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1.
Nature ; 619(7970): 487-490, 2023 Jul.
Article in English | MEDLINE | ID: mdl-37468588

ABSTRACT

Several long-period radio transients have recently been discovered, with strongly polarized coherent radio pulses appearing on timescales between tens to thousands of seconds1,2. In some cases, the radio pulses have been interpreted as coming from rotating neutron stars with extremely strong magnetic fields, known as magnetars; the origin of other, occasionally periodic and less-well-sampled radio transients is still debated3. Coherent periodic radio emission is usually explained by rotating dipolar magnetic fields and pair-production mechanisms, but such models do not easily predict radio emission from such slowly rotating neutron stars and maintain it for extended times. On the other hand, highly magnetic isolated white dwarfs would be expected to have long spin periodicities, but periodic coherent radio emission has not yet been directly detected from these sources. Here we report observations of a long-period (21 min) radio transient, which we have labelled GPM J1839-10. The pulses vary in brightness by two orders of magnitude, last between 30 and 300 s and have quasiperiodic substructure. The observations prompted a search of radio archives and we found that the source has been repeating since at least 1988. The archival data enabled constraint of the period derivative to <3.6 × 10-13 s s-1, which is at the very limit of any classical theoretical model that predicts dipolar radio emission from an isolated neutron star.

2.
Nature ; 601(7894): 526-530, 2022 01.
Article in English | MEDLINE | ID: mdl-35082416

ABSTRACT

The high-frequency radio sky is bursting with synchrotron transients from massive stellar explosions and accretion events, but the low-frequency radio sky has, so far, been quiet beyond the Galactic pulsar population and the long-term scintillation of active galactic nuclei. The low-frequency band, however, is sensitive to exotic coherent and polarized radio-emission processes, such as electron-cyclotron maser emission from flaring M dwarfs1, stellar magnetospheric plasma interactions with exoplanets2 and a population of steep-spectrum pulsars3, making Galactic-plane searches a prospect for blind-transient discovery. Here we report an analysis of archival low-frequency radio data that reveals a periodic, low-frequency radio transient. We find that the source pulses every 18.18 min, an unusual periodicity that has, to our knowledge, not been observed previously. The emission is highly linearly polarized, bright, persists for 30-60 s on each occurrence and is visible across a broad frequency range. At times, the pulses comprise short-duration (<0.5 s) bursts; at others, a smoother profile is observed. These profiles evolve on timescales of hours. By measuring the dispersion of the radio pulses with respect to frequency, we have localized the source to within our own Galaxy and suggest that it could be an ultra-long-period magnetar.

3.
Proc Natl Acad Sci U S A ; 121(9): e2312587121, 2024 Feb 27.
Article in English | MEDLINE | ID: mdl-38381785

ABSTRACT

To ensure a robust immune response to pathogens without risking immunopathology, the kinetics and amplitude of inflammatory gene expression in macrophages need to be exquisitely well controlled. There is a growing appreciation for stress-responsive membraneless organelles (MLOs) regulating various steps of eukaryotic gene expression in response to extrinsic cues. Here, we implicate the nuclear paraspeckle, a highly ordered biomolecular condensate that nucleates on the Neat1 lncRNA, in tuning innate immune gene expression in murine macrophages. In response to a variety of innate agonists, macrophage paraspeckles rapidly aggregate (0.5 h poststimulation) and disaggregate (2 h poststimulation). Paraspeckle maintenance and aggregation require active transcription and MAPK signaling, whereas paraspeckle disaggregation requires degradation of Neat1 via the nuclear RNA exosome. In response to lipopolysaccharide treatment, Neat1 KO macrophages fail to properly express a large cohort of proinflammatory cytokines, chemokines, and antimicrobial mediators. Consequently, Neat1 KO macrophages cannot control replication of Salmonella enterica serovar Typhimurium or vesicular stomatitis virus. These findings highlight a prominent role for MLOs in orchestrating the macrophage response to pathogens and support a model whereby dynamic assembly and disassembly of paraspeckles reorganizes the nuclear landscape to enable inflammatory gene expression following innate stimuli.


