CYRI-B-mediated macropinocytosis drives metastasis via lysophosphatidic acid receptor uptake.

Pancreatic ductal adenocarcinoma carries a dismal prognosis, with high rates of metastasis and few treatment options. Hyperactivation of KRAS in almost all tumours drives RAC1 activation, conferring enhanced migratory and proliferative capacity as well as macropinocytosis. Macropinocytosis is well understood as a nutrient scavenging mechanism, but little is known about its functions in trafficking of signalling receptors. We find that CYRI-B is highly expressed in pancreatic tumours in a mouse model of KRAS and p53-driven pancreatic cancer. Deletion of Cyrib (the gene encoding CYRI-B protein) accelerates tumourigenesis, leading to enhanced ERK and JNK-induced proliferation in precancerous lesions, indicating a potential role as a buffer of RAC1 hyperactivation in early stages. However, as disease progresses, loss of CYRI-B inhibits metastasis. CYRI-B depleted tumour cells show reduced chemotactic responses to lysophosphatidic acid, a major driver of tumour spread, due to impaired macropinocytic uptake of the lysophosphatidic acid receptor 1. Overall, we implicate CYRI-B as a mediator of growth and signalling in pancreatic cancer, providing new insights into pathways controlling metastasis.

Pancreatic cancer is an aggressive disease with limited treatment options. It is also associated with high rates of metastasis ­ meaning it spreads to other areas of the body. Environmental pressures, such as a lack of the nutrients metastatic cancer cells need to grow and divide, can change how the cells behave. Understanding the changes that allow cancer cells to respond to these pressures could reveal new treatment options for pancreatic cancer. When nutrients are scarce, metastatic cancer cells can gather molecules and nutrients by capturing large amounts of the fluid that surrounds them using a mechanism called macropinocytosis. They can also migrate to areas of the body with higher nutrient levels, through a process called chemotaxis. This involves cells moving towards areas with higher levels of certain molecules. For example, cancer cells migrate towards high levels of a lipid called lysophosphatidic acid, which promotes their growth and survival. A newly discovered protein known as CYRI-B has recently been shown to regulate how cells migrate and take up nutrients. It also interacts with proteins known to be involved in pancreatic cancer progression. Therefore, Nikolaou et al. set out to investigate whether CYRI-B also plays a role in metastatic pancreatic cancer. Experiments in a mouse model of pancreatic cancer showed that CYRI-B levels were high in pancreatic tumour cells. And when the gene for CYRI-B was removed from the tumour cells, they did not metastasise. Further analysis revealed that CYRI-B controls uptake and processing of nutrients and other signalling molecules through macropinocytosis. In particular, it ensures uptake of the receptor for lysophosphatidic acid, allowing the metastatic cancer cells to migrate. The findings of Nikolaou et al. reveal that CYRI-B is involved in metastasis of cancer cells in a mouse model of pancreatic cancer. This new insight into how metastasis is controlled could help to identify future targets for treatments that aim to prevent pancreatic cancer cells spreading to distant sites.

Dichotomous role of the serine/threonine kinase MAP4K4 in pancreatic ductal adenocarcinoma onset and metastasis through control of AKT and ERK pathways.

MAP4K4 is a serine/threonine kinase of the STE20 family involved in the regulation of actin cytoskeleton dynamics and cell motility. It has been proposed as a target of angiogenesis and inhibitors show potential in cardioprotection. MAP4K4 also mediates cell invasion in vitro, is overexpressed in various types of cancer, and is associated with poor patient prognosis. Recently, MAP4K4 has been shown to be overexpressed in pancreatic cancer, but its role in tumour initiation, progression, and metastasis is unknown. Here, using the KrasG12D Trp53R172H Pdx1-Cre (KPC) mouse model of pancreatic ductal adenocarcinoma (PDAC), we show that deletion of Map4k4 drives tumour initiation and progression. Moreover, we report that the acceleration of tumour onset is also associated with an overactivation of ERK and AKT, two major downstream effectors of KRAS, in vitro and in vivo. In contrast to the accelerated tumour onset caused by loss of MAP4K4, we observed a reduction in metastatic burden with both the KPC model and in an intraperitoneal transplant assay indicating a major role of MAP4K4 in metastatic seeding. In summary, our study sheds light on the dichotomous role of MAP4K4 in the initiation of PDAC onset, progression, and metastatic dissemination. It also identifies MAP4K4 as a possible druggable target against pancreatic cancer spread, but with the caveat that targeting MAP4K4 might accelerate early tumorigenesis. © 2024 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

Doing community-based research during dual public health emergencies (COVID and overdose).

