The utilisation of vascular limb salvage services in the assessment and management of chronic limb-threatening ischaemia and diabetic foot ulceration: A systematic review.

Specialist vascular limb salvage services have gained prominence as a new model of care to help overcome barriers which exist in the management of patients with chronic limb-threatening ischaemia (CLTI) and/or diabetic foot ulceration (DFU). This systematic review aims to explore the nature of reported services, investigate their outcome in the management of CLTI/DFU, and assess the scope and quality of the evidence base to help make recommendations for future practice and research. A systematic search of MEDLINE, Embase, The Cochrane Library, Scopus and CINAHL, from 1st January 1995 to 18th January 2019, was performed. Specialist vascular limb salvage services were defined as those services conforming to the definition of "centres of excellence" within the 2019 Global Vascular Guidelines. A study protocol was registered at the International Prospective Register of Systematic Reviews (PROSPERO) (CRD42019123325). In total, 2260 articles were screened, with 12 articles (describing 11 services) included in a narrative synthesis. All services ran akin to the "toe-and-flow" model, with a number of services having additional core input from diabetology, microbiology, allied health professionals and/or internal/vascular medicine. Methodological weaknesses were identified within the design of the included articles and only one was deemed of high quality. The inception of services was associated with improved rates of major amputation; however, no significant changes in minor amputation or mortality rates were identified. Further research should adopt more a standardised study design and outcomes measures in order to improve the quality of evidence within the literature.

The contribution of rare and common variants in 30 genes to risk nicotine dependence.

Genetic and functional studies have revealed that both common and rare variants of several nicotinic acetylcholine receptor subunits are associated with nicotine dependence (ND). In this study, we identified variants in 30 candidate genes including nicotinic receptors in 200 sib pairs selected from the Mid-South Tobacco Family population with equal numbers of African Americans (AAs) and European Americans (EAs). We selected 135 of the rare and common variants and genotyped them in the Mid-South Tobacco Case-Control (MSTCC) population, which consists of 3088 AAs and 1430 EAs. None of the genotyped common variants showed significant association with smoking status (smokers vs non-smokers), Fagerström Test for ND scores or indexed cigarettes per day after Bonferroni correction. Rare variants in NRXN1, CHRNA9, CHRNA2, NTRK2, GABBR2, GRIN3A, DNM1, NRXN2, NRXN3 and ARRB2 were significantly associated with smoking status in the MSTCC AA sample, with weighted sum statistic (WSS) P-values ranging from 2.42 × 10(-3) to 1.31 × 10(-4) after 10(6) phenotype rearrangements. We also observed a significant excess of rare nonsynonymous variants exclusive to EA smokers in NRXN1, CHRNA9, TAS2R38, GRIN3A, DBH, ANKK1/DRD2, NRXN3 and CDH13 with WSS P-values between 3.5 × 10(-5) and 1 × 10(-6). Variants rs142807401 (A432T) and rs139982841 (A452V) in CHRNA9 and variants V132L, V389L, rs34755188 (R480H) and rs75981117 (N549S) in GRIN3A are of particular interest because they are found in both the AA and EA samples. A significant aggregate contribution of rare and common coding variants in CHRNA9 to the risk for ND (SKAT-C: P=0.0012) was detected by applying the combined sum test in MSTCC EAs. Together, our results indicate that rare variants alone or combined with common variants in a subset of 30 biological candidate genes contribute substantially to the risk of ND.

The impact of brief tobacco treatment training on practice behaviours, self-efficacy and attitudes among healthcare providers.

INTRODUCTION AND PURPOSE: The need for aggressive efforts to help tobacco users quit remains a healthcare priority. Brief interventions delivered in the healthcare environment continue to be a valuable component of a comprehensive tobacco control policy. Unfortunately, such treatments are offered less often than desired, and quality is variable. Previous research has demonstrated the value of training experiences in increasing treatment availability, quality, as well as improving clinical outcomes. Less is known about how specific clinical activities and other features are impacted as a function of training. These issues were explored within the context of a standardised 5A's (ASK, ADVISE, ASSESS, ASSIST, ARRANGE) brief intervention training program. METHODS: A variety of healthcare providers participated in this study. Survey methodology was employed to collect Practice Behaviour, Self-Efficacy and Attitude ratings at pretraining, post training and 6-month follow-up. Linear mixed effects models were used to evaluate primary outcomes, and linear regression to explore the relationships among clinical variables. RESULTS: Pretraining data suggested overall modest levels of tobacco treatment activity, with limited direct intervention (ASSIST) or follow-up (ARRANGE) efforts. The training experience was shown to have a substantial and sustained impact on 5A's Practice Behaviour ratings, and other clinical indicators (all Pre vs. Post and Pre vs. Follow-up comparisons p < 0.001). Self-Efficacy at post training predicted practice behaviours at follow-up (for ADVISE, ASSESS, ASSIST and ARRANGE: all p's < 0.05). CONCLUSIONS: The value of a structured training experience was confirmed, and findings served to clarify the specific nature of training program impact.

