Cytochrome c maturation: a complex pathway for a simple task?

Post-translational maturation of c-type cytochromes involves covalent attachment of haem to the apocytochrome polypeptide by two thioether bonds. In bacteria, haem attachment occurs in the periplasm, after the separate translocation of haem and the polypeptide across the cytoplasmic membrane. In Escherichia coli, delivery and attachment of the cofactor requires eight or nine specific proteins, which are believed to be organized in a membrane protein complex. After transport across the membrane, haem is attached covalently to the haem chaperone CcmE in an unusual way at a single histidine residue. However, haem binding to CcmE is transient and is succeeded by a further transfer to apocytochrome c. Both haem binding to and release from CcmE involve integral membrane proteins, CcmC and CcmF respectively, which carry a conserved tryptophan-rich motif in a periplasmic domain. Apocytochrome c polypeptides are synthesized as precursors and reach the periplasm by sec-dependent translocation. There they are prepared for haem binding by reduction of the cysteine residues in the motif Cys-Xaa-Xaa-Cys-His, which is characteristic of such proteins. This reduction is achieved in a thio-reduction pathway, whereby electrons are passed from cytoplasmic thioredoxin to the transmembrane protein DsbD, across the membrane, and on to the specific reductases CcmG/CcmH. The merging of the haem delivery and the thio-reduction pathways leads to the stereospecific insertion of haem into various type c cytochromes.     

99mTc(Cu)—mannitol complex: a new agent for dynamic renal function studies

Mannitol has been labelled with ^99mTc by using cuprous chloride as a reducing agent. Blood and kidney clearance of ^99mTc(Cu)-mannitol was slightly faster than that of ^99mTc(Sn)-DTPA in rat and maximum radioactivity ratio of kidneys to blood was 84.6 at 5 min. A comparative study of ^99mTc(Cu)-mannitol, ^99mTc(Sn)-DTPA was made in rabbits by taking serial images of kidneys and bladder with a γ camera. Results show superiority of ^99mTc(Cu)-mannitol over other agents for dynamic renal function studies.     

The KEOPS complex: a rosetta stone for telomere regulation?

The detailed mechanisms underlying telomere capping and its relationship to telomerase activity are still unclear, although many proteins have been implicated in either or both processes. In this issue of Cell, the surprising identification of a new complex, called KEOPS, which promotes both telomere uncapping and elongation is presented.     

The (α-1,6) glycosidic bond of isomaltose: a tricky system for theoretical conformational studies

Stable conformations of β-isomaltose (α-d-glucopyranosyl-(1→6)-β-d-glucose) in gas-phase and aqueous solution are investigated in this study using quantum mechanical calculations. Conformational maps are calculated at HF/6-31G(d,p) level and lower energy structures are sampled in the most stable regions. Entropic and thermal corrections are considered and the Boltzmann population is obtained for conformers that are representative of the 18 most stable regions found on the potential energy surface. B3LYP/6-31+G(d,p) and B3LYP/6-311+G(2d,2p) calculations are used in conformational samplings. Solvation effects are considered through the polarizable continuum model approach. Hydroxymethyl group orientations are investigated for the most stable conformers. The influence of electronic correlation and solvation on the glycosidic linkage preference (TG, GT, and GG) and hydroxymethyl group orientation (tg, gt, and gg) are discussed. Heteronuclear spin coupling constants (³J_C,H) along the glycosidic linkage are calculated and comparison with other theoretical results and experiments is used to validate the obtained structures.     

The Q-cycle reviewed: How well does a monomeric mechanism of the bc(1) complex account for the function of a dimeric complex?

