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1.
Nature ; 574(7777): 211-214, 2019 10.
Article in English | MEDLINE | ID: mdl-31597976

ABSTRACT

About ten per cent of 'massive' stars (those of more than 1.5 solar masses) have strong, large-scale surface magnetic fields1-3. It has been suggested that merging of main-sequence and pre-main-sequence stars could produce such strong fields4,5, and the predicted fraction of merged massive stars is also about ten per cent6,7. The merger hypothesis is further supported by a lack of magnetic stars in close binaries8,9, which is as expected if mergers produce magnetic stars. Here we report three-dimensional magnetohydrodynamical simulations of the coalescence of two massive stars and follow the evolution of the merged product. Strong magnetic fields are produced in the simulations, and the merged star rejuvenates such that it appears younger and bluer than other coeval stars. This can explain the properties of the magnetic 'blue straggler' star τ Sco in the Upper Scorpius association that has an observationally inferred, apparent age of less than five million years, which is less than half the age of its birth association10. Such massive blue straggler stars seem likely to be progenitors of magnetars, perhaps giving rise to some of the enigmatic fast radio bursts observed11, and their supernovae may be affected by their strong magnetic fields12.

2.
J Neurosci ; 43(50): 8700-8722, 2023 12 13.
Article in English | MEDLINE | ID: mdl-37903594

ABSTRACT

Social communication is crucial for the survival of many species. In most vertebrates, a dedicated chemosensory system, the vomeronasal system (VNS), evolved to process ethologically relevant chemosensory cues. The first central processing stage of the VNS is the accessory olfactory bulb (AOB), which sends information to downstream brain regions via AOB mitral cells (AMCs). Recent studies provided important insights about the functional properties of AMCs, but little is known about the principles that govern their coordinated activity. Here, we recorded local field potentials (LFPs) and single-unit activity in the AOB of adult male and female mice during presentation of natural stimuli. Our recordings reveal prominent LFP theta-band oscillatory episodes with a characteristic spatial pattern across the AOB. Throughout an experiment, the AOB network shows varying degrees of similarity to this pattern, in a manner that depends on the sensory stimulus. Analysis of LFP signal polarity and single-unit activity indicates that oscillatory episodes are generated locally within the AOB, likely representing a reciprocal interaction between AMCs and granule cells. Notably, spike times of many AMCs are constrained to the negative LFP oscillation phase in a manner that can drastically affect integration by downstream processing stages. Based on these observations, we propose that LFP oscillations may gate, bind, and organize outgoing signals from individual AOB neurons to downstream processing stages. Our findings suggest that, as in other neuronal systems and brain regions, population-level oscillations play a key role in organizing and enhancing transmission of socially relevant chemosensory information.SIGNIFICANCE STATEMENT The accessory olfactory bulb (AOB) is the first central stage of the vomeronasal system, a chemosensory system dedicated to processing cues from other organisms. Information from the AOB is conveyed to other brain regions via activity of its principal neurons, AOB mitral cells (AMCs). Here, we show that socially relevant sensory stimulation of the mouse vomeronasal system leads not only to changes in AMC activity, but also to distinct theta-band (∼5 Hz) oscillatory episodes in the local field potential. Notably AMCs favor the negative phase of these oscillatory events. Our findings suggest a novel mechanism for the temporal coordination of distributed patterns of neuronal activity, which can serve to efficiently activate downstream processing stages.


Subject(s)
Neurons , Olfactory Bulb , Mice , Male , Female , Animals , Olfactory Bulb/physiology , Neurons/physiology , Cues
3.
J Struct Biol ; : 108131, 2024 Oct 03.
Article in English | MEDLINE | ID: mdl-39368677