Analysis of brain and spinal MRI measures in a common domain to investigate directional neurodegeneration in motor neuron disease.

BACKGROUND: Magnetic resonance imaging (MRI) of the brain and cervical spinal cord is often performed in diagnostic evaluation of suspected motor neuron disease/amyotrophic lateral sclerosis (MND/ALS). Analysis of MRI-derived tissue damage metrics in a common domain facilitates group-level inferences on pathophysiology. This approach was applied to address competing hypotheses of directionality of neurodegeneration, whether anterograde, cranio-caudal dying-forward from precentral gyrus or retrograde, dying-back. METHODS: In this cross-sectional study, MRI was performed on 75 MND patients and 13 healthy controls. Precentral gyral thickness was estimated from volumetric T1-weighted images using FreeSurfer, corticospinal tract fractional anisotropy (FA) from diffusion tensor imaging using FSL, and cross-sectional cervical cord area between C1-C8 levels using Spinal Cord Toolbox. To analyse these multimodal data within a common domain, individual parameter estimates representing tissue damage at each corticospinal tract level were first converted to z-scores, referenced to healthy control norms. Mixed-effects linear regression models were then fitted to these z-scores, with gradients hypothesised to represent directionality of neurodegeneration. RESULTS: At group-level, z-scores did not differ significantly between precentral gyral and intracranial corticospinal tract tissue damage estimates (regression coefficient - 0.24, [95% CI - 0.62, 0.14], p = 0.222), but step-changes were evident between intracranial corticospinal tract and C1 (1.14, [95% CI 0.74, 1.53], p < 0.001), and between C5 and C6 cord levels (0.98, [95% CI 0.58, 1.38], p < 0.001). DISCUSSION: Analysis of brain and cervical spinal MRI data in a common domain enabled investigation of pathophysiological hypotheses in vivo. A cranio-caudal step-change in MND patients was observed, and requires further investigation in larger cohorts.

A Toxoplasma gondii mutant highlights the importance of translational regulation in the apicoplast during animal infection.

Toxoplasma gondii is an obligate intracellular parasite of all warm-blooded animals. We previously described a forward genetic screen to identify T. gondii mutants defective in the establishment of a chronic infection. One of the mutants isolated was disrupted in the 3' untranslated region (3'UTR) of an orthologue of bacterial translation elongation factor G (EFG). The mutant does not have a growth defect in tissue culture. Genetic complementation of this mutant with the genomic locus of TgEFG restores virulence in an acute infection mouse model. Epitope tagged TgEFG localized to the apicoplast, via a non-canonical targeting signal, where it functions as an elongation factor for translation in the apicoplast. Comparisons of TgEFG expression constructs with wild-type or mutant 3'UTRs showed that a wild-type 3'UTR is necessary for translation of TgEFG. In tissue culture, the TgEFG transcript is equally abundant in wild-type and mutant parasites; however, during an animal infection, the TgEFG transcript is increased more than threefold in the mutant. These results highlight that in tissue culture, translation in the apicoplast can be diminished, but during an animal infection, translation in the apicoplast must be fully functional.

Modification of a draw-over vaporizer for use with sevoflurane.

