Hippocampus and retrosplenial cortex combine path integration signals for successful navigation

The current study used fMRI in humans to examine goal-directed navigation in an open field environment. We designed a task that required participants to encode survey-level spatial information and subsequently navigate to a goal location in either first person, third person, or survey perspectives. Critically, no distinguishing landmarks or goal location markers were present in the environment, thereby requiring participants to rely on path integration mechanisms for successful navigation. We focused our analysis on mechanisms related to navigation and mechanisms tracking linear distance to the goal location. Successful navigation required translation of encoded survey-level map information for orientation and implementation of a planned route to the goal. Our results demonstrate that successful first and third person navigation trials recruited the anterior hippocampus more than trials when the goal location was not successfully reached. When examining only successful trials, the retrosplenial and posterior parietal cortices were recruited for goal-directed navigation in both first person and third person perspectives. Unique to first person perspective navigation, the hippocampus was recruited to path integrate self-motion cues with location computations toward the goal location. Last, our results demonstrate that the hippocampus supports goal-directed navigation by actively tracking proximity to the goal throughout navigation. When using path integration mechanisms in first person and third person perspective navigation, the posterior hippocampus was more strongly recruited as participants approach the goal. These findings provide critical insight into the neural mechanisms by which we are able to use map-level representations of our environment to reach our navigational goals

DNA secondary structures and their contribution to mutagenesis in B. subtilis stationary phase cells

It is widely known and accepted that the cause of many mutations in cells are generated during the replication process of actively dividing cells, however more recent research has shown that mutations also arise in non growing conditions, a phenomenon known stationary phase mutagenesis. Much of what is known come from studies in eukaryotic and bacterial models. It is proposed that in nongrowing cells, the process of transcription plays an important role in mutagenesis. I will test the hypothesis that secondary structures formed of DNA generated transcription promote mutagenesis. The sequences transcriptiongenerated structures are speculated to be prone to mutations by exposing regions of single stranded DNA to lesions. To test this hypothesis, I examined the Bacillus subtilis gene thiF, predicted by in silico analysis to be prone to mutations at particular locations during transcription. By altering the base sequence of this gene, the stability of its stem-loop structures is affected, thereby allowing us to test whether transcription of the altered sequence influences accumulation of in thiF. Our assay for detection of mutations is based on reversion to thiamine auxotrophy in cells under conditions of starvation. Ultimately, these experiments will increase our understanding of how mutations occur in cells of all domains of life

Alexithymia predicts loss chasing for people at risk for problem gambling

Background and aimsThe aim of this research was to investigate the relationship between alexithymia and loss-chasing behavior in people at risk and not at risk for problem gambling.MethodsAn opportunity sample of 58 (50 males and 8 females) participants completed the Problem Gambling Severity Index and the Toronto Alexithymia Scale (TAS-20). They then completed the Cambridge Gambling Task from which a measure of loss-chasing behavior was derived.ResultsAlexithymia and problem gambling risk were significantly positively correlated. Subgroups of non-alexithymic and at or near caseness for alexithymia by low risk and at risk for problem gambling were identified. The results show a clear difference for loss-chasing behavior for the two alexithymia conditions, but there was no evidence that low and at-risk problem gamblers were more likely to loss chase. The emotion-processing components of the TAS-20 were shown to correlate with loss chasing.Discussion and conclusionThese findings suggest that loss-chasing behavior may be particularly prevalent in a subgroup of problem gamblers those who are high in alexithymia

Developing the next generation of dissemination and implementation researchers: Insights from initial trainees

BACKGROUND: Dissemination and implementation (D&I) research is a relatively young discipline, underscoring the importance of training and career development in building and sustaining the field. As such, D&I research faces several challenges in designing formal training programs and guidance for career development. A cohort of early-stage investigators (ESI) recently involved in an implementation research training program provided a resource for formative data in identifying needs and solutions around career development. RESULTS: Responses outlined fellows’ perspectives on the perceived usefulness and importance of, as well as barriers to, developing practice linkages, acquiring additional methods training, academic advancement, and identifying institutional supports. Mentorship was a cross-cutting issue and was further discussed in terms of ways it could foster career advancement in the context of D&I research. CONCLUSIONS: Advancing an emerging field while simultaneously developing an academic career offers a unique challenge to ESIs in D&I research. This article summarizes findings from the formative data that outlines some directions for ESIs and provides linkages to the literature and other resources on key points

