Exploring Determinants of Nurse Retention: The Influence of Personal and Professional Values, and Work Environment in Predicting Intent to Leave.

Nurse retention remains a pivotal issue, necessitating urgent strategies aimed at the recruitment and retention of highly qualified nurses. However, there is limited knowledge regarding the influence of nurses' personal and professional values, along with work environment, on predicting intent to leave an organization. Utilizing a secondary analysis approach, this study employed logistic regression to predict intent to leave among registered nurses (n = 671) using results from the Short Schwartz's Value Survey, the Nurses Professional Values Scale-3, and the Practice Environment Scale of the Nursing Work Index. Regression analysis indicates that the work environment including "Participation in Hospital Affairs" (B = -.665, odds ratio = .514), "Nurse Manager Ability, Leadership, and Support" (B = -.448, odds ratio = .639), and "Staffing and Resource Adequacy" (B = -.589, odds ratio = .555) are significant predictors of nurses' intentions to leave. Establishing and maintaining supportive work environments is essential for retention, highlighting the importance of effective leadership.

Benchmarking Enrichment Efforts in the US & Canada Across Species and Enrichment Categories.

Enrichment is important for animal welfare and data quality. Provision of enrichment opportunities varies between species and enrichment category. However, data benchmarking these differences does not exist. Our objective was to characterize enrichment provision and associated factors across species in the US and Canada. Personnel who work with research animals (n = 1098) in the US and Canada voluntarily responded to online promotions and completed a survey about enrichment used for the species they worked with most, their control of and wish for more enrichment, stress or pain in the animals they worked the most with, and demographics. All participants (except those working with rats) received the same questionnaire regardless of species to allow objectivity, as the effects of many enrichment items on some species have not yet been determined. The questionnaire asked about enrichments that were beneficial to at least one species. The provision of enrichment was allocated into 2 outcome variables: diversity and frequency per enrichment category. Results showed a significant interaction between enrichment category and species. Generally, physical, nutritional, and sensory enrichments were provided less often than social enrichment. In addition, nonhuman primates received more diverse and more frequent enrichment than did other species (twice as much as rats and mice). Enrichment was provided less frequently by personnel who wished they could do more than the status quo. Both enrichment frequency and diversity were higher in respondents from Canada, those who had more control over provision, and those who had been in the field longer. While our results cannot be used to determine the quality of enrichment provided to various species, they do provide information on current enrichment practices in the US and Canada and identify differences in implementation by species and enrichment category. The data also indicate provision of enrichment is influenced by factors such as country and individual control over enrichment. This information can also be used to identify areas for greater enrichment efforts for some species (for example, rats and mice) and categories, with the ultimate goal of improving animal welfare.

Exploring Perceptions of Equine Welfare Scenarios Using a Positive Approach.

Horse welfare is a sensitive topic that often results in a variety of strong feelings when discussed in the horse-owning public. This study used a scenario-based questionnaire in a positive psychology approach to assess the public's feelings and discussions about horse welfare. Results indicated themes in important welfare qualities such as turnout, shelter, and ability to express natural behaviors, as well as a positive discussion about welfare. This study provides future implications for further research techniques in this area as well as communicative strategies surrounding equine welfare practices.

Integrated STEM and poultry science curriculum to increase agricultural literacy.

