Short Colon Research Articles

Genomic Evolution of Staphylococcus aureus During Artificial and Natural Colonization of the Human Nose

Staphylococcus aureus can colonize the human vestibulum nasi for many years. It is unknown whether and, how S. aureus adapts to this ecological niche during colonization. We determined the short (1 and 3 months) and mid-term (36 months) genomic evolution of S. aureus in natural carriers and artificially colonized volunteers. Eighty-five S. aureus strains were collected from 6 natural carriers during 3 years and 6 artificially colonized volunteers during 1 month. Multi-locus sequence typing (MLST) and single nucleotide polymorphism (SNP) analysis based on whole-genome sequencing (WGS) were carried out. Mutation frequencies within resident bacterial populations over time were quantified using core genome SNP counts (comparing groups of genomes) and pairwise SNP divergence assessment (comparing two genomes from strains originating from one host and sharing identical MLST). SNP counts (within 1–3 months) in all naturally colonizing strains varied from 0 to 757 (median 4). These strains showed random and independent patterns of pairwise SNP divergence (0 to 44 SNPs, median 7). When the different core genome SNP counts over a period of 3 years were considered, the median SNP count was 4 (range 0–26). Host-specific pairwise SNP divergence for the same period ranged from 9 to 57 SNPs (median 20). During short term artificial colonization the mutation frequency was even lower (0–7 SNPs, median 2) and the pairwise SNP distances were 0 to 5 SNPs (median 2). Quantifying mutation frequencies is important for the longitudinal follow-up of epidemics of infections and outbreak management. Random pattern of pairwise SNP divergence between the strains isolated from single carriers suggested that the WGS of multiple colonies is necessary in this context. Over periods up to 3 years, maximum median core genome SNP counts and SNP divergence for the strains studied were 4 and 20 SNPs or lower. During artificial colonization, where median core genome SNP and pairwise SNP distance scores were 2, there is no early stage selection of different genotypes. Therefore, we suggest an epidemiological cut off value of 20 SNPs as a marker of S. aureus strain identity during studies on nasal colonization and also outbreaks of infection.

Dietary Supplementation with Sea Bass (Lateolabrax maculatus) Ameliorates Ulcerative Colitis and Inflammation in Macrophages through Inhibiting Toll-Like Receptor 4-Linked Pathways

Sea bass (Lateolabrax maculatus) is a kind of food material commonly consumed in daily life. In traditional Chinese medicinal books, it has been indicated that sea bass can be applied for managing many inflammation-associated conditions. However, the studies on the pharmacological mechanisms of inflammation of sea bass remain scarce. Hence, this study aims to investigate the molecular mechanisms of the anti-inflammatory activity of sea bass. Anti-inflammatory activities of sea bass were assessed using dextran sulfate sodium (DSS)-induced colitis in a mice model and lipopolysaccharide (LPS)-activated macrophages model. Low body weight and short colon length were observed in DSS-fed mice that were significantly recovered upon sea bass treatments. Moreover, the colon histopathology score showed that sea bass-treated mice had decreased crypt damage, focal inflammation infiltration and the extent of inflammation, suggesting that treatment with sea bass could attenuate intestinal inflammation. In addition, the in-vitro study conjointly indicated that sea bass could suppress the inflammatory mediators in LPS-activated macrophage by inhibiting the TLR4-linked pathway. The present findings demonstrated that sea bass has an inhibitory effect on TLR4 signaling; thus, it could be a promising candidate for treating inflammation-associated conditions. A further justification for the clinical application of sea bass in treating inflammation-associated conditions is necessary.

