Ancestral polymorphisms shape the adaptive radiation of Metrosideros across the Hawaiian Islands

Some of the most spectacular adaptive radiations begin with founder populations on remote islands. How genetically limited founder populations give rise to the striking phenotypic and ecological diversity characteristic of adaptive radiations is a paradox of evolutionary biology. We conducted an evolutionary genomics analysis of genus Metrosideros, a landscape-dominant, incipient adaptive radiation of woody plants that spans a striking range of phenotypes and environments across the Hawaiian Islands. Using nanopore-sequencing, we created a chromosome-level genome assembly for Metrosideros polymorpha var. incana and analyzed whole-genome sequences of 131 individuals from 11 taxa sampled across the islands. Demographic modeling and population genomics analyses suggested that Hawaiian Metrosideros originated from a single colonization event and subsequently spread across the archipelago following the formation of new islands. The evolutionary history of Hawaiian Metrosideros shows evidence of extensive reticulation associated with significant sharing of ancestral variation between taxa and secondarily with admixture. Taking advantage of the highly contiguous genome assembly, we investigated the genomic architecture underlying the adaptive radiation and discovered that divergent selection drove the formation of differentiation outliers in paired taxa representing early stages of speciation/divergence. Analysis of the evolutionary origins of the outlier single nucleotide polymorphisms (SNPs) showed enrichment for ancestral variations under divergent selection. Our findings suggest that Hawaiian Metrosideros possesses an unexpectedly rich pool of ancestral genetic variation, and the reassortment of these variations has fueled the island adaptive radiation.

Adaptive radiations exhibit extraordinary levels of morphological and ecological diversity (1). Although definitions of adaptive radiation vary (2–7), all center on ecological opportunity as a driver of adaptation and, ultimately, diversification (2, 8–10). Divergent selection, the primary mechanism underlying adaptive radiations, favors extreme phenotypes (11) and selects alleles that confer adaptation to unoccupied or under-utilized ecological niches. Differential adaptation results in divergence and, ultimately, reproductive isolation between populations (12). Adaptive radiations demonstrate the remarkable power of natural selection as a driver of biological diversity and provide excellent systems for studying evolutionary processes involved in diversification and speciation (13).Adaptive radiations on remote oceanic islands are especially interesting, as colonization of remote islands is expected to involve population bottlenecks that restrict genetic variation (14). Adaptive radiations in such settings are especially impressive and even paradoxical, given the generation of high species richness from an initially limited gene pool (15). Several classic examples of adaptive radiation occur on oceanic islands, such as Darwin’s finches from the Galapagos islands (16), anole lizards from the Caribbean islands (9), Hawaiian Drosophilids (17), and Hawaiian silverswords (18), to name a few.Recent advances in genome sequencing and analyses have greatly improved our ability to examine the genetics of speciation and adaptive radiation. By examining sequences of multiple individuals from their natural environment, it has become possible to “catch in the act” the speciation processes between incipient lineages (19). Genomic studies of early stage speciation show that differentiation accumulates in genomic regions that restrict the homogenizing effects of gene flow between incipient species (20). The number, size, and distribution of these genomic regions can shed light on evolutionary factors involved in speciation (19). Regions of high genomic differentiation can also form from evolutionary factors unrelated to speciation, such as linkage associated with recurrent background selection or selective sweeps on shared genomic features (21, 22).Genomic studies of lineages undergoing rapid ecological diversification have begun to reveal the evolutionary mechanisms underlying adaptive radiations. Importantly, these studies highlight the pivotal role of hybridization between populations and the consequent exchange of adaptive alleles that facilitates rapid speciation and the colonization of diverse niches (23–25). Most genomic studies of adaptive radiation involve animal systems, however, in particular, birds and fishes. In plants, genomic studies of adaptive radiation are sparse (26–28), and all examine continent-wide radiations. There are no genomics studies of plant adaptive radiations in geographically restricted systems such as remote islands. Because the eco-evolutionary scenarios associated with adaptive radiations are diverse (5, 29), whether commonalities identified in adaptive radiations in animals (23, 30) are applicable to plants is an open question. For example, the genetic architecture of animal adaptive radiations typically involves differentiation at a small number of genomic regions (31–33). In contrast, the limited insights available for plants suggest a more complex genetic architecture (26).We investigated the evolutionary genomics of adaptive radiation in Metrosideros Banks ex Gaertn. (Myrtaceae) across the Hawaiian Islands. Hawaiian Metrosideros is a landscape-dominant, hypervariable, and highly dispersible group of long-lived (possibly >650 y) (34) woody taxa that are nonrandomly distributed across Hawaii’s heterogeneous landscape, including cooled lava flows, wet forests and bogs, subalpine zones, and riparian zones (35, 36). About 25 taxa or morphotypes are distinguished by vegetative characters ranging from prostate plants that flower a few centimeters above ground to 30-m-tall trees, and leaves range dramatically in size, shape, pubescence, color, and rugosity (35, 37, 38); a majority of these forms are intraspecific varieties or races (provisional varieties) of the abundant species, Metrosideros polymorpha (35, 36, 38). Variation in leaf mass per area within the four Metrosideros taxa on Hawaii Island alone matches that observed for woody species globally (39). Common garden experiments (38, 40–44) and parent–offspring analysis (45) demonstrate heritability of taxon-diagnostic vegetative traits, indicating that taxa are distinct genetic groups and not the result of phenotypic plasticity. Metrosideros taxa display evidence of local adaptation to contrasting environments (46, 47), suggesting ecological divergent selection is responsible for diversification within the group (48). This diversification, which spans the past ∼3.1 to 3.9 million years (49, 50), has occurred despite the group’s high capacity for gene flow by way of showy bird-pollinated flowers and tiny wind-dispersed seeds (36, 51). Lastly, the presence of partial reproductive isolating barriers between taxa is consistent with the early stages of speciation (52). Here, we generated several genomic resources for Hawaiian Metrosideros and used these in population genomics analyses to gain deeper insights into the genomic architecture and evolutionary processes underlying this island adaptive radiation.     

