Y Chromosome Gene Expression in the Blood of Male Patients With Ischemic Stroke Compared With Male Controls

We investigated the origin of XX sex reversal in the insectivorous mole Talpa occidentalis. Cytogenetic, histological and hormonal studies indicate that all XX individuals analyzed from two different populations are true hermaphrodites, with ovotestes. This suggests that XX sex reversal may be the norm in this species. The intersexes are functional fertile females and the trait is transmitted and maintained in the population. Intersexes lack the Y chromosome gene SRY (sex determining region Y gene), shown to be the testis determining gene. These results suggest that XX intersex moles may have arisen from a mutation of a gene located downstream from SRY/TDY in the testis determining pathway.

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Obtaining Human Ischemic Stroke Gene Expression Biomarkers from Animal Models: A Cross-species Validation Study

Scientific Reports ◽

10.1038/srep29693 ◽

2016 ◽

Vol 6 (1) ◽

Cited By ~ 7

Author(s):

Yingying Wang ◽

Yunpeng Cai

Keyword(s):

Gene Expression ◽

Ischemic Stroke ◽

Animal Models ◽

Validation Study

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OCT4Gonadal Gene Expression Related to the Presence of Y-Chromosome Sequences in Turner Syndrome.

10.1210/endo-meetings.2010.part1.p7.p1-304 ◽

2010 ◽

pp. P1-304-P1-304

Author(s):

B Bianco ◽

MVN Lipay ◽

KC Oliveira ◽

AD Guedes ◽

ITN Verreschi

Keyword(s):

Gene Expression ◽

Turner Syndrome ◽

Y Chromosome

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Elevated Lipocalin-2 Can Indicate the Vascular Inflammation in Patients with Ischemic Stroke

Austin Journal of Cerebrovascular Disease & Stroke ◽

10.26420/austinjcerebrovascdisstroke.2019.1081 ◽

2019 ◽

Author(s):

Rajnics P ◽

◽

Kellner A ◽

Nagy F ◽

Alföldi V ◽

...

Keyword(s):

Gene Expression ◽

Ischemic Stroke ◽

Gene Expression Level ◽

Expression Level ◽

Neutrophil Granulocytes ◽

Lipocalin 2 ◽

Relative Gene Expression ◽

Thrombotic Risk ◽

Relative Gene ◽

Relative Gene Expression Level

Purpose: Elevated level of Lipocalin-2 (LCN2), a new acute phase adipokine, was described after ischemic stroke. A number of researchers feel as though that LCN2 originated from the infiltrating neutrophils and other cells in brain after stroke. Others measured elevated LCN2 expression in arteriosclerotic plaque. Therefore we have investigated LCN2 relative gene expression level of blood neutrophil granulocytes in patients with ischemic stroke to assess if elevated LCN2 is the cause or consequence of ischemic stroke. Methods: Laboratory and anamnestic data were collected, which could have a role in development of thrombo-embolic events in patients with ischemic stroke. RNA based method was used to evaluate the relative gene expression level of LCN2. We calculated Odds Ratio (OR) and Confidence Interval (CI) for the association between LCN2 and ischemic stroke. Results: 34 samples were available for evaluation. The LCN 2 relative gene expression level was decreased in 12 cases. In this group, 91% of patients have Atrial Fibrillation (AF) at the time of hospitalisation. The mean LCN2 relative gene expression value was 64.25% (ranges: 34%-115%) in patients with AF. It was significantly lower than in patients with normal sinus rhythm (409.2%; ranges: 127%-1127%; p=0.0003). The elevated LCN2 relative gene expression level significantly (p=0.012) increases the risk of stroke (OR: 12.6) independently from other factors. Conclusions: High LCN2 expression level seems to have strong positive predictive value on ischemic stroke, and may be useful in thrombotic risk stratification of plaque vulnerability in these patients.

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88 Evidence of enhanced immune activation within the tumor microenvironment and the circulation of female patients with high-risk melanoma compared to males

Journal for ImmunoTherapy of Cancer ◽

10.1136/jitc-2021-sitc2021.088 ◽

2021 ◽

Vol 9 (Suppl 3) ◽

pp. A96-A96

Author(s):

Mariam Saad ◽

Aik Choon Tan ◽

Issam El Naqa ◽

Sandra Lee ◽

F Stephen Hodi ◽

...