Mitigation of Colonic Inflammation in Dextran Sulfate Sodium-treated Mice by Dietary Supplementation with Soybean Fiber (P06-079-19)

ObjectivesSoybean fiber (SBF) is an insoluble, but highly fermentable dietary fiber. Previous in vitro fermentation studies with human feces have shown that SBF produces 1.5–8 times more acetate, propionate, and butyrate than oat bran, corn bran, or wheat bran fiber. Short chain fatty acids (SCFA) have been reported to play a key role in maintaining colon health and reducing inflammation. The impact of dietary SBF on colonic inflammation has not previously been examined. Our objective was to determine the anti-inflammatory efficacy of dietary supplementation with SBF in a mouse model of acute colonic inflammation. MethodsMale C57BL/6 J mice (5 weeks old) were randomized to AIN93G diet (CTL) or diet where 40% of the fiber was replaced with SBF (SBF-Hi). After 2 weeks of pretreatment, mice were given 2% dextran sulfate sodium (DSS) as the sole source of drinking fluid for 1 week to induce colonic inflammation. During DSS treatment, mice were maintained on their diet treatments. After DSS treatment, mice were euthanized and colonic inflammation was assessed. ResultsDSS-treated mice had significantly larger spleens and shorter colons than mice treated with water. SBF-Hi mitigated DSS-induced increases in spleen weight (20% lower) and colon shortening (15% longer). Quantitative, reverse transcriptase PCR analysis showed that DSS-treatment increased colonic mRNA expression of interleukin-6 (Il6) and tumor necrosis factor-a (Tnfa) by 3-fold compared to water-treated mice. Dietary supplementation with SBF blunted these increases in Il6 and Tnfa by 87% and 71%, respectively. ConclusionsOur results suggest that dietary supplementation with SBF may be a useful approach to mitigate colonic inflammation. On-going studies are focused on determining fecal levels of SCFA and measuring protein markers of inflammation and gut barrier function. Future studies are needed to evaluate whether the protective effects observed in this study are maintained in situations of more chronic colonic inflammation. Funding SourcesThis work was funded by a grant from the Pennsylvania Soybean Board and by USDA National Institute of Food and Agriculture Appropriations under Project PEN04565.

Why space colonization will be fully automated

In this article we explore a possible scenario of space colonization and its consequences for planet Earth. We argue that in the short term space colonization will take place, but not in the form often presented in scientific and science fiction literature. Space colonies will be fully automated. There are three main reasons to believe that this is the most plausible scenario: 1) space mining is very profitable; 2) humans cannot survive for long periods of time in outer space limiting the prospects for human space colonization (HSC), and 3) automation is already a leading trend on Earth. Crewed missions will have an ancillary function, while machines or human/machine avatars will ‘inhabit’ other celestial bodies, in order to pursue economic enterprises and progress scientific discovery. We also propose some considerations on the speculative hypothesis, elaborated by a few leading futurists, that the development of machine-based learning Artificial Intelligence would lead to the so-called Singularity. In relation to this scenario, we argue that fully automated space colonization (FASC) could be a solution to prevent unwanted side effects of the Singularity, such as competition for resources between humankind and a hostile Artificial Intelligence.

