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Search indexed NASA NTRS and DOE OSTI research on propulsion, heat transfer, battery materials and energy systems. Follow report and document links to the original sources.

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At least 559 records · Page 31
All sourcesNASA NTRSDOE OSTI
DOE OSTI2016

Safety and Efficacy of Occlusion of Large Extra-Prostatic Anastomoses During Prostatic Artery Embolization for Symptomatic BPH

IntroductionDuring PAE, preembolization angiography of the prostatic artery can show large extra-prostatic shunts, at high risk, if embolized, of rectal or penile necrosis. We report our experience with 11 consecutive patients who underwent protective embolization of large extra-prostatic shunts before successful PAE.Materials and MethodsWe treated 11 consecutive male patients (mean age 67 years), part of a series of 55 consecutive male patients referred for PAE to treat LUTS due to BPH, between December 2013 and January 2015. The procedure involved the exclusion of an extra-prostatic shunt originating from the PA, prior to complete bilateral PAE. We compared the safety and efficacy of the 11 shunt exclusions followed by embolization of the PA to the other 44 basic PAE. Clinical success was defined as a decrease of 25 % or eight points of IPSS, QoL <3 or a one-point decrease, and a Qmax improvement of 25 % or 2.5 mL/s.ResultsWe had a 100 % rate of occlusion of the anastomosis. Bilateral embolization of the PA was performed in all patients with no additional time of procedure (p = 0.18), but a significant increase of dose area product (p = 0.03). Distal (PErFecTED) embolization was possible in 64 %. There was no worsening of erectile dysfunction, no rectal or penile necrosis, no immediate or late other clinical complications. Clinical success was 91 % (mean follow-up: 3.5 months), compared to 78 % for the entire PAE group.ConclusionPAE using the protection technique in case of large extra-prostatic shunts is as safe and effective as basic procedures and does not induce any additional time of procedure.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2017

A Randomised Clinical Trial to Compare Coaxial and Noncoaxial Techniques in Percutaneous Core Needle Biopsy of Renal Parenchyma

PurposeTo compare the coaxial and noncoaxial techniques of renal parenchymal core needle biopsy.Materials and MethodsThis is an institutional review board-approved randomised controlled trial comparing 83 patients (male, n = 49) who underwent renal parenchymal core biopsy with coaxial method and 83 patients (male, n = 40) with noncoaxial method. The rate of complications, the number of glomerular profiles, and the procedural time were evaluated in a comparison of the two methods. Correlation between the presence of renal parenchymal disease and the rate of complication was also evaluated.ResultsThe procedural time was significantly shorter in the coaxial technique (coaxial group, 5 ± 1 min; noncoaxial group, 14 ± 2 min; p < 0.001). The rates of complications for the coaxial method was significantly lower than the noncoaxial method (coaxial group, 10.8 %; noncoaxial group, 24.1 %; p = 0.025). There was no significant correlation between gender and the rate of complication. The number of glomerular profiles was significantly higher in patents who underwent renal biopsy with the coaxial method (coaxial group, 18.2 ± 9.1; noncoaxial group, 8.6 ± 5.5; p < 0.001). In the whole study population, the rate of complications was significantly higher in patients with a pathologic renal parenchyma compared to those with a normal parenchyma (19/71 vs. 10/95; p = 0.006).ConclusionsRenal parenchymal biopsy using a coaxial needle is a faster and safer method with a lower rate of complications.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2018

The Interventional Radiology (IR) Gender Gap: A Prospective Online Survey by the Cardiovascular and Interventional Radiological Society of Europe (CIRSE)

AimA prospective online survey was conducted by the Cardiovascular Interventional Radiological Society of Europe (CIRSE) to evaluate the gender gap within interventional radiology (IR) and the barriers facing women in IR.Materials and MethodsA questionnaire (“Appendix”) was devised by the authors and the CIRSE communication and publication team and sent electronically to 750 identifiable female members of CIRSE. Responses were collected from 7 August to 24 August 2017.ResultsThe response rate was 19.9% (n = 149) with highest responses from UK (18%), Italy (11%), Germany (11%), Spain (7%), Netherlands (5%), France (5%), Sweden (4%), USA (4%). 91% of the respondents were between 31 and 46 years, 83% work full time, 62% spend > 50% of their working time in IR, and 67% practice in a university or tertiary referral institution. 85% were in the minority in their department. 52% had no leadership role in their department, but 67% expressed willingness to consider a leadership position. Their main concerns were work/family life balance, the risks of radiation exposure, the effect of pregnancy on training and practice and the male-dominated work environment.ConclusionThis survey highlights issues experienced by women in IR. Clear guidance on concerns regarding radiation exposure particularly during pregnancy is needed. Structured and supportive training is required for female IRs who may wish to train or work flexibly. The male-dominated environment is discouraging, and a scheme to promote female IRs would encourage women to take on senior leadership positions and attract more women into the specialty.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2019

