Impact of obesity on patients undergoing surgery for rectal cancer in Australia and New Zealand.

PURPOSE: Patients with obesity undergoing rectal cancer surgery may have an increased risk of developing complications, though evidence is inconclusive. The aim of this study was to determine the direct impact of obesity on postoperative outcomes using data from a large clinical registry. METHOD: The Binational Colorectal Cancer Audit registry was used to identify patients who underwent rectal cancer surgery in Australia and New Zealand from 2007-2021. Primary outcomes were inpatient surgical and medical complications. Logistic regression models were developed to describe the association between body-mass index (BMI) and outcomes. RESULTS: Among 3,708 patients (median age 66 years [IQR 56.75-75], 65.0% male), 2.0% had a BMI < 18.5 kg/m2, 35.4% had a BMI of 18.5-24.9 kg/m2, 37.6% had a BMI of 25.0-29.9 kg/m2, 16.7% had a BMI of 30.0-34.9 kg/m2, and 8.2% had a BMI ≥ 35.0 kg/m2. Surgical complications occurred in 27.7% of patients with a BMI of 18.5-24.9 kg/m2, 26.6% of patients with a BMI of 25.0-29.9 kg/m2 (OR 0.91, 95% CI 0.76-1.10), 28.5% with a BMI of 30.0-34.9 kg/m2 (OR 0.96, 95% CI 0.76-1.21), and 33.2% with a BMI ≥ 35.0 kg/m2 (OR 1.27, 95% CI 0.94-1.71). Modelling BMI as a continuous variable confirmed a J-shaped relationship. The association between BMI and medical complications was more linear. CONCLUSION: Risk of postoperative complications is increased in patients with obesity undergoing rectal cancer surgery.

Genomics and transcriptomics yields a system-level view of the biology of the pathogen Naegleria fowleri.

BACKGROUND: The opportunistic pathogen Naegleria fowleri establishes infection in the human brain, killing almost invariably within 2 weeks. The amoeba performs piece-meal ingestion, or trogocytosis, of brain material causing direct tissue damage and massive inflammation. The cellular basis distinguishing N. fowleri from other Naegleria species, which are all non-pathogenic, is not known. Yet, with the geographic range of N. fowleri advancing, potentially due to climate change, understanding how this pathogen invades and kills is both important and timely. RESULTS: Here, we report an -omics approach to understanding N. fowleri biology and infection at the system level. We sequenced two new strains of N. fowleri and performed a transcriptomic analysis of low- versus high-pathogenicity N. fowleri cultured in a mouse infection model. Comparative analysis provides an in-depth assessment of encoded protein complement between strains, finding high conservation. Molecular evolutionary analyses of multiple diverse cellular systems demonstrate that the N. fowleri genome encodes a similarly complete cellular repertoire to that found in free-living N. gruberi. From transcriptomics, neither stress responses nor traits conferred from lateral gene transfer are suggested as critical for pathogenicity. By contrast, cellular systems such as proteases, lysosomal machinery, and motility, together with metabolic reprogramming and novel N. fowleri proteins, are all implicated in facilitating pathogenicity within the host. Upregulation in mouse-passaged N. fowleri of genes associated with glutamate metabolism and ammonia transport suggests adaptation to available carbon sources in the central nervous system. CONCLUSIONS: In-depth analysis of Naegleria genomes and transcriptomes provides a model of cellular systems involved in opportunistic pathogenicity, uncovering new angles to understanding the biology of a rare but highly fatal pathogen.

Biodegradability of legacy crude oil contamination in Gulf War damaged groundwater wells in Northern Kuwait.

During the 1991 Gulf War, oil wells in the oil fields of Kuwait were set aflame and destroyed. This resulted in severe crude oil pollution of the countries only fresh water aquifers. Here, for the first time the natural attenuation and biodegradation of the persisting groundwater contamination was investigated to assess potential processes in the aquifer. Biodegradation experiments were conducted under aerobic and multiple anaerobic conditions using microcosms of the contaminated groundwater from Kuwait. Under the conditions tested, a portion of the total petroleum hydrocarbon (TPH) component was degraded, however there was only a slight change in the bulk concentration of the contaminant measured as dissolved organic carbon (DOC), suggesting the presence of a recalcitrant pollutant. Changes in the associated microbial community composition under different reduction-oxidation conditions were observed and known hydrocarbon degraders identified. The results of this study indicate that lingering contaminant still persists in the groundwater and is recalcitrant to further biodegradation, which presents challenges for future remediation plans.

