FBXL5 Regulates IRP2 Stability in Iron Homeostasis via an Oxygen-Responsive [2Fe2S] Cluster.

Cellular iron homeostasis is dominated by FBXL5-mediated degradation of iron regulatory protein 2 (IRP2), which is dependent on both iron and oxygen. However, how the physical interaction between FBXL5 and IRP2 is regulated remains elusive. Here, we show that the C-terminal substrate-binding domain of FBXL5 harbors a [2Fe2S] cluster in the oxidized state. A cryoelectron microscopy (cryo-EM) structure of the IRP2-FBXL5-SKP1 complex reveals that the cluster organizes the FBXL5 C-terminal loop responsible for recruiting IRP2. Interestingly, IRP2 binding to FBXL5 hinges on the oxidized state of the [2Fe2S] cluster maintained by ambient oxygen, which could explain hypoxia-induced IRP2 stabilization. Steric incompatibility also allows FBXL5 to physically dislodge IRP2 from iron-responsive element RNA to facilitate its turnover. Taken together, our studies have identified an iron-sulfur cluster within FBXL5, which promotes IRP2 polyubiquitination and degradation in response to both iron and oxygen concentrations.

Are the Gas-Phase Structures of Molecular Elephants Enduring or Ephemeral? Results from Time-Dependent, Tandem Ion Mobility.

The structural stability of biomolecules in the gas phase remains an important topic in mass spectrometry applications for structural biology. Here, we evaluate the kinetic stability of native-like protein ions using time-dependent, tandem ion mobility (IM). In these tandem IM experiments, ions of interest are mobility-selected after a first dimension of IM and trapped for up to ∼14 s. Time-dependent, collision cross section distributions are then determined from separations in a second dimension of IM. In these experiments, monomeric protein ions exhibited structural changes specific to both protein and charge state, whereas large protein complexes did not undergo resolvable structural changes on the timescales of these experiments. We also performed energy-dependent experiments, i.e., collision-induced unfolding, as a comparison for time-dependent experiments to understand the extent of unfolding. Collision cross section values observed in energy-dependent experiments using high collision energies were significantly larger than those observed in time-dependent experiments, indicating that the structures observed in time-dependent experiments remain kinetically trapped and retain some memory of their solution-phase structure. Although structural evolution should be considered for highly charged, monomeric protein ions, these experiments demonstrate that higher-mass protein ions can have remarkable kinetic stability in the gas phase.

Impact of community health interventions on maternal and child health indicators in the upper east region of Ghana.

BACKGROUND: This paper reports on results of a health system strengthening implementation research initiative conducted the Upper East Region of northern Ghana. Transformative interventions to accelerate and strengthen the health delivery were implemented that included empowering community leaders and members to actively participate in health delivery, strengthening the referral systems through the provision of community transport systems, providing basic medical equipment to community clinics, and improving the skills of critical health staff through training. METHODS: A mixed method design was used to evaluate the impact of the interventions. A quantitative evaluation employed a flexible research design to test the effects of various component activities of the project. To assess impact, a pre-versus-post randomized cluster survey design was used. Qualitative research was conducted with focus group data and individual in depth interviews to gauge the views of various stakeholders associated with the implementation process. RESULTS: After intervention, significant improvements in key maternal and child health indicators such as antenatal and postnatal care coverage were observed and increases in the proportion of deliveries occurring in health facilities and assisted by skilled health personnel relative to pre-intervention conditions. There was also increased uptake of oral rehydration salts (ORS) for treatment of childhood diarrhoea, as well as marked reductions in the incidence of upper respiratory infections (URI). CONCLUSIONS: A pre-and post-evaluation of impact suggests that the programme had a strong positive impact on the functioning of primary health care. Findings are consistent with the proposition that the coverage and content of the Ghana Community-based Health Planning and Services programme was improved by program interventions and induced discernable changes in key indicators of health system performance.

A public health crisis in the university: Impact of crisis response strategies on universities' transparency and post-crisis relationships during COVID 19 pandemic.

