Likelihood ratios for evaluating DNA evidence when the suspect is found through a database search

A crime has been committed, and a DNA profile of the perpetrator is obtained from the crime scene. A suspect with a matching profile is found. The problem of evaluating this DNA evidence in a forensic context, when the suspect is found through a database search, is analysed through a likelihood approach. The recommendations of the National Research Council of the U.S. are derived in this setting as the proper way of evaluating the evidence when finiteness of the population of possible perpetrators is not taken into account. When a finite population of possible perpetrators may be assumed, it is possible to take account of the sampling process that resulted in the actual database, so one can deal with the problem where a large proportion of the possible perpetrators belongs to the database in question. It is shown that the last approach does not in general result in a greater weight being assigned to the evidence, though it does when a sufficiently large amount of the possible perpetrators are in the database. The value of the likelihood ratio corresponding to the probable cause setting constitutes an upper bound for this weight, and the upper bound is only attained when all but one of the possible perpetrators are in the database.     

The effect of relatedness on likelihood ratios and the use of conservative estimates

DNA profiling can be used to identify criminals through their DNA matching that left at the scene of a crime. The strength of the evidence supplied by a match in DNA profiles is given by the likelihood ratio. This, in turn, depends upon the probability that a match would be produced if the suspect is innocent. This probability could be strongly affected by the possibility of relatedness between the suspect and the true source of the scene-of-crime DNA profile. Methods are shown that allow for the possibility of such relatedness, arising either through population substructure or through a family relationship. Uncertainties about the likelihood ratio have been taken as grounds for the use of very conservative estimates of this quantity. The use of such conservative estimates can be shown to be neither necessary nor harmless.Editor's commentsThe author makes a good case for the use of likelihood ratios in presenting evidence. The author cites Nichols and Balding (1991) for the match probability involvingF _ST , and readers will also need to consult Balding and Nichols (1994 and this volume) and Weir (1994). In light of current concern over laboratory errors or fraud, the author's comment that Undetected and unsuspected human error or mischief is potentially a problem in almost all criminal cases, yet no convictions could follow if this possibility was consistently deemed to lead to reasonable doubt is well taken.     

The DNA database search controversy revisited: bridging the Bayesian-frequentist gap

Two different quantities have been suggested for quantification of evidence in cases where a suspect is found by a search through a database of DNA profiles. The likelihood ratio, typically motivated from a Bayesian setting, is preferred by most experts in the field. The so-called np rule has been suggested through frequentist arguments and has been suggested by the American National Research Council and Stockmarr (1999, Biometrics55, 671-677). The two quantities differ substantially and have given rise to the DNA database search controversy. Although several authors have criticized the different approaches, a full explanation of why these differences appear is still lacking. In this article we show that a P-value in a frequentist hypothesis setting is approximately equal to the result of the np rule. We argue, however, that a more reasonable procedure in this case is to use conditional testing, in which case a P-value directly related to posterior probabilities and the likelihood ratio is obtained. This way of viewing the problem bridges the gap between the Bayesian and frequentist approaches. At the same time it indicates that the np rule should not be used to quantify evidence.     

Hierarchical Modeling for Estimating Relative Risks of Rare Genetic Variants: Properties of the Pseudo‐Likelihood Method

Summary Many major genes have been identified that strongly influence the risk of cancer. However, there are typically many different mutations that can occur in the gene, each of which may or may not confer increased risk. It is critical to identify which specific mutations are harmful, and which ones are harmless, so that individuals who learn from genetic testing that they have a mutation can be appropriately counseled. This is a challenging task, since new mutations are continually being identified, and there is typically relatively little evidence available about each individual mutation. In an earlier article, we employed hierarchical modeling ( Capanu et al., 2008 , Statistics in Medicine 27 , 1973–1992) using the pseudo‐likelihood and Gibbs sampling methods to estimate the relative risks of individual rare variants using data from a case–control study and showed that one can draw strength from the aggregating power of hierarchical models to distinguish the variants that contribute to cancer risk. However, further research is needed to validate the application of asymptotic methods to such sparse data. In this article, we use simulations to study in detail the properties of the pseudo‐likelihood method for this purpose. We also explore two alternative approaches: pseudo‐likelihood with correction for the variance component estimate as proposed by Lin and Breslow (1996, Journal of the American Statistical Association 91 , 1007–1016) and a hybrid pseudo‐likelihood approach with Bayesian estimation of the variance component. We investigate the validity of these hierarchical modeling techniques by looking at the bias and coverage properties of the estimators as well as at the efficiency of the hierarchical modeling estimates relative to that of the maximum likelihood estimates. The results indicate that the estimates of the relative risks of very sparse variants have small bias, and that the estimated 95% confidence intervals are typically anti‐conservative, though the actual coverage rates are generally above 90%. The widths of the confidence intervals narrow as the residual variance in the second‐stage model is reduced. The results also show that the hierarchical modeling estimates have shorter confidence intervals relative to estimates obtained from conventional logistic regression, and that these relative improvements increase as the variants become more rare.     

