Development of a graphical resilience framework to understand a coupled human-natural system in a remote arid highland of Baja California Sur.

Hydrological systems are important to society as water resources and effective management requires an understanding of how water and humans influence each other. To describe human-water connections it is necessary to bridge social and natural sciences. To this end, we construct an interdisciplinary graphical framework for evaluating potential human-water system resilience, which is a tool to show the spatial and temporal response to system change of both human and natural systems. This helps to identify the ways that human responses to change relate to changing water resources and identifies important thresholds and potential disconnects that would create vulnerability. We further use this tool to describe a dynamic, coupled human-water system present in the arid Sierra de la Giganta region of Baja California Sur, Mexico. In this remote mountain range, there is a community (self-identifying as Choyeros) who rely on spring water for ranching and subsistence. Using mixed methods of hydrogeochemistry and anthropology, we describe spatial connectivity and temporal changes of both hydrologic and social systems. We use these observations to examine the Choyero response to system changes and explore the topology of the various approaches that the community employs to adapt to changing water availability. The framework guides dialogue to constrain the types of policies, strategies, and responses that help to promote the sustainability of water resources. This framework can be used to compare systems across spatio-temporal scales to produce more generalizable and communicable insights of coupled human-natural systems. Supplementary Information: The online version contains supplementary material available at 10.1007/s11625-022-01101-6.

SMA Identified: Clinical and Molecular Findings From a Sponsored Testing Program for Spinal Muscular Atrophy in More Than 2,000 Individuals.

Background: Spinal muscular atrophy (SMA) linked to chromosome 5q is an inherited progressive neuromuscular disorder with a narrow therapeutic window for optimal treatment. Although genetic testing provides a definitive molecular diagnosis that can facilitate access to effective treatments, limited awareness and other barriers may prohibit widespread testing. In this study, the clinical and molecular findings of SMA Identified-a no-charge sponsored next-generation sequencing (NGS)-based genetic testing program for SMA diagnosis-are reported. Methods: Between March 2018 and March 2020, unrelated individuals who had a confirmed or suspected SMA diagnosis or had a family history of SMA were eligible. All individuals underwent diagnostic genetic testing for SMA at clinician discretion. In total, 2,459 individuals were tested and included in this analysis. An NGS-based approach interrogated sequence and copy number of SMN1 and SMN2. Variants were confirmed by multiplex ligation-dependent probe amplification sequencing. Individuals were categorized according to genetic test results: diagnostic (two pathogenic SMN1 variants), nearly diagnostic (SMN1 exon-7 deletion with a variant of uncertain significance [VUS] in SMN1 or SMN2), indeterminate VUS (one VUS in SMN1 or SMN2), carrier (heterozygous SMN1 deletion only), or negative (no pathogenic variants or VUS in SMN1 or SMN2). Diagnostic yield was calculated. Genetic test results were analyzed based on clinician-reported clinical features and genetic modifiers (SMN2 copy number and SMN2 c.859G>C). Results: In total, 2,459 unrelated individuals (mean age 24.3 ± 23.0 years) underwent diagnostic testing. The diagnostic yield for diagnostic plus nearly diagnostic results was 31.3% (n = 771/2,459). Age of onset and clinical presentation varied considerably for individuals and was dependent on SMN2 copy number. Homozygous deletions represented the most common genetic etiology (96.2%), with sequence variants also observed in probands with clinical diagnoses of SMA. Conclusions: Using a high-yield panel test in a no-charge sponsored program early in the diagnostic odyssey may open the door for medical interventions in a substantial number of individuals with SMA. These findings have potential implications for clinical management of probands and their families.

Optimal Control of Plant Disease Epidemics with Clean Seed Usage.

