Neurophysiological processes reflecting the effects of the immediate past during the dynamic management of actions.

In recent years, there has been many efforts to establish a comprehensive theoretical framework explaining the working mechanisms involved in perception-action integration. This framework stresses the importance of the immediate past on mechanisms supporting perception-action integration. The present study investigates the neurophysiological principles of dynamic perception-action bindings, particularly considering the influence of the immediate history on action control mechanisms. For this purpose, we conducted an established stimulus-response binding paradigm during EEG recording. The SR-task measures stimulus-response binding in terms of accuracy and reaction time differences depending on the degree of feature overlap between conditions. Alpha, beta and theta band activity in distinct time domains as well as associated brain regions were investigated applying time-frequency analyses, a beamforming approach as well as correlation analyses. We demonstrate, for the first time, interdependencies of neuronal processes relying on the immediate past. The reconfiguration of an action seems to overwrite immediately preceding processes. The analyses revealed modulations of theta (TBA), alpha (ABA) and beta band activity (BBA) in connection with fronto-temporal structures supporting the theoretical assumptions of the considered conceptual framework. The close interplay of attentional modulation by gating irrelevant information (ABA) and binding and retrieval processes (TBA) is reflected by the correlation of ABA in all pre-probe-intervals with post-probe TBA. Likewise, the role of BBA in maintaining the event file until retrieval is corroborated by BBA preceding the TBA-associated retrieval of perception-action codes. Following action execution, TBA shifted towards visual association cortices probably reflecting preparation for upcoming information, while ABA and BBA continue to reflect processes of attentional control and information selection for goal-directed behavior. The present work provides the first empirical support for concepts about the neurophysiological mechanisms of dynamic management of perception and action.

Dimerization of the ETO1 family proteins plays a crucial role in regulating ethylene biosynthesis in Arabidopsis thaliana.

ETHYLENE OVERPRODUCER1 (ETO1), ETO1-LIKE1 (EOL1), and EOL2 are members of the Broad complex, Tramtrack, Bric-a-brac (BTB) protein family that collectively regulate type-2 1-aminocyclopropane-1-carboxylic acid synthase (ACS) activity in Arabidopsis thaliana. Although ETO1 and EOL1/EOL2 encode structurally related proteins, genetic studies suggest that they do not play an equivalent role in regulating ethylene biosynthesis. The mechanistic details underlying the genetic analysis remain elusive. In this study, we reveal that ETO1 collaborates with EOL1/2 to play a key role in the regulation of type-2 ACS activity via protein-protein interactions. ETO1, EOL1, and EOL2 exhibit overlapping but distinct tissue-specific expression patterns. Nevertheless, neither EOL1 nor EOL2 can fully complement the eto1 phenotype under control of the ETO1 promoter, which suggests differential functions of ETO1 and EOL1/EOL2. ETO1 forms homodimers with itself and heterodimers with EOLs. Furthermore, CULLIN3 (CUL3) interacts preferentially with ETO1. The BTB domain of ETO1 is sufficient for interaction with CUL3 and is required for homodimerization. However, domain-swapping analysis in transgenic Arabidopsis suggests that the BTB domain of ETO1 is essential but not sufficient for a full spectrum of ETO1 function. The missense mutation in eto1-5 generates a substitution of phenylalanine with an isoleucine in ETO1F466I that impairs its dimerization and interaction with EOLs but does not affect binding to CUL3 or ACS5. Overexpression of ETO1F466I in Arabidopsis results in a constitutive triple response phenotype in dark-grown seedlings. Our findings reveal the mechanistic role of protein-protein interactions of ETO1 and EOL1/EOL2 that is crucial for their biological function in ethylene biosynthesis.

Doublesex controls specification and maintenance of the gonad stem cell niches in Drosophila.