During the COVID 19 pandemic, one of the most critical tasks of the university was to effectively communicate with students, faculty, and staff members. This study aims to explore perceived universities' crisis response messages during the pandemic and examine the effectiveness of each response strategy on public relations outcomes. A survey with 346 university students in the U.S., results showed how defensive and accommodative response strategies differently affected PR outcomes. Accommodative strategies generated higher OPR and greater perceived transparency efforts among students, while several defensive strategies affected students' negative evaluations on post-crisis OPR and perceived transparency of their universities. Such results revealed valuable insights that make significant contributions to theory and practices in university crisis communication and management, especially when dealing with public health crises that are seen as external locus of control.

Evidence That Antibiotics Bind to Human Mitochondrial Ribosomal RNA Has Implications for Aminoglycoside Toxicity.

Aminoglycosides are a well known antibiotic family used to treat bacterial infections in humans and animals, but which can be toxic. By binding to the decoding site of helix44 of the small subunit RNA of the bacterial ribosome, the aminoglycoside antibiotics inhibit protein synthesis, cause misreading, or obstruct peptidyl-tRNA translocation. Although aminoglycosides bind helix69 of the bacterial large subunit RNA as well, little is known about their interaction with the homologous human helix69. To probe the role this binding event plays in toxicity, changes to thermal stability, base stacking, and conformation upon aminoglycoside binding to the human cytoplasmic helix69 were compared with those of the human mitochondrial and Escherichia coli helix69. Surprisingly, binding of gentamicin and kanamycin A to the chemically synthesized terminal hairpins of the human cytoplasmic, human mitochondrial, and E. coli helix69 revealed similar dissociation constants (1.3-1.7 and 4.0-5.4 µM, respectively). In addition, aminoglycoside binding enhanced conformational stability of the human mitochondrial helix69 by increasing base stacking. Proton one-dimensional and two-dimensional NMR suggested significant and specific conformational changes of human mitochondrial and E. coli helix69 upon aminoglycoside binding, as compared with human cytoplasmic helix69. The conformational changes and similar aminoglycoside binding affinities observed for human mitochondrial helix69 and E. coli helix69, as well as the increase in structural stability shown for the former, suggest that this binding event is important to understanding aminoglycoside toxicity.

Prevalence of and Factors Related to Discordance About Prognosis Between Physicians and Surrogate Decision Makers of Critically Ill Patients.

IMPORTANCE: Misperceptions about prognosis by individuals making decisions for incapacitated critically ill patients (surrogates) are common and often attributed to poor comprehension of medical information. OBJECTIVE: To determine the prevalence of and factors related to physician-surrogate discordance about prognosis in intensive care units (ICUs). DESIGN, SETTING, AND PARTICIPANTS: Mixed-methods study comprising quantitative surveys and qualitative interviews conducted in 4 ICUs at a major US medical center involving surrogate decision makers and physicians caring for patients at high risk of death from January 4, 2005, to July 10, 2009. MAIN OUTCOMES AND MEASURES: Discordance about prognosis, defined as a difference between a physician's and a surrogate's prognostic estimates of at least 20%; misunderstandings by surrogates (defined as any difference between a physician's prognostic estimate and a surrogate's best guess of that estimate); differences in belief (any difference between a surrogate's actual estimate and their best guess of the physician's estimate). RESULTS: Two hundred twenty-nine surrogate decision makers (median age, 47 [interquartile range {IQR}, 35-56] years; 68% women) and 99 physicians were involved in the care of 174 critically ill patients (median age, 60 [IQR, 47-74] years; 44% women). Physician-surrogate discordance about prognosis occurred in 122 of 229 instances (53%; 95% CI, 46.8%-59.7%). In 65 instances (28%), discordance was related to both misunderstandings by surrogates and differences in belief about the patient's prognosis; 38 (17%) were related to misunderstandings by surrogates only; 7 (3%) were related to differences in belief only; and data were missing for 12. Seventy-five patients (43%) died. Surrogates' prognostic estimates were much more accurate than chance alone, but physicians' prognostic estimates were statistically significantly more accurate than surrogates' (C statistic, 0.83 vs 0.74; absolute difference, 0.094; 95% CI, 0.024-0.163; P = .008). Among 71 surrogates interviewed who had beliefs about the prognosis that were more optimistic than that of the physician, the most common reasons for optimism were a need to maintain hope to benefit the patient (n = 34), a belief that the patient had unique strengths unknown to the physician (n = 24), and religious belief (n = 19). CONCLUSIONS AND RELEVANCE: Among critically ill patients, discordant expectations about prognosis were common between patients' physicians and surrogate decision makers and were related to misunderstandings by surrogates about physicians' assessments of patients' prognoses and differences in beliefs about patients' prognoses.

