Social immunity of the family: parental contributions to a public good modulated by brood size

Social immunity refers to any immune defence that benefits others, besides the individual that mounts the response. Since contributions to social immunity are known to be personally costly, they are contributions to a public good. However, individuals vary in their contributions to this public good and it is unclear why. Here we investigate whether they are responding to contributions made by others with experiments on burying beetle (Nicrophorus vespilloides) families. In this species, females, males and larvae each contribute to social immunity through the application of antimicrobial exudates upon the carrion breeding resource. We show experimentally that mothers reduce their contributions to social immunity when raising large broods, and test two contrasting hypotheses to explain why. Either mothers are treating social immunity as a public good, investing less in social immunity when their offspring collectively contribute more, or mothers are trading off investment in social immunity with investment in parental care. Overall, our experiments yield no evidence to support the existence of a trade-off between social immunity and other parental care traits: we found no evidence of a trade-off in terms of time allocated to each activity, nor did the relationship between social immunity and brood size change with female condition. Instead, and consistent with predictions from models of public goods games, we found that higher quality mothers contributed more to social immunity. Therefore our results suggest that mothers are playing a public goods game with their offspring to determine their personal contribution to the defence of the carrion breeding resource.     

What a difference a bay makes: natural variation in dietary resources mediates growth in a recently settled herbivorous fish

Processes acting during the early stages of coral reef fish life cycles have a disproportionate influence on their adult abundance and community structure. Higher growth rates, for example, confer a major fitness advantage in larval and juvenile fishes, with larger fish undergoing significantly less mortality. The role of dietary resources in the size-structuring process has not been well validated, especially at the early post-settlement phase, where competition and predation are seen as preeminent drivers of juvenile fish assemblage structure. Here, we report on a size differential of 10–20% between recently settled Siganus spinus rabbitfish recruits from different bays around the Pacific island of Guam. This difference was maintained across multiple recruitment events within and between years. After confirming the validity of our observations through otolith increment analysis, subsequent investigation into the drivers of this variation revealed significant differences in the structure of algal assemblages between bays, congruent with the observed differences in size of the recently settled fish. Gut analyses showed a greater presence of algal types with higher levels of nitrogen and phosphorus in the stomachs of fish from Tanguisson, the bay with the largest observed recruits. To ensure this mechanism was one of causation and not correlation, we conducted a fully factorial experiment in which S. spinus recruits sampled from different bays were reared on all combinations of algal diets representative of the different bays. Recruits on the ‘Tanguisson’ diet grew faster than recruits on other diets, regardless of their origin. We propose that the greater availability of high-quality dietary resources at this location is likely conferring benefits that impact on the population-level dynamics of this species. The spatial and temporal extent of this process clearly implicates food as a limiting resource, capable of mediating fish population dynamics at multiple spatial scales and ontogenetic phases.     

Similarities between a UV-sensitive mutant of yeast and bacterial mutants lacking excision-repair ability

Summary A UV-sensitive and a wild-type strain ofSaccharomyces cerevisiae have been compared with respect to their responses to photoreactivation, retention of the capacity to photoreactivate when stored at 32°C in buffer, and sensitivity to diepoxybutane and nitrosoguanidine. In all these tests the behaviour of the sensitive mutant paralleled bacterial strains lacking excision repair ability. We may tentatively attribute the UV sensitivity in this mutant to a loss of some element of a repair system analogous to excision repair in bacteria.     

The modifying effects of strain and age on the mutagenic specificity of ultraviolet light in Neurospora crassa

Summary Two derivatives of K3/17 ad-3A 38701; inos 37401 of Neurospora crassa are described which show opposite specific reversional responses to UV. Both derivatives carry the same two auxotrophic alleles and appear to differ only in a single gene which influences the pattern of mutagen specificity. The differences between the derivatives only develop after the cultures have been aged for two to four weeks. Various possible explanations are considered.     

