scholarly journals ILC homeostasis phenotyping in various tissues, aging, and sex differences

2021 ◽  
Author(s):  
Alexis S Mobley ◽  
J Jesus Bautista Garrido ◽  
Pedram Honarpisheh ◽  
John d'Aigle ◽  
Louise D McCullough ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Sex Differences ◽  
Cytokine Production ◽  
Descriptive Study ◽  
Lymphoid Cells ◽  
Rna Seq ◽  
Therapeutic Targeting ◽  
Disease Etiology ◽  
Disease States ◽  
Males And Females

Innate lymphoid cells (ILCs) are the innate counterpart to CD4+ T cells that are mediated by the same transcription factors and produce similar cytokines. ILCs are being investigated in many different disease states, but the field current lacks foundational information on ILC representation whether it be in tissues, between males and females, or in aging as these are all vital components in disease etiology and severity. Our descriptive study used flow cytometry to characterize ILCs compared to the entire CD45+ (e.g., lymphocyte) and lineage negative (e.g., ILC) compartments to understand their homeostatic balance and plasticity. Moreover, we defined ILC2 expression and subsets based on their cytokine production and created several mathematical models to elucidate the correlation of extra- and intra-cellular ILC2 markers from least to most complex. ILC studies would benefit from more unbiased, holistic experiments including RNA-seq and mass spectroscopy to further define ILCs in steady-state before adding more complex pathways like different disease states to enhance translational value and therapeutic targeting of these cells.

scholarly journals Therapeutic Targeting of Transcription Factors to Control the Cytokine Release Syndrome in COVID-19

2021 ◽  
Vol 12 ◽  
Author(s):  
Clarissa S. Santoso ◽  
Zhaorong Li ◽  
Jaice T. Rottenberg ◽  
Xing Liu ◽  
Vivian X. Shen ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Cytokine Production ◽  
Lavage Fluid ◽  
Cytokine Release ◽  
Cytokine Release Syndrome ◽  
Rna Seq ◽  
Therapeutic Targeting ◽  
Inflammatory Cytokine Production ◽  
Approved Drugs ◽  
Fda Approved Drugs

Treatment of the cytokine release syndrome (CRS) has become an important part of rescuing hospitalized COVID-19 patients. Here, we systematically explored the transcriptional regulators of inflammatory cytokines involved in the COVID-19 CRS to identify candidate transcription factors (TFs) for therapeutic targeting using approved drugs. We integrated a resource of TF-cytokine gene interactions with single-cell RNA-seq expression data from bronchoalveolar lavage fluid cells of COVID-19 patients. We found 581 significantly correlated interactions, between 95 TFs and 16 cytokines upregulated in the COVID-19 patients, that may contribute to pathogenesis of the disease. Among these, we identified 19 TFs that are targets of FDA approved drugs. We investigated the potential therapeutic effect of 10 drugs and 25 drugs combinations on inflammatory cytokine production, which revealed two drugs that inhibited cytokine production and numerous combinations that show synergistic efficacy in downregulating cytokine production. Further studies of these candidate repurposable drugs could lead to a therapeutic regimen to treat the CRS in COVID-19 patients.

scholarly journals Characterising sex differences of autosomal DNA methylation in whole blood using the Illumina EPIC array

2021 ◽  
Author(s):  
Olivia A Grant ◽  
Yucheng Wang ◽  
Meena Kumari ◽  
Nicolae Radu Zabet ◽  
Leonard C Schalkwyk
Keyword(s):  
Dna Methylation ◽  
Sex Differences ◽  
Whole Blood ◽  
Cpg Islands ◽  
Disease Etiology ◽  
Cpg Sites ◽  
Males And Females ◽  
Methylation Patterns ◽  
First Time ◽  
Epic Array