Keyword(s):

Gene Expression ◽

T Cells ◽

Expression Profiling ◽

Female Gender ◽

National Institutes Of Health ◽

Female Patients ◽

High Risk Melanoma ◽

Risk Melanoma ◽

Male Patients ◽

Written Informed Consent

BackgroundSex differences in tumor immunity and response to immunotherapy were shown in murine models and descriptive analyses from recent clinical trials. We recently reported that female gender is a favorable prognostic marker for survival benefit following ipilimumab and high dose interferon-alfa (HDI) adjuvant therapy of high-risk melanoma in the ECOG-ACRIN E1609 trial (N=1670). Therefore, we investigated differences in candidate immune biomarkers in the circulation and tumor microenvironment (TME) of female and male patients.MethodsGene expression profiling (GEP) was performed on the tumor biopsies of 718 (454 male, 264 female) patients. The primary endpoint was mRNA expression profiling using U133A 2.0 Affymetrix gene chips. Raw microarray data sets were normalized by using the Robust Multi-array Average (RMA) method using Affymetrix Power Tools (APT) as previously published. Multiple probe sets representing the same genes were collapsed by using the probe with maximum gene expression. Gene set enrichment analysis (GSEA) was performed by comparing the female and male tumor samples, and gene sets with FDR q-value <0.1 were deemed as significant. Similarly, peripheral blood (serum and PBMC) samples were tested for soluble (Luminex) and cellular (multicolor flow cytometry) prognostic biomarkers in a subset of patients (N=321; 109 female and 212 male). All patients provided an IRB-approved written informed consent.ResultsAmong the subset of patients tested for circulating biomarkers, females were significantly younger than males (P=0.03). Testing PBMCs, the percentages of CD3+ T cells (P=0.04) and CD3+CD4+ helper T cells (P=0.0005) were significantly higher in female patients compared to males. Also, there were trends toward higher levels of proinflammatory cytokines IL1beta (P=0.07) and IL6 (P=0.06) in females. On the other hand, males had significantly higher percentages of monocytes (P=0.03). Further, there were trends toward higher percentages of CD3+/CD4+/CD25hi+/Foxp3+ (P=0.1) and CD3+/CD4+/CD25+/CD127low+ (P=0.1) T-reg in male patients compared to females. Among the cohort of patients (N=718) with tumor GEP data, females were significantly younger than males (P=0.0009). GEP identified pathways and genes related to immune cell infiltration and activation that were significantly enriched in the tumors of females compared to males (table 1).Abstract 88 Table 1Immune pathways significantly enriched in tumors of femalesConclusionsFemale gender was associated with adjuvant immunotherapeutic benefits and female patients were more likely to have evidence of immune activation within the TME and the circulation, supporting a potentially important role for female related factors in the immune response against melanoma, and these require further investigation.AcknowledgementsWe are grateful to the patients and family members who participated in the E1609 trial and the E1609 trial investigators. This study was conducted by the ECOG-ACRIN Cancer Research Group (Peter J. O’Dwyer, MD and Mitchell D. Schnall, MD, PhD, Group Co-Chairs) and supported by the National Cancer Institute of the National Institutes of Health under the following award numbers: U10CA180794, U10CA180820, U10CA180888, UG1CA233180, UG1CA233184. Biomarkers studies were supported under the following award number: P50CA12197310 (Tarhini and Kirkwood). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.Trial RegistrationNCT01274338Ethics ApprovalThe E1609 study protocol was approved by the institutional review board of each participating institution and conducted in accordance with Good Clinical Practice guidelines as defined by the International Conference on Harmonization. All patients provided an IRB-approved written informed consent.ConsentNot applicable.

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Interrogation of cancer gene dependencies reveals novel paralog interactions of autosome and sex chromosome encoded genes

10.1101/2021.05.21.445116 ◽

2021 ◽

Author(s):

Anna Köferle ◽

Andreas Schlattl ◽

Alexandra Hörmann ◽

Fiona Spreitzer ◽

Alexandra M. Popa ◽

...