BACKGROUND: Draw-over anaesthesia is widely used throughout the developing world, in disaster areas and in military anaesthesia when the supply of pressurized oxygen is unreliable. To date, no draw-over vaporizer has been able to deliver sufficient concentrations of sevoflurane for use in inhalation induction of anaesthesia. A laboratory study to assess the performance of a new vaporizer (DDV2) to deliver sevoflurane in a wide range of situations is described. METHODS: In this study, the concentration of sevoflurane delivered at different dial settings (1-4%) and at different temperatures (20-40°C) in a draw-over mode was measured. The concentration of sevoflurane delivered at different dial settings with continuous flow (6 and 8 litre min(-1)) at 20°C was measured. The maximum possible concentration of sevoflurane that can be delivered by the DDV2 was measured at a continuous flow rate of 8 litre min(-1) at 20, 30, and 40°C. RESULTS: Concentrations of sevoflurane delivered in the draw-over mode were within 0.5% of dialled setting up to 30°C. Above this temperature, higher levels of vapour were delivered. With continuous flow, concentrations of sevoflurane at 20°C were within 0.5% of dialled setting and were stable throughout the duration of the experiment. On the 'induction' setting, concentrations of sevoflurane of between 6.4% and 10.1% could be delivered with continuous flow. CONCLUSIONS: The modifications to the DDV2 allow stable concentrations of sevoflurane to be delivered in draw-over and continuous flow modes over a range of temperatures. With continuous flow, concentrations of sevoflurane sufficient for induction of anaesthesia can be achieved.

Genome-wide association analyses suggested a novel mechanism for smoking behavior regulated by IL15.

Cigarette smoking is the leading preventable cause of death in the United States. Although smoking behavior has a significant genetic determination, the specific genes and associated mechanisms underlying the smoking behavior are largely unknown. Here, we carried out a genome-wide association study on smoking behavior in 840 Caucasians, including 417 males and 423 females, in which we examined approximately 380,000 single nucleotide polymorphisms (SNPs). We found that a cluster of nine SNPs upstream from the IL15 gene were associated with smoking status in males, with the most significant SNP, rs4956302, achieving a P-value (8.80 x 10(-8)) of genome-wide significance. Another SNP, rs17354547 that is highly conserved across multiple species achieved a P-value of 5.65 x 10(-5). These two SNPs, together with two additional SNPs (rs1402812 and rs4956396) were selected from the above nine SNPs for replication in an African-American sample containing 1251 subjects, including 412 males and 839 females. The SNP rs17354547 was replicated successfully in the male subgroup of the replication sample; it was associated with smoking quantity (SQ), the Heaviness of Smoking Index (HSI) and the Fagerstrom Test for Nicotine Dependence (FTND), with P-values of 0.031, 0.0046 and 0.019, respectively. In addition, a haplotype formed by rs17354547, rs1402812 and rs4956396 was also associated with SQ, HSI and FTND, achieving P-values of 0.039, 0.0093 and 0.0093, respectively. To further confirm our findings, we carried out an in silico replication study of the nine SNPs in a Framingham Heart Study sample containing 7623 Caucasians from 1731 families, among which, 3491 subjects were males and 4132 were females. Again, the male-specific association with smoking status was observed, for which seven of the nine SNPs achieved significant P-values (P<0.05) and two achieved marginally significant P-values (P<0.10) in males. Several of the nine SNPs, including the highly conserved one across species, rs17354547, are located at potential transcription factor binding sites, suggesting transcription regulation as a possible function for these SNPs. Through this function, the SNPs may modulate the gene expression of IL15, a key cytokine regulating immune function. As the immune system has long been recognized to influence drug addiction behavior, our association findings suggest a novel mechanism for smoking addiction involving immune modulation through the IL15 pathway.

Bayesian approach to automatic mass-spectrum peak identification in atom probe tomography.

Identification of mass-spectrum peaks is an indispensable step of an atom-probe tomography reconstruction process and can be a time-consuming procedure, vulnerable to errors, if performed manually. We propose a Bayesian approach to the peak identification problem, based on ranking of candidate ions according to their calculated posterior probabilities. The sample model is reconstructed by iteratively accepting top-ranked ions while taking into account prior information, models of experimental errors, and the already accepted ions. The designed approach has been applied to a number of time-of-flight mass spectra, measured for inorganic samples, and enabled a reliable construction of sample models, consistent with the results of manual analysis. Additionally, a "sliding window" approach for an accurate and efficient peak decomposition of a mass spectrum was established on the base of Fisher information.

Beta-arrestins 1 and 2 are associated with nicotine dependence in European American smokers.

