The reaction of cytochrome c with [Fe(EDTA)(H2O)]−

AbstractThe interaction of horse ferricytochrome c with the reagents [Fe(EDTA)(H2O)]− and [Cr(CN)6]3− were studied at pH 7 and 25°C by 1H-NMR spectroscopy. Two binding regions near to the heme crevice of cytochrome c were identified. Both regions bound both reagents but they exhibited different selectivities.The relevance of this finding to the electron-transfer function of cytochrome c is discussed

Trace-level determination of two neonicotinoid insecticide residues in honey bee royal jelly using ultra-sound assisted salting-out liquid liquid extraction followed by ultra-high-performance liquid chromatography-tandem mass spectrometry

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Structural role of the tyrosine residues of cytochrome c

The tertiary structures of horse, tuna, Neurospora crassa, horse [Hse65,Leu67]- and horse [Hse65,Leu74]-cytochromes c were studied with high-resolution 1H n.m.r. spectroscopy. The amino acid sequences of these proteins differ at position 46, which is occupied by phenylalanine in the horse proteins but by tyrosine in the remaining two, and at positions 67, 74 and 97, which are all occupied by tyrosine residues in horse and tuna cytochrome c but in the other proteins are substituted by phenylalanine or leucine, though there is only one such substitution per protein. The various aromatic-amino-acid substitutions do not seriously affect the protein structure

Novel synthesis of O(6)-alkylguanine containing oligodeoxyribonucleotides as substrates for the human DNA repair protein, O(6)-methylguanine DNA methyltransferase (MGMT)

The human DNA repair protein O(6)-methylguanine DNA methyltransferase (MGMT) dealkylates mutagenic O(6)-alkylguanine lesions within DNA in an irreversible reaction which results in inactivation of the protein. MGMT also provides resistance of tumours to alkylating agents used in cancer chemotherapy and its inactivation is therefore of particular clinical importance. We describe a post-DNA synthesis strategy which exploits the novel, modified base 2-amino-6-methylsulfonylpurine and allows access for the first time to a wide variety of oligodeoxyribonucleotides (ODNs) containing O(6)-alkylguanines. One such ODN containing O(6)-(4-bromothenyl)guanine is the most potent inactivator described to date with an IC(50) of 0.1 nM

Age-Dependent Changes in the Cerebrospinal Fluid Proteome by Slow Off-Rate Modified Aptamer Array

An important precondition for the successful development of diagnostic assays of cerebrospinal fluid (CSF) biomarkers of age-related neurodegenerative diseases is an understanding of the dynamic nature of the CSF proteome during the normal aging process. In this study, a novel proteomic technology was used to quantify hundreds of proteins simultaneously in the CSF from 90 cognitively normal adults 21 to 85 years of age. SomaLogic's highly multiplexed proteomic platform can measure more than 800 proteins simultaneously from small volumes of biological fluids using novel slow off-rate modified aptamer (SOMAmer) protein affinity reagents with sensitivity, specificity, and dynamic ranges that meet or exceed those of enzyme-linked immunosorbent assays. In the first application of this technology to CSF, we detected 248 proteins that possessed signals greater than twofold over background. Several novel correlations between detected protein concentrations and age were discovered that indicate that both inflammation and response to injury in the central nervous system may increase with age. Applying this powerful proteomic approach to CSF provides potential new insight into the aging of the human central nervous system that may have utility in discovering new disease-related changes in the CSF proteome

Severity of Depression Predicts Remission Rates Using Transcranial Magnetic Stimulation

Background: Multiple factors likely impact response and remission rates in the treatment of depression with repetitive transcranial magnetic stimulation (rTMS). Notably the role of symptom severity in outcomes with rTMS is poorly understood.Objective/Hypothesis: This study investigated the predictors of achieving remission in patients suffering from depression who receive ≥3 rTMS treatments per week. Methods: Available data on 41 patients treated at Walter Reed National Military Medical Center from 2009 to 2014 were included for analysis. Patients received a range of pulse sequences from 3,000 to 5,000 with left sided or bilateral coil placement. Primary outcome measures were total score on the Patient Health Questionnaire (PHQ-9) or the Quick Inventory of Depressive Symptomatology—Self Rated (QIDS-SR). Remission was defined as a total score less than five, and response was defined as a 50% decrease in the total score on both outcome metrics. Outcomes in patients diagnosed as suffering from mild or moderate depression were compared to those suffering from severe depression. Results: Of the 41 patients receiving treatment, 16 reached remission by the end of treatment. Remission rate was associated with the initial severity of depression, with patients with mild or moderate depression reaching remission at a significantly higher rate than those with severe depression. Total number of rTMS sessions or length of treatment were not predictors of remission. Conclusion: Patients with a baseline level of depression characterized as mild or moderate had significantly better outcomes following rTMS compared to patients with severe depression

Buffered fitness components: Antagonism between malnutrition and an insecticide in bumble bees.

