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1

Salmon, Adam, and Daniel Adekunbi. "CELLULAR RESPIRATION AND RESILIENCE AS A POTENTIAL BIOLOGICAL MECHANISM DRIVING SEX DIFFERENCES IN AGING." Innovation in Aging 6, Supplement_1 (November 1, 2022): 443. http://dx.doi.org/10.1093/geroni/igac059.1735.

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Abstract There are substantial differences in the progression of aging between males and females including in progression and prevalence of disease and longevity. Not all can be explained solely by sex-specific endocrine regulation and growing evidence suggests there are basic biological and genetic differences in sex that drive disparity in physiological function. In this study, we describe metabolic differences at the cellular level that both define some of these biological differences as well as provide a potential mechanism for delineating relevant molecular mechanisms of aging. Using HET3 mice, a genetically heterogeneous model with a consistent female advantage in longevity, we show that primary fibroblast lines retain functional metabolic characteristics, including mitochondrial response and stress resilience, which are representative of the sex of the donor animal. These differences persist even after several rounds of passage using standard culturing techniques suggesting these differences are not driven by direct impact of circulating sex hormones. Moreover, we find that differences in these cellular responses have some predictive power to determine both sex- and individual-specific responses to physiological challenge including obesity and longevity. In addition, we are able to use this model to delineate how donor sex affects cellular responses within defined pillars of aging including proteostasis, metabolic function, and adaption to stress. Overall, our model then provides valuable in defining the cellular responses that contribute to the mammalian aging process.
2

Beikoghli Kalkhoran, Siavash, and Georgios Kararigas. "Oestrogenic Regulation of Mitochondrial Dynamics." International Journal of Molecular Sciences 23, no. 3 (January 20, 2022): 1118. http://dx.doi.org/10.3390/ijms23031118.

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Biological sex influences disease development and progression. The steroid hormone 17β-oestradiol (E2), along with its receptors, is expected to play a major role in the manifestation of sex differences. E2 exerts pleiotropic effects in a system-specific manner. Mitochondria are one of the central targets of E2, and their biogenesis and respiration are known to be modulated by E2. More recently, it has become apparent that E2 also regulates mitochondrial fusion–fission dynamics, thereby affecting cellular metabolism. The aim of this article is to discuss the regulatory pathways by which E2 orchestrates the activity of several components of mitochondrial dynamics in the cardiovascular and nervous systems in health and disease. We conclude that E2 regulates mitochondrial dynamics to maintain the mitochondrial network promoting mitochondrial fusion and attenuating mitochondrial fission in both the cardiovascular and nervous systems.
3

Lu, Jianyun, Jasmin Sponagel, Jill Jones, Hannah Gass, Elena Nunez, Cheryl Frankfater, Sierra Williams-McLeod, et al. "TMET-13. SEX DIFFERENCES IN GLUCOSE METABOLISM AND MITOCHONDRIAL FUNCTION IN GLIOBLASTOMA IMPLICATE HYPOXIA-INDUCIBLE FACTOR 1 ALPHA (HIF1A) ACTIVITY." Neuro-Oncology 24, Supplement_7 (November 1, 2022): vii264. http://dx.doi.org/10.1093/neuonc/noac209.1018.

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Abstract Glioblastoma (GBM) is the most common and aggressive primary brain tumor in adults. It is more prevalent in males and female patients have better survival. Investigating the molecular mechanisms underlying this disparity is imperative for understanding its development and progression as well as developing novel treatment paradigms. Carbohydrate (namely glucose) metabolism is a critical GBM nutrient source for biosynthesis, energetics, and reducing equivalents. Previously, our group discovered that elevated glycolytic activity uniquely predicted the outcomes of male, but not female, lower grade glioma patients. Our goal was to characterize sex differences in GBM carbohydrate metabolism and their effects on cellular phenotype. First, we discovered that male transformed murine astrocytes were more susceptible to glucose deprivation than females. We confirmed this phenotype with irreversible inhibition of hexokinase with 2-deoxyglucose as well as a GLUT1-selective inhibitor. Time-resolved stable isotope tracing of cell metabolism with carbon-13 glucose in transformed astrocytes further supported these findings; male cells had significantly higher rates of glucose uptake and metabolism than female cells. These results were validated with stable isotope metabolomics datasets from human cancer cell lines. Using additional assays of cellular metabolism, we discovered that male transformed astrocytes had a higher glycolytic rate, higher pyruvate kinase activity, higher mitochondrial respiration, and higher mitochondrial mass compared to females. This was validated by a TCGA pancancer analysis that revealed significantly higher expression of nuclear genes involved in mitochondrial regulation in males than in females. This prompted us to identify possible regulators of this metabolic phenotype. We discovered that HIF1A had robust hypoxia-inducible expression that was significantly higher in male transformed astrocytes. Moreover, HIF1A expression as well as its target transcripts were significantly higher in TCGA pancancer tumor datasets. Together, our data underscore the potential for developing sex-specific metabolic targeting approaches for patients with GBM.
4

Liu, Junyan, Rong Zhang, Xiao Xu, Joshua C. Fowler, Tom E. X. Miller, and Tingfa Dong. "Effect of summer warming on growth, photosynthesis and water status in female and male Populus cathayana: implications for sex-specific drought and heat tolerances." Tree Physiology 40, no. 9 (May 30, 2020): 1178–91. http://dx.doi.org/10.1093/treephys/tpaa069.

