The crystal structure of the DNase domain of colicin E7 in complex with its inhibitor Im7 protein

AbstractBackground: Colicin E7 (ColE7) is one of the bacterial toxins classified as a DNase-type E-group colicin. The cytotoxic activity of a colicin in a colicin-producing cell can be counteracted by binding of the colicin to a highly specific immunity protein. This biological event is a good model system for the investigation of protein recognition.Results: The crystal structure of a one-to-one complex between the DNase domain of colicin E7 and its cognate immunity protein Im7 has been determined at 2.3 Å resolution. Im7 in the complex is a varied four-helix bundle that is identical to the structure previously determined for uncomplexed Im7. The structure of the DNase domain of ColE7 displays a novel α/β fold and contains a Zn2+ ion bound to three histidine residues and one water molecule in a distorted tetrahedron geometry. Im7 has a V-shaped structure, extending two arms to clamp the DNase domain of ColE7. One arm (α1∗–loop12–α2∗; where ∗ represents helices in Im7) is located in the region that displays the greatest sequence variation among members of the immunity proteins in the same subfamily. This arm mainly uses acidic sidechains to interact with the basic sidechains in the DNase domain of ColE7. The other arm (loop 23–α3∗–loop 34) is more conserved and it interacts not only with the sidechain but also with the mainchain atoms of the DNase domain of ColE7.Conclusions: The protein interfaces between the DNase domain of ColE7 and Im7 are charge-complementary and charge interactions contribute significantly to the tight and specific binding between the two proteins. The more variable arm in Im7 dominates the binding specificity of the immunity protein to its cognate colicin. Biological and structural data suggest that the DNase active site for ColE7 is probably near the metal-binding site

DNA Binding and Degradation by the HNH Protein ColE7

The bacterial toxin ColE7 bears an HNH motif which has been identified in hundreds of prokaryotic and eukaryotic endonucleases, involved in DNA homing, restriction, repair, or chromosome degradation. The crystal structure of the nuclease domain of ColE7 in complex with a duplex DNA has been determined at 2.5 Å resolution. The HNH motif is bound at the minor groove primarily to DNA phosphate groups at and beyond the 3′ side of the scissile phosphate, with little interaction with ribose groups and bases. This result provides a structural basis for sugar- and sequence-independent DNA recognition and the inhibition mechanism by inhibitor Im7, which blocks the substrate binding site but not the active site. Structural comparison shows that two families of endonucleases bind and bend DNA in a similar way to that of the HNH ColE7, indicating that endonucleases containing a “ββα-metal” fold of active site possess a universal mode for protein-DNA interactions

PERCEPTION FIELD FOR A MOBILE DEVICE TO PROVIDE REAL-TIME DEPTH ESTIMATION FOR DETECTED OBJECTS

A mobile computing device (e.g., a mobile phone, camera, tablet computer, wearable and/or headset device) may include an integrated display device (e.g., a presence-sensitive screen) at which a user interface is presented to provide perception field functionality, which enables real-time depth estimation for static or moving objects that are detected by the mobile computing device based on sensory input from an onboard camera. In various examples, this functionality may be embodied in a portable and flexible library (e.g. Android library) that is installed on the mobile computing device. The purpose of perception field monitoring is to provide fast and efficient algorithms for spatial object mapping to enable real-time distance estimation of static and moving objects on a mobile computing device. The implementation of these algorithms may provide spatial location information of targeted objects, as well as distance information associated with objects that are detected by the device. In certain cases, mobile applications executing on the device may utilize such information to provide assistance to visually impaired users by creating audible alerts

Are associations of leisure-time physical activity with mortality attenuated by high levels of chronic ambient fine particulate matter (PM2.5) in older adults? A prospective cohort study

