Detection and Differentiation of Entomopathogenic Serratia spp. to Inform Reintroduction of the Critically Endangered Lord Howe Island Stick Insect Dryococelus australis.

Once rodents have been successfully eradicated from Lord Howe Island, Australia, the critically endangered Lord Howe Island stick insect (Dryococelus australis (Montrouzier)) may be reintroduced, a century after it was thought to have become extinct. In captive populations of D. australis, elevated mortalities have been associated with bacterial pathogens. To better define the infectious risk posed by entomopathogens to the reintroduction program, we investigated the bacteria isolated from captive D. australis kept at Melbourne Zoo and on Lord Howe Island and from environmental samples and free-living invertebrates collected on various parts of the island. At Melbourne Zoo, Serratia and Pseudomonas spp. were the bacteria most frequently isolated between 2013 and 2019. Serratia spp. were also the organisms most frequently isolated from insects sampled in April 2019 from the captive population on Lord Howe Island. In addition, Serratia spp. were isolated from a range of environmental samples collected on Lord Howe Island during March-April 2019. These environmental isolates had a broader range of biochemical and molecular characteristics than those obtained from the captive insect populations. A large proportion of these isolates were urease positive and had biochemical profiles previously not described for Serratia spp. This study highlights the need for better surveillance for potential pathogens in understudied regions and sites. We conclude that infections caused by Serratia spp. might pose a problem to the captive breeding program for D. australis but that the risk of introducing novel pathogens to Lord Howe Island through infected insects is low. Our study explores some of the potential risks involved in captive breeding and provides a valuable example of using pathogen surveillance to better inform an invertebrate conservation program.

Using Decision Science for Monitoring Threatened Western Snowy Plovers to Inform Recovery.

Western Snowy Plovers (Charadrius nivosus nivosus) are federally listed under the US Endangered Species Act as Threatened. They occur along the US Pacific coastline and are threatened by habitat loss and destruction and excessive levels of predation and human disturbance. Populations have been monitored since the 1970s for distribution, reproduction, and survival. Since the species was federally listed in 1993 and a recovery plan was approved under the US Fish and Wildlife Service in 2007, recovery actions have resulted in growing populations with increased presence at breeding and wintering sites throughout their Pacific Coast range. This success has created logistical challenges related to monitoring a recovering species and a need for identifying and instituting the best monitoring approach given recovery goals, budgets, and the likelihood of monitoring success. We devised and implemented a structured decision analysis to evaluate nine alternative monitoring strategies. The analysis included inviting plover biologists involved in monitoring to score each strategy according to a suite of performance measures. Using multi-attribute utility theory, we combined scores across the performance measures for each monitoring strategy, and applied weighted utility values to show the implications of tradeoffs and find optimal decisions. We evaluated four scenarios for weighting the monitoring objectives and how risk attitude affects optimal decisions. This resulted in identifying six strategies that best meet recovery needs and were Pareto optimal for cost-effective monitoring. Results were presented to the US Fish and Wildlife Service, responsible for monitoring as well as for consideration to ensure consistent monitoring methods across the species' range. Our use of structured decision-making can be applied to cases of other species once imperiled but now on the road to recovery.

The ethics of future trials: qualitative analysis of physicians' decision making.

