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Introduction: Active surveillance (AS) is the preferred primary treatment strategy for men with low-risk clinically localised prostate cancer (PCa); however, the majority of these men still receive radical treatment within 10 years due to disease progression and/or fear of cancer progression. Interventions designed to suppress tumour growth, mitigate fear of cancer progression and precondition men for impending radical treatments are an unmet clinical need. Exercise has been shown to delay the progression of prostate tumours in animal models, improve physical and functional health and manage psychological outcomes in cancer patients; however, these outcomes have not been demonstrated in PCa patients undergoing AS., Methods and Analysis: This phase II randomised controlled trial will randomise 66 men undergoing AS to either an exercise group or a usual care group. The exercise group will perform a 12-week, supervised, high-intensity interval training programme, consisting of 3 sessions/week for 28-40 min/session. The primary outcome will be cardiorespiratory fitness. Secondary outcomes will include immunosurveillance and cancer-related biomarkers, psychosocial outcomes including fear of cancer progression and quality of life and physical function. Exploratory outcomes will include clinical indicators of disease progression. The trial has 80% power to detect a significant between-group difference in VO 2peak of 3.5 mL/kg/min with a two-tailed alpha level <0.05 and a 10% dropout rate., Ethics and Dissemination: The study has received full ethical approval from the Health Research Ethics Board of Alberta - Cancer Committee (Protocol Number: HREBA.CC-17-0248). The findings of the study will be disseminated through public and scientific channels., Trial Registration Number: NCT03203460; Pre-results., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Heterogeneity among particles is an inherent feature that allows nondeterministic prediction of the properties of assembled structures and materials composed of many particles. Here, we report a promising strategy to quantify the heterogeneous and anisotropic interactions between ellipsoid particles using optical laser tweezers. The configuration and separation between two particles at an oil-water interface were optically controlled, and the capillary interaction behaviors were directly observed and measured. As a result, the optimal particle configurations at energetically favorable states were obtained, and the interaction forces between the particles were identified accurately by determining the trap stiffness in the direction of major and minor axes of the particle. Visualization of the capillary field around individual particles confirmed that the capillary interactions were quadrupolar, anisotropic, and heterogeneous. The measurement method presented here can be widely used to quantify interaction fields for various types of anisotropic particles.

The stochastic interface adsorption behaviors of ellipsoid particles were investigated using optical laser tweezers. The particles were brought close to the oil-water interface, attempting to attach forcefully to the interface. Multiple attempts of the particle attachments statistically quantified the dependence of the adsorption probability on the particle aspect ratio. It was found that the adsorption probability proportionally increased with the aspect ratio because of the decrease in electrostatic interactions between the charged particles and the charged interface for higher aspect ratio particles. In addition, the adsorption holding time required for the interface attachments was found to increase as the aspect ratio decreased. Notably, the probabilistic adsorption behaviors of the ellipsoid particles and the holding time dependence revealed that the particle adsorption to the interface occurred stochastically, not deterministically. We also demonstrated that the adsorption behaviors measured on a single-particle scale were consistent with the gravity-induced spontaneous adsorption properties performed on a large scale with regard to the nondeterministic adsorption behaviors and the aspect ratio dependence on the adsorption probability.

Nonalcoholic fatty liver disease is the most common chronic liver disease and can present with advanced fibrosis or nonalcoholic steatohepatitis. The purpose of this study was to investigate the effect of a 7-day intense physical activity intervention on liver fat content in children with obesity. Fifty-seven obese children (mean body mass index: 26.5 ± 3.2 kg/m 2 ; mean age: 12.0 ± 0.8 years) participated in a 7-day physical activity program. All participants were housed together, and their food intake and energy expenditure were strictly controlled. Anthropometric measurements, abdominal computerized tomography scans, and blood analyses were conducted at baseline and post-intervention. Participants lost weight by 2.53 ± 0.85 kg on average (61.0 ± 9.8 vs. 58.5 ± 9.5 kg, p < 0.05), fat mass (16.7 ± 5.1 vs. 15.7 ± 4.9 kg, p < 0.05), and serum insulin (13.7 ± 6.7 vs. 3.5 ± 2.0 μU/mL, p < 0.05). However, liver fat content was increased, presented as liver-to-spleen ratio (LSR) where lower LSR represents higher liver fat content. The intervention increased aspartate transaminase level (29.42 ± 6.78 IU/L vs. 33.50 ± 9.60 IU/L, p < 0.001). The change in liver fat content was not associated with the change in fasting insulin and liver enzymes. Short-term intense physical activity increased liver fat content independent of change in fasting insulin level and liver enzymes. This is the first human study to report increased liver fat content after physical activity-induced rapid weight loss.