Sex-specific development of the gonads is a key aspect of sexual dimorphism that is regulated by Doublesex/Mab3-related transcription factors (DMRTs) in diverse animal species. We find that in mutants for Drosophila dsx, important components of the male and female gonad stem cell niches (hubs and terminal filaments/cap cells, respectively) still form. Initially, gonads in all dsx mutants (both XX and XY) initiate the male program of development, but later half of these gonads switch to form female stem cell niche structures. One individual can have both male-type and female-type gonad niches; however, male and female niches are usually not observed in the same gonad, indicating that cells make a 'group decision' about which program to follow. We conclude that dsx does not act in an instructive manner to regulate male versus female niche formation, as these structures form in the absence of dsx function. Instead, dsx acts to 'tip the balance' between the male or female programs, which are then executed independently of dsx We show that bric a brac acts downstream of dsx to control the male versus female niche decision. These results indicate that, in both flies and mammals, the sexual fate of the somatic gonad is remarkably plastic and is controlled by a combination of autonomous and non-autonomous cues.

Factors associated with home visits by volunteer community health workers to implement a home-fortification intervention in Bangladesh: a multilevel analysis.

OBJECTIVE: BRAC, an international development organization based in Bangladesh, engages community health workers called Shasthya Shebikas (SS) to implement home fortification of foods with micronutrient powders (MNP). We identified factors associated with home visits by SS, at different levels of the BRAC programme-delivery hierarchy, to implement home-fortification interventions. DESIGN: We conducted a cross-sectional survey, semi-structured interviews, and collected programme-related data from sub-districts included in the caregiver survey of BRAC's home-fortification programme and performed multilevel logistic regression modelling to investigate factors associated with home visits by SS. SETTINGS: Sixty-eight sub-districts in Bangladesh. PARTICIPANTS: Caregivers of children aged 6-59 months (n 1408) and BRAC's SS (n 201). RESULTS: Households with older children (0·55; 0·42, 0·72; P < 0·001) and located >300 m from the SS's house (0·67; 0·50, 0·89; P = 0·006) were less likely to have been visited by the SS, whereas those with caregivers who had ≥5 years of schooling (1·53; 1·10, 2·12; P = 0·011) were more likely to have been visited by the SS (adjusted OR; 95 % CI). Households in the catchment area of older SS aged >50 years (0·44; 0·21, 0·90; P = 0·025) were less likely to have been visited by the SS, whereas those with SS who received incentives of >800 BDT (3·00; 1·58, 5·58; P = 0·001) were more likely to have been visited by the SS (adjusted OR; 95 % CI). CONCLUSIONS: The number of home visits is a function of the characteristics of SS, factors that characterize the households they serve and characteristics of their organizational context, particularly to implement home fortification of foods with MNP.

Pregaming: A Field-Based Investigation of Alcohol Quantities Consumed Prior to Visiting a Bar and Restaurant District.

BACKGROUND: Investigations examining the association between pregaming, or the consumption of alcohol prior to attending a social gathering or drinking establishment, and blood alcohol concentrations have primarily relied on estimations (i.e., Widmark equation), rather than objective biologic samples, such as breath alcohol concentration (BrAC). OBJECTIVES: The current study assessed: (1) pregaming, using quantity-based measures, among a sample of college and non-college affiliated bar patrons, (2) associations between pregaming intensity/status and participant intoxication (BrAC), and (3) whether participants who pregamed were more likely to identify as a hazardous drinker. METHODS: 548 bar patrons provided data on the Alcohol Use Disorders Identification Test-Consumption (AUDIT-C) and a single pregaming item assessing quantity of alcohol consumed prior to visiting a bar/restaurant district in 2015. BrAC samples were collected post interview. We used hierarchical linear regression models, respectively, to assess whether pregaming significantly impacted BrAC and whether presence of hazardous drinking predicted pregaming behavior. RESULTS: After controlling for sex, race/ethnicity, age, student status, and Greek affiliation, the linear regression model explained 32.3% (R2 = .323) of the variance of BrAC levels (F(12) = 21.162, p < .001), with 4.30% of the variance explained solely by pregaming (ß = 0.014; p < .001). The linear regression model to assess if harzardous drinking behavior (AUDIT-C) significantly predicted pregaming explained 31.2% (R2 = .312) of the variance of pregaming behavior (F(18) = 13.276, p < .001), with 4.2% of the variance explained solely by AUDIT-C scores (ß = 0.280; p < .001). CONCLUSION: Findings further highlight pregaming as a harmful risk behavior linked to elevated levels of hazardous drinking and intoxication.