BACKGROUND: The decision to conduct a randomized controlled trial (RCT) in a field raises ethical as well as scientific issues. From the clinical equipoise literature, future trials are justifiable if there is "honest, professional disagreement in the community of expert practitioners as to the preferred treatment". Empirical data are sparse about how clinicians apply the principles of equipoise to the justification of future RCTs. For example, selective decontamination of the digestive tract (SDD) is not widely used in critical care practice despite the strength of the evidence base and therefore provides a unique opportunity to learn how clinicians think about the ethics of further RCTs in critical care. METHODS: In an international interview study of views of healthcare professionals about SDD, we undertook a secondary analysis of qualitative data collected using a Theoretical Domains Framework of clinical behaviour. We adopted a general descriptive approach to explore how physicians determined whether another RCT of SDD is ethical. Following a constant comparison approach, three investigators reviewed 54 purposively chosen transcripts from three international regions. We interpreted the data using thematic analysis. RESULTS: We grouped participants' responses into four inter-related themes: 1) cultural norms about evidence and practice within healthcare; 2) personal views about what evidence is current or applicable; 3) the interpersonal and relational nature of professional decision making locally; and 4) an a priori commitment to future trials. The analysis also identified several unresolved tensions regarding when a future RCT should be pursued. These tensions focused on a clash between potential benefits to current individual patients and potential future harms to patients more broadly. CONCLUSIONS: Our study suggests that ethical decision making about future RCTs in the field of SDD does not rely strongly on appeals to evidence, even when the quality of the evidence is reasonably high. Rather, "extra-evidential" reasons, including social, professional, and relational factors, seem to influence opinions regarding the ethics of future trials. Further work is required to see if these conclusions are applicable to other clinical topics and settings.

Impulsivity and Stress Response in Nondependent Smokers (Tobacco Chippers) in Comparison to Heavy Smokers and Nonsmokers.

INTRODUCTION: Tobacco chippers are light smokers with stable patterns of smoking that exhibit lower nicotine dependence severity than heavy smokers. Chippers may provide valuable information about the factors influencing drug dependence. Impulsivity and stress are two factors known to influence smoking. By comparing nondependent smokers (tobacco chippers, n = 25) to dependent smokers (heavy smokers, n = 23) and nonsmokers (n = 25), this study examines the relationship between nicotine dependence, impulsivity, chronic stress, and stress reactivity. METHODS: A total of 73 adult participants completed a study visit that included questionnaires to measure nicotine dependence, chronic stress, personality, affect, withdrawal, and craving. Impulsivity was measured with the delay discounting task and the flanker task. Stress reactivity was assessed by monitoring respiration, heart rate, and salivary cortisol during performance of a titrated Stroop task. Effects of acute stress on affect and craving were examined. RESULTS: Tobacco chippers were as impulsive as heavy smokers on the delay discounting task but no different from nonsmokers on the flanker task. Heavy smokers reported higher perceived stress than chippers and nonsmokers. Perceived stress was a significant predictor of discounting only in heavy smokers. Acute stress induced changes in respiration, heart rate, and heart rate variability. Craving and negative affect increased after stress in both smoking groups, but craving was associated with affect only in chippers. CONCLUSIONS: Tobacco chippers do not differ from heavy smokers in impulsivity, but do differ in perceived stress. One's perception and experience of stress might be associated to nicotine dependence resistance and could inform smoking cessation treatments. IMPLICATIONS: By examining impulsivity, chronic stress, and stress reactivity in nondependent smokers (tobacco chippers) compared to dependent smokers and nonsmokers, this study contributes to the understanding of nicotine addiction and informs smoking cessation programs.

The views of health care professionals about selective decontamination of the digestive tract: an international, theoretically informed interview study.

PURPOSE: Selective decontamination of the digestive tract (SDD) as a prophylactic intervention improves hospital-acquired infection and survival rates. Uptake of SDD is low and remains controversial. This study applied the theoretical domains framework to assess intensive care unit clinicians' views about SDD in regions with limited or no adoption of SDD. MATERIALS AND METHODS: Participants were health professionals with "decisional authority" for the adoption of SDD. Semistructured interviews were conducted as the first round of a Delphi study. Views about SDD adoption, delivery, and further SDD research were explored. Directed content analysis of interview data identified subthemes, which informed item development for subsequent Delphi rounds. Linguistic features of interview data were also explored. RESULTS: One hundred forty-one participants provided interview data. Fifty-six subthemes were identified; 46 were common across regions. Beliefs about consequences were the most widely elaborated theme. Linguistic features of how participants discussed SDD included caution expressed when discussing the risks and benefits and words such as "worry," "anxiety," and "fear" when discussing potential antibiotic resistance associated with SDD. CONCLUSIONS: We identified salient beliefs, barriers, and facilitators to SDD adoption and delivery. What participants said about SDD and the way in which they said it demonstrated the degree of clinical caution, uncertainty, and concern that SDD evokes.