Home Based Primary Care for Patients with Sickle Cell Disease

Background: Sickle cell disease (SCD) is characterized by sickled red blood cells that can cause severely painful vaso-occlusive crises. These crises can cause damage to multiple organs and bring about additional chronic disease, such as avascular necrosis, leg ulcers, pulmonary hypertension, and renal failure. While there are options for disease modification, these are not effective if patients (pts) cannot attend regular doctor visits for their condition to be monitored and for medications to be adjusted. Obstacles to obtaining outpatient primary care include physical disability, environmental factors, transportation, and psychosocial factors. Impaired access to primary care leads to poor clinical outcomes in chronic diseases, such as SCD. This study was conducted to help pts with SCD who had the most barriers to obtaining outpatient primary care.Home based primary care has proven beneficial for pts with chronic illnesses in the past. Utilizing this method, a physician meets with pts in their homes to manage both acute and chronic illnesses. This eliminates many potential barriers for pts with difficulty attending office visits and would provide continuity of care. It also allows physicians to observe other potential factors that could undermine the treatment plans for these pts, and get the correct member of the team to intervene more efficiently.Methods: Outcomes were measured for patient quality of care and health service utilization, both one year prior to and one year after the home visits began. Data was collected from a chart review and included the number of primary care visits, day hospital referrals, and emergency department visits. SCD specific immunizations and the number of prescription refills were also noted. McNemar's test and Wilcoxon signed rank test were used to compare binary and continuous outcomes, respectively, during the years prior to and after home based primary care began.Results: There were 23 SCD pts enrolled in this study, with 13 pts (69% female, 31% male) having completed one full year of home visits. These pts ranged from 26 to 66 years old. Comorbidities include one patient with a history of a myocardial infarction (MI) and two with diabetes mellitus. Other medical history noted were: acute chest syndrome (62%), thrombosis (62%), avascular necrosis (46%), retinopathy (46%), depression (38%), kidney disease (31%), hypertension (31%), pulmonary hypertension (23%), stroke (23%), and iron overload (15%). Most pts had received transfusions (92%), and 77% had taken hydroxyurea.Pts received a median number of 11 home visits (range 7-15) during the 1-year program in which they received home based primary care. The median number of new long term prescriptions increased significantly (p = 0.04) from 1 to 3. Five pts not previously receiving PVC-13 vaccine started to receive it after the initiation of the home visit program (p = 0.06). The total number of immunizations (p = 0.09), months with prescription refills (p = 0.08) both increased slightly. There was no change in the number of new short term prescriptions, breast or colon cancer screening rates, nor influenza, PVC-23, or MenAWCY immunization rates.The median number of reported vaso-occlusive crises per patient decreased from 8 per year to 5 (p = 0.69), and the median number of emergency department visits per patient decreased from 6 visits per year to 3 visits per year (p = 0.80).Conclusion: Overall, home based primary care seems to be a promising alternative for pts with SCD. It had a significant impact on patient quality of care and may improve prescription adherence, but more data are needed to determine if it has an effect on healthcare utilization for pts with SCD. DisclosuresMoore:Ohio State University College of Medicine: Research Funding. Desai:FDA: Research Funding; Pfizer: Research Funding; University of Pittsburgh: Research Funding; Selexy/Novartis: Research Funding; NIH: Research Funding; Ironwood: Other: Adjudication Committee.

Molecular Phylogeny, Diversity and Zoogeography of Net-Winged Beetles (Coleoptera: Lycidae).

We synthesize the evidence from molecular phylogenetics, extant distribution, and plate tectonics to present an insight in ancestral areas, dispersal routes and the effectiveness of geographic barriers for net-winged beetle tribes (Coleoptera: Lycidae). Samples from all zoogeographical realms were assembled and phylogenetic relationships for ~550 species and 25 tribes were inferred using nuclear rRNA and mtDNA markers. The analyses revealed well-supported clades at the rank of tribes as they have been defined using morphology, but a low support for relationships among them. Most tribes started their diversification in Southeast and East Asia or are endemic to this region. Slipinskiini and Dexorini are Afrotropical endemics and Calopterini, Eurrhacini, Thonalmini, and Leptolycini remained isolated in South America and the Caribbean after their separation from northern continents. Lycini, Calochromini, and Erotini support relationships between the Nearctic and eastern Palearctic faunas; Calochromini colonized the Afrotropical realm from East Asia and Metriorrhynchini Afrotropical and Oriental realms from the drifting Indian subcontinent. Most tribes occur in the Oriental and Sino-Japanese realms, the highest alpha-taxonomic diversity was identified in Malesian tropical rainforests. The turn-over at zoogeographical boundaries is discussed when only short distance over-sea colonization events were inferred. The lycid phylogeny shows that poor dispersers can be used for reconstruction of dispersal and vicariance history over a long time-span, but the current data are insufficient for reconstruction of the early phase of their diversification.

Acer palmatum thumb. Ethanol Extract Alleviates Interleukin-6-Induced Barrier Dysfunction and Dextran Sodium Sulfate-Induced Colitis by Improving Intestinal Barrier Function and Reducing Inflammation.