Subject(s)
Paraspeckles , RNA, Long Noncoding , Humans , Animals , Mice , RNA, Long Noncoding/genetics , RNA, Long Noncoding/metabolism , Macrophages/metabolism
4.
N Engl J Med ; 386(4): 305-315, 2022 01 27.
Article in English | MEDLINE | ID: mdl-34937145

ABSTRACT

BACKGROUND: Remdesivir improves clinical outcomes in patients hospitalized with moderate-to-severe coronavirus disease 2019 (Covid-19). Whether the use of remdesivir in symptomatic, nonhospitalized patients with Covid-19 who are at high risk for disease progression prevents hospitalization is uncertain. METHODS: We conducted a randomized, double-blind, placebo-controlled trial involving nonhospitalized patients with Covid-19 who had symptom onset within the previous 7 days and who had at least one risk factor for disease progression (age ≥60 years, obesity, or certain coexisting medical conditions). Patients were randomly assigned to receive intravenous remdesivir (200 mg on day 1 and 100 mg on days 2 and 3) or placebo. The primary efficacy end point was a composite of Covid-19-related hospitalization or death from any cause by day 28. The primary safety end point was any adverse event. A secondary end point was a composite of a Covid-19-related medically attended visit or death from any cause by day 28. RESULTS: A total of 562 patients who underwent randomization and received at least one dose of remdesivir or placebo were included in the analyses: 279 patients in the remdesivir group and 283 in the placebo group. The mean age was 50 years, 47.9% of the patients were women, and 41.8% were Hispanic or Latinx. The most common coexisting conditions were diabetes mellitus (61.6%), obesity (55.2%), and hypertension (47.7%). Covid-19-related hospitalization or death from any cause occurred in 2 patients (0.7%) in the remdesivir group and in 15 (5.3%) in the placebo group (hazard ratio, 0.13; 95% confidence interval [CI], 0.03 to 0.59; P = 0.008). A total of 4 of 246 patients (1.6%) in the remdesivir group and 21 of 252 (8.3%) in the placebo group had a Covid-19-related medically attended visit by day 28 (hazard ratio, 0.19; 95% CI, 0.07 to 0.56). No patients had died by day 28. Adverse events occurred in 42.3% of the patients in the remdesivir group and in 46.3% of those in the placebo group. CONCLUSIONS: Among nonhospitalized patients who were at high risk for Covid-19 progression, a 3-day course of remdesivir had an acceptable safety profile and resulted in an 87% lower risk of hospitalization or death than placebo. (Funded by Gilead Sciences; PINETREE ClinicalTrials.gov number, NCT04501952; EudraCT number, 2020-003510-12.).


Subject(s)
Adenosine Monophosphate/analogs & derivatives , Alanine/analogs & derivatives , Antiviral Agents/therapeutic use , COVID-19 Drug Treatment , Adenosine Monophosphate/adverse effects , Adenosine Monophosphate/therapeutic use , Adult , Aged , Aged, 80 and over , Alanine/adverse effects , Alanine/therapeutic use , Antiviral Agents/adverse effects , COVID-19/complications , COVID-19/mortality , Comorbidity , Disease Progression , Double-Blind Method , Female , Hospitalization/statistics & numerical data , Humans , Male , Middle Aged , Outpatients , SARS-CoV-2/drug effects , Time-to-Treatment , Viral Load
5.
Genome Res ; 2022 Sep 15.
Article in English | MEDLINE | ID: mdl-36109147