Heritability and genomics of gene expression in peripheral blood.

We assessed gene expression profiles in 2,752 twins, using a classic twin design to quantify expression heritability and quantitative trait loci (eQTLs) in peripheral blood. The most highly heritable genes (∼777) were grouped into distinct expression clusters, enriched in gene-poor regions, associated with specific gene function or ontology classes, and strongly associated with disease designation. The design enabled a comparison of twin-based heritability to estimates based on dizygotic identity-by-descent sharing and distant genetic relatedness. Consideration of sampling variation suggests that previous heritability estimates have been upwardly biased. Genotyping of 2,494 twins enabled powerful identification of eQTLs, which we further examined in a replication set of 1,895 unrelated subjects. A large number of non-redundant local eQTLs (6,756) met replication criteria, whereas a relatively small number of distant eQTLs (165) met quality control and replication standards. Our results provide a new resource toward understanding the genetic control of transcription.

Comparison of four methods for assessing the importance of attitudinal beliefs: an international Delphi study in intensive care settings.

OBJECTIVES: Behaviour change interventions often target 'important' beliefs. The literature proposes four methods for assessing importance of attitudinal beliefs: elicitation frequency, importance ratings, and strength of prediction (bivariate and multivariate). We tested congruence between these methods in a Delphi study about selective decontamination of the digestive tract (SDD). SDD improves infection rates among critically ill patients, yet uptake in intensive care units is low internationally. METHODS: A Delphi study involved three iterations ('rounds'). Participants were 105 intensive care clinicians in the United Kingdom, Canada, and Australia/New Zealand. In Round 1, semi-structured interviews were conducted to elicit beliefs about delivering SDD. In Rounds 2 and 3, participants completed questionnaires, rating agreement and importance for each belief-statement (9-point Likert scales). Belief importance was assessed using elicitation frequency, mean importance ratings, and prediction of global attitude (Pearson's correlations; beta-weights). Correlations between indices were computed. RESULTS: Participants generated 14 attitudinal beliefs. Indices had adequate variation (frequencies: 4-94, mean importance ratings: 4.93-8.00, Pearson's correlations: ± 0.09 to ± 0.54, beta-weights: ± 0.01 to ± 0.30). SDD increases antibiotic resistance was the most important belief according to three methods and was ranked second by beta-weights (behind Overall, SDD benefits patients to whom it is delivered). Spearman's correlations were significant for importance ratings with frequencies and correlations. However, other indices were unrelated. The top four beliefs differed according to the measure used. CONCLUSIONS: Results provided evidence of congruence across three methods for assessing belief importance. Beta-weights were unrelated to other indices, suggesting that they may not be appropriate as the sole method. STATEMENT OF CONTRIBUTION: What is already known on this subject? Attitudinal beliefs (specific beliefs about the consequences of performing an action) are key to designing interventions to change intentions and behaviour. The literature reports four methods for assessing the importance of attitudinal beliefs: frequency of elicitation in interviews, importance ratings in questionnaires, and strength of prediction (bivariate and multivariate) of global attitude scores. The congruence between these measures of importance is not known. What does this study add? Four indices of importance were examined in a multi-professional, international study about the use of selective digestive decontamination to prevent infection in intensive care settings. Three indices were correlated with one another. Each method used to assess importance produced a different subset of the most important beliefs. Selection of the most important beliefs should use multiple assessment methods. This evidence suggests that multiple regression approaches may not be appropriate as the sole method for assessing belief importance.

Implementing selective digestive tract decontamination in the intensive care unit: A qualitative analysis of nurse-identified considerations.

