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We applied a systematic global literature survey from the last 2.5 years on spatiotemporal population dynamics - broadly defined - of Lepidopteran forest pests. Articles were summarized according to domain-specific (planetary ecology - remote sensing, evolutionary ecology - genetics and genomics, and theoretical ecology - modeling) contributions to contemporary investigation of the above theme. 'Model systems' dominating our literature survey were native Choristoneura fumiferana and invasive Lymantria dispar. These systems represent opposing ends of a more general equilibrium-disequilibrium gradient, with implications for less-studied taxa. The dynamics of Lepidopteran systems defy simple modeling approaches. Technologies and insights emerging from 'slower' science domains are informing more complex theory, including predictions of spread, impacts, or both posed by more recent invasions and the disrupting effects of climate change., (Published by Elsevier Inc.)

Phosphoglucomutase 1 (PGM1) encodes the metabolic enzyme that interconverts glucose-6-P and glucose-1-P. Mutations in PGM1 cause impairment in glycogen metabolism and glycosylation, the latter manifesting as a congenital disorder of glycosylation (CDG). This unique metabolic defect leads to abnormal N-glycan synthesis in the endoplasmic reticulum (ER) and the Golgi apparatus (GA). On the basis of the decreased galactosylation in glycan chains, galactose was administered to individuals with PGM1-CDG and was shown to markedly reverse most disease-related laboratory abnormalities. The disease and treatment mechanisms, however, have remained largely elusive. Here, we confirm the clinical benefit of galactose supplementation in PGM1-CDG-affected individuals and obtain significant insights into the functional and biochemical regulation of glycosylation. We report here that, by using tracer-based metabolomics, we found that galactose treatment of PGM1-CDG fibroblasts metabolically re-wires their sugar metabolism, and as such replenishes the depleted levels of galactose-1-P, as well as the levels of UDP-glucose and UDP-galactose, the nucleotide sugars that are required for ER- and GA-linked glycosylation, respectively. To this end, we further show that the galactose in UDP-galactose is incorporated into mature, de novo glycans. Our results also allude to the potential of monosaccharide therapy for several other CDG., (Copyright © 2019 American Society of Human Genetics. All rights reserved.)

Beta-ketothiolase (mitochondrial acetoacetyl-CoA thiolase) deficiency is a genetic disorder characterized by impaired isoleucine catabolism and ketone body utilization that predisposes to episodic ketoacidosis. It results from biallelic pathogenic variants in the ACAT1 gene, encoding mitochondrial beta-ketothiolase. We report two cases of beta-ketothiolase deficiency presenting with acute ketoacidosis and "metabolic stroke." The first patient presented at 28 months of age with metabolic acidosis and pallidal stroke in the setting of a febrile gastrointestinal illness. Although 2-methyl-3-hydroxybutyric acid and trace quantities of tiglylglycine were present in urine, a diagnosis of glutaric acidemia type I was initially suspected due to the presence of glutaric and 3-hydroxyglutaric acids. A diagnosis of beta-ketothiolase deficiency was ultimately made through whole exome sequencing which revealed compound heterozygous variants in ACAT1. Fibroblast studies for beta-ketothiolase enzyme activity were confirmatory. The second patient presented at 6 months of age with ketoacidosis, and was found to have elevations of urinary 2-methyl-3-hydroxybutyric acid, 2-methylacetoacetic acid, and tiglylglycine. Sequencing of ACAT1 demonstrated compound heterozygous presumed causative variants. The patient exhibited choreoathethosis 2 months after the acute metabolic decompensation. These cases highlight that, similar to a number of other organic acidemias and mitochondrial disorders, beta-ketothiolase deficiency can present with metabolic stroke. They also illustrate the variability in clinical presentation, imaging, and biochemical evaluation that make screening for and diagnosis of this rare disorder challenging, and further demonstrate the value of whole exome sequencing in the diagnosis of metabolic disorders.