ABSTRACT

The unicellular amoeba Acanthamoeba castellanii is ubiquitous in aquatic environments, where it preys on bacteria. The organism also hosts bacterial endosymbionts, some of which are parasitic, including human pathogens such as Chlamydia and Legionella spp. Here we report complete, high-quality genome sequences for two extensively studied A. castellanii strains, Neff and C3. Combining long- and short-read data with Hi-C, we generated near chromosome-level assemblies for both strains with 90% of the genome contained in 29 scaffolds for the Neff strain and 31 for the C3 strain. Comparative genomics revealed strain-specific functional enrichment, most notably genes related to signal transduction in the C3 strain and to viral replication in Neff. Furthermore, we characterized the spatial organization of the A. castellanii genome and showed that it is reorganized during infection by Legionella pneumophila Infection-dependent chromatin loops were found to be enriched in genes for signal transduction and phosphorylation processes. In genomic regions where chromatin organization changed during Legionella infection, we found functional enrichment for genes associated with metabolism, organelle assembly, and cytoskeleton organization. Given Legionella infection is known to alter its host's cell cycle, to exploit the host's organelles, and to modulate the host's metabolism in its favor, these changes in chromatin organization may partly be related to mechanisms of host control during Legionella infection.

6.
J Immunol ; 211(5): 767-781, 2023 09 01.
Article in English | MEDLINE | ID: mdl-37486212

ABSTRACT

The gut microbiome and intestinal immune system are engaged in a dynamic interplay that provides myriad benefits to host health. However, the microbiome can also elicit damaging inflammatory responses, and thus establishing harmonious immune-microbiome interactions is essential to maintain homeostasis. Gut microbes actively coordinate the induction of anti-inflammatory responses that establish these mutualistic interactions. Despite this, the microbial pathways that govern this dialogue remain poorly understood. We investigated the mechanisms through which the gut symbiont Bacteroides thetaiotaomicron exerts its immunomodulatory functions on murine- and human-derived cells. Our data reveal that B. thetaiotaomicron stimulates production of the cytokine IL-10 via secreted factors that are packaged into outer membrane vesicles, in a TLR2- and MyD88-dependent manner. Using a transposon mutagenesis-based screen, we identified a key role for the B. thetaiotaomicron-encoded NADH:ubiquinone oxidoreductase (NQR) complex, which regenerates NAD+ during respiration, in this process. Finally, we found that disruption of NQR reduces the capacity of B. thetaiotaomicron to induce IL-10 by impairing biogenesis of outer membrane vesicles. These data identify a microbial pathway with a previously unappreciated role in gut microbe-mediated immunomodulation that may be targeted to manipulate the capacity of the microbiome to shape host immunity.


Subject(s)
Bacteroides thetaiotaomicron , Mice , Humans , Animals , Interleukin-10/metabolism , Mutagenesis , Gastrointestinal Tract , Cytokines/metabolism
7.
Immunol Cell Biol ; 102(3): 211-224, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38288547

ABSTRACT

CD4+ forkhead box P3 (FOXP3)+ regulatory T cells (Tregs) are essential in maintaining immune tolerance and suppressing excessive immune responses. Tregs also contribute to tissue repair processes distinct from their roles in immune suppression. For these reasons, Tregs are candidates for targeted therapies for inflammatory and autoimmune diseases, and in diseases where tissue damage occurs. MT-2 cells, an immortalized Treg-like cell line, offer a model to study Treg biology and their therapeutic potential. In the present study, we use clustered regularly interspaced palindromic repeats (CRISPR)-mediated knockdown of FOXP3 in MT-2 cells to understand the transcriptional and functional changes that occur when FOXP3 is lost and to compare MT-2 cells with primary human Tregs. We demonstrate that loss of FOXP3 affects the transcriptome of MT-2 cells and that FOXP3's potential downstream targets include a wide range of transcripts that participate in the cell cycle, promote growth and contribute to inflammatory processes, but do not wholly simulate previously reported human primary Treg transcriptional changes in the absence of FOXP3. We also demonstrate that FOXP3 regulates cell cycling and proliferation, expression of molecules crucial to Treg function and MT-2 cell-suppressive activities. Thus, MT-2 cells offer opportunities to address regulatory T-cell functions in vitro.


