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  1. Article ; Online: Interactions between immune cells recorded.

    Wheeler, Michael A

    Nature

    2024  Volume 627, Issue 8003, Page(s) 277–279

    MeSH term(s) Computational Biology ; Systems Biology ; Immune System
    Language English
    Publishing date 2024-03-06
    Publishing country England
    Document type News
    ZDB-ID 120714-3
    ISSN 1476-4687 ; 0028-0836
    ISSN (online) 1476-4687
    ISSN 0028-0836
    DOI 10.1038/d41586-024-00426-9
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Astrocytes on steroids binge on synapses to cope with stress.

    Wheeler, Michael A / Quintana, Francisco J

    Immunity

    2023  Volume 56, Issue 9, Page(s) 1983–1985

    Abstract: Many mechanisms by which stress mediates its effects within the central nervous system still remain unknown. Byun, Kim, Kim et al. find that early-life stress triggers corticosterone release to drive astrocyte-dependent synapse elimination and altered ... ...

    Abstract Many mechanisms by which stress mediates its effects within the central nervous system still remain unknown. Byun, Kim, Kim et al. find that early-life stress triggers corticosterone release to drive astrocyte-dependent synapse elimination and altered behavior. Thus, this work defines a steroid-sensitive astrocyte transcriptional circuit controlling behavior, highlighting how the study of CNS immunoregulation may shed light on behavior.
    MeSH term(s) Astrocytes ; Synapses ; Central Nervous System ; Steroids
    Chemical Substances Steroids
    Language English
    Publishing date 2023-09-13
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural ; Comment
    ZDB-ID 1217235-2
    ISSN 1097-4180 ; 1074-7613
    ISSN (online) 1097-4180
    ISSN 1074-7613
    DOI 10.1016/j.immuni.2023.08.013
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: The Microbiome and Prostate Cancer Risk.

    Wheeler, Karen M / Liss, Michael A

    Current urology reports

    2019  Volume 20, Issue 10, Page(s) 66

    Abstract: Purpose of the review: There is an abundance of evidence that the human microbiome plays an important and nuanced role in controlling human metabolism, immunity, and cancer. Herein we aim to review the most current research looking at prostate cancer ... ...

    Abstract Purpose of the review: There is an abundance of evidence that the human microbiome plays an important and nuanced role in controlling human metabolism, immunity, and cancer. Herein we aim to review the most current research looking at prostate cancer and its link with the gut and genitourinary microbiome. There is now a host of evidence for a unique genitourinary (GU) microbiome. The prostate microbiota, to include viral, bacterial, fungal, and parasitic contributions, as assessed from formalin-fixed tissue is described nicely in the study by Banerjee et al. Further hierarchical analysis by this group found a unique microbiome signature for higher Gleason score cancers and validation PCR studies noted a marked number of viral genomic insertions into host DNA. Shretha et al. also recently established unique GU microbiomes in patients with prostate cancer or benign prostate pathology based on urine samples. The gut microbiome likely also has an indirect but significant role in prostate cancer development and treatment. Liss et al. and Golombos et al. found significant associations between specific gut microbiota and prostate cancer. Interestingly, the balance of inflammatory and anti-inflammatory bacterial lipopolysaccharides, production of bile salts, and metabolism of dietary fiber to short chain fatty acids all likely play important roles in creating systemic pro- or anti-carcinogenic states. In terms of prostate cancer treatment effects, Sfanos et al. noted a unique microbial signature in patients undergoing oral androgen deprivation therapy (ADT) as compared with prostate cancer patients not on ADT. Patients undergoing ADT also had enrichment of bacterial metabolic pathways promoting androgen synthesis. Together, these studies have identified a unique GU microbiome and linked both the GU microbiome and unique gut microbial signatures with prostate cancer and prostate cancer treatments. Whether this information can be used in cancer prevention, treatment, or diagnosis are areas of ongoing and active research.
    MeSH term(s) Animals ; Gastrointestinal Microbiome/physiology ; Humans ; Male ; Mice ; Microbiota/physiology ; Prostate/microbiology ; Prostate/virology ; Prostatic Neoplasms/etiology ; Prostatic Neoplasms/microbiology ; Prostatic Neoplasms/therapy ; Prostatic Neoplasms/virology ; Urine/microbiology ; Urine/virology ; Urogenital System/microbiology
    Language English
    Publishing date 2019-09-07
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 2057354-6
    ISSN 1534-6285 ; 1527-2737
    ISSN (online) 1534-6285
    ISSN 1527-2737
    DOI 10.1007/s11934-019-0922-4
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article: Integration of transcriptomics and long-read genomics prioritizes structural variants in rare disease.

