Cholelithiasis prevalence and risk factors in individuals with severe or profound intellectual and motor disabilities.

BACKGROUND: The prevalence and risk factors of cholelithiasis in individuals with severe or profound intellectual and motor disabilities (SPIMD) are poorly characterised. Thus, we aimed to investigate the prevalence and risk determinants of cholelithiasis in a cohort with SPIMD under medical care in a residential facility. METHODS: We categorised 84 patients in a residential hospital for persons with SPIMD into groups: those with (Group CL) and without (Group N) cholelithiasis. Gallstones were detected via computed tomography, ultrasonography or both. We evaluated gastrostomy status, nutritional and respiratory support, constipation, and bladder and kidney stones. Data were significantly analysed using univariate and multivariate logistic regression analyses. RESULTS: The prevalence rate of cholelithiasis in our SPIMD cohort was 27%. There were no significant differences in sex, age, weight, height, or Gross Motor Function Classification System between the two groups. However, more patients received enteral nutrition (39.13% vs. 6.56%; P = 0.000751) and were on ventilator support (56.52% vs. 19.67%; P = 0.00249) in Group CL than in Group N. Enteral nutrition [odds ratio (OR) 10.4, 95% confidence interval (CI) 1.98-54.7] and ventilator support (OR 20.0, 95% CI 1.99-201.0) were identified as independent risk factors for the prevalence of cholelithiasis in patients with SPIMD. CONCLUSIONS: Patients with SPIMD demonstrated an increased prevalence of cholelithiasis, with a notable association between nutritional tonic use and respiratory support. Therefore, to emphasise the need for proactive screening, it is crucial to devise diagnostic and therapeutic strategies specific to patients with SPIMD. Further investigation is essential to validate our findings and explore causative factors.

Interleukin-6 and tumour necrosis factor-α cooperatively promote cell cycle regulators and proliferate rheumatoid arthritis fibroblast-like synovial cells.

Objective: To elucidate the roles of interleukin-6 (IL-6) and tumour necrosis factor-α (TNF-α) in cell cycle regulation and proliferation of rheumatoid arthritis fibroblast-like synovial cells (RA-FLSs). Methods: Under stimulation with IL-6/soluble interleukin-6 receptor (sIL-6R) and TNF-α, we examined the expression of cell cycle regulators [p16INK4a, p21Cip1, p27Kip1, cyclin-dependent kinase-4 (CDK4), CDK6, Cyclin D, Cyclin E, and retinoblastoma protein (pRB)] by quantitative polymerase chain reaction, Western blotting, and immunofluorescence staining. The expression of pRB, with or without 10% foetal bovine serum, was examined by Western blotting. DNA synthesis and cell viability were examined by the BrdU assay and WST-8 assay, respectively. After transfection with siRNA/p16INK4a, siRNA/p21Cip1, siRNA/p27Kip1, siRNA/CDK4, or siRNA/CDK6, RA-FLSs were successively stimulated with or without IL-6/sIL-6R or TNF-α to determine cell viability. Results: IL-6/sIL-6R significantly decreased the expression of p16INK4a, and increased p21Cip1, Cyclin E1, CYCLIN D, and pRB. TNF-α decreased the expression of CDK4, and significantly increased p27Kip1, CDK6, Cyclin E1/E2, CYCLIN D, CYCLIN E, pRB, and phosphorylated pRB (phospho-pRB). By immunofluorescence staining, CYCLIN D and phospho-pRB were simultaneously stained in the single cell. In serum-free culture, the expression of pRB was apparently decreased. DNA synthesis and cell viability were significantly increased by IL-6/sIL-6R and TNF-α. Silencing of CDK6 attenuated the cell viability induced by IL-6 and TNF-α. Conclusion: The results indicate that IL-6 and TNF-α interact with each other in regulating the cell cycle and accelerate the proliferation of RA-FLSs.

Abnormal asymmetries in subcortical brain volume in schizophrenia.

