The consequences of using indirect signs that decay to determine species' occupancy

Statistical models of species' distributions rely on data on species' occupancy, or use, of sites across space and/or time. For rare or cryptic species, indirect signs, such as dung, may be the only realistic means of determining their occupancy status across broad spatial extents. However, the consequences of sign decay for errors in estimates of occupancy have not previously been considered. If signs decay very rapidly, then false‐negative errors may occur because signs at an occupied site have decayed by the time it is surveyed. On the other hand, if signs decay very slowly, false‐positive errors may occur because signs remain present at sites that are no longer occupied. We addressed this issue by quantifying, as functions of sign decay and accumulation rates: 1) the false‐negative error rate due to sign decay and, 2) the expected time interval prior to a survey within which signs indicate the species was present; as this time interval increases, false‐positives become more likely. We then applied this to the specific example of koala Phascolarctos cinereus occupancy derived from faecal pellet surveys using data on faecal pellet decay rates. We show that there is a clear trade‐off between false‐negative error rates and the potential for false‐positive errors. For the koala case study, false‐negative errors were low on average and the expected time interval prior to surveys that detected pellets indicate the species was present within less than 2–3 yr. However, these quantities showed quite substantial spatial variation that could lead to biased parameter estimates for distribution models based on faecal pellet surveys. This highlights the importance of observation errors arising from sign decay and we suggest some modifications to existing methods to deal with this issue.     

HLA-A*7401-mediated control of HIV viremia is independent of its linkage disequilibrium with HLA-B*5703

The potential contribution of HLA-A alleles to viremic control in chronic HIV type 1 (HIV-1) infection has been relatively understudied compared with HLA-B. In these studies, we show that HLA-A*7401 is associated with favorable viremic control in extended southern African cohorts of >2100 C-clade-infected subjects. We present evidence that HLA-A*7401 operates an effect that is independent of HLA-B*5703, with which it is in linkage disequilibrium in some populations, to mediate lowered viremia. We describe a novel statistical approach to detecting additive effects between class I alleles in control of HIV-1 disease, highlighting improved viremic control in subjects with HLA-A*7401 combined with HLA-B*57. In common with HLA-B alleles that are associated with effective control of viremia, HLA-A*7401 presents highly targeted epitopes in several proteins, including Gag, Pol, Rev, and Nef, of which the Gag epitopes appear immunodominant. We identify eight novel putative HLA-A*7401-restricted epitopes, of which three have been defined to the optimal epitope. In common with HLA-B alleles linked with slow progression, viremic control through an HLA-A*7401-restricted response appears to be associated with the selection of escape mutants within Gag epitopes that reduce viral replicative capacity. These studies highlight the potentially important contribution of an HLA-A allele to immune control of HIV infection, which may have been concealed by a stronger effect mediated by an HLA-B allele with which it is in linkage disequilibrium. In addition, these studies identify a factor contributing to different HIV disease outcomes in individuals expressing HLA-B*5703.     

Fruit ripening in Vitis vinifera: spatiotemporal relationships among turgor, sugar accumulation, and anthocyanin biosynthesis

This study reports the first observations indicating the spatiotemporal relationships among genetic and physiological aspects of ripening in the berry of Vitis vinifera. At the onset of ripening in the red flesh variety Alicante Bouschet, colour development began in the flesh at the stylar end of the fruit and progressed toward the pedicel end flesh and into the skin. Tissue solute potential and cell turgor also decreased first in the flesh. The decrease in flesh solute potential was due to accumulation of sugars, glucose and fructose, an accumulation that is integral to ripening. Expression of the anthocyanin biosynthesis-related genes VvMybA and VvUFGT was linearly related to the decrease in solute potential. Expression of VvMybA, and to a lesser extent VvUFGT, was correspondingly low in green tissue, higher in the red, stylar end flesh of berries beginning to ripen, and greatest in red berries. In contrast, expression of the abscisic acid biosynthesis-related genes VvNCED1 and VvNCED2 was not correlated with the other spatiotemporal aspects of the onset of ripening. These results, together with earlier work showing that sugar accumulation and acid loss also begin in the stylar flesh in other varieties, indicate that ripening in the grape berry originates in the stylar end flesh.     

Microsecond subdomain folding in dihydrofolate reductase

The characterization of microsecond dynamics in the folding of multisubdomain proteins has been a major challenge in understanding their often complex folding mechanisms. Using a continuous-flow mixing device coupled with fluorescence lifetime detection, we report the microsecond folding dynamics of dihydrofolate reductase (DHFR), a two-subdomain α/β/α sandwich protein known to begin folding in this time range. The global dimensions of early intermediates were monitored by Förster resonance energy transfer, and the dynamic properties of the local Trp environments were monitored by fluorescence lifetime detection. We found that substantial collapse occurs in both the locally connected adenosine binding subdomain and the discontinuous loop subdomain within 35 μs of initiation of folding from the urea unfolded state. During the fastest observable ∼ 550 μs phase, the discontinuous loop subdomain further contracts, concomitant with the burial of Trp residue(s), as both subdomains achieve a similar degree of compactness. Taken together with previous studies in the millisecond time range, a hierarchical assembly of DHFR—in which each subdomain independently folds, subsequently docks, and then anneals into the native conformation after an initial heterogeneous global collapse—emerges. The progressive acquisition of structure, beginning with a continuously connected subdomain and spreading to distal regions, shows that chain entropy is a significant organizing principle in the folding of multisubdomain proteins and single-domain proteins. Subdomain folding also provides a rationale for the complex kinetics often observed.     