The shortage of graduates pursuing careers in the poultry industry is linked to a low awareness and lack of interest. Increasing agricultural literacy could promote engagement in future poultry science opportunities. We developed an integrated STEM curriculum within a poultry science context to assess the program's impact on students' agricultural literacy development. The Elementary Education Gain Grow (E.G.G.) program consists of 5 online modules, an interactive notebook, a simulation game, and a team project. In fall 2019, 480 Indiana 4th and 5th grade students enrolled in the pilot program. A 14-point poultry content-based questionnaire was administered online to students prior to program engagement, between online and team project activities, and at program completion. Student content scores (n = 111; 23.13% response rate) increased from 7.99 (SD = 1.85) preprogram to 9.76 (SD = 2.44) post online modules (P < 0.05; Cohen's d = 0.82) and remained constant throughout the remainder of the program. Student notebook responses (n = 172; 35.83% response rate) provided qualitative data of their self-reported agricultural literacy gains and revealed patterns of increased agricultural literacy relating to the program's learning objectives. These results support the program's ability to increase student agricultural literacy. Teacher feedback (n = 9; 69.2% response rate) suggests that teachers agreed with the program's effectiveness, with qualitative responses highlighting individual experiences. Our pilot program findings support the use of an integrated STEM and poultry science elementary curriculum to increase student agricultural literacy as well as demonstrate the effectiveness of the program as an educational resource.

Changing Human Behavior to Improve Animal Welfare: A Longitudinal Investigation of Training Laboratory Animal Personnel about Heterospecific Play or "Rat Tickling".

Despite evidence for rat tickling's animal welfare benefits, the technique is rarely implemented in part because of a lack of training. This study's purpose was to determine the efficacy of online-only or online + hands-on training programs on key outcomes for rat tickling in comparison to a waitlist control condition. After completing a baseline survey, laboratory animal personnel currently working with rats in the United States were semi-randomized to receive online-only training (n = 30), online + hands-on training (n = 34), or waitlist control (n = 32). Participants received further surveys directly after training and 2 months later. Data were analyzed using general linear mixed models. At the 2-month follow-up compared to baseline, both training groups reported increased implementation, self-efficacy, knowledge, and familiarity of rat tickling while only the online + hands-on training participants reported increased control beliefs (while the waitlist group stayed the same). At the 2-month follow-up compared to the waitlist, hands-on training participants reported increased self-efficacy and familiarity with rat tickling. Overall, findings show that both online-only and online + hands-on training can improve key outcomes for rat tickling. Although online + hands-on training is slightly more effective, the interactive online-only training has the potential to improve widescale implementation of a welfare-enhancing technique.

Laboratory Animal Welfare Meets Human Welfare: A Cross-Sectional Study of Professional Quality of Life, Including Compassion Fatigue in Laboratory Animal Personnel.

Laboratory animal personnel may experience significant stress from working with animals in scientific research. Workplace stress can be assessed by evaluating professional quality of life, which is comprised of compassion fatigue (i.e., burnout and secondary traumatic stress) and compassion satisfaction. This research aimed to explore the associations between risk factors and professional quality of life in laboratory animal personnel. In a cross-sectional, convenience sample design, laboratory animal personnel were recruited from widespread online promotion. A total of 801 personnel in the United States or Canada completed an online survey regarding professional quality of life, social support, euthanasia, enrichment, stress/pain levels, and human-animal interactions. Participants worked in a wide range of settings (e.g., industry, academia), research types (e.g., basic, applied, regulatory), species (e.g., non-human primates, mice), and roles (e.g., animal caretaker, veterinarian). Data were analyzed using general linear models. Personnel who reported higher compassion fatigue also reported lower social support, higher animal stress/pain, higher desire to implement more enrichment, and less control over performing euthanasia (p's < 0.05). Higher burnout was associated with less diverse/frequent enrichment, using physical euthanasia methods, and longer working hours. Higher secondary traumatic stress was associated with more relationship-promoting human-animal interactions (e.g., naming animals) and working as a trainers (p's < 0.05). Higher compassion satisfaction was associated with higher social support, less animal stress/pain, and more human-animal interactions (p's < 0.05). Surprisingly, neither personnel's primary animal type (e.g., non-human primates, mice) nor frequency of euthanasia (e.g., daily, monthly) were associated with professional quality of life (p's > 0.05). Our findings show that the professional quality of life of laboratory animal personnel is associated with several factors. Personnel reporting poorer professional quality of life also reported less social support, higher animal stress/pain, less enrichment diversity/frequency and wished they could provide more enrichment, using physical euthanasia, and less control over performing euthanasia. Poorer professional quality of life was also seen in personnel working as trainers, at universities, and longer hours. This study contributes important empirical data that may provide guidance for developing interventions (e.g., improved social support, decreased animal stress, increased animal enrichment diversity/frequency, greater control over euthanasia) to improve laboratory animal personnel's professional quality of life.

