17 vs 523 in the Baby Boomers and 1211 vs 1247 in the non-Ba

17 vs. 5.23 in the Baby Boomers and 12.11 vs. 12.47 in the non-Baby Boomers, p<0.001). Conclusions In the year following the CDC call, screening rates rose significantly (10%) in the Baby Boomer cohort, but also decreased significantly (10%) in the non-Baby Boomer cohort. Further study is needed to see if these changes were due to healthcare professionals changing their criteria for screening from risk factors to birth cohort. It is of interest that projected rates suggest that screening rates in both cohorts will increase significantly in the second year

following the CDC call to action, which may indicate further changes in screening criteria. Disclosures: Carol Smyth – Employment: Medivo, Inc. Jason Bhan this website – Employment: Medivo Nancy Reau – Advisory Committees or Review Panels: Kadmon, Jannsen, Vertex, Idenix, AbbVie, Jannsen; Grant/Research Support: Vertex, Gilead, Genentech, AbbVie, BMS, Jannsen, BI The following people have nothing to disclose: Tatiana Sorokina, Ajitpal S. Dhaliwal Background and Purpose: In New York City, an estimated 146,500 residents, or 2.4% of the adult population, have chronic HCV infection, and half may be unaware of their infection. In 2013, New York State mandated that primary care providers offer HCV antibody testing to all PLX4032 persons born during 1945-1965

(baby boomers). Many high-risk HCV positive persons medchemexpress are not screened in primary care settings, and, of those who are screened, many do not receive an RNA test to confirm current infection. Check Hep C was designed to integrate HCV testing and linkage to care into community-based

organizations to improve HCV testing rates. Methods: Check Hep C funded 8 organizations at 12 community sites to provide HCV testing and patient navigators in high prevalence neighborhoods. The testing method involved targeted outreach, point of care rapid antibody testing, and, after a positive antibody test, an immediate blood draw for RNA testing. Sites included Federally Qualified Health Centers (FQHC), Syringe Exchange Programs (SEP), and combined FQHC/SEP facilities. A central database collected information including participant demographics, test results, and risk factors. Results: From May 2012 to April 2013, 4,751 individuals were tested. Hispanics comprised 49% of participants, black/non-Hispanic 40%, and white/non-Hispanic 9%. Fifteen percent of participants were homeless at the time of testing, and 50% had a history of incarceration. Ever having injected drugs was reported by 1128 (25%) participants, 361 of whom (33%) reported use in the past 30 days. A total of 880 (19%) were HCV antibody positive. Of 678 antibody positive patients who had an RNA test (77% acceptance rate), 512 (76%) had current infection.

17 vs 523 in the Baby Boomers and 1211 vs 1247 in the non-Ba

17 vs. 5.23 in the Baby Boomers and 12.11 vs. 12.47 in the non-Baby Boomers, p<0.001). Conclusions In the year following the CDC call, screening rates rose significantly (10%) in the Baby Boomer cohort, but also decreased significantly (10%) in the non-Baby Boomer cohort. Further study is needed to see if these changes were due to healthcare professionals changing their criteria for screening from risk factors to birth cohort. It is of interest that projected rates suggest that screening rates in both cohorts will increase significantly in the second year

following the CDC call to action, which may indicate further changes in screening criteria. Disclosures: Carol Smyth – Employment: Medivo, Inc. Jason Bhan see more – Employment: Medivo Nancy Reau – Advisory Committees or Review Panels: Kadmon, Jannsen, Vertex, Idenix, AbbVie, Jannsen; Grant/Research Support: Vertex, Gilead, Genentech, AbbVie, BMS, Jannsen, BI The following people have nothing to disclose: Tatiana Sorokina, Ajitpal S. Dhaliwal Background and Purpose: In New York City, an estimated 146,500 residents, or 2.4% of the adult population, have chronic HCV infection, and half may be unaware of their infection. In 2013, New York State mandated that primary care providers offer HCV antibody testing to all Crizotinib purchase persons born during 1945-1965