ABSTRACT

Amelogenin is an intrinsically disordered protein essential to tooth enamel formation in mammals. Using the latest, advanced small angle X-ray scattering (SAXS) capabilities at synchrotrons and computational models, we revisited measuring the quaternary structure of murine amelogenin as a function of pH and phosphorylation at Ser-16. The SAXS data shows that at the pH extremes, amelogenin exists as an extended monomer at pH 3.0 (Rg = 38.4 Å) and nanospheres at pH 8.0 (Rg = 84.0 Å), consistent with multiple previous observations. At pH 5.0 and above there was no evidence for a significant population of monomeric species. Instead, at pH 5.0 ∼ 80% of the population is a heterogenous dimeric species that increases to ∼ 100% at pH 5.5. The dimer population was observed at all pH > 5 conditions in dynamic equilibrium with a species in the pentamer range at pH < 6.5 and nanospheres at pH 8.0. At pH 8.0 ∼ 40% of the amelogenin remained in the dimeric state. In general, serine-16 phosphorylation of amelogenin appears to modestly stabilize the population of the dimeric species.

4.
Neuroimage ; 300: 120860, 2024 Oct 15.
Article in English | MEDLINE | ID: mdl-39332748

ABSTRACT

PURPOSE: 2-Fluorodeoxyglucose-PET (FDG-PET) is a powerful tool to study glucose metabolism in mammalian brains, but cellular sources of glucose uptake and metabolic connectivity during aging are not yet understood. METHODS: Healthy wild-type mice of both sexes (2-21 months of age) received FDG-PET and cell sorting after in vivo tracer injection (scRadiotracing). FDG uptake per cell was quantified in isolated microglia, astrocytes and neurons. Cerebral FDG uptake and metabolic connectivity were determined by PET. A subset of mice received measurement of blood glucose levels to study associations with cellular FDG uptake during aging. RESULTS: Cerebral FDG-PET signals in healthy mice increased linearly with age. Cellular FDG uptake of neurons increased between 2 and 12 months of age, followed by a strong decrease towards late ages. Contrarily, FDG uptake in microglia and astrocytes exhibited a U-shaped function with respect to age, comprising the predominant cellular source of higher cerebral FDG uptake in the later stages. Metabolic connectivity was closely associated with the ratio of glucose uptake in astroglial cells relative to neurons. Cellular FDG uptake was not associated with blood glucose levels and increasing FDG brain uptake as a function of age was still observed after adjusting for blood glucose levels. CONCLUSION: Trajectories of astroglial glucose uptake drive brain FDG-PET alterations and metabolic connectivity during aging.


Subject(s)
Astrocytes , Brain , Fluorodeoxyglucose F18 , Glucose , Mice, Inbred C57BL , Positron-Emission Tomography , Animals , Fluorodeoxyglucose F18/pharmacokinetics , Astrocytes/metabolism , Positron-Emission Tomography/methods , Mice , Glucose/metabolism , Male , Brain/metabolism , Brain/diagnostic imaging , Female , Aging/metabolism , Radiopharmaceuticals/pharmacokinetics , Neurons/metabolism , Healthy Aging/metabolism , Microglia/metabolism
5.
RNA ; 28(8): 1110-1127, 2022 08.
Article in English | MEDLINE | ID: mdl-35680167

ABSTRACT

Noncoding RNAs (ncRNAs) make up to ∼98% percent of the transcriptome of a given organism. In recent years, one relatively new class of ncRNAs, long noncoding RNAs (lncRNAs), were shown to be more than mere by-products of gene expression and regulation. The unicellular eukaryote Paramecium tetraurelia is a member of the ciliate phylum, an extremely heterogeneous group of organisms found in most bodies of water across the globe. A hallmark of ciliate genetics is nuclear dimorphism and programmed elimination of transposons and transposon-derived DNA elements, the latter of which is essential for the maintenance of the somatic genome. Paramecium and ciliates in general harbor a plethora of different ncRNA species, some of which drive the process of large-scale genome rearrangements, including DNA elimination, during sexual development. Here, we identify and validate the first known functional lncRNAs in ciliates to date. Using deep-sequencing and subsequent bioinformatic processing and experimental validation, we show that Paramecium expresses at least 15 lncRNAs. These candidates were predicted by a highly conservative pipeline, and informatic analyses hint at differential expression during development. Depletion of two lncRNAs, lnc1 and lnc15, resulted in clear phenotypes, decreased survival, morphological impairment, and a global effect on DNA elimination.