Objective: Although several prior works showed the white matter (WM) integrity changes in amnestic mild cognitive impairment (aMCI) and Alzheimer's disease, it is still unclear the diagnostic accuracy of the WM integrity measurements using diffusion tensor imaging (DTI) in discriminating aMCI from normal controls. The aim of this study is to explore diagnostic validity of whole brain automated probabilistic tractography in discriminating aMCI from normal controls., Methods: One hundred-two subjects (50 aMCI and 52 normal controls) were included and underwent DTI scans. Whole brain WM tracts were reconstructed with automated probabilistic tractography. Fractional anisotropy (FA) and mean diffusivity (MD) values of the memory related WM tracts were measured and compared between the aMCI and the normal control groups. In addition, the diagnostic validities of these WM tracts were evaluated., Results: Decreased FA and increased MD values of memory related WM tracts were observed in the aMCI group compared with the control group. Among FA and MD value of each tract, the FA value of left cingulum angular bundle showed the highest area under the curve (AUC) of 0.85 with a sensitivity of 88.2%, a specificity of 76.9% in differentiating MCI patients from control subjects. Furthermore, the combination FA values of WM integrity measures of memory related WM tracts showed AUC value of 0.98, a sensitivity of 96%, a specificity of 94.2%., Conclusion: Our results with good diagnostic validity of WM integrity measurements suggest DTI might be promising neuroimaging tool for early detection of aMCI and AD patients.

Introduction: Mild cognitive impairment (MCI) is a prodromal stage of dementia. The association of body mass index (BMI) and progression to Alzheimer's disease (AD) in MCI subjects according to age, sex, and cognitive intervention remains unknown. We investigated the relationship between BMI and the risk of progression to AD in subjects with MCI, as well as the effect of BMI on progression to AD depending on age, sex, cognitive intervention, and chronic diseases. Methods: Three hundred and eighty-eight MCI subjects were followed for 36.3 ± 18.4 months, prospectively. They underwent neuropsychological testing more than twice during the follow-up period. The MCI subjects were categorized into underweight, normal weight, overweight, and obese subgroups. The associations between baseline BMI and progression to AD over the follow-up period were estimated using Cox proportional hazard regression models. Data were analyzed after stratification by age, sex, cognitive intervention, and chronic diseases. Results: After adjustment for the covariates, the underweight MCI group had a higher risk of progression to AD [hazard ratio (HR): 2.38, 95% confidence interval (CI): 1.17-4.82] relative to the normal weight group. After stratifying by age, sex, cognitive intervention, and chronic diseases, this effect remained significant among females (HR: 3.15, 95% CI: 1.40-7.10), the older elderly ≥75 years old (HR: 3.52, 95% CI: 1.42-8.72), the non-intervention group (HR: 3.06, 95%CI: 1.18-7.91), and the hypertensive group (HR: 4.71, 95% CI: 1.17-18.99). Conclusion: These data indicate that underweight could be a useful marker for identifying individuals at increased risk for AD in MCI subjects. This association is even stronger in females, older elderly subjects, the non-cognitive intervention group, and the hypertensive group.

