Germinating the seeds of three species of Pimelea sect. Epallage (Thymelaeaceae)1

Pimelea trichostachya Lindl., P. simplex F.Muell. and P. elongata Threlfall frequently cause pimelea poisoning of cattle. Fresh seeds of these species, belonging to sect. Epallage (Endl.) Benth. of Pimelea Gaertn. (Thymelaeaceae) are strongly dormant for years when in laboratory storage. Common methods of stimulating germination, such as scarification, dry heat and cold stratification, did not remove much of the dormancy. ‘Smoke water’ stimulated some germination but its effect was unpredictable and many seedlings then grew aberrantly. Exposure of imbibed seeds to gibberellic acid greatly and reliably improved the germination of all three species. However, the manner of application and the concentration of gibberellic acid used had to be appropriate or many young seedlings grew abnormally or died suddenly, limiting successful plant establishment rates. The dormancy type involved is non-deep Type 2 physiological. Ten days of good moisture, in addition to gibberellic acid exposure, is required before appreciable laboratory germination occurs at optimal temperatures. Thus, the mechanism by which gibberellic acid stimulates good germination does not appear to be the same as that which primes seeds for the rapid and prolific germination often seen under natural conditions in arid Australia. Seeds of P. simplex subsp. continua (J.M.Black) Threlfall proved most difficult to germinate and those of P. elongata the easiest.

The pandemic of conflict-related sexual violence and the political economy of gender inequality

Since the 1998 Rome Statute recognized widespread and systematic acts of sexual and gender-based violence (SGBV) as an act of genocide, a war crime and crime against humanity, the last decade has seen historic recognition that egregious acts of sexual violence merit international political and legal attention (UN General Assembly, 1998). Notably there are now no fewer than seven United Nations Security Council resolutions on the cross-cutting theme of Women, Peace and Security.

Production attributes of Merino sheep genetically divergent for wool growth are reflected in differing rumen microbiotas

Divergent genetic selection for wool growth as a single trait has led to major changes in sheep physiology and metabolism, including variations in rumen microbial protein production and uptake of α-amino nitrogen in portal blood. This study was conducted to determine if sheep with different genetic merit for wool growth exhibit distinct rumen bacterial diversity. Eighteen Merino wethers were separated into groups of contrasting genetic merit for clean fleece weight (CFW; low: WG− and high: WG+) and fed a blend of oaten and lucerne chaff diet at two levels of intake (LOI; 1 or 1.5 times maintenance energy requirements) for two seven-week periods in a crossover design. Bacterial diversity in rumen fluid collected by esophageal intubation was characterized using 454 amplicon pyrosequencing of the V3/V4 regions of the 16S rRNA gene. Bacterial diversity estimated by Phylogenetic distance, Chao1 and observed species did not differ significantly with CFW or LOI; however, the Shannon diversity index differed (P=0.04) between WG+ (7.67) and WG− sheep (8.02). WG+ animals had a higher (P=0.03) proportion of Bacteroidetes (71.9% vs 66.5%) and a lower (P=0.04) proportion of Firmicutes (26.6% vs 31.6%) than WG− animals. Twenty-four specific operational taxonomic units (OTUs), belonging to the Firmicutes and Bacteroidetes phyla, were shared among all the samples, whereas specific OTUs varied significantly in presence/abundance (P<0.05) between wool genotypes and 50 varied (P<0.05) with LOI. It appears that genetic selection for fleece weight is associated with differences in rumen bacterial diversity that persist across different feeding levels. Moderate correlations between seven continuous traits, such as methane production or microbial protein production, and the presence and abundance of 17 OTUs were found, indicating scope for targeted modification of the microbiome to improve the energetic efficiency of rumen microbial synthesis and reduce the greenhouse gas footprint of ruminants.

