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1.
Alcohol ; 118: 9-16, 2024 Apr 04.
Article in English | MEDLINE | ID: mdl-38582261

ABSTRACT

On December 8th 2023, the annual Alcohol and Immunology Research Interest Group (AIRIG) meeting was held at the University of Colorado Anschutz Medical Campus in Aurora, Colorado. The 2023 meeting focused broadly on how acute and chronic alcohol exposure leads to immune dysregulation, and how this contributes to damage in multiple tissues and organs. These include impaired lung immunity, intestinal dysfunction, autoimmunity, the gut-Central Nervous System (CNS) axis, and end-organ damage. In addition, diverse areas of alcohol research covered multiple pathways behind alcohol-induced cellular dysfunction, including inflammasome activation, changes in miRNA expression, mitochondrial metabolism, gene regulation, and transcriptomics. Finally, the work presented at this meeting highlighted novel biomarkers and therapeutic interventions for patients suffering from alcohol-induced organ damage.

3.
bioRxiv ; 2024 Feb 07.
Article in English | MEDLINE | ID: mdl-38370762

ABSTRACT

Alcohol Use Disorder (AUD) is a complex and widespread disease with limited pharmacotherapies. Preclinical animal models of AUD use a variety of voluntary alcohol consumption procedures to recapitulate different phases of AUD including binge alcohol consumption and dependence. However, voluntary alcohol consumption in mice is widely variable rendering it difficult to reproduce results across labs. Accumulating evidence indicates that different brands of commercially available rodent chow can profoundly influence alcohol intake. In this study, we investigated the effects of three commercially available and widely used rodent diet formulations on alcohol consumption and preference in C57BL/6J mice using the 24h intermittent access procedure. The three brands of chow tested were LabDiet 5001 (LD 5001), LabDiet 5053 (LD 5053), and Teklad 2019S (TL2019S) from two companies (Research Diets and Envigo respectively). Mice fed LD5001 displayed the highest levels of alcohol consumption and preference followed by LD5053 and TL2019S. We also found that alcohol consumption and preference could be rapidly switched by changing the diet 48h prior to alcohol administration. Sucrose, saccharin, and quinine preference were not altered suggesting that the diets did not alter taste perception. We also found that mice fed LD5001 displayed increased quinine-resistant alcohol intake compared to mice fed TL2019S, suggesting that diets could influence the development of "compulsive" like alcohol consumption. We profiled the gut microbiome of water and alcohol drinking mice that were maintained on different diets and found significant differences in bacterial alpha and beta diversity, which could impact gut-brain axis signaling and alcohol consumption.

4.
Cells ; 12(18)2023 09 13.
Article in English | MEDLINE | ID: mdl-37759490

ABSTRACT

Preclinical studies have shown that chronic alcohol abuse leads to alterations in the gastrointestinal microbiota that are associated with behavior changes, physiological alterations, and immunological effects. However, such studies have been limited in their ability to evaluate the direct effects of alcohol-associated dysbiosis. To address this, we developed a humanized alcohol-microbiota mouse model to systematically evaluate the immunological effects of chronic alcohol abuse mediated by intestinal dysbiosis. Germ-free mice were colonized with human fecal microbiota from individuals with high and low Alcohol Use Disorders Identification Test (AUDIT) scores and bred to produce human alcohol-associated microbiota or human control-microbiota F1 progenies. F1 offspring colonized with fecal microbiota from individuals with high AUDIT scores had increased susceptibility to Klebsiella pneumoniae and Streptococcus pneumoniae pneumonia, as determined by increased mortality rates, pulmonary bacterial burden, and post-infection lung damage. These findings highlight the importance of considering both the direct effects of alcohol and alcohol-induced dysbiosis when investigating the mechanisms behind alcohol-related disorders and treatment strategies.