Subject(s)
Immunosuppression Therapy , T-Lymphocytes, Regulatory , Humans , Cell Line , Immune Tolerance , Forkhead Transcription Factors/metabolism
8.
Glob Chang Biol ; 30(6): e17364, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38864329

ABSTRACT

Thermal regimes of aquatic ecosystems are predicted to change as climate warming progresses over the next century, with high-latitude and high-elevation regions predicted to be particularly impacted. Here, we have modelled alpine stream water temperatures from air temperature data and used future predicted air temperature trajectories (representative concentration pathway [rcp] 4.5 and 8.5) to predict future water temperatures. Modelled stream water temperatures have been used to calculate cumulative degree days (CDDs) under current and future climate conditions. These calculations show that degree days will accumulate more rapidly under the future climate scenarios, and with a stronger effect for higher CDD values (e.g., rcp 4.5: 18-28 days earlier [CDD = 500]; 42-55 days earlier [CDD = 2000]). Changes to the time to achieve specific CDDs may have profound and unexpected consequences for alpine ecosystems. Our calculations show that while the effect of increased CDDs may be relatively small for organisms that emerge in spring-summer, the effects for organisms emerging in late summer-autumn may be substantial. For these organisms, the air temperatures experienced upon emergence could reach 9°C (rcp 4.5) or 12°C (rcp 8.5) higher than under current climate conditions, likely impacting on the metabolism of adults, the availability of resources, including food and suitable oviposition habitat, and reproductive success. Given that the movement of aquatic fauna to the terrestrial environment represents an important flux of energy and nutrients, differential changes in the time periods to achieve CDDs for aquatic and terrestrial fauna may de-couple existing predator-prey interactions.


Subject(s)
Climate Change , Rivers , Temperature , Animals , Aquatic Organisms/physiology , Seasons , Ecosystem , Climate Models
9.
J Int Neuropsychol Soc ; : 1-11, 2024 Jan 29.
Article in English | MEDLINE | ID: mdl-38282390

ABSTRACT

OBJECTIVE: Associations have been found between five-factor model (FFM) personality traits and risk of developing specific predementia syndromes such as subjective cognitive decline (SCD) and mild cognitive impairment (MCI). The aims of this study were to: 1) Compare baseline FFM traits between participants who transitioned from healthy cognition or SCD to amnestic MCI (aMCI) versus non-amnestic MCI (naMCI); and 2) Determine the relationship between FFM traits and risk of transition between predementia cognitive states. METHODS: Participants were 562 older adults from the Einstein Aging Study, 378 of which had at least one follow-up assessment. Baseline data collected included levels of FFM personality traits, anxiety and depressive symptoms, medical history, performance on a cognitive battery, and demographics. Follow-up cognitive diagnoses were also recorded. RESULTS: Mann-Whitney U tests revealed no differences in baseline levels of FFM personality traits between participants who developed aMCI compared to those who developed naMCI. A four-state multistate Markov model revealed that higher levels of conscientiousness were protective against developing SCD while higher levels of neuroticism resulted in an increased risk of developing SCD. Further, higher levels of extraversion were protective against developing naMCI. CONCLUSIONS: FFM personality traits may be useful in improving predictions of who is at greatest risk for developing specific predementia syndromes. Information on these personality traits could enrich clinical trials by permitting trials to target individuals who are at greatest risk for developing specific forms of cognitive impairment. These results should be replicated in future studies with larger sample sizes and younger participants.

10.
AIDS Care ; 36(1): 1-16, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37607246

ABSTRACT

Economic insecurity and poverty present major barriers to HIV care for young people. We conducted a systematic review of the current evidence for the effect of economic interventions on HIV care outcomes among pediatric populations encompassing young children, adolescents, and youth (ages 0-24). We conducted a search of PubMed MEDLINE, Cochrane, Embase, Scopus, CINAHL, and Global Health databases on October 12, 2022 using a search strategy curated by a medical librarian. Studies included economic interventions targeting participants <25 years in age which measured clinical HIV outcomes. Study characteristics, care outcomes, and quality were independently assessed, and findings were synthesized. Title/abstract screening was performed for 1934 unique records. Thirteen studies met inclusion criteria, reporting on nine distinct interventions. Economic interventions included incentives (n = 5), savings and lending programs (n = 3), and government cash transfers (n = 1). Study designs included three randomized controlled trials, an observational cohort study, a matched retrospective cohort study, and pilot intervention studies. While evidence is very limited, some promising findings were observed supporting retention and viral suppression, particularly for those with suboptimal care engagement or with detectable viral load. There is a need to further study and optimize economic interventions for children and adolescents living with HIV.


