Female Liver Research Articles

P-600 cannabinoids exposure during pregnancy affects female offsprings reproduction

Abstract Study question Could in-utero exposure to cannabinoids alter the reproductive health of female offspring? Summary answer Prenatal exposure to cannabinoids causes a reduction of the ovarian reserve in F1 with compromised reproductive lifespan and low birth weight in F1/ F2 generations. What is known already Cannabis use during pregnancy is associated with adverse neonatal outcomes: preterm birth, intrauterine growth retardation, low birth weight, and neurological developmental changes. However, the impact on the germ line is still little known. Cannabis/cannabinoids exert their biological effect by activating two main cannabinoid receptors: CB1 and CB2. We previously demonstrated that fetal oocytes express CB2 receptors at a higher level than CB1. In vitro treatment of fetal oocytes with JWH-133, a selective CB2 agonist, induces an acceleration of meiosis and an increase in the percentage of γ-H2AX-positive cells and in TUNEL-positive cells (apoptotic cells). Study design, size, duration Five pregnant CD1 female mice were intraperitoneally injected with a single dose of JWH-133, at 1.5 mg/kg for 5 days between embryonic period (E) 12.5 to E16.5, while control pregnant females received a vehicle containing saline. At delivery, on post-natal day (PND) 2, 30 and 365, F1 pups were counted, weighted and tissues from females were collected. At adult age, F1 females were mated with control mice and F2 generation was morphologically analysed. Participants/materials, setting, methods Ovaries from control and in utero exposed mice were fixed in paraformaldehyde and stained with Haematoxylin and Eosin (H&E). Gonads were embedded in paraplast and sectioned at 5μm Leica-RM 2035 Microtome. Follicles in each ovary were counted serially in every third section through the entire ovary. Only healthy, non-atretic follicles with visible oocyte nuclei were scored. Main results and the role of chance We demonstrate that in vivo exposure to the cannabinoid JWH-133 during fetal life, through the administration of the drug to pregnant females, causes a significant reduction in the offspring body weight at birth (LBW). Histological analysis of the ovaries isolated from newborn females (PND2) shows a significant reduction of the primordial and primary follicles. This reduced ovarian reserve is observed also at PND30 and at PND365. At old adult age, these females, crossed with control males, show a drastic decrease in their litter size (F2) across the life course in comparison with control females. This suggests that the pool of primordial follicles becomes prematurely depleted in in-utero exposed F1 females, compromising their reproductive lifespan. Moreover, we find that F2 pups from prenatally exposed mothers show LBW but have an unaltered number of ovarian follicles in females. Since F2 pups have never been exposed to the drug, our results suggest that LBW is transmitted from the mother intergenerationally, while the reduced ovarian reserve is a consequence of direct exposure to the drug during fetal life of F1 females and it is not transmitted to the F2 generation. Limitations, reasons for caution The effects observed in mice with JWH-133 cannot be directly translated to cannabis effects since the active principle of cannabis (THC) activates both the cannabinoid receptors. Moreover, this study lacks molecular analysis of gene expression implicated in intergenerational transmission. Wider implications of the findings This is the first direct demonstration that prenatal exposure to cannabinoids could have long-term critical consequences for females’ reproductive health. In humans, diminished ovarian reserve is characterized by poor fertility outcomes and it represents a major challenge in reproductive medicine. Trial registration number not applicable

Study of Quality of life (QoL) of Patients with Common Skin Diseases

The pattern of skin diseases varies from one country to another. In particular, in India, where customs, religions, languages, climate and socioeconomic conditions vary across different parts of the country.It is very important to measure the impact of dermatologic disease on the quality of life. Measurement of the quality of life can be used in clinical research as well as for political and financial purposes relating to the development of dermatological services. Quality of life measures may also be effectively used in auditing clinical activities.This study was conducted in the field practice areas of the Urban and Rural Health Centres, Department of Community Medicine, Jawaharlal Nehru Medical College, Aligarh Muslim University, Aligarh, Uttar Pradesh.It was community based and cross- sectional study. The study period was one year i.e. from June 2016 to May 2017. Inclusion criteria: All individuals of the household. Exclusion Criteria: All who did not gave consent. Sampling Method: Systematic random sampling with Population Proportionate to Size (PPS) was used to draw sample size. Ethical clearance was obtained from ethical committee, JNMC, AMU, Aligarh. Informed verbal consent was taken from each subject before interview(Copy of ethical committee is attached).Results reported that the overall mean QoL Indices score of the study population, the mean for the urban and rural population is almost equal. There was overall moderate effect on quality of life of both males and females in the study population. There was significant moderate effect on quality of life of patients in the older age groups (most affected-51-60yr, followed by 41-50yr, 31-40yr, and 19-30yr) compared to the age group 6-10 years.Measuring the impairment of the quality of life in dermatology patients is an important aspect of management. It allows clinicians to assess the extent and nature of the disability so that an appropriate management regimen can be implemented and its effectiveness assessed

