Grizzly Bear Population Augmentation In The Cabinet Mountains Of Northwest Montana Wayne Kasworm,* USDA Fish and Wildlife Service, Libby

The Cabinet Mountains grizzly bear (Ursus arctos horribilis) population was estimated at 15 or fewer individuals in 1988 and believed to be declining toward extinction. In response to this decline, a test of population augmentation techniques was conducted during 1990- 1994 when four subadult female grizzly bears were transplanted to the area. Two criteria were identified as measures of success: bears must remain in the target area for one year, and bears should ultimately breed with native male grizzly bears and reproduce. Reproductive success of any of the remaining individuals could not be established until 2006 when genetic analysis of hair snag samples collected from 2002-2005 indicated that one of the transplanted bears remained in the Cabinet Mountains and had reproduced. The detected bear was transplanted in 1993 as a 2-year-old and was identified by a hair snag within 5 mi of the original release site. Genetic analysis indicated she had produced at least six offspring, and two of her female offspring had also reproduced. This reproduction indicates that the original test of augmentation was successful with at least one of the transplanted individuals. Success of the grizzly bear augmentation test prompted continuation of this effort. The Northern Continental Divide Ecosystem area of north central Montana has been the source of seven additional bears transplanted to the Cabinet Mountains during 2005-2010. All were female bears except one: a young male was moved in 2010. Two female bears were killed and two female bears left the area. Fates and movements of these bears are discussed

Uneasy entry

The poems in this book center around the theme of human isolation and the desire for communication. I have used the interactions between men and women as symbols of this universal division. The poems in the first section, Connections, are primarily narrative. They explore ways in which two Individuals become aware of the distances between them, their emotional responses to this distance, and various ineffective ways in which they try to bridge the gulf they have just seen open at their feet. The second section, Domestic Lessons, deals with a more personal experience of human isolation. The third section, Caves, is an imaginative attempt to reach the sources of androgyny within the individual, an attempt to come to terms emotionally and intellectually with the knowledge of the co-existence of male and female sensibility in each of us. The aim of the poems, which could be considered rites of passage, is to revitalize and complete in an individually significant way the fragmented myths of childhood. The last section, Sharing Visions, is concerned with moments of true communion between individuals, and the implications of these accidents of grace which allow us to see life for a second through eyes other than our own

A discrete cluster of urinary biomarkers discriminates between active systemic lupus erythematosus patients with and without glomerulonephritis.

BackgroundManagement of lupus nephritis (LN) would be greatly aided by the discovery of biomarkers that accurately reflect changes in disease activity. Here, we used a proteomics approach to identify potential urinary biomarkers associated with LN.MethodsUrine was obtained from 60 LN patients with paired renal biopsies, 25 active non-LN SLE patients, and 24 healthy controls. Using Luminex, 128 analytes were quantified and normalized to urinary creatinine levels. Data were analyzed by linear modeling and non-parametric statistics, with corrections for multiple comparisons. A second cohort of 33 active LN, 16 active non-LN, and 30 remission LN SLE patients was used to validate the results.ResultsForty-four analytes were identified that were significantly increased in active LN as compared to active non-LN. This included a number of unique proteins (e.g., TIMP-1, PAI-1, PF4, vWF, and IL-15) as well as known candidate LN biomarkers (e.g., adiponectin, sVCAM-1, and IL-6), that differed markedly (>4-fold) between active LN and non-LN, all of which were confirmed in the validation cohort and normalized in remission LN patients. These proteins demonstrated an enhanced ability to discriminate between active LN and non-LN patients over several previously reported biomarkers. Ten proteins were found to significantly correlate with the activity score on renal biopsy, eight of which strongly discriminated between active proliferative and non-proliferative/chronic renal lesions.ConclusionsA number of promising urinary biomarkers that correlate with the presence of active renal disease and/or renal biopsy changes were identified and appear to outperform many of the existing proposed biomarkers

Feature selection using a one dimensional naïve Bayes' classifier increases the accuracy of support vector machine classification of CDR3 repertoires.