Bayesian statistical analysis of bacterial diversity

Bacteria play an important role in many ecological systems. The molecular characterization of bacteria using either cultivation-dependent or cultivation-independent methods reveals the large scale of bacterial diversity in natural communities, and the vastness of subpopulations within a species or genus. Understanding how bacterial diversity varies across different environments and also within populations should provide insights into many important questions of bacterial evolution and population dynamics. This thesis presents novel statistical methods for analyzing bacterial diversity using widely employed molecular fingerprinting techniques. The first objective of this thesis was to develop Bayesian clustering models to identify bacterial population structures. Bacterial isolates were identified using multilous sequence typing (MLST), and Bayesian clustering models were used to explore the evolutionary relationships among isolates. Our method involves the inference of genetic population structures via an unsupervised clustering framework where the dependence between loci is represented using graphical models. The population dynamics that generate such a population stratification were investigated using a stochastic model, in which homologous recombination between subpopulations can be quantified within a gene flow network. The second part of the thesis focuses on cluster analysis of community compositional data produced by two different cultivation-independent analyses: terminal restriction fragment length polymorphism (T-RFLP) analysis, and fatty acid methyl ester (FAME) analysis. The cluster analysis aims to group bacterial communities that are similar in composition, which is an important step for understanding the overall influences of environmental and ecological perturbations on bacterial diversity. A common feature of T-RFLP and FAME data is zero-inflation, which indicates that the observation of a zero value is much more frequent than would be expected, for example, from a Poisson distribution in the discrete case, or a Gaussian distribution in the continuous case. We provided two strategies for modeling zero-inflation in the clustering framework, which were validated by both synthetic and empirical complex data sets. We show in the thesis that our model that takes into account dependencies between loci in MLST data can produce better clustering results than those methods which assume independent loci. Furthermore, computer algorithms that are efficient in analyzing large scale data were adopted for meeting the increasing computational need. Our method that detects homologous recombination in subpopulations may provide a theoretical criterion for defining bacterial species. The clustering of bacterial community data include T-RFLP and FAME provides an initial effort for discovering the evolutionary dynamics that structure and maintain bacterial diversity in the natural environment.

Strategic tillage in no-till farming systems in Australia’s northern grains-growing regions: II. Implications for agronomy, soil and environment

In semi-arid sub-tropical areas, a number of studies concerning no-till (NT) farming systems have demonstrated advantages in economic, environmental and soil quality aspects over conventional tillage (CT). However, adoption of continuous NT has contributed to the build-up of herbicide resistant weed populations, increased incidence of soil- and stubble-borne diseases, and stratification of nutrients and organic carbon near the soil surface. Some farmers often resort to an occasional strategic tillage (ST) to manage these problems of NT systems. However, farmers who practice strict NT systems are concerned that even one-time tillage may undo positive soil condition benefits of NT farming systems. We reviewed the pros and cons of the use of occasional ST in NT farming systems. Impacts of occasional ST on agronomy, soil and environment are site-specific and depend on many interacting soil, climatic and management conditions. Most studies conducted in North America and Europe suggest that introducing occasional ST in continuous NT farming systems could improve productivity and profitability in the short term; however in the long-term, the impact is negligible or may be negative. The short term impacts immediately following occasional ST on soil and environment include reduced protective cover, soil loss by erosion, increased runoff, loss of C and water, and reduced microbial activity with little or no detrimental impact in the long-term. A potential negative effect immediately following ST would be reduced plant available water which may result in unreliability of crop sowing in variable seasons. The occurrence of rainfall between the ST and sowing or immediately after the sowing is necessary to replenish soil water lost from the seed zone. Timing of ST is likely to be critical and must be balanced with optimising soil water prior to seeding. The impact of occasional ST varies with the tillage implement used; for example, inversion tillage using mouldboard tillage results in greater impacts as compared to chisel or disc. Opportunities for future research on occasional ST with the most commonly used implements such as tine and/or disc in Australia’s northern grains-growing region are presented in the context of agronomy, soil and the environment.

Double walled carbon nanotubes as ultrafast optical switches

Pristine and molybdenum filled double walled carbon nanotubes (DWNTs) suspended in D2O show excellent ultrafast optical switching properties investigated through femtosecond Z-scan and degenerate pump-probe method using 50 fs pulses with central photon energy of 1.57 eV. For pristine-DWNT, the two photon absorption coefficient, beta and nonlinear refraction coefficient, n2 are 4.9×10−8 cm/W, and 9.5×10−11 cm2/W, respectively, which yield one photon figure of merit, W=133 and two photon figure of merit, T=0.4. The degenerate pump-probe measurements show strong photoinduced bleaching with biexponential decay with time constants ~150 and 600 fs. ©2009 American Institute of Physics

A novel and effective technology for mitigating nitrous oxide emissions from land-applied manures