Recent progress in understanding the Q-cycle mechanism of the bc(1) complex is reviewed. The data strongly support a mechanism in which the Q(o)-site operates through a reaction in which the first electron transfer from ubiquinol to the oxidized iron-sulfur protein is the rate-determining step for the overall process. The reaction involves a proton-coupled electron transfer down a hydrogen bond between the ubiquinol and a histidine ligand of the [2Fe-2S] cluster, in which the unfavorable protonic configuration contributes a substantial part of the activation barrier. The reaction is endergonic, and the products are an unstable ubisemiquinone at the Q(o)-site, and the reduced iron-sulfur protein, the extrinsic mobile domain of which is now free to dissociate and move away from the site to deliver an electron to cyt c(1) and liberate the H(+). When oxidation of the semiquinone is prevented, it participates in bypass reactions, including superoxide generation if O(2) is available. When the b-heme chain is available as an acceptor, the semiquinone is oxidized in a process in which the proton is passed to the glutamate of the conserved -PEWY- sequence, and the semiquinone anion passes its electron to heme b(L) to form the product ubiquinone. The rate is rapid compared to the limiting reaction, and would require movement of the semiquinone closer to heme b(L) to enhance the rate constant. The acceptor reactions at the Q(i)-site are still controversial, but likely involve a "two-electron gate" in which a stable semiquinone stores an electron. Possible mechanisms to explain the cyt b(150) phenomenon are discussed, and the information from pulsed-EPR studies about the structure of the intermediate state is reviewed. The mechanism discussed is applicable to a monomeric bc(1) complex. We discuss evidence in the literature that has been interpreted as shown that the dimeric structure participates in a more complicated mechanism involving electron transfer across the dimer interface. We show from myxothiazol titrations and mutational analysis of Tyr-199, which is at the interface between monomers, that no such inter-monomer electron transfer is detected at the level of the b(L) hemes. We show from analysis of strains with mutations at Asn-221 that there are coulombic interactions between the b-hemes in a monomer. The data can also be interpreted as showing similar coulombic interaction across the dimer interface, and we discuss mechanistic implications.     

RAPD technique for taxonomic studies of Pellia epiphylla‐complex (Hepaticae, Metzgeriales)

The random amplified polymorphic DNA (RAPD) technique was used to study the genomic relationships of three liverworts from the genus Pellia: P. epiphylla, P. borealis and P. neesiana. Altogether 150 characters (150 DNA fragments obtained using PCR) were scored. These characters were used to create a matrix of pairwise distances between all the pairs of taxa. Both distance (UPGMA, Fitch–Margoliash and Neighbor–Joining) and binary character‐state (Wagner and Camin‐Sokal parsimony and compatibility) methods were applied for trees' construction. Our results strongly support distinction of the recently discovered sibling species of P. epiphylla – species N and P. epiphylla – species S, which have an allopatric distribution in Poland (N – North, S – South Poland). Moreover, our data also supports the hypothesis of a hybrid origin (alloploid) of the polyploid P. borealis from P.epiphylla−N×P.epiphylla−S. P. neesiana was excluded as a donor of either of the genomes of P. borealis. This revised version was published online in July 2006 with corrections to the Cover Date.     

Multispectroscopic DNA-binding studies of a terbium(III) complex containing 2,2′-bipyridine ligand

Agarose gel electrophoresis, absorption, fluorescence, viscosity, and circular dichroism (CD) have been used in exploring the interaction of terbium(III) complex, [Tb(bpy)₂Cl₃(OH₂)] where bipy is 2,2′-bipyridine, with Fish salmon DNA. Agarose gel electrophoresis assay, along with absorption and fluorescence studies, reveal interaction between the corresponding complex and FS-DNA. Also, the binding constants (K_b) and the Stern–Volmer quenching constants (K_sv) of Tb(III) complex with FS-DNA were determined. The calculated thermodynamic parameters suggested that the binding of mentioned complex to FS-DNA was driven mainly by hydrophobic interactions. A comparative study of this complex with respect to the effect of iodide-induced quenching, ionic strength effect, and ethidium bromide exclusion assay reflects binding of explicit to the FS-DNA primarily in a groove fashion. CD and viscosity data also support the groove binding mode. Furthermore, Tb(III) complex have been simultaneously screened for their antibacterial and antifungal activities.     

Age and fertility: can women wait until their early thirties to try for a first birth?

Postponing the start of childbearing raises the question of fertility postponed versus fertility foregone. One of the limitations of previous studies of 'How late can you wait?' is that any observed decline in the probability of conception with age could be due to a decline in fecundability with age or due to a decline in coital frequency with age or due to both factors. Using data from a multinational longitudinal study conducted to determine the daily probability of conception among healthy subjects, a discrete-time event history model with long-term survivors (sterile population) is used to study the relationship between age and fecundability for childless women, while controlling for the pattern of intercourse within a menstrual cycle. The findings suggest that women can wait until their early thirties to try for a first birth, providing that they are not already sterile, as the magnitude of the decline in fecundability is very modest and of little practical importance.     