BACKGROUND AND PURPOSE: Although leisure-time physical activity (PA) has established health benefits in older adults, it is equivocal if exercising in environments with high levels of PM2.5 concentrations is equally beneficial for them. To explore the independent and joint associations of ambient PM2.5 and PA with all-cause mortality among adults aged 60 or older and to assess the modifying effect of age (60-74 years vs. 75+ years) on the joint associations. METHODS: A prospective cohort study based on the MJ Cohort repeat examinations (2005-2016) and the Taiwan Air Quality Monitoring Network and death registry linkages (2005-2022). We included MJ Cohort participants aged 60 or more at baseline who attended the health check-ups at least twice (n = 21,760). Metabolic equivalent hours per week (MET-h/week) of leisure-time PA were computed. Multivariable adjusted associations were examined using time-varying Cox proportional hazard models. RESULTS: There were 3539 all-cause deaths over a mean follow-up of 12.81 (SD = 3.67) years. Ambient PM2.5 and physical inactivity are both independently associated with all-cause mortality. The joint associations of PA and PM2.5 concentrations with all-cause mortality differed in the young-old (60-74 years) and the older-old (75+ years) (P for interaction = 0.01); Higher levels of long-term PM2.5 exposures (≥25 μg/m3) had little influence on the associations between PA and mortality in the young-old (HR = 0.68 (0.56-0.83) and HR = 0.72 (0.59-0.88) for participants with 7.5-<15 and 15+ MET-h/week respectively) but eliminated associations between exposure and outcome in the older-old (HR = 0.91 (0.69-01.21) and HR = 1.02 (0.76-1.38) for participants with 7.5-<15 and 15+ MET-h/week). CONCLUSION: Long-term exposures to higher PM2.5 concentrations may eliminate the beneficial associations of PA with all-cause mortality among adults aged 75 and over

Liposome-based polymer complex as a novel adjuvant: enhancement of specific antibody production and isotype switch

The aim of vaccination is to induce appropriate immunity against pathogens. Antibody-mediated immunity is critical for protection against many virus diseases, although it is becoming more evident that coordinated, multifunctional immune responses lead to the most effective defense. Specific antibody (Ab) isotypes are more efficient at protecting against pathogen invasion in different locations in the body. For example, compared to other Ab isotypes, immunoglobulin (Ig) A provides more protection at mucosal areas. In this study, we developed a cationic lipopolymer (liposome-polyethylene glycol-polyethyleneimine complex [LPPC]) adjuvant that strongly adsorbs antigens or immunomodulators onto its surface to enhance or switch immune responses. The results demonstrate that LPPC enhances uptake ability, surface marker expression, proinflammatory cytokine release, and antigen presentation in mouse phagocytes. In contrast to Freund’s adjuvant, LPPC preferentially activates Th1- immunity against antigens in vivo. With lipopolysaccharides or CpG oligodeoxynucleotides, LPPC dramatically enhances the IgA or IgG2A proportion of total Ig, even in hosts that have developed Th2 immunities and high IgG1 serum titers. Taken together, the results demonstrate that the LPPC adjuvant not only increases the immunogenicity of antigens but also modulates host immunity to produce an appropriate Ab isotype by combining with immunomodulators

A Comprehensive Survey of Data Mining-based Fraud Detection Research

This survey paper categorises, compares, and summarises from almost all published technical and review articles in automated fraud detection within the last 10 years. It defines the professional fraudster, formalises the main types and subtypes of known fraud, and presents the nature of data evidence collected within affected industries. Within the business context of mining the data to achieve higher cost savings, this research presents methods and techniques together with their problems. Compared to all related reviews on fraud detection, this survey covers much more technical articles and is the only one, to the best of our knowledge, which proposes alternative data and solutions from related domains.Comment: 14 page

Turbidity Currents, Submarine Landslides and the 2006 Pingtung Earthquake off SW Taiwan

Submarine landslides or slumps may generate turbidity currents consisting of mixture of sediment and water. Large and fast-moving turbidity currents can incise and erode continental margins and cause damage to artificial structures such as telecommunication cables on the seafloor. In this study, we report that eleven submarine cables across the Kaoping canyon and Manila trench were broken in sequence from 1500 to 4000 m deep, as a consequence of submarine landslides and turbidity currents associated with the 2006 Pingtung earthquakes offshore SW Taiwan. We have established a full-scale scenario and calculation of the turbidity currents along the Kaoping canyon channel from the middle continental slope to the adjacent deep ocean. Our results show that turbidity current velocities vary downstream ranging from 20 to 3.7 and 5.7 m/s, which demonstrates a positive relationship between turbidity current velocity and bathymetric slope. The violent cable failures happened in this case evidenced the destructive power of the turbidity current to seafloor or underwater facilities that should not be underestimated

Effects of continuity of care on hospitalizations and healthcare costs in older adults with dementia

