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Abstract In the classical information theoretic framework, information “value” is proportional to how novel/surprising the information is. Recent work building on such notions claimed that false news spreads faster than truth online because false news is more novel and therefore surprising. However, another determinant of surprise, semantic meaning (e.g., information’s consistency or inconsistency with prior beliefs), should also influence value and sharing. Examining sharing behavior on Twitter, we observed separate relations of novelty and belief consistency with sharing. Though surprise could not be assessed in those studies, belief consistency should relate to less surprise, suggesting the relevance of semantic meaning beyond novelty. In two controlled experiments, belief-consistent (vs. belief-inconsistent) information was shared more despite consistent information being the least surprising. Manipulated novelty did not predict sharing or surprise. Thus, classical information theoretic predictions regarding perceived value and sharing would benefit from considering semantic meaning in contexts where people hold pre-existing beliefs.

Abstract The role of N6-methyladenosine (m6A) modification of host mRNA during bacterial infection is unclear. Here, we show that Helicobacter pylori infection upregulates host m6A methylases and increases m6A levels in gastric epithelial cells. Reducing m6A methylase activity via hemizygotic deletion of methylase-encoding gene Mettl3 in mice, or via small interfering RNAs targeting m6A methylases, enhances H. pylori colonization. We identify LOX-1 mRNA as a key m6A-regulated target during H. pylori infection. m6A modification destabilizes LOX-1 mRNA and reduces LOX-1 protein levels. LOX-1 acts as a membrane receptor for H. pylori catalase and contributes to bacterial adhesion. Pharmacological inhibition of LOX-1, or genetic ablation of Lox-1, reduces H. pylori colonization. Moreover, deletion of the bacterial catalase gene decreases adhesion of H. pylori to human gastric sections. Our results indicate that m6A modification of host LOX-1 mRNA contributes to protection against H. pylori infection by downregulating LOX-1 and thus reducing H. pylori adhesion.

Much empirical science involves evaluating alternative explanations for the obtained data. For example, given certain assumptions underlying a statistical test, a "significant" result generally refers to implausibility of a null (zero) effect in the population producing the obtained study data. However, methodological work on various versions of p-hacking (i.e., using different analysis strategies until a "significant" result is produced) questions whether significant p-values might often reflect false findings. Indeed, initial simulations of single studies showed that the potential for finding "significant" but false findings might be much higher than the nominal .05 value when various analysis flexibilities are undertaken. In many settings, however, research articles report multiple studies using consistent methods across the studies, where those consistent methods would constrain the flexibilities used to produce high false-finding rates for simulations of single studies. Thus, we conducted simulations of study sets. These simulations show that consistent methods across studies (i.e., consistent in terms of which measures are analyzed, which conditions are included, and whether and how covariates are included) dramatically reduce the potential for flexible research practices (p-hacking) to produce consistent sets of significant results across studies. For p-hacking to produce even modest probabilities of a consistent set of studies would require (a) a large amount of selectivity in study reporting and (b) severe (and quite intentional) versions of p-hacking. With no more than modest selective reporting and with consistent methods across studies, p-hacking does not provide a plausible explanation for consistent empirical results across studies, especially as the size of the reported study set increases. In addition, the simulations show that p-hacking can produce high rates of false findings for single studies with very large samples. In contrast, a series of methodologically-consistent studies (even with much smaller samples) is much less vulnerable to the forms of p-hacking examined in the simulations.

Abstract Genomic stability maintenance requires correct DNA replication, chromosome segregation, and DNA repair, while defects of these processes result in tumor development or cell death. Although abnormalities in DNA replication and repair regulation are proposed as underlying causes for genomic instability, the detailed mechanism remains unclear. Here, we investigated whether NKX6.3 plays a role in the maintenance of genomic stability in gastric epithelial cells. NKX6.3 functioned as a transcription factor for CDT1 and RPA1, and its depletion increased replication fork rate, and fork asymmetry. Notably, we showed that abnormal DNA replication by the depletion of NKX6.3 caused DNA damage and induced homologous recombination inhibition. Depletion of NKX6.3 also caused copy number alterations of various genes in the vast chromosomal region. Hence, our findings underscore NKX6.3 might be a crucial factor of DNA replication and repair regulation from genomic instability in gastric epithelial cells.