Subcortical structures, which include the basal ganglia and parts of the limbic system, have key roles in learning, motor control and emotion, but also contribute to higher-order executive functions. Prior studies have reported volumetric alterations in subcortical regions in schizophrenia. Reported results have sometimes been heterogeneous, and few large-scale investigations have been conducted. Moreover, few large-scale studies have assessed asymmetries of subcortical volumes in schizophrenia. Here, as a work completely independent of a study performed by the ENIGMA consortium, we conducted a large-scale multisite study of subcortical volumetric differences between patients with schizophrenia and controls. We also explored the laterality of subcortical regions to identify characteristic similarities and differences between them. T1-weighted images from 1680 healthy individuals and 884 patients with schizophrenia, obtained with 15 imaging protocols at 11 sites, were processed with FreeSurfer. Group differences were calculated for each protocol and meta-analyzed. Compared with controls, patients with schizophrenia demonstrated smaller bilateral hippocampus, amygdala, thalamus and accumbens volumes as well as intracranial volume, but larger bilateral caudate, putamen, pallidum and lateral ventricle volumes. We replicated the rank order of effect sizes for subcortical volumetric changes in schizophrenia reported by the ENIGMA consortium. Further, we revealed leftward asymmetry for thalamus, lateral ventricle, caudate and putamen volumes, and rightward asymmetry for amygdala and hippocampal volumes in both controls and patients with schizophrenia. Also, we demonstrated a schizophrenia-specific leftward asymmetry for pallidum volume. These findings suggest the possibility of aberrant laterality in neural pathways and connectivity patterns related to the pallidum in schizophrenia.

Efficacy and safety of live varicella zoster vaccine in diabetes: a randomized, double-blind, placebo-controlled trial.

AIMS: To elucidate varicella zoster virus (VZV)-specific cell-mediated immunity and humoral immunogenicity against live attenuated Oka varicella zoster vaccine concurrently vaccinated with 23-valent pneumococcal polysaccharide vaccine (PPSV23) in elderly people with diabetes mellitus. METHODS: This double-blind randomized controlled single-centre study of 60-70-year-old people with diabetes compared immunity and safety profiles 3 months after one dose of varicella zoster vaccine or placebo. PPSV23 was immunized simultaneously. Primary analysis evaluated cell-mediated immunity using the VZV skin test. Secondary analyses were a VZV interferon-γ enzyme-linked immunospot (ELISPOT) assay and immunoadherence haemagglutination test. Adverse experiences were recorded using diary questionnaires. RESULTS: By intent-to-treat analysis, 27 participants with diabetes who had been administered the vaccine were compared with 27 participants who were given a placebo. Changes in skin test scores were 0.41 ± 0.80 and 0.11 ± 0.93 (P = 0.2155), and geometric mean fold rises of the ELISPOT counts were 1.2 [95% confidence interval (CI) 0.2, 7.9] and 1.2 (95% CI 0.2, 7.3) (P = 0.989) in the vaccine and placebo groups, respectively. The geometric mean titre did not increase 3 months after vaccination in either group. No vaccination-related severe adverse experience was reported and no participant developed herpes zoster. DISCUSSION: Our previous results demonstrated that varicella zoster vaccine safely enhanced VZV-specific immunity in elderly people with or without diabetes. The results of this study showed that varicella zoster vaccine can be used safely, but it cannot boost virus-specific immunity in elderly people with diabetes when administered with concurrent PPSV23. Alternative strategies are needed to prevent VZV-associated diseases in this population.

Primary aldosteronism associated with subclinical Cushing syndrome.

BACKGROUND: Recently, it has been reported that the incidence of primary aldosteronism (PA) among patients with hypertension is much more frequent than previously reported. AIM: In the present study, we investigated the frequency and features of PA associated with subclinical Cushing syndrome (SCS). MATERIAL AND METHODS: Subjects included consecutive patients (no.=39) who were diagnosed as PA and performed adrenal venous sampling between 2003 and 2011 in our institute. RESULTS: In 39 subjects who were diagnosed as PA, 29 patients were operated and 5 cases (12.8%) showed no suppression in low-dose dexamethasone suppression test. Four cases of them were demonstrated to be associated with SCS, and one was associated with overt Cushing syndrome (CS). Post-operatively, 3 cases received replacement therapy of hydrocortisone, while others did not. Pathological findings indicated the diagnosis of aldosterone-producing adenoma in 4 cases associated with SCS, and of idiopathic hyperaldosteronismin in one case associated with overt CS. In all 5 cases, immunohistochemical analysis demonstrated the immunoreactivities of both 3ßHSD and P450c17 in the adrenocortical tumors, the marked cortical atrophy in the zona fasciculata and reticularis, the decreased dehydroepiandrosterone sulfotransferase expression, and suppression of hypothalamo- pituitary-adrenal axis indicating the autonomous secretion of cortisol from the tumor. CONCLUSIONS: The present study suggests that PA is frequently associated with SCS with prevalence of more than 10%, justifying the routine examinations for SCS in PA cases.

