Social isolation and loneliness are increasingly prevalent among older adults in the United States, with implications for morbidity and mortality risk. Little research to date has examined the ...complex person-place transactions that contribute to social well-being in later life. This study aimed to characterize personal and neighborhood contextual influences on social isolation and loneliness among older adults. Interviews were conducted with independent-dwelling men and women (n = 124; mean age 71 years) in the Minneapolis metropolitan area (USA) from June to October, 2015. A convergent mixed-methods design was applied, whereby quantitative and qualitative approaches were used in parallel to gain simultaneous insights into statistical associations and in-depth individual perspectives. Logistic regression models predicted self-reported social isolation and loneliness, adjusted for age, gender, past occupation, race/ethnicity, living alone, street type, residential location, and residential density. Qualitative thematic analyses of interview transcripts probed individual experiences with social isolation and loneliness. The quantitative results suggested that African American adults, those with a higher socioeconomic status, those who did not live alone, and those who lived closer to the city center were less likely to report feeling socially isolated or lonely. The qualitative results identified and explained variation in outcomes within each of these factors. They provided insight on those who lived alone but did not report feeling lonely, finding that solitude was sought after and enjoyed by a portion of participants. Poor physical and mental health often resulted in reporting social isolation, particularly when coupled with poor weather or low-density neighborhoods. At the same time, poor health sometimes provided opportunities for valued social engagement with caregivers, family, and friends. The combination of group-level risk factors and in-depth personal insights provided by this mixed-methodology may be useful to develop strategies that address social isolation and loneliness in older communities.
•Social isolation and loneliness are influenced by personal and neighborhood factors.•Qualitative findings explain variations in trends identified in quantitative models.•Poor health can have both negative and positive effects on social isolation.•Some socially isolated older adults seek solitude and are content, not lonely.•Results are relevant for strategies to address social isolation and loneliness.
Quorum sensing in bacterial virulence Antunes, L Caetano M; Ferreira, Rosana B R; Buckner, Michelle M C ...
Microbiology (Society for General Microbiology),
08/2010, Letnik:
156, Številka:
Pt 8
Journal Article
Recenzirano
Odprti dostop
Bacteria communicate through the production of diffusible signal molecules termed autoinducers. The molecules are produced at basal levels and accumulate during growth. Once a critical concentration ...has been reached, autoinducers can activate or repress a number of target genes. Because the control of gene expression by autoinducers is cell-density-dependent, this phenomenon has been called quorum sensing. Quorum sensing controls virulence gene expression in numerous micro-organisms. In some cases, this phenomenon has proven relevant for bacterial virulence in vivo. In this article, we provide a few examples to illustrate how quorum sensing can act to control bacterial virulence in a multitude of ways. Several classes of autoinducers have been described to date and we present examples of how each of the major types of autoinducer can be involved in bacterial virulence. As quorum sensing controls virulence, it has been considered an attractive target for the development of new therapeutic strategies. We discuss some of the new strategies to combat bacterial virulence based on the inhibition of bacterial quorum sensing systems.
The circumpolar expansion of woody deciduous shrubs in arctic tundra alters key ecosystem properties including carbon balance and hydrology. However, landscape‐scale patterns and drivers of shrub ...expansion remain poorly understood, inhibiting accurate incorporation of shrub effects into climate models. Here, we use dendroecology to elucidate the role of soil moisture in modifying the relationship between climate and growth for a dominant deciduous shrub, Salix pulchra, on the North Slope of Alaska, USA. We improve upon previous modeling approaches by using ecological theory to guide model selection for the relationship between climate and shrub growth. Finally, we present novel dendroecology‐based estimates of shrub biomass change under a future climate regime, made possible by recently developed shrub allometry models. We find that S. pulchra growth has responded positively to mean June temperature over the past 2.5 decades at both a dry upland tundra site and an adjacent mesic riparian site. For the upland site, including a negative second‐order term in the climate–growth model significantly improved explanatory power, matching theoretical predictions of diminishing growth returns to increasing temperature. A first‐order linear model fit best at the riparian site, indicating consistent growth increases in response to sustained warming, possibly due to lack of temperature‐induced moisture limitation in mesic habitats. These contrasting results indicate that S. pulchra in mesic habitats may respond positively to a wider range of temperature increase than S. pulchra in dry habitats. Lastly, we estimate that a 2°C increase in current mean June temperature will yield a 19% increase in aboveground S. pulchra biomass at the upland site and a 36% increase at the riparian site. Our method of biomass estimation provides an important link toward incorporating dendroecology data into coupled vegetation and climate models.