On the basis of our previous identified linkage regions for nicotine dependence (ND), we selected seven and four single nucleotide polymorphisms (SNPs) in the beta-arrestins 1 (ARRB1) and 2 (ARRB2), respectively, to determine the associations of the two genes with ND in a total of 2037 subjects from 602 nuclear families of European American (EA) and African American (AA) origin. ND was assessed by Smoking Quantity (SQ), the Heaviness of Smoking Index (HSI) and the Fagerström Test for ND (FTND) score. Individual SNP analysis indicated that SNPs rs472112 within ARRB1 and rs4790694 within ARRB2 in the EA sample was significantly associated with HSI and FTND score, and the association of rs4790694 for ARRB2 remained significant after correction for multiple testing. Haplotype analysis revealed that haplotype C-G-C-G-G-T within ARRB1 at a frequency of 20%, formed by SNPs rs528833, rs1320709, rs480174, rs5786130, rs611908 and rs472112, was positively associated with HSI and FTND in EAs. We also found a haplotype within ARRB2, C-C-A-T at a frequency of 10.7%, formed by SNPs rs3786047, rs4522461, rs1045280 and rs4790694, that showed a significant positive association with HSI and FTND in the EA sample. No significant associations for either individual SNPs or major haplotype of both ARRB1 and ARRB2 were found in the AA sample. Further, the strength of these associations increased after removing the SQ component from HSI and FTND scores in both the EA and AA samples, suggesting that ARRB1 and ARRB2 play an important role in biological processes involved in the regulation of smoking urgency (that is time to smoke first cigarette). In summary, our results provide the first evidence of a significant association for ARRB1 and ARRB2 variants with ND in an EA sample.

Genome-wide linkage scan for nicotine dependence in European Americans and its converging results with African Americans in the Mid-South Tobacco Family sample.

Previously, we reported a genome-wide scan for nicotine dependence (ND) in the African American (AA) sample of the Mid-South Tobacco Family (MSTF) cohort. In this study, we conducted a genome-wide scan in 629 individuals representing 200 nuclear families of European American (EA) origin of the MSTF cohort with the goals of identifying vulnerability loci for ND in the EAs and determining converging regions across the ethnic groups. We examined 385 autosomal microsatellite markers for ND, which was assessed by smoking quantity (SQ), the Heaviness of Smoking Index (HSI) and the Fagerström test for ND (FTND). After performing linkage analyses using various methods implemented in the GENEHUNTER and SAGE programs, we found eight regions on chromosomes 2, 4, 9-12, 17 and 18 that met the criteria for suggestive linkage to at least one ND measure in the EA sample. Of these, the region on chromosome 4 at 43 cM showed suggestive linkage to indexed SQ, the HSI and the FTND, and the region on chromosome 9 at 24 cM showed suggestive linkage to the HSI and the FTND. To increase detection power, we analyzed a combined AA and EA sample using age, gender and ethnicity as covariates and found that the region on chromosome 12 near marker D12S372 showed significant linkage to SQ. Additionally, we found six regions on chromosomes 9-11, 13 and 18 that showed suggestive linkage to at least one ND measure in the combined sample. When we compared the linkage peaks detected for ND among the two samples and a combined sample, we found that four regions on chromosomes 9 (two regions), 11 and 18 overlapped. On the other hand, we identified five regions on chromosomes 2, 4, 10, 12 and 17 that showed linkage to ND only in the EA sample, and two regions on chromosomes 10 and 13 that showed linkage to ND only in the AA sample. For those linkages identified in only one sample, we found that the combined analysis of AA plus EA samples actually decreased the linkage signal. This indicates that some chromosomal regions may be more homogenous than others across the ethnic samples. All regions except for the one on chromosome 12 have been detected at nominally significant levels in other studies, providing independent replication of ND loci in different populations.

Bitter taste receptor gene polymorphisms are an important factor in the development of nicotine dependence in African Americans.

CONTEXT: Bitter sensitivity varies among individuals and ethnic groups partly due to polymorphisms in taste receptor genes (TAS2Rs). Although previous psychophysical studies suggest that taste status plays a role in nicotine dependence (ND), genetic evidence is lacking. OBJECTIVES: To determine whether single nucleotide polymorphisms (SNPs) in TAS2R16 and TAS2R38 are associated with ND and if the effects differ by sex and ethnicity. DESIGN, SETTING, AND PARTICIPANTS: 2037 individuals from 602 nuclear families of African American (AA) or European American (EA) origin were recruited from the US mid-south states during 1999-2004. MAIN OUTCOME MEASURES: ND was assessed by three measures: indexed Smoking Quantity (SQ), Heaviness of Smoking Index (HSI), and the Fagerström Test for Nicotine Dependence (FTND). Peripheral blood samples were obtained for DNA extraction and genotyping. RESULTS: The TAS2R38 taster haplotype PAV was inversely associated (p = 0.0165), and the non-taster haplotype AVI was positively associated (p = 0.0120), with SQ in AA smokers. The non-taster haplotype was positively associated with all ND measures in AA female smokers (p = 0.01 approximately 0.003). No significant associations were observed in the EA sample. CONCLUSIONS: TAS2R38 polymorphisms are an important factor in determining ND in AAs. Heightened oral sensitivity confers protection against ND. Conversely, decreased sensitivity represents a risk factor for ND, especially in AA females. Together, our findings suggest that taster status plays a role in governing the development of ND and may represent a way to identify individuals at risk for developing ND, particularly in AA smokers.