Fetal outcomes with and without the use of sugammadex in pregnant patients undergoing non-obstetric surgery: a multicenter retrospective study.

BACKGROUND: The influence of sugammadex exposure during pregnancy on progesterone withdrawal and miscarriage is unknown. We aimed to compare the fetal outcomes in pregnant patients who had undergone non-obstetric surgery with and without sugammadex. METHODS: We retrospectively reviewed the medical charts of pregnant women who underwent non-obstetric surgery at three tertiary perinatal care centers in Japan from January 2013 to December 2020. The women were divided into those who received general anesthesia with sugammadex (GA with SGX) and those who received general anesthesia without sugammadex (GA without SGX). We compared miscarriages and preterm births within four weeks after surgery. RESULTS: Among the 124 women, 73 and 51 were included in the GA with SGX and GA without SGX groups, respectively. The two groups showed no differences in the rate of miscarriages or preterm births (3.0 % vs 4.3 %; odds ratio 1.42, 95 % confidence interval 0.19 to 10.47; P = 1.00). The SGX and no SGX groups were missing outcomes for 8.2 % and 7.8 % of cases, respectively. CONCLUSIONS: Having GA with SGX or GA without SGX did not result in different rates of miscarriage or preterm birth within four weeks after the procedure. These findings do not exclude a potential association between sugammadex exposure during pregnancy and adverse pregnancy outcomes. Missing data may have obscured possible adverse outcomes from sugammadex exposure.

Seasonal variations of urinary albumin creatinine ratio in Japanese subjects with Type 2 diabetes and early nephropathy.

AIMS: It has been recognized that blood pressure shows a seasonal variation, but it remains unknown whether diabetic nephropathy shows a seasonal variation. In the present study, we investigated the change in urinary albumin/creatinine ratio in relation to the season in Japanese patients with Type 2 diabetes. METHODS: A total of 430 subjects (275 male, 155 female) with Type 2 diabetes and early nephropathy (defined by UACR 30-300 mg/g creatinine) were included. One year was divided into four seasons and each season was defined as winter (December-February), spring (March-May), summer (June-August), and fall (September-November), and systolic and diastolic blood pressure, serum creatinine levels, and the urinary albumin/creatinine ratio were examined. The estimated glomerular filtration rate was also calculated and evaluated. RESULTS: The mean age (± SE) was 64.8 ± 0.8 years. The mean systolic blood pressure was significantly higher in winter than in summer (136 ± 0.68 vs. 133 ± 0.68 mmHg, P < 0.001). The urinary albumin/creatinine ratio showed a significantly higher value in winter than in summer (72.8 ± 4.4 vs. 54.6 ± 3.4 mg/g creatinine, P < 0.001). The curve of seasonal variation of this ratio showed a similar change to that of systolic blood pressure. No significant seasonal variation was observed in estimated glomerular filtration rate and diastolic blood pressure. CONCLUSIONS: Our results suggest that there is a hitherto unknown seasonal variation in the urinary albumin/creatinine ratio, and that it may be necessary to consider this seasonal change, especially when performing an intervention study of nephropathy.

A Review of the EUSO-Balloon Pathfinder for the JEM-EUSO Program.

EUSO-Balloon is a pathfinder for JEM-EUSO, the mission concept of a spaceborne observatory which is designed to observe Ultra-High Energy Cosmic Ray (UHECR)-induced Extensive Air Showers (EAS) by detecting their UltraViolet (UV) light tracks "from above." On August 25, 2014, EUSO-Balloon was launched from Timmins Stratospheric Balloon Base (Ontario, Canada) by the balloon division of the French Space Agency CNES. After reaching a floating altitude of 38 km, EUSO-Balloon imaged the UV light in the wavelength range ∼290-500 nm for more than 5 hours using the key technologies of JEM-EUSO. The flight allowed a good understanding of the performance of the detector to be developed, giving insights into possible improvements to be applied to future missions. A detailed measurement of the photoelectron counts in different atmospheric and ground conditions was achieved. By means of the simulation of the instrument response and by assuming atmospheric models, the absolute intensity of diffuse light was estimated. The instrument detected hundreds of laser tracks with similar characteristics to EASs shot by a helicopter flying underneath. These are the first recorded laser tracks measured from a fluorescence detector looking down on the atmosphere. The reconstruction of the direction of the laser tracks was performed. In this work, a review of the main results obtained by EUSO-Balloon is presented as well as implications for future space-based observations of UHECRs.