The distribution and use of pathogen-free planting material ("clean seeds") is a promising method to control plant diseases in developing countries. We address the question of minimizing disease prevalence in plants through the optimal usage of clean seeds. We consider the simplest possible S-I model together with a simple economic criterion to be maximized. The static optimization problem shows a diversity of possible outcomes depending on economical and epidemiological parameters. We derive a simple condition showing to what extent subsidizing clean seeds relative to the epidemiological features of the disease may help eradicate or control the disease. Then we consider dynamic optimal control and Pontryagin's maximum principle to study the optimal usage of clean seeds to control the disease. The dynamical results are comparable to the static ones and are even simpler in some sense. In particular, the condition on the critical subsidy rate that makes clean seed usage economically viable is unchanged from the static optimization case. We discuss how these results may apply to the control of maize lethal necrosis in East-Africa.

Gadolinium DTPA Enhancement Characteristics of the Rat Sciatic Nerve after Crush Injury at 4.7T.

BACKGROUND AND PURPOSE: Traumatic peripheral nerve injury is common and results in loss of function and/or neuropathic pain. MR neurography is a well-established technique for evaluating peripheral nerve anatomy and pathology. However, the Gd-DTPA enhancement characteristics of acutely injured peripheral nerves have not been fully examined. This study was performed to determine whether acutely crushed rat sciatic nerves demonstrate Gd-DTPA enhancement and, if so, to evaluate whether enhancement is affected by crush severity. MATERIALS AND METHODS: In 26 rats, the sciatic nerve was crushed with either surgical forceps (6- to 20-N compressive force) or a microvascular/microaneurysm clip (0.1-0.6 N). Animals were longitudinally imaged at 4.7T for up to 30 days after injury. T1WI, T2WI, and T1WI with Gd-DTPA were performed. RESULTS: Forceps crush injury caused robust enhancement between days 3 and 21, while clip crush injury resulted in minimal-to-no enhancement. Enhancement after forceps injury peaked at 7 days and was seen a few millimeters proximal to, in the region of, and several centimeters distal to the site of crush injury. Enhancement after forceps injury was statistically significant compared with clip injury between days 3 and 7 (P < .04). CONCLUSIONS: Gd-DTPA enhancement of peripheral nerves may only occur above a certain crush-severity threshold. This phenomenon may explain the intermittent observation of Gd-DTPA enhancement of peripheral nerves after traumatic injury. The observation of enhancement may be useful in judging the severity of injury after nerve trauma.

Role of adipocyte mitochondria in inflammation, lipemia and insulin sensitivity in humans: effects of pioglitazone treatment.

BACKGROUND/OBJECTIVES: To gain further insight into the role of adipocyte mitochondria in systemic lipid metabolism, inflammation and insulin sensitivity in humans and to provide a better understanding of the mechanisms of action of the peroxisome proliferator-activated receptor gamma agonist pioglitazone. SUBJECTS/METHODS: Mitochondrial DNA (mtDNA) copy number, mitochondrial distribution, mitochondrial and overall cellular protein abundances as well as intrinsic mitochondrial function of subcutaneous adipocytes were assessed by real-time quantitative PCR, MitoTracker staining, global proteomics analyses and NADH cytochrome c reductase activity in insulin-sensitive, normal-glucose-tolerant (NGT) individuals and age, gender, adiposity-matched insulin-resistant individuals with abnormal glucose tolerant (AGT) before and after 3 months of pioglitazone treatment. RESULTS: mtDNA copy number/adipocyte and mtDNA copy number/adipocyte volume were ~55% and ~4-fold lower in AGT than in NGT, respectively, and correlated positively with the M-value of euglycemic clamps and high-density lipoprotein, and negatively with fasting plasma triglyceride, tumor necrosis factor-α and interleukin-6 levels in the entire cohort. mtDNA copy number/adipocyte volume also correlated positively with plasma adiponectin. Pioglitazone, which improved insulin sensitivity, plasma lipids and inflammation, increased the mitochondrial copy number, and led to a redistribution of mitochondria from a punctate to a more reticular pattern as observed in NGT. This was accompanied by disproportionately increased abundances of mitochondrial proteins, including those involved in fat oxidation and triglyceride synthesis. Pioglitazone also increased the abundance of collagen VI and decreased the abundance of cytoskeletal proteins. NADH cytochrome c reductase activity of isolated adipocyte mitochondria was similar in AGT and NGT and unaltered by pioglitazone. CONCLUSIONS: Adipocyte mitochondria are deficient in insulin-resistant individuals and correlate with systemic lipid metabolism, inflammation and insulin sensitivity. Pioglitazone induces mitochondrial biogenesis and reorganization as well as the synthesis of mitochondrial proteins including those critical for lipid metabolism. It also alters extracellular matrix and cytoskeletal proteins. The intrinsic function of adipocyte mitochondria appears unaffected in insulin resistance and by pioglitazone.International Journal of Obesity advance online publication, 31 October 2017; doi:10.1038/ijo.2017.192.