Subject(s)
Alcoholism , Microbiota , Pneumonia, Bacterial , Humans , Animals , Mice , Alcoholism/complications , Dysbiosis/complications , Ethanol
5.
Cell Metab ; 35(10): 1704-1721.e6, 2023 10 03.
Article in English | MEDLINE | ID: mdl-37607543

ABSTRACT

Circadian disruptions impact nearly all people with Alzheimer's disease (AD), emphasizing both their potential role in pathology and the critical need to investigate the therapeutic potential of circadian-modulating interventions. Here, we show that time-restricted feeding (TRF) without caloric restriction improved key disease components including behavioral timing, disease pathology, hippocampal transcription, and memory in two transgenic (TG) mouse models of AD. We found that TRF had the remarkable capability of simultaneously reducing amyloid deposition, increasing Aß42 clearance, improving sleep and memory, and normalizing daily transcription patterns of multiple genes, including those associated with AD and neuroinflammation. Thus, our study unveils for the first time the pleiotropic nature of timed feeding on AD, which has far-reaching effects beyond metabolism, ameliorating neurodegeneration and the misalignment of circadian rhythmicity. Since TRF can substantially modify disease trajectory, this intervention has immediate translational potential, addressing the urgent demand for accessible approaches to reduce or halt AD progression.


Subject(s)
Alzheimer Disease , Mice , Animals , Humans , Alzheimer Disease/therapy , Alzheimer Disease/genetics , Mice, Transgenic , Disease Models, Animal , Circadian Rhythm , Brain/metabolism , Amyloid beta-Peptides
6.
Microorganisms ; 11(7)2023 Jul 21.
Article in English | MEDLINE | ID: mdl-37513022

ABSTRACT

The gut microbiome plays a critical role in maintaining overall health and immune function. However, dysbiosis, an imbalance in microbiome composition, can have profound effects on various aspects of human health, including susceptibility to viral infections. Despite numerous studies investigating the influence of viral infections on gut microbiome, the impact of gut dysbiosis on viral infection and pathogenesis remains relatively understudied. The clinical variability observed in SARS-CoV-2 and seasonal influenza infections, and the presence of natural HIV suppressors, suggests that host-intrinsic factors, including the gut microbiome, may contribute to viral pathogenesis. The gut microbiome has been shown to influence the host immune system by regulating intestinal homeostasis through interactions with immune cells. This review aims to enhance our understanding of how viral infections perturb the gut microbiome and mucosal immune cells, affecting host susceptibility and response to viral infections. Specifically, we focus on exploring the interactions between gamma delta (γδ) T cells and gut microbes in the context of inflammatory viral pathogenesis and examine studies highlighting the role of the gut microbiome in viral disease outcomes. Furthermore, we discuss emerging evidence and potential future directions for microbiome modulation therapy in the context of viral pathogenesis.

7.
J Appl Psychol ; 108(7): 1096-1120, 2023 Jul.
Article in English | MEDLINE | ID: mdl-37023300

ABSTRACT

Recent revelations have brought to light the misconduct of high performers across various fields and occupations who were promoted up the organizational ladder rather than punished for their unethical behavior. Drawing on principles of motivated moral reasoning, we investigate how employee performance biases supervisors' moral judgment of employee unethical behavior and how supervisors' performance-focus shapes how they account for moral judgments in promotion recommendations. We test our model in three studies: a field study of 587 employees and their 124 supervisors at a Fortune 500 telecom company, an experiment with two samples of working adults, and an experiment that directly varied explanatory mechanisms. Evidence revealed a moral double standard such that supervisors rendered less punitive judgment of the unethical acts of higher performing employees. In turn, supervisors' bottom-line mentality (i.e., fixation on achieving results) influenced the degree to which they incorporated their punitive judgments into promotability considerations. By revealing the moral leniency afforded to higher performers and the uneven consequences meted out by supervisors, our results carry implications for behavioral ethics research and for organizations seeking to retain and promote their higher performers while also maintaining ethical standards that are applied fairly across employees. (PsycInfo Database Record (c) 2023 APA, all rights reserved).