Subject(s)
Paramecium tetraurelia , RNA, Long Noncoding , Cell Nucleus/genetics , DNA Transposable Elements/genetics , Gene Rearrangement , Paramecium tetraurelia/genetics , RNA, Long Noncoding/genetics , RNA, Untranslated/genetics
6.
Glob Chang Biol ; 30(3): e17225, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38462708

ABSTRACT

It is well known that biodiversity positively affects ecosystem functioning, leading to enhanced ecosystem stability. However, this knowledge is mainly based on analyses using single ecosystem functions, while studies focusing on the stability of ecosystem multifunctionality (EMF) are rare. Taking advantage of a long-term grassland biodiversity experiment, we studied the effect of plant diversity (1-60 species) on EMF over 5 years, its temporal stability, as well as multifunctional resistance and resilience to a 2-year drought event. Using split-plot treatments, we further tested whether a shared history of plants and soil influences the studied relationships. We calculated EMF based on functions related to plants and higher-trophic levels. Plant diversity enhanced EMF in all studied years, and this effect strengthened over the study period. Moreover, plant diversity increased the temporal stability of EMF and fostered resistance to reoccurring drought events. Old plant communities with shared plant and soil history showed a stronger plant diversity-multifunctionality relationship and higher temporal stability of EMF than younger communities without shared histories. Our results highlight the importance of old and biodiverse plant communities for EMF and its stability to extreme climate events in a world increasingly threatened by global change.


Subject(s)
Ecosystem , Grassland , Biodiversity , Plants , Soil
7.
Phys Rev Lett ; 132(25): 256701, 2024 Jun 21.
Article in English | MEDLINE | ID: mdl-38996263

ABSTRACT

Converting angular momentum between different degrees of freedom within a magnetic material results from a dynamic interplay between electrons, magnons, and phonons. This interplay is pivotal to implementing spintronic device concepts that rely on spin angular momentum transport. We establish a new concept for long-range angular momentum transport that further allows us to address and isolate the magnonic contribution to angular momentum transport in a nanostructured metallic ferromagnet. To this end, we electrically excite and detect spin transport between two parallel and electrically insulated ferromagnetic metal strips on top of a diamagnetic substrate. Charge-to-spin current conversion within the ferromagnetic strip generates electronic spin angular momentum that is transferred to magnons via electron-magnon coupling. We observe a finite angular momentum flow to the second ferromagnetic strip across a diamagnetic substrate over micron distances, which is electrically detected in the second strip by the inverse charge-to-spin current conversion process. We discuss phononic and dipolar interactions as the likely cause to transfer angular momentum between the two strips. Moreover, our Letter provides the experimental basis to separate the electronic and magnonic spin transport and thereby paves the way towards magnonic device concepts that do not rely on magnetic insulators.

8.
J Gen Intern Med ; 39(11): 1962-1968, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38273069

ABSTRACT

BACKGROUND: There are no consistent data on US primary care clinicians and primary care practices owing to the lack of standard methods to identify them, hampering efforts in primary care improvement. METHODS: We develop a pragmatic framework that identifies primary care clinicians and practices in the context of the US healthcare system, and applied the framework to the IQVIA OneKey Healthcare Professional database to identify and profile primary care clinicians and practices in the USA. RESULTS: Our framework prescribes sequential steps to identify primary care clinicians by cross-examining clinician specialties and organizational affiliations, and then identify primary care practices based on organization types and presence of primary care clinicians. Applying this framework to the 2021 IQVIA data, we identified 365,751 physicians with a primary specialty in primary care, and after excluding those who further specialized (24%), served as hospitalists (5%), or worked in non-primary care settings (41%), we determined that 179,369 (49%) of them were actually practicing primary care. We identified 287,506 nurse practitioners and 134,083 physician assistants and determined that 88,574 (31%) and 29,781 (22%), respectively, were delivering primary care. We identified 94,489 primary care practices, and found that 45% of them were with one primary care physician, 15% had two physicians, 12% employed nurse practitioners or physician assistants only, and 19% employed both primary care physicians and specialists. CONCLUSIONS: Our approach offers a pragmatic and consistent alternative to the diverse methods currently used to identify and profile primary care workforce and organizations in the USA.