    Jensen, Tanner D / Ni, Bohan / Reuter, Chloe M / Gorzynski, John E / Fazal, Sarah / Bonner, Devon / Ungar, Rachel A / Goddard, Pagé C / Raja, Archana / Ashley, Euan A / Bernstein, Jonathan A / Zuchner, Stephan / Greicius, Michael D / Montgomery, Stephen B / Schatz, Michael C / Wheeler, Matthew T / Battle, Alexis

    medRxiv : the preprint server for health sciences

    2024  

    Abstract: Rare structural variants (SVs) - insertions, deletions, and complex rearrangements - can cause Mendelian disease, yet they remain difficult to accurately detect and interpret. We sequenced and analyzed Oxford Nanopore long-read genomes of 68 individuals ... ...

    Abstract Rare structural variants (SVs) - insertions, deletions, and complex rearrangements - can cause Mendelian disease, yet they remain difficult to accurately detect and interpret. We sequenced and analyzed Oxford Nanopore long-read genomes of 68 individuals from the Undiagnosed Disease Network (UDN) with no previously identified diagnostic mutations from short-read sequencing. Using our optimized SV detection pipelines and 571 control long-read genomes, we detected 716 long-read rare (MAF < 0.01) SV alleles per genome on average, achieving a 2.4x increase from short-reads. To characterize the functional effects of rare SVs, we assessed their relationship with gene expression from blood or fibroblasts from the same individuals, and found that rare SVs overlapping enhancers were enriched (LOR = 0.46) near expression outliers. We also evaluated tandem repeat expansions (TREs) and found 14 rare TREs per genome; notably these TREs were also enriched near overexpression outliers. To prioritize candidate functional SVs, we developed Watershed-SV, a probabilistic model that integrates expression data with SV-specific genomic annotations, which significantly outperforms baseline models that don't incorporate expression data. Watershed-SV identified a median of eight high-confidence functional SVs per UDN genome. Notably, this included compound heterozygous deletions in
    Language English
    Publishing date 2024-03-26
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2024.03.22.24304565
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Multiple sclerosis: Neuroimmune crosstalk and therapeutic targeting.

    Charabati, Marc / Wheeler, Michael A / Weiner, Howard L / Quintana, Francisco J

    Cell

    2023  Volume 186, Issue 7, Page(s) 1309–1327

    Abstract: Multiple sclerosis (MS) is a chronic inflammatory and degenerative disease of the central nervous system afflicting nearly three million individuals worldwide. Neuroimmune interactions between glial, neural, and immune cells play important roles in MS ... ...

    Abstract Multiple sclerosis (MS) is a chronic inflammatory and degenerative disease of the central nervous system afflicting nearly three million individuals worldwide. Neuroimmune interactions between glial, neural, and immune cells play important roles in MS pathology and offer potential targets for therapeutic intervention. Here, we review underlying risk factors, mechanisms of MS pathogenesis, available disease modifying therapies, and examine the value of emerging technologies, which may address unmet clinical needs and identify novel therapeutic targets.
    MeSH term(s) Humans ; Multiple Sclerosis/drug therapy ; Central Nervous System ; Neuroglia ; Cell Physiological Phenomena ; Inflammation/pathology
    Language English
    Publishing date 2023-03-24
    Publishing country United States
    Document type Journal Article ; Review ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
    ZDB-ID 187009-9
    ISSN 1097-4172 ; 0092-8674
    ISSN (online) 1097-4172
    ISSN 0092-8674
    DOI 10.1016/j.cell.2023.03.008
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: β-Cell Insulin Resistance Plays a Causal Role in Fat-Induced β-Cell Dysfunction In Vitro and In Vivo.

