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Purpose: There is good evidence that ascorbic acid (AA) status influences the onset of post-operative complications in intensive care patients. Light and room temperature cause the spontaneous oxidation of AA. Therefore, the stability of AA during modified sample preparation was investigated.Design: Prospective, single centre study.Methods: The AA plasma concentration was analysed in arterial and venous blood with added ethylene-diamine-tetra-acetic acid (EDTA) from 165 subjects. In addition, EDTA or heparin was added as an anticoagulant in venous blood of 79 subjects. Analyses were carried out using high performance liquid chromatography with ultraviolet detection.Results: In samples of arterial and venous blood with added EDTA it was observed that precision declined with increasing concentrations of AA. In venous samples with added heparin the correlation was low compared with venous samples with EDTA.Conclusion: Any change in our standard method of specimen collection (venous blood with added EDTA) results in AA plasma concentrations with questionable reliability. [ABSTRACT FROM AUTHOR]

Background: Stimulation of ventricular hypertrophy and heart rate are two major cardiac effects of thyroid hormone (TH). The aim of this study was to determine in vivo which TH receptor (TR)-α or β-and which mode of TR action-canonical gene expression or DNA-binding independent noncanonical action-mediate these effects. Methods: We compared global TRα and TRβ knockout mice (TRα KO ; TRβ KO ) with wild-type (WT) mice to determine the TR isoform responsible for T3 effects. The relevance of TR DNA binding was studied in mice with a mutation in the DNA-binding domain that selectively abrogates DNA binding and canonical TR action (TRα GS ; TRβ GS ). Hearts were studied with echocardiography at baseline and after 7 weeks of T3 treatment. Gene expression was measured with real-time polymerase chain reaction. Heart rate was recorded with radiotelemetry transmitters for 7 weeks in untreated, hypothyroid, and T3-treated mice. Results: T3 induced ventricular hypertrophy in WT and TRβ KO mice, but not in TRα KO mice. Hypertrophy was also induced in TRα GS mice. Thus, hypertrophy is mostly mediated by noncanonical TRα action. Similarly, repression of Mhy7 occurred in WT and TRα GS mice. Basal heart rate was largely dependent on canonical TRα action. But responsiveness to hypothyroidism and T3 treatment as well as expression of pacemaker gene Hcn2 were still preserved in TRα KO mice, demonstrating that TRβ could compensate for absence of TRα. Conclusions: T3-induced cardiac hypertrophy could be attributed to noncanonical TRα action, whereas heart rate regulation was mediated by canonical TRα action. TRβ could substitute for canonical but not noncanonical TRα action.

Introduction: Thyroid hormones (THs) are known to have various effects on the cardiovascular system. However, the impact of TH levels on preexisting cardiac diseases is still unclear. Pressure overload due to arterial hypertension or aortic stenosis and aging are major risk factors for the development of structural and functional abnormalities and subsequent heart failure. Here, we assessed the sensitivity to altered TH levels in aged mice with maladaptive cardiac hypertrophy and cardiac dysfunction induced by transverse aortic constriction (TAC)., Methods: Mice at the age of 12 months underwent TAC and received T4 or anti-thyroid medication in drinking water over the course of 4 weeks after induction of left ventricular pressure overload., Results: T4 excess or deprivation in older mice had no or only very little impact on cardiac function (fractional shortening), cardiac remodeling (cardiac wall thickness, heart weight, cardiomyocyte size, apoptosis, and interstitial fibrosis), and mortality. This is surprising because T4 excess or deprivation had significantly changed the outcome after TAC in young 8-week-old mice. Comparing the gene expression of deiodinases (Dio) 2 and 3 and TH receptor alpha (TRα) 1 and the dominant-negative acting isoform TRα2 between young and aged mice revealed that aged mice exhibited a higher expression of TRα2 and Dio3, while expression of Dio2 was reduced compared with young mice. These changes in Dio2 and 3 expressions might lead to reduced TH availability in the hearts of 12-month-old mice accompanied by reduced TRα action due to higher TRα2., Discussion: In summary, our study shows that low and high TH availability have little impact on cardiac function and remodeling in older mice with preexisting pressure-induced cardiac damage. This observation seems to be the result of an altered expression of deiodinases and TRα isoforms, thus suggesting that even though cardiovascular risk is increasing with age, the response to TH stress may be dampened in certain conditions., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Kerp, Gassen, Grund, Hönes, Dörr, Mittag, Härting, Kaiser, Moeller, Lorenz and Führer.)