Subject(s)
HIV Infections , Child , Humans , Adolescent , Child, Preschool , HIV Infections/therapy , Retrospective Studies , Cohort Studies , Viral Load , Medication Adherence , Randomized Controlled Trials as Topic , Observational Studies as Topic
11.
J Geriatr Psychiatry Neurol ; 37(4): 307-317, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38116645

ABSTRACT

OBJECTIVES: Determine whether levels of anxiety and depression, cognitive ability, and self-quarantining during and prior to the pandemic predict decreases in perceived functional ability. DESIGN AND SETTING: Longitudinal data collected from the Canadian Longitudinal Study on Aging (CLSA) COVID-19 Questionnaire Study (2020) and core CLSA study (Follow-Up 1; 2014-2018). PARTICIPANTS: 17 541 CLSA participants. MEASUREMENTS: Self-quarantining behaviours from questionnaires administered at Baseline (April 2020), Monthly, and Exit (December 2020) time points of the CLSA COVID-19 Questionnaire Study, levels of anxiety and depression at Baseline, perceived change in functional ability at Exit, and performance on neuropsychological tests (Rey Auditory Verbal Learning Task, Mental Alternation Task, Animal Fluency Test) and functional ability (Older Americans Resources and Services [OARS] Multidimensional Assessment Questionnaire) from the core CLSA study. RESULTS: Greater cognitive ability pre-pandemic (B = -.003, P < .01), higher levels of anxiety (B = -.024, P < .01) and depressive symptoms (B = -.110, P < .01) at Baseline, and higher frequency of engaging in self-quarantining throughout the COVID-19 survey period (B = -.098, P < .01) were associated with perceived loss in functional ability at Exit. Self-quarantining behaviour was associated with perceived loss in functional ability only at average and high levels of depressive symptoms (B = -.013, P < .01). CONCLUSIONS: Older adults with higher cognitive and lower functional ability prior to the pandemic were at greater risk of decreased perceived functional ability during the first year of the pandemic, as were those who experienced greater levels of anxiety and depressive symptoms during the pandemic. Strategies/interventions to preserve functional ability in older adults with cognitive independence prior to future pandemics are warranted.


Subject(s)
Aging , Anxiety , COVID-19 , Cognition , Depression , Mental Health , Humans , COVID-19/psychology , COVID-19/epidemiology , Aged , Male , Canada/epidemiology , Female , Longitudinal Studies , Depression/psychology , Depression/epidemiology , Anxiety/psychology , Anxiety/epidemiology , Aging/psychology , Aging/physiology , Aged, 80 and over , SARS-CoV-2 , Neuropsychological Tests/statistics & numerical data , Surveys and Questionnaires , Cognitive Dysfunction/psychology , Cognitive Dysfunction/epidemiology
12.
J Phys Chem A ; 2024 Jul 05.
Article in English | MEDLINE | ID: mdl-38968334

ABSTRACT

The surface of Titan, Saturn's icy moon, is believed to be composed of various molecular minerals with a great diversity in structure and composition. Under the surface conditions, 93 K and 1.45 atm, most small molecules solidify and form minerals, including acetylene and ammonia. These two compounds can not only form single-component solids but also a 1:1 binary cocrystal that exhibits intriguing rotor phase behavior. This cocrystal is a putative mineral on Titan and other planetary bodies such as comets. In addition, the structure of the cocrystal is relevant to fundamental science as it can help better understand the emergence of rotor phases. Here, we present a detailed vibrational neutron spectroscopic study supported by a neutron powder diffraction study on the cocrystal and the single-phase solids. The experimentally observed spectral bands were assigned based on theoretical calculations. The established spectra-properties correlations for the cocrystal corroborate the observed properties. To the best of our knowledge, this study presents the first example of the application of neutron vibrational spectroscopy in studying Titan-relevant organic minerals.