Detailed understanding of forest disturbance interactions is needed for effective forecasting, modelling, and management. Insect outbreaks are a significant forest disturbance that alters forest structure as well as the distribution and connectivity of combustible fuels at broad spatial scales. The effect of insect outbreaks on fire activity is an important but contentious issue with significant policy consequences. The eastern spruce budworm (Choristoneura fumiferana) is a native defoliating insect in eastern North America whose periodic outbreaks create large patches of dead fir and spruce trees. Of particular concern to fire and forest managers is whether these patches represent an increased fire risk, if so, for how long, and how the relationship between defoliation and fire risk varies through space and time. Previous work suggests a temporary increase in flammability in budworm-killed forests, but regional and seasonal variability in these relationships has not been examined. Using an extensive database on historical lightning-caused fire ignitions and spruce budworm defoliation between 1963 and 2000, we assess the relative importance of cumulative defoliation and fire weather on the probability of ignition in Ontario, Canada. We modeled fire ignition using a generalized additive logistic regression model that accounts for temporal autocorrelation in fire weather. We compared two ecoregions in eastern Ontario (Abitibi Plains) and western Ontario (Lake of the Woods) that differ in terms of climate, geomorphology, and forest composition. We found that defoliation has the potential to both increase and decrease the probability of ignition depending on the time scale, ecoregion, and season examined. Most importantly, we found that lagged spruce budworm defoliation (8-10 yr) increases the risk of fire ignition whereas recent defoliation (1 yr) can decrease this risk. We also found that historical defoliation has a greater influence on ignition risk during the spring than during the summer fire season. Given predicted increases in forest insect activity due to global change, these results represent important information for fire management agencies that can be used to refine existing models of fire risk., (© 2016 by the Ecological Society of America.)

Through their influence on effective population sizes, sex ratio skew affects population dynamics. We examined spatial variation in female-biased sex ratios in the mountain pine beetle (Dendroctonus ponderosae Hopkins) outbreak in western Canada to better understand how environmental context affects sex ratio skew. Our specific objectives were to: 1) characterize spatial variation in mountain pine beetle sex ratio; 2) test previously asserted hypotheses that beetle sex ratio varies with tree diameter and year in outbreak; and 3) develop predictive models of sex ratio skew for larval and adult populations. Using logistic regression, we modeled the probability that an individual beetle (n = 2,369) was female as a function of multiple environmental variables across 34 stands in British Columbia and Alberta, Canada. We identified a consistent female-biased sex ratio with significantly greater skew in adults (2:1, n = 713) than in larvae (1.76:1, n = 1,643). We found that the proportion of larval females increased with decreasing tree size and with outbreak age. However, adults did not respond to tree size and larvae did not respond to outbreak age. Predictive models differed between larvae and adults. All identified models perform well and included predictors related to weather, tree diameter, and year in outbreak. Female-biased sex ratios appear to originate from differential male mortality during development rather than from sex-biased oviposition, suggesting sex ratio skew is not the cause of outbreaks, but rather a consequence., (© The Authors 2016. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Congenital disorders of glycosylation (CDG) arise from pathogenic mutations in over 100 genes leading to impaired protein or lipid glycosylation. ALG1 encodes a β1,4 mannosyltransferase that catalyzes the addition of the first of nine mannose moieties to form a dolichol-lipid linked oligosaccharide intermediate required for proper N-linked glycosylation. ALG1 mutations cause a rare autosomal recessive disorder termed ALG1-CDG. To date 13 mutations in 18 patients from 14 families have been described with varying degrees of clinical severity. We identified and characterized 39 previously unreported cases of ALG1-CDG from 32 families and add 26 new mutations. Pathogenicity of each mutation was confirmed based on its inability to rescue impaired growth or hypoglycosylation of a standard biomarker in an alg1-deficient yeast strain. Using this approach we could not establish a rank order comparison of biomarker glycosylation and patient phenotype, but we identified mutations with a lethal outcome in the first two years of life. The recently identified protein-linked xeno-tetrasaccharide biomarker, NeuAc-Gal-GlcNAc2 , was seen in all 27 patients tested. Our study triples the number of known patients and expands the molecular and clinical correlates of this disorder., (© 2016 WILEY PERIODICALS, INC.)