(baby boomers). Many high-risk HCV positive persons MCE are not screened in primary care settings, and, of those who are screened, many do not receive an RNA test to confirm current infection. Check Hep C was designed to integrate HCV testing and linkage to care into community-based

organizations to improve HCV testing rates. Methods: Check Hep C funded 8 organizations at 12 community sites to provide HCV testing and patient navigators in high prevalence neighborhoods. The testing method involved targeted outreach, point of care rapid antibody testing, and, after a positive antibody test, an immediate blood draw for RNA testing. Sites included Federally Qualified Health Centers (FQHC), Syringe Exchange Programs (SEP), and combined FQHC/SEP facilities. A central database collected information including participant demographics, test results, and risk factors. Results: From May 2012 to April 2013, 4,751 individuals were tested. Hispanics comprised 49% of participants, black/non-Hispanic 40%, and white/non-Hispanic 9%. Fifteen percent of participants were homeless at the time of testing, and 50% had a history of incarceration. Ever having injected drugs was reported by 1128 (25%) participants, 361 of whom (33%) reported use in the past 30 days. A total of 880 (19%) were HCV antibody positive. Of 678 antibody positive patients who had an RNA test (77% acceptance rate), 512 (76%) had current infection.

Results: We tested 1,249 individuals for HCV from December 2012 t

Results: We tested 1,249 individuals for HCV from December 2012 to February 2014. Anti-HCV seroprevalence was 4.2% (n =52). Ninety-two percent (n=48) of patients with a reactive antibody test accepted an offer for same-day phlebotomy; 81% (n=42) had successful confirmatory testing performed. We contacted 98% (n=41) of patients with their confirmatory test results. Sixty-nine percent (n=36) of anti-HCV positive patients had detectable HCV RNA. Thirty-six percent (n=13) Vemurafenib mw of chronically infected patients were uninsured, 62% (n=8) have since obtained insurance and a primary care provider (PCP). With case management, 64% (n=23) of chronically infected patients obtained

a referral to an HCV subspecialist and 58% (n=21) were linked to subspecialty care. Obtaining a referral for sub-specialty care, even with assistance of a patient navigator, was a barrier for 26% (n=8) of individuals who had a PCP. Treatment and SVR outcomes are forthcoming. Conclusions: Utilizing same day phlebotomy for confirmatory testing in community based programs is an effective means for improving the HCV cascade of care. Obtaining a referral to an HCV subspecialist is an obstacle for individuals diagnosed in community

based testing programs. Aggressive patient navigation services can reduce barriers and enhance outcomes for linkage and retention of HCV positive see more individuals in care. Disclosures: Stacey B. Trooskin – Advisory Committees or Review Panels: Gilead Sciences; Grant/Research Support: Gilead Sciences Amy Nunn – Consulting: Mylan; Grant/Research Support: Gilead The following people

have nothing to disclose: Hwajin Lee, Joanna Poceta, Caitlin Towey, Sophie C. Feller, Annajane Yolken, Najia Luqman, Ta-Wanda Preston, Erin Smith Background: HCV genotypes are clinically important for predicting the response to and determining the duration of therapy. Especially with the advent of new DAAs demonstrating that these regimens medchemexpress depend on the HCV genotypes, determining genotypes is very important. Some studies indicated that using the 5′NC region to define HCV genotypes led to mis-classification of genotype 6 into genotype 1. These errors were not seen when using NS5B or core regions. Aim: – Identify HCV genotypes using 5′NC and NS5B regions. -Confirm previous studies that indicated mis- classification of HCV genotypes using 5′NC. – Establish prevalence of HCV genotypes using NS5B. Methods: This was a retro- sectional study. We studied 3 groups of patients: Group I included 3686 patients using 5′NC region (male 48.86%, female 51,14% with mean age of patients 49.20 ± 11.48 from January 2007 to August 2011); Group II included 176 patients using NS5B (male 43.19%, female 56.81% with mean age of patients 50.01 ± 8.63 from August 2013 to May 2014); Group III included 101 patients with genotype 1 using 5′NC who were randomly genotyped again by using NS5B (male 41.58%, female 58.42% with mean age of patients 53.12 ± 11.02 from August 2013 to April 2014).

