Classification of porcine reproductive and respiratory syndrome clinical impact in Ontario sow herds using machine learning approaches.

Since the early 1990s, porcine reproductive and respiratory syndrome (PRRS) virus outbreaks have been reported across various parts of North America, Europe, and Asia. The incursion of PRRS virus (PRRSV) in swine herds could result in various clinical manifestations, resulting in a substantial impact on the incidence of respiratory morbidity, reproductive loss, and mortality. Veterinary experts, among others, regularly analyze the PRRSV open reading frame-5 (ORF-5) for prognostic purposes to assess the risk of severe clinical outcomes. In this study, we explored if predictive modeling techniques could be used to identify the severity of typical clinical signs observed during PRRS outbreaks in sow herds. Our study aimed to evaluate four baseline machine learning (ML) algorithms: logistic regression (LR) with ridge and lasso regularization techniques, random forest (RF), k-nearest neighbor (KNN), and support vector machine (SVM), for the clinical impact classification of ORF-5 sequences and demographic data into high impact and low impact categories. First, baseline classifiers were evaluated using different input representations of ORF-5 nucleotides, amino acid sequences, and demographic data using a 10-fold cross-validation technique. Then, we designed a consensus voting ensemble approach to aggregate the different types of input representations for genetic and demographic data for classifying clinical impact. In this study, we observed that: (a) for abortion and pre-weaning mortality (PWM), different classifiers gained improvement over baseline accuracy, which showed the plausible presence of both genotypic-phenotypic and demographic-phenotypic relationships, (b) for sow mortality (SM), no baseline classifier successfully established such linkages using either genetic or demographic input data, (c) baseline classifiers showed good performance with a moderate variance of the performance metrics, due to high-class overlap and the small dataset size used for training, and (d) the use of consensus voting ensemble techniques helped to make the predictions more robust and stabilized the performance evaluation metrics, but overall accuracy did not substantially improve the diagnostic metrics over baseline classifiers.

Latent burnout profiles of veterinarians in Canada: Findings from a cross-sectional study.

BACKGROUND: Although burnout is often discussed as 'present' or 'not-present', the conceptual framework of an engagement-burnout continuum is more accurate and useful. Recognition of individuals' transitional states of burnout also allows for earlier detection of issues and tailored interventions to address the full burnout spectrum. METHODS: Previously reported Maslach Burnout Inventory-Human Services Scale (MBI-HSS) data from a 2017 national survey of 1272 veterinarians across Canada were re-analysed using a latent profile analysis to classify individuals along the engagement-burnout continuum. RESULTS: Four clusters were identified: engaged (10.8%), ineffective (18.9%), overextended (29.6%) and burnout (40.7%). These results indicate that most participants (89.2%) had one, or a combination, of high exhaustion, high depersonalisation and low professional efficacy. LIMITATIONS: This cross-sectional study represents data from one point in time and may be subject to response bias. CONCLUSION: We discuss strategies-particularly long-term, organisational-level interventions-to promote engagement and help address workplace issues contributing to inefficacy, overextension and burnout in the veterinary profession. We also recommend MBI data be analysed via latent profiles to provide a more nuanced view of burnout, allow for earlier recognition of workplace issues and facilitate more meaningful interventions and comparisons across populations.

Community science reveals links between migration arrival timing advance, migration distance and wing shape.

Substantial global data show that many taxa are shifting their phenologies in response to climate change. For birds, migration arrival dates in breeding regions have been shifting earlier, and there is evidence that both evolutionary adaptation and behavioural flexibility influence these shifts. As more efficient flyers may be able to demonstrate more flexibility to respond to changing conditions during migratory flight, we hypothesize that differences among passerine species in flight efficiency, as reflected by morphology, may be associated with the magnitude of shifts in arrival date in response to climate warming. We applied a logistic model to 18 years of eBird data to estimate mean arrival date for 44 common passerines migrating to northeast North America. We then used linear mixed-effects models to estimate changes in mean arrival date and compared these changes to morphological proxies for flight efficiency and migratory distance using phylogenetic generalized least squares models. On average, passerine species shifted their arrival dates 0.120 days earlier each year, with 27 of the 44 species shifting to significantly earlier arrival times, and two shifting to significantly later ones. Of the 15 species with non-significant shifts, 13 trended toward earlier arrivals. Longer migration distances and higher wing aspect ratios were associated with greater shifts toward earlier arrivals. Migration distance and aspect ratio were also significantly correlated to each other. This suggests that changes in arrival date are affected by factors pertaining to migratory flight over long distances namely, flight efficiency and migration distance. These traits may be able predict the magnitude of arrival date shift, and by extension identify species that are most at risk to climate change due to inflexible arrival timing.