Subject(s)
Physicians, Primary Care , Primary Health Care , Humans , Primary Health Care/organization & administration , United States , Databases, Factual
9.
Langmuir ; 40(8): 4350-4360, 2024 Feb 27.
Article in English | MEDLINE | ID: mdl-38364791

ABSTRACT

Ceria nanomaterials with facile CeIII/IV redox behavior are used in sensing, catalytic, and therapeutic applications, where inclusion of CeIII has been correlated with reactivity. Understanding assembly pathways of CeO2 nanoparticles (NC-CeO2) in water has been challenged by "blind" synthesis, including rapid assembly/precipitation promoted by heat or strong base. Here, we identify a layered phase denoted Ce-I with a proposed formula CeIV(OH)3(NO3)·xH2O (x ≈ 2.5), obtained by adding electrolytes to aqueous cerium ammonium nitrate (CAN) to force precipitation. Ce-I represents intermediate hydrolysis species between dissolved CAN and NC-CeO2, where CAN is a commonly used CeIV compound that exhibits unusual aqueous and organic solubility. Ce-I features Ce-(OH)2-Ce units, representing the first step of hydrolysis toward NC-CeO2 formation, challenging prior assertions about CeIV hydrolysis. Structure/composition of poorly crystalline Ce-I was corroborated by a pair distribution function, Ce-L3 XAS (X-ray absorption spectroscopy), compositional analysis, and 17O nuclear magnetic resonance spectroscopy. Formation of Ce-I and its transformation to NC-CeO2 is documented in solution by small-angle X-ray scattering (SAXS) and in the solid-state by transmission electron microscopy (TEM) and powder X-ray diffraction. Morphologies identified by TEM support form factor models for SAXS analysis, evidencing the incipient assembly of Ce-I. Finally, two morphologies of NC-CeO2 are identified. Sequentially, spherical NC-CeO2 particles coexist with Ce-I, and asymmetric NC-CeO2 with up to 35% CeIII forms at the expense of Ce-I, suggesting direct replacement.

10.
Ann Fam Med ; 22(3): 244-246, 2024 May 28.
Article in English | MEDLINE | ID: mdl-38429105

ABSTRACT

The United States is facing a social isolation and loneliness crisis. In response, the US Surgeon General issued an advisory in May 2023 recommending actions that health care, community programs, and social services can take to collaboratively improve social connection. Primary care has a critical role to play in implementing the Surgeon General's recommendations. We present social isolation and loneliness as medical issues and highlight next steps for the primary care sector to combat this epidemic.Annals Early Access article.


Subject(s)
Loneliness , Primary Health Care , Social Isolation , Humans , Loneliness/psychology , Social Isolation/psychology , United States , COVID-19/psychology , COVID-19/epidemiology , Epidemics
11.
Environ Res ; 257: 119238, 2024 Sep 15.
Article in English | MEDLINE | ID: mdl-38815717

