the mock-infected population, its activity was significantly in- creased by RV infection, by 141% (to 241% ⫾ 15%) in A549 cells, by 131% (to 231% ⫾ 31%) in MCF-7 cells, and by 99 (to 199% ⫾ 31%) in Vero cells. Hence, the extents of upregulation of complex II activity were very similar between the three cell lines. The only noticeable difference in complex II activity between RV-infected Vero and MCF-7 cells (72 hpi) versus A549 cells (24 hpi) lies in the time point of complex II peak activity. Complex IV activity, except at 48 hpi for MCF-7 cells, is significantly downregulated in all three cell lines. The highest level of downregulation of complex IV, by 46% (to 54% ⫾ 15%), was observed for A549 cells. The activity of complex III was moderately increased, by 60% (to 160% ⫾ 27%) in A549 cells, by 42% (to 142% ⫾ 23%) in MCF-7 cells, and by 44% (to 144% ⫾ 17%) in Vero cells. The same applies for complex I, with a slight increase, of 22% (increase to 122% ⫾ 26%), in Vero cells and an increase of 53% (increase to 153% ⫾ 26%) in A549 cells. MCF-7 cells, however, showed no increase in complex I activity. The next attempt was to determine the speci- ficity of these alterations. As a control virus, MV strain Edmon- ston was used, as all three cell lines applied in this study are sus- ceptible to MV. MV, like RV, replicates in the cytoplasm, but in contrast to RV, it is not known to be associated with mitochon- FIG 1 (A) Analysis of the replication kinetics of RV in Vero, MCF-7, and A549 cells and (B) activities of mitochondrial respiratory chain complexes I, II, III, and IV. (A) Mean RV genomic and subgenomic RNA copies were determined for 12, 24, 48, and 72 hpi by RT-qPCR. (B) Enzyme activities were determined by spectrophotometric assays and normalized to citrate synthase activity. Vero, MCF-7, and A549 cells were mock infected after 24 h of cultivation. Samples were collected at further incubation periods of 24, 48, and 72 h.
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We developed in this paper a novel and efficient algorithm for the computation of homology groups and ho- mology generators that works at the level of chain complexes, and hence allows handling a variety of geometric complexes. The main idea is based on organizing sequences of cell reductions into a structure of directed acyclic graphs, which makes it possible to derive global projection formulas and perform large collections of reductions at once. In this method, the boundary operators of the complex are not explicitly updated after each reduction step. Instead, this information is always preserved implicitly within the data structures and processed globally for each reduction graph allowing reducing considerably the computational time.
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has also been described in non-mitochondrial disorders linked to genes such as APTX coding for aprataxin and causing ataxia occulomotor-apraxia , BRAF coding for serine/threonine-protein kinase B-Raf and causing car- diofaciocutaneous syndrome , ACADVL causing very long-chain Acyl-CoA dehydrogenase deficiency or NPC causing Niemann-Pick-type C disease . Here, we report for the first time a secondary CoQ 10 defect asso-
Autism is classified as a psychiatric disorder which is characterised entirely by behaviours. Recent studies however, have presented evidence for systemic physiological abnormalities in ASD. The studies reviewed herein provide support to the idea of a link between mitochondrial dysfunction and the behavioural phenotype of autism. A number of different techniques have been employed to investigate a range of potential aspects of this link and many have reported decreased mitochondrial gene expression, decreased activity of electron transport chain complexes and abnormal levels of peripheral markers of mitochondrial function. However, due to the variation and inconsistency in techniques used, there are limitations to the studies reviewed here. These limitations make it difficult to determine whether mitochondrial dysfunction is a feature of all individuals with ASD, whether it is a cause or an effect of autism and whether such dysfunctions are localised to specific regions of the brain. Even in light of these however, there are consistent encouraging findings across the different studies and methodologies, indicating that mitochondrial disease may be commonly linked with autism and may be critical in the causal pathway that determines atypicalities in brain function and structure in autism. While further work is required, many studies have reported a stronger association between mitochondrial abnormalities and ASD in children, thereby providing indirect support for a causal role.