Complex Sex Differences in Life Expectancy in French Guiana.

In the complex context of French Guiana, different vulnerabilities and different risk factors between genders may lead to complex differences in health outcomes, mortality, and life expectancy. Our aim was, thus, to compare male and female mortality and life expectancy, to compare it between French Guiana and mainland France, and to look at temporal trends and the main specific causes of death in order to identify actionable singularities. National databases were used to obtain life expectancy at birth, at 20, 40, and 60 years, and mortality statistics. Standardized death rates and causes of death for French Guiana and mainland France were obtained through the CEPIDC, which analyzes information from death certificates. When comparing with mainland France, life expectancy at birth was significantly shorter both in males and females (mean = -2.9 years); life expectancy at 20 years, which allows to remove the effect of the greater child mortality in French Guiana, was also shorter in French Guiana for males (mean = -1.8 years) and females (mean = -2 years). The differences between mainland France and French Guiana regarding life expectancy at 40 and 60 years (mean = -1.5 and -1.3 years) was mainly found among females, males in French Guiana life expectancy at 40 and 60 years was closer to that in mainland France (mean = -0.8 and -0.6 years). Although they have a greater life expectancy at birth than men, women in French Guiana are substantially more affected by overweight/obesity and type 2 diabetes. The observed patterns of life expectancy at different ages presumably reflect the burden of external causes and AIDS in males and perhaps metabolic diseases in women.

Comparative life history patterns of female gorillas.

Several theories have been proposed to explain the impact of ecological conditions on differences in life history variables within and between species. Here we compare female life history parameters of one western lowland gorilla population (Gorilla gorilla gorilla) and two mountain gorilla populations (Gorilla beringei beringei). We compared the age of natal dispersal, age of first birth, interbirth interval, and birth rates using long-term demographic datasets from Mbeli Bai (western gorillas), Bwindi Impenetrable National Park and the Virunga Massif (mountain gorillas). The Mbeli western gorillas had the latest age at first birth, longest interbirth interval, and slowest surviving birth rate compared to the Virunga mountain gorillas. Bwindi mountain gorillas were intermediate in their life history patterns. These patterns are consistent with differences in feeding ecology across sites. However, it is not possible to determine the evolutionary mechanisms responsible for these differences, whether a consequence of genetic adaptation to fluctuating food supplies ("ecological risk aversion hypothesis") or phenotypic plasticity in response to the abundance of food ("energy balance hypothesis"). Our results do not seem consistent with the extrinsic mortality risks at each site, but current conditions for mountain gorillas are unlikely to match their evolutionary history. Not all traits fell along the expected fast-slow continuum, which illustrates that they can vary independently from each other ("modularity model"). Thus, the life history traits of each gorilla population may reflect a complex interplay of multiple ecological influences that are operating through both genetic adaptations and phenotypic plasticity.

Homage to Georgios Papanikolaou: A pilgrimage to his birthplace.

As a cancer epidemiologist focused on the science of cervical cancer prevention and control, the author journeyed to the home of his hero, Georgios Nikolaou Papanikolaou, whose pioneering contribution of the cervicovaginal cytology test (the Pap test) has saved countless female lives over generations throughout the world, laying the groundwork for one of the most beautiful stories in public health.