The wave-impacted waters off exposed sandy beaches support marine megafauna, including dolphins, whales, sharks, rays and turtles. To characterise variation in megafaunal assemblages in this challenging habitat, we used drone-based remote sensing to survey marine megafauna off 23 beaches along 1050 km of the New South Wales (NSW, Australia) coast from 2017 to 2020. The surveys occurred from September to May and included 17,085 drone flights, with megafaunal abundances standardised by flight hours. In total, we identified 3838 individual animals from 16 taxa, although no megafauna was observed off 5 of the 23 beaches surveyed. Bottlenose dolphins were the most commonly sighted taxa and accounted for 82.3% of total megafaunal abundance. Cownose (6.7%) and eagle (3.4%) rays were the next most abundant taxa, with potentially dangerous sharks being rarely sighted (

Much empirical science involves evaluating alternative explanations for the obtained data. For example, given certain assumptions underlying a statistical test, a "significant" result generally refers to implausibility of a null (zero) effect in the population producing the obtained study data. However, methodological work on various versions of p-hacking (i.e., using different analysis strategies until a "significant" result is produced) questions whether significant p-values might often reflect false findings. Indeed, initial simulations of single studies showed that the potential for finding "significant" but false findings might be much higher than the nominal.05 value when various analysis flexibilities are undertaken. In many settings, however, research articles report multiple studies using consistent methods across the studies, where those consistent methods would constrain the flexibilities used to produce high false-finding rates for simulations of single studies. Thus, we conducted simulations of study sets. These simulations show that consistent methods across studies (i.e., consistent in terms of which measures are analyzed, which conditions are included, and whether and how covariates are included) dramatically reduce the potential for flexible research practices (p-hacking) to produce consistent sets of significant results across studies. For p-hacking to produce even modest probabilities of a consistent set of studies would require (a) a large amount of selectivity in study reporting and (b) severe (and quite intentional) versions of p-hacking. With no more than modest selective reporting and with consistent methods across studies, p-hacking does not provide a plausible explanation for consistent empirical results across studies, especially as the size of the reported study set increases. In addition, the simulations show that p-hacking can produce high rates of false findings for single studies with very large samples. In contrast, a series of methodologically-consistent studies (even with much smaller samples) is much less vulnerable to the forms of p-hacking examined in the simulations. [ABSTRACT FROM AUTHOR]

Oral Veillonella species are among the early colonizers of the human oral cavity. We constructed a small, single-selectable-marker shuttle plasmid, examined its ability to be transformed into diverse oral Veillonella strains, and assessed its potential use for expressing a gene encoding an oxygen-independent fluorescent protein, thus generating a fluorescent Veillonella parvula strain. Because tetracycline resistance is common in Veillonella , we replaced genes encoding ampicillin- and tetracycline-resistance in a previously described shuttle plasmid (pBSJL2) with a chloramphenicol acetyltransferase gene. The resulting plasmid pCF1135 was successfully introduced into four strains representing V. parvula and V. atypica by either natural transformation or electroporation. We then modified this plasmid to express a gene encoding an oxygen-independent fluorescent protein in V. parvula SKV38. The resulting strain yielded a fluorescence signal intensity ∼16 times higher than the wild type in microplate-based fluorimetry experiments. While fluorescence microscopy demonstrated that planktonic cells, colonies, and biofilms of fluorescent V. parvula could also be imaged, photobleaching was a significant issue. In conclusion, we anticipate this genetic system and information provided here will facilitate expanded studies of oral Veillonella species' properties and behavior. [ABSTRACT FROM AUTHOR]

Abstract Background Helicobacter pylori-mediated gastric carcinogenesis is initiated by a plethora of signaling events in the infected gastric epithelial cells (GECs). The E3 ubiquitin ligase seven in absentia homolog 2 (Siah2) is induced in GECs in response to H. pylori infection. Posttranslational modifications of Siah2 orchestrate its function as well as stability. The aim of this study was to evaluate Siah2 phosphorylation status under the influence of H. pylori infection and its impact in gastric cancer progression. Methods H. pylori-infected various GECs, gastric tissues from H. pylori-infected GC patients and H. felis-infected C57BL/6 mice were evaluated for Siah2 phosphorylation by western blotting or immunofluorescence microscopy. Coimmunoprecipitation assay followed by mass spectrometry were performed to identify the kinases interacting with Siah2. Phosphorylation sites of Siah2 were identified by using various plasmid constructs generated by site-directed mutagenesis. Proteasome inhibitor MG132 was used to investigate proteasome degradation events. The importance of Siah2 phosphorylation on tumorigenicity of infected cells were detected by using phosphorylation-null mutant and wild type Siah2 stably-transfected cells followed by clonogenicity assay, cell proliferation assay, anchorage-independent growth and transwell invasion assay. Results Siah2 was phosphorylated in H. pylori-infected GECs as well as in metastatic GC tissues at residues serine6 (Ser6) and threonine279 (Thr279). Phosphorylation of Siah2 was mediated by MRCKβ, a Ser/Thr protein kinase. MRCKβ was consistently expressed in uninfected GECs and noncancer gastric tissues but its level decreased in infected GECs as well as in metastatic tissues which had enhanced Siah2 expression. Infected murine gastric tissues showed similar results. MRCKβ could phosphorylate Siah2 but itself got ubiquitinated from this interaction leading to the proteasomal degradation of MRCKβ and use of proteasomal inhibitor MG132 could rescue MRCKβ from Siah2-mediated degradation. Ser6 and Thr279 phosphorylated-Siah2 was more stable and tumorigenic than its non-phosphorylated counterpart as revealed by the proliferation, invasion, migration abilities and anchorage-independent growth of stable-transfected cells. Conclusions Increased level of Ser6 and Thr279-phosphorylated-Siah2 and downregulated MRCKβ were prominent histological characteristics of Helicobacter-infected gastric epithelium and metastatic human GC. MRCKβ-dependent Siah2 phosphorylation stabilized Siah2 which promoted anchorage-independent survival and proliferative potential of GECs. Phospho-null mutants of Siah2 (S6A and T279A) showed abated tumorigenicity.

