Spatial and Climatic Factors Influence Ambrosia Beetle (Coleoptera: Curculionidae) Abundance in Intensively Managed Plantations of Eastern Black Walnut.

Invasive ambrosia beetles are among the most economically important pests of forest and plantation trees world-wide. The development of effective management guidelines for these pests in plantations of high-value hardwood species is hindered by a lack of baseline information regarding their seasonal abundance and dispersal behavior. By analyzing long-term monitoring data from intensively-managed plantations of eastern black walnut (Juglans nigra L.) in north-central Indiana, we identified key spatial and climatic variables that could improve the timing and precision of management actions to reduce ambrosia beetle populations. We also used geospatial analyses to compare species-specific spatial patterns of population density and evaluate the sensitivity of the trap density deployed in our long-term monitoring efforts. Xyleborinus saxesenii Ratzeburg and Xylosandrus crassiusculus Matschulsky (Coleoptera: Curculionidae) were more abundant during the spring in years preceded by a hot, dry growing season, and cold winter. Both species were positively associated with plantation edges during the fall flight period. However, X. saxesenii was less abundant in plantations close to forest corridors, whereas X. crassiusculus was more abundant in plantations closer to woodlots and other walnut plantations. Geospatial analysis revealed X. crassiusculus is active in larger, more spatially continuous patches than X. saxesenii, and that 200-m trap spacing is likely to be sufficient to detect both species in the spring flight period but may be insufficient to detect X. saxesenii during the fall flight period. Our findings underscore the power and utility of long-term monitoring to improve management strategies.

Does attrition affect estimates of association: A longitudinal study.

Survey research frequently involves missing cases attributable to refusals to participate, lack of success in accessing all potential respondents or loss to follow-up in longitudinal studies. There is concern that those not recruited or those lost are a select group whose absence from a study may bias the findings of the study. This study provides a test of the extent to which selective loss to follow-up in a longitudinal study may lead to biased findings. The Mater-University Study of Pregnancy collected baseline information for 7718 pregnant women. Follow-ups occurred five years, 14 years, 21 years and 27 years after the birth, for 6753 eligible women. Participants at baseline were partitioned according to follow-up status for each follow-up. We compare baseline (at recruitment) measures of association, with these same measures of association for those retained in the study (Group A) and those lost to follow-up (Group B) at each phase of data. Using univariate logistic regression we compared the strength of association between maternal mental health and various baseline socio-demographic factors for different rates of loss to follow-up. Estimates of association at baseline, and at each follow-up are similar irrespective of the rate of loss to follow-up and whether the comparison is with those retained in the study or those lost to follow-up. There were no statistically significant differences in 90.8% of baseline comparisons with Group A, and 96.9% of comparisons with Group B measures of association. We conclude that differential loss to follow-up rarely affects estimates of association. We suggest that loss to follow-up may produce misleading findings only in circumstances where loss to follow-up is combined with a number of other sources of bias.

Young adult pregnancy status and the risk of developing overweight and obesity among women and men.

Pregnancies can end in miscarriage, birth or termination. Although it is well known that pregnancy results in weight gain across the life course, it is unknown whether pregnancies which end in termination and miscarriage contribute to this. The study used a sub-sample of 3630 adult offspring from the original cohort of the Mater University of Queensland Study of Pregnancy (MUSP) and its outcomes, in Brisbane, Australia. Anthropometric data were measured at 5, 14 and 21 years of age and experience of pregnancy including termination, miscarriage and births were self-reported at 21 years. Multivariable analyses were conducted to determine whether pregnancy status of young people independently associated with overweight or obesity status. The women who had at least one birth were more likely to have overweight (odds ratio [OR] 1.52; 95% confidence interval [CI]: 1.01, 2.27) or obese (OR 2.38; 95% CI: 1.58, 3.59) compared to women who did not experience any pregnancy. Women whose pregnancies were terminated or miscarried were at the same risk of overweight or obesity as women who did not experience any pregnancy. For men, there is no association between the pregnancies in their partners and the mean difference in their body mass index. Young women whose pregnancies result in a birth, but not terminations or miscarriages, are at greater risk of having overweight or obesity following the birth.