The female-breadwinner well-being ‘penalty’: differences by men’s (un)employment and country

Abstract This article examines the relationship between female breadwinning and life satisfaction in heterosexual couples. We extend previous research by treating the man’s employment status as a variable that helps to explain rather than confounds this relationship, and by comparing multiple countries through regression analyses of European Social Survey data (Rounds 2–9). Results provide evidence of a female-breadwinner well-being ‘penalty’: men and women are less satisfied with their lives under the female-breadwinner arrangement versus the dual-earner and male-breadwinner alternatives. The penalty is marginal when the male partner is part-time employed but sizeable when he is jobless. However, there are gender differences: after controls for composition, gender-role attitudes, and partners’ relative incomes, the penalty becomes negligible for women while remaining large for men. Analyses suggest these gender differences are linked to high male unemployment among female-breadwinner couples: whereas women appear roughly equally adversely affected by a male partner’s unemployment as by their own, men report substantially higher well-being when she is unemployed instead of him. Country comparisons indicate that while this female-breadwinner well-being penalty is largest in more conservative contexts, especially Germany, it is fairly universal across Europe. So, even in countries where women’s employment is more widespread and cultural and institutional support for the male-breadwinner model is weaker, unemployed men with breadwinner wives are not immune from the social stigma and psychological difficulties associated with their gender non-conformity.

조직 내 개인특성과 제도적 차별이 여성의 삶의 만족에 미치는 영향

This study examines the mediating effect of job satisfaction on individual characteristics, institutional discrimination, and life satisfaction among female workers. Recently, the concept of labor has been applied not only as a means of livelihood but also as a means of pursuing happiness in life. There is a growing interest in the relationship between female job satisfaction and life satisfaction. given the importance of utilizing female labor as an alternative to economic revitalization and the aging population problem, Using data from the Korean Longitudinal Survey of Women and Families, this study examined the effects of individual characteristics and institutional discrimination on life satisfaction through stepwise regression to verify the mediating effect of job satisfaction. The results showed that individual characteristics and perceptions of institutional discrimination had a significant impact on job satisfaction and life satisfaction. Job satisfaction partially mediated the relationship between individual characteristics and discrimination perception and life satisfaction. Female workers who were dissatisfied with performance recognition and interpersonal relationships within the organization had lower job satisfaction levels. This study reveals that female workers with institutional discrimination show lower life satisfaction levels.

Investigation of Adherence to Immunosuppressive Therapy, Perceived Spousal Support and Sexual Dysfunction in Female Liver Recipients

Investigation of Adherence to Immunosuppressive Therapy, Perceived Spousal Support and Sexual Dysfunction in Female Liver Recipients

Health performance and economic growth in sub-Saharan Africa: new evidence based on quantile regressions

PurposeThe present study investigates the nexus between health performance dynamics and economic growth in 43 countries in sub-Saharan Africa for the period 2004–2018.Design/methodology/approachFour health performance dynamics are used, notably: total life expectancy, male life expectancy, female life expectancy and risk of maternal death. The empirical evidence is based on quantile regressions (QRs) in order to put into perspective the conditional distribution of economic growth.FindingsThe following findings are established: (1) total life expectancy and male life expectancy increase economic growth exclusively in the 10th and 90th quantiles of economic growth; (2) female life expectancy boosts economic growth in the 90th quantile of economic growth and (3) the risk of maternal death reduces economic growth in the 75th and 90th quantiles of economic growth. Policy implications are discussed.Originality/valueThe study complements the literature on the nexus between health performance and economic growth by assessing the nexuses throughout the conditional distribution of economic growth.

Epidemiology and Causes of Primary Adrenal Insufficiency in Children: A Population-Based Study.

Incidence and causes of primary adrenal insufficiency (PAI) have not been comprehensively studied in children. Our objective was to describe the epidemiology and to assess causes of PAI in Finnish children. A population-based descriptive study of PAI in Finnish patients aged 0-20 years.Diagnoses referring to adrenal insufficiency in children born in 1996-2016 were collected from the Finnish National Care Register for Health Care. Patients with PAI were identified by studying patient records. Incidence rates were calculated in relation to person-years in the Finnish population of same age. Of the 97 patients with PAI, 36% were female. The incidence of PAI was highest during the first year of life (in females 2.7 and in males 4.0/100 000 person-years). At 1-15 years of age, the incidence of PAI in females was 0.3/100 000 and in males 0.6/100 000 person-years. Cumulative incidence was 10/100 000 persons at age of 15 years and 13/100 000 at 20 years. Congenital adrenal hyperplasia was the cause in 57% of all patients and in 88% of patients diagnosed before age of 1 year. Other causes among the 97 patients included autoimmune disease (29%), adrenoleukodystrophy (6%), and other genetic causes (6%). From the age of 5 years, most of the new cases of PAI were due to autoimmune disease. After the first-year peak, the incidence of PAI is relatively constant through ages 1-15 years, and 1 out of 10 000 children are diagnosed with PAI before the age of 15 years.