Sex differences are known to play a role in disease etiology, progression and outcome. Previous studies have revealed autosomal epigenetic differences between males and females in some tissues, including differences in DNA methylation patterns. Here, we report for the first time an analysis of autosomal sex differences in DNAme using the Illumina EPIC array in human whole blood (n=1171). We identified 554 sex-associated differentially methylated CpG sites (saDMPs) with the majority found to be hypermethylated in females (70%). These saDMP's are enriched in CpG islands and CpG shores and located preferentially at 5'UTRs, 3'UTRs and enhancers. Additionally, we identified 311 significant sex associated differentially methylated regions (saDMRs). Transcription factor binding site enrichment revealed enrichment of transcription factors related to critical developmental processes and sex determination such as SRY and SOX9. Our study reports a reliable catalogue of sex associated CpG sites and elucidates several characteristics of these sites.

scholarly journals Sex Difference in Self-Reported Sexual Functioning Among Frail Older Adults

2020 ◽  
Vol 4 (Supplement_1) ◽  
pp. 313-313
Author(s):  
Brianne Olivieri-Mui ◽  
Sandra Shi ◽  
Ellen McCarthy ◽  
Dae Kim
Keyword(s):  
Older Adults ◽  
Logistic Regression ◽  
Sex Differences ◽  
Sexual Function ◽  
Older Adult ◽  
Sexual Functioning ◽  
Social Life ◽  
Well Being ◽  
Adult Males ◽  
Males And Females

Abstract Frailty may differentially impact how older adult males and females perceive sexual functioning, an important part of well-being. We assessed the level of frailty (robust, pre-frail, frail) for anyone with data on 11 sexual functioning questions asked in wave 2 of the National Social Life, Health, and Aging Project, 2010-2011 (n=2060). Questions covered five domains: overall sexual function (OSF), sexual function anxiety (SFA), changes in sexual function (CSF), erectile/vaginal dysfunction (EVD), and masturbation. Logistic regression identified sex differences in frailty and reporting worse sexual functioning. Linear regression predicted the number of domains reported as worse. Among males (n=1057), pre-frailty meant higher odds of reporting SFA (OR 1.8 95%CI 1.2-6.6), CSF (OR 1.7 95%CI 1.1-2.7), and EVD (OR 1.5 95%CI 1.0-2.2). Among females (n=1003), there was no difference in reporting by frailty. Females were more likely to report worse OSF (Robust: OR 7.4, 95%CI 4.8-11.4; Pre-frail: OR 6.2, 95%CI 3.9-9.9; Frail: OR 3.4 95%CI 1.7-6.6), but less likely to report SFA (Robust OR .3, 95%CI .2-.5; Pre-frail OR .2, 95%CI .1-.3; Frail OR .2 95%CI .1-.3). Pre-frail and frail females reported fewer domains as worse (Pre-frail coefficient -0.21 SE 0.09, Frail -0.43 SE 0.14). As frailty worsened, males reported more domains as worse (Pre-frail 0.24 SE 0.07, Frail 0.29 SE 0.08). Self-reported sexual functioning differs by sex at all levels of frailty, and reporting by males, but not females, changes with frailty. Providers should be aware that sexual functioning is of importance to both sexes despite varying degrees of frailty.

scholarly journals AP2M1 Supports TGF-β Signals to Promote Collagen Expression by Inhibiting Caveolin Expression

2021 ◽  
Vol 22 (4) ◽  
pp. 1639
Author(s):  
Saerom Lee ◽  
Ga-Eun Lim ◽  
Yong-Nyun Kim ◽  
Hyeon-Sook Koo ◽  
Jaegal Shim
Keyword(s):  
Rna Seq ◽  
Gene Encoding ◽  
Caveolin 1 ◽  
Collagen Expression ◽  
Disease States ◽  
Tumor Growth Factor ◽  
Complex Process ◽  
Collagen Protein ◽  
Complex Regulation ◽  
Collagen Genes

