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The enrichment of Fusobacterium nucleatum (Fn) has been identified in CRC patients and associated with worse outcomes. However, whether Fn was involved in the metastasis of CRC was not well determined. Here, we found that the abundance of Fn was significantly increased in CRC patients with lymph nodes metastasis. To further clarify the role of Fn in CRC metastasis, we performed transwell and wound healing assays after incubating CRC cell lines with or without Fn and injected Fn-treated or untreated CRC cells into nude mice via tail vein. The results indicated that Fn infection promoted CRC cells migration in vitro, as well as lung metastasis in vivo. Interestingly, colonization of Fn was detected in metastatic lung lesions of nude mice by fluorescence in situ hybridization. Mechanistically, RNA sequencing and validation study revealed that Fn significantly upregulated the expression of long non-coding RNA Keratin7-antisense (KRT7-AS) and Keratin7 (KRT7) in CRC cells. Importantly, Fn-induced CRC lung metastasis was attenuated by the depletion of KRT7-AS. In addition, KRT7-AS facilitated CRC cells migration by upregulating KRT7. Subsequently, we found that NF-κB signaling pathway was involved in the upregulation of KRT7-AS upon Fn infection. In conclusion, Fn infection upregulated KRT7-AS/KRT7 by activating NF-κB pathway, which promoted CRC cell migration in vitro and metastasis in vivo.

Conventional wisdom (rational choice theory) assumes that individuals are destined to collectively destroy vital ecological systems due to their narrow self-interest. In contrast, Humanistic Rational Choice Theory (HRCT) assumes individuals can cooperatively self-govern, devising effective conservation agreements and governance systems to constrain self-interest for mutual benefit. To test this assumption, we examined the motivational, perceptual, and cooperative outcomes of communication in a resource dilemma experiment. HRCT assumes that poorly managed dilemmas undermine people's fundamental needs (e.g., procedural justice, security, equity), motivating them to self-govern. Groups that make decisions fairly (e.g., democratically) and enforce their agreements, should satisfy their collective needs better, ensuring better institutional acceptance and trust, thereby improving cooperation and sustainability. Small groups of four (N = 41 groups) harvested valuable resources from a shared pool without communication (Phase 1), with communication (Phase 2), and then without communication (Phase 3). Groups destroyed the resource and reported low need satisfaction during Phase 1. During Phase 2, most groups created governance systems, greatly improving their need satisfaction (ds≥1.32), trust (d = 2.30), cooperation and resource sustainability (η2=0.87). Democratically governed groups reported the greatest need satisfaction, intrinsic motivation (i.e., institutional internalization and acceptance), and trust, especially if they primarily used positive social sanctions (e.g., praise) to enforce their agreements. Negative sanctions (e.g., shaming, threats) backfired, unless used in democratic groups. These factors accounted for 47% of the variance in Phase 3 voluntary cooperation and resource sustainability. Groups self-governed to collectively satisfy their interdependent fundamental needs.

High-fat feeding (HFF) leads to gut dysbiosis through unclear mechanisms. We hypothesize that bile acids secreted in response to high-fat diets (HFDs) may act on intestinal Paneth cells, leading to gut dysbiosis. We found that HFF resulted in widespread taxonomic shifts in the bacteria of the ileal mucosa, characterized by depletion of Lactobacillus and enrichment of Akkermansia muciniphila, Clostridium XIVa, Ruminococcaceae, and Lachnospiraceae, which were prevented by the bile acid binder cholestyramine. Immunohistochemistry and in situ hybridization studies showed that G protein–coupled bile acid receptor (TGR5) expressed in Paneth cells was upregulated in the rats fed HFD or normal chow supplemented with cholic acid. This was accompanied by decreased lysozyme+ Paneth cells and α-defensin 5 and 6 and increased expression of XBP-1. Pretreatment with ER stress inhibitor 4PBA or with cholestyramine prevented these changes. Ileal explants incubated with deoxycholic acid or cholic acid caused a decrease in α-defensin 5 and 6 and an increase in XBP-1, which was prevented by TGR5 antibody or 4PBA. In conclusion, this is the first demonstration to our knowledge that TGR5 is expressed in Paneth cells. HFF resulted in increased bile acid secretion and upregulation of TGR5 expression in Paneth cells. Bile acid toxicity in Paneth cells contributes to gut dysbiosis induced by HFF.