Mollifying green skepticism: Effective strategies for inspiring green participation in the hospitality industry.

Environmental awareness is a growing concern for consumers, and effective green messaging strategies are crucial for businesses. This 2 × 2 between-subject experiment investigates the influence of message style and sidedness on consumer participation in green practices and explores the role of message usefulness and skepticism. Our results show that a narrative message style and a two-sided message increase perceived usefulness, reduce skepticism, and lead to greater behavioral intent. Further, the study supports the moderated serial mediation role of message usefulness and skepticism. These findings offer significant implications for businesses seeking to promote sustainable practices and engage consumers in green initiatives.

Temperature and Host Plant Impacts on the Development of Spodoptera litura (Fabricius) (Lepidoptera: Noctuidae): Linear and Nonlinear Modeling.

The tobacco cutworm, Spodoptera litura (Fabricius) (Lepidoptera: Noctuidae), is one of the most serious pests in field crops, vegetables, and ornamentals. Temperatures (15, 20, 25, 27, 30, 35, and 40 °C), host plants (soybean (Glycine max (L.)), maize (Zea mays L.), groundnut (Arachis hypogaea L.) and azuki bean (Vigna angularis (Willd.) Ohwi & H. Ohashi,), and the artificial diet-dependent developmental parameters and survival of S. litura were examined in this study. Stage-specific parameters such as threshold development temperature (LDT) and thermal constant (K) (Degree day (DD)) were determined by linear and nonlinear models (Sharpe-Schoolfield-Ikemoto), respectively. The total developmental time (egg-adult) decreased with increasing temperature on host plants and with an artificial diet. The total immature developmental time varied from 106.29, 107.57, 130.40, 111.82, and 103.66 days at 15 °C to 22.47, 21.25, 25.31, 18.30, and 22.50 days at 35 °C on soybean, maize, groundnut, azuki bean, and artificial diet, respectively. The LDT for the total immature completion was 7.50, 9.48, 11.44, 12.32, and 7.95 °C on soybean, maize, groundnut, azuki bean, and artificial diet, respectively. The K for the total immature completion was 587.88, 536.84, 517.45, 419.44, and 586.95 DD on soybean, maize, groundnut, azuki bean, and artificial diet, respectively. Temperature and host plant interaction also influenced the longevity and survival of adults. The findings of this study can be used to predict the number of generations, spring emergence, and population dynamics of S. litura. The nutrient content analysis of the host plants is discussed in terms of the developmental patterns of S. litura.

Innovative approach to reveal source contribution of dissolved organic matter in a complex river watershed using end-member mixing analysis based on spectroscopic proxies and multi-isotopes.

Dissolved organic matter (DOM) in river watersheds dynamically changes based on its source during a monsoon period with storm event. However, the variations in DOM in urban and rural river watersheds that are dominated by point and non-point sources have not been adequately explored to date. We developed an innovative approach to reveal DOM sources in complex river watershed systems during pre-monsoon, monsoon, and post-monsoon periods using end-member mixing analysis (EMMA) by combining multi-isotope values (δ13C-DOC, δ15N-NO3 and δ18O-NO3) and spectroscopic indices (fluorescence index [FI], biological index [BIX], humification index [HIX], and specific UV absorbance [SUVA]). Several potential end-members of DOM sources were collected from watersheds, including top-soils, groundwater, plant group (fallen leaves, riparian plants, suspended algae), and different effluents (cattle and pig livestock, agricultural land, urban, industry facility, swine treatment facility and wastewater treatment facility). Concentrations of dissolved organic carbon, dissolved organic nitrogen, NO3-N, and NH4-N increased during the monsoon period with an increase in the input of anthropogenic DOM, which have higher HIX values owing to the flushing effect. The results of EMMA indicate that soil and agricultural effluents accounted for a substantial contribution of anthropogenic DOM at varying rates based on seasons. We also found that results of EMMA based on combining spectroscopic indices and δ13C-DOC isotope values were more accurate in tracing DOM sources with respect to land-use characteristics compared to applying only spectroscopic indices. The positive relationship between FI, BIX and δ15N-NO3 were revealed that nitrate would be decomposed from DOM affected by intensive agricultural activities. In addition, consistent with the EMMA results, the molecular composition of the DOM was clearly evidenced by a large number of CHON formulas, accounting for over 50% of the total characterized compounds, including pesticides and pharmaceuticals used in agriculture farmland and livestock. Our results clearly demonstrated that EMMA based on combing multi-stable isotopes and spectroscopic indices could be trace the DOM source, which is important for understanding changes in the DOM quality, and application of nitrate isotopes and molecular analysis supports in-depth interpretation. This study provides easy and intuitive techniques for the estimation of the relative impacts of DOM sources in complex river watersheds, which can be verified in various ways rather than relying on a single technique approach.