OBJECTIVE: To describe factors senior critical care nurses identify as being important to address when introducing selective digestive tract decontamination (SDD) in the clinical setting. BACKGROUND: Critically ill patients are at risk of developing ventilator-associated pneumonia (VAP). SDD is one strategy shown to prevent VAP and possibly improve survival in the critically ill. METHODS: We performed a secondary analysis of qualitative data obtained from 20 interviews. An inductive thematic analysis approach was applied to data obtained from senior critical care nurses during phase two of a multi-methods study. RESULTS: There were four primary considerations identified that should be addressed or considered prior to implementation of SDD. These considerations included education of health care professionals, patient comfort, compatibility of SDD with existing practices, and cost. CONCLUSIONS: Despite a lack of experience with, or knowledge of SDD, nurses were able to articulate factors that may influence its implementation and delivery. Organizations or researchers considering implementation of SDD should include nurses as key members of the implementation team.

Clinical stakeholders' opinions on the use of selective decontamination of the digestive tract in critically ill patients in intensive care units: an international Delphi study.

INTRODUCTION: Selective decontamination of the digestive tract (SDD) is a prophylactic antibiotic regimen that is not widely used in practice. We aimed to describe the opinions of key 'stakeholders' about the validity of the existing evidence base, likely consequences of implementation, relative importance of their opinions in influencing overall practice, likely barriers to implementation and perceptions of the requirement for further research to inform the decision about whether to embark on a further large randomised controlled trial. METHODS: This was a Delphi study informed by comprehensive framework of possible determinants of health professionals' behaviour to study Critical Care practice in four countries. There were four key stakeholder participant groups including ICU physicians, pharmacists, clinical leads, and clinical microbiologists/ infectious disease physicians. Round one comprised participant interviews and Rounds two and three were online questionnaires using Delphi method. RESULTS: In this study, 141 participants were recruited of whom 82% were retained. Participants rated themselves as knowledgeable about SDD. Antibiotic resistance was identified as the most important issue. SDD was seen as a low clinical priority but few participants reported strong opposition. There was moderate agreement that research to date has not adequately addressed concerns about antibiotic resistance and lacks generalizability. Participants indicated equipoise with regard to benefits and harms of SDD, and indicated strong support for a further randomised trial. CONCLUSIONS: Clinicians have clinical equipoise about the effectiveness of SDD. Future research requires longer follow up to assess antibiotic resistance as well as greater validity/generalizability to provide definitive answers on the effectiveness of decontamination and effects on antibiotic resistance. SDD was regarded as not being a high clinical priority, which may limit future trial participation. These results have identified that further large randomised controlled trial of SDD in critical care is both warranted and appropriate.

Mind-body practices: an alternative, drug-free treatment for smoking cessation? A systematic review of the literature.

OBJECTIVE: The limited success of current smoking cessation therapies encourages research into new treatment strategies. Mind-body practices such as yoga and meditation have the potential to aid smoking cessation and become an alternative drug-free treatment option. The aim of this article is to assess the efficacy of yoga and other meditation-based interventions for smoking cessation, to identify the challenges of clinical trials applying mind-body treatments, and to outline directions for future research on these types of therapies to assist in smoking cessation. METHODS: A systematic review of the scientific literature. RESULTS: Fourteen clinical trials met the inclusion criteria defined for this review. Each article was reviewed thoroughly, and evaluated for quality, design, and methodology. Although primary outcomes differed between studies, the fourteen articles, most with limitations, reported promising effects supporting further investigation of the use of these practices to improve smoking cessation. CONCLUSIONS: The literature supports yoga and meditation-based therapies as candidates to assist smoking cessation. However, the small number of studies available and associated methodological problems require more clinical trials with larger sample sizes and carefully monitored interventions to determine rigorously if yoga and meditation are effective treatments.

Body image and eating attitudes and behaviors among adolescent heart and lung transplant recipients: a brief report.