Laboratory animal welfare and human attitudes: A cross-sectional survey on heterospecific play or "rat tickling".

INTRODUCTION: Laboratory rat welfare is critically influenced by laboratory animal personnel through their implementation, or lack of implementation, of various enrichment techniques. One such promising technique is heterospecific play, or "rat tickling", which mimics aspects of rat rough-and-tumble play and can contribute to improving welfare, but may be infrequently implemented. The theory of planned behavior can be used to study implementation by measuring intentions and beliefs about rat tickling, including behavioral attitudes (whether it is good or bad), subjective norms (whether there is social/professional pressure to provide it), and control beliefs (whether they feel in control of providing it). Therefore, the objective of this study was to identify current rat tickling prevalence and predictors among laboratory animal personnel in the United States and Canada. Our hypothesis was that rat tickling prevalence would be low and associated with beliefs about the practice, enrichment, and laboratory animals in general. METHODS: Laboratory animal personnel were recruited from widespread online promotion. A total of 794 personnel (mean = 40±11 years, 80% white, 80% female) completed at least 50% of the mixed methods online survey and met inclusion criteria of currently working with laboratory rats in the USA or Canada. The survey included questions about demographics, enrichment practices and beliefs, attitudes towards rats, general positive behaviors (e.g. talking to laboratory animals), and both practices and beliefs about rat tickling. Qualitative data were coded using thematic analysis. Quantitative data were analyzed using general linear models. RESULTS: Laboratory personnel reported low levels of rat tickling implementation, with 89% of participants reporting using it never or rarely. Laboratory personnel reported 2 key benefits (handling: 61%, welfare: 55%) and 3 key barriers (time: 59%, personnel: 22%, and research: 22%) to rat tickling using qualitative analysis. Current and planned rat tickling were positively associated with more positive beliefs (social/professional pressure p<0.0001, control of providing tickling p<0.0001) and familiarity with tickling (p<0.0001). Current rat tickling was also positively associated with more positive general behaviors towards laboratory animals, such as naming animals (p<0.0001). Future rat tickling was positively associated with more positive attitudes about it (p<0.0001) and a desire to implement more enrichment (p<0.01). CONCLUSION: Our findings show that even though rat tickling implementation is currently low, it is positively associated with personnel beliefs, familiarity, general attitudes, and a desire for more enrichment. That is, laboratory animal personnel were more likely to provide rat tickling if they were more familiar with it, thought providing it was both good and under their control, and felt subject to social/professional pressure, as well as if they wanted to provide more enrichment and generally had more positive behaviors towards laboratory animals. There is potential to increase rat tickling by increasing personnel familiarity with the procedure through training, decreasing the time required, and changing personnel beliefs-thereby improving rat welfare.

The pedagogical value of testing: how far does it extend?

Information is generally more memorable after it is studied and tested than when it is only studied. One must be cautious to use this phenomenon strategically, however, due to uncertainty about whether testing improves memorability for only tested material, facilitates learning of related non-tested content, or inhibits memory of non-tested material. 52 second-year Pharmacy students were asked to study therapeutic aspects of gastroesophageal reflux disease and peptic ulcer disease. One group was given 30 min to study. Another was given 20 min to study and 10 min to complete a 10-item test. Two weeks later a 40-item test was delivered to both groups that contained (a) the 10 learning phase questions, (b) 10 new questions drawn from the studied material, (c) 10 new questions about therapeutics in different disease states, and (d) 10 new questions drawn from more general pharmaceutical knowledge (e.g., basic physiology and drug characteristics). Moderate to large retrieval-enhanced learning effects were observed for both questions about material that was tested (22.9% difference in scores, p < 0.05, d = 0.60) and questions about material that was studied without being tested (18.9% difference, p < 0.05, d = 0.75). Such effects were not observed for questions that were not part of the study material: therapeutic questions that addressed different disease states (1.8% difference, p > 0.7, d = 0.08) or generic pharmaceutical questions (7.4% difference, p > 0.2, d = 0.32). Being tested made it more likely that students would report reviewing the material after the initial learning session, but such reports were not associated with better test performance. The benefit of mentally retrieving information from studied material appears to facilitate the retrieval of information that was studied without being tested. Such generalization of the benefit of testing can increase the flexibility of test-based pedagogic interventions.