Although delusion of theft (DT) is the most frequent type of delusion in Alzheimer's disease (AD), its relationship to cognitive functions remains unclear. The aim of this study was to demonstrate the relationship between DT and cognitive functions in mild AD. Two hundred eighty-nine mild AD patients were enrolled in this study. These subjects were classified into three groups: patients with no delusions (ND, n=82), patients with paranoid delusions (PD, n=114) and patients with DT (n=93). Cognitive functions and their associations with the degree of delusion were compared among the three groups. The results showed that verbal Fluency scores were significantly lower in the PD group than in the DT and ND groups. Word List Recall scores were significantly lower in the DT group than in the PD and ND groups. Interestingly, delusion severity measured with the Neuropsychiatric Inventory delusion subscale correlated negatively with the Word List Recall scores in the DT group. In this study, we demonstrated that episodic memory functions in mild AD patients were associated with DT, but not with PD. Further studies might be needed to clarify the pathophysiology of delusions associated with AD.

Purpose: Body mass index (BMI) may not be appropriate for different populations. Therefore, the World Health Organization (WHO) suggested 25 kg/m 2 as a measure of obesity for Asian populations. The purpose of this report was to compare the oncologic outcomes of laparoscopic colorectal resection with BMI classified from the WHO Asia-Pacific perspective., Patients and Methods: All patients underwent laparoscopic colorectal resection from September 2006 to March 2015 at a tertiary referral hospital. A total of 2408 patients were included and classified into four groups: underweight (n = 112, BMI <18.5 kg/m 2 ), normal (n = 886, 18.5-22.9 kg/m 2 ), pre-obese (n = 655, 23-24.9 kg/m 2 ) and obese (n = 755, >25 kg/m 2 ). Perioperative parameters and oncologic outcomes were analysed amongst groups., Results: Conversion rate was the highest in the underweight group (2.7%, P < 0.001), whereas the obese group had the fewest harvested lymph nodes (21.7, P < 0.001). Comparing oncologic outcomes except Stage IV, the underweight group was lowest for overall (P = 0.007) and cancer-specific survival (P = 0.002). The underweight group had the lowest proportion of national health insurance but the highest rate of medical care (P = 0.012)., Conclusion: The obese group had the fewest harvested lymph nodes, whereas the underweight group had the highest estimated blood loss, conversion rate to open approaches and the poorest overall and cancer-specific survivals., Competing Interests: There are no conflicts of interest

Heterogeneous capillary interactions between ellipsoid particles at the oil-water interface were measured via optical laser tweezers. Two trapped particles were aligned in either tip-to-tip (tt) or side-to-side (ss) configurations via the double-trap method and were released from the optical traps, leading to particle-particle attractions due to the capillary forces caused by quadrupolar interface deformation. On the basis of image analysis and calculations of the Stokes drag force, the capillary interactions between two ellipsoid particles with the same aspect ratio (E) were found to vary with the particle pairs that were measured, indicating that the interactions were nondeterministic or heterogeneous. Heterogeneous capillary interactions could be attributed to undulation of the interface meniscus due to chemical and/or geometric particle heterogeneity. The power law exponent for the capillary interaction U cap ≈ r -β was found to be β ≈ 4 and was independent of the aspect ratio and particle configuration in long-range separations. Additionally, with regard to the tt configuration, the magnitude of the capillary force proportionally increased with the E value (E > 1) when two ellipsoid particles approached each other in the tt configuration.

Objective: Previous research has indicated that there are potential associations between education and total hippocampal volume in the trajectory of Alzheimer's disease (AD). However, the correlation between education and hippocampal subfield volumes in the progression of AD has yet to be understood. This study examined the relationship between education, which is a standard proxy for cognitive reserve, and hippocampal subfield volumes in healthy and amnestic mild cognitive impairment (aMCI) groups., Subjects and Methods: Thirty-eight subjects with aMCI and 39 healthy control subjects underwent 3 T magnetic resonance imaging, and hippocampal subfield volumes were measured by automated segmentation. Multiple linear regression analysis was used to determine the association between education and hippocampal subfield volumes., Results: Education had a significant negative correlation with the left parasubiculum, presubiculum, and subiculum volumes in the aMCI group. In addition, multiple subfield volumes including left parasubiculum, left/right presubiculum, left cornus ammonis (CA)3, and left CA4 showed a significant correlation with the neuropsychological test scores in the control group and aMCI group., Conclusion: These findings contribute to a better understanding of the association between education, hippocampal subfield volumes, and amnestic cognitive functions in the early phase of AD., Competing Interests: Disclosure The authors report no conflicts of interest in this work.