Background: Primary deficiencies in mannosylation of N-glycans are seen in a majority of patients with congenital disorders of glycosylation (CDG). We report the discovery of a series of novel N-glycans in sera, plasma, and cultured skin fibroblasts from patients with CDG having deficient mannosylation., Method: We used LC-MS/MS and MALDI-TOF-MS analysis to identify and quantify a novel N-linked tetrasaccharide linked to the protein core, an N-tetrasaccharide (Neu5Acα2,6Galβ1,4-GlcNAcβ1,4GlcNAc) in plasma, serum glycoproteins, and a fibroblast lysate from patients with CDG caused by ALG1 [ALG1 (asparagine-linked glycosylation protein 1), chitobiosyldiphosphodolichol β-mannosyltransferase], PMM2 (phosphomannomutase 2), and MPI (mannose phosphate isomerase)., Results: Glycoproteins in sera, plasma, or cell lysate from ALG1-CDG, PMM2-CDG, and MPI-CDG patients had substantially more N-tetrasaccharide than unaffected controls. We observed a >80% decline in relative concentrations of the N-tetrasaccharide in MPI-CDG plasma after mannose therapy in 1 patient and in ALG1-CDG fibroblasts in vitro supplemented with mannose., Conclusions: This novel N-tetrasaccharide could serve as a diagnostic marker of ALG1-, PMM2-, or MPI-CDG for screening of these 3 common CDG subtypes that comprise >70% of CDG type I patients. Its quantification by LC-MS/MS may be useful for monitoring therapeutic efficacy of mannose. The discovery of these small N-glycans also indicates the presence of an alternative pathway in N-glycosylation not recognized previously, but its biological significance remains to be studied., (© 2015 American Association for Clinical Chemistry.)

Context: The current obesity epidemic is attributed to complex interactions between genetic and environmental factors. However, a limited number of cases, especially those with early-onset severe obesity, are linked to single gene defects. Rapid-onset obesity with hypothalamic dysfunction, hypoventilation and autonomic dysregulation (ROHHAD) is one of the syndromes that presents with abrupt-onset extreme weight gain with an unknown genetic basis., Objective: To identify the underlying genetic etiology in a child with morbid early-onset obesity, hypoventilation, and autonomic and behavioral disturbances who was clinically diagnosed with ROHHAD syndrome. Design/Setting/Intervention: The index patient was evaluated at an academic medical center. Whole-exome sequencing was performed on the proband and his parents. Genetic variants were validated by Sanger sequencing., Results: We identified a novel de novo nonsense mutation, c.3265 C>T (p.R1089X), in the retinoic acid-induced 1 (RAI1) gene in the proband. Mutations in the RAI1 gene are known to cause Smith-Magenis syndrome (SMS). On further evaluation, his clinical features were not typical of either SMS or ROHHAD syndrome., Conclusions: This study identifies a de novo RAI1 mutation in a child with morbid obesity and a clinical diagnosis of ROHHAD syndrome. Although extreme early-onset obesity, autonomic disturbances, and hypoventilation are present in ROHHAD, several of the clinical findings are consistent with SMS. This case highlights the challenges in the diagnosis of ROHHAD syndrome and its potential overlap with SMS. We also propose RAI1 as a candidate gene for children with morbid obesity.

Dispersal determines the flux of individuals, energy and information and is therefore a key determinant of ecological and evolutionary dynamics. Yet, it remains difficult to quantify its importance relative to other factors. This is particularly true in cyclic populations in which demography, drift and dispersal contribute to spatio-temporal variability in genetic structure. Improved understanding of how dispersal influences spatial genetic structure is needed to disentangle the multiple processes that give rise to spatial synchrony in irruptive species. In this study, we examined spatial genetic structure in an economically important irruptive forest insect, the spruce budworm (Choristoneura fumiferana) to better characterize how dispersal, demography and ecological context interact to influence spatial synchrony in a localized outbreak. We characterized spatial variation in microsatellite allele frequencies using 231 individuals and seven geographic locations. We show that (i) gene flow among populations is likely very high (Fst  ≈ 0); (ii) despite an overall low level of genetic structure, important differences exist between adult (moth) and juvenile (larvae) life stages; and (iii) the localized outbreak is the likely source of moths captured elsewhere in our study area. This study demonstrates the potential of using molecular methods to distinguish residents from migrants and for understanding how dispersal contributes to spatial synchronization. In irruptive populations, the strength of genetic structure depends on the timing of data collection (e.g. trough vs. peak), location and dispersal. Taking into account this ecological context allows us to make more general characterizations of how dispersal can affect spatial synchrony in irruptive populations., (© 2014 John Wiley & Sons Ltd.)