Intermittent Versus Continuous and Intermittent Medications for Pain and Sedation After Pediatric Cardiothoracic Surgery; A Randomized Controlled Trial.

OBJECTIVES: Compare continuous infusions of morphine and midazolam in addition to intermittent doses with an intermittent only strategy for pain and sedation after pediatric cardiac surgery. DESIGN: Randomized controlled trial. SETTING: Advocate Children's Hospital, Oak Lawn, IL. PATIENTS: Sixty patients 3 months to 4 years old with early extubation after pediatric cardiac surgery. INTERVENTIONS: Patients received a continuous infusion of morphine and midazolam or placebo for 24 hours. Both groups received intermittent morphine and midazolam doses as needed. MEASUREMENTS AND MAIN RESULTS: Gender, age, bypass time, and surgical complexity were not different between groups. Scheduled ketorolac and acetaminophen were used in both groups and were not associated with adverse events. The mean, median, and maximum Faces, Legs, Activity, Cry, And Consolability score were not different between groups. There was no significant difference in number of intermittent doses received between groups. The total morphine dose was higher in the continuous/intermittent group (0.90 vs 0.23 mg/kg; p < 0.01). The total midazolam dose was also higher in the continuous/intermittent group (0.90 vs 0.18 mg/kg; p < 0.01). The hospital length of stay was longer in the continuous/intermittent group (8.4 vs 4.9 d; p = 0.04). CONCLUSIONS: Pain was not better controlled with the addition of continuous infusions of morphine and midazolam when compared with intermittent dosing only. Use of continuous infusions resulted in a significantly higher total dosage of these medications and a longer length of stay.

Fast and accurate HLA typing from short-read next-generation sequence data with xHLA.

The HLA gene complex on human chromosome 6 is one of the most polymorphic regions in the human genome and contributes in large part to the diversity of the immune system. Accurate typing of HLA genes with short-read sequencing data has historically been difficult due to the sequence similarity between the polymorphic alleles. Here, we introduce an algorithm, xHLA, that iteratively refines the mapping results at the amino acid level to achieve 99-100% four-digit typing accuracy for both class I and II HLA genes, taking only [Formula: see text]3 min to process a 30× whole-genome BAM file on a desktop computer.

Allele-level HLA matching for umbilical cord blood transplantation for non-malignant diseases in children: a retrospective analysis.