Results: We tested 1,249 individuals for HCV from December 2012 t

Results: We tested 1,249 individuals for HCV from December 2012 to February 2014. Anti-HCV seroprevalence was 4.2% (n =52). Ninety-two percent (n=48) of patients with a reactive antibody test accepted an offer for same-day phlebotomy; 81% (n=42) had successful confirmatory testing performed. We contacted 98% (n=41) of patients with their confirmatory test results. Sixty-nine percent (n=36) of anti-HCV positive patients had detectable HCV RNA. Thirty-six percent (n=13) BVD-523 concentration of chronically infected patients were uninsured, 62% (n=8) have since obtained insurance and a primary care provider (PCP). With case management, 64% (n=23) of chronically infected patients obtained

a referral to an HCV subspecialist and 58% (n=21) were linked to subspecialty care. Obtaining a referral for sub-specialty care, even with assistance of a patient navigator, was a barrier for 26% (n=8) of individuals who had a PCP. Treatment and SVR outcomes are forthcoming. Conclusions: Utilizing same day phlebotomy for confirmatory testing in community based programs is an effective means for improving the HCV cascade of care. Obtaining a referral to an HCV subspecialist is an obstacle for individuals diagnosed in community

based testing programs. Aggressive patient navigation services can reduce barriers and enhance outcomes for linkage and retention of HCV positive Small molecule library individuals in care. Disclosures: Stacey B. Trooskin – Advisory Committees or Review Panels: Gilead Sciences; Grant/Research Support: Gilead Sciences Amy Nunn – Consulting: Mylan; Grant/Research Support: Gilead The following people

have nothing to disclose: Hwajin Lee, Joanna Poceta, Caitlin Towey, Sophie C. Feller, Annajane Yolken, Najia Luqman, Ta-Wanda Preston, Erin Smith Background: HCV genotypes are clinically important for predicting the response to and determining the duration of therapy. Especially with the advent of new DAAs demonstrating that these regimens medchemexpress depend on the HCV genotypes, determining genotypes is very important. Some studies indicated that using the 5′NC region to define HCV genotypes led to mis-classification of genotype 6 into genotype 1. These errors were not seen when using NS5B or core regions. Aim: – Identify HCV genotypes using 5′NC and NS5B regions. -Confirm previous studies that indicated mis- classification of HCV genotypes using 5′NC. – Establish prevalence of HCV genotypes using NS5B. Methods: This was a retro- sectional study. We studied 3 groups of patients: Group I included 3686 patients using 5′NC region (male 48.86%, female 51,14% with mean age of patients 49.20 ± 11.48 from January 2007 to August 2011); Group II included 176 patients using NS5B (male 43.19%, female 56.81% with mean age of patients 50.01 ± 8.63 from August 2013 to May 2014); Group III included 101 patients with genotype 1 using 5′NC who were randomly genotyped again by using NS5B (male 41.58%, female 58.42% with mean age of patients 53.12 ± 11.02 from August 2013 to April 2014).

Results: We tested 1,249 individuals for HCV from December 2012 t

Results: We tested 1,249 individuals for HCV from December 2012 to February 2014. Anti-HCV seroprevalence was 4.2% (n =52). Ninety-two percent (n=48) of patients with a reactive antibody test accepted an offer for same-day phlebotomy; 81% (n=42) had successful confirmatory testing performed. We contacted 98% (n=41) of patients with their confirmatory test results. Sixty-nine percent (n=36) of anti-HCV positive patients had detectable HCV RNA. Thirty-six percent (n=13) Alpelisib order of chronically infected patients were uninsured, 62% (n=8) have since obtained insurance and a primary care provider (PCP). With case management, 64% (n=23) of chronically infected patients obtained

a referral to an HCV subspecialist and 58% (n=21) were linked to subspecialty care. Obtaining a referral for sub-specialty care, even with assistance of a patient navigator, was a barrier for 26% (n=8) of individuals who had a PCP. Treatment and SVR outcomes are forthcoming. Conclusions: Utilizing same day phlebotomy for confirmatory testing in community based programs is an effective means for improving the HCV cascade of care. Obtaining a referral to an HCV subspecialist is an obstacle for individuals diagnosed in community

