basicsynbio and the BASIC SEVA collection: software and vectors for an established DNA assembly method

Standardized deoxyribonucleic acid (DNA) assembly methods utilizing modular components provide a powerful framework to explore designs and iterate through Design–Build–Test–Learn cycles. Biopart Assembly Standard for Idempotent Cloning (BASIC) DNA assembly uses modular parts and linkers, is highly accurate, easy to automate, free for academic and commercial use and enables hierarchical assemblies through an idempotent format. These features enable applications including pathway engineering, ribosome binding site (RBS) tuning, fusion protein engineering and multiplexed guide ribonucleic acid (RNA) expression. In this work, we present basicsynbio, open-source software encompassing a Web App (https://basicsynbio.web.app/) and Python Package (https://github.com/LondonBiofoundry/basicsynbio), enabling BASIC construct design via simple drag-and-drop operations or programmatically. With basicsynbio, users can access commonly used BASIC parts and linkers while designing new parts and assemblies with exception handling for common errors. Users can export sequence data and create instructions for manual or acoustic liquid-handling platforms. Instruction generation relies on the BasicBuild Open Standard, which is parsed for bespoke workflows and is serializable in JavaScript Object Notation for transfer and storage. We demonstrate basicsynbio, assembling 30 vectors using sequences including modules from the Standard European Vector Architecture (SEVA). The BASIC SEVA vector collection is compatible with BASIC and Golden Gate using BsaI. Vectors contain one of six antibiotic resistance markers and five origins of replication from different compatibility groups. The collection is available via Addgene under an OpenMTA agreement. Furthermore, vector sequences are available from within the basicsynbio application programming interface with other collections of parts and linkers, providing a powerful environment for designing assemblies for bioengineering applications

Fake people, real effects : the presence of virtual onlookers can impair performance and learning

Can effects of social influence be elicited in virtual contexts, and if so, under which conditions can they be observed? Answering these questions has theoretical merit, as the answers can help broaden our understanding of the interaction mechanisms described by social psychology. The increasing popularity of immersive media in training applications, however, has made these questions of practical significance. Virtual reality (VR), in particular, is a weapon of choice in designing training and education simulations, as it can be used to generate highly realistic characters and environments. As a consequence, it is key to understand under which circumstances virtual ‘others’ can facilitate or impede performance and – especially – learning. In this study, we investigated the impact of virtual onlookers on an adapted Serial Reaction Time (SRT) task that was presented in VR. In each trial, participants responded to a series of spherical stimuli by tapping them with handheld controllers when they lit up. Depending on the experiment block, the sequence order was either the permutation of a fixed order (and therefore predictable given the first stimulus), or fully random (and therefore unpredictable). Participants were divided into three groups (audience variable), depending on the environment in which the task was set: a group without onlookers (none condition), a group with a computer-generated audience (CGI condition), and a group being watched by a prerecorded audience (filmed condition). Results showed that the presence of a virtual audience can hamper both overall performance and learning, particularly when the audience appears more realistic. This study further reinforces the notion that the effects of social influence transcend the physical presence of others, but rather extend to virtual audiences

Skittle: A 2-Dimensional Genome Visualization Tool

<p>Abstract</p> <p>Background</p> <p>It is increasingly evident that there are multiple and overlapping patterns within the genome, and that these patterns contain different types of information - regarding both genome function and genome history. In order to discover additional genomic patterns which may have biological significance, novel strategies are required. To partially address this need, we introduce a new data visualization tool entitled Skittle.</p> <p>Results</p> <p>This program first creates a 2-dimensional nucleotide display by assigning four colors to the four nucleotides, and then text-wraps to a user adjustable width. This nucleotide display is accompanied by a "repeat map" which comprehensively displays all local repeating units, based upon analysis of all possible local alignments. Skittle includes a smooth-zooming interface which allows the user to analyze genomic patterns at any scale.</p> <p>Skittle is especially useful in identifying and analyzing tandem repeats, including repeats not normally detectable by other methods. However, Skittle is also more generally useful for analysis of any genomic data, allowing users to correlate published annotations and observable visual patterns, and allowing for sequence and construct quality control.</p> <p>Conclusions</p> <p>Preliminary observations using Skittle reveal intriguing genomic patterns not otherwise obvious, including structured variations inside tandem repeats. The striking visual patterns revealed by Skittle appear to be useful for hypothesis development, and have already led the authors to theorize that imperfect tandem repeats could act as information carriers, and may form tertiary structures within the interphase nucleus.</p