Introducing an Integrated Model of Adults' Wearable Activity Tracker Use and Obesity Information-Seeking Behaviors From a National Quota Sample Survey.

BACKGROUND: Research from multiple perspectives to investigate adults' use of wearable activity-tracking devices is limited. We offer a multiperspective model and provide empirical evidence of what leads to frequent usage of wearable health technologies from a large, nationally representative survey sample. OBJECTIVE: This study aims to explore factors affecting the use of wearable activity-tracking devices among health consumers from the perspectives of individual health beliefs (perceived severity, perceived susceptibility, perceived benefits, and self-efficacy) and information-seeking behaviors. METHODS: Our Integrated Model of Wearable Activity Tracker (IMWAT) use and proposed hypotheses were validated and tested with data collected from a telephone survey with a national quota sample. The data were analyzed using a variety of statistical techniques, including structural equation analysis. RESULTS: The sample comprised 2006 participants. Our results showed that the perceived benefits of physical activity, perceived susceptibility, and self-efficacy toward obesity were significant predictors of information-seeking behaviors, which, in turn, mediated their effects on the use of wearable activity trackers. Perceptions of obesity severity directly promoted wearable device usage. CONCLUSIONS: This study provided a new and powerful theoretical model that combined the health beliefs and information-seeking behaviors behind the use of wearable activity trackers in the adult population. The findings provide meaningful implications for developers and designers of wearable health technology products and will assist health informatics practitioners and obesity prevention communicators.

Prevalence of Macular Abnormalities Identified Only on Optical Coherence Tomography in Korean Patients Scheduled for Cataract Surgery.

PURPOSE: To assess the prevalence of macular abnormalities identified only on macular optical coherence tomography (OCT) which were not suspected by biomicroscopic fundus examination, and examine the clinical outcome of patients with these macular abnormalities during preoperative evaluation for cataract surgery in a large series of Korean patients.<br/>. METHODS: Macular OCT was performed on patients scheduled for routine cataract surgery by the same physician at Seoul St. Mary's Hospital, between June 2018 and November 2019. The patients' medical records were reviewed retrospectively to obtain demographic data and the results of preoperative evaluation before cataract surgery. Patients were divided into two groups based on the preoperative macular OCT. RESULTS: normal and abnormal OCT groups. RESULTS: Nine hundred eighty-seven eyes (698 patients) were included in this study. Macular OCT identified abnormalities in 44 eyes (4.5%) of 35 patients (5.0%). Twenty-one eyes (2.1%) had age-related macular degeneration, 20 eyes (2.0%) had epiretinal membrane, and three eyes (0.3%) had lamellar hole. Patients with macular abnormalities identified on macular OCT had a statistically significant higher mean age than those who had normal OCT findings (p < 0.001). Best-corrected visual acuity was worse in patients with abnormal macular OCT after cataract surgery (p = 0.048). CONCLUSIONS: In the preoperative evaluation for cataract surgery in Korean patients, one in every 20 patients had macular abnormalities identified only on macular OCT in spite of unremarkable macular findings on biomicroscopic funduscopy. Age was significantly higher in patients with abnormal macular OCT findings. Thus, inclusion of macular OCT examination in preoperative screening before routine cataract surgery would be beneficial.

Regional Differences in the Diets of Adélie and Emperor Penguins in the Ross Sea, Antarctica.