based testing programs. Aggressive patient navigation services can reduce barriers and enhance outcomes for linkage and retention of HCV positive MG-132 concentration individuals in care. Disclosures: Stacey B. Trooskin – Advisory Committees or Review Panels: Gilead Sciences; Grant/Research Support: Gilead Sciences Amy Nunn – Consulting: Mylan; Grant/Research Support: Gilead The following people

have nothing to disclose: Hwajin Lee, Joanna Poceta, Caitlin Towey, Sophie C. Feller, Annajane Yolken, Najia Luqman, Ta-Wanda Preston, Erin Smith Background: HCV genotypes are clinically important for predicting the response to and determining the duration of therapy. Especially with the advent of new DAAs demonstrating that these regimens medchemexpress depend on the HCV genotypes, determining genotypes is very important. Some studies indicated that using the 5′NC region to define HCV genotypes led to mis-classification of genotype 6 into genotype 1. These errors were not seen when using NS5B or core regions. Aim: – Identify HCV genotypes using 5′NC and NS5B regions. -Confirm previous studies that indicated mis- classification of HCV genotypes using 5′NC. – Establish prevalence of HCV genotypes using NS5B. Methods: This was a retro- sectional study. We studied 3 groups of patients: Group I included 3686 patients using 5′NC region (male 48.86%, female 51,14% with mean age of patients 49.20 ± 11.48 from January 2007 to August 2011); Group II included 176 patients using NS5B (male 43.19%, female 56.81% with mean age of patients 50.01 ± 8.63 from August 2013 to May 2014); Group III included 101 patients with genotype 1 using 5′NC who were randomly genotyped again by using NS5B (male 41.58%, female 58.42% with mean age of patients 53.12 ± 11.02 from August 2013 to April 2014).

However, the utility of high resolution impedance manometry (HRiM

However, the utility of high resolution impedance manometry (HRiM) in the Chinese population has not been evaluated. The study aimed to investigate the normal reference of esophageal motility in healthy volunteers (as defined by Chicago classification) using HRiM. Methods: Healthy, fasted volunteers underwent HRiMin a supine position with ten liquid swallows and ten viscous swallows. Integrated relaxation pressure (IRP), distal contractile integral (DCI), contractile Tamoxifen chemical structure front velocity (CFV),

and distal latency (DL) were calculated. The interquartile ranges and the 95th percentile range for each metric were obtained. Results: Forty-two healthy volunteers were enrolled with 411 total liquid swallows and 398 viscous swallows available for analysis. Cilomilast in vitro We established 20.5 mmHg of IRP and 3195 mmHg●s●cm of DCI as the 95th percentile for liquid swallows. Using the reference range defined by Chicago

classification, we observed 6.3% (26/411) weak peristalsis and 0.7% (3/411) failed peristalsis for liquid swallows; twelve (28.6%, 12/42) and two (4.7%, 2/42) individuals were diagnosed as esophagogastric junction (EGJ) outflow obstruction and weak peristalsis for liquid swallows. Compared with liquid swallows, viscous swallows had a decreased IRP (P = 0.000) and CFV (P = 0.000), and an unchanged DCI (P = 0.211). Conclusion: We established HRiM normative data of both liquid and viscous swallows from healthy Chinese volunteers. The IRP and CFV were significantly decreased in the viscous swallows compared with those of the liquid swallows. Key Word(s): 1. HRM; Manometric Data Liquid swallow Viscous swallow P value Median (IQR) 95th percenlile Median (IQR) 95th percentile Bolus clearance (%) 91 (90, 100) 100 80 (73, 90) 100 0.000 Bolus transit time (s) 6.9 (6.5, 7.6) 11.0 7.4 (6.9, 8.8) 10.2 0.000 IRP (mmHg) EFT 14.1 (12.3, 16.1) 20.5 12.8 (11.4, 14.3) 23.2 0.000 DCI (mmHg●s●cm)