Subject(s)
Morals , Social Behavior , Adult , Humans , Problem Solving , Judgment , Organizations
8.
JBMR Plus ; 7(1): e10703, 2023 Jan.
Article in English | MEDLINE | ID: mdl-36699637

ABSTRACT

People living with HIV (PLWH) represent a vulnerable population to adverse musculoskeletal outcomes due to HIV infection, antiretroviral therapy (ART), and at-risk alcohol use. Developing measures to prevent skeletal degeneration in this group requires a grasp of the relationship between alcohol use and low bone mass in both the PLWH population and its constituents as defined by sex, age, and race. We examined the association of alcohol use with serum biochemical markers of bone health in a diverse cohort of PLWH enrolled in the New Orleans Alcohol Use in HIV (NOAH) study. To explore the effects of alcohol on bone in the context of HIV and ART and the role of estrogen, we conducted a parallel, translational study using simian immunodeficiency virus (SIV)+/ART+ female rhesus macaques divided into four groups: vehicle (Veh)/Sham; chronic binge alcohol (CBA)/Sham; Veh/ovariectomy (OVX); and CBA/OVX. Clinical data showed that both osteocalcin (Ocn) and procollagen type I N-propeptide (PINP) levels were inversely associated with multiple measures of alcohol consumption. Age (>50 years) significantly increased susceptibility to alcohol-associated suppression of bone formation in both female and male PLWH, with postmenopausal status appearing as an additional risk factor in females. Serum sclerostin (Scl) levels correlated positively with measures of alcohol use and negatively with Ocn. Micro-CT analysis of the macaque tibias revealed that although both CBA and OVX independently decreased trabecular number and bone mineral density, only OVX decreased trabecular bone volume fraction and impacted cortical geometry. The clinical data implicate circulating Scl in the pathogenesis of alcohol-induced osteopenia and suggest that bone morphology can be significantly altered in the absence of net change in osteoblast function as measured by serum markers. Inclusion of sophisticated tools to evaluate skeletal strength in clinical populations will be essential to understand the impact of alcohol-induced changes in bone microarchitecture. © 2022 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

9.
Mar Pollut Bull ; 185(Pt A): 114234, 2022 Dec.
Article in English | MEDLINE | ID: mdl-36257244

ABSTRACT

This study establishes baseline water quality characteristics for the Gold Coast Broadwater, southern Moreton Bay (Australia) utilising routinely monitored parameters between 2016 and 2021, across 18 sites. Combined site mean concentrations of NOx-N, NH3-N and total nitrogen were 11.4 ± 33.4 µg/L, 12.7 ± 27.2 µg/L, and 169 ± 109 µg/L, respectively, whilst PO4-P and total phosphorous were 7.30 ± 5.10 µg/L and 21.7 ± 14.1 µg/L. Additionally, total suspended solids and turbidity combined site means were 6.6 ± 6.0 mg/L and 3.4 ± 2.9 NTU, respectively. During high rainfall periods nutrient concentrations increased by up to >200-, >150-, 15-, 12- and >12-fold for NOx-N, NH3-N, TN, PO4-P and TP, respectively, compared to quiescent conditions. Furthermore, TSS and NTU values increased by up to 15- and 40-fold during periods of measured rainfall compared to quiescent conditions.


Subject(s)
Water Pollutants, Chemical , Water Quality , Bays , Environmental Monitoring , Nitrogen/analysis , Phosphorus/analysis , Water Pollutants, Chemical/analysis
10.
J Stud Alcohol Drugs ; 83(5): 695-703, 2022 09.
Article in English | MEDLINE | ID: mdl-36136440