Ulcerative colitis is one inflammatory bowel disease (IBD) and is caused by diverse factors, including the extent and duration of intestinal inflammation. We investigated the effect of Acer palmatum thumb. ethanol extract (KIOM-2015E) on the expression of tight junction proteins and the levels of inflammation in the cell model induced with interleukin-6- (IL-6-) and mouse model of dextran sodium sulfate (DSS) induced with acute colitis. KIOM-2015E (100 mg/kg) was orally administered once per day to BALB/C mice with colitis induced by administration of 5% DSS in drinking water. KIOM-2015E did not affect viability in Caco-2 cells. Also, KIOM-2015E repaired the IL-6-induced intestinal barrier dysfunction in Caco-2 cells. Furthermore, KIOM-2015E recovered the loss of body weight and the abnormally short colon lengths in the DSS-induced model of acute colitis. Moreover, KIOM-2015E significantly inhibited the decrease of zonula occluden-1 and occludin in colonic tissue relative to the DSS-treated control group. KIOM-2015E also significantly inhibited the expression of IL-6 and tumor necrosis factor-α in the level of serum relative to the control group. Collectively, these data suggest that KIOM-2015E protects colitis principally by improving intestinal barrier function and promoting anti-inflammatory responses. In turn, these effects inhibit macrophage infiltration into the colon and thus may be a candidate treatment for IBD.

The Establishment of a Lung Colonization Assay for Circulating Tumor Cell Visualization in Lung Tissues.

Metastasis is the major cause of cancer death. The role of circulating tumor cells (CTCs) in promoting cancer metastasis, in which lung colonization by CTCs critically contributes to early lung metastatic processes, has been vigorously investigated. As such, animal models are the only approach that captures the full systemic process of metastasis. Given that problems occur in previous experimental designs for examining the contributions of CTCs to blood vessel extravasation, we established an in vivo lung colonization assay in which a long-term-fluorescence cell-tracer, carboxyfluorescein succinimidyl ester (CFSE), was used to label suspended tumor cells and lung perfusion was performed to clear non-specifically trapped CTCs prior to lung removal, confocal imaging, and quantification. Polymeric fibronectin (polyFN) assembled on CTC surfaces has been found to mediate lung colonization in the final establishment of metastatic tumor tissues. Here, to specifically test the requirement of polyFN assembly on CTCs for lung colonization and extravasation, we performed short term lung colonization assays in which suspended Lewis lung carcinoma cells (LLCs) stably expressing FN-shRNA (shFN) or scramble-shRNA (shScr) and pre-labeled with 20 μM of CFSE were intravenously inoculated into C57BL/6 mice. We successfully demonstrated that the abilities of shFN LLC cells to colonize the mouse lungs were significantly diminished in comparison to shScr LLC cells. Therefore, this short-term methodology may be widely applied to specifically demonstrate the ability of CTCs within the circulation to colonize the lungs.

Intestinal immunity in hypopituitary dwarf mice: effects of age.

Hypopituitary dwarf mice demonstrate advantages of longevity, but little is known of their colon development and intestinal immunity. Herein we found that Ames dwarf mice have shorter colon and colonic crypts, but larger ratio of mesenteric lymph nodes (MLNs) over body weight than age-matched wild type (WT) mice. In the colonic lamina propria (cLP) of juvenile Ames mice, more inflammatory neutrophils (Ā: 0.15% vs. 0.03% in WT mice) and monocytes (Ā: 7.97% vs. 5.15%) infiltrated, and antigen presenting cells CD11c+ dendritic cells (Ā: 1.39% vs. 0.87%), CD11b+ macrophages (Ā: 3.22% vs. 0.81%) and gamma delta T (γδ T) cells (Ā: 5.56% vs. 1.35%) were increased. In adult Ames dwarf mice, adaptive immune cells, such as IL-17 producing CD4+ T helper (Th17) cells (Ā: 8.3% vs. 4.7%) were augmented. In the MLNs of Ames dwarf mice, the antigen presenting and adaptive immune cells also altered when compared to WT mice, such as a decrease of T-regulatory (Treg) cells in juvenile Ames mice (Ā: 7.7% vs.10.5%), but an increase of Th17 cells (Ā: 0.627% vs.0.093%). Taken together, these data suggest that somatotropic signaling deficiency influences colon development and intestinal immunity.