Tachykinins Stimulate Release of Peptide Hormones (Glucagon-Like Peptide-1) and Paracrine (Somatostatin) and Neurotransmitter (Vasoactive Intestinal Polypeptide) from Porcine Ileum Through NK-1 Receptors

The effects of infusion of the two tachykinins,substance P (SP) and neurokinin A (NKA), and ofcapsaicin on the release of glucagon-like peptide-1(GLP-1), somatostatin, and vasoactive intestinalpolypeptide (VIP) were studied in isolated, vascularlyperfused ileal segments. SP (10-8 M) stimulated GLP-1,somatostatin, and VIP release to 141.8 ± 6.6% (N= 18), 230.3 ± 38.7% (N = 21), and 359.7 ±60.5% (N = 22) of basal output, respectively. NKA(10^-8 M) only stimulated VIP release (to181.2 ± 16.7% of basal release, N = 22). Theeffects of SP and NKA were blocked by the NK-1 receptorantagonist CP96345 (10^-6 M). Infusion of atropine(10^-6 M) had no effect on the SP-inducedGLP-1 release, but partly inhibited the effect of SP onsomatostatin and VIP release, and the effect of NKA onVIP release. Capsaicin infusions (10^-5 M) significantlystimulated both GLP-1, somatostatin, and VIP release to111.1 ± 4.5% (N = 9), 138.0 ± 15.8% (N =9) and 208.3 ± 63.8% (N = 8) of basal release,respectively. Simultaneous addition of receptor antagonists to all threetachykinin receptors (CP96345, SR48968, and SR142801,all at 10^-6 M) significantly inhibited theeffect of capsaicin on VIP release, whereas the releaseof GLP-1 and somatostatin was unaffected. Weconclude that tachykinins potently stimulate the releaseof GLP-1, somatostatin, and VIP in the porcine ileum viaNK-1 receptors. The effect on somatostatin and VIP is partly mediated via cholinergic neurons.Sensory neurons releasing tachykinins could be involvedin the regulation of VIPergic neurons.     

Children with celiac disease and high tTGA are genetically and phenotypically different