ABSTRACT

BACKGROUND: Despite plausible behavioral and physiological pathways, limited evidence exists on how daily temperature variability is associated with acute mental health-related episodes. OBJECTIVES: We aimed to explore associations between daily temperature range (DTR) and mental health-related hospital visits using data of all hospital records in New York State during 1995-2014. We further examined factors that may modify these associations, including age, sex, hospital visit type and season. METHODS: Using a case-crossover design with distributed lag non-linear DTR terms (0-6 days), we estimated associations between ZIP Code-level DTR and hospital visits for mood (4.6 million hospital visits), anxiety (2.4 million), adjustment (∼368,000), and schizophrenia disorders (∼211,000), controlling for daily mean temperature, via conditional logistic regression models. We assessed potential heterogeneity by age, sex, hospital visit type (in-patient vs. out-patient), and season (summer, winter, and transition seasons). RESULTS: For all included outcomes, we observed positive associations from period minimum DTR (0.1 °C) until 25th percentile (5.2 °C) and between mean DTR (7.7 °C) and 90th percentile (12.2 °C), beyond which we observed negative associations. For mood disorders, an increase in DTR from 0.1 °C to 12.2 °C was associated with a cumulative 16.0% increase (95% confidence interval [CI]: 12.8, 19.2%) in hospital visit rates. This increase was highest during transition seasons (32.5%; 95%CI: 26.4, 39.0%) compared with summer (10.7%; 95%CI: 4.8, 16.8%) and winter (-1.6%; 95%CI: -7.6, 4.7%). For adjustment and schizophrenia disorders, the strongest associations were seen among the youngest group (0-24 years) with almost no association in the oldest group (65+ years). We observed no evidence for modification by sex and hospital visit type. DISCUSSION: Daily temperature variability was positively associated with mental health-related hospital visits within specific DTR ranges in New York State, after controlling for daily mean temperature. Given uncertainty on how climate change modifies temperature variability, additional research is crucial to comprehend the implications of these findings, particularly under different scenarios of future temperature variability.


Subject(s)
Temperature , New York , Humans , Male , Female , Middle Aged , Adult , Aged , Young Adult , Adolescent , Seasons , Mental Disorders/epidemiology , Hospitalization/statistics & numerical data , Cross-Over Studies , Mental Health/statistics & numerical data , Schizophrenia/epidemiology , Child , Child, Preschool
12.
J Acoust Soc Am ; 155(4): 2875-2890, 2024 04 01.
Article in English | MEDLINE | ID: mdl-38682913

ABSTRACT

Numerical simulations of head-related transfer functions (HRTFs) conventionally assume a rigid boundary condition for the pinna. The human pinna, however, is an elastic deformable body that can vibrate due to incident acoustic waves. This work investigates how sound-induced vibrations of the pinna can affect simulated HRTF magnitudes. The work will motivate the research question by measuring the sound-induced vibrational patterns of an artificial pinna with a high-speed holographic interferometric system. Then, finite element simulations are used to determine HRTFs for a tabletop model of the B&K 5128 head and torso simulator for a number of directions. Two scenarios are explored: one where the pinna is modeled as perfectly rigid, and another where the pinna is modeled as linear elastic with material properties close to that of auricular cartilage. The findings suggest that pinna vibrations have negligible effects on HRTF magnitudes up to 5 kHz. The same conclusion, albeit with less certainty, is drawn for higher frequencies. Finally, the importance of the elastic domain's material properties is emphasized and possible implications for validation studies on dummy heads 1as well as the limitations of the present work are discussed in detail.


Subject(s)
Computer Simulation , Ear Auricle , Finite Element Analysis , Head , Sound , Vibration , Humans , Ear Auricle/physiology , Ear Auricle/anatomy & histology , Head/physiology , Head/anatomy & histology , Holography/methods , Interferometry/methods , Elasticity , Numerical Analysis, Computer-Assisted , Models, Biological , Motion , Acoustic Stimulation
13.
Phytochem Anal ; 2024 Jul 21.
Article in English | MEDLINE | ID: mdl-39034429

ABSTRACT

INTRODUCTION: Untargeted metabolomics is a powerful tool that provides strategies for gaining a systematic understanding of quantitative changes in the levels of metabolites, especially when combining different metabolomic platforms. Vanilla is one of the world's most popular flavors originating from cured pods of the orchid Vanilla planifolia. However, only a few studies have investigated the metabolome of V. planifolia, and no LC-MS or GC-MS metabolomics studies with respect to leaves have been performed. OBJECTIVE: The aim of the study was to comprehensively characterize the metabolome of different organs (leaves, internodes, and aerial roots) of V. planifolia. MATERIAL AND METHODS: Characterization of the metabolome was achieved using two complementary platforms (GC × GC-MS, LC-QToF-MS), and metabolite identification was based on a comparison with in-house databases or curated external spectral libraries. RESULTS: In total, 127 metabolites could be identified with high certainty (confidence level 1 or 2) including sugars, amino acids, fatty acids, organic acids, and amines/amides but also secondary metabolites such as vanillin-related metabolites, flavonoids, and terpenoids. Ninty-eight metabolites showed significantly different intensities between the plant organs. Most strikingly, aglycons of flavonoids and vanillin-related metabolites were elevated in aerial roots, whereas its O-glycoside forms tended to be higher in leaves and/or internodes. This suggests that the more bioactive aglycones may accumulate where preferably needed, e.g. for defense against pathogens. CONCLUSION: The results derived from the study substantially expand the knowledge regarding the vanilla metabolome forming a valuable basis for more targeted investigations in future studies, e.g. towards an optimization of vanilla plant cultivation.