Helicobacter pylori recurrence in developed and developing countries: meta-analysis of 13C-urea breath test follow-up after eradication

Objective: Recurrence of Helicobacter pylori infection after eradication is rare in developed countries and more frequent in developing countries. Most recurrent cases are attributed to recrudescence (recolonization of the same strain within 12 months) rather than to reinfection (colonization with a new strain after more than 12 months). The aim of the study was to analyze recurrence rates in developed and developing countries and to deduce the relative roles of recrudescence and reinfection. Methods: The PubMed database was searched up to January 31, 2007 using the keywords “Helicobacter pylori” or “H. pylori” and “recurrence” or “recrudescence,” or “reinfection.” Only prospective case studies in adults that used the ¹³C‐urea breath test (¹³CUBT) were included. Meta‐analyses were performed with statdirect Statistical software, version 2.6.1, StatsDirect Ltd, Chesire, UK. Results: The literature search yielded 10 studies of H. pylori recurrence in developed countries (3014 patients followed for 24–60 months) and 7 studies in developing countries (2071 patients followed for 12–60 months). The calculated annual recurrence rates were 2.67% and 13.00%, respectively. Nested meta‐analysis of cases with a longer follow‐up after eradication revealed an annual recurrence rate of 1.45% (RR 0.54) in developed countries and 12.00% (RR 0.92) in developing countries. Conclusions: The similarity of the annual recurrence rates during the first year after eradication and the annual recurrence rates in the second year after successful eradication in developing countries supports reinfection as the main cause in the second period. Therefore, a different approach for follow‐up of H. pylori eradication may be needed between developed and developing countries.     

A peptide resource for the analysis of Staphylococcus aureus in host–pathogen interaction studies

Staphylococcus aureus is an opportunistic human pathogen, which can cause life‐threatening disease. Proteome analyses of the bacterium can provide new insights into its pathophysiology and important facets of metabolic adaptation and, thus, aid the recognition of targets for intervention. However, the value of such proteome studies increases with their comprehensiveness. We present an MS–driven, proteome‐wide characterization of the strain S. aureus HG001. Combining 144 high precision proteomic data sets, we identified 19 109 peptides from 2088 distinct S. aureus HG001 proteins, which account for 72% of the predicted ORFs. Peptides were further characterized concerning pI, GRAVY, and detectability scores in order to understand the low peptide coverage of 8.7% (19 109 out of 220 245 theoretical peptides). The high quality peptide‐centric spectra have been organized into a comprehensive peptide fragmentation library (SpectraST) and used for identification of S. aureus‐typic peptides in highly complex host–pathogen interaction experiments, which significantly improved the number of identified S. aureus proteins compared to a MASCOT search. This effort now allows the elucidation of crucial pathophysiological questions in S. aureus‐specific host–pathogen interaction studies through comprehensive proteome analysis. The S. aureus‐specific spectra resource developed here also represents an important spectral repository for SRM or for data‐independent acquisition MS approaches. All MS data have been deposited in the ProteomeXchange with identifier PXD000702 ( http://proteomecentral.proteomexchange.org/dataset/PXD000702 ).     

Sex and seasonal differences in hippocampal volume and neurogenesis in brood‐parasitic brown‐headed cowbirds (Molothrus ater)

Brown‐headed cowbirds (Molothrus ater) are one of few species in which females show more complex space use than males. Female cowbirds search for, revisit, and parasitize host nests and, in a previous study, outperformed males on an open field spatial search task. Previous research reported a female‐biased sex difference in the volume of the hippocampus, a region of the brain involved in spatial memory. Neurons produced by adult neurogenesis may be involved in the formation of new memories and replace older neurons that could cause interference in memory. We tested for sex and seasonal differences in hippocampal volume and neurogenesis of brood‐parasitic brown‐headed cowbirds and the closely related non‐brood‐parasitic red‐winged blackbird (Agelaius phoeniceus) to determine whether there were differences in the hippocampus that reflected space use in the wild. Females had a larger hippocampus than males in both species, but hippocampal neurogenesis, measured by doublecortin immunoreactivity (DCX+), was greater in female than in male cowbirds in the absence of any sex difference in blackbirds, supporting the hypothesis of hippocampal specialization in female cowbirds. Cowbirds of both sexes had a larger hippocampus with greater hippocampal DCX+ than blackbirds. Hippocampus volume remained stable between breeding conditions, but DCX+ was greater post‐breeding, indicating that old memories may be lost through hippocampal reorganization following breeding. Our results support, in part, the hypothesis that the hippocampus of cowbirds is specialized for brood parasitism. © 2016 Wiley Periodicals, Inc. Develop Neurobiol 76: 1275–1290, 2016     