Discrepancy between true distance of tibial tuberosity advancement and cage size: An ex vivo study.

OBJECTIVE: To determine the discrepancy between true distance of tibial tuberosity advancement (tTTA) and the most commonly used cages. The null hypothesis was that tTTA would be within 1.5 mm difference of the cage size. STUDY DESIGN: Ex vivo study. SAMPLE POPULATION: Eight foam cortical shell specimens modeled from canine tibias. METHODS: Modified tibial tuberosity advancement (TTA) was performed to allow repeated measurement of the tTTA. The Pearson correlation test was used to evaluate the relationships of tTTA and cage sizes (P < .05). The difference between tTTA and cage size was calculated to establish the degree of underadvancement during the TTA. RESULTS: Two hundred forty tTTA measurements were recorded. The tTTA was less than each corresponding cage size (P < .001). Four cage sizes resulted in a difference greater than 1.5 mm (P < .001-.04). The 6-mm cage resulted in median tTTA of 4.3 mm, which did not differ significantly from 4.5 mm (range, 3.2-6.65). The median underadvancement ranged from 1.7 to 2.5 mm for the tested cage sizes. The percentage underadvancement ranged from 21% to 28% for the tested cage sizes. CONCLUSION: The tTTA was less than the corresponding cage sizes by at least 1.5 mm in all except the 6-mm cage. CLINICAL SIGNIFICANCE: Selection of a larger cage size during the TTA may be advantageous to compensate for underadvancement and to minimize the risk of residual cranial tibial translation.

Biodegradability of polar compounds formed from weathered diesel.

Once released into the environment, petroleum is exposed to biological and physical weathering processes which can lead to the formation and accumulation of highly recalcitrant polar compounds. These polar compounds are often challenging to analyse and can be present as an "unresolved complex mixture" (UCM) in total petroleum hydrocarbon (TPH) analyses and can be mistaken for natural organic matter. Existing research on UCMs comprised of polar compounds is limited, with a majority of the compounds remaining unidentified and their long-term persistence unknown. Here, we investigated the potential biodegradation of these recalcitrant polar compounds isolated from weathered diesel contaminant, and the changes in the microbial community composition associated with the biodegradation process. Microcosms were used to study the biodegradability of the polar compounds under various aerobic and anaerobic conditions and the results compared against the biodegradation of fresh diesel. Under all conditions tested, the majority of the polar UCM contaminant remained recalcitrant to biodegradation. The degradation was limited to the TPH portion of the polar UCM, which represented a minor fraction of the total polar UCM concentration. Changes in microbial community composition were observed under different redox conditions and in the presence of different contaminants. This work furthers the understanding of the biodegradation and long-term recalcitrance of polar compounds formed through weathering at contaminated legacy sites.

Characterization of a Drinking Water Distribution Pipeline Terminally Colonized by Naegleria fowleri.

Free-living amoebae, such as Naegleria fowleri, Acanthamoeba spp., and Vermamoeba spp., have been identified as organisms of concern due to their role as hosts for pathogenic bacteria and as agents of human disease. In particular, N. fowleri is known to cause the disease primary amoebic meningoencephalitis (PAM) and can be found in drinking water systems in many countries. Understanding the temporal dynamics in relation to environmental and biological factors is vital for developing management tools for mitigating the risks of PAM. Characterizing drinking water systems in Western Australia with a combination of physical, chemical and biological measurements over the course of a year showed a close association of N. fowleri with free chlorine and distance from treatment over the course of a year. This information can be used to help design optimal management strategies for the control of N. fowleri in drinking-water-distribution systems.

Discrimination of plant-parasitic nematodes from complex soil communities using ecometagenetics.