A Study To Assess The Prevalence Of Exercise-Induced Bronchoconstriction In Inter-County Hurling.

Exercise-Induced Bronchoconstriction (EIB) is an acute, transient airway narrowing occurring after exercise which may impact athletic performance. Studies report 10% of the general population and up to 90% of asthmatics experience EIB. Ninety-two players from three elite hurling squads underwent a spirometric field-based provocation test with real-time heart rate monitoring and lactate measurements to ensure adequate exertion. Players with a new diagnosis of EIB and those with a negative field-test but with a previous label of EIB or asthma underwent further reversibility testing and if negative, methacholine challenge. Eight (8.7%) of players had EIB, with one further athlete having asthma with a negative field test. Interestingly, only three out of 12 players who had previously been physician-labelled with EIB or asthma had their diagnosis objectively confirmed. Our study highlights the role of objective testing in EIB.

Improved integrative framework combining association data with gene expression features to prioritize Crohn's disease genes.

Genome-wide association studies in Crohn's disease (CD) have identified 140 genome-wide significant loci. However, identification of genes driving association signals remains challenging. Furthermore, genome-wide significant thresholds limit false positives at the expense of decreased sensitivity. In this study, we explored gene features contributing to CD pathogenicity, including gene-based association data from CD and autoimmune (AI) diseases, as well as gene expression features (eQTLs, epigenetic markers of expression and intestinal gene expression data). We developed an integrative model based on a CD reference gene set. This integrative approach outperformed gene-based association signals alone in identifying CD-related genes based on statistical validation, gene ontology enrichment, differential expression between M1 and M2 macrophages and a validation using genes causing monogenic forms of inflammatory bowel disease as a reference. Besides gene-level CD association P-values, association with AI diseases was the strongest predictor, highlighting generalized mechanisms of inflammation, and the interferon-γ pathway particularly. Within the 140 high-confidence CD regions, 598 of 1328 genes had low prioritization scores, highlighting genes unlikely to contribute to CD pathogenesis. For select regions, comparably high integrative model scores were observed for multiple genes. This is particularly evident for regions having extensive linkage disequilibrium such as the IBD5 locus. Our analyses provide a standardized reference for prioritizing potential CD-related genes, in regions with both highly significant and nominally significant gene-level association P-values. Our integrative model may be particularly valuable in prioritizing rare, potentially private, missense variants for which genome-wide evidence for association may be unattainable.

Sequencing an Ashkenazi reference panel supports population-targeted personal genomics and illuminates Jewish and European origins.