Background: Helicobacter pylori (H. pylori) infection is associated with remodeling of gastric microbiota. However, comprehensive analyses of the impact of H. pylori infection, eradication therapy and probiotic supplementation on gut microbiota are still lacking. We aimed to provide evidence for clinical decision making. Methods: Seventy H. pylori-positive and 35 H. pylori-negative patients (group C) were enrolled. H. pylori-positive patients were randomly assigned to group A (14-day bismuth-containing quadruple therapy) and group B (quadruple therapy supplemented with Clostridium butyricum). Stool samples of group A and B were collected on day 0, 14 and 56 while stool samples of group C were collected on day 0. Gut microbiota was investigated by 16S rRNA sequencing. Findings: The Sobs index (richness estimator) was significantly higher in H. pylori-positive samples than H. pylori-negative samples (p

This study argues that scholars and policy-makers need to understand environmental activists better to bridge the gap between growing activism and policy. Conventional wisdom is that environmental activists generally support stronger climate policies. But there is still little understanding about diversity of views within activist groups when it comes to specific policies, and existing studies indicate that their views are not uniform, which can weaken their impact as a group. Activists might unite to demand change, but not necessarily agree on details of the desired change. Exploring the differences within the group, this paper focuses on how to nudge those who already share favorable attitudes towards policies that mitigate climate change. The motivation has been to see, in presence of general support for stronger environmental policies, whether this support could be channeled into more specific policies. We first take on a methodological challenge to construct an index of environmental predisposition. Then drawing from existing social-behavioral scholarship, we analyze results of an experimental survey with select treatments previously reported as promising. In November and December 2019, we collected responses from 119 participants at the Fridays for Future demonstrations in Germany. The results indicate that there are indeed important differences within the group, and nudging effects exist even in this rather strongly predisposed group, with participants assigned to the experimental group showing higher levels of support for the introduction of a carbon tax that is traditionally seen as a difficult policy to gain widespread public support. We find that those who score neither too high nor too low are more likely to respond to nudging. Yet, the effects vary for general outcomes such as policy support, behavioral intentions, and environmental citizenship. Overall, the findings show the value of understanding the heterogeneity of individual views within environmental movements better and directing interventions in large resource systems such as climate to specific issues and target groups for accelerating transformations towards sustainability.

Alterations in gut microbiota are postulated to be an etiologic factor in the pathogenesis of irritable bowel syndrome (IBS). To determine whether IBS patients in China exhibited differences in their gut microbial composition, fecal samples were collected from diarrhea-predominant IBS (IBS-D) and healthy controls and evaluated by 16S ribosomal RNA gene sequence and quantitative real-time PCR. A mouse model of postinfectious IBS (PI-IBS) was established to determine whether the altered gut microbiota was associated with increased visceral hypersensitivity. The results indicated that there were significant differences in the bacterial community profiles between IBS-D patients and healthy controls. Prevotella was more abundant in fecal samples from IBS-D patients compared with healthy controls (p

We used psychological methods to investigate how two prominent interventions, participatory decision making and enforcement, influence voluntary cooperation in a common-pool resource dilemma. Groups (N=40) harvested resources from a shared resource pool. Individuals in the Voted-Enforce condition voted on conservation rules and could use economic sanctions to enforce them. In other conditions, individuals could not vote (Imposed-Enforce condition), lacked enforcement (Voted condition), or both (Imposed condition). Cooperation was strongest in the Voted-Enforce condition (Phase 2). Moreover, these groups continued to cooperate voluntarily after enforcement was removed later in the experiment. Cooperation was weakest in the Imposed-Enforce condition and degraded after enforcement ceased. Thus, enforcement improved voluntary cooperation only when individuals voted. Perceptions of procedural justice, self-determination, and security were highest in the Voted-Enforced condition. These factors (legitimacy, security) increased voluntary cooperation by promoting rule acceptance and internalized motivation. Voted-Enforce participants also felt closer to one another (i.e., self-other merging), further contributing to their cooperation. Neither voting nor enforcement produced these sustained psychological conditions alone. Voting lacked security without enforcement (Voted condition), so the individuals who disliked the rule (i.e., the losing voters) pillaged the resource. Enforcement lacked legitimacy without voting (Imposed-Enforce condition), so it crowded out internal reasons for cooperation. Governance interventions should carefully promote security without stifling fundamental needs (e.g., procedural justice) or undermining internal motives for cooperation.

Allowing resource users to communicate in behavioural experiments on commons dilemmas increases the level of cooperation. In actual common pool resource dilemmas in the real world, communication is costly, which is an important detail missing from most typical experiments. We conducted experiments where participants must give up harvesting opportunities to communicate. The constrained communication treatment is compared with the effect of limited information about the state of the resource and the actions of the other participants. We find that despite making communication costly, performance of groups improves in all treatments with communication. We also find that constraining communication has a more significant effect than limiting information on the performance of groups.