Discovery of a Nitric Oxide-Responsive Protein in Arabidopsis thaliana.

In plants, much like in animals, nitric oxide (NO) has been established as an important gaseous signaling molecule. However, contrary to animal systems, NO-sensitive or NO-responsive proteins that bind NO in the form of a sensor or participating in redox reactions have remained elusive. Here, we applied a search term constructed based on conserved and functionally annotated amino acids at the centers of Heme Nitric Oxide/Oxygen (H-NOX) domains in annotated and experimentally-tested gas-binding proteins from lower and higher eukaryotes, in order to identify candidate NO-binding proteins in Arabidopsis thaliana. The selection of candidate NO-binding proteins identified from the motif search was supported by structural modeling. This approach identified AtLRB3 (At4g01160), a member of the Light Response Bric-a-Brac/Tramtrack/Broad Complex (BTB) family, as a candidate NO-binding protein. AtLRB3 was heterologously expressed and purified, and then tested for NO-response. Spectroscopic data confirmed that AtLRB3 contains a histidine-ligated heme cofactor and importantly, the addition of NO to AtLRB3 yielded absorption characteristics reminiscent of canonical H-NOX proteins. Furthermore, substitution of the heme iron-coordinating histidine at the H-NOX center with a leucine strongly impaired the NO-response. Our finding therefore established AtLRB3 as a NO-interacting protein and future characterizations will focus on resolving the nature of this response.

Examining Differences in Breath Alcohol Concentration (BrAC) Levels and Hazardous Drinking by Smoking Status Among a Sample of College Student Bar Patrons.

While the association between current smoking and alcohol consumption is well known, the relationship between social smoking and alcohol consumption is less understood. The purpose of this study was to examine the association between smoking status and two alcohol consumption measures in a sample of college student bar patrons. The data used in this study was collected in fall 2015. Study participants (N = 415) were college student bar patrons who agreed to complete an interview that assessed smoking status (i.e., regular smoker, social smoker, non-smoker) and two alcohol consumption measures: (1) breath alcohol concentration (BrAC) levels (using a handheld breathalyzer device) and (2) hazardous drinking scores (using the AUDIT-C scale). We conducted one-way ANOVAs with Bonferroni correction to examine differences in BrAC levels and hazardous drinking scores by smoking status. Among sample participants, 25.3% were regular smokers, 14.7% were social smokers, and 60.0% were non-smokers. Smokers had significantly higher BrAC levels than social smokers and non-smokers. Regular smokers also had significantly higher hazardous drinking scores than social smokers and non-smokers. The BrAC levels and hazardous drinking scores of social smokers and non-smokers were not significantly different. The drinking habits of social smokers reflected those of non-smokers and being a regular smoker was associated with higher drinking levels than the rest of the sample. Because of the association found between alcohol consumption and regular smoking, combining efforts to reduce these behaviors in college students might be advantageous.

Concussion History, Hazardous Drinking, and BrAC Levels Among a Sample of Bar Patrons, 2015.

BACKGROUND: Alcohol consumption and experiencing a concussion are positively correlated. Concussion history has not been examined previously in any alcohol field study (i.e., conducted in a natural setting). OBJECTIVE: To better understand the relationship between concussion history and alcohol consumption. METHODS: We conducted two anonymous field studies among a 2015 sample of bar patrons (N = 544; 62.5% males) in a college town to assess concussion history and two alcohol consumption measures: (1) breath alcohol concentration (BrAC) levels and (2) hazardous drinking scores (based on the AUDIT-C). Next, we conducted a logistic regression analysis to predict concussion history using the two alcohol consumption measures and other potential covariates (i.e., age, gender, race, college student status). RESULTS: Among participants in our sample, the average BrAC level was.070 (SD =.053) and the average hazardous drinking score was 4.7 (SD = 2.5). Less than half of participants indicated that they had experienced a concussion in their lifetime (235; 43.2%). The logistic regression model indicated that hazardous drinking scores were significantly, positively associated with having experienced a concussion, whereas other covariates (i.e., BrAC, age, gender, race, college student status) did not significantly predict concussion history. Conclusions/Importance: Hazardous drinkers were more likely to have experienced a concussion. Therefore, the relationship found in this sample, between hazardous drinking behavior and concussion history, points to hazardous drinking as a possible risk factor for having had a concussion in the past.