Congenital pouch colon: Our experience with coloplasty.

Background:Congenital pouch colon (CPC) or congenital short colon is an entity found mainly in Indian subcontinent. In CPC, colon is replaced with partially or completely abnormal pouch connected to the genitourinary tract by a fistula (colovesical). Management protocol is different in different institute. In this article, we are sharing our three stage standard management approach; principle and technique of coloplasty in cases in which colon length is not adequate for pull through and their follow-up. This study aims to show the result of coloplasty in complete CPC.Materials and Methods:This is retrospective observational study, of 5 years duration. The medical record of these patients was reviewed for demographic information, clinical features, investigations performed, operative notes, post-operative events and the outcome of surgery.Results:Total of 626 ARM cases were managed in 5 years duration in which 64 were of pouch colon. The age of presentation was 1–15 days. In fifty patients who completed their, all stage in that 34 patients were in which coloplasty were done in rest of 16 cases excision of CPC and colonic pull through done in view of adequate colonic length (type III and IV) for pull through. In 34 patient in which coloplasty were done showed satisfactory cosmetic and functional out came after stoma closer in follow-up.Conclusions:Properly created coloplasty and three stage procedure for complete pouch colon give better result and less complications. Excision of pouch is not requiring in all cases of CPC.

Basic Science Luminal

Basic Science Luminal

Fermented herbal formula KIOM-MA-128 protects against acute colitis induced by dextran sodium sulfate in mice

BackgroundColitis is a well-known subtype of inflammatory bowel disease and is caused by diverse factors. Previous research has shown that KIOM-MA elicits anti-inflammatory and anti-allergic effects on various diseases. KIOM-MA-128, our novel herbal formula, was generated from KIOM-MA using probiotics to improve the therapeutic efficacy. We investigated whether KIOM-MA-128 has protective activity in a mouse model of acute colitis induced by dextran sodium sulfate (DSS).MethodsColitis was induced by DSS administered to ICR mice in drinking water. KIOM-MA-128 (125 or 250 mg/kg) was orally administered once per day. The body weights of the mice were measured daily, and colonic endoscopies were performed at 5 and 8 days. Colon length as well as histological and cytokine changes were observed at the end of drug administration.ResultsKIOM-MA-128 has pharmacological activity in an acute colitis model. KIOM-MA-128 reduced the loss of body weight and disease activity index (DAI) and inhibited the abnormally short colon lengths and the colonic damage in this mouse model of acute colitis. Moreover, KIOM-MA-128 suppressed pro-inflammatory cytokine expression and maintained the integrity of the tight junctions during DSS-induced colitis.ConclusionThe results indicated that KIOM-MA-128 protects against DSS-induced colitis in mice and suggested that this formula might be a candidate treatment for inflammatory bowel disease (IBD).

Type V Pouch Colon, Prune Belly Syndrome, and Congenital Anterior Urethrocutaneous Fistula.

Congenital pouch colon (CPC) or short colon syndrome is a rare type of anorectal malformation(ARM). Type V is the rarest form of CPC. We present a 1-day-old male child with type V CPC with prune belly syndrome and congenital anterior urethrocutaneous fistula (CAUF).

Prophylactic Oral Administration of Magnesium Ameliorates Dextran Sulfate Sodium-Induced Colitis in Mice through a Decrease of Colonic Accumulation of P2X7 Receptor-Expressing Mast Cells.