Background: Previous research has separated spatial patterns of intra- and interregional intrinsic brain connectivity, as evaluated by regional homogeneity (ReHo) and functional connectivity (FC), respectively, in prodromal Alzheimer's disease (AD). Moreover, the intra- and interregional intrinsic brain connectivities have been demonstrated to have a significant relationship with each other., Objective: To explore FCs from brain regions which display a difference in ReHo between an amnestic mild cognitive impairment (aMCI) group and healthy controls (HC) and to examine the relationship of intra- and interregional intrinsic brain connectivity to cognitive function in both groups., Methods: Thirty-four subjects with aMCI and 38 HC underwent 3T MRI scanning and a battery of neuropsychological tests., Results: The aMCI group exhibited significantly higher ReHo in the left putamen and lower ReHo in the left inferior temporal gyrus than the HC. Furthermore, both groups showed a distinctive functional connectivity pattern seeded from 2 regions of interest which exhibited significant ReHo differences between the groups. In the HC group, only ReHo exhibited significant associations with memory performance, but in the aMCI group, only FC seeded from the left inferior temporal gyrus showed significant correlations with memory performance., Conclusions: By approaching both intra- and interregional intrinsic brain activities in the early stages of AD, the findings of this research provide insights into the early pathogenesis of AD as related to memory performance., (© 2018 S. Karger AG, Basel.)

Purpose: Dysregulated expression of PLD1 has emerged as a hallmark feature of colorectal cancer, which remains a major cause of mortality worldwide. Aberrant activation of Wnt/β-catenin signaling is a critical event in the development of colorectal cancer. Here, we investigated molecular crosstalk between the Wnt/β-catenin and PI3K/Akt pathways via inhibitor of β-catenin and T-cell factor (ICAT), a negative regulator of Wnt/β-catenin signaling. We also explored the effect of PLD1 inhibition on growth of colorectal cancer hyperactivated by Wnt/β-catenin and PI3K/Akt signaling. Experimental Design: Expression of ICAT via targeting of PLD1 was assessed in vivo in Apc Min/ + mice, an AOM/DSS model, and in vitro using various colorectal cancer cells. The relationship between ICAT/PLD1 expression and prognostic survival value of 153 colorectal cancer patients was examined. The therapeutic efficacy of PLD1 inhibitor was determined using a patient-derived xenograft model carrying APC and PI3K mutations. Results: PLD1 promoted the Wnt/β-catenin signaling pathway by selectively downregulating ICAT via the PI3K/Akt-TopBP1-E2F1 signaling pathways. Low PLD1 expression and high ICAT expression were significantly associated with increased survival in colorectal cancer patients and vice versa. Furthermore, PLD1 inhibition suppressed growth of colorectal cancer activated by the Wnt/β-catenin and PI3K signaling pathways. Conclusions: These results suggest that PLD1 linked to ICAT mediates molecular crosstalk between the Wnt/β-catenin and PI3K/Akt pathways and thus could be proposed as a novel colorectal cancer prognostic biomarker. These results may assist in the clinical development of a PLD1 inhibitor for treatment of colorectal cancer patients carrying APC and PI3KCA mutations. PLD1, a nodal modifier, acts as a potential therapeutic target for the treatment of colorectal cancer hyperactivated by the Wnt/β-catenin and PI3K/Akt signaling pathways. Clin Cancer Res; 23(23); 7340-50. ©2017 AACR ., (©2017 American Association for Cancer Research.)