Inferring larval taxonomy and morphology in Maladera species (Coleoptera: Scarabaeidae: Sericini) using DNA taxonomy tools

Based on a comparative molecular study of scarab chafers we matched adult and larval instars to identify and describe unknown larvae of Sericini. Here, we use for the first time a two‐fold DNA taxonomy approach based on: (i) mitochondrial and nuclear DNA markers of a local sample (from Nepal) of adults and larvae, in combination with character and tree‐based species delimitation methods; and (ii) a global search of cytochrome c oxidase subunit I (cox1) sequences with GenBank data. In the latter analysis we used a sequence of a specimen that resulted in the first analysis conspecific with the larvae of Maladera affinis (Blanchard) as the query sequence in GenBank, and checked in a minimum evolution tree whether larva–adult matches from the local approach were altered through interference with other taxa of the worldwide database. Both approaches unambiguously identified the unknown larvae as belonging to M. affinis and Maladera cardoni (Brenske). Based on this robust framework of taxonomic identification we could associate names to the larval morphology of the third larval instar of these two Nepalese Maladera species, which are both known for their economical importance in agriculture. They are described here in detail and are compared with known related taxa, especially with Maladera castanea (Arrow).     

Variation in trophic cascade strength is triggered by top–down process in an ant–wasp‐fig system

Changes in the strength of trophic cascades over time have been associated with dramatic shifts in community structure and function. However, the pattern, process, and potential underlying mechanism of temporal variation in trophic cascades remains relatively unexplored. A top–down trophic cascade has been documented for the effects of predacious weaver ants Oecophylla smaragdina on the success of fig tree Ficus racemosa seed production. Ants cause high mortality of non‐pollinating fig wasps Sycophaga mayri that parasitize fruits, leading to greater success for the pollinating fig wasp–fig tree mutualists. Here, using a design in which pairs of branches were selected on a tree, and ants were excluded from one of each pair, we quantified the magnitude of the trophic cascade in the cool–dry, hot–dry and rainy (hot–wet) seasons in Xishuangbanna, southwest China. We also recorded the daily behavioral dynamics of ants and fig wasps in different seasons and analyzed the correlation between behavioral, activity and trophic cascade strength. We found that the strength of the trophic cascade was strong in the hot–dry season, diminished in the rainy season and disappeared in the cool–dry season in this system. The strength of species interactions between ants and non‐pollinating fig wasps, is positively correlated with trophic cascade strength, indicating that trophic cascade strength is determined by a top–down process when the community is well established. Moreover, because pollinating fig wasps, Ceratosolen fusciceps, play a central role in the establishment of fig wasp communities, when C. fusciceps wasps are absent, the community quickly disassembles as is the case in the cool–dry season. In summary, the strength of the trophic cascade is triggered by top–down processes, however, the occurrence of the trophic cascade is determined by a keystone species that plays a central role in assembly of the community.     

Loss of the Birt–Hogg–Dubé gene product folliculin induces longevity in a hypoxia‐inducible factor–dependent manner

Signaling through the hypoxia‐inducible factor hif‐1 controls longevity, metabolism, and stress resistance in Caenorhabditis elegans. Hypoxia‐inducible factor (HIF) protein levels are regulated through an evolutionarily conserved ubiquitin ligase complex. Mutations in the VHL gene, encoding a core component of this complex, cause a multitumor syndrome and renal cell carcinoma in humans. In the nematode, deficiency in vhl‐1 promotes longevity mediated through HIF‐1 stabilization. However, this longevity assurance pathway is not yet understood. Here, we identify folliculin (FLCN) as a novel interactor of the hif‐1/vhl‐1 longevity pathway. FLCN mutations cause Birt–Hogg–Dubé syndrome in humans, another tumor syndrome with renal tumorigenesis reminiscent of the VHL disease. Loss of the C. elegans ortholog of FLCN F22D3.2 significantly increased lifespan and enhanced stress resistance in a hif‐1‐dependent manner. F22D3.2, vhl‐1, and hif‐1 control longevity by a mechanism distinct from insulin‐like signaling. Daf‐16 deficiency did not abrogate the increase in lifespan mediated by flcn‐1. These findings define FLCN as a player in HIF‐dependent longevity signaling and connect organismal aging, stress resistance, and regulation of longevity with the formation of renal cell carcinoma.     