(341) Prevalence of Sexual Disorders in a Sample of Patients Suffering from Breast Cancer

Abstract Introduction There is scarce evidence on prevalence of sexual disorders at large and particularly in the region where I work and practice psychiatry and sexology. Not to mention, lack or research and evidence in regard to sexual disorders among females suffering from Breast Cancer. Objective Assess the prevalence of females suffering from a sexual disorder in my region is a challenge on its own - checking in the prevalence of females suffering from a sexual disorder while in the course of treatment from Breast Cancer is another challenge since sex could be the last thing they want to talk about – possibly. Methods 1000 female patients were randomly selected at the outpatient clinic of a national cancer hospital over the course of four consecutive months by initial simple questionnaire inquiring about mood, sleep, appetite, level of energy, relationship with partner, intimacy with partner and frequency of having sex and if there is any problems or pain experienced during sex. Those reported to have any sexual symptoms or complaints were taken to sexual interview using the PLISSIT model. When necessary, the partner was called in for assessment too. To implement the first simple survey - I had to psychosexual educate personnel in Pain clinic - where the survey was distributed beside psychiatry clinic - and recruit 4 psychology students under training to help conducting the survey - so I could reach the 1000 sample within the course of four months. Symptoms of depressive mood, disturbed appetite and disturbed sleep, lack of energy, were associated with sexual disorder. Results N 708 patients 70 % reported turbulent marital relationship and distant partners before or after illness. N 738 patients reported suffering from a diagnosable sexual disorder mainly Female Sexual Interest/Arousal Disorder plus or minus vaginal dryness as a sequel of chemotherapy regimen indicated at the time. N 200 patients 20% reported partners to be suffering from a diagnosable sexual disorder mainly erectile disorder and/or sexual disorder due to substance use disorder. While N 292 30% reported good relationship with their caring husbands and flowing sexual life fostered by warm intimacy. Conclusions Sexual disorders are widespread and remarkably under diagnosed and overlooked in the treatment of breast cancer while prevalence is approaching 80 %. It would be interesting to take this research to the next level and study the prevalence of female sexual interest/arousal disorder in relation to each and every chemotherapeutic agent versus surgery and radiotherapy as well as hormonal therapy between females who underwent female genital mutilation surgery (circumcised) versus those who are not circumcised. It is very important to early diagnose and treat sexual disorders to restore intimacy and create a better quality of life for females suffering from breast cancer - better adherence on follow up and less stress to counteract relapse of cancer. Disclosure No

Maternal pre-conceptional glyphosate exposure impacts the offspring hepatic and ovarian proteome.

Glyphosate (GLY) is an herbicide used for rural and urban weed control. Urinary GLY in women is associated with shortened gestational length yet effects of GLY on offspring due to maternal exposure are unclear. This study tested the hypothesis that maternal chronic pre-conceptional GLY exposure would cause phenotypic and molecular changes in F1 offspring. Female C57BL/6 mice (7-week-old; n = 40) received saline vehicle control (CT; n = 20) or GLY (2 mg/kg; n = 20) daily per os for 10 weeks. At dosing completion, females were housed with unexposed males and divided into Cohort 1 who were euthanized at gestation day 14 (n = 10 per treatment) and Cohort 2 who completed gestation (n = 10 per treatment). F1 female ovarian and liver samples underwent LC-MS/MS and bioinformatic analysis. Maternal exposure did not affect litter (P > .05) sex ratio, or embryonic or neonatal gross phenotypes. In Cohort 2 offspring, no treatment effect on (P > .05) offspring anogenital distance, puberty onset, or ovarian follicular composition was noted. Body weight was increased (P < .05) in male GLY-exposed compared with CT dam offspring. F1 females from GLY-exposed dams had altered (P < .05) abundance of 54 ovarian and 110 hepatic proteins. Pathways altered in the ovary (false discovery rate [FDR] ≤ 0.07) included thermogenesis and phosphatidylinositol-3 kinase-AKT signaling and in liver (FDR ≤ 0.08) included metabolic, glutathione metabolism, oxidative phosphorylation, non-alcoholic fatty liver disease, and thermogenesis. Thus, pre-conceptional GLY exposure affected offspring phenotypic and molecular profiles potentially impacting reproductive health.