Identification of independent association signals and putative functional variants for breast cancer risk through fine-scale mapping of the 12p11 locus.

BACKGROUND: Multiple recent genome-wide association studies (GWAS) have identified a single nucleotide polymorphism (SNP), rs10771399, at 12p11 that is associated with breast cancer risk. METHOD: We performed a fine-scale mapping study of a 700 kb region including 441 genotyped and more than 1300 imputed genetic variants in 48,155 cases and 43,612 controls of European descent, 6269 cases and 6624 controls of East Asian descent and 1116 cases and 932 controls of African descent in the Breast Cancer Association Consortium (BCAC; http://bcac.ccge.medschl.cam.ac.uk/ ), and in 15,252 BRCA1 mutation carriers in the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). Stepwise regression analyses were performed to identify independent association signals. Data from the Encyclopedia of DNA Elements project (ENCODE) and the Cancer Genome Atlas (TCGA) were used for functional annotation. RESULTS: Analysis of data from European descendants found evidence for four independent association signals at 12p11, represented by rs7297051 (odds ratio (OR) = 1.09, 95 % confidence interval (CI) = 1.06-1.12; P = 3 × 10(-9)), rs805510 (OR = 1.08, 95 % CI = 1.04-1.12, P = 2 × 10(-5)), and rs1871152 (OR = 1.04, 95 % CI = 1.02-1.06; P = 2 × 10(-4)) identified in the general populations, and rs113824616 (P = 7 × 10(-5)) identified in the meta-analysis of BCAC ER-negative cases and BRCA1 mutation carriers. SNPs rs7297051, rs805510 and rs113824616 were also associated with breast cancer risk at P < 0.05 in East Asians, but none of the associations were statistically significant in African descendants. Multiple candidate functional variants are located in putative enhancer sequences. Chromatin interaction data suggested that PTHLH was the likely target gene of these enhancers. Of the six variants with the strongest evidence of potential functionality, rs11049453 was statistically significantly associated with the expression of PTHLH and its nearby gene CCDC91 at P < 0.05. CONCLUSION: This study identified four independent association signals at 12p11 and revealed potentially functional variants, providing additional insights into the underlying biological mechanism(s) for the association observed between variants at 12p11 and breast cancer risk.

Community perceptions of behaviour change communication interventions of the maternal neonatal and child health programme in rural Bangladesh: an exploratory study.

BACKGROUND: This qualitative study explored community perceptions of the components of the behaviour change communication (BCC) intervention of the BRAC Improving Maternal, Neonatal and Child Survival (IMNCS) programme in rural Bangladesh. METHODS: Semi-structured interviews, key informant interviews, focus group discussions and informal group discussions were conducted to elicit community views on interpersonal communication (IPC), printed materials, entertainment education (EE) and mass media, specifically (a) acceptance of and challenges presented by different forms of media, (b) comprehensibility of terms; printed materials and entertainment education and (c) reported influence of BCC messages. RESULTS: IMNCS BCC interventions are well accepted by the community people. IPC is considered an essential aspect of everyday life and community members appreciate personal interaction with the BRAC community health workers. Printed materials assisted in comprehension and memorization of messages particularly when explained by community health workers (CHW) during IPC. Enactment of maternal, neonatal and child health (MNCH) narratives and traditional musical performances in EE helped to give deep insight into life's challenges and the decision making that is inherent in pregnancy, childbirth and childcare. EE also improved memorization of the messages. Some limitations were identified in design of illustrations which hampered message comprehension. Some respondents were unable to differentiate between pregnancy, delivery and postpartum danger signs. Furthermore some women were afraid to view the illustrations of danger signs as they believed seeing that might be associated with the development of these complications in their own lives. Despite these barriers, participants stated that the IMNCS BCC interventions had influenced them to take health promoting decisions and seek MNCH services. CONCLUSIONS: Community based maternal and newborn programmes should revise BCC interventions to strengthen IPC, using rigorously tested print materials as aids and stand-alone media. Messages about birth preparedness (especially savings), recognition of danger signs and immediate self-referral to biomedical health services should be carefully aligned and effectively delivered to women, men and older members of the community. Messaging should utilize gendered storyline and address the seasonal cycles of conception, birth, antenatal, post-natal care and childhood illnesses. Future research should identify how best to combine IPC, printed materials, traditional cultural forms, and incorporate use of social media and mass media in different field situations.

