Cyclic nucleotides attenuate lipid peroxidation-mediated neuron toxicity

Recent studies suggest that increased lipid peroxidation and lipid peroxidation products, such as 4-hydroxynonenal (HNE), contribute to neuronal loss in conditions associated with oxidative stress. The focus of the present study was to determine possible neuroprotective effects of elevated cyclic nucleotide levels against lipid peroxidation and HNE-mediated neural toxicity. Application of 8-bromo derivative analogs of cAMP or cGMP resulted in attenuation of HNE-induced increases in mitochondrial calcium, reactive oxygen species, and neuron loss. Similar results were obtained when neural cells were pretreated with the phosphodiesterase inhibitors zaprinast or isobutylmethylxanthanine (IBMX). These data are consistent with a possible neuroprotective role for elevated cyclic nucleotide levels in disorders associated with increases in lipid peroxidation and HNE.     

Ubiquitin binds to a short peptide segment of hydrolase UCH-L3: a study by FCS, RIfS, ITC and NMR

Screening for small peptidic affinity tags for the detection of ubiquitin and ubiquitinated proteins yielded the dodecapeptide amide DPDELRFNAIAL-NH(2) as a specific ubiquitin-interacting ligand. A peptide collection--based on crystal structures with ubiquitin-interacting proteins--was designed and confirmed by sequence comparison of ubiquitin-interacting motifs. Four independent physical detection methods demonstrated that the peptide binds to monomeric ubiquitin with an affinity of about 10 muM and with fast on and off rates. Fluorescence correlation spectroscopy with fluorescent peptides showed specific interaction with ubiquitin. Reflectometric interference spectroscopy with surface-immobilized peptides and isothermal calorimetry measurements confirmed the specific binding of ubiquitin and fast rate constants. (1)H,(15)N heteronuclear NMR localised the interaction site across the beta sheet of ubiquitin. The peptide aligns well with the ubiquitin-interacting motif and represents a lead structure for the rational design of high-affinity tags for targeting ubiquitinated protein in vitro and in vivo.     

Molecular adsorption on V2O3(0001)/Au(111) surfaces

The adsorption of carbon monoxide (CO), propane (C₃H₈) and propene (C₃H₆) on V₂O₃(0001) films grown on Au(111) was studied by Temperature Programmed Desorption (TPD) and X-ray Photoelectron Spectroscopy (XPS). The “oxidized” surface (i.e., as prepared exhibiting V=O termination), the “reduced” surface (i.e., V=O groups being removed by electron irradiation), as well as the oxygen pre-covered reduced surface were investigated. Both TPD and XPS indicate that the oxidized surface has little affinity for CO adsorption, while the reduced surface readily binds CO (CO amount approx. 10 times higher). Accordingly, CO can be used to titrate the presence or absence of vanadyl oxygen (via adsorption on the vanadium atoms) but also of defects like surface oxygen vacancies. For propane and propene, desorption of the parent molecules was the major process, i.e., surface reactions were absent under the applied conditions. When oxygen was pre-adsorbed on the reduced surface, the adsorption properties resembled that of the oxidized surface, i.e., the vanadyl groups were (partially) re-established. TPD and XPS provide a handle to differentiate the binding sites on the V₂O₃ surface. Dedicated to Prof. Konrad Hayek.     

Causes of failure of surgery on the lumbar spine

An interinstitutional study on the failed back surgery syndrome (FBSS) has determined that failure to recognize or adequately treat lateral stenosis of the lumbar spine with resultant nerve irritation and/or compression comprised the primary etiology in 57% to 58% of patients. Other common causes were recurrent or persistent disk herniation and lumbosacral adhesive arachnoiditis. The diagnosis of stenosis was made either by high-resolution CT scan of the lumbar spine or by directly testing lateral canal and for animal patency at the time of surgery. It is now appreciated that the process of degenerative disk disease, particularly when enhanced by diskectomy, results in progressive loss of intervertebral disk volume and predisposes to future ipsilateral or contralateral lateral spinal stenosis. Degenerative disk disease is ultimately a bilateral process and therefore surgical exposure should be bilateral. The direct and indirect costs of FBSS to patients and to society as well as the toll in human suffering are very high. This is particularly a matter of concern when it is realized that for many FBSS patients, surgery could have been avoided in the first place by preventive care or by innovative conservative treatment. When surgery is indicated, adequate diagnostic tests and the execution of appropriate procedures based upon this information should largely prevent the failed back surgery syndrome.     