1527 (1188, 2104) 3195 1476 (1036, 2040) 3198 0.211 CFV (cm/s) 4.6 (4.0, 5.3) 6.9 4.3 (3.5, 4.6) 6.2 0.000 DL(s) 5.2 (4.9, 6.0) 7.1 5.4 (5.0, 6.3) 7.5 0.000 Presenting Author: YAN CHEN Additional Authors: JUANJUAN XU, SHI LIU, XIAOHUA HOU Corresponding Author: SHI LIU Affiliations: Huazhong University 上海皓元 of Science and Technology Objective: Loss of interstitial cells of Cajal (ICC) contributes to gastrointestinal motility disorders in diabetic patients. EA at ST36 is an effective therapy to relieve gastrointestinal symptoms. However, little is known about the effects of EA at ST36 on gastric motility and whether ICC was involved in diabetic rats. Methods: Rats were randomized into normal control, DM, DM+SEA, DM+LEA and DM+HEA group. Body weight and blood glucose screened during the experiment. Gastric emptying was studied by the phenol red method.

2) In Mz-ChA-1 cells, miR-148a expression was decreased to 025-

2). In Mz-ChA-1 cells, miR-148a expression was decreased to 0.25- ± 0.03-fold, and miR-152 expression was decreased to 0.23- ± 0.02-fold relative to H69 nonmalignant human cholangiocytes. Similar reductions in expression were also seen in malignant KMCH and TFK cells. The reduced expression of this group of miRNAs is consistent with increased expression of DNMT-1 in cholangiocarcinoma, Maraviroc datasheet and suggests that this group of miRNAs may be involved in deregulation of genomic methylation in human cholangiocarcinoma. A recent study of miRNA expression in intrahepatic cholangiocarcinoma samples showed reduced expression of miR-148a and miR-152 in cholangiocytes compared with normal liver tissues,20 but these were not aberrantly

expressed in malignant tissues. These hypoxia-inducible factor cancer may reflect differences in anatomical site of origin between these tumors and the cell lines used in our study. Notably, miR-148a expression is reduced in metastatic hepatocellular carcinoma supporting its potential as an oncosuppressor RNA gene. Chromosomal aberrations in genomic regions encoding miRNAs could contribute to altered expression in tumors. In order to evaluate the relationship between chromosomal aberrations and miRNA expression in biliary cancers, we evaluated the frequency

of chromosomal loss in the regions corresponding to miR-130a (11q12.1), miR-130b (22q11.21), miR-148a (7p15.2), miR-152 (17q21.32), and miR-301 (17q22) in intrahepatic and extrahepatic cholangiocarcinoma, using a comprehensive cytogenetic database (http://www.progenetix.de/∼pgscripts/progenetix). Chromosomal losses were observed in 11% in the sites of miR-152 and miR-301 and in 22% in the site of miR-130a of extrahepatic bile ducts tumors, while no losses were detected for the location of miR-148a and miR-130b. In

intrahepatic bile duct tumors, losses in both sites of chromosome 17 were detected in 6%, while no losses were observed in the sites of miR-148a and miR-130a. The highest frequency (11.8%) of losses was observed MCE for the site of miR-130b. Analysis of chromosomal changes in Mz-ChA-1 using a bacterial artificial chromosome array comparative genomic hybridization analysis did not show any significant changes in copy number for clones encompassing the genomic site of these miRNAs. Thus, chromosomal alterations do not account for altered expression of these microRNAs in Mz-ChA-1 cells. To determine the role of this specific group of miRNAs on IL-6–mediated DNMT-1 expression, Mz-ChA-1 human cholangiocarcinoma cells were stably transfected to overexpress IL-6 (Mz-IL-6 cells). When implanted as xenografts in athymic nude mice, the growth rate of Mz-IL-6 xenografts was increased compared with Mz-1 control cell xenografts, in conjunction with a decrease in the number of TUNEL-positive (apoptotic) cells.3 We used an miRNA microarray to assess the expression of human miRNAs in Mz-IL-6 cell lines overexpressing IL-6 and in Mz-IL-6–derived xenografts.