14.
Gesundheitswesen ; 86(4): 263-273, 2024 Apr.
Article in German | MEDLINE | ID: mdl-38579731

ABSTRACT

BACKGROUND: Memory clinics can contribute significantly to a qualified diagnosis of dementia. Since the accessibility of medical facilities is an important predictor for their utilisation, the aim of this study was to determine the accessibility of memory clinics for persons with dementia in Bavaria. METHODS: We used a Geographic Information System (GIS) to determine travel times to the nearest memory clinic for all Bavarian municipalities based on OpenStreetMap road network data. RESULTS: The majority of the modelled persons with dementia in Bavaria (40%; n = 93,950) live in communities with an average travel time of 20 to 40 minutes to the nearest memory clinic. Almost 7,000 (3%) require more than one hour. Especially persons from rural communities have to travel significantly longer distances than people from urban areas. CONCLUSION: In view of demographic developments, there is an urgent need for memory clinics to be accessible throughout the country for all persons with dementia, regardless of where they live. The systematic development of memory clinics in areas with long travel times or the establishment of mobile diagnostic services could help to improve dementia care.


Subject(s)
Dementia , Travel , Humans , Germany/epidemiology , Geographic Information Systems , Ambulatory Care Facilities , Health Services Accessibility , Dementia/diagnosis , Dementia/epidemiology
15.
J Am Chem Soc ; 145(14): 7800-7809, 2023 Apr 12.
Article in English | MEDLINE | ID: mdl-36976754

ABSTRACT

Covalent organic frameworks (COFs) have emerged as versatile platforms for the separation and storage of hazardous gases. Simultaneously, the synthetic toolbox to tackle the "COF trilemma" has been diversified to include topochemical linkage transformations and post-synthetic stabilization strategies. Herein, we converge these themes and reveal the unique potential of nitric oxide (NO) as a new reagent for the scalable gas-phase transformation of COFs. Using physisorption and solid-state nuclear magnetic resonance spectroscopy on 15N-enriched COFs, we study the gas uptake capacity and selectivity of NO adsorption and unravel the interactions of NO with COFs. Our study reveals the clean deamination of terminal amine groups on the particle surfaces by NO, exemplifying a unique surface passivation strategy for COFs. We further describe the formation of a NONOate linkage by the reaction of NO with an amine-linked COF, which shows controlled release of NO under physiological conditions. NONOate-COFs thus show promise as tunable NO delivery platforms for bioregulatory NO release in biomedical applications.

16.
J Am Chem Soc ; 145(24): 13241-13248, 2023 Jun 21.
Article in English | MEDLINE | ID: mdl-37231627

ABSTRACT

Herein, we report a facile postsynthetic linkage conversion method giving synthetic access to nitrone-linked covalent organic frameworks (COFs) from imine- and amine-linked COFs. The new two-dimensional (2D) nitrone-linked covalent organic frameworks, NO-PI-3-COF and NO-TTI-COF, are obtained with high crystallinity and large surface areas. Nitrone-modified pore channels induce condensation of water vapor at 20% lower humidity compared to their amine- or imine-linked precursor COFs. Thus, the topochemical transformation to nitrone linkages constitutes an attractive approach to postsynthetically fine-tune water adsorption properties in framework materials.