Inter-Seasonal Influenza is Characterized by Extended Virus Transmission and Persistence

The factors that determine the characteristic seasonality of influenza remain enigmatic. Current models predict that occurrences of influenza outside the normal surveillance season within a temperate region largely reflect the importation of viruses from the alternate hemisphere or from equatorial regions in Asia. To help reveal the drivers of seasonality we investigated the origins and evolution of influenza viruses sampled during inter-seasonal periods in Australia. To this end we conducted an expansive phylogenetic analysis of 9912, 3804, and 3941 hemagglutinnin (HA) sequences from influenza A/H1N1pdm, A/H3N2, and B, respectively, collected globally during the period 2009-2014. Of the 1475 viruses sampled from Australia, 396 (26.8% of Australian, or 2.2% of global set) were sampled outside the monitored temperate influenza surveillance season (1 May – 31 October). Notably, rather than simply reflecting short-lived importations of virus from global localities with higher influenza prevalence, we documented a variety of more complex inter-seasonal transmission patterns including “stragglers” from the preceding season and “heralds” of the forthcoming season, and which included viruses sampled from clearly temperate regions within Australia. We also provide evidence for the persistence of influenza B virus between epidemic seasons, in which transmission of a viral lineage begins in one season and continues throughout the inter-seasonal period into the following season. Strikingly, a disproportionately high number of inter-seasonal influenza transmission events occurred in tropical and subtropical regions of Australia, providing further evidence that climate plays an important role in shaping patterns of influenza seasonality.     

Hormonal Contraception and the Risk of HIV Acquisition: An Individual Participant Data Meta-analysis

BackgroundObservational studies of a putative association between hormonal contraception (HC) and HIV acquisition have produced conflicting results. We conducted an individual participant data (IPD) meta-analysis of studies from sub-Saharan Africa to compare the incidence of HIV infection in women using combined oral contraceptives (COCs) or the injectable progestins depot-medroxyprogesterone acetate (DMPA) or norethisterone enanthate (NET-EN) with women not using HC.ConclusionsThis IPD meta-analysis found no evidence that COC or NET-EN use increases women’s risk of HIV but adds to the evidence that DMPA may increase HIV risk, underscoring the need for additional safe and effective contraceptive options for women at high HIV risk. A randomized controlled trial would provide more definitive evidence about the effects of hormonal contraception, particularly DMPA, on HIV risk.     

N-terminal acetylation of α-synuclein induces increased transient helical propensity and decreased aggregation rates in the intrinsically disordered monomer

The conformational properties of soluble α-synuclein, the primary protein found in patients with Parkinson's disease, are thought to play a key role in the structural transition to amyloid fibrils. In this work, we report that recombinant 100% N-terminal acetylated α-synuclein purified under mild physiological conditions presents as a primarily monomeric protein, and that the N-terminal acetyl group affects the transient secondary structure and fibril assembly rates of the protein. Residue-specific NMR chemical shift analysis indicates substantial increase in transient helical propensity in the first 9 N-terminal residues, as well as smaller long-range changes in residues 28-31, 43-46, and 50-66: regions in which the three familial mutations currently known to be causative of early onset disease are found. In addition, we show that the N-terminal acetylated protein forms fibrils that are morphologically similar to those formed from nonacetylated α-synuclein, but that their growth rates are slower. Our results highlight that N-terminal acetylation does not form significant numbers of dimers, tetramers, or higher molecular weight species, but does alter the conformational distributions of monomeric α-synuclein species in regions known to be important in metal binding, in association with membranes, and in regions known to affect fibril formation rates.     

A systematic study of the effect of physiological factors on beta2-microglobulin amyloid formation at neutral pH