Meaningful engagement and partnerships with people who use drugs are essential to conducting research that is relevant and impactful in supporting desired outcomes of drug consumption as well as reducing drug-related harms of overdose and COVID-19. Community-based participatory research is a key strategy for engaging communities in research that directly affects their lives. While there are growing descriptions of community-based participatory research with people who use drugs and identification of key principles for conducting research, there is a gap in relation to models and frameworks to guide research partnerships with people who use drugs. The purpose of this paper is to provide a framework for research partnerships between people who use drugs and academic researchers, collaboratively developed and implemented as part of an evaluation of a provincial prescribed safer supply initiative introduced during dual public health emergencies (overdose and COVID-19) in British Columbia, Canada. The framework shifts from having researchers choose among multiple models (advisory, partnership and employment) to incorporating multiple roles within an overall community-based participatory research approach. Advocacy by and for drug users was identified as a key role and reason for engaging in research. Overall, both academic researchers and Peer Research Associates benefited within this collaborative partnerships approach. Each offered their expertise, creating opportunities for omni-directional learning and enhancing the research. The shift from fixed models to flexible roles allows for a range of involvement that accommodates varying time, energy and resources. Facilitators of involvement include development of trust and partnering with networks of people who use drugs, equitable pay, a graduate-level research assistant dedicated to ongoing orientation and communication, technical supports as well as fluidity in roles and opportunities. Key challenges included working in geographically dispersed locations, maintaining contact and connection over the course of the project and ensuring ongoing sustainable but flexible employment.

Systematic Review of Models of Effective Community Specialist Palliative Care Services for Evidence of Improved Patient-Related Outcomes, Equity, Integration, and Health Service Utilization.

Background: The benefits of palliative care programs are well documented. However, the effectiveness of specialist palliative care services is not well established. The previous lack of consensus on criteria for defining and characterizing models of care has restrained direct comparison between these models and limited the evidence base to inform policy makers. A rapid review for studies published up to 2012 was unable to find an effective model. Aim: To identify effective models of community specialist palliative care services. Design: A mixed-method synthesis design reported according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) reporting guidelines. Prospero: CRD42020151840. Data sources: Medline, PubMed, EMBASE, CINAHL and the Cochrane Database of Systematic Reviews were searched in September 2019 for primary research and review articles from 2012 to 2019. Supplementary search was conducted on Google in 2020 for policy documents to identify additional relevant studies. Results: The search yielded 2255 articles; 36 articles satisfied the eligibility criteria and 6 additional articles were identified from other sources. Eight systematic reviews and 34 primary studies were identified: observational studies (n = 24), randomized controlled trials (n = 5), and qualitative studies (n = 5). Community specialist palliative care was found to improve symptom burden/quality of life and to reduce secondary service utilization across cancer and noncancer diagnoses. Much of this evidence relates to face-to-face care in home-based settings with both round-the-clock and episodic care. There were few studies addressing pediatric populations or minority groups. Findings from qualitative studies revealed that care coordination, provision of practical help, after-hours support, and medical crisis management were some of the factors contributing to patients' and caregivers' positive experience. Conclusion: Strong evidence exists for community specialist palliative care to improve quality of life and reducing secondary service utilization. Future research should focus on equity outcomes and the interface between generalist and specialist care.

Collagen VI expression is negatively mechanosensitive in pancreatic cancer cells and supports the metastatic niche.