ABSTRACT

OBJECTIVE: We characterized lifetime drinking trajectories among persons living with HIV (PLWH) and examined how trajectories are related to health. METHOD: Adults (ages 20-71) were recruited between 2015 and 2017 for a cohort study examining the impact of alcohol use on geriatric comorbidities in PLWH in New Orleans. The New Orleans Alcohol Use in HIV (NOAH) Study (n = 356; 68.8% male) included in-person interviews, anthropometric measurements, and biospecimen collection. Average monthly drinks per decade of life was derived from participants' reported average quantity and frequency of alcoholic beverages for each decade. Health indicators included CD4 count, viral load, health-related quality of life, frailty, comorbidities, body mass index, heavy drinking, anxiety, depression, and posttraumatic stress disorder. Participants also reported lifetime experiences with homelessness and incarceration. Latent curve modeling was applied in MPlus to derive lifetime drinking trajectories. Latent trajectory parameters were modeled as predictors of physical, mental, and social health, controlling for demographics. RESULTS: Alcohol consumption increased significantly between the teen years and midlife (31-40), declining thereafter through ages 50-60. Significant interindividual differences were observed in all trajectory parameters. Persons with higher starting points of alcohol consumption showed worse mental health (depression and anxiety) and social experiences (homelessness and incarceration history) at study baseline. A steeper increase in volume of alcohol consumption after ages 10-20 was associated with worse health-related quality of life, greater frailty and comorbidities, and greater odds of current heavy drinking. CONCLUSIONS: Understanding lifetime alcohol consumption patterns is important in addressing physical and mental health among adult PLWH.


Subject(s)
Frailty , HIV Infections , Adolescent , Adult , Aged , Alcohol Drinking/epidemiology , Alcohol Drinking/psychology , Child , Cohort Studies , Female , HIV Infections/epidemiology , HIV Infections/psychology , Health Status , Humans , Male , Middle Aged , Quality of Life , Young Adult
11.
Sci Adv ; 8(35): eabn9867, 2022 Sep 02.
Article in English | MEDLINE | ID: mdl-36054362

ABSTRACT

Seasonal changes in day length (photoperiod) affect numerous physiological functions. The suprachiasmatic nucleus (SCN)-paraventricular nucleus (PVN) axis plays a key role in processing photoperiod-related information. Seasonal variations in SCN and PVN neurotransmitter expression have been observed in humans and animal models. However, the molecular mechanisms by which the SCN-PVN network responds to altered photoperiod is unknown. Here, we show in mice that neuromedin S (NMS) and vasoactive intestinal polypeptide (VIP) neurons in the SCN display photoperiod-induced neurotransmitter plasticity. In vivo recording of calcium dynamics revealed that NMS neurons alter PVN network activity in response to winter-like photoperiod. Chronic manipulation of NMS neurons is sufficient to induce neurotransmitter switching in PVN neurons and affects locomotor activity. Our findings reveal previously unidentified molecular adaptations of the SCN-PVN network in response to seasonality and the role for NMS neurons in adjusting hypothalamic function to day length via a coordinated multisynaptic neurotransmitter switching affecting behavior.

12.
Alcohol Clin Exp Res ; 46(11): 2041-2053, 2022 11.
Article in English | MEDLINE | ID: mdl-36124866

ABSTRACT

BACKGROUND: Antiretroviral therapy has improved life expectancy among people living with HIV (PLWH). Despite increased longevity, PLWH are at increased risk of age-related comorbidities, including frailty. We examined the relationship between body composition and frailty among PLWH, and moderation of this relationship by substance use, physical activity (PA), and physical function. METHODS: Participants (n = 341; 71% male, 48 ± 10 years, body mass index (BMI) = 27.3 ± 7.0 kg/m2 ) enrolled in the New Orleans Alcohol Use in HIV (NOAH) study underwent measures of body composition, muscle strength, and gait speed. Whole blood phosphatidylethanol (PEth) was measured, and substance use and PA were self-reported. Frailty risk measures included the 58-Item Deficit Index (DI58) and the Veterans Aging Cohort Study (VACS) Index 1.0, where higher scores indicate greater frailty risk. RESULTS: Multivariable linear regression adjusted for age, sex, and race showed that higher fat-free mass index (FFMI), body fat (%), waist-to-hip ratio, and body mass index (BMI) ≥ 25.0 kg/m2 vs. < 25.0 kg/m2 were significantly (p < 0.05) associated with decreased frailty risk measured by the VACS Index, whereas adjusted analyses showed no association between body composition variables and the DI58 score. Recent alcohol use, muscle strength, and PA, but not lifetime alcohol use or gait speed, significantly moderated associations between body composition variables and frailty risk with medium-to-large effect sizes. Subgroup analyses revealed a negative relationship between DI58 and FFMI among people with PEth > 8 ng/ml and negative relationships of VACS Index with FFMI and WHR in people with lower muscle strength. Overweight or obese BMI categories were positively associated with DI58 in people with lower muscle strength or higher PA level but negatively associated in those with higher muscle strength. CONCLUSIONS: Our findings indicate that body composition has significant modulatory effects on frailty risk in PLWH, where obesity increases the risk of frailty and greater muscle mass may be protective, even in individuals who use alcohol. These results highlight the importance of considering body composition, physical activity, and physical function in assessing frailty risk in PLWH, particularly among individuals who use alcohol. Moreover, they support the implementation of physical activity interventions to ameliorate the risk of frailty in aging PLWH.