A double-click approach to the protecting group free synthesis of glycoconjugates.

The use of a bi-functional linker, containing an alkyne and an alkene, allows the protecting group free conjugation of reducing sugars to thiols via a double click process. Firstly the linker is attached to the sugar via one-pot glycosyl azide formation and Cu-catalysed azide-alkyne cycloaddition. Photochemical thiol-ene click reaction then allows conjugation to a range of thiols, including cysteine residues of peptides.

The association between adolescent psychopathology and subsequent physical activity in young adulthood: a 21-year birth cohort study.

BACKGROUND: The beneficial effects of physical activity (PA) for both physical and mental wellbeing are well established. Given that adolescence presents a critical developmental period during which life-long patterns of PA become established, the exploration of the longitudinal impact of adolescent psychopathology on adult PA status is of interest. METHODS: We analysed prospective data from 3663 young adults who participated in the Mater-University of Queensland Study of Pregnancy. Psychopathology was measured using the Youth Self-Report (YSR) at age 14. Participants' engagement in three types of PA (vigorous exercise, moderate exercise and walking) at age 21 were dichotomised into either 'none' or 'any'. For our main analysis, we examined the association between the YSR score and subsequent PA engagement using logistic regression. We also conducted sensitivity analyses of longitudinal associations between the YSR internalising and externalising symptoms score at age 14 and PA engagement at age 21. RESULTS: We found no longitudinal association between the total YSR score at age 14 and PA engagement at age 21. In addition, there was no longitudinal association between the YSR internalising or externalising symptoms and PA engagement. CONCLUSION: Our findings suggest that there is no longitudinal association between adolescent psychopathology and PA in young adulthood.

Chicken egg fetal liver DNA and histopathologic effects of structurally diverse carcinogens and non-carcinogens.

Chicken egg fetal livers were evaluated for histopathological changes produced by four genotoxic hepatocarcinogens: 2-acetylaminofluorene (AAF), aflatoxin B1 (AFB1), benzo[a]pyrene (BaP), diethylnitrosamine (DEN); four structurally related non- or weakly- carcinogenic comparators: fluorene (FLU), aflatoxin B2 (AFB2), benzo[e]pyrene (BeP), N-nitrosodiethanolamine (NDELA); two epigenetic hepatocarcinogens: clofibric acid (CFA), phenobarbital (PB); and the non-carcinogen, D-mannitol (MAN). CFA, PB and MAN were also assessed for formation of DNA adducts using the 32P nucleotide postlabeling (NPL) assay and for DNA breaks using the comet assay. CFA was also assessed in enhanced comet assay for oxidative DNA damage induction. Eggs were dosed on days 9- 11 of incubation. For genotoxicity evaluation, livers were collected 3h after the last dose. Liver qualitative histopathology assessment was performed on days 12 and 18 of incubation. CFA was negative for DNA adducts but yielded clear evidence of DNA breaks due to oxidative stress. PB and MAN produced no DNA adducts or breaks. Liver to body weight ratios were not affected in most groups, but were decreased in DEN groups, and increased after PB dosing. Livers from control groups, FLU, AFB2, BeP, NDELA, CFA, and MAN groups, displayed a typical hepatocellular trabecular pattern at both time points. In contrast, the four genotoxic carcinogens induced time- and dose- related interference with fetal liver cell processes of proliferation, migration and differentiation, leading to hepatocellular and cholangiocellular pleomorphic dysplasia and re-(de-) differentiation with distortion of the trabecular pattern. In addition, dosing with the high dose of DEN produced gallbladder agenesis. PB induced hepatocellular hypertrophy, interference with migration, expressed as distortion of the trabecular pattern, and a moderate cholangiocellular dysplasia. In summary, histopathological analysis of chicken fetal livers revealed developmental anomalies, as well as genotoxicity-induced and, in the case of PB, adaptive morphological changes. Thus, the model provides histopathological outcomes of molecular effects.

Maternal depression and family adversity: Linked pathways to offspring depression?