BACKGROUND: Adolescents with chronic illnesses are at increased risk for body image and eating disorders; however, this has not been investigated in solid organ transplant recipients. Adolescent transplant recipients are a vulnerable cohort because of the sustained follow-up and immune-suppressing therapies, which often include steroids and may lead to weight gain and cosmetic changes. Consequences of body dissatisfaction such as disordered behaviors have not been well studied in transplant recipients. PURPOSE: To examine body image, eating attitudes, and behaviors among 28 adolescent thoracic transplant recipients. METHODS: Adolescent (11-18 years old) heart and lung transplant recipients a minimum of 3 months after transplant provided informed written consent and completed a standardized questionnaire package about eating attitudes and behaviors; body image and drive for thinness; actual, perceived, and desired weight; and medical and anthropometric information (eg, body mass index) during regular transplant clinics. RESULTS: Of 25 heart and 3 lung transplant recipients (54% female; median age, 14.5 years; median, 1.6 years after transplant), 37% perceived their current weight as too high or low. Moreover, 81% were dissatisfied with their current weight (38% wanted to lose and 44% wanted to gain weight), yet few engaged in disordered behaviors. CONCLUSIONS: Despite high levels of self-reported body dissatisfaction, low rates of disordered behaviors were observed. Weight dissatisfaction was high (81%) but bidirectional (to lose or to gain weight). Future assessment of disordered eating behaviors should include insidious activities such as medication nonadherence, in addition to traditional weight-control behaviors such as binge eating, strict dieting, or assiduous exercise. Further research will delineate the impact of body dissatisfaction and eating behaviors and outcomes on long-term transplant survivors, older adolescent cohorts, and other recipients of solid organ transplants.

Beliefs about causes of colon cancer by English-as-a-Second-Language Chinese immigrant women to Canada.

Colon cancer is the second leading cause of cancer death for Canadians. Immigrants underutilize screening and may be at greater risk of late stage diagnosis and death from the disease. This mixed-methods study investigated the self-reported causes of colon cancer by 66 English-as-a-Second-Language Chinese immigrant women to Canada after reading a fact sheet which listed two causes of colon cancer (polyps and cause unknown) and six ways to help prevent colon cancer (lifestyle, diet, weight, smoking, alcohol, and screening). Women correctly named or described both causes (6.1%) or one cause (22.7%), could not name or describe either cause (19.7%), or named or described causes not included on the fact sheet (54.5%). The most common causes reported by participants were "risk factors": diet (53.0%), family history (28.8%), and lifestyle (22.7%). Women confused cause with risk factor and infrequently mentioned screening. Possible reasons for their reported beliefs are discussed.

Comparing written and oral measures of comprehension of cancer information by English-as-a-Second-Language Chinese immigrant women.

The Short Test of Functional Health Literacy for Adults (S-TOFHLA) and Cloze test are commonly used tools to measure comprehension of health information (i.e., health literacy); however, little is known about their use in English-as-a-Second-Language (ESL) populations. In this study, we compared written (Cloze test) and oral (Teach Back) measures of colon cancer information comprehension among ESL Chinese immigrant women to Canada. Performances on colon cancer-specific measures were compared to a general measure of health literacy (S-TOFHLA). On the S-TOFHLA, Cloze, and Teach Back, respectively, the following percentage of participants had adequate comprehension: 62.1%, 14.8%, and 89.7%. Correlation between performance on the Cloze and Teach Back was significant albeit weakly so (r = 0.38, p = 0.04); performances on the S-TOFHLA and Teach Back were not correlated. Measures of health literacy skill that require written English language skills may not be appropriate for measuring understanding of health information for ESL populations.

Predicting health literacy among English-as-a-second-Language older Chinese immigrant women to Canada: comprehension of colon cancer prevention information.

Inadequate health literacy has been identified as a barrier to the utilization of health-care services, including cancer screening. This study examined predictors of health literacy among 106 older Chinese immigrant women to Canada and how colon cancer information presented in their first versus second language affected health literacy skill. Only 38.7% of the women had adequate health literacy based on Short Test of Functional Health Literacy for Adults, and 54.3% had adequate comprehension of the colon cancer information. Comprehension of the cancer information was significantly lower among women who received the information in English compared with those who received the information in Chinese. Age, acculturation, self-reported proficiency reading English, and education were significant predictors of health literacy but varied depending on the measure of health literacy used and language of the information. Presentation of cancer prevention information in one's first rather than second language improves health literacy but does not eliminate comprehension difficulties for older ESL Chinese immigrants.