OBJECTIVES/SPECIFIC AIMS: Objectives and goals of this study are to (i) determine whether IBS-D patients randomized to either rifaximin or low FODMAP diet show improvement in IBS-related symptoms; and (2) identify using longitudinal analyses how SIBO status and fecal microbiota features associate with response to either rifaximin or low FODMAP dietary intervention. METHODS/STUDY POPULATION: 42 patients ≥ 18 years of age who meet Rome IV criteria for IBS-D will be randomized to receive either rifaximin or low FODMAP diet intervention. The primary outcome will be the proportion of responders to intervention which is defined as ≥ 30% reduction in mean daily abdominal pain or bloating by visual analog scale compared with baseline. Exclusion criteria will include: (a) history of microscopic colitis, inflammatory bowel disease, celiac disease, or other organic disease that could explain symptoms, (b) prior gastrointestinal surgery, other than appendectomy or cholecystectomy > 6 months prior to study initiation, (c) prior use of rifaximin or formal dietary interventions for IBS-D, (d) use of antibiotics within the past 3 months, or (e) use of probiotics within 1 month of study entry. Glucose hydrogen breath tests will be performed at the beginning and end of the trial to evaluate for SIBO. Fecal samples will be collected at 0, 2, and 6 weeks to determine changes in fecal microbial composition and structure. RESULTS/ANTICIPATED RESULTS: This study seeks to examine whether longitudinal analyses of small intestinal and colonic microbiota can subtype IBS-D subjects into clinically relevant phenotypes. A total of 18 subjects have been enrolled into the study. Clinical variables, hydrogen breath test results, and fecal microbiota data are being collected for ongoing analysis. DISCUSSION/SIGNIFICANCE OF IMPACT: Results from this study may help move treatment of IBS from a purely symptom based approach to a more individualized approach by stratifying IBS-D patients into distinct clinical phenotypes which are amenable to targeted therapeutic approaches.

In traditional public good experiments participants receive an endowment from the experimenter that can be invested in a public good or kept in a private account. In this paper we present an experimental environment where participants can invest time during five days to contribute to a public good. Participants can make contributions to a linear public good by logging into a web application and performing virtual actions. We compared four treatments, with different group sizes and information of (relative) performance of other groups. We find that information feedback about performance of other groups has a small positive effect if we control for various attributes of the groups. Moreover, we find a significant effect of the contributions of others in the group in the previous day on the number of points earned in the current day. Our results confirm that people participate more when participants in their group participate more, and are influenced by information about the relative performance of other groups.

Mammalian cerebral cortex is accepted as being critical for voluntary motor control, but what functions depend on cortex is still unclear. Here we used rapid, reversible optogenetic inhibition to test the role of cortex during a head-fixed task in which mice reach, grab, and eat a food pellet. Sudden cortical inhibition blocked initiation or froze execution of this skilled prehension behavior, but left untrained forelimb movements unaffected. Unexpectedly, kinematically normal prehension occurred immediately after cortical inhibition, even during rest periods lacking cue and pellet. This ‘rebound’ prehension was only evoked in trained and food-deprived animals, suggesting that a motivation-gated motor engram sufficient to evoke prehension is activated at inhibition’s end. These results demonstrate the necessity and sufficiency of cortical activity for enacting a learned skill.

PurposeTo assess the response to pexidartinib treatment in six cohorts of adult patients with advanced, incurable solid tumors associated with colony-stimulating factor 1 receptor (CSF1R) and/or KIT proto-oncogene receptor tyrosine kinase activity.Patients and methodsFrom this two-part phase I, multicenter study, pexidartinib, a small-molecule tyrosine kinase inhibitor that targets CSF1R, KIT, and FMS-like tyrosine kinase 3 (FLT3), was evaluated in six adult patient cohorts (part 2, extension) with advanced solid tumors associated with dysregulated CSF1R. Adverse events, pharmacokinetics, and tumor responses were assessed for all patients; patients with tenosynovial giant cell tumor (TGCT) were also evaluated for tumor volume score (TVS) and patient-reported outcomes (PRO). CSF1 transcripts and gene expression were explored in TGCT biopsies.ResultsNinety-one patients were treated: TGCT patients (n = 39) had a median treatment duration of 511 days, while other solid tumor patients (n = 52) had a median treatment duration of 56 days. TGCT patients had response rates of 62% (RECIST 1.1) and 56% (TVS) for the full analysis set. PRO assessments for pain showed improvement in patient symptoms, and 76% (19/25) of TGCT tissue biopsy specimens showed evidence of abnormal CSF1 transcripts. Pexidartinib treatment of TGCT resulted in tumor regression and symptomatic benefit in most patients. Pexidartinib toxicity was manageable over the entire study.ConclusionsThese results offer insight into outcome patterns in cancers whose biology suggests use of a CSF1R inhibitor. Pexidartinib results in tumor regression in TGCT patients, providing prolonged control with an acceptable safety profile.