Background: From autumn 2020 until spring 2021 Germany experienced the second wave of SARS-CoV‑2 infections. As in the previous wave, the older population in nursing homes was hard hit by this infection because of the lack of available vaccines. Due to the multimorbidity in this susceptible group the mortality was high., Methods: Retrospectively collected patient data of geriatric patients treated from 1 October 2020 to 31 March 2021 due to proven SARS-CoV‑2 infection were evaluated concerning the duration of symptoms, hospital stay, and laboratory results. The results are presented descriptively and significance tests were performed with t‑test and log-rank test to reveal some risk factors for a worse outcome., Results: A total of 168 patients aged from 65 to 97 years were included, with a mean mortality rate of 28% and was highest in the age group over 90 years old. Most patients died within the first 10 days of hospitalization. Intensive care treatment prolonged the hospital stay by 6 days, but the average survival time became equal at the end. Risk factors for worse outcome and the need of intensive care treatment were neutrophilia, lymphopenia, high levels of ferritin and high D‑dimer levels on the day of admission. Age, short duration of symptoms and pre-existing dementia, administration of neuroleptic drugs and antidepressants increased the risk of death., (© 2023. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Introduction: A diabetic foot infection (DFI) contributes to high mortality and morbidity in diabetics due to its often rapid progressive and intricately treatable infection. DFIs are usually a polymicrobial infection and characterizing the entire bacterial load is still challenging. Prompt and effective treatment of DFI is nevertheless mandatory to safe limbs and lives. It is therefore crucial to know the local pathogen spectrum and its antibiotic susceptibility., Methods and Material: For a 12-month period, we investigated 353 individuals with infected diabetic foot ulcer, their bacterial diversity, and antimicrobial susceptibility at fist-time visit in a Diabetic Foot Care Center in southern Germany., Results: Cultures yielded 888 species, most of them gram-positive cocci (primary Staphylococcus aureus ). The gram-negative sector was mainly formed by Pseudomonas aeruginosa and Enterobacteriacae . Because the prevalence of multiresistant species was surprisingly low (0.9% of isolated strains), we suggest penicillins with β-lactamase inhibitor in case of gram-positive-dominated infection or piperacillin/tazobactam or rather carbapenems with equal efficacy when gram-negative species are involved.

In tRNA Asp , tRNA Asn , tRNA Tyr , and tRNA His of most bacteria and eukaryotes, the anticodon wobble position may be occupied by the modified nucleoside queuosine, which affects the speed and the accuracy of translation. Since eukaryotes are not able to synthesize queuosine de novo, they have to salvage queuine (the queuosine base) as a micronutrient from food and/or the gut microbiome. The heterodimeric Zn 2+ containing enzyme tRNA-guanine transglycosylase (TGT) catalyzes the insertion of queuine into the above-named tRNAs in exchange for the genetically encoded guanine. This enzyme has attracted medical interest since it was shown to be potentially useful for the treatment of multiple sclerosis. In addition, TGT inactivation via gene knockout leads to the suppressed cell proliferation and migration of certain breast cancer cells, which may render this enzyme a potential target for the design of compounds supporting breast cancer therapy. As a prerequisite to fully exploit the medical potential of eukaryotic TGT, we have determined and analyzed a number of crystal structures of the functional murine TGT with and without bound queuine. In addition, we have investigated the importance of two residues of its non-catalytic subunit on dimer stability and determined the Michaelis-Menten parameters of murine TGT with respect to tRNA and several natural and artificial nucleobase substrates. Ultimately, on the basis of available TGT crystal structures, we provide an entirely conclusive reaction mechanism for this enzyme, which in detail explains why the TGT-catalyzed insertion of some nucleobases into tRNA occurs reversibly while that of others is irreversible.