    Ivovic, Aleksandar / Yung, Justin Hou Ming / Oprescu, Andrei I / Vlavcheski, Filip / Mori, Yusaku / Rahman, S M Niazur / Ye, Wenyue / Eversley, Judith A / Wheeler, Michael B / Woo, Minna / Tsiani, Evangelia / Giacca, Adria

    Endocrinology

    2024  Volume 165, Issue 5

    Abstract: In the classical insulin target tissues of liver, muscle, and adipose tissue, chronically elevated levels of free fatty acids (FFA) impair insulin signaling. Insulin signaling molecules are also present in β-cells where they play a role in β-cell ... ...

    Abstract In the classical insulin target tissues of liver, muscle, and adipose tissue, chronically elevated levels of free fatty acids (FFA) impair insulin signaling. Insulin signaling molecules are also present in β-cells where they play a role in β-cell function. Therefore, inhibition of the insulin/insulin-like growth factor 1 pathway may be involved in fat-induced β-cell dysfunction. To address the role of β-cell insulin resistance in FFA-induced β-cell dysfunction we co-infused bisperoxovanadate (BPV) with oleate or olive oil for 48 hours in rats. BPV, a tyrosine phosphatase inhibitor, acts as an insulin mimetic and is devoid of any antioxidant effect that could prevent β-cell dysfunction, unlike most insulin sensitizers. Following fat infusion, rats either underwent hyperglycemic clamps for assessment of β-cell function in vivo or islets were isolated for ex vivo assessment of glucose-stimulated insulin secretion (GSIS). We also incubated islets with oleate or palmitate and BPV for in vitro assessment of GSIS and Akt (protein kinase B) phosphorylation. Next, mice with β-cell specific deletion of PTEN (phosphatase and tensin homolog; negative regulator of insulin signaling) and littermate controls were infused with oleate for 48 hours, followed by hyperglycemic clamps or ex vivo evaluation of GSIS. In rat experiments, BPV protected against fat-induced impairment of β-cell function in vivo, ex vivo, and in vitro. In mice, β-cell specific deletion of PTEN protected against oleate-induced β-cell dysfunction in vivo and ex vivo. These data support the hypothesis that β-cell insulin resistance plays a causal role in FFA-induced β-cell dysfunction.
    MeSH term(s) Animals ; Insulin Resistance/physiology ; Insulin-Secreting Cells/drug effects ; Insulin-Secreting Cells/metabolism ; Rats ; Mice ; Male ; PTEN Phosphohydrolase/metabolism ; Oleic Acid/pharmacology ; Insulin/metabolism ; Mice, Inbred C57BL ; Insulin Secretion/drug effects ; Fatty Acids, Nonesterified/metabolism ; Rats, Sprague-Dawley
    Chemical Substances PTEN Phosphohydrolase (EC 3.1.3.67) ; Oleic Acid (2UMI9U37CP) ; Insulin ; Fatty Acids, Nonesterified
    Language English
    Publishing date 2024-04-08
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
    ZDB-ID 427856-2
    ISSN 1945-7170 ; 0013-7227
    ISSN (online) 1945-7170
    ISSN 0013-7227
    DOI 10.1210/endocr/bqae044
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Predictors of participants' retention-socioeconomic factors or nonadherence: insights from a urological clinical prospective study.

    Wheeler, Allison J / Garg, Harshit / Kaushik, Dharam / Mansour, Ahmed / Pruthi, Deepak / Liss, Michael A

    Trials

    2022  Volume 23, Issue 1, Page(s) 970

    Abstract: Background: To investigate various patient-level variables, specifically socioeconomic status, as risk factors for withdrawal in a recently completed clinical study. We specifically investigated a non-interventional prospective study assessing the role ... ...