Keyword(s):

Y Chromosome ◽

Therapeutic Strategy ◽

Sex Chromosome ◽

De Novo ◽

Chromosome Loss ◽

Potential Candidate ◽

Loss Of Function ◽

Male Patients ◽

Tumour Cell Lines ◽

Paralog Gene

Genetic networks are characterized by extensive buffering. During tumour evolution, disruption of these functional redundancies can create de novo vulnerabilities that are specific to cancer cells. In this regard, paralog genes are of particular interest, as the loss of one paralog gene can render tumour cells dependent on a remaining paralog. To systematically identify cancer-relevant paralog dependencies, we searched for candidate dependencies using CRISPR screens and publicly available loss-of-function datasets. Our analysis revealed >2,000 potential candidate dependencies, several of which were subsequently experimentally validated. We provide evidence that DNAJC15-DNAJC19, FAM50A-FAM50B and RPP25-RPP25L are novel cancer relevant paralog dependencies. Importantly, our analysis also revealed unexpected redundancies between sex chromosome genes. We show that chrX- and chrY- encoded paralogs, as exemplified by ZFX-ZFY, DDX3X-DDX3Y and EIF1AX-EIF1AY, are functionally linked so that tumour cell lines from male patients with Y-chromosome loss become exquisitely dependent on the chrX-encoded gene. We therefore propose genetic redundancies between chrX- and chrY- encoded paralogs as a general therapeutic strategy for human tumours that have lost the Y-chromosome.

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Forensic application of Y-chromosomal STR analysis in Lithuanian population

Biologija ◽

10.6001/biologija.v61i2.3140 ◽

2015 ◽

Vol 61 (2) ◽

Author(s):

Giedrė Ruzgaitė ◽

Marija Čaplinskienė ◽

Rima Baranovienė ◽

Jūratė Jankauskienė ◽

Jolanta Kukienė ◽

...

Keyword(s):

Y Chromosome ◽

Gene Pool ◽

Haplotype Diversity ◽

Haplotype Frequency ◽

Reference Database ◽

Match Probability ◽

Str Analysis ◽

Str Markers ◽

Forensic Casework ◽

Chromosome Gene

This paper presents a comprehensive Y-chromosomal STR haplotype analysis in the Lithuanian population in order to evaluate Lithuanians’ Y chromosome diversity, to infer genetic relations between Lithuanian and other European neighbouring populations and to introduce population reference data for generation of reliable Y-STR haplotype frequency estimates to be used in the quantitative assessment of Y-STR haplotype match in the forensic casework. Data were collected from the peripheral blood samples of 194 unrelated males throughout various regions of Lithuania. The amplification of 17 Y-STRs was carried out in one multiplex PCR using an AmpFlSTR® Yfiler<sup>TM</sup> PCR Amplication Kit according to the supplier’s protocol. The results indicated that the Y-chromosomal haplotype diversity in the Lithuanian population rises as the number of the analyzed Y-STRs is increased. However, all additional Y-STR loci are not hypervariable and only their whole makes a large diversity of Y-STR haplotypes in Lithuanian males. The analysis of molecular variance revealed low but significant interpopulation differences except the pair of Lithuanian and Latvian populations. The phylogenetic analysis showed that the clustered Y chromosome gene pool of Lithuanians and Latvians has a closer phylogenetic relation to Russian and Estonian populations and is less genetically related to other neighbouring populations of Belarus and Poland. Yet Y-STRs alleles and haplotypes differentiate effectively inside the Lithuanian population and between Lithuanians and its geographical neighbours excluding the Latvian population. Comparison of the Y-STR data suggests that Lithuanian and Latvian populations are closely related not only by geography and language but also by the Y chromosome gene pool represented by forensic Y-STR markers. Consequently, more forensic Y-STR markers should be included in the Y-STR haplotype in order to achieve a resolution between the Y chromosomes of Lithuanian and Latvian males. Lithuanian Y-STR haplotype data were submitted to the 34th release of the Y-STR Haplotype Reference Database 3.0 for match probability calculations in the forensic casework.

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Hyperexpression of TLR2 and TLR4 in patients with ischemic stroke in acute period of the disease

Medical Immunology (Russia) ◽

10.15789/1563-0625-hot-1971 ◽

2020 ◽

Vol 22 (4) ◽

pp. 665-674

Author(s):

L. V. Gankovskaya ◽

L. V. Stakhovskaya ◽

V. V. Grechenko ◽

E. A. Koltsova ◽

O. S. Uvarova ◽

...