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Abstract Effects of climate warming on tree growth and physiology may be driven by direct thermal effects and/or by changes in soil moisture. Dioecious tree species usually show sexual spatial segregation along abiotic gradients; however, few studies have assessed the sex-specific responses to warming in dioecious trees. We investigated the sex-specific responses in growth, photosynthesis, nonstructural carbohydrate (NSC), water-use efficiency and whole-plant hydraulic conductance (KP) of the dioecious tree species Populus cathayana Rehd. under +4 °C elevated temperature with and without supplemental water. For both sexes, high-temperature treatments significantly decreased growth (height and biomass), photosynthetic rate (A), the ratio of A to dark respiration rate, stomatal conductance (gs), transpiration rate, NSC, leaf water potential and KP, but increased water-use efficiency (estimated from carbon isotope composition). Under warming with supplemental water, most traits of females did not change relative to ambient conditions, but traits of males decreased, resulting in greater sexual differences. Females showed a lower KP, and their gs and A responded more steeply with water-related traits than males. These results show that the effect of summer warming on growth and photosynthesis was driven mainly by soil moisture in female P. cathayana, while male performance was mainly related to temperature. Females may experience less thermal stress than males due to flexible water balance strategy via stomata regulation and water use.
5

Buchholz, Friedrich, and Reinhard Saborowski. "Metabolic and enzymatic adaptations in northern krill,Meganyctiphanes norvegica, and Antarctic krill,Euphausia superba." Canadian Journal of Fisheries and Aquatic Sciences 57, S3 (December 1, 2000): 115–29. http://dx.doi.org/10.1139/f00-168.

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The Antarctic krill, Euphausia superba, is restricted to the Antarctic Ocean. The northern krill, Meganyctiphanes norvegica, is extremely widely distributed from the arctic North Atlantic to the warm Mediterranean. Respiration measurements showed no seasonal differences in rates determined in krill from the thermally stable Clyde Sea (Scotland) and the cooler but variable Danish Kattegat. In the warm Ligurian Sea, where temperatures are stable, krill showed higher rates in April than in September, indicating reactions to the short but intensive productive season. Krill can passively benefit from enhancements of overall metabolism when ascending into upper, warmer water strata during their pronounced diel vertical migration. Michaelis-Menten constants (Km) of citrate synthase (CS) were compared. In terms of respiration and enzyme regulation, krill from the Ligurian Sea stand apart: temperature and nutrition appear to be of different influence, relatable to genetic differentiation in the species. In contrast, Kmof CS in E. superba is temperature independent, highlighting the species' stenothermal physiology. A basal level of activity of digestive enzymes ensures immediate utilization of patchy food sources. Specific induction, including that of chitinases, indicating omnivory in both species, underlines krill's exceptional capacity to adapt to highly variable trophic environments. Processes of moult, growth, and reproduction are locally and seasonally adjusted.
6

Murni Yuliastuti, Christina, Th tatik Pujiastuti, and Sr Lucilla Suparmi, CB. "Perbedaan Tekanan Darah Sebelum dan Sesudah Exercise Intradialysis Pada Pasien Hemodialisis di Unit Hemodialisis Rumah Sakit Panti Rahayu Gunung Kidul." I Care Jurnal Keperawatan STIKes Panti Rapih 2, no. 2 (October 8, 2021): 156–69. http://dx.doi.org/10.46668/jurkes.v2i2.194.

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ABSTRACT Background: Hemodialysis defines as a process of cleaning the blood from waste substances through a filtering process outside the body. Patients with chronic renal failure undergoing hemodialysis often experience complications including hypotension. Several references state an alternative intervention to prevent complications of hypotension in hemodialysis patients with an Intradialytic exercise. Intradialytic exercise is a planned and gradual form of exercise that includes various stages of flexibility exercise, strengthening exercise and cardiovascular exercise performed during hemodialysis. Intradialytic exercise is aimed to improve the work of the heart, respiration and improve hemodialysis regulation for the better. Objective: This study was aimed to determine the difference in blood pressure before and after intradialytic exercise in patients undergoing hemodialysis. Methods: This research design used a quasi-experimental design with pre-test and post-test with control design. The samples were 38 respondents who taken by total sampling at the Hemodialysis Unit of Panti Rahayu Hospital. The samples were divided into the intervention group who undertook intradialytic exercise for 4 weeks, each respondent experiences twice a week, while the control group who did routine hemodialysis and independent exercise. Results: The results showed that the distribution of the characteristics of the respondents was 51-54 years old (18.41%) the sex was mostly male (63.2%) Most of them (55.3%) underwent hemodialysis for less than 2 years. Statistically, it was known that there was no significant difference in blood pressure before and after intradialytic exercise inside patient’s body of the control and intervention groups. There was no significant difference in blood pressure between the intervention group compared to the control group, but there was a dynamic difference in blood pressure in patients who did intradialytic exercise. Conclusion: There was dynamics of differences in blood pressure in patients undergoing intradialytic exercise, it is recommended that hemodialysis nurses at Panti Rahayu Hospital take care patients during hemodialysis so that these interventions are routinely carried out.
7

Murni Yuliastuti, Christina, Th Tatik Pujiastuti, and Sr Lucilla Suparmi, CB. "Perbedaan Tekanan Darah Sebelum dan Sesudah Exercise Intradialysis Pada Pasien Hemodialisis di Unit Hemodialisis Rumah Sakit Panti Rahayu Gunung Kidul." I Care Jurnal Keperawatan STIKes Panti Rapih 2, no. 2 (October 8, 2021): 156–69. http://dx.doi.org/10.46668/jurkes.v2i2.196.