Introduction People with dementia have high rates of hospitalization, and a share of these hospitalizations might be avoidable with appropriate ambulatory care, also known as potentially preventable hospitalization (PAH). This study investigates the associations between continuity of care and healthcare outcomes in the following year, including all-cause hospitalization, PAHs, and healthcare costs in patients with dementia. Methods This is a longitudinal retrospective cohort study of 69,658 patients with dementia obtained from the Taiwan National Health Insurance Research Database. The Continuity of Care Index (COCI) was calculated to measure the continuity of dementia-related visits across physicians. The PAHs were classified into five types as defined by the Medicare Ambulatory Care Indicators for the Elderly (MACIEs). Logistic regression models were used to examine the effect of COCI on all-cause hospitalizations and PAHs, while generalized linear models were used to analyze the effect of COCI on outpatient, hospitalization, and total healthcare costs. Results The high COCI group was significantly associated with a lower likelihood of all-cause hospitalization than the low COCI group (OR = 0.848, 95%CI: 0.821–0.875). The COCI had no significant effect on PAHs but was associated with lower outpatient costs (exp(β) = 0.960, 95%CI: 0.941 ~ 0.979), hospitalization costs (exp(β) = 0.663, 95%CI: 0.614 ~ 0.717), total healthcare costs (exp(β) = 0.962, 95%CI: 0.945–0.980). Conclusion Improving continuity of care for dementia-related outpatient visits is recommended to reduce hospitalization and healthcare costs, although there was no statistically significant effect of continuity of care found on PAHs

Incidence Rate and Predictors of Globus Pallidus Necrosis after Charcoal Burning Suicide

Objective: This study examined predictors of globus pallidus necrosis as there was a paucity of literature of globus pallidus necrosis resulted from carbon monoxide poisoning after charcoal burning suicide. Methods: A total of 67 patients who had attempted charcoal burning suicide were recruited and stratified into two subgroups based on either presence (n = 40) or absence (n = 27) of globus pallidus necrosis. Demographic, clinical, laboratory, and radiographic data were obtained for cross-sectional analysis. All patients were followed to investigate the risks for mortality. Results: The patients aged 36.8 ± 11.1 years (67.2%) were male. Patients with globus pallidus necrosis were younger (p = 0.044) and had less hypertension (p = 0.015) than patients without globus pallidus necrosis. Furthermore, patients with globus pallidus necrosis suffered from severer medical complications, i.e., fever (p = 0.008), acute myocardial injury (p = 0.022), acute rhabdomyolysis (p = 0.022), and neuropsychiatric symptoms (p < 0.001) than patients without globus pallidus necrosis. Moreover, patients with globus pallidus necrosis received less hyperbaric oxygen therapy than without necrosis (p = 0.024). Two patients (3.0%) died on arrival. In a multivariable regression model, it was revealed that acute myocardial injury (odds ratio 4.6, confidence interval 1.1-18.9, p = 0.034) and neuropsychiatric symptoms (odds ratio 8.0, confidence interval 2.0-31.4, p = 0.003), decreased blood bicarbonate level (odds ratio 0.8, confidence interval 0.7-1.0, p = 0.032), and younger age (odds ratio 0.9, confidence interval 0.9-1.0, p = 0.038) were significant predictors for globus pallidus necrosis. Conclusion: Although patients who had attempted charcoal burning suicide had a low mortality rate (3.0%), globus pallidus necrosis was not uncommon (59.7%) in this population. Further studies are warranted.Chang Gung Memorial Hospital, Linkou, TaiwanChang Gung Memorial Hospital [CLRPG3D0016, CORPG5G0051]Open access journalThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

Developing a lifestyle intervention program for overweight or obese preconception, pregnant and postpartum women using qualitative methods.

The time period before, during and after pregnancy represents a unique opportunity for interventions to cultivate sustained healthy lifestyle behaviors to improve the metabolic health of mothers and their offspring. However, the success of a lifestyle intervention is dependent on uptake and continued compliance. To identify enablers and barriers towards engagement with a lifestyle intervention, thematic analysis of 15 in-depth interviews with overweight or obese women in the preconception, pregnancy or postpartum periods was undertaken, using the integrated-Promoting Action on Research Implementation in Health Services framework as a guide to systematically chart factors influencing adoption of a novel lifestyle intervention. Barrier factors include time constraints, poor baseline knowledge, family culture, food accessibility, and lack of relevant data sources. Enabling factors were motivation to be healthy for themselves and their offspring, family and social support, a holistic delivery platform providing desired information delivered at appropriate times, regular feedback, goal setting, and nudges. From the findings of this study, we propose components of an idealized lifestyle intervention including (i) taking a holistic life-course approach to education, (ii) using mobile health platforms to reduce barriers, provide personalized feedback and promote goal-setting, and (iii) health nudges to cultivate sustained lifestyle habits