Modulation of chaperone gene expression in mutagenized Saccharomyces cerevisiae strains developed for recombinant human albumin production results in increased production of multiple heterologous proteins.

The yeast Saccharomyces cerevisiae has been successfully established as a commercially viable system for the production of recombinant proteins. Manipulation of chaperone gene expression has been utilized extensively to increase recombinant protein production from S. cerevisiae, focusing predominantly on the products of the protein disulfide isomerase gene PDI1 and the hsp70 gene KAR2. Here we show that the expression of the genes SIL1, LHS1, JEM1, and SCJ1, all of which are involved in regulating the ATPase cycle of Kar2p, is increased in a proprietary yeast strain, developed by several rounds of random mutagenesis and screening for increased production of recombinant human albumin (rHA). To establish whether this expression contributes to the enhanced-production phenotype, these genes were overexpressed both individually and in combination. The resultant strains showed significantly increased shake-flask production levels of rHA, granulocyte-macrophage colony-stimulating factor, and recombinant human transferrin.

Genetic Gains for Grain Yield in CIMMYT's Semi-Arid Wheat Yield Trials Grown in Suboptimal Environments.

Wheat (Triticum aestivum L.) is a major staple food crop grown worldwide on >220 million ha. Climate change is regarded to have severe effect on wheat yields, and unpredictable drought stress is one of the most important factors. Breeding can significantly contribute to the mitigation of climate change effects on production by developing drought-tolerant wheat germplasm. The objective of our study was to determine the annual genetic gain for grain yield (GY) of the internationally distributed Semi-Arid Wheat Yield Trials, grown during 2002-2003 to 2013-2014 and developed by the Bread Wheat Breeding program at the CIMMYT. We analyzed data from 740 locations across 66 countries, which were classified in low-yielding (LYE) and medium-yielding (MYE) environments according to a cluster analysis. The rate of GY increase (GYC) was estimated relative to four drought-tolerant wheat lines used as constant checks. Our results estimate that the rate of GYC in LYE was 1.8% (38.13 kg ha-1 yr-1), whereas in MYE, it was 1.41% (57.71 kg ha-1 yr-1). The increase in GYC across environments was 1.6% (48.06 kg ha-1 yr-1). The pedigrees of the highest yielding lines through the coefficient of parentage analysis indicated the utilization of three primary sources-'Pastor', 'Baviacora 92', and synthetic hexaploid derivatives-to develop drought-tolerant, high and stably performing wheat lines. We conclude that CIMMYT's wheat breeding program continues to deliver adapted germplasm for suboptimal conditions of diverse wheat growing regions worldwide.

Arsenic solid-phase speciation and reversible binding in long-term contaminated soils.

Historic arsenic contamination of soils occurs throughout the world from mining, industrial and agricultural activities. In Australia, the control of cattle ticks using arsenicals from the late 19th to mid 20th century has led to some 1600 contaminated sites in northern New South Wales. The effect of aging in As-mobility in two dip-site soil types, ferralitic and sandy soils, are investigated utilizing isotopic exchange techniques, and synchrotron X-ray adsorption spectroscopy (XAS). Findings show that historic soil arsenic is highly bound to the soils with >90% irreversibly bound. However, freshly added As (either added to historically loaded soils or pristine soils) has a significantly higher degree of As-accessibility. XAS data indicates that historic soil arsenic is dominated as Ca- (svenekite, & weilite), Al-(mansfieldite), and Fe- (scorodite) like mineral precipitates, whereas freshly added As is dominated by mineral adsorption surfaces, particularly the iron oxy-hydroxides (goethite and hematite), but also gibbsite and kaolin surfaces. SEM data further confirmed the presence of scorodite and mansfieldite formation in the historic contaminated soils. These data suggest that aging of historic soil-As has allowed neoformational mineral recrystallisation from surface sorption processes, which greatly reduces As-mobility and accessibility.

