Search

Bread wheat (Triticum aestivum) is a globally dominant crop and major source of calories and proteins for the human diet. Compared with its wild ancestors, modern bread wheat shows lower genetic diversity, caused by polyploidisation, domestication and breeding bottlenecks1,2. Wild wheat relatives represent genetic reservoirs, and harbour diversity and beneficial alleles that have not been incorporated into bread wheat. Here we establish and analyse extensive genome resources for Tausch’s goatgrass (Aegilops tauschii), the donor of the bread wheat D genome. Our analysis of 46 Ae. tauschiigenomes enabled us to clone a disease resistance gene and perform haplotype analysis across a complex disease resistance locus, allowing us to discern alleles from paralogous gene copies. We also reveal the complex genetic composition and history of the bread wheat D genome, which involves contributions from genetically and geographically discrete Ae. tauschiisubpopulations. Together, our results reveal the complex history of the bread wheat D genome and demonstrate the potential of wild relatives in crop improvement.

Conservation, restoration and land management are increasingly implemented at landscape scales1,2. However, because species interaction data are typically habitat- and/or guild-specific, exactly how those interactions connect habitats and affect the stability and function of communities at landscape scales remains poorly understood. We combine multi-guild species interaction data (plant–pollinator and three plant–herbivore–parasitoid communities, collected from landscapes with one, two or three habitats), a field experiment and a modelling approach to show that multi-habitat landscapes support higher species and interaction evenness, more complementary species interactions and more consistent robustness to species loss. These emergent network properties drive improved pollination success in landscapes with more habitats and are not explained by simply summing component habitat webs. Linking landscape composition, through community structure, to ecosystem function, highlights mechanisms by which several contiguous habitats can support landscape-scale ecosystem services.

Small Island Developing States (SIDS) include 37 UN member countries sharing economic, environmental, and social vulnerabilities and intractable health challenges. In over 80% of SIDS, more than one in six adults die prematurely from a non-communicable disease (NCD), with poor diet being a major factor. Complex upstream food system determinants include marginalised local food production and reliance on low nutritional quality food imports. These drivers need to be seen against colonial and post-colonial political–economic legacies as well as the environmental and climate crises that challenge local production systems. A range of policy commitments (eg, the 2023 Bridgetown Declaration on NCDs and Mental Health) highlight these complex interdependencies and call for cross-sectoral food system policies to improve food security, food sovereignty, and nutrition, including integrating measures for climate change adaptation and mitigation. Although addressing these intersecting challenges will also depend on global efforts, the unique approach of SIDS can inform other settings.

Sustainable agriculture requires balancing crop yields with the effects of pesticides on non-target organisms, such as bees and other crop pollinators. Field studies demonstrated that agricultural use of neonicotinoid insecticides can negatively affect wild bee species1,2, leading to restrictions on these compounds3. However, besides neonicotinoids, field-based evidence of the effects of landscape pesticide exposure on wild bees is lacking. Bees encounter many pesticides in agricultural landscapes4–9and the effects of this landscape exposure on colony growth and development of any bee species remains unknown. Here we show that the many pesticides found in bumble bee-collected pollen are associated with reduced colony performance during crop bloom, especially in simplified landscapes with intensive agricultural practices. Our results from 316 Bombus terrestriscolonies at 106 agricultural sites across eight European countries confirm that the regulatory system fails to sufficiently prevent pesticide-related impacts on non-target organisms, even for a eusocial pollinator species in which colony size may buffer against such impacts10,11. These findings support the need for postapproval monitoring of both pesticide exposure and effects to confirm that the regulatory process is sufficiently protective in limiting the collateral environmental damage of agricultural pesticide use.