with findings in the abovementioned studies (Creutzberg et al 2003; Casaburi et al 2004), suggest that treatment with anabolic steroids alone might be useful for preventing respiratory failure only in patients receiving corticosteroids. In our study, we found that bodyweight was decreased after treatment with ND. This is in agreement with other studies, finding decreased bodyweight in male rats after treatment with ND (Bisschop et al 1997). Circulating endogenic androgens may play a role. Surpassing the physiological level of androgens in males has been reported to result in depression of the natural production of testosterone (Ryan 1981), downregulation of androgen- binding receptors (Rance and Max 1984), decrease in appetite (Kochakian and Endahl 1959), and a metabolic conversion to excess estradiol (Hickson and Kurowski 1986). The natural production of testosterone is indeed decreased in ND-treated hamsters in our study, which is shown by lower serum testosterone levels in the ND groups. In conclusion, this study shows that the activity of mitochondrial respiratory chain complexes in the diaphragm in both normal and emphysematous hamsters was equal, and that treatment with ND did not change this activity. In emphysematous hamsters, administration of ND decreased the activity of SCC compared with ND treatment in normal hamsters. Furthermore, we have shown that bodyweight of hamsters treated with ND was decreased after treatment compared with initial values, and that treatment with ND resulted in significantly lower serum testosterone levels in both normal and emphysematous hamsters. Taking all results together, our data do not support the use of anabolic steroids in preventing respiratory failure caused by fatigue of the diaphragm.
In this article we proposed derivation of the wave function of a quantum sys- tem from the functional representation of the state of this system. There is considered representation of creation and annihilation operators by boun- dary and co-boundary operators of chain and co-chain complexes on the physical space.
The condansation reactions of 2,6-diaminopyridine with diacetyl in the presence of Ln(III) ions produces open chain complexes as a result of Schiff base condensations. These complexes contain free ketonic groups. The condansation reactions of these complexes with a diamine have been studied in presence of glacial acetic acid which cause ring closer and formation of macrocyclic complexes. These complexes have been characterized on the basis of elemental analyses, conductance, magnetic moment and spectral data. On the basis of aforesaid studies probable structures of the complexes have been proposed.
We report the case of a 10-year-old Spanish girl with mutations in NADK2 . Prenatal central nervous system abnormalities showed ventriculomegaly, colpocephaly, and hypoplasia of the corpus callosum. At birth, axial hypotonia, uncoordinated movements, microcephaly, and generalized cerebellar atrophy were detected. Metabolic investigations revealed high lysine, lactate, and pipecolic acid levels in blood and cerebrospinal fluid. Pyruvate carboxylase and pyruvate dehydrogenase activity in fibroblasts were normal. Beginning at birth she received biotin, thiamine, and carnitine supplementation. A lysine-restricted diet was started when she was 1 month old. Because pipecolic acid was high, pyridoxine was added to treatment. At 3 years old, astatic myoclonic epilepsy appeared, with no response to levetiracetam. We switched pyridoxine to pyridoxal phosphate, with electroclinical improvement. Because the activity of mitochondrial respiratory chain complexes III and IV was slightly low in muscle, other cofactors such as ubidecarenone, idebenone, vitamin E, and creatine were added to the treatment. At 8 years old, plasma acylcarnitine testing was performed, and high levels of 2-trans, 4-cis-decadienoylcarnitine were found. Whole exome sequencing identified a homozygous splice site mutation in NADK2 (c.956+6T>C; p.Trp319Cysfs*21). This substitution generates exon skipping, leading to a truncated protein. In fact, NADK2 messenger RNA and the corresponding protein were almost absent. Now, at 10 years of age she presents with ataxia and incoordination. She has oromotor dysphasia but is able to understand fluid language and is a very friendly girl. We hypothesize that the patient’s clinical improvement could be due to her lysine-restricted diet together with cofactors and pyridoxal phosphate administration.
pairing between global gauge field configurations and observables, which allows us to show that our class of observables separates all possible gauge field configurations. Two appendices at the end of the paper summarize some of the more technical details which are used in the main text. In Appendix A we review the (dual) Dold-Kan correspondence, which is an important technical tool for our constructions. In Appendix B we summarize the explicit techniques to compute homotopy (co)limits for chain complexes of Abelian groups given in [Dug, Section 16.8] and [Rod14].