Serum cytokine profiling in neonates with hypoxic ischemic encephalopathy.

BACKGROUND: The fetal brain is vulnerable to severe and sustained hypoxia during and after birth, which can lead to hypoxic-ischemic encephalopathy (HIE). HIE is characterized by clinical and laboratory evidence of acute or subacute brain injury. The role of cytokines in the pathogenesis of brain injury and their relation to neurological outcomes of asphyxiated neonates are not fully understood. In this study, we investigated cytokine profile related to cerebral palsy (CP) with neonatal hypoxic ischemic encephalopathy (HIE) and HIE severity. METHODS: Eligible subjects were HIE newborns with a gestational age between 36 and 42 weeks. We included newborns who was born at our NICU and did not admit to NICU as healthy controls. The study comprised 52 newborns, including 13 with mild to severe HIE and 39 healthy control. Serum cytokine profiles were performed using a LUMINEX cytokine kit (R&D Systems). RESULTS: VEGF, MCP-1, IL-15, IL-12p70, IL-12p40, IL-1Ra, IL-2, IL-6, IL-7, IL-8, IL-10, IFN-γ, G-CSF and eotaxin in the HIE patients were significantly increased compared with the healthy neonates. In the subgroup analysis, IL-6 and G-CSF were significantly increased in CP infants (n = 5) compared with non-CP infants (n = 8). Five and eight HIE patients were classified into the mild HIE and moderate-severe HIE groups, respectively. IL-6, 10, 1Ra, and G-CSF in the moderate-severe HIE group were significantly higher than those in the mild HIE group. CONCLUSION: We demonstrated that higher serum IL-6 and G-CSF at birth in HIE patients were associated with CP and moderate-severe HIE.

Exendin-4 protects pancreatic beta cells from the cytotoxic effect of rapamycin by inhibiting JNK and p38 phosphorylation.

It has been reported that the immunosuppressant rapamycin decreases the viability of pancreatic beta cells. In contrast, exendin-4, an analogue of glucagon-like peptide-1, has been found to inhibit beta cell death and to increase beta cell mass. We investigated the effects of exendin-4 on the cytotoxic effect of rapamycin in beta cells. Incubation with 10 nM rapamycin induced cell death in 12 h in murine beta cell line MIN6 cells and Wistar rat islets, but not when coincubated with 10 nM exendin-4. Rapamycin was found to increase phosphorylation of c-Jun amino-terminal kinase (JNK) and p38 in 30 minutes in MIN6 cells and Wistar rat islets while exendin-4 decreased their phosphorylation. Akt and extracellular signal-regulated kinase (ERK) were not involved in the cytoprotective effect of exendin-4. These results indicate that exendin-4 may exert its protective effect against rapamycin-induced cell death in pancreatic beta cells by inhibiting JNK and p38 signaling.

An 8-month-old boy with congenital fibromuscular dysplasia presenting with shock caused by sudden renal hemorrhage.

Fibromuscular dysplasia (FMD) is a non-atheromatous, non-inflammatory, multifocal segmental angiopathy. FMD is the most common cause of pediatric renovascular hypertension. Aneurysmal formation of the main renal artery and distal branches is a rare complication of FMD in infancy. We report an 8-month-old boy with FMD presenting with shock caused by sudden renal hemorrhage that necessitated removal of one kidney. A diagnosis of renovascular hypertension resulting from intimal type FMD with aneurysmal formation was made on the basis of the presence of hypertension, elevation of PRA and aldosterone activity, pathological findings and the results of renal angiography. Our findings suggest that it is therefore necessary to consider FMD with aneurysmal formation as a possible cause of hypertension and renal hemorrhage in infants.

Two patients with focal segmental glomerulosclerosis complicated by cyclosporine-induced reversible posterior leukoencephalopathy syndrome.