Characteristics of miRNAs Present in Bovine Sperm and Associations With Differences in Fertility.

Small non-coding RNAs have been linked to different phenotypes in bovine sperm, however attempts to identify sperm-borne molecular biomarkers of male fertility have thus far failed to identify a robust profile of expressed miRNAs related to fertility. We hypothesized that some differences in bull fertility may be reflected in the levels of different miRNAs in sperm. To explore such differences in fertility that are not due to differences in visible metrics of sperm quality, we employed Next Generation Sequencing to compare the miRNA populations in Bos taurus sperm from bulls with comparable motility and morphology but varying Sire Conception Rates. We identified the most abundant miRNAs in both populations (miRs -34b-3p; -100-5p; -191-5p; -30d-4p; -21-5p) and evaluated differences in the overall levels and specific patterns of isomiR expression. We also explored correlations between specific pairs of miRNAs in each population and identified 10 distinct pairs of miRNAs that were positively correlated in bulls with higher fertility and negatively correlated in comparatively less fertile individuals. Furthermore, 8 additional miRNA pairs demonstrated the opposite trend; negatively correlated in high fertility animals and positively correlated in less fertile bulls. Finally, we performed pathway analysis to identify potential roles of miRNAs present in bull sperm in the regulation of specific genes that impact spermatogenesis and embryo development. Together, these results present a comprehensive picture of the bovine sperm miRNAome that suggests multiple potential roles in fertility.

A content analysis of Canadian influencer crisis messages on Instagram and the public's response during COVID-19.

Successful mitigation of emerging infectious disease requires that the public adopt recommended behaviours, which is directly influenced by effective crisis communication. Social media has become an important communication channel during COVID-19 where official actors, influencers, and the public are co-creating crisis messages. Our research examined COVID-19-related crisis messages across Canadian influencer accounts within news media, politicians, public health and government, science communicators, and brand influencer and celebrities, posted on Instagram between December 2019 and March 2021 for Health Belief Model and Extended Parallel Processing Model constructs and the corresponding public comment sentiment and engagement. Thirty-three influencer accounts resulted in a total of 2,642 Instagram posts collected, along with 461,436 comments, which showed overall low use of constructs in both captions and images. Further, most posts used no combinations (n = 0 or 1 construct per post) of constructs in captions and images and very infrequently used captions that combined threat (severity and susceptibility) with cues to action and efficacy. Brand influencers and celebrities, politicians, and science communicators had above average post engagement while public health and government and news media had lower. Finally, most influencers saw the largest proportion of neutral sentiment comments. Crisis messages must be designed to include combinations of constructs that increase message acceptance and influence risk perception and efficacy to increase the adoption of recommended and mandated behaviours.

Molecular Acquisition, Cleaning and Evaluation in R (MACER) - A tool to assemble molecular marker datasets from BOLD and GenBank.

Molecular sequence data is an essential component for many biological fields of study. The strength of these data is in their ability to be centralised and compared across research studies. There are many online repositories for molecular sequence data, some of which are very large accumulations of varying data types like NCBI's GenBank. Due to the size and the complexity of the data in these repositories, challenges arise in searching for data of interest. While data repositories exist for molecular markers, taxa and other specific research interests, repositories may not contain, or be suitable for, more specific applications. Manually accessing, searching, downloading, accumulating, dereplicating and cleaning data to construct project-specific datasets is time-consuming. In addition, the manual assembly of datasets presents challenges with reproducibility. Here, we present the MACER package to assist researchers in assembling molecular datasets and provide reproducibility in the process.

Examining Social Media Crisis Communication during Early COVID-19 from Public Health and News Media for Quality, Content, and Corresponding Public Sentiment.

Rising COVID-19 cases in Canada in early 2021, coupled with pervasive mis- and disinformation, demonstrate the critical relationship between effective crisis communication, trust, and risk protective measure adherence by the public. Trust in crisis communication is affected by the communication's characteristics including transparency, timeliness, empathy, and clarity, as well as the source and communication channels used. Crisis communication occurs in a rhetorical arena where various actors, including public health, news media, and the public, are co-producing and responding to messages. Rhetorical arenas must be monitored to assess the acceptance of messaging. The quality and content of Canadian public health and news media crisis communication on Facebook were evaluated to understand the use of key guiding principles of effective crisis communication, the focus of the communication, and subsequent public emotional response to included posts. Four hundred and thirty-eight posts and 26,774 anonymized comments were collected and analyzed. Overall, the guiding principles for effective crisis communication were inconsistently applied and combined. A limited combination of guiding principles, especially those that demonstrate trustworthiness, was likely driving the negative sentiment uncovered in the comments. Public health and news media should use the guiding principles consistently to increase positive sentiment and build trust among followers.