Land-applied manures produce nitrous oxide (N2O), a greenhouse gas (GHG). Land application can also result in ammonia (NH3) volatilisation, leading to indirect N2O emissions. Here, we summarise a glasshouse investigation into the potential for vermiculite, a clay with a high cation exchange capacity, to decrease N2O emissions from livestock manures (beef, pig, broiler, layer), as well as urea, applied to soils. Our hypothesis is that clays adsorb ammonium, thereby suppressing NH3 volatilisation and slowing N2O emission processes. We previously demonstrated the ability of clays to decrease emissions at the laboratory scale. In this glasshouse work, manure and urea application rates varied between 50 and 150 kg nitrogen (N)/ha. Clay : manure ratios ranged from 1 : 10 to 1 : 1 (dry weight basis). In the 1-year trial, the above-mentioned N sources were incorporated with vermiculite in 1 L pots containing Sodosol and Ferrosol growing a model pasture (Pennisetum clandestinum or kikuyu grass). Gas emissions were measured periodically by placing the pots in gas-tight bags connected to real-time continuous gas analysers. The vermiculite achieved significant (P ≤ 0.05) and substantial decreases in N2O emissions across all N sources (70% on average). We are currently testing the technology at the field scale; which is showing promising emission decreases (~50%) as well as increases (~20%) in dry matter yields. This technology clearly has merit as an effective GHG mitigation strategy, with potential associated agronomic benefits, although it needs to be verified by a cost–benefit analysis.

Monopolising Names? : The Protection of Geographical Indications in the European Community

Marketing of goods under geographical names has always been common. Aims to prevent abuse have given rise to separate forms of legal protection for geographical indications (GIs) both nationally and internationally. The European Community (EC) has also gradually enacted its own legal regime to protect geographical indications. The legal protection of GIs has traditionally been based on the idea that geographical origin endows a product exclusive qualities and characteristics. In today s world we are able to replicate almost any prod-uct anywhere, including its qualities and characteristics. One would think that this would preclude protec-tion from most geographical names, yet the number of geographical indications seems to be rising. GIs are no longer what they used to be. In the EC it is no longer required that a product is endowed exclusive characteristics by its geographical origin as long as consumers associate the product with a certain geo-graphical origin. This departure from the traditional protection of GIs is based on the premise that a geographical name extends beyond and exists apart from the product and therefore deserves protection itself. The thesis tries to clearly articulate the underlying reasons, justifications, principles and policies behind the protection of GIs in the EC and then scrutinise the scope and shape of the GI system in the light of its own justifications. The essential questions it attempts to aswer are (1) What is the basis and criteria for granting GI rights? (2) What is the scope of protection afforded to GIs? and (3) Are these both justified in the light of the functions and policies underlying granting and protecting of GIs? Despite the differences, the actual functions of GIs are in many ways identical to those of trade marks. Geographical indications have a limited role as source and quality indicators in allowing consumers to make informed and efficient choices in the market place. In the EC this role is undermined by allowing able room and discretion for uses that are arbitrary. Nevertheless, generic GIs are unable to play this role. The traditional basis for justifying legal protection seems implausible in most case. Qualities and charac-teristics are more likely to be related to transportable skill and manufacturing methods than the actual geographical location of production. Geographical indications are also incapable of protecting culture from market-induced changes. Protection against genericness, against any misuse, imitation and evocation as well as against exploiting the reputation of a GI seem to be there to protect the GI itself. Expanding or strengthening the already existing GI protection or using it to protect generic GIs cannot be justified with arguments on terroir or culture. The conclusion of the writer is that GIs themselves merit protection only in extremely rare cases and usually only the source and origin function of GIs should be protected. The approach should not be any different from one taken in trade mark law. GI protection should not be used as a means to mo-nopolise names. At the end of the day, the scope of GI protection is nevertheless a policy issue.