Background: Bilophila wadsworthia, a strictly anaerobic, sulfite-reducing bacterium and common member of the human gut microbiota, has been associated with diseases such as appendicitis and colitis. It is specialized on organosulfonate respiration for energy conservation, i.e., utilization of dietary and host-derived organosulfonates, such as taurine (2-aminoethansulfonate), as sulfite donors for sulfite respiration, producing hydrogen sulfide (H 2 S), an important intestinal metabolite that may have beneficial as well as detrimental effects on the colonic environment. Its taurine desulfonation pathway involves the glycyl radical enzyme (GRE) isethionate sulfite-lyase (IslAB), which cleaves isethionate (2-hydroxyethanesulfonate) into acetaldehyde and sulfite., Results: We demonstrate that taurine metabolism in B. wadsworthia 3.1.6 involves bacterial microcompartments (BMCs). First, we confirmed taurine-inducible production of BMCs by proteomic, transcriptomic and ultra-thin sectioning and electron-microscopical analyses. Then, we isolated BMCs from taurine-grown cells by density-gradient ultracentrifugation and analyzed their composition by proteomics as well as by enzyme assays, which suggested that the GRE IslAB and acetaldehyde dehydrogenase are located inside of the BMCs. Finally, we are discussing the recycling of cofactors in the IslAB-BMCs and a potential shuttling of electrons across the BMC shell by a potential iron-sulfur (FeS) cluster-containing shell protein identified by sequence analysis., Conclusions: We characterized a novel subclass of BMCs and broadened the spectrum of reactions known to take place enclosed in BMCs, which is of biotechnological interest. We also provided more details on the energy metabolism of the opportunistic pathobiont B. wadsworthia and on microbial H 2 S production in the human gut., (© 2021. The Author(s).)

The diabetic foot syndrome (DFS) is the most important cause for non-traumatic major amputation in adult individuals and actually one of the most frightening events in diabetics' life. Despite the often protracted treatment of infected DFS at the end patients are often confronted with amputation. We investigated 352 individuals with infected DFS in two age separated-groups. Older individuals presented with significant worse renal function and lower HbA1c on day of admittance. Most detected ulcers involved the plantar sides of the metatarsal heads (MTH) and the toes. We saw an age-dependent translocation of foot ulcers from plantar and hindfoot to the forefoot and toes. In average every third wound provoked amputation, in the majority (94%) minor amputations, only 1.9% major amputations occurred. Lesions of the 5 th toe or its MTH and interdigital or interphalangeal joint ulcers led to amputation in more than 60%. Worse renal function and WBC above 11 tsd/µl were linked with higher amputation risk. But in particular current scoring systems like SINBAD or Wagner-Armstrong scale and thus finally clinician's assessment of the wound situation gave a substantial hint for subsequent amputation - regardless of age., Competing Interests: The authors declare no conflict of interest., (Thieme. All rights reserved.)

Background: In current sports science, the important role of sleep quality for health and peak performance is well acknowledged. More precisely, it is evident that the negative combination of stressful factors, low resources, and bad sleep habits causes short-term performance losses as well as long-term health consequences. As the maximization of human performance consisting of multiple fixed workloads is the main motivation in CrossFit® (CF), the aim of the present study was to investigate the influence of high sleep quality on performance in CrossFit® athletes (CFA) and the different training categories that are addressed in CF., Methods: In total, 149 CFA (81 females, 68 males; 32.01 ± 7.49 years old, 2.56 ± 1.77 active years in CF) filled in the online survey comprising the Pittsburgh Sleep Quality Index (PSQI) and CF performance-specific questions., Results: It was found that CFA with high sleep quality reported higher values in all performance-related outcomes. Especially in Hero-/Girl-Workouts (χ2 = (1, n = 83) = 9.92, p = .002, φ = 0.37) and Gymnastics (χ2 = (1, n = 129) = 8.74, p = .003, φ = 0.28), performance differed significantly between good and poor sleeping CFA. Since those CF categories are highly technical- and cognitive-demanding high sleep quality seems to play a fundamental role in complex motor skill learning and performance development., Conclusions: These results reveal for the first time the positive effects of high sleep quality for performance in CFA and could be used as basis for future studies. Future research should also develop and empirically test suitable interventions to foster high sleep quality in CFA., Trial Registration: The study was conducted according to the guidelines of the Declaration of Helsinki, and approved by the Ethics Committee of University of the Federal Armed Forces Munich, Germany (06/04/2018)., (© 2021. The Author(s).)