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ABSTRACT Background:Hemodialysis defines as a process of cleaning the blood from waste substances through a filtering process outside the body. Patients with chronic renal failure undergoing hemodialysis often experience complications including hypotension. Several references state an alternative intervention to prevent complications of hypotension in hemodialysis patients with an Intradialytic exercise. Intradialytic exercise is a planned and gradual form of exercise that includes various stages of flexibility exercise, strengthening exercise and cardiovascular exercise performed during hemodialysis. Intradialytic exercise is aimed to improve the work of the heart, respiration and improve hemodialysis regulation for the better. Objective:This study was aimed to determine the difference in blood pressure before and after intradialytic exercise in patients undergoing hemodialysis. Methods:This research design used a quasi-experimental design with pre-test and post-test with control design. The samples were 38 respondents who taken by total sampling at the Hemodialysis Unit of Panti Rahayu Hospital. The samples were divided into the intervention group who undertook intradialytic exercise for 4 weeks, each respondent experiences twice a week, while the control group who did routine hemodialysis and independent exercise. Results:The results showed that the distribution of the characteristics of the respondents was 51-54 years old (18.41%) the sex was mostly male (63.2%) Most of them (55.3%) underwent hemodialysis for less than 2 years. Statistically, it was known that there was no significant difference in blood pressure before and after intradialytic exercise inside patient’s body of the control and intervention groups. There was no significant difference in blood pressure between the intervention group compared to the control group, but there was a dynamic difference in blood pressure in patients who did intradialytic exercise. Conclusion:There was dynamics of differences in blood pressure in patients undergoing intradialytic exercise, it is recommended that hemodialysis nurses at Panti Rahayu Hospital take care patients during hemodialysis so that these interventions are routinely carried out.
8

Miotto, Paula M., Chris McGlory, Tanya M. Holloway, Stuart M. Phillips, and Graham P. Holloway. "Sex differences in mitochondrial respiratory function in human skeletal muscle." American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 314, no. 6 (June 1, 2018): R909—R915. http://dx.doi.org/10.1152/ajpregu.00025.2018.

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Mitochondrial bioenergetic contributions to sex differences in human skeletal muscle metabolism remain poorly defined. The primary aim of this study was to determine whether mitochondrial respiratory kinetics differed between healthy young men and women in permeabilized skeletal muscle fibers. While men and women displayed similar ( P > 0.05) maximal respiration rates and abundance of mitochondrial/adenosine diphosphate (ADP) transport proteins, women had lower ( P < 0.05) mitochondrial ADP sensitivity (+30% apparent Km) and absolute respiration rates at a physiologically relevant ADP concentration (100 μM). Moreover, although men and women exhibited similar carnitine palmitoyl transferase-I protein content- and palmitoyl-CoA-supported respiration, women displayed greater sensitivity to malonyl-CoA-mediated respiratory inhibition. These data establish baseline sex differences in mitochondrial bioenergetics and provide the foundation for studying mitochondrial function within the context of metabolic perturbations and diseases that affect men and women differently.
9

Klymenko, M. R. "NARCISSISTIC SELF-REGULATION: STUDYING SEX DIFFERENCES." Habitus, no. 40 (2022): 115–20. http://dx.doi.org/10.32782/2663-5208.2022.40.18.

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10

Сулаєва, О. М., and Н. І. Белемець. "Sex differences in regulation of adipose tissue." Clinical endocrinology and endocrine surgery, no. 4(60) (November 27, 2017): 11–20. http://dx.doi.org/10.24026/1818-1384.4(60).2017.118729.

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11

Davy, Brenda M., Emily L. Van Walleghen, and Jeb S. Orr. "Sex differences in acute energy intake regulation." Appetite 49, no. 1 (July 2007): 141–47. http://dx.doi.org/10.1016/j.appet.2007.01.010.

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12

Halperin Kuhns, Victoria L., and Owen M. Woodward. "Sex Differences in Urate Handling." International Journal of Molecular Sciences 21, no. 12 (June 16, 2020): 4269. http://dx.doi.org/10.3390/ijms21124269.

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Hyperuricemia, or elevated serum urate, causes urate kidney stones and gout and also increases the incidence of many other conditions including renal disease, cardiovascular disease, and metabolic syndrome. As we gain mechanistic insight into how urate contributes to human disease, a clear sex difference has emerged in the physiological regulation of urate homeostasis. This review summarizes our current understanding of urate as a disease risk factor and how being of the female sex appears protective. Further, we review the mechanisms of renal handling of urate and the significant contributions from powerful genome-wide association studies of serum urate. We also explore the role of sex in the regulation of specific renal urate transporters and the power of new animal models of hyperuricemia to inform on the role of sex and hyperuricemia in disease pathogenesis. Finally, we advocate the use of sex differences in urate handling as a potent tool in gaining a further understanding of physiological regulation of urate homeostasis and for presenting new avenues for treating the constellation of urate related pathologies.
13

De Marinis, Elisabetta, Chiara Martini, Anna Trentalance, and Valentina Pallottini. "Sex differences in hepatic regulation of cholesterol homeostasis." Journal of Endocrinology 198, no. 3 (July 4, 2008): 635–43. http://dx.doi.org/10.1677/joe-08-0242.

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Physiological sex differences may influence metabolic status and then alter the onset of some diseases. According to recent studies, it is now well established that females are more protected from hypercholesterolemia-related diseases, such as cardiovascular diseases until menopause. Female protection from hypercholesterolemia is mediated by the hypolipidemic properties of estrogens, even if mechanisms underlying this protection remain still debated. Even though the regulatory mechanisms of cholesterol homeostasis maintenance are well known, few data are available on the supposed differences between male and female in these processes. So, the aim of this work was to define, through an in vivo study, the putative sex-dependent regulation of the processes underlying cholesterol homeostasis maintenance. We examined 3-hydroxy 3-methylglutaryl coenzyme A reductase and its regulatory protein network as well as the amount of low-density lipoprotein receptor and cholesterol. The study was conducted in the liver and plasma of male and female rats, on adults and during postnatal development, and on 17-β-estradiol-treated male rats. Our data support that physiological differences in proteins involved in cholesterol balance are present between the sexes and, in particular, 3-hydroxy 3-methylglutaryl coenzyme A reductase shows lower activity and expression in female and 17-β-estradiol-treated male rats than in adult untreated male. Our data suggest that sex differences in enzyme expression depend on variation in regulatory proteins and seem to be related to estrogen presence. This work adds new evidence in the complicated picture of sex-dependent cellular physiology and establishes a new role for reductase regulatory proteins as a link between estrogen protective effects and cholesterol homeostasis.
14

Shingo, Matsuda. "Sex differences in biological mechanism of fear regulation." Proceedings for Annual Meeting of The Japanese Pharmacological Society 95 (2022): 2—S20–1. http://dx.doi.org/10.1254/jpssuppl.95.0_2-s20-1.