AIM:To investigate whether celiac disease(CD)patients with tissue-transglutaminase antibody(tTGA)≥100 U/mL are different from patients with lower tTGA levels.METHODS:Biopsy-proven(MarshⅢ)pediatric CD patients(n=116)were prospectively included between March 2009 and October 2012.The biopsies were evaluated by a single pathologist who was blinded to all of the patients’clinical data.The patients were distributed into 2 groups according to their tTGA level,which was measured using enzyme-linked immunoassay:tTGA≥100 U/mL and Ttga<100 U/mL.The patients’characteristics,symptoms,human leukocyte antigen(HLA)genotype and degree of histological involvement were compared between the 2 groups.RESULTS:A total of 34(29.3%)children had tTGA values<100 U/mL and 82(70.7%)tTGA levels of≥100 U/mL.Patients with high tTGA levels had lower average body weight-for-height standard deviation scores(SDS)than did patients with tTGA<100 U/mL(-0.20±1.19 SDS vs 0.23±1.03 SDS,P=0.025).In the low tTGA group,gastrointestinal symptoms were more common(97.1%vs 75.6%,P=0.006).More specifically,abdominal pain(76.5%vs 51.2%;P=0.012)and nausea(17.6%vs 3.7%,P=0.018)were more frequent among patients with low tTGA.In contrast,patients with solely extraintestinal manifestations were only present in the high tTGA group(18.3%,P=0.005).These patients more commonly presented with aphthous stomatitis(15.9%vs 0.0%,P=0.010)and anemia(32.9%vs 11.8%,P=0.019).In addition,when evaluating the number of CD-associated HLA-DQ heterodimers(HLA-DQ2.5,HLA-DQ2.2 and HLA-DQ8),patients with low tTGA levels more commonly had only1 disease-associated heterodimer(61.8%vs 31.7%,P=0.005),while patients with high tTGA more commonly had multiple heterodimers.Finally,patients with tTGA≥100 U/mL more often had a MarshⅢc lesion(73.2%vs 20.6%,P≤0.001)while in patients with low tTGA patchy lesions were more common(42.4%vs6.8%,P≤0.001).CONCLUSION:Patients with tTGA≥100 U/mL show several signs of more advanced disease.They also carry a larger number of CD     

Child and youth care in American and Europe: A history of fruitful mutual influences in special education and in therapy

Regarding services for children with special needs, there has been a long tradition of international exchange of new ideas and practices. Between Europe and North America these mutual influences have been particularly strong. Some important themes and issues in recent decades include the psychodynamic movement, the educateur profession, learning disabilities, behavior modification, Makarenko-inspired collectives for young people with drug problems in Scandinavia, and deinstitutionalization in Italy. There is a need for greater international communication but also for some caution against the precipitate adoption of novel and trendy ideas.     

A 17q21.31 microduplication, reciprocal to the newly described 17q21.31 microdeletion, in a girl with severe psychomotor developmental delay and dysmorphic craniofacial features

Array-CGH analysis using 244k Agilent oligoarray revealed a de novo 17q21.31 microduplication in a 10-year-old girl with severe psychomotor developmental delay, facial dysmorphism, microcephaly, abnormal digits and hirsutism. The duplication encompassed the MAPT and CRHR1 genes and was reciprocal to the recently described 17q21.31 microdeletion, associated with a recognizable clinical phenotype. Genotyping showed that the duplication was derived from non-allelic homologous recombination of paternal H1 and H2 haplotypes. To our knowledge this is the first report of a patient with a 17q21.31 microduplication.     

Effect of dairy calcium or supplementary calcium intake on postprandial fat metabolism, appetite, and subsequent energy intake

BACKGROUND: High calcium intake has been shown to increase fecal fat excretion. OBJECTIVE: Our aim was to examine whether a high calcium intake from dairy products or from supplements affects postprandial fat metabolism and appetite through fat malabsorption. DESIGN: Four different isocaloric meals were tested in 18 subjects according to a randomized crossover design. The test meals contained high (HC meal: 172 mg/MJ), medium (MC meal: 84 mg/MJ), or low (LC meal: 15 mg/MJ) amounts of calcium from dairy products or a high amount of calcium given as a calcium carbonate supplement (Suppl meal: 183 mg/MJ). Concentrations of plasma total triacylglycerol, chylomicron triacylglycerol, serum total cholesterol, HDL cholesterol, cholecystokinin, glucagon-like peptide 1, ghrelin, peptide YY, glucose, and insulin and appetite sensation were measured before and at regular intervals until 420 min postprandially. RESULTS: Dairy calcium significantly diminished the postprandial lipid response. The baseline adjusted area under the curve for chylomicron triacylglycerol was approximately 17% lower after the MC meal (P = 0.02) and approximately 19% lower after the HC meal (P = 0.007) than after the LC meal and approximately 15% lower after the MC meal (P = 0.0495) and approximately 17% lower after the HC meal (P = 0.02) than after the Suppl meal. No consistent effects of calcium on appetite sensation, or on energy intake at the subsequent meal, or on the postprandial responses of cholecystokinin, glucagon-like peptide 1, ghrelin, peptide YY, insulin, or glucose were observed. CONCLUSIONS: Increased calcium intakes from dairy products attenuate postprandial lipidemia, most probably because of reduced fat absorption, whereas supplementary calcium carbonate does not exert such an effect. This may be due to differences in the chemical form of calcium or to cofactors in dairy products. Calcium did not affect appetite sensation, glucose metabolism, or gut hormone secretion.     