Reversible posterior leukoencephalopathy syndrome (RPLS) is a distinctive clinicoradiological entity observed in a variety of clinical settings. Cyclosporine (CyA)-RPLS has been reported in a few patients with focal segmental glomerulosclerosis (FSGS); however, there had been no reports on developed RPLS after the re-administration of CyA treatment. We report two patients with FSGS who developed CyA-induced RPLS and summarize the results of a literature review for similar patients. The two patients with FSGS presented here were a 4-year-old boy and a 9-year-old boy, who presented with steroid-resistant nephrotic syndrome (NS) and were treated with CyA. The first patient developed CyA-induced RPLS at the 7th day after the start of CyA treatment, and the second patient at the 16th day after the re-start of CyA treatment. The two patients complained of a visual disorder and exhibited signs of a disturbance in consciousness and hypertension. Electroencephalography (EEG) examinations revealed a generalized slow wave pattern, and magnetic resonance imaging (MRI) disclosed an area of high signal intensity in the white matter. Subsequently, CyA was discontinued and neurological symptoms improved and recrudescence of RPLS did not occur. Our findings suggest that patients with FSGS and NS who are treated with CyA should be closely monitored for the possible onset of RPLS, presenting as a disturbance in consciousness, visual disturbances and/or convulsions.

Superinfection of five Wolbachia in the alnus ambrosia beetle, Xylosandrus germanus (Blandford) (Coleoptera: Curuculionidae).

Wolbachia bacteria are among the most common endosymbionts in insects. In Wolbachia research, the Wolbachia surface protein (wsp) gene has been used as a phylogenetic tool, but relationships inferred by single-locus analysis can be unreliable because of the extensive genome recombination among Wolbachia strains. Therefore, a multilocus sequence typing (MLST) method for Wolbachia, which relies upon a set of five conserved genes, is recommended. In this study, we examined whether the alnus ambrosia beetle, Xylosandrus germanus (Blandford), is infected with Wolbachia using wsp and MLST genes. Wolbachia was detected from all tested specimens of X. germanus (n=120) by wsp amplification. Five distinct sequences (i.e. five alleles) for wsp were found, and labeled as wXge1-5. MLST analysis and molecular phylogeny of concatenated sequences of MLST genes identified wXge3 and wXge5 as closely-related strains. The detection rate of wXge4 and wXge1 was 100% and 63.3%, respectively; wXge2, wXge3 and wXge5 were detected from less than 15% of specimens. We performed mitochondrial haplotype analyses that identified three genetic types of X. germanus, i.e. Clades A, B and C. Wsp alleles wXge1, wXge2 and wXge4 were detected in all clade A beetles; wXge2 allele was absent from Clades B and C. We concluded that (i) five wsp alleles were found from X. germanus, (ii) use of MLST genes, rather than the wsp gene, are more suited to construct Wolbachia phylogenies and (iii) wsp alleles wXge2 and wXge3/wXge5 would infect clade A and clade B/C of X. germanus, respectively.

Asef, a link between the tumor suppressor APC and G-protein signaling.

The adenomatous polyposis coli gene (APC) is mutated in familial adenomatous polyposis and in sporadic colorectal tumors. Here the APC gene product is shown to bind through its armadillo repeat domain to a Rac-specific guanine nucleotide exchange factor (GEF), termed Asef. Endogenous APC colocalized with Asef in mouse colon epithelial cells and neuronal cells. Furthermore, APC enhanced the GEF activity of Asef and stimulated Asef-mediated cell flattening, membrane ruffling, and lamellipodia formation in MDCK cells. These results suggest that the APC-Asef complex may regulate the actin cytoskeletal network, cell morphology and migration, and neuronal function.

Peripheral facial palsy after bilateral sagittal split ramus osteotomy: case report.

Bilateral sagittal split ramus osteotomy (BSSRO) is commonly used in orthognathic surgery. Although abnormal sensation in areas that are innervated by the inferior alveolar nerve is a well-known neurological complication of mandibular osteotomy, facial palsy is rare postoperatively. We present a case of peripheral facial palsy that developed the day after BSSRO to correct a mandibular protrusion in a 42-year-old man. Oral prednisolone was begun on the second day postoperatively, and was gradually tapered off over time. One month after operation, he had gradually recovered all movements in his right facial muscle and, after two months, had completely recovered without residual asymmetry. Possible causes of the palsy were compression of the facial nerve as a result of the insertion of a retractor around the posterior border of the ramus, and postoperative oedema. Peripheral facial palsy after BSSRO should be considered a rare, but possible, complication and as such, should be mentioned in consent forms.