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15

Joyner, Michael J., B. Gunnar Wallin, and Nisha Charkoudian. "Sex differences and blood pressure regulation in humans." Experimental Physiology 101, no. 3 (August 16, 2015): 349–55. http://dx.doi.org/10.1113/ep085146.

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16

Sherman, Gary D., Leslie K. Rice, Ellie Shuo Jin, Amanda C. Jones, and Robert A. Josephs. "Sex differences in cortisol's regulation of affiliative behavior." Hormones and Behavior 92 (June 2017): 20–28. http://dx.doi.org/10.1016/j.yhbeh.2016.12.005.

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17

Shi, H., and D. J. Clegg. "Sex differences in the regulation of body weight." Physiology & Behavior 97, no. 2 (May 2009): 199–204. http://dx.doi.org/10.1016/j.physbeh.2009.02.017.

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18

Tramunt, Blandine, Sarra Smati, Naia Grandgeorge, Françoise Lenfant, Jean-François Arnal, Alexandra Montagner, and Pierre Gourdy. "Sex differences in metabolic regulation and diabetes susceptibility." Diabetologia 63, no. 3 (November 21, 2019): 453–61. http://dx.doi.org/10.1007/s00125-019-05040-3.

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AbstractGender and biological sex impact the pathogenesis of numerous diseases, including metabolic disorders such as diabetes. In most parts of the world, diabetes is more prevalent in men than in women, especially in middle-aged populations. In line with this, considering almost all animal models, males are more likely to develop obesity, insulin resistance and hyperglycaemia than females in response to nutritional challenges. As summarised in this review, it is now obvious that many aspects of energy balance and glucose metabolism are regulated differently in males and females and influence their predisposition to type 2 diabetes. During their reproductive life, women exhibit specificities in energy partitioning as compared with men, with carbohydrate and lipid utilisation as fuel sources that favour energy storage in subcutaneous adipose tissues and preserve them from visceral and ectopic fat accumulation. Insulin sensitivity is higher in women, who are also characterised by higher capacities for insulin secretion and incretin responses than men; although, these sex advantages all disappear when glucose tolerance deteriorates towards diabetes. Clinical and experimental observations evidence the protective actions of endogenous oestrogens, mainly through oestrogen receptor α activation in various tissues, including the brain, the liver, skeletal muscle, adipose tissue and pancreatic beta cells. However, beside sex steroids, underlying mechanisms need to be further investigated, especially the role of sex chromosomes, fetal/neonatal programming and epigenetic modifications. On the path to precision medicine, further deciphering sex-specific traits in energy balance and glucose homeostasis is indeed a priority topic to optimise individual approaches in type 2 diabetes prevention and treatment.
19

Farrell, Maureen C., Richard J. Giza, and Cyndya A. Shibao. "Race and sex differences in cardiovascular autonomic regulation." Clinical Autonomic Research 30, no. 5 (September 7, 2020): 371–79. http://dx.doi.org/10.1007/s10286-020-00723-z.

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20

Branovets, Jelena, Mervi Sepp, Svetlana Kotlyarova, Natalja Jepihhina, Niina Sokolova, Dunja Aksentijevic, Craig A. Lygate, Stefan Neubauer, Marko Vendelin, and Rikke Birkedal. "Unchanged mitochondrial organization and compartmentation of high-energy phosphates in creatine-deficient GAMT−/− mouse hearts." American Journal of Physiology-Heart and Circulatory Physiology 305, no. 4 (August 15, 2013): H506—H520. http://dx.doi.org/10.1152/ajpheart.00919.2012.

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Disruption of the creatine kinase (CK) system in hearts of CK-deficient mice leads to changes in the ultrastructure and regulation of mitochondrial respiration. We expected to see similar changes in creatine-deficient mice, which lack the enzyme guanidinoacetate methyltransferase (GAMT) to produce creatine. The aim of this study was to characterize the changes in cardiomyocyte mitochondrial organization, regulation of respiration, and intracellular compartmentation associated with GAMT deficiency. Three-dimensional mitochondrial organization was assessed by confocal microscopy. On populations of permeabilized cardiomyocytes, we recorded ADP and ATP kinetics of respiration, competition between mitochondria and pyruvate kinase for ADP produced by ATPases, ADP kinetics of endogenous pyruvate kinase, and ATP kinetics of ATPases. These data were analyzed by mathematical models to estimate intracellular compartmentation. Quantitative analysis of morphological and kinetic data as well as derived model fits showed no difference between GAMT-deficient and wild-type mice. We conclude that inactivation of the CK system by GAMT deficiency does not alter mitochondrial organization and intracellular compartmentation in relaxed cardiomyocytes. Thus, our results suggest that the healthy heart is able to preserve cardiac function at a basal level in the absence of CK-facilitated energy transfer without compromising intracellular organization and the regulation of mitochondrial energy homeostasis. This raises questions on the importance of the CK system as a spatial energy buffer in unstressed cardiomyocytes.
21

Peng, F., Y. Quangang, X. Xue, J. Guo, and T. Wang. "Effects of rodent-induced land degradation on ecosystem carbon fluxes in an alpine meadow in the Qinghai–Tibet Plateau, China." Solid Earth 6, no. 1 (March 4, 2015): 303–10. http://dx.doi.org/10.5194/se-6-303-2015.