The Ashkenazi Jewish (AJ) population is a genetic isolate close to European and Middle Eastern groups, with genetic diversity patterns conducive to disease mapping. Here we report high-depth sequencing of 128 complete genomes of AJ controls. Compared with European samples, our AJ panel has 47% more novel variants per genome and is eightfold more effective at filtering benign variants out of AJ clinical genomes. Our panel improves imputation accuracy for AJ SNP arrays by 28%, and covers at least one haplotype in ≈ 67% of any AJ genome with long, identical-by-descent segments. Reconstruction of recent AJ history from such segments confirms a recent bottleneck of merely ≈ 350 individuals. Modelling of ancient histories for AJ and European populations using their joint allele frequency spectrum determines AJ to be an even admixture of European and likely Middle Eastern origins. We date the split between the two ancestral populations to ≈ 12-25 Kyr, suggesting a predominantly Near Eastern source for the repopulation of Europe after the Last Glacial Maximum.

A study to assess inhaler technique and its potential impact on asthma control in patients attending an asthma clinic.

OBJECTIVES: The aim of this study was to evaluate inhaler technique and symptom control in patients with poorly controlled asthma at baseline and at follow-up in a dedicated asthma clinic in a tertiary hospital. We also investigated the impact of asthma on these patients' quality of life. METHODS: Patients referred to a newly established asthma clinic in Cork University Hospital were prospectively recruited over a 6-month period. Their inhaler technique was assessed by a pulmonary nurse specialist using a validated scoring system. They received instruction on inhaler usage when scores were suboptimal. Patients completed a validated asthma control questionnaire (ACQ) and asthma quality of life questionnaire (AQLQ). At follow-up 3-4 months later, the inhaler technique was reassessed and the ACQ questionnaire repeated. RESULTS: Forty-six patients were recruited (female = 74%), and 40/46 were followed up. Mean [SD] FEV1 % predicted at baseline = 76.5% [21.5]. About 63% of the patients were classified as incorrectly using their inhaler at their initial assessment. This decreased to 20% at follow-up, indicating an overall significant improvement in inhaler usage post-training (p = 0.003). ACQ scores improved significantly from median [interquartile range] 2.70 [1.66] to 2.00 [1.90] (p = 0.002). Baseline measurement indicated that patients' quality of life was moderately affected by asthma, with a median AQLQ score of 4.75 [1.97]. CONCLUSION: This study demonstrates the importance of educating and formally assessing inhaler technique in patients with asthma as a part of their ongoing clinical review.

Common misconceptions in molecular ecology: echoes of the modern synthesis.

The field of molecular ecology has burgeoned into a large discipline spurred on by technical innovations that facilitate the rapid acquisition of large amounts of genotypic data, by the continuing development of theory to interpret results, and by the availability of computer programs to analyse data sets. As the discipline grows, however, misconceptions have become enshrined in the literature and are perpetuated by routine citations to other articles in molecular ecology. These misconceptions hamper a better understanding of the processes that influence genetic variation in natural populations and sometimes lead to erroneous conclusions. Here, we consider eight misconceptions commonly appearing in the literature: (i) some molecular markers are inherently better than other markers; (ii) mtDNA produces higher F(ST) values than nDNA; (iii) estimated population coalescences are real; (iv) more data are always better; (v) one needs to do a Bayesian analysis; (vi) selective sweeps influence mtDNA data; (vii) equilibrium conditions are critical for estimating population parameters; and (viii) having better technology makes us smarter than our predecessors. This is clearly not an exhaustive list and many others can be added. It is, however, sufficient to illustrate why we all need to be more critical of our own understanding of molecular ecology and to be suspicious of self-evident truths.

Reefs and islands of the Chagos Archipelago, Indian Ocean: why it is the world's largest no-take marine protected area.