Arctic shrub expansion yields numerous feedbacks to climate and carbon cycling, the spatial extent of which are poorly understood. This research attempts to improve understanding of spatial drivers of shrub expansion by (a) modeling the relationship between climate and shrub growth across a tundra landscape and (b) estimating shrub biomass under current and future climate regimes.
We present the CHAOS-7 model of the time-dependent near-Earth geomagnetic field between 1999 and 2020 based on magnetic field observations collected by the low-Earth orbit satellites
Swarm
, ...CryoSat-2, CHAMP, SAC-C and Ørsted, and on annual differences of monthly means of ground observatory measurements. The CHAOS-7 model consists of a time-dependent internal field up to spherical harmonic degree 20, a static internal field which merges to the LCS-1 lithospheric field model above degree 25, a model of the magnetospheric field and its induced counterpart, estimates of Euler angles describing the alignment of satellite vector magnetometers, and magnetometer calibration parameters for CryoSat-2. Only data from dark regions satisfying strict geomagnetic quiet-time criteria (including conditions on IMF
B
z
and
B
y
at all latitudes) were used in the field estimation. Model parameters were estimated using an iteratively reweighted regularized least-squares procedure; regularization of the time-dependent internal field was relaxed at high spherical harmonic degree compared with previous versions of the CHAOS model. We use CHAOS-7 to investigate recent changes in the geomagnetic field, studying the evolution of the South Atlantic weak field anomaly and rapid field changes in the Pacific region since 2014. At Earth’s surface a secondary minimum of the South Atlantic Anomaly is now evident to the south west of Africa. Green’s functions relating the core–mantle boundary radial field to the surface intensity show this feature is connected with the movement and evolution of a reversed flux feature under South Africa. The continuing growth in size and weakening of the main anomaly is linked to the westward motion and gathering of reversed flux under South America. In the Pacific region at Earth’s surface between 2015 and 2018 a sign change has occurred in the second time derivative (acceleration) of the radial component of the field. This acceleration change took the form of a localized, east–west oriented, dipole. It was clearly recorded on ground, for example at the magnetic observatory at Honolulu, and was seen in
Swarm
observations over an extended region in the central and western Pacific. Downward continuing to the core–mantle boundary, we find this event originated in field acceleration changes at low latitudes beneath the central and western Pacific in 2017.
The potential strengths and limitations of the Landsat systems for water clarity and colored dissolved organic matter (CDOM) measurement were evaluated in Minnesota in the summers of 2013 and 2014. ...Optical water quality characteristics, including chlorophyll a, total suspended solids (TSS), dissolved organic carbon (DOC), and CDOM were collected along with imagery from Landsats 7 and 8. Sites represented a wide range of concentrations of CDOM, chlorophyll, and mineral suspended solids (MSS), the primary factors that affect reflectance. Clear images from September 24, 2013 (Landsat 7) and September 16, 2013 (Landsat 8) acquired for northern Minnesota eight days apart allowed comparison of the respective ETM+ and OLI sensors for CDOM measurements. We examined a wide variety of potential band and band ratio models and found some two-variable models that included the NIR band worked well for Landsat 8 (R2=0.82) and reasonably well for Landsat 7 (R2=0.74). The commonly used green/red model had a poor fit for both sensors (R2=0.24, 0.25), and five sites with high MSS were clear outliers. Exclusion of these sites and other sites not included with the Landsat 7 dataset yielded a less optically complex subset of 20 coincident lakes. For this subset strong models were found for many band and band ratio models, including the commonly used green/red model with R2=0.79 for Landsat 7 and R2=0.81 for Landsat 8. The less optically complex subset may explain why the green/red model has worked well in other areas. For optically complex waters CDOM models that used the new Landsat 8 ultra-blue and narrower NIR band worked best for the full dataset indicating that the new bands and other Landsat 8 characteristics, such as higher radiometric sensitivity and improved signal-to-noise ratios, improve CDOM measurements.
