Me2N)3PAu]3O}+BF4−, {[Me2N)3PAu]3NP(NMe2)32+ {BF−4}2 and the Precursor Molecule (Me2N)3PNSiMe3
Authors: Bauer Andreas , Mitzel Norbert W. , Schier Annette , Schmidbaur Hubert , Rankin David W. H.
Published: July 2007

[Tris(dimethylamino)phosphane]gold(I) chloride, μ‐tris‐{[tris(dimethylamino)phosphane]gold(I)}oxonium tetrafluoroborate, {μ3‐tris(dimethylamino)phosphaneimidotris[tris(dimethylamino)phosphane]gold(I)}(2+) bis(tetrafluoroborate) and N‐trimethylsilyltris(dimethylamino)phosphaneimine were prepared using modifications of established procedures. Their structures were determined in single‐crystal X‐ray diffraction studies. The ligand (Me2N)3P, here introduced into gold(I) chemistry for the first time, lends high stability to these compounds through efficient steric shielding of the reaction sites and through a balanced electronic substituent effect. The structural details of the (Mr2N)3P groups are of current interest because of the unusual nonequivalent configuration of the nitrogen atoms in the dimethylamino groups. This behaviour has been observed for most of the (Me2N)3P units in the compounds studied in this work.
Self‐Assembly of Copper(I) Halide Networks Containing Tetra‐ or Pentameric Ethylcycloarsoxane (C2H5AsO)n (m = 4,5) as a flexible Bridging Unit
Authors: Häusler Thomas , Sheldrick William S.
Published: July 2007

In complexes of ethylcycloarsoxane (C2H3AsO)n, the oligomer size n is influenced by the coordinated metal atom. Cyclic tetramers are observed in the porous sheet structures of ∞2[Cu2Br2{cyclo‐(C2H5AsO)4}3] (1) and 2∞ [Cu3I3{cyclo‐(C2H5As0)4)2] (2), prepared by the reaction of the appropriate copper(I) halide with (C2H5AsO)n in acetonitrile. Both complexes contain μ1κAs1:2κAs3‐coordinated (C2H5AsO)4 ligands as molecular bridging units between individual copper(I) centres leading to large respectively 36‐ and 40‐membered rings. An analogous bridging mode is found in the cyclic oligomers [cyclo‐(ReBr(CO)3{μ‐[cyclo‐(C2H5AsO)}}4](3) formed by reacting {ReBr(CO)5] with (C2H5AsO)n in refluxing toluene. – In contrast both [(NH4){cyclo‐ (C2H5AsO)5}2][Ag(SCN)]2 (4) and 2∞[(Cs(cyclo‐(C2H5‐AsO)3]2} Cu2(μ‐I)I2] (5) contain pentamers (C2H5AsO)5, which coordinate the NH+4 and Cs+ cations κ5O in a pentagonal antiprismatic fashion. In 5, prepared by self‐assembly from CsI, CuI, and (C2H5AsO)n in acetonitrile, [Cs[cyclo‐{C2H5AsO}5)2]+ sandwich cations are linked thorough μ‐1κAs1:2κAs2‐coordinated [Cu2l3]− units into polymeric chains. This coordination pattern reflects the unique ring size adaptability of the ambidentate (C2J5AsO)n ligand.