Pancreatic cancer is a deadly and highly metastatic disease, although how metastatic lesions establish is not fully understood. A key feature of pancreatic tumours is extensive fibrosis and deposition of extracellular matrix (ECM). While pancreatic cancer cells are programmed by stimuli derived from a stiff ECM, metastasis requires loss of attachment and adaptation to a softer microenvironment at distant sites. Growing evidence suggests that stiff ECM influences pancreatic cancer cell behaviour. Here, we argue that this influence is reversible and that pancreatic cancer cells can be reprogrammed upon sensing soft substrates. Using engineered polyacrylamide hydrogels with tuneable mechanical properties, we show that collagen VI is specifically upregulated in pancreatic cancer cells on soft substrates, due to a lack of integrin engagement. Furthermore, the expression of collagen VI is inversely correlated with mechanosensing and activity of YAP (also known as YAP1), which might be due to a direct or indirect effect on transcription of genes encoding collagen VI. Collagen VI supports migration in vitro and metastasis formation in vivo. Metastatic nodules formed by pancreatic cancer cells lacking Col6a1 display stromal cell-derived collagen VI deposition, suggesting that collagen VI derived from either cancer cells or the stroma is an essential component of the metastatic niche. This article has an associated First Person interview with Vasileios Papalazarou, joint first author of the paper.

Identifying behaviours for survival and wellness among people who use methamphetamine with opioids in British Columbia: a qualitative study.

BACKGROUND: British Columbia (BC) has been in a state of public health emergency since 2016, due to the unprecedented numbers of fatal and non-fatal drug toxicity (i.e. overdose) events. Methamphetamine detection in illicit drug toxicity deaths increased from 14% in 2012 to 43% in 2020 suggesting a concerning trend of concurrent methamphetamine and opioid use in BC, consistent with rising patterns identified across North America. People who use methamphetamine concurrently with opioids face an elevated risk of harm. This study aimed to identify behaviours for survival and wellness practiced by people who concurrently use methamphetamine and opioids. METHODS: One-on-one semi-structured interviews were conducted by peer research assistants in person and by telephone. Thematic analysis was carried out to identify patterns in behaviours participants described as important to their safety in the context of concurrent use of methamphetamine and opioids. RESULTS: Participants (n = 22) were distributed across the province with at least four participants from each of the five geographic health regions: 64% self-identified as men, and 50% self-identified as Indigenous. Daily methamphetamine use was reported by 72.7% of participants, and 67.3% reported using alone either often or always. Participants made several considerations and adaptations in order to balance the perceived benefits and risks of their use of methamphetamine with opioids. Two overarching themes were identified to describe how participants adapted their use for survival and wellness. The first was personal safety behaviours which included self-regulation and self-care behaviours. The second was interpersonal safety behaviours which included using alongside peers, and engaging with peer-led services (e.g. community outreach organizations) and public health-led services (e.g. overdose prevention sites) to reduce the risk of harm. Participants identified many gaps in available services to meet their diverse needs. CONCLUSIONS: This manuscript identified diversity in participants' methamphetamine and opioid use (i.e. frequency, route of administration), and a range of behaviours that were performed to improve wellness and survival while using methamphetamine and opioids. Harm reduction and treatment responses must be robust and adaptable to respond to the diversity of patterns of substance use among people who use methamphetamine and opioids concurrently, so as to not perpetuate harm and leave people behind.

Optimizing metastatic-cascade-dependent Rac1 targeting in breast cancer: Guidance using optical window intravital FRET imaging.

Assessing drug response within live native tissue provides increased fidelity with regards to optimizing efficacy while minimizing off-target effects. Here, using longitudinal intravital imaging of a Rac1-Förster resonance energy transfer (FRET) biosensor mouse coupled with in vivo photoswitching to track intratumoral movement, we help guide treatment scheduling in a live breast cancer setting to impair metastatic progression. We uncover altered Rac1 activity at the center versus invasive border of tumors and demonstrate enhanced Rac1 activity of cells in close proximity to live tumor vasculature using optical window imaging. We further reveal that Rac1 inhibition can enhance tumor cell vulnerability to fluid-flow-induced shear stress and therefore improves overall anti-metastatic response to therapy during transit to secondary sites such as the lung. Collectively, this study demonstrates the utility of single-cell intravital imaging in vivo to demonstrate that Rac1 inhibition can reduce tumor progression and metastases in an autochthonous setting to improve overall survival.

The Arp2/3 complex is crucial for colonisation of the mouse skin by melanoblasts.