Determining the impact of an artificial intelligence tool on the management of pulmonary nodules detected incidentally on CT (DOLCE) study protocol: a prospective, non-interventional multicentre UK study

\ua9 Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. INTRODUCTION: In a small percentage of patients, pulmonary nodules found on CT scans are early lung cancers. Lung cancer detected at an early stage has a much better prognosis. The British Thoracic Society guideline on managing pulmonary nodules recommends using multivariable malignancy risk prediction models to assist in management. While these guidelines seem to be effective in clinical practice, recent data suggest that artificial intelligence (AI)-based malignant-nodule prediction solutions might outperform existing models. METHODS AND ANALYSIS: This study is a prospective, observational multicentre study to assess the clinical utility of an AI-assisted CT-based lung cancer prediction tool (LCP) for managing incidental solid and part solid pulmonary nodule patients vs standard care. Two thousand patients will be recruited from 12 different UK hospitals. The primary outcome is the difference between standard care and LCP-guided care in terms of the rate of benign nodules and patients with cancer discharged straight after the assessment of the baseline CT scan. Secondary outcomes investigate adherence to clinical guidelines, other measures of changes to clinical management, patient outcomes and cost-effectiveness. ETHICS AND DISSEMINATION: This study has been reviewed and given a favourable opinion by the South Central-Oxford C Research Ethics Committee in UK (REC reference number: 22/SC/0142).Study results will be available publicly following peer-reviewed publication in open-access journals. A patient and public involvement group workshop is planned before the study results are available to discuss best methods to disseminate the results. Study results will also be fed back to participating organisations to inform training and procurement activities. TRIAL REGISTRATION NUMBER: NCT05389774

Cold gas accretion in galaxies

Evidence for the accretion of cold gas in galaxies has been rapidly accumulating in the past years. HI observations of galaxies and their environment have brought to light new facts and phenomena which are evidence of ongoing or recent accretion: 1) A large number of galaxies are accompanied by gas-rich dwarfs or are surrounded by HI cloud complexes, tails and filaments. It may be regarded as direct evidence of cold gas accretion in the local universe. It is probably the same kind of phenomenon of material infall as the stellar streams observed in the halos of our galaxy and M31. 2) Considerable amounts of extra-planar HI have been found in nearby spiral galaxies. While a large fraction of this gas is produced by galactic fountains, it is likely that a part of it is of extragalactic origin. 3) Spirals are known to have extended and warped outer layers of HI. It is not clear how these have formed, and how and for how long the warps can be sustained. Gas infall has been proposed as the origin. 4) The majority of galactic disks are lopsided in their morphology as well as in their kinematics. Also here recent accretion has been advocated as a possible cause. In our view, accretion takes place both through the arrival and merging of gas-rich satellites and through gas infall from the intergalactic medium (IGM). The infall may have observable effects on the disk such as bursts of star formation and lopsidedness. We infer a mean ``visible'' accretion rate of cold gas in galaxies of at least 0.2 Msol/yr. In order to reach the accretion rates needed to sustain the observed star formation (~1 Msol/yr), additional infall of large amounts of gas from the IGM seems to be required.Comment: To appear in Astronomy & Astrophysics Reviews. 34 pages. Full-resolution version available at http://www.astron.nl/~oosterlo/accretionRevie

Metformin Attenuates Palmitate-Induced Endoplasmic Reticulum Stress, Serine Phosphorylation of IRS-1 and Apoptosis in Rat Insulinoma Cells

Lipotoxicity refers to cellular dysfunctions caused by elevated free fatty acid levels playing a central role in the development and progression of obesity related diseases. Saturated fatty acids cause insulin resistance and reduce insulin production in the pancreatic islets, thereby generating a vicious cycle, which potentially culminates in type 2 diabetes. The underlying endoplasmic reticulum (ER) stress response can lead to even β-cell death (lipoapoptosis). Since improvement of β-cell viability is a promising anti-diabetic strategy, the protective effect of metformin, a known insulin sensitizer was studied in rat insulinoma cells. Assessment of palmitate-induced lipoapoptosis by fluorescent microscopy and by detection of caspase-3 showed a significant decrease in metformin treated cells. Attenuation of β-cell lipotoxicity was also revealed by lower induction/activation of various ER stress markers, e.g. phosphorylation of eukaryotic initiation factor 2α (eIF2α), c-Jun N-terminal kinase (JNK), insulin receptor substrate-1 (IRS-1) and induction of CCAAT/enhancer binding protein homologous protein (CHOP). Our results indicate that the β-cell protective activity of metformin in lipotoxicity can be at least partly attributed to suppression of ER stress