For water clarity measured as Secchi depth (SD), we compared September 1, 2008 Landsat 7 and August 22, 2013 Landsat 8 images from path 28 using stepwise regression to identify the best model using all bands and band ratios including the new blue and narrower NIR band. The best water clarity model for Landsat 8 used the OLI 2/4 band ratio plus OLI band 1 and was nearly identical with a model using the OLI 2/4 band ratio plus OLI band 2. The latter model is similar to the model used for previous Landsat water clarity assessments, which used the ETM+ 1/3 band ratio plus ETM+ band 1. For SD measurements we found strong relationships with both sensors, with only slight improvements for the OLI sensor for the lakes in our datasets. In contrast to some previous reports that indicated Landsat 7's ETM+ lacked sufficient sensitivity for reliable retrieval of CDOM, we found that overall both sensors worked well for water clarity and CDOM measurements. This will allow their continued use for current and historical measurements of important water characteristics on a regional scale.
•Landsats 7 and 8 data were compared for mapping CDOM and clarity of inland lakes.•Landsat 8 was better for estimating CDOM than Landsat 7 in optically complex waters.•Landsat 8 was only a slight improvement over Landsat 7 for measuring water clarity.•Landsats 7 and 8 will continue and enhance remote sensing of regional water quality.
Nonalcoholic fatty liver disease (NAFLD) is a chronic condition affecting one quarter of the global population. Although primarily linked to obesity and metabolic syndrome, undernutrition and the ...altered (dysbiotic) gut microbiome influence NAFLD progression. Both undernutrition and NAFLD prevalence are predicted to considerably increase, but how the undernourished gut microbiome contributes to hepatic pathophysiology remains far less studied. Here, we present undernutrition conditions with fatty liver features, including kwashiorkor and micronutrient deficiency. We then review the gut microbiota-liver axis, highlighting key pathways linked to NAFLD progression within both overnutrition and undernutrition. To conclude, we identify challenges and collaborative possibilities of emerging multiomic research addressing the pathology and treatment of undernourished NAFLD.
SUMMARY
We present investigations of rapidly rotating convection in a thick spherical shell geometry relevant to planetary cores, comparing results from quasi-geostrophic (QG), 3-D and hybrid QG-3D ...models. The 170 reported calculations span Ekman numbers, Ek, between 10−4 and 10−10, Rayleigh numbers, Ra, between 2 and 150 times supercritical and Prandtl numbers, Pr, between 10 and 10−2. The default boundary conditions are no-slip at both the ICB and the CMB for the velocity field, with fixed temperatures at the ICB and the CMB. Cases driven by both homogeneous and inhomogeneous CMB heat flux patterns are also explored, the latter including lateral variations, as measured by Q*, the peak-to-peak amplitude of the pattern divided by its mean, taking values up to 5. The QG model is based on the open-source pizza code. We extend this in a hybrid approach to include the temperature field on a 3-D grid. In general, we find convection is dominated by zonal jets at mid-depths in the shell, with thermal Rossby waves prominent close to the outer boundary when the driving is weaker. For the thick spherical shell geometry studied here the hybrid method is best suited for studying convection at modest forcing, $Ra \le 10 \, Ra_c$ when Pr = 1, and departs from the 3-D model results at higher Ra, displaying systematically lower heat transport characterized by lower Nusselt and Reynolds numbers. We find that the lack of equatorially-antisymmetric motions and z-correlations between temperature and velocity in the buoyancy force contributes to the weaker flows in the hybrid formulation. On the other hand, the QG models yield broadly similar results to the 3-D models, for the specific aspect ratio and range of Rayleigh numbers explored here. We cannot point to major disagreements between these two data sets at Pr ≥ 0.1, with the QG model effectively more strongly