Neuropsychological and psychosocial effects of the FMR-1 full mutation: Case report of monozygotic twins discordant for the fragile X syndrome.

An extensive evaluation was conducted with 16-yr-old monozygotic twins concordant for the fragile X full mutation but discordant for mental retardation. The clearly affected twin had an IQ score of 47; 77% of her neuropsychological z scores were at least 2 SDs below average. Her sister had an IQ score of 105 and average neuropsychological performance. However, each girl demonstrated relative verbal strengths and visual-spatial weaknesses. Their parents rated each girl as having significant problems with attention, conduct, anxiety-withdrawal, and hyperactivity. The girls did not rate themselves as having significant anxiety. These findings are consistent with group data on females with fragile X and demonstrate the wide range of effects associated with the fragile X full mutation. This case report implicates the importance of a psychosocial phenotype of fragile X independent of cognitive ability level. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Correlates of fatigue in older women with heart failure

OBJECTIVE: To examine the relative contribution of psychologic factors and physical symptoms to the variance in fatigue in older women with heart failure. METHODS: Eighty women who had been hospitalized in the previous 12 months for heart failure were interviewed. Fifty-seven women completed second interviews 18 months after the first interview. RESULTS: Fatigue was the most frequently occurring physical symptom at both measurement times, and it significantly increased with time. Other physical symptoms contributed uniquely to the variance in fatigue at both measurement times, but psychologic factors did not. At time 1, sleep difficulties, chest pain, and weakness each explained unique variance in fatigue. At time 2, dyspnea was the only variable that explained unique variance in fatigue (9%). Dyspnea also explained a significant portion of the variance (7%) in time 2 fatigue, when time 1 fatigue was controlled. CONCLUSIONS: Fatigue in older women with heart failure is related more to other physical symptoms than psychologic factors.     

Post-translational heterocyclic backbone modifications in the 43-peptide antibiotic microcin B17. Structure elucidation and NMR study of a 13C,15N-labelled gyrase inhibitor

Microcin B17 (McB17), the first known gyrase inhibitor of peptidic nature, is produced by ribosomal synthesis and post-translational modification of the 69-residue precursor protein by an Escherichia coli strain. To elucidate the chemical structure of the mature 43-residue peptide antibiotic, fermentation and purification protocols were established and optimized which allowed the isolation and purification of substantial amounts of highly pure McB17 (non-labelled, 15N-labelled and 13C/15N-labelled peptide. By ultraviolet-absorption spectroscopy. HPLC-electrospray mass spectrometry and GC-mass spectrometry, amino acid analysis, protein sequencing, and, in particular, multidimensional NMR, we could demonstrate and unequivocally prove that the enzymic modification of the precursor backbone at Gly-Cys and Gly-Ser segments leads to the formation of 2-aminomethylthiazole-4-carboxylic acid and 2-aminomethyloxazole-4-carboxylic acid, respectively. In addition, two bicyclic modifications 2-(2-aminomethyloxazolyl)thiazole-4-carboxylic acid and 2-(2-aminomethylthiazolyl)oxazole-4-carboxylic acid were found that consist of directly linked thiazole and oxazole rings derived from one Gly-Ser-Cys and one Gly-Cys-Ser segment. Analogous to the thiazole and oxazole rings found in antitumor peptides of microbial and marine origin, these heteroaromatic ring systems of McB17 presumably play an important role in its gyrase-inhibiting activity, e.g. interacting with the DNA to trap the covalent protein-DNA intermediate of the breakage-reunion reaction of the gyrase.     

Performance of children with ADHD on the Rey-Osterrieth complex figure: a pilot neuropsychological study

This study evaluates the performance of boys with Attention Deficit Hyperactivity Disorder (ADHD) on the Rey-Osterrieth Complex Figure (ROCF) taking into consideration familiality and comorbid psychiatric and learning disorders (LD). Sixty-five children with ADHD performed at developmentally lower levels of Copy Organization and Recall Style than did 45 controls. ADHD children with LD scored significantly lower on Copy Organization than did ADHD children without LD, whereas psychiatric comorbidity and familiality had no effect. These results suggest that a developmental analysis of the ROCF identifies organizational difficulties associated with ADHD and that these impairments cannot simply be attributed to comorbidities associated with ADHD.