Establishing a Platform for Interest and Education in Interventional Radiology Amongst Radiology Trainees

Purpose: Over recent times, procedural Radiologists have begun to establish themselves as the distinct subspecialty of Interventional Radiology (IR). The Interventional Radiology Society of Australasia (IRSA) was established in 1982 to share collaborative ideas, encourage research, and promote education. IRSA developed a weekend registrar workshop attended by Radiology Registrars from Australia and New Zealand. In the 2018 event, we surveyed the Registrars to identify their interest in IR training before and after the workshop. Materials and Methods: The event was held over a weekend and consisted of both lectures and hands-on workshops. A survey was handed to all 67 registrants of the workshop and there was a 55% response rate including 78% of females in attendance. Results: Before the workshop, trainees rated their interest in IR training at a mean of 3.7 out of 5. After the workshop, trainees rated their interest in IR training as an average of 4.4 out of 5 (p < 0.001). The difference in interest between males and females before the workshop (4.0 vs. 3.1) was significant (p = 0.003), however after the workshop (4.5 vs. 4.1) was not significant (p = 0.07). The change in interest from attending the workshop was significant between genders, p = 0.03 (male interest increased mean 0.5, female increased mean 1.0). Conclusion: We show that a program of lectures and workshops designed to generate interest in IR leads to a significant increase in training interest, particularly amongst females. Other subspecialty groups should consider this type of intervention and promote ongoing education and inspiration. Level of Evidence: Cross-sectional study, Level IV.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2019

CT-Guided Percutaneous Needle Biopsy in Patients with Suspected Retroperitoneal Fibrosis: A Retrospective Cohort Study

Purpose: The outcome of CT-guided biopsy in patients with suspected retroperitoneal fibrosis (RF), regarded as technically challenging, remains unclear. This study aimed to evaluate the results of CT-guided biopsy in patients with lesions considered in the differential diagnosis of RF and compare them with results from patients with other retroperitoneal lesions. Materials and Methods: Patients who underwent CT-guided biopsy of retroperitoneal lesions between January 2010 and September 2018 were retrospectively reviewed. The study cohort with retroperitoneal lesions surrounding the infra-abdominal aorta, iliac vessels, and/or ureters was divided into two groups: Group F included patients with lesions for which RF was considered in the differential diagnosis, and Group C comprised patients with a retroperitoneal mass or lymphadenopathy. Lesion size and depth, and biopsy details including technical success, position, procedure time, diagnostic yield, and complications between the two groups were compared. Results: Group F included 27 patients (mean age 68.5 years ± 11.6, 17 male) and Group C 30 patients (mean age 65.0 years ± 11.8, 16 male). The short axis was significantly smaller in Group F than in Group C (19 mm vs 26 mm, P = 0.041), and procedure time was significantly longer in Group F than in Group C (31.5 min ± 13.2 vs 20.3 min ± 8.4, P = 0.001). Technical success rate (93% vs 100%), accuracy (93% vs 93%), and complications (3.7% vs 10%) between Groups F and C were not significantly different. Conclusions: CT-guided biopsy of patients with suspected RF is considered safe and effective.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2018

Ectopic Organogenesis after Allotransplantation of Freshly Removed or Cryopreserved Neonatal Testicle under the Renal Capsule in Rats

In experiments on white outbred male rats, a freshly removed (20 experiments) or cryopreserved (10 experiments) testicle from newborn rats (1-2 days after birth) was transplanted under the renal capsule after bilateral orchiectomy. In all experiments with transplantation of freshly removed testicle, it was engrafted. In 3 months, histological examination revealed the formation of mature seminiferous tubules, but spermatogenesis was blocked at the stage of spermatogonia; groups of proliferating Leydig cells in the loose connective tissue between the tubules were also seen. In 6 and 12 months, the status of the seminiferous tubules remained unchanged, but structures typical of the epididymis and developing vas deferens were revealed. The number of proliferating Leydig cells increased. The initially low testosterone concentration in the blood of castrated males increased significantly as soon as in 1 month after transplantation and grew up to 3 months, remaining at a level ~50% of normal. Engraftment of cryopreserved neonatal testicular tissue was observed in 60% cases, however, engrafted tissue, similar to the fresh one, retained the ability for organogenesis with the formation of mature seminiferous tubules, epididymis, and groups of proliferating Leydig cells. The dynamics of blood testosterone concentration in rats with cryopreserved and fresh transplantation was similar. Subcapsular transplantation did not adversely affect the kidneys, which was seen from normal histological structure of the kidneys and creatinine and urea concentrations in the blood.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2015