Sex, Nutrition, and NAFLD: Relevance of Environmental Pollution.

Non-alcoholic fatty liver disease (NAFLD) is the most common form of chronic liver disease and represents an increasing public health issue given the limited treatment options and its association with several other metabolic and inflammatory disorders. The epidemic, still growing prevalence of NAFLD worldwide cannot be merely explained by changes in diet and lifestyle that occurred in the last few decades, nor from their association with genetic and epigenetic risk factors. It is conceivable that environmental pollutants, which act as endocrine and metabolic disruptors, may contribute to the spreading of this pathology due to their ability to enter the food chain and be ingested through contaminated food and water. Given the strict interplay between nutrients and the regulation of hepatic metabolism and reproductive functions in females, pollutant-induced metabolic dysfunctions may be of particular relevance for the female liver, dampening sex differences in NAFLD prevalence. Dietary intake of environmental pollutants can be particularly detrimental during gestation, when endocrine-disrupting chemicals may interfere with the programming of liver metabolism, accounting for the developmental origin of NAFLD in offspring. This review summarizes cause-effect evidence between environmental pollutants and increased incidence of NAFLD and emphasizes the need for further studies in this field.

Economic growth and female labour force participation in an ageing society: evidence from Southeast Asia

ABSTRACT This study examines the impact of female labour participation and life expectancy on economic growth in Southeast Asia economies using non-stationary panel data techniques. The study utilizes balanced panel data spanning from 1992 to 2020, encompassing ten countries in Southeast Asia. The results reveal that economic growth, female labour participation, and other factors are cointegrated. The findings indicate that trade openness has a negative impact on economic growth. However, we find that female labour participation, female longevity, female education, domestic investment, and foreign direct investment have a positive long-term effect on economic growth. Our study also highlights that the effect of female labour participation on growth varies depending on female longevity. We find that female labour participation positively impacts economic growth but changes negatively when countries exhibit a high level of female life expectancy.

Fatal, non-fatal burden of cancer in the elderly in China, 2005–2016: a nationwide registry-based study

BackgroundAs populations age, cancer burden becomes increasingly conspicuous. This study quantified the cancer burden of the elderly (≥ 60 years) in China, based on the China Cancer Registry Annual Report to provide epidemiological evidence for cancer prevention and control.MethodsData on cancer cases and deaths among the elderly aged ≥ 60 years were collected from the China Cancer Registry Annual Report, 2008–2019. Potential years of life lost (PYLL) and disability-adjusted life years (DALY) were calculated to analyze fatalities and the non-fatal burden. The time trend was analyzed using the Joinpoint model.ResultsFrom 2005 to 2016, the PYLL rate of cancer in the elderly was stable between 45.34‰ and 47.62‰, but the DALY rate for cancer decreased at an average annual rate of 1.18% (95% CI: 0.84–1.52%). The non-fatal cancer burden in the rural elderly was higher than that of the urban elderly. Lung, gastric, liver, esophageal, and colorectal cancers were the main cancers causing the cancer burden in the elderly, and accounted for 74.3% of DALYs. The DALY rate of lung cancer in females in the 60–64 age group increased (annual percentage change [APC] = 1.14%, 95% CI: 0.10–1.82%). Female breast cancer was one of the top five cancers in the 60–64 age group, with DALY rates that also increased (APC = 2.17%, 95% CI: 1.35–3.01%). With increasing age, the burden of liver cancer decreased, while that of colorectal cancer rose.ConclusionsFrom 2005 to 2016, the cancer burden in the elderly in China decreased, mainly reflected in the non-fatal burden. Female breast and liver cancer were a more serious burden in the younger elderly, while colorectal cancer burden was mainly observed in the older elderly.

Sex steroids have opposing effects on heart rate of juveniles, Gambusia holbrooki.