Aim: Infection of a diabetic foot ulcer (DFU) is common. More than the half of DFUs become infected and 15-20% of them necessitate amputation in course of treatment. Diabetic foot infection (DFI) is therefore the major cause for non-traumatic lower limb amputation in Germany. Prompt and effective treatment of DFI is mandatory to safe limbs and lives. We investigated if there are relevant differences in evoked inflammatory response between different species and age-separated groups. We further investigated if there is an impact of ulcer localization on bacterial diversity., Methods: For a 12-month period, we investigated 353 individuals with infected DFU, their laboratory results and bacterial diversity at first-time visit in a Diabetic Foot Care Center in Southern Germany., Results: The ulcer microbiota was dominated by gram-positive species, primary Staphylococcus aureus. The gram-negative sector was mainly formed by Pseudomonas aeruginosa and Enterobacteriaceae (Proteus spp., Enterobacter spp., Escherichia coli and Klebsiella spp.). With increase in age, P. aeruginosa and S. aureus became more frequent, while Streptococci decreased. Ischemic and/or deep wounds were more likely to bear gram-negative species. Inflammatory response did not differ between gram-positive and gram-negative species, while Streptococci and Proteus spp. induced the highest serum inflammation reaction in their category. Streptococci, Enterobacter spp. and E. coli were more frequent in summer, while Enterococci spp., coagulase-negative Staphylococci and P. aeruginosa were more prevalent in winter half-year. DFIs of the forefoot and plantar side are mostly caused by gram-positive species, while Enterobacteriaceae were most frequent in plantar ulcerations., Conclusion: Gram-positive species dominate bacterial spectrum in DFI. With increase in age, S. aureus, Streptococci and Pseudomonas aeruginosa became more frequent. The inflammatory response did not differ significantly between different species, but gram-negative species were slightly but not significant more frequent in ischemic wounds. Climatic distinction like summer or winter half-year as well as foot ulcer localization seems to influence bacterial diversity in DFUs.

Bacterial tRNA-guanine transglycosylase (Tgt) is involved in the biosynthesis of the modified tRNA nucleoside queuosine present in the anticodon wobble position of tRNAs specific for aspartate, asparagine, histidine, and tyrosine. Inactivation of the tgt gene leads to decreased pathogenicity of Shigella bacteria. Therefore, Tgt constitutes a putative target for Shigellosis drug therapy. Since it is only active as homodimer, interference with dimer-interface formation may, in addition to active-site inhibition, provide further means to disable this protein. A cluster of four aromatic residues seems important to stabilize the homodimer. We mutated residues of this aromatic cluster and analyzed each mutated variant with respect to the dimer and thermal stability or enzyme activity by applying native mass spectrometry, a thermal shift assay, enzyme kinetics, and X-ray crystallography. Our structural studies indicate a strong influence of pH on the homodimer stability. Apparently, protonation of a histidine within the aromatic cluster supports the collapse of an essential structural motif within the dimer interface at slightly acidic pH.

Polyaxial locking plate fixation is a widely performed treatment for femoral shaft, periprosthetic, and peri-implant fractures in elderly patients. This study's purpose was to compare patient outcomes following the open technique (OT) and less invasive techniques (LIT). Data were gathered from 44 patients with 46 fractures treated with polyaxial locking plate between 2010-2015. Twenty fractures underwent the OT and 26 had a LIT. Long-term assessments for 83% of the fractures were done at a median of 23 months postoperatively. Bone healing rates were 82% in the OT and 100% in the LIT group (p=0.0688). The difference in the median duration of the surgery (OT 120 minutes, LIT 73 minutes) (p< 0.001) was the main statistically significant finding. Both surgical techniques resulted in similarly favourable outcomes. The LIT would be the preferred operating technique, especially when treating patients more susceptible to intra- and/or postoperative morbidity.

EU regulations call for the use of alternative methods to animal testing. During the last decade, an increasing number of alternative approaches have been formally adopted. In parallel, new 3Rs-relevant technologies and mechanistic approaches have increasingly contributed to hazard identification and risk assessment evolution. In this changing landscape, an EPAA meeting reviewed the challenges that different industry sectors face in the implementation of alternative methods following a science-driven approach. Although clear progress was acknowledged in animal testing reduction and refinement thanks to an integration of scientifically robust approaches, the following challenges were identified: i) further characterization of toxicity pathways; ii) development of assays covering current scientific gaps, iii) better characterization of links between in vitro readouts and outcome in the target species; iv) better definition of alternative method applicability domains, and v) appropriate implementation of the available approaches. For areas having regulatory adopted alternative methods (e.g., vaccine batch testing), harmonised acceptance across geographical regions was considered critical for broader application. Overall, the main constraints to the application of non-animal alternatives are the still existing gaps in scientific knowledge and technological limitations. The science-driven identification of most appropriate methods is key for furthering a multi-sectorial decrease in animal testing., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)