BACKGROUND: The standard for selecting unrelated umbilical cord blood units for transplantation for non-malignant diseases relies on antigen-level (lower resolution) HLA typing for HLA-A and HLA-B, and allele-level for HLA-DRB1. We aimed to study the effects of allele-level matching at a higher resolution-HLA-A, HLA-B, HLA-C, and HLA-DRB1, which is the standard used for adult unrelated volunteer donor transplantation for non-malignant diseases-for umbilical cord blood transplantation. METHODS: We retrospectively studied 1199 paediatric donor-recipient pairs with allele-level HLA matching who received a single unit umbilical cord blood transplantation for non-malignant diseases reported to the Center for International Blood and Marrow Transplant Research or Eurocord and European Group for Blood and Marrow Transplant. Transplantations occurred between Jan 1, 2000, and Dec 31, 2012. The primary outcome was overall survival. The effect of HLA matching on survival was studied using a Cox regression model. FINDINGS: Compared with HLA-matched transplantations, mortality was higher with transplantations mismatched at two (hazard ratio [HR] 1·55, 95% CI 1·08-2·21, p=0·018), three (2·04, 1·44-2·89, p=0·0001), and four or more alleles (3·15, 2·16-4·58, p<0·0001). There were no significant differences in mortality between transplantations that were matched and mismatched at one allele (HR 1·18, 95% CI 0·80-1·72, p=0·39). Other factors associated with higher mortality included recipient cytomegalovirus seropositivity (HR 1·40, 95% CI 1·13-1·74, p=0·0020), reduced intensity compared with myeloablative conditioning regimens (HR 1·36, 1·10-1·68, p=0·0041), transplantation of units with total nucleated cell dose of more than 21 × 107 cells per kg compared with 21 × 107 cells per kg or less (HR 1·47, 1·11-1·95, p=0·0076), and transplantations done in 2000-05 compared with those done in 2006-12 (HR 1·64, 1·31-2·04, p<0·0001). The 5-year overall survival adjusted for recipient cytomegalovirus serostatus, conditioning regimen intensity, total nucleated cell dose, and transplantation period was 79% (95% CI 74-85) after HLA matched, 76% (71-81) after one allele mismatched, 70% (65-75) after two alleles mismatched, 62% (57-68) after three alleles mismatched, and 49% (41-57) after four or more alleles mismatched transplantations. Graft failure was the predominant cause of mortality. INTERPRETATION: These data support a change from current practice in that selection of unrelated umbilical cord blood units for transplantation for non-malignant diseases should consider allele-level HLA matching at HLA-A, HLA-B, HLA-C, and HLA-DRB1. FUNDING: National Cancer Institute; National Heart, Lung, and Blood Institute; National Institute for Allergy and Infectious Diseases; US Department of Health and Human Services-Health Resources and Services Administration; and US Department of Navy.

How transplant centers deal with the dextran shortage: recommendations for comparing alternatives.

BACKGROUND: In the United States, dextran 40 in 0.9% NaCl is the preferred reagent for the thawing and preparation of cord blood units for hematopoietic stem cell transplantation. The recurring nationwide shortage of this reagent could have implications that extend to the avoidance of cord blood for transplantation. STUDY DESIGN AND METHODS: To address the shortage, the National Marrow Donor Program and its Cord Blood Advisory Group sought to identify available alternative reagents or manufacturers. A sample of transplant centers (TCs) were surveyed to determine their process to compare these alternatives. The TCs were then asked to share their comparability protocols for review. RESULTS: The 12 TCs that responded to the survey studied various types of alternative reagents and manufacturers of the standard dextran 40 in 0.9% NaCl. Four TCs submitted their protocols from which a model comparability protocol was created for centers who need assistance. CONCLUSION: Whether comparing dextran 40 in 0.9% NaCl to that of a different manufacturer or a different reagent, the results of the comparability studies submitted by the TCs indicated equivalency. During a shortage, the model comparability study protocol can be used as a reference to establish an alternative to dextran 40 in 0.9% NaCl.

Chemical Screening in Zebrafish.

Phenotypic small molecule screens in zebrafish have gained popularity as an unbiased approach to probe biological processes. In this chapter we outline basic methods for performing chemical screens with larval zebrafish including breeding large numbers of embryos, plating larval fish into multi-well dishes, and adding small molecules to these wells. We also highlight important considerations when designing and interpreting the results of a phenotypic screen and possible follow-up approaches, including popular methods used to identify the mechanism of action of a chemical compound.

Show Horse Welfare: Horse Show Competitors' Understanding, Awareness, and Perceptions of Equine Welfare.