Built on our recent work that heart rates and function in G holbrooki are sexually dimorphic, this study assessed whether the species is an appropriate model to study sex-hormone effects on heart physiology. With a hypothesis that 17β-estradiol (E2) and 17α-methyltestosterone (MT) regulate the heart rate of juvenile G. holbrooki in a sex-specific manner, genetic males and females were treated with E2 and MT, respectively and the HR (bpm) was measured an hour following treatment using light-cardiogram. Results showed the HR (bpm) of both sexes were significantly (p < 0.05) altered compared to controls. Specifically, the E2 accelerated HR in the males and conversely MT decelerated the HR in the females. The normal expression levels of estrogen (erα and erβ) and G protein-coupled estrogen (gper) receptor genes were significantly higher (p < 0.05) in female than male hearts. Interestingly, the activity of the erβ in the heart of the MT-treated females reversed and was significantly lower (p < 0.05) than those of males while erα and gper were non-responsive. In contrast, significant down- and up-regulation of erα and gper, respectively occurred in the liver of MT-treated females. Morphological observations suggest that MT caused hepatomegaly, somewhat resembling an inflating balloon, perhaps induced by the accumulation of unexpelled gases. While E2 induced ventricular angiogenesis in males was likely due to an influx of blood supply caused by the increased heart rates. Collectively, the results demonstrate that the juvenile G. holbrooki heart readily responds to E2/MT in a sex-specific manner.

Exploring the relationship between adiponectin and reproductive transition among diabetic and non-diabetic women

Introduction and Aim: The reproductive aging and the menopausal transition is a period of life in females which is well associated with several changes in the adipose tissue and the hormones. Little is known about the circulating levels of adiponectin and the status of the reproductive age. The aim of the study was to understand whether these transition changes affect the levels of adiponectin in the blood and the BMI.&#x0D; &#x0D; Materials and Methods: This was a cross sectional study with 73 diabetic females matched with 106 nondiabetic females. The subjects were between the age of 30-60 years. Serum adiponectin levels were estimated using precoated ELISA technique and BMI was calculated.&#x0D; &#x0D; Results: The study subjects showed age matched distribution. BMI showed significant difference between normal and diabetic subjects but failed to hold the significant difference when grouped based on their reproductive transition. Adiponectin failed to show any significant difference between diabetic and normal subjects, but adiponectin levels differed well with the reproductive group in diabetics only (p=0.008) and in normal subjects the difference was not statistically significant (p=0.07).&#x0D; &#x0D; Conclusion: This study does not hold up changes in BMI because of a transition in reproductive age and this causes a change in levels of adiponectin. However, the effect of diabetes on adiponectin level seems to be valid. The variation in the level of adiponectin is because of diabetes in the menopause state. Further the adiponectin and BMI did not show any significant difference between the age groups which shows that age is not a contributing factor for changes in BMI and levels of adiponectin.

Unraveling the Host Genetic Background Effect on Internal Organ Weight Influenced by Obesity and Diabetes Using Collaborative Cross Mice.

Type 2 diabetes mellitus (T2DM) is a severe chronic epidemic that results from the body's improper usage of the hormone insulin. Globally, 700 million people are expected to have received a diabetes diagnosis by 2045, according to the International Diabetes Federation (IDF). Cancer and macro- and microvascular illnesses are only a few immediate and long-term issues it could lead to. T2DM accelerates the effect of organ weights by triggering a hyperinflammatory response in the body's organs, inhibiting tissue repair and resolving inflammation. Understanding how genetic variation translates into different clinical presentations may highlight the mechanisms through which dietary elements may initiate or accelerate inflammatory disease processes and suggest potential disease-prevention techniques. To address the host genetic background effect on the organ weight by utilizing the newly developed mouse model, the Collaborative Cross mice (CC). The study was conducted on 207 genetically different CC mice from 8 CC lines of both sexes. The experiment started with 8-week-old mice for 12 weeks. During this period, one group maintained a standard chow diet (CHD), while the other group maintained a high-fat diet (HFD). In addition, body weight was recorded bi-weekly, and at the end of the study, a glucose tolerance test, as well as tissue collection (liver, spleen, heart), were conducted. Our study observed a strong effect of HFD on blood glucose clearance among different CC lines. The HFD decreased the blood glucose clearance displayed by the significant Area Under Curve (AUC) values in both populations. In addition, variation in body weight changes among the different CC lines in response to HFD. The female liver weight significantly increased compared to males in the overall population when exposed to HFD. Moreover, males showed higher heritability values than females on the same diet. Regardless of the dietary challenge, the liver weight in the overall male population correlated positively with the final body weight. The liver weight results revealed that three different CC lines perform well under classification models. The regression results also varied among organs. Accordingly, the differences among these lines correspond to the genetic variance, and we suspect that some genetic factors invoke different body responses to HFD. Further investigations, such as quantitative trait loci (QTL) analysis and genomic studies, could find these genetic elements. These findings would prove critical factors for developing personalized medicine, as they could indicate future body responses to numerous situations early, thus preventing the development of complex diseases.