The number of patients with colitis has been increasing year by year. Recently, intestinal inflammation, as one of the factors for its onset, has been demonstrated to be induced by P2X7 receptor-mediated activation of colonic immune cells such as mast cells. Activation of P2X7 receptor (P2X7R) is known to be inhibited by divalent metal cations such as magnesium, but whether or not magnesium administration prevents/relieves colitis is unknown so far. Here, we report that oral (per os (p.o.)) administration of MgCl2 and ingestion of commercially available magnesium-rich mineral hard water relieves dextran sulfate sodium (DSS)-induced colitis in mice. Colitis was induced through ingestion of a 3% (w/v) DSS solution ad libitum for 10 d. Brilliant blue G (BBG, a P2X7R antagonist), MgCl2 or magnesium-rich mineral hard water was administered p.o. to mice via gastric intubation once a day or ad libitum from a day before DSS administration for 11 times or 11 d, respectively. DSS-treated mice exhibited a low disease activity index, a short colon and a high histological score compared to in control mice. As BBG (250 mg/kg, p.o.), administration of a MgCl2 solution (100 or 500 mg/kg, p.o.) and ad libitum ingestion of the magnesium-rich mineral hard water (212 ppm as magnesium) partially, but significantly, attenuated the severity of colitis by decreasing the accumulation of P2X7R-immunopositive mast cells in the colon. Therefore, prophylactic p.o. administration/ingestion of magnesium is considered to be partially effective to protect mice against DSS-induced colitis by inhibiting P2X7R-mediated activation/accumulation of colonic mast cells.

Natural Orifice Specimen Extraction With Single Stapling Colorectal Anastomosis for Laparoscopic Anterior Resection: Feasibility, Outcomes, and Technical Considerations.

Double and triple stapling techniques to close the rectal stump in laparoscopic anterior resection are fraught with technical drawbacks that could possibly be avoided with the use of the single stapling technique. However, little is known of its safety in laparoscopic surgery or outcomes when combined with natural orifice specimen extraction. This study aims to analyze the feasibility and the operative and immediate postoperative outcomes of single-stapled anastomosis and natural orifice specimen extraction with conventional techniques. It intends to evaluate technical variations related to colon, mesentery, and pelvic anatomy characteristics. A consecutive series of 188 patients underwent elective surgery for benign or malignant lesions between 10 and 40 cm from the anal verge, 5 cm or less in diameter on radiological examination, stage T1 to T3, Nx, M0, with 2 different methods of rectal stump closure (pursestring vs linear-stapled closure) associated with single or double stapling and per anus vs conventional specimen extraction. This study was conducted at China Medical University Hospital, Taiwan, a tertiary referral center, between January 2012 and April 2015. The main outcomes measured are feasibility and operative and immediate postoperative outcomes. Single-stapled resection with natural orifice specimen extraction was feasible in 94% patients with an 11% perioperative morbidity rate. The patients required statistically significantly less analgesia, had earlier return of bowel movements, and shorter hospital stay, whereas there was no statistically significant difference in the overall readmission rate and overall morbidity, including anastomotic leakage. This was a single-center, retrospective case-matched study. Anatomic variations (short colon and short mesentery) can be managed adequately with intracorporeal anvil head fixation. The single stapling technique is feasible and as safe as conventional double stapling techniques, although it is technically more demanding. The transanal endoscopic operation platform can be useful when the rectal stump is long.

Global expression analysis of the response to microaerobiosis reveals an important cue for endophytic establishment of Azoarcus sp. BH72.

The endophyte Azoarcus sp. BH72, fixing nitrogen microaerobically, encounters low O2 tensions in flooded roots. Therefore, its transcriptome upon shift to microaerobiosis was analyzed using oligonucleotide microarrays. A total of 8.7% of the protein-coding genes were significantly modulated. Aerobic conditions induced expression of genes involved in oxidative stress protection, while under microaerobiosis, 233 genes were upregulated, encoding hypothetical proteins, transcriptional regulators, and proteins involved in energy metabolism, among them a cbb3 -type terminal oxidase contributing to but not essential for N2 fixation. A newly established sensitive transcriptional reporter system using tdTomato allowed to visualize even relatively low bacterial gene expression in association with roots. Beyond metabolic changes, low oxygen concentrations seemed to prime transcription for plant colonization: Several genes known to be required for endophytic rice interaction were induced, and novel bacterial colonization factors were identified, such as azo1653. The cargo of the type V autotransporter Azo1653 had similarities to the attachment factor pertactin. Although for short term swarming-dependent colonization, it conferred a competitive disadvantage, it contributed to endophytic long-term establishment inside roots. Proteins sharing such opposing roles in the colonization process appear to occur more generally, as we demonstrated a very similar phenotype for another attachment protein, Azo1684. This suggests distinct cellular strategies for endophyte establishment.