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Although there is a wealth of knowledge available on the structure of the individual electron transport chain complexes, their supramolecular organization into ‘ respirasomes ’ is relatively an under-studied area. This is mainly because these complexes are functionally active even when isolated as individual complexes and the detergent used to solubilize them out of the inner membrane partially destroys the supramolecular assembly. Previously, two models have been proposed for the organiza- tion of the respiratory chain. The random collision model or the ‘ﬂ uid state ’ model, proposed by Hackenbrock  was accepted by many investigators in the ﬁ eld. According to the model complex I – IV moves freely by lateral diffusion in the inner mitochondrial membrane and electron transfer is based on random collisions of the involved components. Ubiquinone and cytochrome c have a diffusion rate that is faster than the bulkier complexes. This model was backed by studies on mobility of the complexes and subsequently supported by kinetic analysis of steady state respiration and saturation kinetics of electron transfer. In contrast, several other lines of evidence support the ‘ solid state ’ model which promotes the idea of preferential associations and spe- ci ﬁ c aggregation of the complexes: a) a mild puri ﬁ cation and separa- tion protocol (BN-PAGE) and immunoprecipitation results in co- puri ﬁ cation of more than one complex [70,71]; b) ﬂ ux control experiments favours the supramolecular organization of the com- plexes rather than their individual occurrence ; c) organization into supercomplexes leads to improved stabilization of individual complexes ; d) mutations leading to a loss of complex III prevents supercomplex formation and leads to a secondary loss of complex I ; e) the complexes are present in vivo at de ﬁ ned stoichiometries
(11) (a) González-Prieto, R.; Fleury, B.; Schramm, F.; Zoppellaro, G.; Chandrasekar, R.; Fuhr, O.; Lebedkin, S.; Kappes, M.; Ruben, M. Tuning the Spin-Transition Properties of Pyrene- Decorated 2,6-Bispyrazolylpyridine Based Fe(II) Complexes. Dalton Trans. 2011, 40, 7564– 7570. (b) Santoro, A.; Kershaw Cook, L. J.; Kulmaczewski, R.; Barrett, S. A.; Cespedes, O.; Halcrow, M. A. Iron(II) Complexes of Tridentate Indazolylpyridine Ligands: Enhanced Spin- Crossover Hysteresis, and Ligand-Based Fluorescence. Inorg. Chem. 2015, 54, 682–693.
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This system is essentially composed of only monomer/polymer. This technique is most commonly used for polymerisations which proceed through functional groups in a stepwise manner and then the method merely involves heating the straight monomer or monomer mixture (sometimes with addition of a small amount of a catalyst to increase the reaction rate). The system is maintained in a fluid state by keeping the temperature sufficiently high. In this type of reaction there is a progressive increase in molecular weight and the high viscosity of the resultant polymer melt can lead to handling difficulties. When the technique o f bulk polymerisation is applied to polymerisations, which involve chain reactions, the monomer is heated with a small amount o f appropriate initiator. Again there is a substantial rise in viscosity as the concentration o f polymer (which is soluble in the monomer) increases and this can lead to difficulty in dissipating the high exothermic heat of reaction which is usually a feature of such polymerisations. As there is a possibility of localised overheating leading to degradation and discoloration of the polymer, bulk polymerisation is seldom practiced with large batches. Bulk polymerisation results in a relatively pure polymer.
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Long chain free fatty acids interfere with the inhibitory action of phenethylbiguanide and related compounds on mitochondrial respiration in vitro. This interference depends on binding of fatty acids to mitochondria and diminishes with decreasing chain length. Reversal of guanidine-derivative inhibition by fatty acids differs from that caused by dinitrophenol in that the effect of fatty acid is achieved without alteration in coupling or respiratory control. The binding of phenethylbiguanide to mitochondria is inhibited by both fatty acid and dinitrophenol. Serum albumin potentiates the inhibitory potency of guanidine derivatives, probably by removing endogenous mitochondrial free fatty acids.
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Nevertheless, wherever p o s s ib le , ta k in g due care, these methods may be employed. As alre a d y in d ica te d (Section 1 .4 .2 ), previous v ib r a tio n a l assignments fo r (PR^)HgX2 complexes, which are g e n e ra lly in fe rre d to have d im e ric C2^ s tru c tu re s , are f a r from r e lia b le due to lack o f consistency and lack o f a fir m c r y s ta llo g ra p h ic b a sis. The c r y s ta Ilo g ra p h ic data presented in Section 2.2 have shown th a t o n ly in the case o f (PPh^)HgX2 (X=CI, Br o r I) has the proposal fo r a dim e ric s tru c tu re based on th e v ib r a tio n a l spectra been confirm ed. The assignments made to j u s t i f y these proposals however,
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Synthetic metallopolymers have acquired ample attention recently due to their potential applications as precursors to functional soft materials. Organometallic polymers combine the best of both organic and inorganic polymers. Polyferrocenes comprise the major portion of organometallic polymers. Therefore, quest for new monomeric precursors to organometallic polymers has expediated. One efficient method for obtaining main-chain metallopolymers is ring opening polymerization (ROP) of strained cyclic metallacyclophanes (MCPs). Organometallic polymers containing cyclopentadienyl-cobalt-cyclobutadiene (CpCoCb) have been targeted since the early 1990’s due to their isoelectronic nature (cf. ferrocene) with three major groups working in this area. The early CpCoCb containing polymers were prepared by alkyne dimerization of a bis-alkyne at the Co(I) centre, which did not provide good control over the molecular weights of the polymers generated.