Country-scale carbon accounting of the vegetation and mineral soils of Finland

The increase in global temperature has been attributed to increased atmospheric concentrations of greenhouse gases (GHG), mainly that of CO2. The threat of severe and complex socio-economic and ecological implications of climate change have initiated an international process that aims to reduce emissions, to increase C sinks, and to protect existing C reservoirs. The famous Kyoto protocol is an offspring of this process. The Kyoto protocol and its accords state that signatory countries need to monitor their forest C pools, and to follow the guidelines set by the IPCC in the preparation, reporting and quality assessment of the C pool change estimates. The aims of this thesis were i) to estimate the changes in carbon stocks vegetation and soil in the forests in Finnish forests from 1922 to 2004, ii) to evaluate the applied methodology by using empirical data, iii) to assess the reliability of the estimates by means of uncertainty analysis, iv) to assess the effect of forest C sinks on the reliability of the entire national GHG inventory, and finally, v) to present an application of model-based stratification to a large-scale sampling design of soil C stock changes. The applied methodology builds on the forest inventory measured data (or modelled stand data), and uses statistical modelling to predict biomasses and litter productions, as well as a dynamic soil C model to predict the decomposition of litter. The mean vegetation C sink of Finnish forests from 1922 to 2004 was 3.3 Tg C a-1, and in soil was 0.7 Tg C a-1. Soil is slowly accumulating C as a consequence of increased growing stock and unsaturated soil C stocks in relation to current detritus input to soil that is higher than in the beginning of the period. Annual estimates of vegetation and soil C stock changes fluctuated considerably during the period, were frequently opposite (e.g. vegetation was a sink but soil was a source). The inclusion of vegetation sinks into the national GHG inventory of 2003 increased its uncertainty from between -4% and 9% to ± 19% (95% CI), and further inclusion of upland mineral soils increased it to ± 24%. The uncertainties of annual sinks can be reduced most efficiently by concentrating on the quality of the model input data. Despite the decreased precision of the national GHG inventory, the inclusion of uncertain sinks improves its accuracy due to the larger sectoral coverage of the inventory. If the national soil sink estimates were prepared by repeated soil sampling of model-stratified sample plots, the uncertainties would be accounted for in the stratum formation and sample allocation. Otherwise, the increases of sampling efficiency by stratification remain smaller. The highly variable and frequently opposite annual changes in ecosystem C pools imply the importance of full ecosystem C accounting. If forest C sink estimates will be used in practice average sink estimates seem a more reasonable basis than the annual estimates. This is due to the fact that annual forest sinks vary considerably and annual estimates are uncertain, and they have severe consequences for the reliability of the total national GHG balance. The estimation of average sinks should still be based on annual or even more frequent data due to the non-linear decomposition process that is influenced by the annual climate. The methodology used in this study to predict forest C sinks can be transferred to other countries with some modifications. The ultimate verification of sink estimates should be based on comparison to empirical data, in which case the model-based stratification presented in this study can serve to improve the efficiency of the sampling design.

Phylogeography and hybrid swarms: history of brackish water bivalve diversity in North European marginal seas

This study addressed the large-scale molecular zoogeography in two brackish water bivalve molluscs, Macoma balthica and Cerastoderma glaucum, and genetic signatures of the postglacial colonization of Northern Europe by them. The traditional view poses that M. balthica in the Baltic, White and Barents seas (i.e. marginal seas) represent direct postglacial descendants of the adjacent Northeast Atlantic populations, but this has recently been challenged by observations of close genetic affinities between these marginal populations and those of the Northeast Pacific. The primary aim of the thesis was to verify, quantify and characterize the Pacific genetic contribution across North European populations of M. balthica and to resolve the phylogeographic histories of the two bivalve taxa in range-wide studies using information from mitochondrial DNA (mtDNA) and nuclear allozyme polymorphisms. The presence of recent Pacific genetic influence in M. balthica of the Baltic, White and Barents seas, along with an Atlantic element, was confirmed by mtDNA sequence data. On a broader temporal and geographical scale, altogether four independent trans-Arctic invasions of Macoma from the Pacific since the Miocene seem to have been involved in generating the current North Atlantic lineage diversity. The latest trans-Arctic invasion that affected the current Baltic, White and Barents Sea populations probably took place in the early post-glacial. The nuclear genetic compositions of these marginal sea populations are intermediate between those of pure Pacific and Atlantic subspecies. In the marginal sea populations of mixed ancestry (Barents, White and Northern Baltic seas), the Pacific and Atlantic components are now randomly associated in the genomes of individual clams, which indicates both pervasive historical interbreeding between the previously long-isolated lineages (subspecies), and current isolation of these populations from the adjacent pure Atlantic populations. These mixed populations can be characterized as self-supporting hybrid swarms, and they arguably represent the most extensive marine animal hybrid swarms so far documented. Each of the three swarms still has a distinct genetic composition, and the relative Pacific contributions vary from 30 to 90 % in local populations. This diversity highlights the potential of introgressive hybridization to rapidly give rise to new evolutionarily and ecologically significant units in the marine realm. In the south of the Danish straits and in the Southern Baltic Sea, a broad genetic transition zone links the pure North Sea subspecies M. balthica rubra to the inner Baltic hybrid swarm, which has about 60 % of Pacific contribution in its genome. This transition zone has no regular smooth clinal structure, but its populations show strong genotypic disequilibria typical of a hybrid zone maintained by the interplay of selection and gene flow by dispersing pelagic larvae. The structure of the genetic transition is partly in line with features of Baltic water circulation and salinity stratification, with greater penetration of Atlantic genes on the Baltic south coast and in deeper water populations. In all, the scenarios of historical isolation and secondary contact that arise from the phylogeographic studies of both Macoma and Cerastoderma shed light to the more general but enigmatic patterns seen in marine phylogeography, where deep genetic breaks are often seen in species with high dispersal potential.