Abstract Background Little is known about associations between perceived stress, psychosocial factors (social support, emotional coping, coping self-efficacy, and autonomous motivation), and depressive symptoms in low-income overweight or obese mothers of young children. Using baseline data of a lifestyle intervention study, this secondary analysis investigates whether perceived stress might mediate the associations between the psychosocial factors and depressive symptoms. Methods Convenience sampling was applied. Low-income overweight or obese mothers of young children were recruited from the Special Supplemental Nutrition Program for Women, Infants, and Children in Michigan, US. Survey data were collected through phone interviews. Participants (N = 740) responded to valid surveys measuring perceived stress, social support, emotional coping, coping self-efficacy, autonomous motivation, and depressive symptoms. Composite indicator structural equation modeling was performed to test for potential mediation. Results When investigating the potential role of perceived stress as a mediator, the indirect effects of social support (b = − 2.10, p < 0.01), emotion coping (b = − 3.81, p < 0.05), and coping self-efficacy (b = − 7.53, p < 0.01) on depressive symptoms through perceived stress were significant, but the indirect effect of autonomous motivation was not. Conclusion Future intervention studies aiming to alleviate depressive symptoms in low-income overweight or obese mothers of young children might consider including practical strategies to promote social support, emotional coping, and coping self-efficacy to reduce perceived stress, which might potentially decrease depressive symptoms. Trial registration Clinical Trials NCT01839708 ; registered February 28, 2013.

Communicators commonly present two-sided messages to avoid being perceived as biased. This approach equates bias with one-sidedness rather than divergence from the position supported by available data. Messages often concern topics with mixed qualities: a product is exceptional but expensive; a politician is inexperienced but ethical. For these topics, providing a two-sided message should reduce perceived bias according to both views of bias as one-sidedness and divergence from available data. However, if perceived bias follows divergence from available data, for topics viewed as one-sided (univalent), a two-sided message should not reduce perceived bias. Across five studies, acknowledging two sides reduced perceived bias for novel topics. In two of the studies, two-sidedness no longer reduced perceived bias for topics viewed as univalent. This work clarifies that people conceptualize bias as a divergence from available data, not simply one-sidedness. It also clarifies when and how to leverage message-sidedness to reduce perceived bias. [ABSTRACT FROM AUTHOR]

Abstract Background Genipin is a compound derived from gardenia fruit extract. Although Genipin has anti-tumor effects in various cancers, its effect and mechanism in gastric cancer remain unclear. Here, we investigated the relationship between the anticancer effect of Genipin and signal transducer and activator of transcription (Stat3)/myeloid cell leukemia-1 (Mcl-1) in human gastric cancers. Methods MTT assays were performed to determine the cell viability of gastric cancer and gastric epithelial cell lines (AGS, MKN45, SNU638, MKN74, HFE-145). A TUNEL assay and Western blotting were carried out to investigate apoptosis. Stat3 activity was measured by proteome profiler phospho kinase array, immunofluorescence and immunoblotting. Mitochondria function was monitored with an XF24 analyzer and by flow cytometry, confocal microscopy using fluorescent probes for general mitochondrial membrane potential (MMP). Results Genipin induced apoptosis in gastric cancer cells, including AGS and MKN45 cells. Genipin also reduced Mcl-1 mRNA and protein levels. Furthermore, we found that phosphorylation of Stat3 is regulated by Genipin. Additionally, the protein level of phospho Janus kinase 2 (JAK2) was decreased by Genipin treatment, indicating that the Stat3/JAK2/Mcl-1 pathway is suppressed by Genipin treatment in gastric cancer cells. Mcl-1 is closely related to mitochondrial function. These findings suggest that Genipin contributes to the collapse of mitochondrial functions like MMP. Conclusions Genipin induced apoptosis by suppressing the Stat3/Mcl-1 pathway and led to mitochondrial dysfunction. Our results reveal a novel mechanism for the anti-cancer effect of Genipin in gastric cancer.