The Chagos Archipelago was designated a no-take marine protected area (MPA) in 2010; it covers 550 000 km2, with more than 60 000 km2 shallow limestone platform and reefs. This has doubled the global cover of such MPAs.It contains 25-50% of the Indian Ocean reef area remaining in excellent condition, as well as the world's largest contiguous undamaged reef area. It has suffered from warming episodes, but after the most severe mortality event of 1998, coral cover was restored after 10 years.Coral reef fishes are orders of magnitude more abundant than in other Indian Ocean locations, regardless of whether the latter are fished or protected.Coral diseases are extremely low, and no invasive marine species are known.Genetically, Chagos marine species are part of the Western Indian Ocean, and Chagos serves as a 'stepping-stone' in the ocean.The no-take MPA extends to the 200 nm boundary, and. includes 86 unfished seamounts and 243 deep knolls as well as encompassing important pelagic species.On the larger islands, native plants, coconut crabs, bird and turtle colonies were largely destroyed in plantation times, but several smaller islands are in relatively undamaged state.There are now 10 'important bird areas', coconut crab density is high and numbers of green and hawksbill turtles are recovering.Diego Garcia atoll contains a military facility; this atoll contains one Ramsar site and several 'strict nature reserves'. Pollutant monitoring shows it to be the least polluted inhabited atoll in the world. Today, strict environmental regulations are enforced.Shoreline erosion is significant in many places. Its economic cost in the inhabited part of Diego Garcia is very high, but all islands are vulnerable.Chagos is ideally situated for several monitoring programmes, and use is increasingly being made of the archipelago for this purpose.

Conserved features of cancer cells define their sensitivity to HAMLET-induced death; c-Myc and glycolysis.

HAMLET is the first member of a new family of tumoricidal protein-lipid complexes that kill cancer cells broadly, while sparing healthy, differentiated cells. Many and diverse tumor cell types are sensitive to the lethal effect, suggesting that HAMLET identifies and activates conserved death pathways in cancer cells. Here, we investigated the molecular basis for the difference in sensitivity between cancer cells and healthy cells. Using a combination of small-hairpin RNA (shRNA) inhibition, proteomic and metabolomic technology, we identified the c-Myc oncogene as one essential determinant of HAMLET sensitivity. Increased c-Myc expression levels promoted sensitivity to HAMLET and shRNA knockdown of c-Myc suppressed the lethal response, suggesting that oncogenic transformation with c-Myc creates a HAMLET-sensitive phenotype. Furthermore, HAMLET sensitivity was modified by the glycolytic state of tumor cells. Glucose deprivation sensitized tumor cells to HAMLET-induced cell death and in the shRNA screen, hexokinase 1 (HK1), 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 1 and hypoxia-inducible factor 1α modified HAMLET sensitivity. HK1 was shown to bind HAMLET in a protein array containing ∼8000 targets, and HK activity decreased within 15 min of HAMLET treatment, before morphological signs of tumor cell death. In parallel, HAMLET triggered rapid metabolic paralysis in carcinoma cells. Tumor cells were also shown to contain large amounts of oleic acid and its derivatives already after 15 min. The results identify HAMLET as a novel anti-cancer agent that kills tumor cells by exploiting unifying features of cancer cells such as oncogene addiction or the Warburg effect.

Human ATP synthase beta is phosphorylated at multiple sites and shows abnormal phosphorylation at specific sites in insulin-resistant muscle.

AIMS/HYPOTHESIS: Insulin resistance in skeletal muscle is linked to mitochondrial dysfunction in obesity and type 2 diabetes. Emerging evidence indicates that reversible phosphorylation regulates oxidative phosphorylation (OxPhos) proteins. The aim of this study was to identify and quantify site-specific phosphorylation of the catalytic beta subunit of ATP synthase (ATPsyn-beta) and determine protein abundance of ATPsyn-beta and other OxPhos components in skeletal muscle from healthy and insulin-resistant individuals. METHODS: Skeletal muscle biopsies were obtained from lean, healthy, obese, non-diabetic and type 2 diabetic volunteers (each group n = 10) for immunoblotting of proteins, and hypothesis-driven identification and quantification of phosphorylation sites on ATPsyn-beta using targeted nanospray tandem mass spectrometry. Volunteers were metabolically characterised by euglycaemic-hyperinsulinaemic clamps. RESULTS: Seven phosphorylation sites were identified on ATPsyn-beta purified from human skeletal muscle. Obese individuals with and without type 2 diabetes were characterised by impaired insulin-stimulated glucose disposal rates, and showed a approximately 30% higher phosphorylation of ATPsyn-beta at Tyr361 and Thr213 (within the nucleotide-binding region of ATP synthase) as well as a coordinated downregulation of ATPsyn-beta protein and other OxPhos components. Insulin increased Tyr361 phosphorylation of ATPsyn-beta by approximately 50% in lean and healthy, but not insulin-resistant, individuals. CONCLUSIONS/INTERPRETATION: These data demonstrate that ATPsyn-beta is phosphorylated at multiple sites in human skeletal muscle, and suggest that abnormal site-specific phosphorylation of ATPsyn-beta together with reduced content of OxPhos proteins contributes to mitochondrial dysfunction in insulin resistance. Further characterisation of phosphorylation of ATPsyn-beta may offer novel targets of treatment in human diseases with mitochondrial dysfunction, such as diabetes.