Ratios of T-cell immune-effectors with tumour associated macrophages and PD-1/PD-L1 axis immune-checkpoint molecules, as prognosticators in diffuse large B cell lymphoma: A population-based study

Background Risk-stratification of diffuse large B-cell lymphoma (DLBCL) requires identification of patients with disease that is not cured despite initial R-CHOP. Although the prognostic importance of the tumour microenvironment (TME) is established, the optimal strategy to quantify it is unknown. Methods The relationship between immune-effector and inhibitory (checkpoint) genes was assessed by NanoString™ in 252 paraffin-embedded DLBCL tissues. A model to quantify net anti-tumoural immunity as an outcome predictor was tested in 158 R-CHOP treated patients, and validated in tissue/blood from two independent R-CHOP treated cohorts of 233 and 140 patients respectively. Findings T and NK-cell immune-effector molecule expression correlated with tumour associated macrophage and PD-1/PD-L1 axis markers consistent with malignant B-cells triggering a dynamic checkpoint response to adapt to and evade immune-surveillance. A tree-based survival model was performed to test if immune-effector to checkpoint ratios were prognostic. The CD4*CD8:(CD163/CD68)*PD-L1 ratio was better able to stratify overall survival than any single or combination of immune markers, distinguishing groups with disparate 4-year survivals (92% versus 47%). The immune ratio was independent of and added to the revised international prognostic index (R-IPI) and cell-of-origin (COO). Tissue findings were validated in 233 DLBCL R-CHOP treated patients. Furthermore, within the blood of 140 R-CHOP treated patients immune-effector:checkpoint ratios were associated with differential interim-PET/CT+ve/-ve expression.

Using multi-label classification for acoustic pattern detection and assisting bird species surveys

Acoustics is a rich source of environmental information that can reflect the ecological dynamics. To deal with the escalating acoustic data, a variety of automated classification techniques have been used for acoustic patterns or scene recognition, including urban soundscapes such as streets and restaurants; and natural soundscapes such as raining and thundering. It is common to classify acoustic patterns under the assumption that a single type of soundscapes present in an audio clip. This assumption is reasonable for some carefully selected audios. However, only few experiments have been focused on classifying simultaneous acoustic patterns in long-duration recordings. This paper proposes a binary relevance based multi-label classification approach to recognise simultaneous acoustic patterns in one-minute audio clips. By utilising acoustic indices as global features and multilayer perceptron as a base classifier, we achieve good classification performance on in-the-field data. Compared with single-label classification, multi-label classification approach provides more detailed information about the distributions of various acoustic patterns in long-duration recordings. These results will merit further biodiversity investigations, such as bird species surveys.

Electrocardiographic repolarization variables in detecting myocardial infarction and ischemic injury : From body surface potential mapping to a single lead

The aim of the studies was to improve the diagnostic capability of electrocardiography (ECG) in detecting myocardial ischemic injury with a future goal of an automatic screening and monitoring method for ischemic heart disease. The method of choice was body surface potential mapping (BSPM), containing numerous leads, with intention to find the optimal recording sites and optimal ECG variables for ischemia and myocardial infarction (MI) diagnostics. The studies included 144 patients with prior MI, 79 patients with evolving ischemia, 42 patients with left ventricular hypertrophy (LVH), and 84 healthy controls. Study I examined the depolarization wave in prior MI with respect to MI location. Studies II-V examined the depolarization and repolarization waves in prior MI detection with respect to the Minnesota code, Q-wave status, and study V also with respect to MI location. In study VI the depolarization and repolarization variables were examined in 79 patients in the face of evolving myocardial ischemia and ischemic injury. When analyzed from a single lead at any recording site the results revealed superiority of the repolarization variables over the depolarization variables and over the conventional 12-lead ECG methods, both in the detection of prior MI and evolving ischemic injury. The QT integral, covering both depolarization and repolarization, appeared indifferent to the Q-wave status, the time elapsed from MI, or the MI or ischemia location. In the face of evolving ischemic injury the performance of the QT integral was not hampered even by underlying LVH. The examined depolarization and repolarization variables were effective when recorded in a single site, in contrast to the conventional 12-lead ECG criteria. The inverse spatial correlation of the depolarization and depolarization waves in myocardial ischemia and injury could be reduced into the QT integral variable recorded in a single site on the left flank. In conclusion, the QT integral variable, detectable in a single lead, with optimal recording site on the left flank, was able to detect prior MI and evolving ischemic injury more effectively than the conventional ECG markers. The QT integral, in a single-lead or a small number of leads, offers potential for automated screening of ischemic heart disease, acute ischemia monitoring and therapeutic decision-guiding as well as risk stratification.