The extracellular matrix (ECM) is important for normal development and disease states, including inflammation and fibrosis. To understand the complex regulation of ECM, we performed a suppressor screening using Caenorhabditis elegans expressing the mutant ROL-6 collagen protein. One cuticle mutant has a mutation in dpy-23 that encodes the μ2 adaptin (AP2M1) of clathrin-associated protein complex II (AP-2). The subsequent suppressor screening for dpy-23 revealed the lon-2 mutation. LON-2 functions to regulate body size through negative regulation of the tumor growth factor-beta (TGF-β) signaling pathway responsible for ECM production. RNA-seq analysis showed a dominant change in the expression of collagen genes and cuticle components. We noted an increase in the cav-1 gene encoding caveolin-1, which functions in clathrin-independent endocytosis. By knockdown of cav-1, the reduced TGF-β signal was significantly restored in the dpy-23 mutant. In conclusion, the dpy-23 mutation upregulated cav-1 expression in the hypodermis, and increased CAV-1 resulted in a decrease of TβRI. Finally, the reduction of collagen expression including rol-6 by the reduced TGF-β signal influenced the cuticle formation of the dpy-23 mutant. These findings could help us to understand the complex process of ECM regulation in organism development and disease conditions.

scholarly journals Stem cell treatment improves post stroke neurological outcomes: a comparative study in male and female rats

2021 ◽  
pp. svn-2020-000834
Author(s):  
Koteswara Rao Nalamolu ◽  
Bharath Chelluboina ◽  
Casimir A Fornal ◽  
Siva Reddy Challa ◽  
David M Pinson ◽  
...  
Keyword(s):  
Stem Cells ◽  
Sex Differences ◽  
Motor Function ◽  
Infarct Volume ◽  
Female Rats ◽  
Human Umbilical Cord ◽  
Male And Female ◽  
Post Stroke ◽  
Male And Female Rats ◽  
Males And Females

Background and purposeThe therapeutic potential of different stem cells for ischaemic stroke treatment is intriguing and somewhat controversial. Recent results from our laboratory have demonstrated the potential benefits of human umbilical cord blood-derived mesenchymal stem cells (MSC) in a rodent stroke model. We hypothesised that MSC treatment would effectively promote the recovery of sensory and motor function in both males and females, despite any apparent sex differences in post stroke brain injury.MethodsTransient focal cerebral ischaemia was induced in adult Sprague-Dawley rats by occlusion of the middle cerebral artery. Following the procedure, male and female rats of the untreated group were euthanised 1 day after reperfusion and their brains were used to estimate the resulting infarct volume and tissue swelling. Additional groups of stroke-induced male and female rats were treated with MSC or vehicle and were subsequently subjected to a battery of standard neurological/neurobehavioral tests (Modified Neurological Severity Score assessment, adhesive tape removal, beam walk and rotarod). The tests were administered at regular intervals (at days 1, 3, 5, 7 and 14) after reperfusion to determine the time course of neurological and functional recovery after stroke.ResultsThe infarct volume and extent of swelling of the ischaemic brain were similar in males and females. Despite similar pathological stroke lesions, the clinical manifestations of stroke were more pronounced in males than females, as indicated by the neurological scores and other tests. MSC treatment significantly improved the recovery of sensory and motor function in both sexes, and it demonstrated efficacy in both moderate stroke (females) and severe stroke (males).ConclusionsDespite sex differences in the severity of post stroke outcomes, MSC treatment promoted the recovery of sensory and motor function in male and female rats, suggesting that it may be a promising treatment for stroke.

scholarly journals OP0013 SEX DIFFERENCES IN AUTOIMMUNE DISEASE SUSCEPTIBILITY; A MULTI-OMIC APPROACH

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 8.1-8
Author(s):  
G. Robinson ◽  
K. Waddington ◽  
J. Peng ◽  
A. Radziszewska ◽  
H. Peckham ◽  
...  
Keyword(s):  
Sex Differences ◽  
Lipid Metabolism ◽  
Sex Hormones ◽  
Cell Function ◽  
Immune Cell ◽  
Density Lipoprotein ◽  
Hormone Treatment ◽  
Immune Cell Function ◽  
Immune Cell Subsets ◽  
Males And Females