Persistent demographic differences in colorectal cancer screening utilization despite Medicare reimbursement

BACKGROUND: Colorectal cancer screening is widely recommended, but often under-utilized. In addition, significant demographic differences in screening utilization exist. Insurance coverage may be one factor influencing utilization of colorectal cancer screening tests. METHODS: We conducted a retrospective analysis of claims for outpatient services for Washington state Medicare beneficiaries in calendar year 2000. We determined the proportion of beneficiaries utilizing screening fecal occult blood tests, flexible sigmoidoscopy, colonoscopy, or double contrast barium enema in the overall population and various demographic subgroups. Multiple logistic regression analysis was used to determine the relative odds of screening in different demographic groups. RESULTS: Approximately 9.2% of beneficiaries had fecal occult blood tests, 7.2% had any colonoscopy, flexible sigmoidoscopy, or barium enema (invasive) colon tests, and 3.5% had invasive tests for screening indications. Colonoscopy accounted for 41% of all invasive tests for screening indications. Women were more likely to receive fecal occult blood test screening (OR 1.18; 95%CI 1.15, 1.21) and less likely to receive invasive tests for screening indications than men (OR 0.80, 95%CI 0.77, 0.83). Whites were more likely than other racial groups to receive any type of screening. Rural residents were more likely than urban residents to have fecal occult blood tests (OR 1.20, 95%CI 1.17, 1.23) but less likely to receive invasive tests for screening indications (OR 0.89; 95%CI 0.85, 0.93). CONCLUSION: Reported use of fecal occult blood testing remains modest. Overall use of the more invasive tests for screening indications remains essentially unchanged, but there has been a shift toward increased use of screening colonoscopy. Significant demographic differences in screening utilization persist despite consistent insurance coverage

Longitudinal, population-based study of racial/ethnic differences in colorectal cancer survival: impact of neighborhood socioeconomic status, treatment and comorbidity

<p>Abstract</p> <p>Background</p> <p>Colorectal cancer, if detected early, has greater than 90% 5-year survival. However, survival has been shown to vary across racial/ethnic groups in the United States, despite the availability of early detection methods.</p> <p>Methods</p> <p>This study evaluated the joint effects of sociodemographic factors, tumor characteristics, census-based socioeconomic status (SES), treatment, and comorbidities on survival after colorectal cancer among and within racial/ethnic groups, using the SEER-Medicare database for patients diagnosed in 1992–1996, and followed through 1999.</p> <p>Results</p> <p>Unadjusted colorectal cancer-specific mortality rates were higher among Blacks and Hispanic males than whites (relative rates (95% confidence intervals) = 1.34 (1.26–1.42) and 1.16 (1.04–1.29), respectively), and lower among Japanese (0.78 (0.70–0.88)). These patterns were evident for all-cause mortality, although the magnitude of the disparity was larger for colorectal cancer mortality. Adjustment for stage accounted for the higher rate among Hispanic males and most of the lower rate among Japanese. Among Blacks, stage and SES accounted for about half of the higher rate relative to Whites, and within stage III colon and stages II/III rectal cancer, SES completely accounted for the small differentials in survival between Blacks and Whites. Comorbidity did not appear to explain the Black-White differentials in colorectal-specific nor all-cause mortality, beyond stage, and treatment (surgery, radiation, chemotherapy) explained a very small proportion of the Black-White difference. The fully-adjusted relative mortality rates comparing Blacks to Whites was 1.14 (1.09–1.20) for all-cause mortality and 1.21 (1.14–1.29) for colorectal cancer specific mortality. The sociodemographic, tumor, and treatment characteristics also had different impacts on mortality within racial/ethnic groups.</p> <p>Conclusion</p> <p>In this comprehensive analysis, race/ethnic-specific models revealed differential effects of covariates on survival after colorectal cancer within each group, suggesting that different strategies may be necessary to improve survival in each group. Among Blacks, half of the differential in survival after colorectal cancer was primarily attributable to stage and SES, but differences in survival between Blacks and Whites remain unexplained with the data available in this comprehensive, population-based, analysis.</p