The Last Glacial Maximum (LGM) was a global climate event, which had significant repercussions for the spatial distribution and demographic history of prehistoric populations. In Eurasia, the LGM coincides with a potential bottleneck for modern humans and may mark the divergence date for Asian and European populations (Keinan et al., 2007). In this research, the impact of climate variability on human populations in the Iberian Peninsula during the Last Glacial Maximum (LGM) is examined with the aid of downscaled high-resolution (16 × 16 km) numerical climate experiments. Human sensitivity to short time-scale (inter-annual) climate variability during this key time period, which follows the initial modern human colonisation of Eurasia and the extinction of the Neanderthals, is tested using the spatial distribution of archaeological sites. Results indicate that anatomically modern human populations responded to small-scale spatial patterning in climate variability, specifically inter-annual variability in precipitation levels as measured by the standard precipitation index. Climate variability at less than millennial scale, therefore, is shown to be an important component of ecological risk, one that played a role in regulating the spatial behaviour of prehistoric human populations and consequently affected their social networks., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Drosophila suzukii is an introduced pest insect that feeds on undamaged, attached fruit. This diet is distinct from the fallen, discomposing fruits utilized by most other species of Drosophila. Since the bacterial microbiota of Drosophila, and of many other animals, is affected by diet, we hypothesized that the bacteria associated with D. suzukii are distinct from that of other Drosophila. Using 16S rDNA PCR and Illumina sequencing, we characterized the bacterial communities of larval and adult D. suzukii collected from undamaged, attached cherries in California, USA. We find that the bacterial communities associated with these samples of D. suzukii contain a high frequency of Tatumella. Gluconobacter and Acetobacter, two taxa with known associations with Drosophila, were also found, although at lower frequency than Tatumella in four of the five samples examined. Sampling D. suzukii from different locations and/or while feeding on different fruits is needed to determine the generality of the results determined by these samples. Nevertheless this is, to our knowledge, the first study characterizing the bacterial communities of this ecologically unique and economically important species of Drosophila.

Here we present the draft genome of Tatumella sp. strain UCD-D_suzukii, the first member of this genus to be sequenced. The genome contains 3,602,931 bp in 72 scaffolds. This strain was isolated from Drosophila suzukii larvae as part of a larger project to study the microbiota of D. suzukii.

Objectives: To compare quantiferon-TB gold "in tube" (QFT-IT) with the conventional tuberculin skin test (TST) for the diagnosis of latent tuberculosis infection (LTBI) in HIV-infected adults in a setting highly endemic for tuberculosis with BCG vaccinated population in Bangalore, Karnataka, India., Patients and Methods: The study population (100 BCG-vaccinated adults) was divided into 4 groups: HIV patients with TB patient contact, HIV patients with past history of TB, TB patients (positive control), and healthy volunteers (negative control)., Results: Overall agreement between TST and QFT-IT was 52.4% (κ = 0.22). Increasing the TST cutoff value from 5 mm to 10 mm among HIV-positive groups resulted in better agreement 62.5% in Group 1 and 81.2% in Group 2., Discussion: In a setting with high TB prevalence, the TST gives increased false positives in HIV-positive groups if 5 mm is used as the cutoff value. This could be minimized by increasing the cutoff to 10 mm., Conclusion: The 2-step approach (initial testing of all cases with TST and confirmation of only those positive in TST by testing with QFT-IT) will be economical and help in treating LTBI cases in lower middle income countries like India.