Differential regulation of apoptosis in slow and fast twitch muscles of aged female F344BN rats

Age-related muscle atrophy is characterized by decreases in muscle mass and is thought be mediated, at least in part, by increases in myocyte apoptosis. Recent data has demonstrated that the degree of muscle loss with aging may differ between males and females while other work has suggested that apoptosis as indicated by DNA fragmentation may be regulated differently in fast- and slow-twitch muscles. Herein, we investigate how aging affects the regulation of muscle apoptosis in the fast-twitch extensor digitorum longus (EDL) and slow-twitch soleus muscles of young (6-month), aged (26-month), and very aged (30-month) female Fischer 344/NNiaHSD × Brown Norway/BiNia (F344BN) rats. Tissue sections were stained with hydroethidium for ROS and protein extract was subjected to immunoblotting for assessing apoptotic markers. Our data suggest that decreases in muscle mass were associated with increased DNA fragmentation (TUNEL positive) and increases in reactive oxygen species (ROS) as determined by hydroethidium staining in both the EDL and soleus. Similar to our previous work using aged male animals, we observed that the time course and magnitude of changes in Bax, Bcl-2, caspase-3, caspase-9, and cleavage of α-fodrin protein were regulated differently between muscles. As a result, These data suggest that aging in the female F344BN rat is associated with decreases in muscle mass, elevations in ROS level, increased muscle cell DNA fragmentation, and alterations in cell membrane integrity and that apoptotic mechanisms may differ between fiber types.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2017

Noninvasive PET quantitative myocardial blood flow with regadenoson for assessing cardiac allograft vasculopathy in orthotopic heart transplantation patients