Pangenomes are collections of annotated genome sequences of multiple individuals of a species1. The structural variants uncovered by these datasets are a major asset to genetic analysis in crop plants2. Here we report a pangenome of barley comprising long-read sequence assemblies of 76 wild and domesticated genomes and short-read sequence data of 1,315 genotypes. An expanded catalogue of sequence variation in the crop includes structurally complex loci that are rich in gene copy number variation. To demonstrate the utility of the pangenome, we focus on four loci involved in disease resistance, plant architecture, nutrient release and trichome development. Novel allelic variation at a powdery mildew resistance locus and population-specific copy number gains in a regulator of vegetative branching were found. Expansion of a family of starch-cleaving enzymes in elite malting barleys was linked to shifts in enzymatic activity in micro-malting trials. Deletion of an enhancer motif is likely to change the developmental trajectory of the hairy appendages on barley grains. Our findings indicate that allelic diversity at structurally complex loci may have helped crop plants to adapt to new selective regimes in agricultural ecosystems.

ObjectiveIdentification of patients at risk of adverse outcome from heart failure (HF) at an early stage is a priority. Growth differentiation factor (GDF)-15 has emerged as a potentially useful biomarker. This study sought to identify determinants of circulating GDF-15 and evaluate its prognostic value, in patients at risk of HF or with HF but before first hospitalisation.MethodsProspective, longitudinal cohort study of 2166 consecutive patients in stage A–C HF undergoing cardiovascular magnetic resonance and measurement of GDF-15. Multivariable linear regression investigated determinants of GDF-15. Cox proportional hazards modelling, Net Reclassification Improvement and decision curve analysis examined its incremental prognostic value. Primary outcome was a composite of first hospitalisation for HF or all-cause mortality. Median follow-up was 1093 (939–1231) days.ResultsMajor determinants of GDF-15 were age, diabetes and N-terminal pro-B-type natriuretic peptide, although despite extensive phenotyping, only around half of the variability of GDF-15 could be explained (R20.51). Log-transformed GDF-15 was the strongest predictor of outcome (HR 2.12, 95% CI 1.71 to 2.63) and resulted in a risk prediction model with higher predictive accuracy (continuous Net Reclassification Improvement 0.26; 95% CI 0.13 to 0.39) and with greater clinical net benefit across the entire range of threshold probabilities.ConclusionIn patients at risk of HF, or with HF but before first hospitalisation, GDF-15 provides unique information and is highly predictive of hospitalisation for HF or all-cause mortality, leading to more accurate risk stratification that can improve clinical decision making.Trial registration numberNCT02326324.

COVID-19 has led to marked increases in healthcare worker distress. Studies of these phenomena are often limited to a particular element of distress or a specific subset of healthcare workers. We administered the Moral Injury Symptom Scale for Healthcare Professionals, Copenhagen Burnout Inventory, Patient Health Questionnaire-9, and Generalized Anxiety Disorder-7 via online survey to 17,000 employees of a large academic medical center between December 2021 and February 2022. A total of 1945 participants completed the survey. Across all roles, the prevalence of moral injury, burnout, depression, and anxiety were 40.9%, 35.3%–60.6%, 25.4%, and 24.8%, respectively. Furthermore, 8.1% had been bothered by thoughts that they would be better off dead or of hurting themselves for “several days” or more frequently. Healthcare workers across all roles and practice settings are experiencing unsustainable levels of distress, with 1 in 12 regularly experiencing thoughts of self-harm.

People living with HIV (PLWH) are at higher risk of reactivation of Chagas disease, a neglected tropical disease, caused by Trypanosoma cruzi. There are no data from UK HIV clinics on the prevalence of T. cruzi. We implemented T. cruziscreening at our clinic as part of routine care for PLWH with epidemiological risk factors. Among 86 patients screened, none had positive serology: one seropositive patient was identified due to increased clinician awareness. Implementing T. cruziscreening as part of routine clinical care was feasible, though labour intensive and identified at-risk individuals.