Peroxisome proliferator-activated receptor β/δ (PPARβ/δ) is a ligand-regulated nuclear receptor with essential functions in metabolism and inflammation. We have synthesized a new derivative [methyl 3-(N-(4-(hexylamino)-2-methoxyphenyl)sulfamoyl)thiophene-2-carboxylate (ST247) structurally related to the published PPARβ/δ inhibitory ligand methyl 3-(N-(2-methoxy-4-(phenylamino)phenyl)sulfamoyl)thiophene-2-carboxylate (GSK0660). ST247 has a higher affinity to PPARβ/δ than GSK0660, and at equimolar concentrations, it more efficiently 1) induces the interaction with corepressors both in vitro and in vivo, 2) inhibits the agonist-induced transcriptional activity of PPARβ/δ, and 3) down-regulates basal level expression of the peroxisome proliferator responsive element-driven PPARβ/δ target gene ANGPTL4. Methyl 3-(N-(4-(tert-butylamino)-2-methoxyphenyl)sulfamoyl)thiophene-2-carboxylate (PT-S58), another high-affinity derivative from our series, also efficiently inhibits agonist-induced transcriptional activation, but in contrast to ST247, it does not enhance the interaction of PPARβ/δ with corepressors. PT-S58 rather prevents corepressor recruitment triggered by the inverse agonist ST247. These findings classify ST247 as an inverse agonist, whereas PT-S58 is the first pure PPARβ/δ antagonist described to date. It is noteworthy that ST247 and PT-S58 are also effective on PPRE-independent functions of PPARβ/δ: in monocytic cells, both ligands modulate expression of the activation marker CCL2 in the opposite direction as an established PPARβ/δ agonist. The possibility to differentially modulate specific functions of PPARβ/δ makes these novel compounds invaluable tools to advance our understanding of PPARβ/δ biology.

Structure-based drug design is an integral part of industrial and academic drug discovery projects. Initial lead structures are, in general, optimized in terms of affinity using iterative cycles comprising synthesis, biological evaluation, computational methods, and structural analysis. X-ray crystallography commonly suggests the existence of a single well-defined state, termed binding mode, which is generally assumed to be consistent in a series of similar ligands and therefore used for the following optimization process. During the further development of symmetrically disubstituted 3,4-amino-pyrrolidines as human immunodeficiency virus type 1 protease inhibitors, we discovered that, by modification of the P1/P1' moieties of our lead structure, the activity of the inhibitors towards the active-site mutation Ile84Val was altered, however, not being explainable with the initial underlying structure-activity relationship. The cocrystallization of the most potent derivative in complex with the human immunodeficiency virus type 1 protease surprisingly led to two different crystal forms (P2(1)2(1)2(1) and P6(1)22). Structural analysis revealed two completely different binding modes; the interaction of the pyrrolidine nitrogen atom with the catalytic aspartates remains as the only similarity. The study presented clearly demonstrates that structural biology has to escort the entire lead optimization process not to fail by an initially observed binding orientation., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Purpose of the Study: While evaluating radiotherapy results in patients with primary and secondary optic nerve sheath meningiomas (ONSM) treated between 1993 and 2002, a large amount of data about early signs and symptoms has been collected which might be helpful for establishing an early diagnosis., Methods: We have reviewed the charts of the patients available at the Centre of Ophthalmology, collecting especially pretreatment data., Results: 112 patients, 4 with bilateral tumours, 83 % female were included. Mean age was 51.7 years. Visual acuity loss with relative afferent pupillary defect was the main symptom and sign in primary ONSM (38 patients). Median interval between first symptoms and diagnosis was 12 months. Optic discs were in approximately one half atrophic, the other half were swollen, and only rarely normal (3 cases only). Retinociliary shunt vessels were seen in 10 cases. Nerve fibre bundle defects were the major visual field finding (including constriction and central scotoma). Visual acuity was better than 0.5 (20 / 40) in 46 % and worse than 0.1 (20 / 200) in 30 %. In secondary ONSM, the interval to diagnosis was with a median of 6 months shorter than in primary ONSM. Approximately half of the optic discs were atrophic, only 6 % were swollen. Even here nerve fibre bundle defects were dominating, only 7 % had vertical hemianopic defect. Visual acuity was better than 0.5 (20 / 40) in 30 % and in worse than 0.1 (20 / 200) 22 %. 45 % had ocular motility disorders., Discussion: Vertical hemianopic defects were surprisingly rare. The high rate of nerve fibre bundle defects and the relatively high number of patients with good visual acuity might explain why this disorder is occasionally mistaken for glaucoma. A typical clinical appearance can be outlined: mainly mid-aged women, slowly progressing visual loss, frequently motility disorders, relative afferent pupillary defect, nerve fibre bundle defects and atrophic or--mainly in primary ONSM--swollen optic disc form the characteristic picture., ((c) Georg Thieme Verlag KG Stuttgart-New York.)