Subject(s)
Frailty , HIV Infections , Humans , Male , Female , Frailty/diagnosis , Frailty/epidemiology , Cohort Studies , Cross-Sectional Studies , Body Composition/physiology , Muscle Strength/physiology , Exercise , Obesity , HIV Infections/epidemiology
13.
Pulm Circ ; 12(3): e12124, 2022 Jul.
Article in English | MEDLINE | ID: mdl-36092794

ABSTRACT

Cardiac magnetic resonance (CMR) imaging is used to assess the right ventricle (RV) of pulmonary hypertensive (PH) patients and more recently to track changes in response to therapy. We wished to investigate if repeat CMRs could be used to assess ventricular changes in the Sugen 5416 hypoxic (Su/Hx) rat model of PH treated with the dual endothelin receptor antagonist Macitentan. Male Sprague Dawley Su/Hx rats were dosed for 3 weeks with either vehicle or Macitentan (30 mg/kg) daily, control rats received only vehicle. All rats underwent three CMR scans; before treatment, 2 weeks into treatment, and end of the study. A separate group of Su/Hx and control rats, treated as above, underwent terminal hemodynamic measurements. Using terminal and CMR measurements, Macitentan was found to lower RV systolic pressure pulmonary artery remodeling and increase RV ejection fraction but not change RV hypertrophy (RVH). Repeat CMRs determined that Su/Hx rats treated with Macitentan had significantly reversed RVH via reducing RV mass as well as reducing elevated left ventricular eccentricity index; reductions in RV mass were also observed in Su/Hx vehicle rats exposed to normoxic conditions. We have demonstrated that repeat CMRs can be used to assess the volume and structural changes in the ventricles of the Su/Hx rat model. Using repeat CMRs has allowed us to build a more complete picture of the response of the RV and the left ventricle to treatment. It is unknown if these effects are a consequence of direct action on the RV or secondary to improvements in the lung vasculature.

14.
Front Immunol ; 13: 839390, 2022.
Article in English | MEDLINE | ID: mdl-35634279

ABSTRACT

CD4+ T cell differentiation to pro-inflammatory and immunosuppressive subsets depends on immunometabolism. Pro-inflammatory CD4+ subsets rely on glycolysis, while immunosuppressive Treg cells require functional mitochondria for their differentiation and function. Previous pre-clinical studies have shown that ethanol (EtOH) administration increases pro-inflammatory CD4+ T cell subsets; whether this shift in immunophenotype is linked to alterations in CD4+ T cell metabolism had not been previously examined. The objective of this study was to determine whether ethanol alters CD4+ immunometabolism, and whether this affects CD4+ T cell differentiation. Naïve human CD4+ T cells were plated on anti-CD3 coated plates with soluble anti-CD28, and differentiated with IL-12 in the presence of ethanol (0 and 50 mM) for 3 days. Both Tbet-expressing (Th1) and FOXP3-expressing (Treg) CD4+ T cells increased after differentiation. Ethanol dysregulated CD4+ T cell differentiation by increasing Th1 and decreasing Treg CD4+ T cell subsets. Ethanol increased glycolysis and impaired oxidative phosphorylation in differentiated CD4+ T cells. Moreover, the glycolytic inhibitor 2-deoxyglucose (2-DG) prevented the ethanol-mediated increase in Tbet-expressing CD4+ T cells but did not attenuate the decrease in FOXP3 expression in differentiated CD4+ T cells. Ethanol increased Treg mitochondrial volume and altered expression of genes implicated in mitophagy and autophagosome formation (PINK1 and ATG7). These results suggest that ethanol impairs CD4+ T cell immunometabolism and disrupts mitochondrial repair processes as it promotes CD4+ T cell differentiation to a pro-inflammatory phenotype.