The introgression of chromosome segments from wild relatives is an established strategy to enrich crop germplasm with disease-resistance genes1. Here we use mutagenesis and transcriptome sequencing to clone the leaf rust resistance gene Lr9, which was introduced into bread wheat from the wild grass species Aegilops umbellulata2. We established that Lr9encodes an unusual tandem kinase fusion protein. Long-read sequencing of a wheat Lr9introgression line and the putative Ae. umbellulata Lr9donor enabled us to assemble the ~28.4-Mb Lr9translocation and to identify the translocation breakpoint. We likewise cloned Lr58, which was reportedly introgressed from Aegilopstriuncialis3, but has an identical coding sequence compared to Lr9. Cytogenetic and haplotype analyses corroborate that the two genes originate from the same translocation event. Our work sheds light on the emerging role of kinase fusion proteins in wheat disease resistance, expanding the repertoire of disease-resistance genes for breeding.

Atopic dermatitis (AD) is the most common chronic inflammatory skin disease in the general population. Skin barrier dysfunction is the central abnormality leading to AD. The cause of skin barrier dysfunction is complex and rooted in genetic mutations, interactions between the immune pathway activation and epithelial cells, altered host defense mechanisms, as well as environmental influences that cause epithelial cell activation and release of alarmins (such as thymic stromal lymphopoietin) that can activate the type 2 immune pathway, including generation of interleukins 4 and 13, which induces defects in the skin barrier and increased allergic inflammation. These inflammatory pathways are further influenced by environmental factors including the microbiome (especially Staphylococcus aureus), air pollution, stress, and other factors. As such, AD is a syndrome involving multiple phenotypes, all of which have in common skin barrier dysfunction as a key contributing factor. Understanding mechanisms leading to skin barrier dysfunction in AD is pointing to the development of new topical and systemic treatments in AD that helps keep skin borders secure and effectively treat the disease.

Early supports to enhance social development in children with autism are widely promoted. While oxytocin has a crucial role in mammalian social development, its potential role as a medication to enhance social development in humans remains unclear. We investigated the efficacy, tolerability, and safety of intranasal oxytocin in young children with autism using a double-blind, randomized, placebo-controlled, clinical trial, following a placebo lead-in phase. A total of 87 children (aged between 3 and 12 years) with autism received 16 International Units (IU) of oxytocin (n= 45) or placebo (n= 42) nasal spray, morning and night (32 IU per day) for twelve weeks, following a 3-week placebo lead-in phase. Overall, there was no effect of oxytocin treatment over time on the caregiver-rated Social Responsiveness Scale (SRS-2) (p= 0.686). However, a significant interaction with age (p= 0.028) showed that for younger children, aged 3–5 years, there was some indication of a treatment effect. Younger children who received oxytocin showed improvement on caregiver-rated social responsiveness ( SRS-2). There was no other evidence of benefit in the sample as a whole, or in the younger age group, on the clinician-rated Clinical Global Improvement Scale (CGI-S), or any secondary measure. Importantly, placebo effects in the lead-in phase were evident and there was support for washout of the placebo response in the randomised phase. Oxytocin was well tolerated, with more adverse side effects reported in the placebo group. This study suggests the need for further clinical trials to test the benefits of oxytocin treatment in younger populations with autism.

ABSTRACTResearch shows that college education and college major are related to attitudes about gender. However, little research has focused on within-major gender differences, and studies that do frequently rely on small, college-specific samples. Larger, national datasets frequently do not include information on college major and are often cross-sectional, making it difficult to account for selection processes. Using the General Social Survey and several advanced statistical analyses that partially address selection effects, we ask: “Do patterns of gender ideology vary among those who have completed different college majors?” We find that men with degrees in education are more egalitarian than other men, while women with degrees in primarily male-dominated fields like mathematics and engineering have more egalitarian views than other women. Conditioning on college major selection, we find that women with degrees in professional areas, health, humanities, and technology, engineering, and mathematics (TEM) fields are more egalitarian than men with the same degree, while men with degrees in education have more egalitarian gender ideologies than women with the same degree.