Taming the EHR (Electronic Health Record) - There is Hope.

With increasing diffusion of EHR technology over the last half decade, clinician burnout is rising. As healthcare is a complex and highly regulated field, the rapid and mass adoption of EHR technology has created disruption for highly skilled workers such as clinicians. Although, much has been written about dissatisfaction with the EHR (electronic health record), a paucity of immediate solutions exists in the literature. This article suggests three actionable steps health systems and clinicians can make to expedite gains from and mitigate the effect of the EHR on clinical practice.

Measurement of fallout radionuclides, (239)(,240)Pu and (137)Cs, in soil and creek sediment: Sydney Basin, Australia.

Soil and sediment samples from the Sydney basin were measured to ascertain fallout radionuclide activity concentrations and atom ratios. Caesium-137 ((137)Cs) was measured using gamma spectroscopy, and plutonium isotopes ((239)Pu and (240)Pu) were quantified using accelerator mass spectrometry (AMS). Fallout radionuclide activity concentrations were variable ranging from 0.6 to 26.1 Bq/kg for (137)Cs and 0.02-0.52 Bq/kg for (239+240)Pu. Radionuclides in creek sediment samples were an order of magnitude lower than in soils. (137)Cs and (239+240)Pu activity concentration in soils were well correlated (r(2) = 0.80) although some deviation was observed in samples collected at higher elevations. Soil ratios of (137)Cs/(239+240)Pu (decay corrected to 1/1/2014) ranged from 11.5 to 52.1 (average = 37.0 ± 12.4) and showed more variability than previous studies. (240)Pu/(239)Pu atom ratios ranged from 0.117 to 0.165 with an average of 0.146 (±0.013) and an error weighted mean of 0.138 (±0.001). These ratios are lower than a previously reported ratio for Sydney, and lower than the global average. However, these ratios are similar to those reported for other sites within Australia that are located away from former weapons testing sites and indicate that atom ratio measurements from other parts of the world are unlikely to be applicable to the Australian context.

Accumulation of plutonium in mammalian wildlife tissues following dispersal by accidental-release tests.

We examined the distribution of plutonium (Pu) in the tissues of mammalian wildlife inhabiting the relatively undisturbed, semi-arid former Taranaki weapons test site, Maralinga, Australia. The accumulation of absorbed Pu was highest in the skeleton (83% ± 6%), followed by muscle (10% ± 9%), liver (6% ± 6%), kidneys (0.6% ± 0.4%), and blood (0.2%). Pu activity concentrations in lung tissues were elevated relative to the body average. Foetal transfer was higher in the wildlife data than in previous laboratory studies. The amount of Pu in the gastrointestinal tract was highly elevated relative to that absorbed within the body, potentially increasing transfer of Pu to wildlife and human consumers that may ingest gastrointestinal tract organs. The Pu distribution in the Maralinga mammalian wildlife generally aligns with previous studies related to environmental exposure (e.g. Pu in humans from worldwide fallout), but contrasts with the partitioning models that have traditionally been used for human worker-protection purposes (approximately equal deposition in bone and liver) which appear to under-predict the skeletal accumulation in environmental exposure conditions.

Functional characterization and genetic mapping of alk8.

The novel type I TGFbeta family member receptor alk8 is expressed both maternally and zygotically. Functional characterization of alk8 was performed using microinjection studies of constitutively active (CA), kinase modified/dominant negative (DN), and truncated alk8 mRNAs. CA Alk8 expression produces ventralized embryos while DN Alk8 expression results in dorsalized phenotypes. Truncated alk8 expressing embryos display a subtle dorsalized phenotype closely resembling that of the identified zebrafish dorsalized mutant, lost-a-fin (laf). Single-strand conformation polymorphism (SSCP) analysis was used to map alk8 to zebrafish LG02 in a region demonstrating significant conserved synteny to Hsa2, and which contains the human alk2 gene, ACVRI. Altogether, these functional, gene mapping and phylogenetic analyses suggest that alk8 may be the zebrafish orthologue to human ACVRI (alk2), and therefore extend previous studies of Alk2 conducted in Xenopus.