Keyword(s):

Gene Expression ◽

Innate Immunity ◽

Ischemic Stroke ◽

Peripheral Blood ◽

Surface Expression ◽

Control Group ◽

Peripheral Blood Leukocytes ◽

Blood Leukocytes ◽

Healthy Donors ◽

Tlr4 Gene

Pathogenesis of ischemic stroke is actively involved in the system of innate immunity. Under conditions of cerebral ischemia, a number of biologically active substances are released that interact with innate immunity receptors, in particular TLR2 and TLR4, which exacerbate inflammation in brain tissue. Identification of predictor markers at the level of the innate immunity system may foresee the clinical course of ischemic stroke and ensure timely treatment. Our objective was to study expression of TLR2 and TLR4 receptors in peripheral blood leukocytes in patients with ischemic stroke in the dynamics of the disease. 27 people were included in the study. The main group consisted of patients with ischemic stroke of varying severity (n = 19). Patients of the main group were divided into two subgroups: with an NIHSS index value of < 10 (n = 10) and > 10 (n = 9). The control group included healthy donors with no history of acute and chronic inflammatory diseases (n = 8). Peripheral blood leukocytes were used as the test material. To determine expression of the TLR2 and TLR4 genes, RT-PCR in real time was used. Surface expression of TLRs was determined by flow cytometry. A study of the TLR2 and TLR4 gene expression showed that on the 1st, 3rd and 7th day post-stroke, the TLR4 gene expression in patients was significantly increased, when compared to the control group (p < 0.01), whereas TLR2 gene expression on the 3rd day of the disease was not statistically different from the control group. A study of surface expression of receptors showed that the average TLR2 fluorescence intensity on the patients’ peripheral blood monocytes was significantly increased on the 1st and 3rd day of disease when compared to the control group. The surface expression of TLR4 on monocytes has a statistically significant increase only on day 7. Assessment of surface expression of TLRs in subgroups with different severity values by NIHSS showed that patients with a NIHSS index > 10 had a significantly higher level of surface of TLR2 expression over the observation period, while the largest difference in TLR4 expression in the subgroups was observed on the 1st day of the disease (p < 0.05). Patients with ischemic stroke showed an increase in TLR2 and TLR4 expression at the gene and protein level, compared to healthy donors. These indices can be considered possible predictors for clinical prognosis of ischemic stroke.

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Clinical Impact of Estradiol/Testosterone Ratio in Patients with Acute Ischemic Stroke

10.21203/rs.3.rs-33503/v3 ◽

2020 ◽

Author(s):

Jung-Won Choi ◽

In Woo Ryoo ◽

Jun Yeong Hong ◽

Kyung-Yul Lee ◽

Hyo Suk Nam ◽

...

Keyword(s):

Ischemic Stroke ◽

Acute Ischemic Stroke ◽

Sex Hormones ◽

Control Group ◽

Control Groups ◽

Sexual Hormones ◽

Stroke Group ◽

Male Patients ◽

And Control

Abstract Background: Sex hormones may be associated with a higher incidence of ischemic stroke or stroke-related events. In observational studies, lower testosterone concentrations are associated with infirmity, vascular disease, and adverse cardiovascular risk factors. Currently, female sexual hormones are considered neuroprotective agents. The purpose of this study was to assess the role of sex hormones and the ratio of estradiol/testosterone (E/T) in patients with acute ischemic stroke (AIS).Methods: Between January 2011 and December 2016, 146 male patients with AIS and 152 age- and sex-matched control subjects were included in this study. Sex hormones, including estradiol, progesterone, and testosterone, were evaluated in the AIS patient and control groups. We analyzed the clinical and physiological levels of sex hormones and hormone ratios in these patients.Results: The E/T ratio was significantly elevated among patients in the stroke group compared to those in the control group (P = 0.001). Categorization of data into tertiles revealed that patients with the highest E/T ratio were more likely to have AIS [odds ratio (OR) 3.084; 95% Confidence interval (CI): 1.616-5.886; P < 0.001) compared with those in the first tertile. The E/T ratio was also an independent unfavorable outcome predictor with an adjusted OR of 1.167 (95% CI: 1.053-1.294; P = 0.003).Conclusions: These findings support the hypothesis that increased estradiol and reduced testosterone levels are associated with AIS in men.

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