Background:Males and females have altered immune responses resulting in variation in autoimmune and cardiovascular disease risk (CVR). Recently, these differences have played a role in the inflammatory response to COVID-19. Sex differences exist in the frequency and activity of immune-cell subsets but mechanisms underlying sexual dimorphism remain unknown. Juvenile-onset systemic lupus erythematosus (JSLE) is an autoimmune disorder that commonly emerges during puberty, has a strong female prevalence (female:male ratio, 4.5:1) and results in an increased CVR. JSLE is characterised by chronic inflammation and dyslipidaemia, where cardiovascular disease is a leading cause of mortality for patients. Our previous work identified a link between immune cell function and lipid metabolism in adult-onset SLE. We hypothesised that sex hormones could influence both lipid metabolism and immune cell function and this could determine sex-specific susceptibility to JSLE and associated CVR.Objectives:We investigated the role of sex hormones in modifying systemic lipid metabolism and inflammation.Methods:Nuclear magnetic resonance spectroscopy based serum metabolomics measuring over 130 lipoproteins (14-subsets with lipid compositions), flow cytometry measuring immune-cells, and RNA-sequencing were used to assess the metabolic and immune profile in young, pre/post-pubertal males (n=10/17) and females (n=10/23) and in individuals with gender-dysphoria (GD) under cross-hormone treatment (trans-male/female, n=26/25). This analysis was also performed on a cohort of post-pubertal male (n=12) and female (n=23) JSLE patients. Data was analysed by logistic regression, balanced random forest machine learning (BRF-ML), differential gene expression (DEG) and pathway analysis.Results:Post-pubertal males had significantly reduced cardio-protective high-density lipoprotein (HDL) subsets (p<0.0001) and increased cardio-pathogenic very-low-density lipoprotein subsets (p<0.0001) compared to females. These differences were not observed pre-puberty and were reversed significantly by cross-hormone treatment in GD individuals, suggesting that sex hormones regulate lipid metabolism in-vivo.BRF-ML (28 immune-cell subsets) identified an increased frequency of anti-inflammatory regulatory T-cells (Tregs) in post-pubertal males compared to females (p=0.0097). These Tregs were also more suppressive in males compared to females. Differences in Treg frequency were seen pre-puberty and were not altered by sex hormone treatment in GD individuals. However, Treg DEGs and functional transcriptomic pathways altered between post-pubertal males and females, including those involved in inflammatory signalling, overlapped with those altered by hormones in GD, suggesting hormones may also drive Treg functional changes. In addition, HDL metabolites modified by hormones showed differential associations with Treg phenotypes between post-pubertal males and females.Strikingly, sex differences in lipoproteins and Tregs were lost in JSLE, suggesting hormone signalling could be dysregulated in the pathogenesis of autoimmunity and could increase CVR for patients.Conclusion:Sex hormones drive altered lipoprotein metabolism and functional transcriptomic pathways in Tregs. Males have a lipoprotein profile associated with increased CVR, but a more anti-inflammatory immune profile compared to females. Together, this could explain sex differences in inflammatory disease susceptibilities and inform future sex-specific therapeutic strategies for the management of both JSLE and CVR.Acknowledgements:Lupus UKRosetrees TrustVersus ArthritisNIHR UCLH Biomedical Research CentreDisclosure of Interests:None declared

scholarly journals Sex differences in outcomes after arthroscopic bankart repair

2020 ◽  
Vol 6 (1) ◽  
pp. e000965
Author(s):  
Natalie A Lowenstein ◽  
Peter J Ostergaard ◽  
Daniel B Haber ◽  
Kirsten D Garvey ◽  
Elizabeth G Matzkin
Keyword(s):  
Mental Health ◽  
Sex Differences ◽  
Patient Reported Outcomes ◽  
Strength Function ◽  
Bankart Repair ◽  
Level Of Evidence ◽  
Arthroscopic Bankart Repair ◽  
Patient Reported ◽  
Males And Females