Many plant pathogens are microscopic, cryptic, and difficult to diagnose. The new approach of ecometagenetics, involving ultrasequencing, bioinformatics, and biostatistics, has the potential to improve diagnoses of plant pathogens such as nematodes from the complex mixtures found in many agricultural and biosecurity situations. We tested this approach on a gradient of complexity ranging from a few individuals from a few species of known nematode pathogens in a relatively defined substrate to a complex and poorly known suite of nematode pathogens in a complex forest soil, including its associated biota of unknown protists, fungi, and other microscopic eukaryotes. We added three known but contrasting species (Pratylenchus neglectus, the closely related P. thornei, and Heterodera avenae) to half the set of substrates, leaving the other half without them. We then tested whether all nematode pathogens-known and unknown, indigenous, and experimentally added-were detected consistently present or absent. We always detected the Pratylenchus spp. correctly and with the number of sequence reads proportional to the numbers added. However, a single cyst of H. avenae was only identified approximately half the time it was present. Other plant-parasitic nematodes and nematodes from other trophic groups were detected well but other eukaryotes were detected less consistently. DNA sampling errors or informatic errors or both were involved in misidentification of H. avenae; however, the proportions of each varied in the different bioinformatic pipelines and with different parameters used. To a large extent, false-positive and false-negative errors were complementary: pipelines and parameters with the highest false-positive rates had the lowest false-negative rates and vice versa. Sources of error identified included assumptions in the bioinformatic pipelines, slight differences in primer regions, the number of sequence reads regarded as the minimum threshold for inclusion in analysis, and inaccessible DNA in resistant life stages. Identification of the sources of error allows us to suggest ways to improve identification using ecometagenetics.

Graph neural networks-enhanced relation prediction for ecotoxicology (GRAPE).

Exposure to toxic chemicals threatens species and ecosystems. This study introduces a novel approach using Graph Neural Networks (GNNs) to integrate aquatic toxicity data, providing an alternative to complement traditional in vivo ecotoxicity testing. This study pioneers the application of GNN in ecotoxicology by formulating the problem as a relation prediction task. GRAPE's key innovation lies in simultaneously modelling 444 aquatic species and 2826 chemicals within a graph, leveraging relations from existing datasets where informative species and chemical features are augmented to make informed predictions. Extensive evaluations demonstrate the superiority of GRAPE over Logistic Regression (LR) and Multi-Layer Perceptron (MLP) models, achieving remarkable improvements of up to a 30% increase in recall values. GRAPE consistently outperforms LR and MLP in predicting novel chemicals and new species. In particular, GRAPE showcases substantial enhancements in recall values, with improvements of ≥ 100% for novel chemicals and up to 13% for new species. Specifically, GRAPE correctly predicts the effects of novel chemicals (104 out of 126) and effects on new species (7 out of 8). Moreover, the study highlights the effectiveness of the proposed chemical features and induced network topology through GNN for accurately predicting metallic (74 out of 86) and organic (612 out of 674) chemicals, showcasing the broad applicability and robustness of the GRAPE model in ecotoxicological investigations. The code/data are provided at https://github.com/csiro-robotics/GRAPE.

Realized impact of COVID-19 related disruptions on the National Bowel Cancer Screening Program.

BACKGROUND: Colorectal cancer is the second most common cause of cancer mortality in Australia (1). The National Bowel Cancer Screening Program (NBCSP) aims to reduce mortality through early detection with a biennial faecal occult blood test for Australians aged 50-74 years (2). Modelling predicted COVID-19 would reduce participation and delay colonoscopies despite the NBCSP continuing during the pandemic (3). This study analyses the realized impact of COVID-19 related disruptions on the NBCSP and the effect on mortality. METHODS: NBCSP participation, time to colonoscopy and annualized mortality were compared before and during COVID-19. The effect on mortality was determined using a validated microsimulation model (4, 5). RESULTS: From 1 January 2018 to 31 December 2019, 2 497 317 people participated in the NBCSP and 168 390 received a colonoscopy, compared to 2 490 265 and 162 573 from 1 January 2020 to 31 December 2021. Relative participation decreased 6 % and the proportion of colonoscopies performed within the recommended 120 days increased 14.5%. A disproportionally greater impact was observed outside major cities and in lower socioeconomic areas. An estimated 98-111 additional colorectal cancer deaths resulted from 3 % fewer colonoscopies performed during the pandemic. CONCLUSION: This study presents the most comprehensive analysis of the realized impact of COVID-19 on the NBCSP. Catch-up screening would be best targeted at Australians from rural and lower socioeconomic areas where participation remains low. Streamlined referral pathways and additional colonoscopy provisioning is required as less than two thirds of screen positive patients receive a colonoscopy within the recommended 120 days.

Prokaryotic microbial ecology as an ecosurveillance tool for eukaryotic pathogen colonisation: Meiothermus and Naegleria fowleri.