Einkorn (Triticum monococcum) was the first domesticated wheat species, and was central to the birth of agriculture and the Neolithic Revolution in the Fertile Crescent around 10,000 years ago1,2. Here we generate and analyse 5.2-Gb genome assemblies for wild and domesticated einkorn, including completely assembled centromeres. Einkorn centromeres are highly dynamic, showing evidence of ancient and recent centromere shifts caused by structural rearrangements. Whole-genome sequencing analysis of a diversity panel uncovered the population structure and evolutionary history of einkorn, revealing complex patterns of hybridizations and introgressions after the dispersal of domesticated einkorn from the Fertile Crescent. We also show that around 1% of the modern bread wheat (Triticum aestivum) A subgenome originates from einkorn. These resources and findings highlight the history of einkorn evolution and provide a basis to accelerate the genomics-assisted improvement of einkorn and bread wheat.

Background: Inhomogeneous patterns of chromatin-chromatin contacts within 10–100-kb-sized regions of the genome are a generic feature of chromatin spatial organization. These features, termed topologically associating domains (TADs), have led to the loop extrusion factor (LEF) model. Currently, our ability to model TADs relies on the observation that in vertebrates TAD boundaries are correlated with DNA sequences that bind CTCF, which therefore is inferred to block loop extrusion. However, although TADs feature prominently in their Hi-C maps, non-vertebrate eukaryotes either do not express CTCF or show few TAD boundaries that correlate with CTCF sites. In all of these organisms, the counterparts of CTCF remain unknown, frustrating comparisons between Hi-C data and simulations. Results: To extend the LEF model across the tree of life, here, we propose the conserved-current loop extrusion (CCLE) modelthat interprets loop-extruding cohesin as a nearly conserved probability current. From cohesin ChIP-seq data alone, we derive a position-dependent loop extrusion rate, allowing for a modified paradigm for loop extrusion, that goes beyond solely localized barriers to also include loop extrusion rates that vary continuously. We show that CCLE accurately predicts the TAD-scale Hi-C maps of interphase Schizosaccharomyces pombe, as well as those of meiotic and mitotic Saccharomyces cerevisiae, demonstrating its utility in organisms lacking CTCF. Conclusions: The success of CCLE in yeasts suggests that loop extrusion by cohesin is indeed the primary mechanism underlying TADs in these systems. CCLE allows us to obtain loop extrusion parameters such as the LEF density and processivity, which compare well to independent estimates.

Heart failure (HF) most commonly occurs in patients who have had a myocardial infarction (MI), but factors other than MI size may be deterministic. Fibrosis of myocardium remote from the MI is associated with adverse remodeling. We aimed to 1) investigate the association between remote myocardial fibrosis, measured using cardiovascular magnetic resonance (CMR) extracellular volume fraction (ECV), and HF and death following MI, 2) identify predictors of remote myocardial fibrosis in patients with evidence of MI and determine the relationship with infarct size.

ABSTRACTAnimals must sense their surroundings and be able to distinguish between relevant and irrelevant cues. An enticing area of research aims to uncover the mechanisms by which animals respond to chemical signals that constitute critical sensory input. In this review, we describe the principles of a model chemosensory system: the Drosophilalarva. While distinct in many ways, larval behaviour is reminiscent of the dogmatic goals of life: to reach a stage of reproductive potential. It takes into account a number of distinct and identifiable parameters to ultimately provoke or modulate appropriate behavioural output. In this light, we describe current knowledge of chemosensory anatomy, genetic components, and the processing logic of chemical cues. We outline recent advancements and summarize the hypothesized neural circuits of sensory systems. Furthermore, we note yet-unanswered questions to create a basis for further investigation of molecular and systemic mechanisms of chemosensation in Drosophilaand beyond.