Contrast-enhanced MR imaging of brain lesions: a large-scale intraindividual crossover comparison of gadobenate dimeglumine versus gadodiamide.

BACKGROUND AND PURPOSE: The higher relaxivity of gadobenate dimeglumine compared with gadodiamide is potentially advantageous for contrast-enhanced brain MR imaging. This study intraindividually compared 0.1-mmol/kg doses of these agents for qualitative and quantitative lesion enhancement. MATERIALS AND METHODS: Adult patients with suggested or known brain lesions underwent 2 identical MR imaging examinations at 1.5T, one with gadobenate dimeglumine and the other with gadodiamide. The agents were administered in randomized order separated by 3-14 days. Imaging sequences and postinjection acquisition timing were identical for the 2 examinations. Three blinded readers evaluated images qualitatively for diagnostic information (lesion extent, delineation, morphology, enhancement, and global preference) and quantitatively for contrast-to-noise ratio (CNR). RESULTS: One hundred thirteen of 138 enrolled patients successfully underwent both examinations. Final diagnoses were intra-axial tumor, metastasis, extra-axial tumor, or other (47, 27, 18, and 21 subjects, respectively). Readers 1, 2, and 3 demonstrated global preference for gadobenate dimeglumine in 63 (55.8%), 77 (68.1%), and 73 (64.6%) patients, respectively, compared with 3, 2, and 3 patients for gadodiamide (P < .0001, all readers). Highly significant (P < .0001, all readers) preference for gadobenate dimeglumine was demonstrated for all qualitative end points and for CNR (increases of 23.3%-34.7% and 42.4%-48.9% [spin-echo and gradient-refocused echo sequences, respectively] for gadobenate dimeglumine compared with gadodiamide). Inter-reader agreement was good for all evaluations (kappa = 0.47-0.69). Significant preference for gadobenate dimeglumine was demonstrated for all lesion subgroup analyses. CONCLUSION: Significantly greater diagnostic information and lesion enhancement are achieved on brain MR imaging with 0.1-mmol/kg gadobenate dimeglumine compared with gadodiamide at an equivalent dose.

High connectivity on a global scale in the pelagic wahoo, Acanthocybium solandri (tuna family Scombridae).