Naegleria fowleri has been detected in drinking water distribution systems (DWDS) in Australia, Pakistan and the United States and is the causative agent of the highly fatal disease primary amoebic meningoencephalitis. Previous small scale field studies have shown that Meiothermus may be a potential biomarker for N. fowleri. However, correlations between predictive biomarkers in small sample sizes often breakdown when applied to larger more representative datasets. This study represents one of the largest and most rigorous temporal investigations of Naegleria fowleri colonisation in an operational DWDS in the world and measured the association of Meiothermus and N. fowleri over a significantly larger space and time in the DWDS. A total of 232 samples were collected from five sites over three-years (2016-2018), which contained 29 positive N. fowleri samples. Two specific operational taxonomic units assigned to M. chliarophilus and M. hypogaeus, were significantly associated with N. fowleri presence. Furthermore, inoculation experiments demonstrated that Meiothermus was required to support N. fowleri growth in field-collected biofilms. This validates Meiothermus as prospective biological tool to aid in the identification and surveillance of N. fowleri colonisable sites.

Impacts of inundation and drought on eukaryote biodiversity in semi-arid floodplain soils.

Floodplain ecosystems are characterized by alternating wet and dry phases and periodic inundation defines their ecological character. Climate change, river regulation and the construction of levees have substantially altered natural flooding and drying regimes worldwide with uncertain effects on key biotic groups. In southern Australia, we hypothesized that soil eukaryotic communities in climate change affected areas of a semi-arid floodplain would transition towards comprising mainly dry-soil specialist species with increasing drought severity. Here, we used 18S rRNA amplicon pyrosequencing to measure the eukaryote community composition in soils that had been depleted of water to varying degrees to confirm that reproducible transitional changes occur in eukaryotic biodiversity on this floodplain. Interflood community structures (3 years post-flood) were dominated by persistent rather than either aquatic or dry-specialist organisms. Only 2% of taxa were unique to dry locations by 8 years post-flood, and 10% were restricted to wet locations (inundated a year to 2 weeks post-flood). Almost half (48%) of the total soil biota were detected in both these environments. The discovery of a large suite of organisms able to survive nearly a decade of drought, and up to a year submerged supports the concept of inherent resilience of Australian semi-arid floodplain soil communities under increasing pressure from climatic induced changes in water availability.

Pelvic floor training improves faecal incontinence and obstructed defaecation despite the presence of rectal intussusception.

BACKGROUND: Rectal intussusception is often observed in patients with faecal incontinence and obstructed defaecation. The aim of this study is to assess if pelvic floor training improves faecal incontinence and obstructed defaecation in patients with rectal intussusception. METHODS: Case notes of all patients referred to Bankstown Hospital Pelvic Floor Clinic between 2013 and 2018 for the management of faecal incontinence and obstructed defaecation and rectal intussusception were retrospectively reviewed using a prospectively maintained database. St Mark's faecal incontinence and Cleveland clinic constipation scores were obtained from patients before and after they underwent pelvic floor training. RESULTS: One hundred and thirty-one patients underwent pelvic floor training at Bankstown Hospital Pelvic Floor Clinic between 2013 and 2018. Sixty-one patients had rectal intussusception (22 low-grade and 39 high-grade). Median St Marks score improved following pelvic floor training from 8 to 1 (P < 0.001). Median Cleveland Clinic constipation score improved from 8 to 5 (P < 0.001). In patients with low grade rectal intussusception, pelvic floor training improved median St Mark's score from 3 to 0 (P = 0.003), whereas Cleveland Clinic constipation score improved from 9 to 7 (P < 0.001). In patients with high-grade rectal intussusception, pelvic floor training improved median St Mark's score from 9 to 2 (P < 0.001), whereas median Cleveland Clinic constipation score improved from 8 to 4 (P < 0.001). CONCLUSION: Pelvic floor training without biofeedback therapy improves faecal incontinence and obstructed defaecation. Improvement in symptoms is unrelated to rectal intussusception observed on proctography or at examination under anaesthesia in these patients.

Robotic-assisted versus laparoscopic rectal surgery in obese and morbidly obese patients: ACS-NSQIP analysis.