Background: Risk stratification and early detection of cardiac allograft vasculopathy (CAV) is essential in orthotopic heart transplantation (OHT) patients. This study assesses the changes in myocardial blood flow (MBF) noninvasively in OHT patients using quantitative cardiac PET with regadenoson. Methods: Twelve patients (Group 1) (8 males, 4 females, mean age 55 ± 7 years) with no history of post OHT myocardial ischemia were enrolled 5.4 ± 2.0 years after OHT. Fifteen patients (Group 2) (9 males, 6 females, mean age 71 ± 9 years) with intermediate pretest probability but not documented evidence for coronary artery disease (CAD) were also included to serve as control. Global and regional MBFs were assessed using dynamic {sup 13}N-NH{sub 3} PET at rest and during regadenoson-induced hyperemia. The coronary flow reserve (CFR) was also calculated as the ratio of hyperemic to resting MBF. Results: Mean regadenoson-induced rate-pressure products were similar in both groups, while there was an increase in resting rate-pressure product in Group 1 patients. Both mean and median values of resting MBF were higher in Group 1 than Group 2 patients (1.33 ± 0.31 and 1.01 ± 0.21 mL/min/g for Groups 1 and 2, respectively, P < .001), while mean hyperemic MBF values were similar in both Groups (2.68 ± 0.84 and 2.64 ± 0.94 mL/min/g, P = NS) but median hyperemic MBF values were lower in Group 1 than Group 2 patients (2.0 vs. 2.60 mL/min/g, P = .018). Both mean and median CFR values demonstrated a significant reduction for Group 1 compared to Group 2 patients (2.07 ± 0.74 vs 2.63 ± 0.48, P = .025). Conclusions: This study suggests that the MBF in OHT patients may be abnormal at resting state with diminished CFR. This hints that the epicardial and microvascular coronary subsystem may be exacerbated after OHT leading to the gradual progression of CAV. [French] French Abstract: Contexte: Cette étude pilote par tomographie a positrons évalue de manière quantitative les changements de perfusion myocardique et le risque de vasculopathie coronaire après transplantation cardiaque chez l’être humain. Méthodes: Douze patients (groupe 1) (8 hommes, 4 femmes, âge moyen 55 ± 7 ans) sans antécédents d'ischémie myocardique post-chirurgicale ont été étudiés après 5,4 ± 2,0 ans après transplantation cardiaque. Quinze patients (groupe 2) (9 hommes, 6 femmes, âge moyen 71 ± 9 ans) avec une probabilité intermédiaire mais sans signes objectifs de maladie coronarienne ont servi de contrôles. Les donnes de perfusion myocardique globales et régionales ont été évaluées par tomographie à positrons l'aide de{sup 13}N-NH3 au repos et durant l'hyperémie induite par le vasodilatateur coronarien régadénoson. La réserve de flux coronarien a été calculée sur base du rapport entre le flux myocardique hyperhémique induit par le régadénoson et le flux myocardique au repos. Résultats: les double produits (fréquence cardiaque x tension artérielle) moyens après régadénoson furent similaires chez les deux groups de patients. Par contre le double produit au repos était plus élevé dans le groupe de patient transplantés. Les valeurs moyennes et médianes de perfusion myocardique globale au repos ont été calculées à 1.33 ± 0.31 ml/min/g dans le groupe de patients transplantés et 1.01 ± 0.21 ml/min/g dans le groupe control (P < 0.001). Après régadénoson, les valeurs moyennes de perfusion myocardique se sont avérées similaires dans les deux groupes (2,68 ± 0,84 et 2,64 ± 0,94 ml/min/g, P > 0.05). Néanmoins les valeurs médianes se sont avérées inferieures dans le groupe 1 comparativement au groupe control (2,0 versus 2,60 ml/min/g; P = 0,018). Les valeurs moyennes et médianes de réserve de flux myocardique mesurées étaient significativement réduites chez les patient transplantés (2,07 ± 0,74) en comparaison aux patients du groupe 2 (2,63 ± 0,48; P = 0.025). Conclusion: La perfusion myocardique au repos peut s’avérer anormale après transplantation cardiaque et s’accompagner d’une diminution de la réserve du flux coronaire. Cette étude pilote suggère que les vaisseaux épicardiques et la micro-vascularisation du myocarde peuvent être atteints après transplantation et conduire à la maladie coronaire du greffon. [Spanish] Spanish Abstract: Antecedentes: la estratificación de riesgo y detección temprana de la vasculopatía del aloinjerto cardiaco (VAC) es esencial en los pacientes con trasplante cardiaco ortotópico (TCO). El presente estudio evalúa de forma no invasiva los cambios en el flujo sanguíneo miocárdico (FSM) en pacientes con TCO utilizando el PET cardiaco cuantitativo con regadenoson. Métodos: Doce pacientes (Grupo 1) (8 hombres, 4 mujeres, edad promedio 55 ± 7 años) sin historia de isquemia miocárdica posterior al TCO fueron incluidos después de 5.4 ± 2.0 años de ser trasplantados. Quince pacientes (Grupo 2) (9 hombres, 6 mujeres, edad promedio 71 ± 9 años) con probabilidad pre-prueba intermedia pero sin evidencia documentada de enfermedad arterial coronaria (EAC) fueron incluidos como grupo control. El FSM global y regional fueron evaluados utilizando el estudio PET dinámico con {sup 13}N-NH{sub 3} en reposo y durante la inducción de hiperemia con regadenoson. La reserva de flujo coronario (RFC) también fue calculada como la proporción entre el FSM hiperémico y el de reposo. Resultados: el producto de velocidad-presión promedio inducido por regadenoson fue similar en ambos grupos, mientras que existió un incremento de este producto velocidad-presión durante el reposo en el Grupo 1 de pacientes. Los valores de la media y mediana del FSM de reposo fueron mayores en el Grupo 1 que el Grupo 2 de pacientes (1.33 ± 0.31 y 1.01 ± 0.21 mL/min/g para los Grupos 1 y 2, respectivamente, P < 0.001). La media de los valores del FSM hiperémico fueron similares en ambos grupos (2.68 ± 0.84 and 2.64 ± 0.94 mL/min/g, P = NS), sin embargo la mediana fue menor en el Grupo 1 que en el Grupo 2 (2.0 vs. 2.60 mL/min/g, P = .018). Tanto la media como la mediana para los valores de la RFC demostraron una disminución significativa en el Grupo 1 comparada con el Grupo 2 (2.07 ± 0.74 vs. 2.63 ± 0.48, P = 0.025). Conclusiones: El presente estudio sugiere que el FSM en pacientes con TCO puede estar alterado en reposo con una RFC disminuida. Esto indica que los sistemas coronarios epicardico y microvascular pudieran estar inflamados posterior al TCO conduciendo a una progresión gradual de la VAC. [Chinese] Chinese Abstract: 背景: 对于原位心脏移植 (OHT) 病人, 早期检测移植心脏血管病变 (CAV) 和进行危险分层是必要的。 本研究拟通过类伽腺苷定 心脏 PET 显像, 非侵入性地评估 OHT 病人心肌血流 (MBF) 的变化。 方法: 研究对象分为两组。 第一组, 12个病人 (8 男, 4女, 平均 55 ± 7岁), OHT 后 5.4 ± 2.0 年, 没有 OHT 后心肌缺血。 第二组 (对照组), 15 个病人 (9 男, 6 女, 平均 71 ± 9 岁), 中等冠心病可能, 但尚未确诊。 分别于静息及类伽腺苷药物负荷下, 动态采集 {sup 13}N-NH{sub 3} PET 图像, 获得整体和局部 MBF。冠脉血流储备 (CFR) 通过负荷 MBF /静息 MBF 计算而得。 结果: 类伽腺苷负荷时, 反映心肌耗氧 的心率血压乘积在两组间没有差异, 但在静息时, 第一组明显高于第二组。静息时, 第一组 MBF 的平均值高于第二组 (1.33 ± 0.31 vs. 1.01 ± 0.21 mL/min/g, P < 0.001); 负荷时, 两组 MBF 的平均值无差异 (2.68 ± 0.84 vs. 2.64 ± 0.94 mL/min/g, P = NS), 但 MBF 的中位数第一组要低于第二组 (2.0 vs. 2.60 mL/min/g, P = 0.018), 且第一组 CFR 的平均值明显低于第二组 (2.07 ± 0.74 vs. 2.63 ± 0.48, P = 0.025)。 结论: 在原位心脏移植病人中, 冠脉血流储备以及静息心肌血流 均呈现明显异常。提示原位心脏移植后, 冠状动脉心外膜血管与微小血管功能均受损, 进而将逐渐导致移植心脏血管病变。 关键词: 动态PET, 类伽腺苷, 冠状动脉血流储备, 原位心脏移植, 移植心脏血管病变。.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2019