There is conflicting evidence about the contribution of maternal depression and family adversity to depression experienced by offspring. Because maternal depression and family adversity are related, there is a need to determine how they independently contribute to offspring depression. Data are from a long-running prospective birth cohort study (Mater-University of Queensland Study of Pregnancy and its outcomes - MUSP). For this study some 2200 offspring were followed up at 30 years of age. We first examine the association between maternal depression and family adversity over the period from the pregnancy to the child reaching adulthood. Then we consider the extent to which maternal depression and family adversity trajectories over this period predict CIDI/DSM-IV episodes of depression in the offspring of these mothers at 30 years of age. We find a strong bi-directional association between maternal depression and family experiences of adverse life events over the entire period the child is at home. After adjustment, children reared in a family experiencing high levels of adverse life events are more likely to experience a lifetime ever DSM-IV diagnosis of depression, are more likely to have experienced multiple episodes of lifetime ever depression, and are more likely to report their first episode of depression was at a younger age. The findings suggest the association between maternal depression and offspring depression appears to be partly attributable to the higher levels of family adversity characteristic of depressed mothers.

Trajectories of maternal depression: a 27-year population-based prospective study.

AIMS: To identify distinct trajectories of depression experienced by a population-based sample of women over a 27-year period and to assess the validity of the derived trajectories. METHOD: The Mater University of Queensland Study of Pregnancy is a birth cohort study which commenced in 1981. Women (N = 6753) were interviewed at their first clinic visit, at 6 months, then 5, 14, 21 and 27 years after the birth of their child, using the Delusions Symptoms - States Inventory. Some 3561 (52.7%) women were followed up at 27 years, with 3337 (49.4%) of the sample completing the Composite International Diagnostic Interview (CIDI). Depression trajectories over a 27-year period were identified using Latent Class Growth Modelling (LCGM). LCGM was used to identify respondents with similar patterns of depression over a 27-year period. At the 27-year follow-up women who completed the CIDI, were stratified according to their trajectory group membership. RESULTS: Three trajectory groups, each with different life-course patterns of depression were identified. The low/no symptoms of depression trajectory group comprised 48.4% of women. The mid-depression group (41.7%) had a consistent pattern of occasional symptoms of depression. The high/escalating trajectory group comprised 9.9% of the women in the study. We then examined each trajectory group based on their completion of the CIDI at the 27-year follow-up. Using the CIDI, 27.0% of women in the study had met the DSM-IV criteria for lifetime ever depression by their mean age of 46.5 years. The responses to the CIDI differed greatly for each of the trajectory groups, suggesting that the trajectories validly reflect different life histories of depression. The high/escalating trajectory group had an earlier age of first onset, more frequent episodes, longer duration of each episode of depression and experienced higher levels of impairment for their episodes of depression. For the high symptoms trajectory group, clinically significant depression is estimated to be experienced by women almost one in every 6 days of their life. CONCLUSION: While symptoms of depression are commonly experienced in a large community-based sample of women, a minority of women experience many episodes of depression in their lifetime. It is this group of women who are most impaired and should be of most concern, and who should be the main target of prevention and treatment initiatives.

Chimeric Allografts Induced by Short-Term Treatment With Stem Cell-Mobilizing Agents Result in Long-Term Kidney Transplant Survival Without Immunosuppression: A Study in Rats.

Transplant tolerance allowing the elimination of lifelong immunosuppression has been the goal of research for 60 years. The induction of mixed chimerism has shown promise and has been extended successfully to large animals and to the clinic; however, it remains cumbersome and requires heavy early immunosuppression. In this study, we reported that four injections of AMD3100, a CXCR4 antagonist, plus eight injections of low-dose FK506 (0.05 mg/kg per day) in the first week after kidney transplantation extended survival, but death from renal failure occurred at 30-90 days. Repeating the same course of AMD3100 and FK506 at 1, 2 and 3 mo after transplant resulted in 92% allograft acceptance (n = 12) at 7 mo, normal kidney function and histology with no further treatment. Transplant acceptance was associated with the influx of host stem cells, resulting in a hybrid kidney and a modulated host immune response. Confirmation of these results could initiate a paradigm shift in posttransplant therapy.