Rural‐Urban Differences in In‐Hospital Mortality Among Admissions for End‐Stage Liver Disease in the United States

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/151328/1/lt25587_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/151328/2/lt25587.pd

Relative Expression Levels Rather Than Specific Activity Plays the Major Role in Determining In Vivo AKT Isoform Substrate Specificity

The AKT protooncogene mediates many cellular processes involved in normal development and disease states such as cancer. The three structurally similar isoforms: AKT1, AKT2, and AKT3 exhibit both functional redundancy and isoform-specific functions; however the basis for their differential signalling remains unclear. Here we show that in vitro, purified AKT3 is ∼47-fold more active than AKT1 at phosphorylating peptide and protein substrates. Despite these marked variations in specific activity between the individual isoforms, a comprehensive analysis of phosphorylation of validated AKT substrates indicated only subtle differences in signalling via individual isoforms in vivo. Therefore, we hypothesise, at least in this model system, that relative tissue/cellular abundance, rather than specific activity, plays the dominant role in determining AKT substrate specificity in situ

Integration of vanHAX downstream of a ribosomal RNA operon restores vancomycin resistance in a susceptible Enterococcus faecium strain

During the genomic characterisation of Enterococcus faecium strains (n = 39) collected in a haematology ward, we identified an isolate (OI25), which contained vanA-type vancomycin resistance genes but was phenotypically susceptible to vancomycin. OI25 could revert to resistance when cultured in the presence of vancomycin and was thus considered to be vancomycin-variable. Long-read sequencing was used to identify structural variations within the vancomycin resistance region of OI25 and to uncover its resistance reversion mechanism. We found that OI25 has a reduced ability to positively regulate expression of the vanHAX genes in the presence of vancomycin, which was associated with the insertion of an IS6-family element within the promoter region and the first 50 bp of the vanR gene. The vancomycin-resistant revertant isolates constitutively expressed vanHAX genes at levels up to 36,000-fold greater than OI25 via co-transcription with a ribosomal RNA operon. The vancomycin-resistant revertants did not exhibit a significant growth defect. During VRE outbreaks, attention should be paid to contemporaneous vancomycin-susceptible strains as these may carry silent vancomycin resistance genes that can be activated through genomic rearrangements

Tobacco industry manipulation of tobacco excise and tobacco advertising policies in the Czech Republic : an analysis of tobacco industry documents

Background: The Czech Republic has one of the poorest tobacco control records in Europe. This paper examines transnational tobacco companies' (TTCs') efforts to influence policy there, paying particular attention to excise policies, as high taxes are one of the most effective means of reducing tobacco consumption, and tax structures are an important aspect of TTC competitiveness. Methods and Findings: TTC documents dating from 1989 to 2004/5 were retrieved from the Legacy Tobacco Documents Library website, analysed using a socio-historical approach, and triangulated with key informant interviews and secondary data. The documents demonstrate significant industry influence over tobacco control policy. Philip Morris (PM) ignored, overturned, and weakened various attempts to restrict tobacco advertising, promoting voluntary approaches as an alternative to binding legislation. PM and British American Tobacco (BAT) lobbied separately on tobacco tax structures, each seeking to implement the structure that benefitted its own brand portfolio over that of its competitors, and enjoying success in turn. On excise levels, the different companies took a far more collaborative approach, seeking to keep tobacco taxes low and specifically to prevent any large tax increases. Collective lobbying, using a variety of arguments, was successful in delaying the tax increases required via European Union accession. Contrary to industry arguments, data show that cigarettes became more affordable post-accession and that TTCs have taken advantage of low excise duties by raising prices. Interview data suggest that TTCs enjoy high-level political support and continue to actively attempt to influence policy. Conclusion: There is clear evidence of past and ongoing TTC influence over tobacco advertising and excise policy. We conclude that this helps explain the country's weak tobacco control record. The findings suggest there is significant scope for tobacco tax increases in the Czech Republic and that large (rather than small, incremental) increases are most effective in reducing smoking. Please see later in the article for the Editors' Summary