Purpose: Pancreatic cancer clinical trials open in the United States and their accrual were examined to identify opportunities to accelerate progress in the treatment of pancreatic cancer., Methods: Pancreatic cancer-specific clinical trials open in the United States in the years 2011 and 2012 were obtained from the Pancreatic Cancer Action Network database. Accrual information was obtained from trial sponsors., Results: The portfolio of pancreatic cancer clinical trials identified by type (adenocarcinoma or neuroendocrine), phase, disease stage, and treatment approach is reported. More than half of trials for patients with pancreatic ductal adenocarcinoma applied biologic insights to new therapeutic approaches, and 38% focused on optimization of radiation or chemotherapy delivery or regimens. In 2011, pancreatic cancer trials required total enrollment of 11,786 patients. Actual accrual to 93.2% of trials was 1,804 patients, an estimated 4.57% of the patients with pancreatic cancer alive in that year. The greatest need was for patients with resectable cancer. Trials open in 2011 enrolled an average of 15% of their total target accrual. Physician recommendations greatly influenced patients' decision to enroll or not enroll onto a clinical trial. Matching to a clinical trial within a 50-mile radius and identifying trials for recurrent/refractory disease were documented as challenges for patient accrual., Conclusion: Overall trial enrollment indicates that pancreatic cancer trials open in 2011 would require 6.7 years on average to complete accrual. These results suggest that harmonizing patient supply and demand for clinical trials is required to accelerate progress toward improving survival in pancreatic cancer.

Background: Tuberculosis (TB), a dreadful disease known to mankind continues to be a problem in a developing country like India. The incidence of people getting infected with TB is on the rise due to compounding factors like coinfection with the human immunodefiency virus and multidrug-resistant strains. There is a definitive need for early diagnosis and treatment of TB to curb transmission of the infection. Direct smear microscopy, though cheap and rapid, lacks sensitivity. Isolation of Mycobacterium tuberculosis in culture requires a long time, because of which there is a need for a rapid method which has good sensitivity and specificity for the detection of M. tuberculosis. The present study was undertaken to determine the test which diagnoses TB rapidly and to compare the sensitivity of smear microscopy, concentration method, rapid slide culture, and Lowenstein - Jensen (LJ) culture., Materials and Methods: Sputum samples of 200 patients were subjected to direct smear and concentration by modified Petroff's method. The concentrated sputum was also taken for slide culture using human blood medium and inoculated on LJ media., Results: LJ culture was positive in 47 (23.5%) cases, of which three were nontubercular mycobacteria. Using LJ culture as the standard method, the sensitivity of direct smear, concentration method, and rapid slide culture method was 68, 83, and 89%, respectively, and specificity was 100% in all the three tests., Conclusion: Rapid slide culture showed good sensitivity which was comparable to and next in efficacy to LJ culture and this technique can be adopted in the Revised National Tuberculosis Control Program (RNTCP) as it is a rapid, cheap, sensitive, and specific method.

Microbial parasites of animals include bacteria, viruses, and various unicellular eukaryotes. Because of the difficulty in studying these microorganisms in both humans and disease vectors, laboratory models are commonly used for experimental analysis of host-parasite interactions. Drosophila is one such model that has made significant contributions to our knowledge of bacterial, fungal, and viral infections. Despite this, less is known about other potential parasites associated with natural Drosophila populations. Here, we surveyed sixteen Drosophila populations comprising thirteen species from four continents and Hawaii and found that they are associated with an extensive diversity of trypanosomatids (Euglenozoa, Kinetoplastea). Phylogenetic analysis finds that Drosophila-associated trypanosomatids are closely related to taxa that are responsible for various types of leishmaniases and more distantly related to the taxa responsible for human African trypanosomiasis and Chagas disease. We suggest that Drosophila may provide a powerful system for studying the interactions between trypanosomatids and their hosts.

Understanding the physical and genetic structure of hybrid zones can illuminate factors affecting their formation and stability. In north-central Alberta, lodgepole pine (Pinus contorta Dougl. ex Loud. var. latifolia) and jack pine (Pinus banksiana Lamb) form a complex and poorly defined hybrid zone. Better knowledge of this zone is relevant, given the recent host expansion of mountain pine beetle into jack pine. We characterized the zone by genotyping 1998 lodgepole, jack pine, and hybrids from British Columbia, Alberta, Saskatchewan, Ontario, and Minnesota at 11 microsatellites. Using Bayesian algorithms, we calculated genetic ancestry and used this to model the relationship between species occurrence and environment. In addition, we analyzed the ancestry of hybrids to calculate the genetic contribution of lodgepole and jack pine. Finally, we measured the amount of gene flow between the pure species. We found the distribution of the pine classes is explained by environmental variables, and these distributions differ from classic distribution maps. Hybrid ancestry was biased toward lodgepole pine; however, gene flow between the two species was equal. The results of this study suggest that the hybrid zone is complex and influenced by environmental constraints. As a result of this analysis, range limits should be redefined.