The population genetic structure and phylogeography of wahoo, Acanthocybium solandri, were investigated on a global scale with intron six of lactate dehydrogenase-A (ldhA6, 8 locations, N = 213) and mtDNA cytochrome b (Cytb, 10 locations, N = 322). Results show extensive sharing of haplotypes across the wahoo's entire global range, and analyses were unable to detect significant structure (nuclear F(ST) = 0.0125, P = 0.106; mtDNA Phi(ST) < 0.0001, P = 0.634). Power analyses indicated 95% confidence in detecting nuclear F(ST) > or = 0.0389 and mtDNA Phi(ST) > or = 0.0148. These findings appear unique, as most other tunas, billfishes, and oceanic sharks exhibit significant population structure on the scale of East-West Atlantic, Atlantic vs. Indian-Pacific, or East-West Pacific. Overall nuclear heterozygosity (H = 0.714) and mtDNA haplotype diversity (h = 0.918) are both high in wahoo, while overall mtDNA nucleotide diversity (pi = 0.006) and nuclear nucleotide diversity (pi = 0.004) are uniformly low, indicating a recent increase in population size. Coalescence analyses yield an estimate of effective female population size (NeF) at approximately 816,000, and a population bottleneck approximately 690,000 years ago. However, conclusions about population history from our Cytb data set are not concordant with a control region survey, a finding that will require further investigation. This is the first example of a vertebrate with a single globally distributed population, a finding we attribute to extensive dispersal at all life stages. The indications of a worldwide stock for wahoo reinforce the mandate for international cooperation on fisheries issues.

Global phylogeography and seascape genetics of the lemon sharks (genus Negaprion).

Seascapes are complex environments, and populations are often isolated by factors other than distance. Here we investigate the role of coastal habitat preference and philopatry in shaping the distribution and population structure of lemon sharks. The genus Negaprion comprises the amphiatlantic lemon shark (N. brevirostris), with a relict population in the eastern Pacific, and its Indo-West Pacific sister species, the sicklefin lemon shark (N. acutidens). Analyzing 138 individuals throughout the range of N. brevirostris (N = 80) and N. acutidens (N = 58) at microsatellite loci (nine and six loci, respectively) and the mitochondrial control region, we find evidence of allopatric speciation corresponding to the Tethys Sea closure (10-14 million years ago) and isolation of the eastern Pacific N. brevirostris population via the emergence of the Isthmus of Panama (approximately 3.5 million years ago). There is significant isolation by oceanic distance (R(2) = 0.89, P = 0.005), defined as the maximum distance travelled at depths greater than 200 m. We find no evidence for contemporary transatlantic gene flow (m, M = 0.00) across an oceanic distance of approximately 2400 km. Negaprion acutidens populations in Australia and French Polynesia, separated by oceanic distances of at least 750 km, are moderately differentiated (F(ST) = 0.070-0.087, P < or = 0.001; Phi(ST) = 0.00, P = 0.99), with South Pacific archipelagos probably serving as stepping stones for rare dispersal events. Migration between coastally linked N. brevirostris populations is indicated by nuclear (m = 0.31) but not mitochondrial (m < 0.001) analyses, possibly indicating female natal site fidelity. However, philopatry is equivocal in N. acutidens, which has the lowest control region diversity (h = 0.28) of any shark yet studied. Restricted oceanic dispersal and high coastal connectivity stress the importance of both local and international conservation efforts for these threatened sharks.

Population genetic structure of Earth's largest fish, the whale shark (Rhincodon typus).

Large pelagic vertebrates pose special conservation challenges because their movements generally exceed the boundaries of any single jurisdiction. To assess the population structure of whale sharks (Rhincodon typus), we sequenced complete mitochondrial DNA control regions from individuals collected across a global distribution. We observed 51 single site polymorphisms and 8 regions with indels comprising 44 haplotypes in 70 individuals, with high haplotype (h = 0.974 +/- 0.008) and nucleotide diversity (pi = 0.011 +/- 0.006). The control region has the largest length variation yet reported for an elasmobranch (1143-1332 bp). Phylogenetic analyses reveal no geographical clustering of lineages and the most common haplotype was distributed globally. The absence of population structure across the Indian and Pacific basins indicates that oceanic expanses and land barriers in Southeast Asia are not impediments to whale shark dispersal. We did, however, find significant haplotype frequency differences (AMOVA, Phi(ST) = 0.107, P < 0.001) principally between the Atlantic and Indo-Pacific populations. In contrast to other recent surveys of globally distributed sharks, we find much less population subdivision and no evidence for cryptic evolutionary partitions. Discovery of the mating and pupping areas of whale sharks is key to further population genetic studies. The global pattern of shared haplotypes in whale sharks provides a compelling argument for development of broad international approaches for management and conservation of Earth's largest fish.