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Abstract. The widespread land degradation in an alpine meadow ecosystem would affect ecosystem carbon (C) balance. Biomass, soil chemical properties and carbon dioxide (CO2) of six levels of degraded lands (D1–D6, according to the number of rodent holes and coverage) were investigated to examine the effects of rodent-induced land degradation on an alpine meadow ecosystem. Soil organic carbon (SOC), labile soil carbon (LC), total nitrogen (TN) and inorganic nitrogen (N) were obtained by chemical analysis. Soil respiration (Rs), net ecosystem exchange (NEE) and ecosystem respiration (ER) were measured by a Li-Cor 6400XT. Gross ecosystem production (GEP) was the sum of NEE and ER. Aboveground biomass (AGB) was based on a linear regression with coverage and plant height as independent variables. Root biomass (RB) was obtained by using a core method. Soil respiration, ER, GEP and AGB were significantly higher in slightly degraded (D3 and D6, group I) than in severely degraded land (D1, D2, D4 and D5, group II). Positive values of NEE average indicate that the alpine meadow ecosystem is a weak C sink during the growing season. The only significant difference was in ER among different degradation levels. Rs, ER and GEP were 38.2, 44.3 and 46.5% higher in group I than in group II, respectively. Similar difference of ER and GEP between the two groups resulted in an insignificant difference of NEE. Positive correlations of AGB with ER, NEE and GEP, and relatively small AGB and lower CO2 fluxes in group II, suggest the control of AGB on ecosystem CO2 fluxes. Correlations of RB with SOC, LC, TN and inorganic N indicate the regulation of RB on soil C and N with increasing number of rodent holes in an alpine meadow ecosystem in the permafrost region of the Qinghai–Tibet Plateau (QTP).
22

Mallay, Sarah, Robert Gill, Adrian Young, and Ryan J. Mailloux. "Sex-dependent Differences in the Bioenergetics of Liver and Muscle Mitochondria from Mice Containing a Deletion for glutaredoxin-2." Antioxidants 8, no. 8 (July 26, 2019): 245. http://dx.doi.org/10.3390/antiox8080245.

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Our group recently published a study demonstrating that deleting the gene encoding the matrix thiol oxidoreductase, glutaredoxin-2 (GRX2), alters the bioenergetics of mitochondria isolated from male C57BL/6N mice. Here, we conducted a similar study, examining H2O2 production and respiration in mitochondria isolated from female mice heterozygous (GRX2+/−) or homozygous (GRX2−/−) for glutaredoxin-2. First, we observed that deleting the Grx2 gene does not alter the rate of H2O2 production in liver and muscle mitochondria oxidizing pyruvate, α-ketoglutarate, or succinate. Examination of the rates of H2O2 release from liver mitochondria isolated from male and female mice revealed that (1) sex has an impact on the rate of ROS production by liver and muscle mitochondria and (2) loss of GRX2 only altered ROS release in mitochondria collected from male mice. Assessment of the bioenergetics of these mitochondria revealed that loss of GRX2 increased proton leak-dependent and phosphorylating respiration in liver mitochondria isolated from female mice but did not alter rates of respiration in liver mitochondria from male mice. Furthermore, we found that deleting the Grx2 gene did not alter rates of respiration in muscle mitochondria collected from female mice. This contrasts with male mice where loss of GRX2 substantially augmented proton leaks and ADP-stimulated respiration. Our findings indicate that some fundamental sexual dimorphisms exist between GRX2-deficient male and female rodents.
23

Lamartiniere, C. A. "Endocrine regulation of sex differences in hepatic histidase activity." Biochemical Journal 231, no. 3 (November 1, 1985): 785–87. http://dx.doi.org/10.1042/bj2310785.

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Hepatic histidase activity in adult female rats is twice that in adult male rats. Hypophysectomy and thyroidectomy result in a significant increase in hepatic histidase activities in males, but not in females. This effect on histidase is reversed by the exogenous administration of tri-iodothyronine, but not by ectopic pituitary glands or purified pituitary hormones.
24

Nielsen, H. C. "Testosterone Regulation of Sex Differences in Fetal Lung Development." Experimental Biology and Medicine 199, no. 4 (April 1, 1992): 446–52. http://dx.doi.org/10.3181/00379727-199-43379.

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25

Wade, Juli. "Genetic regulation of sex differences in songbirds and lizards." Philosophical Transactions of the Royal Society B: Biological Sciences 371, no. 1688 (February 19, 2016): 20150112. http://dx.doi.org/10.1098/rstb.2015.0112.

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Sex differences in the morphology of neural and peripheral structures related to reproduction often parallel the frequency of particular behaviours displayed by males and females. In a variety of model organisms, these sex differences are organized in development by gonadal steroids, which also act in adulthood to modulate behavioural expression and in some cases to generate parallel anatomical changes on a seasonal basis. Data collected from diverse species, however, suggest that changes in hormone availability are not sufficient to explain sex and seasonal differences in structure and function. This paper pulls together some of this literature from songbirds and lizards and considers the information in the broader context of taking a comparative approach to investigating genetic mechanisms associated with behavioural neuroendocrinology.
26

Hodes, G. E., M. L. Pfau, A. Brancato, H. F. Ahn, and S. J. Russo. "Epigenetic regulation of sex differences in susceptibility to stress." European Neuropsychopharmacology 27 (October 2017): S550. http://dx.doi.org/10.1016/s0924-977x(17)31052-0.

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27

Farhang, Borzoo, Shanna Diaz, Stephanie L. Tang, and Edward J. Wagner. "Sex differences in the cannabinoid regulation of energy homeostasis." Psychoneuroendocrinology 34 (December 2009): S237—S246. http://dx.doi.org/10.1016/j.psyneuen.2009.04.007.

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28

Hutchison, J. B., C. Beyer, R. E. Hutchison, and A. Wozniak. "Sex differences in the regulation of embryonic brain aromatase." Journal of Steroid Biochemistry and Molecular Biology 61, no. 3-6 (April 1997): 315–22. http://dx.doi.org/10.1016/s0960-0760(97)80029-5.

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29

Bangasser, Debra A., Samantha R. Eck, Alexander M. Telenson, and Madeleine Salvatore. "Sex differences in stress regulation of arousal and cognition." Physiology & Behavior 187 (April 2018): 42–50. http://dx.doi.org/10.1016/j.physbeh.2017.09.025.