Objective: Multiple sclerosis (MS) is considered a chronic inflammatory and demyelinating disease of the central nervous system. Evidence that axonal and neuronal pathology contributes to the disease is accumulating, however, the distribution of neuronal injury as well as the underlying mechanisms have not yet been fully clarified. Here, we investigated the role of neuronal cell loss in MS and its animal model, experimental autoimmune encephalomyelitis (EAE)., Methods: We performed electrophysiological investigations in MS patients, including assessment of compound muscle action potentials and motor unit numbers and quantified neuronal cell loss in human MS samples and different EAE models by high-precision stereology., Results: Both electrophysiological and morphological analyses indicated a massive loss of lower motor neurons in MS patients. We regularly found dying spinal motor neurons surrounded by CD3+ (CD4+ as well as CD8+) T cells expressing tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). We observed a similar degree of damage and immune attack in different variants of EAE; the lower motor neurons were preserved in adoptive transfer EAE induced with TRAIL-deficient T lymphocytes., Interpretation: Our study indicates that damage to lower motor neurons and TRAIL-mediated inflammatory neurodegeneration in the spinal cord contribute to MS pathology.

HIV protease is a well-established drug target in antiviral chemotherapy. Immense research efforts have been made to discover effective inhibitors, thus making the enzyme one of the most studied and best characterized proteins. Although the protease exhibits high flexibility, all approved drugs target virtually the same protein conformation. The development of viral cross-resistance demands the generation of inhibitors with novel scaffolds and deviating modes of binding. Herein we report the design and the short, high-yielding stereoselective synthesis of a series of chiral, symmetric pyrrolidine-based inhibitors targeting the open-flap conformation of the protease. The obtained co-crystal structure with one derivative provides a valuable starting point for further inhibitor design.

The active site of several oxygen binding proteins can be mimicked with the ferric iron protoporphyrin IX derivative hemin, coordinating two imidazole molecules and embedded in sodium dodecyl sulfate (SDS) micelles; the detergent simulates the hydrophobic cavity of heme proteins. We studied the low-frequency vibrational modes of the porphyrin-iron-imidazole bonding in infrared absorbance spectra. Assignment of the metal-ligand vibrations to signals at 396, 387, and 378 cm(-1) was performed by isotope labeling of the imidazole ligand. These modes were also found to be temperature-dependent and to display a linear increase of signal intensity between 25 and 150 K and, with a different slope, between 150 and 300 K. The modes at 396 and 399 cm(-1) show for 25 K an up-shift about 4 cm(-1) and the signal at 378 cm(-1) a small downshift, indicating the involvement of antisymmetric stretching modes and, in the latter, of bending motions. Anharmonic couplings to doming modes are discussed, and the doming mode and hydrogen-bonding signature spectral range between 300 and 100 cm(-1) is presented.

Absorbance Fourier transform infrared (FTIR) spectra of model compounds for heme proteins such as protoporphyrin-IX, hemin, and hematin have been directly compared to the data of electrochemically induced FTIR difference spectra of small c-type proteins, i.e., microperoxidase-11, and cytochrome c. A band at 840-830 cm(-1) occurring in all studied samples dominated the spectra. The position of this vibrational mode depends on pH and the oxidation state, and could be assigned to the gamma(CH) mode of the porphyrin ring. Further features, such as the ring vibrations sensitive for the presence of iron and its oxidation state, are shown in the low-frequency infrared region between 750 and 650 cm(-1)., ((c) 2006 Wiley Periodicals, Inc.)