13.
Alcohol Alcohol ; 59(2)2024 Jan 17.
Article in English | MEDLINE | ID: mdl-38123479

ABSTRACT

This systematic review investigates the bidirectional relationship between alcohol consumption and disrupted circadian rhythms. The goal of this study was to identify (i) the types of circadian rhythm disruptors (i.e. social jet lag, extreme chronotypes, and night shift work) associated with altered alcohol use and (ii) whether sex differences in the consequences of circadian disruption exist. We conducted a search of PubMed, Embase, and PsycINFO exclusively on human research. We identified 177 articles that met the inclusion criteria. Our analyses revealed that social jet lag and the extreme chronotype referred to as eveningness were consistently associated with increased alcohol consumption. Relationships between night shift work and alcohol consumption were variable; half of articles reported no effect of night shift work on alcohol consumption. Both sexes were included as participants in the majority of the chronotype and social jet lag papers, with no sex difference apparent in alcohol consumption. The night shift research, however, contained fewer studies that included both sexes. Not all forms of circadian disruption are associated with comparable patterns of alcohol use. The most at-risk individuals for increased alcohol consumption are those with social jet lag or those of an eveningness chronotype. Direct testing of the associations in this review should be conducted to evaluate the relationships among circadian disruption, alcohol intake, and sex differences to provide insight into temporal risk factors associated with development of alcohol use disorder.


Subject(s)
Jet Lag Syndrome , Sleep , Humans , Male , Female , Circadian Rhythm , Risk Factors , Alcohol Drinking/adverse effects , Alcohol Drinking/epidemiology , Surveys and Questionnaires
14.
Fam Community Health ; 47(1): 66-79, 2024.
Article in English | MEDLINE | ID: mdl-37747843

ABSTRACT

Communities can play an important role in protecting children and supporting vulnerable families. However, there is currently a lack of understanding of what communities actually think and do regarding these groups. The purpose of this study was to review and synthesize evidence on community attitudes and behaviors toward vulnerable families. A rapid systematic literature review was conducted, supplemented by 6 semistructured interviews with experienced practitioners. Four databases were searched using key words related to community attitudes and behaviors, parents and families, and family and child protection services. Database searches returned 10 135 unique records, of which 23 met the inclusion criteria. The identified articles investigated a range of attitudes and behaviors, including reporting abuse and neglect; assisting victims of intimate partner violence; attitudes toward parenting practices; and participating in activities that build social support and social capital. Correlates of these attitudes and behaviors included sociodemographic characteristics, individual differences, community characteristics, and incident characteristics. A number of interventions to change community attitudes and behaviors were also identified. Practitioners indicated that success factors for interventions included facilitating active participation from community members; using multifaceted approaches; and increasing empathy toward vulnerable families. Despite increasing evidence around how community members think and act toward vulnerable families, more (particularly review-level) research is needed to determine how to effectively change these attitudes and behaviors.


Subject(s)
Child Rearing , Parents , Child , Humans , Attitude , Family Relations , Social Support
15.
J Res Adolesc ; 2024 May 02.
Article in English | MEDLINE | ID: mdl-38698712

ABSTRACT

The goals of this article are to (a) describe and contrast conceptual characteristics of periods of developmental sensitivity, disturbance, and stasis, and (b) translate these concepts to testable analytic models with an example dataset. Although the concept of developmental sensitivity is widely known, the concepts of developmental stasis and disturbance have received less attention. We first define the concepts and their principles and then, using repeated measures data on impulsivity and alcohol use from adolescence to young adulthood, propose the dual latent change score (LCS) growth model as one analytic approach for evaluating evidence for key characteristics of these developmental concepts via examination of intraindividual time-varying associations.