Laparoscopic rectal surgery within the confines of a narrow pelvis may be associated with a high rate of open conversion. In the obese and morbidly obese patient, the complexity of laparoscopic surgery increases substantially. Robotic technology is known to reduce the risk of conversion, but it is unclear if it can overcome the technical challenges associated with obesity. The ACS NSQIP database was used to identify obese patients who underwent elective laparoscopic or robotic-assisted rectal resection from 2015 to 2016. Obesity was defined as a body mass index (BMI) greater than or equal to 30 kg/m2. Morbid obesity was defined as a BMI greater than or equal to 35 kg/m2. The primary outcome was unplanned conversions to open. Other outcomes measures assessed included anastomotic leak, operative time, surgical site infections, length of hospital stay, readmissions and mortality. Statistical analyses were performed using SPSS 22.0 (IBM SPSS, USA). 1490 patients had robotic-assisted and 4967 patients had laparoscopic rectal resections between 2015 and 2016. Of those patients, 561 obese patients had robotic-assisted rectal resections and 1824 patients underwent laparoscopic rectal surgery. In the obese cohort, the rate of unplanned conversion to open in the robotic group was 14% compared to 24% in the laparoscopic group (P < 0.0001). Median operative time was significantly longer in the robotic group (248 min vs. 215 min, P < 0.0001). There was no difference in anastomotic leak or systemic sepsis between the laparoscopic and robotic rectal surgery groups. In morbidly obese patients (BMI ≥ 35 kg/m2), the rate of unplanned conversion to open in the robotic group was 19% compared to 26% in the laparoscopic group (P < 0.027). There was no difference in anastomotic leak, systemic sepsis or surgical site infection rates between robotic and laparoscopic rectal resection. Multivariate analysis showed that robotic-assisted surgery was associated with fewer unplanned conversions to open (OR 0.28, P < 0.0001). Robotic-assisted surgery is associated with a decreased risk of conversion to open in obese and morbidly obese patients when compared to conventional laparoscopic surgery. However, robotic surgery was associated with longer operative time and despite improvement in the rate of conversion to open, there was no difference in complications or length of stay. Our findings are limited by the retrospective non-randomised nature of the study, demographic differences between the two groups, and the likely difference in surgeon experience between the two groups. Large randomised controlled studies are needed to further explore the role of robotic rectal surgery in obese and morbidly obese patients.

Improved short-term outcomes of laparoscopic versus open resection for colon and rectal cancer in an area health service: a multicenter study.

BACKGROUND: Evidence demonstrates short-term benefits of laparoscopic surgery for colon cancer. The situation for rectal cancer is less clear. OBJECTIVES: This review assessed the use and short-term outcomes of elective open and laparoscopic colon and rectal cancer resections within an area health service. DESIGN: This was a multicenter, retrospective review of a prospective database. SETTINGS: All elective colon and rectal cancer resections in the western zone of Sydney South West Area Health Service from 2001 until 2008 were included. PATIENTS: Included were 1721 patients who underwent either a laparoscopic colon (n = 434) or rectal (n = 157) resection or an open colon (n = 742) or rectal (n = 388) resection. MAIN OUTCOME MEASURES: : Outcome measures included operating time, blood loss, adequacy of resection, conversion rate, intensive care unit admission, length of stay, and 26 acute postoperative complications. RESULTS: Patients were matched for age, sex, ASA, BMI, and tumor stage. Laparoscopic surgery increased in frequency. Fewer patients experienced a complication in both the laparoscopic colon (28.8 vs 54.4%; p < 0.0001) and rectal (41.4 vs 60.3%; p < 0.0001) group irrespective of age. Laparoscopic operating time for colon and rectal cancer was 24.1 minutes (p < 0.0001) and 25.8 minutes (p < 0.0001) longer, with a low conversion-to-open rate (6.5% and 8.3%; p = 0.44). Laparoscopic surgery resulted in fewer transfusions (0.4 vs 0.7 units; p = 0.0028) and length of stay (7 vs 10 days; p = 0.0011) for colon cancers, and reduced intraoperative hemoglobin drop (20.5 vs 24.8; p = 0.029) and intensive care unit admissions (26.8 vs 36.3%; p = 0.032) for rectal cancers. LIMITATIONS: : This was a nonrandomized study with rectal cancers more often resected with the open technique (71.2 vs 28.8%; p < 0.001). CONCLUSIONS: Within an area health service, elective laparoscopic resection for colon and rectal cancer had improved short-term outcomes in comparison with open surgery.

Non-additive gene interactions underpin molecular and phenotypic responses in honey bee larvae exposed to imidacloprid and thymol.