Chimeric Allografts Induced by Short-Term Treatment With Stem Cell Mobilizing Agents Result in Long-Term Kidney Transplant Survival Without Immunosuppression: II, Study in Miniature Swine.

Transplantation is now lifesaving therapy for patients with end-stage organ failure but requires lifelong immunosuppression with resultant morbidity. Current immunosuppressive strategies inhibit T cell activation and prevent donor-recipient engagement. Therefore, it is not surprising that few host cells are demonstrated in donor grafts. However, our recent small animal studies found large numbers of recipient stem cells present after transplantation and pharmacological mobilization, resulting in a chimeric, repopulated organ. We now confirm these findings in a well-characterized large animal preclinical model. Here, we show that AMD3100 and FK506 mobilization of endogenous stem cells immediately post kidney transplantation combined with repeat therapy at 1, 2, and 3 months led to drug-free long-term survival in maximally immunologically mismatched swine. Three long-term recipients have stable chimeric transplants, preserved antidonor skin graft responses, and normal serum creatinine levels despite withdrawal of all medication for 3 years.

Generational increase in obesity among young women: a prospective analysis of mother-daughter dyads.

BACKGROUND/OBJECTIVES: Increases in obesity in young adults over recent decades are shown by national survey data but have yet to be replicated using prospective data. We aim to quantify the increase in obesity and overweight over two generations of young adult women using prospective measures of body mass index (BMI). SUBJECTS/METHODS: Data are from the Mater University Study of Pregnancy (MUSP), a prospective pre-birth cohort study started in 1981 in Brisbane, Australia. Analyses were restricted to 992 mother-daughter dyads who were at similar ages at the time they were assessed and for whom measures of BMI were available. We also conducted an additional analysis to test whether there was a similar increase amongst father-son dyads. We used multinomial logistic regression for clustered data to compare the same prospective measures of BMI categories between mother and daughters. RESULTS: Controlling for a number of sociodemographic and lifestyle factors in the female sample, daughters had 5.04 (3.03, 8.85) times the odds of being obese and 2.54 (1.86, 3.54) times the odds of being overweight compared with their mothers. A large increase in obesity was also observed in the male sample. CONCLUSIONS: Using a longitudinal design to partly account for familial confounding of obesity risk factors, this study confirms a large and concerning increases in obesity rates over two generations of young adults and suggests increases in obesity over the past 20 years may be greater than previously anticipated.

The urinary bladder carcinogen propoxur does not produce genotoxic effects in the urinary bladder of Wistar male rats.

Propoxur (PPX) is a carbamate insecticide which induced urinary bladder cancer in Wistar rats when fed at 5000ppm in Altromin 1321 diet (1321). In the present investigation, PPX was studied for induction of several key events related to modes of action (MOA) of carcinogenicity in urinary bladders (UBs). Wistar rats were administered the compound for 28 days at 8000ppm in Provini Liba SA 3883 diet, which is similar to the 1321 diet. o-Anisidine HCl (AH) was used as a genotoxic UB carcinogenic comparator, and trisodium nitrilotriacetate (NTA) as an epigenetic UB carcinogen comparator. Along with the non-dosed control and three test substance groups (PPX, AH, NTA), four more groups were additionally fed 2% ammonium chloride (AC) in the diet to acidify the urine, since 1321 was reported to increase urinary pH. AC did acidify the urine, as expected, although the 3883 diet itself did not increase pH values above 8. In the alkaline comet assay, AH produced DNA single strand breaks (SSBs) in the UB urothelium (UBU) irrespective of AC administration, whereas PPX and NTA did not. In the nucleotide (32)P-postlabeling assay (NPL), AH produced DNA adducts irrespective of AC administration, whereas PPX and NTA did not. Routine (H&E) histopathology evaluation of the UBU did not reveal any hyperplasia or evidence of luminal microprecipitates or calculi in any of the groups. Assessment of UBU proliferation as measured by immunohistochemistry of proliferating cell nuclear antigen, revealed that NTA and NTA plus AC increased the replicating fraction (RF). Also AH plus AC, but not AH alone, increased the RF of UBU, whereas PPX groups were not significantly different from controls. Thus, the results reveal no evidence for DNA SSBs, binding, or alteration of DNA synthesis in the UBU by PPX, while demonstrating UBU DNA damage by AH and showing that NTA does not damage DNA, but causes increased UBU proliferation. The findings are in accord with a genotoxic MOA for AH, and an epigenetic MOA for NTA. The MOA of PPX does not involve genotoxicity and may be specific to the 1321 diet.