Characterization of a novel allergenic protein from the octocoral Scleronephthya gracillima (Kuekenthal) that corresponds to a new GFP‐like family named Akane

Certain marine organisms have been known to cause allergic reactions among occupational fishermen. We have previously reported that bronchial asthma among the workers engaged in spiny lobster fishing in Japan was caused by octocorals such as Dendronephthya sp. and Scleronephthya gracillima (previously named Alcyonium gracillimum). Now we have found another octocoral, Scleronephthya gracillima (Kuekenthal), which causes the allergic disease in fishermen. The octocoral was characterized as a new green fluorescent protein (GFP)‐like family. The new allergen has a molecular mass of 27 kDa in 1D and 2D SDS‐PAGE under reduced conditions. The 27 kDa component was determined to be an allergen by western blotting, ECL immune staining method and absorption of patient sera with the antigen. Furthermore, the combination of analysis with LC‐ESI‐MS/MS and MASCOT search in the NCBInr database concluded the 27 kDa component had the sequence YPADI/LPDYFK, and that the 22 kDa component had the sequence QSFPEGFSWER, which both matched a GFP‐like protein in Acropora aculeus and in Montastraea annularis. Further analysis by MALDI‐TOF/MS/MS and MASCOT search in the NCBInr database of all 27 kDa eight spot components from 2D SDS‐PAGE indicated that the sequence QSFPEGFSWER also matched as GFP‐like protein in Lobophyllia hemprichii and Scleractinia sp. To our knowledge, this is the first report of the new allergenic protein that corresponds to a new GFP‐like protein named Akane, and which has fluorescent emissions in the red and green part of the spectra at 628 nm and 508 nm, respectively.     

rangeMapper: a platform for the study of macroecology of life‐history traits

Aim To introduce rangeMapper, an R package for the study of the macroecological patterns of life‐history traits, and demonstrate its capabilities using three case studies. The first case study addresses an important topic in conservation biology: biodiversity hotspots. Specifically, we investigate the congruence between global hotspots of three parameters that describe avian diversity: species richness, endemic species richness and relative body mass diversity. The second case study investigates a topic of relevance for macroecology: the inter‐specific relationship between range size and body size for avian assemblages, and how it varies geographically. The third case study tackles a methodological problem in macroecology: the influence of map resolution on statistical inference, i.e. the question of whether and how the relationship between species richness and body mass varies with map resolution. Innovation rangeMapper offers a tight integration of spatial and statistical tools for macroecological projects and it relies on a high‐performance database engine which makes it suitable for managing projects using a large number of species. rangeMapper's architecture follows closely the concepts described by Gaston et al. (2008 Journal of Biogeography, 35 , 483–500) and its flexibility allows for both complex data manipulation procedures and easy implementation of new functions. By choosing case studies to cover various technical and conceptual issues we demonstrate rangeMapper's capabilities to address a wide array of questions. Main conclusion rangeMapper ( http://cran.r‐project.org/package=rangeMapper ) is an open source front end software which can be used to address questions in both fundamental ecological research and conservation biology.     

Identification and Nucleotide Sequence of a Tobacco rattle virus RNA-1 Variant that Causes Spraing Disease in Potato cv. Bintje

An isolate of Tobacco rattle virus (TRV) obtained from a site in the Netherlands induced symptoms of spraing disease in tubers of the potato variety Bintje, which is generally considered to be resistant to infection by TRV. The isolate contained two phenotypically distinguishable RNA‐1 variants, one of which was shown to carry the determinant for the ability to cause spraing in cv. Bintje. The nucleotide sequence of the coding region of this RNA‐1 was determined and found to differ at 5.2–5.4% of positions from other TRV RNA‐1 sequences in the database. The amino acid sequences of the predicted translation products were between 92 and 99% identical to those of a TRV RNA‐1 that did not cause spraing in cv. Bintje, with P1b being the most divergent and the replicase read‐through domain the least.     