    Abstract Background: To investigate various patient-level variables, specifically socioeconomic status, as risk factors for withdrawal in a recently completed clinical study. We specifically investigated a non-interventional prospective study assessing the role of novel imaging as a biomarker for cancer upgradation in prostate cancer for this objective.
    Methods: In this retrospective analysis, we assessed the association between various patient-level factors including clinic-demographic factors, socioeconomic status, and the number of non-adherences with the participants' retention or withdrawal from the study. For socioeconomic status (SES), we used the zip code-based Economic Innovation Group Distressed Community Index (DCI) which classifies into five even distress tiers: prosperous, comfortable, mid-tier, at-risk, or distressed. Low SES was defined as those with a DCI Distress tier of at-risk or distressed. We compared values between the two retention and withdrawal groups using t-test, chi-square test, and logistic regression analysis.
    Results: Of 273 men screened, 123 men were enrolled. Among them, 86.2% (106/123) retained through the study whereas 13.8% (17/123) withdrew from the study. The mean (SD) age was 64 (6.4) years. Overall, 31.7% (39/123) were Hispanics and 24.3% (30/123) were African Americans. The median (IQR) DCI score was 34 (10.3, 68.1) and 30.8% (38/123) of patients belonged to low SES. The median DCI score in participants who retained in the study was statistically similar to those who withdrew from the study (p=0.4). Neither the DCI tiers (p=0.7) nor the low SES (p=0.9) were associated with participants' retention or withdrawal of the study. In terms of non-adherence, all participants in the withdrawn group had at least one non-adherent event compared to 48.1% in the retained group (p<0.001). Repetitive non-adherence was significantly higher in participants who withdrew from the study vs those who retained in the study [88.2% vs 16.9%, p <0.001]. On multivariate logistic regression analysis, the number of non-adherences (OR=12.5, p<0.001) and not DCI (OR=0.99, p=0.7) appeared to be an independent predictor for participants' retention or withdrawal from the study.
    Conclusions: Expanding diverse inclusion and limiting withdrawal with real-time non-adherence monitoring will lead to more efficient clinical research and greater generalizability of results.
    MeSH term(s) Male ; Humans ; Middle Aged ; Prospective Studies ; Retrospective Studies ; Socioeconomic Factors ; Income
    Language English
    Publishing date 2022-12-02
    Publishing country England
    Document type Journal Article
    ZDB-ID 2040523-6
    ISSN 1745-6215 ; 1468-6694 ; 1745-6215
    ISSN (online) 1745-6215
    ISSN 1468-6694 ; 1745-6215
    DOI 10.1186/s13063-022-06901-w
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: Protocol for inducing inflammation and acute myelin degeneration in larval zebrafish.

    Jaronen, Merja / Wheeler, Michael A / Quintana, Francisco J

    STAR protocols

    2022  Volume 3, Issue 1, Page(s) 101134

    Abstract: ... to neurodegeneration. For complete details on the use and execution of this profile, please refer to Wheeler et al ...

    Abstract This protocol details the induction of inflammation and acute myelin degeneration in larval zebrafish with a duration of <10 days. We describe the use of this model to screen the effects of candidate compounds on inflammation, followed by RNA isolation, and qPCR-based quantification of gene expression. We then outline the steps for bioinformatic analysis of the mechanisms associated with the compounds. This protocol can be used in combination with drugs and genetic targeting to identify pathways that contribute to neurodegeneration. For complete details on the use and execution of this profile, please refer to Wheeler et al. (2019).
    MeSH term(s) Animals ; Demyelinating Diseases ; Inflammation ; Larva/metabolism ; Myelin Sheath ; Zebrafish/genetics
    Language English
    Publishing date 2022-01-28
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ISSN 2666-1667
    ISSN (online) 2666-1667
    DOI 10.1016/j.xpro.2022.101134
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  9. Article ; Online: Turning coldspots into hotspots: targeted recruitment of axis protein Hop1 stimulates meiotic recombination in Saccharomyces cerevisiae.

    Shodhan, Anura / Xaver, Martin / Wheeler, David / Lichten, Michael

    Genetics

    2022  Volume 222, Issue 1

    Abstract: The DNA double-strand breaks that initiate meiotic recombination are formed in the context of the meiotic chromosome axis, which in Saccharomyces cerevisiae contains a meiosis-specific cohesin isoform and the meiosis-specific proteins Hop1 and Red1. Hop1 ...