Subject(s)
CD4-Positive T-Lymphocytes , Lymphocyte Activation , Cell Differentiation , Ethanol/pharmacology , Forkhead Transcription Factors/metabolism
15.
Sci Total Environ ; 833: 155201, 2022 Aug 10.
Article in English | MEDLINE | ID: mdl-35421488

ABSTRACT

Estuarine ecosystems have very high ecological and economic value, and also act as a buffer for coastal oceans by processing nutrient inputs from terrestrial sources. However, ongoing pressures from increased urbanisation and agriculture, overlaid by climate change, has reduced inflows and increased nutrient loads that challenge the health and buffering capacity of these ecosystems. This study aimed to investigate whether restoring the bioturbating activity of Simplisetia aequisetis (Polychaeta: Nereididae) and other macrofauna could improve biogeochemical conditions in 'hostile' (i.e. hypersaline, sulfide-rich) sediments. To achieve this aim, we conducted an in situ experiment in the Coorong estuarine-lagoon ecosystem, translocating hostile hypersaline sediments, devoid of bioturbating macrofauna, to a 'healthy' (lower salinity) location where macrobenthic fauna naturally occur, and manipulating the S. aequisetis density in the sediments. Porewater, solid-phase, and diffusive equilibrium and diffusive gradient in thin-films (DET/DGT) measurements showed that bioturbation by macrobenthic fauna significantly influenced sediment biogeochemistry and remediated hostile conditions in sediment within a short time (four weeks) irrespective of S. aequisetis density. Bioturbation promoted sediment oxygenation, while salinity and the concentrations of total organic carbon and porewater sulfide, ammonium, and phosphate all decreased over time at all sediment depths. This research highlights the importance of macrobenthic communities and their functional traits for improving sediment conditions, promoting resilience to eutrophication, providing a nature-based remediation option, and in general ensuring healthy functioning of estuarine ecosystems.


Subject(s)
Ecosystem , Polychaeta , Animals , Eutrophication , Geologic Sediments , Oceans and Seas , Sulfides
16.
Alcohol ; 101: 45-51, 2022 06.
Article in English | MEDLINE | ID: mdl-35306109

ABSTRACT

People living with HIV (PLWH) are at increased risk for noncommunicable diseases such as lung disease in part due to opportunistic infections including pneumonia. HIV infection is associated with increased prevalence of impaired lung function and abnormal gas exchange. Alcohol use disorder (AUD) is exceedingly common in PLWH and is associated with higher risk of pneumonia in PLWH. Alcohol use may lead to lung damage through several mechanisms. Data on the long-term effect of AUD on pulmonary function in PLWH are sparse and conflicting. To evaluate this relationship, we conducted a cross-sectional analysis of adult PLWH in care in Louisiana. We hypothesized that chronic alcohol use would be associated with subsequent pulmonary dysfunction in a dose-dependent fashion. All participants performed standardized spirometry on study entry. In total, 350 participants with acceptable spirometry were included in this analysis. Thirty-one percent of participants were female. Women reported less lifetime alcohol use and less smoking; however, they reported more chronic respiratory symptoms. In adjusted models, total lifetime alcohol use was not associated with spirometry measures of pulmonary function. HIV-related variables (CD4 count and viral load) were also not associated with measures of pulmonary function. We then conducted sex-stratified analyses to eliminate residual confounding of sex and similarly found no association of total lifetime alcohol use and pulmonary function. We found no association of AUDIT score or early life alcohol use and pulmonary function. In latent class factor analysis, current heavy alcohol use was associated with lower measures of pulmonary function as compared to former heavy alcohol use. In summary, in this cohort of New Orleanian men and women living with HIV with robust measures of alcohol use, though total lifetime alcohol use and early life alcohol use were not associated with pulmonary function, current heavy alcohol use was associated with impaired pulmonary function.