Collaborating in the Time of COVID-19: The Scope and Scale of Innovative Responses to a Global Pandemic.

The emergence of COVID-19 spurred the formation of myriad teams to tackle every conceivable aspect of the virus and thwart its spread. Enabled by global digital connectedness, collaboration has become a constant theme throughout the pandemic, resulting in the expedition of the scientific process (including vaccine development), rapid consolidation of global outbreak data and statistics, and experimentation with novel partnerships. To document the evolution of these collaborative efforts, the authors collected illustrative examples as the pandemic unfolded, supplemented with publications from the JMIR COVID-19 Special Issue. Over 60 projects rooted in collaboration are categorized into five main themes: knowledge dissemination, data propagation, crowdsourcing, artificial intelligence, and hardware design and development. They highlight the numerous ways that citizens, industry professionals, researchers, and academics have come together worldwide to consolidate information and produce products to combat the COVID-19 pandemic. Initially, researchers and citizen scientists scrambled to access quality data within an overwhelming quantity of information. As global curated data sets emerged, derivative works such as visualizations or models were developed that depended on consistent data and would fail when there were unanticipated changes. Crowdsourcing was used to collect and analyze data, aid in contact tracing, and produce personal protective equipment by sharing open designs for 3D printing. An international consortium of entrepreneurs and researchers created a ventilator based on an open-source design. A coalition of nongovernmental organizations and governmental organizations, led by the White House Office of Science and Technology Policy, created a shared open resource of over 200,000 research publications about COVID-19 and subsequently offered cash prizes for the best solutions to 17 key questions involving artificial intelligence. A thread of collaboration weaved throughout the pandemic response, which will shape future efforts. Novel partnerships will cross boundaries to create better processes, products, and solutions to consequential societal challenges.

HACSim: an R package to estimate intraspecific sample sizes for genetic diversity assessment using haplotype accumulation curves.

Assessing levels of standing genetic variation within species requires a robust sampling for the purpose of accurate specimen identification using molecular techniques such as DNA barcoding; however, statistical estimators for what constitutes a robust sample are currently lacking. Moreover, such estimates are needed because most species are currently represented by only one or a few sequences in existing databases, which can safely be assumed to be undersampled. Unfortunately, sample sizes of 5-10 specimens per species typically seen in DNA barcoding studies are often insufficient to adequately capture within-species genetic diversity. Here, we introduce a novel iterative extrapolation simulation algorithm of haplotype accumulation curves, called HACSim (Haplotype Accumulation Curve Simulator) that can be employed to calculate likely sample sizes needed to observe the full range of DNA barcode haplotype variation that exists for a species. Using uniform haplotype and non-uniform haplotype frequency distributions, the notion of sampling sufficiency (the sample size at which sampling accuracy is maximized and above which no new sampling information is likely to be gained) can be gleaned. HACSim can be employed in two primary ways to estimate specimen sample sizes: (1) to simulate haplotype sampling in hypothetical species, and (2) to simulate haplotype sampling in real species mined from public reference sequence databases like the Barcode of Life Data Systems (BOLD) or GenBank for any genomic marker of interest. While our algorithm is globally convergent, runtime is heavily dependent on initial sample sizes and skewness of the corresponding haplotype frequency distribution.

The utility of joinpoint regression for estimating population parameters given changes in population structure.

The method of joinpoint regression has been used in numerous domains to assess changes in time series data, including such things as cancer mortality rates, motor vehicle collision mortalities, and disease risk. To help improve estimation of population parameters for use in ecological risk assessment and management, we present a simulation and analysis to describe the utility of this method for the ecological domain. We demonstrate how joinpoint regression can accurately identify if the population structure changes based on time series of abundance, as well as identify when this change occurs. In addition, we compare and contrast population parameter estimates derived through joinpoint and surplus production methods to those derived from standard surplus production methods alone. When considering a change point at 32 years (out of a 64 year simulation), the joinpoint regression model was able, on average, to estimate a joinpoint time of 32.31 years with a variance of 6.82 and 95% confidence interval for the mean relative bias of (0.0085, 0.0112). The model was able to consistently estimate population parameters, with variance of these estimations decreasing as the change in these population parameters increased. We conclude that joinpoint regression be added to the list of methods employed by those who assess ecological risk to allow for a more accurate and complete understanding of population dynamics.