A qualitative study of cancer information seeking among English-as-a-second-Language older Chinese immigrant women to canada: sources, barriers, and strategies.

Little is known about the cancer information seeking experiences of Chinese immigrants despite reported disparities in cancer burden and use of cancer screening. This research used semi-structured interviews to the explore cancer information seeking preferences and experiences of 50 English-as-a-second-language older Chinese immigrant women to Canada with different levels of health literacy. Directed content analysis was used to identify three main themes: sources of cancer information, barriers to cancer information seeking, and strategies used during information seeking. Health literacy did not distinguish the women on any of the major themes. The women expressed strong preferences for interpersonal and interactive cancer information from their physician and trusted others, such as friends and family. Barriers to cancer information seeking included language difficulties and limited time with physicians. The results emphasize the need for cancer information that reinforces cultural norms, language familiarity, and other values specific to cultural identities, such as interpersonally oriented values.

Predicting breast and colon cancer screening among English-as-a-second-language older Chinese immigrant women to Canada.

Little is known about the cancer screening behaviors of older ESL Chinese immigrant women. To explore predictors of colon and breast cancer screening in this population, 103 Mandarin- and Cantonese-speaking immigrant women ages 50 years and older were recruited. Participants completed questionnaires to evaluate screening behaviors, health literacy, and demographic characteristics. Eighty-five percent self-reported that they were current breast cancer screeners, and 75% were current colon cancer screeners. Recommendation from a physician, having a female physician, and high or moderate proficiency in English predicted current mammography screening. Physician recommendation, first language, and self-efficacy predicted use of colon cancer screening. Bivariate analyses also revealed an association between use of colon cancer screening and greater health literacy and longer residency in Canada. Important predictors of screening emerged that potentially informs interventions to increase cancer prevention among older Chinese immigrants. The essential role of physician recommendation was identified for both breast and colon cancer screening.

Acceptability and face validity of a geriatric self-medication assessment tool.

BACKGROUND: A majority of community-dwelling older adults manage their own medication regimens. This study describes the development and first phase of testing of the Self-Medication Assessment Tool (SMAT), designed to screen for cognitive and functional deficits in relation to medication self-management among community-dwelling geriatric patients. OBJECTIVE: To evaluate the face validity of the SMAT and to determine its acceptability among pharmacists. METHODS: An instrument was designed, with 5 assessment scales to measure function, cognition, medication recall, and 2 aspects of adherence. The instrument included a standardized test kit and instructions for testers. Focus groups interviews, individual interviews, and surveys were used to determine the reactions of community and hospital-based pharmacists to the tool. Transcripts of the focus group and individual interviews were coded for main themes. Pharmacists' ratings of usefulness, thoroughness, and ease of use, as well as their willingness to use the instrument, were compared with a neutral rating on a 7-point scale by means of 1-sample t tests. RESULTS: Focus group interviews or individual interviews were conducted with 17 pharmacists and 3 pharmacy students (out of a potential population of about 300) who responded to an invitation to participate. The pharmacists felt that the tool would be useful in identifying difficulties with medication management and potential interventions, and they expressed a willingness to use it in their respective practices. Pharmacists working in hospital settings were slightly more willing than community pharmacists to use the tool. Interviewees highlighted ways to improve the tool before testing of its psychometric properties in the planned second phase of this project. CONCLUSIONS: The SMAT had strong face validity and was particularly acceptable for use by pharmacists in hospital settings.

Child and parental perspectives of multidimensional quality of life outcomes after kidney transplantation.