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30

Mak, Amanda K. Y., Zhi-guo Hu, John X. X. Zhang, Zhuangwei Xiao, and Tatia M. C. Lee. "Sex-related differences in neural activity during emotion regulation." Neuropsychologia 47, no. 13 (November 2009): 2900–2908. http://dx.doi.org/10.1016/j.neuropsychologia.2009.06.017.

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31

Liang, Yun, J. Michelle Kahlenberg, and Johann E. Gudjonsson. "A vestigial pathway for sex differences in immune regulation." Cellular & Molecular Immunology 14, no. 7 (May 22, 2017): 578–80. http://dx.doi.org/10.1038/cmi.2017.28.

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32

Raznahan, Armin, and Christine M. Disteche. "X-chromosome regulation and sex differences in brain anatomy." Neuroscience & Biobehavioral Reviews 120 (January 2021): 28–47. http://dx.doi.org/10.1016/j.neubiorev.2020.10.024.

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33

Abel, Jean LeBeau, and Emilie F. Rissman. "Location, location, location: Genetic regulation of neural sex differences." Reviews in Endocrine and Metabolic Disorders 13, no. 3 (May 24, 2011): 151–61. http://dx.doi.org/10.1007/s11154-011-9186-0.

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34

Edmunds, Jane S., Clayton L. Ivie, Elizabeth P. Ott, Dain W. Jacob, Sarah E. Baker, Jennifer L. Harper, Camila M. Manrique-Acevedo, and Jacqueline K. Limberg. "Sex differences in the effect of acute intermittent hypoxia on respiratory modulation of sympathetic activity." American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 321, no. 6 (December 1, 2021): R903—R911. http://dx.doi.org/10.1152/ajpregu.00042.2021.

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Sex-related differences in respiratory modulation of sympathetic activity have been observed in rodent models of sleep apnea [intermittent hypoxia (IH)]. In light of sex disparities in the respiratory response to acute IH in humans as well as changes in respiratory modulation of muscle sympathetic nerve activity (MSNA) in clinical sleep apnea, we examined sex-related differences in respiratory modulation of MSNA following acute IH. We hypothesized that respiratory modulation of MSNA would be altered in both male and female participants after IH; however, the respiratory patterning of MSNA following IH would be sex specific. Heart rate, MSNA, and respiration were evaluated in healthy male ( n = 21, 30 ± 5 yr) and female ( n = 10, 28 ± 5 yr) participants during normoxic rest before and after 30 min of IH. Respiratory modulation of MSNA was assessed by fitting polynomials to cross-correlation histograms constructed between sympathetic spikes and respiration. MSNA was elevated after IH in male (20 ± 6 to 24 ± 8 bursts/min) and female (19 ± 8 to 22 ± 10 bursts/min) participants ( P < 0.01). Both male and female participants exhibited respiratory modulation of MSNA ( P < 0.01); however, the pattern differed by sex. After IH, modulation of MSNA within the breath was reduced in male participants ( P = 0.03) but increased in female participants ( P = 0.02). Both male and female adults exhibit changes in respiratory patterning of MSNA after acute IH; however, this pattern differs by sex. These data support sex disparities in respiratory modulation of MSNA and may have implications for conditions such as sleep apnea.
35

Qian, Jingyi, Christopher J. Morris, Rosanna Caputo, Wei Wang, Marta Garaulet, and Frank A. J. L. Scheer. "Sex differences in the circadian misalignment effects on energy regulation." Proceedings of the National Academy of Sciences 116, no. 47 (November 4, 2019): 23806–12. http://dx.doi.org/10.1073/pnas.1914003116.

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Shift work causes circadian misalignment and is a risk factor for obesity. While some characteristics of the human circadian system and energy metabolism differ between males and females, little is known about whether sex modulates circadian misalignment effects on energy homeostasis. Here we show—using a randomized cross-over design with two 8-d laboratory protocols in 14 young healthy adults (6 females)—that circadian misalignment has sex-specific influences on energy homeostasis independent of behavioral/environmental factors. First, circadian misalignment affected 24-h average levels of the satiety hormone leptin sex-dependently (P < 0.0001), with a ∼7% decrease in females (P < 0.05) and an ∼11% increase in males (P < 0.0001). Consistently, circadian misalignment also increased the hunger hormone ghrelin by ∼8% during wake periods in females (P < 0.05) without significant effect in males. Females reported reduced fullness, consistent with their appetite hormone changes. However, males reported a rise in cravings for energy-dense and savory foods not consistent with their homeostatic hormonal changes, suggesting involvement of hedonic appetite pathways in males. Moreover, there were significant sex-dependent effects of circadian misalignment on respiratory quotient (P < 0.01), with significantly reduced values (P < 0.01) in females when misaligned, and again no significant effects in males, without sex-dependent effects on energy expenditure. Changes in sleep, thermoregulation, behavioral activity, lipids, and catecholamine levels were also assessed. These findings demonstrate that sex modulates the effects of circadian misalignment on energy metabolism, indicating possible sex-specific mechanisms and countermeasures for obesity in male and female shift workers.
36

Nicholas, Lisa M., Mototsugu Nagao, Laura C. Kusinski, Denise S. Fernandez-Twinn, Lena Eliasson, and Susan E. Ozanne. "Exposure to maternal obesity programs sex differences in pancreatic islets of the offspring in mice." Diabetologia 63, no. 2 (November 26, 2019): 324–37. http://dx.doi.org/10.1007/s00125-019-05037-y.