The Arp2/3 complex is essential for the assembly of branched filamentous actin, but its role in physiology and development is surprisingly little understood. Melanoblasts deriving from the neural crest migrate along the developing embryo and traverse the dermis to reach the epidermis, colonising the skin and eventually homing within the hair follicles. We have previously established that Rac1 and Cdc42 direct melanoblast migration in vivo We hypothesised that the Arp2/3 complex might be the main downstream effector of these small GTPases. Arp3 depletion in the melanocyte lineage results in severe pigmentation defects in dorsal and ventral regions of the mouse skin. Arp3 null melanoblasts demonstrate proliferation and migration defects and fail to elongate as their wild-type counterparts. Conditional deletion of Arp3 in primary melanocytes causes improper proliferation, spreading, migration and adhesion to extracellular matrix. Collectively, our results suggest that the Arp2/3 complex is absolutely indispensable in the melanocyte lineage in mouse development, and indicate a significant role in developmental processes that require tight regulation of actin-mediated motility.

Training Nontechnical Skills in Ward Rounds to Improve Team Performance.

OBJECTIVE: To assess the utility of simulated ward rounds to train healthcare professionals in nontechnical skills using a qualitative analysis of participant feedback. DESIGN: We developed simulated scenarios to train members of the surgical healthcare team in nontechnical skills, derived from observations of real ward rounds. Participants performed the simulated ward rounds as a team, led by a Urology trainee. Scenarios were carried out using actors as patients, and a simulated "switchboard" for phone conversations. Throughout the scenarios, distractions were introduced and directed at different members of the participating team. Following each scenario, a whole group debrief took place to discuss and provide feedback on performances. All participants completed a 2-part feedback form comprising of questions answered on a Likert scale, as well as free-text responses. SETTING: All simulations took place in a high-fidelity simulated ward bay. Observers were in a separate room, where the scenarios were projected on a screen in real-time. PARTICIPANTS: Thirty-five healthcare professionals in the department of Urology attended this session. There was no restriction on professional background or seniority for attendees. RESULTS: The qualitative thematic analysis revealed that participants commented positively on the type of scenarios, but would have preferred if more participants could partake in scenarios. The attendees also commended the use of debriefs between scenarios. Suggestions were also given regarding types of scenarios; and involved ensuring that participants are well briefed before each scenario. CONCLUSIONS: This simulated ward round exercise was positively received by participants. The approach to derive scenarios from real ward round observations permitted a variety of the main themes of nontechnical skills to be tested, and improved the fidelity of the simulation. The reflections expressed by participants demonstrate a need for this training, and drives our initiative to raise awareness and develop nontechnical skills in a controlled environment, supported with transparent discussion and feedback.

N-WASP Control of LPAR1 Trafficking Establishes Response to Self-Generated LPA Gradients to Promote Pancreatic Cancer Cell Metastasis.

Pancreatic ductal adenocarcinoma is one of the most invasive and metastatic cancers and has a dismal 5-year survival rate. We show that N-WASP drives pancreatic cancer metastasis, with roles in both chemotaxis and matrix remodeling. lysophosphatidic acid, a signaling lipid abundant in blood and ascites fluid, is both a mitogen and chemoattractant for cancer cells. Pancreatic cancer cells break lysophosphatidic acid down as they respond to it, setting up a self-generated gradient driving tumor egress. N-WASP-depleted cells do not recognize lysophosphatidic acid gradients, leading to altered RhoA activation, decreased contractility and traction forces, and reduced metastasis. We describe a signaling loop whereby N-WASP and the endocytic adapter SNX18 promote lysophosphatidic acid-induced RhoA-mediated contractility and force generation by controlling lysophosphatidic acid receptor recycling and preventing degradation. This chemotactic loop drives collagen remodeling, tumor invasion, and metastasis and could be an important target against pancreatic cancer spread.

Fam49/CYRI interacts with Rac1 and locally suppresses protrusions.

Actin-based protrusions are reinforced through positive feedback, but it is unclear what restricts their size, or limits positive signals when they retract or split. We identify an evolutionarily conserved regulator of actin-based protrusion: CYRI (CYFIP-related Rac interactor) also known as Fam49 (family of unknown function 49). CYRI binds activated Rac1 via a domain of unknown function (DUF1394) shared with CYFIP, defining DUF1394 as a Rac1-binding module. CYRI-depleted cells have broad lamellipodia enriched in Scar/WAVE, but reduced protrusion-retraction dynamics. Pseudopods induced by optogenetic Rac1 activation in CYRI-depleted cells are larger and longer lived. Conversely, CYRI overexpression suppresses recruitment of active Scar/WAVE to the cell edge, resulting in short-lived, unproductive protrusions. CYRI thus focuses protrusion signals and regulates pseudopod complexity by inhibiting Scar/WAVE-induced actin polymerization. It thus behaves like a 'local inhibitor' as predicted in widely accepted mathematical models, but not previously identified in cells. CYRI therefore regulates chemotaxis, cell migration and epithelial polarization by controlling the polarity and plasticity of protrusions.