Deregulated expression of a novel component of TFTC/STAGA histone acetyltransferase complexes, rat SGF29, in hepatocellular carcinoma: possible implication for the oncogenic potential of c-Myc.

c-Myc N-terminal conserved domains, MbI and MbII, are essential for c-Myc-mediated transformation and transactivation. These domains recruit the STAGA (SPT3-TAF9-GCN5-acetyltransferase) coactivator complex, but not TFTC (TATA-binding protein-free TAF-containing) to the target gene promoter. Although components of this complex are well conserved between yeast and mammals, four mammalian orthologs of yeast SPT8, SPT20, SGF11 and SGF29 remain to be identified. Here, we isolated a rat ortholog of yeast SGF29, a component of yeast SAGA (SPT-ADA-GCN5-acetyltransferase) complex. Both rat (r) SGF29 and c-myc mRNAs were overexpressed in five out of the eight tested rodent tumor cells. rSGF29 directly interacted with rADA3 and co-immunoprecipitated with two other TFTC/STAGA components, rGCN5 and rSPT3. rSGF29 was recruited to the c-Myc target gene promoters together with c-Myc, and it activated c-Myc target gene expressions. Downregulation of rSGF29 suppressed the expression of c-Myc target genes and inhibited anchorage-independent growth and tumorigenicity and lung metastasis of rat hepatoma K2 cells when injected into nude mice. These results show that rSGF29 is a novel component of TFTC/STAGA complexes and could be involved in the c-Myc-mediated malignant transformation.

Factors associated with the practice of nursing staff sharing information about patients' nutritional status with their colleagues in hospitals.

BACKGROUND/OBJECTIVES: Nursing staff have an important role in patients' nutritional care. The aim of this study was to demonstrate how the practice of sharing a patient's nutritional status with colleagues was affected by the nursing staff's attitude, knowledge and their priority to provide nutritional care. SUBJECTS/METHODS: The participants were 492 nursing staff. We obtained participants' demographic data, the practice of sharing patients' nutritional information and information about participants' knowledge, attitude and priority of providing nutritional care by the questionnaire. We performed partial correlation analyses and linear regression analyses to describe the relationship between the total scores of the practice of sharing patients' nutritional information based on their knowledge, attitude and priority to provide nutritional care. RESULTS: Among the 492 participants, 396 nursing staff (80.5%) completed the questionnaire and were included in analyses. Mean±s.d. of total score of the 396 participants was 8.4±3.1. Nursing staff shared information when they had a high nutritional knowledge (r=0.36, P<0.01) and attitude (r=0.13, P<0.05); however, their correlation coefficients were low. In the linear regression analyses, job categories (ß=-0.28, P<0.01), knowledge (ß=0.33, P<0.01) and attitude (ß=0.10, P<0.05) were independently associated with the practice of sharing information. Nursing staff's priority to provide nutritional care practice was not significantly associated with the practice of sharing information. CONCLUSIONS: Knowledge and attitude were independently associated with the practice of sharing patients' nutrition information with colleagues, regardless of their priority to provide nutritional care. An effective approach should be taken to improve the practice of providing nutritional care practice.

Wnt signalling and the actin cytoskeleton.

The tumour suppressor adenomatous polyposis coli (APC) is mutated in sporadic and familial colorectal tumours. APC binds to beta-catenin, a key component of the Wnt signalling pathway, and induces its degradation. In addition to this role, there is increasing evidence for additional roles of APC, including the organization of cytoskeletal networks. APC interacts with microtubules and accumulates at their plus ends in membrane protrusions. Also, it has been reported that APC is associated with the plasma membrane in an actin-dependent manner. Moreover, APC interacts with IQGAP1, an effector of Rac1 and Cdc42, and APC-stimulated guanine nucleotide exchange factor (Asef), a Rac1-specific guanine nucleotide exchange factor (GEF). IQGAP1 mediates association of APC with cortical actin in the leading edge of migrating cell and both proteins are required for cell polarization and directional migration. APC interacts with Asef and stimulates its activity, thereby regulating the actin cytoskeletal network, cell morphology, adhesion and migration. Truncated mutant APCs present in colorectal tumour cells activate Asef constitutively and contribute to their aberrant migratory properties, which may be important for adenoma formation as well as tumour progression to invasive malignancy.