Different waves of effector genes with contrasted genomic location are expressed by Leptosphaeria maculans during cotyledon and stem colonization of oilseed rape

Leptosphaeria maculans, the causal agent of stem canker disease, colonizes oilseed rape (Brassica napus) in two stages: a short and early colonization stage corresponding to cotyledon or leaf colonization, and a late colonization stage during which the fungus colonizes systemically and symptomlessly the plant during several months before stem canker appears. To date, the determinants of the late colonization stage are poorly understood; L. maculans may either successfully escape plant defences, leading to stem canker development, or the plant may develop an 'adult-stage' resistance reducing canker incidence. To obtain an insight into these determinants, we performed an RNA-sequencing (RNA-seq) pilot project comparing fungal gene expression in infected cotyledons and in symptomless or necrotic stems. Despite the low fraction of fungal material in infected stems, sufficient fungal transcripts were detected and a large number of fungal genes were expressed, thus validating the feasibility of the approach. Our analysis showed that all avirulence genes previously identified are under-expressed during stem colonization compared with cotyledon colonization. A validation RNA-seq experiment was then performed to investigate the expression of candidate effector genes during systemic colonization. Three hundred and seven 'late' effector candidates, under-expressed in the early colonization stage and over-expressed in the infected stems, were identified. Finally, our analysis revealed a link between the regulation of expression of effectors and their genomic location: the 'late' effector candidates, putatively involved in systemic colonization, are located in gene-rich genomic regions, whereas the 'early' effector genes, over-expressed in the early colonization stage, are located in gene-poor regions of the genome.

Abstract 4153: Abnormal expression of MUC1 mucin on colon epithelia stimulates production of pro-inflammatory cytokines promoting colitis-associated colon cancer in a murine model

Abstract MUC1 is a transmembrane glycoprotein aberrantly expressed in human adenocarcinoma as well as chronic inflammatory conditions. We have previously demonstrated that the tumor form of MUC1, in association with p65, upregulates the expression of pro-inflammatory cytokines in the tumor microenvironment, including IL-6 and TNF-alpha, by modulating their transcriptional activity in epithelial cancer cells. Here, we explored the mechanism underlying MUC1/p65-induced transcription of IL-6 and TNF-alpha in colon cancer cells and its significance for the microenviroment of colitis that is known to be the precursor to cancer. We used a mouse model of colitis-associated colon cancer where wild type (WT) and human MUC1 transgenic (MUC1.Tg) mice are given carcinogen azoxymethane (AOM), followed by three cycles of 1.2% dextran sodium sulfate (DSS) in drinking water to induce colitis. MUC1.Tg showed higher tumor incidence, decreased survival, increased body weight loss and shorter colon length. These features accelerated the severity of inflammation-induced colon cancer. Consistent with our previous in vitro data, expression of NF-kB family members was higher in MUC1.Tg mice compared to WT. We previously showed that in tumors, MUC1/p65 complex modulated the expression of histone methyltransferase Enhancer of Zeste protein-2 (EZH2) and interaction with pro-inflammatory cytokine promoters. In order to understand the significance of MUC1/p65-modulated cytokines in progressive colitis that gives rise to colon cancer, we analyzed infiltration of inflammatory cells into the inflamed colon tissues. The number of infiltrating macrophages was much higher in AOM/DSS-treated MUC1.Tg mice compared to WT. ELISA assay and gene expression analyses demonstrated that the treatment with AOM/DSS in the presence of human MUC1 on the colonic epithelia resulted in a significant increase in M1 type macrophage-associated genes, including IL-6, TNF-alpha and iNOS, whereas M2 type macrophage markers such as Arginase 1, Ym1, and IL-10 were drastically reduced when compared to colon tissues of treated WT mice. Taken together, our findings reveal a pro-inflammatory role for MUC1 in colitis-related carcinogenesis. Our study also provides a mechanism by which MUC1 accelerates tumor initiation and progression. Citation Format: Sandra Cascio, Jacque Faylo, Jia Xue, Olivera Finn. Abnormal expression of MUC1 mucin on colon epithelia stimulates production of pro-inflammatory cytokines promoting colitis-associated colon cancer in a murine model. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4153.