Kidney transplantation is an optimal therapy for pediatric patients with end-stage kidney disease. This pilot study sought to examine multidimensional QOL outcomes after kidney transplant using VAQOL and General Health, the PedsQL 4.0, PedsQL End Stage Renal Disease Module, and Impact on Family Module. Sample included 12 adolescents aged 13-18 yr and their parent; three children aged eight to 12 yr and their parent; and six parents of children aged two to seven yr. All were 73 months post transplant. The median age at transplant was 9.3 yr and median time since transplant was 3.2 yr. VAQOL mean was 7.7/10 (child report) and 7.3/10 (parent report); the mean general health was 7.4/10. High levels of fatigue (> or =5/10) were reported in 43%. PedsQL subscale mean values were lower than healthy reference scores. PedsQL Renal Module demonstrated great concern with physical appearance and physical symptoms (thirst and headaches), difficulty with peer and family interaction, and school disruption. Low scores on parental emotional function depict the negative impact of transplant on family functioning. Discordance exists between child and parental reports of QOL. Prospective studies are needed to explore multidimensional QOL to improve long-term outcomes after pediatric kidney transplant.

Endogenous truncated TrkB.T1 receptor regulates neuronal complexity and TrkB kinase receptor function in vivo.

Pathological or in vitro overexpression of the truncated TrkB (TrkB.T1) receptor inhibits signaling through the full-length TrkB (TrkB.FL) tyrosine kinase receptor. However, to date, the role of endogenous TrkB.T1 is still unknown. By studying mice lacking the truncated TrkB.T1 isoform but retaining normal spatiotemporal expression of TrkB.FL, we have analyzed TrkB.T1-specific physiological functions and its effect on endogenous TrkB kinase signaling in vivo. We found that TrkB.T1-deficient mice develop normally but show increased anxiety in association with morphological abnormalities in the length and complexity of neurites of neurons in the basolateral amygdala. However, no behavioral abnormalities were detected in hippocampal-dependent memory tasks, which correlated with lack of any obvious hippocampal morphological deficits or alterations in basal synaptic transmission and long-term potentiation. In vivo reduction of TrkB signaling by removal of one BDNF allele could be partially rescued by TrkB.T1 deletion, which was revealed by an amelioration of the enhanced aggression and weight gain associated with BDNF haploinsufficiency. Our results suggest that, at the physiological level, TrkB.T1 receptors are important regulators of TrkB.FL signaling in vivo. Moreover, TrkB.T1 selectively affects dendrite complexity of certain neuronal populations.

Developmental analysis of Lingo-1/Lern1 protein expression in the mouse brain: interaction of its intracellular domain with Myt1l.

Lingo-1 (also known as Lern1) is a component of the Nogo receptor complex that mediates intracellular signaling in response to myelin associated inhibitors (MAIs): NogoA, MAG, and Omgp. Signaling through Nogo receptor extends to more than its well known role in preventing axon regeneration after lesion in the CNS, being implicated in neuronal functional maturation. Using Lingo-1-deficient mice, it has been demonstrated that Lingo-1 plays relevant roles in oligodendrocyte differentiation during brain development, and that treatment with Lingo-1 antagonists can improve axon regeneration after lesion in adult mice by decreasing MAI mediated signaling. However, a detailed description of the pattern of expression of Lingo-1 protein in correlation with the other partners of Nogo receptor is missing. Here, we show that components of the Nogo receptor complex, Lingo-1, NgR1, p75, and TROY coexist in mouse brain in a defined time window only at later postnatal stages. We have also determined the Lingo-1 distribution showing expression in particular subsets of neurons, but not in myelinating mature oligodendrocytes. Surprisingly, Lingo-1 is expressed at early developmental stages without NgR1, which supports the notion that Lingo-1 may participate in other activities in developing neurons different from oligodendrocyte maturation or axon extension inhibition in the adult. Finally, we propose that the intracellular domain of Lingo-1 contributes to signaling and show that it interacts with the postmitotic neuronal specific zinc finger protein Myt1l, suggesting that Lingo-1 may regulate Myt1l transcription factor activity by affecting its subcellular localization.