The purpose of this study was to gain a better understanding of stock-type horse show competitors' understanding of welfare and level of concern for stock-type show horses' welfare. Data were collected through an online questionnaire that included questions relating to (a) interest and general understanding of horse welfare, (b) welfare concerns of the horse show industry and specifically the stock-type horse show industry, (c) decision-making influences, and (d) level of empathic characteristics. The majority of respondents indicated they agree or strongly agree that physical metrics should be a factor when assessing horse welfare, while fewer agreed that behavioral and mental metrics should be a factor. Respondent empathy levels were moderate to high and were positively correlated with the belief that mental and behavioral metrics should be a factor in assessing horse welfare. Respondents indicated the inhumane practices that most often occur at stock-type shows include excessive jerking on reins, excessive spurring, and induced excessive unnatural movement. Additionally, respondents indicated association rules, hired trainers, and hired riding instructors are the most influential regarding the decisions they make related to their horses' care and treatment.

Show Horse Welfare: The Viewpoints of Judges, Stewards, and Show Managers.

The purpose of this study was to gain a better understanding of the current state of stock-type show horse welfare based on the perceptions of show officials and to identify potential means of preventing and intervening in compromises to show horse welfare. Thirteen horse show officials, including judges, stewards, and show managers, were interviewed. Findings revealed the officials had an incomplete understanding of nonhuman animal welfare and a high level of concern regarding the public's perception of show horse welfare. The officials attributed most of the frequently observed compromises to show horse welfare to (a) novices', amateurs', and young trainers' lack of experience or expertise, and (b) trainers' and owners' unrealistic expectations and prioritization of winning over horse welfare. The officials emphasized a need for distribution of responsibility among associations, officials, and individuals within the industry. Although the officials noted recent observable positive changes in the industry, they emphasized the need for continued improvements in equine welfare and greater educational opportunities for stakeholders.

Functional assembly of accessory optic system circuitry critical for compensatory eye movements.

Accurate motion detection requires neural circuitry that compensates for global visual field motion. Select subtypes of retinal ganglion cells perceive image motion and connect to the accessory optic system (AOS) in the brain, which generates compensatory eye movements that stabilize images during slow visual field motion. Here, we show that the murine transmembrane semaphorin 6A (Sema6A) is expressed in a subset of On direction-selective ganglion cells (On DSGCs) and is required for retinorecipient axonal targeting to the medial terminal nucleus (MTN) of the AOS. Plexin A2 and A4, two Sema6A binding partners, are expressed in MTN cells, attract Sema6A(+) On DSGC axons, and mediate MTN targeting of Sema6A(+) RGC projections. Furthermore, Sema6A/Plexin-A2/A4 signaling is required for the functional output of the AOS. These data reveal molecular mechanisms underlying the assembly of AOS circuits critical for moving image perception.

Analysis of p53 transactivation domain mutants reveals Acad11 as a metabolic target important for p53 pro-survival function.

The p53 tumor suppressor plays a key role in maintaining cellular integrity. In response to diverse stress signals, p53 can trigger apoptosis to eliminate damaged cells or cell-cycle arrest to enable cells to cope with stress and survive. However, the transcriptional networks underlying p53 pro-survival function are incompletely understood. Here, we show that in oncogenic-Ras-expressing cells, p53 promotes oxidative phosphorylation (OXPHOS) and cell survival upon glucose starvation. Analysis of p53 transcriptional activation domain mutants reveals that these responses depend on p53 transactivation function. Using gene expression profiling and ChIP-seq analysis, we identify several p53-inducible fatty acid metabolism-related genes. One such gene, Acad11, encoding a protein involved in fatty acid oxidation, is required for efficient OXPHOS and cell survival upon glucose starvation. This study provides new mechanistic insight into the pro-survival function of p53 and suggests that targeting this pathway may provide a strategy for therapeutic intervention based on metabolic perturbation.

Inappropriate p53 activation during development induces features of CHARGE syndrome.