Use of abandoned structures by Przewalski’s wild horses and other wildlife in the Chernobyl Exclusion Zone

Przewalski’s wild horses (Equus ferus przewalski) are an endangered species and current conservation efforts aim to maintain genetic diversity and reintroduce wild populations. From 1998-2004, 36 Przewalski’s horses were introduced in the Chernobyl Exclusion Zone (CEZ) with no subsequent direct management, and current population size and genetic diversity are unknown. We used remote cameras positioned at the entrance of abandoned structures within the CEZ to elucidate visitation of these structures by Przewalski’s horses and other large mammals to assess the use of this method for monitoring the horse population within the CEZ. We estimated frequency of structure use in winter (Nov 2016 – Feb 2017) and summer (Mar 2018 – Oct 2018) periods and estimated basic group characteristics such as group type (all male vs. mixed sex), group size, and number of foals. Przewalski’s horses were detected 35 times at 9 of 10 monitored structures in winter and 149 times at all 8 monitored structures in summer. Eight other mammalian species were documented using abandoned structures. Mixed sex groups of horses contained 5.30 ± 0.25 adults and 1.00 ± 0.12 foals (Mean± S.E.). Furthermore, all-male groups contained 1.59 ± 0.15 individuals. Our data suggest Przewalski’s horses routinely use abandoned structures in the CEZ with visitation patterns tending to be nocturnal in winter and crepuscular in summer. Congregation of horses in these structures could have implications for future monitoring of the population by providing detailed information on demographics, population size, and genetic diversity which would benefit management plans for this population and provide a baseline for future work.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2021

High-Grade Vulvar, Vaginal, and Anal Precancers Among U.S. Adolescents and Young Adults After Human Papillomavirus Vaccine Introduction

Since human papillomavirus vaccine introduction, incidence rates of cervical precancers have decreased; however, the vaccine's impact on noncervical anogenital precancers has not been shown. These precancers are identified opportunistically and are not collected routinely by most cancer registries. This study examined the incidence rates of high-grade (intraepithelial lesions grade 3) vulvar, vaginal, and anal precancers among persons aged 15–39 years using 2000–2017 data from select cancer registries covering 27.8% of the U.S. population that required reporting of these precancers. Trends in incidence rates were evaluated with Joinpoint regression. Analyses were conducted in 2020. High-grade vulvar precancer rates declined by 21.0% per year after human papillomavirus vaccine introduction among females aged 15–19 years. In addition, high-grade vaginal precancer rates declined by 19.1% per year among females aged 15–29 years after human papillomavirus vaccine introduction. Compared with that in the prevaccine period when high-grade anal precancer rates were increasing, anal precancer rates after human papillomavirus vaccine introduction were stable among females aged 15–29 years and among males aged 30–39 years. Among males aged 15–29 years, the rates increased over the entire period but less so after human papillomavirus vaccine introduction. In conclusion, opportunistically-detected high-grade vulvar and vaginal precancers among females aged 15–29 years decreased and anal precancers stabilized in years after the introduction of the human papillomavirus vaccine, which is suggestive of the impact of the vaccine on noncervical human papillomavirus cancers.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2023

Extrapair offspring of the blue-footed booby show no sign of higher fitness in the first 10 years of life