Noninvasive paternity assignment in Gombe chimpanzees

The relative success of chimpanzee male mating strategies, the role of male dominance rank and the success of inbreeding avoidance behaviour can only be assessed when paternities are known. We report the probable paternities of 14 chimpanzees included in a long‐term behavioural study of chimpanzees (Pan troglodytes schweinfurthii) at Gombe National Park, Tanzania. DNA samples were collected noninvasively from shed hair and faeces and genotyped using 13–16 microsatellite loci characterized in humans. All 14 offspring could be assigned to fathers within the community. While there is a positive relationship between male rank and reproductive success, we demonstrate that a range of male mating strategies (possessiveness, opportunistic mating and consortships) can lead to paternity across all male ranks. Several adult females were at risk of breeding with close male relatives. Most successfully avoided close inbreeding but in one case a high‐ranking male in the community mated with his mother and produced an offspring. In contrast to recent data on chimpanzees (P. t. verus) from the Taï forest, Côte d’Ivoire, no evidence of extra‐group paternity was observed in our study. Reanalysis of Taï data using a likelihood approach casts doubt on the occurrence of extra‐group paternity in that community as well.     

Molecular and morphological evidence supports the species status of the Mahachai fighter Betta sp. Mahachai and reveals new species of Betta from Thailand

Two regions of mitochondrial (mt) DNA, cytochrome c oxidase subunit 1 (COI) and 16S rRNA, were sequenced in nine species of Betta from Thailand and Indonesia. Most species showed little intraspecific COI variation (adjusted mean = 0·48%) including the putative species Betta sp. Mahachai, but one species (Betta smaragdina) included three lineages showing much greater divergence (7·03–13·48%) that probably represent overlooked species. These findings were confirmed by maximum likelihood analysis and Bayesian inference, which revealed well‐supported corresponding monophyletic clades. Based on these results and morphological differences, the putative species Betta sp. Mahachai from central Thailand is a species distinct from other members of the B. splendens group and represents a new and hitherto undescribed species. Furthermore, this study also demonstrated the probable existence of two overlooked Betta species found in the Khorat plateau basin, illustrating the utility of mitochondrial genetic markers in the revelation of overlooked diversity.     

The trypanolytic factor of human serum: many ways to enter the parasite,a single way to kill

Humans have developed a particular innate immunity system against African trypanosomes, and only two Trypanosoma brucei clones (T. b. gambiense, T. b. rhodesiense) can resist this defence and cause sleeping sickness. The main players of this immunity are the primate‐specific apolipoprotein L‐I (apoL1) and haptoglobin‐related protein (Hpr). These proteins are both associated with two serum complexes, a minor subfraction of HDLs and an IgM/apolipoprotein A‐I (apoA1) complex, respectively, termed trypanosome lytic factor (TLF) 1 and TLF2. Although the two complexes appear to lyse trypanosomes by the same mechanism, they enter the parasite through various modes of uptake. In case of TLF1 one uptake process was characterized. When released in the circulation, haemoglobin (Hb) binds to Hpr, hence to TLF1. In turn the TLF1–Hpr–Hb complex binds to the trypanosome haptoglobin (Hp)–Hb receptor, whose original function is to ensure haem uptake for optimal growth of the parasite. This binding triggers efficient uptake of TLF1 and subsequent trypanosome lysis. While Hpr is involved as TLF ligand, the lytic activity is due to apoL1, a Bcl‐2‐like pore‐forming protein. We discuss the in vivo relevance of this uptake pathway in the context of other potentially redundant delivery routes.     

Outcrossing potential between 11 important genetically modified crops and the Chilean vascular flora

The potential impact of genetically modified (GM) crops on biodiversity is one of the main concerns in an environmental risk assessment (ERA). The likelihood of outcrossing and pollen‐mediated gene flow from GM crops and non‐GM crops are explained by the same principles and depend primarily on the biology of the species. We conducted a national‐scale study of the likelihood of outcrossing between 11 GM crops and vascular plants in Chile by use of a systematized database that included cultivated, introduced and native plant species in Chile. The database included geographical distributions and key biological and agronomical characteristics for 3505 introduced, 4993 native and 257 cultivated (of which 11 were native and 246 were introduced) plant species. Out of the considered GM crops (cotton, soya bean, maize, grape, wheat, rice, sugar beet, alfalfa, canola, tomato and potato), only potato and tomato presented native relatives (66 species total). Introduced relative species showed that three GM groups were formed having: a) up to one introduced relative (cotton and soya bean), b) up to two (rice, grape, maize and wheat) and c) from two to seven (sugar beet, alfalfa, canola, tomato and potato). In particular, GM crops presenting introduced noncultivated relative species were canola (1 relative species), alfalfa (up to 4), rice (1), tomato (up to 2) and potato (up to 2). The outcrossing potential between species [OP; scaled from ‘very low’ (1) to ‘very high’ (5)] was developed, showing medium OPs (3) for GM–native relative interactions when they occurred, low (2) for GMs and introduced noncultivated and high (4) for the grape‐Vitis vinifera GM–introduced cultivated interaction. This analytical tool might be useful for future ERA for unconfined GM crop release in Chile.