The need for community-led, integrated and innovative monitoring programmes when responding to the health impacts of climate change.

In Northern Canada, climate change has led to many acute and interrelated health and environmental impacts experienced among Inuit populations. Community-based monitoring, in which community members participate in monitoring initiatives using various forms of technology, is a key strategy increasingly used to detect, monitor and respond to climate change impacts. To better understand the landscape of existing environmental and health monitoring programmes mobilising different technologies and operating in the North we conducted a review that used environmental scan methodologies to explore and contextualise these programmes. We consulted with academic researchers with experience in community-led monitoring, conducted systematic searches of grey and peer-reviewed literature, and conducted a secondary search for environment-health mobile-phone applications. Following specific criteria, we identified 18 monitoring programmes using information and communication technologies in the North, and three global monitoring mobile-phone applications, which cumulatively monitored 74 environment and health indicators. Several themes emerged, including the need for: (1) community leadership, (2) indicators of environment and/or human health and (3) innovative technology. This synthesis supports the development of community-led, environment-health monitoring programmes that use innovative technology to monitor and share information related to the health implications of climate change in and around Indigenous communities throughout the Circumpolar North.

Incomplete estimates of genetic diversity within species: Implications for DNA barcoding.

DNA barcoding has greatly accelerated the pace of specimen identification to the species level, as well as species delineation. Whereas the application of DNA barcoding to the matching of unknown specimens to known species is straightforward, its use for species delimitation is more controversial, as species discovery hinges critically on present levels of haplotype diversity, as well as patterning of standing genetic variation that exists within and between species. Typical sample sizes for molecular biodiversity assessment using DNA barcodes range from 5 to 10 individuals per species. However, required levels that are necessary to fully gauge haplotype variation at the species level are presumed to be strongly taxon-specific. Importantly, little attention has been paid to determining appropriate specimen sample sizes that are necessary to reveal the majority of intraspecific haplotype variation within any one species. In this paper, we present a brief outline of the current literature and methods on intraspecific sample size estimation for the assessment of COI DNA barcode haplotype sampling completeness. The importance of adequate sample sizes for studies of molecular biodiversity is stressed, with application to a variety of metazoan taxa, through reviewing foundational statistical and population genetic models, with specific application to ray-finned fishes (Chordata: Actinopterygii). Finally, promising avenues for further research in this area are highlighted.

Fetal sex alters maternal anti-Mullerian hormone during pregnancy in cattle.

Anti-Mullerian hormone (AMH) is expressed by both male and female fetuses during mammalian development, with males expressing AMH earlier and at significantly higher concentration. The aim of the current study was to explore the potential impact of pregnancy and fetal sex on maternal AMH and to determine if plasma (Pl) AMH or placenta intercotyledonary membrane and cotyledonary AMH receptor 2 (AMHR2) mRNA expression differ in pregnant cows carrying male vs. female fetuses. AMH levels in blood were measured using a bovine optimized ELISA kit. Cows pregnant with a male fetus were observed to have a significantly greater difference in Pl AMH between day 35 and 135 of gestation. Average fetal AMH level between 54 and 220days of gestation was also observed to be significantly higher in male vs. female fetuses. Intercotyledonary membranes and cotyledons were found to express AMHR2 between days 38 and 80 of gestation at similar levels in both fetal sexes. These findings support the hypothesis that fetal sex alters maternal Pl AMH during pregnancy in cattle.

YY1 and CTCF orchestrate a 3D chromatin looping switch during early neural lineage commitment.