Spatial patterns and determinants of species richness of alien and native plants in the Nujiang River valley

Biological invasion has attracted widespread attention because invasive species threaten native biodiversity and weaken ecosystem services. Based on field investigation of vegetation in Nujiang River valley, Northwest Yunnan, we analyzed the spatial patterns of native and invasive species richness, and the effects of topography, climate, and roadside habitat disturbance on the invasive versus native plant species richness. We recorded 26 exotic invasive plant species that belong to 13 families and 21 genera, and 1,145 native plant species, belonging to 158 families and 628 genera. Along the Nujiang River valley, species richness of invasive plants decreased with increasing latitude and altitude, while species richness of native plants increased with increasing latitude, and showed a hump-shaped pattern with elevation. A generalized linear model was used to estimate the roles of roadside disturbance, climate, topography and soil nutrients on the distribution of both native and invasive species richness. Results of hierarchical variation partitioning revealed that roadside habitat disturbance had primary impact on the distribution of two groups of species. Pre·研究报告· 390 生 物 多 样 性 Biodiversity Science 第 24 卷 cipitation was the climatic determinant of invasive species diversity, and small-scale topographic factors, especially aspect, mainly affected native species diversity. It is likely that native species became drought-resistant in the evolutionary process while invasive species failed to adapt themselves to the local arid environments due to the short colonization time. This research supports the hypothesis that resource availability is the main factor limiting plant invasion, and highlights the negative effects of human activity on biodiversity. In addition, results of structural equation modelling revealed that native communities aren’t resistant to plant invasion. The negative relationship between invasive and native species richness reflects the different responses of the two group species to environmental factors.

Clinical Outcomes of Reoperation for Failed Antireflux Operations

Up to 18% of patients undergoing antireflux operations will require reoperation. Authors caution that with each additional reoperation, fewer patients achieve satisfaction. The quality of life in patients who underwent revision operations was compared with patients who underwent primary antireflux operations to determine the effectiveness of revision operations. We retrospectively reviewed patients who underwent revision after failed antireflux operations from 2004 to 2014. Patients were divided into two groups: first reoperation (Reop[1]) and more than one reoperation (Reop[>1]). For comparison, a control group of patients who underwent primary antireflux operations was included. Patients underwent quality of life assessment preoperatively and postoperatively. We identified 105 reoperative patients: 94 Reop(1), 11 Reop(>1), and 112 controls. The primary reason for failure was combined fundoplication herniation and slippage. Morbidity, mortality, and readmission rates were similar in all groups. Postoperative outcomes were improved in all groups but to a lesser degree in subsequent reoperations. Gastroesophageal Reflux Disease Health-Related Quality of Life: controls, 20.0 to 2.0; Reop(1), 26.5 to 4.0; and Reop(>1), 13.0 to 2.0. Quality of Life in Reflux and Dyspepsia: controls, 4.5 to 7.0; Reop(1), 3.7 to 6.7; and Reop(>1), 3.5 to 5.8. Dysphagia Severity Score: controls, 44.0 to 45.0; Reop(1), 36.0 to 45.0; and Reop(>1), 30.8 to 45.0. Patients undergoing revision antireflux operations have improved quality of life, relatively normal swallowing, and primary symptom resolution at a median of 20 months postoperatively. However, patients who undergo more than one reoperation have lower quality of life scores and less improvement in dysphagia, suggesting that other procedures such as Roux-en-Y or short colon interposition, should be considered after a failed initial reoperation.