MicroRNA (miR) sponges containing miR binding sequences constitute a potentially powerful molecular therapeutic strategy. Recently, naturally occurring circular RNAs (circRNAs) were shown to function as efficient miR sponges in cancer cells. We hypothesized that synthetic circRNA sponges could achieve therapeutic loss-of-function targeted against specific miRs. Linear RNA molecules containing miR-21 binding sites were transcribed in vitro; after dephosphorylation and phosphorylation, circularization was achieved using 5′-3′ end-ligation by T4 RNA ligase 1. circRNA stability was assessed using RNase R and fetal bovine serum. Competitive inhibition of miR-21 activity by a synthetic circRNA sponge was assessed using luciferase reporter, cell proliferation, and cell apoptosis assays in three gastric cancer cell lines. circRNA effects on downstream proteins were also delineated by Tandem Mass Tag (TMT) labeling (data available via ProteomeXchange identifier PRIDE: PXD008584), followed by western blotting. We conclude that artificial circRNA sponges resistant to nuclease digestion can be synthesized using simple enzymatic ligation steps. These sponges inhibit cancer cell proliferation and suppress the activity of miR-21 on downstream protein targets, including the cancer protein DAXX. In summary, synthetic circRNA sponges represent a simple, effective, convenient strategy for achieving targeted loss of miR function in vitro, with potential future therapeutic application in human patients. Keywords: synthetic circular RNA, microRNA sponge, microRNA loss-of-function, gastric carcinoma, molecular therapy

Evidence link bacterial enterotoxins to apparent crypt-cell like cells (CCLCs), and Alpha Defensin 5 (DEFA5) expansion in the colonic mucosa of Crohn's colitis disease (CC) patients. These areas of ectopic ileal metaplasia, positive for Paneth cell (PC) markers are consistent with diagnosis of CC. Retrospectively, we: 1. Identified 21 patients with indeterminate colitis (IC) between 2000-2007 and were reevaluation their final clinical diagnosis in 2014 after a followed-up for mean 8.7±3.7 (range, 4-14) years. Their initial biopsies were analyzed by DEFA5 bioassay. 2. Differentiated ulcer-associated cell lineage (UACL) analysis by immunohistochemistry (IHC) of the CC patients, stained for Mucin 6 (MUC6) and DEFA5. 3. Treated human immortalized colonic epithelial cells (NCM460) and colonoids with pure DEFA5 on the secretion of signatures after 24hr. The control colonoids were not treated. 4. Treated colonoids with/without enterotoxins for 14 days and the spent medium were collected and determined by quantitative expression of DEFA5, CCLCs and other biologic signatures. The experiments were repeated twice. Three statistical methods were used: (i) Univariate analysis; (ii) LASSO; and (iii) Elastic net. DEFA5 bioassay discriminated CC and ulcerative colitis (UC) in a cohort of IC patients with accuracy. A fit logistic model with group CC and UC as the outcome and the DEFA5 as independent variable differentiator with a positive predictive value of 96 percent. IHC staining of CC for MUC6 and DEFA5 stained in different locations indicating that DEFA5 is not co-expressed in UACL and is therefore NOT the genesis of CC, rather a secretagogue for specific signature(s) that underlie the distinct crypt pathobiology of CC. Notably, we observed expansion of signatures after DEFA5 treatment on NCM460 and colonoids cells expressed at different times, intervals, and intensity. These factors are key stem cell niche regulators leading to DEFA5 secreting CCLCs differentiation 'the colonic ectopy ileal metaplasia formation' conspicuously of pathogenic importance in CC.

Individuals reliably feel more attracted to those with whom they share similar attitudes. However, this affective liking does not always predict affiliative behavior, such as pursuing a friendship. The present research examined factors that influence the extent to which similarity-based affective attraction increases willingness to affiliate (i.e., behavioral attraction) – one potential step toward engaging in affiliative behavior. Research on attitude strength has identified attitude properties, such as confidence, that predict when an attitude is likely to impact relevant outcomes. We propose that when one’s attitudes possess these attitude strength-related properties, affective attraction to those who share that attitude will be more likely to spark willingness to affiliate. Across four studies on a variety of topics, participants (N = 428) reported their attitudes and various attitude properties regarding a topic. They were introduced to a target and learned the target’s stance on the issue. Participants reported their affective attraction and willingness to pursue friendship with the target. Consistent with past research, attitude similarity predicted affective attraction. More importantly, the relation between affective attraction and willingness to affiliate with the target was moderated by the attitude strength-related properties. A mini meta-analysis found this effect to be consistent across the four studies.