Subject(s)
Alcoholism , HIV Infections , Lung Diseases , Pneumonia , Adult , Alcoholism/epidemiology , CD4 Lymphocyte Count , Cross-Sectional Studies , Female , HIV Infections/complications , HIV Infections/epidemiology , Humans , Lung , Male
17.
Microbiol Immunol ; 66(6): 330-341, 2022 Jun.
Article in English | MEDLINE | ID: mdl-35067963

ABSTRACT

The gut microbiota has a fundamental role in the development and the maturation of the host immune system. Both innate and adaptive immune cells have critical functions in microbial pathogen containment and clearance, but the regulation of the commensal microbiome ecosystem in the gastrointestinal tract by these major immune cell populations is incompletely defined. The role of specific innate and adaptive immune cell in the regulation of the microbiota in the intestinal tract biogeographically was investigated. Dendritic cells, macrophages, CD4+ T-cells, CD8+ T-cells, and B-cells were depleted using monoclonal antibodies and clodronate liposomes, and the microbial communities were determined by 16S rRNA gene sequencing. With specific immune cell depletion, distinct microbiota changes were observed. In general, immune cell depleted mice had higher microbiota richness and evenness at all gut anatomical sites. At each gut segment, samples from immune cell-depleted animals clustered away from the isotype/liposome control mice. This was especially dramatic for the small intestinal microbiota. Specifically, Enterobacteriaceae, Bacteroides acidifaciens, and Mucispirillum schaedleri were highly enriched in the mucosa and lumen of the small intestine in immune cell-deficient animals. Further, the mucosal microbiota had higher microbiota evenness compared with luminal microbiota at all gut segments, and the UniFrac distance between B cell depleted and isotype control mice was the largest in the duodenum followed by the ileum and colon. Taken together, the data suggest that innate and adaptive immune cells specifically contribute to the regulation of the gut microbiota's biogeographical distribution along the gastrointestinal tract, and microbiota in the duodenum mucosa are more responsive to host immune changes compared with other anatomical sites.


Subject(s)
Gastrointestinal Microbiome , Microbiota , Adaptive Immunity , Animals , CD4-Positive T-Lymphocytes , Immunity, Innate , Mice , RNA, Ribosomal, 16S/genetics
18.
Mol Metab ; 57: 101431, 2022 03.
Article in English | MEDLINE | ID: mdl-34974160

ABSTRACT

OBJECTIVE: The increasing prevalence of obesity makes it important to increase the understanding of the maturation and function of the neuronal integrators and regulators of metabolic function. METHODS: Behavioral, molecular, and physiological analyses of transgenic mice with Sine oculis 3 (Six3) deleted in mature neurons using the Synapsincreallele. RESULTS: Conditional deletion of the homeodomain transcription factor Six3 in mature neurons causes dwarfism and weakens circadian wheel-running activity rhythms but increases general activity at night, and improves metabolic function, without impacting pubertal onset or fertility in males. The reduced growth in 6-week-old Six3fl/fl:Synapsincre (Six3syn) males correlates with increased somatostatin (SS) expression in the hypothalamus and reduced growth hormone (GH) in the pituitary. In contrast, 12-week-old Six3syn males have increased GH release, despite an increased number of the inhibitory SS neurons in the periventricular nucleus. GH is important in glucose metabolism, muscle function, and bone health. Interestingly, Six3syn males have improved glucose tolerance at 7, 12, and 18 weeks of age, which, in adulthood, is associated with increased % lean mass and increased metabolic rates. Further, 12-week-old Six3syn males have reduced bone mineralization and a lower bone mineral density, indicating that reduced GH levels during early life cause a long-term reduction in bone mineralization. CONCLUSION: Our study points to the novel role of Six3 in post-proliferative neurons to regulate metabolic function through SS neuron control of GH release.