To identify the dietary composition and characteristics of both Adélie (Pygoscelis adeliae) and Emperor (Aptenodytes forsteri) penguins at four breeding sites, we performed stable carbon (δ13C) and nitrogen (δ15N) isotope analysis of down samples taken from penguin chicks. Adélie Penguin chicks at Cape Hallett mostly fed on Antarctic krill (Euphausia superba; 65.5 ± 3.5%), a reflection of the prevalence of that species near Cape Hallett, and no significant differences were noted between 2017 and 2018. However, Adélie Penguin chicks at Inexpressible Island, located near Terra Nova Bay, fed on both Antarctic silverfish (Pleuragramma antarctica; 42.5%) and ice krill (Euphausia crystallorophias; 47%), reflecting the high biomass observed in Terra Nova Bay. Meanwhile, no significant difference was noted between the two breeding sites of the Emperor Penguin. Emperor Penguin chicks predominantly fed on Antarctic silverfish (74.5 ± 2.1%) at both breeding sites (Cape Washington and Coulman Island), suggesting that diet preference represents the main factor influencing Emperor Penguin foraging. In contrast, the diet of the Adélie Penguin reflects presumed regional differences in prey prevalence, as inferred from available survey data.

Relationship between eyelid margin irregularity and meibomian gland dropout.

PURPOSE: To examine the relationship between lid margin abnormalities and meibomian gland loss in infrared meibography. METHODS: This study was a retrospective chart review of 170 patients with dry eye disease. A correlation analysis between eyelid margin abnormalities and meibomian gland dropout in infrared meibography was performed using data from 141 eyes. We graded the following eyelid margin abnormalities: irregular lid margin, vascular engorgement, plugging, anterior placement of the mucocutaneous junction, exposed terminal duct, and presence of tattoos. Multiple regression analyses were performed with meiboscore (meibomian gland dropout grade) as the dependent variable and age, sex, lid margin abnormality grades, and total grading score of lid margin abnormalities as the covariates. In addition, Meibomian glands structure were examined in those with eyelid margin dimpling using meibography in 25 eyes. RESULTS: In the multiple regression analysis, an irregular lid margin in the upper eyelid was associated with a higher meiboscore after controlling for age and sex (coefficients B = 1.379, p = 0.025). Other lid margin abnormalities did not significantly affect the meiboscore. In the lower eyelids, irregular lid margin (coefficients B = 0.602, p = 0.009) and total grading score of lid margin abnormality were associated with higher meiboscores (coefficients B = 0.100, p = 0.022). Of the 25 eyes with dimples, 21 (84%) showed focal or complete meibomian gland loss at the site. CONCLUSIONS: Lid margin abnormalities were found to be associated with meibomian gland dropout.

Why People Don't Use Facebook Anymore? An Investigation Into the Relationship Between the Big Five Personality Traits and the Motivation to Leave Facebook.

This study linked the big five personality traits with motivational factors to leave Facebook based on a survey of 218 former Facebook users. The big five were related with eight main factors retrieved from existing literature. Results showed that neuroticism was positively related to addiction, banality, peer pressure, and privacy while conscientiousness was negatively related to peer pressure, addiction, annoyance, and emergence of new platforms. Openness was positively related with banality but negatively with addiction and peer pressure. Theoretical and practical interpretations are also discussed.

Attenuated Visual Function in Patients with Major Depressive Disorder.

BACKGROUND: We sought to investigate visual function, primarily, and structural changes in retinal ganglion cells, secondarily, in patients with major depressive disorder. METHODS: A total of 50 normal participants and 49 patients with major depressive disorder were included in this cross-sectional study. The participants underwent 24-2 standard automated perimetry and spectral-domain optical coherence tomography. RESULTS: The pattern standard deviation (PSD) in the visual field test was higher in the major depressive disorder patients than in the normal control subjects (P = 0.017). The patients with major depressive disorder showed reduced minimum ganglion cell-inner plexiform layer (GCIPL) thickness relative to the normal control participants (P = 0.015). The average score on the Hamilton Depression Rating scale showed a significant correlation with the PSD, minimum GCIPL thickness, and inferior GCIPL thickness (r = 0.265, P = 0.009; r = -0.239, P = 0.017; and r = -0.204, P = 0.043, respectively). The multivariate analysis of factors associated with PSD showed old age and a high Hamilton Depression Rating score to be relevant (P = 0.002 and 0.028, respectively). CONCLUSIONS: Visual function was decreased and the GCIPL thickness was reduced in major depressive disorder patients. The retinal neurodegenerative process in depression might be considered in patients with depression.