16.
J Acoust Soc Am ; 155(2): 1437-1450, 2024 02 01.
Article in English | MEDLINE | ID: mdl-38364047

ABSTRACT

Odontocetes produce clicks for echolocation and communication. Most odontocetes are thought to produce either broadband (BB) or narrowband high-frequency (NBHF) clicks. Here, we show that the click repertoire of Hector's dolphin (Cephalorhynchus hectori) comprises highly stereotypical NBHF clicks and far more variable broadband clicks, with some that are intermediate between these two categories. Both NBHF and broadband clicks were made in trains, buzzes, and burst-pulses. Most clicks within click trains were typical NBHF clicks, which had a median centroid frequency of 130.3 kHz (median -10 dB bandwidth = 29.8 kHz). Some, however, while having only marginally lower centroid frequency (median = 123.8 kHz), had significant energy below 100 kHz and approximately double the bandwidth (median -10 dB bandwidth = 69.8 kHz); we refer to these as broadband. Broadband clicks in buzzes and burst-pulses had lower median centroid frequencies (120.7 and 121.8 kHz, respectively) compared to NBHF buzzes and burst-pulses (129.5 and 130.3 kHz, respectively). Source levels of NBHF clicks, estimated by using a drone to measure ranges from a single hydrophone and by computing time-of-arrival differences at a vertical hydrophone array, ranged from 116 to 171 dB re 1 µPa at 1 m, whereas source levels of broadband clicks, obtained from array data only, ranged from 138 to 184 dB re 1 µPa at 1 m. Our findings challenge the grouping of toothed whales as either NBHF or broadband species.


Subject(s)
Dolphins , Echolocation , Animals , Acoustics , Vocalization, Animal , Sound Spectrography
17.
Am J Physiol Lung Cell Mol Physiol ; 324(2): L199-L210, 2023 02 01.
Article in English | MEDLINE | ID: mdl-36594854

ABSTRACT

Sex as a biological variable is an essential element of preclinical research. Sex-specific differences in lung volume, alveolar number, body weight, and the relationship between lung and body weight result in important questions about generating equivalent injuries in males and females so that comparisons in their responses can be assessed. Few studies compare stimulus dosing methods for murine lung models investigating immune responses. To examine sex-specific effects, we explored several dosing techniques for three stimuli, LPS, Streptococcus pneumoniae, and influenza A, on survival, injury parameters in bronchoalveolar lavage (BAL), and immune cell numbers in single-cell lung suspensions after injury. These data demonstrate that body weight-based dosing produced fewer differences between sexes when compared with injury initiated with inocula containing the same number of organisms. Comparison of the lung and body weights showed that females had a greater lung-to-body weight ratio than males. However, in LPS-induced injury, adjusting the dose for sex differences in this ratio in addition to body weight provided no new information about sex differences compared with dosing by body weight alone, most likely due to the variability in measures of the immune response. Studies evaluating BAL volumes revealed that smaller but more lavages resulted in greater returns and lower protein concentrations, particularly in the smaller female lungs. Thus, designing dosing and measurement methods that generate equivalent injuries facilitates comparison of immune responses between sexes. Continued development of methods for both induction and evaluation of injury will likely facilitate identification of sex differences in immune responses.


Subject(s)
Lipopolysaccharides , Pneumonia , Mice , Female , Male , Animals , Lipopolysaccharides/pharmacology , Lung , Cell Count , Body Weight
18.
Acta Neuropathol ; 145(4): 395-408, 2023 04.
Article in English | MEDLINE | ID: mdl-36681782