Population genetics and phylogeography of sea turtles.

The seven species of sea turtles occupy a diversity of niches, and have a history tracing back over 100 million years, yet all share basic life-history features, including exceptional navigation skills and periodic migrations from feeding to breeding habitats. Here, we review the biogeographic, behavioural, and ecological factors that shape the distribution of genetic diversity in sea turtles. Natal homing, wherein turtles return to their region of origin for mating and nesting, has been demonstrated with mtDNA sequences. These maternally inherited markers show strong population structure among nesting colonies while nuclear loci reveal a contrasting pattern of male-mediated gene flow, a phenomenon termed 'complex population structure'. Mixed-stock analyses indicate that multiple nesting colonies can contribute to feeding aggregates, such that exploitation of turtles in these habitats can reduce breeding populations across the region. The mtDNA data also demonstrate migrations across entire ocean basins, some of the longest movements of marine vertebrates. Multiple paternity occurs at reported rates of 0-100%, and can vary by as much as 9-100% within species. Hybridization in almost every combination among members of the Cheloniidae has been documented but the frequency and ultimate ramifications of hybridization are not clear. The global phylogeography of sea turtles reveals a gradient based on habitat preference and thermal regime. The cold-tolerant leatherback turtle (Dermochelys coriacea) shows no evolutionary partitions between Indo-Pacific and Atlantic populations, while the tropical green (Chelonia mydas), hawksbill (Eretmochelys imbricata), and ridleys (Lepidochelys olivacea vs. L. kempi) have ancient separations between oceans. Ridleys and loggerhead (Caretta caretta) also show more recent colonization between ocean basins, probably mediated by warm-water gyres that occasionally traverse the frigid upwelling zone in southern Africa. These rare events may be sufficient to prevent allopatric speciation under contemporary geographic and climatic conditions. Genetic studies have advanced our understanding of marine turtle biology and evolution, but significant gaps persist and provide challenges for the next generation of sea turtle geneticists.

Mixed-stock analysis reveals the migrations of juvenile hawksbill turtles (Eretmochelys imbricata) in the Caribbean Sea.

Hawksbill turtles (Eretmochelys imbricata) migrate between nesting beaches and feeding habitats that are often associated with tropical reefs, but it is uncertain which nesting colonies supply which feeding habitats. To address this gap in hawksbill biology, we compile previously published and new mitochondrial DNA (mtDNA) haplotype data for 10 nesting colonies (N = 347) in the western Atlantic and compare these profiles to four feeding populations and four previously published feeding samples (N = 626). Nesting colonies differ significantly in mtDNA haplotype frequencies (Phi(ST) = 0.588, P < 0.001), corroborating earlier conclusions of nesting site fidelity and setting the stage for mixed-stock analysis. Feeding aggregations show lower but significant structure (Phi(ST) = 0.089, P < 0.001), indicating that foraging populations are not homogenous across the Caribbean Sea. Bayesian mixed-stock estimates of the origins of juveniles in foraging areas show a highly significant, but shallow, correlation with nesting population size (r = 0.378, P = 0.004), supporting the premise that larger rookeries contribute more juveniles to feeding areas. A significant correlation between the estimated contribution and geographical distance from nesting areas (r = -0.394, P = 0.003) demonstrates the influence of proximity on recruitment to feeding areas. The influence of oceanic currents is illustrated by pelagic stage juveniles stranded in Texas, which are assigned primarily (93%) to the upstream rookery in Yucatan. One juvenile had a haplotype previously identified only in the eastern Atlantic, invoking rare trans-oceanic migrations. The mixed-stock analysis demonstrates that harvests in feeding habitats will impact nesting colonies throughout the region, with the greatest detriment to nearby nesting populations.