Beta(2)-microglobulin (beta(2)m) forms amyloid fibrils that deposit in the musculo-skeletal system in patients undergoing long-term hemodialysis. How beta(2)m self-assembles in vivo is not understood, since the monomeric wild-type protein is incapable of forming fibrils in isolation in vitro at neutral pH, while elongation of fibril-seeds made from recombinant protein has only been achieved at low pH or at neutral pH in the presence of detergents or cosolvents. Here we describe a systematic study of the effect of 11 physiologically relevant factors on beta(2)m fibrillogenesis at pH 7.0 without denaturants. By comparing the results obtained for the wild-type protein with those of two variants (DeltaN6 and V37A), the role of protein stability in fibrillogenesis is explored. We show that DeltaN6 forms low yields of amyloid-like fibrils at pH 7.0 in the absence of seeds, suggesting that this species could initiate fibrillogenesis in vivo. By contrast, high yields of amyloid-like fibrils are observed for all proteins when assembly is seeded with fibril-seeds formed from recombinant protein at pH 2.5 stabilized by the addition of heparin, serum amyloid P component (SAP), apolipoprotein E (apoE), uremic serum, or synovial fluid. The results suggest that the conditions within the synovium facilitate fibrillogenesis of beta(2)m and show that different physiological factors may act synergistically to promote fibril formation. By comparing the behavior of wild-type beta(2)m with that of DeltaN6 and V37A, we show that the physiologically relevant factors enhance fibrillogenesis by stabilizing fibril-seeds, thereby allowing fibril extension by rare assembly competent species formed by local unfolding of native monomers.     

Modulation of transplanaramine platinum complex reactivity by systematic modification of carrier and leaving groups

Transplatinum planaramine complexes with carboxylate ligands as leaving groups, trans-[Pt(O₂CR)₂(L)(L′)] (L = L′ = pyridine; L = NH₃, L′ = pyridine, isoquinoline, thiazole, quinoline, etc.), are potential anticancer complexes with cytotoxicity in some cases equivalent to that of cisplatin. The carboxylate complexes are, as a family, very water-soluble and surprisingly stable towards hydrolysis - resembling carboplatin in their reactivity. Their pharmacological properties can be systematically modified by steric and electronic effects of the donor groups as well as in the leaving carboxylate ligands. Previously, we have recognized the leaving group formate as having appropriate kinetics for bioligand substitution [1]. In this paper we directly compared the effect on biological properties of a pyridine versus isoquinoline-based carrier group. Binding to calf thymus DNA was similar for both compounds but the distortions produced on DNA, as assessed by T_m (melting temperature) and an ethidium bromide fluorescence reporter assay, were more marked for the isoquinoline ligand. Model studies with 5′-GMP (5′-guanosinemonophosphate) confirmed these trends, with the product trans-[Pt(5′-GMP)₂(NH₃)(isoquinoline)] showing evidence of restricted rotation caused by steric hinderance of three rigid planar rings on the central platinum. A cross-linking assay on pUC19 plasmid confirmed a higher % of interstrand adducts for the isoquinoline compound. This “enhanced” reactivity was matched by higher cytotoxicity in HCT116 human colon tumor cells, and also with enhanced cellular accumulation. Thus, a combination of systematic biophysical and biological studies indicates that trans-[Pt(O₂CH)₂(NH₃)(isoquinoline)] has the most promising range of chemical and biological properties for further development and examination.     

Functional Analysis of the VirSR Phosphorelay from Clostridium perfringens

Toxin production in Clostridium perfringens is controlled by the VirSR two-component signal transduction system, which comprises the VirS sensor histidine kinase and the VirR response regulator. Other studies have concentrated on the elucidation of the genes controlled by this network; there is little information regarding the phosphorelay cascade that is the hallmark of such regulatory systems. In this study, we have examined each step in this cascade, beginning with autophosphorylation of VirS, followed by phosphotransfer from VirS to VirR. We also have studied the effects of gene dosage and phosphorylation in vivo. We have used random and site-directed mutagenesis to identify residues in VirS that are important for its function and have identified a region in the putative sensory domain of VirS that appeared to be essential for function. In vitro phosphorylation studies showed that VirSc, a truncated VirS protein that lacked the N-terminal sensory domain, was capable of autophosphorylation and could subsequently act as a phosphodonor for its cognate response regulator, VirR. Conserved residues of both VirS and VirR, including the D57 residue of VirR, were shown to be essential for this process. By use of Targetron technology, we were able to introduce a single copy of virR or virR_D57N onto the chromosome of a virR mutant of C. perfringens. The results showed that in vivo, when virR was present in single copy, the production of wild-type levels of perfringolysin O was dependent on the presence of virS and an unaltered D57 residue in VirR. These results provide good evidence that phosphorylation is critical for VirR function.