Simulation in urology to train non-technical skills in ward rounds.

OBJECTIVE: To report our experience of an exercise designed to train newly appointed urology trainees in non-technical skills on ward rounds as a part of a simulation 'boot camp', through a qualitative analysis of participant feedback on the utility of this method of training. PATIENTS AND METHODS: The simulations took place in a high-fidelity simulated ward bay. Forty-eight doctors with formal urology training ranging between 2 and 60 months (mean 19.1 ± 11.6 months) took part. Thirty-one participants were on a formal urology specialty training pathway. The remaining participants were core (pre-specialty) surgical trainees. The entry requirement was that participants must be junior-level urologists, ideally at the beginning of specialty training. Participants individually led a simulated ward round, which was devised using actors to play patients and a simulated 'switchboard' for telephone conversations. Distractions were introduced deliberately for participants to manage an emergent urology-related scenario. 'Freeze-frames' were used to 'pause' the ward round, whereby observing consultants provided feedback on performance. After the simulated exercises, a whole-group structured debriefing took place. Non-Technical Skills for Surgeons (NOTSS) scores were generated for participants by seven consultant urologists. Participants completed a two-part feedback form. Part one involved nine questions scored on a Likert scale, and part two required free-text responses. RESULTS: The mean (±sd) itemized NOTSS scores for situational awareness, decision-making, communication and teamwork, and leadership were 3.01 (±0.15), 2.95 (±0.16), 3.05 (±0.19), and 2.98 (±0.15), respectively. From the thematic analysis, participants commented positively on the number of scenarios per participant, the use of actors as patients and real staff, and the use of freeze-frames for immediate feedback. Residents also provided suggestions for distractions to be considered in the future. CONCLUSIONS: This simulated ward round was generally well received by participants, and the obtained feedback provides an insight into how this can be adapted to maximize the benefits for new specialty residents. The mean NOTSS scores indicated that non-technical skills performances could be improved. This supports our rationale to train non-technical skills in a safe environment to bolster career transition into positions of greater decision-making autonomy.

Loss of N-WASP drives early progression in an Apc model of intestinal tumourigenesis.

N-WASP (WASL) is a widely expressed cytoskeletal signalling and scaffold protein also implicated in regulation of Wnt signalling and homeostatic maintenance of skin epithelial architecture. N-WASP mediates invasion of cancer cells in vitro and its depletion reduces invasion and metastatic dissemination of breast cancer. Given this role in cancer invasion and universal expression in the gastrointestinal tract, we explored a role for N-WASP in the initiation and progression of colorectal cancer. While deletion of N-wasp is not detectably harmful in the murine intestinal tract, numbers of Paneth cells increased, indicating potential changes in the stem cell niche, and migration up the crypt-villus axis was enhanced. Loss of N-wasp promoted adenoma formation in an adenomatous polyposis coli (Apc) deletion model of intestinal tumourigenesis. Thus, we establish a tumour suppressive role of N-WASP in early intestinal carcinogenesis despite its later pro-invasive role in other cancers. Our study highlights that while the actin cytoskeletal machinery promotes invasion of cancer cells, it also maintains normal epithelial tissue function and thus may have tumour suppressive roles in pre-neoplastic tissues. © 2018 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.

Coordination by Cdc42 of Actin, Contractility, and Adhesion for Melanoblast Movement in Mouse Skin.