According to the good genes and genetic compatibility hypotheses, females of socially monogamous species obtain genetic benefits for their offspring by performing extrapair copulations with males of higher quality than their social mates or males with whom they are more genetically compatible. If extrapair offspring do receive genetic benefits in the form of advantageous alleles or more compatible allele combinations, they should outperform their within-pair half-siblings' survival and/or reproductive output. Here, in this study, we followed 52 extrapair and 737 within-pair blue-footed booby, Sula nebouxii, offspring during their first 10 years of life (excluding the embryonic period and the first 10 days after hatching) to assess whether they differed in fledging probability, fledgling body condition, recruitment probability, age at first reproduction, number of breeding events or accumulated breeding success. Extrapair and within-pair offspring did not differ in any of these proxies of fitness. Furthermore, we found that extrapair offspring were equally likely to occur in any hatching position. However, differences in fledgling production over the lifetime could not be ruled out, and because only within-pair production of eggs and fledglings was tallied, the possibility remains that extrapair offspring could produce more extrapair offspring later in life than do within-pair offspring. Furthermore, the possibility of context-dependent genetic benefits occurring only under stressful conditions cannot be discounted because our sample of offspring was obtained in a single exceptionally favourable reproductive season.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2011

Fto colocalizes with a satiety mediator oxytocin in the brain and upregulates oxytocin gene expression

Highlights: {yields} The majority of neurons synthesizing a satiety mediator, oxytocin, coexpress Fto. {yields} The level of colocalization is similar in the male and female brain. {yields} Fto overexpression in hypothalamic neurons increases oxytocin mRNA levels by 50%. {yields} Oxytocin does not affect Fto expression through negative feedback mechanisms. -- Abstract: Single nucleotide polymorphisms in the fat mass and obesity-associated (FTO) gene have been associated with obesity in humans. Alterations in Fto expression in transgenic animals affect body weight, energy expenditure and food intake. Fto, a nuclear protein and proposed transcription co-factor, has been speculated to affect energy balance through a functional relationship with specific genes encoding feeding-related peptides. Herein, we employed double immunohistochemistry and showed that the majority of neurons synthesizing a satiety mediator, oxytocin, coexpress Fto in the brain of male and female mice. We then overexpressed Fto in a murine hypothalamic cell line and, using qPCR, detected a 50% increase in the level of oxytocin mRNA. Expression levels of several other feeding-related genes, including neuropeptide Y (NPY) and Agouti-related protein (AgRP), were unaffected by the FTO transfection. Addition of 10 and 100 nmol oxytocin to the cell culture medium did not affect Fto expression in hypothalamic cells. We conclude that Fto, a proposed transcription co-factor, influences expression of the gene encoding a satiety mediator, oxytocin.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2012

Apolipoprotein E-knockout mice show increased titers of serum anti-nuclear and anti-dsDNA antibodies

Highlights: Black-Right-Pointing-Pointer Titers of ANA and anti-dsDNA antibodies were higher in ApoE{sup -/-} than C57B6/L mice. Black-Right-Pointing-Pointer Spleen was greater and splenocyte apoptosis lower in ApoE{sup -/-} than B6 mice. Black-Right-Pointing-Pointer Level of TLR4 was lower in spleen tissue of ApoE{sup -/-} than B6 mice. Black-Right-Pointing-Pointer The TLR4 pathway may participate in maintaining the balance of splenocyte apoptosis. Black-Right-Pointing-Pointer The TLR4 pathway may participate in antibody production in spleen tissue. -- Abstract: Apolipoprotein E-knockout (ApoE{sup -/-}) mice, atherosclerosis-prone mice, show an autoimmune response, but the pathogenesis is not fully understood. We investigated the pathogenesis in female and male ApoE{sup -/-} mice. The spleens of all ApoE{sup -/-} and C57BL/6 (B6) mice were weighed. The serum IgG level and titers of anti-nuclear antibody (ANA) and anti-double-stranded DNA (anti-dsDNA) antibody were assayed by ELISA. Apoptosis of spleen tissue was evaluated by TUNEL. TLR4 level in spleen tissue was tested by immunohistochemistry and Western blot analysis. Levels of MyD88, p38, phosphorylated p38 (pp38), interferon regulatory factor 3 (IRF3) and Bcl-2-associated X protein (Bax) in spleen tissue were detected by Western blot analysis. We also survey the changes of serum autoantibodies, spleen weight, splenocyte apoptosis and the expressions of TLR4, MyD88, pp38, IRF3 and Bax in spleen tissue in male ApoE{sup -/-} mice after 4 weeks of lipopolysaccharide (LPS), Toll-like receptor 4 ligand, administration. ApoE{sup -/-} mice showed splenomegaly and significantly increased serum level of IgG and titers of ANA and anti-dsDNA antibody as compared with B6 mice. Splenocyte apoptosis and the expression of TLR4, MyD88, pp38, IRF3 and Bax in spleen tissue were significantly lower in ApoE{sup -/-} than B6 mice. The expression of TLR4, MyD88, IRF3, pp38, and Bax differed by sex in ApoE{sup -/-} spleen tissue. The down-regulation of TLR4 signal molecules induced by LPS led to decreased expression of Bax and increased serum titers of ANA and anti-dsDNA antibody. Therefore, the TLR4 signal pathway may participate in maintaining the balance of splenocyte apoptosis and autoantibody production in ApoE{sup -/-} mice.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2012