MOTIVATION: Somatic DNA recombination, the hallmark of vertebrate adaptive immunity, has the potential to generate a vast diversity of antigen receptor sequences. How this diversity captures antigen specificity remains incompletely understood. In this study we use high throughput sequencing to compare the global changes in T cell receptor β chain complementarity determining region 3 (CDR3β) sequences following immunization with ovalbumin administered with complete Freund's adjuvant (CFA) or CFA alone. RESULTS: The CDR3β sequences were deconstructed into short stretches of overlapping contiguous amino acids. The motifs were ranked according to a one-dimensional Bayesian classifier score comparing their frequency in the repertoires of the two immunization classes. The top ranking motifs were selected and used to create feature vectors which were used to train a support vector machine. The support vector machine achieved high classification scores in a leave-one-out validation test reaching  : >90% in some cases. SUMMARY: The study describes a novel two-stage classification strategy combining a one-dimensional Bayesian classifier with a support vector machine. Using this approach we demonstrate that the frequency of a small number of linear motifs three amino acids in length can accurately identify a CD4 T cell response to ovalbumin against a background response to the complex mixture of antigens which characterize Complete Freund's Adjuvant. AVAILABILITY AND IMPLEMENTATION: The sequence data is available at www.ncbi.nlm.nih.gov/sra/?term¼SRP075893 The Decombinator package is available at github.com/innate2adaptive/Decombinator The R package e1071 is available at the CRAN repository https://cran.r-project.org/web/packages/e1071/index.html CONTACT: [email protected] information: Supplementary data are available at Bioinformatics online

Specificity, Privacy, and Degeneracy in the CD4 T Cell Receptor Repertoire Following Immunization.

T cells recognize antigen using a large and diverse set of antigen-specific receptors created by a complex process of imprecise somatic cell gene rearrangements. In response to antigen-/receptor-binding-specific T cells then divide to form memory and effector populations. We apply high-throughput sequencing to investigate the global changes in T cell receptor sequences following immunization with ovalbumin (OVA) and adjuvant, to understand how adaptive immunity achieves specificity. Each immunized mouse contained a predominantly private but related set of expanded CDR3β sequences. We used machine learning to identify common patterns which distinguished repertoires from mice immunized with adjuvant with and without OVA. The CDR3β sequences were deconstructed into sets of overlapping contiguous amino acid triplets. The frequencies of these motifs were used to train the linear programming boosting (LPBoost) algorithm LPBoost to classify between TCR repertoires. LPBoost could distinguish between the two classes of repertoire with accuracies above 80%, using a small subset of triplet sequences present at defined positions along the CDR3. The results suggest a model in which such motifs confer degenerate antigen specificity in the context of a highly diverse and largely private set of T cell receptors

Social Determinants of Health Are Associated with Markers of Renal Injury in Adolescents with Type 1 Diabetes.

OBJECTIVE: To examine the relationship between the social determinants of health and markers of early renal injury in adolescent patients with type 1 diabetes (T1D). STUDY DESIGN: Renal outcomes included estimated glomerular filtration rate (eGFR) and albumin-creatinine excretion ratio (ACR). Differences in urinary and serum inflammatory markers also were assessed in relation to social determinants of health. Regression analysis was used to evaluate the association between the Ontario Marginalization Index (ON-Marg) as a measure of the social determinants of health, patient characteristics, ACR, eGFR, and renal filtration status (hyperfiltration vs normofiltration). RESULTS: Participants with T1D (n = 199) with a mean age of 14.4 ± 1.7 years and diabetes duration of 7.2 ± 3.1 years were studied. Mean eGFR was 122.0 ± 19.4 mL/min/1.73 m2. Increasing marginalization was positively associated with eGFR (P < .0001) but not with ACR (P = .605). Greater marginalization was associated with greater median levels of urinary interleukin (IL)-2, IL-12 (p40), macrophage-derived chemokine, monocyte chemoattractant protein-3, and tumor necrosis factor-β and serum IL-2. ON-Marg was significantly associated with eGFR after we controlled for age, sex, body mass index z score, ethnicity, serum glucose, and hemoglobin A1c in linear regression. A similar association between hyperfiltration and ON-Marg score was observed in multivariable logistic regression. CONCLUSION: Increasing marginalization is significantly associated with both eGFR and hyperfiltration in adolescents with T1D and is associated with significant changes in urinary inflammatory biomarkers. These findings highlight a potentially important interaction between social and biological determinants of health in adolescents with T1D