Discovering mentorship information from author collaboration networks

Researchers are assessed from a researcher-centric perspective - by quantifying a researcher's contribution to the field. Citation and publication counts are some typical examples. We propose a student-centric measure to assess researchers on their mentoring abilities. Our approach quantifies benefits bestowed by researchers upon their students by characterizing the publication dynamics of research advisor-student interactions in author collaboration networks. We show that our measures could help aspiring students identify research advisors with proven mentoring skills. Our measures also help in stratification of researchers with similar ranks based on typical indices like publication and citation counts while being independent of their direct influences.

Ion channel gene variants predisposing to severe human ventricular arrhythmias

Congenital long QT syndrome (LQTS) with an estimated prevalence of 1:2000-1:10 000 manifests with prolonged QT interval on electrocardiogram and risk for ventricular arrhythmias and sudden death. Several ion channel genes and hundreds of mutations in these genes have been identified to underlie the disorder. In Finland, four LQTS founder mutations of potassium channel genes account for up to 40-70% of genetic spectrum of LQTS. Acquired LQTS has similar clinical manifestations, but often arises from usage of QT-prolonging medication or electrolyte disturbances. A prolonged QT interval is associated with increased morbidity and mortality not only in clinical LQTS but also in patients with ischemic heart disease and in the general population. The principal aim of this study was to estimate the actual prevalence of LQTS founder mutations in Finland and to calculate their effect on QT interval in the Finnish background population. Using a large population-based sample of over 6000 Finnish individuals from the Health 2000 Survey, we identified LQTS founder mutations KCNQ1 G589D (n=8), KCNQ1 IVS7-2A>G (n=1), KCNH2 L552S (n=2), and KCNH2 R176W (n=16) in 27 study participants. This resulted in a weighted prevalence estimate of 0.4% for LQTS in Finland. Using a linear regression model, the founder mutations resulted in a 22- to 50-ms prolongation of the age-, sex-, and heart rate-adjusted QT interval. Collectively, these data suggest that one of 250 individuals in Finland may be genetically predisposed to ventricular arrhythmias arising from the four LQTS founder mutations. A KCNE1 D85N minor allele with a frequency of 1.4% was associated with a 10-ms prolongation in adjusted QT interval and could thus identify individuals at increased risk of ventricular arrhythmias at the population level. In addition, the previously reported associations of KCNH2 K897T, KCNH2 rs3807375, and NOS1AP rs2880058 with QT interval duration were confirmed in the present study. In a separate study, LQTS founder mutations were identified in a subgroup of acquired LQTS, providing further evidence that congenital LQTS gene mutations may underlie acquired LQTS. Catecholaminergic polymorphic ventricular tachycardia (CPVT) is characterized by exercise-induced ventricular arrhythmias in a structurally normal heart and results from defects in the cardiac Ca2+ signaling proteins, mainly ryanodine receptor type 2 (RyR2). In a patient population of typical CPVT, RyR2 mutations were identifiable in 25% (4/16) of patients, implying that noncoding variants or other genes are involved in CPVT pathogenesis. A 1.1 kb RyR2 exon 3 deletion was identified in two patients independently, suggesting that this region may provide a new target for RyR2-related molecular genetic studies. Two novel RyR2 mutations showing a gain-of-function defect in vitro were identified in three victims of sudden cardiac death. Extended pedigree analyses revealed some surviving mutation carriers with mild structural abnormalities of the heart and resting ventricular arrhythmias suggesting that not all RyR2 mutations lead to a typical CPVT phenotype, underscoring the relevance of tailored risk stratification of a RyR2 mutation carrier.