Generation of ER{alpha}-floxed and knockout mice using the Cre/LoxP system

Highlights: Black-Right-Pointing-Pointer ER{alpha} floxed and knockout mice were generated. Black-Right-Pointing-Pointer Disruption of the ER{alpha} gene results in sterility in both male and female mice. Black-Right-Pointing-Pointer ER{alpha}{sup -/-} mice have ovaries with hemorrhagic follicles and hypoplastic uterus. Black-Right-Pointing-Pointer Female ER{alpha}{sup -/-} mice develop obesity. -- Abstract: Estrogen receptor alpha (ER{alpha}) is a nuclear receptor that regulates a range of physiological processes in response to estrogens. In order to study its biological role, we generated a floxed ER{alpha} mouse line that can be used to knock out ER{alpha} in selected tissues by using the Cre/LoxP system. In this study, we established a new ER{alpha} knockout mouse line by crossing the floxed ER{alpha} mice with Cre deleter mice. Here we show that genetic disruption of the ER{alpha} gene in all tissues results in sterility in both male and female mice. Histological examination of uterus and ovaries revealed a dramatically atrophic uterus and hemorrhagic cysts in the ovary. These results suggest that infertility in female mice is the result of functional defects of the reproductive tract. Moreover, female knockout mice are hyperglycemic, develop obesity and at the age of 4 months the body weight of these mice was more than 20% higher compared to wild type littermates and this difference increased over time. Our results demonstrate that ER{alpha} is necessary for reproductive tract development and has important functions as a regulator of metabolism in females.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2013

NGF induces adult stem Leydig cells to proliferate and differentiate during Leydig cell regeneration

Highlights: •Nerve growth factor has shown significant changes on mRNA levels during Adult Leydig cells regeneration. •We established the organ culture model of rat seminiferous tubules with ethane dimethyl sulphonate (EDS) treatment. •Nerve growth factor has shown proliferation and differentiation-promoting effects on Adult stem Leydig cells. •Nerve growth factor induces progenitor Leydig cells to proliferate and differentiate and immature Leydig cells to proliferate. -- Abstract: Nerve growth factor (NGF) has been reported to be involved in male reproductive physiology. However, few reports have described the activity of NGF during Leydig cell development. The objective of the present study was to examine the role of NGF during stem-Leydig-cell (SLC) regeneration. We investigated the effects of NGF on Leydig-cell (LC) regeneration by measuring mRNA levels in the adult rat testis after ethane dimethanesulfonate (EDS) treatment. Furthermore, we used the established organ culture model of rat seminiferous tubules to examine the regulation of NGF during SLC proliferation and differentiation using EdU staining, real-time PCR and western blotting. Progenitor Leydig cells (PLCs) and immature Leydig cells (ILCs) were also used to investigate the effects of NGF on LCs at different developmental stages. NGF mRNA levels changed significantly during Leydig-cell regeneration in vivo. In vitro, NGF significantly promoted the proliferation of stem Leydig cells and also induced steroidogenic enzyme gene expression and 3β-HSD protein expression. The data from PLCs and ILCs showed that NGF could increase Cyclin D1 and Hsd 17b3 mRNA levels in PLCs and Cyclin D1 mRNA levels in ILCs. These results indicate that NGF may play an important role during LC regeneration by regulating the proliferation and differentiation of LCs at different developmental stages, from SLCs to PLCs and from PLCs to ILCs. The discovery of this effect of NGF on Leydig cells will provide useful information for developing new potential therapies for PADAM (Partial Androgen Deficiency in the Aging Male)

60 APPLIED LIFE SCIENCES↗
DOE OSTI2014

Apolipoprotein E-knockout mice on high-fat diet show autoimmune injury on kidney and aorta