The role of calcium ions in the stability and instability of a thermolysin-like protease

Thermolysin and other secreted broad-specificity proteases, such as subtilisin or alpha-lytic protease, are produced as pre-pro-proteins that stay at least partially unfolded while in the cytosol. After secretion, the pro-proteases fold to their active conformations in a process that includes the autolytic removal of the pro-peptide. We review the life cycle of the thermolysin-like protease from Bacillus stearothermophilus in light of the calcium dependent stability and instability of the N-terminal domain. The protease binds calcium ions in the regions that are involved in the autolytic maturation process. It is generally assumed that the calcium ions contribute to the extreme stability of the protease, but experimental evidence for TLP-ste indicates that at least one of the calcium ions plays a regulatory role. We hypothesize that this calcium ion plays an important role as a switch that modulates the protease between stable and unstable states as appropriate to the biological need.     

Atomic resolution insights into curli fiber biogenesis

Bacteria produce functional amyloid fibers called curli in a controlled, noncytotoxic manner. These extracellular fimbriae enable biofilm formation and promote pathogenicity. Understanding curli biogenesis is important for appreciating microbial lifestyles and will offer clues as to how disease-associated human amyloid formation might be ameliorated. Proteins encoded by the curli specific genes (csgA-G) are required for curli production. We have determined the structure of CsgC and derived the first structural model of the outer-membrane subunit translocator CsgG. Unexpectedly, CsgC is related to the N-terminal domain of DsbD, both in structure and oxido-reductase capability. Furthermore, we show that CsgG belongs to the nascent class of helical outer-membrane macromolecular exporters. A cysteine in a CsgG transmembrane helix is a potential target of CsgC, and mutation of this residue influences curli assembly. Our study provides the first high-resolution structural insights into curli biogenesis.     

Late immature mortality is the major influence on reproductive success of African black beetle, Heteronychus arator (Fabricius) (Coleoptera: Scarabaeidae), in a Mediterranean-climate region of Australia

In field and laboratory studies, mortality of African black beetle, Heteronychus arator, in the winter-rainfall, Mediterranean-type climate region of south-western Australia was higher in the late immature stages during summer than in the early immature stages that occur during spring, a contrast to summer-rainfall climatic regions. Greatest mortality occurred around the pupal stage in contrasting soil types, despite drying differences in summer and supplementary watering in some plots. Sampling of natural populations confirmed experimental results that mortality in late immature stages is the major factor limiting H. arator populations under a Mediterranean-type climate. Inter-generation increase in H. arator abundance was uncommon, explaining the consistent abundance typically observed between years in south-western Australia. Random dispersal of newly emerged adults in autumn was inferred to restore uniformity in adult abundance between areas of varying favourability for immature survival.     

Infant and child mortality in three culturally contrasting states of India.

Using cross-sectional, individual-level survey data from Maharashtra, Tamil Nadu and Uttar Pradesh collected under the Indian National Family Health Survey programme of 1992-93, statistical modelling was used to analyse the impact of a range of variables on the survival status of children during their first 2 years of life. Attention was focused on the potential impact of the mother's autonomy. The strongest predictors of mortality were demographic and biological factors, breast-feeding behaviour, and use and knowledge of health services. Variables that can be interpreted as being related to maternal autonomy, such as the presence of a mother-in-law in the household, did not have a significant direct effect on child survival at the individual level, and their indirect effects were very limited.     

Microsecond hydrophobic collapse in the folding of Escherichia coli dihydrofolate reductase, an alpha/beta-type protein

Using small-angle X-ray scattering combined with a continuous-flow mixing device, we monitored the microsecond compaction dynamics in the folding of Escherichia coli dihydrofolate reductase, an alpha/beta-type protein. A significant collapse of the radius of gyration from 30 A to 23.2 A occurs within 300 micros after the initiation of refolding by a urea dilution jump. The subsequent folding after the major chain collapse occurs on a considerably longer time-scale. The protein folding trajectories constructed by comparing the development of the compactness and the secondary structure suggest that the specific hydrophobic collapse model rather than the framework model better explains the experimental observations. The folding trajectory of this alpha/beta-type protein is located between those of alpha-helical and beta-sheet proteins, suggesting that native structure determines the folding landscape.