01) Although these data are preliminary and require independent

01). Although these data are preliminary and require independent confirmation, it is possible that these polymorphisms could increase RAC1 expression enough in vivo to decrease efficacy of thiopurine therapy when administered at a standard dose. The authors reported a non-significant trend toward higher frequencies of the −289C and VNTR-3 alleles in IBD patients who did not develop leucopenia on azathioprine (P = 0.079, OR = 0.18, 95% CI 0.02–1.49).37

This observation arguably supports the hypothesis that these promoter polymorphisms do increase RAC1 expression in vivo and may influence the efficiency and toxicity of thiopurine therapy. Does an ABCC4 polymorphism account for enhanced thiopurine sensitivity?  Multi-drug resistance protein 4 (MRP4) is an ATP-dependent efflux pump that is able to transport 6-TGNs out of cells.38 Overexpression of this pump and the concurrent downregulation of influx transporters (plasma membrane Selleckchem GS1101 nucleoside transporters, NTs) have

been shown to confer resistance of human leukemic cell lines to thiopurine drugs.39 Analysis of the accumulation and efflux of radio-labeled 6-mercatopurine, revealed that the leukaemic cells that overexpressed MRP4 effluxed 72.3% of 6-mercaptopurine as 6TGNs into the culture medium within 1 h compared with 23.7% of 6-TGNs by the control cell line.39 Conversely, murine models have demonstrated that a deficiency in MRP4 expression results in accumulation of 6-TGNs HCS assay to toxic concentrations in myeloid progenitor cells. Krishnamurthy et al.40 tested the 6-mercaptopurine sensitivity of Mrp4+/+ and Mrp4−/− mice by administering intraperitoneal injections of this thiopurine to the mice each day for 15 days. By day 13 all Mrp4−/− medchemexpress mice were dead, whereas > 75% of wild type mice were alive at day 15. Bone marrow cell 6-TGN concentrations in Mrp4−/− mice

were 10 times higher than the concentrations found in Mrp4+/+ mice. Moreover myeloid progenitor cells after 5 days of treatment were reduced by 74% in Mrp4−/− mice but only by < 20% in Mrp4+/+ mice.40 The gene coding for human MRP4 (ABCC4) is highly polymorphic.41 At least one variant has been identified that significantly impairs the functioning of this pump and may explain why some IBD patients who have normal TPMT activity, still develop 6-TGN-induced myelotoxicity. The nonsynomous ABCC4 SNP 2269G>A (rs3765534, E857K) codes a variant MRP4 protein, which is unable to effectively localize to the plasma membrane.40 In HEK293 cells the 5-fold reduction in cell surface expression resulted in enhanced 6-mercaptopurine cytotoxicity, with an EC50 of 9.7 µmol/L versus 17.3 µmol/L in cells expressing the wild type (2269G) allele (P < 0.05).40 The frequency of the minor allele (2269A) is 15–22% in Japanese and 8.3% in Han Chinese, but less than 1% in Caucasians and Africans. Ban et al.

01) Although these data are preliminary and require independent

01). Although these data are preliminary and require independent confirmation, it is possible that these polymorphisms could increase RAC1 expression enough in vivo to decrease efficacy of thiopurine therapy when administered at a standard dose. The authors reported a non-significant trend toward higher frequencies of the −289C and VNTR-3 alleles in IBD patients who did not develop leucopenia on azathioprine (P = 0.079, OR = 0.18, 95% CI 0.02–1.49).37

This observation arguably supports the hypothesis that these promoter polymorphisms do increase RAC1 expression in vivo and may influence the efficiency and toxicity of thiopurine therapy. Does an ABCC4 polymorphism account for enhanced thiopurine sensitivity?  Multi-drug resistance protein 4 (MRP4) is an ATP-dependent efflux pump that is able to transport 6-TGNs out of cells.38 Overexpression of this pump and the concurrent downregulation of influx transporters (plasma membrane AZD6738 nucleoside transporters, NTs) have

been shown to confer resistance of human leukemic cell lines to thiopurine drugs.39 Analysis of the accumulation and efflux of radio-labeled 6-mercatopurine, revealed that the leukaemic cells that overexpressed MRP4 effluxed 72.3% of 6-mercaptopurine as 6TGNs into the culture medium within 1 h compared with 23.7% of 6-TGNs by the control cell line.39 Conversely, murine models have demonstrated that a deficiency in MRP4 expression results in accumulation of 6-TGNs ABC294640 solubility dmso to toxic concentrations in myeloid progenitor cells. Krishnamurthy et al.40 tested the 6-mercaptopurine sensitivity of Mrp4+/+ and Mrp4−/− mice by administering intraperitoneal injections of this thiopurine to the mice each day for 15 days. By day 13 all Mrp4−/− MCE公司 mice were dead, whereas > 75% of wild type mice were alive at day 15. Bone marrow cell 6-TGN concentrations in Mrp4−/− mice