A prospective study of cigarette smoking and basal cell carcinoma.

To investigate the relationship between smoking and primary basal cell carcinoma (BCC), we analyzed data from a 16 year prospective study among randomly selected adults in Nambour, Queensland, Australia. Participants underwent a skin examination in 1992 and took part in an intervention study and follow-up. Information about complexion type and smoking habits including duration and number of cigarettes smoked per day and sun exposure behavior were collected at baseline in 1992, with updates to end of follow-up in 2007. Newly-diagnosed BCCs were ascertained from regional pathology laboratories. Relative risks (RR) of BCC among former and current smokers were estimated using generalized linear models specifying a Poisson distribution with robust error variance and (log) person-years at-risk as offset, adjusting for BCC risk factors. From 1992 to 2007, 281 BCCs were diagnosed in 1,277 participants with available smoking history and no past BCC. Relative to non-smokers, a non-significant inverse association between current smoking and BCC was seen (RR 0.69; 95 % CI 0.45-1.05) but not for former smokers (RR 1.05; 95 % CI 0.84-1.31). Amongst current smokers, inverse associations with BCC were found in those who smoked for up to 18 years (RR 0.44) but not more and those who smoked up to 15 cigarettes per day but not more. The associations with both current and former smoking varied by degree of sunburn propensity. The modest inverse association between current smoking and BCC is considered unlikely to be causal given lack of clear relation with duration or intensity of smoking.

Successful transplantation of kidney allografts in sensitized rats after syngeneic hematopoietic stem cell transplantation and fludarabine.

Current methods to remove donor-specific HLA antibody (DSA) from sensitized patients remain imperfect. We tested novel approaches to desensitization using an animal model of allogeneic sensitization with skin grafts from dark agouti (DA) to Lewis rats. At the peak IgG alloantibody response we transplanted DA kidneys into nephrectomized Lewis recipients (n = 6) and all died within 10 days from antibody-mediated rejection (AMR). Allogeneic hematopoietic stem cell transplants (HSCT) from DA donors failed to engraft after lethal or sub-lethal irradiation. Sensitized rats given lethal irradiation plus syngeneic green fluorescent protein (GFP) + HSCT had repopulation of blood, spleen, thymus and lymph nodes by GFP+ cells. At 2 months after HSCT, serum DSA levels were reduced 60-70% and DSA (IgG) production in cultured splenocytes was also significantly decreased. However, there was only a modest improvement in graft survival from an average of 6.5 to 13.9 (n = 9) days. Adding seven daily doses of fludarabine to the preconditioning regimen resulted in long-term survival (>90 days) in 7 out of 10 rat kidney allografts. We conclude that syngeneic HSCT performed after preconditioning with irradiation and fludarabine can reduce DSA, prevent DSA rebound and AMR, enabling successful transplantation in animals with strong antibody reactivity to the donor MHC.

Exome sequencing of pleuropulmonary blastoma reveals frequent biallelic loss of TP53 and two hits in DICER1 resulting in retention of 5p-derived miRNA hairpin loop sequences.

Pleuropulmonary blastoma is a rare childhood malignancy of lung mesenchymal cells that can remain dormant as epithelial cysts or progress to high-grade sarcoma. Predisposing germline loss-of-function DICER1 variants have been described. We sought to uncover additional contributors through whole exome sequencing of 15 tumor/normal pairs, followed by targeted resequencing, miRNA analysis and immunohistochemical analysis of additional tumors. In addition to frequent biallelic loss  of TP53 and mutations of NRAS or BRAF in some cases, each case had compound disruption of DICER1: a germline (12 cases) or somatic (3 cases) loss-of-function variant plus a somatic missense mutation in the RNase IIIb domain. 5p-Derived microRNA (miRNA) transcripts retained abnormal precursor miRNA loop sequences normally removed by DICER1. This work both defines a genetic interaction landscape with DICER1 mutation and provides evidence for alteration in miRNA transcripts as a consequence of DICER1 disruption in cancer.