Purpose: We estimated the incidence of anastomosis leakage and explore possible risk factors and oncologic outcomes following laparoscopic right-side colon resection among colon cancer patients., Materials and Methods: We retrospectively analyzed 423 patients who were diagnosed with appendiceal, cecal, ascending, or hepatic flexure colon cancer who underwent laparoscopic colonic resection and anastomosis between September 2006 and July 2014. We compared short-term and long-term outcomes between no-leakage and leakage groups., Results: There were 16 cases of right-side anastomosis leakage in a total 423 colon cancer cases (3.78%). The risk of leakage was increased in smokers (odds ratio=6.592, P=0.007) and with a longer operating time (odds ratio=1.024, P<0.001). There were no significant differences between the groups in local recurrence (P=0.106), overall survival (P=0.055), or cancer-specific survival (P=0.235)., Conclusions: Smoking and long operating time are risk factors for right-side colon anastomosis. There were no significant differences in oncologic outcomes.

Background and Aims: Elevated circulating insulin is associated with increased risk of recurrence and cancer mortality in early-stage colorectal cancer (CRC). We conducted a randomized controlled trial to determine the effect of a 12-week home-based exercise program on fasting insulin, adipocytokines, and physical function in CRC survivors., Methods: One hundred and twenty-three stage II-III CRC patients were randomly assigned to either a home-based exercise (n=62) or standard care control group (n=61) for 12weeks. Home-based exercise consisted of aerobic and resistance training, with a goal of obtaining ≥18 metabolic equivalent task (MET)-h/wk. Participants in the exercise group were instructed to participate in >18MET-h/wk. of aerobic and resistance exercise while the participants in the control group were asked to maintain their usual daily activity. The primary outcome was fasting insulin levels. Secondary outcomes were adiponectin, TNF-α levels and 6min walk distance from baseline to post-intervention., Results: After the 12-weeks, moderate-vigorous physical activity participation increased from 9.1±14.7MET-h/wk. to 26.6±21.7MET-h/wk. in the exercise group, with no change in the control group (p<0.01 for group and time interaction). Circulating insulin level decreased by 1μU/ml (6.0±3.9 vs. 5.0±3.5, p=0.009) in the exercise group with no change in the control group (p=0.022 for group and time interaction). A similar trend was observed in TNF-α (p=0.030 for group and time interaction). Six minute walk distance increased by 25.2m in the exercise group with no change in the control group (p=0.061 for group and time interaction)., Conclusions: The 12week home-based exercise program increased level of physical activity and decreased circulating insulin levels in CRC survivors., (Copyright © 2017 Elsevier Inc. All rights reserved.)

The heterogeneous adsorption behaviors of charged colloidal particles to oil-water interfaces were quantitatively and statistically investigated. Using optical laser tweezers, the particles in a sessile water drop formed in an oil phase were laterally translated toward the slope of the oil-water interface and their attachment to the interface was attempted. The adsorption probability was found to logarithmically decrease as the ionic strength decreased and to depend on the holding time during which an optically trapped particle was held at the position closest to the interface. Non-unity of the adsorption probability at particular salt concentrations and the holding time dependence offer an important clue that the particle adsorption to the interface is not deterministic but stochastic. The stochastic adsorption process can be attributed to the surface heterogeneity of colloidal particles that consequently leads to changes in the electrostatic interactions between the particles and the interface. We also demonstrated that the salt dependence on the adsorption properties of the particles, as measured by optical laser tweezers, was consistent with their bulk behaviors with regard to the stability of particle-stabilized emulsions. Furthermore, we revealed the gravity-induced spontaneous adsorption of the particles to the interface under conditions of sufficiently strong ionic strength.