Presymptomatic risk assessment for chronic non-communicable diseases

The prevalence of common chronic non-communicable diseases (CNCDs) far overshadows the prevalence of both monogenic and infectious diseases combined. All CNCDs, also called complex genetic diseases, have a heritable genetic component that can be used for pre-symptomatic risk assessment. Common single nucleotide polymorphisms (SNPs) that tag risk haplotypes across the genome currently account for a non-trivial portion of the germ-line genetic risk and we will likely continue to identify the remaining missing heritability in the form of rare variants, copy number variants and epigenetic modifications. Here, we describe a novel measure for calculating the lifetime risk of a disease, called the genetic composite index (GCI), and demonstrate its predictive value as a clinical classifier. The GCI only considers summary statistics of the effects of genetic variation and hence does not require the results of large-scale studies simultaneously assessing multiple risk factors. Combining GCI scores with environmental risk information provides an additional tool for clinical decision-making. The GCI can be populated with heritable risk information of any type, and thus represents a framework for CNCD pre-symptomatic risk assessment that can be populated as additional risk information is identified through next-generation technologies.Comment: Plos ONE paper. Previous version was withdrawn to be updated by the journal's pdf versio

Early changes in cardiovascular structure and function in adolescents with type 1 diabetes.

BACKGROUND: Children with type 1 diabetes (T1D) are at higher risk of early adult-onset cardiovascular disease. We assessed cardiovascular structure and function in adolescents with T1D compared with healthy controls and the relationships between peripheral vascular function and myocardial parameters. METHODS AND RESULTS: 199 T1D [14.4 ± 1.6 years, diabetes duration 6.2 (2.0-12.8) years] and 178 controls (14.4 ± 2.1 years) completed endothelial function by flow mediated vasodilatation (FMD), arterial stiffness using pulse wave velocity (PWV) along with M-mode, pulse wave and tissue Doppler, and myocardial deformation echocardiographic imaging. Systolic (113 ± 10 vs. 110 ± 9 mmHg; p = 0.0005) and diastolic (62 ± 7 vs. 58 ± 7 mmHg; p < 0.0001) blood pressures, carotid femoral PWV and endothelial dysfunction measurements were increased in T1D compared with controls. Systolic and diastolic left ventricular dimensions and function by M-mode and pulse wave Doppler assessment were not significantly different. Mitral valve lateral e' (17.6 ± 2.6 vs. 18.6 ± 2.6 cm/s; p < 0.001) and a' (5.4 ± 1.1 vs. 5.9 ± 1.1 cm/s; p < 0.001) myocardial velocities were decreased and E/e' (7.3 ± 1.2 vs. 6.7 ± 1.3; p = 0.0003) increased in T1D. Left ventricular mid circumferential strain (-20.4 ± 2.3 vs. -19.5 ± 1.7 %; p < 0.001) was higher, whereas global longitudinal strain was lower (-19.0 ± 1.9 vs. -19.8 ± 1.5 % p < 0.001) in T1D. CONCLUSIONS: Adolescents with T1D exhibit early changes in blood pressure, peripheral vascular function and left ventricular myocardial deformation indices with a shift from longitudinal to circumferential shortening. Longitudinal follow-up of these changes in ongoing prospective trials may allow detection of those most at risk for cardiovascular abnormalities including hypertension that could preferentially benefit from early therapeutic interventions.Funding was provided by the Juvenile Diabetes Research Foundation- Canadian Clinical Trial Network (JDRF-CCTN), the Canadian Diabetes Association, the Heart and Stroke Foundation of Canada and the Sick Kids Labatt Family Heart Center Innovation fund. Funding was also provided by the British Heart Foundation, Diabetes UK and the Juvenile Diabetes Research Foundation