Global insect biodiversity declines due to reduced fitness are linked to interactions between environmental stressors. In social insects, inclusive fitness depends on successful mating of reproductives, i.e. males and queens, and efficient collaborative brood care by workers. Therefore, interactive effects between malnutrition and environmental pollution on sperm and feeding glands (hypopharyngeal glands (HPGs)) would provide mechanisms for population declines, unless buffered against due to their fitness relevance. However, while negative effects for bumble bee colony fitness are known, the effects of malnutrition and insecticide exposure singly and in combination on individuals are poorly understood. Here we show, in a fully-crossed laboratory experiment, that malnutrition and insecticide exposure result in neutral or antagonistic interactions for spermatozoa and HPGs of bumble bees, Bombus terrestris, suggesting strong selection to buffer key colony fitness components. No significant effects were observed for mortality and consumption, but significant negative effects were revealed for spermatozoa traits and HPGs. The combined effects on these parameters were not higher than the individual stressor effects, which indicates an antagonistic interaction between both. Despite the clear potential for additive effects, due to the individual stressors impairing muscle quality and neurological control, simultaneous malnutrition and insecticide exposure surprisingly did not reveal an increased impact compared to individual stressors, probably due to key fitness traits being resilient. Our data support that stressor interactions require empirical tests on a case-by-case basis and need to be regarded in context to understand underlying mechanisms and so adequately mitigate the ongoing decline of the entomofauna

Porous metal–organic frameworks for enhanced performance silicon anodes in lithium-ion batteries

Maintaining the physical integrity of electrode microstructures in Li-ion batteries is critical to significantly extend their cycle life. This is especially important for high-capacity anode materials such as silicon, whose operational volume expansion exerts huge internal stress within the anode, resulting in electrode destruction and capacity fade. In this study, we demonstrate that by incorporating metal–organic frameworks (MOFs) with carboxylate organic linkers into Si-based anodes, a stable and flexible pore network is generated to maximize and maintain Li-ion flux throughout the electrode’s architecture. We show that the zirconium carboxylate MOF UiO-67 is a versatile comaterial to boost performance and mitigate the rate of anode degradation that presently limits the lifetime of Si anodes. The cage-like pores in UiO-67 and flexural properties of the 4,4′-biphenyldicarboxylate organic linker are proposed to create robust “ionophores” in the anode film to enhance longer term durability and performance

Diet and bone mineral density study in postmenopausal women from the TwinsUK registry shows a negative association with a traditional English dietary pattern and a positive association with wine

Background: The effect of diet on bone mineral density (BMD) remains controversial, mainly because of difficulties in isolating dietary factors from the confounding influences of age, lifestyle, and genetic factors. Objective: The aim of this study was to use a novel method to examine the relation between BMD and diet. Design: A co-twin control study design with linear regression modeling was used to test for associations between BMD and habitual intakes of calcium, vitamin D, protein, and alcohol plus 5 previously identified dietary patterns in postmenopausal women from the TwinsUK registry. This approach exploited the unique matching of twins to provide an estimate of an association that was not confounded by age, genetic background, or shared lifestyle. Results: In >2000 postmenopausal women (BMD data on 1019, 1218, and 1232 twin pairs at the hip neck, hip, and spine, respectively), we observed a positive association between alcohol intake (from wine but not from beer or spirits) and spine BMD (P = 0.01) and a negative association with a traditional 20th-century English diet at the hip neck (P = 0.01). Both associations remained borderline significant after adjustment for mean twin-pair intakes (P = 0.04 and P = 0.055, respectively). Other dietary patterns and intakes of calcium, vitamin D, and protein were unrelated to BMD. Conclusion: Our results showed that diet has an independent but subtle effect on BMD; wine intake was positively associated with spine BMD, whereas a traditional (20th-century) English diet had a negative association with hip BMD