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Abstract Aims/hypothesis Obesity during pregnancy increases offspring type 2 diabetes risk. Given that nearly half of women of child-bearing age in many populations are currently overweight/obese, it is key that we improve our understanding of the impact of the in utero/early life environment on offspring islet function. Whilst a number of experimental studies have examined the effect of maternal obesity on offspring islet architecture and/or function, it has not previously been delineated whether these changes are independent of other confounding risk factors such as obesity, postnatal high-fat-feeding and ageing. Thus, we aimed to study the impact of exposure to maternal obesity on offspring islets in young, glucose-tolerant male and female offspring. Methods Female C57BL/6J mice were fed ad libitum either chow or obesogenic diet prior to and throughout pregnancy and lactation. Offspring were weaned onto a chow diet and remained on this diet until the end of the study. An IPGTT was performed on male and female offspring at 7 weeks of age. At 8 weeks of age, pancreatic islets were isolated from offspring for measurement of insulin secretion and content, mitochondrial respiration, ATP content, reactive oxygen species levels, beta and alpha cell mass, granule and mitochondrial density (by transmission electron microscopy), and mRNA and protein expression by real-time RT-PCR and Western blotting, respectively. Results Glucose tolerance was similar irrespective of maternal diet and offspring sex. However, blood glucose was lower (p < 0.001) and plasma insulin higher (p < 0.05) in female offspring of obese dams 15 min after glucose administration. This was associated with higher glucose- (p < 0.01) and leucine/glutamine-stimulated (p < 0.05) insulin secretion in these offspring. Furthermore, there was increased mitochondrial respiration (p < 0.01) and density (p < 0.05) in female offspring of obese dams compared with same-sex controls. Expression of mitochondrial and nuclear-encoded components of the electron transport chain, L-type Ca2+ channel subtypes that play a key role in stimulus-secretion coupling [Cacna1d (p < 0.05)], and oestrogen receptor α (p < 0.05) was also increased in islets from these female offspring of obese dams. Moreover, cleaved caspase-3 expression and BAX:Bcl-2 were decreased (p < 0.05) reflecting reduced susceptibility to apoptosis. In contrast, in male offspring, glucose and leucine/glutamine-stimulated insulin secretion was comparable between treatment groups. There was, however, compromised mitochondrial respiration characterised by decreased ATP synthesis-driven respiration (p < 0.05) and increased uncoupled respiration (p < 0.01), reduced docked insulin granules (p < 0.001), decreased Cacna1c (p < 0.001) and Cacna1d (p < 0.001) and increased cleaved caspase-3 expression (p < 0.05). Conclusions/interpretation Maternal obesity programs sex differences in offspring islet function. Islets of female but not male offspring appear to be primed to cope with a nutritionally-rich postnatal environment, which may reflect differences in future type 2 diabetes risk.
37

Rutkai, Ibolya, Somhrita Dutta, Prasad V. Katakam, and David W. Busija. "Dynamics of enhanced mitochondrial respiration in female compared with male rat cerebral arteries." American Journal of Physiology-Heart and Circulatory Physiology 309, no. 9 (November 2015): H1490—H1500. http://dx.doi.org/10.1152/ajpheart.00231.2015.

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Mitochondrial respiration has never been directly examined in intact cerebral arteries. We tested the hypothesis that mitochondrial energetics of large cerebral arteries ex vivo are sex dependent. The Seahorse XFe24 analyzer was used to examine mitochondrial respiration in isolated cerebral arteries from adult male and female Sprague-Dawley rats. We examined the role of nitric oxide (NO) on mitochondrial respiration under basal conditions, using Nω-nitro-l-arginine methyl ester, and following pharmacological challenge using diazoxide (DZ), and also determined levels of mitochondrial and nonmitochondrial proteins using Western blot, and vascular diameter responses to DZ. The components of mitochondrial respiration including basal respiration, ATP production, proton leak, maximal respiration, and spare respiratory capacity were elevated in females compared with males, but increased in both male and female arteries in the presence of the NOS inhibitor. Although acute DZ treatment had little effect on mitochondrial respiration of male arteries, it decreased the respiration in female arteries. Levels of mitochondrial proteins in Complexes I–V and the voltage-dependent anion channel protein were elevated in female compared with male cerebral arteries. The DZ-induced vasodilation was greater in females than in males. Our findings show that substantial sex differences in mitochondrial respiratory dynamics exist in large cerebral arteries and may provide the mechanistic basis for observations that the female cerebral vasculature is more adaptable after injury.
38

Wang, Chunmei, and Yong Xu. "Mechanisms for sex differences in energy homeostasis." Journal of Molecular Endocrinology 62, no. 2 (February 2019): R129—R143. http://dx.doi.org/10.1530/jme-18-0165.

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Sex differences exist in the regulation of energy homeostasis. Better understanding of the underlying mechanisms for sexual dimorphism in energy balance may facilitate development of gender-specific therapies for human diseases, e.g. obesity. Multiple organs, including the brain, liver, fat and muscle, play important roles in the regulations of feeding behavior, energy expenditure and physical activity, which therefore contribute to the maintenance of energy balance. It has been increasingly appreciated that this multi-organ system is under different regulations in male vs female animals. Much of effort has been focused on roles of sex hormones (including androgens, estrogens and progesterone) and sex chromosomes in this sex-specific regulation of energy balance. Emerging evidence also indicates that other factors (not sex hormones/receptors and not encoded by the sex chromosomes) exist to regulate energy homeostasis differentially in males vs females. In this review, we summarize factors and signals that have been shown to regulate energy homeostasis in a sexually dimorphic fashion and propose a framework where these factors and signals may be integrated to mediate sex differences in energy homeostasis.
39

McFarlane, Sarah V., Katherine E. Mathers, and James F. Staples. "Reversible temperature-dependent differences in brown adipose tissue respiration during torpor in a mammalian hibernator." American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 312, no. 3 (March 1, 2017): R434—R442. http://dx.doi.org/10.1152/ajpregu.00316.2016.