Background: Previous multicenter randomized trials demonstrated that omitting mechanical bowel preparation (MBP) did not increase anastomotic leakage rates or other infectious complications. However, the most serious concern regarding the omission of MBP is ongoing fecal peritonitis after anastomotic leakage occurs. The aim of this study was to compare the clinical manifestations and severity of anastomotic leakage between patients who underwent MBP and those who did not., Methods: This study was a single-center retrospective review of a prospectively maintained database. From January 2006 to September 2013, 1369 patients who underwent elective rectal cancer resection with primary anastomosis were identified and analyzed., Results: Anastomotic leakage rates were not significantly different between patients who did not undergo MBP (77/831, 9.27%) and those who did (42/538, 7.81%). However, a significantly lower rate of clinical leakage requiring surgical exploration was observed in the leakage without MBP group (30/77, 39.0%) compared with the leakage with MBP group (30/42, 71.4%) (P = 0.001). There were no significant differences in the clinical severity of anastomotic leakage as assessed by the length of hospital stay, time to resuming a normal diet, length of antibiotic use, ileus rate, transfusion rate, ICU admission rate, and mortality rate between the leakage without MBP and leakage with MBP groups., Conclusion: MBP was not found to affect the clinical severity of anastomotic leakage in elective rectal cancer surgery.

Purpose: Recently, common application of sphincter-saving resection in rectal cancer has led to acceptance of a 1-cm distal resection margin (DRM). The aim of this study was to evaluate oncologic outcomes of a DRM ≤1 cm in sphincter-saving resection for rectal cancer. The outcomes of a DRM ≤0.5 cm was also evaluated., Methods: We reviewed prospectively collected data from 415 patients who underwent sphincter-saving resection for mid and low rectal cancer between September 2006 and December 2012 at Korea University Anam Hospital. Patients were divided into two groups according to DRM measured in a formalin fixed specimen: ≤1 cm (n = 132) and >1 cm (n = 283). The DRM ≤1 cm group was divided into two subgroups: ≤0.5 cm (n = 45) and >0.5, ≤1 cm (n = 87)., Results: Median follow-up periods were 47.2 months. The 5-year local recurrence rate was 8.8% in the DRM ≤1 cm group and 8.5% in the DRM >1 cm group (p = 0.630). The 5-year disease-free survival rate was 75.1 and 76.3% (p = 0.895), and the 5-year overall survival rate was 82.6 and 85.9% (p = 0.401), respectively. In subanalysis of the DRM ≤1 cm group, there was also no significant difference in the local recurrence and survival., Conclusions: There was no significant difference in local recurrence and survival based on DRM length. We found that DRM length less than 1 cm was not a prognostic factor for local recurrence or survival.

We investigated the geometric and chemical factors of nonspherical Janus particles (i.e., Janus ellipsoids) with regard to the pinning and unpinning behaviors of the Janus boundary at the oil-water interface using attachment energy numerical calculations. The geometric factors were characterized by aspect ratio ( AR ) and location of the Janus boundary ( α ) separating the polar and apolar regions of the particle. The chemical factor indicated the supplementary wettability ( β ) of the two sides of the particle with identical deviations of apolarity and polarity from neutral wetting. These two factors competed with each other to determine particle configurations at the interface. In general, the critical value of β ( β c ) required to preserve the pinned configuration was inversely proportional to the values of α and AR . From the numerical calculations, the empirical relationship of the parameter values of Janus ellipsoids was found; that is, λ = Δ β c / Δ α ≈ 0.61 A R - 1.61 . Particularly for the Janus ellipsoids with AR > 1, the β c value is consistent with the boundary between the tilted only and the tilted equilibrium/upright metastable region in their configuration phase diagram. We believe that this work performed at the single particle level offers a fundamental understanding of the manipulation of interparticle interactions and control of the rheological properties of particle-laden interfaces when particles are used as solid surfactants.

Phospholipase D (PLD) regulates downstream effectors by generating phosphatidic acid. Growing links of dysregulation of PLD to human disease have spurred interest in therapeutics that target its function. Aberrant PLD expression has been identified in multiple facets of complex pathological states, including cancer and inflammatory diseases. Thus, it is important to understand how the signaling network of PLD expression is regulated and contributes to progression of these diseases. Interestingly, small molecule PLD inhibitors can suppress PLD expression as well as enzymatic activity of PLD and have been shown to be effective in pathological mice models, suggesting the potential for use of PLD inhibitors as therapeutics against cancer and inflammation. Here, we summarize recent scientific developments regarding the regulation of PLD expression and its role in cancer and inflammatory processes., (© 2014 by The American Society for Biochemistry and Molecular Biology, Inc.)