Understanding the cumulative risk of chemical mixtures at environmentally realistic concentrations is a key challenge in honey bee ecotoxicology. Ecotoxicogenomics, including transcriptomics, measures responses in individual organisms at the molecular level which can provide insights into the mechanisms underlying phenotypic responses induced by one or more stressors and link impacts on individuals to populations. Here, fifth instar honey bee larvae were sampled from a previously reported field experiment exploring the phenotypic impacts of environmentally realistic chronic exposures of the pesticide imidacloprid (5 µg.kg-1 for six weeks) and the acaricide thymol (250 g.kg-1 applied via Apiguard gel in-hive for four weeks), both separately and in combination. RNA-seq was used to discover individual and interactive chemical effects on larval gene expression and to uncover molecular mechanisms linked to reported adult and colony phenotypes. The separate and combined treatments had distinct gene expression profiles which represented differentially affected signaling and metabolic pathways. The molecular signature of the mixture was characterised by additive interactions in canonical stress responses associated with oxidative stress and detoxification, and non-additive interactions in secondary responses including developmental, neurological, and immune pathways. Novel emergent impacts on eye development genes correlated with long-term defects in visual learning performance as adults. This is consistent with these chemicals working through independent modes of action that combine to impact common downstream pathways, and highlights the importance of establishing mechanistic links between molecular and phenotypic responses when predicting effects of chemical mixtures on ecologically relevant population outcomes.

The role of predicted chemotactic and hydrocarbon degrading taxa in natural source zone depletion at a legacy petroleum hydrocarbon site.

Petroleum hydrocarbon contamination is a global problem which can cause long-term environmental damage and impacts water security. Natural source zone depletion (NSZD) is the natural degradation of such contaminants. Chemotaxis is an aspect of NSZD which is not fully understood, but one that grants microorganisms the ability to alter their motion in response to a chemical concentration gradient potentially enhancing petroleum NSZD mass removal rates. This study investigates the distribution of potentially chemotactic and hydrocarbon degrading microbes (CD) across the water table of a legacy petroleum hydrocarbon site near Perth, Western Australia in areas impacted by crude oil, diesel and jet fuel. Core samples were recovered and analysed for hydrocarbon contamination using gas chromatography. Predictive metagenomic profiling was undertaken to infer functionality using a combination of 16 S rRNA sequencing and PICRUSt2 analysis. Naphthalene contamination was found to significantly increase the occurrence of potential CD microbes, including members of the Comamonadaceae and Geobacteraceae families, which may enhance NSZD. Further work to explore and define this link is important for reliable estimation of biodegradation of petroleum hydrocarbon fuels. Furthermore, the outcomes suggest that the chemotactic parameter within existing NSZD models should be reviewed to accommodate CD accumulation in areas of naphthalene contamination, thereby providing a more accurate quantification of risk from petroleum impacts in subsurface environments, and the scale of risk mitigation due to NSZD.

Drosophila Cip4 and WASp define a branch of the Cdc42-Par6-aPKC pathway regulating E-cadherin endocytosis.

BACKGROUND: Integral to the function and morphology of the epithelium is the lattice of cell-cell junctions known as adherens junctions (AJs). AJ stability and plasticity relies on E-Cadherin exocytosis and endocytosis. A mechanism regulating E-Cadherin (E-Cad) exocytosis to the AJs has implicated proteins of the exocyst complex, but mechanisms regulating E-Cad endocytosis from the AJs remain less well understood. RESULTS: Here we show that Cdc42, Par6, or aPKC loss of function is accompanied by the accumulation of apical E-Cad intracellular punctate structures and the disruption of AJs in Drosophila epithelial cells. These punctate structures derive from large and malformed endocytic vesicles that emanate from the AJs; a phenotype that is also observed upon blocking vesicle scission in dynamin mutant cells. We demonstrate that the Drosophila Cdc42-interacting protein 4 (Cip4) is a Cdc42 effector that interacts with Dynamin and the Arp2/3 activator WASp in Drosophila. Accordingly, Cip4, WASp, or Arp2/3 loss of function also results in defective E-Cadherin endocytosis. CONCLUSION: Altogether our results show that Cdc42 functions with Par6 and aPKC to regulate E-Cad endocytosis and define Cip4 and WASp as regulators of the early E-Cad endocytic events in epithelial tissue.

Drosophila exocyst components Sec5, Sec6, and Sec15 regulate DE-Cadherin trafficking from recycling endosomes to the plasma membrane.

The E-Cadherin-catenin complex plays a critical role in epithelial cell-cell adhesion, polarization, and morphogenesis. Here, we have analyzed the mechanism of Drosophila E-Cadherin (DE-Cad) localization. Loss of function of the Drosophila exocyst components sec5, sec6, and sec15 in epithelial cells results in DE-Cad accumulation in an enlarged Rab11 recycling endosomal compartment and inhibits DE-Cad delivery to the membrane. Furthermore, Rab11 and Armadillo interact with the exocyst components Sec15 and Sec10, respectively. Our results support a model whereby the exocyst regulates DE-Cadherin trafficking, from recycling endosomes to sites on the epithelial cell membrane where Armadillo is located.