Estimating BrAC from transdermal alcohol concentration data using the BrAC estimator software program.

BACKGROUND: Transdermal alcohol sensor (TAS) devices have the potential to allow researchers and clinicians to unobtrusively collect naturalistic drinking data for weeks at a time, but the transdermal alcohol concentration (TAC) data these devices produce do not consistently correspond with breath alcohol concentration (BrAC) data. We present and test the BrAC Estimator software, a program designed to produce individualized estimates of BrAC from TAC data by fitting mathematical models to a specific person wearing a specific TAS device. METHODS: Two TAS devices were worn simultaneously by 1 participant for 18 days. The trial began with a laboratory alcohol session to calibrate the model and was followed by a field trial with 10 drinking episodes. Model parameter estimates and fit indices were compared across drinking episodes to examine the calibration phase of the software. Software-generated estimates of peak BrAC, time of peak BrAC, and area under the BrAC curve were compared with breath analyzer data to examine the estimation phase of the software. RESULTS: In this single-subject design with breath analyzer peak BrAC scores ranging from 0.013 to 0.057, the software created consistent models for the 2 TAS devices, despite differences in raw TAC data, and was able to compensate for the attenuation of peak BrAC and latency of the time of peak BrAC that are typically observed in TAC data. CONCLUSIONS: This software program represents an important initial step for making it possible for non mathematician researchers and clinicians to obtain estimates of BrAC from TAC data in naturalistic drinking environments. Future research with more participants and greater variation in alcohol consumption levels and patterns, as well as examination of gain scheduling calibration procedures and nonlinear models of diffusion, will help to determine how precise these software models can become.

The relationship between drinking games and intentions to continue drinking, intentions to drive after drinking, and adverse consequences: results of a field study.

BACKGROUND: Drinking games have become a nearly universal aspect of excessive drinking on university campuses with 50-62% of college students reporting playing drinking games in the past month. Participation in drinking games has been correlated with numerous negative consequences and increased consumption of alcohol. OBJECTIVES: The present study addresses the influence of drinking games on three drinking-related outcomes: problems experienced the night of the drinking event, the intent to keep drinking, and the intent to drive after drinking. METHODS: The data collected for the present study were part of a study testing environmental influences of drinking behaviors of young adults. A total of 226 randomly selected parties (representing 1725 partygoers) were selected for study inclusion. Three multilevel logistic regression models tested the relationship between drinking games and the three drinking-related outcomes. RESULTS: Participants who reported playing drinking games were 1.58 times more likely to report continued drinking intentions than participants who did not play drinking games. If drinking games were observed at a party, participants were 2.38 times more likely to plan to drive while intoxicated. Additionally, participants who reported playing drinking games were 1.59 times more likely to report experiencing a drinking-related problem than participants who did not play drinking games. CONCLUSION: Drinking games have consequences beyond increasing the level of intoxication; they contribute to problematic behavior at individual and environmental levels. Preventing drinking games is warranted.

TRAF3 suppression encourages B cell recruitment and prolongs survival of microbiome-intact mice with ovarian cancer.