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.jsr.2009.04.005 Byline: Charles C. Liu (a), Simon G. Hosking (a)(b), Michael G. Lenne (a) Keywords: Fatigue; Sleepiness; Lane position; Steering wheel; Intelligent Transport Systems Abstract: Driver drowsiness is a significant contributing factor to road crashes. One approach to tackling this issue is to develop technological countermeasures for detecting driver drowsiness, so that a driver can be warned before a crash occurs. Author Affiliation: (a) Accident Research Centre, Monash University, Building 70, Clayton VIC, 3800, Australia (b) Air Operations Division, Defence Science & Technology Organisation, Fisherman's Bend, VIC, 3207, Australia

Plant immunity is triggered following the perception of pathogen-derived molecules by plant receptor proteins. Two protein families, membrane-localized receptor-like kinases (RLK) and intracellular nucleotide-binding leucine-rich repeat (NLR) receptors, play key roles in pathogen perception and in the initiation of downstream signaling cascades that lead to defense responses. In addition to RLKs and NLRs, recent research has identified additional protein families that function as plant resistance (R) proteins. In particular, the botanical tribe Triticeae, which includes the globally important crop species wheat and barley, has played a significant role in the discovery of ‘unconventional’ R proteins. In this review, we will summarize the current knowledge on unconventional R genes in Triticeae and the proteins they encode. The knowledge on unconventional R proteins will not only broaden our understanding of plant–pathogen interactions but also have great implications for disease resistance breeding in crops.

The study objectives were to describe the incidence, risk factors, and outcomes of acute kidney injury after cardiopulmonary bypass in Jamaica.

Diagnostics and treatment of developmental dysplasia of the hip (DDH) are highly variable in clinical practice. To obtain more uniform and evidence-based treatment pathways, we developed the ‘Dutch guideline for DDH in children < 1 year’. This study describes recommendations for unstable and decentered hips.The Appraisal of Guidelines for Research and Evaluation criteria (AGREE II) were applied. A systematic literature review was performed for six predefined guideline questions. Recommendations were developed, based on literature findings, as well as harms/benefits, patient/parent preferences, and costs (GRADE).The systematic literature search resulted in 843 articles and 11 were included. Final guideline recommendations are (i) Pavlik harness is the preferred first step in the treatment of (sub) luxated hips; (ii) follow-up with ultrasound at 3–4 and 6–8 weeks; (iii) if no centered and stable hip after 6–8 weeks is present, closed reduction is indicated; (iv) if reduction is restricted by limited hip abduction, adductor tenotomy is indicated; (v) in case of open reduction, the anterior, anterolateral, or medial approach is advised, with the choice based on surgical preference and experience; (vi) after reduction (closed/open), a spica cast is advised for 12 weeks, followed by an abduction device in case of residual dysplasia.This study presents recommendations on the treatment of decentered DDH, based on the available literature and expert consensus, as Part 2 of the first official and national evidence-based ‘Guideline for DDH in children < 1 year’. Part 1 describes the guideline sections on centered DDH in a separate article.

Despite the high incidence of developmental dysplasia of the hip (DDH), treatment is very diverse. Therefore, the Dutch Orthopedic Society developed a clinical practice guideline with recommendations for optimal and uniform treatment of DDH. This article summarizes the guideline on centered DDH (i.e. Graf types 2A–C).The guideline development followed the criteria of Appraisal of Guidelines for Research and Evaluation II. A systematic literature review was performed to identify randomized controlled trials and comparative cohort studies including children <1 year with centered DDH. Articles were included that compared (1) treatment with observation, (2) different abduction devices, (3) follow-up frequencies, and (4) discontinuation methods. Recommendations were based on Grading Recommendations Assessment, Development, and Evaluation, which included the literature, clinical experience and consensus, patient and parent comfort, and costs.Out of 430 potentially relevant articles, 5 comparative studies were included. Final guideline recommendations were (1) initially observe 3-month-old patients with centered DDH, start abduction treatment if the hip does not normalize after 6–12 weeks; (2) prescribe a Pavlik harness to children <6 months with persisting DDH on repeated ultrasonography, consider alternative abduction devices for children >6 months; (3) assess patients every 6 weeks; and (4) discontinue the abduction device when the hip has normalized or when the child is 12 months.This paper presents a summary of part 1 of the first evidence-based guideline for treatment of centered DDH in children <1 year. Part 2 presents the guideline on decentered DDH in a separate article.