Prognostic factors of cytomegalovirus retinitis after hematopoietic stem cell transplantation.

PURPOSE: To identify the visual prognostic factors in patients with cytomegalovirus (CMV) retinitis after hematopoietic stem cell transplantation (HSCT). METHODS: This retrospective cohort study included 4241 patients who underwent HSCT from April 1, 2010 to March 31, 2019 at Seoul St. Mary's Hospital. Of them, 1063 patients presented CMV viremia, and 67 patients (93 eyes) were diagnosed with CMV retinitis. We enrolled 66 patients (91 eyes). The main outcomes included the initial best-corrected visual acuity (BCVA), BCVA at the diagnosis of retinitis and last visit, involved retinal zone, peak CMV DNA levels in the peripheral blood and aqueous humor, time between HSCT and the diagnosis of retinitis, time between the diagnosis of viremia and retinitis, complications, recurrence, survival, and so on. RESULTS: The mean BCVA (logarithm of the minimum angle of resolution) values before HSCT, at the time of retinitis diagnosis, and at the last visit were 0.041 ± 0.076, 0.262 ± 0.529, and 0.309 ± 0.547, respectively. Multiple regression analysis revealed that the involved zone (P = 0.001), time between HSCT and retinitis diagnosis (P = 0.019), and survival status (P = 0.001) were associated with the final visual acuity. CONCLUSIONS: The final visual prognosis was worse in patients with greater invasion of the central retinal zone, those with a longer interval between HSCT and the diagnosis of retinitis, and those who died. Prompt diagnosis of CMV retinitis through periodic fundus examinations of patients with CMV viremia can prevent severe vision loss. Once CMV viremia is confirmed, we recommend fundus examinations to be immediately performed and repeated every 2 weeks for at least 2 months, even if the CMV DNA titer in the peripheral blood becomes negative.

Collision-Induced Unfolding Is Sensitive to the Polarity of Proteins and Protein Complexes.

Collision-induced unfolding (CIU) uses ion mobility to probe the structures of ions of proteins and noncovalent complexes as a function of the extent of gas-phase activation prior to analysis. CIU can be sensitive to domain structures, isoform identities, and binding partners, which makes it appealing for many applications. Almost all previous applications of CIU have probed cations. Here, we evaluate the application of CIU to anions and compare the results for anions with those for cations. Towards that end, we developed a "similarity score" that we used to quantify the differences between the results of different CIU experiments and evaluate the significance of those differences relative to the variance of the underlying measurements. Many of the differences between anions and cations that were identified can be attributed to the lower absolute charge states of anions. For example, the extents of the increase in collision cross section over the full range of energies depended strongly on absolute charge state. However, over intermediate energies, there are significant difference between anions and cations with the same absolute charge state. Therefore, CIU is sensitive to the polarity of protein ions. Based on these results, we propose that the utility of CIU to differentiate similar proteins or noncovalent complexes may also depend on polarity. More generally, these results indicate that the relationship between the structures and dynamics of native-like cations and anions deserve further attention and that future studies may benefit from integrating results from ions of both polarities.

The real you? The role of visual cues and comment congruence in perceptions of social attractiveness from facebook profiles.

The purpose of this study was to examine the effects of social cues in self-presentations and the congruence of other-generated comments with the self-presentation in people's evaluations of a profile owner. A 2 (level of social cues: high vs. low) × 2 (congruent vs. incongruent) × 2 (order) × 2 (multiple messages) mixed-subject experiment was conducted with 104 college students. The results showed that a profile owner was perceived less socially attractive when other-generated comments were incongruent with the profile owner's self-presentation. No matter how people package themselves with extravagant self-presentations, it cannot be very successful without validation from others. Interestingly, an interaction effect between congruence and the level of social cues suggested that perceived popularity was low in the incongruent condition regardless of level of social cue. Theoretical and practical implications were also discussed.