Localization and functional importance of GPR125 in the liver

Of all of the protein families in the human genome, G protein-coupled receptors (GPCRs) comprise the largest, representing approximately 3-4% of all human genes. To identify high-expressing GPRs with unknown functions in the liver, we performed a TaqMan array screen using both male and female C57BL6 livers with expression normalized to GAPDH. Amongst others, we identified high expression of adhesion GPCR (aGPCR) GPR125 whose ΔCt value was 17.2. As a comparison, the Glucagon receptor - which plays an essential role in liver glucose homeostasis - had a similar ΔCt value of 16.0 supporting the importance of furthering our understanding of GPR125. aGPCRs are classified by their unique N-terminal domain containing, among others, a GPCR auto proteolysis-inducing (GAIN) domain which contains the GPS cleavage site. The presence of this domain, ubiquitous among almost all aGPCRs, facilitates the cleavage and non-covalent attachment of the N-Terminal (NTF) and C-Terminal Fragments (CTF). When the NTF is displaced (via mechanosensation or protein-protein binding), this is thought to expose a tethered ligand leading to GPCR activation. However GPR125 is atypical, as the GPS site does not contain the classical His-Leu/Thr sequence (where cleavage occurs between the leucine and threonine) that is thought to be necessary for cleavage, and instead contains an Ser-Leu/Ser sequence. Despite this, recent studies have shown that cleavage can occur, although whether it contains a tethered agonist has yet to be investigated. To test this, synthetic peptides corresponding to the β-strand immediately following the predicted GPS domain were synthesized and tested for activation using the PRESTO-TANGO assay, a luminescence readout to indicate receptor activation. Indeed, we determined that GPR125 is activated by a tethered ligand with maximal activation detected with the complete β-strand and 2 additional c-terminal amino acids. Notably, when the peptide was lengthened, we observed a loss of activation suggesting that the maintenance of the helical structure is critical for GPR125 activation. By using RNA scope, an in-situ hybridization assay, we localized GPR125 to the cuboidal endothelial cells in the lining of the bile duct, as well as some generalized localization to hepatocytes. This localization was confirmed through antibody staining which revealed that GPR125 localizes to the basolateral membrane of cholangiocytes. This localization, coupled with previous findings in the Zebrafish model, suggest that GPR125 may play a critical role in liver development and repair following bile duct injury. Efforts are currently underway to test this using an adenoviral delivery of CRISPR-Cas9-GPR125 guide RNAs to generate a liver-specific knockout. NIDDK and NIH Common Fund This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

“Scotch! Scotch! Scotch!”: The Inoperative Domestic Scene in Chantal Akerman's Saute ma ville

Abstract This article reads Chantal Akerman's short film Saute ma ville (Blow Up My Town, Belgium, 1968) with and against texts by Giorgio Agamben, Gilles Deleuze, and Herman Melville. Rather than being merely a precursor to Akerman's later genre-defining efforts in recording female domestic life, I propose that Saute ma ville displays the potentiality for domestic labor itself to be a destituent practice, rather than an expected component of reproductive, conventionally gendered work. The way that Akerman mobilizes the inoperative actions of her protagonist — a “girl without references” — in her “preference not to” perform the supportive labor of the domestic space and in so doing literally “blow up her town” makes this early work interpretable as structurally concerned and politically motivated recit in the mode of her later films, rather than merely narrative-focused histoire. The protagonist of the film, in her Chaplinesque resistance to allow household chores to sustain her home, displays a conceptual paradigm in which those still separated from politics and from the space of the polis may yet act politically. Reading the film with Melville's Bartleby the Scrivener and Deleuze's and Agamben's responses to that text puts pressure on the limits of Agamben's thought on inoperativity and reinscribes the importance of Akerman's deeply affective cinematography within an anti-capitalist feminist critique.