Myocardial fibrosis, measured using magnetic resonance extracellular volume (ECV), associates with adverse outcome in heart failure with preserved ejection fraction (HFpEF). In the PIROUETTE (The Pirfenidone in Patients with Heart Failure and Preserved Left Ventricular Ejection Fraction) trial, the novel anti-fibrotic agent pirfenidone reduced myocardial fibrosis. We sought to identify baseline characteristics that associate with myocardial fibrotic burden, the change in myocardial fibrosis over a year, and predict response to pirfenidone in patients with HFpEF. Amongst patients enrolled in the PIROUETTE trial (n = 107), linear regression models were used to assess the relationship between baseline variables and baseline myocardial ECV, with change in myocardial ECV adjusting for treatment allocation, and to identify variables that modified the pirfenidone treatment effect. Body mass index, left atrial reservoir strain, haemoglobin and aortic distensibility were associated with baseline ECV in stepwise modelling, and systolic blood pressure, and log N-terminal pro B-type natriuretic peptide were associated with baseline ECV in clinically-guided modelling. QRS duration, left ventricular mass and presence of an infarct at baseline were associated with an increase in ECV from baseline to week 52. Whilst QRS duration, presence of an infarct, global longitudinal strain and left atrial strain modified the treatment effect of pirfenidone when considered individually, no variable modified treatment effect on multivariable modelling. Baseline characteristics were identified that associate with myocardial fibrosis and predict change in myocardial fibrosis. No variables that independently modify the treatment effect of pirfenidone were identified (PIROUETTE, NCT02932566).

OBJECTIVE--The purpose of this study was to compare quality of life (QoL) and treatment satisfaction using insulin glargine plus insulin lispro with that using NPH insulin plus unmodified human insulin [...]

Background: Longer-term mortality benefit and cost-effectiveness for abdominal aortic aneurysm (AAA) screening are uncertain. Objective: To estimate the benefits, in terms of AAA-related and all-cause mortality, and cost-effectiveness of ultrasonography screening for AAA in a group that was invited to screening compared with a group that was not invited at a mean 7-year follow-up. Design: Randomized trial. Setting: 4 centers in the United Kingdom. Patients: Population-based sample of 67 770 men age 65 to 74 years. Intervention: Patients with an AAA detected at screening had surveillance and were offered surgery after predefined criteria were met. Measurements: Mortality data were obtained after flagging on the national database. Unit costs obtained from large samples were applied to individual event data for the cost analysis. Results: The hazard ratio was 0.53 (95% Cl, 0.42 to 0.68) for AAA-related mortality in the group invited for screening. The rupture rate in men with normal results on initial ultrasonography has remained low: 0.54 rupture (Cl, 0.25 to 1.02 ruptures) per 10 000 person-years. In terms of all-cause mortality, the observed hazard ratio was 0.96 (Cl, 0.93 to 1.00). At the 7-year follow-up, cost-effectiveness was estimated at $19 500 (Cl, $12 400 to $39 800) per life-year gained based on AAA-related mortality and $7600 (Cl, $3300 to [infinity]) per life-year gained based on all-cause death. (All values are reported in U.S. dollars [U.K. 1[pounds sterling] = U.S. $1.58]). Limitation: Inclusion of deaths from aortic aneurysm at an unspecified site, which may include some thoracic aortic aneurysms, may have underestimated the treatment effect. Conclusions: These results from a large, pragmatic randomized trial show that the early mortality benefit of screening ultrasonography for AAA is maintained in the longer term and that the cost-effectiveness of screening improves over time.