driven than the hybrid case due to its cylindrically averaged thermal boundary conditions. When Pr is decreased, the range of agreement between the hybrid and 3-D models expands, for example up to $Ra \le 15 \, Ra_c$ at Pr = 0.1, indicating the hybrid method may be better suited to study convection in the low Pr regime. We thus observe a transition between two regimes: (i) at Pr ≥ 0.1 the QG and 3-D models agree in the studied range of Ra/Rac while the hybrid model fails when $Ra\gt 15\, Ra_c$ and (ii) at Pr = 0.01 the QG and 3-D models disagree for $Ra\gt 10\, Ra_c$ while the hybrid and 3-D models agree fairly well up to $Ra \sim 20\, Ra_c$. Models that include laterally varying heat flux at the outer boundary reproduce regional convection patterns that compare well with those found in similarly forced 3-D models. Previously proposed scaling laws for rapidly rotating convection are tested; our simulations are overall well described by a triple balance between Coriolis, inertia and Archimedean forces with the length-scale of the convection following the diffusion-free Rhines-scaling. The magnitude of Pr affects the number and the size of the jets with larger structures obtained at lower Pr. Higher velocities and lower heat transport are seen on decreasing Pr with the scaling behaviour of the convective velocity displaying a strong dependence on Pr. This study is an intermediate step towards a hybrid model of core convection also including 3-D magnetic effects.
Type III secretion systems (T3SSs) are protein transport nanomachines that are found in Gram-negative bacterial pathogens and symbionts. Resembling molecular syringes, T3SSs form channels that cross ...the bacterial envelope and the host cell membrane, which enable bacteria to inject numerous effector proteins into the host cell cytoplasm and establish trans-kingdom interactions with diverse hosts. Recent advances in cryo-electron microscopy and integrative imaging have provided unprecedented views of the architecture and structure of T3SSs. Furthermore, genetic and molecular analyses have elucidated the functions of many effectors and key regulators of T3SS assembly and secretion hierarchy, which is the sequential order by which the protein substrates are secreted. As essential virulence factors, T3SSs are attractive targets for vaccines and therapeutics. This Review summarizes our current knowledge of the structure and function of this important protein secretion machinery. A greater understanding of T3SSs should aid mechanism-based drug design and facilitate their manipulation for biotechnological applications.
EGFR exon 20 insertions (Ex20Ins) account for 4% to 10% of EGFR activating mutations in non-small cell lung cancer (NSCLC). EGFR Ex20Ins tumors are generally unresponsive to first- and ...second-generation EGFR inhibitors, and current standard of care for NSCLC patients with EGFR Ex20Ins is conventional cytotoxic chemotherapy. Therefore, the development of an EGFR TKI that can more effectively target NSCLC with EGFR Ex20Ins mutations represents a major advance for this patient subset. Osimertinib is a third-generation EGFR TKI approved for the treatment of advanced NSCLC harboring EGFR T790M; however, the activity of osimertinib in EGFR Ex20Ins NSCLC has yet to be fully assessed. Using CRISPR-Cas 9 engineered cell lines carrying the most prevalent Ex20Ins mutations, namely Ex20Ins D770_N771InsSVD (22%) or Ex20Ins V769_D770InsASV (17%), and a series of patient-derived xenografts, we have characterized osimertinib and AZ5104 (a circulating metabolite of osimertinib) activities against NSCLC harboring Ex20Ins. We report that osimertinib and AZ5104 inhibit signaling pathways and cellular growth in Ex20Ins mutant cell lines
and demonstrate sustained tumor growth inhibition of EGFR-mutant tumor xenograft harboring the most prevalent Ex20Ins
The antitumor activity of osimertinib and AZ5104 in NSCLC harboring EGFR Ex20Ins is further described herein using a series of patient-derived xenograft models. Together these data support clinical testing of osimertinib in patients with EGFR Ex20Ins NSCLC.
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