ObjectivesRisk factors for anterior shoulder dislocation include young age, contact activities and male sex. The influence of sex on patient-reported outcomes of arthroscopic Bankart repair (ABR) is unclear, with few studies reporting potential differences. This study’s purpose was to compare patient-reported outcomes of males and females following ABR.MethodsProspectively collected data was analysed for 281 patients (males: 206, females: 75) after ABR with preoperative, 1-year and 2-year follow-up responses. The Wilcoxon signed-rank and χ2 tests, preoperative, 1 year and 2 year follow-up results were examined to determine differences of scores in males versus females.ResultsNo statistically significant sex differences were observed in Simple Shoulder Test (SST), American Shoulder and Elbow Surgeons (ASES), Visual Analogue Scale (VAS) or Single Assessment Numerical Evaluation (SANE) Scores at 1-year or 2-year follow-up. Females had lower Veterans RAND 12-item health survey (VR-12) mental health subscores at 2-year follow-up (females: 52.3±9.0, males: 55.8±7.6, p=0.0016). Females were more likely to report that treatment had ‘exceeded expectations’ at 2-year follow-up regarding motion, strength, function and normal sports activities.ConclusionResults of study demonstrate that ABR has similar outcomes for both males and females. There were no statistically significant sex-related differences in SST, ASES, VAS or SANE scores following ABR. VR-12 mental health subscores showed a minimal difference at 2-year follow-up, with lower scores in females.Level of evidenceRetrospective cohort study; level II.

scholarly journals No sex differences in learning in wild bumblebees

2021 ◽  
Author(s):  
Felicity Muth ◽  
Amber D Tripodi ◽  
Rene Bonilla ◽  
James P Strange ◽  
Anne S Leonard
Keyword(s):  
Sex Differences ◽  
Associative Learning ◽  
Sierra Nevada ◽  
Comparative Cognition ◽  
Natural Populations ◽  
Interspecific Variation ◽  
Learning Task ◽  
Learning Ability ◽  
Learning Performance ◽  
Males And Females

Abstract Females and males often face different sources of selection, resulting in dimorphism in morphological, physiological, and even cognitive traits. Sex differences are often studied in respect to spatial cognition, yet the different ecological roles of males and females might shape cognition in multiple ways. For example, in dietary generalist bumblebees (Bombus), the ability to learn associations is critical to female workers, who face informationally rich foraging scenarios as they collect nectar and pollen from thousands of flowers over a period of weeks to months to feed the colony. While male bumblebees likely need to learn associations as well, they only forage for themselves while searching for potential mates. It is thus less clear whether foraging males would benefit from the same associative learning performance as foraging females. In this system, as in others, cognitive performance is typically studied in lab-reared animals under captive conditions, which may not be representative of patterns in the wild. In the first test of sex and species differences in cognition using wild bumblebees, we compared the performance of Bombus vancouverensis nearcticus (formerly bifarius) and Bombus vosnesenskii of both sexes on an associative learning task at Sierra Nevada (CA) field sites. Across both species, we found that males and females did not differ in their ability to learn, although males were slower to respond to the sucrose reward. These results offer the first evidence from natural populations that male bumblebees may be equally as able to learn associations as females, supporting findings from captive colonies of commercial bees. The observed interspecific variation in learning ability opens the door to using the Bombus system to test hypotheses about comparative cognition.

scholarly journals P110 Sex differences in hand osteoarthritis symptoms and function

Rheumatology ◽  
2021 ◽  
Vol 60 (Supplement_1) ◽  
Author(s):  
Brona Dinneen ◽  
David Heath ◽  
Mohammed Tauseef Ghaffar ◽  
Miriam O'Sullivan ◽  
Carmel Silke ◽  
...  
Keyword(s):  
Sex Differences ◽  
Pain Intensity ◽  
Motor Skills ◽  
Functional Assessment ◽  
Functional Ability ◽  
Fine Motor ◽  
Hand Osteoarthritis ◽  
Fine Motor Skills ◽  
Males And Females ◽  
And Function