Predictors of change in weight and waist circumference: 15-year longitudinal study in Australian adults.

BACKGROUND/OBJECTIVES: This study examines which socio-demographic and lifestyle characteristics are associated with weight and waist circumference (WC) change in a cohort of Australian adults over a 15-year period (1992-2007). Further, it tests the effect of period of birth (birth cohort) on mean weight and WC at two time points, 15 years apart. SUBJECTS/METHODS: Up to three repeated measures of weight (n=1437) and WC (n=1317) were used. Self-reported data on socio-demographic and lifestyle characteristics were derived from repeated questionnaires. Multivariable models, stratified by sex, were adjusted for potential confounders. RESULTS: Participants born more recently were heavier, on average, than those in the same age group 15 years earlier, but there was no such secular trend in WC. Age at baseline was associated with change in weight and WC, but the pattern was different: participants gained weight up to age 55 years, while WC gain continued to 65 years. In women, higher level of recreational physical activity was associated with lower WC gain (P<0.05). Parity was also associated with WC change in women (P<0.05), but there was no linear trend. CONCLUSIONS: Age was the most important factor associated with change in weight and WC in both sexes, apparently reducing the influence of all potential covariates. Among women, physical activity and parity were also associated with change in weight and WC. This study provides longitudinal evidence to support public health efforts that address the continuous increases in average weight and WC of many populations around the world.

Can foster care ever be justified for weight management?

Article nine of the UN Convention of the Rights of the Child states that 'Children must not be separated from their parents unless it is in the best interests of the child.' We describe the impact that placing a child into care can have on long-standing and intractable obesity when this is a component of a child safeguarding strategy. Significant weight loss was documented in a male adolescent following his placement into foster care due to emotional harm and neglect within his birth family. The child's body mass index (BMI) dropped from a peak of 45.6 to 35 over 18 months. We provide brief details of two further similar cases and outcomes. Childhood obesity is often not the sole concern during safeguarding proceedings. Removal from an 'obesogenic' home environment should be considered if failure by the parents/carers to address the obesity is a major cause for concern. It is essential that all other avenues have been explored before removing a child from his birth family. However, in certain circumstances we feel it may be justified.

Identification of key residues involved in adrenomedullin binding to the AM1 receptor.

BACKGROUND AND PURPOSE: Adrenomedullin (AM) is a peptide hormone whose receptors are members of the class B GPCR family. They comprise a heteromer between the GPCR, the calcitonin receptor-like receptor and one of the receptor activity-modifying proteins 1-3. AM plays a significant role in angiogenesis and its antagonist fragment AM22-52 can inhibit blood vessel and tumour growth. The mechanism by which AM interacts with its receptors is unknown. EXPERIMENTAL APPROACH: We determined the AM22-52 binding epitope for the AM1 receptor extracellular domain using biophysical techniques, heteronuclear magnetic resonance spectroscopy and alanine scanning. KEY RESULTS: Chemical shift perturbation experiments located the main binding epitope for AM22-52 at the AM1 receptor to the C-terminal 8 amino acids. Isothermal titration calorimetry of AM22-52 alanine-substituted peptides indicated that Y52, G51 and I47 are essential for AM1 receptor binding and that K46 and P49 and R44 have a smaller role to play. Characterization of these peptides at the full-length AM receptors was assessed in Cos7 cells by cAMP assay. This confirmed the essential role of Y52, G51 and I47 in binding to the AM1 receptor, with their substitution resulting in ≥100-fold reduction in antagonist potency compared with AM22-52 . R44A, K46A, S48A and P49A AM22-52 decreased antagonist potency by approximately 10-fold. CONCLUSIONS AND IMPLICATIONS: This study localizes the main binding epitope of AM22-52 to its C-terminal amino acids and distinguishes essential residues involved in this binding. This will inform the development of improved AM receptor antagonists.