The individual molecular pathways downstream of Cdc42, Rac, and Rho GTPases are well documented, but we know surprisingly little about how these pathways are coordinated when cells move in a complex environment in vivo. In the developing embryo, melanoblasts originating from the neural crest must traverse the dermis to reach the epidermis of the skin and hair follicles. We previously established that Rac1 signals via Scar/WAVE and Arp2/3 to effect pseudopod extension and migration of melanoblasts in skin. Here we show that RhoA is redundant in the melanocyte lineage but that Cdc42 coordinates multiple motility systems independent of Rac1. Similar to Rac1 knockouts, Cdc42 null mice displayed a severe loss of pigmentation, and melanoblasts showed cell-cycle progression, migration, and cytokinesis defects. However, unlike Rac1 knockouts, Cdc42 null melanoblasts were elongated and displayed large, bulky pseudopods with dynamic actin bursts. Despite assuming an elongated shape usually associated with fast mesenchymal motility, Cdc42 knockout melanoblasts migrated slowly and inefficiently in the epidermis, with nearly static pseudopods. Although much of the basic actin machinery was intact, Cdc42 null cells lacked the ability to polarize their Golgi and coordinate motility systems for efficient movement. Loss of Cdc42 de-coupled three main systems: actin assembly via the formin FMNL2 and Arp2/3, active myosin-II localization, and integrin-based adhesion dynamics.

Increased levels of 3-hydroxykynurenine parallel disease severity in human acute pancreatitis.

Inhibition of kynurenine 3-monooxygenase (KMO) protects against multiple organ dysfunction (MODS) in experimental acute pancreatitis (AP). We aimed to precisely define the kynurenine pathway activation in relation to AP and AP-MODS in humans, by carrying out a prospective observational study of all persons presenting with a potential diagnosis of AP for 90 days. We sampled peripheral venous blood at 0, 3, 6, 12, 24, 48, 72 and 168 hours post-recruitment. We measured tryptophan metabolite concentrations and analysed these in the context of clinical data and disease severity indices, cytokine profiles and C-reactive protein (CRP) concentrations. 79 individuals were recruited (median age: 59.6 years; 47 males, 59.5%). 57 met the revised Atlanta definition of AP: 25 had mild, 23 moderate, and 9 severe AP. Plasma 3-hydroxykynurenine concentrations correlated with contemporaneous APACHE II scores (R2 = 0.273; Spearman rho = 0.581; P < 0.001) and CRP (R2 = 0.132; Spearman rho = 0.455, P < 0.001). Temporal profiling showed early tryptophan depletion and contemporaneous 3-hydroxykynurenine elevation. Furthermore, plasma concentrations of 3-hydroxykynurenine paralleled systemic inflammation and AP severity. These findings support the rationale for investigating early intervention with a KMO inhibitor, with the aim of reducing the incidence and severity of AP-associated organ dysfunction.

Loss of strumpellin in the melanocytic lineage impairs the WASH Complex but does not affect coat colour.

The five-subunit WASH complex generates actin networks that participate in endocytic trafficking, migration and invasion in various cell types. Loss of one of the two subunits WASH or strumpellin in mice is lethal, but little is known about their role in mammals in vivo. We explored the role of strumpellin, which has previously been linked to hereditary spastic paraplegia, in the mouse melanocytic lineage. Strumpellin knockout in melanocytes revealed abnormal endocytic vesicle morphology but no impairment of migration in vitro or in vivo and no change in coat colour. Unexpectedly, WASH and filamentous actin could still localize to vesicles in the absence of strumpellin, although the shape and size of vesicles was altered. Blue native PAGE revealed the presence of two distinct WASH complexes, even in strumpellin knockout cells, revealing that the WASH complex can assemble and localize to endocytic compartments in cells in the absence of strumpellin.

Vocal coselection in rat pup ultrasonic vocalizations.

Selective breeding and natural selection that select for one trait often bring along other correlated traits via coselection. Selective breeding for an infantile trait, high or low call rates of isolation-induced ultrasonic vocalization of rat pups, also alters functions of some brain systems and emotional behaviors throughout life. We examined the effect of breeding for call rate on acoustic parameters that are of communicative significance. Selecting for higher call rate produced calls of significantly increased amplitude and bandwidth relative to a randomly bred line. Selecting for lower rate produced calls of decreased duration. These nonmorphological, functional trait changes demonstrate enhanced communicatory potential and energy expenditure for the High line and the opposite for the Low line. This demonstration of coselection in a communicatory system suggests an underlying heritable suite of linked acoustic vocalization characteristics that in noisy environments could enhance dam-pup communication and lead to selection of emotionality traits with beneficial responses to stress.

The Possibilities of Reducing Food Choice to Improve the Performance of College Foodservices.