ABSTRACT

Hippocampal sclerosis (HS) is associated with advanced age as well as transactive response DNA-binding protein with 43 kDa (TDP-43) deposits. Both hippocampal sclerosis and TDP-43 proteinopathy have also been described in chronic traumatic encephalopathy (CTE), a neurodegenerative disease linked to exposure to repetitive head impacts (RHI). However, the prevalence of HS in CTE, the pattern of TDP-43 pathology, and associations of HS and TDP-43 with RHI are unknown. A group of participants with a history of RHI and CTE at autopsy (n = 401) as well as a group with HS-aging without CTE (n = 33) was examined to determine the prevalence of HS and TDP-43 inclusions in CTE and to compare the clinical and pathological features of HS and TDP-43 inclusions in CTE to HS-aging. In CTE, HS was present in 23.4%, and TDP-43 inclusions were present in 43.3% of participants. HS in CTE occurred at a relatively young age (mean 77.0 years) and was associated with a greater number of years of RHI than CTE without HS adjusting for age (p = 0.029). In CTE, TDP-43 inclusions occurred frequently in the frontal cortex and occurred both with and without limbic TDP-43. Additionally, structural equation modeling demonstrated that RHI exposure years were associated with hippocampal TDP-43 inclusions (p < 0.001) through increased CTE stage (p < 0.001). Overall, RHI and the development of CTE pathology may contribute to TDP-43 deposition and hippocampal sclerosis.


Subject(s)
Chronic Traumatic Encephalopathy , Hippocampal Sclerosis , Neurodegenerative Diseases , TDP-43 Proteinopathies , Humans , Aged , Chronic Traumatic Encephalopathy/pathology , Aging , TDP-43 Proteinopathies/pathology , DNA-Binding Proteins/metabolism
19.
Support Care Cancer ; 31(12): 724, 2023 Nov 28.
Article in English | MEDLINE | ID: mdl-38012463

ABSTRACT

PURPOSE: Growing recognition of the gut microbiome as an influential modulator of cancer treatment efficacy and toxicity has led to the emergence of clinical interventions targeting the microbiome to enhance cancer and health outcomes. The highly modifiable nature of microbiota to endogenous, exogenous, and environmental inputs enables interventions to promote resilience of the gut microbiome that have rapid effects on host health, or response to cancer treatment. While diet, probiotics, and faecal microbiota transplant are primary avenues of therapy focused on restoring or protecting gut function in people undergoing cancer treatment, the role of physical activity and exercise has scarcely been examined in this population. METHODS: A narrative review was conducted to explore the nexus between cancer care and the gut microbiome in the context of physical activity and exercise as a widely available and clinically effective supportive care strategy used by cancer survivors. RESULTS: Exercise can facilitate a more diverse gut microbiome and functional metabolome in humans; however, most physical activity and exercise studies have been conducted in healthy or athletic populations, primarily using aerobic exercise modalities. A scarcity of exercise and microbiome studies in cancer exists. CONCLUSIONS: Exercise remains an attractive avenue to promote microbiome health in cancer survivors. Future research should elucidate the various influences of exercise modalities, intensities, frequencies, durations, and volumes to explore dose-response relationships between exercise and the gut microbiome among cancer survivors, as well as multifaceted approaches (such as diet and probiotics), and examine the influences of exercise on the gut microbiome and associated symptom burden prior to, during, and following cancer treatment.


Subject(s)
Gastrointestinal Microbiome , Neoplasms , Probiotics , Sports , Humans , Gastrointestinal Microbiome/physiology , Exercise/physiology , Neoplasms/therapy , Diet , Probiotics/therapeutic use
20.
Child Dev ; 94(2): 497-511, 2023 Mar.
Article in English | MEDLINE | ID: mdl-36408792

ABSTRACT

The study examined the moderating role of children's affect-biased attention to angry, fearful, and sad adult faces in the link between interparental conflict and children's distinct forms of involvement. Participants included 243 preschool children (Mage  = 4.60 years, 56% female) and their parents from racially (48% African American, 43% White) and socioeconomically (median annual household income = $36,000) diverse backgrounds. Data collection took place in the Northeastern United States (2010-2014). Utilizing a multi-method, multi-informant, longitudinal design, attention away from anger selectively amplified the link between interparental conflict and children's subsequent coercive involvement (ß = -.15). Greater attention to fear potentiated the pathway between interparental conflict and children's later cautious (ß = .14) and caregiving involvement (ß = .15). Findings are interpreted in the context of environmental sensitivity models.


Subject(s)
Attentional Bias , Family Conflict , Child, Preschool , Adult , Humans , Female , Male , Longitudinal Studies , Anger , Parents , Parent-Child Relations
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