17.
Am J Epidemiol ; 192(4): 644-657, 2023 04 06.
Article in English | MEDLINE | ID: mdl-36562713

ABSTRACT

Distributed lag models (DLMs) are often used to estimate lagged associations and identify critical exposure windows. In a simulation study of prenatal nitrogen dioxide (NO2) exposure and birth weight, we demonstrate that bias amplification and variance inflation can manifest under certain combinations of DLM estimation approaches and time-trend adjustment methods when using low-spatial-resolution exposures with extended lags. Our simulations showed that when using high-spatial-resolution exposure data, any time-trend adjustment method produced low bias and nominal coverage for the distributed lag estimator. When using either low- or no-spatial-resolution exposures, bias due to time trends was amplified for all adjustment methods. Variance inflation was higher in low- or no-spatial-resolution DLMs when using a long-term spline to adjust for seasonality and long-term trends due to concurvity between a distributed lag function and secular function of time. NO2-birth weight analyses in a Massachusetts-based cohort showed that associations were negative for exposures experienced in gestational weeks 15-30 when using high-spatial-resolution DLMs; however, associations were null and positive for DLMs with low- and no-spatial-resolution exposures, respectively, which is likely due to bias amplification. DLM analyses should jointly consider the spatial resolution of exposure data and the parameterizations of the time trend adjustment and lag constraints.


Subject(s)
Air Pollutants , Air Pollution , Pregnancy , Female , Humans , Air Pollutants/analysis , Particulate Matter/analysis , Birth Weight , Nitrogen Dioxide
18.
J Neuroinflammation ; 20(1): 47, 2023 Feb 24.
Article in English | MEDLINE | ID: mdl-36829182

ABSTRACT

AIM: We aimed to investigate the impact of microglial activity and microglial FDG uptake on metabolic connectivity, since microglial activation states determine FDG-PET alterations. Metabolic connectivity refers to a concept of interacting metabolic brain regions and receives growing interest in approaching complex cerebral metabolic networks in neurodegenerative diseases. However, underlying sources of metabolic connectivity remain to be elucidated. MATERIALS AND METHODS: We analyzed metabolic networks measured by interregional correlation coefficients (ICCs) of FDG-PET scans in WT mice and in mice with mutations in progranulin (Grn) or triggering receptor expressed on myeloid cells 2 (Trem2) knockouts (-/-) as well as in double mutant Grn-/-/Trem2-/- mice. We selected those rodent models as they represent opposite microglial signatures with disease associated microglia in Grn-/- mice and microglia locked in a homeostatic state in Trem2-/- mice; however, both resulting in lower glucose uptake of the brain. The direct influence of microglia on metabolic networks was further determined by microglia depletion using a CSF1R inhibitor in WT mice at two different ages. Within maps of global mean scaled regional FDG uptake, 24 pre-established volumes of interest were applied and assigned to either cortical or subcortical networks. ICCs of all region pairs were calculated and z-transformed prior to group comparisons. FDG uptake of neurons, microglia, and astrocytes was determined in Grn-/- and WT mice via assessment of single cell tracer uptake (scRadiotracing). RESULTS: Microglia depletion by CSF1R inhibition resulted in a strong decrease of metabolic connectivity defined by decrease of mean cortical ICCs in WT mice at both ages studied (6-7 m; p = 0.0148, 9-10 m; p = 0.0191), when compared to vehicle-treated age-matched WT mice. Grn-/-, Trem2-/- and Grn-/-/Trem2-/- mice all displayed reduced FDG-PET signals when compared to WT mice. However, when analyzing metabolic networks, a distinct increase of ICCs was observed in Grn-/- mice when compared to WT mice in cortical (p < 0.0001) and hippocampal (p < 0.0001) networks. In contrast, Trem2-/- mice did not show significant alterations in metabolic connectivity when compared to WT. Furthermore, the increased metabolic connectivity in Grn-/- mice was completely suppressed in Grn-/-/Trem2-/- mice. Grn-/- mice exhibited a severe loss of neuronal FDG uptake (- 61%, p < 0.0001) which shifted allocation of cellular brain FDG uptake to microglia (42% in Grn-/- vs. 22% in WT). CONCLUSIONS: Presence, absence, and activation of microglia have a strong impact on metabolic connectivity of the mouse brain. Enhanced metabolic connectivity is associated with increased microglial FDG allocation.