BACKGROUND: College administrative and management leaders, foodservice personnel, and student residents value social, nutritional, financial, and environmental sustainability in their dining expectations. Menu choice reduction looks promising as a strategy to achieve these goals. However, foodservice research about dominant attitudes across these stakeholders is limited. OBJECTIVE: To identify qualitative views from all stakeholders about choice reduction to ensure that any changes to the meal service are not to the detriment of consumer satisfaction. DESIGN: A comprehensive list of 74 statements representing the spectrum of attitudes surrounding choice was generated by searching a variety of resources, including academic literature and Internet sites, and by conducting semistructured interviews with stakeholders. A final set of 42 statements resulted from researcher scrutiny for optimum balance, clarity, appropriateness, simplicity, and applicability. A new sample of participants was then asked to sort these 42 statements into a normal distribution grid from "strongly disagree" to "strongly agree." PARTICIPANTS/SETTING: A purposive convenience sample of stakeholders (staff n=5 and residents n=4) was used to identify statements about choice reduction. A second sample of stakeholders (staff n=6 and residents n=29) were recruited to sort the final 42 statements. STATISTICAL ANALYSES PERFORMED: Q methodology analysis techniques were used. This involved conducting a by-person factor analysis, using the centroid factor extraction method because of the permissiveness it allows for data exploration. A varimax factor rotation to enhance interpretability of the results identified shared viewpoints. RESULTS: Three dominant viewpoints toward the possibility of choice reduction in the meal service were identified. Factor 1 was "health driven" (in which healthiness was paramount). Factor 2 was "variety seekers" (in which choice had instrumental value). Factor 3 was "choice lovers" (in which choice had intrinsic value). CONCLUSIONS: Although participants could see a number of benefits of choice reduction, strong attitudinal barriers existed toward adopting choice reduction initiatives. These barriers need to be overcome to avoid dissatisfaction with the foodservice should choice reduction measures be implemented.

Getting a taste for food waste: a mixed methods ethnographic study into hospital food waste before patient consumption conducted at three New Zealand foodservice facilities.

Foodservice organizations, particularly those in hospitals, are large producers of food waste. To date, research on waste in hospitals has focused primarily on plate waste and the affect of food waste on patient nutrition outcomes. Less focus has been placed on waste generation at the kitchen end of the hospital food system. We used a novel approach to understand reasons for hospital food waste before consumption and offer recommendations on waste minimization within foodservices. A mixed methods ethnographic research approach was adopted. Three New Zealand hospital foodservices were selected as research sites, all of which were contracted to an external foodservice provider. Data collection techniques included document analyses, observations, focus groups with kitchen staff, and one-on-one interviews with managers. Thematic analysis was conducted to generate common themes. Most food waste occurred during service and as a result of overproduction. Attitudes and habits of foodservice personnel were considered influential factors of waste generation. Implications of food waste were perceived differently by different levels of staff. Whereas managers raised discussion from a financial perspective, kitchen staff drew upon social implications. Organizational plans, controls, and use of pre-prepared ingredients assisted in waste minimization. An array of factors influenced waste generation in hospital foodservices. Exploring attitudes and practices of foodservice personnel allowed an understanding of reasons behind hospital food waste and ways in which it could be minimized. This study provides a foundation for further research on sustainable behavior within the wider foodservice sector and dietetics practice.

Loss of Scar/WAVE complex promotes N-WASP- and FAK-dependent invasion.

BACKGROUND: The Scar/WAVE regulatory complex (WRC) drives lamellipodia assembly via the Arp2/3 complex, whereas the Arp2/3 activator N-WASP is not essential for 2D migration but is increasingly implicated in 3D invasion. It is becoming ever more apparent that 2D and 3D migration utilize the actin cytoskeletal machinery differently. RESULTS: We discovered that WRC and N-WASP play opposing roles in 3D epithelial cell migration. WRC depletion promoted N-WASP/Arp2/3 complex activation and recruitment to leading invasive edges and increased invasion. WRC disruption also altered focal adhesion dynamics and drove FAK activation at leading invasive edges. We observed coalescence of focal adhesion components together with N-WASP and Arp2/3 complex at leading invasive edges in 3D. Unexpectedly, WRC disruption also promoted FAK-dependent cell transformation and tumor growth in vivo. CONCLUSIONS: N-WASP has a crucial proinvasive role in driving Arp2/3 complex-mediated actin assembly in cooperation with FAK at invasive cell edges, but WRC depletion can promote 3D cell motility.