CXXC5 is a member of a small subset of proteins containing CXXC-type zinc-finger domain. Here, we show that CXXC5 is a transcription factor activating Flk-1, a receptor for vascular endothelial growth factor. CXXC5 and Flk-1 were accumulated in nucli and membrane of mouse embryonic stem cells (mESCs), respectively, during their endothelial differentiation. CXXC5 overexpression induced Flk-1 transcription in both endothelium-differentiated mESCs and human umbilical vein endothelial cells (HUVECs). In vitro DNA binding assay showed direct interaction of CXXC5 on the Flk-1 promoter region, and mutation on its DNA-binding motif abolished transcriptional activity. We showed that bone morphorgenetic protein 4 (BMP4) induced CXXC5 transcription in the cells, and inhibitors of BMP signaling suppressed the CXXC5 induction and the consequent Flk-1 induction by BMP4 treatment. CXXC5 knockdown resulted in suppression of BMP4-induced stress fiber formation (56.8 ± 1.3% decrease, P<0.05) and migration (54.6 ± 1.9% decrease, P<0.05) in HUVECs. The in vivo roles of CXXC5 in BMP-signaling-specific vascular development and angiogenesis were shown by specific defect of caudal vein plex vessel formation (57.9 ± 11.8% decrease, P<0.05) in cxxc5 morpholino-injected zebrafish embryos and by suppression of BMP4-induced angiogenesis in subcutaneously injected Matrigel plugs in CXXC5(-/-) mice. Overall, CXXC5 is a transcriptional activator for Flk-1, mediating BMP signaling for differentiation and migration of endothelial cell and vessel formation.

In the present study, we used the SOD1(G93A) mutant transgenic mice as an in vivo model of amyotrophic lateral sclerosis (ALS) and performed immunohistochemical studies to investigate the changes of insulin-like growth factor-binding protein 4 (IGFBP4) in the central nervous system. Decreased expression of IGFBP4 was obvious in the cerebral cortex, hippocampus, cerebellar cortex and inferior olive of SOD1(G93A) transgenic mice. In the cerebral cortex, there was a significant decrease in IGFBP4 immunoreactivity in the pyramidal cells. In the hippocampal formation, IGFBP4 immunoreactivity was also decreased in the pyramidal cells of CA1-3 areas and the granule cells of dentate gyrus. In the cerebellar cortex, IGFBP4 immunoreactivity was prominent in the granular layer in wtSOD1 transgenic mice, compared to that in SOD1(G93A) transgenic mice. IGFBP4 immunoreactivity was decreased in the inferior olive of SOD1(G93A) transgenic mice. This study, showing decreased IGFBP4 in different brain regions of SOD1(G93A) transgenic mice, may provide clues to understanding the differential susceptibility of neural structures in ALS, suggesting a role of IGFBP4 in an abnormality of cognitive and/or motor function in ALS. The mechanisms and functional implications of these decreases require elucidation.

Porcine endogenous retroviruses (PERVs) in the pig genome represent a potential risk of infection in pig-to-human transplantation and are transmitted vertically. The solitary long terminal repeat (LTR) elements of the PERVs affect the replication properties of the individual viruses via their repeat sequences and by encoding a set of specific transcription factors. We examined the promoter activities of solitary LTR elements belonging to the PERV-A and -B families of the Korean domestic pig (KDP) using luciferase reporters. Three of the LTR structures (of PERV-A5-KDP, PERV-A7-KDP, PERV-A8-KDP) had different promoter activities in human HCT116 cells and monkey Cos7 cells, and potential negatively and positively acting regions affecting transcription were identified by deletion analysis. These data suggest that specific sequences in the U3 region of a given LTR element can affect the activities of promoter or enhancer elements in the PERV.