BACKGROUND: Ovarian cancer (OC) is known for exhibiting low response rates to immune checkpoint inhibitors that activate T cells. However, immunotherapies that activate B cells have not yet been extensively explored and may be a potential target, as B cells that secrete immunoglobulins have been associated with better outcomes in OC. Although the secretion of immunoglobulins is often mediated by the microbiome, it is still unclear what role they play in limiting the progression of OC. METHODS: We conducted an in-vivo CRISPR screen of immunodeficient (NSG) and immune-intact wild type (WT) C57/BL6 mice to identify tumor-derived immune-escape mechanisms in a BRAC1- and TP53-deficient murine ID8 OC cell line (designated ITB1). To confirm gene expression and signaling pathway activation in ITB1 cells, we employed western blot, qPCR, immunofluorescent staining, and flow cytometry. Flow cytometry was also used to identify immune cell populations in the peritoneum of ITB1-bearing mice. To determine the presence of IgA-coated bacteria in the peritoneum of ITB1-bearing mice and the ascites of OC patients, we employed 16S sequencing. Testing for differences was done by using Deseq2 test and two-way ANOVA test. Sequence variants (ASVs) were produced in Qiime2 and analyzed by microeco and phyloseq R packages. RESULTS: We identified tumor necrosis factor receptor-associated factor 3 (TRAF3) as a tumor-derived immune suppressive mediator in ITB1 cells. Knockout of TRAF3 (TRAF3KO) activated the type-I interferon pathway and increased MHC-I expression. TRAF3KO tumors exhibited a growth delay in WT mice vs. NSG mice, which was correlated with increased B cell infiltration and activation compared to ITB1 tumors. B cells were found to be involved in the progression of TRAF3KO tumors, and B-cell surface-bound and secreted IgA levels were significantly higher in the ascites of TRAF3KO tumors compared to ITB1. The presence of commensal microbiota was necessary for B-cell activation and for delaying the progression of TRAF3KO tumors in WT mice. Lastly, we observed unique profiles of IgA-coated bacteria in the ascites of OC-bearing mice or the ascites of OC patients. CONCLUSIONS: TRAF3 is a tumor-derived immune-suppressive modulator that influences B-cell infiltration and activation, making it a potential target for enhancing anti-tumor B-cell responses in OC.

Cognitive and Neural Mechanisms of Behavior Therapy for Tics: A Perception-Action Integration Approach.

European clinical guidelines recommend the use of Exposure and Response Prevention (ERP) and Comprehensive Behavioral Intervention for Tics (CBIT) as first-line treatments for tic disorders. Although ongoing efforts in research are being made to understand the mechanisms underlying these behavioral approaches, as of yet, the neurophysiological mechanisms behind behavioral interventions are poorly understood. However, this is essential to tailor interventions to individual patients in order to increase compliance and efficacy. The Theory of Event Coding (TEC) and its derivative BRAC (Binding and Retrieval in Action Control) provide a theoretical framework to investigate cognitive and neural processes in the context of tic disorders. In this context, tics are conceptualized as a phenomenon of enhanced perception-action binding, with premonitory urges constituting the perceptual and the motor or vocal expression constituting the action part of an event file. Based on this, CBIT is assumed to strongly affect stimulus-response binding in the context of response selection, whereas the effects of ERP presumably unfold during stimulus-response binding in the response inhibition context. Further studies are needed to clarify the neurophysiological processes underlying behavioral interventions to enable the individualization and further development of therapeutic approaches for tic disorders.

Disruption of a BTB-ZF transcription factor causes female sterility and melanization in the larval body of the silkworm, Bombyx mori.

The dilute black (bd) of the silkworm Bombyx mori is a recessive mutant that produces a grayish-black color in the larval integument, instead of the characteristic white color found in wild-type larvae. In addition, eggs produced by bd females are sterile due to a deficiency in the micropylar apparatus. We identified candidate genes responsible for the bd phenotype using publicly available RNA-seq data. One of these candidate genes was homologous to the maternal gene required for meiosis (mamo) of Drosophila melanogaster, which encodes a broad-complex, tramtrack, and bric-à-brac-zinc finger (BTB-ZF) transcription factor essential for female fertility. In three independent bd strains, the expression of the B. mori mamo (Bmmamo) was downregulated in the larval integument. Using a CRISPR/Cas9-mediated knockout strategy, we found that Bmmamo knockout mutants exhibit a grayish-black color in the larval integument and female infertility. Moreover, larvae obtained from the complementation cross between bd/+ mutants and heterozygous knockouts for the Bmmamo also exhibited a grayish-black color, indicating that Bmmamo is responsible for the bd phenotype. Gene expression analysis using Bmmamo knockout mutants suggested that the BmMamo protein suppresses the expression of melanin synthesis genes. Previous comparative genome analysis revealed that the Bmmamo was selected during silkworm domestication, and we found that Bmmamo expression in the larval integument is higher in B. mori than in the wild silkworm B. mandarina, suggesting that the Bmmamo is involved in domestication-associated pigmentation changes of the silkworm.