Abstract Background/Aims  There is currently no consensus regarding sex-related differences in pain intensity and functional abilities among patients with hand osteoarthritis (OA). In this study we determine sex-related differences in pain intensity and functional ability among patients with hand OA, as assessed by a self-report questionnaire and by performance-based tests. Methods  Using the AUSCAN tool for symptom and functional assessment of hand OA with dynamometry we prospectively accessed patients meeting the ACR criteria for hand osteoarthritis. Using this analysis, assessments of pain and function were compared in male and female patients. The outcome measures included self-reported pain measures, functional assessment and dynamometry measures. Results  The study population included 106 patients (90 females and 16 males) with a mean age of males 48.44 (7.48) and females 52.67 (9.43). All patients with symptomatic hand osteoarthritis meeting ACR Criteria. When accessing difference between sexes, men were found to be significantly heavier (p = 0.003) and have greater grip and pinch strength.As part of function and pain assessments there was a significant correlation between difficulty with fine motor skills such as difficulty doing buttons, difficulty when doing jewellery, or peeling vegetables associated with pain when turning objects e.g. doorknobs, taps and faucets for men in comparison to women. Difficulty in these fine motor skills also correlated with stiffness on wakening and pain on lifting heavy objects regardless of sex. A Mann-Whitney U test was run on 106 participants to determine if there were differences in pain or functional scores between males and females. This reviled Median score for males () and females () was statistically significantly different,There were sex differences noted in the correlation associated with pain with rotational movements e.g. turning objects and functional difficulty with fine motor movements including difficulty when doing up buttons ( Males r(14) = -0.109, p = 0.698, Females r(88) =0.489, p = &lt;0.01 value.= ), difficulty when doing jewellery ( Males r(14) =-0.265, p = 0.339.= Females r(88) = 0.570, p = &lt;0.01) , difficulty peeling vegetables ( Males r(14) = -0.207, p = 0.458 Females r(88) = 0.519, &lt;0.01 ) Conclusion  The results demonstrate the presence of sex differences in patients suffering from hand osteoarthritis self-reported functional ability and pain scales. These differences indicate the need for further studies to explore the mechanisms of hand OA and to understanding the specific impact of gender on the development and progression of disease. With further understanding we can obtain the proper strategy to provide better individualised treatment. It also highlights that rehabilitation programs should consider these differences and each patients’ performance limitations in order to address the specific needs of each individual patient. In doing so, improved pain and functional status will improve morbidity in hand OA Disclosure  B. Dinneen: None. D. Heath: None. M. Ghaffar: None. M. O'Sullivan: None. C. Silke: None. B. Whelan: None.

Sex differences in melanotic encapsulation responses (immunocompetence) in the damselfly Lestes forcipatus Rambur

2002 ◽  
Vol 80 (9) ◽  
pp. 1578-1583 ◽  
Author(s):  
Christopher P Yourth ◽  
Mark R Forbes ◽  
Robert L Baker
Keyword(s):  
Sex Differences ◽  
Immune Responses ◽  
Life Histories ◽  
Mass Gain ◽  
Sexually Dimorphic ◽  
Foreign Objects ◽  
Males And Females ◽  
And Gender ◽  
Parasitic Mites ◽  
Melanotic Encapsulation

A few studies have shown that male and female invertebrates differ in immunity and that these differences appear related to differences in sexual dimorphism and gender differences in life histories. Melanotic encapsulation of foreign objects in insects is one form of immunity. The damselfly Lestes forcipatus Rambur is moderately sexually dimorphic, and much is known about patterns of mass gain in congeners relating to differences in life history between males and females. In this study, females were more immunoresponsive than males under controlled temperatures, following emergence, and at a time when parasitic mites were challenging these hosts. However, males and females that overlapped in mass at emergence did not differ in their immune responses. Males in better condition at emergence were more immunoresponsive than lighter males, but this relation was not found in females. Sex differences in immune expression may have implications for how females versus males are able to deal with challenges from parasites, under varying environmental conditions.

Sign in / Sign up

Export Citation Format

Share Document