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distorted octahedral geometry, with equatorial positions occupied by three N atoms from the tridentate ligand (average Cu—N = 2.004 A ˚ ) and one O atom from a bidentate sulfate anion [Cu—O = 1.963 (2) A ˚ ]. The axial positions are occupied by one O atom from a coordinating water molecule [Cu—O = 2.230 (3) A ˚ ] and one weakly bonded O atom [Cu—O = 2.750 (2) A ˚ ] from the bidentate sulfate ion. The complex molecules are connected through O—H O hydrogen bonds between the coordinating water molecules and sulfate ions from neighboring complexes, forming a double chain parallel to the c axis. The chains are stabilized through additional hydrogen bonds by one of the non-coordinating water molecules bridging between neighboring strands of the double chains. The remaining three water molecules fill the interstitial space between the double chains and are involved in an intricate hydrogen-bonding network that consolidates the structure.
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Transition metal complexes of chiral ligands attract wide- spread attention from the viewpoint of their structures, molecular recognition, and molecular processes (Whitesides et al., 1995; Philp & Stoddart, 1996). As model systems for pyridoxal-potentiated enzymes, N-salicylidene-l-amino acids are being applied to synthesize a series of transition metal± chiral ligand complexes. Several N-salicylidene-l-amino acid± transition metal complexes have been synthesized and studied, using amino acids with different side-chain groups, such as valine (Rajak et al., 1999), glutamic acid (Korhonen et al., 1984), phenylalanine (Marinovich et al., 1999), alanine (Warda, 1999) and methionine (Palacios et al., 1989).
gene products and metabolites. In our case, exome sequencing, where the raw data was filtered for genes pre- viously described in mitochondrial disease, revealed one suspected pathogenic mutation in a mitochondrial gene; a deletion of one nucleotide (c.399delA) causing a frame- shift (p.Glu133AspfsTer25) in BCS1L. Since this mutation is predicted to lead to severe protein truncation it was deemed very probably damaging. As the respiratory chain investigations in the patient’ s muscle had revealed a complex III defect and due to the severe phenotype, the finding of a pathogenic mutation in BCS1L made it a strong candidate. We therefore analyzed the whole gene using qPCR of all coding exons, but no CNVs were detected. Hereafter, SNVs that were previously deemed non-pathogenic were analyzed in silico and the splice prediction tools SPIDEX and NetGene2 suggested the synonymous nucleotide exchange c.306A > T (p.Gly102=) could introduce an intra-exonic splice site whose use would produce a frameshifted transcript and thus be potentially pathogenic. According to in silico prediction the probability of use of the correct and aberrant cryptic splice sites was essentially the same (0.69 and 0.67, re- spectively), predicting about 50% of normally spliced
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Earlier reports reveal that the L protein is not only a com- ponent of GDC but also a component of the E3 subunit of the ␣ -ketoacid dehydrogenase complexes, comprised of pyruvate dehydrogenase, ␣ -ketoglutarate dehydrogenase, and the branched chain ␣ -ketoacid dehydrogenase. Our results indi- cate that T. vaginalis possessess a single L protein encoded by an independent gene. Furthermore, the in vitro interaction of the recombinant T. vaginalis glycine cleavage H and L proteins indicated the possibility of the presence of the GDC multien- zyme complex in the hydrogenosome. To date, members of ␣ -ketoacid dehydrogenase complexes have not been identified in T. vaginalis; however, the possibility of the L protein playing an important role as a component of the E3 subunit of the ␣ -ketoacid dehydrogenase complexes in the hydrogenosomes cannot be excluded. In the pea (P. sativum), the mitochondrial L protein was found to be encoded by a single gene and shared between ␣ -ketoacid dehydrogenase complexes and GDC (10). In Arabidopsis thaliana, two genes encoding mitochondrial di- hydrolipoamide dehydrogenase (mtLPD1 and mtLPD2) have been reported. mtLPD seems to provide L protein for GDC, whereas the mtLPD2 gene product mainly interacts with ␣ - ketoacid dehydrogenases (26, 27). However, from the high sequence identity between mtLPD1 and mtLPD2 (92%), the authors concluded that both L proteins can work in either multienzyme complex. Plasmodium falciparum has two dihy- drolipoamide dehydrogenase isoforms encoded by two dif- ferent genes. It has been demonstrated that both genes are functional, with one of them being part of a pyruvate dehy- drogenase complex that is present exclusively in the apico- plast of Plasmodium and the other probably involved in both the ␣ -ketoacid dehydrogenase complex and the GDC in the mitochondria (29, 37).
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Apparently, both studied complexes have a different organization in the solid state, as it is evident from their diffractograms (Figure S3, SI). If for 1 their molecular structure was determined form SCXRD date, then a lack of the single crystal structure for 2 does not permit us to explain definitely why the magnetic behavior of this compound is so different compared with 1. However, our conclusion that 2 is a 1D coordination chain is based on a totality of the experimental facts. At first, the compound 2, having a ratio [Mn(SB + )] 3+ / [W(CN) 8 ] 3- = 1:1, is insoluble in any solvent and can
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