CTCF is an architectural protein with a critical role in connecting higher-order chromatin folding in pluripotent stem cells. Recent reports have suggested that CTCF binding is more dynamic during development than previously appreciated. Here, we set out to understand the extent to which shifts in genome-wide CTCF occupancy contribute to the 3D reconfiguration of fine-scale chromatin folding during early neural lineage commitment. Unexpectedly, we observe a sharp decrease in CTCF occupancy during the transition from naïve/primed pluripotency to multipotent primary neural progenitor cells (NPCs). Many pluripotency gene-enhancer interactions are anchored by CTCF, and its occupancy is lost in parallel with loop decommissioning during differentiation. Conversely, CTCF binding sites in NPCs are largely preexisting in pluripotent stem cells. Only a small number of CTCF sites arise de novo in NPCs. We identify another zinc finger protein, Yin Yang 1 (YY1), at the base of looping interactions between NPC-specific genes and enhancers. Putative NPC-specific enhancers exhibit strong YY1 signal when engaged in 3D contacts and negligible YY1 signal when not in loops. Moreover, siRNA knockdown of Yy1 specifically disrupts interactions between key NPC enhancers and their target genes. YY1-mediated interactions between NPC regulatory elements are often nested within constitutive loops anchored by CTCF. Together, our results support a model in which YY1 acts as an architectural protein to connect developmentally regulated looping interactions; the location of YY1-mediated interactions may be demarcated in development by a preexisting topological framework created by constitutive CTCF-mediated interactions.

Bovine piRNA-like RNAs are associated with both transposable elements and mRNAs.

PIWI proteins and their associated piRNAs have been the focus of intensive research in the past decade; therefore, their participation in the maintenance of genomic integrity during spermatogenesis has been well established. Recent studies have suggested important roles for the PIWI/piRNA system outside of gametogenesis, based on the presence of piRNAs and PIWI proteins in several somatic tissues, cancers, and the early embryo. Here, we investigated the small RNA complement present in bovine gonads, gametes, and embryos through next-generation sequencing. A distinct piRNA population was present in the testis as expected. However, we also found a large population of slightly shorter, 24-27 nt piRNA-like RNA (pilRNAs) in pools of oocytes and zygotes. These oocyte and embryo pilRNAs exhibited many of the canonical characteristics of piRNAs including a 1U bias, the presence of a 'ping-pong' signature, genomic clustering, and transposable element targeting. Some of the major transposons targeted by oocyte and zygote pilRNA were from the LINE RTE and ERV1 classes. We also identified pools of pilRNA potentially derived from, or targeted at, specific mRNA sequences. We compared the frequency of these gene-associated pilRNAs to the fold change in the expression of respective mRNAs from two previously reported transcriptome datasets. We observed significant negative correlations between the number of pilRNAs targeting mRNAs, and their fold change in expression between the 4-8 cell and 8-16 cell stages. Together, these results represent one of the first characterizations of the PIWI/piRNA pathway in the translational bovine model, and in the novel context of embryogenesis.

Systemic and local anti-Mullerian hormone reflects differences in the reproduction potential of Zebu and European type cattle.

This study was conducted to evaluate plasma anti-Mullerian hormone (Pl AMH), follicular fluid AMH (FF AMH) and granulosa cell AMH transcript (GC AMH) levels and their relationships with reproductive parameters in two cattle subspecies, Bos taurus indicus (Zebu), and Bos taurus taurus (European type cattle). Two-dimensional ultrasound examination and serum collection were performed on Zebu, European type and crossbreed cows to determine antral follicle count (AFC), ovary diameter (OD) and Pl AMH concentration. Slaughterhouse ovaries for Zebu and European type cattle were collected to determine FF AMH concentrations, GC AMH RNA levels, AFC, oocyte number, cleavage and blastocyst rate. Additionally GC AMH receptor 2 (AMHR2) RNA level was measured for European type cattle. Relationship between AMH and reproductive parameters was found to be significantly greater in Zebu compared to European cattle. Average Pl AMH mean ± SE for Zebu and European cattle was 0.77 ± 0.09 and 0.33 ± 0.24 ng/ml respectively (p = 0.01), whereas average antral FF AMH mean ± SE for Zebu and European cattle was 4934.3 ± 568.5 and 2977.9 ± 214.1 ng/ml respectively (p < 0.05). This is the first published report of FF and GC AMH in Zebu cattle. Levels of GC AMHR2 RNA in European cattle were correlated to oocyte number (p = 0.01). Crossbred animals were found more similar to their maternal Zebu counterparts with respect to their Pl AMH to AFC and OD relationships. These results demonstrate that AMH reflects differences between reproduction potential of the two cattle subspecies therefore can potentially be used as a reproductive marker. Furthermore these results reinforce the importance of separately considering the genetic backgrounds of animals when collecting or interpreting bovine AMH data for reproductive performance.

Biological Response of Positron Emission Tomography Scan Exposure and Adaptive Response in Humans.