Association of Kaiso and partner proteins in oral squamous cell carcinoma.

Objectives: 1. Identification of protein expression and subcellular localization of E-cadherin (E-cad), p120 catenin (P120ctn), and Kaiso in oral cancer (OC). 2. To study the protein expression of cyclin D1 and c-Myc (Kaiso targets) and determine their relationship with the expression and localization of Kaiso. Methods: Histological grading was performed in accordance with Broder's criteria. Expression and localization data for E-cad, p120ctn, Kaiso, cyclin D1, and c-Myc were acquired using immunohistochemistry. Data were analyzed using SPSS version 21. The chi-square test was used to measure the statistical significance of associations, with p < 0.05 as statistically significant. Results: Of 47 OC cases, 36% showed low E-cad expression and 34% showed low p120ctn. Low Kaiso expression was recognized in 78% of tumor specimens. Aberrant cytoplasmic localization of p120ctn was seen in 80.8% cases. Cytoplasmic Kaiso localization was appreciated in 87% of tumor tissues, whereas 29.7% lacked any nuclear Kaiso. Kaiso expression was significantly associated with the expression of cyclin D1 but not with c-Myc. Conclusion: The present study identified a change in the localization of Kaiso in OC. The significance of this in relation to OC and tumor prognosis needs to be investigated with further studies using larger sample sizes and more sensitive molecular tools.

Ferroptosis model system by the re-expression of BACH1.

Ferroptosis is a regulated cell death induced by iron-dependent lipid peroxidation. The heme-responsive transcription factor BTB and CNC homology 1 (BACH1) promotes ferroptosis by repressing the transcription of genes involved in glutathione (GSH) synthesis and intracellular labile iron metabolism, which are key regulatory pathways in ferroptosis. We found that BACH1 re-expression in Bach1-/- immortalized mouse embryonic fibroblasts (iMEFs) can induce ferroptosis upon 2-mercaptoethanol removal, without any ferroptosis inducers. In these iMEFs, GSH synthesis was reduced, and intracellular labile iron levels were increased upon BACH1 re-expression. We used this system to investigate whether the major ferroptosis regulators glutathione peroxidase 4 (Gpx4) and apoptosis-inducing factor mitochondria-associated 2 (Aifm2), the gene for ferroptosis suppressor protein 1, are target genes of BACH1. Neither Gpx4 nor Aifm2 was regulated by BACH1 in the iMEFs. However, we found that BACH1 represses AIFM2 transcription in human pancreatic cancer cells. These results suggest that the ferroptosis regulators targeted by BACH1 may vary across different cell types and animal species. Furthermore, we confirmed that the ferroptosis induced by BACH1 re-expression exhibited a propagating effect. BACH1 re-expression represents a new strategy for inducing ferroptosis after GPX4 or system Xc- suppression and is expected to contribute to future ferroptosis research.

Using Oral Rehydration Therapy (ORT) in the Community.

For ORT to have a maximum impact on public health it should be used in the community, in the home. A number of programs have been developed over the years to extend ORT to home use. One of the most successful approaches was the Oral Therapy Education Program (OTEP) developed by BRAC, the world's largest NGO. Mothers were taught in the home by an OTEP worker using seven simple messages and a demonstration. The program, which led to high levels of use and knowledge retention, is described. What the OTEP and other successful home-based programs have demonstrated is that home care of diarrhea using ORS can be effectively implemented and can have a positive impact on the reduction of diarrhea morbidity and mortality.

Effects of a multi-component alcohol prevention intervention at sporting events: a quasi-experimental control group study.