Recently, there has been an increased interest in using behavioral experiments to study hypotheses on the governance of social-ecological systems. A diversity of software tools are used to implement such experiments. We evaluated various publicly available platforms that could be used in research and education on the governance of social-ecological systems. The aims of the various platforms are distinct, and this is noticeable in the differences in their user-friendliness and their adaptability to novel research questions. The more easily accessible platforms are useful for prototyping experiments and for educational purposes to illustrate theoretical concepts. To advance novel research aims, more elaborate programming experience is required to either implement an experiment from scratch or adjust existing experimental software. There is no ideal platform best suited for all possible use cases, but we have provided a menu of options and their associated trade-offs.

With ongoing efforts in the United States to further develop the availability of computer science education in the public schools, federal, state, and local educational agencies are increasing efforts to encourage and promote the inclusion of computer science and programming skills in the middle school curriculum (Grover, Pea, & Cooper, 2015). The goal for the Online Content Modules: Computer Science in the Middle Grades project was the development of five online content modules with a focus on computer science instruction in three public school districts in West Tennessee, and disseminated through a week-long professional development summer institute.

With ongoing efforts in the United States to further develop the availability of computer science education in the public schools, federal, state, and local educational agencies are increasing efforts to encourage and promote the inclusion of computer science and programming skills in the middle school curriculum (Grover, Pea, & Cooper, 2015). The goal for the Online Content Modules: Computer Science in the Middle Grades project was the development of five online content modules with a focus on computer science instruction in three public school districts in West Tennessee, and disseminated through a week-long professional development summer institute.

Researchers have frequently found that leadership plays a key role in the successful and effective implementation of technology in K-12 school districts (Meltzer & Sherman, 1997; Schiller, 2002; Bliss & Bliss, 2003; Anderson & Dexter, 2005). A key component of the Michigan Freedom To Learn (FTL): One-to-One Learning initiative evaluation was to obtain valid data from a rigorous and comprehensive research study to gauge the impacts of the program relative to its primary goals. An evaluative research component examining the effectiveness of leadership in FTL initiative as perceived by FTL teachers and lead teachers was added as an extension to the initial multi-year evaluation plan to examine the roles of school leadership (principals, assistant principals, or others) in relationship to the effective implementation of the FTL laptop program. This paper summarizes the 2007-2008 evaluation results of the leadership survey distributed to Michigan Freedom to Learn (FTL) program teachers, in their effort to improve student learning and achievement in Michigan schools through the integration of laptop computers with teaching and learning in K-12 classrooms. The results obtained from the survey provided insight into the relationships between the identified leadership attributes and successful program implementation.

While it is well-documented that appropriate training of teachers in the use of technological tools is an important variable in predicting success of technology integration (Faseyitan & Hirschbuhl, 1994), a variable that is less often considered is that of the time spent or different levels of immersion in a technology integration training program (Stuhlmann & Taylor, 1999). This factor must be considered to be separate and distinct from the variable of overall experience as a teacher in the classroom, and/or teacher age. This paper is based on a selected portion of the results of a five-year evaluative study of the teachers implementing a technology integration program in a rural school district located in the Southwestern United States. The fifth year design included analysis of observation data by year(s) of teacher participation in the program, as Novice, having 1 to 2 years of experience; Experienced with 4 to 5 years. The purpose for the focus on this aspect of the evaluation was to determine what differences, if any, existed between novice (to the program training) and experienced (in the program training) teachers in how and to what degree technology is integrated into classroom instruction. The findings reflect differences of varying degrees in certain areas of instructional strategies and technology integration that should be considered for further investigation.

The Memphis Literacy Academy (MLA) is a partnership between the Memphis City Schools and The University of Memphis' College of Education, with the primary focus on urban education. The purpose of the MLA is to train elementary teachers and principals in urban schools in grades K-3, and special education classrooms from selected Memphis schools on research-proven "comprehensive reading" instruction practices for urban children (Cooter, 2004). The principal investigators for the grant funding the MLA partnership incorporated a technology component to support, enhance, and facilitate communications for the MLA program. Several options were researched before a decision was made as to the nature and purpose of the technology to be incorporated into the MLA program. After exploring numerous avenues to accomplish the technology component integration, the decision was made by the MLA project members to utilize the open-source software (OSS) course management platform, Moodle.