Subject(s)
Dwarfism , Homeodomain Proteins , Animals , Dwarfism/genetics , Dwarfism/metabolism , Eye Proteins/metabolism , Homeodomain Proteins/genetics , Homeodomain Proteins/metabolism , Male , Mice , Mice, Transgenic , Nerve Tissue Proteins/genetics , Nerve Tissue Proteins/metabolism , Neurons/metabolism
19.
J Appl Psychol ; 107(9): 1561-1578, 2022 Sep.
Article in English | MEDLINE | ID: mdl-34647783

ABSTRACT

Models of trust have focused on the notion that an employee's trust in a coworker is based on that coworker's trustworthiness and the employee's trust propensity-a generalized tendency to believe others are trustworthy. Although these models capture the general assessment of risk associated with trusting a particular coworker, they provide insufficient insight into why an employee might take the risk associated with trust on a particular day. Bringing the concept of risk propensity-the tendency to accept or avoid risk-from the decision-making literature into the trust literature, we build a model of trust that suggests employees' trusting behaviors stem from both their calculated assessment of risk (encapsulated in trustworthiness and trust propensity) and their tendency to take those risks. We draw on motivated reasoning theory (Kunda, 1990) and the decision-making literature to suggest that employees' daily strivings for achievement, affiliation, stimulation, and security induce a biased reasoning process that influences employees' risk propensity that day. Our test of this theoretical model demonstrates that generalized work motives have an indirect effect on employees' trust in their coworkers, through risk propensity, that goes above and beyond established bases of trust. (PsycInfo Database Record (c) 2022 APA, all rights reserved).


Subject(s)
Motivation , Trust , Humans
20.
Alcohol Alcohol ; 57(2): 226-233, 2022 Mar 12.
Article in English | MEDLINE | ID: mdl-34611697

ABSTRACT

AIMS: To assess whether binge drinking and heavy alcohol use are associated with increased sugar and fat consumption among a Southern cohort of people living with HIV (PWH). METHODS: This was a cross-sectional analysis of PWH enrolled in the New Orleans Alcohol use in HIV (NOAH) Study (n = 215). Binge and heavy drinking were identified through a 30-day Alcohol Timeline-Followback and dietary intake was assessed through a 24-hour dietary recall. RESULTS: Participants were 65.4% male, 83.3% Black, with a mean age of 49.2 ± 9.9. Heavy drinkers consumed more total calories than abstainers (P = 0.035) and low-to-moderate drinkers (P = 0.024), and binge drinkers consumed more calories than non-binge drinkers (P = 0.025). Binge and heavy drinkers had significantly higher intake of total and saturated fat in grams. However, substantially increased caloric intake among these participants led to non-significant associations for alcohol use with high total and saturated fat intake as a percent of total energy intake (%TEI). Binge drinkers had lower odds of consuming high sugar as a %TEI (odds ratio: 0.31 [0.14, 0.68]). Additionally, sugar intake predicted total and saturated fat intake, and this association was slightly higher among binge drinkers (total fat P-value: 0.12). CONCLUSIONS: In this population of PWH, while binge and heavy drinking predicted higher caloric and fat intake in grams, binge drinkers were less likely to consume a high-sugar diet. This analysis suggests that interventions focused on reduced alcohol use may be especially beneficial in reducing metabolic disease burden in PWH if supplemented with information on incorporating lower energy-dense foods with reduced fat.


Subject(s)
Binge Drinking , HIV Infections , Adult , Alcohol Drinking/epidemiology , Binge Drinking/epidemiology , Cross-Sectional Studies , Ethanol , Female , HIV Infections/epidemiology , Humans , Male , Middle Aged , Sugars
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