BACKGROUND AND AIMS: Alcohol intoxication among spectators and related problems are common at sporting events. This study estimated the impact a multi-component community-based alcohol prevention intervention, implemented at Swedish Premier Football (soccer) League matches, had on intoxication levels among spectators and refusal rates of alcohol service to, and arena entry of, obviously intoxicated spectators. DESIGN: A quasi-experimental controlled study using a repeated cross-sectional design. SETTING AND PARTICIPANTS: Spectators and sport arenas in Stockholm and Gothenburg, Sweden. INTERVENTION AND COMPARATOR: The intervention was implemented in Stockholm and consisted of community mobilisation and collaboration, training of staff and improved enforcement and policy work. Gothenburg was the comparison area and received usual care. MEASUREMENTS: Primary outcomes were spectators' mean breath alcohol concentration (BrAC), proportion of spectators with high intoxication levels, (defined as BrAC ≥0.1%), overserving at licensed premises inside arenas and refused arena entry of obviously intoxicated spectators. Baseline data were collected during 2015 and follow-up during 2016 and 2017. FINDINGS: BrAC assessments (n = 10 188), arena entry attempts (n = 201) and alcohol purchase attempts at premises inside arenas (n = 495) were collected. There was evidence that the refusal rates of alcohol purchase at premises inside arenas improved differently between study areas and over time (adjusted odds ratio [aOR] = 0.28, 95% CI = 0.07, 1.06, P = 0.060, Bayes factor [BF] = 8.60). In both study areas, the arena entry refusal rates improved over time (aOR = 5.87, 95% CI = 1.16, 29.83, P = 0.033, BF = 17.7), but evidence that the rates improved differently between study areas and over time was equivocal (aOR = 0.57, 95% CI = 0.09, 3.56, P = 0.543, BF = 1.2). Mean BrAC levels decreased over time in both study areas (ß = -0.032, 95% CI = -0.050, -0.015, P < 0.001), and differently (ß = 0.104, 95% CI = 0.061, 0.146, P < 0.001), but evidence for an interaction effect was equivocal (ß = -0.002, 95% CI = -0.022, 0.018, P = 0.868, BF = 1.0). Evidence was equivocal regarding whether the proportion of spectators with high intoxication levels decreased differently between study areas and over time (aOR = 1.17, 95% CI = 0.91, 1.50, P = 0.220, BF = 2.2). CONCLUSIONS: A multi-component community-based alcohol prevention intervention at sporting events may have increased staff intervention toward obviously intoxicated spectators. It was not clear whether this translated into a reduction in intoxication, which can be explained by improvements in the comparison area.

ZBTB20 regulates WNT/CTNNB1 signalling pathway by suppressing PPARG during hepatocellular carcinoma tumourigenesis.

BACKGROUND & AIMS: Zinc finger and BTB domain containing 20 (ZBTB20) has been implicated as a potential oncogene in liver cancer. However, knockout studies have shown it to be a transcriptional repressor of the alpha-foetoprotein (Afp) gene in adult liver, and reduced levels of ZBTB20 allow for upregulation of AFP with increased tumour severity in certain cases of hepatocellular carcinoma (HCC). As there are many discrepancies in the literature regarding its role in liver tumourigenesis, the aim of this study was to elucidate the role of ZBTB20 in HCC tumourigenesis. METHODS: A reverse genetic study using the Sleeping Beauty (SB) transposon system in mice was performed to elucidate the role of ZBTB20 in HCC tumourigenesis. In vitro ZBTB20 gain- and loss-of-function experiments were used to assess the relationship amongst ZBTB20, peroxisome proliferator activated receptor gamma (PPARG) and catenin beta 1 (CTNNB1). RESULTS: Transgenic overexpression of ZBTB20 in hepatocytes and in the context of transformation related protein (T r p53) inactivation induced hepatic hypertrophy, activation of WNT/CTNNB1 signalling, and development of liver tumours. In vitro overexpression and knockout experiments using CRISPR/Cas9 demonstrated the important role for ZBTB20 in downregulating PPARG, resulting in activation of the WNT/CTNNB1 signalling pathway and its downstream effectors in HCC tumourigenesis. CONCLUSIONS: These findings demonstrate a novel interaction between ZBTB20 and PPARG, which leads to activation of the WNT/CTNNB1 signalling pathway in HCC tumourigenesis. LAY SUMMARY: ZBTB20 has been implicated as a potential oncogene in liver cancer. Herein, we uncover its important role in liver cancer development. We show that it interacts with PPARG to upregulate the WNT/CTNNB1 signalling pathway, leading to tumourigenesis.