The first collective protest of black African migrants in postcolonial France (1960–1975): a struggle for housing and rights

The study of the political activism of black African diasporas in France after the independence era remains a neglected area of research. This paper fills a gap in the literature by exploring the first notable postcolonial protests in the country by sub-Saharan migrants. The struggle of black African workers against their dire housing conditions opened up a ‘cycle of collective action’ that led to the better-known Sonacotra migrant hostels (foyers) rent strike of 1975–1980. Even before the Sonacotra strike, however, black African workers had been able to call on the authorities from both their origin and residence countries and to mobilize transnational networks in order to support their demands. This article provides the first comprehensive historical study of this decisive period. It highlights how ethnic ties are intertwined with political and social ones, focusing on the solidarities that these migrants developed in political networks and in their neighbourhoods.     

The Q-cycle reviewed: How well does a monomeric mechanism of the bc1 complex account for the function of a dimeric complex?

Recent progress in understanding the Q-cycle mechanism of the bc₁ complex is reviewed. The data strongly support a mechanism in which the Q_o-site operates through a reaction in which the first electron transfer from ubiquinol to the oxidized iron–sulfur protein is the rate-determining step for the overall process. The reaction involves a proton-coupled electron transfer down a hydrogen bond between the ubiquinol and a histidine ligand of the [2Fe–2S] cluster, in which the unfavorable protonic configuration contributes a substantial part of the activation barrier. The reaction is endergonic, and the products are an unstable ubisemiquinone at the Q_o-site, and the reduced iron–sulfur protein, the extrinsic mobile domain of which is now free to dissociate and move away from the site to deliver an electron to cyt c₁ and liberate the H⁺. When oxidation of the semiquinone is prevented, it participates in bypass reactions, including superoxide generation if O₂ is available. When the b-heme chain is available as an acceptor, the semiquinone is oxidized in a process in which the proton is passed to the glutamate of the conserved -PEWY- sequence, and the semiquinone anion passes its electron to heme b_L to form the product ubiquinone. The rate is rapid compared to the limiting reaction, and would require movement of the semiquinone closer to heme b_L to enhance the rate constant. The acceptor reactions at the Q_i-site are still controversial, but likely involve a “two-electron gate” in which a stable semiquinone stores an electron. Possible mechanisms to explain the cyt b₁₅₀ phenomenon are discussed, and the information from pulsed-EPR studies about the structure of the intermediate state is reviewed.The mechanism discussed is applicable to a monomeric bc₁ complex. We discuss evidence in the literature that has been interpreted as shown that the dimeric structure participates in a more complicated mechanism involving electron transfer across the dimer interface. We show from myxothiazol titrations and mutational analysis of Tyr-199, which is at the interface between monomers, that no such inter-monomer electron transfer is detected at the level of the b_L hemes. We show from analysis of strains with mutations at Asn-221 that there are coulombic interactions between the b-hemes in a monomer. The data can also be interpreted as showing similar coulombic interaction across the dimer interface, and we discuss mechanistic implications.     

The virulence–transmission trade-off in vector-borne plant viruses: a review of (non-)existing studies

The adaptive hypothesis invoked to explain why parasites harm their hosts is known as the trade-off hypothesis, which states that increased parasite transmission comes at the cost of shorter infection duration. This correlation arises because both transmission and disease-induced mortality (i.e. virulence) are increasing functions of parasite within-host density. There is, however, a glaring lack of empirical data to support this hypothesis. Here, we review empirical investigations reporting to what extent within-host viral accumulation determines the transmission rate and the virulence of vector-borne plant viruses. Studies suggest that the correlation between within-plant viral accumulation and transmission rate of natural isolates is positive. Unfortunately, results on the correlation between viral accumulation and virulence are very scarce. We found only very few appropriate studies testing such a correlation, themselves limited by the fact that they use symptoms as a proxy for virulence and are based on very few viral genotypes. Overall, the available evidence does not allow us to confirm or refute the existence of a transmission–virulence trade-off for vector-borne plant viruses. We discuss the type of data that should be collected and how theoretical models can help us refine testable predictions of virulence evolution.     

Pisodonophis boro (ophichthidae: anguilliformes): Specialization for head‐first and tail‐first burrowing?