The biological effects of exposure to radioactive fluorodeoxyglucose ((18)F-FDG) were investigated in the lymphocytes of patients undergoing positron emission tomography (PET) procedures. Low-dose, radiation-induced cellular responses were measured using 3 different end points: (1) apoptosis; (2) chromosome aberrations; and (3) γH2AX foci formation. The results showed no significant change in lymphocyte apoptosis, or chromosome aberrations, as a result of in vivo (18)F-FDG exposure, and there was no evidence the PET scan modified the apoptotic response of lymphocytes to a subsequent 2 Gy in vitro challenge irradiation. However, lymphocytes sampled from patients following a PET scan showed an average of 22.86% fewer chromosome breaks and 39.16% fewer dicentrics after a subsequent 2 Gy in vitro challenge irradiation. The effect of (18)F-FDG exposure on phosphorylation of histone H2AX (γH2AX) in lymphocytes of patients showed a varied response between individuals. The relationship between γH2AX foci formation and increasing activity of (18)F-FDG was not directly proportional to dose. This variation is most likely attributed to differences in the factors that combine to constitute an individual's radiation response. In summary, the results of this study indicate(18)F-FDG PET scans may not be detrimental but can elicit variable responses between individuals and can modify cellular response to subsequent radiation exposures.

MicroRNA-34 family expression in bovine gametes and preimplantation embryos.

BACKGROUND: Oocyte fertilization and successful embryo implantation are key events marking the onset of pregnancy. In sexually reproducing organisms, embryogenesis begins with the fusion of two haploid gametes, each of which has undergone progressive stages of maturation. In the final stages of oocyte maturation, minimal transcriptional activity is present and regulation of gene expression occurs primarily at the post-transcriptional level. MicroRNAs (miRNA) are potent effectors of post-transcriptional gene silencing and recent evidence demonstrates that the miR-34 family of miRNA are involved in both spermatogenesis and early events of embryogenesis. METHODS: The profile of miR-34 miRNAs has not been characterized in gametes or embryos of Bos taurus. We therefore used quantitative reverse transcription PCR (qRT-PCR) to examine this family of miRNAs: miR-34a, -34b and -34c as well as their precursors in bovine gametes and in vitro produced embryos. Oocytes were aspirated from antral follicles of bovine ovaries, and sperm cells were isolated from semen samples of 10 bulls with unknown fertility status. Immature and in vitro matured oocytes, as well as cleaved embryos, were collected in pools. Gametes, embryos and ovarian and testis tissues were purified for RNA. RESULTS: All members of the miR-34 family are present in bovine spermatozoa, while only miR-34a and -34c are present in oocytes and cleaved (2-cell) embryos. Mir-34c demonstrates variation among different bulls and is consistently expressed throughout oocyte maturation and in the embryo. The primary transcript of the miR-34b/c bicistron is abundant in the testes and present in ovarian tissue but undetectable in oocytes and in mature spermatozoa. CONCLUSIONS: The combination of these findings suggest that miR-34 miRNAs may be required in developing bovine gametes of both sexes, as well as in embryos, and that primary miR-34b/c processing takes place before the completion of gametogenesis. Individual variation in sperm miR-34 family abundance may offer potential as a biomarker of male bovine fertility.

Luman/CREB3 recruitment factor regulates glucocorticoid receptor activity and is essential for prolactin-mediated maternal instinct.

The hypothalamic-pituitary-adrenal (HPA) axis is a major part of the neuroendocrine system in animal responses to stress. It is known that the HPA axis is attenuated at parturition to prevent detrimental effects of glucocorticoid secretion including inhibition of lactation and maternal responsiveness. Luman/CREB3 recruitment factor (LRF) was identified as a negative regulator of CREB3 which is involved in the endoplasmic reticulum stress response. Here, we report a LRF gene knockout mouse line that has a severe maternal behavioral defect. LRF(-/-) females lacked the instinct to tend pups; 80% of their litters died within 24 h, while most pups survived if cross-fostered. Prolactin levels were significantly repressed in lactating LRF(-/-) dams, with glucocorticoid receptor (GR) signaling markedly augmented. In cell culture, LRF repressed transcriptional activity of GR and promoted its protein degradation. LRF was found to colocalize with the known GR repressor, RIP140/NRIP1, which inhibits the activity by GR within specific nuclear punctates that are similar to LRF nuclear bodies. Furthermore, administration of prolactin or the GR antagonist RU486 restored maternal responses in mutant females. We thus postulate that LRF plays a critical role in the attenuation of the HPA axis through repression of glucocorticoid stress signaling during parturition and the postpartum period.