Summary points Inconsistency of studies' resets in a meta-analysis reduces the confidence of recommendations about treatment Inconsistency is usually assessed with a test for heterogeneity, but problems of power can [...]

Identifying people who are at risk of being admitted to hospital (hospitalised) for heart failure and death, and particularly those who have not previously been hospitalised for heart failure, is a priority. We aimed to develop and externally validate a prognostic model involving contemporary deep phenotyping that can be used to generate individual risk estimates of hospitalisation for heart failure or all-cause mortality in patients with, or at risk of, heart failure, but who have not previously been hospitalised for heart failure.

Mining has been a major contributor to economic development in Australia since British arrival in the late 1700s, with little to no thought regarding the long-term environmental consequences. This study assesses the metal pollution legacy caused by different smelting methods and mining activities during the British colonialism in western Tasmania. This region was the largest copper producer in the Southern Hemisphere during the 20th century. Lake sediments from Basin Lake and Owen Tarn, 12 and 5 km from Queenstown’s mines, respectively, were used to reconstruct historical metal contamination. Temporal changes in metal concentrations (iron, copper, arsenic, selenium and lead) were assessed in relation to the scale of mining activities and the technologies used. Sedimentation rates and metal influxes increased from 1900, reflecting the beginning of copper mining in Mount Lyell. Observed metal concentrations peaked after 1930, coinciding with the introduction of large-scale open-cut operations and an expansion of the mining machinery used. All elements underwent at least minor enrichment (EF 1-3) during the lifespan of the mine, with lead and copper undergoing extremely severe enrichment (EF > 50). Although smelters contributed to metal increases in the lakes, large open-cut large operations in the 1930s contributed most to metal contamination. Local metal deposition from mining-related activities decreased significantly once operations decreased, with selenium and arsenic decreasing nearly to background levels within 50 years. Lead and copper, the elements which underwent major enrichment, have not yet reached background values. The ecological consequences include the current degraded local landscape, poor water quality and disrupted local biota. Knowledge about the environmental impacts of mining in western Tasmania is less known compared to other sites around the world with a similar history. Our results demonstrate the urgent need to develop better policies and remediation programs that can mitigate the consequences of metal pollution from abandoned mines in Australia.

Type 1 diabetes is a complex disorder with multiple genetic loci and environmental factors contributing to disease etiology. In the current study, a human type 1 diabetes candidate region on chromosome 1q42 was mapped at high marker density in a panel of 616 multiplex type 1 diabetic families. To facilitate the identification and evaluation of candidate genes, a physical map of the 7-cM region surrounding the maximum logarithm of odds (LOD) score (2.46, P = 0.0004) was constructed. Genes were identified in the 500-kb region surrounding the marker yielding the peak LOD score and evaluated for polymorphism by resequencing. Single-nucleotide polymorphisms (SNPs) identified in these genes as well as other anonymous markers were tested for allelic association with type 1 diabetes by both family-based and case-control methods. A haplotype formed by common alleles at three adjacent markers (D1S225, D1S2383, and D1S251) was preferentially transmitted to affected offspring in type 1 diabetic families (nominal P = 0.006). These findings extend the evidence supporting the existence of a type 1 diabetes susceptibility locus on chromosome 1q42 and identify a candidate region amenable to positional cloning efforts., Type 1 diabetes arises from tissue-specific autoimmune destruction of the insulin-secreting pancreatic islet cells and results in life-long dependence on exogenously administered insulin. Both genetic and environmental factors contribute to [...]

The sting of the jack jumper ant in Tasmania can lead to fatal anaphylactic shock. Article describes four fatal cases in 1980 through 1999, and recommends better education of people with known sting allergy, increased use of adrenaline therapy and development of better hyposensitization therapy.