    Abstract The DNA double-strand breaks that initiate meiotic recombination are formed in the context of the meiotic chromosome axis, which in Saccharomyces cerevisiae contains a meiosis-specific cohesin isoform and the meiosis-specific proteins Hop1 and Red1. Hop1 and Red1 are important for double-strand break formation; double-strand break levels are reduced in their absence and their levels, which vary along the lengths of chromosomes, are positively correlated with double-strand break levels. How axis protein levels influence double-strand break formation and recombination remains unclear. To address this question, we developed a novel approach that uses a bacterial ParB-parS partition system to recruit axis proteins at high levels to inserts at recombination coldspots where Hop1 and Red1 levels are normally low. Recruiting Hop1 markedly increased double-strand breaks and homologous recombination at target loci, to levels equivalent to those observed at endogenous recombination hotspots. This local increase in double-strand breaks did not require Red1 or the meiosis-specific cohesin component Rec8, indicating that, of the axis proteins, Hop1 is sufficient to promote double-strand break formation. However, while most crossovers at endogenous recombination hotspots are formed by the meiosis-specific MutLγ resolvase, crossovers that formed at an insert locus were only modestly reduced in the absence of MutLγ, regardless of whether or not Hop1 was recruited to that locus. Thus, while local Hop1 levels determine local double-strand break levels, the recombination pathways that repair these breaks can be determined by other factors, raising the intriguing possibility that different recombination pathways operate in different parts of the genome.
    MeSH term(s) Chromosomal Proteins, Non-Histone/genetics ; Chromosomal Proteins, Non-Histone/metabolism ; DNA Breaks, Double-Stranded ; DNA-Binding Proteins/genetics ; Homologous Recombination ; Meiosis/genetics ; Saccharomyces cerevisiae/genetics ; Saccharomyces cerevisiae/metabolism ; Saccharomyces cerevisiae Proteins/genetics ; Saccharomyces cerevisiae Proteins/metabolism
    Chemical Substances Chromosomal Proteins, Non-Histone ; DNA-Binding Proteins ; HOP1 protein, S cerevisiae ; REC8 protein, S cerevisiae ; Saccharomyces cerevisiae Proteins
    Language English
    Publishing date 2022-07-25
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Intramural
    ZDB-ID 2167-2
    ISSN 1943-2631 ; 0016-6731
    ISSN (online) 1943-2631
    ISSN 0016-6731
    DOI 10.1093/genetics/iyac106
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  10. Article ; Online: Cervical Ripening and Induction of Labor.

    Wheeler, Vernon / Hoffman, Ariel / Bybel, Michael

    American family physician

    2022  Volume 105, Issue 2, Page(s) 177–186

    Abstract: Induction of labor is a common obstetric procedure, and approximately one-fourth of pregnant patients undergo the procedure. Although exercise and nipple stimulation can increase the likelihood of spontaneous labor, sexual intercourse may not be ... ...

    Abstract Induction of labor is a common obstetric procedure, and approximately one-fourth of pregnant patients undergo the procedure. Although exercise and nipple stimulation can increase the likelihood of spontaneous labor, sexual intercourse may not be effective. Acupuncture has been used for labor induction; however, it has not been shown to increase vaginal delivery rates. There is strong evidence that membrane sweeping can increase the likelihood of spontaneous labor within 48 hours. Cervical preparation or ripening is often needed before induction. Some evidence shows that the use of nonpharmacologic approaches such as osmotic dilators and cervical ripening balloons reduce time to delivery. The effect of amniotomy on labor is uncertain. Pharmacologic intervention with oxytocin or prostaglandins is effective for cervical ripening and induction of labor. Combining a balloon catheter with misoprostol is a common practice and has been shown to decrease time to delivery in a small study.
    MeSH term(s) Cervical Ripening ; Female ; Humans ; Labor, Induced/methods ; Misoprostol/therapeutic use ; Oxytocics ; Oxytocin ; Pregnancy
    Chemical Substances Oxytocics ; Misoprostol (0E43V0BB57) ; Oxytocin (50-56-6)
    Language English
    Publishing date 2022-02-15
    Publishing country United States
    Document type Journal Article
    ZDB-ID 412694-4
    ISSN 1532-0650 ; 0002-838X ; 0572-3612
    ISSN (online) 1532-0650
    ISSN 0002-838X ; 0572-3612
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