were 10 times higher than the concentrations found in Mrp4+/+ mice. Moreover myeloid progenitor cells after 5 days of treatment were reduced by 74% in Mrp4−/− mice but only by < 20% in Mrp4+/+ mice.40 The gene coding for human MRP4 (ABCC4) is highly polymorphic.41 At least one variant has been identified that significantly impairs the functioning of this pump and may explain why some IBD patients who have normal TPMT activity, still develop 6-TGN-induced myelotoxicity. The nonsynomous ABCC4 SNP 2269G>A (rs3765534, E857K) codes a variant MRP4 protein, which is unable to effectively localize to the plasma membrane.40 In HEK293 cells the 5-fold reduction in cell surface expression resulted in enhanced 6-mercaptopurine cytotoxicity, with an EC50 of 9.7 µmol/L versus 17.3 µmol/L in cells expressing the wild type (2269G) allele (P < 0.05).40 The frequency of the minor allele (2269A) is 15–22% in Japanese and 8.3% in Han Chinese, but less than 1% in Caucasians and Africans. Ban et al.

Communal nursing is unlikely, however, because unweaned ice rats

Communal nursing is unlikely, however, because unweaned ice rats nipple cling to the mother only (Willan, 1990). Ice rats occupy underground burrows and accrue the benefits of huddling (Hinze & Pillay, 2006), as occurs in alpine marmots Marmota marmota (Arnold, 1988). Therefore, group living in ice rats, as for many other small mammals (Canals et al., 1998), could be explained by the social thermoregulation hypothesis; huddling occurs belowground even in summer when burrow

temperatures regularly drop to 0°C at night (Hinze et al., 2006). Another benefit is the reduced per capita cost of burrow construction (i.e. the burrow-sharing hypothesis) because the construction and maintenance of the burrow system involve the collective efforts of all colony members (Hinze et al., 2006). We tested two other hypotheses, resource dispersion, as seen in Blanford’s fox Vulpes cana (Geffen et al., 1992), and food competition, as seen in the striped field mouse Apodemus agrarius (Gliwicz, Selleckchem CDK inhibitor 1981), which could also explain group living in ice rats. Despite mutual avoidance aboveground, colony members overlapped spatially, indicating that they forage

in the same areas but at different times. This is a key assumption of the resource dispersion hypothesis. The patchiness of food resources in the alpine environment of the Maluti mountains indicates high environmental heterogeneity, and utilizing the same resources at different times possibly reduces direct competition selleck inhibitor (Carr & MacDonald, 1986), although we cannot rule out the possibility of exploitation competition as we did not measure fitness of individuals. Spatial overlap with minimal temporal overlap resembles temporal territoriality (Leyhausen, 1965). Temporal avoidance may be phylogenetically constrained in ice rats because temporal territoriality occurs

medchemexpress in the related vlei rat (Davis, 1972). Members of an ice rat colony competed aggressively for a prized food (apple) in winter. Mutual avoidance and/or aggression may be related to defence of limited resources (Ostfeld, 1990). Despite having a wide diet of green food plants, ice rats feed selectively from particular food patches, preferring wetland sedges (Schwaibold & Pillay, 2010); such selectivity may drive competition to forage alone. Ice rats also displayed mutual avoidance in summer, almost never occurring within 4 m of one another. The alpine environment is characterized by short growing seasons (Schwaibold & Pillay, 2010) and ice rats possibly defend food patches to obtain sufficient energy to meet reproductive demands (Schwaibold & Pillay, 2003). Therefore, like other larger mammals (e.g. Ethiopian wolves Canis simensis; Sillero-Zubiri et al., 2004), the food competition hypothesis is likely to be a driver of solitary foraging in ice rats. The main functional consequences of group living in mammals involve reducing predation risk (Schradin, 2004), acquiring and defending resources and enhancing reproductive success (Silk, 2007).