Environmental change has a wide range of ecological consequences, including species extinction and range expansion. Many studies have shown that insect species respond rapidly to climatic change. A mountain pine beetle epidemic of record size in North America has led to unprecedented mortality of lodgepole pine, and a significant range expansion to the northeast of its historic range. Our goal was to determine the spatial genetic variation found among outbreak population from which genetic structure, and dispersal patterns may be inferred. Beetles from 49 sampling locations throughout the outbreak area in western Canada were analysed at 13 microsatellite loci. We found significant north-south population structure as evidenced by: (i) Bayesian-based analyses, (ii) north-south genetic relationships and diversity gradients; and (iii) a lack of isolation-by-distance in the northernmost cluster. The north-south structure is proposed to have arisen from the processes of postglacial colonization as well as recent climate-driven changes in population dynamics. Our data support the hypothesis of multiple sources of origin for the outbreak and point to the need for population specific information to improve our understanding and management of outbreaks. The recent range expansion across the Rocky Mountains into the jack/lodgepole hybrid and pure jack pine zones of northern Alberta is consistent with a northern British Columbia origin. We detected no loss of genetic variability in these populations, indicating that the evolutionary potential of mountain pine beetle to adapt has not been reduced by founder events. This study illustrates a rapid range-wide response to the removal of climatic constraints, and the potential for range expansion of a regional population., (© 2012 Blackwell Publishing Ltd.)

Increases in the extent and severity of spruce budworm (Choristoneura fumiferana Clem.) outbreaks over the last century are thought to be the result of changes in forest structure due to forest management. A corollary of this hypothesis is that manipulations of forest structure and composition can be used to reduce future forest vulnerability. However, to what extent historical forest management has influenced current spatial patterns of spruce budworm host species is unknown. To identify landscape-scale spatial legacies of forest management in patterns of spruce budworm host species (i.e., Abies balsamea and Picea spp.), we analyzed remotely sensed forest data from the Border Lakes landscape of northern Minnesota and northwestern Ontario. Our study area contains three regions with different management histories: (1) fine-scale logging patterns in Minnesota, (2) coarse-scale logging patterns in Ontario, and (3) very limited logging history in the Boundary Waters Canoe Area and adjacent Quetico Provincial Park. We analyzed forest basal-area data using wavelets and null models to identify: (1) at which scales forest basal area is structured, (2) where those scales of pattern are significantly present, and (3) whether regions of local significance correspond to regional boundaries that separate the study area. Results indicate that spatial patterns in host basal area are created by nonstationary processes and that these processes are further constrained by lakes and wetlands. Wavelet analysis combined with significance testing revealed a bimodal distribution of scale-specific wavelet variance and separate zones of host species basal area that partially correspond with regional boundaries, particularly between Minnesota and the Wilderness region. This research represents one of the first comparisons of forest spatial structure in this region across an international border and presents a novel method of two-dimensional wavelet analysis that can be used to identify significant scale-specific structure in spatial data.

We used exome sequencing to identify the genetic basis of combined malonic and methylmalonic aciduria (CMAMMA). We sequenced the exome of an individual with CMAMMA and followed up with sequencing of eight additional affected individuals (cases). This included one individual who was identified and diagnosed by searching an exome database. We identify mutations in ACSF3, encoding a putative methylmalonyl-CoA and malonyl-CoA synthetase as a cause of CMAMMA. We also examined a canine model of CMAMMA, which showed pathogenic mutations in a predicted ACSF3 ortholog. ACSF3 mutant alleles occur with a minor allele frequency of 0.0058 in ∼1,000 control individuals, predicting a CMAMMA population incidence of ∼1:30,000. ACSF3 deficiency is the first human disorder identified as caused by mutations in a gene encoding a member of the acyl-CoA synthetase family, a diverse group of evolutionarily conserved proteins, and may emerge as one of the more common human metabolic disorders.