Highlights: • Titers of ANA and anti-dsDNA antibodies were similar in ApoE{sup −/−} and Fas{sup −/−} mice. • The spleen weights and glomerular areas were similar in ApoE{sup −/−} and Fas{sup −/−} mice. • Expressions of IgG and C3 in glomeruli were similar in ApoE{sup −/−} and Fas{sup −/−} mice. • IgG, C3 and macrophage infiltration in aortic plaques were found in ApoE{sup −/−} mice. - Abstract: Background: Apolipoprotein E-knockout (ApoE{sup −/−}) mice is a classic model of atherosclerosis. We have found that ApoE{sup −/−} mice showed splenomegaly, higher titers of serum anti-nuclear antibody (ANA) and anti-dsDNA antibody compared with C57B6/L (B6) mice. However, whether ApoE{sup −/−} mice show autoimmune injury remains unclear. Methods and results: Six females and six males in each group, ApoE{sup −/−}, Fas{sup −/−} and B6 mice, were used in this study. The titers of serum ANA, anti-dsDNA antibody and creatinine and urine protein were measured by ELISA after 4 months of high-fat diet. The spleen weight and the glomerular area were determined. The expressions of IgG, C3 and macrophage in kidney and atherosclerotic plaque were detected by immunostaining followed by morphometric analysis. Similar to the characteristics of Fas{sup −/−} mice, a model of systemic lupus erythematosus (SLE), ApoE{sup −/−} mice, especially female, displayed significant increases of spleen weight and glomerular area when compared to B6 mice. Also, elevated titers of serum ANA, anti-dsDNA antibody and creatinine and urine protein. Moreover, the expressions of IgG, C3 and macrophage in glomeruli and aortic plaques were found in ApoE{sup −/−} mice. In addition, the IgG and C3 expressions in glomeruli and plaques significantly increased (or a trend of increase) in female ApoE{sup −/−} mice compared with males. Conclusions: Apolipoprotein E-knockout mice on high-fat diet show autoimmune injury on kidney and aorta.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2017

Decreased expression of orexin 1 receptor in adult mice testes during alloxan-induced diabetes mellitus perturbs testicular steroidogenesis and glucose homeostasis

Diabetes mellitus (DM) affects male reproductive system and causes infertility. The male reproductive health is largely dependent upon uptake and proper utilization of glucose by testicular cells. Results show involvement of orexin A (OXA) and its receptor (OX1R) in regulation of steroidogenesis and glucose homeostasis in adult mice testis. However, the role of OX1R in regulation of testicular functions during hyperglycemia has not been investigated so far. The present study, therefore, examined the role of OX1R in regulation of steroidogenesis and glucose homeostasis in testis of adult mice during alloxan-induced type 1 DM. A significant decrease was noted in body weight and testis weight in alloxan-treated mice compared to controls. The blood glucose level, however, was markedly increased in treated animals than in controls. Further, serum and intratesticular level of testosterone, activities of testicular steroidogenic enzymes, and expressions of various steroidogenic markers, OX1R, glucose transporter 3 (GLUT3) and Wilms' tumor gene (WT1) were downregulated in treated mice. The level of glucose, activity of lactate dehydrogenase (LDH) and lactate concentration in the testes of diabetic mice were also decreased; a significant increase in the number of testicular apoptotic cells with concomitant increase in the expression of caspase-3 was noted in these mice. Furthermore, DM affected germ cell proliferation with decreased expression of proliferating cell nuclear antigen (PCNA). Results thus suggest that type 1 DM impairs testicular steroidogenesis and glucose homeostasis through inhibition of OXA/OX1R signaling cascade due to decreased OX1R expression in adult mice, thereby affecting germ cell survival and their proliferation in the testis. - Highlights: • Alloxan monohydrate treatment reduces expression of testicular OX1R in adult mice. • Decreased expression of OX1R perturbs testicular steroidogenesis. • Reduced expression of OX1R affects testicular glucose homeostasis. • Impairment in OX1R expression disturbs germ cell survival and proliferation.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

RNA interference in vivo in Schistosoma japonicum: Establishing and optimization of RNAi mediated suppression of gene expression by long dsRNA in the intra-mammalian life stages of worms

Schistosomes are parasitic platyhelminths that threaten over 600 million people globally. In recent years, RNA interference (RNAi) has been widely used as a molecular tool in research into the genomic function of parasites. We aim to develop effective protocols for application of RNAi technology in the intra-mammalian life stages of Schistosoma japonicum. In this work, the expression of the parasite gene encoding cathepsin B1 (SjCB1) was targeted by exposing the worms to 10 μg of long dsRNA dissolved in 0.1 ml of 0.7% NaCl injected into the tail vein of infected mice. This method was effective and specific for eliciting SjCB1 gene suppression in both male and female adult worms in vivo (>79.4% in male and >91.5% in female knockdown relative to control). In 60 cercaria infected mice, RNAi suppression of gene expression was best achieved by using 10 μg of target dsRNA for at least 4 days. The recommended procedure for interference producing long-term suppression was an injection of dsRNA on the first day of infection with booster injections administered every 4 days for up to 26 days. Long-term suppression of three published functional genes (peroxiredoxin-1, mago nashi, insulin receptor) in S. japonicum provided more information about the role of the expression of these genes in producing particular phenotypes. The protocols described here may be more convenient, economical and applicable, than currently available technology and have contributed to the observation of more phenotypes during worm development from schistosomula to adult. These approaches may promote and facilitate further studies into functional schistosome genomics.

60 APPLIED LIFE SCIENCES↗