Fat oxidation rates are higher during running compared with cycling over a wide range of intensities

The aim of the present study was to compare the intensity that elicits maximal fat oxidation (Fat(max)) determined using a cycle-ergometer and a treadmill-based protocol. Twelve moderately trained male subjects (66.9 +/- 1.8 mL. kg(-1). min(-1)) performed 2 graded exercise tests to exhaustion. One test was performed on a cycle ergometer while 1 test was performed on a motorized treadmill; stage duration during both trials was 3 minutes. Gas exchange measurements and heart rate (HR) recordings were performed throughout exercise. Fat oxidation rates were calculated using stoichiometric equations. Maximal fat oxidation rates were significantly higher during running compared with cycling (0.65 +/- 0.05 v 0.47 +/- 0.05 g. min(-1)). However, the intensity, which elicited maximal fat oxidation, was not significantly different between the cycle ergometer and treadmill test (62.1 +/- 3.1 v 59.2 +/- 2.8% Vo(2)max, respectively). Fat oxidation rates were significantly higher during the treadmill test compared with the cycle ergometer test from 55 to 80%Vo(2)max. Maximal oxygen uptake and maximal HR were significantly higher during the treadmill test. It was concluded that fat oxidation rates were higher during walking compared with cycling. Maximal fat oxidation was 28% higher when walking compared with cycling, but the intensity, which elicits maximal fat oxidation, is not different between these 2 exercise modes.     

Nutrient analysis explained for non-chemists by using interactive e-learning material

The diverse educational and professional background of individuals involved in food composition data work presents challenges in their training. In particular, it is difficult to explain chemical analysis of nutrients to individuals lacking a background in chemistry. Therefore an interactive e-learning module entitled “Nutrient Analysis for Non-chemists” was developed. Interactive e-learning provides a powerful set of tools to stimulate a learning process tailored to the needs and background of course members. In its design, specific aims derived from theories on learning and instruction were first formulated: motivate the student; provide an authentic learning context; visualize important concepts; promote active learning; and avoid unnecessary cognitive load. The e-learning module developed contains a large variety of interactive exercises, animations, and background information. The following four topics or cases were elaborated: Fats and Fatty Acids, Proteins and Amino Acids, Carbohydrates and Fiber, and Elements. In diverse educational settings, the module was evaluated by course members of postgraduate courses who highly appreciated it with an overall score of 4.5 on a 5-point scale. The e-learning module that was developed can be nicely integrated into a blended learning course on food composition data. However, it is also very well suited for individual distance learning.     

Factor V leiden homozygosity, dyspnea, and reduced pulmonary function

BACKGROUND: Factor V Leiden homozygosity predisposes patients to deep venous thrombosis and major pulmonary thromboembolism. Consequently, factor V Leiden homozygosity could, via unrecognized repeated minor pulmonary thromboemboli, cause chronic pulmonary disease. We tested the hypothesis that factor V Leiden homozygosity is associated with pulmonary symptoms and signs. METHODS: We studied a general population sample of 9253 individuals from the Copenhagen City Heart Study who were examined in 1991-1994. Of these, 6475 participants were also examined in 1976-1978 and/or 1981-1983. End points were dyspnea and lung function. RESULTS: Among 20 factor V Leiden homozygotes, a mean +/- SD of 32% +/- 11% had severe dyspnea compared with 6% +/- 0.3% of 8534 noncarriers (chi(2) test; P<.001). The corresponding adjusted odds ratio for severe dyspnea was 5.4 (95% confidence interval, 1.9-15.7). During follow-up, forced expiratory volume in 1 second and forced vital capacity were 5% to 10% lower in homozygotes vs noncarriers (analysis of variance; P = .003 and P = .03). The annual mean +/- SD loss of forced expiratory volume in 1 second and forced vital capacity was 39 +/- 8 mL/y and 35 +/- 8 mL/y in homozygotes vs 21 +/- 10 mL/y and 15 +/- 10 mL/y in noncarriers (t test; P = .03 and P = .04), respectively. Factor V Leiden heterozygosity (n = 699) did not influence pulmonary symptoms and signs. CONCLUSION: We demonstrate a previously unrecognized clinical presentation of factor V Leiden homozygosity with severe dyspnea and decreased pulmonary function.