Subject(s)
Fluorodeoxyglucose F18 , Microglia , Animals , Mice , Microglia/metabolism , Fluorodeoxyglucose F18/metabolism , Progranulins/metabolism , Brain/metabolism , Positron-Emission Tomography , Membrane Glycoproteins/metabolism , Receptors, Immunologic/metabolism
19.
Nat Mater ; 21(3): 345-351, 2022 03.
Article in English | MEDLINE | ID: mdl-34845364

ABSTRACT

Progress in understanding crystallization pathways depends on the ability to unravel relationships between intermediates and final crystalline products at the nanoscale, which is a particular challenge at elevated pressure and temperature. Here we exploit a high-pressure atomic force microscope to directly visualize brucite carbonation in water-bearing supercritical carbon dioxide (scCO2) at 90 bar and 50 °C. On introduction of water-saturated scCO2, in situ visualization revealed initial dissolution followed by nanoparticle nucleation consistent with amorphous magnesium carbonate (AMC) on the surface. This is followed by growth of nesquehonite (MgCO3·3H2O) crystallites. In situ imaging provided direct evidence that the AMC intermediate acts as a seed for crystallization of nesquehonite. In situ infrared and thermogravimetric-mass spectrometry indicate that the stoichiometry of AMC is MgCO3·xH2O (x = 0.5-1.0), while its structure is indicated to be hydromagnesite-like according to density functional theory and X-ray pair distribution function analysis. Our findings thus provide insight for understanding the stability, lifetime and role of amorphous intermediates in natural and synthetic systems.


Subject(s)
Carbon Dioxide , Magnesium Hydroxide , Carbon Dioxide/chemistry , Carbonates , Magnesium Hydroxide/chemistry , Temperature , Water/chemistry
20.
Epidemiology ; 34(5): 700-711, 2023 09 01.
Article in English | MEDLINE | ID: mdl-37255240

ABSTRACT

BACKGROUND: People using electricity-dependent durable medical equipment (DME) may be vulnerable to health effects from wildfire smoke, residence near wildfires, or residence in evacuation zones. To our knowledge, no studies have examined their healthcare utilization during wildfires. METHODS: We obtained 2016-2020 counts of residential Zip Code Tabulation Area (ZCTA) level outpatient, emergency department (ED), and inpatient visits made by DME-using Kaiser Permanente Southern California members 45+. We linked counts to daily ZCTA-level wildfire particulate matter (PM) 2.5 and wildfire boundary and evacuation data from the 2018 Woolsey and 2019 Getty wildfires. We estimated the association of lagged (up to 7 days) wildfire PM 2.5 and residence near a fire or in an evacuation zone and healthcare visit frequency with negative binomial and difference-in-differences models. RESULTS: Among 236,732 DME users, 10 µg/m 3 increases in wildfire PM 2.5 concentration were associated with the reduced rate (RR = 0.96; 95% confidence interval [CI] = 0.94, 0.99) of all-cause outpatient visits 1 day after exposure and increased rate on 4 of 5 subsequent days (RR range 1.03-1.12). Woolsey Fire proximity (<20 km) was associated with reduced all-cause outpatient visits, whereas evacuation and proximity were associated with increased inpatient cardiorespiratory visits (proximity RR = 1.45; 95% CI = 0.99, 2.12, evacuation RR = 1.72; 95% CI = 1.00, 2.96). Neither Getty Fire proximity nor evacuation was associated with healthcare visit frequency. CONCLUSIONS: Our results support the hypothesis that wildfire smoke or proximity interrupts DME users' routine outpatient care, via sheltering in place. However, wildfire exposures were also associated with increased urgent healthcare utilization in this vulnerable group.


Subject(s)
Air Pollutants , Wildfires , Humans , Air Pollutants/analysis , Durable Medical Equipment , Hospitalization , Environmental Exposure/adverse effects , Particulate Matter/analysis , Smoke/adverse effects , California/epidemiology
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