The rice paddy eel, Pisodonophis boro (P. boro), is of special interest because of its peculiar burrowing habits. P. boro penetrates the substrate tail-first, a technique common for ophichthids, but it is able to burrow head-first as well. P. boro exhibits three feeding modes: inertial feeding, grasping, and spinning. Rotational feeding is a highly specialized feeding mode, adopted by several elongate, aquatic vertebrates and it is likely that some morphological modifications are related to this feeding mode. The detailed morphology of the head and tail of P. boro is examined with the goal to apportion the anatomical specializations among head-first burrowing, tail-first burrowing, and rotational feeding. The reduced eyes, covered with thick corneas may be beneficial for protection during head-first burrowing, but at the same time decreased visual acuity may have an impact on other sensory systems (e.g. cephalic lateral line system). The elongated and pointed shape of the skull is beneficial for substrate penetration. The cranial bones and their joints, which are fortified, are advantageous for resisting high mechanical loads during head-first burrowing. The aponeurotic connection between epaxial and jaw muscles is considered beneficial for transferring these forces from the body to the head during rotational feeding. Hypertrophied jaw muscles facilitate a powerful bite, which is required to hold prey during spinning movements and variability in the fiber angles of subdivisions of jaw muscles may be beneficial for preventing the lower jaw from being dislodged or opened. Furthermore, firm upper (premaxillo-ethmovomerine complex) and lower jaws (with robust coronoid processes) and high neurocranial rigidity are advantageous for a solid grip to hold prey during rotational feeding. The pointed shape of the tail and the consolidated caudal skeleton are beneficial for their tail-first burrowing habits. It is quite likely that the reduction of the caudal musculature is related to the tail-first burrowing behavior because the subtle movements of the caudal fin rays are no longer required.     

Do inhibitor studies demonstrate a role for poly(ADP-ribose) in DNA repair?

3-Aminobenzamide, an inhibitor of poly(ADP-ribose) synthesis, has been commonly used in attempts to demonstrate a regulatory role for the polymer during a late stage of repair. When a range of inhibitor concentrations was used paradoxical results were obtained. Up to 1 mM, 3-aminobenzamide appeared to reduce DNA break frequencies in cells damaged by methyl methane sulfonate; at doses of 2 mM and above, it appeared to increase break frequencies. In the high concentration range, many nonspecific side effects and cellular toxicity predominate. Evidence used to assert a role for poly(ADP-ribose) synthesis during ligation has usually been derived from experiments using high concentrations of 3-aminobenzamide, but these may be attributed to toxic side effects. 3-Aminobenzamide stimulates a large increase in repair replication which does not result from increased excision of damaged sites or an increased patch length but may be attributable to other cellular effects such as endogenous nuclease attack on DNA. The cellular effects of 3-aminobenzamide are therefore complicated by nonspecific effects over a commonly used concentration range and evidence for a specific regulatory role of poly(ADP-ribose) in DNA repair is weak.     

The synaptonemal complex: a structure necessary for pairing, recombination or organization of the meiotic chromosome?

The synaptonemal complex (SC) is a prominent and evolutionaly well conserved structure which is strictly meiotic. Several evidences from mutant phenotypes support the hypothesis that recombination and SC formation are mutually interdependent processes. Moreover, the SC recombination nodules correspond in number and location to the crossing-over events. However, recent data confirm that SC formation does not require initiation of recombination, and several observations indicate that full synapsis is not required for recombination. The potential roles played by the SC will be discussed in the following framework: First, although not required for homology recognition, the SC could promote interhomolog interactions in situations where the normal processes have failed (interlocking, heterologous pairing, etc.); Second, polymerization of the SC components might permit the recombination process to progress by modulating the number and localisation of reciprocal versus nonreciprocal exchanges (i.e. interference) and; Third, the SC may play an important role in meiotic chromosome structure and especially in inter-sister interactions.     

Pedobesia simple (Kützing) comb. nov. (Chlorophyta), a new name for P. lamourouxii and its first report from the Indian Ocean

The green alga Pedobesia lamourouxii (J. Agardh) Feldmann et al. (Bryopsidales) is reported from the northern Arabian Sea on the basis of collections from the Sultanate of Oman and Socotra Island (Yemen). Vegetative and sporangial plants as well as the ecology are described. These collections constitute the first record of this widely distributed species for the Indian Ocean. In the course of this study we discovered that Bryopsis simplex Kützing is an older taxonomic synonym, and thus we propose Pedobesia simplex (Kützing) comb. nov. as the correct name for this species. A specimen of Bryopsis simplex in the Leiden Herbarium (L) is designated as lectotype.