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Although seasonal modifications of brown adipose tissue (BAT) in hibernators are well documented, we know little about functional regulation of BAT in different phases of hibernation. In the 13-lined ground squirrel, liver mitochondrial respiration is suppressed by up to 70% during torpor. This suppression is reversed during arousal and interbout euthermia (IBE), and corresponds with patterns of maximal activities of electron transport system (ETS) enzymes. Uncoupling of BAT mitochondria is controlled by free fatty acid release stimulated by sympathetic activation of adipocytes, so we hypothesized that further regulation at the level of the ETS would be of little advantage. As predicted, maximal ETS enzyme activities of isolated BAT mitochondria did not differ between torpor and IBE. In contrast to this pattern, respiration rates of mitochondria isolated from torpid individuals were suppressed by ~60% compared with rates from IBE individuals when measured at 37°C. At 10°C, however, mitochondrial respiration rates tended to be greater in torpor than IBE. As a result, the temperature sensitivity (Q10) of mitochondrial respiration was significantly lower in torpor (~1.4) than IBE (~2.4), perhaps facilitating energy savings during entrance into torpor and thermogenesis at low body temperatures. Despite the observed differences in isolated mitochondria, norepinephrine-stimulated respiration rates of isolated BAT adipocytes did not differ between torpor and IBE, perhaps because the adipocyte isolation requires lengthy incubation at 37°C, potentially reversing any changes that occur in torpor. Such changes may include remodeling of BAT mitochondrial membrane phospholipids, which could change in situ enzyme activities and temperature sensitivities.
40

Guajardo, Herminio M., та Rita J. Valentino. "Sex differences in μ-opioid regulation of coerulear-cortical transmission". Neuroscience Letters 746 (лютий 2021): 135651. http://dx.doi.org/10.1016/j.neulet.2021.135651.

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41

Gardener, Elyse K. T., Andrea R. Carr, Amy MacGregor, and Kim L. Felmingham. "Sex Differences and Emotion Regulation: An Event-Related Potential Study." PLoS ONE 8, no. 10 (October 30, 2013): e73475. http://dx.doi.org/10.1371/journal.pone.0073475.

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42

Björntorp, Per A. "Sex differences in the regulation of energy balance with exercise." American Journal of Clinical Nutrition 49, no. 5 (May 1, 1989): 958–61. http://dx.doi.org/10.1093/ajcn/49.5.958.

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43

Ptak, W., Z. Dobrowolski, J. Marcinkiewicz, and A. Gryglewski. "Sex differences in regulation of contact sensitivity reaction in mice." Clinical Immunology and Immunopathology 47, no. 3 (January 1988): 289–95. http://dx.doi.org/10.1016/s0090-1229(88)80007-2.

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44

Smetana, Peter, and Marek Malik. "Sex differences in cardiac autonomic regulation and in repolarisation electrocardiography." Pflügers Archiv - European Journal of Physiology 465, no. 5 (February 13, 2013): 699–717. http://dx.doi.org/10.1007/s00424-013-1228-x.

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45

Lovejoy, J. C., and A. Sainsbury. "Sex differences in obesity and the regulation of energy homeostasis." Obesity Reviews 10, no. 2 (March 2009): 154–67. http://dx.doi.org/10.1111/j.1467-789x.2008.00529.x.

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46

Ng, Martin K. C., Wendy Jessup, and David S. Celermajer. "Sex-related differences in the regulation of macrophage cholesterol metabolism." Current Opinion in Lipidology 12, no. 5 (October 2001): 505–10. http://dx.doi.org/10.1097/00041433-200110000-00005.

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47

Sharma, Salil, and Mansoureh Eghbali. "Influence of sex differences on microRNA gene regulation in disease." Biology of Sex Differences 5, no. 1 (2014): 3. http://dx.doi.org/10.1186/2042-6410-5-3.

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48

Coyne, Michelle Anne, Jamie C. Vaske, Danielle L. Boisvert, and John Paul Wright. "Sex Differences in the Stability of Self-Regulation Across Childhood." Journal of Developmental and Life-Course Criminology 1, no. 1 (February 25, 2015): 4–20. http://dx.doi.org/10.1007/s40865-015-0001-6.

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49

Arnold, Arthur P., and Aldons J. Lusis. "Understanding the Sexome: Measuring and Reporting Sex Differences in Gene Systems." Endocrinology 153, no. 6 (March 20, 2012): 2551–55. http://dx.doi.org/10.1210/en.2011-2134.

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The current male bias in biomedical research should be eliminated. The large sex differences in incidence and progression of diseases mean that sex-biased factors are an untapped source of factors that protect from disease. Greater understanding will come from intensified study of the “sexome,” which is the sum of sex-biased effects on gene networks and cell systems. The global search for sites and mechanisms of sex-specific regulation in diverse tissues will provide unanticipated insights into physiological regulation and targets for novel therapies.
50

Oliva, Meritxell, Manuel Muñoz-Aguirre, Sarah Kim-Hellmuth, Valentin Wucher, Ariel D. H. Gewirtz, Daniel J. Cotter, Princy Parsana, et al. "The impact of sex on gene expression across human tissues." Science 369, no. 6509 (September 10, 2020): eaba3066. http://dx.doi.org/10.1126/science.aba3066.

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Many complex human phenotypes exhibit sex-differentiated characteristics. However, the molecular mechanisms underlying these differences remain largely unknown. We generated a catalog of sex differences in gene expression and in the genetic regulation of gene expression across 44 human tissue sources surveyed by the Genotype-Tissue Expression project (GTEx, v8 release). We demonstrate that sex influences gene expression levels and cellular composition of tissue samples across the human body. A total of 37% of all genes exhibit sex-biased expression in at least one tissue. We identify cis expression quantitative trait loci (eQTLs) with sex-differentiated effects and characterize their cellular origin. By integrating sex-biased eQTLs with genome-wide association study data, we identify 58 gene-trait associations that are driven by genetic regulation of gene expression in a single sex. These findings provide an extensive characterization of sex differences in the human transcriptome and its genetic regulation.

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