CHARGE syndrome is a multiple anomaly disorder in which patients present with a variety of phenotypes, including ocular coloboma, heart defects, choanal atresia, retarded growth and development, genitourinary hypoplasia and ear abnormalities. Despite 70-90% of CHARGE syndrome cases resulting from mutations in the gene CHD7, which encodes an ATP-dependent chromatin remodeller, the pathways underlying the diverse phenotypes remain poorly understood. Surprisingly, our studies of a knock-in mutant mouse strain that expresses a stabilized and transcriptionally dead variant of the tumour-suppressor protein p53 (p53(25,26,53,54)), along with a wild-type allele of p53 (also known as Trp53), revealed late-gestational embryonic lethality associated with a host of phenotypes that are characteristic of CHARGE syndrome, including coloboma, inner and outer ear malformations, heart outflow tract defects and craniofacial defects. We found that the p53(25,26,53,54) mutant protein stabilized and hyperactivated wild-type p53, which then inappropriately induced its target genes and triggered cell-cycle arrest or apoptosis during development. Importantly, these phenotypes were only observed with a wild-type p53 allele, as p53(25,26,53,54)(/-) embryos were fully viable. Furthermore, we found that CHD7 can bind to the p53 promoter, thereby negatively regulating p53 expression, and that CHD7 loss in mouse neural crest cells or samples from patients with CHARGE syndrome results in p53 activation. Strikingly, we found that p53 heterozygosity partially rescued the phenotypes in Chd7-null mouse embryos, demonstrating that p53 contributes to the phenotypes that result from CHD7 loss. Thus, inappropriate p53 activation during development can promote CHARGE phenotypes, supporting the idea that p53 has a critical role in developmental syndromes and providing important insight into the mechanisms underlying CHARGE syndrome.

Intravital correlated microscopy reveals differential macrophage and microglial dynamics during resolution of neuroinflammation.

Many brain diseases involve activation of resident and peripheral immune cells to clear damaged and dying neurons. Which immune cells respond in what way to cues related to brain disease, however, remains poorly understood. To elucidate these in vivo immunological events in response to brain cell death we used genetically targeted cell ablation in zebrafish. Using intravital microscopy and large-scale electron microscopy, we defined the kinetics and nature of immune responses immediately following injury. Initially, clearance of dead cells occurs by mononuclear phagocytes, including resident microglia and macrophages of peripheral origin, whereas amoeboid microglia are exclusively involved at a later stage. Granulocytes, on the other hand, do not migrate towards the injury. Remarkably, following clearance, phagocyte numbers decrease, partly by phagocyte cell death and subsequent engulfment of phagocyte corpses by microglia. Here, we identify differential temporal involvement of microglia and peripheral macrophages in clearance of dead cells in the brain, revealing the chronological sequence of events in neuroinflammatory resolution. Remarkably, recruited phagocytes undergo cell death and are engulfed by microglia. Because adult zebrafish treated at the larval stage lack signs of pathology, it is likely that this mode of resolving immune responses in brain contributes to full tissue recovery. Therefore, these findings suggest that control of such immune cell behavior could benefit recovery from neuronal damage.

Cas adaptor proteins organize the retinal ganglion cell layer downstream of integrin signaling.

Stratification of retinal neuronal cell bodies and lamination of their processes provide a scaffold upon which neural circuits can be built. However, the molecular mechanisms that direct retinal ganglion cells (RGCs) to resolve into a single-cell retinal ganglion cell layer (GCL) are not well understood. The extracellular matrix protein laminin conveys spatial information that instructs the migration, process outgrowth, and reorganization of GCL cells. Here, we show that the ß1-Integrin laminin receptor is required for RGC positioning and reorganization into a single-cell GCL layer. ß1-Integrin signaling within migrating GCL cells requires Cas signaling-adaptor proteins, and in the absence of ß1-Integrin or Cas function retinal neurons form ectopic cell clusters beyond the inner-limiting membrane (ILM), phenocopying laminin mutants. These data reveal an essential role for Cas adaptor proteins in ß1-Integrin-mediated signaling events critical for the formation of the single-cell GCL in the mammalian retina.